Tuesday, January 14, 2025

The Fasted 50K and Heavy Cream Cholesterol Experiment - Preview

 

The purpose of this piece is to preview a bit of an experiment I’m intending to perform in the near future. I’m calling it the “50k and Heavy Cream Cholesterol Experiment” because, well…I’m going to run 50 kilometers and drink a lot of heavy cream and sample lipid levels a number of times. Read on for details, reasoning, and predictions.


The Plan

The plan, broadly speaking, is to asses the effects of both an excessive dose of running and excessive saturated fat consumption on my lipid levels (LDL-C, HDL-C, triglycerides). These two interventions won’t be concurrent, but stacked immediately on top of one another over the course of a handful of days. Ideally, the plan is to begin this next Monday, January 20th. I say ideally because a major factor in the timing is finding a day when I’m healthy enough to even run the 50k. As I’ve described recently, I still commonly miss days of exercise (and work) due to neurological complications. And of the days I’m healthy enough to get out the door to run, on exceedingly few could I reasonably hope to run a reliably strong 50k. This makes finding a good opportunity to carry out this experiment in the course of normal day to day life difficult at best. But as luck would have it, I’m on vacation this week and have a reasonable expectation of feeling pretty good when I return.

So, fly home on Sunday the 19th and run the 50k on the 20th. Beginning that evening and continuing for 3 full days after, I will consume a purely carnivore diet with as much saturated fat and dietary cholesterol as I can tolerate. The aim will be to consume several thousand calories per day above baseline, but exact numbers will depend on how exactly it feels to so greatly overindulge multiple days in a row (Despite the name I used in the title, I will not be consuming only heavy cream. Massive quantities of it, yes, but also meat, cheese, and butter). Baseline diet, for the record, is an animal-based ketogenic diet averaging about 80% calories from fat and fewer than 10g of carbohydrate per day.

The planned schedule is as follows:

Monday AM: Lipid Panel #1/Baseline

Monday AM: 50 kilometer run

Monday PM: Lipid Panel #2

Monday PM – Thursday PM: Heavy saturated fat consumption

Tuesday AM: Lipid Panel #3

Tuesday PM: Lipid Panel #4 (non-fasted)

Wednesday AM: Lipid Panel #5

Thursday AM: Lipid Panel #6

Friday AM: Lipid Panel #7/Final

 

What I’m Hoping to Measure

As you almost certainly know, the traditional paradigms surrounding diet and cholesterol suggest that consuming too much saturated fat and dietary cholesterol drives an increase in serum LDL cholesterol levels (in turn considered to be the prime driver of atherosclerotic cardiovascular disease). I, however, object to that paradigm, believing instead that the greatest factor influencing LDL-C levels is the body’s reliance on lipoproteins as an important delivery system.

Probably the most important cargo that lipoproteins carry are triglycerides, to be either stored as body fat or used as an energy source by the body. Which brings me to an important caveat that I’ve yet to mention – the 50 kilometer run will be carried out entirely in the fasted state. I will be consuming exactly zero calories before or during the run, not eating anything on the day until after my post-run blood draw.

This is a fairly extreme measure of course. Exceedingly few people ever run that far in a fasted state, and ever fewer (possibly zero?) have ever measured the effect of that effort on lipid levels. The American Heart Association and others suggest that saturated fat consumption is the greatest factor in raising cholesterol levels, with a lack of exercise a strong contender for number two. Conventual wisdom also tends to suggest that LDL-C levels don’t change rapidly, but instead over weeks or even months. It would stand to reason, then, that LDL-C should probably be largely unchanged between my first and second blood draws. Perhaps they might even tick down a fraction, as the intervening hours between the first and second blood draws will maximize typical guidelines for lowering cholesterol (plenty of exercise, zero fat consumption). If instead LDL-C increased during the run, it might require an update, or at least a caveat attached, to the typical paradigm.

Lets skip now to the final blood draw. This is, clearly, the extreme opposite end of the spectrum with respect to traditional cholesterol risk factors. I won’t exercise the three days between the 50k and the final blood draw, but I will eat so, so much saturated fat. And its flipping so aggressively from one extreme to the other that makes this fun. Again, a traditional medical mindset would suggest that LDL-C should clearly increase throughout the week as I binge saturated fat and dietary cholesterol. It may not increase a lot, as its only for a few days, but one would certainly expect it to start trending up in the face of such prodigious fat consumption (Just for fun – the AHA recommends capping saturated fat intake at ~13 grams per day. I intend to consume 25-30 times more than that each day. Essentially a month’s “worth” of saturated fat per day). So again, if the so-called expected outcome is not observed, it may suggest a shortcoming of the current conventional wisdom.

I’ll further expand on the day 2 blood draws momentarily, but the intervening lipid panels are largely to track trends throughout the week. I intended to skip the middle three blood draws at first, as its really the first and last days that will capture the full effect, but decided it would be more interesting to have a more complete dataset.

 

Predictions

Baseline/LP1 – I will have, by conventional standards, elevated LDL-C at baseline. I don’t know how elevated necessarily, but certainly it will be a number that would concern your average physician. On the contrary, I expect reasonably high HDL-C and low triglycerides that would be quite good by conventional standards. All of these values derive from the fact that I am a metabolically healthy individual consuming an exceedingly low-carbohydrate diet and thus relying on fatty acids for energy.  

