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REPLAY: Post-COVID Syndrome with Dr. Adrian Lopresti and Dr. Cliff Harvey

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REPLAY: Post-COVID Syndrome with Dr. Adrian Lopresti and Dr. Cliff Harvey

Dr. Cliff Harvey, Registered Clinical Nutritionist, describes the risk factors of long COVID, busting the myth that long COVID is reserved for those with pre-existing health conditions and extending it to healthy and athletic people. Together with our ambassador, Dr. Adrian Lopresti, Cliff highlights the role of nutritional status in post-COVID syndrome and shares treatment options to support those with nutritional deficiencies, while discussing the importance of a thorough dietary analysis. 

Rounding the conversation off with a discussion on lifestyle factors relevant to the management of long COVID, this podcast is a must-listen for all natural medicine practitioners. 

Covered in this episode

[00:33] Welcoming Dr. Cliff Harvey
[03:36] Long COVID doesn’t present the same for everyone
[06:03] The most common symptoms of long COIVD
[07:46] How is long COVID diagnosed?
[09:03] Other terms for long COVID
[12:23] Connections between nutrition, severe COVID, and long COVID
[15:51] Accurately assessing nutrient status is more than a diet diary
[20:13] Using apps to properly assess diet 
[21:45] Supplementation is critical for long covid recovery
[24:33] Using N-acetyl cysteine as a precursor to glutathione
[26:48] CoQ10, quercetin and others to support mitochondrial health and  combat fatigue
[28:22] Medicinal mushrooms to reduce oxidation and inflammation 
[30:58] Vitamin C
[31:46] Lifestyle and exercise
[35:19] Summarising today’s discussion
[38:49] Thanking Cliff and closing remarks

Key takeaways

  • Long COVID, also referred to as post-COVID syndrome or post-COVID condition is defined as the continuation of symptoms following the infection of COVID-19 beyond one to three months. Symptoms can vary, including fatigue, brain fog, respiratory symptoms, depression, loss of smell, loss of taste, cognitive effects, muscle dysfunction and loss. Diagnosis of long COVID is done by exclusion. 
  • Long COVID is prevalent in people who have experienced severe COVID infection generally, however, it can extend to all COVID infections including those that are considered health and fit with mild COVID infection. 
  • Post-viral complications are not unique to COVID-19. Epstein-Barr, influenzas and mononucleosis may involve post-viral complications. 
  • Risk factors for long COVID, similar to COVID-19 are excess adiposity and obesity, metabolic syndrome and people with pre-existing immune dysregulation problems. However, being fit and healthy does not exclude a person from experiencing long COVID. 
  • Nutritional insufficiency including reduced vitamin and mineral and macronutrient intake increases the risk of long COVID, making dietary analysis important when supporting these patients. 
  • Targeted supplementation of vitamins, minerals and antioxidants can support patients experiencing long COVID. 
  • Exercise with long COVID is important for recovery, however, intensity and duration should be carefully considered. Low volume, high load strength training may suit patients with long COVID. 

Resources and further reading

Dr. Cliff Harvey 

Dr. Cliff Harvey
Holistic Performance Institute
Dr. Cliff Harvey research papers
Article: ‘Nutrition and COVID-19: What do we know?’ Holistic Performance Institute, 2022
Research: 'Does micronutrient insufficiency increase the risk of COVID-19 vaccine adverse events? A case-driven medical hypothesis’, Journal of Holistic Performance, 2022
Article: ‘Can nutrition affect COVID vaccine adverse effects?’ Holistic Performance Institute, 2022

Dr. Anna E. S. Brooks 

Dr. Brooks' Research papers

Cronometer App 

Cronometer app

Long COVID diagnosis 

Research: ‘Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management’ International Journal of Environmental Research and Public Health, 2021
Research: ‘Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study’, British Journal of General Practice, 2021
Research: ‘Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification’, International Journal of Environmental Research and Public Health, 2021

Long COVID  

Research: ‘Long COVID: An overview’ Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 2021
Article: ‘Preliminary evidence on long COVID in children’, Wiley Public Health Emergency Collection, 2021

