Browse the evidence

Therapeutic doses of glucocorticoids (methylprednisolone) significantly increase 24-hour energy expenditure and spontaneous food intake in healthy young men, primarily by suppressing sympathetic nervous system activity and stimulating appetite.

If you are taking therapeutic doses of glucocorticoids like methylprednisolone, expect a significant increase in hunger and energy expenditure. The drug suppresses your sympathetic nervous system, which reduces energy burning and increases appetite. To manage weight, you must actively monitor and control food intake, as your body's natural regulation will shift towards consuming more calories.

Integration of food and nutrition into healthcare systems requires sustainable funding, clinician education, and rigorous research to be effective and scalable.

Advocate for your healthcare system to integrate food interventions. This means pushing for sustainable funding, better clinician nutrition education, and rigorous research to ensure these programs are effective and accessible.

Gastric accommodation (proximal stomach relaxation) is a primary physiological mechanism for controlling meal volume and satiation, and its impairment contributes to functional dyspepsia and gastroesophageal reflux disease (GORD).

If you suffer from early fullness or bloating (functional dyspepsia), standard 'motility' drugs might not help because the issue may be your stomach's inability to relax and accommodate food (gastric accommodation). Therapies that target this relaxation, such as specific receptor agonists (e.g., buspirone, tandospirone, or acotiamide where available), may offer symptomatic relief by improving how your stomach stretches.

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia (IH) and hypercapnia, which trigger gut microbiota dysbiosis, intestinal barrier impairment, and altered metabolites, leading to systemic oxidative stress, inflammation, and sympathetic activation.

If you have OSAS, treating the airway collapse is essential to stop the cycle of intermittent hypoxia that damages your gut and increases systemic inflammation. This goes beyond just feeling rested; it prevents long-term metabolic and cardiovascular harm.

Nocturnal rostral fluid shift, where fluid accumulated in the legs during the day redistributes to the neck upon lying down, increases tissue pressure and upper airway collapsibility, predisposing individuals to OSAS.

If you have leg swelling, try elevating your legs during the day or wearing compression stockings. This can reduce the amount of fluid that shifts to your neck at night, potentially easing airway collapse.

Mitochondrial dysfunction, driven by the accumulation of somatic mtDNA mutations and altered dynamics (fission/fusion imbalance), is a primary hallmark and causal driver of aging and age-related pathologies, rather than merely a consequence.

Focus on interventions that stimulate mitochondrial biogenesis and quality control, such as exercise (which induces mitohormesis) and metabolic stressors. The goal is to maintain the balance between creating new mitochondria (biogenesis) and removing damaged ones (mitophagy) to prevent the accumulation of dysfunction that drives aging.

Reactive Oxygen Species (ROS) are not the primary cause of aging; instead, they are a consequence of mitochondrial dysfunction, and moderate ROS increases can extend lifespan via mitohormesis.

Avoid excessive antioxidant supplementation that might blunt the adaptive benefits of exercise. Embrace moderate metabolic stress (like exercise) which generates ROS as a signal to improve mitochondrial efficiency and longevity.

In patients with nonalcoholic steatohepatitis (NASH), circulating bile acid profiles are significantly altered, characterized by increased primary bile acids (specifically conjugated cholate and taurocholate) and decreased secondary bile acids, which correlates with increased severity of hepatic steatosis, inflammation, and fibrosis.

This research highlights that NASH involves specific disruptions in bile acid metabolism, particularly an increase in primary bile acids like cholate and a decrease in secondary ones. While this paper does not prescribe a specific diet, it suggests that the composition of bile acids is a key driver of liver damage. Future interventions may focus on modulating bile acid profiles (e.g., via FXR agonists or dietary fiber to influence microbiome-derived secondary bile acids) to reduce inflammation and fibrosis risk.

Metformin produces a gene expression pattern closely aligned with long-term calorie restriction in mice, making it a promising calorie restriction mimetic candidate.

Metformin, a common diabetes drug, has been shown in mice to activate genes similar to those activated by calorie restriction. While this makes it a candidate for anti-aging benefits, the paper does not recommend it as a standalone longevity supplement for healthy humans without medical supervision, noting it is one of several candidates under investigation.

PPARgamma activation in immune cells (macrophages, dendritic cells, T cells) suppresses pro-inflammatory signaling pathways (NF-kB, AP-1) via transrepression, reducing the production of inflammatory cytokines like TNF-alpha, IL-1beta, and IL-6.

Chronic inflammation is linked to metabolic disease. PPARgamma activation (naturally or via drugs) helps calm this inflammation by blocking key inflammatory signals in immune cells.

Chronic elevation of glucocorticoids (stress) combined with insulin availability drives the redistribution of stored energy specifically into intraabdominal fat depots, leading to abdominal obesity.

If you are chronically stressed, your body is biologically primed to store fat in your abdomen, even if your total calorie intake isn't drastically higher than usual. This happens because stress hormones (glucocorticoids) and insulin work together to move fat from your limbs to your midsection. To combat this, managing chronic stress is as important as diet, because lowering stress hormones can help reverse this specific fat redistribution pattern.

Glucocorticoids increase the motivation (incentive salience) to eat, while insulin determines the preference for high-density (sweet/fat) foods.

Stress doesn't just make you eat more; it makes you crave high-fat, high-sugar foods more intensely. This is because stress hormones increase the 'drive' to eat, while insulin makes those specific foods taste better and feel more rewarding. To manage this, focus on stress reduction and avoiding highly palatable foods when stressed, as your brain will be biologically primed to seek them out.

Muscle-specific PPARγ is not required for the antidiabetic effects of thiazolidinediones (TZDs); TZDs improve glucose homeostasis and insulin sensitivity in the absence of muscle PPARγ.

