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.

 

 

2024 in Review Part 2 - Running 50 Miles is Easier Than Going to Work

 

Part 1 Here

Ok, so…By early 2024 I was 100% confident that my lasting symptoms were being driven by metabolic impairment of the brain. But knowing this and being able to do a lot about it are two different things. In the spring, I was offered an opportunity to change offices at work, from one of extreme tension and hostility to one that was far superior on both professional and interpersonal levels. And while this role was “better” by basically any metric you’d use to typically judge a job, it was also a bit more cognitively intensive.

To be clear…I was suffering on a daily basis in my previous role as well, but in a way that was often a touch more manageable. I could usually girt my teeth and continue to function in my day-to-day life, judiciously using leave (both personal leave and leave without pay) to manage the worst bits and sometimes string together stretches of days in which I felt nearly normal. This is how, for example, I was able to win a small trail race last fall after being away from work for almost 4 weeks in a 6 week stretch.

The new role, revolving around airspace and routing automation, wasn’t an extreme increase in workload in theory. But I also no longer had a boss fighting tooth and nail to shield me from fulfilling my job duties, as I had previously. I did a bit more work now - but having largely existed on a knife’s edge for so long anyway, this incremental increase in cognitive effort took a fairly extreme toll.

The most ironic part of all of this continues to be the fact that I can, at least when I feel well enough, continue to exercise at a high level without issue (and in fact, as I’ll discuss in part 3, its as important as anything in managing my condition). My brain doesn’t work but my body still does. To that end, despite barely running all spring, I was able to complete a 50 mile run in June of this year. I had been in Oklahoma City for 2.5 weeks for a very, very relaxed training course related to my new role and had just enough good health to exercise during most of my time there.

Nothing to do on the weekend was a good enough reason to drive to NW Arkansas for a 50 mile “backyard” style race. It followed the typical format of a backyard ultra – 4.1666 miles every hour on the hour – but instead of an endless race of attrition, it simply ended with a time raced on lap 12. So all told, a very easy way to get a 50 miler done in a bit over 11.5 hours. True to standard, I felt quite rough race morning and during the early laps, but improved considerably throughout and had an enjoyable experience overall.

That race was the end of the highlight reel though. Work has been too hard, and I’m not entirely sure my health hasn’t actually been slowly deteriorating as a result of the constant inflammatory stress that results from forcing my brain to do things it really can’t. The coping mechanisms over the summer were less than stellar – binge eating and alcohol (again, for reasons I’ll explain) both moderate symptoms enough to maintain some semblance of function. Not any kind of health, mind you, but enough function to work 25-30 hours a week while keeping the neurological complications on the right side of bedridden. Unsurprisingly, I gained about 10 pounds in 10 weeks employing this reactive strategy of brain energy management.

Meanwhile, I’d been fighting all year to find a doctor wiling to order the test (a PET scan of my brain) that I knew would prove the significant metabolic deficits driving my condition. I don’t really remember how many doctors I asked and how many times I was told no, even by doctors who seemed to agree right up until it was time to order the test. Finally, a neurologist at Johns Hopkins (one of I think 13 neurologists I’ve now seen) agreed to order the PET scan. Not that he necessarily wanted to - He was really just placating me and told me straight up that I was probably wrong about what the test results would show.

Well…as you can probably guess, I was not wrong. The PET scan confirmed impaired brain metabolism in the temporal, parietal, and frontal lobes, as well as parts of the limbic system, including the hippocampus. In short, a lot of my brain wasn’t working properly to produce energy. Unfortunately though, being right about the problem doesn’t do much to solve the problem. I could certainly be confident in my approach at least, which would now be a fair bit more diligent than briefly plugging holes with alcohol or excessive carb intake.

I finally this fall made the decision to commit long term to a strictly therapeutic ketogenic diet. I had been hesitant to make that change since successfully reintroducing fruit, but it seemed like an obvious best option moving forward. I’ll discuss more in the next section, but ketones are an alternatives source of brain fuel that can somewhat mitigate the negative effects of metabolic impairment without the obvious consequences of alcohol or binging on dried mango. My diet now consists of less animal protein, but more added fats such as tallow, butter, and heavy cream. I also consume a few servings of MCT oil daily as a source of additional fat, all as part of an effort to not only minimize carbs (like on a standard low-carb/keto diet) but to maximize fat ratio in an effort to drive ketones as high as practical.

