Browse the evidence

Elevated GDF15 plasma levels are not a causal factor in cardiometabolic diseases such as obesity, type 2 diabetes, or cardiovascular disease, but rather serve as a biomarker of metabolic stress.

Do not rely on GDF15 levels to predict or treat obesity directly. While high GDF15 is a strong warning sign for heart disease and mortality, increasing it artificially (as done in animal studies) does not appear to cause weight loss in humans. Focus on established metabolic health markers instead.

Higher Body Mass Index (BMI) causally increases GDF15 plasma levels, identifying BMI as a driver of GDF15 elevation rather than the reverse.

High GDF15 is a consequence of higher body weight, not the cause. Managing BMI is the primary lever; GDF15 levels will naturally decrease as metabolic stress is reduced.

Obeticholic acid (25 mg/day) improves liver fibrosis in patients with MASH and stage 2-3 fibrosis, but does not significantly resolve MASH activity compared to placebo.

Obeticholic acid (25 mg daily) can significantly improve liver scarring (fibrosis) in patients with advanced MASH, but it does not reliably eliminate the inflammation (MASH) itself. The main barrier is itching (pruritus). This treatment is for specific high-risk patients, not general MASLD.

Pioglitazone (PPAR-gamma agonist) resolves MASH and reduces fibrosis stage, but its use is limited by adverse effects including fluid retention, weight gain, and osteopenia.

Pioglitazone can resolve MASH and reduce liver scarring, but it causes weight gain and fluid retention, which can worsen heart failure risk. It is generally limited by these side effects, particularly in older women due to fracture risk.

Five days of bed rest does not significantly alter skeletal muscle mitochondrial protein content, enzyme activity, or dynamics (fission/fusion/biogenesis/mitophagy markers) in healthy older adults.

For older adults facing short hospital stays (around 5 days), do not panic about losing metabolic health or mitochondrial density. While muscle mass may decrease, the cellular machinery for energy production remains largely intact during this specific timeframe, suggesting that immediate post-discharge recovery of metabolic function is feasible without needing to rebuild mitochondrial content from scratch.

GIP receptor antagonism, specifically via the peptide GIP(3-30)NH2, increases GIP receptor surface expression and prevents internalization, thereby resensitizing the receptor for subsequent activation by endogenous or exogenous agonists.

Blocking the GIP receptor with specific antagonists like GIP(3-30)NH2 doesn't just turn off the signal; it keeps the receptors on the cell surface ready to receive signals. This resensitization may help overcome the impaired GIP response often seen in type 2 diabetes and obesity, potentially enhancing the effects of other treatments like GLP-1 agonists.

Nutrient-based front-of-pack labeling systems (like Health Star Rating) can assign high health scores to ultra-processed foods, creating a 'health halo' that misleads consumers about the nutritional quality of convenience foods, sports/diet foods, and meat alternatives.

When evaluating packaged foods, do not rely solely on front-of-pack labels like the Health Star Rating. These systems focus on nutrients (sugar, sodium, fiber) but ignore how processed the food is. Look for the ingredient list: if it contains industrial additives, emulsifiers, or protein isolates, it is likely ultra-processed, even if it has a high health score. Prioritize whole, minimally processed foods over highly processed ones with 'good' nutrient profiles.

Higher body mass index (BMI) is associated with increased striatal dopamine tone in humans, as indicated by the differential displacement of low-affinity PET tracers ([11C]raclopride) compared to high-affinity tracers ([18F]fallypride).

This research suggests that higher body weight is linked to higher baseline (tonic) dopamine levels in the brain's reward centers, which may blunt the response to specific rewards. While this paper does not offer a direct intervention, it implies that weight loss might normalize dopamine tone, potentially improving reward sensitivity. However, the causal direction (does weight cause high dopamine or vice versa?) remains unproven in this cross-sectional study.

Antioxidant supplementation (specifically Vitamin C and E) can attenuate exercise-induced adaptations, such as mitochondrial biogenesis and improvements in VO2max, by interfering with reactive oxygen species (ROS) signaling pathways.

Be cautious with high-dose antioxidant supplements (like Vitamin C and E) if you are training for endurance. They might blunt the fitness gains you are working for by interfering with your body's natural signaling. It is likely better to get antioxidants from food sources rather than high-dose supplements during training blocks.

Standard long-term weight management RCTs for severe obesity (BMI ≥35 kg/m2) systematically exclude or underrepresent underserved groups (low SES, racial minorities, mental health conditions), rendering the evidence base non-generalizable to the populations most at risk of severe obesity.

Current weight management guidelines for severe obesity are largely based on research that excludes the people who need them most (those with lower income, mental health issues, or minority backgrounds). If you belong to an underserved group, standard advice may not work for you because it wasn't tested on people like you. Seek programs that explicitly adapt to your cultural, socioeconomic, and logistical needs, rather than assuming standard protocols will be effective.

Handgrip strength reference values for European adults aged 50+ vary significantly by age, sex, and geographic region, with Northern and Western Europe showing higher absolute strength than Southern and Central/Eastern Europe, and standing position yielding higher values than sitting.

If you are over 50, do not compare your handgrip strength to a generic global average. Use the specific reference values for your age group, sex, and European region (Northern, Western, Southern, or Central/Eastern) to accurately assess your muscle health. Standing grip is typically higher than sitting; ensure you are comparing like with like.

Exogenous testosterone administration (200 mg/week) does not alter whole-body energy expenditure, substrate oxidation, or skeletal muscle metabolic gene expression during a severe energy deficit in healthy men.

If you are a healthy man in a calorie deficit and exercising heavily, taking testosterone will not change how your body burns fat or carbs compared to not taking it. It helps preserve muscle mass, but it does not boost your metabolism or fat loss. Focus on your exercise volume and calorie intake for metabolic adaptations.

