Browse the evidence

Nonalcoholic steatohepatitis (NASH) is associated with a significantly higher risk of colorectal adenomas and cancer compared to simple steatosis or healthy controls.

If you have NASH (inflammatory fatty liver), you have a significantly higher risk of developing colon polyps and cancer compared to those with simple fatty liver. Discuss with your doctor whether you need earlier or more frequent colorectal cancer screening.

Pharmacological inhibition of the GH/IGF-1 axis, specifically using the GH receptor antagonist pegvisomant, lowers IGF-1 levels and improves insulin sensitivity, making it a candidate for extending healthspan.

Pegvisomant, a drug used for acromegaly, lowers IGF-1 and improves insulin sensitivity. It is being considered for longevity therapy. It requires medical supervision to monitor liver function. Do not self-administer.

Exogenous leptin administration is safe and produces statistically significant but clinically modest weight loss in humans, primarily in those with leptin deficiency, while most obese individuals exhibit leptin resistance.

Leptin therapy is safe and can lead to weight loss, but it is not a cure-all for obesity. It works best for the rare individuals who are truly leptin-deficient. For the majority of obese people who have high leptin levels (leptin resistance), the weight loss is modest and similar to other existing medications. Daily injections are required, though side effects are generally mild (skin redness).

Melatonin supplementation reduces body weight and visceral fat deposition in aging animals by increasing energy expenditure through brown adipose tissue activation and white adipose tissue browning, independent of changes in food intake.

While melatonin is widely known for sleep, this review suggests it may also support weight management in aging individuals by boosting energy expenditure and reducing visceral fat, likely through its effect on brown fat. This effect appears independent of calorie restriction. For humans, maintaining natural melatonin production by avoiding night light might be as important as supplementation.

Anabolic steroids promote muscle growth and strength, but their efficacy in improving physical function and quality of life in clinical populations (e.g., cachexia, elderly) remains unproven.

While anabolic steroids can increase muscle mass, current evidence does not confirm they improve physical function or quality of life in sick or elderly patients. Do not expect functional benefits without specific training.

Sulphur-containing amino acids in high-protein diets may raise blood pressure by causing a loss of nephron mass, posing a risk for subjects with obesity, metabolic syndrome, or type 2 diabetes.

If you have high blood pressure, obesity, or type 2 diabetes, be cautious with very high protein intakes, especially from sources high in sulphur-containing amino acids (like some animal proteins). Monitor your blood pressure and consult a doctor, as high protein might negatively impact kidney function (nephron mass) in these specific groups.

Pharmacological inhibition of mTOR (e.g., rapamycin) extends lifespan in mice, but systemic blockade in humans may accelerate sarcopenia and frailty due to impaired muscle protein synthesis, requiring tissue-specific targeting.

Rapamycin extends lifespan in mice, but its use in humans is currently limited by side effects and potential harm to muscle mass. It is not yet a recommended anti-aging strategy for humans.

Exposure to microplastics (MPs) and their chemical additives (e.g., phthalates, bisphenols) acts as an obesogen by disrupting lipid and energy metabolism through the activation of nuclear receptors (PPARs, RXR) and altering adipogenesis.

You are likely exposed to microplastics daily through air, dust, and food. While you cannot eliminate all exposure, you can reduce it by avoiding heating food in plastic containers, using glass or stainless steel for hot beverages, and filtering drinking water. The paper suggests these exposures may contribute to metabolic disruption via hormonal pathways.

Interleukin-33 (IL-33) improves insulin resistance and reduces adiposity by promoting the polarization of macrophages toward the anti-inflammatory M2 phenotype and activating innate lymphoid type 2 cells (ILC2s).

Research suggests that IL-33, a naturally occurring cytokine, may help reduce fat and improve insulin sensitivity by shifting immune cells in fat to a protective state. This is currently a research finding in animals, not a standard human treatment.

Consumption of flavanol-rich cocoa (approx. 821 mg flavanols/day) induces vasodilation via nitric oxide (NO) system activation, providing a mechanism for protection against coronary events.

To potentially support vascular health, consider consuming cocoa products specifically rich in flavanols (around 800mg/day of flavanols). This amount is significantly higher than typical milk chocolate and may require high-cocoa dark chocolate or specific supplements. The benefit comes from stimulating nitric oxide production, which helps blood vessels dilate.

Selective GSK-3 inhibitors (CHIR 98014, CHIR 99021) potentiate insulin-stimulated glucose transport and lower blood glucose in insulin-resistant states without causing hypoglycemia.

This research identifies a class of drugs (GSK-3 inhibitors) that can improve how insulin works in people with insulin resistance, helping to lower blood sugar without the risk of dangerous lows. While not a lifestyle intervention, it highlights that targeting specific enzymes can restore insulin sensitivity.

Psychological stress is associated with reduced fertility and lower ART success rates, although the evidence is considered equivocal due to measurement difficulties and lack of consensus on defining stress.

While the link between stress and fertility is not fully understood, managing stress through counseling, support groups, or relaxation techniques may improve your chances of conception, especially during ART. However, do not blame yourself for infertility if you are stressed; it is a complex biological process.

High caffeine consumption (>500 mg/day) is associated with reduced fecundity and delayed conception, although the evidence is considered equivocal.