The only other “intervention” so to speak remains the same as always – exercise as much as possible. Exercise increases metabolic activity in the brain. The more I exercise, and the longer each session is, the better I tend to feel. Days in which I fail to exercise before work are almost uniformly worse than when I do, and carry with them a high risk of failing to make it through the day. It certainly took a few weeks for the exercise to begin normalizing – while I had previously spent long stretches of time eating zero carbs on a pure carnivore diet, it was when my health was generally too poor to exercise anyway. A commitment to an approximately zero carb diet in the context of training and exercise was largely unchartered territory.

Where am I now? Ketosis is roughly as effective as binge eating and alcohol at mitigating extreme symptom presentation. The big difference is that its much healthier overall, and indeed I’ve now reversed most of the weight I gained gorging over the summer. Unfortunately, being roughly as effective still means I’m not well enough to get through the work week. I do manage to exercise most days, especially if I run in the mornings early in the week, although it often falls apart in concert with my struggles at work. I still spend quite a bit of time in pain, with sleep problems, numbness, and dizziness permeating most of my days. I do think the ketosis blunts this to a degree, of course, and so “catastrophic” episodes that leave me briefly bedridden and unable to run for a week at a time are less frequent than they otherwise may be.

I’m continuing to try to combine deep ketosis with frequent exercise to the best of my ability, while limiting cognitive strain where I’m able (It’s taken a very long time to write this for largely that reason). Beyond that, though, there’s very little to be done. There is no medical treatment for impaired brain metabolism (part of the reason some doctors wouldn’t order the test) and no particular reason to be confident this will ever get better after all this time. In fact, impaired brain metabolism is a hallmark characteristic of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. In a more “normal” patient, such findings would generally be expected to continue degrading over time and would likely foretell progressive impairment and damage to the brain and nervous system.

In part 3, I’ll explain why I don’t think that worrying forecast necessarily applies to me and discuss brain metabolism more broadly in the context of my condition. 

Part 3 Here

2024 In Review, Part 1 - A New Paradigm of Brain Dysfunction

Its been a while

In fact its been a good solid year since I’ve written anything here about my health and life journey. Part of that is because things have been fairly dynamic, and part of that is because things have been fairly difficult.

While everything I’ve previously discussed about my health has been through the lens of autoimmune issues, it was already becoming increasingly clear a year or more ago that the situation had been evolving and that an updated paradigm was warranted. While the autoimmune issues were very real – you don’t just test positive for every marker of Lupus without an autoimmune problem – and the likely root cause of my overall condition, my symptoms were becoming increasingly decoupled from acute immune triggers. This had been the case since at least mid-2023, after my second week+ long fast. By this point, I had fasted for a week on two occasions, for 3-5 days on several more, and for 36-48 hours probably dozens of times. I had adhered for long stretches to a pure carnivore diet, and only gently introduced the (theoretically) safest non-carnivore options like organic fruit and honey. To my knowledge, this is the only evidence-based approach to seriously fighting autoimmune disease and, one way or another, I had largely moved past these issues by the end of 2023.

What was also clear, however, is that I wasn’t healthy. In retrospect, I was still struggling to totally move on from the autoimmune paradigm and was sometimes shoehorning symptom triggers into that myopic view when it wasn’t warranted. To make things worse, the realization that the resolution of autoimmune markers and reduction in autoimmune triggers weren’t going to portend a full-scale return to health was fairly demoralizing. That can all be seen by simply looking back one year, at some musings that I’m not overly proud to have written.

What I knew very clearly at the time but was not fully exploring was that I struggled quite a bit at work. And this was despite the fact that my work was, um…..not particularly challenging. Bluntly and briefly, I was under the supervision of a boss who put her greatest efforts into ensuring that as much work as possible was shunted away from our department. It was a boring, uncomfortable work environment, but certainly not a busy one. Still, I did enough work to know that my symptoms were exacerbated and magnified by the effort. Conversely, symptoms diminished whenever I was away, and able to fully rest my cognitive faculties.

