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 20^th. 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 19^th and run the 50k on the 20^th. 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.

2024 In Review Part 3 - Impaired Brain Metabolism and How to Deal with It

 

Part 1 Here, Part 2 Here

As I outlined in the previous section, the major long-term issue I’m dealing with at this point is widespread impaired brain metabolism - Most areas of my brain are deficient in their capacity to produce energy through traditional means. What I’m going to do here is expand a bit on what that means and how that works.

In a standard, simplified framework the brain is considered to run entirely or nearly entirely on glucose. This makes the cells of your brain and nervous system distinct from nearly every other cell in your body, which can seamlessly blend glucose and fatty acids as fuel sources in various proportions. Your muscle cells, for example, can freely convert fatty acids to energy through a process called beta-oxidation, essentially the “burning” of pure fatty acids.

But beta-oxidation doesn’t occur in the brain or nervous system. Thus, the typical understanding (which is indeed true in a general sense) is that the brain must use glucose for its required energy production. What happens in a range of neurodegenerative and other neurological conditions, however, is that your brain simply doesn’t take up and utilize glucose to a degree sufficient to meet energy demands. I would contend that the reason this usually happens, typically in an aging, metabolically unhealthy population, is related to chronic hyperglycemia, hyperinsulinemia, and insulin resistance. The same insulin resistance and chronically elevated insulin that characterize diabetes and other chronic metabolic conditions manifest in the brain as well (you may have heard Alzheimer’s referred to as “type 3 diabetes” at some point) and usher in a gradual, years-long degradation of metabolic function.

That situation, obviously, does not apply to me. My metabolic health is fantastic, and there was no gradual onset over the course of years or decades. My onset was acute, the result of whatever exact autoimmune reaction was triggered in response to the Pfizer Covid-19 vaccine. While my onset was clearly sudden, its hard to establish exactly how sudden. It may have been nearly instantaneous with the initial autoimmune manifestation, or it may have been exacerbated over months of severe autoimmune symptoms. Regardless, it was not the typical insidious onset you’d see in chronic neurodegenerative disease.

PET Scan Results

So what does my testing show? Unfortunately, there aren’t a ton of clues. The way a PET scan works is by essentially administering an IV of radioactive glucose and observing the reactive signature “light up” as those radioactive molecules are utilized in the brain. The more glucose each part of the brain uses, the brighter and redder that area will show up on a scan. A localized red spot, for example, might indicate a tumor greedily gobbling up glucose at an increased rate. Conversely, areas that take up less glucose than you might expect are a blue-green color. This is what you might see a dementia patient slowly losing functional capacity as their ability to convert glucose to energy wanes.

My brain had a lot of blue and green areas, indicating widespread failure to take up and/or utilize glucose at a level consistent with my brain’s energy needs. But there isn’t much more to it than that. The PET scan doesn’t tell us exactly what is damaged, or how and why that damage prevents proper function (although I do have ideas). I also don’t have a neat and tidy number attached to the result - There’s no highly quantitative assessment that lets me tell you how deficient my brain function is. I also don’t know anything about the rest of my nervous system, which may very well be suffering from the same defects. The only thing I really know for sure is that my brain doesn’t produce energy properly and that attempts to force it to through basically any level of mental effort result in a range of neurological complications as it ultimately fails to meet the demand, instead propagating whatever inflammatory damage drives symptoms for hours, days, or even weeks after the effort.

Dietary Approach to Impaired Brain Metabolism

 

Thankfully, the other thing I know for sure is how best to handle this situation to hold myself together as well as I’m able. That notion that your brain only uses glucose for energy? That’s highly simplified, and alternative sources can be leveraged to provide various degrees of relief. Unfortunately, this is a topic on which most physicians appear to have stunningly little education or understanding, which has led to more than a couple dead-end conversations with neurologists who frankly have no understanding of brain metabolism (more on that at a later date, but it includes one doctor trying to tell me that because she didn’t know what they meant, that the test results may be unrelated to my symptoms and that I was probably just depressed. She then tried to prove her point by googling impaired brain metabolism and showing me the first result…which listed only epilepsy, Parkinson’s, and Alzheimer’s as typical manifestations of such brain dysfunction).