If you are taking a TZD (like rosiglitazone or pioglitazone), you do not need to worry that your muscle PPARγ status determines whether the drug will work for your blood sugar. The drug's ability to improve insulin sensitivity does not depend on the PPARγ receptor being present in your skeletal muscle. The benefit is likely mediated through other tissues, such as adipose tissue or the liver.

Skeletal muscle PPARγ is required for the maintenance of normal adiposity and hepatic insulin sensitivity, but not for insulin-stimulated glucose uptake in muscle itself.

For general health, maintaining healthy muscle PPARγ activity (through exercise and diet) may help prevent excess fat storage and liver insulin resistance, even if it doesn't directly change how muscles burn glucose during exercise. This highlights the importance of muscle health for overall metabolic balance.

Obesity is associated with elevated circulating succinate levels, which are determined by a specific gut microbiota signature characterized by a higher ratio of succinate-producing bacteria (Prevotellaceae, Veillonellaceae) to succinate-consuming bacteria (Odoribacteraceae, Clostridaceae).

High circulating succinate, linked to obesity and cardiovascular risk, is driven by an imbalance in gut bacteria (too many producers, too few consumers). Weight loss interventions, particularly those involving a Mediterranean diet, can restore this balance by reducing succinate-producing bacteria and increasing succinate-consuming ones, thereby lowering circulating succinate levels.

Chronic caloric overfeeding resulting in a 10% weight gain causes a more than 3-fold elevation in basal serum leptin levels in healthy humans, correlating linearly with increased body fat percentage.

Gaining 10% of your body weight through overfeeding causes your leptin levels to triple. This is a normal physiological response to increased fat mass, not a malfunction. The paper suggests this high leptin state is associated with the development of leptin resistance, where the body's ability to use leptin to regulate energy balance is impaired.

Acute massive overfeeding (120 Cal/kg over 12 hours) causes a moderate (~40%) rise in serum leptin that persists into the next morning, independent of insulin levels.

Eating a large amount of food in one day (120 Cal/kg) causes your leptin levels to rise by about 40% and stay elevated overnight. This happens even if your insulin levels don't change in the same way, suggesting leptin responds directly to the energy intake.

Acarbose treatment improves metabolic parameters (BMI, insulin resistance, lipid profile) in type 2 diabetes patients by altering gut microbiota to increase the ratio of primary to secondary bile acids, but this benefit is contingent on the patient's baseline microbiota composition.

If you are starting treatment for Type 2 Diabetes, ask your doctor about the potential role of your gut health. This research suggests that a specific type of diabetes medication (Acarbose) works better for people who have a certain gut bacteria profile (high Bacteroides). It alters bile acids to improve metabolism, not just blood sugar. This is not a general recommendation for all patients, but a stratification strategy.

Activation of AMP-activated protein kinase (AMPK) in adipose tissue inhibits lipolysis and fatty acid efflux, thereby reducing plasma free fatty acid availability.

While exercise and fasting activate AMPK, this enzyme actually helps keep fat stored within fat cells for local use rather than releasing it into the blood. This reduces the amount of fat circulating in your bloodstream, which helps improve insulin sensitivity in muscles.

Activation of AMPK in adipose tissue stimulates fatty acid oxidation and inhibits lipogenesis (fat synthesis) by inactivating Acetyl-CoA Carboxylase (ACC).

AMPK activation helps fat cells burn fat for energy and stops them from creating new fat, primarily by blocking a key enzyme called ACC.

Heat processing, particularly sterilization at high temperatures (110-120°C), can negatively impact protein quality by causing Maillard reactions that destroy essential amino acids like Lysine, Methionine, and Cysteine, thereby lowering the PDCAAS.

Be aware that ultra-high temperature (UHT) or sterilized milk products have lower protein quality scores (PDCAAS) compared to pasteurized milk. This is due to high heat destroying essential amino acids like Lysine. For general adult consumption, this difference may be negligible if total protein intake is high, but for infant formulas or specific medical nutrition, pasteurized options may offer better amino acid availability.

Maintenance of a reduced body weight induces leptin-reversible changes in regional neural activity in response to visual food stimuli, specifically increasing activity in brainstem, limbic, and executive control regions while decreasing activity in the hypothalamus and cingulate gyrus, thereby driving increased hunger and food intake.

If you have lost weight, your brain is biologically wired to make you hungrier and more responsive to food cues due to lower leptin levels. This is not a failure of willpower but a physiological defense mechanism. To maintain weight loss, you may need strategies that specifically address this increased neural drive, such as environmental control or potentially future pharmacological aids that mimic leptin's effect on the brain.

Vegetarian and vegan diets do not show clear differences in total mortality, stroke mortality, or cancer rates (colorectal, breast, prostate) compared to non-vegetarians, although IHD mortality is lower.

Switching to a vegetarian diet improves heart health but does not necessarily extend your total lifespan compared to a healthy omnivorous diet. Focus on the specific benefits for heart health and weight management rather than expecting a dramatic increase in overall longevity.

Hypertrophic white adipocytes in obesity secrete pro-inflammatory cytokines (TNFα, IL-6, IL-1β) and adipokines (leptin, resistin) that induce local and systemic insulin resistance and chronic inflammation, leading to metabolic disorders like type 2 diabetes and cardiovascular disease.

If you are obese, your fat tissue is actively sending signals that promote inflammation and insulin resistance, which worsens your metabolic health. This is not just 'extra weight'; it is a biologically active state. Addressing obesity through sustainable lifestyle changes can reduce the secretion of these harmful adipokines and improve metabolic markers.