Browse the evidence

Metformin protects against cardiac ischemia-reperfusion injury and improves heart failure outcomes post-MI by activating AMPK, which promotes glycolysis and prevents mitochondrial permeability transition pore (mPTP) opening.

If you have had a heart attack, metformin (even in low doses) may help protect your heart muscle from further damage by improving energy use in heart cells. This benefit extends to non-diabetic heart failure patients as well, improving heart pumping function.

Fermentable dietary fiber (e.g., guar gum) increases body weight and fat mass in high-fat diet-fed mice compared to non-fermentable fiber (e.g., oat fiber) due to increased energy extraction via short-chain fatty acid (SCFA) production.

If you are trying to lose weight, not all fiber is equal. Fermentable fibers (like guar gum) are broken down into energy (SCFAs) by your gut bacteria, which can add calories and potentially promote weight gain, especially if your diet is high in fat. Non-fermentable fibers (like insoluble oat fiber) are less likely to contribute extra energy and may be more effective for weight management in high-fat diets.

Agmatine, a polyamine-related compound produced by gut bacteria and plants, reduces body weight gain, fat depots, and atherosclerotic lesions in high-fat diet-fed animal models.

Agmatine, found in plants and produced by gut bacteria, shows promise in animal studies for reducing fat accumulation and atherosclerosis in obese models. However, specific dosing and human efficacy are not established in this review. It is not currently a standard clinical recommendation for weight loss.

Consumption of cooked, high-starch plant foods (specifically underground storage organs) was an essential evolutionary driver for the expansion of the human brain and body size during the Pleistocene by providing the preformed glucose required for high-energy tissues.

While modern humans do not need to eat like Pleistocene hominins, this research highlights that digestible carbohydrates, particularly from starchy plants, are a natural and efficient fuel source for the brain. Cooking increases the bioavailability of these carbohydrates, suggesting that processed, low-fiber, or raw starches may not provide the same evolutionary or metabolic benefits as whole, cooked starchy foods.

Defective nitric oxide (NO) production and mitochondrial biogenesis are central mechanisms driving visceral adiposity, insulin resistance, and cardiovascular risk in the metabolic syndrome.

If you struggle with obesity and insulin resistance, standard calorie counting may fail because your body's energy sensors (mitochondria) are defective, signaling an 'energy emergency' that drives hunger and reduces energy expenditure. Addressing the root cause may require interventions that support mitochondrial health and nitric oxide production, rather than just focusing on willpower or simple caloric restriction, which might further suppress already defective lipid oxidation.

Altered gut microbiota in obesity increases digestible energy uptake from food through enhanced expression of nutrient transporters and fermentation enzymes, leading to increased caloric absorption.

Your gut bacteria can extract more calories from the same amount of food if they are altered. This is one reason why two people might eat the same diet but have different weights. Focusing on gut health through fiber and diverse foods might help optimize energy extraction.

Orexin system deficiency or dysfunction causes obesity in animal models by reducing spontaneous physical activity (SPA) and energy expenditure, independent of caloric intake.

Focus on increasing spontaneous physical activity (fidgeting, standing, non-exercise movement) as a metabolic lever. If you struggle with weight despite dieting, consider that your body's arousal/energy regulation systems (potentially involving orexin) might be suppressing your natural movement. Incorporating more non-exercise movement may help regulate energy expenditure.

Replacing dextrose with lipid emulsions in parenteral nutrition reduces hyperglycemia and its associated complications (infections, mortality) in critically ill patients.

For ICU patients unable to eat, using lipid emulsions to provide about 30% of calories helps avoid dangerous high blood sugar levels caused by glucose-heavy formulas. Monitor triglyceride levels closely and reduce lipid doses if they exceed 400 mg/dL to prevent liver stress.

Resveratrol reduces de novo lipogenesis (fat synthesis) and fatty acid uptake in adipose tissue by inhibiting enzymes like FAS, ACC, and LPL.

Resveratrol appears to reduce the body's ability to synthesize new fat (lipogenesis) and take up fatty acids from the blood (via LPL inhibition) in animal models. This contributes to reduced fat depots, particularly in obese subjects. The effect is seen on enzymes like FAS and ACC.

Resveratrol enhances brown adipose tissue (BAT) thermogenesis and increases fatty acid oxidation in skeletal muscle and liver.

Resveratrol may increase energy expenditure by stimulating brown fat thermogenesis and boosting fatty acid oxidation in muscles and the liver. This effect is observed in animal models and contributes to fat loss, though its magnitude in humans is less established.

Specialized suction lipectomy (liposuction) using lymphatic-sparing techniques is an effective treatment for reducing lipedema volume and pain.

Seek a plastic surgeon specializing in lipedema who uses lymphatic-sparing techniques (like water-assisted liposuction). Expect to use compression therapy post-surgery.

Chronic undernutrition is associated with dysregulated PPARα and FXR signaling, leading to decreased bile acid levels, suppressed secretion of complement and coagulation factors, and increased autophagy.

