Metabolic Syndrome
Episodes
Continuous glucose monitors, or CGMs, are wearable devices that allow users to monitor their blood glucose levels through a tiny sensor placed under the skin.
In this clip, Dr. Steve Horvath describes research suggesting that caloric restriction, especially when it is reversing obesity or metabolic syndrome, may slow epigenetic aging.
Dr. Charles Raison discusses how a pro-inflammatory environment, such as that which occurs with obesity, can contribute to the risk of depression.
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1 out of 3 Americans has prediabetes. Could continuous glucose monitors help? | Dr. Michael Snyder ClipContinuous glucose monitors, or CGMs, are wearable devices that allow users to monitor their blood glucose levels through a tiny sensor placed under the skin.
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In this clip, Dr. Steve Horvath describes research suggesting that caloric restriction, especially when it is reversing obesity or metabolic syndrome, may slow epigenetic aging.
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Obesity, metabolic syndrome and depression, is inflammation the underlying link? | Charles Raison ClipDr. Charles Raison discusses how a pro-inflammatory environment, such as that which occurs with obesity, can contribute to the risk of depression.
Topic Pages
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Sugar-sweetened beverages (SSBs)
Frequent SSB consumption amplifies hepatic de novo lipogenesis, fostering insulin resistance, visceral adiposity, dyslipidemia, thereby driving metabolic syndrome.
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Ultra-processed Foods (UPFs)
Ultra-processed foods' refined carbohydrates, emulsifiers, saturated fats provoke gut dysbiosis, chronic inflammation, insulin resistance, collectively precipitating metabolic syndrome.
News & Publications
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Raising blood ketone levels with an oral supplement improves metabolic health in a rat model, mimicking effects commonly linked to fasting or ketogenic diets. https://doi.org/10.1152/ajpcell.00453.2025
Metabolic syndrome, a cluster of conditions including high blood pressure, high blood sugar, and excess body fat, is a major risk factor for heart disease and diabetes, and may be improved by raising blood ketone levels. However, achieving this often requires strict dietary interventions like fasting or ketogenic diets, which many people find difficult to sustain. That's why scientists tested whether raising ketones with a simple oral supplement could reproduce some of these protective effects without requiring major lifestyle changes.
The team studied a strain of rats prone to metabolic health problems. One group received drinking water with 20 percent 1,3-butanediol, a compound converted by the body into the ketone β-hydroxybutyrate. Another group was given plain water. To see how the compound affected the animals, the researchers measured outcomes related to metabolism, fat storage, cardiovascular function, and gene regulation.
The supplemented rats showed broad improvements compared with controls:
- Blood levels of β-hydroxybutyrate rose, confirming the compound increased ketones.
- Body weight and fasting glucose decreased.
- Average systolic blood pressure over 24 hours dropped in both sexes.
- A specific chemical tag on DNA-packaging proteins increased in kidney, liver, and heart in both sexes, and in skeletal muscle in males.
- Increases in this chemical tag correlated with higher expression of lipid‑metabolism genes in female kidney and male heart.
- Measures of fuel use showed a shift toward greater reliance on fat for energy.
- Inflammation signals in the kidney fell in females, and blood chemistry suggested healthier liver function in males.
These findings suggest that β-hydroxybutyrate does more than just provide fuel. By attaching to histones, it changes how DNA is packaged, making fat metabolism genes more active. This epigenetic mechanism, meaning a change in gene activity without altering DNA itself, appears to help the body burn more fat and improve metabolic health. Importantly, some of the effects differed between organs and between males and females, indicating that the response is not uniform across the body.
Conclusion:
The work suggests a shortcut to some of the benefits often linked to fasting or ketogenic diets. Because the results come from a small animal study, it's uncertain how much they apply to humans, but they provide a compelling starting point for testing ketone-based therapies in metabolic diseases. Learn more about ketone supplements and the ketogenic diet in episode #74 featuring Dr. Dominic D'Agostino. -
Adolescent obesity often persists into adulthood and raises cardiometabolic risks, but altering the gut microbiome may help shift long-term health trajectories. Researchers tested whether taking capsules containing gut microbes from healthy donors during adolescence could leave durable clinical and microbiome changes years later.
Researchers followed up on a previous trial where adolescents received either gut microbiota from healthy lean adults or a placebo. About four years later, 55 participants returned for assessment. The team measured body composition, metabolic markers, and gut microbial and viral profiles using DNA sequencing.
At the four year visit, several cardiometabolic and body composition measures favored the transplant group:
- Waist circumference was 10 cm lower in the fecal transplant group.
- Total body fat percentage was 4.8 points lower.
- A metabolic syndrome severity score was lower.
- The inflammation marker hs-CRP was 68 percent lower.
- HDL cholesterol was 0.16 mmol per liter higher.
These health differences were accompanied by lasting shifts in the gut microbiome. Adolescents who received donor microbes had a more diverse and markedly reshaped gut microbiome compared with placebo. Signatures of donor bacteria could still be detected years later, and participants who took up more donor strains soon after treatment tended to retain more of them long term. The gut bacteriophages – viruses that infect bacteria – also showed lasting donor patterns. Some of these microbial and viral differences were linked with healthier metabolic scores and weight change, although these links cannot prove cause and effect.
Conclusion:
A single course of oral fecal microbiota transplant during adolescence was followed by lower central adiposity and body fat, lower systemic inflammation, and a better composite metabolic risk score about four years later, while BMI remained similar. However, it's important to mention that BMI is a limited measure because it doesn't distinguish between fat and lean mass and can therefore miss meaningful shifts in fat distribution. The gut microbiome continued to show donor traits, which might help explain the observed health effects. However, the study has limitations: it was unblinded, had high dropout rates, didn't track medication or lifestyle changes continuously, and used a statistical approach that may increase false positives. Overall, the results are promising, but they warrant cautious interpretation and further confirmation. Learn more about the microbiome in episode #70 featuring Dr. Eran Elinav. -
Taurine supplementation can help regulate blood glucose and lower blood pressure, reducing risk factors associated with metabolic syndrome. pubmed.ncbi.nlm.nih.govObesity Diabetes Cholesterol Triglycerides Blood Pressure Metabolic Syndrome Taurine Stroke Cardiovascular Supplements
Metabolic syndrome is a cluster of conditions that includes hypertension, high blood glucose, excess abdominal fat, and abnormal blood lipids. Having metabolic syndrome markedly increases a person’s risk of cardiovascular disease, type 2 diabetes, and stroke. A recent meta-analysis found that taurine supplementation improves conditions associated with metabolic syndrome.
Researchers analyzed the findings of 25 studies (with more than 1,000 participants) investigating links between taurine supplementation and metabolic syndrome. They also explored the effects of taurine dose and examined secondary outcomes of taurine supplementation, including body composition, lipid profile, and blood glucose control.
They found that taurine doses ranged from 0.5 to 6 grams, with study durations ranging from five days to one year. On average, taurine supplementation reduced systolic blood pressure by 4 mmHg, diastolic blood pressure by 1.5 mmHg, fasting blood glucose by 6 milligrams per deciliter, and triglycerides by 18 milligrams per deciliter. The researchers did not observe an effect on high-density lipoprotein cholesterol. The reduction in diastolic blood pressure and fasting blood glucose was dose-dependent, with higher doses eliciting more robust effects.
These findings suggest that taurine supplementation improves factors associated with metabolic syndrome. Interestingly, other research shows that an acute bout of exercise increases blood taurine levels, providing a mechanistic link between exercise and better metabolic health.
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Morning exercise outperforms afternoon workouts in enhancing cardiometabolic health in people with metabolic syndrome. physoc.onlinelibrary.wiley.com
The idea that exercise benefits metabolic health is widely accepted. But whether the benefits of exercise are greater depending on when one exercises – morning versus afternoon – is a matter of considerable debate. A recent study shows that morning exercise reduces blood pressure, fasting insulin, and insulin resistance better than afternoon exercise in people with metabolic syndrome.
Metabolic syndrome is a constellation of conditions characterized by abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoproteins. Having metabolic syndrome increases a person’s risk of cardiovascular disease and type 2 diabetes. Roughly one-third of adults between the ages of 20 and 60 have metabolic syndrome.
The study involved 139 adults with metabolic syndrome who agreed to participate in three supervised high-intensity interval training sessions every week for 16 weeks. About a third of the participants performed their exercise in the morning, a third did so in the afternoon, and a third didn’t engage in any exercise. Researchers measured the participants' body composition, cardiorespiratory fitness, maximal fat oxidation, blood pressure, and blood metabolites before and after the intervention.
They found that both exercise groups demonstrated greater body fat loss, reduced waist circumference (nearly an inch), and lower diastolic blood pressure than those who didn’t exercise. However, when comparing the morning exercise group to the afternoon group, they found that morning exercise was more effective at reducing systolic blood pressure (4 percent drop vs. 1 percent), lowering fasting insulin (12 percent drop vs. 5 percent), and decreasing insulin resistance (14 percent drop vs. 4 percent).
These findings suggest that morning exercise boosts cardiometabolic health better than afternoon exercise. The investigators posited that these effects may be related to circadian rhythms, which influence the body’s response to exercise and dietary intake.
Finding the time or motivation to exercise in the morning may be challenging for many. Fortunately, most experts agree that some exercise is better than none, as long as it’s not too close to bedtime. Learn more in this clip featuring Dr. Rhonda Patrick.
