Browse the evidence

The ketogenic diet, by emphasizing high protein (1.2-2.0 g/kg) and high fat while excluding fruits/vegetables, may increase the risk of kidney stones, metabolic acidosis, and albuminuria due to high dietary acid load and lack of alkali precursors.

If you follow a ketogenic diet and have a history of kidney stones or kidney disease, be aware that the high acid load from animal proteins and lack of fruits/vegetables may increase your risk of stone formation and metabolic acidosis. Monitor your health and consider incorporating low-carb vegetables to balance acid load.

Activation of the alternative bile acid synthetic pathway, specifically via increased CYP7B1 expression and non-12α-hydroxylated bile acids (e.g., CDCA, TUDCA), improves glucose and lipid metabolism by reducing lipid absorption and enhancing energy expenditure.

Focus on dietary patterns or interventions that support the alternative bile acid pathway, such as consuming polyphenol-rich foods like Pu-erh tea (theabrownin) or fermented foods that may influence gut microbiota bile salt hydrolase activity. This shift favors non-12α-hydroxylated bile acids, which are associated with improved glucose tolerance and reduced lipid absorption in metabolic disease contexts.

Inhibition of intestinal bile salt hydrolase (BSH) activity by compounds like theabrownin or riboflavin increases conjugated bile acids in the distal ileum, which inhibits intestinal FXR signaling and upregulates hepatic CYP7B1, thereby promoting the alternative bile acid pathway.

Consider incorporating Pu-erh tea or other sources of theabrownin into your diet. These compounds may inhibit bacterial enzymes in the gut, leading to a favorable shift in bile acid signaling that supports metabolic health.

High levels of 12α-hydroxylated bile acids (derived from the classical pathway) are associated with metabolic disorders like insulin resistance and type 2 diabetes, whereas a higher ratio of non-12α-hydroxylated bile acids is beneficial.

Monitor bile acid profiles if possible; a lower ratio of 12α-hydroxylated bile acids (like cholic acid) to non-12α-hydroxylated bile acids (like chenodeoxycholic acid) may be a marker of better metabolic health.

High-dose long-chain omega-3 supplementation (>4.4 g/day) may worsen glucose metabolism, including increasing the risk of diabetes diagnosis and raising HbA1c and fasting glucose.

If you are taking very high doses of omega-3 (more than 4.4 grams per day), be aware that this might negatively impact your blood sugar levels. While the evidence is not definitive, it suggests a potential risk of worsening glucose control at these high doses. Consult your doctor before maintaining such high doses.

Increasing alpha-linolenic acid (ALA) intake may increase fasting insulin levels by approximately 7%, but has little or no effect on other glucose metabolism markers.

If you are increasing your intake of alpha-linolenic acid (found in flaxseed, canola, and walnuts), be aware that it might slightly increase your fasting insulin levels. While the effect on blood sugar itself is negligible, this insulin change is worth monitoring if you have insulin resistance.

Aging induces a shift in mesenchymal stem cell lineage toward adipogenesis and away from osteoblastogenesis, driven by low-grade chronic inflammation (LGCI) from Western diets, resulting in osteosarcopenic obesity.

Focus on reducing inflammation through diet (increasing Omega-3s, decreasing Omega-6s) rather than just weight loss, as visceral fat drives the loss of bone and muscle in aging.

Transfeminine hormone therapy is associated with an increased risk of venous thromboembolism (VTE), particularly with oral ethinyl estradiol or conjugated equine estrogen, whereas transdermal estradiol may mitigate this risk.

If you are a transgender woman on hormone therapy, be aware that oral conjugated equine estrogen carries a higher risk of blood clots than oral estradiol or transdermal estrogen. If you have risk factors like smoking, obesity, or a history of blood clots, discuss transdermal estrogen (patch/gel) with your doctor to minimize thrombotic risk.

Gut microbiota dysbiosis, specifically involving Escherichia Coli producing the CIpB protein, may contribute to eating disorder pathology by mimicking satiety hormones and triggering autoimmune reactions.

Current research suggests gut health may play a role in eating disorders, but it is not yet a primary treatment target. Focus on established treatments like nutritional rehabilitation and therapy. Future probiotics or microbiome-targeted therapies may emerge, but are not currently standard care.

Psychological stress negatively impacts male fertility by reducing luteinizing hormone and testosterone pulsing, which in turn impairs spermatogenesis and sperm quality.

If you are trying to conceive, high levels of psychological stress can physically lower your sperm count and motility by disrupting hormonal signals. Managing stress through counseling or lifestyle changes may help improve semen quality, as stress is a modifiable factor.

Gut microbiota-derived succinate acts as a signaling metabolite that regulates host energy metabolism and immune function via the SUCNR1 receptor, with effects ranging from beneficial metabolic improvements to pathological inflammation depending on context and receptor signaling integrity.

Focus on dietary fiber and diverse plant foods to support a healthy gut microbiome that produces balanced succinate levels. Avoid excessive processed foods that may cause dysbiosis. While succinate itself is not a direct supplement, its production by beneficial bacteria (like Prevotella) is linked to improved glucose metabolism.

Irisin has anti-inflammatory properties in adipose tissue, suppressing pro-inflammatory cytokines and promoting the switching of macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) state.

Managing obesity reduces systemic inflammation. While irisin contributes to this anti-inflammatory effect, the primary benefit comes from overall weight loss and exercise, not from targeting inflammation via irisin alone.

Maternal health factors during pregnancy, specifically high BMI and diet, influence the infant's gut microbiota composition and long-term vulnerability to obesity and diabetes.

