Dr. Rhonda Patrick: Micronutrients for Health & Longevity

Dr. Rhonda Patrick

• Dr. Rhonda Patrick is a podcaster and educator in the fields of mitochondria, metabolism, stress, and brain and body health
• Her podcast, Found My Fitness, is a leading source of information on brain and body health, behavioral tools, micronutrients, supplements, and other protocols
• Dr. Patrick’s research focuses on mitochondrial metabolism, apoptosis (healthy cell death), and cancer biology
• She has published articles in prestigious journals such as Science, Nature, Cell Biology, and Trends in Cell Biology

Micronutrients for Brain and Body Health

• Dr. Patrick discusses the major categories of micronutrients essential for brain and body health
• She provides clear explanations of the biological mechanisms of micronutrients and actionable tools for optimizing brain and body health
• Dr. Patrick also discusses behavioral protocols, such as the use of heat and cold for optimizing metabolism, longevity, and cardiovascular health

Intermittent Challenges and Hormesis

Plants and Hormesis

• Debate on whether plants are good or bad for us 
  • Some compounds in plants can be harmful, but in small amounts, they provide a hormetic response
  • Example: Sulfurophane in broccoli and broccoli sprouts 
    • Activates NRF2 pathway, which helps detoxify carcinogens
    • Can negate increased cancer risk in individuals with certain genetic predispositions
    • Broccoli sprouts have up to 100 times more sulfurophane than broccoli
  • Cooking can reduce sulfurophane levels, but adding mustard seed powder can increase it

Cold and Heat Exposure

• Cold and heat exposure can activate stress response pathways 
  • Example: Heat shock proteins activated by both cold and heat
  • Overlap between stressors and the genetic pathways they activate
• Appropriate doses of cold and heat exposure can be beneficial 
  • Too much cold or heat can be harmful or even lethal
    Broccoli and Mustard Seed Powder Benefits
• Eating cooked broccoli with mustard seed powder can recover beneficial compounds 
• Lightly steaming broccoli and adding mustard seed powder provides a slightly spicy taste
• Consuming broccoli and mustard seed powder can activate the NRF2 pathway, which has various health benefits

Moringa Powder Benefits

• Moringa powder is a cousin to sulfuraphane and activates the NRF2 pathway similarly
• Can be added to smoothies for easy consumption
• No affiliation with any specific brand, but Cooley Cooley Moringa powder is science-​​backed and researched by Dr. Jed Fahey

NRF2 Pathway Activation

• Activating the NRF2 pathway can lead to various health benefits
• Preconditioning with sulfuraphane can protect animals from hypoxia or ischemic stroke conditions
• Sulfuraphane may have potential benefits for traumatic brain injury (TBI) and neurodegenerative diseases like Alzheimer’s
• NRF2 is expressed in neurons, lungs, liver, and plasma cells, providing protection to various cells in the body
• DNA damage can be lowered by consuming broccoli sprout powder, which activates the NRF2 pathway

Autism and Sulfuraphane

• Sulfuraphane has been shown in randomized controlled trials to help treat autism and autistic symptoms
• It may have benefits related to oxidative stress and glutathione in the brain, which could be relevant for TBI treatment
  Glutathione and Sulforaphane
• Glutathione increased in the brain after taking sulforaphane 
  • Important because some compounds in supplement form don’t cross the blood-​​brain barrier or get metabolized differently
• More studies needed to determine the impact of glutathione on treatment

Top Nutrients for Brain and Body

• Omega‑3 fatty acids (marine omega‑3 fatty acids) 
  • Found in marine animals, cold water fish, and fatty fish
  • Three types: ALA (plant-​​based), EPA (icosapentinoic acid), and DHA (docahexanoic acid)

Omega‑3 Sources

• Fish oil supplements vs. krill oil supplements 
  • Krill oil: phospholipid form of DHA and EPA
  • Fish oil: triglyceride form (high quality) or ethyl ester form (lower quality, less bioavailable) 
    • Ethyl ester form should be taken with food
• Prescription omega-​​3s: Lavaza (mixture of DHA and EPA) and Vasipa (highly purified EPA) 
  • Prescribed for high triglycerides and dysregulation of lipids
  • Dosage: 4 grams per day

Omega‑3 Recommendations

• Splitting EPA and DHA intake: not necessary but can be done
• Over-​​the-​​counter fish oil supplements can be beneficial for those without a prescription

