Browse the evidence

Nicotinamide mononucleotide (NMN) supplementation increases NAD+ levels in aged organisms, which reverses age-related declines in mitochondrial function, insulin sensitivity, and cognitive performance.

Current evidence for NMN's anti-aging benefits comes from animal studies showing improved metabolic and cognitive health. Human clinical trials are ongoing, but no efficacy data is yet available. Do not expect proven anti-aging results in humans until more clinical data is published.

NMN supplementation improves specific age-related physiological declines, including insulin sensitivity, vascular function, and cognitive performance, in aged animal models.

Animal studies show NMN can improve insulin sensitivity, blood vessel health, and memory in old age. However, these results have not been confirmed in humans. Wait for clinical trial results before expecting these specific benefits.

Gender-affirming hormone therapy (GHT) with estrogen in transgender females (TGF) is associated with an increased risk of myocardial infarction and ischemic stroke compared to cisgender females, whereas testosterone therapy in transgender males (TGM) does not show consistent evidence of increased cardiovascular or cerebrovascular disease risk.

If you are a transgender woman taking estrogen, be aware that your risk of heart attack and stroke may be higher than that of cisgender women, so regular cardiovascular check-ups are important. If you are a transgender man taking testosterone, current evidence does not show a significantly increased risk of heart or brain vessel disease, though blood pressure and lipids should still be monitored.

Gender-affirming hormone therapy (GHT) is associated with alterations in blood pressure, with some studies showing increases in both transgender females and males, while others show decreases or no change depending on the formulation and duration of therapy.

Your blood pressure may change after starting hormones. It can go up or down depending on the type of hormone and how long you've been taking it. Regular monitoring is key to catching any changes early.

Gender-affirming hormone therapy (GHT) with estrogen in transgender females (TGF) is associated with an increased risk of venous thromboembolism (VTE), whereas no increased risk of VTE has been demonstrated in transgender males (TGM).

If you are a transgender woman taking estrogen, be aware that your risk of blood clots may be higher than that of cisgender women, especially with oral formulations. Transdermal estrogen may carry a lower risk. Discuss formulation options with your provider.

SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes by regulating key enzymatic pathways including PPARα and SREBF1c.

SIRT1 activity is crucial for healthy fat cell function, promoting mitochondrial health and lipid metabolism. While boosting NAD+ precursors like NMN can support this pathway in cell models, human application requires understanding that SIRT1 is just one part of a complex metabolic system.

Lipedema is a distinct adipose tissue disorder characterized by disproportionate lower extremity fat that is resistant to caloric restriction, diet, and exercise, unlike lifestyle-induced obesity.

If you have disproportionate leg fat that does not shrink with diet or exercise, and your feet are spared, consult a specialist familiar with lipedema. Standard weight loss advice will likely fail and increase distress.

Specialized suction lipectomy (liposuction) using lymphatic-sparing techniques is an effective treatment for reducing lipedema volume and pain.

Seek a plastic surgeon specializing in lipedema who uses lymphatic-sparing techniques (like water-assisted liposuction). Expect to use compression therapy post-surgery.

Engaging in novel cognitive experiences and environmental enrichment stimulates neuronal plasticity mechanisms (such as neurogenesis and synaptogenesis) and promotes cognitive integrity, thereby ameliorating cognitive aging.

To maintain cognitive health as you age, prioritize learning new skills and seeking novel experiences. The paper suggests that 'environmental enrichment'—such as learning a new language, instrument, or complex hobby—triggers the brain's plasticity mechanisms (like neurogenesis and synaptogenesis). This active engagement is more effective than passive activities because the novelty itself stimulates the necessary neural adaptations.

Plasma levels of NAD+ and NADP+ significantly decline with age, while levels of their reduced forms (NADH, NADPH) and catabolites (NAM, MeNAM, ADPR) increase, indicating a dysregulated NAD+ metabolome in normal aging.

This study confirms that NAD+ levels drop significantly as you age, which is linked to cellular energy and repair issues. While this paper doesn't prescribe a fix, it highlights that this decline is a key feature of aging and suggests that maintaining or boosting NAD+ levels (e.g., through precursors like NR or NMN, as mentioned in references) might be a viable strategy for healthspan.

Targeting the fundamental biological processes of aging (geroscience) delays or softens multiple age-related chronic diseases simultaneously, thereby extending healthspan more effectively than treating individual diseases in isolation.

Focus on lifestyle factors known to influence aging biology (such as caloric restriction, exercise, and metabolic health) rather than waiting for specific diseases to manifest. The goal is to delay the onset of multiple age-related conditions simultaneously by improving the body's underlying resilience and repair mechanisms.

Chronic undernutrition is associated with dysregulated PPARα and FXR signaling, leading to decreased bile acid levels, suppressed secretion of complement and coagulation factors, and increased autophagy.

