Browse the evidence

Adipocyte ACLY facilitates the activation of the transcription factor ChREBP, which is necessary for glucose uptake and de novo lipogenesis in adipose tissue.

This mechanism highlights why healthy fat storage is important for metabolic health. If the enzymes that help fat cells store energy properly are disrupted, sugar may end up in the liver instead, causing harm.

The PI3K-Akt-mTOR signaling pathway is a key mechanism linking obesity and diabetes to cancer, as it is sensitive to nutrient status and cell energy states.

Understanding that high insulin and nutrient levels activate cancer-promoting pathways highlights why maintaining healthy weight and blood sugar is crucial for cancer prevention.

Tanycytic release of VEGF-A is the mechanistic mediator that allows hypoglycemia to increase GLP-1 receptor agonist entry into the brain.

This is a basic science finding. It suggests that the health of specialized brain cells (tanycytes) and their production of VEGF are critical for GLP-1 drugs to work centrally.

Bariatric surgery is the most effective long-term treatment for severe obesity, significantly reducing risks of CVD, type 2 diabetes, and adverse pregnancy outcomes, yet access is inequitable due to socioeconomic and structural barriers.

If you have severe obesity and comorbidities, bariatric surgery is the most effective treatment for long-term health. Seek out high-volume centers and ensure your insurance covers the procedure and follow-up care.

Supplementation with 3g/day of HMB (calcium or free acid) does not significantly enhance fat-free mass or strength gains in young adults undergoing resistance exercise training compared to placebo.

If you are a young adult (under 45) doing resistance training, taking 3g of HMB daily will not give you more muscle or strength than training alone. Save your money.

Supplements such as chromium, zinc, vitamin D, vitamin E, cinnamon, and fenugreek are not recommended by the ADA for routine use in T2DM due to lack of significant effect on HbA1c.

Do not rely on supplements like chromium, cinnamon, or fenugreek to control your blood sugar. The American Diabetes Association recommends against their routine use because they do not significantly improve HbA1c levels. Focus on a balanced diet instead.

Intensive lifestyle intervention (caloric restriction, meal replacements, and physical activity) fails to reduce the incidence of major cardiovascular events in overweight or obese individuals with type 2 diabetes, despite achieving significant long-term weight loss and improvements in cardiovascular risk factors.

For individuals with type 2 diabetes, intensive lifestyle changes (diet, exercise, behavioral support) are still recommended because they improve weight, fitness, and other risk factors (like blood pressure and blood sugar), even if they do not directly reduce the risk of heart attacks or strokes. Focus on the overall health benefits rather than just cardiovascular event reduction.

Federal dietary guidelines that recommend reducing intake of meat, dairy, and processed foods face systematic political pressure and lobbying from food industry producers, resulting in diluted, ambiguous, or industry-favorable language in official policy documents.

Understand that when federal guidelines seem to contradict previous advice or seem vague (e.g., 'moderation'), it often reflects political compromise with food industries rather than a change in nutritional science. Stick to the consistent core principles: prioritize fruits, vegetables, and grains, and limit high-fat meats and processed foods, regardless of the specific wording of the current edition.

There is a significant disconnect between mechanistic research (e.g., mTOR signaling) and applied intervention studies, leading to a lack of systematic translation of basic science into concrete intervention strategies.

Current research often fails to bridge the gap between molecular science and practical advice. For now, focus on the proven basics: consistent resistance training and adequate protein intake, rather than trying to optimize based on complex molecular mechanisms that haven't been fully translated into practical protocols.

SGLT2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status.

If you have heart failure, especially with reduced ejection fraction, ask your doctor about SGLT2 inhibitors like empagliflozin or dapagliflozin. These drugs help your heart pump better and reduce hospitalizations, even if you don't have diabetes.

Most other interventions for medical conditions and health-risk behaviors in SMI populations have low or insufficient strength of evidence.

While metformin, behavioral interventions, bupropion, and varenicline have strong evidence, most other interventions for medical conditions and health-risk behaviors in SMI populations lack sufficient evidence. Future research should focus on long-term interventions and implementation strategies.

Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia do not reduce the subsequent development or prevalence of diabetic retinopathy for up to 20 years.

If you have prediabetes or are at risk for type 2 diabetes, preventing or delaying the onset of diabetes through lifestyle changes or medication (like metformin) does not guarantee that you will avoid eye damage (retinopathy). Retinopathy can start during the prediabetic stage. Therefore, regular eye exams are crucial for people with prediabetes, regardless of whether they successfully prevent diabetes.

A long-term intensive lifestyle intervention (caloric restriction and increased physical activity) does not significantly reduce the prevalence of electrocardiographic left ventricular hypertrophy (ECG-LVH) in overweight or obese adults with type 2 diabetes.

