The Study That MIGHT Change Lipidology

Last weekend, UCLA cardiologist Dr. Matthew Budoff presented preliminary baseline data at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease that could theoretically, potentially, eventually, help turn the fields of lipidology and cardiology on their heads. 

The first of its kind prospective (ie. forward-looking) study directly assesses arterial plaque and calcification in a population of individuals with extremely high LDL-C resulting from a very low carbohydrate diet (Why this happens HERE). This population, while not entirely uncommon, is largely unstudied and may offer a number of clues to the true nature of lipid behavior and cardiovascular disease. 

Why is this? Because these individuals have very, very high LDL-C - an average of 272 mg/dl. Remember, conventional medical guidance considers an LDL-C above 100 mg/dl to be "high" while average is something around 120 mg/dl. 272 mg/dl is way past the 99th percentile and is more than 40% higher than the American Heart Association's threshold for automatic, no-questions-asked high-intensity statin therapy. Factor in the subject's average age of 56 years and they should, in theory, seem like a no-brainer for lipid-lowering therapy. 

These people should be at extreme risk for cardiovascular disease, should they not? Well, yes...if the traditional paradigm is correct. But the lipid-heart hypothesis is not nearly the settled science the AHA, pharmaceutical companies, and the medical establishment would have you believe. Instead, there are I believe two principle theories by which atherosclerotic cardiovascular disease may develop: 

•  Theory 1 is that LDL-C and LDL particles themselves are the direct, primary, and uniquely necessary elements of atherosclerotic disease. Elevated levels of LDL particles and LDL-C increase your risk for such disease by increasing the chance that, over time, more and more of these particles will become trapped in the wall of the blood vessel and ultimately lead to the development of plaque, arterial occlusion, etc. This is the common theory advanced by the medical industry. 

• Theory 2 is that LDL particles damaged as a result of oxidative stress or hyperglycemia are the target of immune cells whose function is to trap the damaged particles for recycling and removal. When poor metabolic efficiency, hyperglycemia, and increased oxidative stress lead to an excessive number of damaged LDL particles, this process occurs at a greatly increased rate. The development of plaque, arterial occlusion, etc. is fundamentally an inability of the body to remove and recycle these damaged particles as quickly as they accumulate. I've written many thousands of words about why I favor this theory. 

Now the subjects in this study are excellent candidates to test these theories because they not only have very high LDL-C, but also good metabolic health (HDL = 90, Triglycerides = 64, BP = 117/76, A1C = 5.4%). This means the key sentence in Theory 2 ("poor metabolic efficiency, hyperglycemia, and increased oxidative stress...") is of limited relevance and allows a unique opportunity to compare the two theories. If Theory 1 is correct, these individuals should rapidly develop cardiovascular disease. If Theory 2 is correct, they should not.

So far we only have preliminary, baseline date, which you can watch be presented HERE, but which I'll summarize briefly:

CAC and plaque scores for low-carb and control groups

• The researchers assessed two direct measures of atherosclerotic disease - coronary artery calcification and a "total plaque score" (calculated via CT angiography). These were measured in both the low-carbohydrate group and a control group matched for age, metabolic health, etc. The only major difference between the two groups was LDL-C, which was more than twice as high in the low-carb group. 

• The researchers will assess both of these metrics again in another year to assess any disease progression in each group

• The majority of subjects in each group had coronary artery calcification scores (CACs) of 0, indicating no calcification (CACs of significantly at-risk individuals commonly range from 100-400 or higher).

• Total Plaque Score is calculated from 0 to 45 (0-3 at each of 15 different potential plaque sites). In the low-carb group, the median subject had a TPS of 0 with an interquartile range (the middle 50%) of 0-2. No subject had a TPS greater than 12. The control group had a median TPS of 1 with an interquartile range of 0-4. The difference between the two groups was not statistically significant. 

• There was no difference in CAC or TPS between the low-carb, high LDL-C group and the control group.

• There was no relationship in either group between LDL-C levels and measured plaque.

Now, it should be noted that CACs and TPSs of 0 are not particularly remarkable. In fact a little more than half of 56 year olds have a CAC of 0 (you can play around on this NLHBI site if you'd like to see). Its normal and healthy to be free of coronary calcification. But what makes this study so potentially fascinating is that these subjects aren't considered "healthy" in a traditional sense. Years of extremely high LDL-C should predict the impending doom of atherosclerosis, but so far at least this group shows little and often no disease progression whatsoever. In fact, their cardiovascular disease state is indistinguishable from matched subjects with good metabolic health and no elevated LDL-C. 

