Browse the evidence

Higher genetically predicted BMI causally increases the risk of renal, acute diabetic crisis, and infective deaths.

Higher BMI is strongly linked to death from kidney disease, severe diabetic episodes, and infections. Preventing these outcomes requires addressing underlying metabolic health.

Energy expenditure can be increased through specific physiological mechanisms independent of physical activity, including UCP1-dependent thermogenesis in brown/beige fat, futile cycling of substrates (creatine, glucose, lipids), and ion pumping (Na+/K+-ATPase, SERCA).

Your body burns calories through several active processes beyond just moving around. These include generating heat in fat tissue (thermogenesis), running 'futile' metabolic cycles that burn energy as heat, and maintaining electrical gradients in cells. While you can't easily control these directly, understanding them helps explain why some medications work better than others. Future treatments may target these specific pathways to help you burn more calories passively.

Semaglutide provides robust cardiovascular risk reduction (MACE) in patients with Type 2 Diabetes and established cardiovascular disease, independent of glycemic control improvements.

If you have obesity and established heart disease, semaglutide (2.4mg weekly) significantly reduces your risk of major adverse cardiovascular events (MACE), even if you do not have diabetes. This benefit is driven by weight loss and cardiometabolic improvement, not just blood sugar control.

Heart disease and stroke remain the leading causes of death globally, with significant disparities in prevalence and mortality across different racial and ethnic groups, necessitating targeted public health interventions to address structural racism and health equity.

Focus on managing key risk factors like blood pressure, cholesterol, and blood sugar, while being aware of and addressing potential systemic barriers to healthcare access.

Obesity drives insulin resistance and type 2 diabetes through the accumulation of free fatty acids and pro-inflammatory cytokines in non-adipose tissues, which activate kinases (PKC, JNK, IKKβ) that inhibit insulin receptor signaling.

If you have obesity, your risk for type 2 diabetes is significantly higher due to biological changes in your fat tissue and blood. This isn't just about 'eating less'; it's about how your body processes energy. Addressing obesity through sustainable lifestyle changes can mitigate these specific biological risks.

A cumulative deficit frailty index, constructed from 26 non-traditional health deficits, is a stronger predictor of cardiovascular events and mortality than traditional risk scores (like Framingham) and provides incremental prognostic value independent of those traditional factors.

If you are over 65 or have heart disease risk factors, ask your doctor to assess your 'frailty' using a deficit accumulation model (checking for symptoms, lab abnormalities, and functional limitations), not just standard cholesterol and blood pressure numbers. This assessment predicts heart attacks and death more accurately than traditional scores and can help prioritize preventive care.

Body weight regulation is not governed by a single fixed set-point, but rather by a dynamic equilibrium where energy expenditure passively adjusts to match intake, creating a 'zone of indifference' bounded by upper and lower intervention points.

Do not assume your body has a rigid 'set point' that fights against you. Your weight settles at a level where your energy expenditure matches your intake. If your environment changes (e.g., more food, less activity), your weight will drift until your expenditure rises to match the new intake. Understanding this passive feedback helps explain why small, sustained environmental changes lead to gradual weight gain over years.

Alternate-day fasting does not produce superior weight loss, weight maintenance, or cardioprotection compared to daily calorie restriction in metabolically healthy obese adults.

If you are obese and metabolically healthy, alternate-day fasting is not a magic bullet for better weight loss or heart health compared to simply eating less every day. It is equally effective for weight loss but may be harder to stick to long-term, as evidenced by higher dropout rates. Choose the diet you can sustain consistently.

Bariatric surgery (specifically Roux-en-Y gastric bypass) produces the largest and most durable weight loss among current treatments, serving as a benchmark for efficacy, though individual response varies significantly.

If lifestyle and medications fail, bariatric surgery (like RYGB) is the most effective option for significant, sustained weight loss, averaging over 30% loss. It is considered the benchmark for efficacy, though it requires lifelong medical follow-up.

Intermittent energy restriction (IER) diets (time-restricted eating, alternate-day fasting, and 5:2 diet) do not produce superior improvements in body weight, fat mass, or cardiometabolic risk markers compared to continuous energy restriction (CER) when total energy intake is matched.

If your goal is weight loss or better metabolic health, you do not need to adopt a complex intermittent fasting schedule. A standard daily calorie restriction diet is equally effective. Focus on maintaining a consistent caloric deficit rather than restricting your eating window, unless you personally prefer the structure of fasting.

Global age-standardised mean BMI in children and adolescents increased significantly from 1975 to 2016, with obesity prevalence rising from 0.7% to 5.6% in girls and 0.9% to 7.8% in boys, while underweight prevalence decreased.

Track your child's growth using standard BMI percentiles for their age and sex, not just absolute weight. Recognize that both underweight and obesity carry significant health risks. In many regions, underweight remains a larger burden than obesity, so nutritional support should address both ends of the spectrum.

