Dr. Peter Attia: Exercise, Nutrition, Hormones for Vitality & Longevity

Assessing Health and Blood Work

• Blood work can be helpful in assessing health, but has limitations
• Useful for those focused on living longer and improving health span
• Blood work can help address:
• Atherosclerotic disease: good predictor of risk if you know what to look for
• Cancer: less helpful, but can provide some insight
• Neurodegenerative disease: limited in predicting risk
• Metabolic disease: can provide useful information on risk factors

Blood Work Frequency and Age

• No one-​​size-​​fits-​​all answer
• Depends on individual’s goals, health status, and risk factors
• Generally, start getting blood work in your 20s or 30s
• Frequency can vary from every 6 months to every 2 years, depending on the individual and their needs

Blood Work for Vitality

• Can provide some insight into factors affecting vitality
• However, blood work has blind spots and may not provide a complete picture

• Functional analyses of performance may be more beneficial for those focused on specific athletic goals
  ApoB and Biomarkers

• ApoB: single most important lipoprotein

• Biomarkers helpful for understanding inflammation, endothelial health, and metabolic health
• Cancer: blood testing not as helpful, metabolic ill health is a modifiable cause
• Neurodegenerative diseases: biomarkers helpful for dementia, especially Alzheimer’s

Blood Testing Frequency

• Early screening important for detecting genetic drivers of atherosclerosis (e.g., LP little A)
• Frequency depends on state of interventions and changes
• Typically, patients might have blood tests 2–4 times a year

DEXA Scans

• DEXA (Dual-​​energy X‑ray Absorptiometry) scan: gold standard for measuring body fat, lean mass, and bone mineral density
• Provides information on body fat, bone mineral density, visceral fat, and appendicular lean mass index and fat-​​free mass index
• More accurate than calipers or buoyancy testing
• Bone mineral density important for understanding risk of osteoporosis and osteopenia, especially in women going through menopause

Emotional State

• Emotional state is an important aspect of health, but not easily assessed through biomarkers

• Building a relationship with patients is crucial for understanding and addressing emotional health
  Bone Mineral Density and Strength Training

• Bone health is crucial for overall health and longevity

  • Over the age of 65, a fall and broken hip can result in a 30–40% chance of death within a year
• Bone mineral density (BMD) is measured using a Z score 
  • A Z score of 0 means you’re at the 50^th percentile for your age and sex
  • A Z score of +1 means you’re one standard deviation above, ‑1 means below
• Strength training is essential for maintaining and improving bone mineral density 
  • Critical window for bone development is up to age 20–25
  • Strength training is especially important for females during this time
  • Powerlifting (heavy loads, low repetitions) is most effective for bone health
  • Strength training should be a lifelong practice to prevent decline in bone health
• Inhaled steroids for asthma and other conditions can impair bone mineral density 
  • Particularly concerning if used during the critical window of development
• Strength training has both local and systemic effects on bone health 
  • Majority of the response is local, as it involves putting a load directly on the bone
  • Diagnosis of osteopenia and osteoporosis is based on left hip, right hip, and lumbar spine measurements
  • However, bone density outside of these regions also matters for overall health

Marginal Decade Exercise

• Marginal decade refers to the last decade of a person’s life
• Exercise involves detailing what one wants their marginal decade to look like
• Helps design a program to achieve those goals
• Useful for anyone, regardless of age

Backcasting

• Backcasting involves working backward from a goal to determine the steps needed to achieve it
• Useful for long-​​term planning, while forecasting is better for short-​​term planning

Prime Movers for Longevity and All-​​Cause Mortality

• Smoking increases all-​​cause mortality risk by 40%
• High blood pressure increases all-​​cause mortality risk by 20–25%

• End-​​stage kidney disease increases all-​​cause mortality risk by 175% (hazard ratio of 2.75)
  Improving Health and Longevity

• Comparing low to high achievers in muscle mass and strength

  • Low muscle mass people have about a 3x hazard ratio (200% increase) in all-​​cause mortality
  • Strength could be 3.5x as a hazard ratio (250% greater risk) if comparing low strength to high strength
• Cardiorespiratory fitness
  • 2x difference in risk of all-​​cause mortality between bottom 25% and top 25% for age and sex in terms of VO2 max
  • 5x difference (400% difference) in all-​​cause mortality between bottom 25% and top 2.5% (elite) for age and sex in terms of VO2 max

