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Q&A #68 with Dr. Rhonda Patrick (3/1/25)

Posted on March 14th 2025 (4 months)

Dr. Rhonda Patrick discusses saturated fats and LDL, luteolin's benefits, glyphosate risks, natural vs. artificial flavors, and black cumin seed effects.

inflammation

Does Grounding Actually Reduce Inflammation? - Rhonda Patrick

Posted on January 21st 2025 (5 months)

In this clip, Dr. Rhonda Patrick evaluates grounding science, its effects on inflammation, and evidence-based strategies to reduce oxidative stress.

inflammation

These Are the 7 Best Ways to Reduce Inflammation

Posted on January 16th 2025 (6 months)

In this clip, Dr. Rhonda Patrick discusses seven ways to reduce inflammation, including diet, supplements, omega-3s, heat stress, and sulforaphane.

Topic Pages

  • Breast milk and breastfeeding

    Maternal breastfeeding transmits anti-inflammatory cytokines, immunoglobulins, and pro-resolving lipid mediators in milk, attenuating neonatal inflammation.

  • Cocoa flavonoids (chocolate)
    stub

    Cocoa flavonoids attenuate inflammation by inhibiting NF-κB activation, modulating MAPK signaling, and suppressing pro-inflammatory cytokine production.

  • Cold exposure

    Cold exposure activates sympathetic noradrenergic signaling, driving vasoconstriction and reduced pro-inflammatory cytokine production, thereby attenuating inflammation.

  • Depression

    Peripheral proinflammatory cytokines infiltrate the brain, activating microglia, altering monoamine metabolism and neuroplasticity, precipitating depressive symptomatology.

  • Neu5Gc

    Neu5Gc-mediated inflammation arises when dietary Neu5Gc incorporates into human glycans, attracting anti-Neu5Gc antibodies and activating complement.

  • Quercetin

    Quercetin attenuates inflammation by inhibiting NF-κB activation, suppressing COX-2 expression, and reducing pro-inflammatory cytokine secretion.

  • Sauna

    Heat stress from sauna activates heat-shock proteins and modulates cytokine profiles, subsequently attenuating systemic low-grade inflammation.

  • Sirtuins

    Sirtuins (SIRT1, SIRT6) deacetylate NF-κB p65 and H3K9, suppressing pro-inflammatory gene transcription.

  • Small vessel disease

    Inflammation induces endothelial dysfunction, leukocyte adherence, and microthrombotic occlusion, precipitating cerebral small vessel disease pathology.

  • Sulforaphane

    Sulforaphane attenuates inflammation by activating Nrf2-driven antioxidant genes and suppressing NF-κB–dependent pro-inflammatory cytokine transcription.

  • Toll-like receptors

    Toll-like receptor engagement by pathogen-associated molecular patterns activates NF-κB and cytokine cascades, initiating and propagating innate inflammatory responses.

News & Publications

  • Anti-inflammatory treatments, particularly omega-3 fatty acids and plant-based compounds, effectively reduce depression symptoms in older adults. www.nature.com
    Omega-3 Inflammation Depression Mental Health NSAID Polyphenol

    Inflammation and depression are often linked, particularly in older adults, who tend to experience chronic low-grade inflammation and elevated rates of depression. A recent study found that anti-inflammatory interventions may help reduce symptoms of depression and the risk of developing depression in older adults.

    Researchers conducted a systematic review and meta-analysis of 31 randomized, placebo-controlled trials that assessed the effects of anti-inflammatory therapies on depression in older adults. The various anti-inflammatory agents included omega-3 fatty acids, nonsteroidal anti-inflammatory drugs, and plant-based compounds. The researchers included only trials with at least 20 participants.

    The analysis revealed that anti-inflammatory treatments were more effective than placebos in reducing depression symptoms among older adults. On average, people receiving these treatments exhibited a moderate improvement in symptom severity compared to those taking a placebo. Omega-3 fatty acids and plant-based compounds, such as curcumin and soy protein, appeared particularly beneficial. There was also some evidence suggesting that these treatments might help prevent depression, although the results were not statistically conclusive.

    These findings suggest that targeting inflammation is a promising strategy for managing depression in older adults, especially those with chronic inflammation. Learn more about links between inflammation and depression in Aliquot #36: Inflammation and Depression, part 2

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  • Long-term adherence to healthy diets more than doubles the likelihood of maintaining good overall health, both mentally and physically, into mid-70s. www.nature.com
    Nutrition Diet Aging Inflammation

    With more than 80% of older adults in the U.S. having at least one chronic health condition, finding ways to support healthy aging has become a public health priority. A recent study found that people who followed healthy diets over the long term were more than twice as likely to age well—physically, mentally, and emotionally—even into their mid-70s.

    Researchers followed adults for 30 years as part of two large, long-running health studies in the U.S. They looked at how closely people followed eight well-known dietary patterns, including the Alternative Healthy Eating Index (AHEI)—a scoring system that reflects how well someone’s diet aligns with current nutrition guidelines. Other patterns included the Mediterranean diet, the DASH diet, a plant-based diet, and the Planetary Health Diet.

    The researchers also examined diets linked to higher levels of inflammation and insulin resistance and the amount of ultra-processed food people ate. They then compared these patterns to a comprehensive measure of healthy aging, including physical function, cognitive ability, mental health, and freedom from major chronic disease.

    They found that people with the highest AHEI scores were 2.43 times more likely to maintain good overall health as they aged, up to 75. Similar benefits appeared for people who followed Mediterranean-style, MIND, and plant-based diets. In contrast, those who ate the most ultra-processed food or followed dietary patterns that drive inflammation and high blood glucose levels were less likely to age in good health.

    These findings suggest that long-term dietary choices can meaningfully influence how well we age—not just how long we live. Learn more about lifestyle factors that prolong healthy aging in this episode featuring Dr. Rhonda Patrick.

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  • Curcumin, a compound derived from turmeric, aids in reducing muscle damage and soreness after intense exercise, potentially speeding up recovery. www.tandfonline.com
    Exercise Performance Inflammation Muscle Curcumin Polyphenol

    Intense exercise—especially eccentric movements like downhill running or heavy weightlifting—can cause microscopic muscle damage, inflammation, and soreness. While this process is part of adaptation, excessive damage can delay recovery and hinder performance. A recent study found that curcumin, a compound derived from turmeric, may help reduce muscle damage and soreness, potentially speeding up recovery.

    Researchers analyzed the findings of 11 studies on curcumin and exercise-induced muscle damage. The various studies focused on healthy adults who exercised regularly and took curcumin before, during, or after workouts.

    The analysis revealed that curcumin supplementation may ease muscle soreness, reduce inflammation, and improve recovery after strenuous exercise. However, the benefits depended on dose (which ranged from 90 milligrams to 2.5 grams), bioavailability, and timing, with post-exercise supplementation appearing most effective.

    These findings suggest that curcumin could be a useful supplement for athletes looking to minimize muscle soreness and recover faster. However, its low bioavailability may limit its effectiveness. In addition, the investigators noted that many of the studies were small, limiting their findings' applicability. Curcumin is a polyphenolic compound. Learn more about polyphenols in our overview article.

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  • Cold-water immersion may offer stress relief and immune benefits, but its effects are highly time dependent. journals.plos.org
    Sleep Inflammation Immune System Mental Health Cold Stress

    Cold-water immersion has surged in popularity, with ice baths and cold showers touted as shortcuts to better health. Advocates claim it improves mood, sharpens focus, and speeds up recovery. A recent study found that while cold exposure temporarily increased inflammation, it reduced stress 12 hours later, improved sleep, and reduced sick days.

    Researchers conducted a systematic review and meta-analysis of 11 studies involving more than 3,100 healthy adults investigating the effects of cold-water exposure on mental and physical health markers, including mood, stress, immunity, inflammation, and sleep quality. Participants in the various studies took cold showers or ice baths at temperatures between 7°C (45°F) and 15°C (59°F) for at least 30 seconds.

    The analysis revealed that inflammation spiked immediately after immersion and stayed elevated for an hour. Interestingly, stress levels dropped 12 hours later but remained unchanged at other time points. Cold exposure did not immediately boost immune function, but a separate analysis linked cold showers to a 29% drop in sickness absence. Participants reported better sleep and overall well-being but no changes in mood.

    These findings suggest that cold-water immersion may offer short-term stress relief and potential immune benefits, with highly time-dependent effects. The effects of cold exposure may be due to hormesis—a compensatory defense response that conditions the body against future stressors. Learn more in Aliquot #97: Thermal Stress, Part II: Unveiling the Power of Cold Exposure on Health and Performance

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  • Long-term, high-dose omega-3 supplementation—2 to 4 grams daily—effectively improves heart function in people with heart failure. pubmed.ncbi.nlm.nih.gov
    Heart Disease Omega-3 Inflammation Mortality Cardiovascular

    Omega-3 fatty acids have long been praised for their health benefits, but their role in treating heart failure has been unclear. While some studies suggest they improve heart function, others have produced mixed results. A recent meta-analysis found that high-dose omega-3 supplementation for a year or more markedly improved heart function and exercise capacity in people with heart failure.

    Researchers analyzed the findings of 14 randomized controlled trials, including more than 9,000 participants with heart failure. They examined the effects of different omega-3 doses and treatment durations on heart function, exercise capacity, biomarkers of heart failure, and overall quality of life. They also analyzed safety outcomes, including dropout rates and overall death rates.

    They found that people who took high doses of omega-3 fatty acids (2,000 to 4,000 milligrams daily) for at least one year had better heart function and improved oxygen consumption during exercise than those in control groups. Lower doses or shorter treatment periods did not produce the same benefits. Importantly, omega-3 supplementation did not increase the risk of adverse events or death.

    These findings suggest that long-term, high-dose omega-3 supplementation effectively improves heart function in people with heart failure. Omega-3s reduce inflammation, a potent contributor to heart failure. Learn more about omega-3s' anti-inflammatory effects in this episode featuring Dr. Bill Harris.

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  • Anthocyanins, potent antioxidants in berries, boost cognitive function in people at higher risk of dementia, particularly those with high inflammation. www.sciencedirect.com
    Brain Diet Inflammation Polyphenol

    Anthocyanins, the compounds that give berries their deep red and purple hues, may do more than add color to a meal. Evidence suggests these potent antioxidants protect brain health, particularly in people at higher risk of dementia. A recent study found that anthocyanins improved cognitive function in people with high inflammation levels, but not those with lower inflammation.

    Researchers conducted a 24-week randomized, placebo-controlled trial to examine anthocyanins' effects on cognition. They categorized participants into two groups based on inflammation levels, using blood biomarkers to make the distinction. Each participant received either anthocyanins or a placebo, and the researchers measured cognitive function before and after the intervention.

    The cognitive test results indicated that participants with high inflammation experienced marked cognitive improvements after anthocyanin treatment, while those with lower inflammation saw no benefit. Interestingly, participants in the high-inflammation group had higher body mass indexes, greater diabetes prevalence, and lower HDL (“good”) cholesterol levels.

    These findings suggest that anthocyanins improve cognitive function among people with high inflammation. Anthocyanins are polyphenolic compounds. Learn more about polyphenols in our overview article.

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  • Regular aerobic exercise in older rats reduces brain inflammation, nerve fiber demyelination, and iron-triggered cell death—potential contributors to Alzheimer's pathology. pubmed.ncbi.nlm.nih.gov
    Exercise Brain Alzheimer's Inflammation Dementia Iron

    The pathological brain changes that drive Alzheimer’s disease may begin as much as 20 years before cognitive signs become evident. However, evidence indicates that exercise can slow or prevent these changes. A recent study involving older rats found that regular aerobic exercise reduces age-related inflammation in the brain and improves the balance between nerve fibers and their protective myelin coating.

    Researchers had older rats exercise on a treadmill for eight weeks. Then, they examined the rats' brain tissue and analyzed changes in tau protein, amyloid plaques, and iron levels.

    They discovered that older rats engaging in regular physical exercise experienced reduced age-related inflammation and improved balance between nerve fibers and their protective myelin coating. They also learned that excessive iron in oligodendrocytes—cells that support and insulate nerve fibers—triggers a type of cell death known as ferroptosis, possibly contributing to the formation of amyloid-beta plaques linked to Alzheimer’s. They identified statistical connections between tau and amyloid proteins (hallmarks of Alzheimer’s), iron levels, and cells in the hippocampus, a brain region crucial for memory.

    These findings indicate that iron plays a critical role in Alzheimer’s pathology, but exercise can mitigate some of these effects. Learn more about preventing and reversing Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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  • Traumatic brain injuries reactivate dormant herpes simplex virus, causing inflammation and accumulation of harmful proteins in the brain, a process potentially linked to Alzheimer's disease. www.science.org
    Brain Alzheimer's Inflammation Virus TBI

    Each year, millions of people sustain a traumatic brain injury (TBI), often resulting in serious, long-term consequences. Research indicates that even one head injury is linked to a higher risk of developing dementia, with the risk increasing further after two or more. A recent study found that TBIs can reactivate dormant herpes simplex virus type 1 (HSV-1), driving neuroinflammation and contributing to the development of Alzheimer’s.

    Researchers created a three-dimensional model of the human brain. Then, they subjected HSV-1-infected and non-infected brain tissue to multiple blows, emulating TBIs and their ensuing pro-inflammatory effects.

    They found that repeated mild blows to HSV-1-infected tissues reactivated the virus, triggering inflammatory processes in the brain and driving the buildup of amyloid-beta and phosphorylated tau—proteins linked to brain damage and memory loss. These harmful effects worsened with additional injuries but didn’t occur in uninfected tissue.

    These findings demonstrate that viral reactivation in the brain may contribute to the development of Alzheimer’s. HSV-1 is the virus responsible for causing cold sores and genital herpes. It infects approximately 80% of people by age 60 and is commonly found in the brains of older adults. In people with the APOE4 gene, HSV-1 markedly increases the risk of Alzheimer’s.

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  • Regular cold showers boost immune responses, increasing levels of immunoglobulins and cytokines critical in protecting against infections. www.sciencedirect.com
    Inflammation Immune System Cold Stress

    Cold exposure has long been used in traditional medicine for its many health benefits. However, recent research demonstrates that cold affects the immune system. A new study found that regular cold showers can increase immune cells and antibodies that protect against infections.

    Researchers assigned 60 healthy adults to one of two groups, one taking cold showers (five to 10 minutes at 10° to 15°C, 50° to 59°F) and the other hot showers (40° to 42°C, 104° to 107.6°F) for 90 days. Showers were brief, lasting just five to 10 minutes. They took blood samples at baseline, 30, 60, and 90 days to measure various immune factors, including immunoglobulins, cytokines, and interferon-gamma levels.

    They found that those who took cold showers had considerably higher levels of immunoglobulins (IgG, IgA, and IgM) and cytokines (interleukin-2 and interleukin-4). In contrast, those who took hot showers experienced decreased IgM levels and no marked changes in cytokine levels.

    These findings suggest that regular cold showers boost the body’s immune responses. Cold showers offer a practical and accessible alternative to full cold-water immersion, requiring no specialized equipment beyond a regular shower, and can be taken conveniently at home. Their brief duration minimizes the risk of hypothermia, making them a safer cold exposure option. Learn about the many health benefits of cold exposure in our comprehensive overview article.

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  • Exposure to fine particulate matter in air pollution more than doubles the risk of developing eczema. journals.plos.org
    Inflammation Pollution Skin Oxidative Stress

    Eczema, a chronic inflammatory skin condition, affects roughly 10% of people in the United States. Evidence suggests that environmental factors, including air pollution, influence the risk of developing eczema. A recent study found that exposure to fine particulate matter (PM2.5), a key component of ambient air pollution, more than doubles the risk of eczema.

    Researchers drew on data from adults enrolled in the All of Us Research Program. They compared people with eczema to those without, linking their zip codes to average annual PM2.5 concentrations. Then, they analyzed the relationship between PM2.5 levels and eczema while adjusting for factors like demographics, smoking, and other skin conditions.

    They found that people with eczema were exposed to higher levels of PM2.5 than those without eczema. People with eczema lived in areas with about 2% higher PM2.5 concentrations, and the risk of eczema increased considerably with higher pollution levels. The odds of having eczema were more than twice as high (158%) in areas with the highest PM2.5 concentrations, even after accounting for smoking and other health conditions.

    These findings suggest that air pollution contributes to the development of eczema. Given that PM2.5 can infiltrate the skin and contribute to skin barrier dysfunction, oxidative stress, and inflammation, addressing air pollution could be a key strategy for preventing and managing eczema. Sulforaphane, a bioactive compound derived from broccoli, promotes the excretion of air pollutants. Learn more in this clip featuring Dr. Jed Fahey.

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  • A nasal spray delivering stem cell-derived extracellular vesicles reduces inflammation and improves brain function in a mouse model of Alzheimer's disease. isevjournals.onlinelibrary.wiley.com
    Brain Alzheimer's Inflammation Stem Cells Memory

    Stem cell-based therapies show promise as treatments for neurodegenerative diseases, including Alzheimer’s. However, transplanting stem cells into the brain carries considerable risks. A recent study found that a nasal spray that delivered neural stem cell extracellular vesicles—tiny particles that carry proteins and genetic material—reduced inflammation and improved brain function in a mouse model of Alzheimer’s disease, offering a safer, less risky approach.

    Researchers used neural stem cell-derived extracellular vesicles created from induced pluripotent stem cells. They administered the vesicles via nasal spray to three-month-old Alzheimer’s model mice. Then, they tracked the vesicles' interaction with brain cells, focusing on microglia and astrocytes, and analyzed gene activity, brain pathology, and behavioral changes.

    They found that the vesicles reduced inflammatory activity in brain cells, decreased levels of amyloid-beta plaques and phosphorylated tau (hallmarks of Alzheimer’s), and improved memory and mood in the mice. These effects persisted for at least two months after treatment without impairing the brain’s immune processes and protein clearance.

    These findings suggest that a nasal spray containing stem cell-derived extracellular vesicles offers a promising new therapy for Alzheimer’s disease, targeting inflammation and preserving brain function while avoiding the risks of direct stem cell transplantation. Other research demonstrates the effectiveness of stem cell therapies for eye diseases. Learn more in this clip featuring Dr. David Sinclair.

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  • Exposure to benzyl butyl phthalate, a common plastic additive in everyday items, was found to cause extensive reproductive cell disruption and DNA damage. journals.plos.org
    Metabolism Inflammation DNA Damage Pollution Environment Genome

    The risks of everyday plastics may go beyond environmental concerns, affecting our reproductive health on a cellular level. Benzyl butyl phthalate (BBP), a common plastic additive found in toys, cleaning products, food packaging, and cosmetics, has been linked to reproductive and developmental impairments. A recent study in worms found that BPP induced abnormalities in chromosome segregation and increased cell death in reproductive cells.

    Researchers exposed C. elegans, a type of roundworm, to four different concentrations of BBP: 1, 10, 100, and 500 micromolar. Then, they measured the chemical’s effects on the worms' chromosomes and cell structure while tracking its metabolism into two primary byproducts: monobutyl phthalate and monobenzyl phthalate.

    They found that exposure to 10 micromolar BBP induced considerable cellular disruption, increasing germ cell apoptosis, abnormalities in chromosome structure, and elevated levels of DNA damage throughout the reproductive tissues. The compound also triggered increased oxidative stress and affected critical genes involved in cell cycle progression and oxidative metabolism.

    These findings suggest that BBP exposure profoundly affects reproductive health by impairing the cellular processes necessary for healthy chromosome segregation and genomic stability. A person’s phthalate burden may contribute to poor metabolic function, inflammation, and cognitive dysfunction. Learn how sauna use induces substantial sweat losses, promoting the excretion of toxic compounds like BBP.

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  • Omega-3 fatty acids reduce inflammation and disease activity in rheumatoid arthritis and lupus—according to an umbrella review of 21 analyses. www.sciencedirect.com
    Omega-3 Inflammation Genetics Arthritis Autoimmunity

    Autoimmune diseases occur when the body mistakenly attacks its own tissues, driving chronic inflammation and tissue damage. However, evidence suggests that omega-3 fatty acids may benefit people with autoimmune diseases. A recent study found that omega-3s help reduce disease severity in rheumatoid arthritis and lupus but are less effective against other autoimmune disorders.

    Researchers conducted an umbrella review to summarize findings from 21 systematic reviews and meta-analyses on the effects of omega-3s on autoimmune diseases. They also used Mendelian randomization—a method that leverages genetic data to identify causal relationships—to explore further whether omega-3s directly influence the risk of developing autoimmune diseases.

    They found that omega-3s were associated with reduced inflammation and disease activity in people with rheumatoid arthritis and lupus. However, they found no clear evidence of omega-3s' effects on other autoimmune diseases, including multiple sclerosis, type 1 diabetes, or Crohn’s disease. The quality of evidence varied, with one high-quality study and several moderate or low-quality studies.

    These findings suggest that omega-3 fatty acids benefit people with certain autoimmune disorders, but their effects vary across different conditions. Omega-3 fatty acids exert robust anti-inflammatory properties due to their formation of specialized pro-resolving molecules (SPMs), a broad class of metabolites that resolve inflammation. Learn more about SPMs in this clip featuring Dr. Bill Harris.

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  • Early exposure to a common pollutant changes the gut microbiome, potentially influencing metabolic health. ehp.niehs.nih.gov
    Microbiome Metabolism Hormones Inflammation Pollution

    Persistent organic pollutants are pervasive environmental toxicants that threaten human health. These compounds break down slowly and are often called “forever chemicals.” Surprisingly, the concern isn’t just that these chemicals affect health but rather the mechanisms by which they do so. A recent study in mice found that exposure to persistent organic pollutants altered the animals' gut microbiome composition, skewing it toward a less beneficial profile.

    Researchers exposed young mice to the persistent organic pollutant tetrachlorodibenzofuran (TCDF), a widely distributed byproduct of various chemical processes. They analyzed the animals' gut microbial composition and assessed the physiological and metabolic effects of the exposure.

    They found that mice exposed to TCDF had lower quantities of short-chain fatty acids, indole-3-lactic acid (an anti-inflammatory compound), and hunger-modulating hormones. Exposed mice also had fewer Akkermansia muciniphila, a type of bacteria that modulates metabolism.

    These findings suggest that early life exposure to persistent organic pollutants alters the gut microbiome in mice, adversely affecting metabolism. Learn about the importance of early life establishment of the gut microbiome in this episode featuring Dr. Eran Elinav.

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  • Consuming olive oil reduces the risk of early death from all causes by 20%. www.nature.com
    Nutrition Cancer Diet Inflammation Mortality Antioxidant Polyphenol Cardiovascular

    Olive oil is rich in bioactive compounds, including polyphenols, carotenoids, and oleic acid. It’s a fundamental component of the Mediterranean diet and is associated with a wide range of health benefits. A recent study found that high olive oil intake—more than 3 tablespoons daily—reduces the risk of early death from all causes by 20%.

    Researchers analyzed data from nearly 23,000 adults enrolled in a long-term cohort study in Italy. Participants completed questionnaires about their olive oil consumption, defined as high (3 tablespoons or more daily) or low (1.5 tablespoons or less daily). The researchers collected information about the participants' lifestyles, assessed their overall diet quality, and measured their biomarkers associated with chronic disease risk.

    They found that compared to low olive oil intake, high intake lowered the risk of early death from all causes by 20%, cancer by 23%, and cardiovascular disease by 25%. However, They found that the effect of high olive oil intake on reducing the risk of dying from all causes and cancer was slightly lower when considering the participants' biomarkers.

    These findings suggest that olive oil reduces the risk of early death from all causes, including cancer and cardiovascular disease. The polyphenols in olive oil exert potent antioxidant, anti-inflammatory, and anti-cancer effects. Learn more about the health benefits of polyphenols in our overview article.

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  • Astaxanthin supplementation and aerobic exercise reduce fatigue, enhance physical performance, and improve cognition. pubmed.ncbi.nlm.nih.gov
    Exercise Performance Inflammation Carotenoids Supplements

    Fatigue is a common condition characterized by persistent tiredness or exhaustion that can affect daily activities. Inflammation is critical in fatigue because it disrupts normal cellular function and energy production. A recent review and meta-analysis found that astaxanthin, a potent antioxidant and anti-inflammatory carotenoid compound, reduces fatigue.

    Researchers analyzed the findings of studies investigating the effects of astaxanthin supplementation on fatigue, cognition, and exercise efficiency. The analysis included 11 randomized controlled trials involving 346 healthy participants. Four of the studies included amateur or professional athletes.

    The researchers found that supplementing with astaxanthin for eight to 12 weeks improved cognition slightly but did not improve reaction time. However, when combined with exercise, astaxanthin enhanced fat oxidation and improved physical performance. Further analysis revealed that the benefits of astaxanthin were more pronounced with aerobic exercise but were dose-dependent, with doses of 20 milligrams or more and supplementation for longer than 12 weeks providing the greatest benefit.

    These findings suggest that astaxanthin reduces fatigue and improves aspects of performance. Astaxanthin is widely available as a dietary supplement but is also present in salmon and salmon roe. Learn more about salmon roe in our overview article.

