Dr. Peter Attia: Improve Vitality, Emotional & Physical Health & Lifespan

The Four Horsemen of Death

• Diseases of atherosclerosis (cardiovascular and cerebrovascular diseases) are the leading cause of death 
  • More prevalent globally than in the United States
  • 18–19 million people die from atherosclerotic cardiovascular disease worldwide
  • Cancer is the second leading cause of death, with 11 million deaths worldwide

Cerebrovascular Disease and Embolic Events

• Brain needs blood flow; interruption of blood flow results in ischemia
• Embolic events: obstruction of blood flow due to clot or plaque rupture 
  • Majority of strokes result from embolic events (4–5 times more common than hemorrhagic strokes)
• Hemorrhagic strokes: rupture of small blood vessels in the brain due to high blood pressure

Blood Pressure and Hemorrhagic Strokes

• Hypertension is the leading driver of hemorrhagic strokes
• Managing blood pressure within the 120/​​80 range is crucial for reducing heart attacks and strokes 
  • More aggressive management of blood pressure is better

Measuring Blood Pressure

• Blood pressure is often underdiagnosed and not measured correctly 
  • Manual blood pressure measurement is more accurate than automated cuffs
  • Blood pressure should be measured after sitting still for five minutes
• Recommendations for measuring blood pressure: 
  • Start with an automated cuff
  • Measure twice a day (morning and afternoon) for two weeks
  • Revisit measurements in a year

Future of Blood Pressure Monitoring

• Continuous blood pressure monitoring devices are being developed and tested

  • Wrist devices that check blood pressure every 15 minutes throughout the day
  • Continuous monitoring could be more important than continuous glucose monitoring for overall health
    Annual Health Checkup and Blood Pressure Monitoring

• Continuous blood pressure monitoring for two weeks as part of annual health checkup

  • Current methods are cumbersome (blood pressure cuff attached to a device)
  • Ideal solution would be a patch that can monitor blood flow and regulate pressure
• Importance of maintaining healthy blood pressure to prevent stroke, bleeding in the brain, and clotting

Preventing Arterial Sclerosis

• Arterial sclerosis is the number one killer
• Three major ways to prevent it: 
  1. Maintain blood pressure at 120/​​80 or better
  2. Don’t smoke or vape
  3. Manage apob bearing lipoproteins (to be discussed in depth later)
• Smoking and blood pressure both damage arteries, but in different ways 
  • Smoking chemically irritates the endothelium (innermost lining of arterial wall)
  • Blood pressure mechanically irritates the endothelium

Smoking Cannabis and Vaping

• No clear evidence that smoking cannabis is better than smoking cigarettes 
  • Dose is usually lower for cannabis smokers, so risk may not fully track
• Vaping is not as bad as smoking but still not good for health 
  • Better alternatives for nicotine consumption: lozenges, gum, etc.
• Inhaling harmful substances can damage lungs and cross the blood-​​brain barrier 
  • Long-​​term consequences of vaping and smoking are still being studied

Air Pollution and Cleaner Energy

• Air pollution from particulate matter (PM 2.5) can cause health issues 
  • Particles less than 2.5 microns can enter the body and cause damage

• Cleaner energy can reduce air pollution and its harmful effects

  • Focus on direct consequences of pollution rather than greenhouse gases
  • More people die from air pollution than from CO2 emissions
    APO B and Cholesterol

• Cholesterol is a lipid, essential for life

  • Synthesized by the body, necessary for cell membranes and hormone production
  • Rare genetic conditions that prevent synthesis result in non-​​viable embryos
• Cholesterol in food largely irrelevant, as it’s esterified and not easily absorbed
• Two main problems with cholesterol: 
  • Not every cell can make as much as it needs all the time 
    • Example: adrenal glands need more cholesterol to produce cortisol during stress
  • Cholesterol is not water soluble, so it cannot be transported easily in the circulatory system
• Solution: lipoproteins
  • Water soluble on the outside, fat soluble on the inside
  • Two main families: ApoB and ApoA 
    • ApoB: low-​​density lipoproteins (LDL), derived from the liver
    • ApoA: high-​​density lipoproteins (HDL), more complex family
• ApoB lipoproteins are atherogenic, meaning they contribute to atherosclerosis 
  • Most species do not have ApoB and are incapable of atherosclerosis
• No evidence that high LDL levels reflect a healthy metabolic need 
  • All functions can be done by HDL (ApoA)
  • Some people have genetic mutations that result in very low ApoB and LDL levels