The notion that I was suffering from impaired brain metabolism was something in which I became increasingly confident over the winter. While specific foods didn’t trigger acute symptom onset like they used to, I could still manipulate symptoms by, for example, binge eating, which would preclude symptom onset in part or entirely. Exercise helped considerably as well, as I was often barely able to shuffle out the door before eventually finding improved health over the course of multiple hours of walk-jogging at an easy effort. These factors, combined with the obvious acute distress that accompanied mental effort either at work or home, largely cemented my new metabolic paradigm of neurological dysfunction.

However, the final nail in the coffin, so to speak, didn’t come until the first weekend in February. I flew to Las Vegas to spend a long weekend with my family, and frankly I felt like shit. I struggled mightily with pain and numbness on the flight, and the plan my wife and I had to show up early for a day of hiking ended with her leaving me behind to hike on her own. After a full week of work, I wasn’t in sufficient neurological health to function at a normal human level.

But, after a couple days wandering around the strip with alcohol in my hand, that had changed considerably. To be clear, this wasn’t some Hangover-esque degree of debauchery. I just simply sipped alcohol (largely not caring how it might affect my symptoms) for most of a couple consecutive days and felt really quite good. As I progressed from shaking in the trailhead parking lot to feeling as well as I had in months, I finally confirmed with certainty the metabolic damage to my brain and abandoned any remnants of the autoimmune paradigm for good.

The reason I was able to do this is because alcohol is, for all intents and purposes, a brain fuel. The traditional notion is that the brain only uses glucose for energy, but this isn’t really true (much more on this in a later post). The brain can also use, among other substrates, alcohol. So while I had once again wrecked my body all week by straining my brain in an energy-deficient state, I had followed it with a relaxed weekend of frequently available energy flowing from large cans of hard seltzer. While the obvious overall health implications still apply, in this case my brain and nervous system were recovering thanks specifically to an uncommonly available energy flow.

I’ll write specifically amount impaired brain metabolism and its consequences in part 3, but for now its enough to know that I had confidently assessed the major problem I was still dealing with. The arduous duel tasks of demonstrating it and dealing with it will comprise part 2.

Part 2 Here, Part 3 Here

Excessive Running Doesn't Kill You the Way Some People Seemingly Wish it Did

 

A paper was published recently in the British Journal of Sports Medicine that sought to examine the longevity of extremely serious endurance athletes, motivated largely by the persistent undercurrent of thought that too much extreme exercise may in fact be harmful, especially for one’s heart. The cohort chosen for this study was an interesting one – the first 200 people to ever run a sub-4 minute mile.¹ The idea here is obvious – these men clearly existed on the very edge of human aerobic exertion for some amount of time and did so long enough ago to have now reached advanced age or death.

While this is an interesting study, the results aren’t necessarily what I’m here to talk about. This really just serves as a jumping off point for the broader topic of “excessive” endurance exercise and mortality, something that pops up in the news every year or two as concerns over the potential cardiovascular harm of serious endurance training are regurgitated anew. Its something I’ve been meaning to write about for a while, so…here we go.

Oh right, the results – the researchers found these world-class milers lived an average of 4.7 years beyond their predicted life expectancy. They didn’t catalogue or analyze cause of death, but did note that among the 7 individuals who died young – before the age of 55 – six died of traumatic causes and one of pancreatic cancer. Not a catastrophic heart among them. But like I said, that isn’t the point of this post. There’s a lot we don’t know about these athletes’ lives, or about their exercise habits later in life, and so we can’t really draw sweeping conclusions. We can, at least, be sure that world-class levels of training and performance in early adulthood did not negatively impact the lifespan of these men relative to the general population.

This isn’t an entirely novel exploration either. A similar, larger study of past Tour de France participants also found significant decreases in all-cause and cardiovascular mortality in later life.² While again we can’t “prove” a lot from this, the fact that elite middle distance running and elite endurance cycling both fail to negatively impact lifespan is certainly credible evidence against the notion that such activity is overwhelmingly damaging to health.

