Browse the evidence

High circulating levels of the artificial sweetener erythritol are associated with a significantly increased risk of major adverse cardiovascular events (MACE), including heart attack and stroke, and directly enhance platelet reactivity and thrombosis potential.

If you consume erythritol (a common artificial sweetener in 'keto' products, sugar-free drinks, and baked goods), be aware that it can accumulate in your blood and make your platelets more likely to form clots. This risk is particularly relevant if you have existing heart disease, diabetes, or high blood pressure. While occasional use may not pose a significant risk for healthy individuals, those at higher cardiovascular risk should consider limiting erythritol intake and consulting their doctor, especially given that levels can remain elevated for days after consumption.

GLP-1 receptor agonists and DPP-4 inhibitors provide effective glucose lowering with weight loss (GLP-1) or weight neutrality (DPP-4) and minimal hypoglycemia risk, outweighing potential risks of pancreatitis or thyroid cancer which lack convincing human evidence.

For patients with Type 2 Diabetes, GLP-1 receptor agonists (like liraglutide or exenatide) and DPP-4 inhibitors (like sitagliptin) are effective, safe options for lowering blood sugar. GLP-1 agonists offer the added benefit of weight loss, while DPP-4 inhibitors are weight-neutral. Current evidence does not support fears of increased pancreatitis or thyroid cancer risk in humans, making these therapies favorable compared to older drugs that cause weight gain or hypoglycemia.

Smaller adipocytes resulting from weight loss exhibit higher insulin sensitivity and enhanced nutrient clearance capacity, which signals energy depletion to the brain and promotes the storage of ingested energy.

Your body's fat cells become more efficient at storing fat when they shrink. This biological efficiency makes it easier to regain weight when you eat, as your body prioritizes storing those calories over burning them.

Weight loss reduces circulating levels of leptin and insulin disproportionately to fat mass loss, signaling energy depletion to the hypothalamus and increasing appetite.

Your body uses hormones like leptin and insulin to signal energy status. After weight loss, these hormones drop more than expected, telling your brain you are starving, which increases hunger and drives you to eat more.

Activation of brown adipose tissue (BAT) via cold exposure, beta-3 agonists, or specific hormonal mediators (FGF21, IL-6, BMPs) improves glucose tolerance and insulin sensitivity in humans and rodents.

To leverage brown fat for metabolic health, expose yourself to mild cold (around 19°C or 66°F) for extended periods (e.g., 12 hours). This activates BAT, increasing energy expenditure and improving insulin sensitivity through the release of hormones like FGF21. While beta-3 agonists work in rodents, they are not yet viable for humans, making cold exposure the primary practical tool.

Tirzepatide, a dual GIP and GLP-1 receptor agonist, produces clinically significant reductions in HbA1c and body weight in patients with type 2 diabetes, with efficacy superior to the selective GLP-1RA dulaglutide.

For patients with type 2 diabetes, tirzepatide offers superior glucose and weight control compared to existing GLP-1 drugs. To minimize stomach upset, it is crucial to follow the prescribed slow dose-escalation schedule (starting at 2.5mg or 4mg and increasing gradually over 8 weeks). This approach balances high efficacy with better tolerability.

Exogenous administration of Peptide YY (PYY) reduces appetite and food consumption by approximately 30% in both lean and obese humans, primarily through inhibition of gut motility and hypothalamic signaling.

Your gut produces a hormone called PYY to tell your brain you are full. In obesity, this signal is often weaker. While injecting PYY works in studies, it is not a standalone cure. Focus on foods that naturally stimulate PYY release (like those reaching the distal small bowel) and respect the satiety signals your body sends, as relying on a single 'magic bullet' hormone therapy is unlikely to succeed long-term.

Chronic low-grade inflammation, driven by obesity and excess nutrient intake, is a primary mechanistic link that causes both insulin resistance and hypertension by impairing insulin signaling and promoting vasoconstriction.