Cholesterol and Brain Health

• Cholesterol is a critical component of synaptogenesis (formation of connections between neurons) in the developing brain 
  • Low-​​fat and low-​​cholesterol diets during early development can impair brain development
• Infants and children have very low levels of cholesterol 
  • Not yet fully myelinated (myelin sheathing around neuronal axons)
  • Myelin is made up of phospholipid and requires cholesterol for synthesis

• Cholesterol is important for brain development, but serum cholesterol levels are not necessarily indicative of brain health

  • The body can synthesize the cholesterol it needs for proper brain function
    Cholesterol Importance in Infants and Children

• Cholesterol is crucial for CNS development in infants and children

• Infants and children have low levels of serum cholesterol 
  • Serum cholesterol levels rise throughout life, with a bump for women at menopause
• Serum cholesterol is only a fraction of the total body pool of cholesterol 
  • Circulatory pool of cholesterol is about 10% of total body cholesterol

Understanding LDL, ApoB, and Cholesterol Measurements

• ApoB refers to the lipoprotein wrapped around an LDL particle 
  • ApoB blood test measures the concentration of LDL and VLDL particles
• LDL cholesterol (LDLC) measures the total concentration of cholesterol in LDLs 
  • ApoB is a better predictor of risk than LDLC

ApoB Levels and Risk Factors

• ApoB is causally related to atherosclerosis 
  • Confirmed by clinical trial literature, epidemiologic literature, and Mendelian randomizations
• Current medical approach assesses 10-​​year risk of Major Adverse Cardiac Event (MACE)
  • Based on cholesterol levels, blood pressure, smoking, family history, etc.
  • If MACE risk is less than 5%, LDL or ApoB treatment is not recommended

• However, if a risk is causal and modifiable, it should be modified regardless of risk tail in duration

  • Treating ApoB levels should be considered, depending on factors like age, existing disease, and family history
  • ApoB levels of 30–40 mg/​​dL (first percentile) may be targeted for high-​​risk individuals
  • ApoB levels in the low 130s raise a huge red flag
    Causality and Individual Risk Factors

• Causality doesn’t guarantee an outcome, e.g., smokers who don’t get lung cancer

• Making judgments about individuals based on heterogeneous population data and causal/​​non-​​causal inferences
• High apob individuals should investigate other risk factors and existing damage
• Devastating angiogram: any amount of calcification or soft plaque, indicating a decade+ of bad histology

Reducing Apob Levels

• Nutrition and fixing insulin resistance can help lower apob
• Elevated triglycerides (over 100 mg/​​dL) can be reduced through carbohydrate restriction
• Exercise plays a minimal role in improving lipids, but can improve insulin sensitivity

Pharmacotherapy for Apob Reduction

• Statins: target HMG-​​CoA reductase enzyme, liver increases LDL receptors in response 
  • Side effects: muscle soreness (5% of people), brain fog, insulin resistance
  • Several statin options available with varying side effect profiles
• Azetamib: blocks Neiman-​​Pick C1-​​like 1 transporter in enterocytes, regulating cholesterol absorption 
  • Side effects: virtually none, occasionally loose stools or elevated transaminases when combined with statins
• PCSK9 inhibitors: discovered by Helen Hobbes, used for familial hypercholesterolemia patients 
  • High cholesterol levels (LDL cholesterol at least 190 mg/​​dL) and high incidence of atherosclerosis
  • Accumulation of cholesterol in tendons and eyes if not managed correctly

Managing High Cholesterol

• Focus on nutrition, exercise, and pharmacotherapy options
• Monitor glucose levels and adjust medications as needed

• Consider individual risk factors and existing damage when making treatment decisions
  PCSK9 Gene and LDL Cholesterol

• PCSK9 gene codes for a protein that degrades LDL receptors

  • Hyper-​​functioning PCSK9 genes lead to fewer LDL receptors, causing high LDL cholesterol levels
  • Hypo-​​functioning PCSK9 genes result in very low LDL cholesterol levels and virtually no heart disease
• Development of PCSK9 inhibitor drugs 
  • Injectable drugs that block the protein, increasing LDL receptors and reducing ApoB in circulation
  • Taken every two weeks

ApoB and Heart Health

• High ApoB levels do not cause immediate symptoms, but increase the risk of heart attacks
• Importance of monitoring ApoB levels, especially with a family history of heart disease
• Treating high ApoB levels can prevent heart attacks, but may not cause immediate improvements in how a person feels

