Browse the evidence

In patients with incident cardiovascular disease, increasing the number of metabolic risk factors (hypertension, dyslipidemia, diabetes) is associated with increased risk of subsequent non-fatal coronary heart disease (CHD) and incident heart failure (HF), regardless of BMI.

While having extra weight might help you survive a heart event, having high blood pressure, high cholesterol, or diabetes makes it much more likely you will have another heart attack or develop heart failure. You must manage these metabolic risk factors aggressively, regardless of your weight.

Implementing FDA voluntary sodium reduction targets in processed foods yields a net positive economic and health benefit for the broader food system workforce, primarily through reduced cardiovascular disease incidence and healthcare costs.

For policymakers and industry leaders: Implementing gradual, national sodium reduction targets in processed foods is economically beneficial for the food system as a whole. The health savings and productivity gains for workers outweigh the costs of reformulation. For consumers: Gradual sodium reduction in processed foods does not significantly impact taste or sales because human taste adapts over time. The primary benefit is a reduction in cardiovascular disease risk.

For workers specifically in the processed food industry, the net monetary benefit of sodium reformulation is negative, meaning the costs of reformulation exceed the health-related cost savings realized by this specific subgroup.

For processed food industry executives: Sodium reformulation may not be economically beneficial for your specific workforce in the short-to-medium term, as the costs of reformulation exceed the health savings for your employees. However, for the broader food system, it is beneficial. Policymakers should consider incentives to offset these costs for the processed food industry.

Ketogenic diets (KD) do not independently reduce energy intake or increase energy expenditure compared to non-ketogenic diets when energy density and behavioral factors are controlled; any observed weight loss is attributable to caloric deficit rather than ketosis itself.

If you are choosing a diet for weight loss, know that a ketogenic diet is not metabolically superior to a high-carbohydrate diet in terms of appetite control or energy expenditure. You will lose weight on either diet if you maintain a caloric deficit. Do not expect ketones to magically suppress your hunger or boost your metabolism beyond what is achieved by simply eating fewer calories.

Anti-obesity medications (GLP-1 RAs, MC4R agonists) and bariatric surgery work by improving appetite control and resetting the fat mass set point, rather than just creating a caloric deficit.

Medications like GLP-1 agonists and surgeries like gastric bypass succeed because they fix the broken biological signals in your brain that tell you when to stop eating. They improve appetite control, making it easier to maintain weight loss without constant willpower.

Short-term calorie restriction (12 weeks) does not reverse the accumulation of effector memory T cells in subcutaneous adipose tissue (SAT) or reduce local inflammatory cytokine levels in obese postmenopausal women, despite inducing weight loss and improving insulin sensitivity.

For obese postmenopausal women, short-term calorie restriction (12 weeks) improves insulin sensitivity but does not reduce inflammation in fat tissue. The immune cells in fat (effector memory T cells) and inflammatory cytokines remain high despite weight loss. This suggests that weight loss alone may not be sufficient to resolve chronic low-grade inflammation in the short term, and longer-term strategies or additional interventions might be needed to target adipose immune cells.

High-temperature cooking and prolonged storage can decrease protein quality by reducing the bioavailability of essential amino acids, particularly lysine, through the Maillard reaction and protein aggregation.

Avoid charring or overcooking meats and grains. High-temperature methods like grilling or prolonged roasting can chemically alter amino acids (especially lysine), reducing the protein's quality. Moderate cooking is generally better for preserving bioavailability.

Metformin treatment alters gut microbiota composition (increasing Escherichia coli, decreasing Intestinibacter bartlettii) to enhance the production of short-chain fatty acids (propionate and butyrate) and modulate bile acid pools, which mediates glucose-lowering effects.

If you take metformin, your gut bacteria are actively helping lower your blood sugar by producing beneficial fats (SCFAs) and signaling molecules. However, this same bacterial shift can cause stomach upset for about 30% of users. If you experience GI distress, it may be linked to this mechanism, and discussing management strategies with your provider is important.

Performing resistance exercise during the follicular phase (high estrogen) does not yield greater muscle protein synthesis or myofibrillar protein breakdown compared to the luteal phase (high progesterone) in naturally cycling women.

You do not need to schedule your resistance training around your menstrual cycle to maximize muscle growth. Whether you are in your follicular (high estrogen) or luteal (high progesterone) phase, your muscles respond to resistance exercise similarly in terms of protein synthesis and breakdown. Consistency in your training program is more important than trying to time your workouts with specific hormonal phases.

Integrating multiple computational gene prioritization methods (SMR, FINEMAP, DEPICT, MAGMA, TWAS, MSC, PoPS, nearest gene) identifies 292 high-confidence candidate genes associated with BMI, many of which regulate neuronal body weight control, circadian rhythm, insulin secretion, and glucose homeostasis.

This research does not offer a direct lifestyle intervention but highlights that obesity has strong genetic underpinnings involving brain regulation, insulin, and circadian rhythms. Understanding these specific biological pathways can help explain why weight loss is difficult for some and points toward future targeted therapies (e.g., drugs affecting GIPR or FGFR1) rather than just willpower-based approaches.

Combined pharmacological administration of oxytocin (OT) and a selective CCKAR agonist (A-71263) produces greater weight loss and fat mass reduction than either agent alone in diet-induced obese mice.

Combining oxytocin with a CCK receptor agonist is more effective for weight loss than using either drug alone. This suggests that future obesity treatments might need to target multiple pathways simultaneously to overcome diet-induced resistance.

Central nervous system atypical protein kinase C (aPKC) activity, specifically the PKC-l isoform in POMC neurons, is required to constrain food intake and prevent diet-induced obesity and glucose intolerance.

