#022 Peter Attia, M.D. on Macronutrient Thresholds for Longevity & Performance, Cancer & More
Dr. Peter Attia, founder of Attia Medical, discusses longevity, the role of diet in aging, and managing growth pathways like mTOR and IGF-1. He also explores Alzheimer's disease risk factors, the importance of insulin sensitivity, and the potential of metabolic strategies for brain health and injury.
Deep Dive Analysis
11 Topic Outline
Introduction to Dr. Peter Attia and Longevity Interests
Challenges in Defining an Optimal Longevity Diet
Understanding mTOR and IGF-1 Growth Pathways
Role of Amino Acids, Insulin, and Carbohydrates in Growth Pathways
Dietary Strategy for Optimizing Macronutrient Intake
The Role of the Gut Microbiome and Inflammation in Aging
ApoE Genotype, Alzheimer's Disease, and Lifestyle Factors
Comparing Cardiac Disease and Alzheimer's Disease Trends
Alzheimer's Disease as Brain Diabetes: A Hypothesis
Brain Metabolism: Lactate, Ketones, and Traumatic Brain Injury
Cancer Metabolism: Warburg Effect and Mitochondrial Function
6 Key Concepts
mTOR Pathway
mTOR, or mammalian target of rapamycin, is a central protein complex responsible for growth in both positive and pathologic senses. It forms two complexes, mTORC1 and mTORC2, with different activities in various tissues, and its overactivity is linked to aging and diseases like cancer.
IGF-1 Pathway
IGF-1 is a growth factor crucial for muscle growth, repair, and neuronal growth. While essential, excessive IGF-1 can promote the growth of damaged cells, contributing to diseases of aging like cancer.
IGF-Binding Protein 3 (IGF-BP3)
IGF-BP3 is a protein that binds and carries IGF-1 in the bloodstream, regulating the amount of active or bioavailable IGF-1. Its levels are inversely related to insulin, meaning lower insulin leads to higher IGF-BP3, reducing free IGF-1.
Neuronal Energy Problem (Alzheimer's)
This hypothesis suggests Alzheimer's disease is fundamentally a problem with neurons' ability to generate energy, akin to brain diabetes. It posits that difficulty getting glucose into the Krebs cycle leads to the disease, with tau plaques and synapse issues being byproducts.
Lactate Shuttle Hypothesis
This theory describes how lactate, generated by astrocytes from glucose, is shuttled into neurons to be used as an energy source. Neurons preferentially use lactate because it is thermodynamically favorable and can directly enter the TCA cycle in mitochondria.
Warburg Effect
In cancer cells, the Warburg effect describes their preference for glycolysis (using glucose for energy) even in the presence of oxygen. This is thought to be an optimization strategy for producing cellular building blocks more quickly, rather than due to dysfunctional mitochondria.
8 Questions Answered
There is no definitive answer, but the approach involves consuming the least amount of protein needed to maintain and grow muscle mass, and the lowest amount of carbohydrates tolerated while maintaining low fasting insulin and limiting post-meal glycemia, with fat filling the remainder of caloric needs.
While the exact amount is unknown, extrapolating from animal data, five grams of leucine during a workout is likely not harmful, especially since free amino acids have a relatively short stay in the body.
Carbohydrates play a role in the IGF-1 pathway indirectly via insulin, as lower insulin levels lead to higher IGF-binding protein 3 (IGF-BP3), which reduces the amount of free, active IGF-1.
Measuring endotoxin release into the bloodstream can serve as a proxy for gut barrier breakdown, but there are concerns about false positives and the lack of a reliable, clinically approved diagnostic test for chronic cases.
Yes, the ApoE2-2 genotype is considered protective against Alzheimer's disease.
The high association between Alzheimer's disease and type 2 diabetes/hyperinsulinemia suggests it may be 'brain diabetes,' a neuronal energy problem, driven by insulin resistance, rather than solely a natural consequence of aging.
Exogenous beta-hydroxybutyrate (BHB) can bypass the impaired glucose metabolism in injured neurons, shunting directly into the TCA cycle and providing an alternative, thermodynamically favorable energy source, thereby overcoming the energy deficit caused by trauma.
Cancer cells are thought to optimize for cellular building blocks, using glycolysis as a quicker, albeit less efficient, process to generate ATP in exchange for components needed for rapid cell proliferation, rather than due to inherently defective mitochondria.
19 Actionable Insights
1. Avoid Smoking
Do not smoke, as it is the single most impactful behavioral change one can make to reduce the risk of heart disease.
