RHR: Community Q&A: Cholesterol, ADHD, Paleo for Children, and Long COVID

In this episode, we discuss:

• Whether LDL particle count is a clear, independent risk factor for cardiovascular disease
• How adults with ADD/ADHD can increase their focus naturally
• Best practices for feeding children a healthy diet
• The leading theories of what causes long COVID, both from a conventional and Functional Medicine standpoint

Show notes:

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Hey, everyone, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, we’re going to do a Q&A episode, starting with a question from Linda.

“Hi, Chris. I just listened to your podcast reevaluating cholesterol and its effect on our health, and I’m totally confused. Just yesterday, I listened to Robb Wolf’s interview with Bill Cromwell of Precision Health Reports, and Bill Cromwell’s assertion in this podcast was that LDL particle count definitely is an independent risk factor for cardiovascular disease and cardiac events, independent of whether there are any other risk factors. Specifically, if you are insulin sensitive, you have a low [lipoprotein insulin resistance] (LPIR) score, good blood pressure, etc. Good fasting insulin, a good fasting glucose level. He says that a high LDL particle count over time is in fact an independent risk factor. So I would love to know your thoughts on his position on this. Thank you so much, Chris. I love all your work.”

Thanks for sending in that question, Linda. We get this question fairly regularly. It’s definitely a good one, and it’s one that I’ve talked about a few times in past episodes, but I’d love to revisit it. Because my thinking on it evolves over time, and there’s always new information to account for, of course. So the first thing I want to look at is whether we actually do have enough data to suggest that LDL particle count [(LDL-P)] is clearly an independent risk factor for cardiovascular disease and cardiac events, independent of other risk factors. In order to really know the answer to that, we would need a very controlled study where you have two groups of people with no other risk factors, but one group has high LDL-P and the other group has normal LDL-P. And then you need to follow those people for quite a long time to track the incidence of cardiovascular events in both groups. We don’t have a study like that.

What we do have is a study of people in the general population, some of whom have high LDL-P, some of whom have normal LDL-P and some who have other risk factors. And pretty much everyone has other risk factors in these types of studies. It’s very rare to have people in these studies that don’t have any other risk factors, and that’s kind of the problem. What researchers might say is that, yes, we can control for those other risk factors. So they control for high blood sugar, they control for hypertension, [and] they control for waist circumference, and then the intention there is to remove the influence of those factors. But my problem with that is that they rarely, if ever, are able to control for all of the other potential risk factors, for example, the health of the gut microbiome. I’ve never seen a study that actually controls for that, and I do think that that could play a meaningful role. And there may be other factors that we’re not even aware of and that we don’t even know to control for. So I’m not convinced that we have the data that can really answer this question.

Of course, you could look at the mechanistic argument. So we know, or at least we think we know because that’s often changing, as well, how atherosclerosis develops. This is something that’s been studied for a long time. It’s not completely a mystery to us. And we know that all other things being equal, if you have a higher concentration of LDL particles in your blood, then there’s a greater chance that one of them will injure the fragile lining of the endothelium of the blood vessel, and that injury then leads to plaque formation, and that plaque, if it becomes unstable, ruptures and becomes the initiating factor for a heart attack. So just on that basis, if you took two hypothetical people that are doppelgangers for one another, every single thing about them is the same except one has high LDL-P and the other has normal LDL-P, then, according to that mechanistic argument, the person with higher LDL-P would be at higher risk of cardiovascular disease. And I don’t think that’s an invalid argument. But I still think that’s not a certainty, and it doesn’t fully answer this question. So that’s one level to look at it.