The trajectory of BMI increase in children and adolescents has decoupled from adults in many high-income countries, where childhood BMI trends have plateaued while adult BMI continues to rise.

In high-income countries, public health efforts for children may be showing results (plateauing BMI), but adult obesity continues to rise. This suggests that childhood interventions are working to some extent, but adult lifestyle factors remain unaddressed. Focus on maintaining childhood gains and addressing adult-specific barriers.

Underweight remains a more prevalent issue than obesity globally for children and adolescents, with the highest burden concentrated in South Asia and parts of Africa.

Do not assume that obesity is the only or main nutrition problem for children. In many parts of the world, underweight is far more common. Nutrition programs must be tailored to address both undernutrition and overnutrition, especially in South Asia and Africa.

Prebiotics are defined as substrates selectively utilized by host microorganisms to confer a health benefit, distinguishing them from non-selective dietary fibers and non-microbial agents.

Not all gut-friendly foods are prebiotics. To be a prebiotic, a substance must be selectively eaten by beneficial bacteria to produce a specific health benefit. Common examples like inulin and FOS fit this, but general fibers like cellulose do not necessarily qualify.

Health benefits from prebiotics are mediated by the selective growth of specific microbial taxa and their metabolic products (e.g., SCFAs), rather than the substrate itself acting directly on host cells.

Prebiotics work by feeding specific gut bacteria. These bacteria then produce beneficial compounds (like short-chain fatty acids) that improve your health. You need a healthy gut microbiome for prebiotics to work.

High systolic blood pressure (SBP) is a leading metabolic risk factor globally, contributing to 7.8% of total disability-adjusted life-years (DALYs) in 2021, with an increasing annual exposure rate of 1.8%.

High blood pressure is a major driver of global disease burden. Regular monitoring and management are crucial for long-term health.

Spending 9.5 or more hours per day sedentary is associated with a statistically significantly higher risk of death.

Avoid sitting for more than 9.5 hours a day. If you have a desk job, incorporate standing breaks and light movement throughout the day. The risk of death increases significantly once sedentary time exceeds this threshold, even if you exercise moderately.

Inflammation and disease burden are critical etiologic criteria for malnutrition, contributing to altered metabolism, increased muscle catabolism, and adverse outcomes.

Malnutrition isn't just about not eating enough; active disease and inflammation can cause muscle loss and metabolic changes even if food intake is normal. Diagnosis must account for these inflammatory drivers.

Hypertension prevalence and mortality burden are significantly higher in low- and middle-income countries compared to high-income countries, with deaths attributable to high blood pressure increasing in Asia and sub-Saharan Africa.

Recognize that hypertension is a major killer in low- and middle-income countries. Support global health initiatives that scale up treatment coverage and improve community effectiveness in these regions.

Chronic low-grade inflammation (inflammaging) is a fundamental endogenous driver of aging, creating a vicious cycle with cellular senescence that leads to organ dysfunction and age-related diseases.

Aging is closely linked to chronic, low-grade inflammation. While this paper is a mechanistic review, the implication is that strategies reducing systemic inflammation may support healthy aging. Focus on lifestyle factors known to modulate inflammation, such as regular physical activity, adequate sleep, and a nutrient-dense diet, as these are foundational to managing 'inflammaging'.

Immunosenescence, characterized by a decline in immune cell function and an increase in pro-inflammatory cytokine secretion, impairs the clearance of senescent cells and pathogens, exacerbating aging.

Immune function declines with age, leading to increased susceptibility to infection and chronic inflammation. Maintaining immune health through vaccination, stress management, and nutrient adequacy is crucial for older adults.

For deaths related to mental/behavioral disorders, neurological conditions, and non-transport accidents, lower BMI (up to 24-27 kg/m²) is associated with increased mortality risk, showing an inverse linear association rather than a J-shape.

Don't assume being thin is always safer. For neurological and mental health-related causes of death, this study found that lower BMI (down to 24-27) was associated with higher risk. Maintaining a healthy weight (not underweight) is important for protecting against these specific outcomes.

Weight stigma and discrimination cause significant physical and psychological harm to individuals with obesity, including increased risks of depression, anxiety, and avoidance of healthcare, thereby undermining public health efforts.

If you have obesity, know that your weight is not a moral failing. Stigma from society or healthcare providers is harmful and can worsen your health by discouraging you from seeking care. You deserve respectful, evidence-based treatment. Healthcare providers should strive to eliminate bias and provide dignified care.

NAD+ serves as a co-substrate for enzymes like sirtuins and PARPs, and as a nucleotide analog in DNA ligation, impacting energy metabolism, DNA repair, and gene expression.

Understanding NAD+ roles helps explain why lifestyle factors like exercise and diet are important for healthspan. NAD+ is not just for energy but also for DNA repair and gene regulation.