2. Optimize Protein Intake
Consume the least amount of protein necessary to maintain and grow muscle mass, but no more, as over-consumption may over-activate growth pathways like mTOR, which are linked to aging and disease. Individual needs vary based on timing, quality, and exercise stimulus.
3. Lower Carbohydrate Intake
Reduce carbohydrate intake to the lowest tolerable point that allows for maintaining a fasting insulin level below 3-4 IU and limiting post-meal hyperinsulinemia (e.g., insulin below 30 one hour after a 75g glucose challenge). This strategy helps keep IGF and mTOR growth pathways in check, which are relevant to aging and disease.
4. Limit Refined Carbs & Sugar
Avoid highly refined carbohydrates, added sugars, and sodas, as their consumption is strongly associated with cancer and inflammation, which can damage the body and contribute to diseases like Alzheimer’s.
5. Prioritize Insulin Sensitivity
Strive to be as insulin sensitive as possible, as this reduces the risk for virtually every disease state, including Alzheimer’s disease, by improving neuronal energy metabolism.
6. Use Fat as Caloric Fill
After optimizing protein and carbohydrate intake according to individual needs and metabolic parameters, use dietary fat to fill the remaining caloric requirements.
7. Sip Leucine During Workouts
If taking branched-chain amino acids during a workout, focus on leucine (around 5 grams) and sip it throughout the workout, as it has a short stay in the body and preferentially stimulates muscle growth.
8. Monitor ApoB/LDL Particle Number
Monitor ApoB or LDL particle number as the single best biomarker for distinguishing your risk of cardiac disease, as it is more predictive than other cholesterol markers.
9. Support Gut Health with Fiber
Consume certain types of fiber from vegetables and fruits to feed beneficial gut bacteria, which generate signaling molecules that positively affect the immune system and reduce inflammation.
10. Be Mindful of Fat’s Gut Impact
Be aware that fat intake can be hard on the gut, and its effects may depend on factors such as whether it’s consumed with protein, existing gut health, and exercise levels.
11. Ensure Adequate Micronutrients
Pay attention to micronutrient intake, such as zinc and magnesium, as they are essential cofactors for enzymes and proteins involved in processes like DNA repair and keeping cancer cells in check.
12. Consider Multi-Day Fasting
Explore multi-day fasting to induce ketosis, which can provide alternative brain fuel (ketones like BHB) and may help overcome neuronal energy deficits.
13. Limit Alcohol with ApoE4
If you have an ApoE4 allele, limit alcohol consumption, as it can induce damage that your body may not repair as well, increasing your risk for Alzheimer’s disease.
14. Avoid Supplemental Antioxidants (with Cancer)
If you have cancer, avoid supplemental dietary antioxidants, as they may blunt the reactive oxygen species signaling that can push primed cancer cells towards death.
15. Increase Brain Insulin Sensitivity
Increase the insulin sensitivity of your brain to reduce the probability of neuronal energy shortage, which can improve your odds for delaying or eliminating Alzheimer’s disease, especially if you have an ApoE4 allele.
16. Consider Exogenous BHB for TBI
For traumatic brain injury (TBI), consider the administration of exogenous beta-hydroxybutyrate (BHB) to overcome neuronal energy deficits and potentially reduce damage.
17. Use Podcast YouTube Videos
For technical discussions, watch the accompanying YouTube video for the podcast, as it includes helpful annotations and dictionary definitions for complex terms.
18. Curate Email Newsletter Subscriptions
Unsubscribe from unnecessary email newsletters (e.g., coupons, horoscopes, penny stock tips) to make room for high-value content like the Found My Fitness newsletter.
19. Support Found My Fitness Podcast
Support the Found My Fitness podcast by pledging a few dollars a month at foundmyfitness.com/crowdsponsor to help fund its content.
6 Key Quotes
That's a fact, but is it a reason?
Dr. Peter Attia
Every one of us has cancer. I mean, at this moment, I have millions of cancer cells in my body, as do you.
Dr. Peter Attia
If the people who live to 100, 105 were all dying in car accidents and plane crashes, you might make the argument that there's two classes of citizens, right?
Dr. Peter Attia
The name of the game is delaying the onset of the big three. The big three being the diseases that will kill 75% of us. So cerebrovascular and cardiovascular, cancer and neurodegenerative.
Dr. Peter Attia
Reducing IGF to only 55% is irrelevant. You could argue 100 different things.
Dr. Peter Attia
Cancer cells are primed to die. So this is the whole basis, most of the basis, behind how chemotherapeutic drugs work.
Dr. Rhonda Patrick