In individuals with type 2 diabetes who carry the haptoglobin (Hp) 2-2 phenotype, maintaining an HbA1c level below 6.5% does NOT significantly reduce the risk of coronary artery disease compared to levels of 7.0-7.9%.

If you have type 2 diabetes and have the haptoglobin 2-2 genetic variant, aiming for an HbA1c below 6.5% may not provide additional protection against heart disease compared to levels of 7.0-7.9%. This suggests that overly aggressive glycemic control might not be necessary or beneficial for cardiovascular health in this specific group.

Current precision nutrition products and nutrigenomics concepts promoted on social media frequently contain misleading or untrue information, particularly regarding the readiness of personalized diets and the ability of specific foods to alter DNA.

Be skeptical of social media posts claiming that specific diets or supplements can change your DNA or that personalized nutrition products are ready for general use. The scientific consensus is that these technologies are not yet ready for broad application, and many products contain misleading or untrue information. Focus on evidence-based dietary patterns rather than unproven genetic tailoring products.

In Type 2 Diabetes, Myocardial Infarction, Hypertension, and Sleep Apnea, elevated C-reactive protein (CRP) is primarily driven by adiposity rather than independent inflammatory pathology, as the association attenuates or reverses upon adjustment for BMI.

If you have high blood pressure, diabetes, or a history of heart issues, your high CRP (inflammation) is likely caused by your weight, not a separate inflammatory disease. Focus on weight loss through diet and lifestyle changes rather than seeking anti-inflammatory medications, as reducing adiposity directly reduces the inflammation.

In Chronic Kidney Disease, Heart Failure, Liver Disease, Psoriasis, Rheumatoid Arthritis, and COPD, elevated CRP is NOT explained by adiposity alone, indicating independent inflammatory pathology driven by end-organ damage or tissue-specific inflammation.

If you have CKD, Heart Failure, Liver Disease, Psoriasis, RA, or COPD, your high CRP is likely due to the disease process itself, not just your weight. While weight management is still beneficial, you likely need specific treatments targeting the organ damage or autoimmune response, as weight loss alone may not resolve the inflammation.

Switching from Tenofovir Alafenamide (TAF) to Tenofovir Disoproxil Fumarate (TDF) in women with HIV results in significant weight loss, indicating TDF has weight-suppressive effects.

If you are a woman with HIV and are gaining weight on a TAF-based regimen, ask your doctor about switching to TDF. Studies show this switch can lead to significant weight loss (approx. 1.6 kg) in women, likely because TDF suppresses weight gain compared to TAF.

In individuals with ideal cardiovascular health (high CVHS), elevated BMI (≥35.0 kg/m²) does not significantly increase the risk of incident atherosclerotic cardiovascular disease (ASCVD) compared to normal BMI, whereas low cardiovascular health strongly predicts ASCVD regardless of BMI.

If you have ideal cardiovascular health (normal blood pressure, lipids, glucose, no smoking, active, healthy diet, good sleep), your risk of heart disease is low even if your BMI is high (≥35). Focus on maintaining these healthy habits rather than trying to lose weight. If your cardiovascular health score is low, your risk is high regardless of your BMI, so prioritize improving lifestyle and metabolic markers.

Classifying individuals by a 'leptin phenotype' (relatively high or low leptin for a given body fat percentage) does not predict differential energy expenditure, metabolic adaptation, or susceptibility to weight change in response to caloric restriction or overfeeding.

Do not rely on fasting leptin levels to predict your weight loss success or failure. Whether your leptin is 'high' or 'low' for your body fat percentage does not appear to change how your body responds to dieting or overeating in terms of energy expenditure or weight change. Focus on sustainable caloric deficits and activity rather than hormonal profiling for prediction.

Markov models are the dominant methodological framework for economic evaluations of obesity interventions, with 85% of reviewed studies utilizing state-transition models.

When evaluating the long-term cost-effectiveness of obesity treatments, decision-makers should expect and look for Markov modeling. This is the standard approach for comparing interventions like bariatric surgery, pharmacotherapy, and lifestyle changes over a patient's lifetime.

Current Markov models for obesity interventions exhibit significant methodological heterogeneity, particularly in how they model the progression of obesity and its impact on costs and utilities.

When comparing economic evaluations of obesity treatments, be aware that different studies use different structures (direct BMI-to-cost vs. BMI-to-complications). This makes direct comparison difficult. Look for studies that use standardized validation and include a broad spectrum of complications.

Diabetes mellitus (DM) and cardiovascular disease (CVD) are the most frequently modeled obesity-related complications in Markov models, with DM appearing in 15/15 models focusing on complications and CVD in 14/15.

If you are looking at an economic evaluation of an obesity treatment, expect it to focus heavily on preventing diabetes and cardiovascular events. These are the main drivers of long-term cost savings and quality-of-life improvements in these models.

Validation practices in Markov models for obesity interventions are inconsistently reported, with only 43% of models reporting validation, limiting the reliability and comparability of these evaluations.

Be cautious when using economic evaluations of obesity treatments that do not report validation. Only 43% of the models reviewed reported validation, which limits their reliability. Look for studies that use standardized validation guidelines like ISPOR.

A 2-week exposure to either a low-carbohydrate (LC) or low-fat (LF) diet does not significantly alter sweet or salty taste detection thresholds or preferences compared to each other.

Switching to a low-carb or low-fat diet for just two weeks will not change your taste buds or your cravings for sweet and salty foods. If you are expecting your food preferences to shift quickly as a result of the diet itself, this short timeframe is likely too short to observe such changes.