If you are trying to conceive, consider limiting your caffeine intake to less than 500 mg per day (about 4-5 cups of coffee). While the evidence is not definitive, reducing caffeine may improve your chances of conception.

Brown adipose tissue (BAT) and inducible beige/brite adipocytes in adult humans actively oxidize metabolic substrates to dissipate energy as heat, a process mediated by uncoupling protein-1 (UCP1) and sympathetic nervous system activation, which is negatively associated with obesity.

Adult humans possess active brown and beige fat, particularly in the neck and upper trunk, which burns energy as heat. This activity is linked to leanness and can be stimulated by cold exposure or specific hormonal factors. While not a magic bullet, leveraging this biology (e.g., through cold exposure) may support weight management efforts.

Daily intraperitoneal administration of Panax ginseng berry extract (150 mg/kg) for 12 days normalizes fasting blood glucose and significantly improves insulin-stimulated glucose disposal in obese, insulin-resistant (ob/ob) mice.

This study shows that Panax ginseng berry extract can significantly improve blood sugar control and insulin sensitivity in obese, diabetic mice. The active component, ginsenoside Re, was also effective at lowering blood sugar, though it did not cause weight loss. While this is an animal study using injections, it suggests that ginseng berry extract may be a potent supplement for managing blood glucose levels in individuals with insulin resistance.

Mandatory quarantine and social isolation induce chronic stress, anxiety, and depression, which physiologically increase sympathetic nervous activity and catecholamines, thereby accelerating atherosclerosis and increasing cardiovascular disease risk.

Understand that the stress of quarantine is not just 'in your head' but has real physical effects on your heart. To mitigate this, actively manage stress through relaxation techniques, maintain social connections virtually, and prioritize sleep to counteract the sympathetic nervous system activation caused by isolation.

Metformin, an FDA-approved AMPK activator, shows promise for extending healthspan and reducing mortality in humans, though its effect on maximum lifespan in long-lived rodents remains unproven.

Metformin is a safe, widely used drug for type 2 diabetes that has been linked to reduced all-cause mortality and extended healthspan in animal models. While it shows promise for longevity, its effect on maximum lifespan in long-lived rodents is not yet proven. It is currently being tested in genetically heterogeneous mice to determine its full potential as an anti-aging therapy.

Oral administration of the intestine-selective FXR inhibitor Gly-MCA prevents and reverses high-fat diet-induced and genetic obesity, insulin resistance, and hepatic steatosis in mice by reducing intestinal ceramide biosynthesis, which restores beige fat thermogenic function.

This research identifies a specific bile acid derivative (Gly-MCA) that, when taken orally, blocks a specific receptor (FXR) in the gut. This blockage reduces harmful fats (ceramides) in the intestine, which allows body fat to burn energy more effectively, leading to weight loss and better blood sugar control in obese mice. While promising, this is currently a preclinical finding in mice and not yet an available human treatment.

Bezafibrate treatment (400 mg/day) combined with lifestyle changes normalizes dysfunctional gene expression in NAFLD by decreasing synthesis genes (ACC1, FAS) and increasing oxidation genes (CPT1a, PPARα).

For NAFLD patients, a combination of bezafibrate (400 mg/day), a strict low-calorie diet, and exercise can normalize the expression of genes involved in fatty acid metabolism. This suggests that targeting PPARα with bezafibrate may be a beneficial treatment strategy.

The cholesterol-lowering effect of soluble dietary fibers via fermentation products (specifically propionate) is inconclusive and likely not the dominant mechanism, as in vivo animal studies often show no change in hepatic cholesterol synthesis despite blood cholesterol reduction.

Don't rely on fiber fermentation (gut health) to lower your cholesterol. Focus on viscous fibers that bind bile acids. The gut benefits of fiber are real, but for heart health, the physical property of viscosity matters more than fermentation.

Oral butyrate supplementation prevents high-fat-diet-induced obesity and reverses established insulin resistance in murine models by reducing adiposity and improving insulin sensitivity.

While human trials are less extensive than animal studies, increasing butyrate production through resistant starches (like cooled potatoes or legumes) or direct supplementation may help manage body weight and insulin sensitivity, especially when combined with a diet high in fat. Consult a doctor before starting supplementation.

Reduced entry of OB protein into the brain, potentially due to high plasma concentrations saturating the transport system, may be a mechanism for reduced sensitivity of the OB protein pathway in obese individuals.

High levels of OB protein in the blood might block its entry into the brain, reducing its effectiveness. This is one possible reason why obesity can be resistant to natural regulatory mechanisms.

Leptin replacement therapy in adults with genetically confirmed leptin deficiency causes profound weight loss, resolution of type 2 diabetes, and recovery of hypogonadism.

If you have a rare genetic condition causing leptin deficiency, leptin replacement therapy can reverse morbid obesity, diabetes, and hypogonadism. However, this does not apply to the vast majority of people with common obesity, who typically have high leptin levels but are resistant to its effects. This treatment is not a general weight-loss solution for the general population.

Weight loss in obese humans significantly increases fasting plasma ghrelin levels, reversing the suppression typically seen in obesity.

When you lose weight, your body naturally produces more ghrelin, the 'hunger hormone.' This study confirms that this increase is a direct result of losing weight and correlates with how much weight you lose. Expect increased hunger as a biological response to your new, lower body weight, not as a personal failing.