• Experiment with going on and off supplements to determine personal benefits
  Omega‑3 and Mental Health

• Omega‑3 fatty acids, particularly EPA, have been shown to improve mood and mental health 
• Inflammation plays a significant role in depression 
  • Omega‑3 fatty acids can help reduce inflammation
• Studies have shown that people taking 2–4 grams of EPA per day can experience reduced depressive symptoms 
  • Some people can lower their SSRI dosage or avoid antidepressants altogether
• Omega‑3 fatty acids can also help with bipolar disorder, schizophrenia, and impulsive behavior

Krill Oil vs. Fish Oil

• DHA in phospholipid form (found in krill oil) is more bioavailable than in triglyceride form (found in fish oil)
• However, krill oil supplements are often low in omega‑3 content and can be rancid
• DHA in phospholipid form may be particularly beneficial for people with the APOE4 gene, which increases the risk of Alzheimer’s disease
• The body can also produce phospholipid DHA from triglyceride forms

Omega‑3 Index and Life Expectancy

• The omega‑3 index measures omega‑3 levels in red blood cells, providing a long-​​term marker of omega‑3 status
• The standard American diet has an omega‑3 index of 5%, while Japan has an index of 10–11%
• Japan has a higher life expectancy, which may be partly due to their higher fish and seafood intake
• Studies have shown that people with an omega‑3 index of 4% or lower have a decreased life expectancy compared to those with an 8% index
  Omega‑3 and Health
• Smokers with high omega‑3 levels have the same life expectancy as non-​​smokers with low omega‑3 levels 
• Omega-​​3s help resolve inflammation and affect many parts of the inflammatory pathway
• Omega-​​3s play a role in aging, brain health, mood, and joint health

Food Sources of Omega‑3

• Plant sources: walnuts, flax seeds (rich in ALA)
• Vegan/​​vegetarian option: microalgae oil (contains DHA)
• Fish sources: sardines, salmon, anchovies
• Grass-​​fed meat has higher levels of ALA compared to conventional meat, but conversion to EPA and DHA is inefficient

Supplementation and Omega‑3 Index

• To increase omega‑3 index from 4% to 8%, supplement with at least 2 grams of omega‑3 per day
• Most Americans have an omega‑3 index of 4–5% without supplementation
• Omega‑3 index measures the percentage of omega-​​3s in red blood cells, which take 120 days to turn over
• Omega Quant offers omega‑3 index testing

Research and Conflicting Data

• Conflicting data may be due to measuring plasma omega‑3 levels instead of the omega‑3 index in red blood cells
• More researchers should use the omega‑3 index for accurate results
  Omega‑3 Index and Randomized Controlled Trials
• Omega‑3 index is a better measurement for omega‑3 levels 
• Randomized controlled trials have limitations
• Collaboration among scientists is needed for progress

Omega‑3 and Mood

• Omega‑3 fatty acids regulate inflammation 
  • Resolvens and specialized pro-​​resolving mediators (SPMs) help resolve inflammation
  • EPA and DHA affect leukotrines, prostaglandins, and platelet aggregation
• Inflammation can inhibit serotonin release 
  • EPA and DHA can blunt inflammatory responses, allowing more serotonin release
• DHA is important for cell membrane fluidity 
  • Affects structure and function of receptors and transporters on neurons
  • Deficiency in DHA can affect serotonin and dopamine receptors

Sources of DHA

• Fish is a good source of DHA and EPA
• Salmon roe (fish eggs) is a high source of phosphatidylcholine DHA

Vitamin D

• Produced when in the sun, but efficiency varies based on factors like melanin, age, and sunscreen use
• Darker skin requires more sun exposure to produce the same amount of vitamin D as lighter skin
• 70% of the US population has inadequate vitamin D levels
• Ideal vitamin D levels are between 40–60 nanograms per milliliter
• Vitamin D is a steroid hormone that binds to a receptor and affects various functions in the body
  Vitamin D and Its Importance
• Vitamin D is a steroid hormone 
  • Regulates more than 5% of the protein-​​encoded human genome
  • Affects immune system, blood pressure, water retention, bone homeostasis, and more
• 70% of the US population is deficient in vitamin D 
  • Deficiency linked to higher all-​​cause mortality, respiratory-​​related mortality, cancer-​​related mortality, and increased risk of multiple sclerosis

