Browse the evidence

In healthy aging men, fat-free mass (primarily skeletal muscle) begins a non-linear decline around age 47, while fat mass increases until approximately age 70-80, resulting in a stable total body weight that masks significant body composition deterioration.

If you are a man over 40, do not rely on body weight or BMI to track your health. Your weight may stay the same while you lose muscle and gain fat. To maintain health, prioritize resistance training to preserve fat-free mass, as aerobic exercise alone was found to be insufficient to prevent this loss in this study.

Indian diets exhibit a significant caloric deficit in protein sources (6-8% of total calories) compared to the EAT-Lancet reference diet (29%), driven by low consumption of legumes, animal proteins, and tree nuts across all income and geographic groups.

Current Indian dietary patterns, even among the wealthy, fail to provide adequate protein, contributing to health issues. To align with healthy standards, individuals must significantly increase intake of protein-rich foods like legumes, nuts, dairy, and potentially animal proteins, while reducing the disproportionate share of calories derived from cereals.

Dietary restriction of specific amino acids, particularly methionine or general protein, inhibits mTORC1 signaling and extends rodent lifespan, offering a sustainable alternative to pharmacological mTOR inhibition.

Consider reducing overall protein intake or specifically restricting methionine (found in high amounts in meat, eggs, and some nuts) to potentially slow aging via mTORC1 inhibition. This can be achieved through plant-based diets which are often lower in methionine. This approach is safer and more sustainable than long-term pharmacological rapamycin use, though it requires careful planning to ensure adequate nutrition.

Orlistat is the only currently available long-term pharmacological treatment for obesity in Europe because it offers a favorable safety profile regarding cardiovascular events and diabetic control, despite being less effective for weight reduction than withdrawn agents.

Take Orlistat (120mg Rx or 60mg OTC) with your three main meals containing fat. If a meal has no fat, skip the dose. Stick to a diet where about 30% of calories come from fat to minimize gastrointestinal side effects, which usually improve over time. Stop the medication if you haven't lost at least 5% of your body weight after 12 weeks.

Long-term high-protein diets (≥25% energy) do not provide superior weight loss, fat loss, or cardiovascular risk reduction compared to low-protein diets when both are low-fat.

If you are trying to lose weight or improve heart health over the long term, simply increasing your protein intake (to ≥25% of calories) will not give you an advantage over a standard low-protein diet, provided both diets are low in fat and you maintain a caloric deficit. Focus on total energy intake and fat quality rather than maximizing protein.

High intake of simple carbohydrates (sucrose, fructose) and high-fat diets disrupt PPAR-alpha and PPAR-gamma balance, leading to reduced beta-oxidation and increased lipogenesis, which drives NAFLD progression.

Both high-fat and high-sugar diets contribute to fatty liver. Reducing intake of added sugars (especially fructose and sucrose) and saturated fats helps restore the balance of PPAR-alpha and PPAR-gamma, reducing liver fat accumulation.

In men aged 45-55, higher intake of total fat and monounsaturated fatty acids is significantly associated with increased 16-year incidence of coronary heart disease, independent of traditional risk factors.

For men in their 40s and 50s, reducing total fat and monounsaturated fat intake, particularly from animal sources, is associated with a lower risk of heart disease over 16 years. This benefit appears independent of cholesterol levels. Aim to align with National Cholesterol Education Project guidelines, which suggest lower total fat (around 30% of energy) and saturated fat (around 10% of energy), as these levels were linked to significantly reduced CHD risk in this demographic.

In men aged 56-65, dietary lipid intake (total fat, saturated, monounsaturated, polyunsaturated, cholesterol) is not significantly associated with the 16-year incidence of coronary heart disease.

For men in their late 50s and 60s, this study did not find a significant link between dietary fat intake and heart disease risk over 16 years. This does not mean diet is unimportant, but the direct link observed in younger men was not detected here. Factors like competing mortality and other age-related health issues may obscure dietary effects. Focus on overall health rather than just lipid intake.

During the initial energy restriction phase of a weight loss program, adipose tissue macrophage gene expression is upregulated, which correlates with lower improvements in insulin sensitivity, whereas during subsequent weight stabilization, macrophage gene expression is downregulated and associated with improved insulin sensitivity.

If you are undertaking a significant weight loss program, be aware that the initial rapid weight loss phase (energy restriction) triggers a distinct inflammatory response in fat tissue (upregulation of macrophage genes) that may temporarily blunt improvements in insulin sensitivity compared to the later stabilization phase. This does not mean the weight loss is ineffective, but it highlights that the body's molecular response evolves over time. Consistency through the stabilization phase is crucial for resolving this inflammatory state and maximizing metabolic health benefits.

Insulin-resistant skeletal muscle exhibits significantly lower abundance of Carnitine Palmitoyltransferase 1B (CPT1B) and specific Complex I subunits, which may contribute to lipid accumulation.

Obese, insulin-resistant individuals have less of the protein (CPT1B) that shuttles fat into mitochondria for burning. This bottleneck may cause fat to accumulate in the muscle, worsening insulin resistance.

Antenatal lifestyle advice does not significantly alter dietary glycaemic index (GI) or glycaemic load (GL) in overweight/obese pregnant women.

