Browse the evidence

Testosterone therapy is conditionally recommended for postmenopausal women with properly diagnosed hypoactive sexual desire disorder (HSDD) to achieve midnormal premenopausal levels, with monitoring for androgen excess.

If you are postmenopausal and have been diagnosed with HSDD, a trial of physiological testosterone may be considered. The goal is to reach midnormal premenopausal levels, not supraphysiological ones. You must be monitored closely for signs of androgen excess, and therapy should be stopped if there is no response within 6 months.

Propionate metabolism in the liver stimulates hepatic gluconeogenesis, which activates hepatic vagal afferents to signal satiety to the brainstem, a mechanism well-established in ruminants but less defined in humans.

Propionate from fiber fermentation may contribute to satiety via liver signaling, but this is likely a secondary effect compared to direct gut hormone release in humans.

Omega-3 fatty acid supplementation reduces cardiovascular morbidity and mortality by lowering triglycerides, reducing blood pressure, and decreasing arrhythmia risk.

To protect your heart, aim for at least two servings of fish per week, ensuring one is oily (like salmon or mackerel). If you don't eat fish, consider a fish oil supplement providing around 1g of EPA/DHA daily, especially if you have existing heart conditions. This is a foundational dietary shift, not a quick fix.

Maternal intake of Omega-3 fatty acids (specifically DHA) reduces the risk of premature birth and improves fetal intellectual development.

If you are pregnant or planning to be, aim for 200mg of DHA daily. The best source is 1-2 servings of oily fish per week. If you are vegetarian, use a fish oil supplement or ensure your infant formula is fortified with DHA, as plant-based ALA is not converted efficiently enough for fetal brain needs.

Accelerated gastric emptying in overweight and obese individuals may contribute to rapid postprandial glucose increases and insulin resistance.

For those with obesity, managing gastric emptying through dietary choices (e.g., fiber) might help stabilize blood sugar. However, more research is needed to confirm this link.

Pharmacological activation of the Nrf2 pathway using small molecule activators (e.g., Bardoxolone methyl, Sulforaphane) shows promise in improving renal function and metabolic indices in animal models, but human trials have shown mixed results with potential cardiovascular risks.

Be cautious with unapproved Nrf2-activating drugs like Bardoxolone methyl. While they showed promise in early trials for kidney function, a later large trial was stopped due to heart-related risks. Do not self-medicate with experimental compounds. Stick to natural dietary sources of Nrf2 activators (like cruciferous vegetables) which are generally safe.

Quercetin improves glucose metabolism and reduces obesity markers in animal models of type 2 diabetes and high-fat diet-induced obesity through MAPK and AMPK signaling pathways.

Animal studies show quercetin can reduce fat mass and improve glucose metabolism by activating specific cellular pathways (MAPK/AMPK). However, these results have not been consistently replicated in human clinical trials, so it should not be relied upon as a primary weight loss or diabetes treatment.

Specific probiotic strains (e.g., Bifidobacterium pseudocatenulatum CECT 7765) can reduce stress-induced corticosterone levels and improve depressive-like behavior in obese animal models by modulating the gut microbiota.

This specific probiotic strain showed promise in reducing stress hormones in obese mice. While human results are not guaranteed, it suggests that targeted probiotic supplementation might be worth exploring for stress and mood management in obesity, alongside diet changes.

A specific myostatin gene variant (Lys 153 Arg) may influence muscle hypertrophy in women, but not in men.

Current evidence is too weak to recommend genetic testing for myostatin variants to guide training. The potential link is interesting but unproven.

Gut microbiota modulate appetite by influencing the metabolism of Tryptophan (Trp) into serotonin (5-HT) and indole derivatives, which regulate satiety and intestinal permeability.

Tryptophan metabolism by gut bacteria influences serotonin levels, which affect appetite. However, because results are inconsistent and depend on dosage and health status, focus on whole-food sources of tryptophan (e.g., turkey, eggs, seeds) rather than high-dose supplements for appetite control.

High glycemic load diets are associated with an increased risk of colorectal and breast cancer, potentially through mechanisms involving hyperinsulinemia, insulin resistance, and insulin-like growth factors (IGFs).

While the evidence is still emerging, choosing low-glycemic index foods may help reduce the risk of colorectal and breast cancer. These foods may help regulate insulin and insulin-like growth factors, which are implicated in cancer development. However, more research is needed to confirm these findings.

Combined diet and exercise interventions during pregnancy do not clearly reduce the risk of pre-eclampsia compared to standard care.

While combining diet and exercise during pregnancy is beneficial for preventing gestational diabetes and may help with caesarean section rates, current evidence does not show it clearly prevents pre-eclampsia. Continue to follow your healthcare provider's advice for managing blood pressure and other pregnancy risks.

Pomegranate-derived phytochemicals, specifically anthocyanins (ATs) and urolithins (metabolites of hydrolyzable tannins), exhibit anti-cancer and cardioprotective bioactivities through mechanisms including aromatase inhibition, apoptosis induction, and oxidative stress reduction.

