← The Peter Attia Drive

#19 - Dave Feldman: stress testing the lipid energy model

Oct 8, 2018 3h 10m 37 insights
<p>In this episode, Dave Feldman, discusses his journey from software engineer to n=1 experimenter, his experience with low-carbohydrate diets, and his hypothesis that cholesterol levels are influenced by energy metabolism.</p> <p> </p> <p><strong>We discuss:</strong></p> <ul> <li>Peter's synthesis of Dave's energy model [<a href="">5:00</a>];</li> <li>Dave's journey from software engineer to cholesterol enthusiast [<a href="">15:00</a>];</li> <li>Standard blood panels, sterol panels, and what moves the needle when it comes to particle numbers [<a href="">18:30</a>];</li> <li>Hyper-responders [<a href="">20:00</a>];</li> <li>Lipoprotein transport [33:45];</li> <li>The lean mass hyper-responder phenotype [47:30];</li> <li>The progression of atherosclerosis, CAC, and CIMT [52:30];</li> <li>Testing for oxidized LDL [55:30];</li> <li>All-cause mortality and clinical endpoints [1:01:15];</li> <li>What does "LDL as causal" mean? [1:05:15];</li> <li>Dave's low carb cholesterol challenge and drug & genetic study qualifications [1:13:15];</li> <li>If all other markers are in an healthy range, but LDL-P is high, is the patient at risk? A couple of case studies, and a self-experiment [1:27:30];</li> <li>Peter's three-day exercise and ketosis experiment [<a href="">1:41:00</a>];</li> <li>What are remnant lipoproteins? [<a href="">1:45:00</a>];</li> <li>What might cause lean mass hyper-responders to have higher LDL particle numbers? [1:53:30];</li> <li>A case study from Dave of a lean mass hyper-responder [1:56:30];</li> <li>Mass balance and cholesterol flux [2:05:30];</li> <li>Can a higher degree of cholesterol explain the lean mass hyper-responder phenotype? [<a href="">2:10:00</a>];</li> <li>Peter's LDL during his keto-fast-keto experiment [2:13:30];</li> <li>Does substituting saturated fats with monounsaturated fats lower LDL-P and LDL-C? [2:15:45];</li> <li>Dave's carb-swap experiments [2:22:15];</li> <li>Dave's carotid intima-media thickness tests [2:41:15];</li> <li>Looking for studies that stratify for high HDL-C and low TG alongside low and high LDL-C [<a href="">2:53:00</a>]; and</li> <li>More</li> </ul> <p> <span> Learn more at <a href="http://www.peterattiamd.com/"><span><u>www.PeterAttiaMD.com</u></span></a></span></p> <p> <span>Connect with Peter on <a href=""> <span> <u>Facebook</u></span></a> | <a href=""> <span> <u>Twitter</u></span></a> | <a href=""> <span> <u>Instagram</u></span></a>.</span></p>
Actionable Insights

1. Proactive Diabetes Prevention

If you have elevated fasting glucose or a family history of type 2 diabetes, proactively research and implement strategies to manage blood glucose levels rather than just monitoring.

2. Avoid Echo Chambers

Actively seek out information and perspectives that challenge your existing beliefs from every side, rather than staying within an echo chamber, to foster a more complete understanding.

3. Embrace Scientific Skepticism

Approach scientific inquiry with skepticism and prioritize the pursuit of truth over advocacy for a particular viewpoint or diet, as this fosters genuine understanding.

4. Contextualize Scientific Literature

When evaluating scientific literature, especially in complex fields like lipidology, recognize that the quality and depth of evidence can vary significantly, and avoid applying the same dismissive lens used for less robust fields like past dietary guidelines.

5. Consult Top Field Experts

To gain the deepest and most accurate understanding of complex scientific topics, seek out and engage with the leading experts in that specific field, who may not be found in popular online forums or general conferences.

6. Personalize Health Decisions

Recognize that population-level health data can obscure individual nuances; seek personalized advice to understand what specific health strategies are most relevant and beneficial for your unique situation.

7. Prioritize Healthspan & Lifespan

When pursuing longevity, consider both increasing lifespan (delaying death) and improving healthspan (quality of life), as patients often prioritize the latter.

8. Indecision Is a Decision

Understand that choosing not to act or decide on a course of action is itself a decision, with its own set of consequences and implications.

9. Address Multiple CVD Risk Factors

Understand that atherosclerosis is driven by multiple factors (lipoproteins, endothelial damage, inflammation), and improving any single risk factor like blood pressure or smoking cessation can lead to better cardiac outcomes.

10. LDL Necessary for Atherosclerosis

Understand that LDL is a necessary, though not sufficient, factor for atherosclerosis development; without LDL over a lifetime, there would be little to no atherosclerosis.

11. Clarify Health Goals & Trade-offs

Clearly define your health concerns, such as reducing cardiovascular disease risk, and consider potential trade-offs, like whether interventions might increase the risk of other conditions like cancer or neurodegenerative disease.

