Browse the evidence

Resting metabolic rate (RMR) is highly homogeneous in healthy young adults after adjusting for metabolically active tissue (total body potassium), with protein turnover explaining only a small but significant fraction (approx. 20%) of the remaining variability.

If you are healthy, your resting metabolism is likely very similar to others of your size and active tissue mass. Don't blame 'slow metabolism' for weight issues; focus on body composition. Protein turnover plays a minor role in RMR differences.

Increased body fat is associated with elevated resting metabolic rate and protein turnover, even after accounting for lean body mass (total body potassium).

Having more body fat does not mean your metabolism is 'slow' relative to your lean mass. In fact, higher fat mass is associated with higher metabolic rate and protein turnover, even when you account for your lean tissue.

Thyroid hormones (T4, T3) and insulin concentrations within the normal euthyroid range do not correlate with resting metabolic rate or protein turnover in healthy young adults.

If your thyroid levels are normal, they are not the primary driver of your metabolic rate differences. Focus on body composition rather than trying to 'optimize' normal hormone levels for metabolic boost.

Simultaneous inhibition of MuRF1 and MuRF2 E3 ubiquitin ligases induces synergistic skeletal and cardiac muscle hypertrophy and increases muscle protein synthesis rates.

This research suggests that blocking both MuRF1 and MuRF2 proteins can significantly increase muscle mass and protein synthesis in mice. However, this is a genetic manipulation not currently available or safe for humans, as it also causes severe heart enlargement and early lethality in a large portion of the subjects. It highlights the potential of these proteins as future drug targets for sarcopenia, but current technology does not allow for safe, targeted inhibition in humans.

Inhibition of MuRF1 and MuRF2 prevents age-related body fat accumulation in mice, resulting in a lean phenotype despite increased muscle mass.

In mice, blocking MuRF1/2 prevents fat gain during aging. This is likely due to the high energy cost of maintaining larger muscles and potentially direct effects on fat metabolism. This is not a current human intervention, but it suggests that increasing muscle metabolic activity might help manage body fat.

SGLT2 inhibitors lower blood glucose in Type 2 Diabetes by blocking renal glucose reabsorption, resulting in increased urinary glucose excretion without causing hypoglycemia.

If you have Type 2 Diabetes, SGLT2 inhibitors are a class of medication that helps your kidneys remove excess sugar through urine. This lowers blood sugar and can help with weight loss, without the risk of dangerously low blood sugar (hypoglycemia) common in other treatments. Be aware of a higher risk for urinary or fungal infections.

Metformin reduces fasting plasma glucose by inhibiting hepatic gluconeogenesis via AMPK activation and reducing free fatty acid plasma concentration.

Metformin is the most common first-line medication for Type 2 Diabetes. It works by reducing the amount of sugar your liver makes and improving your body's sensitivity to insulin. Common side effects include stomach discomfort, which often improves over time.

Sedentary behavior interventions do not produce significant changes in fat-free mass, diastolic blood pressure, fasting glucose, HbA1c, LDL cholesterol, or triglycerides.

Do not expect sedentary reduction to significantly change your blood sugar levels (HbA1c, fasting glucose), cholesterol (LDL, Triglycerides), or muscle mass. While these metrics may show slight beneficial trends, the changes are not statistically significant. Focus on the proven benefits like improved blood pressure and insulin sensitivity instead.

Greater maternal pre-pregnancy BMI is associated with increased offspring fat mass, but this specific maternal effect is small and unlikely to drive the recent obesity epidemic.

Maternal obesity during pregnancy does increase a child's risk of higher fat mass, but the effect is small. It is not the primary driver of the obesity epidemic. Focus on overall family lifestyle and genetics rather than blaming maternal pregnancy weight alone.

Epicardial adipose tissue (EAT) and myocardial steatosis contribute to cardiac dysfunction and atrial fibrillation through lipotoxicity, involving the accumulation of diacylglycerols and ceramides.

Managing overall body fat and metabolic health helps reduce epicardial fat, which may lower the risk of heart rhythm issues and heart failure.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a cardiovascular risk factor, driven by lipotoxicity rather than triglycerides alone.

Treating NAFLD requires addressing the underlying metabolic dysfunction and reducing toxic lipid metabolites, not just lowering liver fat content.

Orlistat is the only currently available long-term pharmacological treatment for obesity in Europe because it offers a favorable safety profile regarding cardiovascular events and diabetic control, despite being less effective for weight reduction than withdrawn agents.

Take Orlistat (120mg Rx or 60mg OTC) with your three main meals containing fat. If a meal has no fat, skip the dose. Stick to a diet where about 30% of calories come from fat to minimize gastrointestinal side effects, which usually improve over time. Stop the medication if you haven't lost at least 5% of your body weight after 12 weeks.

Early-life maternal nutrient restriction (caloric or protein) programs skeletal muscle structure and metabolism, leading to reduced fiber number, altered fiber type composition, and increased susceptibility to metabolic disease and sarcopenia in later life.

