Browse the evidence

Carbohydrate manipulation (loading) increases muscle size in physique athletes primarily through intramuscular glycogen supercompensation and associated water binding, but this strategy lacks experimental validation for aesthetic performance and carries risks of gastrointestinal distress and subcutaneous water retention.

If you are a physique athlete peaking for competition, do not blindly copy endurance athlete carb-loading protocols. Your body may not handle the same loads, leading to 'spilling over' (subcutaneous water) and bloating. Instead, experiment with moderate carbohydrate loads (3-6 g/kg) during training camp to see how your body responds. Minimize the number of variables you change at once (e.g., don't change carbs, water, and sodium simultaneously) to reduce psychological stress and make it easier to identify what works for your specific physiology.

Tirzepatide use is associated with a risk of idiosyncratic acute liver injury, characterized by severe hepatotoxicity and coagulopathy, which resolves upon discontinuation of the drug.

If you are using tirzepatide for weight loss, do not skip liver function tests. While liver injury is rare, it can be severe and rapid. Report any persistent abdominal pain, vomiting, or yellowing of skin/eyes immediately. The drug should be stopped if liver enzymes rise significantly.

HIIT does not significantly improve body mass or BMI in patients with diabesity compared to standard treatment.

Do not expect HIIT to drastically change your weight or BMI if you have diabesity. The primary benefit of this training style for your condition is metabolic (blood sugar and lipids), not weight loss. Manage your expectations regarding the scale.

GLP1:GIP:Gcg triple agonists (SAR441255) show potential for weight loss and neurological benefits, including improved memory in mouse models of TBI and Alzheimer's disease.

GLP1:GIP:Gcg triple agonists like SAR441255 show potential for weight loss and neurological benefits, including improved memory in animal models of TBI and Alzheimer's disease. However, human data is preliminary, and glycemic benefits may be inferior to dual agonists. These therapies are in early development.

Tirzepatide use is associated with a probable risk of severe rhabdomyolysis and necrotising myopathy, potentially mediated by GLP-1 receptor effects on skeletal muscle glucose metabolism.

If you are taking tirzepatide (or similar GLP-1 drugs) and experience sudden, severe muscle pain, swelling, or weakness—especially if it doesn't match your activity level—seek medical attention immediately. Ask for a Creatine Kinase (CK) blood test. Stopping the medication and receiving IV fluids can resolve the condition, as seen in this case.

Adhering to current dietary guidelines (30-35% energy from fat, >50% from carbohydrates) is not associated with increased mortality or morbidity, whereas the PURE study's conclusion that high carbohydrate intake increases risk is invalid due to methodological flaws.

Do not change your macronutrient ratios based on headlines from single observational studies. Stick to established guidelines: moderate fat (30-35% of energy) and high carbohydrates (>50% of energy). Focus on improving diet quality by increasing fiber-rich foods and reducing added sugars and refined starches, as these factors are more critical for mortality risk than the fat-carb ratio itself.

There is a plateau in fat-free mass gains from protein supplementation at approximately 1.62 g/kg/day of total protein intake; exceeding this amount yields no further benefit.

Aim for ~1.6 g of protein per kg of body weight per day. Eating more than this does not provide additional muscle-building benefits from resistance training.

Ketogenic diets may offer unique metabolic benefits for cancer and neurodegenerative diseases through mechanisms like the Warburg effect and ketone utilization by the brain.

For individuals with cancer or neurodegenerative diseases like Alzheimer's, a ketogenic diet may offer metabolic benefits by targeting underlying insulin resistance and mitochondrial dysfunction. It is not a cure but may act synergistically with other treatments. Consult a healthcare provider before starting, as research is ongoing.

Limiting dietary saturated fat intake to 10% of total calories does not reduce cardiovascular disease events or mortality and is not supported by rigorous scientific evidence.

Current guidelines recommend capping saturated fat at 10% of calories, but this paper argues that rigorous evidence does not support this cap for reducing heart disease risk. Instead of focusing solely on limiting saturated fat, consider the source of the fat (food matrix) and your overall dietary pattern, such as carbohydrate intake.

Replacing saturated fats with polyunsaturated fats (PUFA) does not convincingly reduce cardiovascular events or mortality and may have null or adverse effects on stroke risk.

Replacing saturated fats with polyunsaturated fats does not clearly reduce heart disease risk and may increase stroke risk. Focus on the quality of your overall diet and food sources rather than just swapping fat types.

The holiday season does not cause significant weight gain in children or college students, though it may increase body fat in college students.

For children and college students, holiday weight gain is not a significant concern based on current data, though college students may see an increase in body fat.

GLP-1 receptor agonists (GLP-1 RAs) improve skeletal muscle mitochondrial morphology, area, and number in animal models of obesity and type 2 diabetes, but their effect on mitochondrial respiration and mass is inconsistent or neutral.

Current evidence for GLP-1 RAs improving muscle mitochondria comes exclusively from animal and cell studies, not humans. While these studies show improved mitochondrial structure, they do not guarantee preserved muscle mass in people. To protect muscle while using GLP-1s for weight loss, prioritize resistance training and adequate protein intake, as the drug's direct benefit to human muscle mitochondria is not yet proven.

Adherence to a vegan diet does not significantly alter the risk of primary cardiovascular disease events (including coronary heart disease, myocardial infarction, or stroke) compared to non-vegan diets, although it may lower intermediate markers like carotid artery intima-media thickness.