Strength and Fitness Metrics

• Dead hang: 1.5 minutes for a 40-​​year-​​old woman, 2 minutes for a 40-​​year-​​old man
• Air squat at 90 degrees: 2 minutes for both men and women at 40
• Farmer carry: body weight for 2 minutes for men, 75% of body weight for women
• VO2 max: online estimators available to determine approximate VO2 max based on activity

Exercise and Brain Health

• Exercise has been shown to be the single best thing for Alzheimer’s prevention

  • Affects various aspects of the brain, including BDNF, vascular endothelium, glucose disposal, and insulin signaling
  • Other factors, such as EPA and DHA, also play a role in Alzheimer’s prevention, but exercise has the most significant impact
    Exercise and Cognitive Health

• Exercise is crucial for cognitive health and overall well-being

• Going from sedentary to 15 met hours per week can lead to a 50% reduction in risk 
  • Met: metabolic equivalent; 1 met = sitting quietly, 5 mets = brisk walking
• Nobel Prize winners Eric Kandel, Torsten Wiesel, and Richard Axel all exercise regularly and maintain cognitive sharpness

Nicotine and Cognitive Enhancement

• Nicotine can enhance concentration and focus 
  • Can be addictive, so use with caution
  • Some people use nicotine gum or lozenges for cognitive enhancement
• Using stimulants like Adderall for cognitive enhancement is not recommended

Modafinil and Cognitive Enhancement

• Modafinil may provide nootropic benefits for sleep-​​deprived individuals 
  • Unclear if it provides benefits for well-​​rested individuals
• Alpha GPC may help with focus, but should be used sparingly

Environmental Factors and Focus

• Changing our environment can greatly impact our ability to focus 
  • Reducing distractions, such as social media and email, can improve focus

• Developing habits to minimize interruptions can help maintain focus during work
  Hormone Therapies and Hormones

• Female hormone profile: more testosterone than estrogen in absolute amounts

• Estrogen and progesterone cycle in women 
  • Estrogen rises in response to follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH) prepares uterus for pregnancy
  • Progesterone dominates second half of cycle (luteal phase)
  • Stabilizing progesterone can alleviate PMS symptoms
• Menopause symptoms
  • Vasomotor symptoms: night sweats, hot flashes
  • Long-​​term complications: vaginal atrophy, dryness, osteopenia, osteoporosis, brain fog
• Hormone replacement therapy (HRT) history 
  • 1950s: estrogen given to menopausal women
  • 1970s: progesterone added to oppose estrogen and reduce risk of uterine cancer

• Women’s Health Initiative (WHI) study in the 1990s

  • Aimed to test HRT in a randomized prospective trial
  • Two parallel arms: one for women without a uterus, one for women with a uterus
  • Study limitations: older, sicker women; not started when HRT would normally be initiated
  • Results led to medical field turning away from HRT for women
    Clinical Trials and Hormone Replacement Therapy (HRT)

• Disproportionately unhealthy patient population

  • High prevalence of obesity, diabetes, and smoking
• No symptomatic patients included in the study 
  • Rationale: symptomatic patients on placebo would drop out
  • Study design does not mimic real-​​world situations
• Use of conjugated equine estrogen and synthetic progesterone (MPA)
  • Not bioidentical hormones, which are used today
  • Chosen because they were commonly used at the time

HRT and Breast Cancer Risk

• Headline: HRT increases risk of breast cancer by 27% 
  • Misleading, as it only considers relative risk, not absolute risk
• Absolute risk increase: 0.1% (1 case in 1000) 
  • 4 cases per 1000 (placebo) vs. 5 cases per 1000 (estrogen + MPA)
• Estrogen-​​only group showed a 24% risk reduction (not statistically significant) 
  • Suggests synthetic progesterone (MPA) may be the main issue

Current HRT Practices

• Bioidentical hormones (estradiol and progesterone) used today
• Topical estrogen (patches) preferred over oral estrogen 
  • Oral estrogen increases blood clotting risk
• Annual endometrial ultrasound recommended for women on HRT
• Progesterone tolerance varies among women 
  • Progesterone-​​coated IUDs used for local protection in the uterus

