Browse the evidence

Iron status has a dual role in immunity: deficiency impairs immune cell function (B-cells, T-cells), but excess iron during infection can be exploited by pathogens, leading to an evolutionary mechanism of hypoferremia (iron withdrawal) during acute infection.

Maintain healthy iron levels through diet (red meat, beans, leafy greens) to support immune cell function. However, if you have a serious active infection (like malaria or TB) or a condition like hemochromatosis, consult your doctor before taking iron supplements, as excess iron can help pathogens grow. The body naturally restricts iron during infection (hypoferremia) to fight this.

Brown adipose tissue (BAT) activity in adults is negatively correlated with body mass index (BMI) and body fat percentage, and is absent or significantly reduced in obese and elderly populations.

If you are obese or older, your brown fat activity may be lower, making it harder to rely on cold exposure for weight loss. However, this doesn't mean you can't benefit from other aspects of energy expenditure. Focus on overall energy balance, as even small increases in expenditure can have long-term effects.

Genetic factors, particularly polymorphisms affecting neurotransmitter systems (dopamine, serotonin) and metabolic traits (BMI, insulin resistance), significantly increase the risk of developing eating disorders, with distinct genetic architectures for anorexia nervosa versus binge-type disorders.

If you have a family history of eating disorders, you may have a biological predisposition. This is not your fault, but it is a risk factor you can manage. Focus on early identification of symptoms and seek professional support if you notice changes in eating habits or body image, as genetic risk can be mitigated by environmental factors.

Childhood trauma, abuse, and neglect are strongly linked to the development of eating disorders, particularly Bulimia Nervosa and Binge Eating Disorder, through interactions with genetic susceptibility.

If you have experienced childhood trauma, you may be at higher risk for eating disorders. This risk is not inevitable, but it is significant. Trauma-informed therapy and support can help address the underlying emotional pain that may manifest as disordered eating.

Pharmacological inhibition of BCKDK using BT2 reduces plasma branched-chain amino acid (BCAA) and branched-chain alpha-keto acid (BCKA) levels, thereby attenuating obesity-associated insulin resistance in obese mice.

In obese individuals, high levels of branched-chain amino acids (BCAAs) and their metabolites contribute to insulin resistance. This study suggests that enhancing the body's ability to break down BCAAs (via BCKDK inhibition) improves insulin sensitivity. While BT2 is a drug, the findings support the idea that managing BCAA metabolism is key to treating obesity-related metabolic issues.

Reducing dietary protein intake (specifically BCAAs) improves insulin sensitivity in obese mice, whereas increasing BCAA intake exacerbates insulin resistance.

For obese individuals, reducing the intake of branched-chain amino acids (found in high-protein foods like meat, eggs, and dairy) may improve insulin sensitivity. Conversely, high BCAA intake can worsen insulin resistance. This suggests that the quality of protein (BCAA content) is as important as the quantity.

Elevated levels of branched-chain alpha-keto acids (BCKAs) impair insulin signaling by activating mTORC1, independent of BCAAs.

BCKAs, metabolites of BCAAs, directly impair insulin signaling by activating mTORC1. This suggests that managing BCAA metabolism is crucial for preventing insulin resistance, as BCKAs are not just inert byproducts but active contributors to metabolic dysfunction.

Resistin levels are increased in obesity and induce insulin resistance by inhibiting AMPK activity and increasing SOCS3 expression.

Resistin is a hormone that increases with obesity and contributes to insulin resistance by interfering with cellular energy sensors (AMPK). Reducing obesity can lower resistin levels and improve insulin sensitivity.

Higher body weight does not necessarily result in a lower Physical Activity Level (PAL); obese individuals often have similar or higher activity-induced energy expenditure (AEE) than lean individuals due to higher movement costs, despite moving less frequently.

Do not assume that because you are overweight, you burn fewer calories during activity than a lean person. Your body burns more energy to move your mass, so your total activity energy expenditure might be similar to someone leaner who moves more frequently. Weight loss requires creating a deficit, not just assuming you 'don't move enough' compared to others.

Physical Activity Level (PAL) is strongly influenced by genetic predisposition, with 72-78% of the variance in activity levels within a controlled environment attributed to genetic factors.

Accept that your natural tendency to be active or sedentary is largely genetic. This doesn't mean you can't change, but it means you might need to rely more on structure and habit formation than on 'natural' motivation. Don't compare your baseline activity to others who may have a different genetic predisposition.

In healthy individuals consuming low-cholesterol diets, the absolute milligram amount of dietary cholesterol absorbed (not the efficiency of absorption) is strongly and independently correlated with fasting plasma insulin, C-peptide, and glucagon levels, serving as a marker for insulin resistance.

If you are healthy and eat a balanced diet, your body's ability to absorb cholesterol (efficiency) doesn't change much based on what you eat. However, the actual amount of cholesterol you absorb is linked to higher insulin levels. To manage insulin sensitivity, focus on the total amount of cholesterol and fat in your diet rather than trying to alter your body's absorption efficiency.

The ISI0,120 index of insulin sensitivity, derived from oral glucose tolerance test data, is an independent predictor of incident cardiovascular disease (CVD) risk, whereas the fasting-based HOMA-IR index is not independent of the metabolic syndrome.

If you are concerned about heart disease risk and have normal fasting glucose but other metabolic risk factors, a standard fasting insulin test (HOMA-IR) may not tell the whole story. This research suggests that how your body handles sugar after a meal (measured by ISI0,120 via an OGTT) provides independent information about cardiovascular risk that fasting tests miss. Discuss with your doctor whether an Oral Glucose Tolerance Test is warranted for comprehensive risk assessment, especially if you have family history or other metabolic syndrome components.