In cases of severe chronic undernutrition, the body's metabolic sensors (PPARα and FXR) become dysregulated, leading to low bile acids and impaired immune/clotting functions. This suggests that nutritional rehabilitation should potentially target these specific pathways (e.g., bile acid replacement or receptor agonists) to restore normal metabolic function, rather than just providing calories.

Reduction in growth factor signaling, particularly the GH/IGF-1 pathway and cell cycle genes, is a transcriptional signature of aging in various tissues.

Aging is associated with reduced signaling from growth factors like IGF-1. Paradoxically, reducing this signaling (e.g., via genetic manipulation or drugs) can extend lifespan in many organisms, suggesting that lower growth factor signaling may be beneficial for longevity.

A decline in resting energy expenditure (REE) in severely burned patients is a significant predictor of mortality.

Monitor resting energy expenditure in burn patients; a drop in metabolic rate, rather than sustained high expenditure, may signal impending mortality and metabolic exhaustion.

Adherence to a low carbohydrate-high protein diet is associated with increased total and cardiovascular mortality in women, particularly those aged 40-49 at baseline.

If you are a woman considering a low-carb, high-protein diet for long-term weight management, be aware that this specific dietary pattern is linked to higher risks of dying from heart disease and other causes. The benefits for short-term weight loss may come at the cost of long-term survival, especially if you are in your 40s.

General Practitioners' delivery of lifestyle risk factor management (SNAP) is primarily constrained by perceived external controls (time, cost, practice capacity) and provider attitudes (self-efficacy, role congruence) rather than lack of patient motivation alone.

For healthcare providers, effective lifestyle management requires structural support (templates, dedicated time slots) and role reinforcement, not just patient education. For patients, understanding that their provider's capacity and attitude significantly impact the quality of care can help in seeking out providers who prioritize preventive health checks.

Reshaping the food environment requires simultaneous, diverse, and innovative strategies that prioritize long-term household financial management and socially-oriented healthy food practices.

For policymakers: Design interventions that combine financial support (e.g., subsidies for healthy food) with social and cultural support (e.g., community food programs). Avoid siloed approaches.

Phytoecdysteroids (plant-derived ecdysteroids) do not produce anabolic effects in humans comparable to Anabolic-Androgenic Steroids (AAS), despite structural similarities, likely due to poor bioavailability and lack of specific receptor affinity in human muscle tissue.

Do not expect phytoecdysteroid supplements to build muscle like anabolic steroids. While they share structural similarities, current evidence suggests they do not exert the same anabolic effects in humans, likely due to how the body metabolizes them.

Activation of brown adipose tissue in adult humans contributes significantly to total energy expenditure and is negatively correlated with BMI, with activation observed in lean but not obese patients in some studies.

Adults can have functional brown fat that burns calories, especially if they are lean. However, this mechanism may be less active in obese individuals. While cold exposure might help, it is not a guaranteed weight loss solution for everyone, particularly those with obesity.

Fasting-induced changes in the gut microbiome (specifically enrichment of propionate production and depletion of Escherichia coli) and immune cells (MAIT cells) are associated with sustained blood pressure reduction, independent of weight loss.

The benefits of fasting on blood pressure appear linked to gut bacteria changes (increased propionate producers, decreased E. coli) and immune system modulation (reduced inflammatory MAIT cells). These changes occur independently of weight loss, suggesting a direct metabolic/immune mechanism.

There is inconclusive evidence that NMES prevents skeletal-muscle wasting (loss of muscle mass) in critically ill patients.

Do not assume NMES will stop muscle wasting (size loss) in ICU patients. While it helps maintain strength, the evidence for preserving actual muscle mass is mixed. Focus on NMES for its proven ability to maintain functional strength rather than expecting it to fully prevent atrophy.

Pharmacological inhibition or genetic knockdown of hypothalamic Sirt1 reduces food intake and body weight gain in rodents by activating the central melanocortin system.

This research identifies hypothalamic Sirt1 as a key regulator of hunger. Inhibiting this specific enzyme in the brain reduces food intake and body weight in rats by activating the melanocortin system. While not a direct human therapy yet, it highlights Sirt1 as a potential target for treating obesity.

Fasting increases hypothalamic Sirt1 expression and activity, which deacetylates FoxO1 to regulate the central melanocortin system.

Fasting increases the activity of Sirt1 in the brain, which helps regulate hunger signals through the FoxO1 pathway. This suggests that the body's response to fasting involves specific molecular changes in the hypothalamus.

Polyphenols found in the Mediterranean Diet (e.g., from olive oil and red wine) reduce cancer risk by inhibiting inflammatory pathways (NF-κB, COX-2) and modulating signaling molecules (mTOR, sirtuins).

Consume polyphenol-rich foods like extra virgin olive oil, red wine (in moderation), and colorful fruits/vegetables. These contain compounds that help regulate inflammation and cell growth pathways, potentially lowering cancer risk.