#26 - AMA #3: supplements, women's health, patient care, and more
In this AMA episode, Dr. Peter Attia and Bob Kaplan discuss optimal lab reference ranges, women's health, and nutritional strategies like fasting and ketosis for females. They also cover advice for medical students, podcast monetization, and insights on supplements like lithium, berberine, and nicotinamide riboside.
Deep Dive Analysis
22 Topic Outline
Introduction to AMA Episode and Video Release
Peter's Approach to Lab Reference Ranges
Defining Reference Ranges vs. Optimal Ranges
Specific Optimal Ranges for Lipids and Metabolic Markers
Thyroid Hormone Interpretation and Optimal Ranges
Omega-3 Index and Cholesterol Synthesis Markers
IGF-1 Levels and Cycling for Optimal Health
Least Understood Aspects of Women's Health
Fasting and Ketosis Considerations for Females
Advice for Medical Students and Residents
Monetization Strategy for The Drive Podcast
Using Continuous Glucose Monitors (CGM) for Behavioral Control and Calibration
Thoughts and Experience with Lithium Supplementation
Insights on Berberine Supplementation
Rationale and Evolving Science on Baby Aspirin Use
Understanding Heart Rate Variability (HRV) and Its Personal Use
Saturated Fat, Coconut Oil, and Nutritional Epidemiology
Nicotinamide Riboside (NR) Supplementation for Longevity
Recommended Supplement Brands
Finding a 'Peter Attia Clone' Doctor
Personal Experience with Critical Care and Patient Engagement
Latest on ApoE4 and Alzheimer's Disease Prevention
8 Key Concepts
Reference Ranges
Population-based distributions for lab tests that evolve over time, often representing 10th-90th percentile or two standard deviations from the mean. These differ from optimal ranges, which are chosen to optimize for specific health outcomes.
LDL Particle Number (LDL-P)
A measure of the total number of LDL particles. Peter believes this number ought to be below 1000 nmol/L, which is about the 20th percentile, because heart disease is the most ubiquitous cause of death.
Heart Rate Variability (HRV)
The beat-to-beat variation in the time between heartbeats, measured in milliseconds. Higher HRV generally indicates a more parasympathetic (rest and digest) state, while lower HRV can signal stress, overtraining, or poor recovery.
Continuous Glucose Monitor (CGM)
A medical device that measures glucose levels in real-time, providing immediate feedback on how food and activity impact blood sugar. It serves as a powerful behavioral tool and allows for precise calibration of diet and exercise.
Hemoglobin A1C (HbA1c)
A blood test reflecting average blood glucose levels over 2-3 months, based on the assumed lifespan of red blood cells. Peter finds it less helpful than CGM data due to variability in red blood cell lifespan and its inability to show glucose variability.
AMPK Activation
A cellular process stimulated by compounds like metformin and berberine. Its net effect is to decrease hepatic glucose output, signaling the liver to make less glucose.
PCSK9 Inhibition
A mechanism by which berberine (weakly) and certain drugs reduce the degradation of LDL receptors. This leads to lower LDL particle numbers and cholesterol, particularly effective in individuals who overexpress PCSK9.
NAD Precursors (NR/NMN)
Compounds like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are thought to increase cellular NAD+ levels. Recent research suggests oral supplementation primarily benefits the liver, as other cells cannot directly take up these precursors or NAD itself.
16 Questions Answered
He generally takes a harder line on triglycerides (below 100 mg/dL), LDL particle number (below 1000 nmol/L), small LDLP (below 500 nmol/L), oxidized LDL (below 40), C-reactive protein (below 1), uric acid (below 5.0), and ALT/AST (below 20).
Reference ranges are typically statistical norms derived from a population, often representing the 10th to 90th percentile or two standard deviations from the mean. Optimal ranges, in Peter's view, are chosen based on a belief system about what should be physiologically ideal for health, often aiming for levels outside the statistical average.
Peter highlights the profound impact of sex hormone fluctuations during the menstrual cycle and the abrupt loss of estrogen, progesterone, and testosterone during menopause, which he feels is often disregarded by doctors. He also notes an empirical observation about the HPA axis and thyroid function after multiple pregnancies.
He advises caution for women trying to get pregnant, as elevated ketones (signaling food scarcity) may suppress FSH and LH. During pregnancy, while historically possible, he is unsure if it's optimal and suggests a focus on avoiding junk food and refined carbohydrates instead of deliberate ketosis.