Oral Contraception in Women

• Long-​​term effects not well-known
• More women using IUDs for contraception
• Low-​​dose synthetic estrogen sometimes used for symptomatic control

Testosterone Therapy in Women

• Prescribed with caution due to limited data

• Estrogen and progesterone therapy more well-​​supported by research
  Testosterone and Hormone Replacement Therapy in Men

• Testosterone replacement therapy in women is less studied than in men

• In men, focus on free testosterone levels rather than total testosterone
• Ranges for total testosterone: 300‑1200 nanograms per deciliter
• Free testosterone should be about 2% of total testosterone
• Factors affecting SHBG (Sex Hormone Binding Globulin) levels:
• Estradiol: higher levels increase SHBG
• Insulin: lower levels increase SHBG
• Thyroxine: imbalances can interfere with SHBG
• Supplements and medications that can affect SHBG:
• Anavar (Oxandrolone): can lower SHBG in small doses
• Stinging nettle extract: claimed to reduce SHBG, but not proven
• Tongkat Ali: may increase free testosterone, but mechanism unclear
• DHT (Dihydrotestosterone) levels:
• Important for overall well-​​being, but can cause prostate issues
• Finasteride (Propecia) can reduce DHT, but may have side effects
• No known supplements that can profoundly drop DHT levels
• Simplified approach to hormone replacement therapy in men:
• Focus on free testosterone levels as the primary target
• Adjust total testosterone levels to achieve desired free testosterone

• Monitor estradiol levels as the secondary target
  Testosterone Replacement Therapy

• First order question: Will normalizing free testosterone benefit the patient?

• Depends on symptoms and biomarkers
• Testosterone improves glycemic control and insulin signaling
• Methods of testosterone replacement therapy
• Directly or indirectly
• Clomid (Clomiphene) — fertility drug, synthetic hormone 
  • Tells pituitary to secrete FSH and LH
  • Oral, typical starting dose: 50mg three times a week
  • Increases FSH, LH, and testosterone
  • Can cause high levels of Desmonderol, potentially harmful
• HCG — more cumbersome, needs refrigeration, fragile molecule 
  • Subcutaneous injection

Estrogen and Aromatase Inhibitors

• Anastrozole — reduces aromatase activity
• Can cause joint pain, memory issues, severe drops in libido, and fat accumulation if taken in high doses
• Microdoses (0.1mg) used to avoid side effects
• Most patients on testosterone replacement therapy do not need aromatase inhibitors
• Only high aromatizers need it

Testosterone Dosing

• 50mg twice a week is a physiologic dose
• No side effects like acne or gynecomastia
• Can cause testicular atrophy
• Testosterone clinics often give 200mg every two weeks and multiple milligrams of anastrozole

• Incompetent and potentially harmful practices
  Testosterone Therapy and Fertility

• Clomiphene preserves testicular function and volume

  • Used in post-​​cycle therapy for bodybuilders
  • Can be used as ongoing therapy for those with testicular reserve
• HCG (Human Chorionic Gonadotropin) 
  • Analog of luteinizing hormone
  • Crushes endogenous luteinizing hormone levels
  • Can cause FSH and LH to go down at high doses
• Fadogia Agrestis (Nigerian shrub) 
  • Increases luteinizing hormone at lower doses
  • Can cause testicular toxicity at high doses
  • Long-​​term safety and efficacy unknown

• Testosterone Replacement Therapy (TRT)

  • Uses testosterone cypionate (injectable)
  • Aromatase blocker (anastrozole) used to control estrogen levels
  • HCG used to maintain fertility and testosterone if desired
  • Not recommended for men who want to maintain fertility
  • Benefits: improved mood, energy, and overall well-being
  • Cautionary notes: potential side effects include LDL increase, blood pressure increase, water retention, acne, and hair loss/​​growth
  • Low doses (100mg/​​week) typically used to avoid side effects
  • Youngest patients on TRT usually around 40 years old
  • Delaying TRT recommended for younger individuals to preserve fertility and pituitary function
    Clomid and Fertility