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A new study reveals a surprising link between triglycerides and reduced risk of dementia in older adults. www.sciencedaily.com
Triglycerides, the most common type of fat in the body, serve as a vital energy source and aid in absorbing fat-soluble vitamins. However, elevated levels of triglycerides, often associated with unhealthy dietary habits and certain metabolic conditions, have been linked to an increased risk of atherosclerosis, cardiovascular disease, and other metabolic disorders. Now, findings from a recent study suggest that higher triglyceride levels reduce the risk of dementia by as much as 18 percent.
Researchers drew on data from more than 86,000 healthy older adults enrolled in the UK Biobank and ASPREE studies. They measured the participants' triglyceride levels and assessed different aspects of their cognition, such as memory, language, and reasoning. Then, they determined the effects of triglyceride levels on these cognitive measures.
They found that participants with higher triglyceride levels (normal to high-normal) were 18 percent less likely to develop dementia and experienced a slower decline in their overall cognitive abilities over time than those with lower triglyceride levels. Those with the highest levels of triglycerides were 36 percent less likely to develop dementia than those with the lowest levels. These results were consistent even after considering other factors that could affect the outcomes.
These findings suggest that higher triglyceride levels protect against dementia, counter to current thinking about triglycerides. They also highlight the need for further investigation to understand whether this link is causal and whether components of triglycerides benefit cognitive function.
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Breastfeeding benefits mothers by promoting post-partum weight loss and reducing the risk of certain types of cancer later in life. A new study suggests that breastfeeding also supports maternal cardiometabolic health. Women who breastfed for at least six months were leaner and had lower blood pressure than those who didn’t.
Researchers conducted health check-ups on 160 mother-child pairs enrolled in Screening Tests to Predict Poor Outcomes of Pregnancy, a long-term study that assessed women’s risk for pregnancy complications. They assessed the women’s cardiometabolic health via blood pressure, body measurements, and serum metabolic markers (glucose and lipids). They determined breastfeeding duration via the children’s health records.
They found that the cardiometabolic health of women who breastfed for at least six months was considerably better than those who did not breastfeed, as evidenced by lower body mass index (BMI) and blood pressure. These differences persisted even after considering factors like BMI, socioeconomic status during early pregnancy, prenatal smoking, and maternal age during early pregnancy. In women who had experienced pregnancy complications (such as preeclampsia or gestational diabetes), breastfeeding for at least six months reduced blood pressure, insulin, and triglycerides, while increasing HDL cholesterol levels.
These findings suggest that breastfeeding for a minimum of six months benefits the cardiovascular health of mothers, particularly those who experienced pregnancy complications. They also highlight the importance of breastfeeding as a potential means to reduce the risk of cardiovascular issues in women following childbirth. However, the investigators conceded that this was a small study, potentially hindering its translatability to a broad audience. Learn more about the maternal benefits of breastfeeding in our overview article.
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Maternal omega-3 potentiates fetal brown fat via synergistic action of miRNA production and histone modifications, possibly a lifelong benefit www.sciencedirect.com
Omega-3 supplementation during pregnancy promotes brown fat formation in offspring.
A new study in mice showed that omega-3 fatty acid consumption during pregnancy and lactation promoted the formation of brown fat in offspring. Omega-3s also increased energy expenditure and cold resistance.
Researchers fed female mice either a diet rich in omega-3 fatty acids or a diet devoid of omega-3s throughout their pregnancies and lactation. They measured their offspring’s brown fat and energy expenditure and assessed their capacity to maintain their core body temperature in cold temperatures.
They found that the mice whose mothers ate a diet rich in omega-3s had higher concentrations of brown fat than those whose mothers did not consume omega-3s. In addition, they had higher energy expenditure and were more efficient at maintaining their core body temperature in cold temperatures. Genetic analysis revealed that the increase in brown fat synthesis was mediated via epigenetic mechanisms. You can learn more about epigenetic mechanisms in our article here.
Brown fat, also known as brown adipose tissue, is found in all mammals and is particularly abundant in newborns. Unlike white fat, brown fat is metabolically active tissue that is rich in mitochondria. It helps maintain body temperature during cold exposure, during which its uptake of glucose is eightfold higher than that of muscle tissues, driving increases in energy expenditure.
Cold exposure increases brown fat activity in humans, possibly benefitting whole-body glucose utilization and insulin sensitivity. Learn more about the effects of cold exposure in our overview article.
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Dawn-to-dusk fasting reduces disease risk and improves metabolic health in people with metabolic syndrome. medicalxpress.com
One month of dawn-to-dusk fasting decreases proteins that drive atherosclerosis, heart disease, and cancer in people who have metabolic syndrome, a recent study has found. People who fasted also lost weight and saw improvements in their metabolic and cardiovascular health.
The study involved 14 people who had metabolic syndrome – a constellation of health conditions that increases a person’s risk of heart disease, stroke, and type 2 diabetes. Participants fasted (no food or drink) from dawn to dusk for more than 14 hours every day for four weeks. They ate a pre-fast meal (breakfast) before beginning their fast and a post-fast meal (dinner) after ending their fast each day. Researchers analyzed the proteomes (the collective set of proteins) of the participants' peripheral blood mononuclear cells, a type of immune cell.
They found that proteins that drive atherosclerosis, heart disease, and cancer were decreased, but proteins that suppress cancer and inflammation were increased. Interestingly, they found that levels of apolipoprotein B, a protein associated with the development of atherosclerotic heart disease, were markedly lower after a month of fasting, and these lower levels persisted even one week after the fasting period ended. In addition, the participants lost weight, and their insulin resistance and blood pressure improved.
Evidence suggests that fasting flips a metabolic “switch,” liberating fat stores via fatty acid oxidation and ketone production while safeguarding lean muscle mass and function. Consequently, fasting improves overall body composition but also triggers the activation of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease. Learn more about fasting in our overview article.
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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
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.
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“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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Silencing of estrogen receptor α in a brain area of the hypothalamus led to metabolic syndrome in mice. (2007) www.sciencedaily.com
From the article:
Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.
To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.
Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.
When estrogen levels in the VMN dipped, the animals' metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.
The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.
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Vitamin D and estradiol may synergistically help protect against metabolic syndrome. (2019) www.sciencedaily.com
From the article:
Metabolic syndrome has emerged as a major public health concern, affecting 30% to 60% of postmenopausal women worldwide.
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The cross-sectional study included 616 postmenopausal women aged 49 to 86 years who were not taking estrogen and vitamin D/calcium supplements at the beginning of the trial. It concluded there was a positive correlation between vitamin D and estradiol.
Specifically, higher vitamin D was associated with a favorable lipid profile, blood pressure, and glucose level. Estradiol was negatively associated with cholesterol, triglycerides, and blood pressure. These results suggest a synergistic role of vitamin D and estradiol deficiency in developing metabolic syndrome in postmenopausal women.
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Estrogens may act on distinct hypothalamic neurons to regulate energy homeostasis and reproduction, mouse study suggests. (2011) www.sciencedaily.com
From the article:
“When women approach menopause, they gain weight in fat and their energy expenditure goes down,” says Deborah Clegg of the University of Texas Southwestern Medical Center. Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome.
Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.
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The researchers showed female mice lacking ERα [estrogen receptor-α (ERα)] in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.
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Having a large waistline can almost double your risk of dying prematurely even if your body mass index is within the 'normal' range www.sciencedaily.com
Having a large waist circumference may double a person’s risk of premature death.
People with a large waist circumference were roughly twice as likely to die prematurely compared to those with a smaller waist, according to a 2008 study. Notably, every two-inch increase in waist circumference increased the risk of premature death by 17 percent in males and 13 percent in females.
Researchers took various body measurements (body mass index [BMI], waist circumference, and waist-to-hip ratio) from nearly 360,000 adults enrolled in EPIC, an ongoing study in Europe. Then they investigated possible links between these measures and the risk of premature death over a period of about ten years.
They found that males who had a BMI of 25.3 and females who had a BMI of 24.3 were the least likely to die during the study period. However, a person’s waist circumference and waist-to-hip ratio were strongly linked with the risk of dying, even after considering factors that influence risk, including BMI, educational level, smoking status, alcohol consumption, physical activity, and height. For any given BMI, they noted that every five-centimeter (two-inch) increase in waist circumference markedly increased the risk of premature death.
A large waist circumference may be an indicator of visceral fat – body fat that is stored in the abdominal cavity and plays a central role in the links between obesity and systemic inflammation. Health experts recommend having a waist circumference of 40 inches or less for males and 35 inches or less for females.
Similarly, a large waist-to-hip ratio may increase a person’s risk of cardiovascular disease. The World Health Organization recommends having a waist-to-hip ratio of 0.9 or less for males and 0.85 or less for females.
See the Digest story below to learn how heavy drinking may influence waist circumference.
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Heavy drinking into older age adds 4 cm to waistline www.sciencedaily.com
Heavy drinking in later life increases stroke risk and contributes to a larger waist circumference.
Heavy drinking into one’s later life could add more than two inches to their waistline, a new study finds. Drinking heavily also contributes to a greater risk of cardiovascular disease and liver dysfunction.
Researchers asked more than 4,800 people (average age, 69 years) living in the United Kingdom about their alcohol consumption habits. They also took their body measurements and collected information about their overall health.