I’m going to try to keep it pretty basic, but I do want to at least touch on the three main alternative sources your brain can use to produce energy – alcohol, lactate, and ketones. There’s also a fourth “alternative” – the increased consumption and utilization of glucose itself that occurs in response to exercise.

I mentioned previously that alcohol consumption was fairly pivotal in cementing my understanding of my current situation. The fact that alcohol very clearly improves my symptoms and aids recovery from acute severe episodes drastically limits the number of problems I could be dealing with. But alcohol is an easily available source of brain energy, and in fact its one that healthy people prioritize to a degree when they consume it. This isn’t really for “good” reasons – alcohol can’t be stored in the body and is acutely toxic, so your body will make efforts to use it as an energy source in order to clear it from the bloodstream. In a healthy person, this manifests in part as a downregulation of glucose consumption in the brain and a partial replacement of that energy flow with alcohol instead. For me, glucose consumption is chronically decreased anyway, so alcohol just serves to fill in the gap and make me “whole” for a certain period of time.

As I discussed previously, I was strategically using alcohol this year more often than I would have liked from an overall health perspective. I wasn’t drinking for or to any real level of intoxication, just consuming a deliberately gentle flow of a few drinks maybe two to three times a week. It was, very literally, strategic, and often necessary to keep myself semi-functional for another day. This is something I’ve felt the need to do far less frequently in a ketogenic state.

The next alternative fuel source is lactate, which is tough to separate from the increase in glucose utilization during exercise, so we’ll discuss them together. Lactate (or the very closely related lactic acid) is often viewed somewhat negatively or as a “waste” product because it increases in the bloodstream during strenuous exercise. However, in reality its just a byproduct of typical metabolism and only increases in the blood when the ability to clear it can’t match production. Its production increases even at lower levels of exercise intensity, and one of the manors by which it can be cleared is to be taken up by cells (including those in the brain) and converted to pyruvate for direct energy production. Thus, the increase in lactate metabolism during exercise provides an additional partial source of brain energy.

The degree to which that helps me is unclear, however, because it generally happens in concert with increased glucose uptake. A variety of glucose transporters become more active and efficient during exercise (for good reason – to readily provide you with fuel). Its extremely apparent that this effect still occurs for me as well, despite the general impairment of glucose utilization. Its really quite a weird phenomenon – If I’m just barely well enough to get out the door to exercise, I can begin a slow walk/jog/hike and eventually my neurological health will improve. How long that takes seems to depend on how poor I feel – at functional baseline, its 15-20 minutes before function and feeling both start improving. When I’m worse, it can take closer to an hour – and when I’m in that poor of a state, I can continue to noticeably improve for hours if I continue to exercise. To that end, some of my best stretches of health have actually occurred as a result of hiking trips in the mountains. Not only do I completely avoid cognitive strain, but several hours a day (plus some lasting effect after the fact) of increased glucose and lactate metabolism provides sufficient energy availability for basically an entire day.

Now the most important one, in my opinion – ketones. In a low-carbohydrate, low-insulin environment your liver converts some fatty acids to ketone bodies, which can serve various functions including as a fuel source. Ketones are functionally unique from their parent fatty acids in a number of ways, but the most important for the purpose of this discussion is their ability to be directly taken up by the brain and nervous system as an energy source. Thus, a person in a consistent low-carb/low-insulin state can expect to have access to a consistent stream of ketones for energy.

This consistency is a major differentiating factor when compared to other alternatives like alcohol, carbohydrate binges, or exercise. Alcohol and massive carb spikes are of course temporary, acutely unhealthy manners by which a person can increase energy availability. And despite my desire to run and hike all day, exercise is ultimately temporary as well. Ketones, however, are not. Ketones are forever. Provided, that is, that you maintain an environment conducive to their production.