Your early life environment may have set a baseline for your muscle fiber number and metabolic flexibility. While you cannot change your birth history, being aware of this 'programming' can help you prioritize metabolic health (glucose control, protein intake) to counteract potential predispositions to insulin resistance or muscle loss as you age.

Maternal obesity or high-fat diets during gestation program offspring skeletal muscle to exhibit blunted insulin signaling, increased inflammation (TNF-alpha), and reduced myogenesis, predisposing them to insulin resistance and obesity.

Maternal health during pregnancy significantly impacts the child's future metabolic risk. Maintaining a healthy weight and diet during pregnancy is crucial for preventing early programming of insulin resistance.

Weight loss interventions do not reduce miscarriage rates in overweight and obese women, despite improving pregnancy rates.

While losing weight can help you get pregnant, it does not appear to lower your risk of miscarriage. Focus on the benefits of improved pregnancy rates and overall health rather than expecting weight loss to prevent pregnancy loss.

Long-chain n-3 polyunsaturated fatty acids (omega-3) improve insulin sensitivity and glucose homeostasis in animal models of metabolic syndrome, but have none or marginal effects on metabolic control in human Type 2 diabetes patients.

If you have Type 2 Diabetes, taking omega-3 supplements (EPA/DHA) will likely not improve your blood sugar control or insulin sensitivity, even though it may help lower your triglycerides. Do not rely on omega-3s to manage your glucose levels; continue with prescribed antidiabetic medications and lifestyle changes.

In animal models, omega-3 supplementation prevents the development of insulin resistance and obesity by activating PPARα, AMPK, and reducing endocannabinoid tone, mechanisms that are less effective or absent in humans.

This node explains why animal studies often look better than human trials: mice process omega-3s differently (more peroxisome activation) than humans. This is a mechanistic insight, not a direct human protocol.

Caloric restriction (CR) without malnutrition extends healthspan and lifespan across multiple species by modulating nutrient-sensing pathways such as mTORC1, AMPK, and Sirtuins.

To potentially extend healthspan, reduce your caloric intake by 20-30% below your maintenance level without sacrificing essential nutrients. Focus on nutrient-dense foods to avoid malnutrition while triggering metabolic adaptations like autophagy and improved insulin sensitivity.

Short-term administration of atypical antipsychotics (olanzapine and aripiprazole) induces insulin resistance in healthy subjects independent of weight gain, increased food intake, or psychiatric disease.

If you are prescribed olanzapine or aripiprazole, you may develop insulin resistance even if you do not gain weight or change your diet. This is a direct pharmacological effect on your tissues, not a result of your lifestyle. Monitoring blood sugar and insulin sensitivity is crucial, regardless of your body weight changes.

Olanzapine, but not aripiprazole, causes significant postprandial hyperinsulinemia and elevations in GLP-1 and glucagon, coincident with insulin resistance.

Olanzapine uniquely disrupts your gut-hormone signaling (GLP-1 and glucagon) after eating, leading to high insulin spikes. This is different from other antipsychotics like aripiprazole, which cause insulin resistance without these specific hormonal spikes. This suggests olanzapine has a more complex impact on digestion and metabolism.

Sarcopenia predicts significantly worse long-term overall survival (1, 3, and 5 years) and disease-free survival following abdominal surgery for malignancy.

For cancer patients undergoing abdominal surgery, muscle mass is a key prognostic factor. If your scans show sarcopenia, engage in prehabilitation focusing on resistance training and protein intake to potentially improve your long-term survival and disease-free outcomes.

Nutrients-to-limit reformulation of ultra-processed foods fails to improve health outcomes because it enables mal-substitution of ingredients and legitimizes continued high consumption of ultra-processed products.

Do not rely on 'reformulated' or 'low-fat/low-sugar' labels to judge the healthiness of packaged foods. These products are often still ultra-processed and may contain other harmful additives or substitutes. Focus on consuming minimally processed foods instead of trying to optimize the nutrient profile of industrial products.

Mobility difficulties, pain, depression, and sleep problems are significant mediators explaining the association between chronic conditions/multimorbidity and low physical activity in older adults (≥50 years) in LMICs.

For older adults in LMICs with chronic conditions, simply diagnosing the condition isn't enough to increase physical activity. Healthcare providers must also assess and address mobility difficulties, pain, depression, and sleep problems, as these are the primary barriers preventing activity. Interventions should target these mediators to be effective.

Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women by impairing the phosphorylation of protein kinase C-zeta (PKCz) downstream of PI3-kinase, without affecting upstream IRS-1 or mitogenic signaling pathways.

For women with high androgen levels (such as in PCOS), excess testosterone can directly interfere with how fat cells respond to insulin. This happens not by blocking the main insulin signal, but by disrupting a specific downstream step (PKCz) required for glucose uptake. This suggests that managing androgen levels may be crucial for improving insulin sensitivity in these individuals.