The other is looking at risk in general and risk tolerance, and understanding that we’re rarely making changes in a vacuum. So what do I mean by that? Let’s say a patient comes in to see me; they’re overweight, they have high blood sugar, they have other markers of metabolic syndrome, and their LDL-P is, let’s say, fairly normal. But they’ve got all these other markers that put them at risk of not only cardiovascular disease, but diabetes and other poor health outcomes over time. And let’s say I then put that patient on a low-carbohydrate or ketogenic diet, movement routine, etc. And let’s say they have a vast improvement in all of those other metabolic markers. They lose 40 pounds, their waist circumference and [body mass index] drops, [there’s a] reduction of abdominal obesity, their blood pressure drops, their blood sugar drops like a rock, fasting glucose goes down, fasting insulin goes down, hemoglobin A1c goes down, their inflammatory markers like [C-reactive protein] and ferritin go down, they feel way better and their LDL-P goes up, and maybe it even goes up quite a bit. What’s that person going to do? What am I going to suggest to that person?

Here we have a situation where 98 percent of the markers that we would use to assess health have improved with this particular intervention. And one marker has gone up, and gone in a hypothetically wrong direction. So what makes sense in that situation? Are we just looking myopically at the LDL particle number and we’re going to switch, or change that intervention and do something else because that one marker went up, despite the fact that all of those other markers went down or improved, and the patient is feeling vastly better? Are we going to prescribe or recommend a statin drug to possibly bring that LDL-P down while continuing with the dietary and lifestyle intervention that led to the improvement of the other markers? That’s probably what many people would recommend; even lipidologists, like Tom Dayspring and Bill Cromwell, and others in the space might recommend that. But that decision is really personal. It really comes down to each individual.

I’ve had patients who just want to do everything they can to minimize their risk to the greatest extent possible. So maybe that patient would choose to stay on the ketogenic, low-carb diet, and also add a statin in the hopes that they could get all of the benefits [of] the dietary intervention, and also lower the LDL particle count with the statin drug, which is not a sure thing. Sometimes statins are effective for that, and sometimes not so much. But that particular patient may choose to do that. I’ve had a lot of other patients who don’t want to do that. They don’t want to take a statin for any number of reasons, and when they do their own risk assessment, and they figure, okay, I’ve made changes that have dramatically improved my health, virtually across the board, with the only exception being this one marker that went up. And we may not know enough about the impact of this one single marker, especially in the context of all these other markers improving, and I choose to potentially take the risk of living with this elevated marker rather than taking a statin. Of course, there is some middle ground. There are some supplements that we use in practice to help reduce the high LDL-P. We look at underlying causes. We know, for example, that gut infections and disrupted gut microbiome, environmental toxins, heavy metals, [and] other inflammatory conditions can raise LDL particle count. Poor thyroid function. So we would want to look at those and determine if those are playing a role. But even if all of those have already been identified and addressed, and they still have the high LDL-P, some people are going to decide to not take the statin and maybe or maybe not take supplements and just live with that as a potential risk factor because they feel so much better and they have decided, for whatever reason, not to take statins. And I think that’s a perfectly legitimate choice. Like I said, it really comes down to the individual, their own preferences and values, and their own risk assessment and choices that they want to make about their own health. So there’s really no right or wrong answer in that context.

And, I think we’ve kind of lost the ability to do that sort of risk calculation with medical choices. We’re doing it all the time in other ways without even thinking much about it. Every time you step into a car, basically, you’re taking a fairly decent risk. We’d like to think we’re always in control when we’re driving a car. Of course, that’s not the case. And there [are] still 30,000 people, at least a year that die in traffic fatalities, and many more that get in serious accidents. And, we pretty much know that if we were to just go out and drive at five miles an hour, we’d vastly reduce the risk of that, if everybody did that, especially. But we choose to take the risk of driving at a faster speed, because we recognize that we get benefits from that, and we want to continue to live a “normal life” where we get those benefits, instead of doing every possible thing we could do to minimize the risk of driving, of a car accident. Of course, the way we could do that most is to avoid driving in a car at all. And some people might if that’s the way they’re approaching that kind of risk management. But for many people, it’s either a conscious or unconscious calculation that’s done where we are weighing the pros and cons of each choice. And then we make our choice. I think that this is an attitude that we also need to have when it comes to the medical or health choices that we make.

