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Exercise, Nutrition, Hormones for Vitality & Longevity | Dr. Peter Attia

Episode 85 Aug 15, 2022 2h 47m 57 insights
My guest this episode is Dr. Peter Attia, M.D., who trained at Stanford University School of Medicine, Johns Hopkins Hospital and the National Institutes of Health (NIH). Dr. Attia is host of The Drive podcast and is a world expert on behavioral approaches, nutritional interventions, supplementation and pharmacological techniques to improve lifespan, healthspan and athletic performance. We discuss how best to evaluate your health status using routine blood work, body scans and regular tests of physical strength and endurance. Dr. Attia explains what he uses with his patients to “back-cast” their health goals as a way to design their exercise and nutritional programs. We also discuss hormone modulation and replacement therapy for both men and women. We explain how cholesterol and related factors contribute to cardiovascular disease risk and how to monitor and mitigate that risk. Dr. Attia details various supplementation, nutrition, exercise and prescription approaches useful to people in every decade of life to improve vitality, reduce their risk of disease and increase the number of years sustaining peak cognitive and physical health.  For the full show notes, visit hubermanlab.com.
Actionable Insights

1. Define Your ‘Marginal Decade’

Envision and detail what your ‘marginal decade’ (the last decade of your life) should look like, including desired activities and capabilities. This ‘backcasting’ exercise provides a clear objective to design a personalized health program.

2. Backcast Health Goals

After defining your marginal decade, ‘backcast’ by determining the necessary health metrics (e.g., VO2 max, strength) at earlier ages to achieve those future goals. Then, identify current health gaps and design interventions to bridge them.

3. Focus on Lifespan & Healthspan

Adopt a health strategy focused on extending both lifespan (living longer) and healthspan (living better). This involves addressing the ‘four horsemen of disease’: atherosclerotic disease, cancer, neurodegenerative disease, and metabolic disease, which are the primary threats to longevity.

4. Attia’s Rule: Foundational Health First

Prioritize foundational exercise goals (e.g., VO2 max at 75th percentile, dead hang for at least 1 minute, wall sit for at least 2 minutes) before debating nuances of diet or supplements. This ‘Attia’s Rule’ emphasizes mastering core physical capabilities as a prerequisite for advanced health discussions.

5. Maximize Cardiorespiratory Fitness (VO2 Max)

Strive for elite cardiorespiratory fitness (top 2.5% for age and sex in VO2 max) to achieve a 5x reduction in all-cause mortality compared to the bottom 25%. This is identified as the single strongest modifiable behavior for longevity.

6. Prioritize Strength for Longevity

Aim for high strength levels, as low strength is associated with a 250% greater risk of all-cause mortality compared to high strength. This emphasizes the importance of strength training beyond just muscle mass.

7. Prioritize Strength Training for Bone Health

Engage in strength training, particularly powerlifting, as it’s identified as the most effective method for improving bone mineral density by applying shear force to bones. This is especially critical for females before age 25, as it sets a lifelong trajectory for bone health.

8. Lifelong Strength Training for Bones

Continue strength training throughout life, even after the developmental window, to prevent age-related decline in bone mineral density, especially for women post-menopause. It’s never too late to start, and it’s essential to never stop.

9. Full Body Strength Training

To maximize bone mineral density benefits, train the entire body, as the effect of strength training on bone density is primarily local to the loaded bones.

10. Strength Training with Heavy Loads

For strength training, focus on moving heavy loads (80% of 1RM or more) with low repetitions (1-6 reps) and long rest periods, 2-3 times per week. Adapt exercises to individual experience and safety, such as using a leg press for beginners instead of deadlifts.

11. Achieve Dead Hang Goals

Aim for a dead hang of 1.5 minutes for a 40-year-old woman and 2 minutes for a 40-year-old man, adjusting for age and gender. This serves as a measure of grip strength and overall fitness.

