Browse the evidence

Surgical weight loss induces specific psychobiological changes, including altered eating patterns (decreased bingeing, increased satiety) and hormonal shifts (elevated enteroglucagon, decreased pancreatic polypeptide), which help regulate the body weight set point.

Surgery not only restricts food intake but also changes the body's hormonal signals for hunger and satiety, which may help maintain weight loss by altering the body's 'set point'.

Obese humans with Non-Alcoholic Steatohepatitis (NASH) exhibit decreased expression of cytochromes P450 involved in bioactive lipid synthesis, mirroring findings in MyD88-deficient mice.

In advanced liver disease (NASH), the liver's ability to produce protective fats (via CYP450 enzymes) is reduced. This suggests that liver health is a critical component of overall metabolic health, and protecting the liver from fat accumulation may preserve these protective pathways.

Metformin, a common diabetes drug, inhibits mTORC1 and increases longevity in model organisms, with observational data suggesting it may decrease all-cause mortality in humans.

Metformin is a well-tolerated diabetes drug that may offer longevity benefits. While not currently approved for this use, it is a promising candidate for anti-aging therapy, and ongoing trials will clarify its efficacy in healthy individuals.

Dietary supplementation with krill oil or pine nut oil prevents or reverses hepatic steatosis by inhibiting hepatic de novo lipogenesis and enhancing fatty acid oxidation.

If you are at risk for fatty liver, incorporating sources of n-3 polyunsaturated fatty acids, such as krill oil or pine nut oil, may help reduce liver fat accumulation. These supplements work by slowing down the liver's production of new fat and increasing fat burning. However, current evidence is based on animal studies, so human dietary guidelines should prioritize overall healthy fat intake.

Dietary administration of Conjugated Linoleic Acids (CLA), specifically the trans-10,cis-12 isomer, induces hepatic steatosis by stimulating de novo lipogenesis and increasing plasma insulin.

Be cautious with CLA supplements. While they may help reduce body fat, they can also cause fatty liver and increase insulin levels in animal studies. The potential liver damage may outweigh the fat loss benefits.

Dietary supplementation with Allium cepa (onion) extracts, particularly those rich in quercetin and organosulfur compounds, inhibits adipogenesis and promotes browning of white adipose tissue, leading to reduced fat accumulation and improved lipid profiles in preclinical models.

Incorporating onion peel extracts or quercetin-rich onion preparations into your diet may support metabolic health by inhibiting the formation of new fat cells and promoting the browning of white fat. While not a magic bullet for weight loss, it serves as a supportive dietary strategy for managing lipid profiles and insulin sensitivity, particularly when combined with a balanced diet.

Sotagliflozin is a dual SGLT1/SGLT2 inhibitor that reduces postprandial glycemia by blocking intestinal glucose absorption and renal glucose reabsorption.

Sotagliflozin is a newer diabetes medication that works in two places: your intestines and your kidneys. It helps lower blood sugar spikes after meals by preventing sugar absorption in the gut and removing sugar through urine. It is still being studied for long-term safety.

Bilirubin acts as a direct agonist for the nuclear receptor PPARα, binding to its ligand-binding pocket to upregulate lipid-oxidation genes (CPT1, FGF21) and inhibit lipid accumulation, thereby reducing body fat and blood glucose.

This research identifies bilirubin not just as an antioxidant, but as a functional hormone-like molecule that activates PPARα to burn fat. While you cannot simply 'take' bilirubin safely as a supplement in this context, the findings suggest that individuals with naturally higher bilirubin levels (such as those with Gilbert's Syndrome) may have a metabolic advantage regarding fat loss and glucose control due to this specific receptor activation pathway.

Short-term manipulation of energy availability (≤5 days) triggers acute endocrine and metabolic dysregulations, but the long-term physiological effects of chronic LEA remain causally unproven due to a lack of long-duration prospective studies.

While short-term low energy availability clearly disrupts hormones, we lack long-term prospective data to definitively predict the chronic health outcomes of sustained LEA in humans.

Unsupervised anabolic steroid use involves cyclical polypharmacy with doses ranging from 250 to 3200 mg/week, resulting in skeletal muscle hypertrophy but accompanied by frequent physical side effects including acne, striae, and gynaecomastia.

This paper profiles unsupervised steroid users, not a safe protocol. It highlights that high-dose, cyclical steroid use combined with other drugs (polypharmacy) leads to muscle growth but also frequent physical side effects like acne and gynecomastia. Medical professionals should be aware of these physical signs to identify users.

Withdrawal from anabolic steroids frequently causes a reduction in muscle size and strength (reported by 72% of users) and reduced libido (33%), contributing to resumption of use.

Stopping steroid use often leads to a rapid loss of muscle size and strength, as well as reduced libido, which can drive users back to using steroids. This withdrawal cycle is a significant barrier to cessation.

Insulin resistance is a key feature of PCOS, but routine clinical measurement of insulin resistance is not recommended due to the inaccuracy of currently available measures.

