Browse the evidence

Ketogenic diets increase the risk of cardiovascular disease markers, specifically LDL-C elevation, which persists even with weight loss, and are associated with increased risks of kidney stones and chronic kidney disease.

Monitor your LDL cholesterol closely if you follow a ketogenic diet, especially if it is high in animal fats. The risk of kidney stones and chronic kidney disease also increases with high animal protein intake.

Oxidative stress, driven by excessive reactive oxygen species (ROS) from both endogenous (mitochondrial dysfunction, NOX activity) and exogenous (air pollution, UV, smoking) triggers, is a central causal mechanism in cellular senescence and the pathogenesis of aging-related diseases including neurodegeneration, cardiovascular disease, and cancer.

Aging and many chronic diseases are linked to cellular damage from oxidative stress. You can mitigate this by reducing exposure to external triggers like air pollution, UV radiation, and smoking, and by maintaining healthy lifestyle habits such as regular exercise and a balanced diet rich in antioxidants, which help manage internal ROS levels.

Exenatide (2 mg once weekly) significantly reduces alcohol cue reactivity in the ventral striatum and septal area in patients with Alcohol Use Disorder, but does not significantly reduce heavy drinking days in the general AUD population.

Exenatide, a weekly injection used for diabetes and obesity, changes how the brain responds to alcohol cues in addicted individuals, potentially reducing the 'pull' of drinking triggers. However, this neurobiological change did not automatically lead to fewer heavy drinking days for most patients in this study. It suggests that while the drug modifies reward processing, it may not be sufficient as a standalone treatment for reducing actual alcohol consumption in the general AUD population without additional behavioral support.

In obesity, elevated saturated fatty acids and proinflammatory cytokines activate JNK and IKK kinases, which phosphorylate insulin receptor substrate (IRS) on inhibitory serine residues, thereby blocking PI3K/Akt signaling and causing insulin resistance.

If you have excess body fat, your cells are likely resisting insulin due to inflammatory signaling triggered by fats and cytokines. This isn't permanent damage; it's a reversible signaling block. Reducing caloric excess and saturated fat intake can lower the metabolic stress that triggers this inflammatory kinase activity, potentially restoring insulin sensitivity.

NOX2-derived cytosolic ROS production is required for exercise-stimulated glucose uptake and GLUT4 translocation in skeletal muscle.

During moderate-intensity exercise, your body produces specific reactive oxygen species (ROS) via the NOX2 enzyme to signal muscles to take up glucose. This is a necessary signaling event, not just damage. While you don't need to 'increase' ROS intentionally, understanding that some oxidative stress is functional helps explain why extreme antioxidant supplementation might interfere with metabolic adaptations to exercise.

Visual normalization theory posits that increased population exposure to larger body sizes recalibrates internal visual norms, raising the threshold for what is perceived as 'overweight' and causing widespread under-detection of adiposity in self, children, and others.

If you or your family consistently fail to recognize that you are overweight despite objective measures, it may be due to 'visual normalization'—your brain has adapted to larger body sizes as the new normal. To counter this, rely on objective metrics (BMI, waist circumference) rather than visual estimation alone, and be aware that recognizing your status might trigger psychological stress, so seek supportive, non-stigmatizing health resources.

Cold exposure and beta-3 adrenergic agonists are primary physiological and pharmacological agents that induce the browning of white adipose tissue.

Exposing your body to cold temperatures (like cold showers or cool rooms) stimulates your sympathetic nervous system, which can trigger white fat to turn into energy-burning beige fat. Pharmacological beta-3 agonists do this too, but lifestyle cold exposure is the natural, side-effect-free method.

Insulin regulates adipose tissue development and function by activating specific insulin receptor (INSR) splice variants (INSR-A and INSR-B) and downstream signaling cascades (PI3K/AKT), which control glucose uptake, lipid storage, and adipokine secretion.