They found that people who drank heavily in later life were more likely to have higher blood pressure, higher stroke risk, and worse liver function than non-heavy drinkers. Heavy lifetime drinkers were also more likely to have a larger waist circumference – as much as 5.47 centimeters (~2.15 inches) larger – even if they cut back on their alcohol consumption before the age of 50.
Other research has shown that heavy drinking contributes to a large waist circumference, which is associated with a greater risk for cardiovascular disease and type 2 diabetes. Cutting back on alcohol consumption may help reduce waist circumference. Learn how exercise can help reduce cravings for alcohol.
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In older men with low testosterone levels, testosterone replacement therapy improved risk factors for cardiovascular disease and diabetes. (2008) www.sciencedaily.comHormones Diabetes Cholesterol Testosterone Triglycerides Metabolic Syndrome Weight Loss Cardiovascular
From the article:
All 95 men in the studies (ages 34 to 69 years) had the metabolic syndrome. To receive this diagnosis, patients must have three of the following five risk factors: increased waist circumference (abdominal fat), low HDL (“good”) cholesterol, high triglycerides (fats in the blood), high blood pressure, and high blood sugar.
The first study showed that testosterone treatment significantly reduced waist circumference, total cholesterol, LDL (“bad”) cholesterol, triglycerides, and body mass index (a measure of body fat). Treatment also increased “good” cholesterol. Improvements were progressive over 12 months, indicating that benefits may continue past a year, Saad said.
In the second study, the researchers divided the patient population into three groups by age: less than 57 years, 57 to 63 years, and more than 63 years. They found that the oldest men had similar improvements in metabolic risk factors to the youngest men.
Additionally, the investigators looked at the degree of testosterone deficiency before treatment. This beginning level of testosterone deficiency did not predict the beneficial outcome, they found. Men whose subnormal testosterone levels were not as low as the others had similar improvements in metabolic risk factors to men with the lowest levels, according to Saad.
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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
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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Testosterone predominance may increase the prevalence of metabolic syndrome during menopause. (2008) www.sciencedaily.com
From the article:
“Menopause-related testosterone predominance appears to be implicated as a key hormonal change that is associated with the incidence of metabolic syndrome,” said lead investigator Imke Janssen, PhD, assistant professor, Department of Preventive Medicine at Rush University Medical Center.
It was previously thought that estrogen exerted a direct positive effect on cardiovascular disease risk in women, a benefit that was lost as women transitioned from a premenopausal to a postmenopausal state and experienced a loss of estrogen.
“Our study data shows that the change in estrogen level is, at best, a weak and nonsignificant predictor of metabolic syndrome risk,” said Janssen. “A more likely story is that the progressive testosterone predominance exerts a direct negative effect on cardiovascular risk.”
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BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI (~one month per 1-unit BMI increase) onlinelibrary.wiley.com
Higher BMI is associated with epigenetic age acceleration.
Obesity exerts profound effects on the human body, ranging from alterations in the gut microbiota to an increased risk for many chronic diseases. Body mass index (BMI) is a proxy for body fatness and is strongly correlated with disease risk with aging. Findings from a recent study suggest that BMI is associated with epigenetic age acceleration.
Epigenetic age acceleration is a phenomenon that occurs when an individual’s epigenetic (biological) age exceeds their chronological age and can be the result of either intrinsic or extrinsic factors. Intrinsic factors are largely driven by internal physiological factors such as normal metabolism and genetics. Extrinsic factors are those associated with lifestyle and environmental exposures, such as diet, smoking, or exercise.
To rule out the effects of genetics and shared environments, the investigators used data from the Finnish Twin Cohort, an ongoing study of twins and twin families. They gathered BMI data and metabolic health parameters for more than 1,400 participants, including both monozygotic (identical) and dizygotic (fraternal) twins. They measured the participants' epigenetic ages using GrimAge, a type of epigenetic clock that predicts lifespan and healthspan in units of months or years, and tests the effects of lifestyle on biological aging.
They found that for every one-unit increase in BMI, the twins exhibited approximately one month of accelerated epigenetic aging. In twin pairs where one twin was heavier than the other, the heavier twin’s epigenetic age was approximately 5 months older than the lighter twin. They also found that age acceleration was associated with insulin resistance, a risk factor for type 2 diabetes.
These findings suggest that having a higher BMI accelerates epigenetic aging and underscores the importance of maintaining a healthy body weight throughout the lifespan. To learn more about epigenetics and accelerated epigenetic aging, check out these resources, including an overview article and these episodes featuring epigenetic experts Dr. Steve Horvath and Dr. Morgan Levine.
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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
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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Strict 12-week keto without calorie counting: participants lost >5% percent body fat, 44% of their visceral fat, and 48% better insulin sensitivity www.sciencedaily.com
This is a Jeff Volek study and used hard biomarkers, checking ketones daily.
From the article:
In the study, which appears in the journal Military Medicine, participants on the keto diet lost an average of almost 17 pounds and were able, with support of counselors, to maintain ketosis for 12 weeks. As a group, they lost more than 5 percent of their body fat, almost 44 percent of their belly, or visceral, fat and had a 48 percent improvement in insulin sensitivity – a marker that predicts risk of diabetes.
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The ketogenic diets in the study included no caloric restrictions, just guidance about what to eat and what to avoid. Carbs were restricted to about 30 to 50 grams daily, with an emphasis on nuts and non-starchy vegetables.
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Keto diet participants had near-daily check-ins during which they reported blood ketone measurements from a self-administered finger-prick test and received feedback, usually through text messages, from the research team. Ketosis was defined as a blood concentration of ketones, chemicals made in the liver, between 0.5 and 5.0 mM (millimolar).
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Visceral fat and total brain volume inversely linked independent of BMI and insulin resistance: a relationship between dementia and obesity www.sciencedaily.com
From the article:
Preliminary findings suggest a relationship between obesity and dementia that could lead to promising prevention strategies in the future.
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“Our results confirm the inverse association of increasing BMI with lower brain volumes in older adults and with younger, middle-aged adults and extends the findings to a much larger study sample,” […] “More importantly our data suggests a stronger connection between central obesity, particularly the visceral fat component of abdominal obesity, and risk of dementia and Alzheimer’s disease,” Dr. Seshadri added. The research showed the association between visceral adipose tissue and total brain volume was most robust and was also independent of BMI and insulin resistance."
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PCB exposure linked to increased visceral fat: "persistent compound PCB189 was related to a high proportion of fat in the abdomen" www.sciencedaily.com
Exposure to PCBs may increase visceral fat.
Persistent organic pollutants are ubiquitous environmental toxicants that pose considerable threats to human health. These compounds typically degrade slowly and are often referred to as “forever compounds.” A 2012 study found that exposure to the organic pollutants polychlorinated biphenyls (PCBs) was associated with having increased visceral fat.
PCBs were historically used in industrial and chemical applications, such as coolants, transformer insulators, capacitors, motors, paints, and electrical wire coatings. Although PCBs have been banned in the United States, the compounds are widespread in the environment. Exposure to PCBs is associated with an increased risk of adverse health effects, including many chronic disorders, such as cardiovascular disease, diabetes, hypertension, melanoma, and non-Hodgkin’s lymphoma. PCB exposure may also be linked to neurodegenerative disease PCBs bioaccumulate in human muscle and adipose tissue, brain, liver, and lungs and have long elimination half-lives, ranging from 10 to 15 years.
The cross-sectional study involved more than 1,000 adults (70 years and older) living in Sweden. Participants provided information about their medical histories, education level, exercise habits, smoking habits, and medication use. A subset of 287 participants underwent magnetic resonance imaging to assess body fat location and quantity. Investigators collected blood samples from the participants to detect the presence of persistent organic pollutants.
They found that higher blood concentrations of the organic pollutant PCB189, a highly chlorinated PCB, were associated with having greater quantities of visceral fat, suggesting that environmental exposures influence fat deposition in humans. Interestingly, PCB189 exposure and increased visceral fat are associated with type 2 diabetes, potentially providing a mechanistic link between body fat and diabetes risk.
Although exposure to persistent organic pollutants is likely unavoidable, some PCBs are excreted in sweat. Sauna use, which induces copious sweating, may promote PCB excretion. Learn more about the beneficial health effects of sauna use in our overview article.
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Visceral fat may be less circadian than (healthier) subcutaneous fat: only subcutaneous showed circadian rhythmicity in insulin sensitivity www.sciencedaily.com
From the article:
Using samples of adipose tissue from both visceral fat and subcutaneous fat from 18 people who underwent gastric bypass surgery, researchers found that subcutaneous fat has an intrinsic circadian rhythm in insulin sensitivity. Insulin sensitivity reached its maximum around noon, and was more than 50 percent higher than at midnight. Interestingly, the rhythm was not observed in visceral fat.
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“Our study demonstrates that subcutaneous human fat tissue has an internal clock that is able to regulate insulin sensitivity even when outside of the body. This tissue rhythm matches well with what has been observed in humans overall when examining how people cope with a meal or sugar load,”
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Weighted vests may produce changes in body mass through perturbation of a homeostatic "gravitostat," a system regulating appetite by sensing weight www.sciencedaily.com
Exploiting the “gravitostat,” a novel homeostatic mechanism that regulates body weight, promotes weight loss.
