Browse the evidence

High-fat diets increase circulating lipopolysaccharide (LPS) levels (metabolic endotoxemia) through chylomicron-mediated absorption and increased intestinal permeability, leading to subclinical inflammation and insulin resistance.

High-fat meals can trigger gut-derived inflammation (endotoxemia) which contributes to insulin resistance. However, the type of fat matters: emulsified fats (like some vegetable oils) may worsen this effect compared to solid fats (like butter). To minimize this, consider the source and physical state of fats in your diet, and potentially combine high-fat meals with anti-inflammatory foods like flavonoid-rich juices.

Metformin activates AMP-activated protein kinase (AMPK) in hepatocytes and skeletal muscle, which suppresses hepatic glucose production and increases glucose uptake, thereby lowering blood glucose and improving lipid profiles.

Metformin works by activating a cellular energy sensor (AMPK) that tells the liver to stop making glucose and muscles to take up more glucose. This happens without increasing insulin levels, which is why it doesn't cause weight gain or hypoglycemia. Understanding this mechanism highlights that its benefits are tied to cellular energy status rather than direct hormonal stimulation.

Human brown adipose tissue (BAT) is molecularly composed of beige/brite cells rather than classical brown adipocytes, as evidenced by the abundant expression of beige-selective genes (e.g., CITED1, HoxC8/9) and the near-undetectable expression of classical brown fat markers (e.g., Zic1, Lhx8).

Your body's brown fat is likely 'beige' fat, meaning it shares characteristics with fat that can be induced in white fat deposits. This suggests that strategies to 'browns' white fat (like cold exposure or specific hormonal pathways) might be more relevant for humans than trying to activate pre-existing classical brown fat, which appears to be minimal or absent in adults.

Human obesity is characterized by tissue-specific dysregulation of cortisol metabolism, specifically involving increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in adipose tissue and skeletal muscle, leading to elevated intracellular cortisol levels despite normal circulating cortisol.

Standard blood tests for cortisol may appear normal in obesity, masking tissue-specific metabolic stress. The problem lies in how fat and muscle cells convert inactive cortisone into active cortisol via the enzyme 11beta-HSD1. Managing obesity requires addressing this local tissue dysregulation, not just systemic stress markers.

Dietary intake of choline (from phosphatidylcholine/egg yolk) and L-carnitine (from red meat) is metabolized by gut microbiota into trimethylamine (TMA), which is converted by hepatic FMO3 into TMAO, a metabolite that promotes atherosclerosis and increases cardiovascular disease risk.

High intake of red meat (L-carnitine) and egg yolks (choline/phosphatidylcholine) is linked to higher cardiovascular risk through a gut-liver metabolic pathway producing TMAO. While choline is essential, individuals with high cardiovascular risk may benefit from moderating intake of these specific precursors or discussing microbiome-targeted strategies with their provider, rather than relying solely on statins.

Higher objectively measured sedentary time is independently associated with higher 2-hour postchallenge plasma glucose, independent of light and moderate-to-vigorous activity levels.

Sitting for long periods raises your blood sugar after meals, regardless of whether you exercise later. To protect your metabolic health, break up your sitting time. Stand up, walk around, or do light chores frequently throughout the day, rather than relying solely on a single workout session.

Fasting plasma glucose (FPG) is not significantly associated with objectively measured light-intensity or moderate-to-vigorous physical activity after adjusting for confounders like waist circumference.

Do not rely solely on fasting blood sugar tests to judge the effectiveness of your exercise routine. Your body's ability to handle sugar after eating (2-hour post-challenge glucose) is a much more sensitive indicator of how physical activity is improving your metabolic health.

Epigenetic clocks based on DNA methylation levels can predict chronological age and the risk of aging-related diseases.

Epigenetic clocks can measure biological age. This can help assess the efficacy of aging interventions.

MBS significantly reduces the risk of developing obesity-associated cancers and cancer-related mortality.

Undergoing MBS not only helps with weight but also significantly lowers your long-term risk of developing various cancers and dying from cancer compared to remaining obese.

Adults with overweight or obesity exhibit significantly higher faecal concentrations of short-chain fatty acids (SCFAs), including acetate, propionate, butyrate, and valerate, compared to lean adults, suggesting altered colonic fermentation patterns associated with adiposity.

This research highlights that people with higher body weight may have gut bacteria that produce more short-chain fatty acids (SCFAs) from fibre than lean individuals. While fibre is still beneficial for gut health, this finding suggests that the 'efficiency' of gut fermentation differs in obesity. It does not mean you should stop eating fibre, but it implies that individual gut responses to fibre vary significantly based on existing body composition and microbiota.

High-dose aspirin (approx. 7 g/day for 2 weeks) improves glucose metabolism in type 2 diabetes by inhibiting the IKKβ serine kinase pathway, thereby reducing hepatic glucose production and enhancing peripheral insulin sensitivity.

High-dose aspirin (approx 7g/day) significantly improves blood sugar control in type 2 diabetes by targeting inflammation (IKKβ). However, due to significant side effects like tinnitus and gastric risks, it is not recommended for routine treatment. The key takeaway is that targeting the IKKβ pathway is a valid strategy for treating insulin resistance.

In patients with Non-Alcoholic Fatty Liver Disease (NAFLD), the presence and severity of liver fibrosis, rather than the presence of steatohepatitis (NASH) itself, is the primary predictor of liver-related and overall mortality.