Understand that insulin is essential for healthy fat tissue function, including cell survival and the release of beneficial hormones. The goal is not to eliminate insulin, but to maintain sensitivity so it can perform these critical roles without causing metabolic dysfunction.

Visceral adipose tissue (VAT) exhibits higher rates of insulin-stimulated glucose uptake and more rapid insulin signaling activation compared to subcutaneous adipose tissue (SAT), which may contribute to its distinct metabolic impact.

Not all fat is the same. Visceral fat (around organs) is more metabolically active and responsive to insulin than subcutaneous fat (under the skin), which may explain why visceral fat accumulation is more strongly linked to metabolic risks.

Insulin negatively regulates the secretion of resistin and omentin, while positively regulating the secretion of adiponectin, leptin, and other adipokines, thereby influencing systemic insulin sensitivity and energy balance.

Insulin influences the hormones your fat cells release. It boosts beneficial hormones like adiponectin (which improves insulin sensitivity) and leptin (which regulates appetite), while suppressing others like resistin. This complex interplay helps maintain metabolic balance.

Dietary fiber promotes the production of beneficial tryptophan metabolites, specifically indolelactic acid (ILA) and indolepropionic acid (IPA), by making more tryptophan available for Stickland fermentation.

To support gut health and potentially reduce the production of harmful metabolites like indole, incorporate fermentable fibers (such as pectin found in apples) into your diet. This encourages beneficial bacteria to produce protective metabolites (ILA, IPA) and suppresses the production of indole, which is linked to chronic kidney disease risk.

A 76-protein plasma proteomic signature of age (PROage) and its derived measure of biological age acceleration (PROaccel) predict the accumulation of chronic diseases (multimorbidity) and all-cause mortality independent of chronological age.

Your chronological age is not your destiny. This research identifies a specific set of 76 proteins in your blood that act as a 'biological clock.' If your biological age (calculated from these proteins) is higher than your actual age, you are at significantly higher risk for developing multiple chronic diseases and dying earlier. This test can identify 'fast-agers' who may benefit from early, intensive lifestyle or medical interventions to slow down this biological acceleration, rather than waiting for symptoms to appear.

Antidiabetic drugs like metformin and liraglutide exert part of their beneficial effects by modifying gut microbiota composition, specifically by increasing the abundance of Akkermansia muciniphila.

If you are taking metformin or liraglutide, part of their benefit may come from how they change your gut bacteria. This highlights the importance of gut health in diabetes management, even when using medication.

Pharmacological re-activation of AMPK in the liver suppresses hepatic steatosis by inhibiting lipid synthesis and stimulating fatty acid oxidation, whereas genetic loss of AMPK does not cause fatty liver development.

While low AMPK activity is linked to fatty liver, simply having low activity doesn't cause the fat accumulation. However, drugs that activate AMPK (like metformin or specific activators) can help reduce liver fat by blocking fat creation and increasing fat burning. This suggests that targeting AMPK is a valid treatment strategy for fatty liver, even if low AMPK itself isn't the initial cause.

Aging is characterized by a significant decline in adaptive homeostasis capacity, specifically the inability to transiently expand or contract homeostatic ranges in response to sub-toxic stressors, leading to increased susceptibility to damage and mortality.

As you age, your body's ability to bounce back from minor stressors (like mild exercise or dietary changes) diminishes. This isn't just about damage accumulation; it's about losing the signaling capacity to adapt. To maintain healthspan, focus on avoiding chronic, repetitive stressors rather than seeking constant 'hormetic' spikes, as your adaptive reserves are likely compressed.

IGF-1 and insulin signaling are critical for suppressing FoxO-mediated protein degradation, and their reduction contributes to muscle atrophy by releasing FoxO inhibition.

Maintaining healthy insulin and IGF-1 levels is crucial for preventing muscle loss. These hormones not only stimulate muscle growth but also actively suppress muscle breakdown pathways. A balanced diet that supports healthy insulin sensitivity is essential for muscle preservation.