Having overweight or obesity increases a person’s risk of developing many chronic diseases. But losing weight loss is challenging, partly due to homeostatic mechanisms that regulate body weight. Findings from a 2020 study suggest that exploiting a novel homeostatic weight-regulating mechanism called the gravitostat promotes weight loss in humans.
The concept of the gravitostat first emerged in 2017, when scientists implanted small weights into the abdomens of mice and found that the animals’ food intake decreased, promoting weight loss and improving glucose tolerance. They suggested that the gravitostat regulates weight via a negative feedback system involving bone cells called osteocytes. Because osteocytes can sense changes in bone strain, the investigators proposed that increasing the animals’ body weight activated a biological sensor that communicated with the osteocytes of weight-bearing bones to drive changes in eating behaviors and subsequent weight loss.
In the 2020 study, the investigators conducted a randomized controlled trial involving 69 adults with mild obesity (body mass index of 30-35). About half of the participants wore a heavy weighted vest (11 percent of their body weight) for eight hours every day for three weeks, while the other half wore a light vest (1 percent of their body weight). Before and after the intervention, the investigators weighed the participants and analyzed their body composition using bioelectrical impedance.
They found that participants who wore the heavy vest lost an average of 1.37 percent more bodyweight than those who wore the light vest, translating to about 3.5 pounds. Those who wore the heavy vests also lost fat mass and gained fat-free mass. These findings suggest that the gravitostat regulates body weight in humans and exploiting it provides a possible strategy for losing weight.
Overcoming other aspects of bodyweight homeostasis might still prove challenging, however. Research from Dr. Eran Elinav’s lab suggests that metabolic parameters normalize with weight loss, but characteristics of the microbiome remain unchanged. In other words, the microbiome holds a memory of past obesity that promotes weight regain. Preclinical studies indicate that repeated weight cycling shifts gut microbes to a configuration with an altered ability to metabolize flavonoids — compounds that usually help promote the burning of excess energy by adipose tissue. Learn more in this clip featuring Dr. Eran Elinav.
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Visceral fat intimately linked with the hypertensive effect of obesity: "only abdominal fat remained independently associated with hypertension" www.sciencedaily.com
From the article:
For this study, 903 patients enrolled in the Dallas Heart Study were followed for an average of seven years to track development of hypertension. […] Patients also received imaging of visceral fat, or fat located deep in the abdominal cavity between the organs; subcutaneous fat, or visible fat located all over the body; and lower-body fat.
[…]
At the end of the study period, 25 percent of patients developed hypertension. While higher BMI was associated with increased incidence of hypertension, when abdominal fat content, overall fat content and lower-body fat content were factored in, only abdominal fat remained independently associated with hypertension.
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Retinol-binding protein 4 (RBP4) may be a biomarker for visceral fat accumulation: levels of RBP4 double or triple in concentration compared to normal www.sciencedaily.com
From the article:
The researchers, including Barbara Kahn and Timothy Graham of Harvard Medical School and Matthias Blüher of the University of Leipzig in Germany, showed that “retinol-binding protein 4” (RBP4) is produced in much greater amounts by visceral fat compared to the subcutaneous fat that lies just beneath the skin. Moreover, they report that blood serum levels of RBP4 jump in people who are obese, who have double or even triple the concentrations found in individuals of normal weight.
[…]
The only known function of RBP4 was to carry vitamin A (also known as retinol) in the blood, Kahn said.
Large gene expression changes in visceral fat:
n a study of 196 people, the researchers now reveal that RBP4 is indeed preferentially produced in the deep fat that covers organs of the belly. RBP4 gene expression activity levels spiked about 60-fold in the visceral fat of viscerally obese relative to lean study participants, they found. By comparison, visceral fat RBP4 concentrations were increased just 12-fold in obese individuals with a preponderance of subcutaneous fat.
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Removing the visceral fat in female mice reduces intestinal tumors and extends survival (a sex-specific effect) www.sciencedaily.com
From the article:
“There has been some skepticism as to whether obesity per se is a bona fide cancer risk factor, rather than the habits that fuel it, including a poor diet and a sedentary lifestyle,” […] “Although those other lifestyle choices play a role, this study unequivocally demonstrates that visceral adiposity is causally linked to intestinal cancer.”
There was a sex-specific effect:
The researchers then subdivided the groups by gender. In female mice, the removal of visceral fat was significantly related to a reduction in intestinal tumors, but calorie restriction was not. In male mice, calorie restriction had a significant effect on intestinal tumors, but removal of visceral fat did not.
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Greater visceral and total body fat associated with vascular brain injury and impaired cognitive scores www.sciencedaily.com
From the article:
In the study, 9,166 participants were measured by bioelectrical impedance analysis to assess their total body fat.
As well, 6,733 of the participants underwent magnetic resonance imaging (MRI) to measure abdominal fat packed around the organs known as visceral fat, and the MRI also assessed vascular brain injury – areas in the brain affected by reduced blood flow to the brain.
[…]
Co-author Eric Smith, a neurologist, scientist and an associate professor of clinical neurosciences at the University of Calgary, said that “preserving cognitive function is one of the best ways to prevent dementia in old age. This study suggests that one of the ways that good nutrition and physical activity prevent dementia may be by maintaining healthy weight and body fat percentage.”
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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
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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An unexpected way to shed visceral fat through the sebaceous gland: "We believe that we are the first group to show a non-hormonal way to induce this" www.sciencedaily.com
From the article:
Treating obese mice with the cytokine known as TSLP led to significant abdominal fat and weight loss compared to controls […] Unexpectedly, the fat loss was notassociated with decreased food intake or faster metabolism. Instead, the researchers discovered that TSLP stimulated the immune system to release lipids through the skin’s oil-producing sebaceous glands.
Thymic stromal lymphopoietin:
Thymic stromal lymphopoietin (TSLP) is a cytokine – a type of immune system protein – involved in asthma and other allergic diseases. The Kambayashi research group has been investigating the expanded role of this cytokine to activate Type 2 immune cells and expand T regulatory cells. Since past studies have indicated that these cells can regulate energy metabolism, the researchers predicted that treating overweight mice with TSLP could stimulate an immune response, which could subsequently counteract some of the harmful effects of obesity.
“When I looked at the coats of the TSLP-treated mice, I noticed that they glistened in the light. I always knew exactly which mice had been treated, because they were so much shinier than the others,” he said. Kambayashi considered a far-fetched idea – was their greasy hair a sign that the mice were “sweating” out fat from their skin?
Does this mechanism exist in humans?
To examine whether TSLP could potentially play a role in the control of oil secretion in humans, the researchers then examined TSLPand a panel of 18 sebaceous gland-associated genes in a publicly-available dataset. This revealed that TSLPexpression is significantly and positively correlated with sebaceous gland gene expression in healthy human skin.
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Visceral fat may cause pathogenic obesity reinforced through a cycle of chronic inflammation www.sciencedaily.com
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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Brain insulin sensitivity determines fat distribution: insulin sensitivity in the hypothalamus form little visceral, but no influence on subcutaneous www.sciencedaily.com
From the article:
If the person’s brain responds sensitively to the hormone, a significant amount of weight can be lost, unhealthy visceral fat reduced, and the weight loss can be maintained over the long term. However, If the person’s brain responds only slightly or not at all to insulin, the person only loses some weight at the beginning of the intervention and then experiences weight regain. Over the long term, the visceral fat also increases.
[…]
Since the insulin action in the hypothalamus is crucial for the regulation of peripheral energy metabolism, the researchers also investigated how insulin sensitivity in this area of the brain is related to the distribution of body fat. For this purpose, they examined a cross-sectional cohort of 112 participants. The analysis of the data showed that people with high insulin sensitivity in the hypothalamus form little visceral fat. However, insulin sensitivity has no influence on the mass of subcutaneous fat.
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Sugar-sweetened drinks linked to increased visceral fat www.sciencedaily.com
Sugar-sweetened beverage intake increases visceral fat.
Subcutaneous fat is stored just beneath the skin. Commonly associated with a “pear” shape, subcutaneous fat may protect against some diseases. Visceral fat, on the other hand, is stored in the abdominal cavity close to internal organs such as the liver, pancreas, and intestines. An excess of visceral fat, often referred to as central obesity or abdominal obesity, is commonly associated with an “apple” shape and an increased risk of developing many chronic diseases. Findings from a 2016 study suggest that sugar-sweetened beverage intake increases visceral fat deposition.
Sugar-sweetened beverages include commonly consumed products such as soda, sports drinks, energy drinks, and other beverages that contain added sugars. Many sugar-sweetened beverages exceed the recommended maximum daily added sugar intake of 25 grams in a single serving. They are the leading contributor to sugar intake among people living in the United States.
The investigation involved 1,160 participants enrolled in the Third Generation of the Framingham Heart Study who underwent repeated computed tomography scans (approximately six years apart) to assess the amount of fat in their abdominal region, including subcutaneous fat and visceral fat. Participants provided information about their dietary intake, physical activity, overall health, and whether they smoked. Investigators categorized the participants according to their sugar-sweetened beverage or diet soda intake, ranging from non-consumers (drinking none to less than one serving per month) to daily consumers (drinking one or more servings per day.
They found that sugar-sweetened beverage intake was associated with visceral fat gain in a dose-dependent manner, with daily consumers gaining 29 percent more visceral fat over a six-year period than non-consumers. These findings held true even after accounting for the participants' age, gender, physical activity, body mass index, and other factors. Drinking diet soda was not associated with visceral fat gain.