He suggests studying a subject they love in college instead of pre-med, finding ways to help others (like tutoring MCAT students) to reignite enthusiasm, maintaining balance between study and other activities, and frequently interacting with patients to remember the privilege and awe of medicine.
He prefers a listener-supported model (like Sam Harris or Rhonda Patrick) or a subscription-based podcast network (like Netflix for podcasts) over traditional advertising, due to concerns about potential subconscious influence from advertisers.
He uses it as a powerful behavioral tool to control his food choices and avoid glucose spikes, and to calibrate how activity levels, nutrient deprivation, and 'treat' consumption minimize damage. He views it as essential feedback, similar to an RPM tack in a race car.
While acknowledging epidemiological data linking higher groundwater lithium to better mental health, he initially experimented with high doses (600mg/day) under strict medical supervision but found the side effects (nausea) outweighed the benefits. He now takes a low, over-the-counter dose (10-20mg) viewing it as a low-risk, potentially low-reward intervention.
Berberine is a plant extract that acts as a weak AMPK activator (similar to metformin, reducing hepatic glucose output) and a weak PCSK9 inhibitor. He finds its PCSK9 inhibition property more clinically useful, especially in patients with high LDL who might overexpress PCSK9.
Historically, he took it due to a strong family history of heart disease and a positive 'aspirin works' test, aiming to reduce thrombotic events. However, recent studies on low-risk populations show the benefits are very small and often a wash with the small risks (bruising, ulcer), leading him to re-evaluate his personal use and practice.
He uses it to assess sympathetic vs. parasympathetic states, with higher HRV generally indicating better recovery. Personally, he monitors it daily (via Oura Ring) to understand the impact of overtraining, alcohol, poor food choices, and meal timing on his recovery and sleep quality, and as a harbinger of illness.
He dismisses the article as relying on nutritional epidemiology, which he considers the 'lowest form of human inference' due to unreliable data collection (food frequency questionnaires) and low hazard ratios. He believes the case for saturated fat being universally harmless is overstated and that individual responses vary.
He is currently unconvinced that oral NR or NMN supplementation does anything other than enrich supplement companies. Based on recent research, it appears only the liver can take up oral NR/NMN and convert it to NAD; other cells cannot, suggesting only intravenous NR/NMN might increase cellular NAD.
He primarily relies on Jarrow and Pure Encapsulations for most supplements. For EPA/DHA, he recommends Nordic Naturals and Carlson's.
He is not currently accepting new patients due to the team being overworked. He acknowledges the difficulty in finding similar doctors and suggests a future 'matchmaking service' where patients can define what they seek in a doctor, and physicians can post their approaches.
Peter punts this question, stating that he will be conducting a deep-dive interview with neurologist Richard Isaacson (who runs an Alzheimer's prevention clinic) specifically on Alzheimer's and ApoE, which will be released soon.
46 Actionable Insights
1. Prioritize Sleep for Quickest Benefit
Recognize that sleep deprivation causes the quickest and most severe health decline. Prioritize getting sufficient, high-quality sleep as it has the most immediate impact on your overall well-being.
2. Optimize Bedroom Temperature
Set your bedroom temperature to be as cold as humanly possible, aiming for a level where you feel incredibly uncomfortable when first getting under the covers, for optimal sleep quality.
3. Avoid Late-Night Carb-Heavy Meals
Refrain from consuming carb-heavy or ‘shitty’ meals close to bedtime, as this can increase your respiratory rate and diminish sleep quality and recovery.
4. Commit Deeply to Your Health
Dedicate as much effort and emphasis to managing your health as you would to any other deeply cared-for pursuit, such as a hobby or investment, to achieve meaningful results.
5. Be an Engaged Patient
Thoroughly understand your lab results and actively participate in your healthcare discussions, as engaged patients extract the most value from their healthcare team.
6. Critically Evaluate Nutritional Studies
Be highly skeptical of nutritional epidemiology studies, especially those relying on food frequency questionnaires, due to their inherent limitations and often low hazard ratios, which can lead to misleading conclusions.
7. Demand Absolute Risk Data
When evaluating health claims or study results, always consider both relative and absolute risk, along with the study duration, as relative risk alone can be highly misleading.
8. Use CGM for Behavior Control
Utilize a Continuous Glucose Monitor (CGM) as a powerful behavioral tool to avoid unhealthy food choices by making glucose spikes visible and undesirable, thereby motivating healthier eating habits.