Blood Pressure Management

• Exercise, nutrition, and weight management can help lower blood pressure 
  • Zone 2 exercise (low-​​intensity cardio) recommended for 180–240 minutes per week
• Sleep is also important for blood pressure regulation
• Pharmacotherapy may be necessary if lifestyle changes do not lower blood pressure enough 
  • ACE inhibitors and angiotensin receptor blockers are well-​​tolerated medications

Kidney Health and Blood Pressure

• High blood pressure can negatively impact kidney function
• Importance of monitoring kidney function, especially for those aiming to live longer 
  • Current medical practice may not pay enough attention to kidney function
  • Creatinine is commonly used to measure kidney function, but cystatin C is a more accurate biomarker
  • Tolerating low kidney function for a person’s age can lead to future health issues, such as needing dialysis

• Goal: die with compromised kidney function, but never from compromised kidney function
  Hazard Ratio of Kidney Function and Mortality

• Compromised kidney function has a higher hazard ratio of all-​​cause mortality than heart disease

• End-​​stage renal disease has a higher risk of death than high blood pressure, smoking, or cancer

Alcohol and Health

• French Paradox: French people have a slightly lower risk of cardiovascular disease despite consuming fatty foods and wine 
  • Many confounders make this epidemiology unreliable
• No dose of ethanol is considered healthy 
  • Zero to one drink per day may not have measurable harm for most people
  • Risk increases steeply after one drink per day
• Alcohol may not be directly linked to cardiovascular or cerebrovascular disease 
  • Indirect effects through altering insulin sensitivity and sleep
• Ethanol can impact sleep and neurodegenerative diseases, especially dementia

Cancer Statistics and Prevention

• Globally, 11–12 million deaths per year due to cancer
• 1 in 3 to 1 in 4 chance of getting cancer in one’s lifetime
• 1 in 6 chance of dying from cancer
• Prostate and colon cancer are easily screened for and treated in their infancy
• Breast, pancreatic, and glialbustomy multiforme cancers are more complicated
• Cancer is a category of diseases, with different types within each organ 
  • E.g., breast cancer has hormone-​​positive and triple-​​negative types

Genes and Cancer

• Genes play a role in cancer development and risk

• Understanding gene profiles can help in cancer prevention and treatment
  Germline vs. Somatic Mutations in Cancer

• Germline mutations: inherited from parents, present at birth

  • Account for less than 5% of cancer cases
  • Example: BRCA gene mutation, linked to breast cancer
• Somatic mutations: acquired mutations, not inherited 
  • Account for over 95% of cancer cases
  • Major drivers: smoking and obesity

Obesity and Cancer

• Obesity is the second most prevalent environmental driver of cancer
• Obesity is often a proxy for insulin resistance and inflammation 
  • Insulin resistance: present in 2/​​3 to 3/​​4 of obese individuals
  • Inflammation: contributes to immune dysfunction
• Body Mass Index (BMI) is a crude measurement for obesity 
  • Better metric: waist-​​to-​​height ratio (waist circumference should be less than 50% of height)

Cancer Screening and Detection

• Early detection is crucial for effective treatment
• Imaging modalities for screening: 
  • Direct visualization (e.g., skin cancer, colonoscopy)
  • MRI scans (no radiation, but issues with sensitivity and specificity)
  • CT scans (high radiation exposure)
  • Liquid biopsies (blood tests for cell-​​free DNA)
• Radiation exposure concerns: 
  • Airport body scanners and dental X‑rays: low risk
  • CT scans and PET scans: significant radiation exposure
  • Living at high altitudes: increased background radiation exposure

Cancer Prevention and Control

• Limited control over cancer compared to cardiovascular disease
• Focus on avoiding known risk factors (e.g., smoking, obesity)
• No proven anti-​​cancer diet or exercise regimen

• Importance of regular screening and early detection
  Radiation Exposure and Risks

• Fluoroscopic studies and guided injections expose patients to localized high doses of radiation

  • Not a major concern if done infrequently, but should be avoided on a monthly basis
• Medical practitioners contribute significantly to radiation exposure 
  • Patients should ask about radiation exposure (in milliseverts) before undergoing CT scans or imaging studies
  • Aim to minimize exposure to 50 milliseverts per year
• MRI scanners preferred over CT scans due to lack of radiation exposure

Carcinogens in Everyday Life

• Difficult to calculate average risk of carcinogens from solvents, pesticides, and other household items 
  • Ubiquity of these substances may contribute to baseline prevalence of cancer
• Asbestos warnings on buildings may be more about covering liability than actual risk 
  • Risk may be higher when asbestos is agitated or disturbed

