Browse the evidence

NAFLD, particularly biopsy-proven NASH, is associated with a greater prevalence of Chronic Kidney Disease (CKD) and an increased risk of incident CKD.

If you have fatty liver, you are at higher risk for kidney disease, even if you do not have diabetes or high blood pressure. Regular kidney function tests (eGFR and urine analysis) are recommended as part of your standard care to detect early signs of kidney stress.

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).

Voluntary aerobic exercise prevents high-fat diet-induced weight gain and obesity in mice by altering the gut microbiota composition, specifically by increasing the relative abundance of Bacteroidetes and decreasing Firmicutes.

Engaging in regular, voluntary physical activity can help prevent weight gain even when consuming a high-fat diet. This benefit appears to be mediated, in part, by positive changes in gut bacteria (increased Bacteroidetes, decreased Firmicutes), suggesting that movement influences metabolism beyond just burning calories.

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.

Antioxidants yield conflicting results and are heterogeneous regarding type, dose, and duration, making them less reliable than weight loss or TZDs.

Antioxidant supplements do not have consistent, reliable results for treating NASH. The evidence is mixed, and they are not as effective as weight loss. Do not rely on them as a primary treatment.

Current elite athlete dietary guidelines, which recommend low fiber intake to minimize gastrointestinal distress, reduce microbiota diversity and functionality, thereby exacerbating exercise-induced stress, gut permeability, and mood disturbances.

Stop following standard low-fiber athlete diets blindly. While fiber might cause short-term bloating, chronic low intake starves your gut bacteria, leading to a 'leaky gut' and higher stress hormones during training. Gradually increase fiber and prebiotic intake to boost Short Chain Fatty Acids (SCFAs) like butyrate, which strengthen your gut barrier and may improve your mood and stress resilience. Focus on plant polysaccharides and resistant starches to support your microbiome's ability to regulate stress.

Targeting mitochondrial dysfunction through dietary supplements (e.g., NAD+ precursors, antioxidants) and pharmacological agents shows promise in preclinical models but lacks robust clinical translation due to issues with stability and efficacy.

While specific mitochondrial supplements and drugs are being researched, current clinical evidence is limited. The most accessible way to support mitochondrial health remains regular physical activity, which promotes mitochondrial biogenesis and function, alongside a balanced diet that provides necessary nutrients for mitochondrial function.

Mitochondrial transplantation, involving the transfer of healthy mitochondria to damaged cells, is a promising preclinical therapy for various diseases but faces challenges in clinical translation due to unstable vitality and transient effects.

Mitochondrial transplantation is an experimental therapy currently limited to research settings and specific clinical trials. It is not a standard treatment. Patients interested in this therapy should consult with their healthcare provider about available clinical trials.

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.

Early menarche is associated with an increased risk of NAFLD in adulthood, primarily driven by excess adiposity rather than estrogen activation itself.

Women who start their periods early should be vigilant about weight management. Although early estrogen exposure is generally protective, it is often linked to higher body fat later in life, which cancels out that protection and increases the risk of fatty liver disease.

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.

Panax ginseng berry extract reduces body weight in obese mice by decreasing food intake and increasing energy expenditure, whereas its isolated active component, ginsenoside Re, lowers blood glucose without affecting body weight.

The full Panax ginseng berry extract helps obese mice lose weight by making them eat less and burn more energy. However, the specific compound responsible for lowering blood sugar (ginsenoside Re) does not cause weight loss. This suggests that if you are looking for blood sugar control, you might not need the weight-loss effects, and if you want weight loss, you need the full extract, not just the isolated glucose-lowering component.

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.