9. Calibrate Diet & Activity with CGM
Employ CGM data to empirically calibrate how different activity levels, periods of nutrient deprivation, and consumption of treats affect your glucose levels, allowing you to minimize metabolic damage.
10. Aim for Low Glucose Variability
Monitor your glucose standard deviation via CGM and strive for low glucose variability, as this serves as a good proxy for maintaining low insulin levels and better overall metabolic health.
11. Cycle IGF-1 Levels
Instead of consistently maintaining low IGF-1, aim to cycle your IGF-1 levels between high and low, potentially through strategies like fasting and refeeding, to promote tissue regeneration and rejuvenation.
12. Set Stringent Triglyceride Goals
Aim to keep your triglycerides below 100 mg/dL, and ideally lower than your HDL cholesterol (when both are measured in mg/dL), as a more stringent goal than typical lab ranges.
13. Target Optimal LDL Particle Number
Strive to keep your LDL particle number (LDL-P) below 1000 nmol/L, which is approximately the 20th percentile, to significantly reduce your risk of atherosclerotic disease, the most common cause of death.
14. Reduce Small LDLP Levels
Aim to keep your small LDLP below 500 nmol/L, targeting the 25th percentile for improved cardiovascular health.
15. Lower Oxidized LDL Target
Aim for oxidized LDL levels below 40, a more stringent criterion than the typical lab ‘reasonable’ level of 60, to further mitigate cardiovascular risk.
16. Maintain Low C-Reactive Protein
Strive to keep your C-reactive protein (CRP) below 1, which is a more aggressive target than most labs’ ‘reasonable’ level of 2, to indicate lower systemic inflammation.
17. Control Uric Acid Levels
Aim to keep your uric acid levels below 5.0, a stricter goal than typical lab ’normal’ ranges of 6 or 7, to potentially avoid other health consequences beyond gout.
18. Optimize Liver Enzyme Levels
Target ALT and AST levels below 20, which is considerably lower than the typical lab upper limits of 40-44, for optimal liver health.
19. Aim for Optimal Fasting Glucose
Strive to keep your fasting glucose below 90 mg/dL as a key indicator of good metabolic health.
20. Maintain Low Fasting Insulin
Target a fasting insulin level below 6 to indicate healthy insulin sensitivity.
21. Manage Post-Glucose Challenge Levels
Following a 75-gram glucola challenge, aim for 1-hour glucose below 120-130 mg/dL and insulin below 20-30, with 2-hour glucose returning below 100 mg/dL and insulin ideally below 20 or 2x the 1-hour glucose.
22. Optimize Thyroid Hormone Levels
Aim for TSH between 0.5 and 2.0, free T3 above 3.0, and reverse T3 below 12 for biochemically optimal thyroid function, even if symptoms suggest otherwise.
23. Target High EPA/DHA Index
Strive for an EPA/DHA index above 8.5%, and potentially up to 10-12% if no adverse effects like nosebleeds, to optimize fatty acid balance for neurodegenerative and atherosclerotic axes.
24. Monitor Desmosterol with Statins
If taking statins, monitor desmosterol levels and aim to keep them above 0.5 to avoid overly suppressing cholesterol synthesis, exercising caution at the individual level.
25. Avoid Ketosis for Fertility
If a woman is trying to get pregnant, exercise caution with nutritional ketosis, as calorie restriction and elevated ketones can suppress reproductive hormones (FSH and LH).
26. Rethink Ketosis During Pregnancy
The speaker is not convinced that deliberate ketosis is the optimal nutritional strategy for women during pregnancy, despite its ancestral prevalence.
27. Eliminate Junk Food & Refined Carbs
A foundational nutritional strategy is to eliminate junk food, sugar, and highly refined carbohydrates from your diet.
28. Choose College Major by Passion
If considering medicine, study something you genuinely love and are obsessed with mastering in college, rather than just pre-med, as medical school will cover the foundational science in depth.
29. Mentor Others to Combat Burnout
When feeling unhappy or overwhelmed in demanding situations like medical training, find someone who aspires to be in your position and help them, as this can rekindle your enthusiasm and perspective.
30. Maintain Work-Life Balance
During intense periods like medical school or residency, consciously allocate time (e.g., 15% of your non-sleep hours) to replenishing activities like exercise, pleasure reading, or socializing to prevent burnout.