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  • Chronic inflammation in early adulthood can impair cognitive performance by midlife, with 39% of young adults showing high inflammation levels. pubmed.ncbi.nlm.nih.gov
    Brain Alzheimer's Aging Inflammation Memory Dementia

    Research demonstrates that inflammation in later life harms the brain, increasing the risk of dementia and cognitive decline. However, scientists don’t fully understand the effects of inflammation that begins in early adulthood. A recent study found that inflammation during early adulthood markedly impairs cognitive performance in midlife.

    The research involved more than 2,300 young adults (aged 24 to 58) enrolled in the Coronary Artery Risk Development in Young Adults study. Researchers tracked the participants' inflammation levels, measured by C-reactive protein (CRP), for about 18 years. Five years after their last CRP measurement, the participants completed tests that measured their verbal memory, processing speed, executive function, verbal fluency, category fluency, and overall cognition.

    The researchers identified three inflammation patterns among the participants: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Participants with consistently higher CRP levels were 67 percent more likely to experience poor processing speed and 36 percent more likely to have poor executive function than those with stable, low CRP levels. Those with moderate/increasing CRP levels were twice as likely to have poor processing speed. There were no significant associations between CRP levels and memory, verbal fluency, category fluency, or overall cognition.

    One of the many ways inflammation harms the brain is through its effects on pericytes, tiny cells that surround the brain’s blood vessels and help maintain the blood-brain barrier. Inflammation causes pericytes to release pro-inflammatory cytokines, compromising the barrier and facilitating neurodegeneration. Learn more about links between inflammation, pericytes, and cognitive decline in this clip featuring Dr. Axel Montagne.

    These findings indicate that more than one-third of young adults have high inflammation levels, adversely affecting executive function and processing speed by midlife. They also underscore the importance of managing inflammation throughout life. Omega-3 fatty acids have potent anti-inflammatory effects. Learn more in this episode featuring Dr. Bill Harris.

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  • People with inflammatory bowel disease have 49 percent more microplastics in their feces than healthy people, suggesting a potential link between microplastics and chronic gut inflammation. pubs.acs.org
    Gut Inflammation Pollution Intestinal Permeability

    Inflammatory bowel disease (IBD) is an umbrella term for chronic inflammatory conditions that affect the gut, primarily Crohn’s disease and ulcerative colitis. A growing body of evidence suggests that microplastics – tiny plastic particles ranging between 5 millimeters and 100 nanometers – are pro-inflammatory, potentially contributing to chronic disease. A recent study found that people with inflammatory bowel disease had roughly 49 percent more microplastics in their feces than healthy people.

    Researchers measured microplastic concentrations in the feces of 102 participants. Half of the participants had IBD, and the other half were healthy. Participants completed questionnaires about their plastic usage and exposure.

    The researchers found that the fecal concentration of microplastic particles in the feces of participants with inflammatory bowel diseases averaged 41.8 particles per gram of dry matter. In comparison, healthy participants' concentrations averaged 28.0 particles per gram. The various particles were in sheets, fibers, fragments, and pellets; most were smaller than 300 micrometers. Participants with higher fecal concentrations tended to have more severe IBD. The primary sources of microplastic exposure were plastic packaging (for food and water) and dust.

    These findings suggest that microplastic exposure is linked to the disease process of IBD or that IBD might exacerbate microplastic retention in the body. They also add to the growing evidence suggesting that microplastics influence human health. Scientists have found microplastics throughout the human body, including the sputum, lungs, heart, liver, blood, endometrium, testis, amniotic fluid, and placenta00153-1/fulltext).

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  • Exercise preserves cognitive function in mice by inhibiting neuroinflammation. www.sciencedirect.com
    Exercise Brain Inflammation Memory Dementia NRF2

    Cognitive function typically declines with aging, but evidence suggests physical activity can help mitigate some of these declines. A recent study in mice found that exercise improves memory and spatial learning by inhibiting neuroinflammation, primarily via the actions of irisin, a myokine, and brain-derived neurotrophic factor (BDNF), a growth factor and signaling protein.

    Researchers conducted a two-part study to investigate the effects of regular, low-intensity exercise on cognitive function in mouse models of inflammation-driven memory impairment and microglia (brain immune cell) degeneration.

    First, they assessed the animals' neuroprotective and antioxidant marker levels and subjected them to various memory and behavioral tests. They found that exercise reduced memory problems and cognitive losses by increasing the expression of irisin. In turn, irisin activated BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2), reducing inflammation and blocking the activity of BACE-1, an enzyme critical for amyloid-beta production.

    Then, they studied the effects of irisin on microglia. They found irisin blocked the NF-κB/MAPK/IRF3 pro-inflammatory signaling pathway. It also lowered pro-inflammatory markers while increasing the expression of Nrf2.

    Nrf2 is a cellular protein that activates the transcription of more than 200 cytoprotective proteins that protect against oxidative stress due to injury, inflammation, and normal aging processes. It is an element of the Keap1-Nrf2-ARE biological pathway, a mediator of protective responses to oxidative and electrophilic stressors. Hormetic stressors like exercise, heat exposure, and dietary components trigger Nrf2 activity. Sulforaphane, a compound derived from broccoli, is the most potent naturally occurring hormetic inducer of Nrf2 activity. Learn more about Nrf2 in this clip featuring Dr. Jed Fahey.

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  • Microplastic accumulation in arterial plaques increases the risk for cardiovascular disease-related events nearly fivefold. www.nbcnews.com
    Heart Disease Inflammation Bisphenol A Pollution Oxidative Stress Cardiovascular

    Tiny plastic particles, often called microplastics – ranging between 5 millimeters and 100 nanometers – are ubiquitous environmental pollutants. Scientists have identified microplastics in food (especially seafood), soil, drinking water, fresh- and saltwater bodies, and air. A recent study found that microplastics accumulate in human arterial plaques, increasing the risk for cardiovascular disease-related events, such as heart attack or stroke, nearly fivefold.

    The study involved 257 patients undergoing carotid endarterectomy, a procedure in which a surgeon removes plaques from the heart’s arteries. Researchers analyzed the plaque for the presence of microplastics, measured the patients' inflammatory biomarkers, and tracked their health for about three years.

    They found that more than half of the patients (58.4 percent) had microplastics in their arterial plaques, appearing as jagged-edged foreign particles. Those with microplastics in their plaques were 4.53 times more likely to experience a cardiovascular disease-related event during the three-year follow-up than those without microplastics. They were also more likely to be male, younger, and have diabetes, cardiovascular disease, abnormal blood lipids, and higher inflammatory markers.

    These findings suggest that microplastics, a ubiquitous environmental pollutant, accumulate in arterial plaques, markedly increasing the risk of cardiovascular disease-related events. Evidence indicates that microplastic exposure is associated with many other adverse health outcomes. For example, a comprehensive review of the effects of microplastics revealed that microplastics induce oxidative stress and increase the risk for metabolic dysfunction, neurotoxicity, and some cancers. Some of these effects may be due to compounds commonly associated with plastic manufacturing, such as bisphenol A, or BPA, phthalates, and heavy metals that are present in and on microplastics.

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  • Adopting three or more healthy lifestyle behaviors, including no smoking, optimal sleep, and vigorous physical activity, decreases the risk of irritable bowel syndrome by 42 percent. www.theguardian.com
    Exercise Gut Diet Sleep Inflammation Alcohol Tobacco

    Irritable bowel syndrome (IBS) is a digestive disorder characterized by abdominal cramping, gas, diarrhea, and constipation. The condition affects as many as 10 percent of people worldwide and has no cure. A recent study shows that adopting three or more healthy lifestyle behaviors may reduce the risk of IBS by as much as 42 percent.

    The study involved more than 64,000 people enrolled in the UK Biobank database. Researchers collected information about the participants' dietary intake and whether they engaged in any of five healthy lifestyle behaviors: never smoking, getting optimal sleep, engaging in vigorous physical activity, eating a quality diet, and moderating their alcohol intake.

    They found that 11.8 percent of the participants did not practice any of the five critical healthy behaviors; 32.1 percent practiced one, 34.1 percent practiced two, and 21.9 percent practiced three to five healthy behaviors. As participants engaged in more healthy behaviors, their likelihood of developing IBS decreased, with those practicing one healthy behavior having a 21 percent lower risk, those with two healthy behaviors having a 36 percent lower risk, and those engaging in three to five healthy behaviors having a 42 percent lower risk. These findings were consistent across various groups, regardless of age, sex, job status, where they lived, history of gastrointestinal infection, endometriosis, family history of IBS, or other lifestyle habits.

    These findings suggest that adopting multiple healthy lifestyle behaviors, such as not smoking, staying physically active, and getting good sleep, can significantly reduce the risk of developing IBS. Learn more about factors that influence gut health in this episode featuring Dr. Eran Elinav.

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  • Cold exposure boosts mood and enhances brain connectivity. www.mdpi.com
    Brain Inflammation Depression Cold Stress Norepinephrine

    Cold exposure has long been used to reduce muscle soreness and promote muscle recovery after physical activity. However, evidence indicates that regular cold exposure also improves glucose and lipid metabolism, decreases inflammation, enhances immune function, and improves cognitive performance. Now, findings from a recent study suggest that cold exposure improves mood and increases connectivity between brain networks.

    The study involved 33 men and women who were unaccustomed to regular cold exposure. The participants underwent functional magnetic resonance imaging (fMRI) to assess their brain network connectivity before and after soaking in a cold water (20°C, 68°F) bath. They also reported on their mood before and after the intervention.

    The participants reported feeling more active, alert, attentive, proud, and inspired after the cold exposure. The fMRIs revealed that the participants' positive moods correlated with increased connectivity in the default mode, frontoparietal, salience, and visual lateral networks, regions of the brain that contribute to self-reflection, attention, emotion regulation, and visual processing.

    The findings from this small study suggest that short-term cold exposure improves mood by enhancing brain connectivity in regions associated with mood. These benefits may arise from the effects of norepinephrine, a neurotransmitter involved in vigilance, focus, attention, and mood. Norepinephrine release is one of the most consistent and profound physiological responses to cold exposure. Learn more about cold exposure and the mechanisms that drive its effects in our comprehensive overview article.

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  • Time-restricted eating decreases inflammation and leptin — a hormone that regulates food intake. www.sciencedirect.com
    Diet Hormones Inflammation Time-Restricted Eating

    In the setting of obesity, adipocytes (fat cells) enlarge to accommodate immense quantities of fat. These specialized cells eventually become dysfunctional, releasing inflammatory proteins and activating immune cells called macrophages. In turn, macrophage activation promotes a vicious cycle of inflammation and further dysfunction, increasing the risk of many chronic diseases, including cardiovascular disease and cancer. A recent review and meta-analysis found that time-restricted eating reduces inflammatory markers and leptin.

    Researchers reviewed the findings of randomized-controlled trials investigating the effects of time-restricted eating on inflammation. Their analysis included 25 trials involving 936 participants.

    They found that time-restricted eating reduced participants' pro-inflammatory markers (C-reactive protein, TNF-alpha, and interleukin-6) and increased levels of adiponectin, a protein produced by adipose tissue that regulates glucose levels and fatty acid breakdown in the body. Time-restricted eating also reduced the participants' leptin, a hormone that drives food intake.

    These findings suggest that time-restricted eating is a viable strategy for reducing inflammation. Previous research has shown that time-restricted eating promotes weight loss in people with obesity.

    Time-restricted eating is a dietary pattern that limits food intake to certain hours of the day without overtly reducing caloric intake. It exploits the body’s innate 24-hour patterns and provides the body an essential downtime where it can focus on DNA and cellular repair and restoration rather than digestion. The most common version of time-restricted eating is a “16:8” pattern, where all the day’s calories are consumed within an eight-hour window, leaving 16 hours for fasting, including the hours during which a person is asleep. Learn about the many health benefits associated with time-restricted eating in this clip featuring Dr. Satchin Panda.

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  • Flavonoid supplementation emerges as a promising treatment for non-alcoholic fatty liver disease. onlinelibrary.wiley.com
    Inflammation Fatty Liver Polyphenol

    Non-alcoholic fatty liver disease, or NAFLD, causes fat accumulation in the liver, inflammation, and insulin resistance. It’s the most common chronic liver condition among people in the United States, affecting roughly 90 percent of people with obesity, or about 38 percent of the overall population. A recent systematic review and meta-analysis found that flavonoid supplementation reduces the risk of developing NAFLD.

    Researchers reviewed the findings of 12 randomized controlled trials investigating the effects of flavonoid supplementation in people with NAFLD. They found that flavonoid supplementation improved markers of liver function (liver enzymes) and reduced blood lipids (triglycerides and cholesterol), inflammatory markers (TNF-alpha and NF-kappa B), and fat accumulation in the liver, suggesting that flavonoid supplementation is a viable option for managing and treating NAFLD.

    Flavonoids are bioactive compounds found in many fruits and vegetables. Evidence suggests they exert a wide range of beneficial effects in humans, including anti-inflammatory, antioxidant, and lipid-lowering activities, as well as counteracting insulin resistance. Higher flavonoid intake is associated with a lower risk of NAFLD progression in older adults with overweight or obesity.

    Evidence suggests sulforaphane, a bioactive compound derived from broccoli, also benefits liver health. Learn more about sulforaphane in our comprehensive overview article.

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  • 30 milligrams per day of supplemental zinc improves liver function and reduces inflammation in children with nonalcoholic steatohepatitis – an advanced form of fatty liver disease. link.springer.com
    Cholesterol Inflammation Zinc Fatty Liver

    Children with overweight or obesity can develop nonalcoholic steatohepatitis (NASH) – an inflammatory condition in which fat builds up in the liver, replacing healthy tissue. Without intervention, NASH can progress to more advanced forms of liver disease, including cirrhosis and cancer. A recent study found that zinc supplementation improved liver function in children with NASH.

    Researchers gave 60 children with NASH either 30 milligrams of zinc or a placebo daily for four months. Before and after the intervention, they assessed the children’s liver function via ultrasound and measured their liver and inflammatory biomarkers.

    They found that the children who received the zinc supplements had lower serum alanine aminotransferase (a marker of liver damage) and C-reactive protein (a marker of inflammation) than those who took the placebo. They also had higher HDL (“good”) cholesterol.

    The findings from this small study suggest that zinc supplementation improves liver function and reduces liver inflammation in children with NASH. Further study may provide additional evidence supporting zinc’s use in NASH.

    Zinc is an essential nutrient. It plays roles in immune function, protein synthesis, wound healing, DNA synthesis, and cell division and modulates the activity of more than 300 enzymes and 2,000 transcription factors. Learn more about zinc in our comprehensive overview article.

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  • Omega-3 fatty acids relieve symptoms of dry eye disease, especially when taken longer, in higher doses, and with higher EPA percentages. www.ncbi.nlm.nih.gov
    Omega-3 Inflammation Eyes

    Dry eye disease – an inflammatory condition characterized by a stinging, burning, or scratchy sensation in the eyes – affects roughly 8 percent of adults in the U.S. Although several treatments address dry eye symptoms, none target the underlying inflammation. A recent systematic review and meta-analysis found that omega-3 fatty acids alleviate dry eye symptoms and reduce eye inflammation.

    Researchers reviewed the findings of randomized controlled trials investigating the effects of omega-3s on dry eye. Their analysis included 19 trials involving more than 4,200 patients.

    They found that the duration (one to 12 months), total omega-3 dose (128 to 2,000 milligrams), and percentage of eicosapentaenoic acid (EPA, ranging from 7 to 80 percent) varied considerably among the trials. Despite this heterogeneity, the reviewers concluded that omega-3s effectively reduced dry eye symptoms, especially when taken longer, in higher doses, and with higher EPA percentages..

    These findings suggest that omega-3s are viable options for treating dry eye disease. Some of these effects may be due to omega-3s' capacity to enhance tear production and restore the eyes' lipid layer by resolving dysfunction in the meibomian glands (tiny oil glands that line the eyelids' margins), collectively working to alleviate symptoms and improve overall eye health.

    Omega-3 fatty acids exert robust anti-inflammatory properties, likely due to their formation of specialized pro-resolving molecules (SPMs), a broad class of metabolites that resolve inflammation. Learn more about SPMs in this clip featuring Dr. Bill Harris.

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  • Vitamin D promotes tooth remineralization, reducing the risk of cavities. www.ncbi.nlm.nih.gov
    Vitamin D Inflammation Dental

    Tooth decay – a risk factor for cavities and tooth loss – often begins as white spots on the enamel, an early sign of demineralization. Strategies that promote tooth remineralization can reduce the need for invasive dental procedures. A 2022 study found that vitamin D promotes tooth remineralization, potentially reducing the risk of cavities.

    Researchers gave 40 healthy adults vitamin D supplements (1,000 IU) for six weeks. They collected saliva samples from the participants at the beginning of the intervention and again at the third and sixth weeks. They exposed healthy, extracted teeth to an acidic solution to mimic the changes in pH that normally occur in the mouth in response to foods and beverages, causing demineralization. Then, they exposed the teeth to the saliva samples for 12 hours and assessed their mineral content, a measure of hardness.

    They found that the amount of calcium and phosphorus in the teeth decreased considerably after exposure to the acidic solution – an indicator of demineralization. However, both minerals increased in the teeth after exposure to saliva collected from participants taking vitamin D.

    These findings suggest that vitamin D promotes tooth remineralization, potentially reducing the risk of cavities. They also align with other findings showing that vitamin D helps treat gingivitis (gum disease), a major cause of tooth loss.

    Vitamin D is a fat-soluble vitamin and hormone that participates in many physiological processes, including calcium balance, blood pressure regulation, immune function, and cell growth. Poor vitamin D status drives the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Learn more about vitamin D in our comprehensive overview article.

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  • Omega-3s show promise in easing oral mucositis symptoms during head and neck cancer radiation therapy. bmcoralhealth.biomedcentral.com
    Cancer Microbiome Omega-3 Inflammation

    People who undergo radiation therapy for head and neck cancers often experience oral mucositis – inflammation and ulceration of the mouth and throat that makes speaking, chewing, and swallowing difficult. They also demonstrate alterations in the population of the microbes that typically inhabit the mouth – a condition called dysbiosis. However, a recent study found that people who took omega-3 fatty acids before receiving radiation therapy experienced fewer symptoms of oral mucositis than those receiving conventional therapy.

    The study involved 34 patients with head and neck cancer who were about to undergo radiation therapy. Half of the participants received conventional preventive treatment (topical antifungal and anti-inflammatory mouthwash), and the other half received a topical omega-3 gel. Researchers evaluated the patients' symptoms, pain, and quality of life at baseline, three, and six weeks after treatment and assessed changes in their oral microbiomes.

    They found that those who used the topical omega-3 gel exhibited fewer symptoms and had less pain at the six-week point than those who received the conventional treatment. They also had less microbial dysbiosis.

    These findings suggest that omega-3s reduce the symptoms associated with oral mucositis. These effects may be due to omega-3 fatty acids' potent anti-inflammatory, antioxidant, and wound-healing properties. Learn more about omega-3s in our comprehensive overview article.

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  • Long-term nutritional ketosis improves metabolism and reduces inflammatory markers in women. www.mdpi.com
    Diet Metabolism Ketosis Inflammation Insulin Ketogenic Diet

    Nutritional ketosis is a powerful tool for managing weight and moderating inflammation. However, most studies on ketosis have been conducted in men and have only assessed short-term effects. A recent study found that nutritional ketosis reduces blood glucose, insulin, and inflammatory markers in healthy women practicing long-term ketosis.

    Researchers asked ten healthy young women who had been maintaining nutritional ketosis for more than a year to alter their dietary habits to suppress ketosis. The study involved three one-week phases: nutritional ketosis, suppressed ketosis, and return to nutritional ketosis. The researchers measured the women’s ketone levels daily; at the end of each phase, they took their women’s body measurements and assessed their metabolic and inflammatory biomarkers.

    They found that when the women suppressed ketosis, their insulin, IGF-1, glucose, and pro-inflammatory markers increased. However, when they returned to ketosis, those markers returned to baseline levels.

    These findings suggest that nutritional ketosis maintains healthy metabolism and suppresses inflammation without altering metabolic flexibility. Other evidence demonstrates that a ketogenic diet promotes weight loss and reduces cancer risk. Learn how to design the optimal ketogenic diet in this episode featuring Dr. Dominic D'Agostino

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  • Omega-3s protect the heart and muscles against damage incurred during endurance running. www.ncbi.nlm.nih.gov
    Exercise Heart Disease Omega-3 Inflammation Muscle

    The physical stress of marathon running can promote exercise-induced muscle damage, reducing muscle force production, elevating blood cytokines, and driving systemic inflammation. Consequently, despite having high cardiorespiratory and neuromuscular fitness, marathon runners are susceptible to lower extremity muscle injuries, cardiac dysfunction, and arrhythmia, particularly as running intensity escalates. A recent study shows that supplemental omega-3 fatty acids ameliorate some of the harmful effects of endurance running.

    The study involved 24 male long-distance runners. Half of the runners received 3,000 milligrams (mg) of omega-3s (852 mg EPA; 1,602 mg DHA) daily for three weeks, and the other half took a placebo. After the third week of supplementation, the participants performed a downhill running exercise test. The researchers measured the participants' cardiac markers, inflammatory cytokines, and blood lipids and assessed their Omega-3 Index, a measure of omega-3 concentrations in red blood cell membranes.

    They found that the participants' Omega-3 Indices increased from 3.9 to 4.8, roughly 23 percent relative to baseline when they took supplemental omega-3s. Markers of cardiac injury (troponin and creatine kinase isoenzyme MB) and the inflammatory cytokine TNF-alpha decreased. Participants' HDL cholesterol levels also increased.

    These findings suggest that supplemental omega-3s ameliorate some of the harmful effects of endurance running, possibly due to omega-3s' potent anti-inflammatory properties. Learn more about the health effects of omega-3s in this episode featuring Dr. Bill Harris.

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  • Medications induce gray hair re-pigmentation, pointing to potential future therapies. www.ncbi.nlm.nih.gov
    Nutrition Aging Inflammation Drug

    Graying hair is a cardinal sign of aging, typically beginning in a person’s fourth or fifth decade. Nutritional deficiencies, including low intake of protein, vitamin B12, iron, and copper, can contribute to premature graying. However, a recent review found that some medications may promote gray hair re-pigmentation.

    Researchers reviewed 27 studies and case reports of medication-induced gray hair re-pigmentation, totaling 133 patients. They categorized the various drugs as anti-inflammatories, stimulators of melanogenesis (the production of melanin, the pigment responsible for hair, skin, and eye color), vitamins, medications that accumulate in tissues, and those with an undetermined mechanism. Then, they ranked the quality of the evidence for each study or report.

    They found that medications that reduce inflammation or stimulate melanogenesis can promote diffuse re-pigmentation of gray hair. They also found that vitamin B complex supplementation may contribute to the darkening of gray hair, but they cautioned that evidence supporting this finding was weak.

    These findings suggest that certain medications induce gray hair re-pigmentation. Although these drugs aren’t presently recommended for treating gray hair, their mechanisms provide insights into potential targets for future medications aimed at hair re-pigmentation.

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  • Fish oils in intravenous nutrition reduce infection risk by 57 percent and septic risk by 78 percent while shortening hospital stays. www.sciencedirect.com
    Nutrition Omega-3 Inflammation Immune System

    Parenteral nutrition is a method of delivering essential nutrients intravenously when a person is unable to receive nutrition via the digestive system. The solutions used in parenteral nutrition typically include a balanced mix of macro- and micronutrients to support health and promote recovery. A recent review found that parenteral nutrition solutions containing fish oils reduced the risk of infection and sepsis and shortened hospital stays in patients receiving parenteral nutrition.

    Researchers reviewed the findings of 47 randomized controlled trials investigating the effects of parenteral nutrition containing intravenous lipid (fat) emulsions on clinical outcomes in more than 3,600 hospitalized patients. The various emulsions contained one of several lipid types: fish oil, olive oil, medium-chain triglycerides (MCTs), soybean oil, or a combination of MCTs and soybean oil.

    They found that patients who received fish oil were 57 percent less likely to develop an infection than those receiving soybean oil. Similarly, the risk of infection decreased by 41 percent for MCTs/soybean oils and 44 percent for olive oils, compared to soybean oils. Furthermore, the likelihood of sepsis was 78 percent lower with fish oils than soybean oils. Hospital stays decreased by roughly two days among patients receiving fish oils.

    These findings suggest that including fish oil-based lipid emulsions in parenteral nutrition improves outcomes in hospitalized patients. Fish oils are rich in omega-3 fatty acids, which exert potent anti-inflammatory and immunomodulatory properties. Byproducts of omega-3 metabolism called specialized pro-resolving mediators (SPMs) have distinct roles in promoting the resolution of inflammation, restoring homeostasis, and supporting tissue repair. Learn more about SPMs in this episode featuring omega-3 expert Dr. Bill Harris.

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  • Longevity study reveals key blood markers increase chances of living to 100 and beyond. www.sciencealert.com
    Aging Metabolism Inflammation Genetics Blood Test

    By the year 2050, the number of centenarians – people who are 100 years or older – is expected to increase fivefold. Many factors promote centenarians' extraordinary longevity and likely involve the interaction of both lifestyle and genetic variables. A recent study has found that the blood of centenarians differs from their younger counterparts.

    The study followed more than 44,000 people from their mid-60s to late 90s until they died. Of these, 1224 of them lived to 100 years old. Using blood samples collected earlier in the participants' lives, researchers assessed 12 blood-related biomarkers previously associated with aging or early death, including those associated with inflammation and indicators of malnutrition, anemia, and liver, kidney, and metabolic function.

