Browse the evidence

Metabolic and bariatric surgery (MBS) often results in substantial weight regain in patients with monogenic or syndromic obesity, particularly those with MC4R pathway variants, making it less effective than targeted pharmacotherapy for these groups.

If you have a known genetic form of obesity, discuss the long-term risks of bariatric surgery with your doctor. Studies show that patients with MC4R pathway variants often regain significant weight after surgery because the underlying genetic hunger drive remains unaddressed.

Dual incretin agonists (GLP-1/GIP) and triple agonists (GLP-1/GIP/Glucagon) show superior efficacy in reducing liver fat, inflammation, and fibrosis compared to GLP-1 mono-agonists in animal models, suggesting potential for enhanced clinical outcomes in MASLD.

Research suggests that newer 'dual' (GLP-1/GIP) and 'triple' (GLP-1/GIP/Glucagon) agonists may offer even greater benefits for liver health than current GLP-1 drugs, particularly in reducing liver fat and inflammation. These are still largely in clinical trials or early adoption phases for liver disease. If standard GLP-1 therapy is insufficient, discuss these newer multi-agonist options with your hepatologist or endocrinologist, keeping in mind that long-term human data for liver-specific outcomes is still being gathered.

Engineered bacteria (SYNB1020) that overproduce arginine to convert gut ammonia into L-arginine successfully lower systemic ammonia and improve survival in animal models of liver failure, but failed to show efficacy in a Phase Ib/IIa clinical trial for cirrhosis patients.

While engineered bacteria show promise in animals for clearing liver toxins, current clinical trials for liver disease patients have not yet succeeded. Do not expect this specific therapy to be available or effective for cirrhosis at this time.

Engineered bacteria producing GLP-1 or butyrate can improve glucose tolerance, insulin sensitivity, and reduce body weight in animal models of obesity and diabetes.

Research shows that engineered gut bacteria can produce hormones like GLP-1 or butyrate to improve metabolism in animals. This is a promising area for future oral treatments for diabetes and obesity, but it is not yet a standard therapy.

Subcellular trafficking of signaling molecules, such as the localization of mTOR to the lysosomal membrane, is a key regulatory event in the control of muscle protein synthesis, in addition to phosphorylation.

Research is uncovering more complex mechanisms behind muscle growth, such as how signaling molecules move within cells. While this doesn't change immediate training advice, it highlights the complexity of muscle adaptation.

The deuterated-glucose disposal test (2H-GDT), which measures glycolytic glucose metabolism via deuterated water production after an oral glucose load, correlates with insulin sensitivity measured by the clamp.

The deuterated-glucose disposal test offers a physiological measure of glycolysis that correlates with insulin sensitivity. However, its moderate correlation with the gold standard and technical complexity limit its routine clinical utility compared to simpler surrogates.

Activation of Gq-coupled receptors in brown and beige adipocytes generally suppresses thermogenic competence, whereas specific Gq receptors (like GPR120) can boost lipid oxidation and mitochondrial respiration.

The role of Gq receptors in fat burning is complex. While some Gq receptors (like those activated by acetate) may reduce fat-burning capacity, others (like GPR120, activated by fatty acids) can boost it. This complexity makes it a challenging target for simple drug development.

GLP-1 RAs show therapeutic potential in neurological disorders, including Alzheimer's and Parkinson's disease, by reducing amyloid-β/tau pathology, neuroinflammation, and promoting neuronal survival.

GLP-1 medications are being studied for Alzheimer's and Parkinson's disease. Some trials show promise in slowing brain volume loss, but results are mixed. They are not yet a standard treatment for these conditions. Consult a neurologist if interested in clinical trials.

None of the combined antidiabetic therapies (DPP4i, GLP1RA, TZD, SGLT2i) showed a significant change in blood pressure compared to metformin alone in women with PCOS.

Do not expect adding DPP4 inhibitors, GLP1RAs, TZDs, or SGLT2 inhibitors to metformin to significantly lower your blood pressure. Focus on these combinations for glycemic, lipid, or weight management instead.

Prolonged ultra-endurance exercise leads to a significant decrease in hemoglobin and hematocrit, which is primarily due to plasma volume expansion (hemodilution) rather than a loss of red blood cell mass.

Don't panic if your hemoglobin drops after a long race. It's likely due to your blood plasma expanding to help you regulate temperature and blood pressure, not because you lost blood cells. This usually resolves with rest and hydration.

GLP-1 receptor agonists (GLP-1RAs) are associated with an emerging signal of suicidality, including suicidal ideation, attempts, and completed suicide, based on pharmacovigilance data, though large randomized controlled trials have not demonstrated a statistically significant causal increase in risk.

GLP-1 medications (like Ozempic or Wegovy) have been linked to reports of suicidal thoughts in pharmacovigilance databases, creating a safety signal. However, large clinical trials involving thousands of patients have not found a statistically significant increase in psychiatric events compared to placebo. The absolute risk appears to be very low. Clinicians should monitor patients, especially those with a history of mental health conditions, but the proven benefits for weight loss and heart health generally outweigh this rare risk for most users.

Saxagliptin (a DPP-4 inhibitor) is associated with an increased signal of hospitalizations for heart failure (HF), warranting vigilance in high-risk patients.

If you have type 2 diabetes and are at high risk for heart failure, discuss saxagliptin with your doctor. This specific drug has been linked to more hospitalizations for heart failure in some studies, so other options might be safer for your heart.

Chronic consumption of monosodium glutamate (MSG) is associated with increased risk of obesity and weight gain, primarily through mechanisms involving hypothalamic damage, leptin resistance, and altered gut microbiota.