I’m so appreciative of all of our podcast listeners. In this episode of RHR, I answer some frequently asked questions from our “health activist” community. We cover topics such as LDL particle count and cardiovascular disease, a Functional Medicine approach to ADD/ADHD and long COVID, and the best diet for children.

All right, so let’s move on to the next question. This one is from Kerrie.

“How can adults with ADD increase their focus and function naturally, rather than taking medication such as Adderall?”

That’s a great question, Kerrie. This is something that I have done a fair amount of research [on] over the past few years. I think I’ve mentioned this in a recent podcast, but my perspective on this over time has evolved. I think, early on, when I didn’t understand ADHD as well as I do now, I tended to think that it was a diagnosis that was created by pharmaceutical companies so that they could sell more medication both to kids and adults. And I actually don’t think that’s true at this point. I’ve come to understand from a lot more research that ADHD is not a behavioral disorder, which is what it is, unfortunately, still referred to as in many circles, but is a developmental disorder. So what that means is that the brains of people and the nervous systems of people with ADHD develop differently than the brains and nervous systems [of] people without ADHD. And these differences in development are actually evident on brain scans and other objective techniques of measurement. So researchers can actually see changes in the brain and different brain structures in people with ADHD and people without ADHD. And those changes can vary the nature of them depending on the specific type of ADHD, and the age of the person and some other factors. But the point that I’m trying to get at here is that these are real and measurable changes that can be observed. So really, the best way to think about it is that the brain and nervous system of a person with ADHD developed differently than the brain and nervous system of someone without it.

And I think that’s really important because it can help us understand the condition better; it can help us be more understanding and compassionate of people who have it and if you are one of those people, being more compassionate and empathetic toward yourself and understanding that these are differences in your brain and nervous system that are not necessarily worse or better than other nervous systems. They’re just different. And I think there are certainly some advantages to the way that an ADHD brain and nervous system work, and this explains why some very notable famous people have ADHD, Simone Biles, Richard Branson, Elon Musk. People with ADHD tend to seek out novelty and tend not to be satisfied with the status quo; they tend to be very creative and innovative. And that’s a tremendous upside and explains why so many entrepreneurs and creative professionals, actors, etc. have ADHD. The downside is that it can be difficult for people with this condition to focus for long periods. It can be hard for them to organize and structure their thinking and their actions. They have a really difficult time tolerating boredom because of that novelty seeking. And, particularly, if you’re thinking about kids, like asking a kid with ADHD to fit into a highly structured environment in which they’re being asked to learn and study things that they may not be interested in is a total, you couldn’t design a worse environment for a kid or an adult, for that matter, with ADHD.

I know this wasn’t exactly your question, Kerrie, but I wanted to start with that frame, because I think it’s really important to think about it that way. And that actually does end up influencing my process when I treat patients with ADHD and the general approach. So before I talk about any specifics, I want to plug a book that I really love on this topic called Finally Focused. It was written by Dr. James Greenblatt. I actually had Dr. Greenblatt as a guest on the show a while back. So if you search, if you open a web browser and search for Kresser Greenblatt, [the] top result that comes up will be, The Functional Medicine Approach to ADHD, with Dr. Jim Greenblatt. And Dr. Greenblatt was a real pioneer in the field of integrative and Functional Medicine. He’s been treating patients since 1988, going on almost 35 years, and he was really responsible for creating this Functional Medicine approach to treating ADHD. And he’s been doing that for a very long time. I think he is certainly one of the most knowledgeable people in this field. And I highly recommend listening to that podcast or reading the transcript if this is a topic that you’re interested in. It’s been one of my go-to resources, and his work continues to be a go-to resource in my understanding of the condition and then how to treat patients with it.