    They found that higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, and several enzymes involved in metabolism increased the likelihood of reaching 100 years. Notably, centenarians exhibited strikingly consistent biomarker profiles, even from age 65 and beyond, displaying more favorable values than their shorter-lived counterparts.

    Centenarians often carry genetic variants called single-nucleotide polymorphisms associated with longevity. They tend to develop disease much later in life than people of average age span, a phenomenon called “compression of morbidity,” and have longer telomere lengths than adults two to three decades younger. The highest concentrations of centenarians worldwide live in Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica; Ikaria, Greece; and Loma Linda, California.

    The findings from this study demonstrate that biomarkers related to various genetic or lifestyle influences may contribute to greater longevity. Inflammation also plays a role in longevity. Learn more in this clip featuring Dr. Valter Longo.

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  • Exercise reduces inflammation and enhances immune surveillance in people with Lynch syndrome, highlighting its cancer prevention potential. www.medscape.com
    Exercise Cancer Inflammation Immune System

    Lynch syndrome is an inherited condition linked to increased risks of colorectal and endometrial cancers. While exercise is known to curb the risk of many types of cancer, scientists don’t fully understand its effects on Lynch syndrome. A recent study found that regular exercise reduced inflammation and boosted immune surveillance in people with Lynch syndrome.

    The study involved 21 people with Lynch syndrome. About half of the participants engaged in a 12-month cycling program (three sessions per week, 45 minutes per session), while the others received standard care and a single exercise counseling session. Researchers assessed the participants' cardiorespiratory fitness and measured gene expression in colorectal tissue before and after the intervention.

    They found that participants' oxygen consumption increased and colon and blood inflammatory markers decreased in those who exercised but not in those who received standard care. Gene expression analysis revealed heightened levels of natural killer and CD8 T cells in those who exercised.

    Natural killer (NK) cells and CD8 T cells play critical roles in the immune system’s defense against cancer. They are crucial components of the body’s immunosurveillance mechanism, responsible for identifying and eliminating potentially cancerous cells.

    These findings underscore exercise’s potential to intercept cancer in Lynch syndrome and shed light on its immunological effects in high-risk people. Learn about the differential effects of exercise intensity and duration on the body’s immune response in this live Q&A featuring Dr. Rhonda Patrick.

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  • Raising omega-3 fatty acids by 1 percent slows lung function decline almost as much as quitting smoking, new study finds. www.nih.gov
    Omega-3 Inflammation

    Inflammation plays a role in the decline of lung function and the development of chronic obstructive pulmonary disease, a lung condition that affects roughly 300 million people worldwide. However, omega-3s exert robust anti-inflammatory effects. A new study suggests that omega-3 fatty acids might slow the decline of lung function.

    Researchers conducted a two-part study. First, they reviewed data from the National Heart, Lung, and Blood Institute Pooled Cohorts Study, which measured plasma omega-3 concentrations in more than 15,000 participants. The study also assessed the participants' lung function, measured via forced expiratory volume-1 (FEV1) and forced vital capacity (FVC). FEV1 measures the volume of air one can exhale in one second; FVC measures the volume of air one can exhale forcefully in one breath.

    They found that higher concentrations of omega-3s, especially docosahexaenoic acid (DHA), a marine-derived omega-3 fatty acid, delayed lung function decline. Increasing DHA by just 1 percent of total fatty acids slowed forced expiratory volume losses by 1.4 milliliters (mL) per year and forced vital capacity by 2.0 mL per year. To provide context for these effect sizes, note that compared to non-smokers, current and former smokers experience approximately an 8.0 mL per year and 2.0 mL per year more rapid decline in lung function, respectively.

    In the second part of the study, they analyzed genetic data of more than 500,000 participants enrolled in the UK Biobank study to determine how genetic markers that predict dietary omega-3 fatty acid levels correlate with lung health. They found that higher omega-3 concentrations were associated with better lung function.

    These findings suggest that higher blood concentrations of omega-3 fatty acids, especially DHA, can benefit lung health. Learn more about omega-3s in our comprehensive overview article.

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  • Study reveals a sixfold decrease in C-reactive protein levels among obese women who took omega-3s during pregnancy. www.ncbi.nlm.nih.gov
    Obesity Omega-3 Inflammation Pregnancy Supplements CRP

    Pregnant women with obesity often experience high levels of inflammation. But a new study shows that omega-3s may reduce inflammation during pregnancy. Women with obesity who took omega-3 fatty acids during their pregnancies experienced a sixfold reduction in C-reactive protein, a marker of inflammation.

    The study involved 49 pregnant women with obesity. Half of the women took an omega-3 supplement providing 800 milligrams of docosahexaenoic acid (DHA) and 1,200 milligrams of eicosapentaenoic acid (EPA) daily, starting before week 16 of their pregnancies and continuing until delivery. The other half took a placebo containing wheat germ oil. Researchers measured the women’s inflammatory biomarkers before and after the intervention.

    They found that the women’s omega-3 levels increased markedly following the intervention, and their C-reactive protein levels decreased sixfold. Inflammatory gene expression in adipose and placental tissues also decreased.

    These findings suggest that omega-3 fatty acids reduce inflammation in pregnant women with obesity, aligning with evidence demonstrating that omega-3 fatty acids modulate inflammation by inhibiting the production of pro-inflammatory cytokines and eicosanoids. Furthermore, byproducts of omega-3 metabolism called specialized pro-resolving mediators, or SPMs, help resolve inflammation. Learn more about SPMs in this clip featuring omega-3 expert Dr. Bill Harris.

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  • Regular exercise reprograms bone marrow macrophages, inducing lasting mitochondrial changes that accumulate, driving a tempered inflammatory response. www.sciencedaily.com
    Exercise Inflammation Immune System Mitochondria

    Although inflammation is a critical component of the body’s immune response, excess inflammation drives many chronic diseases, such as autoimmune disorders, cardiovascular diseases, diabetes, and cancer. A new study in mice shows that regular exercise reprograms macrophages, altering how they sense and respond to pathogens and reducing inflammation.

    Macrophages are immune cells that participate in pathogen elimination via phagocytosis. Distinguished by their polarization, “M1” macrophages exhibit a proinflammatory phenotype, while “M2” macrophages exhibit an anti-inflammatory phenotype. A high M1 to M2 ratio indicates inflammation and a chronic disease state.

    Researchers collected macrophages from the bone marrow of two groups of mice – one that had exercised regularly for eight weeks and one that had been sedentary. Then they exposed the macrophages to lipopolysaccharide (a bacterial toxin that induces an acute inflammatory reaction) and assessed the cells' responses.

    They found that macrophages from the exercised mice exhibited decreased activation of NF-κB, the primary transcription factor of M1 macrophages. The macrophages also demonstrated reduced expression of inflammation-related genes, increased expression of M2 macrophage-associated genes, and improved mitochondrial function.

    These findings suggest that regular exercise modulates macrophages' responses to inflammation by enhancing their respiratory capacity and altering gene expression, with potential implications for preventing or treating inflammatory diseases. Read more about the benefits of exercise in our overview article.

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  • Microglial dormancy in depression challenges conventional understanding centered on inflammation, but highlights the immune cell's crucial role in neu medicalxpress.com
    Brain Inflammation Depression Immune System

    Chronic inflammation is a dominant feature in people who have depression, suggesting that an overactive immune response drives the disease’s symptoms. But a new study demonstrates something counterintuitive in spite of that: Immune cells in the brain called microglia are less active in people with depression, impairing their ability to clear damaged neuronal connections, undermining neurotrophic support, and driving the disease.

    Researchers studied gene expression in the microglia of brain tissues collected during autopsies of 13 people with depression and 10 healthy people. They also examined gene expression of neuronal factors that regulate microglial function.

    They found that the expression of genes in the microglia of people with depression was markedly lower than that of healthy people, especially genes involved in immune responses and phagocytosis (which facilitates the clearance of damaged cells). In addition, the expression of factors involved in immune suppression (CD200 and CD47) was higher.

    These findings suggest that people with depression have a distinct disease-associated microglia gene expression profile that impairs microglia activity. Microglia play critical roles in the development, homeostasis, and diseases of the central nervous system and contribute to neuronal plasticity in the healthy brain. Microglial changes are common features of many neuropsychiatric disorders, including schizophrenia, autism spectrum disorder, and bipolar disorder. Learn more about microglia suppression in depression in this clip featuring Dr. Charles Raison.

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  • Taurine supplementation extends life by 12 percent in animal studies, pointing to a potentially promising anti-aging strategy that may highlight the r www.cuimc.columbia.edu
    Aging Inflammation DNA Damage Mitochondria Taurine

    Taurine is an amino acid that participates in immune health and neurological function. Findings from a recent study suggest that taurine influences longevity. Mice that received supplemental taurine lived as much as 12 percent longer than those that didn’t.

    Researchers conducted a multi-part experiment in several species. First, they measured blood taurine concentrations in mice, monkeys, and humans at different ages and found that taurine decreased in all three species over time. Notably, taurine concentrations were 80 percent lower in older adult humans than in young children.

    Then they gave middle-aged mice either taurine (1,000 milligrams per kilogram of body weight) or an inactive substance once daily until their natural deaths. Among mice that received taurine, median lifespan increased by 10 to 12 percent, roughly equivalent to about eight years in humans. They repeated their experiment in monkeys, worms, and yeast and observed similar effects. They also found that taurine reduced several hallmarks of aging in all the species studied, including cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation.

    Finally, they measured blood taurine concentrations in humans following an acute bout of exercise. They found that exercise increased the levels of taurine metabolites in the blood, providing a potential mechanism for the anti-aging effects of exercise.

    These findings suggest that supplemental taurine reverses age-related taurine declines and extends both healthspan and lifespan in several species. Learn about other nutrients that influence aging in this episode featuring longevity expert Dr. Bruce Ames.

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  • Eating broccoli may safeguard the gut by increasing the number of goblet and Paneth cells. www.sciencedaily.com
    Gut Diet Inflammation Immune System Sulforaphane

    The list of health attributes of broccoli includes anticancer, antioxidant, and anti-diabetes effects, as well as many others. Now a new study in mice shows that eating broccoli protects the gut. Molecules in broccoli interact with proteins present in the small intestine, increasing the number of cells involved in safeguarding the gut.

    Researchers fed one group of mice a diet containing 15 percent freeze-dried broccoli – roughly equivalent to 3.5 cups of fresh broccoli in the human diet. They fed another group their typical food, which included no broccoli. Then they examined the animals' small intestines to assess the effects of broccoli consumption on the gut.

    They found that molecules in the broccoli – likely phytochemicals, microbiota, or byproducts of metabolism – bound with specific proteins in the gut called aryl hydrocarbon receptors. Subsequently, the number of goblet and Paneth cells in the animals' guts increased. Goblet cells produce mucus, which protects and lubricates the gut to facilitate the passage of food. Paneth cells produce antimicrobial peptides and immune factors that regulate the gut microbial composition.

    These findings suggest that broccoli consumption protects the gut via interaction with the aryl hydrocarbon receptor. Broccoli is a rich source of phytochemicals, including sulforaphane, an isothiocyanate compound with potent antioxidant, anticancer, and anti-inflammatory properties. Learn more about sulforaphane in this episode featuring Dr. Jed Fahey.

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  • Physical activity may protect women against Parkinson's disease. www.medscape.com
    Exercise Parkinson's Inflammation BDNF

    Parkinson’s disease is a neurodegenerative disorder that affects the central nervous system. New research suggests that exercise reduces the risk of developing Parkinson’s disease. Women who regularly engaged in physical activity were 25 percent less likely to develop the disease than inactive women.

    Researchers gathered information about the lifestyles and medical histories of more than 99,000 women and categorized them according to their activity levels. Then, using a statistical method that accounted for the reduced activity that might precede a diagnosis of Parkinson’s disease, they investigated the effects of exercise on Parkinson’s disease risk.

    They found that physical activity levels were consistently lower in women who developed Parkinson’s disease than in those who did not, even up to 29 years before the disease was diagnosed. The difference between the two groups became more pronounced around 10 years before diagnosis. Overall, women with the highest activity levels had a 25 percent lower risk of developing Parkinson’s disease than those with the least activity, even after considering other risk factors.

    These findings suggest that exercise protects women against Parkinson’s disease. The mechanisms that drive this protective effect may be related to exercise’s capacity to regulate key neurotransmitters, promote the release of brain-derived neurotrophic factor (BDNF), ameliorate brain inflammation, and reduce oxidative stress. Interestingly, exercise also benefits people after they have been diagnosed with Parkinson’s disease. Learn more in this clip featuring Dr. Giselle Petzinger.

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  • Omega-3s improve metabolic markers in women with gestational diabetes. www.sciencedirect.com
    Diabetes Insulin Resistance Omega-3 Inflammation Pregnancy Insulin

    Omega-3s improve metabolic markers in women with gestational diabetes.

    Gestational diabetes, a form of diabetes that occurs only during pregnancy, carries many health concerns for women, including an increased risk of developing type 2 diabetes in later life. A new study shows that omega-3 fatty acids may improve metabolic markers associated with gestational diabetes. Women who took omega-3s during their pregnancies had healthier blood glucose, triglyceride, and cholesterol levels than those who didn’t.

    Researchers analyzed the findings of six randomized controlled trials that investigated the effects of omega-3s in women with gestational diabetes. The studies included more than 330 pregnant women, and the duration of the various trials was six weeks. Omega-3 doses ranged from 1 to 2 grams per day.

    They found that across the six studies, markers of glucose metabolism (fasting glucose, fasting insulin, and insulin resistance), lipid metabolism (triglycerides and very low-density lipoprotein cholesterol), and inflammation (C-reactive protein) were lower among women who took omega-3s than those who took a placebo. Levels of high-density lipoprotein cholesterol – often referred to as “good” cholesterol – increased.

    This analysis suggests that omega-3 fatty acids, which are perhaps best known for their cardioprotective and neuroprotective properties, positively influence metabolism in pregnant women. It also aligns with the findings of a previous analysis, which found that compared to women who took a placebo, those who took supplemental omega-3s had considerably lower fasting blood sugar levels and insulin resistance. Learn about other health benefits associated with omega-3s in our comprehensive overview article.

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  • Melatonin, commonly used to improve sleep, may aggravate bowel inflammation by increasing TNF-alpha in acute colitis medicalxpress.com
    Gut Microbiome Inflammation Melatonin

    From the abstract:

    In acute colitis, the hormone (melatonin) (MLT) led to increased clinical, systemic and intestinal inflammatory parameters. During remission, continued MLT administration delayed recovery, increased TNF, memory effector lymphocytes and diminished spleen regulatory cells. MLT treatment reduced Bacteroidetes and augmented Actinobacteria and Verrucomicrobia phyla in mice feces. Microbiota depletion resulted in a remarkable reversion of the colitis phenotype after MLT administration, including a counter-regulatory immune response, reduction in TNF and colon macrophages. There was a decrease in Actinobacteria, Firmicutes and, most strikingly, Verrucomicrobia phylum in recovering mice. Finally, these results pointed to a gut-microbiota-dependent effect of MLT in the potentiation of intestinal inflammation.

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  • Exposure to plastic particles may interfere with sex hormones and promote inflammation. medicalxpress.com
    Hormones Inflammation Environment

    Exposure to plastic particles alters sex hormones and promotes inflammation in rats, a new study shows. Estrogen levels in female rats that inhaled tiny particles of polyamide – commonly known as nylon – decreased and inflammatory cytokines increased.

    Researchers exposed female rats in heat to aerosolized polyamide particles for an average of 4.5 hours. Then they assessed the animals' overall health and measured their cytokine and reproductive hormone levels. They found that after a single exposure to the polyamide particles, the animals' blood pressure increased, estradiol (a form of estrogen) decreased, and pro-inflammatory cytokine interleukin-6 increased.

    Small plastic particles, often referred to as microplastics (ranging between 5 millimeters and 100 nanometers) or nanoplastics (less than 100 nanometers), are ubiquitous environmental pollutants. They have been identified in food (especially seafood), soil, drinking water, fresh- and saltwater bodies, and air.

    Exposure to microplastics is associated with a wide range of negative health outcomes in humans. For example, a comprehensive review of the effects of microplastics revealed that the pollutants induce oxidative stress and increase the risk for metabolic dysfunction, neurotoxicity, and some cancers. Some of these effects may be due to compounds commonly associated with plastic manufacturing, such as bisphenol A, or BPA, phthalates, and heavy metals, that are present in and on microplastics.

    This study demonstrates that even brief exposure to plastic particles is sufficient to alter sex hormones and promote inflammation in female rats.

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  • Magnesium supplementation may reduce inflammation. www.ncbi.nlm.nih.gov
    Nutrition Diet Inflammation CRP

    A 2018 study found that supplemental magnesium reduced levels of C-reactive protein (CRP) – a robust marker of inflammation. Improvements in CRP levels were seen regardless of the dose or duration of supplementation.

    Researchers analyzed the findings of eight randomized, controlled trials that investigated the effects of supplemental magnesium on CRP.

    They found that doses ranged from 320 to 1,500 milligrams per day, and the duration of supplementation ranged from eight hours to just over six months. CRP levels dropped an average of 1.33 milligrams per deciliter (mg/dL) with magnesium supplementation, especially when CRP levels were 2.0 mg/dl or higher. Because normal CRP levels (seen in most healthy adults) are typically less than 0.3 mg/dL and normal or slightly elevated levels are typically 0.3 to 1.0 mg/dL, this reduction represented a considerable change.

    C-reactive protein is a protein that increases up to 1,000-fold at sites of inflammation or infection in response to elevated levels of inflammatory cytokines, especially interleukin-6. It can also increase in the blood following a heart attack, surgery, or trauma. High CRP levels are associated with atherosclerosis, congestive heart failure, atrial fibrillation, and myocarditis, suggesting that CRP participates in the pathophysiology of cardiovascular disease.

    Magnesium is an essential mineral. It is found in green leafy vegetables, whole grains, legumes, and nuts. Poor magnesium status is implicated in several metabolic and inflammatory disorders including hypertension, type 2 diabetes, metabolic syndrome, insulin resistance, and cardiovascular diseases.

    The findings from this meta-analysis suggest that supplemental magnesium reduces inflammation, a driver of many chronic diseases. You can read about other strategies to reduce inflammation in our overview articles on aerobic exercise, sauna use, and cold exposure.

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  • Omega-3s may help reduce bone loss through inhibition of NF-kB, a central mediator of pro-inflammatory gene induction www.sciencedaily.com
    Omega-3 Inflammation Bone

    Omega-3 fatty acids may help reduce bone loss, a 2010 study showed. When astronauts – who often experience bone loss after periods of weightlessness – consumed omega-3s during short-duration space missions, they experienced less bone loss.

    Researchers investigated the effects of omega-3s on bone in various settings that induce or replicate weightlessness-related bone loss: cells in culture, astronauts returning from short-duration shuttle missions, and healthy people who experienced 16 days of ground-based bed rest.

    They found that in cultured cells, omega-3s inhibited the activity of nuclear factor-κB (NF-κB), a signaling molecule that is involved in the pathogenesis of bone loss. When astronauts experienced even short-term weightlessness during space missions, they had elevated NF-κB levels, but those who consumed higher quantities of omega-3s during the missions experienced less bone loss than those who consumed less. Finally, when healthy people who experienced prolonged bed rest were given supplemental omega-3s, they experienced less bone loss than those who did not take omega-3s.

    These findings suggest that omega-3s reduce bone loss in settings of weightlessness or bed rest, with relevance for people on earth who are at risk for bone loss. Resistance training helps support bone health, too. Learn more in this clip featuring Dr. Brad Schoenfeld.

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  • Could omega-3 counteract diseases of aging through epigenetic modification of the IL-6 promoter? www.ncbi.nlm.nih.gov
    Omega-3 Inflammation Genetics

    Higher omega-3 fatty acid consumption could play a unique role in mitigating chronic inflammation by altering the methylation pattern of the interleukin-6 (IL-6) promoter, reducing the activity of this inflammatory cytokine. This epigenetic mechanism highlights omega-3’s capacity to govern gene expression and shape the genetic landscape, transcending its contributions to cell membrane dynamics or mediator production and positioning its effects at the molecular blueprint level rather than merely fine-tuning cellular responses.

    The relationship between IL-6 and human health is multifaceted: Interleukin-6 serves as a critical component of the immune response by mediating the acute phase response and fostering beneficial outcomes such as insulin sensitization after exercise. However, when chronically elevated, it can also contribute to age-related chronic diseases.

    Chronic immune activation is increasingly recognized as a powerful contributor to the aging process. Developing safe and effective strategies to counteract this persistent activation, which intensifies with age, is essential for promoting healthy aging. However, given that IL-6 also plays a role in healthy physiological functions, pharmacological interventions targeting its action overtly may lead to unintended side effects over time.

    A pivotal 2015 study emphasizing the epigenetic effects potentially triggered by increased omega-3 consumption involved over 800 participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). This investigation explored the interplay between genetic factors and dietary changes in influencing inflammatory markers in the blood. Researchers analyzed blood samples to assess various inflammatory markers, methylation levels, and omega-3 concentrations.

    Results demonstrated that individuals with higher concentrations of omega-3s, particularly docosahexaenoic acid (DHA) derived from fatty fish, exhibited lower IL-6 levels and reduced methylation of the IL-6 promoter at a CpG site called cg01770232. This association between lower methylation levels of the IL-6 promoter and reduced circulating IL-6 emphasizes the significance of omega-3s in mitigating chronic inflammation through DNA epigenetics, which may have a profound cumulative impact on human health over time and possibly even longevity.

    DNA methylation is a natural biochemical process that modifies the activity of a DNA segment without altering its sequence, ultimately regulating gene expression. Interleukin-6 is a pro-inflammatory cytokine that is induced in response to infection, trauma, or other disease states. Elevated IL-6 levels have been linked to poor clinical outcomes in cardiovascular disease and an increased risk of premature death from all causes in older adults.

    It is worth noting that some individuals carrying a specific genetic variant of IL-6 did not experience the same methylation changes from omega-3 consumption, which suggests that the genetic makeup of some individuals may influence the degree of beneficial physiological response to omega-3s within certain biological domains.

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  • Dietary fiber may protect against severe headaches or migraines. pubmed.ncbi.nlm.nih.gov
    Diet Inflammation Fiber Migraine

    Eating more fiber may reduce the risk of severe headaches or migraines, a recent study shows. For every 10 grams of dietary fiber consumed, the risk of severe headache or migraine decreased by 11 percent.

    The study involved nearly 13,000 people living in the United States. Participants provided information about their regular dietary fiber intake and the number and severity of their headaches or migraines.

    People who consumed the highest amount of dietary fiber (more than 22 grams per day) were 26 percent less likely to report experiencing severe headaches or migraines than those who consumed the least amount of fiber (less than 7.8 grams per day). For every 10-gram per day increase in dietary fiber intake, the frequency of severe headaches or migraines dropped by 11 percent.

    Dietary fiber refers to the indigestible components of plant-based foods. The fermentation of dietary fibers in the gut produces molecules that modulate immune function by way of T regulatory cells, such as the short-chain fatty acids.

    According to the Dietary Guidelines for Americans, the recommendations for combined fiber intake vary according to age and sex. Women need between 22 and 28 grams of fiber per day, and men need between 28 and 34 grams per day. Most people living in the United States only get about half of the recommended amounts of fiber daily.

    The findings of this study suggest that consuming dietary fiber protects against severe headaches and migraines. Obtaining enough fiber when following a ketogenic diet may prove challenging. Learn how to include fiber in a ketogenic diet in this episode featuring Dr. Dominic D'Agostino.

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  • Higher omega-3 status may confer protection against COVID-19, according to a new study. www.ncbi.nlm.nih.gov
    Omega-3 Inflammation Immune System COVID-19

    Omega-3 fatty acids may protect against COVID-19, a new study shows. People with higher levels of omega-3s in their red blood cells were less likely to contract COVID-19 or require hospitalization if infected.

    Researchers calculated the concentrations of docosahexaenoic acid (DHA), a type of omega-3 derived from fatty fish, in the blood of more than 110,000 people enrolled in the UK Biobank study. They also calculated the participants' Omega-3 Index – a measure of total omega-3 fatty acid concentrations in red blood cells. They reviewed the participants' medical records to determine if they had ever contracted COVID-19 and, if so, the severity and outcome of their disease.

    They found that people with the highest Omega-3 Indices (8 percent) were less likely to contract COVID-19 or have a severe outcome than those with the lowest Indices (3.5 percent). Those with the highest DHA levels were 21 percent less likely to test positive for COVID-19 and 26 percent less likely to be hospitalized due to COVID-19 infection.

    In silico (computer modeling) experiments demonstrate that one of the mechanisms driving omega-3s' protective effects in the setting of COVID-19 may be related to their capacity to prevent the spike protein, the primary antigenic component of SARS-CoV-2, from binding to cellular receptors that allow the virus to enter cells. Other evidence points to the anti-inflammatory properties of omega-3s, which may reduce host inflammatory response and disease severity.

    These findings suggest that omega-3s confer protection against COVID-19. Listen to former FMF guest and omega-3 expert Dr. Bill Harris elaborate on this study.

