Notes for: Outlive

title: Outlive: The Science & Art of Longevity author: Peter Attia published: 2023 edition: 1 ISBN: 978-0593236604

Introduction

• fast deaths are acute injuries and infections for example
• slow deaths are chronic diseases
• Modern medicine (Medicine 2.0) focuses on treating fast deaths and reacting to slow deaths after diseases manifest
  • Medicine 2.0 follows benchmark for health indicators to prescribe treatments
  • but individuals are different and conditions may not manifest
  • it may also be too late to stop chronic diseases
  • inaction may end up causing more harm
• Medicine 3.0 (proposed by the author) emphasises proactive prevention of slow deaths
• The Four Horsemen of slow deaths
  • Type 2 Diabetes and metabolic dysfunction
  • Heart disease (Atherosclerotic Cardiovascular Disease ASCVD)
  • Cancer
  • Neurodegenerative Disease
• Healthspan, not just lifespan, is the focus. To live better (quality) for longer, maintaining physical and cognitive function.

The Four Horsemen

• genetics definitely play a part and increase our inherent risk
• but a lot of risk also comes from our diet and lifestyle
• after learning about the four horsemen, it seems like eating too much coupled with lack of exercise is really a core problem to most diseases.

Type 2 Diabetes / Metabolic Dysfunction

• metabolic dysfunction is the core as it is highly correlated to most chronic diseases
• it boils down to eating too much glucose
• when there is too much glucose in your blood, it will be converted to fats
• the next symptom is visceral fats (fat around the organs)
• Nonalcoholic Fatty Liver Disease NAFLD is highly correlated with obesity and hyperlipidemia (excessive cholesterol)
  • liver turns fatty when it needs to store excess glucose in the blood as fats, and more fats enters than exits the liver
  • the next stage of the disease is Nonalcoholic Steatohepatitis NASH, which is fatty and inflamed liver like hepatitis
• NAFLD and NASH are reversible, as the liver is a very resilient, almost miracle organ. Most common approach is to fight obesity.
• a note on fructose, they are metabolised differently from glucose and will take a shortcut to be stored as fats in our liver
  • so drinking large quantity of liquid fructose (found in all our syrups and drinks) is bad
• insulin resistance is the next symptom to surface after fatty organs
  • when too much glucose is in the blood, the pancreas need to produce more insulin
  • insulin is a hormone to signal to cells to absorb sugar from the blood
  • the cells build resistance to insulin, becoming a vicious cycle where more insulin is required to regulate glucose level
  • eventually, the pancreas becomes overworked, leading to diabetes

Heart Disease

• lipoproteins, are part protein and part lipid molecules. The protein is responsible for transporting the lipid part in our blood around the body, because lipid are not water-soluble.
  • Low-density lipoprotein LDL is commonly known as the “bad cholesterol”
  • High-density lipoprotein HDL is commonly known as the “good cholesterol”
  • but technically there is no difference between the lipid carried by both proteins.
  • so objectively speaking lipids are not bad for your body, they are essential for our body to function
  • LDL tends to get stuck in our blood vessels due to its molecular structure (it can also oxidise and react with other molecules to cause blockages)
  • which is why LDL is correlated with higher risk of heart diseases
  • the LDL protein part is called apolipoprotein B (apoB), and to be more specific, this is the protein signature that causes problem
• there is insufficient evidence to correlate cholesterol ingested in our diet with the cholesterol circulating in our body
  • most of the cholesterol in our blood is produced by our own body
• metabolic dysfunction, when insulin resistance has occurred, causes liver to produce more LDL
  • it also interferes with production of HDL, lowering HDL level
  • insulin resistance also interferes with cholesterol absorption, which stimulate production of more LDL
  • therefore fixing metabolic problems, by improving diet and lifestyle, can also lower LDL

Cancer

• cancer is a disease of aging, and it becomes more prevalent as we age
• cancer is hard to detect, and it is hard to treat. every cancer is different
• cancer cells don’t grow faster than normal cells, their main problem is they don’t stop growing
  • a gene called PTEN mutated and no longer signals to the cell to stop growing
• cancer is also a problem because of metastasis, which spreads the cancer to other parts of the body
• cancer metabolism is slightly different from normal cells
  • normal aerobic cellular respiration converts glucose to many ATP, yielding energy for the cells
  • the Warburg effect or anaerobic glycolysis, where cancer cells consume a lot of glucose but only produce a small amount of ATP and a lot of chemical by-products
  • almost as if producing energy is a by-product, and those chemical outputs are the main objective
  • finding sites with high glucose concentrations indicate possible presence of tumours
  • those chemical products are useful building blocks to create new cells, promoting cancer cells to proliferate
• therefore, again this links to too much glucose in the blood, and obesity is also strongly correlated with cancer
• while we cannot prevent genetic mutations causing cancer, we can prevent too much glucose from providing a hotbed for cancer to thrive
• immunotherapy is a promising and emerging field for treating cancer
• early detection is key, therefore the author recommends getting tested once in a while even when you feel perfectly healthy

