Browse the evidence

Steatosis biomarkers (FLI, NAFLD-LFS, HSI, VAI, TyG) are strongly correlated with insulin resistance (HOMA-IR) independently of the actual amount of liver fat.

These tests are best used to assess your overall metabolic risk (insulin resistance) rather than just liver fat. A high score suggests you are at higher risk for diabetes and cardiovascular issues, regardless of how much fat is actually in your liver.

Lean NAFLD, defined as fatty liver in non-obese individuals, is a significant subset of NAFLD (7-20%) and is associated with insulin resistance and metabolic dysfunction despite normal BMI.

You do not need to be overweight to develop fatty liver. Lean NAFLD affects 7-20% of NAFLD cases and is linked to insulin resistance and metabolic issues. If you have fatty liver, focus on metabolic health markers like blood sugar and insulin sensitivity, not just your weight.

Roux-en-Y gastric bypass (RYGB) achieves superior and durable weight loss compared to purely restrictive procedures (like VBG or AGB) primarily through hormonal mechanisms—specifically the suppression of ghrelin and enhancement of incretins (GLP-1, PYY)—rather than gastric restriction or malabsorption alone.

If you are considering Roux-en-Y gastric bypass, understand that its success relies less on the small stomach pouch size and more on hormonal changes. The surgery suppresses the hunger hormone ghrelin and increases satiety hormones like GLP-1 and PYY. This hormonal shift reduces appetite and improves glucose tolerance, often before significant weight loss occurs. This distinguishes it from purely restrictive surgeries which often fail long-term because they do not alter these hormonal signals.

Acute exercise induces mitophagy in skeletal muscle via an AMPK-dependent phosphorylation of Ulk1 at Serine 555, which is required for targeting damaged mitochondria to lysosomes.

Regular exercise triggers a specific cellular cleanup process (mitophagy) that removes damaged mitochondria. This process is driven by the AMPK-Ulk1 signaling pathway. To ensure this cleanup happens, consistent aerobic exercise is required to activate AMPK, which then phosphorylates Ulk1 to target damaged organelles for degradation.

AMPK is required for exercise-induced mitophagy, as blocking AMPK activity abolishes the increase in mitophagic markers (pure red puncta) following exercise.

If your AMPK pathway is impaired (e.g., due to metabolic disease or specific genetic factors), your body may fail to perform the necessary cleanup of damaged mitochondria after exercise, potentially blunting long-term health benefits.

Ulk1 is required for the targeting of mitochondria to lysosomes during exercise-induced mitophagy, but is not required for lysosomal biogenesis itself.

Ulk1 acts as a specific tagger that directs damaged mitochondria to lysosomes for destruction. Without Ulk1, the cell may still produce more lysosomes, but it fails to effectively target and degrade the damaged mitochondria.

Central administration of recombinant OB protein (leptin) reduces food intake and body weight in lean and ob/ob mice, demonstrating that the protein acts on central neural networks to regulate energy balance.

This paper establishes that leptin (OB protein) is a key hormone that signals fat stores to the brain to regulate eating and energy use. While this review focuses on animal models, it lays the groundwork for understanding why obesity is a biological condition. Future treatments may target this pathway to help regulate body weight.

Obese humans have elevated serum OB protein concentrations that correlate with body fat percentage, suggesting that human obesity is not caused by a deficiency in OB protein but potentially by reduced brain sensitivity to it.

This paper indicates that obese individuals typically have higher levels of OB protein (leptin) than lean individuals. This suggests that obesity is not caused by a lack of this hormone, but potentially by the body's reduced ability to respond to it or transport it to the brain.

Obesity increases susceptibility to Covid-19 through mechanisms including chronic inflammation, immune dysfunction, altered lung mechanics, and increased ACE2 expression.

Obesity contributes to severe Covid-19 through chronic inflammation, immune issues, lung mechanics, and higher ACE2 expression. Weight management and medical care for obesity are important for reducing risk.

Diabetes increases susceptibility to Covid-19 through mechanisms including aggravated inflammatory storms, immune dysfunction, lung injury, and increased ACE2 expression.

Diabetes contributes to severe Covid-19 through chronic inflammation, immune issues, lung injury, and higher ACE2 expression. Good glycemic control and medical care for diabetes are important for reducing risk.

Low heart rate variability (HRV < 20 msec) measured from short resting electrocardiograms predicts significantly higher all-cause mortality in middle-aged and elderly men, independent of coronary heart disease.

Low heart rate variability, measured via a short ECG, is a strong warning sign for increased risk of death from all causes, not just heart disease. For men, maintaining higher HRV (ideally >40 msec) is associated with better long-term survival. This suggests that practices supporting autonomic balance (like stress management and exercise) may be crucial for longevity.

In elderly populations, malnutrition and antibiotic use drive a decline in gut microbiome diversity and stability, increasing frailty and susceptibility to infection.

For older adults, maintaining a diverse, fiber-rich diet and minimizing unnecessary antibiotic use are crucial for preserving gut health and reducing frailty. Community-dwelling elderly with healthy diets can maintain microbiomes similar to young adults, proving that age itself is not the primary driver of decline.

Menopause, particularly when occurring early or via surgical removal of ovaries, accelerates biological aging as measured by epigenetic age acceleration in blood.