12. Achieve Wall Sit Goals

Aim for a 90-degree wall sit of 2 minutes for both men and women at age 40. This serves as a measure of quad strength and stability.

13. Perform Farmer Carries

For men, aim to farmer carry your body weight (half in each hand) for two minutes; for women, aim for 75% of body weight for two minutes. This assesses grip strength, mobility, and overall strength.

14. Exercise for Brain Health

Prioritize regular and substantial exercise, as it is the single most important intervention for brain health, impacting BDNF, vascular endothelium, glucose disposal, and insulin signaling, among other benefits. More exercise leads to greater benefits.

15. Start with 15 MET-Hours/Week

If currently sedentary, aim for at least 15 MET-hours of exercise per week (e.g., three one-hour brisk walks) to achieve a significant reduction (around 50%) in Alzheimer’s risk. Recognize that more exercise offers further benefits.

16. Elevate Marginal Decade Expectations

Shift your perspective on the ‘marginal decade’ from merely performing basic functions to actively engaging in life. Use backcasting to ensure daily behaviors align with higher functional goals.

17. Target Low ApoB for Longevity

For those aiming for extreme longevity (e.g., living to 100), strive to keep ApoB levels below 30 mg/dL, as ApoB is the causative agent of atherosclerosis. Maintaining low levels from a young age can prevent its development.

18. Proactive Atherosclerosis Prevention (Post-45)

For individuals over 45, consider aggressive strategies, often involving statins or other ApoB-lowering drugs (80% of patients in Attia’s practice), to prevent atherosclerosis. This is crucial as it’s the leading cause of death globally.

19. Treat Causative Agents, Not Risk

Adopt a ‘Medicine 3.0’ approach by treating the causative agents of disease (e.g., high ApoB, high blood pressure) proactively, rather than waiting until a 10-year risk assessment (which is heavily skewed by age) indicates a high probability of an event.

20. Individualized Health Optimization

Approach health optimization from an individual perspective, focusing on what is best for personal longevity and healthspan, rather than societal or economic considerations. This simplifies complex health problems.

21. Diet for ApoB Reduction

To reduce ApoB, restrict carbohydrate intake to lower triglycerides and reduce saturated fat intake. These dietary changes can help lower both cholesterol and triglyceride levels, which contribute to ApoB.

22. Consider Statins for ApoB Reduction

For significant ApoB reduction, consider pharmacologic interventions like statins, which inhibit cholesterol synthesis and increase LDL receptors on the liver, pulling LDL out of circulation. Statins generally have a benign side effect profile, with muscle soreness in about 5% of users.

23. Ezetimibe for Cholesterol Absorption

If dietary and lifestyle interventions are insufficient, consider ezetimibe, a drug that blocks cholesterol absorption in the gut. Responsiveness can be predicted by measuring phytosterol levels, with higher levels indicating better response.

24. Bempedoic Acid for Liver Cholesterol

As an alternative to statins, consider bempedoic acid, which blocks cholesterol synthesis specifically in the liver. It has a similar mechanism but fewer side effects, though it may not be as potent as statins.

25. PCSK9 Inhibitors for Potent ApoB

For the most potent ApoB reduction, consider PCSK9 inhibitors, which are antibodies that prevent the degradation of LDL receptors. This leads to significantly lower LDL cholesterol and ApoB levels, effectively mimicking natural immunity to heart disease.

26. Early LP(a) Screening

Get screened for LP(a) early in life, ideally around age 20, as it’s a genetically determined and prevalent driver of atherosclerosis. This marker only needs to be checked once and can provide crucial insight into early cardiovascular risk.

27. Purposeful Blood Testing

Conduct blood tests with a clear purpose, such as monitoring changes, evaluating interventions (e.g., drug efficacy, body composition changes), or rechecking concerning levels, rather than testing just for the sake of it. For patients under active intervention, testing 2-4 times a year is typical.

