Browse the evidence

Genetic variants, specifically PNPLA3 I148M and TM6SF2 E167K, significantly increase the risk of liver disease progression and hepatocellular carcinoma in NAFLD patients, independent of metabolic syndrome severity.

If you have a family history of liver disease or known genetic variants like PNPLA3, you are at higher risk for liver damage even if your weight is normal. This means you need stricter monitoring of liver enzymes and fibrosis markers, and you must be aggressive with lifestyle interventions to reduce liver fat and inflammation.

Wearable sleep-tracking technology introduces healthcare disparities because sensor performance is negatively impacted by person-specific factors such as skin color and obesity, leading to inaccurate data for minority and obese populations.

If you have darker skin or obesity, be aware that consumer sleep wearables may be less accurate for you. Do not use these devices for critical health decisions without verifying their accuracy against clinical standards for your specific body type.

PPARα activation suppresses the liver secretome (including complement and coagulation factors) to conserve energy during fasting, whereas FXR activation induces secretion to support nutrient processing in the fed state.

Your liver actively manages energy by adjusting how much protein it secretes based on whether you are eating or fasting. In the fed state, it produces more proteins (like clotting factors and complement) to support nutrient processing. In the fasted state, it reduces this production to save energy. This suggests that nutritional strategies, particularly for those with metabolic issues or undernutrition, should consider the timing of nutrient intake to align with these natural hormonal switches (PPARα for fasting, FXR for feeding).

PPARα and FXR have opposing effects on autophagy: PPARα induces autophagy during fasting to recover nutrients, while FXR suppresses it during the fed state.

Your body uses autophagy (cellular recycling) to recover nutrients when you are fasting, driven by PPARα. When you eat, FXR suppresses this process. This natural cycle suggests that intermittent fasting may leverage this mechanism to clear cellular debris and recover nutrients, provided the fasting periods are sufficient to trigger PPARα activation.

High-dose phenolic compound supplementation can exhibit pro-oxidant effects and cause toxicity, including liver damage and accelerated tumorigenesis, in certain contexts.

Avoid high-dose polyphenol supplements. While dietary sources are safe, concentrated supplements can become pro-oxidant and cause liver stress or other toxic effects.

Downregulation of genes encoding mitochondrial proteins is a highly conserved hallmark of cellular ageing across multicellular eukaryotes, correlating with reduced mitochondrial function and lifespan.

Aging is associated with a consistent drop in the genetic instructions for making mitochondrial proteins. While this is a hallmark of aging, interventions like caloric restriction or metformin can reverse this specific gene expression change, suggesting that maintaining mitochondrial gene expression levels may be beneficial for healthspan.

Downregulation of ribosomal proteins and ribosome biogenesis factors is a conserved hallmark of cellular ageing, likely serving as a protective programme rather than a cause of pathology.

Aging involves a reduction in the genetic instructions for building ribosomes. This is not a defect but a protective mechanism. Interventions that extend lifespan, such as caloric restriction and rapamycin, also reduce these levels, suggesting that this downregulation is beneficial for longevity.

Dysregulation of immune system genes, specifically the upregulation of inflammation-associated genes (inflammaging), is a conserved transcriptional hallmark of cellular ageing.

Aging is associated with a consistent upregulation of immune and inflammation-related genes. This 'inflammaging' is linked to senescent cells and immune dysfunction. Interventions like metformin can reduce this inflammation, suggesting that managing chronic low-grade inflammation is relevant to healthspan.

Females are protected from inflammation-induced muscle wasting (cancer cachexia) compared to males, likely due to estrogen's ability to blunt inflammatory responses and lower basal ubiquitin-proteasome activity.

For women undergoing cancer treatment involving cachexia, hormonal status (specifically estrogen) may offer some natural protection against severe muscle wasting compared to men. This doesn't mean muscle loss won't happen, but the mechanism is different. Maintaining hormonal balance and managing inflammation are key, as estrogen helps blunt the inflammatory signals that drive this specific type of muscle loss.

Elevated plasma Branched-Chain Amino Acids (BCAAs) are associated with insulin resistance and type 2 diabetes risk, though genetic evidence suggests insulin resistance may drive BCAA levels rather than the reverse.

High levels of BCAAs in your blood are a strong indicator of insulin resistance and future diabetes risk. Interestingly, genetic studies suggest that your body's inability to clear BCAAs (due to insulin resistance) causes the high levels, rather than the BCAAs causing the resistance. If you are insulin resistant, focus on improving metabolic health through diet and exercise rather than just supplementing BCAAs.

DL001 reduces the immunosuppressive effects of mTOR inhibition compared to rapamycin, specifically preserving more T cell and Treg populations.

This study shows that DL001, a selective mTORC1 inhibitor, causes less suppression of T cells and T regulatory cells than standard rapamycin in mice. This suggests that future human applications of selective mTOR inhibitors might have a better safety profile regarding immune function and infection risk, though human trials are needed to confirm this.

Bone marrow adipose tissue (BMAT) is functionally distinct from white and brown adipose tissues, exhibiting high basal glucose uptake but resisting insulin- and cold-stimulated glucose uptake.