31. Seek Patient Interaction in Training
Frequently interact with patients during medical school to remember the unique privilege and awe of the patient-doctor relationship, which can be a powerful motivator against the challenges of medicine.
32. Support Podcasts Directly
If you value a podcast and wish to avoid ads, consider supporting it through a listener support model, which allows content creators to remain independent.
33. Pay Attention to Unsponsored Products
Note products that are recommended without sponsorship, as these are likely genuine endorsements based on personal preference and use.
34. Strive for Higher Heart Rate Variability
Aim for a higher heart rate variability (HRV) as it indicates greater parasympathetic nervous system activity, reflecting a state of rest and recovery.
35. Avoid HRV-Lowering Habits
Be aware that overtraining, alcohol consumption, and poor food choices close to bedtime can significantly lower your HRV and increase your resting heart rate, negatively impacting recovery.
36. Personalize Recovery with HRV Data
Use daily HRV data from wearables (like the Aura Ring) to empirically adjust lifestyle factors such as alcohol intake, meal timing, and room temperature, to find your optimal recovery state.
37. Adjust Activity Based on Readiness Score
Utilize a wearable’s readiness score as an indicator of your body’s recovery, especially after intense cardio workouts, and adjust your training intensity or prioritize rest accordingly.
38. Consider Low-Dose Lithium
Taking low-dose lithium (10-20 mg, over-the-counter) may offer potential mood stabilization benefits with low risk, but its value is considered low-reward and should be discussed with a physician.
39. Do NOT Self-Prescribe High-Dose Lithium
Never take high-dose lithium (e.g., 600 mg/day) without extremely careful medical supervision, including constant blood level monitoring, due to significant risks of side effects and toxicity.
40. Consider Berberine for Glucose/LDL
Berberine, a plant extract, can act as a weak AMPK activator to decrease hepatic glucose output and may weakly inhibit PCSK9, potentially lowering LDL in some individuals; try it to see if LDL improves.
41. Re-evaluate Baby Aspirin for Low Risk
Based on recent studies, if you are in a low-risk population for heart disease, re-evaluate the necessity of taking a baby aspirin, as the benefits may not outweigh the small risks.
42. Walk on Flights, Not Aspirin
Instead of relying on baby aspirin to prevent blood clots on long flights, prioritize getting up and walking around as much as possible, as data does not support aspirin for this purpose.
43. Avoid Oral NAD Precursors (NR/NMN)
Be skeptical of oral nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) supplements, as current research suggests only the liver can effectively take them up and convert them to NAD, limiting systemic benefits.
44. Avoid NAD Infusions
Do not pursue NAD infusions, as cells cannot directly take up NAD; it must be synthesized intracellularly, rendering infusions ineffective for increasing cellular NAD.
45. Choose Reputable Supplement Brands
For general supplements, rely on reputable brands like Jarrow and Pure Encapsulations. For EPA/DHA, consider Carlson’s or Nordic Naturals to ensure quality.
46. Leave a Podcast Review
If you enjoy the podcast, please go to Apple and review it, as this is a valuable way to support the show. If you don’t like it, do not review it.
7 Key Quotes
To be average on the disease that is the most common strikes me as just backwards mathematics.
Peter Attia
If you're trying to optimize to be a rower, a heavyweight rower, you know, someone who rows crew, you'd obviously want to be probably between six foot two and six foot four. Again, I'm making that up. But the point is showing you that you would pick a range that's completely outside of the statistical norm, because you're optimizing for something very particular in that case rowing.
Peter Attia
At any point in life where you're sitting somewhere and you're in a situation and you think it sucks, go and find someone who would give their left nut to be in your situation and go and help them out.
Peter Attia
If the answer isn't hell, yes, don't do it. Cause it's all downhill from there.
Peter Attia
I just can't stand to see spikes of glucose. It just drives me nuts.
Peter Attia
This to me is trying to pick up a penny, call it a dollar inflation. It's picking up a dollar in front of a tricycle. Yeah. At the end of the day, Hey, it's a dollar. It's a dollar more than I had before. And if I'm wrong, the tricycle hitting me is not a lot of work. What you never really want to do is pick up dollars in front of trains.
Peter Attia
I am completely unconvinced that taking supplemental NR or even NMN by mouth is doing anything other than enriching the companies that make those things.
Peter Attia