We'll have to wait until 2024 for follow-up results, in which actual plaque progression in each group will be compared. But if two groups with similar metabolic health yet vastly different LDL-C levels continue to demonstrate identical disease states (or the lack thereof), it would lend significant credence to the notion that metabolic health and other associated factors, rather than LDL Cholesterol, drive chronic cardiovascular disease. Ideally, this would help launch a number of other studies to further challenge common assumptions and explore underappreciated aspects of lipidology and cardiovascular disease. Will that be the case? TBD...

Fuck Around and Find Out....

 ....That Your Underlying Health Is Still in the Trash

This is probably going to get long, and I’m kind of a broken record at this point. This will be the third post this year in which I detail the ways in which I’ve been unable to move fully past my autoimmune condition, or made a mistake, or failed to be as absolutely diligent as is necessary to keep my neurological symptoms at bay. I’ve messed up, again, and the ramifications of doing so have me deeply contemplative. So I’m gonna monologue for a bit.

I won a race a couple months ago. It was amazing, truly one of the greatest days of my life. I overcame so much to get to that point. I wrote about it here – About keeping neurological complications at arm’s length and about the unusual ways in which my body failed to respond like I’m accustomed to when racing.

When things are bad, as they’ve been lately, my fine motor control and muscle function are noticeably impaired to a degree of, I dunno….lets say 30 percent. I twitch and shake, I bump into things, I drop things, I struggle sometimes with balance. I had none of those problems during the race. But it was still there, just a little…tiny…bit. Lets call it 2 or 3 percent now instead. My legs wouldn’t respond quite the right way when running hard. They cramped and seized early in the race and I had to fight my body the last 45 minutes of the race. I won in large part, I think, not by outright running faster but by taking risks on the technical sections and being willing to go all the way over the edge to win a small local race.

I had been eating a lot of dried mango in the week leading into the race. It was a food I had been eating a bit with some regularity in small amounts, but only now was consuming the way I had been consuming blueberries and bananas. And for whatever reason, it doesn’t work for me. It induces neurological symptoms, to at least some degree. It became apparent as I experimented the week after the race that the symptoms I described before my first race – “intermittent headaches, cervical numbness, peripheral fatigue and tingling” – came and went in concert with appreciable mango consumption.

Ok, so we found another food I probably shouldn’t be eating. Easy enough – In fact I raced again the following week to better physical results. This race was hillier and longer, a 25k trail race (or 26.5k, but who’s counting?) in what they call “Mountain Maryland.” I lost – my 23^rd (!!!) career runner-up finish – but raced sooooo much better than I had the week prior. The two of us ran together for 20k before I totally exploded hiking up a ~30% climb with about 4 miles to go. While the week prior my body rebelled in the early miles, this time I had no such problems. I raced normally, and it was great. At this point, in early November, I felt so, so good about things.

A couple days later I got a flu shot. This was the third time since the onset of my autoimmune condition that I’d done so. The first two were basically fine – bad side effects, but difficult to assess any transient effect on my neurological symptoms as they were far more present generally one and two years ago. I had a day of obnoxious side effects again, and took it easy the day after. On day 2, I ran twice just like I had planned. Problem was I shook and trembled the entire way. I felt completely detached from my legs, which simply didn’t move the way I wanted them to. It’s so weird to describe – its like the dial-up internet of motor function, like I can think about moving my leg and then sit and wait for it to finally happen. It’s a very shaky and unstable feeling.

Anyway, I ran twice. Had to stop a bunch to rest. Finally shuffled my way though an awkward 15 miles. And you know what? I did it again the next day. I felt worse and worse as the run progressed, but I got it done. And again the day after that, but this time 22 miles of suck. My resting heart rate was super elevated, I was having hot flashes, my limbs went numb whenever I sat down, my neck and head hurt like hell. But I shuffled through 22 miles anyway. Because I was too stubborn not to. And then I finally snapped a little bit. Those three days had been my worst in months. I was only weeks removed from feeling 100% normal and had 2 more races scheduled in the next few weeks. I was, to put it mildly, frustrated. And I gave into those emotions – I pigged out on cheese, salami, Naked fruit smoothies, plantain chips. Nothing acutely terrible, but several things at once that would all negatively impact my health and symptoms.

The next week, on Thanksgiving, still not feeling quite normal, I trudged through a few miles with my wife before completely giving up mid-run. Things just weren’t right and I had had enough. I told her I was done, I went home and, this time, I gave in completely. It was Thanksgiving after all, family was in town, and I hadn’t been quite right in a couple weeks or more. So what fucking difference would it make if I just let go and acted like a normal person? I drank hard cider, ate mashed potatoes and gravy, ate ice cream…I did Thanksgiving. And I cooked a good turkey, dammit.

