Rhonda Patrick: Latest Insights on Alzheimer’s, Cancer, Exercise, Nutrition, Fasting

Rhonda Patrick on Alzheimer’s Disease and Dementia

• Rhonda Patrick has a personal interest in neurodegenerative diseases due to family history and genetic predisposition
• Alzheimer’s disease field has been focused on the amyloid hypothesis, but there have been many failed trials
• Three major types of dementia: Alzheimer’s disease, small vessel disease, and vascular dementia
• Common risk factors for Alzheimer’s disease: APOE4 allele and type 2 diabetes
• Vascular dysfunction, particularly in the blood-​​brain barrier, seems to be an early event common to all types of dementia, type 2 diabetes, and APOE4

Blood-​​Brain Barrier

• Provides a barrier to prevent unwanted substances from entering the brain
• Allows transport of important nutrients, oxygen, and glucose
• APOE4 and type 2 diabetes can lead to permeability of the blood-​​brain barrier
• Blood-​​brain barrier permeability can be measured in cerebral spinal fluid and plasma
• Occurs decades before the onset of cognitive impairment and is found in more than 50% of all dementias
• Blood-​​brain barrier is essential for removing toxic compounds from the brain through processes like the glymphatic system during sleep

Implications

• Understanding the underlying causes of dementia opens up new avenues for prevention and treatment
• Maintaining the integrity of the blood-​​brain barrier is crucial for brain health

• Blood-​​brain barrier permeability could be a key factor in the development of Alzheimer’s disease and other dementias
  Blood Brain Barrier and Alzheimer’s Disease

• Blood brain barrier dysfunction linked to Alzheimer’s disease

  • Type 2 diabetes doubles the risk of Alzheimer’s disease
  • Disruption of blood brain barrier affects glucose transport and leads to hypometabolism
  • Inflammation and loss of pericytes contribute to blood brain barrier dysfunction

Omega‑3 DHA Transport and Alzheimer’s Disease

• MFSD2A transporter important for omega‑3 DHA transport into the brain 
  • Disruption of this transporter leads to blood brain barrier breakdown and loss of omega‑3 in the brain
  • Transporter decreases with age, rapidly in Alzheimer’s disease, and with APOE4 gene
  • Genetic differences may affect individual response to omega‑3 supplementation

Preventative Measures for Alzheimer’s Disease

• Addressing type 2 diabetes through diet and lifestyle changes
• Ensuring adequate omega‑3 DHA intake, especially for those with genetic predispositions

• Understanding the role of inflammation and blood brain barrier integrity in Alzheimer’s disease development
  Omega‑3 and Blood Brain Barrier Integrity

• Fatty Acid Research Institute investigates the role of omega‑3 in blood brain barrier integrity

• Omega‑3 intake is important for blood brain barrier health
• Low omega‑3 intake from fish identified as one of the top six preventable causes of death
• Omega-​​3s, specifically EPA and DHA, have anti-​​inflammatory properties and are important for brain health

DHA and EPA Importance

• DHA and EPA are both important for brain health
• DHA is specifically transported into the brain, while EPA can diffuse across the blood-​​brain barrier
• Both DHA and EPA have anti-​​inflammatory properties and help resolve inflammation
• Preliminary evidence suggests EPA supplementation may help with depression

Prevention vs. Treatment in Alzheimer’s Disease

• Prevention is a better strategy for Alzheimer’s disease than treatment
• Fixing leaks in the brain and addressing amyloid accumulation is challenging once Alzheimer’s disease has developed
• Prevention strategies include addressing type 2 diabetes, increasing omega‑3 intake, and maintaining overall health
• Type 2 diabetes is not inevitable and can be prevented or managed through lifestyle interventions

Type 2 Diabetes and Aging

• Type 2 diabetes accelerates the aging process and increases the risk of cardiovascular disease, cancer, and Alzheimer’s disease
• Unlike atherosclerosis and cancer, type 2 diabetes is not inevitable with age

• Preventing and managing type 2 diabetes can reduce the risk of other age-​​related diseases and improve overall health
  Type 2 Diabetes and Aging

• Type 2 diabetes accelerates aging

• Morbid obesity often linked to type 2 diabetes and insulin resistance
• Treatment and prevention strategies available, but not always effectively deployed