Late-onset hypogonadism (LOH) defined by sexual symptoms and total testosterone <8 nmol/liter is associated with significant end-organ deficits including lower hemoglobin, bone mineral density, and lean mass, whereas moderate LOH (8-11 nmol/liter) shows only modest tissue-level changes.

If you are an older man experiencing sexual dysfunction (ED, low libido) alongside fatigue or muscle loss, get your testosterone checked. If your levels are below 8 nmol/liter, you likely have Late-Onset Hypogonadism, which is linked to lower bone density, muscle mass, and hemoglobin. However, if your levels are between 8-11 nmol/liter, your metabolic risks are likely due to weight and age, not testosterone, so focus on weight management rather than hormone therapy.

Acute total sleep deprivation enhances brain activation in the anterior cingulate cortex in response to hedonic food stimuli, increasing subjective appetite ratings independent of fasting plasma glucose levels.

If you are sleep-deprived, your brain's reward system becomes hypersensitive to food cues, specifically activating the anterior cingulate cortex. This happens regardless of your actual blood sugar levels. To mitigate this, prioritize getting adequate sleep, as acute sleep loss directly amplifies the neural drive to consume food.

Chronic tissue inflammation, driven by obesity-induced macrophage accumulation and proinflammatory cytokine release, is a major etiologic cause of insulin resistance and beta-cell dysfunction in metabolic disease.

In obesity, fat tissue doesn't just store energy; it becomes inflamed, releasing chemicals that block insulin from working properly in your muscles, liver, and pancreas. This inflammation is a direct cause of Type 2 Diabetes risk. Managing metabolic health requires addressing this underlying inflammatory state, not just caloric intake.

Chronic inflammation in pancreatic islets, driven by macrophage infiltration and proinflammatory cytokines (IL-1β, IL-23, IL-24), causes beta-cell dysfunction and reduced glucose-stimulated insulin secretion (GSIS) in Type 2 Diabetes.

In Type 2 Diabetes, inflammation inside the pancreas damages the insulin-producing beta cells. This isn't just about insulin resistance; the pancreas itself gets inflamed, reducing its ability to secrete insulin when needed. Protecting beta cells from inflammation is a key therapeutic target.

Higher skeletal muscle membrane unsaturation, specifically increased A5 desaturase activity and higher levels of long-chain polyunsaturated fatty acids (C20-22 PUFA), is associated with improved insulin action (glucose disposal) and lower adiposity.

This research suggests that the types of fats you eat influence the structure of your muscle cell membranes. Specifically, diets that support higher levels of polyunsaturated fatty acids (PUFAs) and the enzymes that create them (like A5 desaturase) are linked to better insulin sensitivity. While this study doesn't prescribe a specific diet, it implies that dietary fat quality (specifically the ability to form long-chain PUFAs) is a lever for metabolic health.

Growth Hormone (GH) injections do not increase muscle strength in sarcopenic patients and are associated with frequent side effects.

Do not use Growth Hormone injections to treat sarcopenia. They do not improve strength and cause side effects. Focus on exercise instead.

Ultra-marathon running can lead to temporary pathological changes in organ systems, including the heart, liver, kidneys, and immune system, which typically normalize after the race.

Don't panic if you feel unwell or see abnormal blood work after an ultra-marathon. The paper notes that changes in heart, liver, and kidney biomarkers are common but usually temporary and normalize after recovery. Focus on rest and hydration to allow your body to heal.

Reduced signaling of the Growth Hormone/Insulin-Like Growth Factor (GH/IGF-I) system extends longevity and delays aging in mammals, primarily through enhanced insulin sensitivity, reduced oxidative stress, and increased stress resistance.

Current research in long-lived mouse models suggests that lower levels of Growth Hormone and IGF-I signaling are associated with extended longevity and delayed aging. While GH therapy is marketed for anti-aging, genetic evidence points to reduced signaling as the beneficial pathway. This does not currently translate to a recommended intervention for healthy humans, but highlights the importance of metabolic health and insulin sensitivity.

The protein content of microalgae varies significantly (6-71% of dry matter) and is heavily influenced by environmental factors such as light intensity, temperature, CO2 concentration, and nutrient availability.

When choosing microalgal products, be aware that protein content can vary widely depending on how the algae were grown. Look for products that specify their protein content, as this can range from 6% to over 70% of dry weight depending on cultivation conditions.

Soy protein improves insulin sensitivity and reduces hepatic lipogenesis by downregulating SREBP-1 and upregulating PPAR-alpha pathways.

Soy protein may help manage fat storage at a cellular level by reducing the genes responsible for making fat (SREBP-1) and increasing those responsible for burning fat (PPAR-alpha). This suggests soy protein is metabolically favorable for managing obesity-related metabolic syndrome.

Fiscal measures such as taxes on unhealthy foods (e.g., fat/sugar taxes) and subsidies for healthy foods show potential to improve dietary intake in simulations, but real-world implementation is limited and often ineffective due to low tax rates and inelastic demand.

Small taxes on sugary drinks or snacks rarely change behavior because people keep buying them. However, larger, well-designed fiscal policies (like subsidies for fruits/vegetables or higher taxes on specific nutrients) can be effective, especially for lower-income groups who are more price-sensitive. Revenue from these taxes can fund further health initiatives.

Psychosocial stress and depression enhance postprandial inflammation and metabolic dysregulation (postprandial lipemia) by altering vagal tone, slowing triglyceride clearance, and increasing proinflammatory cytokine production.

Manage stress levels to mitigate their negative impact on post-meal metabolism. Stress can increase inflammation and slow the clearance of fats from your blood after eating. Techniques to reduce stress may help improve metabolic health after meals.