COVID and Nutrition 

Research: ‘The impact of nutrition on COVID-19 susceptibility and long-term consequences’, Brain, Behaviour and Immunity, 2020
Research: ‘Nutrition amid the COVID-19 pandemic: A multi-level framework for action’, European Journal of Clinical Nutrition, 2020
Research: ‘Treating Insulin Resistance with Intermittent Personalized Nutrition to Sustain Metabolic Health and Functioning Immune System for Risk Reduction of Viral Diseases Especially COVID-19 and Long-COVID', Hormone and Metabolic Research, 2022
Research: ‘Lifestyle Adjustments in Long-COVID Management: Potential Benefits of Plant-Based Diets’, Public Health Nutrition, 2021

Lifestyle Support for long COVID 

Research: ‘What should a family physician know about nutrition and physical exercise rehabilitation’ advices to communicate to ‘long-term COVID-19’ patients?’ Postgraduate Medicine, 2022

Further Education 

Nutrition for COVID and post-COVID syndrome: COVID - Nutrition and Lifestyle Medicine, Holistic Performance Institute


Adrian: Hi, and welcome to FX Medicine, where we bring you the latest in evidence-based, integrative, functional, and complementary medicine. FX Medicine acknowledges the traditional custodians of country throughout Australia, where we live and work, and their connections to land, sea, and community. We pay our respect to their elders, past and present, and extend that respect to all Aboriginal and Torres Strait Islander people today.

Joining us on the line today, all the way from New Zealand is Dr. Cliff Harvey, a registered clinical nutritionist with over 20 years of experience. He's well known for using nutrition to help athletes and everyday people to perform at their best. Cliff has completed his master's and doctoral degrees in nutrition focusing on keto flu, ketogenesis, and the identification of markers of carbohydrate tolerance. Cliff is also an avid educator and speaker, has published several books in the areas of nutrition and wellbeing, and is the founder of the Holistic Performance Institute, which provides evidence-based online nutrition education. 

Welcome to FX Medicine, Cliff. Thanks for being with us today.

Cliff: Thanks, Adrian. Good to be with you, mate.

Adrian: Now, I know that you've done a lot of work using nutrition and holistic approaches to help people improve their health, their performance, and their overall well-being, but more recently you've developed an interest in using nutrients, diet supplements, and lifestyle factors to help prevent and treat COVID-19, including long COVID. And this is the topic we wanted to discuss with you today. How did you develop an interest in this area?

Cliff: Good question, Adrian. It wasn't really by design or intention. I was contacted by, initially, it was actually a couple of professional athletes who were suffering from long COVID and they had been put onto me by mutual associates in the industry. And so I started working with them and started noticing a few things that I thought could be really interesting and might add to the clinical knowledge base out there and add to the sort of knowledge overall of long COVID. 

And as I was working with a few of these clients with long COVID, I was contacted by Dr. Anna Brooks from Auckland University. Now she's doing fantastic work looking at two areas really. One is COVID vaccination adverse events, the other is long COVID. And she's really looking at blood markers and what's going on really in-depth with these conditions. So she's really getting into the mechanistic stuff.

Adrian: Yeah.

Cliff: And she thought there might be some potential for us to work with a cohort of people who had long COVID and then also a cohort of people who had suffered COVID vaccination adverse events to look at what was going on. 

And obviously, her angle was to be looking at what's going on within the blood and on a cellular level. And I was really looking within these clients at what was happening with their diets and whether there are any nutrient interactions with long COVID, with COVID vaccination adverse events, how that meshes with what we know from the extant research, and, then again, helping to then sort of guide some clinical practice so that we can get better outcomes for this condition.

Adrian: Okay. Okay. So just going back a little bit, what is long COVID? What's the definition?

Cliff: Well, that's an even better question, Adrian, because there's not really a consensus at this time on what long COVID is. It's generally the post-viral complications that we see after COVID. Well, the definitions can vary. And so some people sort of say that it's anything that lasts longer than sort of a month or so after COVID. Generally, most people say that it's symptoms lasting more than three months after diagnosis with COVID. And it's really a very broad range of symptoms. So people exhibiting these post-viral symptoms sometime, let's say one to three months after COVID, that can then last for quite some time. And the symptoms can involve a lot of different organs and systems within the body ranging from fatigue, for example, up to 72% of patients have experienced fatigue, shortness of breath, cognitive effects, loss of smell, loss of taste, muscle dysfunction, and muscle loss, right through to things like erectile dysfunction. And there's really a very large array of symptoms that people can experience with long COVID.

Adrian: And these are symptoms that they would experience while they had COVID and then it just continues? Or are they new symptoms that appear a month or three months down the track?