• Clomid is used for fertility treatments

• Concerns arise when considering long-​​term use (10 years), not short-​​term use for IVF
• Can be used for 3 months to help stimulate the pituitary gland in some cases

Testosterone Cycling

• Some men cycle on and off testosterone at low dosages
• Example: 8 weeks on testosterone, 8 weeks on HCG, alternating
• This helps maintain testosterone levels while fluctuating between endogenous and exogenous sources

Testosterone and Physical Appearance

• Little correlation between absolute testosterone levels and physical appearance
• Factors like free testosterone, estrogen, training, and nutrition play a role
• Testosterone alone won’t improve appearance; it helps with recovery and muscle protein synthesis, but requires effort and exercise

Cholesterol, Saturated Fat, and Health

• Cholesterol is a crucial component of cell membranes and hormone production
• Dietary cholesterol does not significantly impact serum cholesterol levels
• Cholesterol in food is esterified and cannot pass through the body’s regulatory checkpoint
• Only a small fraction of dietary cholesterol makes its way into circulation

• American Heart Association now acknowledges that dietary cholesterol has no bearing on serum cholesterol levels
  Saturated Fat, Cholesterol, and LDL

• Saturated fat consumption can raise LDL cholesterol in many people

• Cholesterol is a complex ring structure, while saturated fat is a long chain fatty acid with no double bonds
• LDL (low-​​density lipoprotein) is a lipoprotein that transports cholesterol and triglycerides through the bloodstream
• ApoB (apolipoprotein B) is a protein that wraps around LDL and VLDL particles and is a causative agent of atherosclerosis

Atherosclerosis and ApoB

• Atherosclerosis is a lifelong disease that begins developing at a young age
• Autopsies of young people who died in wars show that cardiovascular disease is already taking hold in people as young as 18–20 years old
• ApoB is necessary, but not sufficient, to develop atherosclerosis

Reducing ApoB Levels

• Nutritionally, reducing carbohydrate intake can lower triglycerides, which can help reduce ApoB levels
• Lowering saturated fat intake can also help reduce ApoB levels
• Pure dietary intervention is unlikely to achieve ApoB levels of 30 milligrams per deciliter, which is necessary for preventing atherosclerosis
• Pharmacological interventions, such as statins, can help lower cholesterol and ApoB levels

• Other drugs, such as ezetimibe (which blocks cholesterol reabsorption) and bempedoic acid (which blocks cholesterol synthesis in the liver), can also help lower cholesterol and ApoB levels
  Peptides, PRP, and Stem Cells

• Peptides, PRP (Platelet Rich Plasma), and stem cells are a topic of curiosity and interest

  • However, they are considered “wild wild west” due to lack of clinical trials and data
• Rapamycin is an example of a drug with a significant amount of data supporting its use, despite not having a human clinical trial demonstrating life extension 
  • 84 other pieces of data point in the same direction across various model organisms
• Stem cells, BPC-​​157, and PRP have anecdotal evidence, but lack substantial data 
  • Unclear if they work or not
  • Opportunity cost in terms of time, effort, and finances when considering these treatments

• Example: considering alternative treatments for a shoulder injury

  • Ultimately, surgery may be the best option due to lack of data on alternative treatments
    Stem Cell Injections and Injuries

• Stem cell injections might not work for all injuries

  • Example: Complete laboral tear in the shoulder
• Designing clinical trials to narrow down patient population is crucial 
  • Heterogeneous patient population can lead to null results
• Incentive for legitimizing stem cell procedures is lacking 
  • People making money from unproven procedures
  • Need for a pharma angle or billionaire funding clinical trials

Rehabilitation and Hard Work

• Stem cell injections can be seen as a crutch, avoiding the hard work of rehab
• Importance of dedicated prehab and rehab process 
  • Example: Shoulder surgery recovery requires tedious, uncomfortable exercises
• Faith in the methodology and doing the work is essential

Metabolomics

• Omics: term used to describe the study of something 
  • Genomics: study of genes
  • Proteomics: study of proteins
  • Metabolomics: study of metabolites (e.g., glucose, acetyl COA, lactate)
• Understanding physiologic states and metabolomic profiles 
  • Example: Exercise produces favorable phenotype 
    • Changes in gene expression and metabolites
• Metabolomics can provide insights into disease states and potential treatments