Browse the evidence

Urbanization and higher socioeconomic status (specifically higher education levels in women and white/urban demographics in men) are strongly associated with increased obesity and abdominal obesity rates in South African adults.

If you live in an urban area in South Africa, especially if you are a woman, your risk of obesity is significantly higher due to environmental factors like diet changes and reduced physical labor, not just personal choice. Public health efforts should target urbanization-related lifestyle changes and address cultural perceptions that equate larger body size with health and prosperity. Regular screening using objective measures like waist circumference is recommended, as self-perception of weight is often inaccurate.

In healthy lean men, a significant drop in leptin levels during short-term fasting is both necessary and sufficient to trigger physiological adaptations in the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, as maintaining leptin levels via replacement-dose recombinant leptin prevents these hormonal changes.

If you are lean and healthy, short-term fasting will cause your sex hormones (testosterone) and thyroid signaling to drop. This is a normal, protective response driven by low leptin levels, not a sign of permanent damage. It is reversible once you resume normal eating.

In healthy lean men, the metabolic and neuroendocrine adaptations of the hypothalamic-pituitary-adrenal (HPA), renin-aldosterone, and growth hormone-IGF-1 axes during short-term fasting are independent of leptin levels.

Fasting affects different hormonal systems differently. While reproductive hormones drop due to low leptin, stress hormones (cortisol) and growth hormone changes happen regardless of leptin levels. Do not assume fixing leptin will fix all hormonal responses to starvation.

The standard 1 MET value (3.5 mL O2/kg/min) significantly overestimates resting energy expenditure and total energy expenditure in overweight and obese individuals.

If you are overweight or obese, do not use the standard 1 MET value (3.5 mL O2/kg/min) to estimate your energy expenditure. It will significantly overestimate your resting energy expenditure (by ~20%) and total energy expenditure. Use BMI-specific correction factors or measured resting metabolic rate for more accurate calculations.

Central administration of GLP-1 receptor agonists (specifically liraglutide) stimulates brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning via a hypothalamic mechanism involving the ventromedial nucleus (VMH) and AMPK dephosphorylation, leading to increased energy expenditure independent of food intake.

GLP-1 agonist medications (like liraglutide or exenatide) do more than just make you feel full; they actively increase your body's energy expenditure by stimulating brown fat activity and 'browning' white fat. This happens through a specific pathway in the brain (hypothalamus). For patients with Type 2 Diabetes, adding these drugs to metformin treatment significantly increases resting energy expenditure compared to metformin alone, contributing to weight loss beyond just eating less.

Chronic hyperglycemia induces mitochondrial ROS production and ER stress, creating a vicious cycle that impairs pancreatic beta-cell function and insulin secretion, leading to Type 2 Diabetes.

To protect your beta-cells, focus on preventing chronic high blood sugar. The paper suggests that keeping glucose levels stable reduces the oxidative stress that damages the cells responsible for making insulin. This means prioritizing a diet that prevents glucose spikes and supports mitochondrial health.

Elevated white blood cell count (WBC), serving as a marker of chronic low-grade inflammation, predicts the development of type 2 diabetes and is associated with a worsening of insulin sensitivity independent of adiposity.

High white blood cell counts are a warning sign for future insulin resistance and type 2 diabetes, even in people who are not yet obese. This suggests that chronic, low-grade inflammation is a key driver of metabolic health. To mitigate this risk, focus on reducing systemic inflammation through anti-inflammatory dietary patterns (rich in omega-3s, fiber, and polyphenols), managing stress, and treating any underlying chronic infections or conditions, rather than focusing solely on weight loss.

Sarcopenia (severe muscle depletion measured by cross-sectional imaging) is an independent predictor of increased mortality on the liver transplant waiting list, particularly in patients with lower MELD scores (<15).

For patients with advanced liver disease awaiting transplant, muscle mass is a critical predictor of survival, independent of standard severity scores. Objective assessment of muscle mass (via imaging) is superior to subjective tools like BMI for identifying high-risk patients, particularly those with lower disease severity scores.

Pharmacological elimination of senescent cells (senolytics) or suppression of their secretory phenotype (senomorphics) delays or alleviates multiple age-related pathologies and extends healthspan in animal models.

Current research suggests that clearing senescent cells may help delay age-related diseases. However, effective treatments are still in clinical trials. Do not attempt to self-medicate with unproven supplements claiming to be 'senolytics' without medical supervision, as efficacy and safety are not yet established for general use.

Chronic hyperglycemia and subsequent reactive oxygen species (ROS) production cause pancreatic beta-cell dysfunction and insulin resistance in type 2 diabetes by activating the JNK pathway, which suppresses insulin gene transcription and promotes beta-cell apoptosis.

Focus on managing blood glucose levels to reduce the production of reactive oxygen species, which drives beta-cell damage and insulin resistance. While antioxidants are often marketed for health, current evidence suggests they are not sufficient on their own to treat type 2 diabetes; addressing the root cause (hyperglycemia) is essential.

Reactive oxygen species (ROS) derived from NADPH oxidase activation contribute to the progression of atherosclerosis in diabetic patients by promoting endothelial dysfunction, inflammation, and smooth muscle cell proliferation.

Managing diabetes helps reduce the risk of atherosclerosis by lowering ROS production. Genetic factors also play a role in vulnerability, so comprehensive management of blood sugar and blood pressure is important for vascular health.

High-dose aspirin (approx. 7 g/day) improves glucose metabolism in type 2 diabetes by inhibiting the IKKβ serine kinase pathway, thereby reducing hepatic glucose production and enhancing peripheral insulin sensitivity.