If you have fatty liver, the specific type of liver damage (inflammation vs. simple fat) matters less for your long-term survival than the presence of scarring (fibrosis). You should prioritize getting assessed for fibrosis (e.g., via non-invasive scores like FIB-4 or APRI) rather than just focusing on liver enzymes or the presence of inflammation. Managing metabolic risk factors like diabetes and obesity is crucial to slowing fibrosis progression.

Cardiovascular disease (CVD) is the leading cause of death in NAFLD patients with advanced fibrosis, independent of liver-related mortality.

If you have advanced fatty liver disease, your biggest risk to life is not liver failure, but heart disease. You must aggressively manage cardiovascular risk factors: control blood pressure, manage cholesterol, and keep blood sugar in check. Regular cardiovascular screening is essential.

Weight loss is associated with a statistically nonsignificant decrease in diabetes risk, suggesting that while weight gain is a strong predictor, weight loss may not immediately reverse risk to baseline levels in this cohort.

While preventing weight gain is crucial, do not assume that losing weight will instantly eliminate your diabetes risk if you have a history of obesity. The study suggests weight loss did not significantly reduce risk in this specific analysis, possibly due to the duration of prior obesity.

Medium-term recovery from moderate-to-severe SARS-CoV-2 infection is characterized by persistent multi-organ MRI abnormalities, significantly reduced exercise capacity, and impaired cognitive performance, which correlate with the severity of the initial acute illness.

If you have been hospitalized for COVID-19, do not assume you are fully recovered just because you are discharged. Expect potential long-term effects on your lungs, heart, brain, and energy levels. Seek medical evaluation for persistent breathlessness or fatigue, and consider a gradual, monitored return to physical activity rather than pushing through symptoms, as your exercise capacity may be significantly reduced.

Post-acute SARS-CoV-2 infection is associated with specific brain MRI changes (thalamic T2* signal, white matter diffusivity) and impaired executive/visuospatial cognitive performance, which correlate with the severity of the initial inflammatory response.

If you are experiencing 'brain fog' or difficulty with planning and spatial tasks after COVID-19, it may be linked to structural changes in your brain. Consider a neuropsychological evaluation to assess cognitive function, as these deficits are common and may require specific cognitive rehabilitation strategies.

Post-acute SARS-CoV-2 infection is associated with a higher burden of self-reported depression, anxiety, and impaired quality of life across all domains, independent of physical symptoms.

Do not ignore feelings of depression, anxiety, or a drop in quality of life after COVID-19. These are common, measurable outcomes linked to the severity of your illness. Seek support from mental health professionals, as addressing these issues is a critical part of your overall recovery.

Dietary interventions (resistant starch, non-starch polysaccharides, or weight-loss) induce distinct but relatively minor changes in intestinal microbiota composition compared to strong inter-individual baseline differences.

Diet changes your gut bacteria, but your starting microbiota matters more than the specific diet. If you have high baseline diversity, you might be a 'responder' with distinct changes; if low, you might be a 'non-responder' with stable microbiota. Don't expect diet to be the sole master switch.

Resistant Starch (RS) diets increase Ruminococcus bromii and decrease Lachnospiraceae, while Non-Starch Polysaccharides (NSP) increase Lachnospiraceae and decrease Ruminococcus.

Different fibers feed different bacteria. RS feeds Ruminococcus, while other fibers (NSP) feed Lachnospiraceae. Variety in fiber types may be needed to support diverse bacterial groups.

Body mass index (BMI) increases rapidly with national income until a threshold of approximately $12,500-$17,000 (international dollars), after which it flattens and eventually declines, contradicting the linear 'diseases of affluence' paradigm.

Focus on obesity prevention early in economic development, before income reaches high levels. Interventions should target energy balance (caloric intake and physical activity) during the rapid rise phase, as waiting for high-income lifestyle shifts may be too late for public health goals.

Total cholesterol levels increase with national income, peaking at higher income levels ($18,000) than BMI, and are positively correlated with urbanization.

Monitor cholesterol levels as income rises, particularly in urbanizing areas. Interventions should address dietary fat quality (animal vs. vegetable fats) as income increases.

Obesity-induced chronic low-grade inflammation causes insulin resistance by activating proinflammatory cytokines (TNF-α, IL-6) and signaling pathways (JNK, NF-κB, JAK-STAT), which interfere with insulin signaling and action.

If you are overweight, your body fat is not just stored energy; it is biologically active tissue releasing inflammatory signals that block insulin. Managing weight and reducing visceral fat are critical steps to lowering this inflammation and improving insulin sensitivity.

Specific inflammatory cytokines (TNF-α, IL-6) and signaling pathways (JNK, NF-κB, JAK-STAT) directly impair insulin signaling by causing serine phosphorylation of IRS-1 and reducing GLUT4 expression.

Understanding that inflammation directly blocks insulin action at the cellular level explains why anti-inflammatory strategies or weight loss can improve metabolic health.

Skeletal muscle regeneration and repair are primarily governed by satellite cells (SCs), which transition from a quiescent state to activation, proliferation, and differentiation in response to injury or stress.

To support muscle repair after injury or intense training, ensure adequate rest and nutrition to support the natural satellite cell activation process. The body has a built-in repair system (satellite cells) that activates when needed; supporting this with general health practices is key.