Browse the evidence

Sibutramine was withdrawn from the market because long-term use increases the risk of non-fatal myocardial infarction and stroke in patients with cardiovascular risk factors.

Sibutramine is no longer available because it increases the risk of heart attack and stroke in people with existing heart conditions. It was withdrawn from the market in 2010.

Autoimmune thyroid disease (AITD) is significantly more prevalent in patients with Type 1 Diabetes (T1D) than in the general population, sharing common genetic susceptibility factors.

If you have Type 1 Diabetes, you are at a much higher risk for autoimmune thyroid disease (17-30% prevalence). Regular screening for thyroid function (TSH) and antibodies (TPO) is recommended, even if you feel healthy, to prevent complications and ensure optimal diabetes management.

Long-term DHEA or low-dose testosterone replacement in elderly people with low androgen levels does not produce clinically relevant improvements in body composition, physical performance, insulin sensitivity, or quality of life.

If you are an older adult with low hormone levels, taking DHEA or testosterone patches for 2 years will not make you stronger, fitter, or metabolically healthier, nor will it improve your quality of life. While testosterone might add a tiny amount of fat-free mass in men, it does not translate to better muscle strength or function. The treatment is safe regarding prostate health in this context, but it does not deliver the 'anti-aging' benefits often marketed.

The combination of oral estrogen use with prothrombotic mutations (Factor V Leiden or Prothrombin G20210A) or obesity significantly enhances the risk of venous thromboembolism.

If you have a known blood clotting mutation (like Factor V Leiden) or are overweight/obese, taking oral estrogen significantly increases your risk of blood clots (up to 8 times higher for mutations). However, using transdermal estrogen (patches/gels) does not appear to add extra risk for these high-risk groups, making it a safer choice to discuss with your doctor.

Accelerated brain aging, specifically measured by a cognition-optimized plasma proteomic model (CognitionBrain), predicts Alzheimer's disease progression and cognitive decline independently of and as strongly as the current best blood biomarker, pTau-181.

For those concerned about Alzheimer's, this research suggests that a new blood test measuring brain-specific aging (CognitionBrain) is just as powerful as the current gold standard (pTau-181) and provides additional, independent information. Using both together offers the best prediction of cognitive decline. This highlights the importance of early, multi-faceted biomarker screening for those with family history or risk factors, rather than relying on a single test.

Computed Tomography (CT) imaging at the L3 vertebra is a gold-standard, accurate, and precise method for assessing skeletal muscle cross-sectional area and visceral adipose tissue, allowing for the estimation of whole-body composition from single cross-sectional images.

For patients already undergoing CT scans for medical reasons (like cancer or ICU care), the images can be used to accurately assess muscle mass and fat distribution at the L3 vertebra level. This 'opportunistic' use provides critical nutritional data without exposing the patient to additional radiation.

Glucocorticoid administration induces skeletal muscle atrophy primarily by stimulating the ubiquitin-proteasome system (UPS) via FOXO transcription factors and downregulating IGF-I signaling, while simultaneously inhibiting protein synthesis through mTOR repression.

If you are prescribed glucocorticoids, muscle loss is driven by active molecular switches (FOXO, mTOR) rather than just inactivity. While you cannot stop the medication, being aware that this is a specific biological response helps in seeking targeted counter-measures (like specific nutritional or pharmacological interventions discussed in the paper) rather than assuming the loss is inevitable or purely due to lack of exercise.

Supplementation with synthetic vitamins and antioxidants does not reduce the risk of major cardiovascular events in primary or secondary prevention.

Do not rely on vitamin or antioxidant supplements to prevent heart disease or stroke. This meta-analysis of nearly 300,000 participants found no benefit for major cardiovascular events. Focus on a diet rich in natural fruits and vegetables instead, as the study explicitly notes these findings do not apply to natural food sources.

Hepatic insulin resistance, characterized by failure to suppress hepatic glucose production (gluconeogenesis and glycogenolysis), is a major feature of type 2 diabetes pathophysiology.

Managing fasting blood glucose often requires addressing hepatic glucose output, which can be influenced by weight loss and specific medications that target liver insulin sensitivity.

Using recovery biomarkers (such as doubly labeled water and urinary nitrogen) is the most effective method to validate self-reported dietary intake and quantify measurement error.

For accurate dietary assessment in research, use recovery biomarkers like doubly labeled water or urinary nitrogen to validate self-reported data.

Levothyroxine therapy does not improve thyroid-related symptoms or quality of life in older adults (≥65 years) with subclinical hypothyroidism.

If you are over 65 and have subclinical hypothyroidism (high TSH but normal T4), taking levothyroxine is unlikely to make you feel less tired or improve your quality of life. While the medication will lower your TSH levels, it does not appear to provide clinical benefits for symptoms in this age group.

Dietary polyphenol supplementation generally fails to produce significant anti-oxidative or anti-inflammatory effects in patients with metabolic syndrome, despite theoretical benefits.