LP2 – I expect LDL-C to rise fairly noticeably during the course of the fasted 50 kilometer run. Reliance on stored body fat for energy (or really, the hormonal effects of fasted exercise) will drive a significant increase in the breakdown of stored body fat, which should be largely trafficked through the liver and packaged in VLDL particles. The triglycerides in these VLDL particles will be taken up extremely rapidly by working muscles, causing the VLDL to convert to longer-lived LDL particles. This continuous effect will cause there to be an acute increase in cholesterol containing LDL particles, and thus an increase in measured LDL-C. In addition, I expect measured triglycerides to be extremely low for the same reason (most likely below my “personal best” of 66 mg/dl) as my working muscles rapidly take them up for energy.

Final/LP7 – The expectation here is that this result will also defy conventional wisdom. Not only will the extreme consumption of fatty animal products fail to raise my LDL-C, it will acutely lower levels to below baseline. Rather than relying heavily on stored body fat for energy, I’ll be doing the exact opposite. I’ll be creating a hormonal environment that more heavily emphasizes the storage of fat rather than its breakdown, thereby reducing the production of VLDL particles that would typically move my stored triglycerides around my body. Fewer VLDL particles means fewer LDL particles and thus lower LDL-C. Its worth noting, however, that this effect won’t be as great as it could be due to the compressed timeframe of this experiment. The average lifespan on an LDL particle is in the three and a half day range, and three and a half days before my final blood draw I’ll be producing huge number of VLDL/LDL particles during and immediately after my fasted run. A couple more days of binging would ensure these excess particles would be completely recycled, but frankly I don’t want to do this for that long, so…

Day 2/LP3 – Saving the best for last. This is, to me, the real meat of my experiment. I have strong preconceived assumptions about how the fasted exercise and the fat binge will effect lipids, but the blood draw on Tuesday morning is for me the one that ventures into the great unknown. And frankly, in a lot of ways, it ventures into the collective scientific unknown, as I don’t think anybody has ever documented the effects of such an extreme scenario on lipid levels.

Let’s first asses what this blood draw might look like if we only consider the energy deliver nature of lipids. Remember again that LDL particles have a typical lifespan of 3+ days. This blood draw, maybe 17 hours after the second, will represent only ~20 percent of the lifespan of a typical LDL particle. And while the massive effort between the first two blood draws should generate a significant acute increase in LDL particles, nothing about the rest and recovery after lipid panel 2 should differ greatly from what I’d be doing three to four days earlier. That is to say, there shouldn’t be much reason for the number of particles produced to differ greatly from the number being recycled. It may even be the case that energy demand remains so high in the immediate aftermath of the run and the second blood draw that LDL-C could fractionally increase if I don’t eat enough or quickly enough to fully blunt that effect. So, from a purely energy driven perspective, LDL-C levels at or just above those in lipid panel 2 might be reasonably expected (with triglycerides returning closer to baseline as well).

But…what if energy (and cholesterol) weren’t the only important components being trafficked by lipoproteins? What if another effect were present that could also drive a noticeable change in LDL-C levels? This, essentially, is what I’m hoping to test.

It may be that a very important and underappreciated element that LDL particles transport…is just themselves. After all, lipoproteins are made largely of the same phospholipids that comprise cell membranes throughout the human body. And it could very well be the case that an acute insult to enough of those cell membranes – for example, the damage caused by running 50 kilometers – could cause many LDL particles to be taken up by the cells as raw materials for the repair of these damaged membranes (and/or the creation of new ones).

If this were the case, a reasonable proportion of the existing LDL particles in circulation might leave the bloodstream earlier than expected, thus decreasing LDL-C from the energy driven expectation outlined just above.

To be clear, I don’t have a reasonable guess for what my LDL-C will look like on Tuesday morning. Something wildly different than expected on the post-run or post-binge panels would require some reevaluation of the energy delivery paradigm. However, I’m not making any particular prediction for this lipid panel. I do strongly believe, however, that a decrease in LDL-C from lipid panel 2 to panel 3 would be indicative only of this proposed effect – the endocytosis of LDL particles for the repair of cellular damage. And I think demonstrating this effect would, in theory, go a long ways towards further understanding a transport model of lipoprotein function and even the underlying causes of atherosclerotic cardiovascular disease. If that decrease is in fact observed, I’ll of course have plenty to say about it after the fact.


Summary

So, there you have, in two thousand words – a weeklong experiment to test the extremes of lipid mechanics and assess the ways in which a lipid transport system may best explain lipid behavior. To the best of my knowledge, this is a novel demonstration, at least at this extreme. Studies have demonstrated that a great energy deficit raises LDL-C, and numerous individuals (myself included) have lowered LDL-C while binging on fat. But the extreme, hyper-condensed nature of this N=1 experiment is, I think, without parallel. In particular, the second day’s blood draw, on the back of a such a significant physiological event, has the potential to demonstrate a possible underappreciated characteristic of lipid behavior in the human body. Whether this ultimately demonstrates something significantly novel, or only highlights the importance of lipids in energy deliver, or goes up in flames entirely, remains to be seen. But, regardless, results and summaries should come soon after. To be continued.







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