Browse the evidence

Obesity and metabolic syndrome significantly increase the risk of hepatocellular carcinoma (HCC), with risk escalating as BMI increases and being further amplified by the presence of type 2 diabetes.

Maintaining a healthy body weight is a critical strategy for reducing the risk of liver cancer. The risk of developing hepatocellular carcinoma increases significantly with higher BMI, and this risk is even higher if you have type 2 diabetes. Focus on metabolic health through diet and lifestyle changes to lower this risk.

Palmitic acid is essential for physiological functions including maintaining membrane fluidity, protein palmitoylation, and lung surfactant activity (DPPC), and its deficiency can impair lung function.

Palmitic acid is not just 'bad fat'; it is essential for your lungs (surfactant), cell membranes, and protein signaling. Your body makes it and needs it. The problem arises not from its presence, but from excess production due to sugar and calorie overload.

Epigenetic clocks, particularly those tuned to phenotypic age or mortality risk (e.g., GrimAge), are robust biomarkers for predicting biological aging and adverse health outcomes.

Epigenetic clocks offer a promising way to measure biological age, potentially identifying those aging faster than their chronological age. This could guide personalized interventions to slow aging, though clinical application is still emerging.

In patients with type 2 diabetes, the characteristic dyslipidemia (low HDL, small dense LDL, elevated triglycerides) is strongly associated with increased cardiovascular disease risk, driven by insulin resistance and altered VLDL metabolism.

If you have type 2 diabetes, standard cholesterol tests might not tell the whole story. You are at higher risk for heart disease due to specific changes in your blood fats (like small, dense LDL and low HDL) driven by insulin resistance. This risk exists even if your total LDL looks normal. Managing this requires addressing the underlying insulin resistance through lifestyle changes (diet, exercise) and often medication, not just focusing on total cholesterol numbers.

Age-related muscle atrophy is primarily driven by the loss of muscle fibers and motor units starting around age 50, rather than just the shrinking of existing fibers, and this process is largely independent of physical activity levels.

Understanding that muscle loss is partly due to losing entire muscle fibers (not just shrinking them) helps explain why maintaining muscle mass becomes harder with age. While you can't easily replace lost fibers, you can maximize the size and function of the fibers you have through regular exercise.

Obesity causes approximately 20% of all cancer cases, with specific mechanisms varying by cancer site (e.g., estrogen for breast/endometrial, insulin for colon/prostate, inflammation for others).

Maintaining a healthy weight is one of the most significant actions you can take to reduce your risk of developing many common cancers. While the biological mechanisms vary (hormones, insulin, inflammation), the common denominator is excess body fat. Weight management strategies that reduce adiposity can lower cancer risk across multiple types.

GIP signaling is selectively impaired in type 2 diabetes, reducing its insulinotropic effect, while GLP-1 signaling remains substantially preserved.

In Type 2 Diabetes, your body's natural response to GIP is blunted, which is why GLP-1 based medications are often more effective for stimulating insulin than therapies targeting GIP.

Obesity induces chronic low-grade metabolic inflammation in adipose tissue, primarily through macrophage infiltration and the secretion of pro-inflammatory cytokines like TNF-alpha and IL-6, which directly causes insulin resistance and metabolic dysfunction.

Understanding that obesity creates a biological state of chronic inflammation helps explain why weight loss is difficult and why metabolic health declines. This is not a moral failing but a physiological response where fat tissue actively signals the body to store more fat and resist insulin. Treatments targeting this inflammation (like managing cytokine levels) may be necessary alongside lifestyle changes.

Leptin resistance in obese individuals renders exogenous leptin therapy ineffective for weight loss, despite leptin's potent role in regulating energy balance and satiety.

Leptin supplements or therapies are generally ineffective for weight loss in typical obesity because the body has become resistant to the hormone. This is why simply 'adding more leptin' doesn't work. Focus should be on improving leptin sensitivity through lifestyle changes rather than seeking leptin-based treatments.

Conventional weight loss interventions rarely result in long-term weight maintenance, with the majority of individuals regaining lost weight.

Do not expect to maintain significant weight loss long-term through diet and exercise alone. Focus on health behaviors instead.

The doubly labeled water method provides a valid and accurate measurement of energy expenditure in free-living humans when using moderate isotope doses and correcting for isotopic fractionation.

For accurate energy expenditure tracking in free-living individuals, the doubly labeled water method is the most reliable non-restrictive tool available, provided that moderate isotope doses are used and proper corrections for isotopic fractionation are applied.

Genetically predicted lower alcohol consumption is causally associated with a reduced risk of coronary heart disease and ischaemic stroke, refuting the observational hypothesis that light-to-moderate alcohol intake is cardioprotective.

Current observational advice suggesting light-to-moderate drinking protects the heart is likely incorrect. Genetic evidence indicates that reducing alcohol intake, even for those who drink moderately, lowers the risk of heart disease and stroke. The safest level of alcohol consumption for cardiovascular health is zero or minimal.

Chronically elevated plasma free fatty acid (FFA) levels cause insulin resistance in muscle and liver and impair insulin secretion in pancreatic beta-cells, a process termed lipotoxicity.