28. Annual DEXA Scan for Key Metrics

Get an annual DEXA scan to assess bone mineral density, visceral fat, appendicular lean mass index, and fat-free mass index, as these are more crucial health indicators than just body fat percentage. Ensure the machinery is calibrated and operated by a knowledgeable professional for accurate results.

29. Optimize Free Testosterone (Men)

Focus on optimizing free testosterone levels, aiming for approximately 2% of total testosterone, rather than just total testosterone. High SHBG (Sex Hormone Binding Globulin) can reduce free T; address underlying drivers like estradiol, insulin, and thyroxine.

30. Target Free Testosterone Levels

When considering testosterone therapy, the primary target is free testosterone, aiming for levels that provide clinical benefit and fall within the upper normal physiological range, even if it means total testosterone exceeds typical ranges.

31. Assess Clinical Benefit of TRT

Evaluate whether normalizing free testosterone to the upper normal physiological range will provide clinical benefits, considering symptoms (e.g., low libido, fatigue) and biomarkers like insulin resistance, which testosterone can improve.

32. Delay TRT if Fertility Desired (Men)

If a man wishes to maintain fertility, avoid direct testosterone replacement therapy (TRT) as it can reduce total sperm count. Instead, consider HCG or delay TRT until after reproduction is complete.

33. Delay TRT for Young Men

Young men (e.g., in their 20s) should generally delay TRT, especially if fertility is desired, and instead explore options like HCG to preserve testicular function, unless all other lifestyle factors are optimized and hypogonadism persists.

34. HCG for Testicular Function (Men)

For men with testicular reserve who need to stimulate endogenous testosterone production and preserve testicular function, HCG (human chorionic gonadotropin) can be used as an ongoing therapy, typically via subcutaneous injection, as an alternative to Clomid.

35. Consider Clomid for Testicular Reserve

For men with low testosterone due to insufficient pituitary signaling but intact testicular reserve, a short course (8-12 weeks) of Clomid (50mg three times a week) can stimulate endogenous testosterone production. Note: The speaker’s practice no longer uses Clomid due to concerns about desmostrol levels.

36. Physiologic TRT Dosing (Men)

When pursuing TRT, use low, physiologic doses (e.g., typically no more than 100mg per week, often 70mg twice a week) of testosterone cypionate via subcutaneous injection. This approach aims to normalize free testosterone without the side effects (bloating, acne, hair loss) seen with supraphysiologic doses.

37. Cycle TRT with HCG

Consider cycling TRT (e.g., 8 weeks on testosterone, 8 weeks on HCG) to maintain testosterone levels while fluctuating between endogenous and exogenous production. Alternatively, cycle testosterone on and off to assess natural replenishment.

38. TRT Enhances Capacity, Not Results

Understand that TRT primarily provides the capacity to work harder, recover better, and enhance muscle protein synthesis; it is not a standalone solution. Benefits are only realized when combined with consistent exercise and appropriate nutrition.

39. Leverage Testosterone’s Psychological Effect

Recognize that testosterone, whether endogenous or exogenous, can psychologically make effort feel more rewarding by adjusting amygdala activity. Use this effect to motivate increased physical and mental work.

40. Manage Estradiol for SHBG (Men)

For men with high SHBG due to elevated estradiol (from high aromatase activity), consider using a microdose of an aromatase inhibitor (e.g., anastrozole at 0.1mg 2-3 times/week) to lower estradiol and subsequently reduce SHBG.

41. Microdose Anastrozole for High Estradiol

If estradiol levels exceed 55-60 ng/dL in men on TRT, consider microdosing compounded anastrozole (e.g., 0.1mg two to three times a week) to bring levels into the optimal 30-50 ng/dL range, as higher doses can lead to negative side effects.

42. Address Thyroid Health for SHBG (Men)

Ensure thyroid function is optimal, as an imbalance in thyroxine (T4) can interfere with SHBG levels. Fix any thyroid issues before attempting to modulate SHBG.