This research indicates that the hormonal changes of menopause, especially if early or surgical, may speed up biological aging in blood. While you cannot reverse menopause, being aware of this accelerated biological aging might motivate discussions with healthcare providers about hormone therapy or other strategies to support long-term health, as hormonal changes appear to leave a mark on your body's molecular aging clock.

Menopausal Hormone Therapy (MHT) is associated with lower epigenetic age acceleration in buccal epithelium, suggesting a potential protective effect against epigenetic aging in this tissue.

This study found that women using Menopausal Hormone Therapy (MHT) had lower epigenetic age in their cheek cells (buccal epithelium) compared to non-users. This suggests MHT might help slow biological aging in this specific tissue. However, this effect was not seen in blood, so the overall benefit is complex. Discuss the potential benefits and risks of MHT with your healthcare provider.

Surgical menopause (bilateral oophorectomy) before age 50 is associated with increased epigenetic age acceleration in both blood and saliva.

If you undergo surgical removal of your ovaries before age 50, this study suggests it may accelerate biological aging in your blood and saliva. This highlights the importance of discussing long-term health strategies, such as hormone therapy, with your doctor to manage these potential effects.

Elevated expression of the TXNIP gene in human skeletal muscle and adipose tissue directly inhibits both basal and insulin-stimulated glucose uptake, acting as a key mediator of insulin resistance.

High levels of TXNIP in your muscles and fat cells block your body's ability to use glucose efficiently, contributing to insulin resistance. While you cannot directly 'dose' TXNIP, understanding that insulin normally suppresses this gene suggests that maintaining insulin sensitivity through lifestyle factors (like exercise and diet) may help keep TXNIP levels low, thereby supporting healthy glucose uptake.

Amino acid availability, specifically leucine and arginine, regulates cellular protein synthesis and autophagy via the mTORC1 signaling pathway, where depletion inactivates mTORC1 to trigger autophagy and reduce protein biosynthesis.

To maximize muscle protein synthesis, ensure your diet provides sufficient leucine and arginine to activate the mTORC1 pathway. If these amino acids are depleted, your body shifts to breaking down its own proteins via autophagy. This means the quality and specific amino acid profile of your protein intake matter as much as the total amount.

Systemic amino acid homeostasis is maintained by exchanging essential amino acids for non-essential ones and transferring amino groups from oxidized amino acids to biosynthesis, minimizing net loss through oxidation.

Your body actively recycles amino acids. It swaps essential for non-essential ones and reuses nitrogen from broken-down proteins to make new ones. This minimizes the need to constantly eat protein, though essential amino acids must still be obtained from food.

CD36 fatty acid translocase drives hepatosteatosis onset and progression to NASH by increasing fatty acid influx into hepatocytes, making it a key driver of NAFLD pathogenesis.

Current research suggests that the protein CD36 plays a significant role in moving fatty acids into liver cells, contributing to fatty liver disease. While there is no specific diet protocol mentioned to target CD36 directly, the findings highlight that managing fatty acid influx is critical. Future treatments may target CD36, but for now, standard NAFLD management focusing on reducing metabolic stress is implied.

Saturated fatty acids (SFAs) are more hepatotoxic than unsaturated fatty acids (UFAs) because they induce ER stress, oxidative stress, and apoptosis more effectively.

Not all fats affect the liver equally. Saturated fats are more likely to cause liver damage and inflammation than unsaturated fats. Reducing saturated fat intake may help mitigate liver stress in NAFLD patients.

Elevated plasma levels of Trimethylamine N-oxide (TMAO) are associated with an increased risk of major adverse cardiovascular events, atherosclerosis, and mortality in patients with chronic kidney disease.

If you have Chronic Kidney Disease, high TMAO levels are a strong predictor of heart problems and death. While you should still eat a balanced diet, be aware that high intake of choline (eggs, red meat) and carnitine (red meat) can lead to TMAO production by gut bacteria, potentially increasing cardiovascular risk. Discuss dietary precursors with your nephrologist.

Therapeutic strategies to reduce TMAO levels, including broad-spectrum antibiotics, dietary restriction of precursors, and specific inhibitors like 3,3-dimethyl-1-butanol (DMB), can attenuate atherosclerosis and cardiovascular risk.

Inhibiting TMA production (e.g., via DMB found in some vinegars/oils) or reducing choline/carnitine intake may lower TMAO and protect against atherosclerosis in animal models. Human applications are not yet standard.

M1 macrophage/Kupffer cell polarization drives insulin resistance and NASH progression, while M2 polarization protects against it.

Liver inflammation in NAFLD is driven by immune cells (Kupffer cells) shifting into a pro-inflammatory 'M1' state. Shifting these cells to an 'M2' state is protective. While lifestyle changes help, specific micronutrients like carotenoids are being studied for their ability to force this M2 shift.

Metformin lowers blood glucose primarily by inhibiting mitochondrial complex I in the liver, which reduces ATP production and suppresses gluconeogenesis, rather than through direct activation of AMPK.

Metformin works by slowing down your liver's production of glucose. It does this by mildly affecting the energy factories (mitochondria) in liver cells, which signals the liver to stop making sugar when it doesn't need to. This is why it lowers blood sugar without causing dangerous lows (hypoglycemia) on its own.