So let’s talk a little bit about the basic functional approach. As I’m sure all of [you] who are listening to this [know], we think about things a little bit differently in Functional Medicine. Rather than just taking things to suppress symptoms, we’re trying to get to the root causes of the particular condition. And in the case of ADHD, those can vary a lot. People are different and diverse, and there’s no one underlying root cause of ADHD. It can be different in different people. But the bigger areas that we look at would be nutritional deficiencies; I would say it would be number one. And the most common ones are deficiencies of magnesium and zinc. And then also, one of the trace minerals that doesn’t get a lot of attention, which is lithium, and that is often very low in people with ADHD. Probably the number two area would be the gut, and there’s a number of different abnormalities that can contribute to ADHD in the gut. Those would be everything from small intestinal bacterial overgrowth (SIBO) to undetected parasite or fungal or viral infections to disrupted gut microbiome. Higher levels than you’d want to have unhealthy bacteria and/or lower levels than you’d want of healthy bacteria.

We know that gut bacteria can produce chemicals that affect neurotransmitters in the brain. And there’s a saying in Functional Medicine: fire in the gut, fire in the brain. So that is a shorthand way of saying that if there’s a lot of inflammation and stuff going on in the gut, then that’s going to have a negative impact on what’s happening in the brain and nervous system. Diet is another huge factor, of course. So I think anecdotally, for a long time, like when Jim [Greenblatt] started practicing back in the late ‘80s, and early ‘90s, there was, practitioners, suspected, and just from their own experience, and parents’ experience that eating a Standard American Diet that’s high in processed food and refined sugar contributed to the problem, but we didn’t have the research for that, and now we do. There are studies showing that excess consumption of sugar-sweetened beverages, for example, tends to increase the amount of symptoms in people with ADHD. And there’s a fair amount of research that’s somewhat inconclusive, but there’s certainly some research that suggests that gluten and dairy can contribute. And there’s certainly a lot of anecdotal experience among parents and clinicians like myself that see that a gluten-free and dairy-free diet will often help people with this condition.

And then we have the other lifestyle factors like sleep, physical activity, [and] stress, which all have been shown to play a role in research, as well. So those are the most basic things that I would think about. But then we also have to consider things that are maybe one level out from those basics, if you will. So heavy metal toxicity would be one. It’s not unusual to see kids and adults with these issues have higher levels of metals, like lead, or mercury or cadmium or arsenic. And sometimes copper levels will be elevated, and zinc will be low, as I mentioned before, as one of the potential deficiencies. Infections can play a role, like Lyme disease, chronic Lyme [disease], other tick-borne illnesses, other types of toxins, mold, [and] biotoxins. So just from a general, Functional Medicine perspective, we’d want to be looking at those other potential contributing factors. But if you don’t have a practitioner to do that with, I think, focusing on the basics, the nutritional deficiencies, gut health, diet, and then lifestyle, like sleep and stress management and physical activity would be the most important places to focus.

Now, in terms of supplements, what I’m going to talk about here is very general. The optimal situation would be to get some testing with a practitioner so you can create a protocol that’s individualized for you based on your particular situation. But recognizing that that’s not always possible, I’m going to cover a few of the supplements that Dr. Greenblatt mentions in his book, and that I’ve found to be most helpful in people with ADHD. And these are generally safe and well-tolerated. The caveat here, of course, as always, is if you are taking medications or you have any pre-existing health conditions, you always want to check with your practitioner, whoever you’re working with, before you add a bunch of new supplements.

Dr. Greenblatt has also written a book on [the] nutritional lithium trace mineral, and he’s an expert in this area. He’s done a lot of pioneering work, which has shown that lithium is required for brain function, and although it is a trace mineral that’s present in small amounts in water, his belief, which has not been proven in research yet but through his 35 years of clinical experience, is that individuals with ADHD have a genetically driven higher need for lithium. And one of the ways that you can roughly determine if this might be true for you, is that people [who] have a genetic need for lithium will have higher incidence of family histories of things like substance abuse, ADHD, [or] bipolar disorder, because those things can all be driven by low levels of lithium. So if you look at your family and you see higher rates of addiction or substance abuse, higher rates of suicide or suicidal ideation, family history of ADHD or ADHD-like behavior, or bipolar disorder, then that might clue you in to the possibility that lithium, nutritional lithium is low.

