Browse the evidence

SIRT3 suppresses lipogenesis in hepatocytes by downregulating the expression of Stearoyl-CoA desaturase 1 (SCD1).

Reducing the intake of saturated fats and maintaining metabolic health may help regulate SCD1, a key enzyme in fat synthesis. This complements the autophagy mechanism by reducing the load of new fat entering the liver.

In healthy centenarians, a higher plasma IGF-I/IGFBP-3 molar ratio is significantly associated with improved insulin action (higher whole body glucose disposal) and a more favorable lipid profile (lower triglycerides, free fatty acids, and LDL cholesterol).

For those seeking longevity, maintaining a healthy body composition and insulin sensitivity appears linked to a favorable IGF-I/IGFBP-3 balance. While you cannot directly 'dose' this ratio, the findings suggest that preserving insulin sensitivity and managing body fat may help maintain this hormonal balance, which is associated with better metabolic health in extreme old age.

Oral administration of Lactobacillus plantarum strain Ln4 (5x10^8 CFU/day) attenuates diet-induced obesity, reduces epididymal fat mass, and improves insulin resistance in high-fat diet-fed mice.

This study suggests that consuming Lactobacillus plantarum strain Ln4 (500 million CFU daily) may help mitigate weight gain and improve insulin sensitivity in individuals consuming a high-fat diet. However, these results are from mice; human applicability is not yet established. Do not replace standard medical care with probiotics.

Women with obstructive sleep apnea (OSA) experience similar or worse health consequences, including cardiovascular risk and cognitive impairment, compared to men despite having lower disease severity (lower AHI).

If you are a woman experiencing fatigue, insomnia, or mood disturbances, do not dismiss them just because your sleep study shows a 'mild' Apnea-Hypopnea Index (AHI). Women often suffer significant health consequences and cognitive impairment at lower AHI levels than men. Advocate for treatment based on your quality of life and symptom burden, not just the severity score.

Astaxanthin supplementation (0.02% in diet) ameliorates insulin resistance and stimulates mitochondrial biogenesis in skeletal muscle of high-fat-diet-induced obese mice by activating the AMPK pathway.

In obese mouse models, consuming 0.02% Astaxanthin in the diet for 24 weeks improved insulin sensitivity and increased mitochondrial density in muscle by activating the AMPK pathway. This effect was independent of antioxidant activity in the muscle itself. Human translation requires caution as this was a murine model with specific dietary conditions.

Enobosarm, a selective androgen receptor modulator (SARM), prevents and treats muscle wasting in cancer patients by increasing lean body mass and physical function without the androgenic side effects of traditional anabolic agents.

If you have advanced lung cancer and are starting chemotherapy, ask your doctor about Enobosarm. It is a drug designed to build muscle without the harsh side effects of older steroids. The standard dose is 3mg taken once a day for about 5 months. The goal is to keep your muscle mass from dropping and help you stay physically active.

Obesogens can induce transgenerational obesity through epigenetic modifications (DNA methylation, histone retention, non-coding RNA) that persist in unexposed generations.

Since environmental exposures can affect future generations, minimizing chemical exposure (plastics, pesticides) is crucial for reproductive health and the long-term metabolic health of descendants.

Higher total and free testosterone levels are associated with increased mortality from lung cancer in older men, potentially due to hormonal stimulation of tumor growth or residual confounding by smoking.

In older men, higher testosterone levels were linked to higher lung cancer death rates in this study. However, the authors suggest this might be due to smoking habits rather than testosterone itself. Do not assume high testosterone causes cancer, but be aware of the association in observational data.

Sodium butyrate supplementation prevents high-fat diet-induced obesity and insulin resistance in mice by inducing epigenetic repositioning of the -1 nucleosome in nuclear-encoded mitochondrial genes, thereby restoring skeletal muscle mitochondrial adaptation and complete beta-oxidation.

In this mouse model, adding sodium butyrate to a high-fat diet prevented obesity and insulin resistance by changing how mitochondrial genes were expressed in muscle. This suggests that sodium butyrate might help mitigate the metabolic damage of a poor diet by improving muscle energy processing, independent of calorie counting.

Deficiency in Stearoyl-CoA desaturase 1 (SCD1) improves insulin sensitivity and glucose tolerance in skeletal muscle.

Insulin resistance is linked to how fats are processed in the body. Studies in mice show that reducing SCD1 activity improves how muscles respond to insulin and handles glucose. This suggests that targeting SCD1 could be a strategy for managing type 2 diabetes and insulin resistance.

Activation of brown adipose tissue (BAT) via cold exposure or pharmacological agents increases energy expenditure and reduces body fat mass in animal models, suggesting a viable anti-obesity therapeutic strategy.

Your body has a hidden calorie-burning system called brown fat, which is more active in lean, younger people. You can activate it by exposing yourself to cold temperatures (like cool showers or wearing lighter clothing in winter), which triggers your nervous system to burn fat for heat. While this works well in mice, human results vary, and older or obese individuals may have less active brown fat. Pharmacological drugs targeting this system are in development but not yet available.

Pharmacological activation of brown adipose tissue using natriuretic peptides (NPs) or beta-3 adrenergic agonists can increase energy expenditure and recruit brown-like (beige) fat in white adipose tissue.

