Browse the evidence

Skeletal muscle cells secrete 52 novel myokines and 48 additional contraction-regulated myokines, expanding the known human skeletal muscle secretome beyond previously identified proteins like IL-6 and irisin.

Exercise triggers the release of many more signaling proteins than previously known. While we focus on well-known ones like IL-6, this research confirms that muscle contraction triggers a complex, largely uncharted hormonal response that contributes to health benefits.

Lithium extends lifespan and stress resistance by inhibiting GSK-3 (Shaggy in flies), which subsequently activates the transcription factor NRF-2 (CncC), leading to hormetic stress resistance.

The longevity benefits of lithium are mechanistically linked to the inhibition of GSK-3 and the subsequent activation of NRF-2. This pathway enhances cellular stress resistance (hormesis) without requiring autophagy. This suggests that GSK-3 inhibitors or NRF-2 activators could be viable anti-aging strategies, provided they are dosed to avoid over-activation of NRF-2, which can be detrimental to lifespan.

In rodents, resistin administration impairs glucose tolerance and insulin action, while resistin deletion improves insulin sensitivity and glucose homeostasis.

This finding is specific to rodents and does not directly translate to human treatment. Human resistin biology is different, and targeting resistin in humans has not yielded the same clear benefits as in mice.

MC4R mutations are the most common cause of monogenic obesity, found in 5-6% of severe early-onset obesity cases, and lead to hyperphagia, increased lean mass, and accelerated linear growth.

If you have severe early-onset obesity, ask about MC4R testing. It is the most common genetic cause, and identifying it opens the door to specific treatments.

DNA methylation patterns (epigenetic clocks) are among the best-studied and most accurate molecular biomarkers for predicting chronological age.

DNA methylation tests (epigenetic clocks) are currently the most reliable molecular tool for estimating your biological age, with some tests achieving an error margin of less than 5 years.

Long-term use of single antioxidant supplements (Vitamin E, Beta-carotene) does not prevent cardiovascular disease and may increase the risk of certain adverse events.

Do not take single antioxidant supplements (like Vitamin E or Beta-Carotene) to prevent heart disease. Large studies show they do not work and may even be harmful. Focus on getting antioxidants from a healthy diet instead.

MuRF1 and MuRF2 function cooperatively to downregulate anabolic stretch signals (ANP, MLP) and translational machinery (mTOR pathway) in muscle tissue.

This paper identifies the specific molecular pathway (MuRF1/2 -> mTOR/Stretch signals) that controls muscle growth. Understanding this pathway is crucial for developing future drugs to treat muscle wasting diseases, but no such drugs are currently available for human use.

Sibutramine and Rimonabant, previously approved anti-obesity drugs, were withdrawn from the market due to serious adverse effects, specifically increased cardiovascular risk and psychiatric disorders, respectively.

Do not use Sibutramine or Rimonabant. They have been withdrawn from major markets (EU, USA, Canada) due to serious cardiovascular and psychiatric risks. Orlistat is the primary long-term pharmacological option available.

Long-term exercise training does not significantly reduce the risk of mortality or hospitalization in older adults.

For older adults, engaging in moderate-intensity multicomponent exercise 2-3 times per week for at least a year does not significantly reduce the risk of mortality or hospitalization. However, it does significantly reduce the risk of falls.

Ageing is not a genetically programmed process but results from the lifelong accumulation of somatic damage due to evolutionarily optimized, limited investments in maintenance and repair systems.

Focus on maintaining health and minimizing damage (through diet, exercise, and avoiding toxins) rather than seeking a 'genetic fix' for ageing. Your body's repair systems are limited by evolutionary trade-offs, so supporting them with a healthy lifestyle is the most effective strategy for longevity.

Chemical uncouplers like 2,4-dinitrophenol (DNP) increase energy expenditure but are dangerous and cause severe side effects including hyperpyrexia and death.

Do not use DNP for weight loss. It is a toxin that can cause fatal overheating. The risks far outweigh any potential metabolic benefits.

VLCKD is contraindicated in patients with Type 1 Diabetes, renal failure, liver failure, and certain cardiac conditions due to risks of euglycemic ketoacidosis, electrolyte imbalance, and metabolic stress.

Do not attempt this diet if you have Type 1 Diabetes, kidney or liver disease, or severe heart failure. These conditions make the metabolic shift of ketosis dangerous. Consult your doctor for safer alternatives.

Multi-omics approaches (proteomics, transcriptomics) are necessary to accurately measure and understand the complexity of inflammaging, as single biomarkers like IL-6 or TNF-α are insufficient.

Current single-marker tests for inflammation are limited. Multi-omics approaches offer a more comprehensive view of inflammaging, which may lead to better diagnostics and targeted therapies in the future.

Lorcaserin was withdrawn from the US market in 2020 due to an increased risk of cancer observed in clinical trials, despite showing modest weight loss efficacy.

