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

Posted on March 14th 2025 (3 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 (5 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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