So that’s something that is worth consideration. We’re not talking about lithium here as a treatment that’s used as a medication at higher doses for people with bipolar disorder. We’re talking about nutritional lithium, which is the trace element that’s in water that we drink, typically. You can get supplemental lithium online and in health food stores and stuff like that. And we’re generally talking about a pretty low dose, somewhere between one and five milligrams that’s used for kids or adults. Magnesium is another critical nutrient for ADHD, and there actually is quite a bit of research on this. We also have the collective clinical experience of thousands of clinicians that are doing testing, nutritional testing for people, myself included. And almost universally, Dr. Greenblatt can say that every child or adult that he has tested with ADHD has low levels of magnesium and benefits from magnesium supplementation. And I’m definitely in that camp. I’m not a fan of taking a fistful of supplements forever. But magnesium has been one of the few supplements that I recommend for almost everybody in general. But certainly in people with ADHD. B vitamins are also an important consideration. So folate, in particular. A lot of people with ADHD have either genetic or environmental factors that compromise folate metabolism. So taking folate can be helpful. [Vitamin] B6 plays a very important role in the brain and nervous system, and a lot of people with ADHD don’t get enough.

In terms of getting back, Kerrie, to your very much more specific question about improving focus, Dr. Greenblatt in adults actually prefers the use of rhodiola, which is an herb, a botanical to using prescription stimulants like Ritalin. And he finds that that’s often as effective as the stimulants with fewer side effects. So that’s something that is generally pretty safe to use, especially if you take breaks from it occasionally. And it is probably worth exploring as a natural way of improving focus. Dr. Greenblatt talks about botanical compounds called OPCs in his book, and these are phytochemicals that have a unique impact on brain function. I’ll let you check out the book. I don’t want to go into too much detail here because I want to [move] on to another question. But there are a number of different compounds they have, each with slightly different effects, and they can be taken individually, but I generally tend to prescribe them as a formula just to make it easier. So these are flavonoids, flavonols, cyanidins, and other OPCs; I’ll give you some examples here. Grape extract, wild blueberry extract, pine bark, a green tea extract, which is EGCG, and turmeric all fall into this category. The product that I like to use is called CurcumaSorb Mind that’s from Pure Encapsulations, and that has a nice blend of these OPCs, and it can help with cognitive function [and] emotional well-being. A lot of patients find it to be relaxing and a good stress fighter. So those are a number of things to be aware of in terms of [a] natural functional approach to ADHD. [I] hope that was helpful, Kerrie.

Let’s move on to the next question from Katherine.

“Hi Chris. Thanks for your podcast. I really, really love what you’re doing and really appreciate it. I’ve shared it with so many people. My question as a mom of two young kids is what should we feed our kids? I just got your book The Paleo Cure, and I’m looking to start eating more of a Paleo diet and cutting out grains and dairy for myself. But I’m wondering if you recommend doing the same thing for kids. Should kids also be on a Paleo diet, and how much sugar, if any, should they have? And just some guidelines and some ideas on what’s the best practices for keeping our kids healthy. Okay, thanks a lot.”

Yeah, thanks, Katherine. I know you’re not alone in that question. I’m a father myself; I have a 10-year-old daughter. So I’ve been through this and, of course, lots of friends with kids and lots of patients with kids and lots of people in our coaching programs and practitioner programs with kids. So it’s a really, really important question to be asking, like, how do we set our kids up to eat the most nutrient-dense anti-inflammatory diet that’s going to create a foundation for good health, both physical health and mental health, and send them off into the world with that really solid foundation of resilience and well-being. And it’s not easy, especially in the kind of world that we live in today. Or at least that most of us live in, where there’s constant exposure to processed and refined foods.