43. Preserve DHT Levels (Men)

Avoid substances that impede DHT (dihydrotestosterone) as maintaining appropriate DHT levels can significantly improve well-being, even if it means accepting potential side effects like hair loss.

44. Testosterone Therapy for Women

For women with staggeringly low testosterone levels, difficulty building muscle mass, and low libido, consider topical testosterone therapy to restore levels to a physiologically normal range, though data for this intervention is less robust than for estrogen in women or testosterone in men.

45. Progesterone for PMS Symptoms

For women experiencing PMS symptoms, consider stabilizing progesterone levels during the luteal phase (second half of the menstrual cycle) with a low dose of progesterone, which can alleviate symptoms.

46. IUD for Progesterone Delivery

If a woman cannot tolerate systemic oral progesterone for uterine protection (e.g., due to side effects), consider using a progesterone-coated IUD to deliver local progesterone to the uterus while still allowing for systemic estrogen therapy.

47. Hydration and Electrolyte Protocol

Ensure proper hydration and electrolyte intake by dissolving one packet of Element in 16-32 ounces of water first thing in the morning and during any physical exercise. This is critical for optimal brain and body function, as even slight dehydration can diminish cognitive and physical performance, and electrolytes are vital for cell function, especially neurons.

48. Utilize Meditation and NSDR

Engage in meditation, yoga nidra, or non-sleep deep rest (NSDR) protocols, even for short durations like 10 minutes, to restore cognitive and physical energy and place the brain and body into different states. Apps like Waking Up can provide various programs and durations to suit individual needs.

49. Minimize Environmental Distractions for Focus

To improve focus, actively manage your environment by eliminating distractions like email, social media, and unnecessary internet access, as external stimuli are a major impediment to concentration.

50. Alpha-GPC for Focus

Consider taking 300mg of Alpha-GPC occasionally (1-2 times a day, 1-2 times a week) before cognitive work or workouts to subjectively enhance focus.

51. Nicotine for Cognitive Enhancement (Caution)

Nicotine, in non-smoking forms like lozenges, can be a concentration-enhancing substance, potentially safer than prescription stimulants for cognitive performance. However, it is addictive, and users must be extremely cautious with dosage (e.g., 1mg per cigarette, lozenges often 4-8mg) and be aware of individual addiction potential.

52. GLP-1 Agonists for Weight Management (Caution)

GLP-1 agonists like semaglutide are effective for weight loss, primarily through central hypothalamic effects and improved insulin sensitivity, but they are catabolic, leading to muscle loss alongside fat loss. Dosing typically ranges from 1-2mg weekly, and patients should be aware of potential nausea and the importance of continued behavioral work and avoiding caloric drinks like alcohol to maximize benefits and prevent weight regain.

53. Explore Metabolomics for Health

Stay informed about the emerging field of metabolomics, which studies metabolites and their profiles in various physiological states. This frontier may reveal small molecules that can replicate some protective benefits of exercise, potentially combined with exercise or used as treatments for diseases like diabetes.

54. Rapamycin for Ovarian Health (Future)

While currently only supported by impressive animal models, keep an eye on future clinical trials for rapamycin, as it shows promise as a potent geroprotective molecule that could preserve and extend ovarian health in women.

55. Skepticism on Unproven Therapies

Approach unproven therapies like stem cells, PRP, and BPC-157 with skepticism, as there’s insufficient clinical trial data to confirm their efficacy or whether they fix underlying problems. Focus on interventions with robust evidence, acknowledging the opportunity cost of pursuing unvalidated treatments.

56. Prioritize Consistent Rehab Over ‘Quick Fixes’

For injury recovery, prioritize consistent, dedicated, and often uncomfortable rehabilitation protocols over seeking ‘quick fixes’ like unproven injections. The hard, boring work of rehab is essential for true recovery and functional improvement.

57. Tongkat Ali for Free Testosterone (Mild)

Tongkat Ali may help free up some testosterone by reducing SHBG and can increase libido, though the exact mechanism is unclear and effects are not dramatic.