Excessively Flimsy Evidence

Ok, so the point isn’t to talk about this one study. The point instead is to push back against the creeping notion that excessive endurance training leads to elevated risk of early cardiovascular death. That claim has percolated for upwards of 15 years or more now, largely thanks to the efforts of two cardiologists – James O’Keefe and Carl Lavie. They’ve worked together on a number of papers that frequently make headlines by claiming that excessive running just might kill you. A selection -

·       “Running too fast, too far, and for too many years may speed one’s progress towards the finish line of life”³

·       “Chronic excessive endurance exercise might adversely impact CV health”⁴

·       “Cardiac overuse injury may be associated with more ominous outcomes, including threatening cardiac arrhythmias, accelerated coronary plaque formation, premature aging of the heart, myocardial fibrosis, plaque rupture and acute coronary thrombosis, and even sudden cardiac death”⁵

·       “It is common, in our experience, that mothers tend to urge their offspring not to do marathons and other extreme endurance events. Just as we would all be better off if we heeded our mothers’ advice to eat fruits and vegetables, we would likely do well to not make a habit out of doing marathons”⁶

 

Their position is clear – running very much or very hard is likely to impact your heart in a negative way, which in turn places you at risk of early death. Which….sounds very scary right? Of course it does – you don’t want to accidently run too much and suddenly drop dead because of it. And these guys don’t really beat around the bush. They tell you, and make national news for telling you, that you are playing with fire and placing your health in danger if you run too much.

-------------------------------

You can probably guess what happens next – I look at some of their papers and tell you that their claims are mostly baseless nonsense.

Lets start with a paper titled “Dose of Jogging and Long-Term Mortality: The Copenhagen City Heart Study,” that divides people by volume and frequency of running and tracks deaths over a decade.⁷ The premise is simple enough – the researchers grabbed about 1,000 people from the larger Copenhagen City Heart Study and surveyed their running habits, ultimately breaking them up into the following groups by running status: Sedentary, Light, Moderate, and Strenuous. After 10 years, when counting up the number of deaths, they found that “strenuous joggers have a mortality rate not statistically different from that of the sedentary group.”

There you have it, apparently – Running far and/or frequently is just as bad as not running at all. If you want to be healthy, jog only a small amount and don’t risk damaging your heart. But, of course, this is all ridiculous bullshit. For at least a couple reasons. Deaths are as follows:

 

  

Notice that the actual death rates differ remarkably. 30 percent of the sedentary group died during the follow up. But it wasn’t (specifically) because they were sedentary, although that surely didn’t help. Its because they were in their 60s, on average, when the study began. Meanwhile, there were only 2 total deaths in the much smaller strenuous running group. And it’s the nature of this group that’s such a major problem, for a couple of reasons.

The first is that with a sample size this small, the 2 deaths are essentially “random.” A change of one death in either direction massively changes the outcome. If there had been 3 deaths instead of 2, we might have been subject to headlines about running killing more people than smoking. You simply can’t get any kind of precise number in a tiny population. 

However, this first problem is extremely minor compared to the second – There is no effort made in this study to assess cause of death. They acknowledge as much, somehow blaming that problem on the number of deaths they recorded – “The small number of deaths in each group made it impossible to report different causes of deaths.”

I have no idea why this should make it impossible to report cause of death, but I have no problem whatsoever levying an accusation as to why they’d claim it to be impossible - Its impossible for them to report cause of death because in order to demonstrate that running increases cardiovascular mortality, you need runners to die of cardiac-related causes. And that probably never happened.

Recall that the sedentary group began this study at an average age of 61. The strenuous running group? They were only 38, on average, at the study’s outset (to be clear, they do adjust for the age difference). Which does help explain the low mortality rate, but also helps us make educated guesses about the cause of these 2 deaths (since the researchers won’t tell us). The most common cause of death, by a wide margin, for a person in the 35-44 age group is by accident. In fact, individuals in this age range are some 3.5 times more likely to die by accident, homicide, or suicide than they are by “diseases of the heart,” which account for only about 12% of deaths.⁸ So, knowing literally nothing else about these people except that they died and were most likely in their early 40s, we can estimate that there’s about a 77% chance neither of them died from “diseases of the heart.” 

And that’s why the researchers didn’t attempt to report cause of death. Because the entire point of this paper is only to fabricate “evidence” to support the notion that too much running promotes fatal cardiac consequences. In order to demonstrate that this happens, first you need to demonstrate that running “causes” people to die. And you can only do that by grabbing a very small sample size, hoping at least 2 of them randomly die (again, only random 1 death would have torpedoed their analysis), and then ignoring actual cause of death in order that you may theorize it must be due to cardiac complications. This entire paper pushes the narrative that running is bad for your heart because exactly 2 people (2 people!!) died in what, statistically speaking, was far more likely to be a car crash.