An important note on ketones is that their contribution to the brain’s energy requirements is not demand-driven, but supply-driven – the uptake and utilization of ketones is proportional to their concentration in the bloodstream. Thus, a “standard” ketogenic diet that you or a family member or a friend have probably tried won’t actually help me all that much. The traditional advice to remain under 20 grams of carbs per day will typically only elicit low levels of ketone production, and thus low levels of ketone-based energy. This is basically irrelevant for a person who only endeavors to manage blood sugar and curb sugar cravings, but makes a great deal of difference for me.

Not only is my focus on limiting carbohydrates to something like 5 grams per day, but I also moderate protein intake (as it has a mild insulinogenic effect) and maximize the fat percentage of my diet. This “therapeutic” ketogenic approach focuses on maximizing the concentration of ketones in the bloodstream, and thus the degree to which ketones can provide relief in the face of impaired glucose metabolism.

Unfortunately, the ketone levels I’ve found are necessary to truly prevent the onset of symptoms haven’t really been obtainable in the context of “normal” food consumption. For me, for now, it seems only extended fasting or a heavily fat/oil-based diet that even further minimizes protein and incidental carbs can raise my ketones to the levels necessary to approach true non-symptomatic function (For context – a person on a standard mixed diet usually has ketone levels of 0-0.1mmol/L, a “standard” keto dieter might hang out at 0.5, I bounce around between about 1 and 3, and need something more like 3.5-4+ to ward off symptom onset).

There are other methods of temporarily elevating ketones above my standard baseline. One is exogenous ketones, suddenly widely available in the last couple years. These work great, raising ketone levels by 1-2mmol/L for a couple hours. However, they are quite expensive and only temporary. That said, I do keep them on hand and use them sometimes to escape potentially calamitous situations. Another shortcut, so to speak, is to drink MCT oil. Medium chain triglycerides are essentially too short to be efficiently burned or stored the way longer chain fatty acids would be. Instead, they are preferentially converted to ketones, even if the person drinking them isn’t consuming a ketogenic diet. This is less effective than exogenous ketones, in additional to being kind of tedious and slightly gross. But its very cheap when purchased in bulk, so I do consume several servings a day at strategic times (ie. During work) in an effort to support ketone levels and minimize symptom onset.

Conclusion 

So that’s basically it. My brain doesn’t properly produce energy through traditional means. If I don’t diligently care for the situation, it quickly becomes dire and I’m relatively easily knocked on my ass by simple mental and cognitive tasks. I am, at baseline, still made bedridden by the job I’m trying to work every day. The reason I make it to work more days than not, the reason I can mostly hide my symptoms while I’m there, and the reason I’m able to even go for a brisk walk (let along run multiple hours at a time), is because I approach each day in a deliberate, evidence-based fashion that leaves little wiggle room if I hope to remain functional. The combination of a therapeutic ketogenic diet, ketone-raising supplements, and as much exercise as I can manage keep my brain functioning far above where it otherwise would be. At all hours of the day, I am, often through multiple avenues, closing the substantial gap between the energy demand of my brain and nervous system and the critical shortage of supply that otherwise exists.

The hope in 2025 is not that I will magically get better, because I think at this point it would be naïve to assume that’ll ever happen at all, let alone soon. The hope is simply that I can manage things at a high enough level so as to continue showing up to work while cobbling together enough exercise that I feel like I can, indeed, exercise. The hope is to string together days and weeks away from work that allow for real adventure, be it running or otherwise. And the hope is, at least temporarily, to be fit and healthy enough to accomplish something cool by the end of the year, whatever that may be – and to prove that my life can be completely ripped apart, left broken by autoimmune disease and brain damage, but that I can still exist fully on the other side.