These findings suggest that drinking sugar-sweetened beverages increases visceral fat, potentially contributing to an increased risk of chronic disease. Learn more about sugar-sweetened beverages in our overview article.
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Fibroblast growth factor-2 released by visceral fat tumorigenic: "when the fat secretions had more of FGF2, more of the cells formed cancerous tumors" www.sciencedaily.com
From the article:
A new Michigan State University study now offers new details showing that a certain protein released from fat in the body can cause a non-cancerous cell to turn into a cancerous one. The federally funded research also found that a lower layer of abdominal fat, when compared to fat just under the skin, is the more likely culprit, releasing even more of this protein and encouraging tumor growth.
[…]
“Our study suggests that body mass index, or BMI, may not be the best indicator,” Bernard said. “It’s abdominal obesity, and even more specifically, levels of a protein called fibroblast growth factor-2 that may be a better indicator of the risk of cells becoming cancerous.”
[…]
She also collected visceral fat tissue from women undergoing hysterectomies and found that when the fat secretions had more of the FGF2 protein, more of the cells formed cancerous tumors when transferred into mice.
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Inadequate sleep may preferentially act as a trigger for visceral fat accumulation (randomized controlled crossover study) www.sciencedaily.com
Inadequate sleep drives abdominal fat gains.
Visceral fat is body fat that is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to type 2 diabetes, insulin resistance, inflammatory diseases, certain types of cancer, cardiovascular disease, and other obesity-related conditions. Findings from a recent study suggest that not getting enough sleep increases the risk of developing excess visceral fat.
Sleep is essential for human health. Not getting enough sleep or having poor, fragmented sleep promotes the development of many chronic illnesses, including cardiovascular disease, hypertension, diabetes, stroke, obesity, and depression. Scientists don’t fully understand the mechanisms that drive these effects, but some evidence suggests that disturbances in circadian rhythms play vital roles.
The trial involved 12 healthy young adults (aged 19 to 39 years) who engaged in an in-patient sleep study. Participants were allowed to have either a full night of sleep (nine hours of sleep opportunity) or restricted sleep (four hours of sleep opportunity) for two weeks. After a three-month washout period, participants repeated the study with the opposite sleep experience. The investigators measured the participants’ caloric intake, energy expenditure, body weight, body composition, and fat distribution throughout the study period.
They found that when participants were sleep-restricted, they consumed approximately 13 percent more protein and 17 percent more fat (translating to about 300 calories) daily, but their overall energy expenditure did not change. Sleep-restricted participants also gained weight. Much of this weight was in the abdominal area, with a 9 percent increase in total abdominal fat area and an 11 percent increase in visceral fat, compared to when they got a full night’s sleep.
These findings suggest that insufficient sleep increases caloric intake and promotes weight gain and visceral fat increases. Learn more about the harmful health effects of insufficient sleep in this episode featuring sleep expert Dr. Matt Walker.
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Hunger inhibition hormone leptin directly contributes to cardiovascular disease in those desensitized by obesity by increasing cardiovascular activity www.sciencedaily.com
From the article:
In both cell culture and animal models, the researchers have shown that fat-derived leptin directly activates aldosterone synthase expression in the adrenal glands, resulting in production of more of the steroid hormone aldosterone.
High aldosterone levels are known to contribute to widespread inflammation, blood vessel stiffness and scarring, enlargement and stiffness of the heart, impaired insulin sensitivity and more.
Aldosterone, which is produced by the adrenal gland, has a direct effect on blood pressure by regulating salt-water balance in the body. High levels of aldosterone are an obesity hallmark and a leading cause of metabolic and cardiovascular problems. But exactly how it gets high in obesity was a mystery.
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Extra virgin olive oil high in polyphenols improves antioxidant status in adults. pubmed.ncbi.nlm.nih.gov
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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Seventy percent of adults living in the United States have overweight (BMI greater than 25) or obesity (BMI greater than 30), putting them at increased risk of metabolic disease. Extra fat stored around the body promotes inflammation and insulin resistance, but extra abdominal fat is particularly dangerous. Findings of a recent report suggest consuming foods rich in unsaturated fat and dietary fiber may improve fat distribution in females.
Fat stored in the lower body, called subcutaneous fat, is located just under the skin. Fat stored in the abdominal region, called visceral fat, is wrapped around the internal organs (e.g., the liver, pancreas, and intestines). Visceral fat interferes with lipid metabolism in the liver, promoting insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease. A diet that includes avocados, which are rich in mono-unsaturated fats and dietary fiber, is associated with lower abdominal obesity.
The investigators recruited 105 adults between the ages of 25 and 45 years who had overweight or obesity. They assigned participants to receive meals with avocado (about one Hass avocado) or meals without avocado that were matched for calories and total fat. The two meals contained different amounts of saturated fat, unsaturated fat, and fiber. Participants consumed their assigned meals once per day for 12 weeks and were told not to change their diet in other ways. Participants completed an oral glucose tolerance test to measure insulin resistance and had their body composition measured using X-ray.
In females, avocado consumption decreased visceral adiposity and the ratio of visceral to subcutaneous fat, indicating an improvement in body fat distribution. Both males and females in the control group experienced a loss of subcutaneous fat and an increase in the ratio of visceral to subcutaneous fat, indicating a worsening of body composition over the 12 weeks. Avocado consumption had no effect on insulin resistance.
The authors concluded that avocado consumption improved body fat distribution in females, but had no effects on body fat distribution in males or on insulin resistance in either males or females.
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The body mass index (BMI) is a ratio of weight to height and is one tool for measuring body size in health care and research. Epidemiological research indicates that individuals with a healthy BMI (between 20 and 25) have the lowest risk of cardiovascular disease and death compared to individuals with underweight (BMI less than 18.5), overweight (BMI between 25 and 30), and obesity (BMI greater than 30); however, some people with a healthy BMI experience metabolic dysfunction and an increased risk of death. Authors of the following report explore the condition lipodystrophy, its physiological causes, and its prevalence in the general population.
Lipodystrophy is a condition in which the amount and/or distribution of fat tissue in the body is abnormal. Visceral fat is fat stored in the abdomen and is associated with insulin resistance, elevated triglycerides, and fatty liver. This is in contrast to fat stored in the lower body, called subcutaneous fat, which is not associated with metabolic dysfunction. In short-term studies, people with a healthy BMI and an increased waist-to-hip ratio (i.e., ratio of visceral to subcutaneous fat) are at a three times greater risk of death than people with obesity and no metabolic dysfunction, a condition referred to as metabolically healthy obesity. However, long-term studies (those with greater than 10 years' follow-up) show that people with metabolically healthy obesity have a 24 percent increased risk of death, suggesting metabolically healthy obesity is a transient stage between metabolic health and metabolic disease.
The authors recruited almost 1,000 Caucasian/white participants of varying weight status who were at an increased risk of cardiometabolic disease based on weight, family and personal history of diabetes, and elevated glucose levels. The researchers used magnetic resonance imaging (MRI) to precisely measure body fat amount and distribution. They also measured blood pressure, fasting triglyceride levels, fasting glucose, the inflammatory marker C-reactive protein, insulin resistance, and carotid intima thickness (a measure of atherosclerosis). They defined good metabolic health as having two or fewer of the following criteria: blood pressure greater than 130/85 millimeters of mercury or the use of blood pressure medication; fasting triglycerides greater than 150 milligrams per deciliter; fasting HDL cholesterol (i.e., good cholesterol) less than 40 milligrams per deciliter in males or less than 50 milligrams per deciliter for females; fasting glucose greater than 100 milligrams per deciliter or the use of diabetic medication; C-reactive protein level in the 90th percentile or above; or insulin resistance in the 90th percentile or above.
Compared to people with a healthy BMI and good metabolic health, those with a healthy BMI and more than two metabolic risk factors had more insulin resistance, nonalcoholic fatty liver disease, visceral obesity, less lower body subcutaneous fat, and increased atherosclerosis. However, they did not have an increased prevalence of high blood pressure, high triglycerides, low good cholesterol, or increased inflammation. Compared to people with a healthy BMI and metabolic dysfunction, people with overweight or obesity and metabolic dysfunction had a gradual increase in the prevalence of visceral adiposity, fatty liver, insulin resistance, atherosclerosis, and low subcutaneous fat volume in the lower body as BMI increased. This means that metabolic dysfunction in people with a healthy BMI is most characterized by insulin resistance and atherosclerosis and is most strongly associated with lower subcutaneous fat in the lower body than visceral adiposity in the abdomen. The authors used this to support the existence of a lipodystrophy phenotype in people with a healthy BMI.
The authors conclude that some people with a healthy BMI may still have lipodystrophy that puts them at an increased disease risk compared to individuals with a healthy BMI and normal fat distribution. They recommend early testing of insulin sensitivity and use of medications that increase insulin sensitivity in people with lipodystrophy to lower disease risk.
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Wild blueberry extract improves metabolic function and cognitive performance in middle-aged adults. pubmed.ncbi.nlm.nih.gov
Metabolic function and cognitive performance begin to decline as early as the middle-age years – between the ages of 45 and 65 years. Dietary modification might be a useful strategy for improving or even reversing these declines. A recent study demonstrates that consumption of a wild blueberry extract improves metabolic function and cognitive performance in middle-aged adults.