Vitamin D Synthesis

• Skin is an endocrine organ 
  • Sun exposure triggers the production of vitamin D
  • Efficiency decreases with age
• Vitamin D can be found in fatty fish and fortified foods (e.g., milk, soy milk, almond milk)

Supplementation

• Vitamin D3 is a good form of supplementation 
  • 1,000 IUs of vitamin D raises blood levels by around 5 nanograms per milliliter
• Vitamin D2 is a plant source, often found in fortified foods
• Measure vitamin D levels before and after supplementation to determine effectiveness 
  • Single nucleotide polymorphisms (SNPs) can affect the conversion of vitamin D precursors and impact supplementation needs

Vitamin D and Serotonin

• Vitamin D activates tryptophan hydroxylase 2, an enzyme that converts tryptophan into serotonin in the brain 
  • Serotonin is important for mood regulation
• Vitamin D may also repress tryptophan hydroxylase 1 in the gut

Recommendations

• Get vitamin D levels tested
• Consider supplementation with vitamin D3
• Monitor levels and adjust supplementation as needed
• Time of day and relation to sun exposure may not be crucial factors for supplementation
  Vitamin D and Sun Exposure
• Importance of getting vitamin D levels tested 
• 1,000 to 5,000 IUs of vitamin D3 supplementation considered reasonably safe for most people
• Sun exposure on skin increases hormones like testosterone and estrogen
• Surface area of skin exposed to the sun matters for vitamin D production
• Sunscreen concerns: some compounds in sunscreen can cross the blood-​​brain barrier and be potentially harmful

Magnesium

• 40% of the US population doesn’t get enough magnesium
• Essential mineral involved in vitamin D metabolism, making ATP, and DNA repair enzymes
• Magnesium insufficiency may cause insidious daily damage that is not visible
• DNA repair enzymes require magnesium as a cofactor to function properly
  Magnesium and Diet
• Magnesium is at the center of a chlorophyll molecule 
  • Dark leafy greens are high in magnesium
  • 40% insufficiency in the US due to lack of greens in the diet
• Examples of dark leafy greens: kale, spinach, chard, romaine lettuce
• Cooking can release magnesium from food matrix, but also goes into water 
  • Steaming or incorporating water in cooking can help retain magnesium

Magnesium Supplementation

• Different forms of magnesium: citrate, three and eight, bisclycinate, malate
• Magnesium citrate can cause GI distress at high doses
• Magnesium three and eight may have neuroprotective effects, but more research needed
• Magnesium malate may improve recovery time from exercise

Intermittent Challenges for Health

• Intermittent challenges include: intermittent fasting, cold exposure, heat exposure, exercise
• Cold exposure can lead to long-​​lasting increases in epinephrine (adrenaline) and other neuromodulators
• Cold protocols for metabolism, mood effects, and brown fat stimulation: 
  • 20 seconds of immersion in 49-​​degree Fahrenheit water
  • More research needed to determine optimal protocols
    Cold Exposure and Its Effects
• Cold exposure can increase dopamine levels 
  • Mood-​​enhancing effects can last for hours
  • Different from other dopamine-​​increasing substances (e.g., Adderall, Ritalin, caffeine) that cause a spike and crash
• Cold exposure can cause the release of norepinephrine in the brain 
  • Acts as a hormone and regulates various molecular functions related to cold adaptation
  • Can lead to increased focus and reduced anxiety

UCP One and Cold Adaptation

• Norepinephrine activates a gene called UCP One (Uncoupling Protein One) 
  • Allows mitochondria to produce heat more efficiently than shivering
  • Mitochondria uncouple their energy production, creating heat instead of ATP
• Cold adaptation can lead to increased mitochondria in adipose tissue 
  • Regulated by norepinephrine through a protein called PGC‑1 alpha
  • More mitochondria per adipose cell, allowing for more efficient heat production
  • Referred to as the “browning of fat”

White, Beige, and Brown Fat

• White fat: typical fat cells that store energy
• Beige fat: intermediate fat cells that can be activated to become thermogenic
• Brown fat: fat cells with more mitochondria, darker in appearance, and more efficient at producing heat 
  • Cold exposure can convert white fat to beige fat, and beige fat can take on thermogenic characteristics
  • More cold exposure can lead to more brown fat and better cold tolerance
    Brown Fat and Thermogenesis
• Researchers trying to create a pill to increase brown fat and thermogenesis 
  • Affects metabolism, but not the only factor in weight loss
  • Cold exposure, dietary changes, and exercise also important
• Cold exposure increases mitochondria in muscle tissue 
  • PGC‑1 alpha involved in mitochondrial biogenesis
  • More mitochondria associated with improved muscle mass and endurance