Lorcaserin (Belviq) is no longer available in the US because it was linked to a higher risk of cancer. Do not seek this medication.

Genetic testing for exercise prescription (e.g., predicting 'power' vs 'endurance' response) lacks sufficient scientific evidence and is not currently supported as a scientifically-sound approach.

Do not rely on commercial genetic tests to dictate your training program (e.g., whether you should do more strength or cardio work). The science does not currently support using DNA to prescribe specific training protocols. Focus on proven training principles and monitor your actual response to training.

Athletes should consume 1.4–2.0 g of protein per kg of body weight per day to optimize lean body mass and strength during resistance training.

If you train with weights, aim for 1.4 to 2.0 grams of protein for every kilogram of your body weight each day. This range is the scientific standard for building and keeping muscle while you train hard.

Natural bodybuilders in contest preparation should consume 2.3-3.1 g/kg of lean body mass per day of protein to maximize lean body mass retention.

Calculate your lean body mass (LBM) and multiply it by 2.3 to 3.1 to determine your daily protein target in grams. For example, if your LBM is 150 lbs (approx 68 kg), aim for 156-211 grams of protein per day. This high intake is crucial to prevent muscle loss while you are dieting. If you are leaner or have a larger caloric deficit, aim for the higher end of this range.

Resistance training increases skeletal muscle mass, strength, and physical function in healthy adults compared to no exercise.

If you are a healthy adult, engaging in resistance training is one of the most effective ways to increase muscle mass, strength, and physical function. You do not need a specific complex protocol to see benefits; simply performing resistance exercises against external resistance yields significant improvements compared to doing nothing.

Once-weekly mazdutide (3–6 mg) administered for 24 weeks produces robust, dose-dependent body weight reduction (up to 11.3%) and improves cardio-metabolic risk factors in Chinese overweight or obese adults.

For Chinese adults with obesity or overweight with related health issues, a once-weekly injection of mazdutide (up to 6 mg) for 24 weeks can lead to significant weight loss (up to 11%) and improved heart health markers. While gastrointestinal side effects like nausea are common, they are usually manageable and do not typically cause patients to stop treatment.

Once-weekly subcutaneous tirzepatide (5, 10, and 15 mg) produces significant, dose-dependent weight loss and improvements in cardiometabolic markers compared to placebo in adults with or without type 2 diabetes.

If you are an adult with obesity or overweight (with or without Type 2 Diabetes), once-weekly tirzepatide injections (5-15 mg) are a highly effective medical intervention for weight loss, averaging 8-12% body weight reduction depending on the dose. It also improves blood pressure, blood sugar, and lipids. While you may experience temporary gastrointestinal issues like nausea, these are usually mild and subside over time. This treatment is significantly more effective than older anti-obesity drugs and is generally safe, with no increased risk of serious adverse events compared to placebo.

Survodutide, a dual glucagon and GLP-1 receptor agonist, produces significant weight loss, BMI reduction, and waist circumference reduction in adults with overweight or obesity.

Survodutide is a once-weekly injection that significantly reduces weight, BMI, and waist size. The benefits are greater with higher doses (>2mg/week) and longer treatment durations (>16 weeks). It is particularly effective for individuals under 50 years old. Common side effects are gastrointestinal, but it offers a non-surgical option for weight management.

The efficacy of Survodutide for weight loss is conditional on dose and duration, with doses >2 mg/week and interventions >16 weeks yielding significantly greater reductions in weight and waist circumference.

To maximize weight loss with Survodutide, ensure you are on a dose above 2 mg/week and continue treatment for at least 16 weeks. Lower doses or shorter durations result in less significant weight and waist circumference reduction.

Weekly subcutaneous administration of Tirzepatide (5-15 mg) significantly reduces body weight and body fat percentage in non-diabetic obese patients compared to placebo, with effects comparable to bariatric surgery.

If you are obese and non-diabetic, Tirzepatide is a highly effective weekly injection that can lead to significant weight loss (up to ~21%) and fat loss, outperforming previous GLP-1 drugs. It requires a commitment to weekly injections and lifestyle changes (diet and 150 mins/week exercise), but may offer a better side-effect profile regarding nausea than older drugs due to its dual GIP/GLP-1 mechanism.

A once-weekly synthetic semaglutide formulation (test drug) provides weight loss efficacy and safety comparable to the innovator semaglutide (Wegovy) in Indian adults with obesity over a 24-week period.

If you are an adult in India with obesity who has struggled to lose weight through diet and exercise alone, this study shows that a once-weekly synthetic semaglutide injection works just as well as the brand-name version (Wegovy) over 24 weeks. You can expect to lose about 14-15% of your body weight if you follow the dose-titration schedule (starting low and increasing every 4 weeks) alongside a 500-calorie daily deficit and 150 minutes of weekly exercise. While you may experience common side effects like nausea or constipation, they are generally mild and manageable. This option may be more affordable than the brand name, making it a viable long-term management tool.