Blueberries are rich sources of anthocyanins, a type of flavonoid compound that exerts antioxidant and anti-inflammatory effects. Epidemiological evidence suggests that regular consumption of blueberries reduces a person’s risk of developing cardiovascular disease, cancer, and type 2 diabetes.
The randomized controlled cross-over trial involved 35 people between the ages of 40 and 65 years. After eating a breakfast meal consisting of buttermilk biscuits with unsalted butter and apple jelly, scrambled eggs, and honeydew melon balls, the participants drank a beverage containing 25 grams of freeze-dried blueberries (roughly equivalent to 1 cup of fresh berries) and some flavoring agents. On a separate occasion, participants ate the same breakfast meal and drank a placebo beverage that contained the flavoring agents (and similar caloric content) only. Each of the participants performed cognitive tasks and provided blood samples before and after each meal/treatment. The authors of the study assessed the participants for changes in their episodic memory and executive function as well as plasma levels of glucose, insulin, and triglycerides.
The authors found that the participants who drank the blueberry beverage performed better on the cognitive tests than those who drank the placebo. They also noted that the blueberry beverage drinkers had lower insulin and glucose levels than those who drank the placebo.
These findings suggest that blueberry consumption improves metabolic markers and cognitive performance in middle-aged adults and underscore the importance of regular consumption of flavonoid-rich fruits and vegetables.
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Chloroquine or hydroxychloroquine, when used in combination with metformin, increased risk of death in mice blogs.sciencemag.org
Chloroquine and hydroxychloroquine are antimalarial drugs currently being used under Emergency Use Authorization as treatments for COVID-19. Recently published data from a mouse study suggest that these drugs carry a significant risk of death when either is given in combination with metformin.
Metformin is a drug commonly used to treat type 2 diabetes. It is the fourth most commonly prescribed medication in the United States, with more than 80 million prescriptions for the drug written yearly.
Previous research has demonstrated that chloroquine and metformin, when used independently, exert anti-cancer effects. The current study investigated whether the two drugs, when used in combination, would have a synergistic effect against cancer.
The authors of the study injected mice with saline, chloroquine, hydroxychloroquine, and/or metformin for four weeks. They found that the combination of chloroquine and metformin killed 40 percent of the mice. The combination of hydroxychloroquine and metformin killed 30 to 40 percent of the mice. All the treated mice exhibited high levels of lactate dehydrogenase and creatine kinase – indicators of tissue damage. Some of the mice treated with hydroxychloroquine and metformin exhibited signs of increased autophagy in their hearts, livers, and kidneys.
These findings suggest that when chloroquine or hydroxychloroquine are given in combination with metformin, they can increase the risk of death in mice. Further clinical trials are needed to determine if these findings translate to humans.
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Excess visceral fat promotes inflammation and drives cognitive decline. www.eurekalert.org
Visceral fat – body fat that is stored in the abdominal cavity in close proximity to important internal organs such as the liver, pancreas, and intestines – plays a central role in the interrelationship between obesity and systemic inflammation. Excess visceral fat, often referred to as central or abdominal obesity, is a strong predictor of age-related cognitive decline. A new study in mice demonstrates that having excess visceral fat may impair cognition by activating the NLRP3 inflammasome and promoting the release of interleukin-1 beta (IL-1β).
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. Cryopyrin, also known as NLRP3, is a protein that drives the formation and activation of the NLRP3 inflammasome.
Interleukin-1 beta is a proinflammatory protein present in many cells. NLRP3 inflammasome-driven release of IL-1β activates microglia, the brain’s resident immune cells. Microglia serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and harm.
The authors of the study first determined that mice lacking the gene for NLRP3 did not experience visceral fat-induced brain inflammation and cognitive decline. They also determined that when visceral fat from normal, obese mice was transplanted into these mice, they exhibited higher levels of IL-1β in their hippocampus, an area of the brain associated with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation.
To understand the effects of IL-1β on brain function, the authors of the study fed the mice a high- or low-fat diet for 12 weeks and then assessed the animals' capacity to navigate a water maze. The mice that ate the higher-fat diet experienced greater difficulties negotiating the water maze, compared to those that ate the lower-fat diet. Examination of the animals' brains revealed that the mice that ate the high-fat diet (as well as those that received the fat transplants) had weaker synapses between the neurons involved in learning and memory.
These findings suggest that chronic inflammation driven by excess visceral fat may contribute to cognitive decline by promoting the release of IL-1β and increasing inflammation. Inflammation drives other aspects of brain dysfunction, including those associated with depression. Watch this clip in which Dr. Charles Raison discusses how a pro-inflammatory environment can contribute to the risk of depression.
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Adherence to the Mediterranean diet for one year promotes gut bacteria linked to healthy aging in older adults. www.sciencedaily.com
Frailty is a syndrome that commonly manifests in older adults. It carries an increased risk for poor health outcomes including falls, disability, hospitalization, and death. A key driver in the development of frailty is inflammation, which often accompanies diet-induced changes in the gut microbiota. Findings from a recent study suggest that eating a Mediterranean diet, which is rich in fruits, vegetables, legumes, fish, and fiber, and low in saturated fat and red meat, alters the gut microbiome in older adults to reduce the risk of frailty.
The intervention study involved more than 600 older, non-, pre-frail, or frail older adults living throughout Europe. Roughly half of the participants followed a Mediterranean diet for one year, while the other half, which served as the control group, ate their regular diets. Before and after the one-year intervention, the authors of the study profiled the microbial makeup of the participants' gut microbiome. Whereas the microbiome of the participants from the northern European countries shared many similarities, the participants from Italy had a distinct microbiome.
At the end of the study, the participants who adhered to the Mediterranean diet showed reductions in biomarkers associated with inflammation (such as C-reactive protein and interleukin 17) and improvements in frailty-associated measures (such as handgrip strength, gait speed time, and cognitive function). The authors of the study observed notable changes in the participants' gut microbiomes, which were associated with higher numbers of bacteria that produce short-chain fatty acids – byproducts of dietary fiber metabolism that reduce gut inflammation.
These findings suggest that dietary interventions that promote adherence to a Mediterranean diet may be beneficial in reducing the risk of developing frailty among older adults due to changes in gut microbiota and reduced inflammation.
Interestingly, some of the benefits observed among the participants in this study may be related to their increased intake of essential vitamins and minerals. Without these nutrients, the body has to compensate for the shortages – a concept known as “triaging.” Long-term compensation contributes to aging. Watch this clip in which Dr. Bruce Ames explains this phenomenon in what he calls his triage theory.
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Time-restricted eating may help reduce weight and prevent diabetes and heart disease in people with metabolic syndrome. www.sciencedaily.com
More than a third of adults living in the United States have metabolic syndrome, a constellation of conditions that includes abdominal (central) obesity, high blood pressure, high fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. People who have metabolic syndrome are at increased risk of developing diabetes and heart disease. A new study suggests that time-restricted eating may reduce this risk.
Time-restricted eating is a form of daily fasting that aligns eating and fasting cycles to the body’s innate 24-hour circadian system. People who practice time-restricted eating typically eat during an 8- to 12-hour daytime window and fast during the remaining 12 to 16 hours.
This study involved 19 adults (average age, 59 years) who had metabolic syndrome. Most of the participants were obese, took a statin or antihypertensive drug, and had poor blood glucose control. They followed a time-restricted eating pattern that allowed them to eat during a 10-hour daytime window with a 14-hour overnight fast for 12 weeks. No overt attempt to change physical activity or diet quality or quantity was required.
At the end of the study, participants exhibited reduced waist circumference and body fat, lowered blood pressure, and improvements in lipid profiles and blood glucose control. These findings suggest that time-restricted eating may have potential as an adjunct to current therapies to treat metabolic syndrome.
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Time-restricted eating, a ketogenic diet, and exercise improved cognitive function and markers of metabolism in a woman with ApoE4 and Alzheimer's . www.sciencedirect.comAlzheimer's Ketosis Fasting Insulin Triglycerides Time-Restricted Eating Metabolic Syndrome Ketogenic Diet
Time-restricted eating (TRE), a ketogenic diet, and exercise improved cognitive function and markers of metabolism including triglycerides, VLDL, and HbA1c in a 71-year-old woman with ApoE4 that has mild Alzheimer’s disease and metabolic syndrome (case study).
This is an interesting proof of principle study showing that implementing a nutrition protocol purposed at raising plasma ketones through fasting (TRE) a ketogenic diet and physical exercises can compensate for insulin resistance and the ApoE4 gene in a mild Alzheimer’s patient experiencing cognitive impairment.
The APOE4 gene is the largest risk factor for Alzheimer’s disease besides age itself.
To learn more check out this episode highlight of Dr. Dale Bredesen talking about time-restricted eating and a ketogenic diet in the context of Alzheimer’s disease in people with and without ApoE4.
Episode: https://youtu.be/PWZbeq6MCKU
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The gut microbiome and kynurenine pathway/tryptophan metabolism www.frontiersin.org
[Abstract]
The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance.
Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host’s immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity.
This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation. Moreover, this review provides new insight regarding the influence of the gut microbiota on Trp metabolism. Additional comprehensive analyses of targeted Trp metabolites (including endogenous and bacterial metabolites) are essential for experimental preciseness, as the influence of the gut microbiota cannot be neglected, and may explain contradictory results in the literature.