High Intensity Interval Training (HIIT)

• Can increase mitochondrial biogenesis 
  • Especially beneficial for older individuals
  • Helps maintain healthy, young mitochondria
• Dr. Rhonda Patrick’s exercise routine 
  • 3–4 times a week: 10-​​minute high-​​intensity interval Tabata workouts on a stationary bike (Peloton)
  • Competitive aspect of group classes motivates her to push harder
  • Uses sauna after workouts to maintain elevated heart rate and manage stress

Sauna Use

• Dr. Rhonda Patrick started using the sauna in 2009 
  • Noticed improved stress management and reduced anxiety
  • Releases endorphins and dynorphin, which can help with stress and mood regulation
    Dinorphine and Kappa Opioid Receptor
• Dinorphine: endogenous opioid that binds to the kappa opioid receptor 
  • Responsible for dysphoric feelings during exercise or heat stress
  • Negatively impacts dopamine receptor system
• Kappa opioid receptor binding may sensitize mu opioid receptor 
  • Increases sensitivity to feel-​​good endorphins
  • May have lasting effects on mood and well-being

Sauna Use and Memory

• Sauna use may improve memory and learning 
  • Combination of stress response and vasodilation
  • Increased blood flow to the brain
  • Positive association with the context of the sauna
• Studies show a dose-​​dependent effect of sauna use on dementia and Alzheimer’s disease risk 
  • 4–7 times per week: greater than 60% reduction in risk
  • 2–3 times per week: greater than 20% reduction in risk

Sauna Use and Cardiovascular Health

• Sauna use linked to reduced cardiovascular mortality 
  • 4–7 times per week: 50% reduction in cardiovascular-​​related mortality
  • 2–3 times per week: 24% reduction in cardiovascular-​​related mortality
• Dose-​​dependent effect on sudden cardiac death risk 
  • 4–7 times per week: greater than 60% lower risk
• Duration of sauna use also important 
  • 11 minutes: 8% reduction in cardiovascular disease-​​related death
  • 20 minutes: 50% reduction in cardiovascular disease-​​related death

Sauna Use vs. Moderate Intensity Aerobic Exercise

• Sauna use has similar physiological effects to moderate intensity aerobic exercise 
  • Heart rate elevation, blood pressure increase during activity
  • Resting heart rate decrease, blood pressure improvement after activity
• Sauna use may be beneficial for those unable to engage in traditional exercise 
  • Disabled individuals or those with physical limitations
  • Safety concerns should be considered
    Sauna Use and Health Benefits
• Sauna use can improve cardiorespiratory fitness 
  • Synergistic effect when combined with exercise
• Heat stress from sauna use activates heat shock proteins 
  • Helps maintain proper protein structure in cells
  • Prevents protein aggregation in the brain and arteries
  • Associated with protection against Alzheimer’s disease and cardiovascular health
• Heat shock proteins also associated with human longevity 
  • People with more active heat shock protein 70 live longer on average

Sauna Use Recommendations

• 20 minutes at 170 degrees Fahrenheit, 4 times per week 
  • More frequent use may provide additional benefits
• Avoid sauna use if trying to conceive (for men) 
  • Sperm motility and production decrease with heat exposure
  • Returns to normal after 6 months of avoiding sauna use

Alternatives to Sauna Use

• Hot baths can provide similar benefits 
  • 104 degrees Fahrenheit for 20 minutes (shoulders down)
  • Activates heat shock proteins and increases brain-​​derived neurotrophic factor
  • Protects against muscle atrophy from disuse
  • Can be used when injured or unable to exercise
    Sauna and Exercise for Brain Health
• Sauna use and exercise have positive effects on the brain 
  • Mind wandering and problem-​​solving during exercise
  • Exercise as a longevity drug for the brain
• Load-​​bearing exercises release osteocalcin 
  • Acts like a hormone, travels to the hippocampus
  • Induces neuron proliferation, synapse growth, and BDNF release
• Importance of sharing personal protocols 
  • Helps others find a starting point for their own health journey

Red Light Sauna

• Mixed opinions on red light saunas 
  • Some find them not hot enough
  • Acknowledgment of red light and low-​​level light therapies’ benefits 
    • Nobel Prize in 1988 for phototherapy for lupus
    • Positive effects on biology and health