Blood Pressure and Alzheimer’s Disease

• Hypertension and hyperlipidemia pose risks for cardiovascular disease and Alzheimer’s disease
• Blood pressure may act specifically through the blood-​​brain barrier
• Maintaining good blood pressure is important for reducing Alzheimer’s disease risk
• High blood pressure is associated with dementia risk, especially when developed before midlife
• Cumulative exposure to high blood pressure damages vasculature
• Exercise and sauna can improve blood pressure

Precision Nutrition and Genetics

• In the next decade, more information on precision nutrition may be available
• Genetic makeup can influence response to macronutrient and micronutrient intake
• Advances in technology and AI may lead to exponential growth in understanding gene-​​diet interactions
• Precision nutrition may help clear up conflicting data in nutrition studies

Challenges in Nutrition Studies

• Nutrition studies are often messy and difficult to design
• Confounding factors include baseline levels of nutrients and individual genetic differences
• Comparing nutrition studies to drug trials is difficult due to differences in starting points and outcomes

• Better-​​designed nutrition trials, such as those for vitamin D, are needed to determine the value of supplementation
  Exercise and Brain Health

• Exercise has a greater impact on the reduction of risk of Alzheimer’s disease than any other intervention

  • Other interventions include sleep, nutrition, and managing type 2 diabetes
• Mechanisms by which exercise benefits brain health: 
  • Intensity of exercise matters for neurobiological effects
  • Lactate generation during high-​​intensity exercise 
    • Lactate is used by the brain as an energy source
    • Lactate acts as a signaling molecule, increasing vascular endothelial growth factor (VEGF) and brain-​​derived neurotrophic factor (BDNF) at the blood-​​brain barrier 
      • VEGF helps grow new vessels and repair damaged ones
      • BDNF is important for long-​​term potentiation, neuroplasticity, and memory retention
  • Sheer force of blood flow during vigorous exercise increases BDNF production in endothelial cells lining blood vessels
  • Exercise increases BDNF production in various organs and tissues, including the brain, muscle, and plasma

Lactate and Brain Health

• Lactate was once thought to be a harmful byproduct of exercise, but it is now known to have benefits 
  • Lactate is generated when mitochondria in muscle cells cannot produce enough energy (ATP) during high-​​intensity exercise
  • Lactate is consumed by the brain and other organs as an energy source
  • Lactate acts as a signaling molecule, increasing VEGF and BDNF at the blood-​​brain barrier 
    • VEGF helps grow new vessels and repair damaged ones
    • BDNF is important for long-​​term potentiation, neuroplasticity, and memory retention
• Increasing lactate levels during exercise may have neurobiological benefits

Aerobic Capacity and Brain Health

• Aerobic capacity can be thought of as a pyramid with a wide base and a high peak 
  • The base represents the zone 2 threshold, or how much work can be done while keeping lactate at a low level (around 2 millimole)
  • The peak represents the ability to perform high-​​intensity exercise and generate high lactate levels

• Training at both ends of the spectrum (low-​​intensity and high-​​intensity) is important for maximizing aerobic capacity and brain health benefits
  VO2 Max and Lactate Training

• Pyramid analogy for training: build it wide and tall

• VO2 max sets: 3–8 minutes of all-​​out effort
• Lactate peaks provide benefits to the brain
• Athletes can clear lactate quickly

Tabata Training

• High-​​intensity interval training: 20 seconds on, 10 seconds off
• Generates lactate as a consequence of intensity
• Can be done in various ways to diversify training
• Hard to make performance gains if done all-​​out 5 days a week

Blood Flow Restriction

• Can be used to increase lactate levels during weightlifting
• Pooling lactate in legs during lower body workouts, then releasing it systemically

Training Zones

• Zone 2: moderate intensity
• Zone 3: higher intensity
• Zone 4: even higher intensity, held indefinitely for maximum wattage
• Zone 6: maximal effort, only sustainable for 10 seconds
• Functional Threshold Power (FTP): maximum power one can hold for 1 hour, used to set training zones in cycling and Peloton

Peloton and FTP Test

• Peloton ranks users based on average wattage or kilojoules
• FTP test on Peloton measures average wattage over 20 minutes, multiplied by 0.9

• Zones 1–7 are a function of power, not heart rate, and are based on FTP number
  High-​​Intensity Interval Training (HIIT) and Sauna Use

• High-​​intensity interval training (HIIT) can increase mitochondrial biogenesis