Cliff: Yeah, and that's where it can get interesting because generally, long COVID is most prevalent in most people who have experienced severe COVID. So often it is an extension of those symptoms, but the signals can be quite different as well.

Adrian: Yeah.

Cliff: And interestingly, in the cohort of people that I've worked with, they haven't always had severe COVID, but they have had fairly severe long COVID effects. So it can vary. And this is why it's such a complex condition because it varies in terms of the symptoms that people exhibit, the organs and systems that are affected, and how it plays out temporarily.

So some people, like I say, have severe COVID and that progresses into severe long COVID, or they have severe COVID and some long COVID symptoms or no long COVID symptoms. Others don't really experience much with respect to COVID, but then they have fairly severe and debilitating long COVID symptoms. So it's a tricky one and there are a lot of reasons for that, and it sort of crosses over a lot of different parameters.

Adrian: Okay. So you've got fatigue, is that the most prominent symptom that is displayed in long COVID?

Cliff: We think so. I mean, probably based on the research, up to three-quarters of people with long COVID are experiencing severe fatigue. Shortness of breath probably follows that. So respiratory symptoms and shortness of breath, maybe up to half of people experience that. The cognitive effects, which get a lot of attention probably affect a quarter to a third of people. So it's actually not as prevalent, but that's also something that we see in a lot of people who don't necessarily experience the other severe effects of long COVID. And then less frequently we see things like that loss of smell, loss of taste. And other things like muscle dysfunction and muscle loss are pretty prevalent as well. So they're certainly worth considering and probably not something that a lot of people think about because generally, people are thinking about the fatigue, brain fog, shortness of breath, those types of things as being the most apparent symptoms.

Adrian: All right. So the cognitive effects are like your brain fog, is it memory and attention problems and things like that too, and low mood? Do they experience kind of depressive symptoms and anxiety and things like that?
Cliff: Yeah, so most commonly we see things like brain fog and memory loss. But, yeah, depression is certainly part of the picture of long COVID. And there is from memory some research showing that there is specific damage to neurons, which is highly associated with those depressive symptoms. So there's something certainly happening there that's more than just depression driven by say fatigue, or depression driven by sort of transient changes and fuelling in the brain, for example. There is actually some cell destruction there that's causing some of these symptoms too.

Adrian: With these people who are presenting, is there a test or any assessments that are done, or was it just basically based on symptoms? Is there any blood markers that kind of indicate long COVID or anything like that at all?

Cliff: Not really at this stage. It very much is a condition of exclusion. So if other things are excluded, like getting another virus or having another infection of some type or having some other type of illness, if those are all excluded and someone has those symptoms after a COVID infection, it's typically put down to long COVID. There are potentially some things that may be used that might have some utility in the future. I know that they're looking at various types of MRIs using chemical markers to look at pulmonary damage.

Adrian: Yeah.

Cliff: And that might be a really good indicator of long COVID, but it's probably not going to be that precise either because not everyone experiences that particular symptomology or cell destruction to the same extent. But at this stage, it's very much just a diagnosis of exclusion.

Adrian: Okay. All right. So obviously, you have to have had COVID and then depending on the definition that you use one month to three months after you've experienced COVID if you're still experiencing some of the symptoms and they can't be attributed to some other kind of diagnosis, then that's where the diagnosis occurs in long COVID. 

And it's other terms that are used, isn't it? What other terms do use apart from long COVID?

Cliff: Long COVID was something that came from really the mainstream. That wasn't an academic or medical definition, even though it's used a lot within academia now. But more commonly in academia, we would use the terms post-COVID syndrome or post-COVID condition.

Adrian: Yes.

Cliff: So it typically goes by those three names mostly. And it's interesting because this is not a unique event. This is not a unique occurrence with COVID and the SAR-CoV-2 virus, we see post-viral complications from Epstein-Barr virus leading to mononucleosis. We see post-viral complications from influenza. And these are very common. And these do result in that post-viral fatigue, chronic fatigue syndrome, and things like that. 

And so it's not altogether uncommon, but I think what is a little bit distinct is the breadth of tissue and systems that are affected by it, and probably also the indeterminate nature of the length of this condition. Because it's such a new thing, we don't really know. And the estimates can vary widely. I've seen estimates of 6 months, or 12 months, 18 months. It seems to be in the research it looks like an average of about 15 months duration of post-COVID syndrome. But there are people who have had post-COVID syndrome for a long time and their symptoms haven't resolved. So there are a lot of things we don't know about the condition at this stage.