Scientists are developing drugs that mimic the effects of cold exposure by targeting specific hormones (like natriuretic peptides) or receptors (beta-3). These drugs aim to turn your white fat into energy-burning 'beige' fat. While promising in mice, these treatments are still in clinical trials for humans and are not yet available for general use.

Therapeutic silencing of miR-33 using antisense oligonucleotides increases plasma HDL cholesterol levels by targeting cholesterol efflux transporters ABCA1 and ABCG1.

While direct 'miR-33 silencing' is not a current consumer supplement, this research highlights why some individuals struggle with HDL levels despite diet. Future therapies targeting this pathway may offer treatment for dyslipidemia, but current lifestyle interventions (diet/exercise) remain the primary method to influence these genetic pathways naturally.

Inhibition of miR-122 using antisense therapy significantly reduces circulating cholesterol and triglyceride levels in the liver.

Anti-miR-122 therapy is a potential future treatment for fatty liver and high cholesterol. It works by blocking a specific liver RNA (miR-122) that normally promotes cholesterol production. Current management relies on diet and exercise, but this pathway may soon be targetable by drugs.

Overexpression of miR-27a accelerates adipolysis (fat breakdown) by targeting RXRα and PPARγ, thereby reducing lipid storage in cells.

miR-27a promotes fat breakdown. While not a current supplement, understanding this pathway may lead to future treatments for obesity that target fat storage genes.

IL-1β antagonists (e.g., anakinra, gevokizumab) improve glycemia and beta-cell function in type 2 diabetes, but their effect on cardiovascular events is still being determined in large trials.

Blocking specific inflammatory proteins like IL-1β can improve blood sugar control and protect beta-cells in type 2 diabetes. While promising, these treatments are currently biologics (injections) and are still being studied for their long-term impact on heart disease. They represent a targeted approach to the inflammatory component of diabetes.

Salsalate, a non-acetylated salicylate, lowers blood glucose and triglycerides in type 2 diabetes by activating AMPK and inhibiting NF-κB, but its effect on cardiovascular plaque progression is unclear.

Salsalate, a form of salicylate, can lower blood sugar and triglycerides in people with type 2 diabetes by activating AMPK, a key metabolic sensor. While it shows promise for glycemic control, its effect on preventing heart disease (plaque progression) is not yet clear. It is not a standard treatment but may be considered in specific cases.

Overexpression of microRNA miR-519d in human subcutaneous adipose tissue suppresses PPARA protein translation, leading to reduced fatty acid oxidation and increased lipid accumulation (adipocyte hypertrophy).

This research identifies a specific biological mechanism in obese individuals where high levels of miR-519d suppress PPARA, a protein critical for burning fat. This suggests that in some cases of severe obesity, the body's ability to oxidize fatty acids is biologically impaired by this specific microRNA. While this doesn't provide a direct lifestyle fix, it highlights that obesity can involve specific molecular dysregulations in fat tissue, potentially explaining why standard caloric restriction might be less effective or why fat storage persists despite energy deficits.

High-protein diets inhibit the activation of opioid and GABAergic neurons in the nucleus accumbens, thereby reducing the hedonic (reward) response to food.

High-protein diets may reduce the 'craving' or 'wanting' aspect of eating by dampening reward signals in the brain. This can help overcome emotional or hedonic eating triggers.

Extremely high HDL cholesterol levels (e.g., >116 mg/dL in men, >135 mg/dL in women) are associated with increased all-cause mortality.

While increasing HDL through exercise and diet is generally beneficial, aim for moderate levels. Extremely high HDL levels (above 116 mg/dL for men and 135 mg/dL for women) may not provide additional cardiovascular benefits and could be associated with higher mortality risk.

Reduction in melatonin amplitude caused by circadian misalignment correlates with reductions in the amplitude of core body temperature, cortisol, and alertness rhythms.

If your melatonin rhythm is dampened (e.g., due to shift work or jet lag), your other bodily rhythms like body temperature and alertness are likely also dampened. Restoring circadian alignment may help restore the amplitude of these rhythms.

In nondiabetic men with coronary artery disease, higher intake of saturated fatty acids is independently associated with elevated fasting insulin concentrations, indicating a direct link to insulin resistance separate from obesity.

For men with known heart disease, high intake of saturated fats is linked to higher insulin levels, a marker of insulin resistance, regardless of body weight. While this study is observational, it suggests that reducing saturated fat may support better metabolic health in this specific group.

Higher expression of the cardiolipin synthase gene CRLS1 in human subcutaneous adipose tissue is positively correlated with insulin sensitivity and negatively correlated with insulin resistance.

In humans, higher levels of the enzyme that makes cardiolipin (CRLS1) in belly fat are linked to better insulin sensitivity. This suggests that supporting the health of this enzyme might be beneficial for metabolic health, although the exact way to do this is not yet defined.

Elevated circulating asprosin levels are positively associated with insulin resistance, type 2 diabetes, and obesity in adult populations, suggesting asprosin acts as a biomarker for metabolic dysregulation.

If you have insulin resistance or type 2 diabetes, your body may be producing higher levels of the hormone asprosin, which is linked to your condition. While this doesn't change your immediate treatment, it highlights the importance of managing blood sugar and weight, as lower asprosin levels are associated with better metabolic health. Future treatments may target this hormone.