Browse the evidence

Intermittent fasting (IF) regimens improve body composition and cardiometabolic risk factors compared to unrestricted eating, primarily through energy deficit, but do not provide additional benefits over continuous daily caloric restriction when energy balance is matched.

Intermittent fasting works for weight loss and heart health because it helps you eat fewer calories, not because of some magic metabolic switch. If you eat the same amount of calories as someone who eats continuously, you won't get extra benefits from fasting. Use IF if it helps you stick to your calorie goals more easily.

Fasting induces a metabolic switch from glycogenolysis to gluconeogenesis, lipolysis, and ketogenesis, which is considered a main driver of the metabolic health benefits provided by IF.

During fasting, your body switches from burning sugar to burning fat and producing ketones. This metabolic shift is likely why fasting can be healthy, even if it doesn't always lead to more weight loss than just eating less.

Obesity and Type 2 Diabetes are associated with altered secretion patterns of enteroendocrine hormones, specifically decreased GLP-1 and PYY, and increased ghrelin.

In obesity and diabetes, your gut's natural hormone signals are often disrupted, with less 'satiety' hormone (GLP-1) and more 'hunger' hormone (ghrelin). This contributes to the difficulty in managing weight.

The nitrogen balance method used to establish the 0.8 g/kg RDA likely underestimates true protein requirements due to methodological limitations, such as ignoring nonlinearity and metabolic adaptation.

Understand that the old '0.8g/kg' rule was based on a flawed measurement method. It is safer to aim higher, especially if you are active or older.

Fructose consumption, particularly in large amounts or from added sugars, stimulates hepatic de novo lipogenesis and VLDL-triglyceride secretion, increasing intrahepatic fat and cardiovascular risk, whereas glucose and starch have different, often less adverse, metabolic profiles.

Limit added sugars, particularly those high in fructose (like HFCS and sucrose), as they can promote liver fat accumulation and high triglycerides. While whole fruits are healthy due to fiber, be mindful of concentrated fructose sources. Physical activity can mitigate some of these effects by increasing fructose oxidation.

GLP-1 RAs reduce blood pressure and albuminuria in patients with CKD and overweight/obesity, contributing to kidney and cardiovascular protection.

GLP-1 RAs can help lower your blood pressure and reduce protein in your urine (albuminuria), which are important markers for kidney and heart health. This benefit is partly due to weight loss but also direct effects of the medication.

Lifestyle interventions alone are difficult to maintain long-term for weight loss in patients with T2DM and CKD, whereas GLP-1 RAs offer a pharmacological alternative with proven metabolic and organ protection benefits.

While lifestyle changes are important, they are hard to keep up long-term. GLP-1 RAs can help you maintain weight loss and protect your heart and kidneys, making it easier to stick to healthy habits. Talk to your doctor about whether a GLP-1 RA is right for you.

The magnitude of systolic blood pressure reduction with GLP-1 RAs is directly associated with changes in body weight, BMI, and HbA1c, suggesting these metabolic improvements drive the BP benefit.

The blood pressure lowering effect of GLP-1s like semaglutide is largely driven by the weight loss and metabolic improvements (lower A1c/BMI) they cause, rather than a direct effect on blood vessels alone.

Plant-based diets influence the gut microbiome to reduce production of Trimethylamine N-oxide (TMAO), a biomarker associated with increased cardiovascular risk.

Eating a diet rich in diverse plant fibers (vegetables, fruits, legumes, whole grains) feeds beneficial gut bacteria. This reduces the production of TMAO, a compound linked to heart disease risk. You don't need to be vegan to benefit; increasing plant fiber intake is key.

Gut hormones (GLP-1, GIP, CCK, PYY, OXM) regulate food intake and energy homeostasis by acting on the hypothalamus and brainstem via direct circulation or vagus nerve signaling, while ghrelin stimulates appetite.

Understanding that gut hormones like GLP-1 and GIP signal satiety to the brain helps explain why medications mimicking these hormones (like semaglutide and tirzepatide) are effective for weight loss. Conversely, ghrelin signals hunger. This biological basis supports the use of drugs that target these pathways.

NNC9204-1177, a glucagon/GLP-1 receptor co-agonist, produces dose-dependent, clinically relevant weight loss (up to 12.6%) in adults with overweight or obesity, but its clinical development was halted due to unexpected safety signals including increased heart rate, impaired glucose tolerance, and elevated inflammatory markers.

NNC9204-1177 is not available for clinical use because it caused unacceptable side effects like rapid heart rate and inflammation, despite causing significant weight loss. Do not seek this specific compound. However, the mechanism (glucagon/GLP-1 co-agonism) suggests that combining these pathways can be more effective for weight loss than GLP-1 alone, provided safety is managed. Current approved GLP-1 agonists (like semaglutide) do not have this glucagon component and thus avoid this specific safety profile.

GLP-1 receptor agonists (GLP-1RAs) significantly reduce liver fat content and improve histological markers of NASH (resolution without fibrosis worsening) in patients with NAFLD, with efficacy demonstrated across liraglutide, semaglutide, and tirzepatide.

If you have fatty liver disease (NAFLD) or NASH, GLP-1 medications like liraglutide, semaglutide, or tirzepatide are proven to reduce liver fat and improve liver health, often more effectively than placebo. These drugs work through hormonal mechanisms that reduce liver fat independently of weight loss in some cases. While gastrointestinal side effects like nausea are common, they are often manageable. Consult a doctor to see if you are a candidate, especially if you also have Type 2 Diabetes or obesity.

