Browse the evidence

Glucocorticoids promote hepatic de novo lipogenesis (DNL) and VLDL secretion, contributing to hepatic steatosis and increased circulating triglycerides in metabolic syndrome.

Managing chronic steroid use or high cortisol is critical for liver health. Reducing glucocorticoid exposure can help lower liver fat production and improve lipid profiles, reducing the risk of fatty liver disease.

In patients with Non-Alcoholic Steatohepatitis (NASH), elevated fecal primary bile acids (cholic acid and chenodeoxycholic acid) and increased hepatic bile acid synthesis correlate with markers of hepatic injury (steatosis, fibrosis, and elevated liver enzymes).

If you have NASH, your liver is producing and excreting higher levels of bile acids, which are directly linked to liver damage. This isn't just about 'fatty liver' from eating too much; it's a specific metabolic signaling issue. Managing this likely requires addressing the underlying metabolic dysregulation rather than just weight loss alone, as bile acid profiles are a key marker of disease severity.

Perilipin (Plin) suppresses basal lipolysis by sequestering the co-activator Abhd5, preventing it from interacting with and activating Adipose Triglyceride Lipase (Atgl).

This research explains how your body regulates fat burning. In a resting state, a protein called Perilipin acts like a lock on your fat cells, holding back the enzyme (Abhd5) needed to break down fat. Hormones released during exercise (via PKA) unlock this system, releasing the enzyme to activate fat breakdown. This highlights why hormonal signals (like those from exercise or fasting) are crucial for mobilizing stored fat, not just caloric intake.

Phosphorylation of Perilipin at specific sites (Ser-492 and Ser-517) by PKA is required to release Abhd5, allowing it to interact with and activate Atgl, thereby stimulating lipolysis.

This research identifies the specific molecular 'switch' (PKA phosphorylation of Perilipin) that turns on fat burning. When hormones signal the body to use energy, this switch releases the enzyme (Abhd5) that activates fat breakdown. This underscores the importance of hormonal triggers (like exercise or fasting) in mobilizing stored fat.

Knockdown of Abhd5 reduces both basal and stimulated lipolysis, indicating that Abhd5 is essential for triglyceride breakdown independent of Hormone-Sensitive Lipase (HSL).

This research shows that Abhd5 is crucial for fat burning, even when other enzymes (HSL) are blocked. This suggests that fat loss is a multi-enzyme process, and targeting only one pathway may not be sufficient for maximum fat mobilization.

Randomized controlled trials (RCTs) of nonnutritive sweeteners show no consistent effect on BMI, weight, or waist circumference over short-to-medium term follow-up (median 6 months).

Don't expect nonnutritive sweeteners to cause weight loss. Short-term controlled trials show no significant effect on BMI or weight. They can be part of a calorie-reduced diet, but they don't drive weight loss themselves.

Long-chain omega-3 fatty acid supplements do not significantly reduce the risk of cerebrovascular disease in primary or secondary prevention settings.

Do not rely on omega-3 supplements to prevent stroke. Clinical trials show they do not reduce risk, whereas eating fish does. Prioritize whole food sources.

Palmitate (a saturated free fatty acid) induces oxidative stress and endoplasmic reticulum (ER) calcium depletion, triggering a vicious cycle of mitochondrial dysfunction and apoptosis that leads to pancreatic beta-cell failure and insulin resistance.

High levels of saturated fats (specifically palmitate) in the blood can overwhelm cellular machinery, causing stress that damages insulin-producing cells and reduces insulin sensitivity. This risk is heightened in people with existing insulin resistance. However, not all fats behave this way; unsaturated fats (like oleate) can mitigate this damage. Managing saturated fat intake and maintaining a healthy weight to lower circulating free fatty acids are key strategies to prevent this cellular stress cycle.

Prenatal exposure to famine during early and mid-gestation is associated with a doubling of the prevalence of obesity in adulthood.

For individuals with a history of prenatal famine exposure, adult obesity risk may be biologically programmed during early development. This suggests that standard weight loss interventions might face higher resistance due to altered metabolic set points established in utero.

Centenarians and exceptionally long-lived individuals carry a similar burden of common complex disease risk alleles as the general population, suggesting that protective genetic factors buffer these risks rather than an absence of risk alleles.

You cannot change your inherited disease risk alleles, but longevity research suggests that having them does not preclude a long life. The key for the exceptionally long-lived is not the absence of risk, but the presence of protective genetic factors that 'buffer' or mitigate the impact of those risks. Focus on healthspan and managing modifiable factors, as genetic buffering appears to play a critical role in delaying disease onset.

The Tanita foot-to-foot bioelectrical impedance analyser provides body fat estimates with accuracy comparable to conventional tetrapolar impedance systems (Bodystat) when validated against a four-compartment model, despite having slightly wider limits of agreement.

You can use a simple foot-to-foot body fat scale (like the Tanita) at home with confidence. It is just as accurate as more expensive, complex hand-to-foot impedance machines when compared to high-end lab tests. Do not assume that holding handles or using more electrodes makes the reading better; the simpler device performs equivalently.

Peripheral administration of the recombinant GLP-1-albumin fusion protein Albugon activates central nervous system (CNS) satiety and gastrointestinal pathways via vagal afferents, despite its large size preventing direct blood-brain barrier crossing.

This research suggests that large, long-acting GLP-1 therapies (like Albugon) can reduce appetite and improve blood sugar even though they are too big to enter the brain directly. Instead, they stimulate nerves in the gut (vagal afferents) that send signals to the brain's satiety centers. This validates the design of long-acting GLP-1 drugs that rely on peripheral signaling to achieve central effects like reduced hunger.

