Browse the evidence

Activation of AMPK by AICAR abolishes lipid-induced mTOR activation in vitro, confirming that AMPK activation is sufficient to reverse the negative effects of high lipid availability on insulin signaling.

AMPK activation, naturally triggered by exercise, directly inhibits the mTOR pathway which is overactivated by high fat intake. This suggests that boosting AMPK activity (via exercise) is a direct way to counteract the metabolic effects of a high-fat diet.

In older adults, obesity and low HDL cholesterol significantly increase the risk of type 2 diabetes preceded by insulin resistance, but are associated with a lower risk of diabetes preceded by beta-cell dysfunction.

For older adults, high body weight and low HDL cholesterol are strong predictors for developing diabetes driven by insulin resistance, but may actually be associated with a lower risk of diabetes driven by beta-cell failure. This suggests that metabolic subtyping is important for risk assessment in the elderly.

In older adults, higher age, greater adiposity, higher systolic blood pressure, lower HDL, and higher triglycerides are independently associated with greater insulin resistance but better beta-cell function.

In older adults, traditional cardiovascular risk factors like high blood pressure and high triglycerides correlate with higher insulin resistance but are paradoxically associated with better preserved beta-cell function.

Protein intake proportion (20-30%) is not significantly associated with all-cause mortality in Korean adults, although it yields the longest warranty period for mortality exceeding 1%.

For Korean adults, the specific proportion of protein (20-30%) does not significantly impact all-cause mortality risk. However, since traditional Korean diets are high in plant-based proteins, focusing on plant protein sources may be beneficial, as animal protein has been linked to higher mortality in other studies.

Intensive glucose-lowering strategies significantly increase the risk of severe hypoglycemia compared to standard therapy.

If you are on intensive diabetes treatment to lower your blood sugar significantly, be aware that your risk of severe low blood sugar (hypoglycemia) nearly doubles compared to standard treatment. This risk must be weighed against the benefits for your eyes and kidneys. Regular monitoring and awareness of hypoglycemia symptoms are crucial.

Systematically manipulating resistance training variables (load, volume, contraction type, rest intervals) does not produce greater muscle hypertrophy than a standard progressive resistance training protocol in trained young men, despite generating higher total training volume and slightly greater acute myofibrillar protein synthesis.

If you are a trained individual, you do not need to constantly vary your resistance training variables (like load, volume, or rest periods) to maximize muscle growth. A standard progressive resistance training program, performed with high effort (to failure), is just as effective for hypertrophy as a complex, variable program. Focus on consistency and progressive overload rather than frequent changes in exercise selection or parameters.

Mitochondrial dynamics, specifically regulated by Drp1-mediated fission, are essential for maintaining muscle stem cell (satellite cell) regenerative competence and metabolic health throughout adult life.

As you age, your muscle stem cells rely on healthy mitochondrial function to repair tissue. While you cannot directly 'dose' Drp1, you can support mitochondrial health through regular physical activity and adequate nutrition, which are known to promote mitochondrial biogenesis and dynamics. This biological maintenance is key to preserving muscle mass and regenerative ability in adulthood.

When energy balance is maintained, exercise does not induce negative fat balance in lean sedentary, obese sedentary, or lean endurance-trained individuals.

If you exercise but eat back the calories you burned, you will not lose fat. To lose fat through exercise, you must not replace the calories expended. Simply adding exercise without adjusting diet will not create a negative fat balance.

Higher circulating levels of the trans-fatty acid isomer trans/cis-18:2 (t/c-18:2) are associated with increased total mortality and coronary heart disease (CHD) incidence, but only after mutual adjustment for other TFA subtypes.

The isomer t/c-18:2 is linked to higher heart disease risk, particularly when other trans fats are accounted for. Since industrial trans fats (partially hydrogenated oils) are a major source of various trans isomers, avoiding these processed foods helps minimize exposure to potentially harmful isomers like t/c-18:2.

Adding phenotypic and genotypic data to personalized nutrition advice does not provide added benefit over advice based solely on current diet analysis.

Do not pay for expensive genetic or phenotypic testing for personalized nutrition advice. The Food4Me study showed that advice based only on your current diet is just as effective as advice that includes your genes or body metrics.

Providing individualized genetic risk information alone does not motivate behavior change in diet or physical activity.

Do not rely on genetic testing to motivate you to eat better or exercise. Knowing your genetic risk does not change your behavior. Focus on actionable dietary advice instead.

Pioglitazone improves NASH histology without worsening fibrosis in patients with T2DM and MAFLD, but its use is limited by side effects including weight gain, fluid retention, and potential bladder cancer risk.

Pioglitazone (45mg daily) can improve liver inflammation (NASH) in people with type 2 diabetes and fatty liver without worsening scarring. However, it can cause weight gain, fluid retention, and may increase the risk of bladder cancer in some people. It is not recommended for everyone and should be used with caution, especially if you have a history of heart failure or bladder cancer.

In advanced CKD and dialysis patients, higher BMI (including morbid obesity) is associated with better survival outcomes, a phenomenon known as the 'obesity paradox'.

If you are on dialysis, do not try to lose weight. Your higher body weight is actually protecting your life. Focus on eating enough protein and calories to maintain your muscle mass, as losing weight is dangerous for dialysis patients.

Bariatric surgery (specifically Roux-en-Y gastric bypass) induces durable weight loss and type 2 diabetes remission through mechanisms beyond simple caloric restriction, including blunted metabolic adaptation, altered gut hormone secretion (increased GLP-1, PYY), and changes in food preference/hedonics.