Switching to a vegan diet is unlikely to significantly change your risk of having a heart attack or stroke compared to a non-vegan diet, based on current evidence. While vegans may have better intermediate markers like artery thickness, the hard outcomes (heart attacks, strokes) are similar. To maximize heart health on a vegan diet, ensure you are getting adequate B12, Omega-3s (EPA/DHA), and other nutrients, as deficiencies may offset potential benefits.

Vegan diets may be associated with a higher risk of ischemic stroke compared to non-vegan diets, although the finding was not statistically significant.

One study suggested a potential trend toward higher ischemic stroke risk in vegans, but it was not statistically significant. Ensure you are supplementing with B12 and Omega-3s (EPA/DHA) to mitigate any potential risks associated with nutrient deficiencies.

Increases in serum myostatin concentrations following resistance training are positively associated with gains in appendicular skeletal muscle mass in older adults, challenging the view that myostatin solely inhibits muscle growth.

Do not try to manipulate your myostatin levels. This study suggests that myostatin may actually increase as part of the muscle-building process in older adults. Focus on your training and nutrition; do not worry about serum myostatin levels as a barrier to growth.

Targeting hypothalamic AMPK in SF1 neurons using small extracellular vesicles (sEVs) loaded with dominant-negative AMPKα1 plasmids reduces body mass and adiposity by increasing sympathetic nervous system-mediated brown adipose tissue thermogenesis, without affecting food intake.

This technology is currently in preclinical stages (mouse models). While it shows promise for treating obesity by boosting energy expenditure rather than suppressing appetite, it is not yet available for human use. Current clinical options remain focused on lifestyle changes, bariatric surgery, and pharmacological agents like GLP-1 agonists.

Increasing protein intake beyond ~1.8 g/kg/d does not provide additional muscle mass benefits in bodybuilders if total energy intake is already high.

Don't obsess over hitting extremely high protein numbers (like 2.0+ g/kg) if you are already eating enough (around 1.8 g/kg). Focus on your total calories and training intensity instead, as extra protein won't help if your energy balance isn't optimized.

Preclinical evidence suggests GLP-1 receptor agonists may offer cardioprotective benefits beyond weight loss, such as reducing fibrosis and inflammation, but this remains unproven in humans.

Current human trials show GLP-1 benefits are mostly due to weight loss. However, animal studies suggest the drug might also directly reduce heart inflammation and fibrosis. This potential direct benefit is not yet proven in humans, so patients should focus on the proven weight loss benefits while researchers investigate these additional mechanisms.

Combining extended dosing intervals (e.g., every two weeks) with increased dose sizes (e.g., doubling the mg strength) can maintain nearly 100% of the weight loss efficacy while halving the cost.

If you are on a lower dose of a GLP-1 drug (like 5mg tirzepatide) and find the weekly cost prohibitive, ask your doctor about switching to a higher dose (like 10mg or 15mg) taken every two weeks. This strategy can keep your weight loss results nearly identical to taking the lower dose weekly, but at half the cost. This is only possible if your body can handle the higher individual dose without excessive side effects.

At a population level, distributing GLP-1 medications using extended dosing intervals (q2wk) allows twice as many obese adults to be treated for the same total cost, leading to greater reductions in national obesity rates and mortality.

For policymakers and insurers, extending GLP-1 dosing intervals to every two weeks allows the same budget to treat twice as many people. While each individual might lose slightly less weight, the overall public health benefit (reduced obesity and mortality) is significantly higher. This is a key strategy for making these drugs accessible at a national scale.

Percutaneous CT-guided cryovagotomy reduces hunger and caloric intake, leading to statistically significant weight loss and BMI reduction in patients with Class I or II obesity over 6 months.

This procedure targets the vagus nerve to reduce hunger signals. In a small pilot study, it led to an average weight loss of about 5 kg over 6 months in obese patients, largely by reducing their daily calorie intake by about 610 calories. It is not a magic bullet but a tool to help manage appetite.

Treatment with the dual GLP-1/GIP receptor agonist tirzepatide results in a proportional loss of skeletal muscle mass relative to total body weight, with muscle loss constituting approximately 34% of total weight loss in treated patients.

If you are taking tirzepatide, expect to lose some muscle along with fat. This case showed that about one-third of the weight lost was muscle. To counter this, you should prioritize strength training and ensure adequate protein intake, as suggested by the authors, rather than just focusing on the scale number.

Preclinical studies show conflicting results regarding GLP-1 agonists and breast cancer progression: some show inhibition of tumor growth via apoptosis, while others show promotion of growth in aggressive Triple-Negative Breast Cancer (TNBC) cell lines.

Animal studies show mixed results: GLP-1s might slow down some breast cancers but potentially speed up aggressive types (TNBC) in a lab setting. However, large human studies have not found an increased risk of developing breast cancer in people taking these drugs. If you have a history of breast cancer, discuss your specific subtype with your doctor.

Among patients taking oral semaglutide, older adults (65+) achieve significantly better weight loss outcomes than younger adults (<65).

If you are under 65 and taking the oral version of semaglutide, you might not lose as much weight as older patients on the same medication. If weight loss is your primary goal, the injection form is likely a better choice for you, as it provided superior results across all age groups in this study.