Browse the evidence

Intermittent fasting enhances cognitive function and protects against neurodegenerative diseases by increasing BDNF and ketone levels.

Fasting may help your brain stay sharp as you age. It increases BDNF, a protein that supports brain cells, and ketones, which the brain uses efficiently. This might protect against cognitive decline.

Administration of antiangiogenic agents (specifically angiostatin, endostatin, or TNP-470) induces dose-dependent, reversible weight loss and adipose tissue loss in obese animal models without reducing food intake.

This research suggests that blocking the blood vessel growth required for fat tissue expansion can cause fat loss even if you eat the same amount of food. While this is currently only proven in mice using specific drugs (like angiostatin or endostatin), it implies that future treatments might target the blood supply to fat cells rather than just focusing on diet and exercise.

Initiation of testosterone therapy (TT) in men aged 65 years and older is associated with a significantly increased risk of non-fatal myocardial infarction within the first 90 days of prescription.

If you are a man over 65 starting testosterone therapy, be aware that your risk of a heart attack is roughly doubled in the first three months. This risk is highest in men with existing heart disease. Discuss this risk with your doctor, who may monitor you more closely or consider alternative treatments if you have significant cardiovascular history.

Initiation of testosterone therapy (TT) in men under 65 years with a pre-existing history of heart disease is associated with a significantly increased risk of non-fatal myocardial infarction within the first 90 days of prescription.

If you are under 65 but have a history of heart disease, starting testosterone therapy significantly increases your risk of a heart attack in the first three months. This risk is nearly three times higher than baseline. You should discuss this specific risk with your doctor, who may recommend closer monitoring or alternative treatments.

Testosterone therapy (TT) does not significantly increase the risk of non-fatal myocardial infarction in men under 65 years without a history of heart disease.

If you are under 65 and have no history of heart disease, starting testosterone therapy does not appear to significantly increase your risk of a heart attack in the first three months. However, you should still discuss potential risks with your doctor, especially if you have other cardiovascular risk factors.

Gut microbiota composition directly influences systemic inflammation through the production of specific metabolites: Short-Chain Fatty Acids (SCFAs) like butyrate inhibit pro-inflammatory pathways (e.g., NFκB), while Lipopolysaccharides (LPS) and Trimethylamine N-Oxide (TMAO) promote inflammatory cascades and insulin resistance.

Focus on dietary fiber to feed beneficial gut bacteria that produce anti-inflammatory short-chain fatty acids (like butyrate). Reduce intake of high-fat, low-fiber 'Western' diets which may promote pro-inflammatory bacteria and LPS release. Probiotic therapies targeting specific strains (e.g., Faecalibacterium) show promise for reducing inflammation, but individual responses vary.

Sirt1 activation promotes mitochondrial biogenesis through the deacetylation and activation of PGC-1α, a process supported by evidence from caloric restriction and specific Sirt1 activators like resveratrol and SRT1720.

Caloric restriction and compounds that activate Sirt1 (like resveratrol) may support mitochondrial health by activating PGC-1α. However, the evidence is mixed, and results depend heavily on the specific context, dosage, and individual metabolic state. It is not a guaranteed or universal solution for mitochondrial biogenesis.

Sirt1 promotes mitophagy (the turnover of defective mitochondria) through mechanisms involving NAD+ levels and potentially the PINK1/Parkin pathway.

Sirt1 activation, potentially through nicotinamide or SRT1720, may promote the removal of damaged mitochondria (mitophagy). This is part of a broader cellular quality control mechanism that may contribute to longevity and health. More research is needed to fully understand how to harness this for therapeutic benefit.

Exogenous leptin promotes angiogenesis and endothelial cell proliferation by binding to Ob-R receptors and activating tyrosine kinase-dependent pathways (specifically Erk1/2).

This research suggests that high levels of leptin, common in obesity, may actively fuel the growth of new blood vessels in fat tissue. This creates a feedback loop where more fat leads to more leptin, which builds more blood vessels, allowing even more fat storage. Managing leptin levels through weight loss may help reverse this vascular support for adipose tissue.

Testosterone therapy in adult men significantly increases hemoglobin and hematocrit levels and decreases high-density lipoprotein (HDL) cholesterol, but does not significantly affect mortality, cardiovascular events, or prostate outcomes.

If you are considering testosterone therapy, expect your red blood cell counts (hemoglobin/hematocrit) to rise and your good cholesterol (HDL) to drop slightly. You will need regular blood tests to monitor these changes. Current large-scale reviews do not show that testosterone increases your risk of heart attacks, strokes, or prostate cancer, but the long-term safety data is still considered low quality due to short study durations.

GLP-1 receptor agonists (e.g., exenatide, liraglutide) and DPP-IV inhibitors preserve beta-cell mass by stimulating proliferation, neogenesis, and inhibiting apoptosis.

GLP-1 based drugs (injections like exenatide/liraglutide or oral DPP-IV inhibitors like sitagliptin) can help your pancreas make more beta-cells and stop them from dying. This is achieved by mimicking or extending the action of the GLP-1 hormone.

Administration of the probiotic VSL#3 prevents and reverses diet-induced obesity and type 2 diabetes in mice by increasing gut flora-derived butyrate, which stimulates GLP-1 secretion from intestinal L-cells, thereby reducing food intake and improving glucose tolerance.

This research suggests that specific probiotic formulations (like VSL#3) may help manage weight and blood sugar by boosting gut bacteria that produce butyrate. Butyrate then triggers the release of GLP-1, a hormone that reduces appetite and improves glucose handling. While promising in mice, this is not yet a standard human treatment, and individual results may vary based on existing gut microbiome composition.