Bariatric surgery works by changing gut hormones and metabolism, not just by making the stomach smaller. This insight drives the development of non-surgical drugs (like GLP-1 agonists) that mimic these hormonal changes to help with weight loss and diabetes without surgery.

Bariatric surgery improves glucose homeostasis and insulin sensitivity through mechanisms involving increased gut hormone secretion (GLP-1, PYY) and altered bile acid metabolism, independent of weight loss in some models.

Surgery improves blood sugar control not just by weight loss, but by changing how your gut hormones and bile acids work. This can lead to diabetes remission even before significant weight loss occurs.

Obesity accelerates biological cardiovascular ageing by inducing structural and functional cardiac and vascular changes that mimic those of chronological ageing, independent of traditional risk factors.

Your heart ages based on how you treat it, not just your birth year. Obesity forces your heart to work harder and remodels it to look and function like an older, non-obese heart. Losing weight can reverse these changes, effectively turning back the biological clock of your cardiovascular system.

Dieting acts as a self-imposed famine that triggers physiological starvation responses, leading to long-term weight gain and obesity rather than sustained weight loss.

Stop dieting. The paper argues that dietary restriction acts like famine, triggering biological mechanisms that cause long-term weight gain. Instead of restricting calories, focus on accepting your body's natural weight regulation, as lifetime maintainers do not use dieting strategies.

Central nervous system (CNS) activation of the Glucose-dependent Insulinotropic Polypeptide Receptor (GIPR) is required for the synergistic weight loss observed with dual GIPR/GLP-1R agonists.

If you are using a GLP-1 medication for weight loss or diabetes and struggle with side effects or plateauing results, newer dual-acting medications (targeting both GIP and GLP-1 receptors) may offer better weight loss with potentially fewer gastrointestinal side effects. This is because these drugs work on brain pathways that suppress appetite and may reduce the nausea often caused by older GLP-1-only drugs. Consult your doctor about whether a dual-agonist is appropriate for your metabolic health.

Liraglutide-induced weight loss is significantly attenuated in individuals consuming high-carbohydrate diets when hepatic FGF21 signaling is absent, indicating that FGF21 mediates the appetite-suppressing effects of GLP-1 receptor agonists specifically in the context of high carbohydrate intake.

If you are using a GLP-1 receptor agonist like liraglutide, your weight loss results may be suboptimal if you consume a high-carbohydrate diet. This is because the drug relies on a hormone called FGF21 to help suppress appetite, and this hormone is most effective at reducing food intake when carbohydrates are present. To maximize weight loss, consider reducing your carbohydrate intake, as this may enhance the drug's ability to engage the FGF21 pathway and promote greater weight reduction.

Individuals with overweight or obesity who enroll in weight loss programs but receive no active intervention (minimal contact control) lose an average of approximately 1 kg over 12 months, contradicting the assumption that they would gain weight.

If you are struggling with weight, know that your motivation to change is a powerful tool in itself. Studies show that simply enrolling in a program, being weighed regularly, and receiving brief advice from a professional can lead to an average loss of about 1 kg in the first year, even without a strict diet or exercise plan. This baseline loss validates your effort and suggests that engagement is a critical first step.

A three-week ketogenic diet shifts tryptophan metabolism to increase kynurenic acid and decrease quinolinic acid, potentially promoting mitochondrial protection and reducing neuroinflammation.

Following a ketogenic diet may shift your body's processing of tryptophan away from potentially neurotoxic byproducts (quinolinic acid) toward protective ones (kynurenic acid). This suggests a potential neuroprotective benefit of long-term ketosis.

Transforming urban provisioning systems through integrated spatial planning and supply-side innovations (e.g., active mobility, green infrastructure, clean energy) reduces cardiometabolic risk factors and improves cardiovascular health outcomes.

Advocate for and utilize urban designs that prioritize walking, cycling, and access to green spaces. If you live in a city, look for 'walkable' neighborhoods with mixed land use. If infrastructure is lacking, support policy changes for better transit and pedestrian safety, as these systemic changes directly lower your risk of cardiovascular disease and help maintain a healthy weight.

The rs3758391 C/T single-nucleotide polymorphism in the human SIRT1 promoter determines the magnitude of SIRT1 upregulation in skeletal muscle during long-term calorie restriction, with the T allele facilitating greater expression than the C allele.

If you are following a calorie-restricted diet, your genetic variant rs3758391 in the SIRT1 gene influences how much your muscle's SIRT1 levels rise. Individuals with the T allele (CT or TT genotypes) experience a significantly larger increase in SIRT1 expression after 6 months of restriction compared to those with the CC genotype. This does not mean CC individuals fail to adapt, but their molecular response is blunted. This effect is not seen after only 3 months of restriction, suggesting robust, long-term caloric deficit is required to observe these genetic differences.

Low total energy expenditure (TEE), specifically reduced expenditure for physical activity, facilitates rapid weight gain in genetically susceptible individuals by providing surplus energy for fat deposition.

If you are prone to weight gain, your body may naturally expend less energy through physical activity than others. This isn't just a result of being overweight; it's a mechanism that drives weight gain. To counteract this, you must consciously increase your physical activity levels, as your body may not naturally adjust its expenditure to match higher intake. While you may not see massive fat loss from exercise alone, it is a necessary lever to prevent surplus energy storage.