Furthermore, this is the only paper I can find in which O’Keefe or Lavie actually produce data to support their argument, although of course I’m using the term “support” in only the loosest possible sense. They do occasionally reference other pieces of data, but only in ridiculous and hyperbolic ways. For example, the claim that “considerable evidence has established the link between high levels of physical activity and all-cause and cardiovascular disease-specific mortality” is seemingly only supported by findings that higher levels of exercise fail to reduce (but not increase!) cardiovascular deaths in patients that previously suffered a heart attack.^9,10

 

Excessive Bullshitting

We aren’t done. Lets now consider another paper O’Keefe and friends wrote a few years later, in part about how the previous paper helps prove excess exercise to be detrimental to health. This paper begins by claiming the following:

 

“Middle-aged and older individuals engaging in excessive strenuous endurance exercise appear to be at increased risk for a variety of adverse effects—mostly CV in nature”¹¹

Which is a claim indeed. And a claim that is, ostensibly, well-supported – the authors attach 18 unique references to this claim. That’s a lot! That makes the claim seem more credible! That’s probably why they included so many! And listen, I won’t claim to be entirely innocent of the same tactic. I’ve added more references than necessary at times because more studies confirming the same finding add weight to said finding. But the huge, major, overwhelming difference between me and these clowns is that when I cite 18 references, all 18 of them are absolutely going to support the statement I’m making. On the other hand, among our 18 studies cited here, apparently demonstrating that strenuous exercise increases CV risk, is one that reaches the following conclusion:

 

“We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum”¹²

 

And another that found “excessive” vigorous exercisers in fact die the least:

 

“Among people reporting any activity, there was an inverse dose-response relationship between proportion of vigorous activity and mortality. Our findings suggest that vigorous activities should be endorsed in clinical and public health activity guidelines to maximize the population benefits of physical activity.”¹³

 

And another that found that…

 

“In the analyses of change in running behaviors and mortality, persistent runners had the most significant benefits”¹⁴

 

And here’s a fourth!

 

“Higher levels of physical activity were associated with greater gains in life expectancy”¹⁵

 

So that’s 4 studies that find “excessive” exercise to be at least as, if not more, healthy than moderate levels, yet all 4 are cited as evidence that excess running has the power to kill. There’s a fifth paper I can’t access behind a paywall, and then 13 additional papers authored at least in part by O’Keefe, Lavie, or both, in which they repeatedly cite their own theories as basis for the next paper in a circular logic kind of way. This is a time-honored tradition for these gentleman, who over the course of some 15 years have created a catalogue of essays on the theoretical dangers of running that cite greater and greater numbers of their previous musings, each paper counting as an additional “evidence” about the potential harm of excessive running.

All these papers do, for the most part, is repeat each other and reference themselves back and forth in order to increase the volume of papers that suggest the same thing. They will, of course, throw in scary bits about exactly what it is that’s killing you when you run too much, like sudden cardiac death (SCD). And here’s the thing – SCD is, unfortunately, real. Something like 1 in 100,000 marathon or Ironman participants will simply drop dead. Some people are going to be unlucky. Occasionally, some person with an underlying heart condition may die during great physical exertion. However, the notion that SCD is proof of running’s cardiac destruction is ridiculous, particularly when the risk of SCD during a particular bout of physical activity is as much as 30 times lower in the most physically active individuals vs. their sedentary counterparts.¹⁶

 

Excessive Risks?

Are there any real risks that I’m thus far underselling? Maybe…The most legitimate and most commonly cited as a cause of SCD is probably atrial fibrillation or other arrhythmias developing from extreme endurance training. One of O’Keefe and Lavie’s many papers on the dangers of running includes the following graph:

And such arrhythmias do in fact seem more common among extreme endurance athletes later in life, although (as suggested by those massive uncertainty lines), this isn’t a particularly consistent finding. Beyond that, its difficult to figure out what such an increase would even mean. I can’t find any studies, for example, that show elevated rates of arrythmias among endurance athletes and then also track mortality and CVD data for years to assess potential negative consequences of those arrythmias. It’s possible that arrhythmias could increase while still remaining benign in nature.