This paper reviews laboratory and animal studies showing that compounds in pomegranate (like anthocyanins and urolithins) can inhibit cancer cell growth and support heart health in controlled settings. However, it explicitly notes that these findings have not been confirmed in human clinical trials. Do not use pomegranate supplements as a treatment for cancer or heart disease without consulting a physician, as the clinical efficacy and dosage protocols for humans are not established.

Higher abundance of Dysosmobacter welbionis in the human gut is negatively correlated with Body Mass Index (BMI), fasting glucose, and glycated hemoglobin (HbA1c) in obese individuals with metabolic syndrome.

In humans with obesity and metabolic syndrome, higher levels of Dysosmobacter welbionis in the gut are associated with lower BMI, better blood sugar control, and lower HbA1c. This suggests that maintaining or increasing this bacterium may be beneficial for metabolic health.

Hesperidin reduces obesity and lipid accumulation by activating AMPK and PPAR signaling pathways, which regulates lipid and glucose metabolism, while simultaneously reducing inflammation via NF-κB inhibition and oxidative stress.

This paper reviews how hesperidin, a compound found in citrus fruits, may help with obesity in animal studies by improving how the body handles fat and sugar. However, it explicitly states that human clinical trials are lacking. Therefore, you cannot currently rely on hesperidin supplements for weight loss based on this evidence alone; more research is needed to establish safe and effective human dosing.

Resveratrol improves insulin sensitivity in older adults with impaired glucose tolerance, supporting its potential as an intervention to delay aging based on its effects on the insulin/IGF-1 pathway.

Resveratrol may improve insulin sensitivity in older adults with impaired glucose tolerance. While more research is needed, it represents a potential dietary supplement to support metabolic health. Consult a healthcare provider before starting.

Obesity may be characterized by a 'NEAT Conservers' phenotype, where the brain's response to signals that stimulate movement (like orexin) is dulled, leading to low NEAT and weight gain.

Understand that your brain may have a 'dulled' response to movement signals, making it harder to stay active. This is not a moral failing. Use environmental strategies (like walking desks) and behavioral techniques (like STRIPE) to overcome this biological resistance.

Time-Restricted Feeding (TRF) shows profound metabolic benefits in rodents (improved glucose tolerance, reduced adiposity/steatosis) even without energy restriction, but human studies are sparse, mixed, and methodologically limited, with some showing worsened glycaemia.

If you try Time-Restricted Feeding (TRF), limit your eating window to 10-12 hours daily. Be aware that human evidence is mixed; some studies show worsened glycaemia, possibly due to timing (e.g., evening eating) or methodological issues. Monitor your blood glucose and lipids, and consider experimenting with earlier eating windows if possible, as this may align better with circadian biology.

Caloric restriction extends lifespan in humans by modulating epigenetic markers, specifically through DNA hypermethylation of the p16INK4a gene promoter and SIRT1-mediated deacetylation.

Research suggests that the longevity benefits of CR in humans may involve specific epigenetic changes, such as the silencing of the p16INK4a gene (a marker of cellular senescence) via DNA methylation and SIRT1 activation. This provides a biological basis for why CR might slow aging, though it does not yet translate to a guaranteed lifespan extension protocol for individuals.

Weight loss interventions in overweight and obese men do not show consistent or significant improvements in fertility outcomes due to a lack of high-quality randomized studies.

For overweight or obese men seeking to improve fertility, current evidence is insufficient to recommend specific weight loss protocols, though general health benefits apply. More research is needed.

Exercise induces a phenotypic switch in white adipose tissue (WAT) to thermogenic 'beige' adipocytes via multiple mechanisms including myokine secretion (irisin, IL-6, meteorin-like), natriuretic peptides, and angiogenesis, although the metabolic benefit and necessity of this process in humans remain uncertain.

Exercise likely triggers biological changes in fat tissue (browning) in animals, but this hasn't been proven to happen or help in humans. Don't rely on 'browning' as a weight loss strategy; focus on the proven benefits of exercise like improved insulin sensitivity and cardiovascular health.

Intermittent Fasting (IF) in normal-weight subjects may cause adverse metabolic effects, including increased visceral fat, muscle insulin resistance, and increased intramyocellular triglycerides, which are not seen with Intermittent Energy Restriction (IER) or Continuous Energy Restriction (CER).

If you are already lean, avoid total fasting (0 calories). It may cause your body to store fat in your muscles and liver, worsening insulin sensitivity. Stick to partial restriction (eating some food) if you want to try intermittent fasting.

Asprosin promotes hepatic glucose production (gluconeogenesis) and stimulates appetite (orexigenic effect) via central and peripheral signaling pathways, although the reproducibility of these effects is controversial due to reagent quality issues.

Research suggests asprosin might increase hunger and liver glucose output, but studies are inconsistent. Some early positive findings may have been due to experimental errors. Until the science is settled, focus on proven methods for managing hunger and blood sugar like balanced nutrition and exercise.

Asprosin may have a protective role in cardiovascular disease by preventing cardiomyocyte apoptosis and improving mesenchymal stromal cell function in myocardial infarction models.

Current research indicates asprosin might protect heart cells from damage in diabetic conditions and improve stem cell therapy outcomes for heart attacks. However, this is still in early research stages. For now, managing cardiovascular risk factors remains the standard of care.