Neurodegenerative Diseases

• Alzheimer’s disease is caused by a handful of mutation in some specific genes that promotes accumulation of certain protein in the brain
  • although there are also reports that shows that patients without build up of those proteins (like Amyloid-beta) also exhibits symptoms of the disease
  • detection is usually too late, and modern medicine has not been able to cure this disease
  • the same can be said for other diseases like Parkinson’s (which affects movements)
• one way to slow the damage
  • building cognitive reserves (brain’s capacity to perform) by doing new stimulating tasks
  • building movement reserves (the body’s capacity to perform) by exercising
• the brain metabolise glucose differently by absorbing glucose directly from the blood, without insulin signals
  • this ensures the brain is a top priority to function in our body
  • insulin resistance, and prolonged period of high blood glucose level, will damage the brain (mechanistically)
  • hippocampus has high concentration of insulin receptors, and high insulin level is affecting memory functions
• deep sleep is like a garbage collection process
  • poor or disrupted sleep increases risk of dementia
  • accompanied by high stress and elevated cortisol levels, it multiplies the risk
  • hypercortisolemia (excess cortisol due to stress) inhibits release of melatonin, which makes sleep more difficult
• some other approaches that can help
  • surprisingly, oral and gum health is related to inflammatory markers, which seems to correlate with the disease
  • therefore, brush and floss regularly
  • regular saunas (4 x 20min sessions, 82 degree Celsius) seems to also help reduce risk
  • intake of vitamin B and omega-3 fatty acid also seems to help
• strategy in summary
  • what is good for the heart is also good for the brain (vascular health)
  • what is good for the liver is also good for the brain (metabolic health)
  • time is key, start early
  • most powerful prevention is exercise

Framework and Tactics

Exercise

• therefore four pillars to take note of

Aerobic Efficiency: Zone 2

• long, steady-state cardio for mitochondrial health and fat oxidation
• approximately 70-85 percent of peak heart rate
• the talk test - the exercise is working you hard, but you are still able to talk and complete a sentence
• zone 2 output is highly variable and based on individual fitness
• about 3 hours per week (4x 45 mins sessions)
• measure the watts we produce per kg of our mass to track our zone 2 progression
  • 2 watts/kg, for a reasonably fit person
  • 3 watts/kg, very fit
  • 4 watts/kg, professional athletes

Maximum Aerobic Output: VO2 Max

• Interval training for cardiovascular fitness and longevity
• Longer intervals than HIIT, ranging from 3-8 minutes
  • e.g. 4 mins high effort, 4 mins jogging pace, 6 reps

Strength

• building and maintaining muscle mass
• this is crucial to prevent muscle loss that comes from aging, and also help maintain body functions
• we lose muscle faster as we get older
• bone density also improves when we perform high load-bearing activity
  • bones respond to mechanical tension
  • estrogen is the key hormone in mediating the mechanical signal (weight-bearing) to a chemical one, telling the body to lay more bones
• actions to focus on, which helps with movements at older age
  • grip strength
  • concentric (muscle shortening) and eccentric (muscle lengthening) loading for all movements.
    • this allows us to lift weights up and put them back down, steadily with control.
    • eccentric strength in our quads is what allows us to move down hill safely without injuring our knees
  • pulling motions
  • hip-hinging movements

Stability

• as we age, our muscle loss accelerates. if we are injured and that disrupts our training routine, it will snowball our decline
• therefore, not injuring ourselves is important
• proper breathing
• proper forms during training
• mobility trainings

Nutrition

• the key questions to answer before we solve our problems are
  • are we under-nourished or over-nourished
  • are we under-muscled or adequately muscled
  • are we metabolically healthy or not
• depending on our current state, some diets may or may not suit us

Categories of Diet

• Caloric Restriction CR
  • make sure we take in fewer calories without compromising on nutrients
  • it is challenging as we need to measure our intakes and fight the hunger to not snack or cheat
• Dietary Restriction DR
  • avoid intake of specific type of food
  • this only works if it also results in CR
  • perhaps because your main problem is consuming too much soda, and you are cutting it for example
  • so it is specific to individual needs, and not all diet will work for everyone if it doesn’t address the specific problem
• Time Restriction TR
  • also called intermittent fasting
  • this cuts calories as it limits the time we eat
  • but a common downside is we end up protein deficient
  • it will be worst if a person ends up losing weight because of muscle loss
  • but it may be necessary to use fasting to perform a metabolic reboot in extreme cases