Bone marrow fat is not just inert storage; it is a metabolically active tissue that consumes significant glucose at rest but does not respond to insulin or cold like other fats. This suggests that managing overall metabolic health involves factors beyond just visible subcutaneous or visceral fat, and that bone marrow fat may play a larger role in systemic glucose regulation than previously assumed.

SGLT-2 inhibitors produce modest weight loss (2.1-2.7 kg) in people with Type 2 Diabetes by inducing glucose-mediated osmotic diuresis, but are not yet approved specifically for obesity treatment.

SGLT-2 inhibitors (like Jardiance or Forxiga) are used for Type 2 Diabetes and cause modest weight loss (2-3 kg) by peeing out glucose. They are not approved for obesity treatment in non-diabetics, and the weight loss is less significant than with GLP-1 drugs.

Poor dietary intake in low-income groups is an emergent property of a complex adaptive system that sustains a food environment increasing the accessibility, availability, affordability, and acceptability of unhealthy foods.

For policymakers and advocates: Do not rely solely on 'food desert' fixes like new supermarkets. Interventions must simultaneously address household financial strain, social/cultural norms, and the systemic drivers that make unhealthy food the rational choice for low-income households.

Dietary intake in low-income groups is driven more by demand-side factors (social, cultural, economic) than by supply-side factors (accessibility, availability).

For health educators: Nutrition education alone is ineffective if it doesn't address the economic and social realities of low-income households. Interventions must focus on making healthy choices financially viable and socially supported, not just 'known'.

Metabolomic biomarkers, particularly Branched-Chain Amino Acids (BCAAs), aromatic amino acids, and specific lipids (ceramides, sphingomyelins), can predict the onset and progression of Metabolic Syndrome and Type 2 Diabetes before clinical symptoms appear.

Current standard blood tests may miss early metabolic dysfunction. Emerging research shows that specific amino acids and lipids rise before diabetes symptoms appear. Until these tests are routine, focus on early lifestyle changes if you have risk factors like central obesity.

Iodine supplementation during preconception, pregnancy, and postpartum periods corrects maternal iodine insufficiency but shows no significant benefit for preventing preterm birth, low birthweight, or improving child neurodevelopment.

If you are pregnant or planning pregnancy, iodine supplementation is recommended to correct iodine deficiency, which is common. However, do not expect this supplementation to prevent preterm birth, low birth weight, or significantly boost your child's intelligence or motor development beyond what is achieved by correcting the deficiency. Stick to recommended prenatal doses.

Circadian misalignment induces a gene expression profile in skeletal muscle that favors fatty acid metabolism over glucose metabolism, potentially leading to substrate competition and reduced insulin sensitivity.

Your muscles change how they use fuel based on your schedule. When you are misaligned (e.g., working nights), your muscles switch to burning more fat and less glucose, which can interfere with insulin's ability to store glucose. This is driven by changes in gene expression. Maintaining a consistent schedule helps keep your muscle metabolism balanced.

Dietary nitrate supplementation does not improve performance in highly trained endurance athletes during cycling or running, likely due to higher baseline nitric oxide bioavailability.

If you are an elite endurance athlete, stop wasting money on beetroot juice for running or cycling; it won't help you. Focus on training.

Hepatic lipid accumulation acts as a primary driver of systemic metabolic dysfunction by serving as ligands for PPARs, which upregulate gluconeogenic, lipogenic, and ketogenic genes, thereby promoting hyperglycemia and hyperlipidemia.

If you have fatty liver, your liver is actively contributing to your metabolic issues (like high blood sugar) by sending chemical signals that tell your body to produce more glucose and store more fat. Treating the fatty liver is not just about removing fat; it is about stopping these active signals that drive systemic disease.

The typical hormonal environment in fatty liver disease—hyperinsulinemia, hyperglucagonemia, hypercortisolemia, and growth hormone deficiency—synergistically encourages further hepatic steatosis by dysregulating adipose lipolysis and hepatic lipid handling.

Your body's hormone levels (insulin, cortisol, glucagon) are not just bystanders in fatty liver; they actively drive more fat into the liver. Addressing insulin resistance and stress is key to breaking this cycle.

Fructose consumption promotes hepatic de novo lipogenesis (DNL) and NAFLD development through both substrate provision and independent upregulation of lipogenic transcription factors (SREBP1c and ChREBP), even in the absence of insulin signaling.

High amounts of fructose (especially from added sugars or juices) directly stimulate your liver to make new fat, even if you aren't insulin resistant. This process is unique to fructose compared to glucose.

Higher levels of dispositional optimism are associated with a longer life span and greater odds of achieving exceptional longevity (survival to age 85+), independent of demographics, health conditions, and health behaviors.

Cultivating a realistic positive outlook on the future is associated with living significantly longer. This is not about ignoring reality, but about maintaining confidence in your ability to handle challenges. This trait is linked to healthier behaviors like better diet and exercise, which drive the longevity benefit. Since optimism can be learned, engaging in practices that build resilience and positive goal-setting may support a longer life.

Accumulation of senescent endothelial cells and vascular smooth muscle cells drives the progression of atherosclerosis and hypertension.

Cellular aging in blood vessels contributes to heart disease and high blood pressure. Managing cardiovascular risk factors may help slow this process.