12. Avoid Health Confirmation Bias

Be wary of confirmation bias in health and diet, recognizing that even beneficial interventions can have downsides or not be universally optimal, and avoid overly simplistic ‘black and white’ thinking.

13. Integrate New Data Thoughtfully

When new research emerges, integrate it thoughtfully into the existing body of scientific knowledge to refine understanding, rather than immediately dismissing decades of established data.

14. Actively Fill Knowledge Gaps

Recognize and acknowledge personal knowledge gaps, and actively pursue learning and information to fill them as quickly as possible.

15. MUFA for Keto Hyper-Responders

For individuals on a ketogenic diet experiencing a ‘hyper-response’ with very high LDL, replacing saturated fats with monounsaturated fats (e.g., olive oil, macadamia nuts) may significantly lower LDL without changing total fat intake.

16. Pre-Low-Carb Lipid Test

Before starting a low-carb diet, get a particle count test to establish a baseline, as this can help in understanding subsequent changes in lipid profiles.

17. Baseline Sterol Panel

Obtain a sterol panel (measuring desmosterol for synthesis and phytosterols for absorption) at baseline to understand the underlying drivers of LDL particle number.

18. Consider Cholesterol Synthesis

For lean mass hyper-responders, consider that increased endogenous cholesterol synthesis, rather than just energy trafficking, may be the primary driver of their elevated LDL levels.

19. Carb Threshold for LDL-C

Experiment with carbohydrate intake, as increasing net carbs to a certain threshold (e.g., around 90g/day for 3 days for one individual) may lead to a substantial drop in LDL-C for some individuals.

20. Caloric/Fat Deprivation for LDL

Caloric deprivation (fasting) and fat deprivation appear to be general principles that lead to a reduction in LDL levels.

21. Statin Diabetes Risk Awareness

Be aware that while statins do not cause Alzheimer’s disease, they can slightly increase the risk of diabetes in a susceptible subset of patients over time, emphasizing the need for individualized assessment of medication side effects.

22. Understand LDL’s Role

Understand that the primary purpose of the LDL particle is to transport cholesterol, including its role in reverse cholesterol transport from the periphery back to the liver.

23. HDL’s Diverse Immune Roles

Appreciate that HDL particles play critical roles not only in reverse cholesterol transport but also in immune function, carrying immunoglobulins and other proteins.

24. Liver as Body’s Energostat

Appreciate the liver’s central and robust role as the body’s ’energostat,’ constantly sensing and regulating circulating energy and metabolites, likely through ATP levels.

25. Understand Chylomicron & HDL Roles

Recognize that chylomicrons primarily deliver fat-based energy from the gut, while HDL particles are generally involved in support operations not directly related to energy delivery.

26. Understand LDL Half-Life

Understand that the normal half-life of an LDL particle is about a day, but it can be pathologically extended by factors like ApoC3, increasing residence time.

27. Insulin Impacts Lipoprotein Residence

Understand that ApoC3 levels tend to correlate with insulin, meaning hyperinsulinemia (e.g., in type 2 diabetes) can increase the residence time of VLDL and LDL particles, potentially increasing their burden.

28. Monitor ApoC3 as Therapeutic Target

Stay informed about emerging therapeutic targets in lipid management, such as antisense oligonucleotides aimed at impairing ApoC3, which could impact lipoprotein residence time.

29. CIMT/CAC for Advanced Disease

Recognize that Carotid Intima-Media Thickness (CIMT) and Coronary Artery Calcium (CAC) scores are indicators of advanced atherosclerotic disease, not early biomarkers of risk, and should be interpreted accordingly.

30. Assess Quality of Life Impact

When evaluating health risks and interventions, consider not only the risk of death but also the potential impact of events like heart attacks or procedures on long-term quality of life and functional capacity.

31. Recognize Biological Non-linearity

Understand that many biological phenomena and their effects are not linear, meaning that increasing or decreasing a factor may have different outcomes at different levels.

32. Share All Symptoms, Stay Open

When dealing with novel or unusual health phenotypes, share all observed symptoms and remain open to the possibility of as-yet-undetermined risks, even with cautious optimism.

33. Weigh Efficacy & Cost in Healthcare

When making healthcare decisions, differentiate between the efficacy of a treatment and its cost or value, recognizing that the latter often involves individual or insurance-based decisions.

34. Insight 34

For questions or deeper understanding of podcast topics, papers, or people discussed, check the robust show notes available on peteratiyahmd.com.

35. Insight 35

Sign up for the weekly email at peteratiyahmd.com to receive updates on Peter’s activities, interesting papers, and relevant insights.

36. Insight 36

If you enjoy the podcast, consider leaving a review on Apple Podcasts to support the show.

37. Insight 37

If you prefer to skip the lengthy introduction, fast forward approximately five minutes into the episode.