Browse the evidence

Adipokines such as resistin and leptin play a role in insulin resistance, with resistin exhibiting insulin-antagonistic effects and leptin signaling influencing adiponectin expression.

Managing body weight can help normalize adipokine levels, potentially improving insulin sensitivity by reducing resistin and restoring healthy leptin-adiponectin balance.

Oral butyrate supplementation reduces appetite and prevents diet-induced obesity primarily by activating the gut-brain neural circuit (vagal nerve) to suppress orexigenic neurons and increase sympathetic outflow to brown adipose tissue.

Oral butyrate supplementation (specifically sodium butyrate mixed into a high-fat diet at 5% weight/weight in this study) reduces food intake and prevents obesity in mice. The key is that it must be taken orally to trigger the gut-brain-vagus nerve pathway; injecting it does not work. It works by suppressing hunger signals in the brain and activating brown fat to burn energy. For humans, this suggests that dietary sources of butyrate (like fiber fermentation) or oral supplements might help manage appetite and weight, but the exact effective dose and long-term safety in humans require further clinical validation.

Dietary arachidonic acid (ARA) supplementation improves cognitive function in elderly individuals with low baseline serum ARA levels and enhances visual acuity and cognitive development in preterm infants when added to formula.

If you are elderly and have low arachidonic acid levels, or if you are feeding a preterm infant, ensuring adequate ARA intake (via diet or supplementation) is critical for cognitive and visual development. For the general healthy adult, ARA is an essential component of cell membranes and brain function, so avoiding it is unnecessary and potentially detrimental.

Exposure to microplastics (MPs) and their chemical additives (e.g., phthalates, bisphenols) acts as an obesogen by disrupting lipid and energy metabolism through the activation of nuclear receptors (PPARs, RXR) and altering adipogenesis.

You are likely exposed to microplastics daily through air, dust, and food. While you cannot eliminate all exposure, you can reduce it by avoiding heating food in plastic containers, using glass or stainless steel for hot beverages, and filtering drinking water. The paper suggests these exposures may contribute to metabolic disruption via hormonal pathways.

Mandatory quarantine and social isolation induce chronic stress, anxiety, and depression, which physiologically increase sympathetic nervous activity and catecholamines, thereby accelerating atherosclerosis and increasing cardiovascular disease risk.

Understand that the stress of quarantine is not just 'in your head' but has real physical effects on your heart. To mitigate this, actively manage stress through relaxation techniques, maintain social connections virtually, and prioritize sleep to counteract the sympathetic nervous system activation caused by isolation.

Oral butyrate supplementation prevents high-fat-diet-induced obesity and reverses established insulin resistance in murine models by reducing adiposity and improving insulin sensitivity.

While human trials are less extensive than animal studies, increasing butyrate production through resistant starches (like cooled potatoes or legumes) or direct supplementation may help manage body weight and insulin sensitivity, especially when combined with a diet high in fat. Consult a doctor before starting supplementation.

Beta cell dedifferentiation, where beta cells lose their identity and insulin production capability without dying, contributes to beta cell deficit in T2D.

In T2D, some beta cells may not be dead but 'silenced' (dedifferentiated). Restoring blood glucose levels might allow them to regain function, offering a potential therapeutic target.

Pharmacological interventions targeting aging pathways (e.g., rapamycin, metformin, resveratrol) show potential to decelerate vascular aging but are limited by side effects and are not yet recommended for healthy individuals.

Do not use anti-aging drugs like rapamycin or metformin for healthy aging without medical supervision. Focus on lifestyle changes first, as they are safer and more effective. Pharmacological options are currently reserved for specific medical conditions.

Elafibranor (PPAR alpha/delta agonist) and Obeticholic Acid (FXR ligand) show promise in resolving NASH and improving fibrosis in clinical trials.

Elafibranor and Obeticholic Acid are emerging pharmacological treatments showing improvement in NASH and fibrosis in trials. They are not yet universally approved for NASH but are in Phase 3 testing.

Liraglutide (GLP-1 analogue) barely met the primary endpoint for NASH resolution in a small trial, while Sitagliptin showed no effect on liver histology.

GLP-1 therapies like Liraglutide show marginal benefit for NASH resolution, while others like Sitagliptin show no histological benefit. They are not primary treatments.

Specific blood lipid profiles (e.g., levels of triglycerides, lysophosphatidylcholine, and apolipoprotein E alleles) correlate with human aging and exceptional longevity.

Your blood lipid profile and ApoE genotype are markers of your biological aging and disease risk. While you cannot change your genotype, monitoring triglycerides and lysophosphatidylcholine levels may provide insights into your metabolic health. Focus on maintaining healthy lipid levels through diet and exercise.

SIRT3 polymorphisms are associated with human longevity, with specific variants being more common in centenarians.

Genetic variants in SIRT3 may play a minor role in human longevity, but evidence is inconsistent. Lifestyle interventions like calorie restriction and exercise remain the most reliable way to influence healthspan.

Bariatric surgery (BS) induces initial weight loss through foregut exclusion-mediated hormonal upregulation of satiety hormones (GLP-1, PYY) and downregulation of ghrelin, but long-term weight regain (WR) is driven by the subsequent normalization or decline of these hormonal levels, alongside behavioral factors like dietary non-adherence and grazing.