  • Forces adaptations on mitochondria to make more mitochondria
  • Can be done in a short amount of time (10 minutes a day)
• Strength training can also provide benefits in a short amount of time (30 minutes a day, 4 times a week) 
  • Requires focus and intensity during the workout
• Sauna use can improve memory and increase heat shock proteins and brain-​​derived neurotrophic factor (BDNF)
  • Temperature typically between 175–180°F
  • Duration between 20–30 minutes
  • Can be done after a workout or at a different time of day
• During pregnancy, sauna use may be avoided due to potential risks to the fetus 
  • Exercise during pregnancy can still provide benefits
• Hot tub use at night can help improve sleep quality 
  • Can be done in addition to sauna use during the day

• Exercise intensity may be linked to reduced dementia risk and improved cognitive function
  Cognitive Health and Exercise

• Effort and time put into exercise correlates with cognitive health benefits

• Longitudinal study on women and Alzheimer’s risk 
  • Women with higher cardiorespiratory fitness had a significant reduction in Alzheimer’s risk
  • Moderate fitness levels also showed a reduction in risk
• Questionnaire studies show a linear dose-​​response effect 
  • More effort and training led to greater benefits in reducing dementia risk

Gender Differences in Exercise Response

• Women have a higher risk of Alzheimer’s disease than men
• Possible differences in metabolic, hormonal, and immune system responses to exercise
• No clear data on gender differences in exercise response

Exercise and Cancer

• Elite athletes (Olympians) have a lower risk of dying from cancer 
  • 1.5 to 2 years of life saved from not dying from cancer
  • 5 to 6 years of overall lifespan extension compared to the general population
• Cancer prevention studies focus on aerobic exercise 
  • Certain types of cancer more responsive to exercise, such as breast and colon cancer
  • Lifetime risk of breast cancer for women is 1 in 8, colon cancer is 1 in 23 for women and 1 in 25 for men

• Strength training studies focus on cancer-​​related mortality, not prevention
  Exercise and Cancer Prevention

• Breast and colon cancer show robust response to physical activity

  • Cancer mortality reduced by 50%
  • Cancer recurrence reduced by 50%
• More exercise needed for cancer prevention than cardiovascular benefits 
  • 300 minutes a week of moderate intensity exercise or 150 minutes of vigorous exercise recommended
• Exercise may have direct effects on cancer prevention 
  • Myokines decrease growth factors secreted by cancer cells
  • Anti-​​inflammatory response from exercise
• Exercise improves insulin sensitivity and weight loss, which can reduce cancer risk
• Physical activity can reduce cancer metastasis and mortality 
  • Sheer force from blood flow during exercise can kill circulating tumor cells
• Exercise is the only panacea for reducing risk of cancer, Alzheimer’s disease, dementia, cardiovascular disease, and type 2 diabetes

Exercise, Obesity, and Satiety

• Exercise makes individuals more sensitive to satiety hormones
• Exercising individuals have a better sense of nutrient requirement
• Exercise provides a feedback loop for energy balance and nutrient intake

• Exercise is important for overall health and cancer prevention, despite challenges with obesity and hunger signals
  Alcohol Consumption and Health Risks

• Moderate drinking in women can increase the risk of breast cancer

  • Some studies suggest a lifetime risk of 1 in 6
• Obesity and physical inactivity also impact breast cancer risk
• No amount of alcohol is considered healthy 
  • Low doses (4–7 drinks per week) may have immeasurable harm
• Alcohol consumption can negatively affect sleep 
  • Poor sleep is linked to increased Alzheimer’s and cardiovascular disease risk
• APOE4 carriers may be more susceptible to the harmful effects of alcohol 
  • They may also be more affected by poor sleep

Exercise and Sleep

• Wearing a continuous glucose monitor (CGM) can show the effects of sleep interruption on glucose levels 
  • Exercise can help counteract these effects
• Poor sleep is associated with higher all-​​cause mortality, but only in people who are not physically active 
  • Exercise can “forgive” many health sins

Protein Intake and Muscle Mass

• Competing ideas in science: 
  • Lower protein intake is associated with a longer life (mostly from animal studies)
  • Higher protein intake is necessary for maintaining muscle mass and overall health

• Further research is needed to reconcile these ideas and determine optimal protein intake for health and longevity
  Reconciling Protein Intake and Longevity

• Conflicting literature on protein intake and longevity

  • Lower protein intake associated with more frailty and shorter life
  • Higher protein intake potentially linked to cancer risk
• Struggle to find the minimum effective dose of protein 
  • Difficult to measure outside of a lab setting