Non-beverage energy density and hyper-palatability (high sodium/fat or sodium/carb combinations) in ultra-processed foods positively predict meal energy intake and drive excess consumption.

Be aware that ultra-processed foods are engineered to be hyper-palatable and have high energy density (excluding beverages). This combination drives you to eat more without you necessarily feeling fuller. Choose foods with lower energy density and less engineered hyper-palatability.

Orlistat reduces body weight by inhibiting gastric and pancreatic lipases, thereby reducing the absorption of dietary fats, with efficacy demonstrated in obese patients.

Orlistat helps you lose weight by blocking the absorption of about 30% of the fat you eat. You take it with meals, but you must keep your fat intake low (less than 30% of calories) to avoid unpleasant gastrointestinal side effects. It is effective for weight loss, especially when combined with a hypocaloric diet, but may be less effective than newer GLP-1 drugs.

The combination of bupropion and naltrexone reduces body weight by stimulating POMC neurons to decrease energy intake and increase expenditure, with naltrexone blocking negative feedback to enhance this effect.

Bupropion/naltrexone is a combination pill that helps reduce appetite and increase energy expenditure by acting on brain pathways. It is effective for weight loss in people with obesity and comorbidities like hypertension or diabetes. However, it is not suitable for everyone, particularly those with a history of seizures or eating disorders. Consult your doctor to determine if it is safe for you.

Long-term adherence to a ketogenic diet carries risks of nutritional deficiencies, electrolyte disturbances, and potential renal stones (nephrolithiasis), requiring strict monitoring.

If you follow a ketogenic diet long-term, monitor your electrolytes (sodium, potassium, magnesium) and ensure you are getting essential vitamins through supplementation or carefully chosen food sources to prevent deficiencies and kidney stones.

Female sex is significantly associated with a hyper-response (>15% total body weight loss) to subcutaneous GLP-1 analogue therapy compared to non-response, whereas male sex is not.

If you are a woman taking a GLP-1 medication like semaglutide or liraglutide for obesity, you are statistically more likely to achieve significant weight loss (hyper-response) than a man taking the same medication. This is likely due to physiological differences in how your body processes the drug and regulates appetite hormones. Men may need higher doses to achieve similar results. If you are not losing weight, discuss dose adjustment or alternative treatments with your doctor rather than stopping abruptly.

Tirzepatide treatment in adults with obesity but without pre-existing type 2 diabetes significantly reduces the incidence of new-onset type 2 diabetes compared to semaglutide.

If you have obesity and are at risk for type 2 diabetes, tirzepatide may be a more effective option than semaglutide for preventing the onset of the disease. This is based on real-world data showing a 27% lower risk of developing type 2 diabetes with tirzepatide compared to semaglutide over a one-year follow-up period. Consult your doctor to see if this treatment is appropriate for you.

Tirzepatide treatment in adults with pre-existing type 2 diabetes significantly reduces the risk of major adverse cardiovascular events (MACE), including all-cause mortality and cerebral infarction, compared to semaglutide.

If you have type 2 diabetes, tirzepatide may offer greater cardiovascular protection than semaglutide, including a lower risk of heart attack, stroke, and death. This is based on real-world data showing a 46% lower risk of major adverse cardiovascular events with tirzepatide compared to semaglutide over a one-year follow-up period. Consult your doctor to see if this treatment is appropriate for you.

High carbohydrate intake (defined as the highest category in prospective cohorts) is associated with a significantly increased risk of cardiovascular disease (CVD), with a pooled hazard ratio of 1.15 compared to the lowest intake.

If you consume a high-carbohydrate diet, particularly if carbohydrates make up more than 60% of your total daily calories, consider reducing this proportion. This meta-analysis suggests that lowering high carbohydrate intake is associated with a lower risk of cardiovascular disease. Focus on balancing macronutrients rather than eliminating carbs entirely.

The association between high carbohydrate intake and increased CVD risk is significantly stronger in Asian populations (1.52-fold increase) compared to non-Asian populations (no significant association), with risk escalating dramatically when carbohydrate intake exceeds 60% of total energy.

If you are of Asian descent, be particularly mindful of your carbohydrate intake. The risk of heart disease increases significantly if carbohydrates make up more than 60% of your calories. Consider reducing your intake of refined carbohydrates and rice to lower this risk.

Orlistat provides modest weight loss and cardiovascular risk reduction, but its efficacy is heavily dependent on dietary fat restriction.

Orlistat is an older weight loss medication that works by blocking fat absorption. It is less effective than newer drugs and requires you to eat a low-fat diet to avoid unpleasant gastrointestinal side effects like oily diarrhea. It may offer some cardiovascular benefits for people with metabolic syndrome.

Phentermine/topiramate combination therapy results in significant weight loss but is associated with increased heart rate and potential psychiatric side effects.

Phentermine/topiramate is a combination pill that can lead to significant weight loss. However, it can increase your heart rate and cause psychiatric side effects like anxiety or depression. It requires careful monitoring by a doctor, and if you don't lose enough weight after a few months, the treatment may be stopped.

Bariatric surgery, particularly Roux-en-Y gastric bypass and biliopancreatic diversion, induces Type 2 Diabetes remission in a majority of patients through mechanisms exceeding simple caloric restriction, including hormonal changes (GLP-1, PYY) and altered gut microbiome.

For eligible patients with obesity and T2DM, bariatric surgery is the most potent intervention for achieving remission, often outperforming medication. It works by altering gut hormones that improve insulin sensitivity, not just by making the stomach smaller. Consultation with a bariatric specialist is required to assess eligibility based on BMI and diabetes duration.