If your kid goes to school, they’re seeing other kids that are eating gummy bears and cheese doodles and drinking juice boxes. And if they go to birthday parties, junk food is ubiquitous in the environment. So if you’re a parent that’s trying to feed your kid well, you’re fighting an uphill battle or swimming upstream, whatever you want to call it, for sure. So, there’s that added challenge. It’s not just what do you feed your kid at home? But it’s also how do you navigate this almost constant exposure to junk food? And how do you do all of that without contributing to any kind of unhealthy relationship with food. This is one thing I’ve had to learn as a parent, and over time have, I think, gotten a little bit better with. Although I think I still have some room for growth. Me, being me and the position that I’m in and understanding what I understand about [the] importance of food choices, especially early on in my daughter’s life, I was pretty rigid about what we fed her and what she had access to. But [I] pretty quickly noticed that that strategy has its own issues. I think, from a purely biological perspective in what she’s eating, it makes sense. But there are also other considerations, like her mental and emotional health, her sense of feeling like she’s part of a group, feeling included, not feeling like she’s always on the periphery. Having times where she gets to eat things that she doesn’t typically get to eat. So treats and things that she looks forward to in that way.

And I think all of that is important and needs to be considered when you’re thinking about this question. Where there is more to life than health and food, as I’ve said before, and setting up a situation where the boundaries and the restrictions are just so rigid and tight, could actually backfire. Because if there’s something that’s true about humans in general and kids, in particular, is that what you resist persists, or we tend to push back on limits and boundaries. And the harder or more rigid those are, the more pushback there is. So ultimately, the goal is that we want our kids to be eventually able to make their own good food choices without us intervening at all. So I think any kind of strategy that we set up, that should be the ultimate goal.

So getting back to the question, yes, a Paleo type of diet is definitely appropriate for kids, but I want to add some caveats to that. The first is that often when people begin a Paleo diet, they either intentionally or unintentionally really reduce carbohydrate intake because they’re cutting out most of the sources of bad carbs, like bread and cookies and candy and sugar-sweetened beverages and things like that, [which] really make the biggest contribution to carbohydrate intake. But then they’re also cutting out whole grains and legumes, [and] I think it’s a stretch to call them unhealthy. I think a lot of people don’t do that well with them. But I wouldn’t necessarily say that they’re unhealthy. And they also tend to be higher-carbohydrate foods and dairy sometimes, as well. So you’re cutting all of that out and not replacing it with other Paleo-friendly carbohydrate-dense foods like cassava or taro or plantains or things like that. Then you’re often going to end up on a pretty low-carb diet, and that might be fine for you as an adult, and sometimes it’s not fine. Some people get into trouble that way if they have conditions for which a low-carb diet isn’t great. But it’s not generally a good idea for kids, especially younger kids and teens [who] are really active. They will tend to need a higher carbohydrate intake.

One way of achieving that is by using the other Paleo-friendly starches and higher-carbohydrate sources that I mentioned. So more whole fruit, the roots and tubers, like sweet potatoes, yuca or cassava, plantains; these are Paleo-friendly starches that are pretty high in carbohydrate. But I would also consider, as I mentioned in the book, foods like potatoes, normal potatoes, white rice, and even modest amounts of pseudo grains like amaranth or quinoa, buckwheat, and even modest amounts of other grains, if you tolerate them, okay. [If] you don’t have a gut issue or other issues, it’s occasionally gluten-free bread, or pancakes made from almond flour, or there [are] so many options now for things that you can get in this category. Those can often be helpful for kids to round out the diet; add some carbohydrates back in, make it a little more fun and satisfying, where you get to have, maybe you have pancake day on Sunday, and kids look forward to that. And if you start with that, from the beginning, almond flour pancakes are just what they know, as pancakes. And they usually love it.