Animal Studies and Protein Intake

• Animal studies show protein restriction can lead to longer life and reduced cancer risk 
  • However, these studies may not translate well to humans
  • Animals in sterile environments not exposed to same stimuli as humans
  • Mice die from different diseases than humans
• Importance of muscle mass and strength in humans 
  • Exercise and protein intake crucial for maintaining muscle mass and strength
  • Sarcopenia (loss of muscle mass) has devastating effects on aging population
  • Increasing protein intake and strength training necessary to avoid sarcopenia

Questionable Cancer Risk from Higher Protein Intake

• No clear data showing increased cancer risk from higher protein intake in humans
• Need to compare potential cancer risk to the offset of sarcopenia 
  • Sarcopenia has a clear negative impact on mortality
• Confusion may stem from C. elegans studies 
  • Knocking out certain genes doubled lifespan, suggesting low protein intake is key to longevity
  • However, this may not translate well to humans

IGF‑1 and Protein Intake

• IGF‑1 (insulin-​​like growth factor 1) is a growth factor

  • In the context of a tumor, can allow tumor cells to override cell death mechanisms
  • However, it is unclear if higher protein intake significantly increases cancer risk in humans
  • More research needed to understand the relationship between protein intake, IGF‑1, and cancer risk
    IGF‑1 and Protein Intake

• IGF‑1 (Insulin-​​like Growth Factor 1) is important for muscle repair, neurogenesis, and brain health

• Exercise increases IGF‑1 levels in the brain and muscles
• Controversy exists over whether high IGF‑1 levels contribute to tumor growth
• Protein intake and IGF‑1 levels may be related, but the relationship is not well understood

Protein Intake and Aging

• Recommended daily allowance (RDA) for protein may be outdated and too low
• Older adults may need more protein due to anabolic resistance (decreased muscle protein synthesis)
• Aim for 1 gram of protein per pound of body weight (2.2 grams per kilo)
• Protein quality and amino acid content are important factors to consider

Protein Intake Strategies

• Incorporate protein into meals and snacks
• Use protein shakes and supplements to reach protein goals
• Focus on high-​​quality protein sources, such as whey protein and venison jerky sticks
• Protein intake should be a priority in dietary planning, especially for older adults and those engaging in strength training

Strength Training and Bone Mineral Density

• Strength training is important for maintaining muscle mass and bone mineral density

• Protein intake and strength training should be prioritized for overall health and longevity
  Protein Intake and Weight Loss

• Overweight or obese individuals may not need to focus as much on protein intake

  • They can focus on caloric restriction and training to offset lean mass loss
• Protein target of 2 grams per pound for satiating benefits and thermogenic effect
• Time-​​restricted eating can lead to skipping meals and reduced protein intake 
  • Can result in muscle loss, especially without resistance training

Fasting and Time Restricted Eating

• Time restricted feeding can be effective for weight loss with a small enough feeding window 
  • Problem: difficult to get enough protein in a single meal
  • Solution: have protein snacks outside of the feeding window
• Fasting can be at odds with adequate maintenance of muscle 
  • As people age, muscle maintenance becomes a higher priority

Circadian Rhythm and Eating

• Benefits to eating within circadian rhythm 
  • Eating late at night can inhibit insulin secretion and raise glucose levels
• Gut rest and digestion rest are important for DNA repair mechanisms and autophagy 
  • Autophagy occurs when not digesting food
• Exercise can induce autophagy and provide benefits 
  • Unclear how long one would need to fast to achieve similar benefits

• Difficult to extrapolate from mice studies on fasting and autophagy

  • Cumulative effect of eating within circadian window may have a positive impact on metabolism
    Circadian Component and Eating Habits

• Most people in the United States eat within a 15-​​hour window

• Unclear if this is harmful or not, especially for those who exercise
• Circadian component may play a role in the impact of eating habits
• Nighttime food restriction can improve sleep quality

Changing Perspectives and Following Data

• As a scientist, it’s important to reassess beliefs and practices as new data emerges
• Supplements taken and perspectives on health can change over time
• Continual reassessment is necessary due to the constant development of new tools and understanding

Rhonda Patrick’s Content and Platforms

• Found My Fitness podcast
• In-​​depth articles on Foundmyfitness​.com
• Short, to-​​the-​​point content on Instagram and Twitter (@foundmyfitness)

Lactate and Beta-Hydroxybutyrate

• Lactate and beta-​​hydroxybutyrate are both signaling molecules
• Both have effects on traumatic brain injury (TBI) and Alzheimer’s disease
• More research is needed to understand the neurobiological effects of lactate and beta-hydroxybutyrate
• Exercise can produce both lactate and beta-hydroxybutyrate