Macronutrients

• alcohol
  • there is no health benefit to alcohol.
• carbohydrates
  • it is the primary source of energy
  • but overconsumption causes increased blood glucose level, which is bad
  • continuous glucose monitoring CGM can be a useful tool, even for healthy people, to monitor changes in glucose levels as we go about our daily lives
• lessons from CGM
  • refined carbs causes faster and higher glucose spike.
  • less processed carbs (contains more fibre), blunt the glucose impact. recommend 50g of fibre a day? (that’s a lot)
  • rice and oatmeal are surprisingly glycemic (cause sharp rise in glucose level)
  • brown rice is only slightly less glycemic than long-grain white rice
  • fructose does not get measured by GCM
  • timing, duration, intensity of exercise affects glucose level
    • aerobic exercise is most efficacious at removing glucose from circulation
    • high-intensity exercise and strength training tend to increase glucose transiently
  • bad night sleep or less sleep causes a jump in peak glucose response and overall levels
  • stress, via cortisol and other stress hormones, impact glucose level even while fasting or having CR.
    • it is difficult to quantify, but it is most obvious during sleep or periods long after meal, when the body releases more glucose into circulation
  • non-starchy vegetables (broccoli, spinach) have virtually no impact on blood sugar
  • foods high in protein and fat (eggs, beef short ribs) have no effect on blood sugar
  • but large quantity of lean protein (chicken breast) elevates glucose level slightly.
  • protein shakes, especially if low in fat, have a more pronounce effect on elevating glucose level
  • stacking all above effects in positive or negative directions, can be powerful
  • tracking our own behaviour using CGM may create its own Hawthorne effect, which compels us to change our behaviour
• protein
  • recommended amount 1.6g protein per kg body mass per day for maintenance
  • for active people, can consume up to 2.2g per kg
  • it can be a lot of protein, so recommended to split into 4 servings a day
  • no need to worry about consuming too much
  • the most important macronutrients
• fats
  • it has a bad rap of leading to higher cholesterol
  • fats are important to maintain metabolic balance and brain health
  • eating fats makes us feel more satiated than eating carbs
  • all food always contains all groups of fats, saturated fatty acid SFA, monounsaturated fatty acids MUFA, and polyunsaturated fatty acids PUFA.
    • PUFA can be separated into omega-6 and omega-3 variants
    • omega-3 can be subdivided in to marine (EPA, DHA) and non-marine (ALA) sources.
    • marine sources e.g. are salmon and seafood
    • non-marine sources e.g. are flaxseeds and nuts
  • some food like olive oil contains more MUFA, but it still contains other fat groups
  • recommended fats consumption
    • boost MUFA consumption to 50-55% of total fats
    • SFA cut down to 15-20%
    • make up the remaining with PUFA
  • in practice
    • eat more olive oil, avocado, nuts
    • cut back on butter and lard
    • reduce omega-6 rich oil like corn, soybean, sunflower oil
    • increase high omega-3 marine PUFAs from seafood (almost always requires supplement for EPA and DHA)

Best Diet

• it is the one you can sustain
• aim to lower calorie intake
• increase protein intake and build muscle mass
• control lipid levels
• while also reducing blood glucose level

Sleep

• poor sleep affects metabolic health, cognitive function, immune system, and emotional well-being

How to improve sleep

• don’t drink alcohol
• don’t eat anything less than 3 hours before bedtime (ideally longer). it is ok to sleep with just a little bit of hunger
• abstain from stimulating electronic, beginning two hours before bed
• at least one hour before bed (if not, more) avoid doing anything anxiety-producing or stimulating
• hot shower or sauna or hot tub prior to bed. hitting a cool bed and lowering body temperature signals your brain the time to sleep
• room should be cool. cool mattress can help. mid-60s F (or 17-19 C)
• darken room completely. eye shade can help.
• provide ample time to prepare for bed
• fix wake-up time, even on weekend
• don’t obsess over our sleep. clock-watching makes it harder to fall asleep. anxiety over our sleep metrics also affects our sleep.

Emotional Health

• seek help from therapist
• we might be struggling with some trauma that we are not aware of
• it affects our relationships with others
• we can be fit and healthy mechanically, but having miserable relationships with those around us, which contradicts our focus on healthspan