Do not rely on polyphenol supplements to reduce inflammation or oxidative stress if you have Metabolic Syndrome. The evidence shows these supplements generally do not significantly improve these specific markers in humans, even if they help with weight or blood pressure. Focus on whole dietary patterns like the Mediterranean diet instead.

Breast-feeding does not have important antiobesity effects in children.

Breastfeed if you can, as it has many benefits for mother and child, but do not expect it to prevent obesity. It is not a reliable tool for weight management in children.

Insulin is the primary hormonal inhibitor of lipolysis, acting by activating phosphodiesterase-3B to lower cAMP levels and preventing hormone-sensitive lipase (HSL) activation.

Insulin is the body's main signal to stop breaking down fat. High insulin levels (e.g., from high carbohydrate intake) will inhibit lipolysis. To maximize fat mobilization, managing insulin through dietary composition and timing is important, but it is just one part of the complex regulation involving catecholamines and other factors.

Daily supplementation with 1000 mg elemental calcium and 400 IU vitamin D3 does not reduce the incidence of invasive breast cancer in postmenopausal women.

For postmenopausal women, taking 1000 mg of calcium and 400 IU of vitamin D3 daily will not reduce the risk of developing invasive breast cancer. While these supplements are important for bone health, they should not be used as a strategy for breast cancer prevention.

Glucocorticoids (corticosteroids) act as a primary synchronizing signal from the central SCN to peripheral clocks, particularly in the liver, regulating up to 60% of the hepatic transcriptome.

Cortisol rhythms help synchronize your liver's metabolism to the day. Disrupting this rhythm (e.g., through stress or irregular sleep) may impair liver function and detoxification pathways.

Moderate to high intensity aerobic and strength exercise training does not slow cognitive impairment in people with mild to moderate dementia and may potentially worsen it, despite improving physical fitness.

For caregivers of individuals with mild to moderate dementia, prescribing moderate to high intensity aerobic and strength exercise is unlikely to slow cognitive decline and may slightly accelerate it on standard tests, though the clinical relevance is uncertain. However, this regimen significantly improves physical fitness (e.g., walking distance). Therefore, exercise should be prescribed primarily for physical health and functional independence, not for cognitive preservation, with careful monitoring for adverse events.

PPARgamma mutations (loss-of-function) cause familial partial lipodystrophy type 3 (FPLD3), characterized by lack of subcutaneous fat in extremities and metabolic complications like type 2 diabetes.

Fat distribution is partly genetic. If you have a rare condition like FPLD3, your fat distribution and metabolic risks are driven by specific genetic mutations.

Therapeutic CPAP does not significantly improve glycaemic control (HbA1c) or insulin resistance (measured by euglycaemic clamp and HOMA) in men with established type 2 diabetes and obstructive sleep apnoea.

If you have type 2 diabetes and sleep apnoea, using CPAP will help you feel less sleepy and improve your quality of life, but it will not lower your blood sugar or fix insulin resistance on its own. You still need to manage your diabetes with diet, medication, or other treatments specifically designed for metabolic control.

The intrinsic human circadian period averages 24.1 to 24.2 hours, not 25 hours as previously estimated in older studies.

Your body clock is naturally slightly longer than 24 hours. To stay aligned with the day, you need to manage light exposure, especially in the evening, to prevent your clock from drifting later.

Mutations in the leptin-melanocortin pathway genes (LEP, LEPR, POMC, PCSK1, MC4R) cause severe, early-onset obesity through hyperphagia and altered energy expenditure.

If you have severe early-onset obesity, ask your doctor about genetic testing. For some, specific medications (like leptin therapy) can be highly effective because they target the root biological cause.

GLP-2 (specifically the analogue teduglutide) promotes intestinal mucosal growth and nutrient absorption, making it an effective treatment for short bowel syndrome (SBS).

For patients with short bowel syndrome who rely on intravenous nutrition, teduglutide (a GLP-2 analogue) is an approved daily injection that helps the intestine grow and absorb more nutrients. This can reduce the need for intravenous feeding. It is specifically designed to resist breakdown in the body, making it effective for chronic use.

Prenatal exposure to severe famine during the third trimester of gestation causes a significant reduction in birth weight, whereas exposure during the first trimester is associated with an increase in birth weight.

This historical natural experiment demonstrates that the timing of nutritional deprivation during pregnancy has distinct, opposing effects on fetal growth. Third-trimester starvation reduces birth weight, while first-trimester starvation is associated with increased birth weight, likely due to adaptive placental mechanisms. This highlights that 'malnutrition' is not a monolithic concept; its impact depends entirely on the developmental stage of the fetus.

The APOE2 allele is a protective factor for longevity, while the APOE4 allele is deleterious, with APOE being the only locus to consistently achieve genome-wide significance in GWAS of longevity.

The APOE2 gene variant is associated with a longer lifespan, while APOE4 is associated with a shorter one. While you cannot change your APOE status, understanding your genotype may inform your approach to cardiovascular and cognitive health management, as these are key pathways affected by APOE.