Browse the evidence

Dietary restriction (including caloric restriction, intermittent fasting, and ketogenic diets) extends healthspan and lifespan by promoting the clearance of senescent cells (senolysis), metabolic reprogramming, and epigenetic rejuvenation.

To leverage dietary restriction for longevity, you can adopt strategies like caloric restriction (eating less without being malnourished), intermittent fasting (eating within specific windows like 16:8), or ketogenic diets (high fat, low carb). These regimens aim to trigger biological processes like clearing out old cells (senolysis) and improving metabolic health, which may extend your healthspan. Start with small changes, like a shorter eating window, and ensure your diet remains nutrient-dense.

Performing leg press exercises with a knee flexion range of motion of approximately 100 degrees yields quadriceps femoris muscle hypertrophy equivalent to performing the exercise with maximum individualized knee flexion (peak ROM) in resistance-trained individuals.

If you are an experienced lifter, you do not need to force your leg press to the absolute bottom if it causes pain or technical breakdown. Stopping at approximately 100 degrees of knee flexion (where your shins are roughly perpendicular to the floor or slightly past) will build your quads just as effectively as going as deep as physically possible. Focus on reaching failure with good form at this depth rather than chasing extreme depth.

Animal protein intake may have a mild protective association with cancer mortality, but plant protein intake is not associated with cancer mortality risk.

While animal protein may have a mild protective association with cancer mortality, plant protein does not show this specific benefit in this study. You do not need to avoid animal protein for cancer prevention, and plant protein is not uniquely protective.

Psychosocial factors (confidence, social support, emotional eating) and metabolic status are stronger predictors of weight loss success in behavioral obesity treatment than diet type (low-fat vs. low-carb) or demographic variables alone.

If you are starting a weight loss program, your success is less about whether you choose low-fat or low-carb and more about your mindset and environment. Assess your confidence in sticking to the plan, manage emotional eating, and ensure your social circle is supportive. If you struggle with emotional eating, seek specific psychological support alongside dietary changes.

Changes in soluble LDL receptor (sLDLR) levels are strongly associated with changes in atherogenic lipoprotein phenotype (ALP) markers, including triglycerides, VLDL, and small LDL particles, independent of diet type (low-carbohydrate vs. low-fat) and BMI change.

This research highlights that soluble LDL receptor (sLDLR) levels track closely with atherogenic lipid profiles (high triglycerides, small LDL) during weight loss, regardless of whether you choose a low-carb or low-fat diet. While sLDLR itself is not a standard clinical target, its association with these markers suggests that individuals with high sLDLR may have a specific metabolic phenotype (atherogenic dyslipidemia) that requires careful monitoring of lipid health during weight loss interventions.

Tirzepatide treatment significantly reduces food cravings and preferences for energy-dense foods (high fat, high sugar, fast food fats) in people with obesity, independent of caloric restriction.

If you struggle with intense cravings for high-fat or high-sugar foods, tirzepatide can help reduce these urges. This isn't just about willpower; the medication physiologically lowers the 'pull' of these foods, making it easier to stick to a healthy diet.

Tirzepatide specifically reduces cravings for fast-food fats (e.g., pizza, hamburgers) more than other high-fat foods (e.g., sausage, fried fish).

Tirzepatide may be particularly effective at reducing cravings for specific fast-food items like pizza and burgers compared to other high-fat foods.

GLP-1 receptor agonist (GLP-1RA) treatment in obese individuals causes a modest absolute decrease in skeletal muscle mass, but preserves or improves relative muscle mass and strength, resulting in maintained or enhanced physical performance.

If you are taking GLP-1 medications for weight loss, expect a small, normal amount of muscle loss alongside your fat loss. This is not pathological wasting; your muscles are actually working better relative to your new body weight. Focus on maintaining strength through activity, as your mobility and endurance may actually improve.

Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 receptor agonists are indicated for patients with type 2 diabetes who are inadequately controlled on oral antihyperglycemic drugs (OADs) with an HbA1c less than 10% and within 2% of their glycemic goal, or for those already on basal insulin who remain above goal.

If you are taking oral diabetes medications but your blood sugar is still too high (HbA1c less than 10% and within 2% of your target), or if you are already on basal insulin but your levels are still above goal, ask your doctor about a fixed-ratio combination (FRC). These are single injections that combine a long-acting insulin with a GLP-1 medication. They are designed to lower blood sugar effectively, minimize weight gain, and reduce the number of injections you need to manage compared to traditional basal-bolus therapy.

For patients with Type 2 Diabetes requiring basal insulin, a glycated hemoglobin (HbA1c) goal of less than 7% is appropriate, whereas a goal of less than 6.5% is less likely to be appropriate due to increased risks of hypoglycemia and weight gain.

If you are on basal insulin, aim for an HbA1c of less than 7%. Trying to get it below 6.5% when you are on insulin can increase your risk of dangerous low blood sugar and weight gain without providing significant additional long-term benefits. Your doctor should adjust your goal based on your specific health situation, but <7% is generally the safe target for insulin users.

Incretin receptor activators (GLP-1RA and GIP/GLP-1 dual agonists) cause a reduction in skeletal muscle mass (SMM) that is proportional to fat loss, with approximately 5% of lean body mass lost for every 10% reduction in total body weight, potentially leading to sarcopenia in a subset of treated patients.

If you are taking GLP-1RA or similar weight-loss medications, be aware that you will lose some muscle along with fat. To minimize this, engage in structured exercise programs and discuss monitoring your muscle mass with your doctor, especially if you are older or have existing frailty.

The ratio of serum creatinine to cystatin C (Sarcopenia Index, SI) is a valid, non-invasive biomarker for estimating skeletal muscle mass and predicting mortality in sarcopenic populations, including those treated with GLP-1RA.

Ask your doctor about using a Sarcopenia Index (SI), calculated from your routine creatinine and cystatin C blood tests, to monitor your muscle health while on weight-loss medications. This simple calculation can help detect muscle loss early.

Orforglipron significantly improves lipid profiles, including reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increases in HDL cholesterol, independent of weight loss magnitude.

Orforglipron not only helps with weight loss but also significantly improves heart health markers. It lowers bad cholesterol (LDL) and triglycerides while raising good cholesterol (HDL). These improvements occur alongside weight loss and contribute to a lower risk of cardiovascular disease, making it a comprehensive treatment for obesity-related metabolic risks.

Delaying the onset of type 2 diabetes by two years in individuals with obesity is associated with a 3.7-year increase in median life expectancy and reduced long-term mortality, primarily driven by lower cardiovascular mortality.

For individuals with obesity, preventing or delaying the onset of type 2 diabetes is a critical lever for extending life expectancy. This study suggests that even a modest two-year delay in developing diabetes can add nearly four years to your life, largely by protecting your heart. Focus on metabolic health markers (like blood sugar and insulin sensitivity) as aggressively as you focus on weight, as the timing of diabetes onset directly impacts how long you live.

Treatment with extended-release naltrexone/bupropion (NB) produces weight loss that is disproportionately derived from fat mass rather than lean mass compared to placebo, resulting in a favorable shift in the lean-to-fat mass ratio.

If you are using naltrexone/bupropion for weight loss, the medication helps you lose more fat and preserve more muscle than dieting alone. This is beneficial for long-term metabolic health. Ensure you are following a caloric deficit and staying active as instructed.

Consuming 50g of isomaltulose (ISO) as a preload before a mixed meal significantly enhances the secretion of gut hormones GLP-1, GIP, and PYY compared to sucrose (SAC), with a particularly pronounced effect on PYY levels in both healthy individuals and those with Type 2 Diabetes.