This study proves that inhibiting the IKKβ pathway improves insulin sensitivity in type 2 diabetes. However, high-dose aspirin is too toxic for routine use. The practical takeaway is that IKKβ is a valid therapeutic target for developing safer diabetes medications, rather than using aspirin itself.

Administration of recombinant human Fibroblast Growth Factor 19 (FGF19) increases metabolic rate and reverses diet-induced and leptin-deficient diabetes in mice without reducing food intake.

This research identifies FGF19, a hormone, as a potent driver of metabolic rate and glucose control in mice. While not a current human supplement, it suggests that targeting FGF19 pathways could be a viable strategy for treating obesity and type 2 diabetes by increasing energy expenditure rather than restricting food intake.

FGF19 increases metabolic rate and improves glucose homeostasis by increasing fatty acid oxidation and decreasing liver triglycerides, mediated by the suppression of Acetyl CoA Carboxylase 2 (ACC2) and increased leptin receptor expression in the liver.

FGF19 works by telling the liver to burn more fat. It does this by turning off ACC2 (a gatekeeper for fat storage) and turning up leptin receptors (sensitivity to the fat-regulating hormone leptin).

Brown Adipose Tissue (BAT) activation is not essential for FGF19 to increase metabolic rate and reverse obesity/diabetes, as FGF19 remains effective in mice with diminished BAT (UCP-DTA mice).

You don't need 'active' brown fat for FGF19 to help with weight and blood sugar. It works through other pathways, primarily in the liver.

Thiazolidinediones (specifically pioglitazone) improve liver steatosis and inflammation but cause significant weight gain.

Pioglitazone can improve liver inflammation and fat, but it causes significant weight gain. This trade-off makes it less ideal than weight loss alone for many patients. It is a prescription medication, so discuss the risks and benefits with your doctor.

In older adults, BMI is a poor indicator of obesity-related mortality risk because it fails to distinguish between fat mass and lean muscle mass, which have opposing effects on survival.

If you are over 65, do not rely on BMI alone to judge your health risks. Because muscle mass naturally declines with age, a 'normal' BMI might hide high body fat and low muscle, which is dangerous. Focus on maintaining muscle strength and mass through resistance training and adequate protein, rather than just chasing a specific number on the scale.

Current global supplies of EPA and DHA from traditional marine sources are insufficient to meet human nutritional requirements, creating a supply-demand gap of over 0.4 to 1 million tonnes annually.

You cannot rely on current global fish stocks alone to meet recommended Omega-3 intake levels for everyone. The system is already strained. Consumers should look for products fortified with novel, sustainable sources of EPA/DHA (like algae oils) to ensure adequate intake without contributing to overfishing.

Novel sources of EPA and DHA, such as genetically modified oilseed crops (canola/camelina) and microalgae, can fully replace fish oil in aquaculture feeds without negative impacts on fish growth or health.

Look for farmed fish fed with novel Omega-3 sources (algae or GM plant oils). These products often have higher or equal Omega-3 levels compared to standard farmed fish and support sustainable fishing practices.

Circulating levels of the ob protein (leptin) and ob mRNA expression in adipose tissue are directly regulated by the state of energy stores, increasing with obesity and decreasing with starvation.

This research confirms that your body produces more of this fat-regulating hormone as you gain weight, not less. This suggests that obesity involves a resistance to this signal rather than a simple deficiency. Therefore, simply taking this hormone as a supplement is unlikely to be effective for weight loss in obese individuals, as the body's response to it is already elevated.

Multiplatform metabolomics profiling of fasting blood samples can identify specific metabolic signatures—including elevated branched-chain amino acids, ketone bodies, and altered lipid ratios, alongside decreased 1,5-anhydroglucitol—that distinguish individuals with type 2 diabetes from healthy controls, even under sub-clinical conditions.

For individuals concerned about diabetes risk, this research suggests that looking beyond standard blood sugar tests to a broader metabolic profile (including fats, amino acids, and gut-related metabolites) may offer earlier detection of metabolic dysfunction. This approach could help identify those at high risk for complications before clinical symptoms appear, enabling more personalized monitoring and prevention strategies.

Intermittent fasting does not significantly affect Glycosylated Hemoglobin (HbA1c), Low-Density Lipoprotein Cholesterol (LDL-C), or High-Density Lipoprotein Cholesterol (HDL-C) compared to control diets.

If your primary goal is to lower LDL cholesterol or improve HbA1c, intermittent fasting alone may not be sufficient. While it helps with weight, blood pressure, and triglycerides, it does not significantly change LDL, HDL, or long-term blood sugar markers (HbA1c). You may need to combine IF with other dietary strategies or medications to address these specific markers.

Caloric restriction (CR) extends lifespan and delays age-related diseases in mammals by modulating multiple metabolic pathways, including reduced insulin/IGF-1 signaling, lower thyroid hormone levels, and increased adiponectin, though its translation to human lifespan extension remains unproven.

While rigorous caloric restriction extends lifespan in animals, its effect on human lifespan is unproven. However, moderate caloric restriction combined with exercise can improve healthspan, reduce disease risk, and preserve muscle and bone density in middle-aged adults without the severe side effects of extreme dieting.

Attenuated Insulin/IGF-1 Signaling (IIS) extends lifespan in model organisms, but in humans, low IGF-1 is associated with increased risk of cardiovascular disease, diabetes, and osteoporosis, creating a paradox where the mechanism that extends lifespan in animals may be detrimental in humans.

While reducing IIS extends lifespan in animals, humans with naturally low IGF-1 face higher risks of heart disease, diabetes, and bone loss. Therefore, simply trying to lower insulin/IGF-1 or boost it via GH therapy without medical supervision is not a straightforward longevity strategy for humans.