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  • Resistance training helps cells identify and eliminate abnormal, misfolded proteins. www.sciencedaily.com
    Exercise Inflammation

    A new study shows that resistance exercise helps the body’s cells identify and eliminate misfolded proteins – key players in the pathogenesis of many human diseases, including diabetes, atherosclerosis, and neurodegenerative diseases.

    The study involved 30 older adults who engaged in an eight-week resistance training program in which they exercised twice a week. Before and after the exercise intervention, researchers measured changes in the number of key proteins in the participants' blood involved in inflammation, aging, and cellular stress responses.

    They also measured levels of IRE1, a protein that detects stress in the endoplasmic reticulum – a part of the cell that ensures misfolded proteins don’t escape into the body’s circulation or accumulate in the cell. IRE1 must be activated to be effective.

    They found that none of the proteins involved in inflammation, aging, and cellular stress responses were changed after the intervention. However, the ratio of activated IRE1 to inactivated IRE1 was higher among those who engaged in resistance training, suggesting that resistance training supports the identification and elimination of misfolded proteins – yet another way in which resistance training benefits health.

    Resistance training involves pushing or pulling against the resistance of an object, such as weights, bands, or even one’s own body weight. These exercises exert powerful forces on the bones, slowing bone loss and promoting bone accretion. Learn more about resistance training in this episode featuring Dr. Brad Schoenfeld.

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  • Early-life obesity increases the risk of macular degeneration later in life. www.sciencedaily.com
    Obesity Metabolism Inflammation Immune System Eyes

    Obesity in early life induces changes in immune cells that may increase the risk of macular degeneration later in life, a study in mice has found. These changes linger even after weight loss and the restoration of normal metabolism.

    Researchers fed mice a diet that promoted weight gain early in life. Then they studied the effects of having excess body fat on the animals' adipose tissue macrophages – a type of immune cell found in fat. Later, they put the mice on a diet that promoted weight loss.

    They found that having excess body fat induced epigenetic changes in the macrophages that, in turn, induced an inflammatory response. This pro-inflammatory response persisted even after the mice lost weight. They also found that the macrophages could migrate from the fatty tissue to other parts of the body, including the eyes, where they could contribute to the onset of macular degeneration.

    Macular degeneration is the leading cause of blindness worldwide. Having excess body fat is the second leading risk factor for macular degeneration. In fact, a person’s risk of developing macular degeneration increases by 75 percent with each 0.1 increase in their waist-to-hip ratio – a measure of abdominal obesity.

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  • Higher magnesium intake may cut type 2 diabetes risk in half. diabetesjournals.org
    Diabetes Inflammation Magnesium

    Nearly half of all people living in the United States are deficient in magnesium. However, people with higher magnesium intake were nearly half as likely to develop type 2 diabetes than those with lower intake, a 2010 study found. Those with higher magnesium intake also had lower markers of inflammation.

    Researchers conducted a long-term study in nearly 5,000 healthy young adults to investigate the role that lifestyle and other factors play in the risk of developing cardiovascular disease. They quantified their magnesium intake and measured their inflammatory markers.

    They found that those with the highest dietary magnesium intake were 47 percent less likely to develop type 2 diabetes over a 20-year period than those with the lowest intake, even after taking other risk factors into consideration. Levels of inflammatory markers, including C-reactive protein, interleukin-6, and fibrinogen – a protein that participates in clot formation – were lower among those with higher magnesium intake.

    Magnesium is an essential mineral and a cofactor for hundreds of the body’s enzymes. Magnesium deficiency is linked with an increased risk of cardiovascular disease, osteoporosis, and metabolic disorders, including hypertension and type 2 diabetes. Current magnesium intakes among people living in the United States are below recommended levels (400-420 milligrams per day for men and 310-320 milligrams per day for women).

    This study highlights the role dietary magnesium plays in health and underscores the mineral’s importance in the human diet. Dietary sources rich in magnesium include green leafy vegetables, unrefined grains, legumes, beans, and nuts. Try this magnesium-rich smoothie recipe to get more of this essential nutrient in your diet.

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  • Red food dye promotes inflammation in the gut, altering the gut microbiota. www.sciencedaily.com
    Gut Diet Inflammation

    Exposure to a dye found in many commonly consumed foods may increase the risk of developing inflammatory bowel diseases, a new study finds. The dye impairs gut barrier function and increases serotonin production, altering the gut microbiota.

    Researchers fed mice either normal mouse chow or mouse chow that contained a red food dye called Allura Red for 12 weeks and assessed their gut health. Allura Red, also known as FD&C Red 40 or Food Red 17, is used in many food products, including candy, soft drinks, dairy products, and some breakfast cereals.

    The researchers found that exposure to the dye when the mice were young heightened the animals' susceptibility to colitis (a type of inflammatory bowel disease) later in life. Mice that developed colitis had higher gut serotonin levels and impaired gut barrier function.

    Elevated gut serotonin promotes gut inflammation and is a common feature of inflammatory bowel diseases. Impaired gut barrier function drives intestinal permeability (also known as “leaky gut”) – a condition in which gaps form between the cells that line the gut. Intestinal permeability allows pathogens to leak through the intestinal barrier and pass directly into the bloodstream, promoting inflammation.

    The findings from this study suggest that exposure to a commonly used food additive increases the risk of developing inflammatory bowel disease by promoting intestinal permeability. Read more about intestinal permeability in our overview article.

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  • Estrogen therapy may reduce susceptibility and inflammatory responses to urinary tract infections in postmenopausal women, mouse study suggests.(2013) www.sciencedaily.com
    Hormones Inflammation Estrogen

    From the article:

    To simulate menopause in mice, scientists surgically remove their ovaries. Like menopausal women, the mice no longer make estrogen.

    To rule out the possibility that the stress of surgery affects the risk of urinary tract infections, the researchers conducted the same surgery in other mice but put the ovaries back in, maintaining their ability to make estrogen.

    When researchers gave both groups of mice urinary tract infections, the menopausal mice had higher levels of infectious bacteria in their urine. Most of the bacteria came from barrier cells, which line the interior of the bladder. These cells are the first to be infected by the bacteria.

    “When the barrier cells are lost, they need to be replaced immediately,” Mysorekar says. “In the menopausal mice, we found that this replacement process was stopping short of completion. That left cells under barrier cells exposed, and they are much more vulnerable to infection.”

    The menopausal mice had more bacterial reservoirs, which are pockets of infection that may provide a place for the bacteria to hide during antibiotic treatment. After treatment stops, the reservoirs can reseed the infection.

    In earlier research, Mysorekar had identified an important regulator of the barrier cell repair process. In the new study, she showed that low estrogen levels disable this regulator.

    The bladders of the menopausal mice also had higher levels of immune inflammatory compounds known as cytokines.

    “The cytokines caused inflammation that left the bladder in bad shape,” Mysorekar says. “It’s possible that damage caused by inflammation increases the bacteria’s ability to break into bladder tissue and create reservoirs of infection.”

    In the control mice, which had normal estrogen levels, cytokine levels and inflammatory damage were both significantly lower. When researchers gave the menopausal mice estrogen, their cytokine levels and inflammatory damage also decreased significantly, as did reservoirs of infectious bacteria.

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  • Loss of estrogen receptor alpha led to aspects of metabolic syndrome, inflammation, and acceleration of atherosclerosis in mice. (2011) www.sciencedaily.com
    Hormones Insulin Resistance Inflammation Estrogen Blood Sugar Metabolic Syndrome Cardiovascular

    From the article:

    This early preclinical study in female mice demonstrated that removing estrogen regulator alpha alone was enough to reduce the immune system’s protective process and promote increased fat accumulation and accelerate atherosclerosis development. Without this protein, the mice developed additional aspects of metabolic syndrome such as glucose intolerance, insulin resistance and inflammation.

    This estrogen receptor is also expressed in many other non-reproductive tissues such as fat, muscle and liver and can also act independent of the hormone estrogen. However, little is known about the receptor’s actions in these tissues that are involved in blood-sugar regulation, which plays an integral role in metabolic syndrome.

    […]

    “Impairment of this receptor’s function could also play a role in the heightened incidence of metabolic syndrome being seen in younger women,”

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  • Estrogen may increase susceptibility to inflammatory disease by negatively affecting wound healing and protective lipid mediator circuits. (2012) www.sciencedaily.com
    Hormones Inflammation Eyes Estrogen Autoimmunity

    From the article:

    To make this discovery, Gronert and colleagues administered a mild abrasion injury to the front of the eye of genetically similar male and female mice, and analyzed wound healing by image analysis. To test the role of estrogen, they gave male mice estrogen eye drops and/or drugs that activate specific estrogen receptors. Gene expression of essential enzymes was quantified for the formation of protective lipid signals, specific receptors that mediate their bioactivity, as well as estrogen receptors in mouse corneas and human/mouse epithelial cell cultures. The formation of protective lipid signals was analyzed by a mass-spectrometry based lipidomic method. They found that estrogen negatively affects a highly evolved protective lipid circuit, called “15-lipoxygenase-Lipoxin A4” that has recently emerged as an important protective pathway in many diseases. This pathway balances the activity of pro-inflammatory signals to promote wound healing and to keep inflammation within safe ranges.

    “This study goes a long way to explaining gender differences in inflammation and its resolution,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “It’s long been known that women suffer more than men from chronic inflammatory diseases such as lupus or rheumatoid arthritis; this study suggests that estrogen itself is responsible for that difference and pinpoints the molecular pathways that estrogen affects. Molecules that promote the resolution of inflammation show promise as new treatments for autoimmune disease.”

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  • Osteoporosis therapy consisting of estrogen, vitamin D and calcium reduced prevalence of severe periodontitis in postmenopausal women by 44%. (2017) www.sciencedaily.com
    Vitamin D Hormones Inflammation Estrogen Calcium

    From the article:

    In the Menopause article “Association between osteoporosis treatment and severe periodontitis in postmenopausal women,” 492 postmenopausal Brazilian women aged 50 to 87 years, 113 in osteoporosis treatment and 379 not treated, were evaluated to determine whether osteoporosis treatment could help increase the bone mineral density in their jaws and, subsequently, improve overall oral health.

    The study found that the rate of occurrence of severe periodontitis was 44% lower in the postmenopausal osteoporosis-treatment group than in the untreated group. Treatment consisted of systemic estrogen alone or estrogen plus progestin, as well as calcium and vitamin D supplements, for a minimum of six months.

    “Osteoporosis can occur throughout the body, including the jaw, and lead to an increased risk of periodontal disease,” says Dr. JoAnn Pinkerton, NAMS executive director.

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  • Testosterone replacement therapy decreased respiratory hospitalizations by up to 9.1% in COPD patients. (2018) www.sciencedaily.com
    Hormones Inflammation Testosterone

    From the article:

    “Previous studies have suggested that testosterone replacement therapy may have a positive effect on lung function in men with COPD [chronic obstructive pulmonary disease],” said Jacques Baillargeon, UTMB professor in preventive medicine and community health. “However, we are the first to conduct a large scale nationally representative study on this association.”

    […]

    “We found that testosterone users had a greater decrease in respiratory hospitalizations compared with non-users. Specifically, middle-aged testosterone replacement therapy users had a 4.2 percent greater decrease in respiratory hospitalizations compared with non-users and older testosterone replacement therapy users had a 9.1 percent greater decrease in respiratory hospitalizations compared with non-users,” said Baillargeon. “The findings suggest that testosterone replacement therapy may slow the progression of disease in men with COPD.”

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  • Testosterone may protect against inflammation by reducing phospholipase D activity in immune cells, cell study suggests. (2011) www.sciencedaily.com
    Hormones Inflammation Immune System Testosterone Cardiovascular

    From the publication:

    “In a series of analyses we have shown that cells from men and women react in a different manner to inflammatory stimuli,” Dr. Carlo Pergola from the Institute of Pharmacy of University Jena explains. Thus, certain immune cells of women produced nearly twice as many pro-inflammatory substances than those of men. Together with colleagues from Tübingen (Germany), Stockholm (Sweden) and Naples (Italy) the Jena researchers pursued the molecular basis for these differences and published their findings in their current study. To this aim, they isolated immune cells of male and female donors and analyzed in test tubes the activity of the enzymes responsible for the production of pro-inflammatory substances. They found that in male cells the enzyme phospholipase D is less active than in the female ones. “Interestingly, the activity of the enzyme is reduced after treatment with testosterone also in the female immune cells“, Dr. Pergola defines a crucial result.

    Based on these findings, the Jena pharmacists concluded that the male sex hormones play a key role in the modulation of the immune response. This would also explain another phenomenon that has been previously noticed, that is, testosterone can protect men from arteriosclerosis.

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  • Low levels of testosterone may increase long-term risk of death by 33% in men over 50 years old. (2007) www.sciencedaily.com
    Hormones Inflammation Testosterone Mortality Metabolic Syndrome

    From the publication:

    In the study, Laughlin and co-workers looked at death, no matter the cause, in nearly 800 men, ages 50 to 91 years, who were living in Rancho Bernardo, California. The participants have been members of the Rancho Bernardo Heart and Chronic Disease Study since the 1970s. At the beginning of the 1980s, almost one-third of these men had suboptimal blood testosterone levels for men their age.

    The group with low testosterone levels had a 33 percent greater risk of death during the next 18 years than the men with higher testosterone. This difference was not explained by smoking, drinking, physical activity level or pre-existing diseases (such as diabetes or heart disease).

    In this study, “low testosterone” levels were set at the lower limit of the normal range for young adult men. Testosterone declines slowly with aging in men and levels vary widely, with many older men still having testosterone levels in the range of young men. Twenty-nine percent of Rancho Bernardo men had low testosterone.

    Distinguishing Factors

    Men with low testosterone were more likely to have elevated markers of inflammation, called inflammatory cytokines, which contribute to many diseases. Another characteristic that distinguished the men with low testosterone was a larger waist girth along with a cluster of cardiovascular and diabetes risk factors related to this type of fat accumulation. Men with low testosterone are three times more likely to have the metabolic syndrome than men with higher testosterone levels;

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  • Low testosterone levels may herald rheumatoid arthritis in men. (2013) www.sciencedaily.com
    Obesity Hormones Inflammation Testosterone Tobacco Arthritis

    From the article:

    Sex hormones are thought to play a part in the development of rheumatoid arthritis, and both men and women with the condition tend to have lower levels of testosterone in their blood than healthy people. But it is not clear whether this is a contributory factor or a consequence of the disease.

    The researchers based their findings on participants of the Swedish Malmo Preventive Medicine Program (MPMP), which began in 1974 and tracked the health of more than 33,000 people born between 1921 and 1949.

    […]

    After taking account of smoking and body mass index, both of which can affect the risk of rheumatoid arthritis, **men with lower levels of testosterone in their blood samples were more likely to develop the disease.

    This was **statistically significant for those who tested negative for rheumatoid factor when they were diagnosed.

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  • Chronic poor sleep activates the immune system and promotes inflammation. rupress.org
    Sleep Inflammation Immune System

    A new study shows that chronic poor sleep increases immune cell numbers and promotes inflammation, but good, consistent sleep helps maintain a healthy balance of white blood cells and supports normal immune function.

    The study involved 14 healthy adults who experienced two six-week sleep protocols – one in which they got sufficient sleep (about 7.5 hours) every night and one in which they got about 6 hours of sleep every night – separated by a six-week break. The investigators measured inflammatory markers in the participants' blood every morning and afternoon of the last two weeks of each protocol.

    They found that when the participants didn’t get enough sleep, their afternoon blood samples had higher levels of immune cells called monocytes and markers of immune activation compared to when they got enough sleep. Poor sleep also induced epigenetic changes in stem cells that produce immune cells, reducing their progeny’s diversity and tipping the balance of immune cell production toward an inflammatory profile.

    Sleep has profound effects on human health. Not getting enough sleep or having poor, fragmented sleep drives an increase in the production of myeloid cells, a type of white blood cell that predominates in aging and activates inflammasomes – drivers of inflammation.

    These findings suggest that sleep preserves healthy immune cell production, thereby reducing inflammation. Learn more about the health benefits of sleep in this episode featuring Dr. Matthew Walker.

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  • Testosterone may protect men from stomach inflammation, mouse study suggests. (2021) www.sciencedaily.com
    Autoimmunity Hormones Inflammation Testosterone

    From the article:

    In researching mice without either glucocorticoids or testosterone, Busada, his research partner John Cidlowski – a senior investigator with the National Institutes of Health – and their colleagues observed that males' stomach inflammation increased as much as the females' did.

    What’s more, when he and his team gave testosterone to the female mice, their inflammation vanished.

    “We were able to completely rescue them from their stomach inflammation,” Busada said. “We proved that androgens were the hormones giving male mice that double layer of protection from inflammation. In the females, the only anti-inflammatory hormone was glucocorticoids. In males, it could be either glucocorticoids or androgens. This study potentially explains why women have a much higher incidence of autoimmune and chronic inflammatory diseases.”

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  • Higher omega-6:omega-3 ratios may be associated with progressive increases in TNF-α and interleukin-6 levels as depressive symptoms increase. (2007) www.sciencedaily.com
    Omega-3 Inflammation Depression IL-6 TNF-Alpha

    From the article:

    The study, conducted in OSU’s Institute for Behavioral Medicine Research, focused on a group of 43 middle-aged to elderly men and women, nearly half of which were the caregiver spouses of people with Alzheimer’s or other dementias. By including caregivers who typically report greater stress and more depression than similar ad ults who are not caregiving, the researchers could look at how depression and diet might interact to affect inflammation.

    […]

    The analysis showed that participants who had much more omega-6 – compared to omega-3 – fatty acids, and who also were reporting more symptoms of depression, had much higher levels of IL-6 and TNF-alpha, two cytokines which enhance inflammation.

    “The data suggest that higher depression and a poorer diet in terms of omega-3 can work together to promote inflammation. Other researchers have shown that clinically depressed people – those with more severe depression – often have lower omega-3 levels in their blood, and several studies have shown that supplementing diets with omega-3 improves depression,” Kiecolt-Glaser said, although the reason isn’t clear.

    […]

    “This study has shown that even in people who did not take supplements, maybe just a little bit more omega-3, could help reduce their markers for both stress and depression,” Belury said.

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  • Omega-3 supplementation altered interleukin-6 levels by -12% (vs +36% in placebo group) and TNF-α by -2.3% (vs +12% in placebo group). (2012) www.sciencedaily.com
    Obesity Omega-3 Inflammation IL-6 TNF-Alpha

    From the article:

    The scientists recruited 138 adults – 45 men and 93 women – who were in good health, but who were either overweight or obese and lived sedentary lives. Their average age was 51 years. Based on body mass index, a measure of weight relative to height, 91 percent of the participants were overweight and 47 percent were obese.

    […]

    Participants received either a placebo or one of two different doses of omega-3 fatty acids – either 2.5 grams or 1.25 grams per day. The supplements were calibrated to contain a ratio of the two fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than does DHA.

    After four months, participants who had taken the omega-3 supplements had significantly lower levels in their blood of two proteins that are markers of inflammation, also called pro-inflammatory cytokines. The low-dose group showed an average 10 percent decrease in the cytokine interleukin-6 (IL-6), and the high-dose group’s overall IL-6 dropped by 12 percent. In comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

    Levels of the cytokine tumor necrosis factor-alpha (TNF-a) also dropped, but in a more modest way, by 0.2 percent and 2.3 percent in the low- and high-dose groups, respectively. The placebo group’s TNF-a increased by an average of 12 percent.

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  • Interleukin-6, CRP and triglycerides are likely shared causal risk factors for depression and coronary heart disease. (2019) www.sciencedaily.com
    Brain Heart Disease Inflammation Depression Triglycerides IL-6 CRP

    From the article:

    Together, these results suggest that the link between heart disease and depression cannot be explained by a common genetic predisposition to the two diseases. Instead, it implies that something about an individual’s environment – such as the risk factors they are exposed to – not only increases their risk of heart disease, but at the same time increases their risk of depression.

    […]

    Of these common biomarkers, they found that triglycerides (a type of fat found in the blood) and the inflammation-related proteins IL-6 and CRP were also risk factors for depression.

    Both IL-6 and CRP are inflammatory markers that are produced in response to damaging stimuli, such as infection, stress or smoking. Studies by Dr Khandaker and others have previously shown that people with elevated levels of IL-6 and CRP in the blood are more prone to develop depression, and that levels of these biomarkers are high in some patients during acute depressive episode. Elevated markers of inflammation are also seen in people with treatment resistant depression. This has raised the prospect that anti-inflammatory drugs might be used to treat some patients with depression. Dr Khandaker is currently involved in a clinical trial to test tocilizumab, an anti-inflammatory drug used for the treatment of rheumatoid arthritis that inhibits IL-6, to see if reducing inflammation leads to improvement in mood and cognitive function in patients with depression.

    While the link between triglycerides and coronary heart disease is well documented, it is not clear why they, too, should contribute to depression. The link is unlikely to be related by obesity, for example, as this study has found no evidence for a causal link between body mass index (BMI) and depression.

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  • Maternal immune activation during pregnancy is associated with changes in the newborns' stimulus processing and long-term development. (2018) www.sciencedaily.com
    Brain Inflammation Pregnancy Autism Schizophrenia IL-6 CRP

    From the article:

    Blood drawn from mothers during their third trimester was tested for levels of IL-6 and CRP – two proteins that are found at higher levels when the immune system is activated. Peterson’s team also monitored fetal heart rate as an indicator for nervous system development. The team found that CRP did correlate with variability of the fetal heart rate, which is influenced heavily by the nervous system, indicating that maternal inflammation was already beginning to shape brain development.

    When the babies were born, they were given MRI scans in their first few weeks of life, providing researchers a unique view of early neural development and the influence of prenatal factors. Brain imaging revealed a striking finding – significant changes in the communication between specific brain regions correlated with elevated maternal IL-6 and CRP levels. These brain regions are known collectively as the salience network, whose job is to filter stimuli coming into the brain and determine which deserve attention.

    […]

    “The salience network sifts through that information and decides what is important and warrants action.” Disturbances in the functioning of this network, as well as various kind of infection and other triggers of a pregnant woman’s immune response, have been linked to development of psychiatric illnesses, such as schizophrenia and autism spectrum disorders.

    […]

    The correlations of elevated maternal inflammatory markers were not limited to the newborn period, but continued to persist into toddlerhood. When the babies turned 14 months of age, researchers assessed them for motor skills, language development, and behavior. Following the established Bayley Scales of Infant and Toddler Development-Third Edition, Peterson found significant changes in the scores of toddlers born to mothers with elevated levels of both IL-6 and CRP.

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  • Stress-induced chronic inflammation is associated with depression and other diseases. (2015) www.sciencedaily.com
    Exercise Brain Inflammation Depression Stress Meditation Mental Health NSAID IL-6 CRP

    From the article:

    The authors found that in addition to being linked to numerous physical health issues, including cancer and diabetes, systemic inflammation is linked to mental health issues such as depression. Among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.

    Fagundes said chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children. Other contributing factors are a high-fat diet and high body mass index.

    […]

    The study also found that depression caused by chronic inflammation is resistant to traditional therapy methods, but can be treated with activities such as yoga, meditation NSAIDS and exercise.

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  • Social rank and rank uncertainty predicted levels of the pro-inflammatory proteins CRP, IL-6 and TNF-alpha in monkeys. (2016) www.sciencedaily.com
    Brain Inflammation IL-6 TNF-Alpha CRP

    From the article

    The team found that social rank and rank uncertainty predicted key risk factors for poor health, specifically pro-inflammatory proteins (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) which are risk factors for chronic diseases such as cardiovascular disease and diabetes.

    […]

    The researchers discovered that high ranking monkeys with low certainty of their social status showed higher markers of inflammation, which can be a sign of a chronic disease state such as diabetes, than those with very certain status. So high-ranking monkeys may experience some health risks, but only when their position is questionable and they are consequently at risk of losing their status.

    The opposite pattern was found for low ranking monkeys – high dominance certainty was associated with higher markers of inflammation, whereas low certainty was associated with lower levels of inflammatory proteins. Monkeys that are uncertain in their low rank might have opportunities for upward mobility in the hierarchy, which may be associated with better health outcomes.

    Vandeleest said the results of the study show that status uncertainty alone may be a risk factor for acute diseases. The results also indicate that uncertainty in status over longer periods in relationship to rank are related to chronic disease states as well.

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  • RCT suggests that TNF-alpha antagonism may improve depressive symptoms in patients with high inflammatory biomarkers. (2012) www.sciencedaily.com
    Brain Inflammation Depression TNF-Alpha CRP

    From the article:

    Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation.

    […]

    Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment.

    When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab [TNF inhibitor] than to placebo.

    Inflammation in this study was measured using a simple blood test that is readily available in most clinics and hospitals and measures C-reactive protein or CRP. The higher the CRP, the higher the inflammation, and the higher the likelihood of responding to the drug.

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  • Evidence in mice suggests that TNF-alpha release in response to viral infection causes learning problems. (2017) www.sciencedaily.com
    Brain Inflammation Memory TNF-Alpha

    From the article:

    Evidence in mice suggests that the entry of a virus anywhere in the bloodstream turns on “first responder” immune cells called CX3CR1highLY6Clow monocytes, which then release the inflammatory signaling protein TNF-α. According to the authors of the study, TNF-α then travels to the brain where it blocks the formation of nerve cell connections needed to turn sensory information into memories.