While general healthy eating advice improves overall diet quality, it may not specifically lower your glycaemic index or load. If managing blood sugar is a specific concern, more targeted dietary strategies may be needed beyond general lifestyle advice.

Peri-operative protein or amino acid supplementation does not significantly improve muscle strength (quadriceps or handgrip) or functional outcomes in total joint arthroplasty patients.

Do not expect protein supplements to restore your leg strength after surgery. The evidence shows they help keep muscle mass from shrinking, but they do not significantly improve strength or walking ability on their own. You must combine supplementation with physical therapy and exercise to regain strength.

Improvements in household technology (electrification and appliance diffusion) did not cause the mid-20th century baby boom; instead, evidence shows a negative correlation between technology access and fertility rates.

This paper refutes the economic theory that household technology drives fertility increases. It argues that the baby boom was not caused by appliances like washing machines or refrigerators, pointing to negative correlations between technology access and birth rates, and noting that the Amish, who limited technology use, still had a baby boom.

Carriers of the TM6SF2 E167K genetic variant exhibit increased susceptibility to progressive nonalcoholic steatohepatitis (NASH) and advanced fibrosis due to impaired hepatic secretion of very-low-density lipoproteins (VLDL), resulting in toxic triglyceride accumulation in hepatocytes.

If you have the TM6SF2 E167K genetic variant, your liver is less efficient at exporting fat. This means fat builds up in your liver cells, causing inflammation and scarring (NASH/fibrosis) even if your blood lipid levels are low. Standard 'fatty liver is benign' advice may be dangerous for you; you require closer monitoring of liver health via biopsy or advanced imaging if risk factors are present.

Circulating levels of soluble CD36 (sCD36) are abnormally elevated in NAFLD patients and positively correlate with the histological grade of hepatic steatosis, suggesting its utility as a biomarker.

Soluble CD36 levels in the blood may serve as a biomarker to assess the severity of fatty liver disease. This is a diagnostic tool rather than a treatment target for patients at this stage.

MCP-1/CCR2 and RANTES/CCR5 chemokine signaling pathways are critical for macrophage recruitment and the progression of hepatic steatosis to NASH.

Chemokines like MCP-1 and RANTES recruit inflammatory immune cells to the liver, worsening NAFLD. Blocking these pathways (currently experimental) or reducing their expression through diet/lifestyle may help mitigate liver inflammation.

Macrophage polarization towards the M1 pro-inflammatory phenotype is driven by glycolysis and the accumulation of TCA cycle intermediates (succinate, itaconate), which promotes the production of inflammatory cytokines (IL-1β) and contributes to metabolic disease.

Chronic low-grade inflammation, driven by immune cells like macrophages, is a key factor in metabolic disease. Supporting a healthy gut microbiome helps prevent the metabolic reprogramming of immune cells that leads to this inflammation.

Knocking down hepatic Adipose Triglyceride Lipase (ATGL) causes hepatic steatosis by blocking triacylglycerol (TAG) hydrolysis and reducing fatty acid oxidation.

Your liver has a specific enzyme (ATGL) that breaks down stored fat. If this enzyme is suppressed, your liver stores more fat (steatosis) and burns less of it, even if you aren't eating excess calories. Maintaining healthy hepatic ATGL activity is crucial for preventing fatty liver and ensuring fatty acids are burned for energy rather than stored.

Depletion of Kupffer cells (liver macrophages) improves insulin signaling and hepatic insulin sensitivity in obese mice.

Targeting liver inflammation may be a viable strategy for improving insulin sensitivity, though current clinical applications of macrophage depletion are limited.

Domestic economic development, urbanization, and women's empowerment drive global increases in BMI, whereas economic and cultural globalization do not significantly predict weight gain.

Focus on understanding how your country's economic development, urbanization, and social changes (like women's workforce participation) impact your community's health. Simply opening markets to global goods does not automatically cause obesity; domestic socio-economic transitions are the stronger drivers.

In severely burned patients, delivering caloric intake exceeding 1.2 times resting energy expenditure (REE) increases fat mass accretion without attenuating the erosion of lean body mass.

For severe burn patients, feeding significantly above measured energy needs (specifically >1.2x REE) will not save muscle; it will only add fat. Since muscle loss is driven by the injury's metabolic response rather than just caloric deficit, excessive feeding is counterproductive for body composition, adding fat without preserving lean mass.

In insects (Drosophila, fruit flies, crickets), lifespan is determined by the protein-to-carbohydrate (P:C) ratio rather than total caloric intake, with lower P:C ratios extending longevity.

For insects, lowering the protein-to-carbohydrate ratio extends life. For humans, this suggests that focusing solely on calorie restriction may be less effective than optimizing the balance of protein and carbohydrates, though direct human protocols are not yet established.

Pharmacological agents such as thiazolidinediones (TZDs), BMP7, and COX2 can induce 'browning' in white adipose tissue (WAT), converting white fat cells into brown-like adipocytes that express UCP1 and increase energy expenditure.

While drugs like TZDs can turn white fat into brown-like fat in mice, these are prescription medications with side effects and are not recommended for general use. The research highlights a potential future therapeutic avenue rather than a current lifestyle intervention.