In cases of severe chronic undernutrition, the body's metabolic sensors (PPARα and FXR) become dysregulated, leading to low bile acids and impaired immune/clotting functions. This suggests that nutritional rehabilitation should potentially target these specific pathways (e.g., bile acid replacement or receptor agonists) to restore normal metabolic function, rather than just providing calories.

A decline in resting energy expenditure (REE) in severely burned patients is a significant predictor of mortality.

Monitor resting energy expenditure in burn patients; a drop in metabolic rate, rather than sustained high expenditure, may signal impending mortality and metabolic exhaustion.

Activation of brown adipose tissue in adult humans contributes significantly to total energy expenditure and is negatively correlated with BMI, with activation observed in lean but not obese patients in some studies.

Adults can have functional brown fat that burns calories, especially if they are lean. However, this mechanism may be less active in obese individuals. While cold exposure might help, it is not a guaranteed weight loss solution for everyone, particularly those with obesity.

Adropin34-76 treatment reduces incomplete fatty acid oxidation and increases the CoA/acetyl-CoA ratio in skeletal muscle, indicating improved mitochondrial function in obese mice.

This study indicates that obesity can lead to mitochondrial dysfunction, specifically incomplete fatty acid oxidation, which contributes to metabolic issues. Adropin treatment was shown to correct this by improving mitochondrial function. This suggests that maintaining healthy mitochondrial function is crucial for metabolic health, and future therapies may target these pathways.

The COVID-19 pandemic led to decreased food intake, skipping warm meals, and weight loss in a subset of older adults, predisposing them to undernutrition.

If you are an older adult, be aware that the pandemic's stress and isolation may have led you to eat less, skip meals, or lose weight. This is a common reaction, especially for those who are older, live alone, or have functional limitations. To manage this, try to eat smaller, more frequent meals and focus on nutrient-dense foods.

The increase in overweight and obesity in Brazil is primarily driven by a 'contemporary Western lifestyle' characterized by dietary changes (increased consumption of fast food, processed foods, and dining out) and reduced physical activity due to urbanization and technological adoption.

To combat rising obesity, focus on structural changes: promote access to healthy foods, encourage active transportation, and limit the marketing of processed foods, rather than just telling individuals to 'eat less and move more'.

Reductions in physical activity, particularly occupational and domestic physical activity, due to technological adoption (appliances, transportation) and lifestyle changes (TV, computer use), contribute to obesity.

Incorporate more movement into your daily routine, not just structured exercise. Take the stairs, walk for transport, and do household chores actively to boost daily energy expenditure.

Caloric restriction and specific phytochemicals (e.g., resveratrol, tea catechins) can extend healthspan and modulate aging-related epigenetic marks.

Consider incorporating caloric restriction or consuming phytochemical-rich foods (like those found in tea and grapes) to potentially slow age-related epigenetic changes and support longevity.

Black tea theaflavins (TF-1, TF-2, TF-3) reduce hepatic lipid accumulation and fatty acid synthesis while stimulating fatty acid oxidation in human hepatocytes (HepG2) and high-fat diet-fed rats by activating AMPK via the LKB1 and ROS pathways.

Black tea contains theaflavins, which appear to help reduce liver fat and improve lipid metabolism by activating AMPK, a key energy sensor. While this study used high concentrations in cells and rats, drinking black tea as part of a healthy diet may offer metabolic benefits, particularly for those with fatty liver or obesity risk, though it is not a substitute for medical treatment.

Gut microbiota composition differs between lean and obese individuals, with obese phenotypes showing a higher Firmicutes-to-Bacteroidetes ratio, which may enhance energy harvest from the diet.

Obesity is associated with a gut microbiome that extracts more energy from food. While changing this ratio is challenging, a diet rich in fiber may support a healthier microbiome profile.

Caloric restriction (CR) extends lifespan in many species, but its benefits in humans are uncertain and potentially offset by increased mortality risk associated with low body weight.

While caloric restriction works in animals, extreme restriction in humans may increase mortality risk. Aim for moderate, sustainable eating habits that support metabolic health rather than striving for very low body weight.

Mitochondrial DNA mutations and dysfunction contribute to aging, but the extent to which they drive normal aging versus progeroid syndromes is still debated.

Mitochondrial health is important for aging, but focusing solely on mtDNA mutations may be misleading. A holistic approach to health, including exercise and nutrition, supports mitochondrial function.

A ketogenic diet significantly reduces maximal work load and work load at lactate threshold compared to a mixed diet in off-road cyclists, indicating compromised high-intensity performance.

If you are an endurance cyclist, switching to a high-fat, low-carb diet for a month during your base training phase can significantly boost your aerobic capacity (VO2max) and lactate threshold, largely because you lose weight and your body becomes more efficient at burning fat. However, be prepared for a drop in your maximum sprint power and high-intensity efforts, as your body will have less glycogen for those explosive moves. This is a trade-off: better endurance efficiency for less top-end speed.