For individuals with type 2 diabetes and obesity, engaging in a long-term intensive lifestyle intervention (diet and exercise) is unlikely to reverse electrocardiographic signs of left ventricular hypertrophy, even if it helps maintain weight loss. While lifestyle changes are crucial for overall health, patients should not expect this specific cardiac structural improvement as a guaranteed outcome of modest weight loss.

Commercial direct-to-consumer (DTC) genetic tests for personalized nutrition often lack scientific backing, provide insufficient result descriptions, and draw inferences that are not supported by robust evidence, particularly when based on single gene variants.

Be skeptical of DTC genetic nutrition tests. They are largely unregulated and often base advice on single genes, ignoring the complex polygenic nature of health. The paper states these tests often lack scientific backing. Use them for curiosity, not as a substitute for evidence-based dietary guidelines.

Insulin-lowering diets have not yet been conclusively demonstrated to improve cancer-specific endpoints such as tumor response, disease-specific survival, or overall survival in clinical settings.

Do not rely on insulin-lowering diets as a cure or primary treatment for metastatic cancer. While they improve metabolic health and are safe, they have not been proven to extend life or shrink tumors in humans. Use them only as an adjunct to standard care under medical supervision.

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly reduces cardiovascular death, all-cause mortality, and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk.

If you have type 2 diabetes and are at high risk for heart problems, empagliflozin is a medication that can significantly lower your risk of dying from heart issues, dying from any cause, and being hospitalized for heart failure. It works by helping your kidneys remove sugar and water, which also helps lower blood pressure and weight. While it does increase the risk of genital infections, the cardiovascular benefits are substantial for high-risk individuals.

There is currently insufficient evidence to determine the specific impact of obesity on central blood pressure and its modification after bariatric surgery, as no studies have evaluated 24-hour central BP changes at medium or long term post-surgery.

While bariatric surgery lowers peripheral blood pressure, we do not yet know how it affects central (aortic) blood pressure over the long term. Future research is needed to understand if central BP improves as much as peripheral BP after surgery.

Combined estrogen plus progestin therapy increases the risk of coronary heart disease, stroke, pulmonary embolism, and invasive breast cancer in healthy postmenopausal women, outweighing benefits for fracture prevention and colorectal cancer reduction.

For healthy postmenopausal women considering hormone therapy primarily to prevent heart disease or other chronic conditions, current evidence from the Women's Health Initiative indicates that the risks (including heart disease, stroke, blood clots, and breast cancer) outweigh the benefits (reduced hip fractures and colorectal cancer). Therefore, this regimen is not recommended for primary prevention.

Semaglutide treatment is associated with a significantly higher risk of diabetic retinopathy complications compared to placebo in patients with type 2 diabetes, particularly those with preexisting retinopathy.

If you have type 2 diabetes and are taking semaglutide, be aware that it may increase the risk of eye problems, especially if you already have diabetic retinopathy. Regular eye exams are essential to monitor for any changes. The cardiovascular benefits of semaglutide are significant, but managing eye health is a critical part of your overall care plan.

Beta-3 adrenergic receptors are not strictly required for brown adipose tissue function or thermogenesis, as evidenced by species lacking them (guinea pigs) or mice genetically ablated for beta-3 receptors, which compensate via beta-1 receptors.

You do not need beta-3 receptors to activate brown fat. The body can use beta-1 receptors to achieve the same thermogenic result if beta-3 receptors are absent or non-functional.

Global adult body-mass index (BMI) has significantly increased from 1975 to 2014, with obesity prevalence surpassing underweight prevalence in the majority of countries by 2014.

Global trends show that average body weight has been steadily increasing for decades. This is not a temporary fluctuation but a long-term shift. Public health efforts are currently failing to halt this rise, meaning individual efforts to maintain a healthy weight may face increasing environmental and societal headwinds.

Severe and morbid obesity are increasing globally, with significant regional disparities, particularly in Polynesia and Micronesia.

Severe obesity is becoming more common, especially in certain regions. This is a serious health risk that requires attention and support, not stigma.

Conjugated equine estrogen (CEE) alone does not reduce the incidence of coronary heart disease in postmenopausal women with prior hysterectomy.

If you have had a hysterectomy and are considering hormone therapy for heart disease prevention, current evidence shows it does not work for that purpose. While it may help with bone density (hip fractures), it increases stroke risk. Do not use CEE solely to protect your heart.

Conjugated equine estrogen (CEE) increases the risk of stroke in postmenopausal women with prior hysterectomy.

If you are considering CEE for menopausal symptoms, be aware that it increases your risk of stroke by about 39%. This risk is significant enough that CEE is not recommended for chronic disease prevention.