Browse the evidence

Influx of free fatty acids (FFAs) and triglyceride-rich lipoproteins into skeletal muscle induces inflammation and insulin resistance via activation of TLR4, PKC, and JNK pathways.

High levels of circulating fats, especially saturated fats, can flood into muscle cells, causing inflammation and blocking insulin. Managing blood fat levels through diet (reducing saturated fats) and exercise can help prevent this lipid-induced insulin resistance.

In older adults (over ~80 years), maintaining a gut microbiome that becomes increasingly unique (divergent from common profiles) and depletes core genera like Bacteroides is a marker of healthy ageing and predicts higher survival rates.

For older adults, the composition of your gut microbiome matters more than just its diversity. Research suggests that as you age, your microbiome naturally becomes more unique to you. This 'drift' away from common bacterial profiles (specifically a decrease in Bacteroides) is linked to better health and survival. Instead of focusing solely on boosting common bacteria, focus on a varied diet that supports a unique microbial ecosystem, as indicated by the production of specific amino acid derivatives in the blood.

Long-term calorie restriction (CR) prevents age-related large artery stiffening and endothelial dysfunction by reducing oxidative stress and inflammation.

To improve vascular health and slow aging, consider reducing your daily caloric intake by 25% while ensuring you get all necessary nutrients. This approach, validated by the CALERIE trial, has been shown to reduce cardiovascular risk factors and slow biological aging in nonobese adults.

Lipodystrophy (loss of adipose tissue) causes the same metabolic syndrome and insulin resistance as obesity, proving that adipose tissue is essential for metabolic health.

Do not aim for extremely low body fat levels. Your body needs adipose tissue to store energy safely. If you lose too much fat, it can lead to insulin resistance and metabolic syndrome, similar to obesity. Maintain a healthy amount of fat, particularly subcutaneous fat, to support metabolic health.

Biologic mechanisms linking physical activity, sedentary behavior, and obesity to cancer risk include effects on endogenous insulin sensitivity, chronic sex steroids, metabolic hormones, and inflammation.

Understanding that exercise and weight management affect hormones and inflammation helps explain why these lifestyle factors prevent cancer.

Obesity disrupts female fertility through multiple mechanisms including HPO axis deregulation, adipokine-mediated inflammation, and oocyte quality reduction, leading to anovulation and reduced IVF success rates.

If you are obese, your fertility is likely compromised even if your periods are regular. This is due to hormonal imbalances and inflammation affecting egg quality and implantation. Weight loss through lifestyle modification is proven to restore menstrual cyclicity and ovulation, improving conception chances.

Adipokines (leptin, adiponectin, resistin, etc.) released by adipose tissue in obesity directly interfere with ovarian function, insulin sensitivity, and endometrial receptivity, contributing to infertility.

Your fat tissue is not just storage; it acts as an endocrine organ releasing hormones that disrupt your reproductive system. This is why weight loss helps.

The DunedinPoAm DNA methylation algorithm accurately quantifies the pace of biological aging (rate of decline in system integrity) rather than just chronological age, serving as a valid surrogate endpoint for testing interventions that slow aging.

This paper introduces a blood test (DunedinPoAm) that measures how fast your body is aging biologically, distinct from your chronological age. It is currently a research tool used to validate interventions like caloric restriction (CALERIE trial) that slow aging. For now, it is not a commercial consumer product, but it validates that slowing biological aging is measurable and that interventions like calorie restriction can impact this rate.

Genetic predisposition for longer habitual sleep duration is causally linked to an increased risk of schizophrenia, and conversely, genetic risk for schizophrenia causes longer sleep duration, indicating a bidirectional causal relationship.

If you naturally sleep longer than average (e.g., >8-9 hours), it may be partly due to your genetics. This paper suggests a causal link between longer sleep and higher schizophrenia risk, but also that schizophrenia risk drives longer sleep. Focus on overall mental health monitoring rather than trying to force shorter sleep, as sleep duration is largely genetically fixed.

Bacterial translocation of lipopolysaccharide (LPS) from the gut to the bloodstream (metabolic endotoxemia) due to increased intestinal permeability ('leaky gut') triggers systemic inflammation and insulin resistance.

Avoid excessive intake of saturated fats and refined sugars, which are linked to increased intestinal permeability and higher circulating LPS levels, thereby reducing the risk of inflammation-driven insulin resistance.

Initiating supplemental parenteral nutrition (SPN) within the first week of ICU admission provides no clinically important benefit compared to enteral nutrition (EN) alone.

Do not start supplemental parenteral nutrition (SPN) in the first week of ICU stay for average critically ill patients. Focus on enteral nutrition (EN) tolerance. Consider SPN only after day 7 if EN remains insufficient, especially for malnourished patients.

Providing similar energy intake via parenteral nutrition (PN) as compared to enteral nutrition (EN) in the first week of critical illness results in similar clinical outcomes.

If a critically ill patient cannot tolerate enteral nutrition (EN), parenteral nutrition (PN) is an acceptable alternative. Ensure similar energy intake and monitor for glycemic control and catheter-related infections. Cost and convenience may guide the choice.