Take, for example, a study examining previous finishers of the 90km Vasaloppet ski race. The researchers demonstrated that future arrythmias were more likely in older participants and those who completed more editions of the race, while being lowest among the slowest finishers. They did not, however, “observe higher incidence of sudden cardiac death with higher number of completed races or finishing time,” although this only considered Vasaloppet finishers and not the general population.¹⁷ Meanwhile, a second study on largely the same population of finishers demonstrated significant reductions in death and cardiovascular complications relative to the general populations – With a trend towards greatest reductions among the oldest competitors and those who had finished the greatest number of races. There’s just no good evidence that any increase in arrythmias among endurance athletes translates to tangible mortality risk.¹⁸

 

Conclusion

So…will running a bunch place you at increased risk for future cardiovascular complications or death? Probably not. We can say a couple things with pretty high confidence. One, that the most extreme levels of endurance training and racing inarguably improve cardiovascular health and future health outcomes. Two, that those extreme levels of training probably offer little to no additional health benefit vs. more moderate levels. We can say with somewhat less confidence that you may be placing yourself at increased risk for future arrhythmias by training at high volume and intensities. We can’t really say with any confidence at all if those arrhythmias would translate into any tangible consequence.

So, no, I don’t deny the possibility that sudden cardiac death or arrythmias could result from extreme levels of endurance training. But there is no data whatsoever that suggests this risk translates into negative consequences on a population level. Serious endurance athletes, by and large, are healthier than and live longer than most other people. To any degree that negative cardiac complications occur, they occur only at the margins. They occur only as statistical noise, that does little to limit the greatly increased cardiac/cardiovascular health of persistent life-long endurance athletes.

For my own two cents, given the dearth of evidence linking extreme endurance competition to cardiac complications, I’d wager an unfortunate soul is a lot more likely to discover or exacerbate an underlying heart condition during extreme exercise than they are to breed a new one (but, unlike certain others, I’m willing to admit this is largely conjecture on my part). I’d also venture a guess that, to whatever degree future cardiac complications may arise in this population, that they may be just as well linked to the “anything goes” sugar-guzzling mindset that permeates much of both elite and recreational endurance pursuits. If I were offering candid advice, it would be that there are no real downsides to avoiding the underlying dietary drivers of cardiovascular disease – sugar, seed oils, grains – or ensuring easy training is indeed sufficiently easy (we perhaps agree here, as O’Keefe uses the hilariously arbitrary pace of 10 minutes/mile as slow enough to be safe).

I can’t say what will happen to your heart if you train your ass off for the next 15 years. What I can say, unequivocally, is that people who train their ass off for years on end absolutely live longer and suffer fewer cardiovascular complications than the average person. And there’s some important nuance there – people typically don’t train their asses off for health reasons. Even if there were a tangible argument for moderating, maybe half a year of expected lifespan, I don’t think most serious athletes would be interested in making that trade.

And they shouldn’t have to. The claim that “running too fast, too far, and for too many years may speed one’s progress towards the finish line of life” is not only highly irresponsible but is in fact an outright fabrication. When literally zero of the first 200 sub-4 milers die of early cardiovascular complications, when Tour de France cyclists outlive the general population by years, when no evidence has ever, ever, ever demonstrated an increase in early death among highly competitive endurance athletes (and when “great” maximal oxygen consumption is associated much longer lifespan than “good” oxygen consumption¹⁹)…Statements like these exist beyond the realm of conjecture or hypothesis. They, instead, are fantasy.

I won’t claim to know that there is literally no risk when one engages in extreme endurance competition, but I will certainly accuse O’Keefe and Lavie of fabricating evidence to push the narrative that it may kill you. Not only do they use twisted data to support their agenda, they support their narrative with evidence that is entirely contrary to their claims. This is not a mistake, or a misrepresentation, or a small stretching of the truth on their end. It is a lie, an outright fabrication. It is not something fit to be print in an academic journal, and it is not something a respectable journalist should be engaged in promoting. It is a scare tactic, for reasons still not clear to me. But they have a clear agenda, and they have proven time and time again that they will lie to promote it.

While I must, as always, stress that this is not medical advice (you should probably see a doctor if your heart is doing something weird...), it is absolutely a claim that these fearmongers are stoking baseless fear for reasons unknown, and a steadfast opinion that you should probably just go ahead and relax and head out for that run. 

