Hemoglobin A1C is an imperfect measure of kidney function because it varies based on red blood cell turnover rate; creatinine (the conventional kidney function marker) is equally flawed, overestimating kidney function in people with low muscle mass and underestimating it in people with high muscle mass or recent exercise.

Eccentric strength (force during muscle lengthening) is as important as concentric strength (force during muscle shortening) but often neglected; eccentric weakness, not concentric weakness, is the primary cause of falls and injuries in aging populations, particularly on stairs and stepping off curbs.

Attia gained approximately 13-14 pounds of lean mass in 12 months through conscious protein intake of one gram per pound of body weight and hypertrophy-focused training, without using anabolic steroids.

Exercise is the single most important modifiable behavior to reduce the risk of Alzheimer's disease, Parkinson's disease, and Lewy body dementia; this was determined through extensive literature analysis and remains consistent even with current, expanded research tools.

Lactate measurement (via finger-prick point-of-care testing) provides an accurate threshold for zone 2 aerobic training; a lactate level of 1.7-2.0 millimoles per liter indicates the appropriate zone 2 intensity for most people, though RPE (rate of perceived exertion) is a practical proxy for those without testing equipment.

Sensitivity and specificity of a diagnostic test are insufficient to interpret results; one must also know the pretest probability (prevalence) of the condition to calculate positive and negative predictive values, which reveal the actual likelihood that a positive or negative test result indicates the true disease status.

Attia has experienced poor sleep nights after social dinners with friends when he ate late and drank, but consciously chooses to accept this tradeoff because the value of time with friends outweighs the sleep cost; this exemplifies deliberate tradeoff thinking rather than rigid optimization.

Life expectancy has doubled from approximately 40 years in 1900 to 80+ years today, but when the top eight infectious diseases are removed from mortality analysis, there is effectively no change in mortality rates from 1900 to the present, indicating Medicine 2.0 succeeded at acute care but failed at chronic disease prevention.

Protein consumption should target one gram per pound of body weight, distributed across meals with each meal containing 20-25 grams minimum to prevent gluconeogenesis (conversion to glucose) and no more than approximately 50 grams per serving to avoid excessive conversion.

Medicine 1.0 (pre-late 17th century to late 19th century) was characterized by having no scientific basis whatsoever, relying on rationalization about gods and bad humors, with Hippocrates' insight that diseases were caused by nature rather than gods being arguably the apex of Medicine 1.0 thinking.

Appendicular Lean Mass Index (ALMI) north of the 75th percentile is associated with longer, better lives, and Attia targets the 90th to 97th percentile as a personal goal because the data are unambiguous on this correlation with lifespan.

Grip strength is one of the most highly correlated predictors of longevity and risk of dementia, showing a monotonic decline in both dementia onset and death risk as grip strength decreases, and this association likely reflects causation (that training grip strength improves outcomes) rather than mere correlation.

GRAIL (a liquid biopsy test using cell-free DNA methylation patterns) can detect cancer presence and estimate origin organ; it has low sensitivity (poor at detecting stage 1-2 cancer, ~20% for most histologies) but high specificity (good at confirming absence of cancer); the positive and negative predictive values depend on pretest probability (cancer prevalence in the population tested).

CGM is not necessary for living a longer, healthier life; it is simply one tool for understanding glucose regulation, and many people achieve excellent health outcomes without it.

Branch chain amino acids (BCAAs) have largely fallen out of favor in practice despite their theoretical mTOR-stimulating properties, because they don't remain bioavailable long enough, they provide insufficient total amino acid content, and the timing window for muscle protein synthesis is broad enough that post-workout whey protein is more practical and effective.

For individuals over 40 who don't smoke, approximately 80 percent will die from one of four causes: atherosclerotic cardiovascular disease, cancer, neurodegenerative disease, or metabolic disease (type 2 diabetes and related conditions), with accidental death being a minor additional factor.

It is better to extend the period of life lived without a chronic disease rather than to extend the period of time lived with a chronic disease; stated differently, early cancer is preferable to late cancer with longer total lifespan, and early heart disease is preferable to late heart disease with extended survival.

High VO2 max (top 2.5% of population) and muscular strength are the two metrics with the most powerful positive impact on lifespan and all-cause mortality, comparable to or exceeding the protective effect of not smoking, not having kidney disease, not having diabetes, and not having high blood pressure.

Moving from the bottom 25th percentile to the 25th-50th percentile of fitness cuts all-cause mortality risk in half at any point in time, meaning the greatest return on fitness investment is for those starting from very low baseline fitness.

Extreme fasting (up to 10-day water-only fasts quarterly, plus routine 7-day fasts and 3-day monthly fasts) combined with daily resistance training while in a fasted state resulted in significant muscle loss over three years, despite attempting to maintain muscle protein synthesis through exercise.