In this episode of Ventures, my guest Dave Feldman (@DaveKeto) and I discuss a variety of topics related to lipids, immunology, ketogenic diets, and the future of health tech. I first came across Dave’s work when I noticed my cholesterol levels (specifically LDL-C) raised significantly when fasting and/or low-carb dieting, and I found that there is a large community of people who have noticed the same phenomenon. Dave has helped pioneer efforts to formulate hypotheses around why this might be the case, and why LDL levels in our blood may be considerably more complex than we’ve been led to believe.

You can watch this episode below or listen on Apple Podcasts, Spotify, Google Podcasts, or wherever you get your podcasts.

In this episode, we cover a wide variety of topics, including:

3:20 - Initial setup and motivation for the conversation

4:16 - Dave’s intro, his backstory, and his journey into N=1 experiments

8:07 - Introduction to basic lipidology

12:54 - Introduction to the basic lipid panel: Total Cholesterol, LDL-C, HDL-C, and Triglycerides… and why LDL-C goes up for most people when they eat less food or eat low-carb.  Explanation of chylomicrons and the VLDL to LDL transition.

16:47 - The Feldman protocol (i.e. 85% of folks see their LDL drop when consuming a lot of calories/fat)

17:11 - What are the likely purposes of having LDL particles stick around the bloodstream in humans for a few days? Or is LDL just a waste product that serves no purpose? What role does LDL play in the immune response and the potential fight against cancer?

22:11 - Description of the study where lipopolysaccharide killed mice with low LDL.

23:17 - Description of why LDL undergoes endocytosis to deliver cargo to tissues around the body.

24:55 - Why are the antioxidant features of LDL important? Why is it a problem to have too many free radicals floating around in our blood stream?

27:33 - Loss of PCSK9 function results in less complications from heart disease, but not all-cause mortality. A discussion on the importance of looking at all-cause mortality.

29:52 - Further discussion on immunology and free radicals. What is the purpose of having free radicals in the body in the first place?

32:19 - What is the purpose of oxidative stress and inflammation?

35:42 - A conversation about statins, PCSK9 inhibitors, and drug studies in general targeted at lowering LDL-C.

42:13 - How do statins work to lower cholesterol? What is the mechanism?

44:36 - Why historically has so much attention been paid to cholesterol and heart disease? How do low-carb diets fit into this picture?

48:04 - Why does LDL-C shoot up when fasting?

49:08 - What is HDL?

50:40 - How could LDL be related to fighting COVID-19?  

52:48 - Coming back to Dave’s story, what is Dave up to now? What is his most recent N=1 experiment? (Testing oxidized LDL and oxidized phospholipids in a low-carb/high-fat caloric deficit and surplus compared to control intake)

59:34 - What are Dave’s hypotheses for the expected data for this most recent experiment? (Key thing he’s looking for is a low amount of oxidized phospholipids).

1:00:47 - How should low-carb dieters be thinking, generally, about inflammation and LDL? How should we think about data from people who lack LDL receptors?

1:05:46 - What’s going on with people who see increased inflammation when they consume carbs?

1:08:10 - How should people think about the size/impact of LDL particles and their ability to “shoot holes” like beebees in vascular cell walls.

1:16:02 - Why do we care about how/why LDL particles get on the inside vascular cell walls? What does Dave think is going on when this happens?

1:20:40 - What is Dave’s overall advice for people, at the end of the day, that are concerned about their elevated LDL-C when going on low-carb, high-fat diets?

1:25:38 - Why are triglyceride levels typically low in people on low-carb, high-fat diets?

1:28:40 - More elaboration on Dave’s hypothesis that LDL particles are recruited, by endothelial cells, to inflammation sites in vascular walls to help the immune response and healing process.  

1:33:01 - What would LDL particles be “triaged” for in areas of inflammation?

1:33:55 - What would Dave study right now if he had a full lab to run an experiment?

1:35:15 - What’s causing the inflammation damage on vascular cell walls in heart disease?

1:39:17 - Dave’s belief that the story of atherosclerosis has less to do with the damage to the tissue and more to do with the inhibition of the repair. He describes why having low insulin is important and why many illnesses result in a lack of hunger.  

1:40:28 - What’s up with high susceptibility to electrolyte imbalances on low-carb diets? What are the mechanisms involved here?

1:45:02 - What advice does Dave have to investors and entrepreneurs learning about lipidology, heart disease, etc..?

1:47:30 - What opportunities exist for startups considering tackling the problem of heart disease and obesity?  

1:51:42 - The need for an insulin sensor; Dave’s call-to-action for continuous insulin monitoring.

1:52:54 - Where can people learn more about Dave and his work? https://cholesterolcode.com/ and https://twitter.com/daveketo and https://www.facebook.com/groups/CholesterolCode/ and https://www.facebook.com/groups/LeanMassHyperResponder/ 

Finally, to dive further down the rabbit hole, I’d recommend this recent podcast from Peter Attia and Tom Dayspring on Lipidology, which refers back to their mega series from a couple years ago on the topic as well.