    […]

    Researchers also measured the levels of pro-inflammatory signaling proteins (cytokines) in mice at several time points after the injection of poly(I:C), and found a larger, longer-lasting increase in levels of TNF-α than in other cytokines. Given their findings, the team guessed that the impact of systemic immune response on brain cell connections was executed through TNF-α signaling. Indeed, mice engineered to lack TNF-α signals in white blood cells saw neither a drop in dendritic spine formation nor in motor learning ability when exposed to the viral mimetic.

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  • Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013) www.sciencedaily.com
    Brain Inflammation Depression IL-6

    Psychosocial stress promotes the release of IL-6, potentially driving the development of depression.

    Psychosocial stress, such as that experienced with divorce, discrimination, trauma, or the death of a child, can have profound effects on the human body. For example, evidence indicates that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a 2013 study suggest that psychosocial stress promotes the release of interleukin 6 (IL-6), potentially driving the development of depression.

    IL-6 is a pro-inflammatory cytokine that plays an important role as a mediator of fever and the body’s immune response. It is produced by almost all immune cells and is induced in the context of infection, autoimmunity, or cancer. Many physiological processes are influenced by IL-6, including glucose metabolism, blood cell production, neuroendocrine regulation, and fatigue, among others. IL-6 levels are often elevated in people who have depression.

    The investigators conducted their study using mice that had undergone radiation to destroy their bone marrow, compromising their immune function. Then they transplanted bone marrow from mice that exhibited either high or low levels of IL-6 levels in response to stress into the immune-compromised animals. Then they exposed the animals to a social stressor.

    They found that mice that received transplants from those that exhibited high IL-6 levels in response to stress demonstrated more depression-like behaviors than the mice that received transplants from those that exhibited low IL-6 levels. These findings suggest that IL-6 promotes a pro-inflammatory state that promotes depression-like symptoms in response to psychosocial stress. Identifying therapeutic strategies that inhibit IL-6 may benefit people who are vulnerable to the effects of psychosocial stress.

    Interestingly, hyperthermia, such as that experienced with sauna use or hot baths, has been shown to reduce IL-6 levels. Learn more about the beneficial effects of sauna use in our overview article.

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  • Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021) www.sciencedaily.com
    Brain Inflammation Depression Mental Health IL-6

    Microglia and IL-6 drive the negative mood often associated with inflammation.

    People who have certain neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, or stroke, often exhibit low mood. Evidence suggests that inflammation plays a role in the pathogenesis of these neurological disorders and likely influences mood, as well. Findings from a 2021 study suggest that microglia activation drives the low mood often associated with neurological disorders.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    The investigators used chemogenetics, a research technique that uses drugs or other chemicals to modulate neural activity, to stimulate microglia activation in the brains of mice. They noted that levels of interleukin-6 (IL-6, a pro-inflammatory cytokine) and prostaglandins (hormone-like molecules that are involved in inflammation) increased in the animals' brains. In addition, the animals exhibited a low mood. Blocking microglia activity restored the animals' positive mood, however.

    These findings suggest that microglia drive the low mood often associated with inflammation and that IL-6 is a prominent player in this process. Learn more about the role of inflammation and mood in this episode featuring Dr. Charles Raison.

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  • Probiotics may improve inflammation-associated behavioral changes in mice by lowering TNF-alpha blood levels. (2015) www.sciencedaily.com
    Inflammation Probiotics Behavior TNF-Alpha

    Probiotics attenuate inflammation-associated sickness behaviors.

    The gut-brain axis, a bidirectional signaling pathway between the gastrointestinal tract and the nervous system, plays critical roles in human health. Key elements of this pathway are the tens of trillions of microbes that comprise the intestinal microbiota. Findings from a 2015 study suggest that probiotics attenuate inflammation-associated sickness behaviors.

    Probiotics are typically defined as live microorganisms that, when consumed in sufficient amounts, confer a health benefit on the consumer. They contain a variety of microorganisms, but Lactobacillus and Bifidobacterium bacteria are among the most common. Probiotics can be found in yogurt, kefir, kimchi, and other fermented foods and are widely available as dietary supplements.

    Sickness behaviors are adaptive behavioral changes that occur during infection or chronic inflammatory disorders and may include lethargy, depressed mood, appetite loss, sleepiness, pain, or confusion. Evidence suggests that tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine produced by immune cells, activates microglia (the brain’s resident immune cells) and recruits white blood cells to the brain, driving the development of inflammation-associated sickness behaviors.

    The investigators used a model of liver inflammation in mice to study the effects of a probiotic on inflammation-associated sickness behavior. Mice with this form of liver inflammation typically have high levels of pro-inflammatory cytokines and exhibit distinct sickness behaviors. They fed the mice either a probiotic or a placebo and then they studied the animals' behavior. They also measured TNF-alpha levels in the animals' blood and the number of activated immune cells in the animals' brains.

    They found that although the probiotic did not reduce the severity of liver inflammation in the mice, it did reduce sickness behaviors better than the placebo. Mice that received the probiotics also had lower TNF-alpha levels and fewer activated immune cells in their brains compared to mice that received a placebo.

    These findings suggest that probiotics attenuate inflammation-associated sickness behaviors in mice, likely via modulation of the gut-brain axis. Learn about factors to consider when choosing a probiotic supplement in this clip featuring Dr. Jed Fahey.

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  • TNF-alpha production within the brain may partially explain the behavioral changes in mice with cholestatic liver damage. (2006) www.sciencedaily.com
    Brain Inflammation Behavior TNF-Alpha

    TNF-alpha in the brain drives sickness behaviors associated with liver disease.

    Many liver disorders cause behavioral symptoms, often referred to as sickness behaviors, such as fatigue, loss of appetite, and “brain fog.” Evidence suggests that these symptoms arise from alterations in the central nervous system, but scientists don’t fully understand what drives them. Findings from a 2006 study suggest that sickness behaviors in the setting of cholestasis, a common liver disorder, are caused by the presence of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, in the brain.

    Cholestasis is characterized by impaired bile flow and subsequent retention of bile acids, bilirubin, and other substances, including lipopolysaccharide, an endotoxin, in the liver and blood. It is a common disorder of pregnancy but can affect all demographics, including children. Most people with cholestasis report experiencing sickness behaviors, especially fatigue, which occurs in roughly 86 percent of people with the disorder.

    TNF-alpha is produced by many types of immune cells. It exists in soluble and transmembrane forms, both of which mediate a variety of opposing physiological and pathological functions, depending on which of its receptors it binds to. For example, binding to TNF receptor 1 promotes apoptosis (programmed cell death) and inflammation; binding to TNF receptor 2 promotes cell survival, resolution of inflammation, immunity, and cellular repair. Elevated TNF-alpha is associated with chronic pain syndromes and anxious behaviors.

    The investigators tied off the bile ducts of healthy mice to induce cholestasis. Then they isolated endothelial cells from the blood vessels in the animals' brains to see if the cells were activated and if the cells interacted with immune cells. They also measured TNF-alpha production by monocytes (white blood cells).

    They found that endothelial cells were activated in the setting of cholestasis, and these activated cells readily interacted with immune cells that had been recruited to the brain. In turn, the immune cells increased their production of TNF-alpha. In light of the known effects of TNF-alpha on sickness behaviors, these findings suggest that TNF-alpha production in the brain mediates sickness behaviors in mice with liver disease.

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  • In a mendelian randomization study, genetically predicted levels of interleukin 6 (IL-6) were associated with neuropsychiatric disorders. www.sciencedaily.com
    Brain Inflammation Mental Health Genetics IL-6

    IL-6 may drive inflammation in neuropsychiatric disorders.

    Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.

    The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.

    The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.

    They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.

    These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.

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  • Can chronic use of anti-inflammatory agents paradoxically promote chronic inflammation through compensatory host response? pubmed.ncbi.nlm.nih.gov
    Heart Disease Inflammation NSAID Cardiovascular

    NSAIDs may promote a paradoxical pro-inflammatory effect, increasing the risk of blood clots and cardiovascular events.

    Non-steroidal anti-inflammatory drugs, or NSAIDs, are among the most widely used drugs worldwide, available in both prescription and over-the-counter forms, such as aspirin, ibuprofen, naproxen, and others. Despite the drugs' anti-inflammatory effects, their chronic use is associated with a higher risk of acute clot-related cardiovascular events, such as heart attack, stroke, or deep-vein thrombosis. Authors of a 2005 article posited that NSAIDs induce a rebound effect that promotes inflammation, driving the formation of blood clots and predisposing a person to acute cardiovascular events.

    Inflammation is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes. Inflammation initiates the clotting process and impairs the activity of natural anti-clotting mechanisms.

    Most NSAIDs, with the exception of aspirin, dampen inflammation via the inhibition of cyclooxygenases, a family of pro-inflammatory enzymes. However, evidence from animal studies suggests that when these enzymes are inhibited, the body responds by producing more of the enzymes. The authors posited that by turning off the body’s natural inflammatory processes, NSAIDs might drive a compensatory response – ramping up the activity of pro-inflammatory pathways.

    Lifestyle behaviors may reduce inflammation and the need for NSAIDs. For example, sauna use reduces levels of pro-inflammatory C-reactive protein and increases levels of anti-inflammatory protein interleukin (IL)-10. Similarly, cold exposure decreased the pro-inflammatory protein IL-2 and the inflammatory E2 series of prostaglandins while increasing the anti-inflammatory protein IL-10. Other lifestyle behaviors that may reduce inflammation include exercise, meditation, and dietary intake of polyphenols.

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  • Inflammation is critical in aortic dissection, and IL-6 plays the central role in the process. (2009) www.sciencedaily.com
    Inflammation Aneurysm

    From the article:

    To profile the inflammatory attack that produces aortic dissection, Brasier’s group injected the hormone angiotensin into both ordinary lab mice and those genetically modified to “knock out” IL-6 or a cellular receptor for another molecule also involved, known as MCP-1. The human samples, used to substantiate a link between the mouse findings and human disease, came from volunteers undergoing surgical aortic dissection repair without a family history of the disease.

    “Angiotensin is a blood-pressure regulating hormone – people who have what we call essential high blood pressure have increased production of angiotensin, and it’s the target for anti-hypertension therapies,” Brasier said. “What we’ve found in earlier studies is that it has an inflammatory role as well, causing cells in blood vessel walls to produce IL-6 as well as MCP-1. And this study showed us that MCP-1 helps recruit monocytes [a type of white blood cell] to the vessel where IL-6 activates them.”

    Playing host to a large number of cells meant for immune defense is bad news for an aorta already strained by an aneurysm, since activated white blood cells produce proteins that destabilize the structure of the vessel. At the same time, signals produced by the activated white blood cells encourage the blood vessel to generate more IL-6.

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  • Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults www.mdpi.com
    Brain Aging Inflammation Small Vessel Disease

    Gum disease may increase the risk of white matter hyperintensities, a type of brain lesion.

    White matter hyperintensities are brain lesions that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. High blood pressure is the primary contributor to white matter hyperintensity formation, but other factors likely play roles, as well. Findings from a 2020 study suggest that periodontitis is associated with white matter hyperintensities.

    Periodontitis is a chronic inflammatory condition of the gums, characterized by red, tender, swollen, or bleeding gums. It is typically caused by poor oral hygiene and is more common with age, manifesting in more than two-thirds of adults over the age of 65 years. Periodontitis is diagnosed using a periodontal probe, which is used to assess the depth of pockets in the gum. In a healthy mouth, a pocket can be anywhere from 1 to 3 millimeters deep. Deeper pockets are indicators of gum inflammation and disease.

    The study involved more than 400 adults (average age, 54 years) who underwent a routine dental exam that included pocket depth probing. The investigators performed MRI scans on the participants to identify the presence of white matter hyperintensities, which were classified according to their size, number, and severity. They gathered information about the participants' general health and lifestyles and measured their C-reactive protein (CRP, a biomarker of inflammation). They found that nearly half of the participants had white matter hyperintensities. Those who did were nearly three times more likely to be at least 65 years old, more than twice as likely to have elevated systolic blood pressure, and nearly twice as likely to have deeper pocket depth (6 millimeters or more). Having white matter hyperintensities was not associated with the participants' CRP levels.

    These findings suggest that older age, elevated blood pressure, and periodontitis are associated with an increased risk of developing white matter hyperintensities, but inflammation is not a driver of this association. Evidence indicates that white matter hyperintensities are predictive of the amount and degree of leakage of the blood-brain barrier leakage. Learn more in our overview article.

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  • Systemic immune-inflammation index is associated with white matter hyperintensity volume: among cSVD pathologies, WMH may be more inflammation-related www.nature.com
    Brain Aging Inflammation Small Vessel Disease

    From the article:

    Systemic immune-inflammation index (SII) is a novel inflammatory marker based on the composition ratio of blood cell counts. In this study, we evaluated the association between the SII and cerebral small vessel disease (cSVD) in health check-up participants. We evaluated participants from our health check-up registry between 2006 and 2013. The SII was calculated using the following formula: SII = (platelet count × neutrophil count)/lymphocyte count. cSVD was assessed by considering white matter hyperintensity (WMH) volume, lacunes, and cerebral microbleeds (CMBs). A total of 3187 participants were assessed. In multivariable linear regression analysis, the SII was significantly related to WMH volume [β = 0.120, 95% confidence interval (CI) 0.050–0.189]. However, lacunes and CMBs showed no statistical significance with the SII. In the subgroup analysis by age, the SII was significantly associated with WMH volume only in participants aged ≥ 60 years (β = 0.225, 95% CI 0.068–0.381). In conclusion, a high SII was associated with cSVD. Since this association was more pronounced in WMH than in lacunes or CMBs, WMH might be closer to the inflammation-related pathological mechanisms.

    Age-related changes in systemic inflammation:

    Interestingly, the close association between the SII and WMH volume in our study was significant only in older participants aged ≥ 60 years. This might be related to the aging-related changes in the homeostatic maintenance of our body’s inflammation and immunity (e.g., inflammaging, immunosenescence, and homeostenosis)

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  • Antidepressant effects of omega-3 EPA may occur in the brain even though brain content is low (it is present in microglia and involved in signaling) www.sciencedirect.com
    Brain Omega-3 Inflammation Depression Immune System Behavior

    From the article:

    It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve important roles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.

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  • Obese when compared to those with normal body fat had much higher inflammation: 53% higher CRP, 30% higher TNF-a, 17% higher WBC count, 42% higher IL6 linkinghub.elsevier.com
    Obesity Aging Metabolism Inflammation Immune System Metabolic Syndrome IL-6

    Strong link between accumulated visceral fat and chronic inflammation.

    A person’s waist-to-hip ratio compares their waist measurement to that of their hips. A high ratio can be an indicator of excess fat accumulation around the waist, often referred to as visceral fat. Findings from a 2005 study suggest that visceral fat is associated with markers of inflammation.

    Visceral fat is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to increased risk of cardiovascular disease and other chronic diseases. Many factors drive visceral fat accumulation, including poor sleep, an obesogenic diet, and sugar-sweetened beverage intake, among others.

    The study involved more than 3,000 healthy males and females (18 to 89 years old) living in Greece. The investigators calculated the participants' body mass index (BMI) and measured their waist and hip circumferences. Participants provided blood samples for the assessment of inflammatory biomarkers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), amyloid A (an apolipoprotein secreted in the acute stage of inflammation), white blood cells, and interleukin-6 (IL-6).

    The investigators found that approximately 36 percent of the males and 43 percent of the females had excess visceral fat. Approximately 20 percent of the males and 15 percent of the females had obesity. Participants with greater visceral fat had 53 percent higher CRP, 30 percent higher TNF-alpha), 26 percent amyloid A, 17 percent higher white blood cell counts, and 42 percent higher IL-6, compared to participants with normal fat distribution. The relationship between visceral fat and inflammatory markers was stronger than that between obesity and inflammation, even when considering the participants' age, income, education, and other potential confounding factors.

    These findings suggest that visceral fat and inflammatory processes are linked. The investigators posited that excess accumulation of visceral fat may increase the risk for cardiovascular disease by driving inflammation.

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  • Nerve Stimulation Promotes Resolution of Inflammation. neurosciencenews.com
    Brain Inflammation

    Vagus nerve stimulation promotes the resolution of inflammation.

    Inflammation is a necessary component of the body’s immune response. But unresolved inflammation is harmful to the body and can promote a wide range of chronic diseases. Findings from a recent study suggest that stimulation of the vagus nerve promotes the resolution of inflammation.

    The vagus nerve is the tenth cranial nerve. Its name, “vagus,” comes from the Latin term for “wandering” – a characteristic of the nerve, which arises in the brain and extends to organs in the neck, chest, and abdomen. The vagus nerve is the primary component of the parasympathetic nervous system, which regulates many crucial biological processes, including mood control, digestion, heart rate, and immune response. Evidence from animal studies suggests that stimulating the vagal nerve reduces the release of proinflammatory cytokines that drive acute inflammation.

    Using a mild electrical current, the investigators stimulated the vagus nerve of mice. Then, after inducing an inflammatory response in the animals' abdomens, they measured neutrophils (immune cells) and anti-inflammatory markers in fluid taken from the abdominal region.

    They found that mice that received the vagus nerve stimulation had higher levels of specialized pro-resolving mediators, or SPMs, in their abdominal fluid. SPMs are byproducts of omega-3 fatty acid metabolism that play critical roles in resolving inflammation. The stimulated mice also had fewer neutrophils in their abdominal fluid, an indication that neutrophil infiltration had ceased, a key process in the resolution of inflammation.

    These findings suggest that vagus nerve stimulation promotes the resolution of inflammation via the promotion of SPM biosynthesis. Learn more about SPMs and omega-3 metabolism in this episode featuring Dr. Bill Harris.

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  • Plasmacytoid dendritic cells (pDCs) are a special immune cell that accumulate in visceral fat, producing lymphoid structures driving secondary disease www.sciencedaily.com
    Obesity Inflammation Immune System Metabolic Syndrome Visceral Fat

    An obesogenic diet drives immune cell activation.

    Although the role of dietary fat intake in obesity is a matter of considerable controversy, research has identified complex interrelationships between dietary components, inflammation, and immune function. For example, some evidence suggests that consumption of a diet high in fat drives inflammatory processes in the central nervous system and peripheral tissues, including the liver, adipose tissue, skeletal muscle, and gut, promoting metabolic dysfunction and weight gain. Findings from a recent study suggest that a high-fat diet promotes the activity of plasmacytoid dendritic cells, a type of immune cell.

    Plasmacytoid dendritic cells, also known as natural interferon-producing cells, are critical components of both the innate and adaptive immune response. These specialized cells secrete copious amounts of type 1 interferons in response to a viral infection and then differentiate into professional antigen-presenting cells, which can stimulate T cell activity. Chronic stimulation of the plasmacytoid dendritic cells is linked with the development of autoimmune disorders and certain types of cancer. Although plasmacytoid dendritic cells are somewhat rare, they have been identified in visceral adipose tissue.

    The investigators fed multiple groups of mice either a high-fat diet or standard chow for three weeks. They gave one group of mice on the high-fat diet a drug that blocks the migration of plasmacytoid dendritic cells into the visceral adipose tissue. Then they analyzed the animals’ blood, peripheral tissue, lymphatic organs, and visceral adipose tissue for the presence of plasmacytoid dendritic cells.

    They found that after three weeks of a high-fat diet, plasmacytoid dendritic cells increased in the blood, liver, spleen, and visceral adipose tissue. The cells were especially abundant in fat-associated lymphoid clusters within the visceral adipose tissue. The animals on the high-fat diet gained weight and exhibited poor glucose tolerance, indicating metabolic dysfunction. Their visceral adipose tissue weight doubled during the three-week diet. Animals that received the drug that blocked plasmacytoid dendritic cell migration did not gain weight and demonstrated better glucose tolerance.

    These findings suggest that an obesogenic diet drives visceral and peripheral weight gain, promotes glucose intolerance, and increases immune cell activation in the visceral adipose tissue of mice.

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  • Visceral fat may cause pathogenic obesity reinforced through a cycle of chronic inflammation www.sciencedaily.com
    Obesity Inflammation Metabolic Syndrome Intestinal Permeability Visceral Fat

    Scientist proposes that the bodies decision to promote visceral fat rather than subcutaneous fat may be due to underlying biological switches triggered partly by malnutrition.

    The evolutionary advantage of visceral fat:

    Sometimes called “the abdominal policeman,” a VAT-rich structure called the omentum, a loosely hanging fold of the membrane lining the abdominal cavity, sticks to wounds, foreign objects such as shrapnel and infection sites like a bandage full of antibiotics. In fact, surgeons sometimes use pieces of omentum to control severe postoperative infections. VAT surrounds the small intestine, defending the body from ingested pathogens and toxins.

    […]

    In the past, the role of visceral fat as part of the immune system may have been more widely important than it is today because starvation and infections were more common. West-Eberhard proposes that in fetuses subject to nutritional stress, more energy may be stored as fat around the abdominal organs rather than as fat under the skin (subcutaneous fat or SAT).

    Chronic inflammatory feedback loop promotes development of visceral fat:

    In overweight individuals, a dangerous feedback loop may develop: increased VAT leads to increased chronic inflammation, which, in turn, leads to increased insulin resistance leading to further VAT storage and increased susceptibility to disease.

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  • Air pollution may promote the production of autoantibodies against tight-junctions and neural proteins: neuroinflammation in children in Mexico City www.sciencedaily.com
    Brain Alzheimer's Inflammation Pollution Autoimmunity Blood-Brain Barrier

    Exposure to air pollution promotes the production of autoantibodies against tight-junctions of the blood-brain barrier.

    Separately, evidence has also shown that even very young children show evidence of amyloid-beta build up under these conditions.

    From the article:

    The study found when air particulate matter and their components such as metals are inhaled or swallowed, they pass through damaged barriers, including respiratory, gastrointestinal and the blood-brain barriers and can result in long-lasting harmful effects.

    The results found that the children living in Mexico City had significantly higher serum and cerebrospinal fluid levels of autoantibodies against key tight-junction and neural proteins, as well as combustion-related metals.

    “We asked why a clinically healthy kid is making autoantibodies against their own brain components,” Calderón-Garcidueñas said. “That is indicative of damage to barriers that keep antigens and neurotoxins away from the brain. Brain autoantibodies are one of the features in the brains of people who have neuroinflammatory diseases like multiple sclerosis.”

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  • Inherited Parkinson's LRRK2 mutations promote excessive inflammatory cytokines that cross blood-brain barrier, trigger neuron damage via microglia www.sciencedaily.com
    Brain Parkinson's Aging Inflammation Immune System Blood-Brain Barrier Lipopolysaccharide

    From the article:

    Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent – the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.

    When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.

    Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.

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  • Chronic systemic inflammation induced by lipopolysaccharide can cause microglia to attack the blood-brain barrier www.sciencedaily.com
    Obesity Inflammation Immune System Toll-Like Receptors Blood-Brain Barrier Lipopolysaccharide

    Obesity promotes circulation of lipopolysaccharide. In animals, chronic systemic inflammation, experimentally induced by injection with LPS, also known as “LPS challenge,” can cause microglia into the brain to switch from protecting the blood-brain barrier to damaging it.

    From the article:

    Nearly 50 percent of all dementias, including Alzheimer’s, begins with the breakdown of the smallest blood vessels in the brain and their protective “gatekeeper cells,” according to a Keck School of Medicine of USC study.

    […]

    A key point of interest was the systemic inflammation induced by injecting the mice with an inflammation-inducing substance. Such injections resulted in the movement of microglia to the blood vessels and increased the permeability of the blood-brain barrier within a few days. Then, the microglia initially acted to protect the blood-brain barrier and limit increases in permeability, but as inflammation progressed, the microglia reversed their behavior by attacking the components of the blood-brain barrier, thus increasing the barrier’s permeability. The subsequent leakage of molecules into the brain had the potential to cause widespread inflammation in the brain and consequent damage to neurons (cells of the nerves).

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  • 50% of all dementias and Alzheimers may start with leaky blood-brain barrier www.sciencedaily.com
    Alzheimer's Aging Inflammation Dementia Blood-Brain Barrier Lipopolysaccharide

    From the article:

    “Many scientists have focused their Alzheimer’s disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier – with leaky blood vessels in the brain,” said Berislav Zlokovic, senior author of the study

    Reducing fibrinogen that enters the brain through leaky gatekeeping may be important for preventing decline:

    Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produces myelin), to die.

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  • Spike proteins that extrude from SARS-CoV-2 promote inflammatory responses on the endothelial cells that form the blood-brain barrier. www.sciencedaily.com
    Brain Inflammation Immune System COVID-19 Blood-Brain Barrier

    SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    COVID-19 is widely regarded as a respiratory illness, but evidence suggests it affects multiple organ systems, including the central nervous system. For example, some people with COVID-19 experience headaches, nausea, vomiting, or “brain fog” – indicators of neurological involvement. Evidence from a 2020 study suggests that SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2), a protein that is widespread among the body’s tissues and plays important roles in blood pressure control. Once inside the cell, SARS-CoV-2 replicates, triggering a robust immune response and eliciting widespread inflammation.