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Why Broth is Beautiful: Essential Roles for Proline, Glycine and Gelatin - Weston A Price www.westonaprice.org
Gelatin’s traditional reputation as a health restorer has hinged primarily on its ability to soothe the GI tract. “Gelatin lines the mucous membrane of the intestinal tract and guards against further injurious action on the part of the ingesta,” wrote Erich Cohn of the Medical Polyclinic of the University of Bonn back in 1905. Cohn recommended gelatin to people with “intestinal catarrh”–an inflammation of the mucus membrane now called irritable bowel syndrome. Interestingly, the type of gelatin used in follow-up experiments done on people with even more serious intestinal diseases was specified as a “concentrated calves foot broth.”37 This form of gelatin would have been rich in cartilage and bone and presumably provide a better amino acid profile than straight collagen. A 1999 German study also proved the truth of the saying “Man ist was man isst.” Their study was inspired by reports of the positive influence of gelatin on degenerative diseases of the musculo-skeletal system and curiosity about the “therapeutic mechanism and the absorption dynamics.” Mice fed radioactive gelatin hydrolysate were compared to control mice administered radioactive proline. They found that 95 percent of the gelatin was absorbed within the first 12 hours, and the labeled gelatin found in the tissues was similar to that of labeled proline with one exception–the absorption and accumulation of gelatin in the cartilage was twice as high. This suggested a salutary effect of gelatin on cartilage metabolism that would not occur with the ingestion of proline alone. They concluded, “These results demonstrate intestinal absorption and cartilage tissue accumulation of gelatin hydrolysate and suggest a potential mechanism for previously observed clinical benefits of orally administed gelatin.”51 - See more at: http://www.westonaprice.org/health-topics/why-broth-is-beautiful-essential-roles-for-proline-glycine-and-gelatin/#sthash.G5l30GLj.dpuf
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[TIMELINE] Joe Rogan Experience #502 with Dr. Rhonda Patrick www.foundmyfitness.comOmega-3 Depression Insulin Fatty Liver Vitamin A Isothiocyanates Antioxidant Protein Dairy Blood Sugar Metabolic Syndrome Myrosinase
This is the full minute-by-minute timeline for JRE #502. Click here to watch the video on YouTube.
- 00:02:42 - Starts off by talking about kappa opioids and dynorphin and how you feel stress right before important events
- 00:04:24 - Joe talks about how great you feel after a competition (fight)
- 00:05:35 - Talks about how capsaicin in spicy food also induces a release of endorphins via dynorphin agonization
- 00:06:22 - Briefly mentions sauna/hyperthermic conditioning article featured on 4-Hour Workweek
- 00:06:45 - Description of hormesis and how this is part of the mechanism of action for things like EGCGs in green tea and polyphenols in fruit.
- 00:07:50 - Joe brings up that Rhonda suggested mycotoxin might be hormetic previously, Rhonda clarifies this was entirely and highly speculative. Includes jazz hands.
- 00:08:45 - Joe mentions that his best decisions are made after a good workout. He does not trust his judgment if he has not got a good workout in.
- 00:09:15 - Discussion of exercise and how it grows new brain cells (neurogenesis) via the BDNF pathway and how the growth of new brain cells allows you to forget other memories.
- 00:11:20 - Joe mentions how people in highschool that never left your small hometown sometimes remember stuff you don’t. Get out of the small town, highschool friends. Make new memories.
- 00:12:00 - Talks about how amygdala activation from either extreme excitement or fear increases episodic memory.
- 00:12:15 - Talks about her new paper and how serotonin plays a role in brain function/dysfunction, behavior, and episodic memory.
- 00:13:38 - Joe brings up MDMA burnout and suggests serotonin’s role in episodic memory may be why the MDMA/roller burnout stereotype exists
- 00:15:00 - Explanation of what receptor down-regulation is and why it adds enormous complexity to understanding the effects of drugs, like SSRIs.
- 00:16:27 - Discussion of “Serotonin Syndrome.”
- 00:17:22 - Most serotonin is actually made in the gut, not the brain.
- 00:17:44 - Discussion of how the genes that convert tryptophan to serotonin found in the gut (TPH1) and in the brain (TPH2) are show a characteristic nucleotide sequence known as a “Vitamin D Response Element” that seems to indicate, for the most part, that Vitamin D represses the production of serotonin in the gut (TPH1) and increases serotonin in the brain (TPH2). This is the subject of Rhonda’s most recent academic paper: “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”
- 00:18:45 - Serotonin made in the gut has been shown to cause gastrointestinal inflammation by activating T cells and causing them to proliferate. Knocking out TPH1 in a mouse model of colitis ameliorates the inflammation associated with the disorder.
- 00:21:55 - Theoretical vitamin D mechanism may play a role in the development of autism by depriving developing foetus of serotonin that serves as an “early brain morphogen” when mothers are deficient in vitamin D.
- 00:23:45 - Autism appears to be developing early in utero (during pregnancy) and seems to show indications of being at least partially related to environment.
- 00:24:00 - Estrogen can activate TPH2 in lieu of Vitamin D and thus may explain why autism is predominantly found in males.
- 00:24:30 - Gut inflammation is common among autistics.
- 00:24:45 - Explains 5-HTP bypasses the normal tryptophan hydroxylase (TPH) conversion, and because of that it can be converted into serotonin more rapidly… but (hypothetically) too soon and in the gut instead of the brain.
- 00:25:35 - Tryptophan gets transported into the brain in order to be converted into serotonin by tryptophan hydroxylase (TPH2) but competes with BCAAs for transport into the brain, which are transported preferentially.
- 00:25:55 - Tryptophan is less abundant of an amino acid than branch chain amino acids like leucine in protein.
- 00:26:55 - Joe asks Rhonda if T cell activation/proliferation in the context of TPH1 has relevance for AIDS.
- 00:28:00 - Joe relates how “New Mood” (Onnit’s product) was originally called “Roll Off.”
- 00:30:30 - Joe quips that it was recently experimentally validated in mice that DMT is produced in the pineal glands of mice during sleep, goes on to talk about speculation that near death experiences relating to altered perception from endogenous DMT release.
- 00:35:10 - Plays a video of a jaguar eating hallucinogenic plants.
- 00:37:20 - Talks about monoamine oxidase
- 00:38:40 - Merits of “theoretical papers” (like “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”)
- 00:39:37 - 70% of population is vitamin d deficient. Segways to awesome infographic created by @tjasonwright which covers a ton of the basic facts about vitamin D.
- 00:43:02 - BaadBobby’s Dad turned Joe onto TA-65. TA-65 has been shown to increase telomere length, but theres a guy who sued the company producing it. Anecdotally, BaadBobby’s dad had improvements in eyesight.
- 00:45:00 - Explanation of what telomeres are.
- 00:48:50 - Special enzyme telomerase rebuilds telomeres, but it’s found mostly only in stem cells… and more importantly: cancer cells. Cancer cells hijack this telomerase normally reserved for stem cells to live forever. Strangely… Mice, unlike humans, actually express telomerase in all of their cells and don’t have telomere shortening.
- 00:50:10 - Werner’s syndrome involves excessive telomere shortening.
- 00:53:33 - Explains how aging is a function of DNA damage and discusses DNA damage assay (test) that Rhonda performs.
- 00:55:30 - Obesity link to increased DNA damage.
- 00:56:50 - Talks about TA-65’s active ingredient in a study was shown to genuinely increase telomerase activity and length of telomeres.
- 00:58:22 - TA-65 study showed a 40% increase in telomere length in white blood cells in some humans studied.
- 00:58:44 - Second study on TA-65 using special mouse model from well-known lab also showed re-activation of telomerase, and even began reversing aging of their tissues. Mice notably did not get cancer. Reinforces findings of first study.
- 01:01:30 - Still concerned TA-65 could encourage the growth of pre-cancerous cells.
- 01:02:00 - Joe brings up alkalizing diet for cancer prevention (he’s a skeptic).
- 01:03:05 - Bad bacteria in gut is affected by pH.
- 01:06:20 - Joe brings up argument that sugar consumption affects growth of cancer.
- 01:07:50 - Explains because cancer cells become glycolytic which is why people fixate on sugar as a potential cancer cell.
- 01:08:40 - Rhonda mentions that taking away glucose, but allowing continued presence of glutamine allowed cancer cells to keep growing in vitro.
- 01:09:50 - Folic acid needed in the absence of cancer because you need it to build new DNA – but this is a problem if you do have a cancer because it can be a bad thing for the same reasons (folic acid needs to produce DNA because cancer cells are highly proliferative).
- 01:12:00 - Glucosinolates are cleaved into isothiocyanates by myrosinase which is de-activated by heat. Isothiocyanates are potent anti-cancer agents. Recent anti-kale stuff is, in a way, anti-isothiocyanates. Additionally, if you boil kale and de-activate myrosinase you’re actually decreasing the amount of isothiocynates by removing myrosinase.
- 01:14:00 - Kale thyroid stuff is probably only relevant if you’re very deficient in iodine – probably better to continue getting your isothiocyanates for cancer preventative reasons rather than sweating this stuff.
- 01:16:35 - Rhonda mentions tumor suppressor genes, which are activated by hormesis (good stress triggered by things like isothiocyanates).
- 01:19:20 - Joe brings up Dave Asprey’s take on boiling kale to remove oxalic acid.