Very low sodium intake (<3g/day) can increase cardiovascular risk by activating the renin-angiotensin-aldosterone system and sympathetic nervous system, leading to insulin resistance and increased mortality.

Avoid extremely low sodium diets. While reducing excess salt is good, going to the other extreme can trigger stress hormones and increase heart risk. A moderate intake is best for most people.

Adipokines such as resistin and leptin play a role in insulin resistance, with resistin exhibiting insulin-antagonistic effects and leptin signaling influencing adiponectin expression.

Managing body weight can help normalize adipokine levels, potentially improving insulin sensitivity by reducing resistin and restoring healthy leptin-adiponectin balance.

Moderate alcohol consumption (6–48 g/day) is associated with a significantly reduced risk of developing type 2 diabetes compared to abstainers, exhibiting a U-shaped relationship where heavy consumption (>48 g/day) offers no such benefit.

If you do not drink, this evidence does not recommend you start. However, if you already consume alcohol moderately (up to ~48g/day, roughly 1-4 drinks depending on the beverage), this meta-analysis suggests you may have a lower risk of developing type 2 diabetes compared to those who abstain completely. Heavy drinking (>48g/day) eliminates this benefit. Note that this is observational data; lifestyle factors like physical activity and weight management remain the primary drivers of diabetes risk.

Oral butyrate supplementation reduces appetite and prevents diet-induced obesity primarily by activating the gut-brain neural circuit (vagal nerve) to suppress orexigenic neurons and increase sympathetic outflow to brown adipose tissue.

Oral butyrate supplementation (specifically sodium butyrate mixed into a high-fat diet at 5% weight/weight in this study) reduces food intake and prevents obesity in mice. The key is that it must be taken orally to trigger the gut-brain-vagus nerve pathway; injecting it does not work. It works by suppressing hunger signals in the brain and activating brown fat to burn energy. For humans, this suggests that dietary sources of butyrate (like fiber fermentation) or oral supplements might help manage appetite and weight, but the exact effective dose and long-term safety in humans require further clinical validation.

Dietary arachidonic acid (ARA) supplementation improves cognitive function in elderly individuals with low baseline serum ARA levels and enhances visual acuity and cognitive development in preterm infants when added to formula.

If you are elderly and have low arachidonic acid levels, or if you are feeding a preterm infant, ensuring adequate ARA intake (via diet or supplementation) is critical for cognitive and visual development. For the general healthy adult, ARA is an essential component of cell membranes and brain function, so avoiding it is unnecessary and potentially detrimental.

Conjugated Linoleic Acid (CLA) shows potent anti-carcinogenic and anti-lipogenic effects in animal models, but human evidence is currently insufficient to confirm these benefits at typical dietary intakes.

Do not rely on CLA supplements for fat loss or cancer prevention based on current evidence. The doses required to see benefits in animals are much higher than what humans typically eat or can safely supplement. Focus on whole foods like dairy and meat which contain natural CLA, but do not expect therapeutic effects from supplementation.

Higher urinary concentrations of specific phthalate metabolites (MBzP, MEHHP, MEOHP, MEP) are associated with increased waist circumference, and higher concentrations of MBP, MBzP, and MEP are associated with increased insulin resistance (HOMA) in adult U.S. males.

This study suggests that common environmental chemicals (phthalates) may contribute to belly fat and insulin resistance in men. While you can't eliminate all exposure, you can reduce it by avoiding plastic food containers, heating food in plastic, and choosing products with fewer fragrances (where some phthalates are found). However, focus primarily on proven factors: maintain a healthy weight, exercise regularly, and eat a balanced diet, as these have a much larger impact on your metabolic health.

Performance-enhancing drug (PED) use, particularly anabolic-androgenic steroids (AAS), is associated with a wide variety of severe adverse health effects including cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders, as well as an increased risk of death.

If you are using performance-enhancing drugs, especially anabolic steroids, you are at significant risk for serious health problems including heart disease, liver damage, hormonal imbalances, and even death. The doses used are far higher than what the body naturally produces, and combining them with other drugs increases these risks. This is not just an issue for athletes; it affects a large number of non-athletes as well. Seek medical advice if you are using these substances.

Shift work, particularly night shift work involving exposure to light at night, is associated with an increased risk of breast cancer.

Women who work night shifts have a higher risk of breast cancer, likely because artificial light at night suppresses melatonin. If you work nights, minimizing light exposure during work hours and ensuring total darkness during daytime sleep may help mitigate this risk.

Serum estrone (E1) and estradiol (E2) are positively associated with bone mineral density (BMD) in elderly men, independent of testosterone levels.

Elderly men should understand that estrogen (derived from testosterone) is vital for bone health. Low estrogen levels, even if testosterone is normal, can contribute to bone loss. Monitoring bioavailable estrogen may be as important as testosterone for preventing osteoporosis in aging men.

Activation of the bile acid receptor FXR using agonists like Obeticholic Acid (OCA) improves liver histology (NAFLD Activity Score and fibrosis) in patients with NASH, though it may negatively impact lipid profiles by increasing LDL and decreasing HDL cholesterol.

If you have NASH, your doctor might prescribe Obeticholic Acid (25mg daily) to improve liver scarring and inflammation. Be aware that this medication often raises LDL cholesterol and lowers HDL, so your lipid levels will need close monitoring. It resolves NASH in about 1 in 5 patients, so it is not a guaranteed cure but a tool to manage disease progression.

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.