This research highlights that obesity is not just about calories in vs. calories out, but involves specific brain signaling pathways (like aPKC in POMC neurons) that regulate hunger. Disrupting these pathways can lead to increased food intake and weight gain, even if the diet is high-fat. This suggests that targeting these neural mechanisms could be a potential therapeutic strategy for obesity.

GLP-1RAs exert their therapeutic effects through complex intracellular signaling pathways, specifically activating ERK1/2, AMPK, cAMP, MAPK, and PKC, which regulate insulin secretion, cell proliferation, and inflammation.

The effectiveness of GLP-1 medications is driven by their ability to activate specific cellular pathways (ERK1/2, AMPK, cAMP, MAPK, PKC). These pathways control insulin release, cell growth, and inflammation, which is why these drugs work for both diabetes and potentially other conditions like cancer or cardiovascular disease.

High-fat diets (HFD) induce obesity and metabolic dysfunction by altering gut microbiota composition and downregulating tight junction proteins (claudin-1, claudin-2, claudin-3, ZO-1, occludin), leading to increased intestinal permeability ('leaky gut') and systemic inflammation.

Diets very high in fat (over 35% of calories) can damage your gut lining by reducing the proteins that hold gut cells together, allowing toxins into your bloodstream and causing inflammation. This process contributes to obesity and metabolic issues. To protect your gut barrier, focus on balanced fat intake rather than extreme high-fat diets, and consider fats that support microbiome health.

Real-world clinical practice fails to implement existing NAFLD guidelines, resulting in widespread underdiagnosis and suboptimal awareness.

Healthcare providers should utilize clear, simplified screening algorithms to identify at-risk patients, as current real-world implementation of guidelines is suboptimal.

Breast cancer survivors have significantly reduced cardiorespiratory fitness (peak VO2) compared to healthy controls, primarily due to impaired central cardiovascular function (lower stroke volume and cardiac output) rather than peripheral muscle extraction deficits.

Breast cancer treatment can reduce your heart's ability to pump blood during exercise, leading to lower fitness levels. This is a physiological change, not just 'being out of shape.' Targeted aerobic exercise can help improve this cardiovascular function.

GLP-1 receptor agonists delay gastric emptying, increasing the risk of pulmonary aspiration during anesthesia, necessitating specific perioperative holding periods or gastric assessment before elective surgery.

If you are taking a GLP-1 weight loss drug (like Ozempic or Wegovy) and need elective surgery, tell your surgeon and anesthesiologist immediately. These drugs slow down your stomach, which can cause dangerous aspiration during anesthesia. You may need to hold your medication for 1-3 weeks before surgery, or your surgery might be postponed until your stomach is empty. Do not skip doses without consulting your care team, as this can affect your blood sugar and weight management.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events (MACEs) and all-cause mortality in patients with type 2 diabetes, independent of glycemic control, through anti-inflammatory and plaque-stabilizing mechanisms.

If you have type 2 diabetes and high cardiovascular risk, GLP-1RAs like semaglutide or liraglutide can significantly reduce your risk of heart attack, stroke, and death. This benefit comes from stabilizing plaque and reducing inflammation, not just lowering blood sugar. Discuss these options with your doctor, especially if you have existing heart disease.

Bariatric surgery (specifically Roux-en-Y gastric bypass) can establish a new, lower body weight set point by altering gastrointestinal signals to the brainstem, thereby suppressing the counterregulatory hunger and hypometabolism typically seen after diet-induced weight loss.

For morbid obesity, surgery may be necessary to reset the body's defended weight. Unlike dieting, which triggers hunger, surgery appears to suppress this hunger biologically. However, it is invasive and requires lifelong management.

Acute moderate altitude hypoxia (2320m) does not enhance the hormonal (GH, Cortisol, Testosterone) or inflammatory (IL-6, IL-10, TNF-alpha) response to a single hypertrophy-oriented resistance training session compared to normoxia.

If you are training at moderate altitude (approx 2300m), do not expect a single resistance training session to trigger a superior acute hormonal or inflammatory response compared to training at sea level. The anabolic signaling environment (GH, Testosterone) remains similar to normoxia. Focus on maintaining training volume and intensity rather than relying on altitude for acute hormonal amplification.

Capsaicin or capsiate supplementation does not significantly improve aerobic endurance performance (time-trials or time-to-exhaustion) in healthy adults.

Do not rely on capsaicin or capsiate to improve your running or cycling times. The evidence shows no benefit for aerobic endurance, regardless of whether you do a time trial or exercise until exhaustion.

A ketogenic diet (defined as <50g carbohydrate/day or blood ketones ≥0.5 mM) has largely neutral or detrimental effects on athletic performance compared to a higher-carbohydrate diet, despite significantly increasing fat oxidation rates.

If your goal is to improve athletic performance (endurance, strength, or power), a ketogenic diet is not recommended. While it increases fat burning, it does not translate to better performance and may actually hinder it, especially in elite athletes or high-intensity efforts. Stick to a higher-carbohydrate diet for optimal results.

Obesity increases the risk of nephrolithiasis (kidney stones) through mechanisms including lower urine pH, increased urinary oxalate, uric acid, sodium, and phosphate excretion, and insulin resistance.

Obesity increases your risk of kidney stones by changing your urine chemistry, making it more acidic and increasing stone-forming minerals. Maintaining a healthy weight can help reduce this risk.

Dysbiotic gut microbiota and its derived metabolites (such as TMAO, choline, and hippurate) are shared metabolic biomarkers across cardiometabolic diseases, contributing to inflammation, atherosclerosis, and insulin resistance.

Support gut health through a diverse, fiber-rich diet to potentially lower levels of harmful metabolites like TMAO, which are linked to cardiovascular risk and insulin resistance.