    The blood-brain barrier, a semi-permeable barrier that separates the blood from the brain’s extracellular fluid, prevents the entry of neurotoxic substances into the brain. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators first examined postmortem brain tissue from healthy people as well as people who had been diagnosed with hypertension (high blood pressure) or dementia to identify the presence of ACE2 in the brain blood vessels. They found that not only was ACE2 present in the blood vessels, but it was particularly abundant in people with hypertension or dementia. Then, using an in vitro model of the blood-brain barrier, they assessed the effects of exposure to the SARS-CoV-2 spike protein, the primary infectious particle on the virus. They found that exposure to the spike protein impaired blood-brain barrier function and integrity. Finally, using a tissue model that mimics the movement of fluid in the barrier, they found that the spike protein increased barrier permeability.

    These findings suggest that SARS-CoV-2 binds to ACE2 receptors in the brain and impairs blood-brain barrier function and integrity. These effects may be exacerbated in people with co-existing illnesses such as hypertension or dementia.

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  • Omega-3 pro-resolving mediators resolvins and maresins reduced production of "pathogenic" white blood cels, increased beneficial T regulatory cells www.sciencedaily.com
    Omega-3 Inflammation Immune System

    From the article:

    In the newly published work, the team examined the roles of two resolvins and one maresin in human blood lymphocytes, finding that they reduced the activation and prevented the differentiation of two types of pathogenic white blood cells, Th1 and Th17 cells. The team also found that these molecules could regulate Treg cells, a separate subset of cells that can tamp down the immune response. The team further verified these results in a mouse model deficient in these molecules. Together, these discoveries suggest that pro-resolving lipid mediators influence the balance between pathogenic Th1/Th17 and tolerogenic Treg cells, a balance that is typically altered during chronic inflammatory and autoimmune diseases.

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  • Inflammatory injury from obesity is mediated by activation of TLR4 (but may be ameliorated by omega-3) www.sciencedaily.com
    Brain Obesity Omega-3 Inflammation Toll-Like Receptors Lipopolysaccharide

    Knocking out TLR4 in mice ameliorates obesity-associated inflammation, which may come as no surprise since increased circulation of LPS (a potent activator of TLR4) has been implicated in obesity due to associations with increased presence of LPS binding protein.

    While genetically knocking out TLR4 is probably not a practical solution to the inflammatory cascade associated with human obesity, which may also be a smoking gun in obesity-associated brain shrinkage and diminished cognition, dietary intake of omega-3 fatty acids EPA and DHA may at least be partly ameliorative (see review). Additionally, a study in breast cancer patients showed that 5 grams per day of EPA and DHA ultimately lead to hypermethylation (usually interpreted as suppressive) of TLR4.

    From the article:

    When a person consumes more calories than needed, the excess calories are stored in the form of triglycerides inside fat tissue, also known as white adipose tissue (WAT). Researchers know that in obese people, WAT becomes overworked, fat cells begin to die, and immune cells become activated. But the exact mechanism by which this inflammation occurs isn’t fully understood.

    […]

    After five months on a high-fat diet, the mice lacking Tlr4 had gained just as much weight, and just as much fat, as other mice on a high-fat diet. But the genetically engineered mice – with [fibro-inflammatory progenitors] that could no longer generate the same signals – no longer had high levels of inflammation. Instead, the levels of inflammatory molecules in their WAT were closer to the levels seen in mice on low-fat diets.

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  • Suppression of TLR4 gene shown in animals to protect against retinal cell death associated with acute glaucoma www.sciencedaily.com
    Inflammation Immune System Eyes Toll-Like Receptors

    From the article:

    In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections.

    “This immune response is a double-edge sword because, while these proteins protect us from infection in a normal situation, they stimulate apoptosis (programmed cell death) in retinal cells in cases of acute glaucoma,” said Zhang, who is also a staff physician at the Veterans Affairs San Diego Healthcare System.

    To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein.

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  • TLR4 exacerbates necrotizing enterocolitis, a leading cause of death in premature newborns, by stopping enterocytes from closing wounds in intestines www.sciencedaily.com
    Inflammation Immune System Intestinal Permeability Toll-Like Receptors

    View full publication:

    Blocking signals from a key molecular receptor that normally switches on the intestine’s immune response but instead becomes too intense in the presence of stress and toxins may help reverse necrotizing enterocolitis (NEC), a leading cause of death in premature newborns.

    […]

    But Hackam’s group found that the stresses of oxygen deprivation and bombardment by bacterial toxins, conditions that can occur in premature infants with underdeveloped lungs, stimulate too much production of TLR4. Like an unstoppable alarm, the increased numbers of TLR4 blare out signals that eventually tip the cells into cellular suicide. They also stop enterocytes from migrating to close wounds in the intestines.

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  • Blocking toll-like receptor 4 with Naltrexone reduces alcohol seeking behavior in mice www.sciencedaily.com
    Brain Inflammation Alcohol Circadian Rhythm Behavior Toll-Like Receptors

    The circadian rhythm aspect of drug rewards: “Our body’s circadian rhythms affect the ‘reward’ signals we receive in the brain from drug-related behavior, and the peak time for this reward typically occurs during the evening, or dark phase. We wanted to test what the role of the brain’s immune system might have on that reward, and whether or not we could switch it off.”

    Using naltrexone to block TLR4 reduces alcohol behavior:

    The researchers focused their attention on the immune receptor Toll-like receptor 4 (TLR4). They administered the drug (+)-Naltrexone (pronounced: PLUS-NAL-TREX-OWN), which is known to block TLR4, to mice.

    “Our studies showed a significant reduction in alcohol drinking behavior by mice that had been given (+)-Naltrexone, specifically at night time when the reward for drug-related behavior is usually at its greatest,” Mr Jacobsen says.

    Interestingly and somewhat paradoxically, chronically activating TLR4 through genetic engineering-associated tricks also seems to reduce alcohol seeking in mice.

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  • Beta-hydroxybutyrate produced from a ketogenic diet may improve gout symptoms (animal study) www.sciencedaily.com
    Nutrition Diet Ketosis Inflammation Arthritis NLRP3 Ketogenic Diet

    Beta-hydroxybutyrate reduces symptoms of gout.

    Gout is a painful, debilitating disease that affects more than 8 million people living in the United States. The condition arises when uric acid crystals form in and around the joints, causing inflammation, pain, and impaired mobility. Evidence from a 2017 study suggests that beta-hydroxybutyrate inhibits the activity of the NLRP3 inflammasome, reducing symptoms of gout.

    Beta-hydroxybutyrate is a type of ketone body. It forms in the liver via the breakdown of fatty acids and can be used to produce energy in the mitochondria. Beta-hydroxybutyrate also acts as a signaling molecule that alters gene expression via a wide range of molecular pathways. Ketogenic diets induce beta-hydroxybutyrate production.

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. The NLRP3 inflammasome, in particular, triggers the release of the proinflammatory proteins interleukin (IL)-1 beta and IL-18 and drives pyroptosis, a form of cell death that is triggered by proinflammatory signals and closely linked with inflammation.

    The study involved rats that are prone to developing gout. The investigators fed one group of the rats a normal diet and fed another group a ketogenic diet. After one week, they measured ketones present in the animals' urine. They found that the ketogenic diet induced production of beta-hydroxybutyrate, which in turn protected the animals against uric acid-induced elevations in IL-1 beta. Examination of the animals' joints revealed that the rats that ate the ketogenic diet had less joint inflammation than those fed a normal diet.

    Next, the investigators assessed the effects of beta-hydroxybutyrate on neutrophils, a type of immune cell, from both young and old humans. They found that the compound inhibited the NLRP3 inflammasome-induced IL-1 beta secretion in both young and old neutrophils, suggesting that the ketone plays a role in activating the inflammasome in neutrophils, regardless of age.

    These findings suggest that beta-hydroxybutyrate inhibits the activity of the NLRP3 inflammasome, reducing the symptoms of gout. Researchers do not know if these results translate to humans, however. Learn more about the health effects of beta-hydroxybutyrate in our overview article.

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  • Red wine mitigates the negative neurological effects of high LDL cholesterol even without reducing its levels directly. www.tandfonline.com
    Brain Cholesterol Inflammation Alcohol

    Since the 1980’s, clinicians and researchers have been puzzled by the “French paradox”: the observation that residents of France have a surprisingly low incidence of cardiovascular disease given their high rates of smoking, intakes of saturated fat, and hypercholesterolemia (i.e. abnormally high serum levels of harmful low-density lipoprotein (LDL) cholesterol). A recent study now offers evidence that the negative health impacts of these common risk factors might be effectively mitigated by the French habit of regular red wine consumption.

    The authors of this study examined mice that had been genetically modified to lack LDL receptors – proteins crucial for removing LDLs from the bloodstream and initiating their degradation. This genetic modification, known as a “knock-out”, meant that the mice experienced a virtually life-long state of hypercholesterolemia, which served as the biological backdrop for an experiment on the potential health effects of wine consumption.

    At the age of three months (early mouse adulthood), animals were randomly assigned to receive 60 days of unlimited access to either plain tap water or red wine diluted to yield a 6% ethanol solution. This concentration ensured that the animals consumed the human equivalent of a 5-ounce glass of wine on a daily basis.

    When the researchers tested the mice on a variety of cognitive tasks, they discovered that the water-only group displayed learning and memory impairments characteristic of their poor lipid profiles. Their performance was particularly poor on a short-term memory test, where the animals turned out to be unable to recognize objects they had seen only an hour prior. Long-term memory retention was also compromised. In a test that required the animals to remember the location of an escape platform hidden in a tub of opaque water, the mice swam in the right direction only 20 percent of the time.

    Interestingly, wine-consuming mice were not impaired to the same degree. And while their plasma lipid profiles were no better compared to their water-drinking peers, they had substantially lower levels of several biomarkers of neuroinflammation, such as GFAP and lectin. The findings indicate that red wine compounds might help protect against the negative health outcomes of hypercholesterolemia by interfering with the associated inflammatory processes.

    Link to full study.

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  • Sugar may drive inflammatory bowel disease through the promotion of mucin-consuming microbes. www.science.org
    Gut Diet Inflammation Sugar

    Inflammatory bowel disease (IBD) is an umbrella term for two chronic inflammatory conditions that affect the digestive tract – ulcerative colitis and Crohn’s disease. Symptoms of IBD include diarrhea, rectal bleeding, abdominal pain, fatigue, and weight loss. Evidence indicates that dysbiosis, an imbalance in the types and numbers of microbes in the gut, contributes to the pathogenesis of IBD. And now, findings from a recent study suggest that eating a high-sugar diet promotes dysbiosis and the development of IBD.

    The study involved normal mice and mice that are genetically predisposed to develop colitis. The authors of the study gave a subset of both groups of mice a 10 percent glucose solution (comparable to a sugar-sweetened soft drink) for one week. They gave the normal mice a chemical that causes colitis. Then they measured the inflammatory responses, disease severity, and gut microbial composition in both groups of mice and compared them to mice that did not receive the sugar solution.

    They found that, prior to the mice developing colitis, the sugar did not trigger gut inflammation. However, both groups of mice developed worse symptoms of colitis after drinking the glucose solution. In addition, both groups exhibited higher numbers of bacteria that break down the mucus layer of the gut (specifically, Akkermansia muciniphila and Bacteroides fragilis), contributing to mucus layer destruction, increasing gut permeability. The number of beneficial bacteria in the animals' guts decreased, however.

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  • Turmeric curcumin reduces inflammation in the gut in response to gluten. pubmed.ncbi.nlm.nih.gov
    Gut Inflammation Curcumin Gluten

    “Wheat is a major diet from many years; apart from its nutritious value, the wheat protein gliadin is responsible for many inflammatory diseases like celiac disease (CD), and non-celiac gluten sensitivity (NCGS).”

    “Cells were cultured and exposed to 160 μg/ml of gliadin, 100 μM H2O2, and 10 μM curcumin (3 h pretreatment) followed by the assessment of inflammation.

    “The results show that gliadin increases the advanced oxidation protein products level and the activity of myeloperoxidase and NADPH oxidase expression. It enhances inflammation by increasing expression of pro-inflammatory cytokines, altered expression of anti-inflammatory, and regulatory cytokines. It exacerbates the cellular damage by increasing MMP-2 and 9 and decreasing integrin α and β expression. Gliadin promotes disease pathogenesis by inducing the inflammation and cellular damage which further alter the cellular homeostasis. The pretreatment of curcumin counteracts the adverse effect of gliadin and protect the cells via diminishing the inflammation and help the cell to regain the cellular morphology suggesting phytochemical-based remedial interventions against wheat allergies.”

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  • High-intensity interval training reduces the growth of colon cancer cells www.sciencedaily.com
    Exercise Cancer Inflammation Aerobic

    From the article:

    Exercise may play a role in reducing the growth of colon cancer cells according to new research. The study found that after a short session of high intensity interval training (HIIT), growth of colon cancer cells was reduced, and this also increased indicators of inflammation.

    […]

    “We have shown that exercise may play a role in inhibiting the growth of colon cancer cells. After an acute bout of HIIT there were specific increases in inflammation immediately after exercise, which are hypothesised to be involved in reducing the number of cancer cells.

    This suggests that a physically active lifestyle may be important in tackling human colorectal tumours. We would now like to look at how these changes in growth occur and understand the mechanisms by which biomarkers in the blood can impact cell growth."

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  • Extra virgin olive oil high in polyphenols improves antioxidant status in adults. pubmed.ncbi.nlm.nih.gov
    Inflammation Antioxidant Metabolic Syndrome Polyphenol

    Cardiovascular disease is facilitated by chronic oxidative stress and vascular inflammation. Antioxidant compounds such as the polyphenols found in olive oil may reduce cardiovascular disease risk by resolving oxidative stress and inflammation. Findings of a recent report demonstrate the ability of high-polyphenol olive oil to reduce oxidative stress, especially in adults at high risk for cardiometabolic diseases.

    Oxidative compounds in the bloodstream damage the cells that line blood vessels, called endothelial cells. Increased concentrations of adhesion molecules, proinflammatory cytokines such as interleukin-6 and C-reactive protein, and oxidized low-density lipoprotein (LDL) cholesterol contribute to endothelial dysfunction and the generation of atherosclerotic plaques. Increased concentrations of antioxidant enzymes in the blood decrease oxidative damage and reduce the risk of chronic diseases such as cardiovascular disease.

    The authors recruited 50 participants (between ages 18 and 75 years) who were not consuming dietary supplements or high amounts of olive oil (greater than one tablespoon per day). They assigned participants to consume about four tablespoons per day of either high-polyphenol or low-polyphenol olive oil for three weeks. After a two-week wash-out period, participants consumed the opposite treatment for three weeks. The researchers measured total antioxidant capacity and plasma concentrations of oxidized LDL cholesterol and C-reactive protein (a marker of inflammation) before and after each treatment.

    High-polyphenol olive oil consumption significantly reduced oxidized LDL cholesterol and increased total antioxidant capacity. These changes were greatest in participants who were at high risk for cardiometabolic disease due to their high waist circumference. There were no significant statistical differences between the high-polyphenol and low-polyphenol olive oil treatments.

    Consumption of high-polyphenol olive oil increased antioxidant capacity and reduced markers of inflammation and oxidative stress, especially in participants with high cardiometabolic risk.

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  • Zinc deficiency promotes inflammation and weakens immunity, especially in older adults. pubmed.ncbi.nlm.nih.gov
    Aging Inflammation DNA Damage Immune System Zinc

    Vitamins and minerals are utilized by a wide array of enzymes that protect cells and DNA from damage. Zinc, in particular, is essential for maintaining DNA integrity and adequate antioxidant defenses. A new paper reviewing the work of Dr. Bruce Ames and others highlights the importance of zinc in promoting longevity and preventing chronic diseases.

    Zinc is a metallic mineral that is consumed in the diet from foods such as meat, shellfish, legumes, and fortified foods. Severe zinc deficiency results in growth retardation, hair loss, skin sores, and depressed immunity and is uncommon in developed nations. However, marginal deficiency, which is asymptomatic and dangerous over long periods of time, is likely very common. Children, older adults, and people with altered gastrointestinal function are particularly susceptible to zinc deficiency.

    Zinc is concentrated in the nuclei of cells where it functions to stabilize chromatin (large structures of spooled DNA) and catalyze chemical reactions for DNA repair, replication, and transcription. Along with other metals such as copper, iron, and magnesium, zinc is essential for balancing oxidative and reductive reactions in the cellular environment. One enzyme, copper-zinc superoxide dismutase, neutralizes hydrogen peroxide radicals by accepting an electron at its copper site. By absorbing reactive oxygen species, antioxidant compounds prevent damage to structures such as lipid membranes, enzymes, and DNA.

    The immune system is a major producer of hydrogen peroxide and other oxygen radicals, which attack pathogens and recycle damaged host cells. Adequate zinc intake is essential for moderating the inflammatory response. In particular, zinc inhibits activation of the NF-kappaB pathway, driving the production of inflammatory cytokines such as tumor necrosis factor-alpha. Zinc deficiency increases the risk of developing neurodegenerative and autoimmune diseases through mechanisms that involve over-activation of inflammatory pathways.

    Zinc deficiency further increases one’s risk of disease by reducing the number of pathogen-fighting cells such as antibody-producing B cells, natural killer cells, and monocytes. Reduced pathogenic immunity and increased chronic inflammation are common in old age, but they begin in middle-adulthood and progress over time in parallel, with decreasing zinc absorption and retention. Zinc supplementation in older adults reduces inflammation while increasing production of new immune cells and strengthening the body’s response to vaccines.

    Overall, zinc deficiency accelerates the aging process by impairing antioxidant production and cellular repair mechanisms, over-activating inflammatory pathways, and reducing pathogen defenses. The authors conclude there is good evidence to suggest that supplementing with at least 20 milligrams of zinc per day may be an effective strategy for reducing the adverse effects of aging on the immune system.

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  • A pro-inflammatory diet contributes to brain aging and cognitive decline. n.neurology.org
    Diet Inflammation Dementia

    Inflammation, a critical element of the body’s immune response, occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. As a person ages, their immune system becomes more pro-inflammatory, leading to unresolved or chronic inflammation and driving many age-related diseases and cognitive decline. Authors of a new report suggest that eating a pro-inflammatory diet may further contribute to the inflammatory state associated with aging, driving cognitive decline.

    Diet plays key roles in immune function and inflammation, and robust evidence indicates that some components of diet promote inflammation, while others dampen or even resolve it. To score the inflammatory potential of dietary components, researchers have developed the Diet Inflammatory Index, a quantitative means of assessing the effects of diet on aspects of human health, ranging from inflammatory biomarkers in blood to the presence of chronic disease. The Index, which has been used in hundreds of studies and meta-analyses, is supported by diverse lines of evidence, including laboratory, observational, and interventional studies.

    The authors recruited more than 1,000 older adults (average age, 73 years) who were enrolled in the Hellenic Longitudinal Investigation of Aging and Diet study. They collected detailed information about the types and quantities of the foods that participants regularly ate and assigned each participant’s diet a Diet Inflammation Index score. They tracked the participants for about three years and noted whether they were diagnosed with dementia.

    They found that for every unit increase in the Diet Inflammation Index, the risk for developing dementia increased by 21 percent. As a result, participants whose diets had the highest inflammatory potential were three times more likely to develop dementia than those whose diets had the lowest inflammatory potential.

    These findings suggest that dietary components modulate the inflammatory state associated with aging and drive the risk for developing dementia. Although these findings were based on observational data and do not assign causality, they highlight the roles that lifestyle changes may play in preserving cognitive function in aging. Learn more about how lifestyle changes can influence health and slow the effects of aging in this episode featuring Dr. Elisa Epel.

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  • Eating spices reduces chronic inflammation. academic.oup.com
    Inflammation Immune System Polyphenol Lipopolysaccharide

    Obesity causes chronic inflammation, which promotes atherosclerosis and cardiovascular disease. Previous research suggests that spices such as cinnamon, cumin, and ginger exert short-term anti-inflammatory effects; however, studies with longer durations are needed to confirm these findings. Authors of a recent study found that four weeks of spice consumption reduced inflammation and altered monocyte function in adults at risk of cardiometabolic disease.

    Monocytes are white blood cells that respond to infection by promoting inflammation. Obesity and dyslipidemia cause inappropriate activation of monocytes, promoting chronic inflammation in the arteries. Pro-inflammatory monocytes carrying excess lipids, called foam cells, accumulate in arterial walls, narrowing the arteries and restricting blood flow. Consuming spices that contain anti-inflammatory bioactive compounds may help reduce cardiovascular disease risk.

    The authors recruited 71 participants and assigned them to consume a standard American diet with added spices in three doses: low (a dash), medium (a quarter teaspoon), or high (a half teaspoon). Participants consumed each dose of spices for four weeks and completed the doses in random order. The spice mixture contained the most common spices used in the United States, the most abundant of which were cinnamon, coriander, ginger, cumin, and parsley. Participants provided blood samples at multiple points throughout the study. Finally, the investigators isolated monocytes from the participants’ blood and exposed the cells to bacterial endotoxin in order to promote inflammation.

    Compared to baseline, participants had lower fasting serum levels of the pro-inflammatory cytokine interleukin-6 following four weeks of the medium dose spice blend. The monocytes from these participants also secreted less interleukin-6 when challenged with bacterial endotoxin. Participants consuming the medium and high spice blends had fewer foam cells and more conventional monocytes than participants consuming the low spice blend.

    The authors concluded that spices reduced fasting inflammation and altered monocyte behavior. They did not know why the medium dose was more effective in reducing inflammation than the high dose, but they hypothesized that the high dose of spices may have contained such a high level of polyphenols that it promoted oxidative stress. More research is needed to test this hypothesis. This study was funded by the McCormick Science Institute.

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  • Co-supplementation with magnesium and vitamin D aids weight loss, improves mood, and reduces systemic inflammation. pubmed.ncbi.nlm.nih.gov
    Vitamin D Obesity Inflammation Depression Magnesium IL-6

    For decades, deficiencies in micronutrients such as magnesium and vitamin D have been linked to conditions such as depression and obesity, as well as their associated hallmarks of systemic inflammation. These observations raise questions about whether certain nutritional inadequacies might play a causal role in these conditions and whether supplementation may help regulate symptom severity. Now, a recent randomized double-blind placebo-controlled clinical trial reveals that co-supplementation with magnesium and vitamin D significantly decreases depression scores and body weight in healthy women with obesity.

    The study recruited 102 women with obesity (body mass index, 30–40; ages, 20-45 years) with mild-to-moderate depression and no indication of other health issues such as hormonal dysfunction, autoimmune disease, or diabetes. The study investigators randomly allocated the women to one of four groups to receive varying combinations of a weekly soft gel containing 50,000 international units (IU) of vitamin D, a daily tablet of 250 milligrams magnesium, and/or a placebo. The groups comprised:

    1) Co-supplementation: weekly vitamin D + daily magnesium

    2) Vitamin D only: weekly vitamin D + daily magnesium placebo

    3) Magnesium only: daily magnesium + weekly vitamin D placebo

    4) Control: weekly vitamin D placebo + daily magnesium placebo

    The investigators collected participants’ blood samples at baseline and following eight weeks of supplementation. The samples revealed that while the women on average had adequate baseline serum levels of magnesium and borderline-adequate levels of vitamin D, their health outcomes and biomarkers nonetheless showed the greatest improvements as a result of co-supplementation with both micronutrients. For instance, women who received both magnesium and vitamin D lost more weight over the duration of the intervention compared to all the other groups, in the absence of any observed changes in their dietary patterns. They also showed the greatest average reduction in depression scores over time, although all participants (including controls) exhibited some degree of symptom relief after the eight-week intervention - an observation the researchers attributed in part to the placebo effect.

    The women’s blood samples revealed a similar picture, with co-supplementation outperforming all other conditions (although individual supplementation with either vitamin D or magnesium still yielded significant improvements over controls). For instance, combining magnesium and vitamin D achieved the greatest reduction in plasma levels of pro-inflammatory tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6). It also generated the highest boost in brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1) – a protein widely known for its involvement in regulating autophagy and longevity-promoting genes.

    These findings reveal that co-supplementation with a weekly 50,000 IU dose of vitamin D and a daily 250 mg of magnesium can aid weight loss, enhance mood, and improve a host of blood biomarkers pertaining to systemic inflammation, brain functioning, and longevity. Moreover, the fact that positive health outcomes can be observed despite an absence of marked micronutrient deficiencies raises the possibility that current medical guidelines on adequate ranges of plasma levels and RDAs for vitamin D and magnesium, respectively, may be insufficiently high for optimal health outcomes.

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  • Wearable device may predict inflammatory bowel disease flare-ups. www.sciencedaily.com
    Technology Gut Inflammation

    Inflammatory bowel diseases, a group of conditions characterized by chronic inflammation of the digestive tract, affect the lives of nearly seven million people worldwide. The two most common inflammatory bowel diseases are ulcerative colitis and Crohn’s disease. A report published in 2020 describes a wearable device that detects the presence of biomarkers associated with inflammatory bowel diseases in sweat, potentially signaling a symptom flare.

    A common feature of many inflammatory bowel diseases are periods of remission and relapse, often referred to as “flares.” During flares, interleukin-1 beta (IL-1 beta) and C-reactive protein (CRP), are often elevated. IL-1 beta is a proinflammatory cytokine that mediates the body’s inflammatory response. CRP is a protein that increases in the blood with inflammation and infection.