You could have a pizza night with an almond flour crust, where you make your own pizza at home. And so you can still have these rituals and things that everybody enjoys and looks forward to, and they don’t feel like they’re missing out as much, and they get more carbohydrate, which I think a lot of kids need. So I think that’s a good approach. And in terms of sugar, again, that depends on your tolerance here and how you want to approach this. But one good thing to aim for, I think, is to really limit processed and refined sugar as much as possible and leave that for birthday parties and certain occasions like that, where, you might go out for ice cream or go to a birthday party and let them have a piece of cake if they’re not gluten intolerant or something like that. But whenever you’re at home, you’re favoring, like, if you’re going to make cookies or almond flour cookies, you make it with natural sweeteners, like maple syrup or something. And if you’re going to make any kind of special treats from a Paleo cookbook, that’s usually the types of sugars they use.

Now, those are still sugar. They’re better because they have some nutrients, and they’re more complex sugars in some cases, but they’re still sugar. So you still want to limit those. But if we think of it as a hierarchy, it might be refined sugar in a treat once a week or something like that, and then some naturally sweetened things like homemade cookies. And the nice thing about doing homemade cookies or homemade treats is you can alter the amount of sugar. If we follow a recipe, we’ll often cut the amount of sugar in half and still find sometimes that they taste too sweet to us. So that’s another big advantage of being able to do those things at home. You can really limit the amount of sugar that you put in, even if it’s natural. But even those would still be limited. And then, the majority of the diet should be made up of whole natural nutrient-dense foods. So I think that’s the general approach that I would take in this situation.

All right, I think we have time for one more question. This one is from Tony. Let’s give it a listen.

“Hi Chris. My name is Tony Caralecus; I’m a 32-year-old male from Boston, Mass. I’ve used a lot of your work and material to, actually, over the last few years, [I’ve had] some [gastrointestinal] problems, and [that] really got me into Functional Health and sort of thinking differently. I had SIBO, leaky gut, ended up with [Clostridioides difficile] (C. diff), and a combination of a lot of different things. [I] brought my gut health back to almost normal, but wanted to request a podcast topic or something. I’m a COVID long hauler. I was sick in March, and like many, many people, [I was] really suffering months out. It’s been nine months. I don’t know how much you’ve looked into this, or there’s not much understanding of it whether it’s sort of an immune cascade. I’ve been drawing comparisons to post-line mold toxicity. Maybe MTHFR plays a role, HLA genotyping. I’m not really sure, or maybe it’s viral persistence, and we still have the virus in us. But [I] just figured this might be a good topic as a lot of people I know are suffering from this right now. So I wanted to reach out with it. Thanks again for all your work. Thank you.”

Yeah, Tony, thank you so much for that question. It’s such an important question. Unfortunately, long COVID is affecting a significant number of people and it’s still somewhat mysterious, in its mechanisms, what causes it, and how to address it. I don’t claim to be an expert on long COVID, but I’ve definitely seen a fair share of people who are dealing with it, and we’ve had some success treating it and approaching it from the perspective that I’m going to share here in a second.

I would say there are a few, right now, the leading theories of what causes long COVID, both in the conventional world and in the Functional Medicine world, would be, one would be autoimmunity. We’ve known for many, many years that viral infections are one of the main triggers for the onset of autoimmune diseases. And this is true for lots of different autoimmune diseases, [like multiple sclerosis], rheumatoid arthritis, [and] Crohn’s disease. This is a well-established risk factor in any kind of viral infection. So it should not surprise us at all that SARS[-CoV-2] can also provoke a kind of post-infectious autoimmunity. And there are case reports about this in the scientific literature. For example, there was a study published in [the] Lancet about a 67-year-old man who developed rheumatoid arthritis post-COVID[-19] and a number of other similar case reports. And so I think that, in general, the kind of approach that we take when we look at long COVID, is to almost assume that there’s an autoimmune component unless we’re proven otherwise.