If you had bariatric surgery and are regaining weight, recognize that your body's hormonal signals (hunger/satiety) may have changed back towards pre-surgery levels. This is a known biological mechanism, not just a personal failure. Focus on behavioral strategies (dietary counseling, monitoring) to counteract these biological drives, as hormonal interventions alone have shown mixed results.

Routine screening of serum 25(OH)D levels is not recommended for any population (children, adults, pregnant, obese, dark complexion) in the absence of established clinical indications.

Do not get your vitamin D levels tested unless you have a specific medical condition like hypocalcemia. The guideline states that no specific blood level has been proven to prevent disease, so testing will not change your advice: just take the standard recommended dose.

Sirtuin activation (via overexpression or activators like resveratrol/STACs) delays cellular senescence and extends organismal lifespan in model organisms, primarily through DNA repair, telomere maintenance, and interaction with longevity pathways like IIS and AMPK.

Focus on lifestyle factors that naturally boost Sirtuin activity, such as calorie restriction and exercise, which increase NAD+ levels and activate AMPK. While supplements like resveratrol are popular, their direct efficacy in humans is unproven and potentially mediated by off-target effects. Prioritize sleep, stress management, and balanced nutrition to support genomic stability.

Myostatin acts as a negative regulator of skeletal muscle mass by inhibiting protein synthesis and promoting degradation; blocking myostatin signaling increases muscle mass in animal models but has failed to show clinical efficacy in elevating muscle strength in human muscular dystrophy trials.

While myostatin is a key regulator of muscle size, simply targeting it (e.g., via drugs or genetic mutation) increases mass but has not reliably improved strength in human clinical trials. Current research suggests targeting myostatin alone is insufficient for treating muscle wasting in humans, and other factors like activin A may play larger roles in primates.

Irisin, a myokine derived from FNDC5, promotes skeletal muscle hypertrophy and attenuates denervation-induced atrophy by activating IL-6 signaling and satellite cell elevation, although its role in human pathology remains under investigation.

Irisin shows promise in animal studies for building muscle and preventing atrophy, but its role in humans is still being defined. Exercise increases the precursor protein (FNDC5) in humans, but whether this translates to higher circulating irisin levels is debated. It is not yet a validated therapeutic target for human muscle gain.

Decorin is a myokine that directly binds to and inactivates myostatin, thereby promoting muscle growth by inhibiting myostatin's anti-myogenic effects and increasing pro-myogenic factors like Mighty and Myod1.

Decorin is a muscle-derived protein that helps build muscle by blocking myostatin, the body's natural muscle growth brake. By inactivating myostatin, decorin allows pro-growth signals to dominate. It is currently being studied as a potential treatment for muscle wasting.

Vitamin D deficiency impairs mitochondrial respiration, increases reactive oxygen species (ROS), and accelerates cellular aging and apoptosis.

If you are vitamin D deficient, correcting this status may help protect mitochondrial function and reduce oxidative stress, which are linked to aging.

Elevated plasma DPP-4 activity is positively correlated with obesity (BMI) and insulin resistance, potentially acting as a local mediator linking adipose tissue inflammation and hepatic insulin resistance to the pathogenesis of Type 2 Diabetes.

Higher levels of the enzyme DPP-4 are found in people with obesity and insulin resistance. This enzyme may contribute to inflammation in fat and liver tissue, worsening insulin resistance. While DPP-4 inhibitors treat diabetes by preserving incretins, the underlying high DPP-4 levels in obesity might also play a role in metabolic dysfunction, though this mechanism is still being fully understood.

Cellular senescence and the resulting Senescence-Associated Secretory Phenotype (SASP) are primary drivers of chronic low-grade inflammation (inflammaging) in aging, contributing to age-related diseases such as atherosclerosis, cancer, and diabetes.

Aging is associated with the accumulation of senescent cells that secrete inflammatory signals (SASP), contributing to chronic low-grade inflammation. While lifestyle factors like diet and smoking contribute, they are not the sole drivers; internal biological aging processes play a critical role. Emerging research suggests targeting these senescent cells (senolytics) may be a future strategy to reduce inflammation and improve healthspan.

Specific probiotic strains (Lactobacillus and Bifidobacterium) can reduce body weight gain and fat accumulation in animal models of obesity, though effects are strain-specific and not universal.

If you are considering probiotics for weight management, look for specific strains like Lactobacillus casei Shirota, L. gasseri, L. rhamnosus, or L. plantarum, as well as Bifidobacterium infantis, longum, and breve. However, do not expect all probiotics to work, as some strains have shown no effect or even increased weight gain in studies.

Prebiotics (e.g., oligofructose, inulin) can improve metabolic phenotypes, reduce triglycerides, and increase satiety hormones (GLP-1, PYY) in animal models, potentially aiding weight control.

If you are considering probiotics for weight management, look for specific strains like Lactobacillus casei Shirota, L. gasseri, L. rhamnosus, or L. plantarum, as well as Bifidobacterium infantis, longum, and breve. However, do not expect all probiotics to work, as some strains have shown no effect or even increased weight gain in studies.

Obesogenic endocrine disruptors are lipophilic and bioaccumulate in fat tissue, creating a 'vicious spiral' where increased body fat leads to greater retention of these chemicals, which in turn promotes further fat storage.

Be aware that obesity can trap environmental toxins in your fat, which may then fuel further fat storage. Gradual weight loss is preferable to rapid dieting, as it allows your body time to metabolize and eliminate stored chemicals. Reducing exposure to plastics and personal care products can help break this cycle.