    The authors of the study developed a wearable, watch-like device that monitored levels of IL-1 beta and CRP in the sweat of 20 healthy adults (18 to 65 years old) over a period of up to 30 hours. They studied healthy people to help establish the levels of these two biomarkers in people without inflammatory bowel disease. A removable strip on the device collected the sweat, providing real-time monitoring of the biomarkers. They also measured the biomarkers using a standard assay and compared the two assessments.

    They found that the device was highly accurate at measuring sweat levels of IL-1 beta and CRP, compared to measurements with the standard assay. Their findings demonstrate proof-of-feasibility for a wearable device that can signal an inflammatory bowel disease flare. Use of such a device may offer a non-invasive way to help people with inflammatory bowel disease track their inflammatory status and help guide clinicians' treatment decisions.

    The authors of this study later measured pro-inflammatory proteins in the sweat of people with COVID-19 to predict cytokine storm, a potentially life-threatening condition that occurs when an infection provokes an excessive immune response. They found that their sweat-based sensor detected cytokine levels in passive sweat that correlated with cytokine levels in the patients' blood.

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  • Daily apple consumption decreases multiple markers of obesity-associated inflammation. academic.oup.com
    Diet Obesity Inflammation Polyphenol Intestinal Permeability Endotoxemia Lipopolysaccharide IL-6

    Obesity is characterized by chronic low-grade inflammation, which contributes to the development of cardiovascular disease. While processed foods and beverages high in saturated fats and simple sugars are associated with a higher risk of cardiovascular disease, diets rich in plant-based foods, including fruits, are associated with a lower risk. Findings of a recent report detail the effects of daily apple consumption on inflammation, endotoxemia, and metabolism.

    Causes of obesity-associated inflammation include leaky gut, a condition where the intestinal barrier is compromised, leading to increased levels of bacterial endotoxin (toxins that are released when bacteria die) in the bloodstream (called endotoxemia). This increase in endotoxin levels activates white blood cells to secrete pro-inflammatory cytokines such as interleukin (IL)-6 and IL-17. Plant foods such as apples are beneficial for people with obesity because they are rich in bioactive compounds that decrease inflammation and dietary fibers that strengthen the gut barrier.

    The researchers recruited 46 participants with overweight and obesity and directed them to avoid foods and beverages rich in polyphenols and/or dietary fibers (e.g., coffee, vegetables, grains, beans, and red/purple/blue fruits) for two weeks. Next, they assigned half of the participants to consume three Gala apples per day for six weeks or to avoid apples. Both groups continued to eat a diet with limited polyphenols and dietary fibers. Participants provided blood samples for the collection of white blood cells and measurement of pro-inflammatory cytokines. After isolating the white blood cells, the researchers stimulated them with endotoxin and measured their response.

    Apple consumption decreased plasma C-reactive protein (a pro-inflammatory cytokine) by 17 percent, IL-6 by 12 percent, and endotoxin-binding protein by 20 percent compared with no apple consumption. White blood cells from participants who consumed apples secreted 28 percent less IL-6 and 11 percent less IL-17. While apple consumption increased total antioxidant capacity in blood by 10 percent, it had no effect on cardiovascular disease markers.

    These findings suggest that six weeks of daily Gala apple consumption helped mitigate inflammation in those consuming a diet low in polyphenols and fiber, a common feature of the Western diet pattern. Apple consumption may decrease cardiovascular disease risk in those with obesity, even without weight loss.

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  • Omega-3 supplementation reduces inflammation and cellular aging in response to social stress. www.nature.com
    Aging Omega-3 Inflammation Stress IL-6

    Omega-3 fatty acid consumption reduces the risk of death from cardiovascular disease and all causes. By reducing inflammation, lengthening telomeres, and blunting the body’s response to stress, omega-3 fatty acids lessen the effects of aging on a cellular level. Authors of a recent study tested the effects of omega-3 supplementation on inflammation and telomere length in response to stress.

    Telomeres are often compared to the plastic tips on the end of shoelaces (aiglets) because telomeres protect chromosomes from fraying on the ends. Both acute and chronic stress increase inflammation, which can cause chromosomes to become frayed when telomeres are short. Once chromosomes lose their telomeres, their DNA cannot be replicated, and this accelerates aging.

    The randomized, controlled intervention trial included 138 sedentary, adults with overweight between the ages of 40 and 85 years. The participants received daily supplements providing 2.5 grams of omega-3s, 1.25 grams of omega-3s, or a placebo for four months. Before and after the intervention, the participants took the Trier Social Stress Test, a testing platform in which a person must deliver a speech and perform mental arithmetic in front of an audience. Participants also provided blood and saliva samples as a means to measure cortisol (a stress hormone), telomerase (an enzyme that helps maintain telomere length); anti-inflammatory cytokines, including interleukin (IL)-10 (IL-10); and pro-inflammatory cytokines, including IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha).

    Following the stress test, participants in the placebo group experienced a 24 percent reduction in telomerase activity and a 26 reduction in IL-10; however, both omega-3 groups were protected from this response. This relationship was statistically significant and accounted for baseline stress reactivity, age, waist circumference, and sex. Participants who received 2.5 grams of omega-3s had a 19 percent reduction in cortisol levels and a 33 percent reduction in IL-6 compared to the placebo group.

    The authors concluded that by reducing inflammation and stress hormone levels, omega-3 supplementation may boost cellular repair and slow aging. This decrease in stress response may also translate to reduced risk of depression, making these findings relevant to mental health as well.

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  • Sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells. www.sciencedirect.com
    Inflammation Sulforaphane NRF2 NLRP3

    Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, such as broccoli and broccoli sprouts. It exerts potent anti-inflammatory properties and switches on the activity of a vast array of cellular protective proteins. A new study in mice demonstrates that sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells via inhibition of the NF-kB pathway and altered gene expression.

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. The NLRP3 inflammasome in particular triggers the release of proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18 and drives pyroptosis, a form of cell death that is triggered by proinflammatory signals and closely linked with inflammation.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage.

    NF-kB is a family of proteins present in mammalian cells. NF-kB influences several aspects of the body’s stress response via its participation in signaling pathways that drive pro-inflammatory processes, ultimately regulating DNA transcription, cytokine production, cell survival, and immune function.

    The authors of the study triggered the activity of the NLRP3 inflammasome in mice microglia cells that had been treated with or without sulforaphane. Then they assessed the level of pyroptosis in the cells, measured expression of IL-1β and IL-18, and tracked the activity of NF-kB. They also measured the cells' mitochondrial production of reactive oxygen species and mitochondrial membrane integrity. The cells treated with sulforaphane showed less pyroptosis, reduced expression of IL-1β and IL-18, and impaired NF-kB activity than the untreated cells. Sulforaphane also reduced reactive oxygen species production and helped maintain mitochondrial membrane integrity.

    These findings suggest that sulforaphane protects the brain via inhibition of the NF-kB pathway and subsequent inhibition of the NLRP3 inflammasome.

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  • Moderate fever may protect against acute respiratory distress syndrome in COVID-19. www.frontiersin.org
    Inflammation COVID-19

    The primary cause of death from COVID-19 is acute respiratory distress syndrome (ARDS), a severe form of acute lung injury characterized by rapid breathing, shortness of breath, and a low blood oxygen level. The authors of recent review posit that moderate fever protects against ARDS in COVID-19.

    The body’s fever response is a hallmark of infection and inflammation. An increase in core body temperature of a few degrees (no higher than ~102°F) is generally recognized as safe and improves survival from and resolution of many infections. For example, evidence indicates that people who take medications to reduce fever associated with influenza are 5 percent more likely to die. Conversely, extremely high fever in the setting of systemic inflammation is harmful. Notably, the fever response is diminished in older adults.

    Fundamental to the fever response is a short-term accumulation of heat shock proteins (HSP), a class of proteins that play important roles in providing protection from lung injury. HSPs increase markedly with fever but require a “cool-down” period to maintain their effectiveness. In COVID-19 illness, the increase in HSPs is transient, lasting only about two hours after the onset of fever.

    The authors of the review hypothesized that allowing patients with COVID-19 to experience brief (two hour) periods of fever, followed by administration of medications to reduce fever would maintain the highest levels of protective HSPs. They cautioned that their hypothesis must be tested in large, randomized clinical trials, however.

    The authors also suggested that strategies that promote HSP activation may provide protection against COVID-19. Sauna use, in particular, induces long-term activation of HSPs and is associated with reduced risk of developing certain chronic or acute respiratory illnesses, such as pneumonia. Findings from large epidemiological studies indicate that men who used the sauna four to seven times per week were 41 percent less likely to develop pneumonia than men who used the sauna less often or not at all. Read more about sauna use in our overview article.

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  • A pilot study to investigate the immune modulatory effects of fasting in steroid-naïve mild asthmatics www.ncbi.nlm.nih.gov
    Inflammation Fasting Allergies Asthma NLRP3

    A fasting mimetic diet blunts inflammation and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on: the NLRP3 inflammasome; Th2 cell activation and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study where pulmonary function testing (PFT) and peripheral blood mononuclear cells (PBMCs) extraction was performed 24 hours after fasting, with repeated PFT-testing and blood draw 2.5 hours after refeeding. PFT’s were not changed by a prolonged fast. However, steroid-naïve mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics co-cultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production, and reduced CD4+ T cell Th2 activation compared to refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naïve asthmatics, as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient-level dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study, as well as the potential development of caloric restriction interventions for the treatment of asthma.

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  • Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid pubmed.ncbi.nlm.nih.gov
    Omega-3 Inflammation

    Abstract-
    Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega (n)-3 PUFAs are considered proresolving whereas n-6 PUFAs are classified as proinflammatory. In this study, we characterized the inflammatory response in murine peritonitis and unexpectedly found the accumulation of adrenic acid (AdA), a poorly studied n-6 PUFA. Functional studies revealed that AdA potently inhibited the formation of the chemoattractant leukotriene B4 (LTB4), specifically in human neutrophils, and this correlated with a reduction of its precursor arachidonic acid (AA) in free form. AdA exposure in human monocyte-derived macrophages enhanced efferocytosis of apoptotic human neutrophils. In vivo, AdA treatment significantly alleviated arthritis in an LTB4-dependent murine arthritis model. Our findings are, to our knowledge, the first to indicate that the n-6 fatty acid AdA effectively blocks production of LTB4 by neutrophils and could play a role in resolution of inflammation in vivo.

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  • A compound in blueberries dampens the body's immune response and reduces inflammation. www.eurekalert.org
    Inflammation Immune System Polyphenol

    A critical component of the body’s immune response to pathogens, damaged cells, or irritants is inflammation. Chronic inflammation, however, can promote the development of chronic inflammatory disorders. Findings from a new study suggest that pterostilbene, a polyphenolic compound present in blueberries, can reduce the risk of developing chronic inflammatory disorders by altering the activity of dendritic cells and T cells.

    Pterostilbene is a polyphenolic compound that demonstrates antioxidant, anti-inflammatory, and anti-cancer properties, as well as many other beneficial effects. Closely related to resveratrol, pterostilbene is found in blueberries and a tropical tree commonly known as heartwood.

    Dendritic cells and T cells are key elements of the body’s immune responses. Dendritic cells initiate the adaptive immune response, which in turn activates T cells. Activated T cells produce interleukin (IL)‐2 to facilitate their proliferation and subsequent differentiation into various helper T cells, including Th1, Th2, Th17, or regulatory T cells (Tregs). Over-activation of Th1, Th2, and Th17 cells can lead to immune disorders, such as inflammatory bowel diseases, atopic dermatitis, and psoriasis. Conversely, Treg cells produce IL‐10, an anti-inflammatory protein, to reduce inflammation and impair disease progression.

    The authors of the study used an in vitro cell culture system to assess the effects of pterostilbene and related compounds on immune cell response. They looked at the activity of dendritic cells and T cells in the presence or absence of the compounds to evaluate their immunosuppressive activity.

    They found that pterostilbene suppressed T cell‐proliferation and decreased the Th1 and Th17 population in a dose‐dependent manner but did not affect the population of Th2 cells. The presence of pterostilbene markedly increased Treg differentiation was markedly increased.

    Then the authors of the study assessed the effects of pterostilbene on mice that had ulcerative colitis, a type of inflammatory bowel disease. They gave the mice pterostilbene in their drinking water for a week. They found that the mice that consumed the pterostilbene had fewer symptoms associated with their disease and lower levels of tumor necrosis factor-alpha, a type of pro-inflammatory protein.

    Taken together, these findings indicate that pterostilbene exhibits immunosuppressive activity by directing T cell differentiation toward Treg cells rather than Th1 and Th17 cells. Furthermore, oral consumption of pterostilbene may reduce colonic inflammation associated with an inflammatory bowel disease.

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  • Increased visceral fat impairs cognition through chronic microglial activation mediated by IL-1 beta release [animal research] www.sciencedaily.com
    Brain Inflammation Memory Fat Dementia Weight Loss NLRP3 Visceral Fat

    Scientists find that visceral fat, a type of adipose tissue that produces high levels of inflammatory signals known as adipokines, impair learning and memory in mice by setting off an inflammatory cascade mediated by the release of IL-1 beta, which crosses the blood-brain barrier leading to chronic activation of microglia.

    From the article:

    “We have identified a specific signal that is generated in visceral fat, released into the blood that gets through the blood brain barrier and into the brain where it activates microglia and impairs cognition.”

    Visceral fat as the ring leader:

    They looked further and found that just transplanting the visceral fat caused essentially the same impact as obesity resulting from a high-fat diet, including significantly increasing brain levels of interleukin-1 beta and activating microglia. Mice missing interleukin-1 beta’s receptor on the microglia also were protected from these brain ravages.

    […]

    To measure cognitive ability, the scientists looked at mice’s ability to navigate a water maze after 12 weeks on a high- or low-fat diet. They found it took the normal, or wild type, mice consuming the higher fat diet as well as the visceral transplant recipients with NLRP3 intact longer to negotiate the water maze. In fact, while they could reach a platform they could see, they had trouble finding one beneath the water’s surface that they had been taught to find. Mice with the interleukin-1 receptor knocked out, could find it just fine, Stranahan says.

    The high-fat diet, transplant mice also had weaker connections, or synapses, between neurons involved in learning and memory. Mice on a high-fat diet but missing NLRP3 were spared these changes, like mice on a low-fat diet.

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  • A single bout of aerobic exercise alters more than 9,000 molecules in the blood. www.nytimes.com
    Exercise Insulin Resistance Inflammation

    Exercise elicits a wide range of physiological changes in the body that improve multiple aspects of cardiovascular, neurological, and metabolic health. The molecular mechanisms that drive these improvements are not well understood. Findings from a new study suggest that an acute bout of aerobic exercise alters more than 9,000 distinct molecules in the human body to positively influence health.

    The study involved 36 adults between the ages of 40 and 75 years. The average body mass index among the participants was 28, which is considered overweight. Their steady-state blood glucose levels ranged from 86 to 220 milligrams per deciliter, suggesting a wide range of insulin resistance, from very low to very high.

    The authors of the study collected blood samples from all the participants before exercise and two, 15, 30, and 60 minutes afterward. They collected fasting blood samples from 15 of the participants the morning after the exercise protocol to assess inter-day variability. One group of participants engaged in an acute bout of aerobic exercise on a treadmill for eight to 12 minutes at their maximum capacity. A control group of 14 participants did not perform any exercise.

    Analysis of the participants' blood before and after exercise revealed that an acute bout of aerobic exercise induced extensive changes in 9,815 molecules, including proteins, lipids, genes, immune markers, and many others, that correlate with a person’s aerobic fitness.

    The authors of the study suggested that their findings could lay the groundwork for the development of a simple blood test that measures fitness in the future.

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  • Omega-3 fatty acids decrease oxidative stress and affect biomarkers of aging. www.sciencedaily.com
    Obesity Aging Omega-3 Inflammation

    As the human body ages several changes occur, including the gradual erosion of the protective caps on the ends of chromosomes, known as telomeres. A 2012 study suggests that supplementing with omega-3 fatty acids can counteract telomere shortening and slow aging.

    Telomeres function as a protective buffer against DNA loss during replication and DNA damage caused by inflammation, reactive oxygen species, and other chemical compounds. Telomeres get shorter with age and telomere length is a biological marker for age.

    Previous research has demonstrated that many factors can affect the rate of telomere shortening. The dietary balance of the essential polyunsaturated fatty acids (PUFAs) omega-3 and omega-6 — which influence inflammation — might be a factor. The current study investigated whether blood levels of these polyunsaturated fatty acids affect telomere stability.

    The double-blind randomized controlled trial involved 106 adults between the ages of 40 and 85 years who were sedentary and overweight. The authors of the study provided participants with a supplement containing 1.25 grams or 2.5 grams of omega-3 fatty acids or a placebo. To evaluate the influence of the omega-3 fatty acids versus placebo, the authors measured telomere length, telomerase activity, and markers of oxidative stress (known as F2-isoprostanes). They found that supplementation at both doses lowered the omega-6 to omega-3 fatty acid ratio in the blood, which was associated with longer telomere length. They also observed that omega-3 fatty acid supplementation decreased markers of oxidative stress by 15 percent.

    These findings suggest that consumption of omega-3 fatty acids in quantities high enough to lower the omega-6 to omega-3 ratio in the blood can slow aging.

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  • Vitamin C supplementation restores lifespan in mice with Werner's syndrome (an advanced aging phenotype) www.sciencedaily.com
    Aging Diabetes Vitamin C Inflammation

    From the article:

    Scientists treated both normal mice and mice with a mutation in the gene responsible for Werner’s syndrome (WRN gene) with vitamin C in drinking water. Before treatment, the mice with a mutated WRN gene were fat, diabetic, and developing heart disease and cancer. After treatment, the mutant mice were as healthy as the normal mice and lived a normal lifespan. Vitamin C also improved how the mice stored and burned fat, decreased tissue inflammation and decreased oxidative stress in the WRN mice.

    From actual publication, rather than press release:

    Daily ascorbate supplementation allowed [Werner mice] to recover a normal mean life span and healthy aging. Although the number of animals used in each cohort was not big enough for a statistical testing on maximum life span, ascorbate treatment did prevent the appearance of Werner syndrome characteristic redox imbalance and related genomic damage. It also prevented the liver proinflammatory status observed in [Werner mice].

    What’s someone unexpected about the fact that additional vitamin C restoring mean lifespan is the fact that Werner syndrome is associated with higher-than-usual ascorbate status rather than reduced, so supplementing with vitamin C being beneficial may be somewhat counter to expectation:

    Interestingly, blood ascorbate levels increased with phenotypic progression in [Werner mice]. Ascorbate being protective, it is possible that the retention of vitamin C is a defense mechanism to counterbalance the age‐dependent rise in oxidative stress. We cannot rule out, however, the possibility that the increased ascorbate levels observed in [Werner mice] are due to a modification in ascorbate metabolism only specific to these mice.

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  • Pneumonia-causing bacteria release large amounts of hydrogen peroxide to inactivate the inflammasome and evade the immune response www.sciencedaily.com
    Vitamin C Inflammation Immune System

    From the article:

    The researchers found that bacteria such as pneumococci release large quantities of hydrogen peroxide, and that this causes inactivation of inflammasomes thereby weakening the immune system […] Our studies demonstrate that hydrogen peroxide is an inhibitor of an important component of the inflammatory machinery suggesting that the mechanism we have uncovered is a common strategy employed by many microbes to thrive within us,“ says Saskia Erttmann, first author in the study and former member of Nelson Gekara’s research group.

    Role for vitamin C:

    “One of the best known substances with the ability to neutralize hydrogen peroxide and that could hence boost anti-bacterial immunity are vitamins such as Vitamin C found in fruits. Perhaps the old adage ‘an apple a day keeps the doctor away’ is not off the mark,” adds Nelson Gekara.

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  • Vitamin C reduces C-reactive protein among some groups of people. www.sciencedaily.com
    Obesity Vitamin C Inflammation

    Inflammation is a biological response triggered by the immune system in response to a physical injury or infection. Vitamin C’s immune-boosting and antioxidant properties can mediate the body’s inflammatory response, reducing the symptoms or risk of various diseases. Evidence suggests that vitamin C can lower C-reactive protein, a marker of inflammation.

    C-reactive protein (CRP) is a protein that increases in the blood with inflammation and infection as well as following a heart attack, surgery, or trauma. It is one of several proteins that are often referred to as acute phase reactants. Blood levels of CRP greater than 1 milligram per liter are indicative of elevated cardiovascular disease risk.

    The randomized study involved nearly 400 healthy adults (average age, 44 years) who took 1 gram of vitamin C, 800 international units of vitamin E, or a placebo every day for two months. The findings revealed that vitamin E had no effect on lowering CRP; however, vitamin C supplementation decreased CRP 16.7 percent compared to pre-treatment measurements, but only in participants who had baseline CRP levels above 1 milligram per liter. This reduction in CRP was comparable to those achieved with statins (cholesterol-lowering drugs).

    Interestingly, the study identified a strong link between obesity and elevated CRP levels. Whereas 25 percent of normal-weight people had elevated CRP levels of CRP, 50 percent of overweight participants and 75 percent of obese participants had elevated levels.

    These findings suggest that vitamin C might be able to decrease inflammation to a similar magnitude as some statins in people at a higher risk of cardiovascular disease based on CRP levels.

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  • Vitamin C rapidly improves emotional state of acutely hospitalized patients [1 in 5 in acute-care have scurvy levels of vitamin C] www.sciencedaily.com
    Vitamin C Inflammation Depression Immune System

    Vitamin C, which has previously been shown in some studies to reduce inflammatory markers in conditions like rheumatoid arthritis, may improve emotional state of acutely hospitalized patients.

    From the article:

    Patients administered vitamin C had a rapid and statistically and clinically significant improvement in mood state, but no significant change in mood occurred with vitamin D, the researchers discovered. […] About one in five acute-care patients in our hospital have vitamin C levels so low as to be compatible with scurvy,“ added Hoffer.

    Vitamin C, which concentrates in immune cells called neutrophils and lymphocytes at concentrations 50 to 100-times greater than plasma, play an important role in generating the so-called oxidative burst used by these cells to attack invading bacteria.

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  • Omega-3 fatty acid supplementation increases blood levels of anti-inflammatory molecules for up to 24 hours after ingestion. www.ahajournals.org
    Omega-3 Inflammation Polyunsaturated Fat

    Omega-3 fatty acids are polyunsaturated fats that are essential for human health. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting and the contraction and relaxation of artery walls. Byproducts of omega-3 fatty acid metabolism, called specialized pro-resolving mediators (SPMs), reduce the inflammation that drives many chronic diseases. Findings from a new clinical study suggest that omega-3 fatty acid supplementation increases blood levels of SPMs up to 24 hours after ingestion.

    Four families of SPMs have been identified and include the resolvins, lipoxins, protectins, and maresins. These SPMs promote apoptosis, regulate leukocyte (white blood cell) activity, and reduce the production of proinflammatory mediators.

    The double-blinded, placebo-controlled, crossover study involved 22 healthy volunteers between the ages of 19 and 37 who took a marine oil supplement enriched in omega-3 fatty acids. At 2, 4, 6, and 24 hours after taking the supplement, participants provided blood samples for analysis, which revealed a time- and dose-dependent increase in blood SPM levels that persisted for up to 24 hours.

    Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the process is very inefficient.

    Salmon roe is rich in omega-3 fatty acids, especially DHA. This short recipe video shows a fun, tasty way to eat salmon roe.

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  • Immunization against flagellin provides protection against chronic inflammatory disease in mice presse.inserm.fr
    Inflammation Protein

    A common feature in many chronic inflammatory diseases is dysbiosis – alterations in the type and number of microbes that typically reside in the human gut. Some of these microbes are highly motile due to the presence of flagella, which contributes to the microbes' pathogenic qualities. A new study suggests that immunization against the protein flagellin may confer protection against some chronic inflammatory diseases.

    Flagellins are structural components of the flagella of gram-negative bacteria. Flagella provide bacteria motility, which facilitates penetration of the gut mucosa and drives the activation of pro-inflammatory responses.

    The study involved wild type mice that received weekly peritoneal injections of purified bacterial flagellin for 10 weeks. The injections elicited a robust immune response to the flagellin, manifested in elevated antibody counts that lasted approximately three months after the injections ceased. Furthermore, the gut microbial composition of the mice was changed to a more favorable makeup, and the mice were protected against mucosal penetration, experimentally-induced colitis, and the negative effects of diet-induced obesity.

    These findings suggest that repeated exposure to flagellin proteins immunizes mice against chronic diseases by reducing immune response-related inflammation.

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  • Obese adolescents have decreased white matter in a brain region that connects the right and left hemispheres of the brain (compared to healthy teens). www.sciencedaily.com
    Brain Obesity Inflammation Insulin

    Obese adolescents have decreased white matter in a brain region that connects the right and left hemispheres of the brain (compared to healthy teens). These changes correlated with markers of inflammation and insulin resistance.

    Approximately 20 percent of teens living in the United States are obese. Obesity negatively affects multiple organ systems, including the nervous system. Findings from a new study indicate that the white matter in the brains of obese teens is lower than that of healthy teens.

    Obesity is associated with chronic low-grade inflammation, which can drive many disease processes. A specialized magnetic resonance imaging technique, called diffusion tensor imaging (DTI), can measure this inflammation in the brain.