And sometimes we can confirm that by doing antibody testing that will reveal elevated levels of certain antibodies that shows us that we’re on the right track. But with now over 100 documented autoimmune diseases, and some of them still somewhat mysterious, we don’t really have the capacity to accurately test for all of them, certainly not with a single blood panel. So we’re not always able to confirm it. And we will sometimes just assume that it is even if we don’t have that evidence, and we might start treating it accordingly. So we might suggest an autoimmune protocol (AIP) diet. We might start looking at things like curcumin and glutathione, which we use to help balance and regulate the immune system. Vitamin D, of course. We might consider medications like low-dose naltrexone, which can be helpful in some cases of autoimmunity. And we have seen some success in those cases.

Another mechanism that seems to be coming to the forefront now is blood clotting. There are some studies that suggest that long COVID may be particularly characterized by [an] increase in blood clotting. And when you look at some of the symptoms of long COVID like fatigue, poor exercise tolerance, [and] shortness of breath, those are all symptoms that you would expect with blood clotting. And we’ve got a lot of documented evidence, of course, on how SARS[-CoV-2] contributes to blood clotting. And there was a study actually just published in mid-August, suggesting that blood clotting may be the “root cause” of long COVID syndrome. That was kind of how it was handled in the media. I don’t think there is one root cause, but I think it certainly could be a root cause. In this study, the researchers found that certain markers of blood clotting were significantly elevated in the blood of patients with long COVID compared with healthy controls. Interesting[ly], those clotting markers were higher in patients who required hospitalization, and they also found that higher clotting was directly related to a higher symptom burden of long COVID. This was even true if markers of inflammation had all returned to normal level. So all of the inflammatory markers had gone back to normal, clotting markers were still elevated, and then those were the patients who were sicker, who tended to require hospitalization more, and who tended to be sicker at home.

I think that’s definitely a potential mechanism that’s worth exploring, which we’re starting to do, and that opens up the possibility of looking at things like there are certain natural agents that we know can reduce blood clotting. So the long-chain omega 3 fats, like [eicosapentaenoic acid] (EPA) and [docosahexaenoic acid] (DHA), are example[s] of that. Curcumin is an example of that. And then sulforaphane is another natural agent that can reduce blood clotting. Those are generally safe and well-tolerated, and they can definitely have contraindications. So, especially people who are already on clotting, anticoagulation medicines wouldn’t want to use those and people for whom anticoagulation medications are not a good idea, people with bleeding disorders, etc. So that’s something to be aware of, and definitely a category where you would want to check with your clinician if you fit into one of those categories.

To summarize, unfortunately, we still don’t know enough and looking at it from the perspective of autoimmunity, looking at things to help reduce blood clotting, and then a third thing that has come up is a potential relationship between long COVID and POTS. So, for those that are not aware, POTS is called postural orthostatic tachycardia syndrome. This is a condition of dysautonomia that affects the nervous system. And I’ve definitely seen some cases where this is prevalent, and the symptoms are quite similar. And then I would say related, mast cell activation, which can lead to histamine intolerance, is something that a lot of [folks with] long COVID tend to experience, as well. So POTS can be tricky to treat. I have found more success, and I think, an easier starting point for most folks is to at least start with the thesis that autoimmunity is present and contributing and also potentially, increase blood clotting and work with that and see how far you get as an entry point. And then, for those who are experiencing more POTS-style symptomatology, then that’s another thing that you might explore, and it might be good to try to explore that with a Functional Medicine clinician that has some experience with POTS. Because it can definitely be a tricky condition to treat.

Okay, everybody. That’s it for now. Thanks for sending in your questions, and please keep sending them in to ChrisKresser.com/podcastquestion. We are going to start doing some Q&A episodes again. We get frequent requests for that, and we’re kind of experimenting and changing up the format of the show a little bit. We’ll still be doing interviews, but [we’re] planning to do a few more Q&A episodes and also some solo episodes on particular topics. So you can look out for those in the coming weeks and months. [I] really appreciate all of you listening and being part of this community, and I’ll talk to you next time.

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