In Type 2 Diabetes, high levels of free fatty acids in the blood drive insulin resistance in muscles and the liver, and damage the pancreas's ability to make insulin. This 'lipotoxicity' is caused by fat cells failing to store fat properly, leading to fat accumulating in organs where it shouldn't be. Reducing these fatty acid levels (e.g., via medications like thiazolidinediones or lifestyle changes that improve fat storage capacity) can improve insulin sensitivity.

Adipose tissue acts as an endocrine organ, secreting hormones like leptin and adiponectin that regulate systemic metabolism, insulin sensitivity, and energy expenditure.

Understand that your fat cells send signals to your brain and other organs. Healthy fat levels help regulate hunger (leptin) and insulin sensitivity (adiponectin). Disrupting these signals through extreme dieting or obesity can lead to metabolic dysfunction.

The DASH diet does not significantly affect fasting glucose, Triglycerides (TAG), or HDL cholesterol concentrations.

Do not expect the DASH diet to significantly lower your blood sugar, Triglycerides, or raise your HDL cholesterol. Its primary benefits are on blood pressure and LDL cholesterol. Manage your expectations and focus on the proven benefits.

In patients with impaired glucose tolerance, insulin resistance is caused solely by decreased insulin receptor numbers (receptor defect), resulting in a rightward shift of the dose-response curve without a reduction in maximal glucose disposal capacity.

If you have impaired glucose tolerance (pre-diabetes), your body's ability to process glucose at high insulin levels is likely intact. The primary issue is that you have fewer insulin receptors, so you need higher insulin levels to achieve the same glucose disposal as a healthy person. This suggests that lifestyle interventions improving insulin sensitivity (like exercise) can help compensate for the lower receptor count by making the existing receptors more efficient or by lowering the baseline insulin demand.

In patients with Type II diabetes and fasting hyperglycemia, insulin resistance is caused by both decreased insulin receptors AND a postreceptor defect, leading to a reduced maximal rate of glucose disposal.

For those with established Type II diabetes, simply lowering insulin levels (if possible) or increasing receptor sensitivity is not enough because the cells' internal ability to process glucose is also damaged. Treatment must address both the signaling issue (receptors) and the internal processing issue (postreceptor defects), often requiring medication that bypasses or enhances these pathways.

Insulin's ability to suppress hepatic glucose output is preserved in both impaired glucose tolerance and Type II diabetes, with no postreceptor defect detected in the liver.

Even in Type II diabetes, the liver retains the ability to stop producing glucose when insulin levels are high enough. This suggests that therapies aiming to suppress hepatic glucose production (like metformin or GLP-1 agonists) may still be effective because the liver's basic response mechanism is not broken, just less sensitive.

In postmenopausal women with a normal baseline BMI (<25.0), gaining more than 5% of body weight during follow-up is associated with an increased risk of invasive breast cancer.

Postmenopausal women with a normal weight should be vigilant about avoiding significant weight gain (more than 5% of body weight), as this increases breast cancer risk. This highlights that weight stability is important even for those who are not currently overweight.

The pathophysiological link between NAFLD and CVD is driven by systemic inflammation, endothelial dysfunction, and atherogenic dyslipidemia (specifically high ApoC3 and small dense LDL) resulting from hepatic fat accumulation and insulin resistance.

Understanding that liver fat drives heart risk through inflammation and bad cholesterol helps explain why lifestyle changes (diet/exercise) that reduce liver fat also protect the heart. It is not just about weight loss, but improving metabolic health.

Adding wearable technology for physical activity and diet monitoring to a standard behavioral weight loss intervention results in significantly less long-term weight loss compared to the standard intervention alone.

If you are trying to lose weight long-term, do not rely on a wearable device to do the heavy lifting. This study shows that adding a tracker to a standard weight loss program actually led to worse results than the program alone. Focus on the core behaviors: a sustainable calorie deficit, regular physical activity, and consistent support (like counseling or coaching). The device is optional and may not help; the behavioral change is essential.

There is no global consensus on optimal vitamin D status, with definitions of deficiency and insufficiency varying significantly between organizations, leading to inconsistent prevalence estimates.

Be aware that 'vitamin D deficiency' and 'optimal levels' are defined differently by various health organizations. This makes it difficult to compare studies and determine a single 'perfect' blood level for everyone.

Genetic mutations in the Melanocortin-4 Receptor (MC4R) are a common cause of severe childhood and adult obesity, resulting in hyperphagia and increased fat and lean mass.

If you have severe obesity starting in childhood, ask about genetic testing for MC4R mutations. This is a known genetic cause affecting up to 5% of severe cases. Understanding this can guide medical treatment, as standard weight loss advice may be less effective without addressing the specific receptor dysfunction.

Doubly labeled water (DLW) is the criterion gold standard for assessing total energy expenditure (TEE) in free-living individuals, but it does not provide information on activity type, intensity, or duration.

If you need to know exactly how much total energy a person burns in their daily life, the Doubly Labeled Water technique is the most accurate method available. However, it is expensive and requires collecting urine samples for 7-14 days, so it is mostly used in research rather than clinical practice. For most people, other objective measures like accelerometers are more practical, even if less precise for total energy.