Genetic Screening and Cancer Prevention

• Genetic screening can help identify predispositions to certain diseases (e.g., APOE gene for Alzheimer’s) 
  • In some cases, genetic screening can help with insurance reimbursement for certain tests
• Colon cancer screening should begin no later than age 40 
  • Colonoscopies can prevent colon cancer by detecting and removing polyps
  • Risks of colonoscopies are low but not zero (e.g., electrolyte abnormalities, hypertension, bleeding, perforation)

Whole Body MRI for Cancer Screening

• High sensitivity but low specificity 
  • Can detect cancer but may also identify non-​​cancerous abnormalities
  • Patients should be prepared for potential false positives and further investigation

• Cost of whole body MRI is around $2,500

  • Prinuvo is a company that offers whole body MRI services
    Interview on Neurodegenerative Diseases

• Guest: Chief Technology Officer and Head Radiologist of a diagnostic company

• Technology: Prinuvo scanner, used for diagnostics in various locations across the US
• Company: Biograph, based in the Bay Area

Neurodegenerative Disease Overview

• Age-​​related cognitive decline is common, but the slope of decline can be controlled
• Alzheimer’s dementia represents a steep acceleration of cognitive decline
• Alzheimer’s is the most prevalent form of dementia and neurodegenerative disease 
  • Affects roughly 6 million people in the US (about 2% of the population)
• Other neurodegenerative diseases: Lewy Body dementia, Parkinson’s disease, multiple sclerosis, ALS, Huntington disease
• Vascular dementia is not Alzheimer’s dementia but produces comparable symptoms

Alzheimer’s Disease and Genetics

• Age is the major risk factor for Alzheimer’s, but it’s not modifiable
• APOE gene has three isoforms: E2, E3, and E4 
  • E4 isoform is the original, offered protection against infections (especially parasitic infections in the CNS)
  • E3 isoform appeared 50,000 years ago, E2 isoform appeared 10,000 years ago
• E4 genes are highly associated with Alzheimer’s risk but are not deterministic 
  • Deterministic genes: PSEN1, PSEN2, and APP (make up about 1% of Alzheimer’s cases)
  • People with deterministic genes usually develop Alzheimer’s in their 50s

Controversy Surrounding Alzheimer’s Disease

• Index case for Alzheimer’s had an APP mutation, leading to an overemphasis on amyloid beta
• Amyloid beta is responsible for changes in the brain, but its importance is unclear 
  • Autopsies show some people with no cognitive impairment have brains full of amyloid plaques
  • Many drugs targeting amyloid have been unsuccessful
• Histopathological hallmarks of Alzheimer’s: plaques and tangles 
  • This understanding is now being questioned

Reducing Risk of Neurodegenerative Diseases

• Focus on modifiable risk factors as we age
• Understand the role of genetics, such as APOE isoforms, in Alzheimer’s risk

• Continue researching the importance of amyloid beta and other factors in Alzheimer’s development
  Link Between APP and Alzheimer’s Disease

• APP mutation leads to extra cleavage of amyloid, resulting in misfolding and plaque formation

  • Plaque predisposes individuals to neurofibrillary tangles
• Some early papers in Alzheimer’s research were falsified, setting the field back a decade 
  • Current state of the field is uncertain due to lack of efficacy in anti-​​amyloid therapies and biomarkers

Factors Affecting Brain Health

• Unequivocally true factors for brain health: 
  • Sleep matters
  • Lower LDL cholesterol and apob is better than higher
  • Not having type 2 diabetes matters, being insulin sensitive matters
  • Exercise matters
    • Minimum effective dose: 1 hour of low-​​intensity cardio, 1 hour of strength training, 1 hour of interval training per week
• Avoid head injuries 
  • Sports injuries, car accidents, construction sites, military, etc.
  • Best course of action after a head injury is to avoid further head injuries

Hyperbaric Oxygen for Traumatic Brain Injury (TBI)

• Emerging treatment option, but not yet rigorously studied
• Dom D’Agostino: no convincing evidence yet, but still being researched
• Hyperbaric oxygen is beneficial for wound healing, but other claims (e.g., telomere extension) are not well-supported
• For TBI, the protocol involves 5–6 sessions per week at 2 atmospheres 
  • Time-​​consuming and costly, but potentially beneficial for concussion recovery