Addressing the root cause of inflammation through weight management and reducing processed food intake can simultaneously improve insulin sensitivity and lower blood pressure, as inflammation drives both pathologies.

Obesity-associated health risks (such as type 2 diabetes and coronary heart disease) are not determined solely by body mass index (BMI) or total fat mass, but are critically governed by the location of fat deposition (visceral vs. subcutaneous) and genetic variations in adipokine secretion (e.g., adiponectin).

Do not rely on BMI alone to assess your health risks. Focus on waist circumference and metabolic markers (like blood sugar and lipids) because your genetic makeup and where you store fat (belly vs. hips) determine your actual risk for diabetes and heart disease, not just your total weight.

Truncal obesity (measured by waist/thigh circumference ratio) is significantly correlated with insulin resistance in females but not in males, independent of total body fat percentage.

For women, where fat is stored (truncal vs. lower body) matters for insulin resistance, even if total weight is the same. For men, total body fat percentage is a better predictor than fat distribution.

Adopting low glycaemic index (GI) or low glycaemic load (GL) dietary patterns results in small but clinically significant improvements in glycaemic control (HbA1c) and cardiometabolic risk factors (lipids, inflammation, adiposity) for adults with moderately controlled type 1 and type 2 diabetes, even when concurrent with standard pharmacotherapy.

If you have type 1 or type 2 diabetes, switching to a low GI or GL diet can help lower your HbA1c and improve cholesterol and inflammation, even if you are already taking diabetes medication. You don't need to change everything at once; focus on replacing high-GI carbohydrates (like white bread and sugary drinks) with lower-GI options (like legumes and whole grains). This approach is safe, effective, and works alongside your current treatment plan to help you reach your health goals.

Insulin resistance is a major cardiovascular risk factor in subjects without diabetes and serves as a key link between MAFLD/NASH and cardiovascular disease.

Even if you do not have diabetes, insulin resistance associated with fatty liver disease significantly increases your risk of heart disease. Addressing insulin sensitivity through lifestyle changes is crucial for cardiovascular health, regardless of your diabetes status.

Infusion of beta-hydroxybutyrate (BHB) decreases whole-body leucine oxidation and increases fractional mixed skeletal muscle protein synthesis in humans without altering total protein breakdown (leucine flux).

Infusing beta-hydroxybutyrate (a ketone body) reduces the amount of amino acids your body burns for energy and directs more of them into building muscle protein. This happens without changing how much muscle tissue is broken down overall. The effect is specific to the ketone itself, not just the alkalinity of the blood, suggesting that elevated ketones naturally help preserve muscle mass during metabolic stress.

Adiponectin levels are inversely correlated with visceral fat mass and insulin resistance, and low levels are associated with increased cardiovascular risk.

Adiponectin is a beneficial hormone that improves insulin sensitivity and protects heart health. Its levels tend to be lower in people with high visceral fat. While you cannot directly 'take' adiponectin, lifestyle changes like exercise and weight loss can help increase your body's natural production of it.

Testosterone administration increases muscle strength and mass by enhancing protein synthesis and promoting satellite cell-mediated myonuclear accretion.

Testosterone significantly boosts muscle growth and strength by increasing protein synthesis and adding new nuclei to muscle fibers via satellite cells. This effect is dose-dependent and more pronounced in type I fibers. While effective for enhancement, it carries significant health risks and is banned in sports.

Restoring leptin levels to pre-weight loss concentrations reverses brain activity changes and metabolic adaptations (increased energy expenditure) induced by caloric restriction, thereby sustaining weight loss.

If you have lost weight, your body fights back by lowering leptin, which increases hunger and slows metabolism. This paper suggests that replacing leptin to pre-weight-loss levels can stop this fight-back mechanism. However, this is not a general weight-loss drug for currently obese people, as most have high leptin and don't respond to it. It may be relevant for a small subset of obese individuals with low leptin levels.