- 01:20:10 - Spinach that was either raw, boiled, fried, or frizzled and found that raw and boiling doesn’t affect absorption, but it did very modestly affect minerals in kidneys if raw… didn’t seem to cause kidneys stones (in mice). Probably requires absurd amounts of spinach to cause kidney stones. Just not convinced that it’s bad to eat spinach or kale raw.
- 01:20:20 - Vegetables do make compounds that are sort of “bad for you” but have a net positive effect because they induce hormesis.
- 01:24:33 - JRE consensus of #502 –eating raw spinach and kale is good for you.
- 01:25:10 - Joe throws a curveball by bringing up a documented case of presumed oxalate induced nephropathy (kidney disease) from 1985 to 2010 – only 36 patients documented by paper. Only three patients really suspected that it was caused by raw juicing.
- 01:27:30 - Discussion of vegetable smoothies begins here – specifically using these powerful blenders which leave the fiber in, not juicing.
- 01:28:45 - Brock Lesnar allegedly ate nothing but meat, got diverticulitis.
- 01:29:07 - Putrefying bacteria make nasty smelling hydrogen sulfide farts, use sulfate as source of energy. Needs heme from red meat as a cofactor for creating hydrogen sulfide. Hydrogen sulfide prevents human gut cells from making energy (ATP), and thus causes break-down of gut-mucus barrier.
- 01:32:25 - Brings up episode with Dr. Offitt on Bryan Callen’s podcast. Offitt claims vitamins and antioxidants cause cancer.
- 01:35:20 - Beginning of general debunking of Offitt’s claims.
- 01:36:05 - Randomized double-blind placebo controlled trials are awesome, but using them for nutrition research and expecting the design to perform as effectively is misguided.
- 01:37:30 - Everyone has different levels of vitamins & minerals in their body, but baseline for drugs is always the same: zero. This is an important fundamental difference.
- 01:42:20 - Years of research has to be published even if results aren’t great, and this requires salesmanship. This affects some of the misleading presentation of research.
- 01:43:04 - Joe brings up highly publicized and contentious “Enough is Enough” editorial which was covered at length in podcast #459.
- 01:46:28 - Begin discussion of Vitamin E prostate cancer study (the SELECT trial).
- 01:47:35 - Comparison of Alpha Tocopherol & Gamma Tocopherol forms of vitamin E. Alpha tocopherol serves predominantly as an antioxidant, gamma tocopherol serves as an anti-inflammatory agent by reducing reactive nitrogen species (also an anti-oxidant activity). Alpha tocopherol doesn’t serve the same anti-inflammatory behavior, and this is important because inflammation is a cancer initiator (among other things), and excessive alpha tocopherol consumption depletes gamma tocopherol from tissues.
- 01:50:45 - Study on prostate cancer found that alpha tocopherol and selenium didn’t affect cancer incidence at 5-year followup but at 7.5 year follow-up cancer risk for prostate cancer shot up from taking 400 IU of alpha tocopherol (vitamin E) per day. Importantly, what was found at the 5-year followup was that (relative to baseline) gamma tocopherol was depleted from the tissues. Those who weren’t deficient selenium (& were supplementing) that took the 400 IU of alpha tocopherol didn’t experience the increase in prostate cancer incidence.
- 01:52:05 - One of the proteins selenium is for is important for preventing damage from reactive nitration products. Nitration damage can cause cancer. This is an interesting novel mechanism by which a depletion of gamma tocopherol through a combination of inflammation and an increase in reactive nitratition products might be responsible for the increase cancer incidence found in this study.
- 01:54:00 - Discussion of vegetable smoothie as a good source of vitamin E, and also natural magnesium (from chlorophyll molecules – this was mentioned in JRE #459)
- 01:54:45 - Mixed tocopherol Vitamin E supplements exist which aren’t quite as high dose as 10x the RDA (400 IU) like used in those studies.
- 02:01:18 - RDA for Vitamin D is 600 IU a day. One study showed that 4,000 IU was more appropriate for actually adequately fixing without toxicity in deficient populations. 2000 to 4000 IU of vitamin D is probably a good range except for in cases of severe deficiency.
- 02:03:18 - Offit lumped omega-3 in with “antioxidants that cause cancer”, but this is misleading given the fact that randomized controlled trials have shown that omega-3 supplementation actually reduces all-cause mortality.
- 02:03:39 - 1500 IU of vitamin D a day has been correlated to a 17% reduced cancer risk (overall).
- 02:04:15 - Study based off of self-reported questionaire found that women who took vitamins (supplements) - on a daily basis had the longest telomeres.
- 02:05:45 - She tries to get all her micronutrients, as much as she can, from her diet including vegetable smoothies, fish, etc. However, in addition to her diet she takes: omega-3 fatty acids, vitamin D, a multi-vitamin which has selenium and other trace elements, iodine, B-complex.
- 02:06:30 - B vitamin deficiency is less common due to fortification. However, she supplements B vitamins anyway because changes in mitochondrial membrane rigidity that occurs with age alters the binding affinity (as represented by the constant kM) of important proteins needed to generate energy in the form of ATP which are embedded in the mitochondrial membrane. The Ames lab has partly demonstrated, however, that increasing the concentration of B vitamins compensates for these age related changes caused by changes in the confirmation (shape) of the proteins.
- 02:08:00 - Rhonda increasingly prefers Swanson brand vitamins, but gets omega-3 from nordic naturals.
- 02:10:00 - B vitamins are probably less dangerous because they’re water soluble (excess is more readily excreted, similar to Vitamin C)
- 02:11:00 - Plant form of omega-3, ALA, converts to EPA (normally found in fish) fairly inefficiently at a rate of about 5%.
- 02:12:13 - Microalgae oil is a good alternative to flaxseed oil if you’re trying to meet EPA/DHA needs and avoiding fish oil for one reason or another.
- 02:13:30 - Omega-3 EPA is a potent anti-inflammatory, and DHA is a really component of your cell membranes – and makes up about 40% of the brain.
- 02:13:54 - She takes about 6 pills of her omega-3, which amounts to ~3 “servings” of 800mg of EPA, and 600mg of DHA. (2400 and 1800 mg respectively)
- 02:15:28 - Omega-3 EPA, which can be bought more concentrated for its particular effects, interacts with the arachnidonic acid pathway to reduce inflammation. The arachnicdonic acid pathway is responsible for creating prostaglandins which activate the COX pathway.
- 02:16:05 - 2 grams of EPA per day has been shown to reduce C-reactive protein (CRP), which is a generalized systemic marker for inflammation but is most well known for its use to asses risk of cardiovascular disease.
- 02:17:45 - Omega-3 fatty acids are prone to oxidation. Refrigeration helps with this, however. Also check if they go rancid by smell, if smell bad then probably rancid.
- 02:20:00 - Talks about krill oil. Joe lists off a bunch of points from a Mercola article, and Rhonda points out it’s talking about ordinary effects of omega-3 and suggesting they may not be unique to krill oil.
- 02:27:29 - Recommends Linus Pauling Institute for good, objective source of supplemental micronutrient reviews.
- 02:28:35 - Brief mention of WellnessFX as a useful tool for getting a broad spectrum blood test checking for relevant markers for vitamins, minerals, inflammation, etc.
- 02:31:00 - Whackiness of homepathy discussed. Homeopathy makes use of official sounding measuring system that measures an absurd amount of dilution that actually guarantees that what you’re taking doesn’t actually include the active ingredient the supplement is being marketed for.
- 02:33:25 - Discusses how emerging research showing wisdom teeth has dental pulp stem cells in them and they offer promise for eventually being used as a source of cells that can be differentiated into things like brain cells. You can bank children’s teeth or adult wisdom teeth. Usually like $625 to “process” a tooth, and around $125/year to store it.
- 02:36:16 - They can now take fibroblast cells from skin, the sort that you slough off everyday, and add transcription factors to turn them into “pluripotent” stem cells which can turn into brain cells or liver cells.
- 02:37:35 - Joe brings up study where they took blood of young mice, injected it into old mice, and found the older mice experienced tissue regeneration. Inverse was also true: injecting young mice with old mouse blood increased rate of aging.
- 02:38:54 - Human “methylome” now being studied which is revealing a specific pattern of methylation in DNA that can be used to actually identify the chronological age of people. Since epigenetics is obviously playing an important role in age, this is another promising area of new inquiry that may eventually reveal how to reprogram our cells to “be younger”. Cancer cells show a methylation pattern that is ordinarily associated with old age and are clustered around areas related to DNA repair, mitochondrial metabolism, antioxidant genes (all areas associated with aging).
- 02:43:12 - Scientists are now able to take renal cells excreted in urine and turn them into pluripotent stem cells
- 02:43:45 - Rant about lack of funding in science reducing room for creativity/moonshots.
- 02:48:40 - Joe brings up new studies showing its possible to create artificial blood for transplant.
- 02:50:06 - Inactivating insulin growth factor in c. elegans worms doubles their lifespan from about 15 to 30 days.
- 02:52:40 - Joe asserts (reasonably so) that by age 200 he will most likely be a wizard.
- 02:55:42 - Joe relates the fact that he’s actually been evacuated twice due to large fires in his neck of the woods of L.A.
- 02:57:45 - Rhonda begins plug of iPhone app, website, Twitter, and podcast.