Early aggressive provision of full caloric and protein targets in critically ill patients provides no clinical benefit and may cause harm, whereas permissive underfeeding (restricted feeding) during the acute phase reduces ICU-acquired weakness and improves outcomes.

In the first week of critical illness, do not aim to meet full caloric or protein targets. Instead, use a 'permissive underfeeding' strategy. This approach has been shown to reduce muscle weakness and improve recovery compared to aggressive feeding. Focus on safety and tolerance rather than hitting specific calorie numbers immediately.

Immune-modulating nutrition (supplementation with glutamine, arginine, omega-3 fatty acids, and antioxidants) does not improve outcomes in general critically ill patients and may increase mortality, although it may benefit specific subgroups like severe burn patients.

Do not routinely use immune-modulating supplements (glutamine, arginine, omega-3s) for general critically ill patients. These supplements have been shown to increase mortality or provide no benefit in large trials. They may be considered for specific subgroups like severe burn patients, but this requires specialist judgment.

Bariatric surgery (RYGB and SG) induces sustained weight loss and metabolic improvements through hormonal and neural mechanisms (increased GLP-1/PYY, decreased ghrelin, altered bile acids) rather than solely through caloric restriction or malabsorption.

For patients with severe obesity, bariatric surgery (RYGB or SG) is the most effective treatment for sustained weight loss and metabolic health. The success is largely due to hormonal changes (increased GLP-1/PYY, decreased ghrelin) that reduce hunger and improve glucose control, rather than just eating less. This suggests that non-surgical treatments targeting these same hormones (like GLP-1 agonists) may be effective alternatives for some.

Inhibition of the Insulin/IGF-1 Signaling (IIS) pathway extends lifespan in multiple species by enhancing mitochondrial function, biogenesis, and mitophagy.

Genetic variants that naturally result in lower IGF-1 levels are associated with human longevity. While not a direct prescription, this suggests that the hormonal environment of reduced growth signaling may be protective against aging, distinct from the muscle-building goals of high IGF-1 in youth.

Activation of AMPK by dietary restriction or compounds like metformin extends lifespan by inhibiting mTOR and promoting mitochondrial biogenesis.

Dietary restriction activates AMPK, which improves mitochondrial health and extends lifespan. If strict dieting is not feasible, compounds like metformin (which activate AMPK) or time-restricted eating may offer similar metabolic benefits.

Metformin is not recommended for treating NAFLD or NASH in humans despite improving insulin sensitivity in animal models.

Do not rely on metformin to treat your fatty liver. While it helps control blood sugar in diabetes, studies show it does not improve liver health in people with NAFLD or NASH. Focus on weight loss and dietary changes instead.

Gut microbiota depletion via broad-spectrum antibiotics significantly reduces skeletal muscle endurance and fatigue resistance in healthy mice, an effect mediated by altered glucose homeostasis and muscle glycogen levels rather than changes in muscle mass or mitochondrial function.

Maintaining a healthy gut microbiome is important for muscle endurance. While this study used mice, it suggests that factors disrupting gut bacteria (like broad-spectrum antibiotics) may temporarily reduce your stamina and fatigue resistance. Restoring gut health (natural reseeding) can reverse these effects. Focus on fiber-rich foods and fermented foods to support gut bacteria, which may help optimize glucose availability for your muscles during exercise.

Plasma LEAP2 levels increase with higher body mass, obesity, and postprandial states in humans and mice, acting as an endogenous antagonist to acyl-ghrelin to limit food intake and blood glucose elevation.

Your body produces a hormone called LEAP2 that increases when you are overweight or after you eat. This hormone acts as a brake on the 'hunger hormone' (ghrelin) to prevent you from overeating and spiking blood sugar. This is a natural regulatory mechanism. While high LEAP2 is associated with obesity, it also decreases when you lose weight, suggesting your body's hormonal 'brakes' can adjust as your metabolic state changes.