While insulin resistance is common in PCOS, current clinical tests for it are not accurate enough to guide individual treatment decisions. Focus on lifestyle changes (diet, exercise) which improve insulin sensitivity, rather than seeking specific insulin blood tests.

Certain environmental chemicals (obesogens and diabetogens) can disrupt metabolic homeostasis by acting on nuclear receptors involved in adipogenesis and insulin sensitivity.

Minimize exposure to known environmental chemicals like BPA (found in some plastics) and certain pesticides where possible. While complete avoidance is difficult, reducing exposure may lower the burden on metabolic pathways regulated by nuclear receptors.

Activation of PPARγ (via agonists like TZDs or endogenous upregulation) improves insulin resistance and metabolic homeostasis by enhancing adipose tissue expandability, reducing ectopic lipid accumulation, and promoting browning, rather than solely by reducing fat mass.

Focus on improving the health and capacity of your fat tissue rather than just trying to lose weight. Strategies that support healthy adipose tissue function (like those mediated by PPARs, e.g., through specific medications or lifestyle factors that promote adipogenesis and browning) can improve insulin sensitivity even if body weight remains stable or increases slightly. The key is preventing fat from accumulating in organs like the liver and muscles.

PPARβ/δ activation reduces systemic inflammation and promotes fatty acid oxidation in skeletal muscle and brown adipose tissue, offering potential therapeutic benefits for obesity and insulin resistance.

PPARβ/δ activation shows promise for reducing inflammation and improving metabolism in muscle and fat, though it is still under clinical study.

Soy isoflavones can induce goitrogenic effects in individuals with pre-existing hypothyroidism or iodine deficiency, potentially advancing subclinical hypothyroidism to overt hypothyroidism.

If you have hypothyroidism, consult your doctor before consuming large amounts of soy isoflavones, as they may worsen thyroid function in some cases, especially if iodine intake is adequate.

Gut-derived hormones (CCK, GLP-1, PYY) released by enteroendocrine cells in response to nutrient ingestion activate vagal afferents and hypothalamic centers to inhibit food intake and increase energy expenditure, thereby regulating energy homeostasis.

Your body has a sophisticated biological system that regulates hunger and energy using signals from your gut. When this system is disrupted (as seen in obesity), simple willpower often fails because the biological 'stop' signals (like GLP-1 and CCK) are not functioning correctly. Effective treatments often target these specific pathways (e.g., GLP-1 agonists) to restore the body's natural ability to regulate intake and expenditure.

Repeated administration of CCK leads to desensitization and tolerance, explaining why CCK-derivatives have failed as effective long-term weight-loss treatments.

Early attempts to use CCK mimics for weight loss failed because the body builds tolerance to them. This highlights that simply flooding the system with one satiety signal is not a sustainable long-term strategy without addressing the underlying regulatory mechanisms.

Myostatin inhibition has potential therapeutic applications for Western diseases like COPD, type II diabetes, and obesity, but may have non-traditional side effects.

Myostatin inhibitors are being researched as treatments for serious conditions like COPD and muscular dystrophy. While promising, they are not yet standard care, and researchers are cautious about potential side effects on heart and fat metabolism.

Post-liver transplantation sarcopenia (loss of skeletal muscle mass) is common and significantly increases the risk of new-onset diabetes mellitus and trends toward higher mortality, independent of pre-transplant characteristics or immunosuppression type.

If you have had a liver transplant, do not assume your muscle mass will recover on its own. This study shows that muscle loss is common after surgery and significantly increases your risk of developing diabetes. You should have your muscle mass monitored via CT scans or other methods and discuss specific strategies to preserve or build muscle with your healthcare team, as this impacts your long-term survival and metabolic health.

Deregulation of fatty acid synthase (FASN)-catalyzed de novo fatty acid biogenesis drives a 'lipogenic state' that links insulin resistance, type 2 diabetes, and cancer.

Current evidence suggests that high FASN activity contributes to insulin resistance and cancer risk. While not a direct lifestyle intervention, this highlights the importance of managing insulin levels and metabolic health, potentially through lifestyle changes that improve insulin sensitivity, as FASN is a target for future therapeutics.

Pharmacological inhibition of FASN activity may prevent or reverse insulin-related metabolic disorders and reduce cancer risk.

FASN inhibitors are not yet available, but research suggests they could be a valuable future treatment for insulin resistance and cancer. For now, focusing on insulin sensitivity through lifestyle is the best approach.

Exercise-induced myokines (exerkines) such as SDF1, irisin, and SPARC counteract muscle wasting in diseases like cancer cachexia, COPD, and aging by modulating protein synthesis and degradation pathways.

If you are dealing with muscle loss due to illness or age, regular physical activity is a key treatment. It triggers your muscles to release protective proteins (myokines) that help stop muscle breakdown. You do not need to be an athlete; even moderate aerobic or resistance exercise can help restore these protective factors.

Continuous Positive Airway Pressure (CPAP) treatment for Obstructive Sleep Apnea (OSA) improves insulin resistance in patients without diabetes.

If you have Obstructive Sleep Apnea, using CPAP therapy as prescribed can improve your insulin resistance and metabolic health. Consistent use is key to realizing these benefits.