If you want to boost your gut hormones (GLP-1, PYY) which help regulate appetite and insulin, try eating 50g of isomaltulose (often found in products like Palatinose) about one hour before your main meal. This specific timing and dose triggers a much stronger hormonal response than regular table sugar (sucrose), especially regarding PYY, which is linked to satiety. Note that this did not significantly lower blood glucose in the subsequent meal in this study, so it is a tool for hormonal modulation, not necessarily glycemic control.

Dual and tri-agonists targeting GLP-1, GIP, and Glucagon receptors provide superior metabolic homeostasis and cardiovascular benefits compared to mono-agonists by leveraging cooperative hormonal signaling.

Current GLP-1 treatments are effective, but newer dual and triple hormone therapies (targeting GLP-1, GIP, and Glucagon receptors) offer broader metabolic and cardiovascular benefits. These are available as weekly or daily injections, and in some cases, oral formulations, addressing the burden of daily dosing.

GLP-1 receptor agonists (specifically liraglutide and semaglutide) reduce major adverse cardiovascular events (MACE), with benefits potentially driven by anti-atherogenic or plaque-stabilization properties, particularly in secondary prevention.

If you have Type 2 Diabetes and heart disease, injectable GLP-1 medications like liraglutide or semaglutide have been shown to reduce the risk of heart attack, stroke, and cardiovascular death. These benefits appear to come from protecting blood vessels (anti-atherogenic effects). Oral alternatives like DPP-4 inhibitors do not offer this specific heart protection.

A decrease in total energy intake is independently associated with a loss of muscle mass in patients with Type 2 Diabetes, even when adjusting for physical activity and hypoglycemic agents.

When reducing calories for Type 2 Diabetes, be aware that muscle mass may also decrease. To counteract this, ensure your diet includes adequate protein and incorporate resistance training. Monitoring body composition is important to ensure you are losing fat, not muscle.

Monogenic obesity caused by leptin deficiency can be effectively treated with recombinant leptin therapy, restoring normal appetite regulation.

This intervention is not for the general population. It applies only to a tiny fraction of individuals with confirmed monogenic leptin deficiency. Standard weight loss strategies remain the primary approach for >99% of cases.

Higher relative carbohydrate intake (42-51% of energy) causally reduces hypertension risk by 71% compared to lower intake, independent of protein and fat intake.

If you have hypertension, increasing your carbohydrate intake to represent 42-51% of your total daily energy may help lower your blood pressure risk, provided you adjust other macronutrients accordingly. This finding is based on genetic evidence from large European cohorts, suggesting a causal protective effect of relative carbohydrate intake over protein and fat.

The protective effect of higher carbohydrate intake on hypertension is mediated by improved psychological well-being and reduced adiposity.

Eating a diet with 42-51% of calories from carbohydrates may help lower blood pressure not just by weight management, but also by improving mental health and reducing stress-related factors like depression and anxiety.

Metabolic adaptation (reduced resting metabolic rate beyond prediction based on body composition) persists for at least six years after massive weight loss from extreme caloric restriction and exercise, contradicting claims that baseline measurement errors or stress artifacts explain the finding.

If you have lost a significant amount of weight, expect your metabolism to slow down more than predicted by your new size alone. This is a biological reality, not a personal failure. This adaptation can persist for years, meaning you will likely need to maintain a lower calorie intake or higher activity level than someone who never was obese to keep the weight off. Plan for long-term management, not a quick fix.

Three-dimensional optical (3DO) imaging using the Fit3D ProScanner is a sensitive and accurate tool for monitoring longitudinal changes in body composition (total fat mass, fat-free mass, and appendicular lean mass) compared to dual-energy X-ray absorptiometry (DXA).

Use 3DO imaging (like Fit3D) to track your body composition changes over time rather than relying solely on scale weight. The technology is validated to detect small changes in fat and lean mass comparable to clinical DXA scans. For best results, take multiple scans and average them to minimize error, and focus on trends over weeks rather than day-to-day fluctuations.