Females exhibit greater susceptibility to disuse-induced muscle atrophy compared to males, evidenced by faster onset of muscle loss and greater percent loss of oxidative (Type I) muscle mass during conditions like hindlimb unloading or ICU bed rest.

If you are female, be aware that your muscles may waste away faster than a male's during periods of inactivity (like bed rest or casting). This is partly because you naturally have more 'slow-twitch' muscle fibers, which are more vulnerable to disuse. Prioritize early, gentle movement or specific resistance strategies sooner than you might expect, as your body is biologically predisposed to lose this muscle type faster.

Dietary fiber and probiotic-induced short-chain fatty acids (SCFAs) reduce blood pressure and improve vascular health through G-protein coupled receptor signaling and histone deacetylase inhibition.

Increase your intake of dietary fiber and consider probiotics to boost short-chain fatty acid production. This metabolic shift activates specific receptors (GPR41/43) and enzymes that help lower blood pressure and improve vascular function. Focus on non-starch polysaccharides and low-digestible saccharides found in whole plant foods.

Elevated plasma levels of Trimethylamine-N-oxide (TMAO) are associated with increased risk of cardiovascular disease, thrombosis, and atherosclerosis, primarily through platelet hyper-reactivity and macrophage scavenger receptor stimulation.

High levels of TMAO, produced when gut bacteria metabolize choline and carnitine from foods like red meat and eggs, are linked to higher cardiovascular risk and blood clotting. To mitigate this, balance your intake of these foods with high-fiber diets that may alter microbiota composition, and monitor TMAO levels if you have existing cardiovascular risk factors.

A 6-week very-low-calorie diet (VLCD) significantly improves flow-mediated endothelial vasodilation in overweight adults, with the magnitude of improvement directly correlated with the reduction in fasting plasma glucose levels.

If you are overweight and have endothelial dysfunction (a precursor to heart disease), a short-term, medically supervised very-low-calorie diet (approx. 580 kcal/day) for 6 weeks can significantly improve your blood vessel health. Crucially, this benefit is driven by lowering your blood glucose, not just by losing weight. Ensure you do not have diabetes or other contraindications before attempting this.

Carriers of the ADRB2 Gln27Glu polymorphism experience increased obesity risk when consuming high carbohydrate diets (>49% total energy), whereas non-carriers do not show this specific dietary interaction.

If you carry the ADRB2 Glu27 variant, limiting carbohydrates to less than 49% of your total daily energy intake may help reduce obesity risk. Standard high-carb diets might disproportionately increase your risk compared to non-carriers.

Visceral adiposity, rather than overall body mass index (BMI), is the critical driver of metabolic syndrome comorbidities, including insulin resistance and cardiovascular risk.

Do not rely on BMI alone to assess your health risk. Waist circumference is a better indicator of visceral fat, which drives metabolic syndrome. Even if you are lean, high abdominal fat increases your risk for diabetes and heart disease.

Acute endurance exercise induces a marked increase in plasma follistatin (a myostatin inhibitor) originating from the liver, peaking during recovery rather than during the exercise bout itself.

To maximize the natural release of follistatin (which helps inhibit muscle breakdown by blocking myostatin), engage in sustained endurance exercise (e.g., 3 hours of cycling at moderate intensity). Note that the beneficial hormone levels peak during the recovery period (3 hours post-exercise), not necessarily during the workout itself. This suggests recovery is a critical phase for muscle-protective signaling.

Letrozole is the first-line pharmacological treatment for anovulatory infertility in women with PCOS, offering higher live birth and clinical pregnancy rates compared to Clomiphene Citrate (CC).

If you have PCOS and are struggling with infertility due to lack of ovulation, Letrozole is now the preferred first medication. It works better than the older drug Clomiphene (CC) and has a lower risk of twins and complications. It is often used off-label, so discuss this with your doctor.