 

 

1.           Foulkes S, Hewitt D, Skow R, et al. Outrunning the grim reaper: longevity of the first 200 sub-4 min mile male runners. Br J Sports Med. Published online May 6, 2024. doi:10.1136/bjsports-2024-108386

2.           Marijon E, Tafflet M, Antero-Jacquemin J, et al. Mortality of French participants in the Tour de France (1947–2012). European Heart Journal. 2013;34(40):3145-3150. doi:10.1093/eurheartj/eht347

3.           O’Keefe JH, Lavie CJ. Run for your life … at a comfortable speed and not too far. Heart. 2013;99(8):516-519. doi:10.1136/heartjnl-2012-302886

4.           O’Keefe EL, Torres-Acosta N, O’Keefe JH, Lavie CJ. Training for Longevity: The Reverse J-Curve for Exercise. Mo Med. 2020;117(4):355-361.

5.           O’Keefe JH, Franklin B, Lavie CJ. Exercising for Health and Longevity vs Peak Performance: Different Regimens for Different Goals. Mayo Clinic Proceedings. 2014;89(9):1171-1175. doi:10.1016/j.mayocp.2014.07.007

6.           Bhatti SK, O’Keefe JH, Hagan JC, Lavie CJ. The Lady Doth Protest Too Much, Methinks. Mo Med. 2013;110(1):17-20.

7.           Schnohr P, O ’Keefe James H., Marott JL, Lange P, Jensen GB. Dose of Jogging and Long-Term Mortality. Journal of the American College of Cardiology. 2015;65(5):411-419. doi:10.1016/j.jacc.2014.11.023

8.           nvsr70-09-tables-508.pdf. Accessed May 28, 2024. https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-09-tables-508.pdf

9.           Lavie CJ, Lee D chul, Sui X, et al. Effects of Running on Chronic Diseases and Cardiovascular and All-Cause Mortality. Mayo Clinic Proceedings. 2015;90(11):1541-1552. doi:10.1016/j.mayocp.2015.08.001

10.         Williams PT, Thompson PD. Increased Cardiovascular Disease Mortality Associated With Excessive Exercise in Heart Attack Survivors. Mayo Clinic Proceedings. 2014;89(9):1187-1194. doi:10.1016/j.mayocp.2014.05.006

11.         O’Keefe JH, O’Keefe EL, Lavie CJ. The Goldilocks Zone for Exercise: Not Too Little, Not Too Much. Mo Med. 2018;115(2):98-105.

12.         Arem H, Moore SC, Patel A, et al. Leisure Time Physical Activity and Mortality: A Detailed Pooled Analysis of the Dose-Response Relationship. JAMA Internal Medicine. 2015;175(6):959-967. doi:10.1001/jamainternmed.2015.0533

13.         Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle-aged and Older Australians. JAMA Internal Medicine. 2015;175(6):970-977. doi:10.1001/jamainternmed.2015.0541

14.         Lee D chul, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN. Leisure-Time Running Reduces All-Cause and Cardiovascular Mortality Risk. Journal of the American College of Cardiology. 2014;64(5):472-481. doi:10.1016/j.jacc.2014.04.058

15.         Moore SC, Patel AV, Matthews CE, et al. Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis. PLOS Medicine. 2012;9(11):e1001335. doi:10.1371/journal.pmed.1001335

16.         Out of Hospital Sudden Cardiac Death Among Physically Active and Inactive Married Persons Younger than 65 Years in Slovenia Out of Hospital Sudden Cardiac Death Among Physically Active and Inactive Married Persons Younger than 65 Years in Slovenia. Accessed May 28, 2024. https://www.researchgate.net/publication/265532052_Out_of_Hospital_Sudden_Cardiac_Death_Among_Physically_Active_and_Inactive_Married_Persons_Younger_than_65_Years_in_Slovenia_Out_of_Hospital_Sudden_Cardiac_Death_Among_Physically_Active_and_Inactive_Ma

17.         Andersen K, Farahmand B, Ahlbom A, et al. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study. European Heart Journal. 2013;34(47):3624-3631. doi:10.1093/eurheartj/eht188

18.         Farahmand BY, Ahlbom A, Ekblom Ö, et al. Mortality amongst participants in Vasaloppet: a classical long-distance ski race in Sweden. Journal of Internal Medicine. 2003;253(3):276-283. doi:10.1046/j.1365-2796.2003.01122.x

19.         Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open. 2018;1(6):e183605. doi:10.1001/jamanetworkopen.2018.3605