And I felt it. I forced my way through the next day with ibuprofen and coffee (itself a major trigger of symptoms that I’ve avoided for some time), but spent the next couple days, including my 33^rd birthday, largely in bed. For months I had planned to run 33 miles on my birthday. Its something I had done a couple times when younger and wanted to do again, in part as an exclamation point on my triumph over my autoimmune condition. Instead I spent the day as I described above - I twitched and shook, I bumped into things, I dropped things, I struggled sometimes with balance. I laid on the couch and all my limbs went numb. I had a really bad day.

It was, frankly, really depressing. And this is part of where I get particularly contemplative – for two and a half years I’ve felt like I’m not allowed be upset, or to feel disheartened or frustrated when things are bad. Honestly I feel I’ve been, at least in part, conditioned to feel that way. I’ve been dismissed so frequently that every time I allow myself to experience any human emotion, I feel like I’m providing ammunition to all the doctors who look at half a dozen adverse autoimmune markers and still think this is all in my head.

Last year I had a doctor accuse of me of not actually wanting to be healthy. I tried to explain how massive a difference diet made – a year later literally a difference between winning races and spending all day stuck in bed, numb and twitchy. My approach was not only working, it was and is validated by dozens of studies and academic papers, and a functional understanding of evolutionary biology. But I couldn’t explain why I was approaching things the way I was, because she was raising her voice and cutting me off. She was accusing me of leaning into it, of choosing this, and enjoying this in some perverse way. She was accusing me, if I declined to take an antidepressant for my dizziness, numbness, migraines, impaired motor control, and stabbing neck, face, and cerebral pain, of choosing this for myself and refusing to actually solve the problem. This doctor was not alone in her assumptions.

I was positive for literally every marker of neuropsychiatric lupus. Symptoms of that condition include acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis. I suffered (and when things are bad, still sometimes suffer) from every one of those symptoms. Suffering from mental, neurological, or cognitive symptoms does not mean I’m making this shit up. I’m not faking anything because I like the attention, and I do not want to be sick. It is, contrary to the opinion of seemingly every doctor and every fucking wannabe medical expert, possible for the nervous system to be subject to actual physical damage. Or to be the focus of a persistent autoimmune condition. It does not have to be a goddamn serotonin problem. It does not have to be a mental health problem. It can be a real, legitimate, physical disease.

But its been suggested, over and over, by doctors and “experts” and even normal people in my life that its all in my head. And I think I fight that specifically as hard as I can, for as long as I can. It frankly fucking sucks to be so diligent about everything you do, all day every day. It sucks to not be able to eat “normal” food without going numb and tripping up the stairs.  I should never have done what I did. I should never have eaten those things. I shouldn’t have given in and invited a greater relapse of neurological problems.

But I did. I gave in. Twice in less than two weeks I failed to be optimistic, and tough, and strong. I’ve so relentlessly pursued a return to health and fitness. I’ve run and lived and existed through so much pain and discomfort and impaired function and every so often I’ve failed to keep my head screwed on straight. And it makes me fail like a failure. Like I’ve compromised myself as a person, and proved right all the doctors and people who think I’m making this up, or who think I’m some kind of vaccine conspiracy theorist, or have completely refused to honestly engage with me for whatever other reason.

So where am I now? I’m trying to let go of all that and move on. I don’t really expect anyone wants to read all this but being open about my experiences helps me do those things. I’m trying to forgot about the doctors who have dismissed my condition or tried to simply diagnose me with depression, and accept that every so often I’m going to feel unhappy and frustrated with where my health is at, and that’s fine. I’m trying to accept it as part of the process, rather than view it as weakness or failure. More immediately, I’m about to start my third week- (or so) long fast. I actually feel pretty decent now and am exercising a bit, but given that my underlying health hasn’t progressed as far as I’d been assuming a month or two ago, I think it prudent to fast for a while and see if I can’t take another significant step forward.

Within two weeks, I’m going to feel “perfect” and be running every day. I’ll get back to it, training every day and eating the few things that don’t trigger any symptoms (no mango!) with no real plans to expand my diet any time soon. I don’t think there will be any racing until maybe April or so, but I’m planning on being in much better shape than I was this fall. I don’t have any specific goals in mind right now, but I do think my best races are still in front of me. I am persistently optimistic that this will be the case. And I’m hoping to get there, and be fully healthy, some time in the next calendar year. I guess we'll see...

Thanks for reading. All the best