A mother's health and diet during pregnancy can shape her baby's gut bacteria and long-term metabolic health. Maintaining a healthy weight and diet during pregnancy may support a favorable microbiome for the developing fetus.

Faecal microbiota transplantation (FMT) using autologous stool preserves stimulated C-peptide levels (residual beta-cell function) in patients with new-onset type 1 diabetes over 12 months, whereas allogenic (healthy donor) FMT does not.

For individuals with very recent-onset Type 1 Diabetes, using their own gut bacteria (autologous FMT) may help preserve remaining insulin production, whereas using healthy donor bacteria does not offer this benefit. This is a specialized medical intervention, not a DIY protocol.

Chronic exposure to an obesogenic diet induces low-grade systemic inflammation that causes loss of muscle integrity (intramuscular lipid accumulation, fibrosis, and reduced satellite cell function), which acts as a central driver for musculoskeletal diseases including osteoarthritis, tendinopathy, and osteoporosis.

If you have obesity and joint/muscle pain, weight loss alone may not restore function because the underlying muscle tissue may be damaged by inflammation (fat infiltration, fibrosis). Focus on preserving or rebuilding muscle quality through resistance training and anti-inflammatory dietary patterns, not just weight reduction, as muscle integrity appears to be the key to preventing musculoskeletal disease.

Activation of the Nrf2/Keap1/ARE pathway improves insulin sensitivity, reduces hyperglycemia, and protects pancreatic beta-cells in type II diabetes models, whereas classic direct antioxidants have failed to show benefit.

Focus on lifestyle and dietary choices that naturally support your body's antioxidant defenses (like the Nrf2 pathway) rather than relying on high-dose direct antioxidant supplements. The paper highlights that compounds like sulforaphane (found in cruciferous vegetables) and resveratrol (found in grapes/berries) may help activate this pathway, potentially improving insulin sensitivity and protecting cells, whereas direct antioxidant supplements have not shown clinical benefit for diabetic complications.

Intermittent fasting lowers blood pressure through increased parasympathetic activity mediated by Brain-Derived Neurotrophic Factor (BDNF), leading to reduced heart rate and blood pressure.

If you have high blood pressure, intermittent fasting might help lower it by calming your nervous system (increasing parasympathetic tone). However, this effect is not guaranteed for everyone, and you should monitor your BP. Do not stop prescribed blood pressure medication without consulting your doctor.

Obesity-associated gut dysbiosis contributes to cognitive and mood deficits through the activation of the HPA-axis, leading to glucocorticoid overproduction, and the promotion of a pro-inflammatory milieu (endotoxemia/leaky gut) that causes neuro-inflammation.

If you are obese and experiencing brain fog or mood issues, your gut health may be a contributing factor, not just your weight. The paper suggests that improving diet (fiber, prebiotics) or using specific probiotics might help restore gut balance, reduce inflammation, and lower stress hormones, potentially improving cognitive and emotional health. This is not a cure-all, but a modifiable lever.

Hyperinsulinemia is the primary etiological driver of insulin resistance, obesity, type 2 diabetes, and cardiovascular disease, rather than a compensatory response to insulin resistance.

Focus on lowering baseline insulin levels through dietary changes (e.g., reducing refined carbohydrates and sugars) and increasing hepatic insulin clearance. This may prevent or reverse the progression to insulin resistance, obesity, and type 2 diabetes, as high insulin is the primary driver of these conditions.

Hyperinsulinemia shifts the insulin-to-GH ratio towards insulin, suppressing Growth Hormone and IGF-I, which promotes fat accumulation and reduces energy expenditure.

Reducing insulin levels may restore the natural balance with Growth Hormone, potentially improving lipid breakdown and energy expenditure, aiding in obesity management.

GLP-1 analogs improve skeletal muscle glucose metabolism and glycogen synthesis through non-canonical signaling pathways independent of cAMP.

GLP-1 analogs may help your muscles use glucose more efficiently through a separate pathway than in the pancreas. This contributes to better blood sugar control and energy storage as glycogen.

Gut microbiota-derived short-chain fatty acids (SCFAs) regulate host appetite by binding to G-protein-coupled receptors (FFAR2/FFAR3) to stimulate the secretion of anorexigenic hormones (GLP-1, PYY) and directly acting on hypothalamic neurons.

To leverage gut bacteria for appetite control, consume diverse sources of dietary fiber that ferment into short-chain fatty acids (SCFAs). These metabolites signal satiety hormones like GLP-1 and PYY. Because responses vary by individual microbiota and fiber type, focus on consistent, varied fiber intake rather than a single 'magic' fiber source.

Gut microbiota-derived bacterial protein ClpB acts as a molecular mimic of alpha-MSH, directly activating anorexigenic neurons and stimulating the secretion of satiety hormones (PYY, GLP-1) to induce satiety.

Maintaining a healthy gut microbiome through a diverse diet supports the production of beneficial bacterial proteins like ClpB. These proteins may help regulate appetite by mimicking satiety signals, though this is a secondary mechanism compared to fiber-derived SCFAs.

Resveratrol improves metabolic health and insulin sensitivity by activating SIRT1 and AMPK pathways, leading to increased energy expenditure and lipid mobilization, although its clinical efficacy is limited by extremely low systemic bioavailability due to rapid metabolism.

Resveratrol activates metabolic pathways like SIRT1 in lab settings, but in humans, it is metabolized so quickly that very little reaches your tissues. While it may offer minor metabolic benefits, it is not a magic bullet for weight loss or insulin sensitivity due to poor bioavailability. Focus on diet and exercise instead.