Metabolically healthy obesity (MHO) is not a distinct protective phenotype but rather a transient state characterized by fewer metabolic abnormalities than metabolically unhealthy obesity (MUO), with a high likelihood of progressing to MUO over time.

Do not rely on the label 'metabolically healthy' to ignore metabolic risks. Even if you do not have high blood pressure or diabetes, you may still have insulin resistance or liver fat. Focus on improving insulin sensitivity through diet and activity rather than assuming your current state is safe.

Epigenetic clocks based on DNA methylation levels can predict chronological age and the risk of aging-related diseases.

Epigenetic clocks can measure biological age. This can help assess the efficacy of aging interventions.

MBS significantly reduces the risk of developing obesity-associated cancers and cancer-related mortality.

Undergoing MBS not only helps with weight but also significantly lowers your long-term risk of developing various cancers and dying from cancer compared to remaining obese.

Medium-term recovery from moderate-to-severe SARS-CoV-2 infection is characterized by persistent multi-organ MRI abnormalities, significantly reduced exercise capacity, and impaired cognitive performance, which correlate with the severity of the initial acute illness.

If you have been hospitalized for COVID-19, do not assume you are fully recovered just because you are discharged. Expect potential long-term effects on your lungs, heart, brain, and energy levels. Seek medical evaluation for persistent breathlessness or fatigue, and consider a gradual, monitored return to physical activity rather than pushing through symptoms, as your exercise capacity may be significantly reduced.

Post-acute SARS-CoV-2 infection is associated with specific brain MRI changes (thalamic T2* signal, white matter diffusivity) and impaired executive/visuospatial cognitive performance, which correlate with the severity of the initial inflammatory response.

If you are experiencing 'brain fog' or difficulty with planning and spatial tasks after COVID-19, it may be linked to structural changes in your brain. Consider a neuropsychological evaluation to assess cognitive function, as these deficits are common and may require specific cognitive rehabilitation strategies.

Post-acute SARS-CoV-2 infection is associated with a higher burden of self-reported depression, anxiety, and impaired quality of life across all domains, independent of physical symptoms.

Do not ignore feelings of depression, anxiety, or a drop in quality of life after COVID-19. These are common, measurable outcomes linked to the severity of your illness. Seek support from mental health professionals, as addressing these issues is a critical part of your overall recovery.

Skeletal muscle regeneration and repair are primarily governed by satellite cells (SCs), which transition from a quiescent state to activation, proliferation, and differentiation in response to injury or stress.

To support muscle repair after injury or intense training, ensure adequate rest and nutrition to support the natural satellite cell activation process. The body has a built-in repair system (satellite cells) that activates when needed; supporting this with general health practices is key.

Environmental stressors, specifically inflammation and oxidative stress, contribute to muscle pathophysiology including atrophy, hypertrophy, and fibrosis.

Chronic inflammation and oxidative stress can damage muscle structure, leading to weakness (atrophy) or scarring (fibrosis). Managing overall health to reduce chronic stress and inflammation supports muscle integrity.

The neuromuscular junction (NMJ) is the critical site for transmitting electrical impulses from motor neurons to muscle fibers, relying on the release of acetylcholine (ACh) and its interaction with nicotinic acetylcholine receptors (nAChRs).

Efficient nerve-to-muscle signaling is essential for movement. Disruptions at the neuromuscular junction, such as those seen in Myasthenia Gravis, can cause muscle weakness. Maintaining overall neurological health supports this transmission.

Stepping intensity (cadence) is not independently associated with lower mortality rates after accounting for total step volume.

You do not need to walk fast to reduce your risk of death. Focus on increasing your total number of steps. If you walk slowly, that still counts toward your daily goal. The benefit comes from the volume of steps, not how fast you take them.

Glycemic variability, rather than mean glycemia (HbA1c), is a strong independent prognostic factor for adverse cardiovascular outcomes in type 2 diabetes, driven by oxidative stress and nitric oxide inactivation.

For people with Type 2 Diabetes, managing the ups and downs of blood sugar (glycemic variability) is just as critical, if not more so, than just hitting a target HbA1c number. High variability causes oxidative stress and reduces nitric oxide, damaging blood vessels. Strategies to smooth out glucose levels, such as using DPP-4 inhibitors or dietary modifications that prevent sharp spikes, may offer cardiovascular protection beyond what HbA1c reduction alone achieves.

DPP-4 inhibitors reduce glycemic variability, which leads to a proportional reduction in carotid intimal media thickness (IMT) and oxidative stress, suggesting a reversible early therapeutic target for CVD risk.

DPP-4 inhibitors (a class of diabetes medication) have been shown to reduce daily glucose fluctuations. This reduction in variability is linked to lower oxidative stress and a measurable decrease in carotid artery thickening (IMT) within just 3 months. This suggests that for some patients, these drugs may offer cardiovascular protection by stabilizing blood sugar swings, independent of just lowering the average HbA1c.