    A study involving 59 obese adolescents and 61 normal weight adolescents between the ages of 12 and 16 years used DTI to measure damage to the white matter in the teens' brains. The imaging results revealed that areas of the corpus callosum, a bundle of nerve fibers that connects the left and right hemispheres of the brain, as well as areas of the middle orbitofrontal gyrus, an area responsible for emotional control and reward circuits, were diminished in the obese teens' brains. Damage in these areas was correlated with altered levels of insulin, inflammatory markers, and leptin, a key regulator of appetite, and insulin.

    Future research with DTI imaging techniques may reveal whether these changes in the structure of obese teens' brains are reversible.

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  • Inflammation may play a causal role in diminishing certain cognitive functions. www.birmingham.ac.uk
    Brain Inflammation Depression Protein

    Inflammation is a critical element of the body’s immune response that involves the activity of immune cells, cell-signaling proteins, and pro-inflammatory factors. Chronic inflammation, which occurs on the cellular level in response to toxins or other stressors, is implicated in the development of many chronic illnesses, including cancer, cardiovascular disease, and diabetes. Findings from a new study indicate that inflammation may be a factor in the “brain fog” that commonly accompanies chronic illness.

    The double-blinded placebo-controlled study involved 20 young men (average age, 24 years) who were injected with either a typhoid vaccine or saline. The purpose of the vaccine was to induce mild, transient inflammation, which was confirmed by the participants' blood levels of interleukin-6, a pro-inflammatory molecule.

    Six hours after the participants received their injection, three measures of their brain activity – alerting, orienting, and executive control – were assessed via electroencephalogram (EEG). The EEG results indicated that the participants' capacity for staying alert in preparation for a task was diminished post-vaccine but their other brain activities were unaffected. These findings point to a causal link between inflammation and diminished brain function and may explain why people who suffer from chronic disease often complain of difficulty concentrating or carrying out tasks.

    Interestingly, other studies have used methods similar to those used in this study to show that inflammation plays a causal role in depression. To learn more about the role of inflammation in depression, check out the FMF topic page on depression. Read the whole article or skip to the section on inflammation.

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  • A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression. www.clinicalnutritionjournal.com
    Inflammation Depression Protein

    A pro-inflammatory diet including fast food, processed food, and refined sugar is associated with a 40% increased risk of depression according to a meta-analysis of 11 studies.

    It is always difficult to establish causality with associative studies. With respect to inflammation and depression, there have been some studies establishing causality. For example, healthy individuals injected with proinflammatory cytokines exhibit depressive symptoms compared to those injected with a placebo.

    Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.

    To learn more about the role inflammation plays in depression, check out the animated video we put together on the role inflammation plays in depression.

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  • Cellular stress with changes in microbial profile promotes colorectal cancer development www.sciencedaily.com
    Cancer Microbiome Inflammation Protein Toll-Like Receptors

    Activation of ATF6, a regulator of ER (Endoplasmatic Reticulum) stress, combined with changes in cecal microbial profile, promoted colon adenoma formation.

    [Abstract]

    Methods: We analyzed data from 541 patients with CRC in the TCGA database for genetic variants and aberrant expression levels of unfolded protein response genes. Findings were validated in a cohort of 83 patients with CRC in Germany. We generated mice with intestinal epithelial cell-specific expression of the active form of ATF6 (nATF6IEC) from 2 alleles (homozygous), mice with expression of nATF6IEC from 1 allele (heterozygous), and nATF6IECfl/fl mice (controls). All nATF6IEC mice were housed under either specific-pathogen free or germ-free conditions. Cecal microbiota from homozygous nATF6IEC mice or control mice was transferred into homozygous nATF6IEC mice or control mice. nATF6IEC mice were crossed with mice with disruptions in the myeloid differentiation primary response gene 88 and toll-like receptor adaptor molecule 1 gene (Myd88/TRIF knock-out mice). Intestinal tissues were collected from mice and analyzed by histology, immunohistochemistry, immunoblots, gene expression profiling of unfolded protein response and inflammatory genes, array-based comparative genome hybridization, and 16S rRNA gene sequencing.

    Results: Increased expression of ATF6 was associated with reduced disease-free survival times of patients with CRC. Homozygous nATF6IEC mice developed spontaneous colon adenomas at 12 weeks of age. Compared to controls, homozygous nATF6IEC mice had changes in the profile of their cecal microbiota, increased proliferation of intestinal epithelial cells, and loss of the mucus barrier—all preceding tumor formation. These mice had increased penetration of bacteria into the inner mucus layer and activation of STAT3, yet inflammation was not observed at the pre-tumor or tumor stages. Administration of antibiotics to homozygous nATF6IEC mice greatly reduced tumor incidence, and germ-free housing completely prevented tumorigenesis. Analysis of nATF6IEC MyD88/TRIF knock-out mice showed that tumor initiation and growth required MyD88/TRIF-dependent activation of STAT3. Transplantation of cecal microbiota from nATF6IEC mice and control mice, collected before tumor formation, caused tumor formation in ex–germ-free nATF6IEC mice.

    Conclusions: In patients with CRC, ATF6 was associated with reduced time of disease-free survival. In studies of nATF6IEC mice, we found sustained intestinal activation of ATF6 in the colon to promote dysbiosis and microbiota-dependent tumorigenesis.

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  • Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states (2017) www.nature.com
    Aging Inflammation Caffeine Blood Pressure

    Abstract: Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N4-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions.

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  • Four weeks of using the sauna increased resting anti-inflammatory biomarkers (IL-10). www.ncbi.nlm.nih.gov
    Inflammation Heat Stress Protein

    Four weeks of using the sauna increased resting anti-inflammatory biomarkers (IL-10) and this adaptation happened faster in the already physically active. There was also a small increase in some of the heat shock proteins.

    The sauna protocol used in this study was a little different than other studies I have talked about. This study used two 15 minutes in 208 degrees F separated by a 5-minute cool shower. Previous studies that have shown cardiovascular and brain benefits used a 174 degree F sauna for at least 20 minutes, 4 times a week.

    If you have not already, check out my podcast with Dr. Jari Laukkannen, one of the world’s leading sauna researchers. He gets into the specifics on his research on sauna use for the prevention of cardiovascular disease and Alzheimer’s disease. We also talk about what heat shock proteins are and how they may play a role in Alzheimer’s disease prevention.

    Episode link: https://www.foundmyfitness.com/episodes/jari-laukkanen

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  • Exercise training-induced modification of the gut microbiota persists ..... www.tandfonline.com
    Exercise Gut Microbiome Inflammation

    Full Title: Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice

    Summary: Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota β-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host. KEYWORDS: exercise, microbiome, gut, microbiota, colitis, germ-free, transplant, colonization inflammation, voluntary wheel running

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  • Exercise causes acute elevation of IL-6 which reduces postprandial blood glucose levels and insulin secretion by delaying gastric emptying. www.cell.com
    Exercise Diabetes Inflammation Insulin IL-6

    Exercise causes acute elevation of IL-6 which reduces postprandial blood glucose levels and insulin secretion by delaying gastric emptying in men with type 2 diabetes.

    IL-6 is a cytokine with both negative and positive effects. Chronic elevation of IL-6 reflects ongoing inflammation and is linked to type 2 diabetes and atherosclerosis. In contrast, acute elevation of IL-6 from exercise inhibits inflammatory cytokines and stimulates the production of anti-inflammatory cytokines in humans.

    To learn more about the role of exercise-induced IL-6, the postprandial inflammatory response and their effects on the brain…check out my interview with Dr. Charles Raison. This episode has a timeline, transcript, summary, and glossary to help find and understand the talking points.

    Charles Raison, MD podcast: https://www.foundmyfitness.com/episodes/charles-raison

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  • Using the sauna was associated with a decrease in a biomarker of inflammation (CRP) in a dose-dependent manner. www.ncbi.nlm.nih.gov
    Inflammation Heat Stress Sauna

    A new study found that using the sauna was associated with a decrease in a biomarker of inflammation (CRP) in a dose-dependent manner. The more frequent the sauna use…the more robust the effect of lowering inflammation. This study was published early this year from with one of the world’s leading sauna researchers, Dr. Jari Laukkanen.

    He has also shown dose-dependent effects with sauna use on cardiovascular disease, all-cause mortality, and Alzheimer’s disease. Using the sauna 2-3 times per week (20 minutes at 174º F) was associated with: 27% lower cardiovascular disease risk, 24% lower all-cause mortality, and a 20% lower risk of Alzheimer’s disease compared to men that only used the sauna one time per week. Using the sauna 4-7 times per week (20 minutes at 174º F) was associated with: 50% lower cardiovascular disease risk, 40% lower all-cause mortality, and a 66% lower risk of dementia and a 65% lower risk of Alzheimer’s disease compared to men that used the sauna once a week.

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  • Interlinking the kynurenine pathway, obesity, depression, and inflammation. www.ncbi.nlm.nih.gov
    Abstract Obesity Inflammation Depression

    [Abstract]

    Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity.

    This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases.

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  • A certain type of bacteria found in the small intestine can travel to other organs and initiate the production of auto-antibodies and inflammation. www.sciencedaily.com
    Gut Microbiome Inflammation Autoimmunity

    A certain type of bacteria found in the small intestine (E. gallinarum) can travel to other organs and initiate the production of auto-antibodies and inflammation which both play a role in autoimmune disease.

    A certain species called Enterococcus gallinarum, was found to spontaneously “translocate” outside of the gut to lymph nodes, the liver, and spleen in mice and was found in cultured liver cells of healthy people, and in livers of patients with autoimmune disease.

    Most bacteria in the gut is in the large intestine near the colon and not small intestine. Typically, certain phyla and classes of bacteria that crop up on a low fiber diet and these bacteria possess flagella that allows move or “swim” up the intestines and penetrate the small intestine (where they are not supposed to be). This is often referred to as small intestine bacterial overgrowth.

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  • Itaconate, an anti-microbial metabolite, decreases inflammation via Nrf2-activation www.nature.com
    Inflammation Microbes Antioxidant Protein NRF2 Lipopolysaccharide

    The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.

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  • Air Pollution, health, and genetic risk www.nature.com
    Inflammation Genetics Pollution Environment

    [Abstract] Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges.

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  • Depression may be treated by lowering inflammation. www.telegraph.co.uk
    Inflammation Depression Protein

    The risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein (inflammatory biomarker). Inflammation is caused by a variety of factors including emotional/social stress, poor diet, sedentary lifestyle, poor sleep, and more. While it’s very possible (likely?) that there may be more going on with depression than just inflammation, I believe it’s an incredibly useful lens through which to look at promising avenues to treat or prevent it. We may find in years to come that measuring inflammation may also be useful as a way to track the therapeutic success of a whole lifestyle intervention intended to treat an important biological root cause. Inflammation isn’t just an important component (seemingly) of mental health, however… it’s also an important source of DNA damage, which is a fundamental mechanism of aging itself. This is one reason why it shouldn’t surprise us that lower inflammation is also associated with longer lifespan, prolonged physical function and also cognitive abilities in old age. In fact, it has been suggested that inflammation may be the most important driver of successful longevity that actually increases in its importance with advancing age. My team put together a short animated video explaining how inflammation plays a causal role in depression. I hope you check it out and perhaps we will also find that it’s also visually interesting enough to reach a wider, interested group of people. Animated video: https://www.youtube.com/watch?v=fqyjVoZ4XYg

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  • Brain inflammation found to be 30% higher in people suffering with obsessive-compulsive disorder. www.eurekalert.org
    Brain Omega-3 Inflammation Depression Immune System Anxiety Iron

    There’s very good evidence for systemic inflammation being implicated in mental disorders more generally, but also depression specifically. See the FoundMyFitness video entitled “The Underlying Mechanisms of Depression” to learn about some of the interesting experiments establishing the connection between immune dysfunction and symptoms of depression.

    This study, however, seems to suggest that people with obsessive-compulsive disorder actively have 30% higher brain-related inflammation.

    FTA:

    A chemical dye measured the activity of immune cells called microglia, which are active in inflammation, in six brain areas that play a role in OCD. In people with OCD, inflammation was 32 per cent higher on average in these regions. Inflammation was greater in some people with OCD as compared to others, which could reflect variability in the biology of the illness. […] Another notable finding from the current study - a connection between resisting compulsions and brain inflammation - provides one indicator. At least nine out of 10 people with OCD carry out compulsions, the actions or rituals that people do to try to reduce their obsessions. In the study, people who experienced the greatest stress or anxiety when they tried to avoid acting out their compulsions also had the highest levels of inflammation in one brain area. This stress response could also help pinpoint who may best benefit from this type of treatment.

    In light of the fact that we now know the body’s immune system is afforded direct access to the brain via a network of lymphatic vessels in the meninges, it puts managing systemic inflammation in a whole new light.

    While we may be a long way away from finding a “cure” for people suffering from these disorders, it does make multi-pronged inflammation reduction approaches that much more appealing.

    This could possibly include…

    … and yes, possibly targetted drugs as well. The point is, by establishing inflammation as a missing link in these disorders it opens up a lot of different possible “treatments” that might have a cumulative effect! Interesting times.

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  • Glycemic responses to bread may depend more on the composition of the gut microbiome than the composition of bread (white vs. whole wheat). www.cnn.com
    Nutrition Microbiome Inflammation Sugar

    A small trial including 20 people were given either sourdough whole-grain bread or refined white bread to eat for one week. After a two-week break, each participant switched bread types for another week.

    The study found very surprising results. Consuming either bread type improved cholesterol levels and improved markers of inflammation. The glycemic response was also dependent on the person’s gut microbiome composition and not bread type. This was surprising considering that fiber slows digestion and normally lowers the glycemic response. The bacterial strains that affected the glycemic response were Coprobacter fastidiosus and Lachnospiraceae bacterium, the latter of which has previously been associated with the development of type 2 diabetes.

    More research needs to be done before any definitive conclusions can be made but this study just highlights the potential importance of the gut microbiome in the glycemic response to food. Here is a link to the full study.

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  • VSL#3 improved HDL, insulin sensitivity, LDL, atherogenic factors, and inflammation www.ncbi.nlm.nih.gov
    Gut Obesity Microbiome Insulin Resistance Cholesterol Omega-3 Inflammation Microbes VSL#3 Insulin Triglycerides

    FTA

    … a clinical trial in 60 overweight (BMI > 25), healthy adults, aged 40-60 years. After initial screening, the subjects were randomized into four groups with 15 per group. The four groups received, respectively, placebo, omega-3 fatty acid, probiotic VSL#3, or both omega-3 and probiotic, for 6 weeks. […] The probiotic (VSL#3) supplemented group had a significant reduction in total cholesterol, triglyceride, LDL, and VLDL and had increased HDL (P < 0.05) value. VSL#3 improved insulin sensitivity (P < 0.01), decreased hsCRP and favorably affected the composition of gut microbiota. Omega-3 had a significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota. The addition of omega-3 fatty acid with VSL#3 had a more pronounced effect on HDL, insulin sensitivity and hsCRP. Table showing statistics of the study.

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  • Semi-regular chronic headaches or headaches and ibuprofen/advil/non prescription pain medication.
    Inflammation Meditation Pregnancy Controversial Drug Rhonda Curcumin Vitamin A Dairy

    Hi Rhonda, my wife takes pain medication pretty regularly (at least a 2 in a day a couple of times a week) for headaches and in Joe Rogan’s podcast i heard you mention the negative effects of ibuprofen… Strokes etc…

    I was wondering what you would recommend as a substitute to this issue? I was figuring curcumin could be a possibility. Also, i had an thought about the regular use of pain medication for something like a headache and whether or not regular use could increase the likelihood of headaches. If there is any basis in fact for my thoughts i’d be interested to know as i haven’t really done any research on this.

    Some things to note: She takes contraceptive pills and skips the sugar pills as to not get her period - I feel this is a terrible idea but she won’t listen to me. If you have insight on this, either relating to the original question or as a side note i’d be interested to know your take on it

    Her nutrition is decent. She eats a lot of fruit, nuts, fish and vegetables and takes daily vitamin supplements (fish oil, D3, multi’s, glucosamine, and a few others).

    Cheers Rhonda :)

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  • People that consumed 2 sugary drinks a day are more likely to have poorer memory and smaller overall brain volume. www.sciencedaily.com
    Brain Alzheimer's Inflammation Dementia Sugar Blood Sugar

    People that drank two or more sugary beverages of any kind per day were more likely to have poorer memory, smaller overall brain volume, and a significantly smaller hippocampus. Researchers also found that higher intake of diet soda, at least one per day, was associated with smaller brain volume.

    In a second study, researchers looked at whether participants had suffered a stroke or been diagnosed with dementia due to Alzheimer’s disease. Interestingly, there was no association between sugary beverage intake and stroke or dementia. But people who drank at least one diet soda per day were nearly 3 times as likely to develop stroke and dementia.

    While no of this data proves causation, there is a growing body of research showing that excess refined sugar does increase inflammation which crosses the blood-brain barrier and acceleration brain aging. Regarding the diet soda, there have been studies linking artificial sweeteners to disruption of the gut microbiome which also causes inflammation which can lead to brain aging.

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  • Disruption of the gut microbiome and gut barrier may be the primary cause of age-related inflammation which accelerates the aging process. www.sciencedaily.com
    Gut Microbiome Inflammation Fiber Carbohydrates

    This study showed that older mice have imbalances in the bacterial composition in the gut which then leads to the breakdown of the gut barrier and the release of bacterial products that trigger inflammation and impair immune function.

    We know that inflammation has recently been identified as the key driver of aging in 4 different age groups including elderly, centenarians, semi-supercentenarians, and supercentenarians. We also know that lack of fermentable fiber starves the gut microbiome and causes the bacteria to eat the gut barrier which is made of carbohydrates and this results in the breakdown of the barrier and inflammation.

    For more information on why fermentable fiber is so important for the gut microbiome and what good sources are…listen to my podcast with gut experts, Drs. Justin and Erica Sonnenburg. YouTube: https://youtu.be/gOZcbNw7sng

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  • Sulforaphane (found in broccoli sprouts) causes 20% fat loss by changing gut bacteria & increasing mitochondria in fat in mice. www.sciencedaily.com
    Gut Obesity Microbiome Metabolism Inflammation Sulforaphane Fatty Liver NRF2 Endotoxemia Lipopolysaccharide Visceral Fat

    Sulforaphane from broccoli sprouts causes 20% visceral fat loss by changing gut bacteria and increasing mitochondria in fat in mice. The mice fed sulforaphane also lowered fatty liver and reduced blood glucose levels. Sulforaphane reduced inflammation by decreasing a species of bacteria in the gut that is responsible for producing endotoxin, which is a major source of inflammation. Also, sulforaphane increased the levels of UCP1, which is responsible for increasing mitochondrial biogenesis (the generation of new mitochondria) in fat (called browning of fat). The browning of fat increases fat metabolism and can lead to fat loss. There have been human studies showing that sulforaphane decreases inflammatory biomarkers and improves blood glucose levels. It will be interesting to see future studies looking at these two new functions of sulforaphane in humans. For more information check out my video on sulforaphane or my podcast with Dr. Jed Fahey, who discovered broccoli sprouts are the best source of sulforaphane. Sulforaphane video: https://youtu.be/zz4YVJ4aRfg Sulforaphane podcast: https://youtu.be/Q0lBVCpq8jc

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  • Clinical trial shows whole grains modestly increase good gut bacteria, lower inflammatory gut bacteria, improve immune cells. www.sciencedaily.com
    Microbiome Inflammation Immune System Fiber Gluten

    New clinical trial shows that people that were given whole grains had a modest improvement in a good type of gut bacteria, modestly lowered inflammatory gut bacteria, and modestly increased memory T cells after 6 weeks compared to those given refined grains. Since this study compared gut bacteria, inflammatory biomarkers, and immune cells in people given whole grains versus refined grains it is difficult to draw any conclusions about whole grains compared to no grains. However, there have been other intervention trials that have shown whole grains lowered inflammatory biomarkers possibly through their effect on the microbiome. Also, this intervention trial was only 6 weeks which may also account for the modest effect on the microbiome. Things are probably much more complicated and have a lot to do with gene polymorphisms (which affect an individual’s glucose response), gut health, gluten sensitivity, and other factors. I do not think any absolute conclusions can be drawn from this study but still interesting to think about.

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  • Supplemental probiotics for 12 weeks improved cognition in Alzheimer's patients & also lowered inflammatory markers. www.sciencedaily.com
    Brain Alzheimer's Gut Microbiome Inflammation Probiotics Behavior Insulin Triglycerides Dopamine Norepinephrine Acetylcholine

    The probiotics also lowered triglycerides, VLDL, and markers of insulin resistance. There was no cognitive improvement in the placebo group.

    The participants took 2 billion Bifidobacterium bacteria per day, which is a pretty small quantity of probiotics. It is likely that the probiotics are working through multiple mechanisms such as lowering inflammation and increasing neurotransmitters. Other studies have shown that gut bacteria are able to modulate the levels of GABA, norepinephrine, serotonin, dopamine, and acetylcholine through the gut-brain axis.

    I spoke with the gut experts, Drs. Justin and Erica Sonnenburg, about the importance of the gut microbiome in human health and the various foods (ie. fermentable fiber and other prebiotics) that provide our gut bacteria with the food they need to thrive. Here is the interview (also available on iTunes and Sticher): https://www.youtube.com/watch?v=gOZcbNw7sng

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  • People with the highest fiber intake had ~80% greater chance of living long & healthy life out of all other dietary factors looked at. www.sciencedaily.com
    Gut Aging Microbiome Inflammation Depression Immune System Carbohydrates

    other factors including total carbohydrate intake, glycemic index, glycemic load, and sugar intake. Successful aging was defined as including an absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases including cancer, coronary artery disease, and stroke.

    The gut is a major source of inflammation and also the major regulator of the immune system. Fermentable fiber feeds the beneficial bacteria in the gut which then prevents them from being forced to cannibalize the gut barrier (which causes inflammation) and it allows them to produce signaling molecules (short chain fatty acids) which make the immune system better. Also, many foods that contain fiber such as vegetables and fruits also have many important micronutrients and other plant compounds that play a role in successful aging. For more on the importance of fiber in successful aging watch my interview with the authors of The Good Gut, Drs. Justin and Erica Sonnenburg: https://youtu.be/gOZcbNw7sng

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  • Report on Cryotherapy & Cold-Water Immersion www.foundmyfitness.com
    Exercise Inflammation

    http://www.ncbi.nlm.nih.gov/pubmed/26174323

    Wow, first, thank you so much for putting this 20-page report together!!

    Unfortunately, it creates a dilemma for me and I suspect others who strength train before work. I need to wait a full hour before taking a cold shower (per Wim Hof protocol)?

    Another option for me is to wake up earlier and swim after my strength training to cut into the hour a bit before cold showering. That’s tough as well though: the water at my pool’s gym is cold to replicate competition temperatures. I’m not sure how cold that is, but perhaps it would not be cold enough to trigger these negative consequences to strength and muscle gains. [Note: I swim for cardio due to a herniated disc; so no running, and the elliptical does little to build up wind imo.]

    What a bummer. Any suggestions? The pubmed abstract doesn’t discuss temperatures, but CWI often means pretty darned cold! Would I be fooling myself if I dismiss it as not applicable to my current weight-lifting-to-cold-shower protocol?

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  • New 20-page report on cryotherapy just released! Cold shock boosts norepinephrine up to 5-fold & increase type of immune cell that kills tumor cells. www.foundmyfitness.com
    Exercise Brain Alzheimer's Aging Metabolism Inflammation Memory Immune System Norepinephrine Protein

    This 20-page report explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an effect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.

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  • Pomegranate is metabolized by gut bacteria to produce anti-inflammatory compound Urolithin A that prevents brain plaques. www.sciencedaily.com
    Nutrition Brain Alzheimer's Aging Inflammation Blood-Brain Barrier Urolithin A

    Computational studies suggest urolithin A crosses the blood-brain barrier.

    From the article:

    Alzheimer’s disease is associated with ß-amyloid (Aß) fibrillation, a process in which amyloid proteins in the brain form clumps. To fight the formation of these fibrils, however, a molecule would have to cross the blood-brain barrier – a series of cell junctions that prevent certain substances from entering the brain. In previous work, the researchers showed that a pomegranate extract has anti-Alzheimer’s effects in animals, but they did not identify the compounds responsible.

    […]

    Computational studies found that polyphenols could not cross the blood-brain barrier, but that urolithins could. Urolithins are anti-inflammatory and neuroprotective compounds that are formed when ellagitannins, a type of polyphenol, are metabolized by gut bacteria. The researchers then showed that urolithins reduced Aß fibrillation levels in vitro.

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  • Beta-hydroxybutyrate produced from a ketogenic diet, fasting, or high-intensity exercise dampens inflammation via blocking of the NLRP3 inflammasome www.sciencedaily.com
    Exercise Diet Ketosis Inflammation Fasting Immune System NLRP3 Ketogenic Diet

    From the article:

    BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.

    Working with mice and human immune cells, Dixit and colleagues focused on how macrophages – specialized immune cells that produce inflammation – respond when exposed to ketone bodies and whether that impacts the inflammasone complex.

    The team introduced BHB to mouse models of inflammatory diseases caused by NLP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a ketogenic diet, which elevates the levels of BHB in the bloodstream.

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