The ER22/23EK polymorphism is associated with a lower risk of dementia, fewer white matter lesions, and significantly better survival rates in the elderly.

If you are elderly and carry the ER22/23EK variant, you have a genetic advantage for longevity and brain health. This variant is linked to lower dementia risk and better survival. Focus on maintaining this advantage through stress management and a healthy lifestyle, as your biology is naturally protected against the negative effects of cortisol on the brain.

Higher body mass index (BMI) in genetically identical individuals is associated with a gut microbiota network enriched in butyrate-producing bacteria (Eubacterium ventriosum, Roseburia intestinalis) and higher fecal butyrate/valerate levels, whereas lower BMI is associated with a network of primary fiber degraders (Oscillospira guillermondii).

This research suggests that a higher BMI is linked to a gut environment that produces more butyrate and valerate, driven by specific bacteria like Roseburia and Eubacterium. Conversely, a lower BMI is linked to bacteria that specialize in breaking down complex fibers (primary degraders). While this doesn't prescribe a specific diet, it highlights that the *function* of your gut bacteria (what they produce) may be more important for energy balance than just the total number of bacteria or simple ratios.

Transnational food and beverage corporations (TFBCs) drive the nutrition transition in Asia by leveraging market power to increase the availability, affordability, and desirability of ultra-processed foods, leading to rising rates of obesity and diet-related non-communicable diseases.

Understand that your food environment is not neutral. Transnational corporations actively shape what is available, how much it costs, and how appealing it is. To protect your health, prioritize unprocessed foods from sources less influenced by these corporate supply chains, such as local markets or home preparation, and be critical of marketing claims for ultra-processed products.

Activation of the nuclear receptor FXR in enteroendocrine L-cells inhibits GLP-1 production by suppressing glycolysis and proglucagon transcription, whereas FXR deactivation (via deficiency or bile acid sequestrants) increases GLP-1 and improves glucose tolerance.

This research highlights that the specific bile acid receptor targeted matters for glucose control. While TGR5 agonists increase GLP-1, FXR activation suppresses it. Therefore, therapies aiming to boost GLP-1 (like bile acid sequestrants) work partly by deactivating FXR, not just by activating TGR5. This suggests that optimal treatments might combine TGR5 activation with FXR inhibition to maximize GLP-1 production.

The kynurenine/tryptophan (Kyn/Trp) ratio in blood serves as a robust biomarker for the rate of physiological aging (inflammaging) and predicts age-related diseases and mortality.

You can monitor your Kyn/Trp ratio as a blood test to assess your biological aging rate and risk for age-related diseases. A higher ratio indicates increased inflammatory activity associated with aging. This is a diagnostic tool, not a treatment, but it helps identify who might benefit from lifestyle interventions targeting inflammation.

Mitochondrial dysfunction, including impaired beta-oxidation and increased ROS production, is a major contributing factor to NAFLD progression.

Healthy mitochondria are crucial for liver health. Exercise and weight loss help improve mitochondrial function, which may reduce liver damage.

Chronic exposure to high concentrations of fatty acids (lipid overload) inhibits AMPK activity, primarily through ceramide-dependent activation of protein phosphatase 2A (PP2A), contributing to insulin resistance and metabolic syndrome.

Excessive intake of fatty acids, particularly saturated fats like palmitate, can inhibit AMPK activity via ceramide and phosphatase pathways. This inhibition is linked to insulin resistance and metabolic syndrome. Managing lipid intake is crucial for maintaining healthy energy sensing.

Chronic exposure to high glucose concentrations inhibits AMPK activity, potentially as a protective mechanism to limit glucose uptake and prevent oxidative stress during hyperglycemia.

High glucose levels inhibit AMPK activity. This inhibition may serve as a protective mechanism to limit further glucose uptake and prevent oxidative stress. Maintaining stable blood glucose levels helps preserve healthy AMPK function.

Oral conjugated estrogen (0.625 mg/day) and combined oral estrogen/progestin (0.625 mg estrogen + 2.5 mg medroxyprogesterone acetate) significantly reduce plasma PAI-1 levels by approximately 50% in postmenopausal women, thereby enhancing systemic fibrinolysis.

For postmenopausal women, oral hormone replacement therapy (specifically conjugated estrogen) significantly lowers PAI-1, a protein that inhibits blood clot breakdown, by about half. This suggests oral estrogen may improve the body's ability to dissolve clots. However, transdermal (patch) estrogen does not appear to have this effect, and the net cardiovascular benefit is uncertain because oral estrogen might also increase other clotting risks in some women. This is not a standalone treatment for heart disease prevention without considering individual risk factors.

Oral conjugated estrogen therapy enhances systemic fibrinolysis, as evidenced by increased D-dimer levels, which correlates inversely with the reduction in PAI-1 levels.

When oral estrogen lowers PAI-1, it functionally increases the breakdown of blood clots (fibrinolysis), shown by higher D-dimer levels. This suggests oral estrogen may help prevent clot-related cardiovascular events by keeping the blood's clot-dissolving system active.

Transdermal estradiol (0.1 mg/day) does not significantly alter PAI-1 levels or enhance fibrinolysis in postmenopausal women, unlike oral estrogen.

If you use estrogen patches (transdermal), you likely will not get the fibrinolytic (clot-dissolving) benefits seen with oral estrogen pills. The patch does not significantly change PAI-1 levels.

Long-term athletic training and the resulting lower lifetime estrogen exposure significantly reduce the risk of breast and reproductive system cancers in women.

Starting athletic training early in life (high school or earlier) and maintaining it through college can significantly lower your lifetime risk of breast and reproductive cancers. This benefit is likely due to lower lifetime estrogen exposure associated with lower body fat levels.