While MSG is legally safe, emerging research suggests high chronic intake, especially from processed foods with hidden MSG, may disrupt appetite regulation and contribute to weight gain. To mitigate potential risk, prioritize whole foods and check labels for hidden sources like hydrolyzed protein or yeast extract.

Increasing protein intake from a moderate level (1.8 g/kg/day) to a high level (2.9 g/kg/day) does not provide additional satiety benefits for resistance-trained individuals in a caloric deficit.

If you are training and cutting calories, aim for about 1.8g of protein per kg of body weight. Going higher to 2.9g won't help you feel fuller or fight hunger any better, so don't stress about forcing extra protein just for satiety reasons.

Long-acting GLP-1 receptor agonists (GLP-1RAs) attenuate obesity and reverse leptin resistance by reshaping gut microbiota to increase Akkermansia muciniphila, which produces inosine to activate the macrophage A2A pathway, thereby reducing adipocyte leptin levels.

This research suggests that GLP-1 medications (like semaglutide or liraglutide) may work partly by changing your gut bacteria to produce a molecule called inosine. This molecule helps reduce leptin, a hormone that regulates fat storage. While you cannot directly control this pathway, maintaining gut health through diet may support the effectiveness of these medications.

Specific additives found in UPFs, such as carrageenan and endocrine-disrupting chemicals like Bisphenol-A (BPA) and acrylamide, contribute to T2DM risk through mechanisms involving insulin resistance, inflammation, and gut microbiota alteration.

Be aware that certain additives (carrageenan, specific emulsifiers) and packaging-derived chemicals (BPA, phthalates) in UPFs may promote insulin resistance and inflammation. Reducing intake of products containing these specific ingredients, especially sugary beverages and processed meats, may lower T2DM risk.

Tirzepatide may allow some patients with moderate OSA (AHI 15-30) who are asymptomatic (except for snoring) to discontinue CPAP, as the benefit of CPAP in this subgroup is unclear.

If you have moderate OSA and are not sleepy (only snoring), ask your doctor if you can try tirzepatide alone. Since CPAP's benefit in asymptomatic moderate OSA is unclear, tirzepatide might resolve your OPA without the need for a machine. This requires monitoring and may not be suitable for everyone.

Adding 250 mg of protease enzymes (ProHydrolase) to 26 g of whey protein post-resistance exercise does not increase the total amino acid exposure (AUC) or anabolic signaling (mTOR/p70S6K phosphorylation) compared to consuming 26 g of whey protein alone in trained males.

If you are taking whey protein after your workout, adding a specific protease enzyme blend (like ProHydrolase) does not provide any additional benefit for muscle protein synthesis or total amino acid absorption compared to taking whey protein by itself. You do not need to buy specialized enzyme-enhanced proteins to maximize your results; standard whey protein is sufficient.

GLP-1 receptor agonists may have disease-modifying effects on osteoarthritis and osteoporosis by reducing inflammation and promoting bone formation.

If you have joint pain or weak bones, ask your doctor if your GLP-1 medication might offer extra protection. While weight loss is the main benefit, these drugs may also reduce inflammation in joints and help maintain bone density.

GLP-1 receptor agonists (GLP-1RAs) reduce the risk of hepatic decompensation events in patients with type 2 diabetes and compensated cirrhosis compared to DPP4 inhibitors and sulfonylureas.

If you have type 2 diabetes and compensated cirrhosis, GLP-1 receptor agonists may help reduce your risk of serious liver complications like fluid buildup or bleeding compared to other common diabetes medications. Discuss the benefits and risks with your doctor.

In obese or overweight individuals with low glucose effectiveness (Sg), subclinical reactive hypoglycemia (SRH) acts as a biological driver for frequent snacking, creating a vicious cycle that promotes obesity.

If you struggle to stop snacking despite gaining weight, it may not be a failure of willpower but a metabolic response. Specifically, if you have low glucose effectiveness, your body may drop into subclinical hypoglycemia after meals, triggering intense hunger to protect your brain. To break this cycle, focus on lifestyle factors that improve glucose effectiveness, such as regular walking (≥8000 steps/day) and reducing high-fat/sugar intake, rather than relying solely on willpower to resist snacks.

Menstrual cycle symptoms are widespread and severe in resistance-trained athletes, with 92% reporting symptoms and 76% reporting cramps, yet MC irregularities are not more common than in the general exercising population.

Expect menstrual symptoms like cramps and fatigue to be common (92% prevalence) regardless of your competitive level. However, do not assume your resistance training is causing irregular periods; your cycle regularity is likely similar to other women. Focus on managing the high prevalence of symptoms (like cramps and fatigue) through tracking and potentially hormonal or lifestyle interventions.

GLP-1 receptor agonists (GLP-1 RAs) reduce alcohol consumption and craving in patients with Alcohol Use Disorder (AUD) by modulating the mesolimbic dopamine reward pathway.

If you have AUD, especially if you also have obesity or Type 2 Diabetes, GLP-1 medications (like Semaglutide) may help reduce your alcohol intake and cravings by affecting brain reward pathways. This is an emerging off-label use, so discuss it with your doctor, particularly if standard treatments have failed or caused side effects.

Preoperative factors such as duration of diabetes, high HbA1c, and insulin use predict failure of T2DM remission after bariatric surgery.

If you have had diabetes for a long time or require high doses of insulin, your chances of complete remission after surgery are lower. This highlights the importance of considering surgery earlier in the disease course, before beta-cell function is severely compromised.