Supplements for Brain Health

• Many supplements are considered for brain health, but evidence is unimpressive 
  • Examples: TheraCumin, magnesium with L‑threonate, methylated vitamins, EPA, DHA
• Potential benefits may outweigh potential costs, but the impact is likely small compared to the “big four” factors for brain health 
  • Exercise, sleep, insulin sensitivity, and lipid management

Accidental Death

• Two categories: accidental death and automotive death
• Accidental deaths can include falls, hiking accidents, and other unexpected events

• Importance of taking precautions to avoid accidental death and prioritizing overall safety and well-​​being
  Accidental Deaths and Their Causes

• Automotive accidents, falls, and overdoses are the top three causes of accidental deaths

  • Accidental deaths are a significant number of deaths once above 20 years old
  • Car accidents are constant throughout life, slightly more common under 60 than over 60
• Fentanyl-​​related deaths have become a major issue, especially for those under 65 
  • Fentanyl is being found in counterfeit drugs, including opioids, sedatives, and even stimulants like Adderall
  • Deaths from fentanyl poisoning are primarily due to respiratory inhibition
  • Fentanyl-​​related deaths have increased by almost 20% per year since 2019

Deaths of Despair

• Deaths of despair include suicide, alcohol-​​related deaths, and accidental overdoses 
  • These numbers have been increasing rapidly, driven primarily by fentanyl use
  • In 2021, there were approximately 210,000 deaths of despair in the United States, up from 180,000 in 2020 and 150,000 in 2019

Accidental Deaths in Aging Population

• For those over 65, the risk of accidental death from falls is extremely high 
  • Falls can lead to immediate death or set off a chain of events leading to death within twelve months
  • 12-​​month mortality rate after a fall-​​related injury (e.g., broken femur or hip) for those 65 or older is between 15% and 30%

Preventing Falls and Maintaining Muscle Health

• Ability to jump and land is correlated with a lower risk of falls or less severe injuries from falls

  • Hallmark of aging in muscles is atrophy of type 2 (fast-​​twitch) muscle fibers
  • To age well, it’s essential to engage in training that strengthens and minimizes the atrophy of type 2 fibers 
    • This includes strength training, reactivity training, explosive training, and training that involves jumping and landing
  • Eccentric strength (brakes) is also crucial, as injuries are more likely to occur during the eccentric phase of movement
    Stepping Down vs. Stepping Up

• Stepping down is more likely to cause injury than stepping up

  • Stepping down requires applying brakes, which is where people often falter
  • Walking downhill is more challenging than uphill due to the need to slow down

Broad Jump as a Test

• Broad jump is a good test for explosive movement and landing stability 
  • Aim to jump 6ft and stick the landing
  • Indicates the ability to control muscles and maintain balance

Aging and Falls

• Older people are more susceptible to falls and injuries 
  • Example: Author’s mother tripped on an uneven stone and broke her hand
  • Broken bones in older age can lead to immobility, muscle loss, and decreased quality of life

Four Pillars of Longevity Through Exercise

1. Strength
2. Stability
3. Aerobic efficiency

4. Aerobic peak output

5. Aim to maximize the area of the “pyramid” (aerobic base and peak)

6. Stability training is crucial for aging well and preventing falls

Emotional Health

• Emotional health is an important aspect of longevity and quality of life 
  • Without good emotional health, increased lifespan may be a curse
• Emotional health is the hardest to define and manage 
  • Author’s greatest struggle and top risk factor for longevity

• Emotional health is essential for overall well-​​being and should be addressed alongside physical and cognitive health
  Defining Emotional Health

• Emotional health is difficult to define and quantify

  • Components of emotional health include: 
    • Connectivity with others and maintaining healthy relationships
    • Having a sense of purpose
    • Regulating emotions
    • Experiencing fulfillment and satisfaction
    • Being present in the moment
• Emotional health deficits are common and can be addressed through self-​​awareness and effort

The Importance of Presence

• Presence is a strong predictor of happiness 
  • A study by Dan Gilbert’s Lab found that the degree of presence in an activity was a stronger predictor of happiness than the activity itself
  • Presence is a fairly rare feature for most people and may require more effort in modern times
• Balancing presence with other aspects of life can be challenging 
  • For example, being present with children while also managing other responsibilities and thoughts

Struggling with Presence

• Even those who appear to be present may struggle with maintaining focus and staying in the moment 
  • The mind can easily wander to other tasks or concerns
  • Recognizing this tendency and working to improve presence can lead to better emotional health and overall well-being