Adrian: So obviously, for some people it just kind of resolves over time, but there's still many people 12 to 18 months down the track who are still experiencing symptoms.

Cliff: Yeah. And for a lot of people, the symptoms resolve quite quickly, you know?

Adrian: Yeah.

Cliff: And there's this almost graduation from COVID where most people recover within even sort of six days, and then most people will recover by about six weeks. And then there are a portion of people who then will retain symptoms for quite some time. So, yeah, it's very indeterminant.

Adrian: And what are the rates at the moment with regards to people experiencing long COVID? Is there an estimate on rates?

Cliff: Yeah, it does vary depending on the study, but we think around 35% of people infected with COVID will suffer post-COVID syndrome.

Adrian: Oh, that's a lot. Wow.

Cliff: It's quite a lot. It's a little bit higher than say the post-viral complications from influenza, which are probably up to about 30%. Probably a little bit less than the post-viral complications for Epstein-Barr virus, which I think from memory are around 50%. But those people who are hospitalised with COVID, so those who have severe COVID, the rate of people who go on to have post-COVID syndrome or long COVID is probably up to about 85%. So a lot of those people who are in hospital with COVID are going to go on to have post-COVID syndrome and long COVID. 

And that makes sense to me completely. When we look at the nutrient interactions with COVID and the nutrient interactions with post-COVID syndrome, they're very, very similar. And so I think we are seeing similar risk factors and we are seeing similar nutrient interactions so it makes a lot of sense that those people with the most severe COVID are going to go on to have post-COVID syndrome as well.

Adrian: So you've obviously got then severity, so the more severe hospitalisation that increased the risk of having post-COVID. Is there a difference with regards to sex, males/females suffering more than one or the other?

Cliff: I'm not sure actually, Adrian. I don't know off the top of my head the sex differences. I don't know if there is a large sex difference. And it's certainly not one of the biggest risk factors to my knowledge. The biggest risk factors tend to be very similar actually to COVID. So it's people who are with excess adiposity, or we might say with obesity, people who have metabolic syndrome, people who have preexisting immune dysregulation problems. And they tend to make up the majority of those people who go on to have long COVID. But interestingly, in the group that I've been working with, it's been an atypical group. So the cohort of people that I've been working with have, by and large, been young or relatively young. I consider them relatively young because most of them are my age or younger.

So they're relatively young, generally in pretty good health, pretty good shape off. A lot of them are athletes. They're active people. A lot of them are relatively affluent. So these are people who would not be the typical candidates for severe COVID or the typical candidates for severe long COVID symptoms. But many of them are suffering from these symptoms and they are pretty severe. 

And so that's why we've started to look a lot deeper into what's going on with these nutrient interactions. And I think it's really interesting because we're starting to see some commonalities. And really those commonalities are that everyone that we've evaluated to this date has had an insufficient intake of at least one or more of the essential vitamins and minerals. They are often not replete with protein, omega3 essential fatty acids. And usually, it's a number of essential vitamins and minerals that they're not getting in sufficient amounts. And this is interesting because I think there are a lot of people walking around in this situation. 

And pre-COVID, we had been looking into doing research on undernutrition. And that research was put on ice because of COVID. We lost a lot of our funding, it was very hard to get participants, things like that. So we put that research on ice. But the COVID situation has shown us that a lot of people are undernourished in some sense. And the research will tell us that as well. Since we've been doing our case research, other research has emerged where other scientists have been looking into the nutrient intakes of people and have been looking at commonalities within that. There are some really interesting numbers here. 

For example, 72% of people with long COVID aren't meeting their energy requirements. So they're under-fuelled. About 56% of people with long COVID are not meeting their protein requirements. About 45% or more have insufficient vitamin D levels. And overall, nearly two-thirds of people with long COVID are malnourished in some way. So not getting at least one or more of those essential vitamins and minerals in sufficient amounts. So it's an interesting thing and I think it's showing us that a lot of people nowadays are not getting all that they require from diet alone.

Adrian: So this is then through their diet. So obviously, their nutrient intake through their diet is compromised in some way? Or are you also saying that if you do a blood test for them though they might be eating a good diet, but let's say, for example, if their iron is low. Are you doing the assessment through dietary assessments?

Cliff: Really good question, because, at this stage, we are mostly looking at food analysis. So we're looking across the board on what they're taking in and seeing whether that's sufficient. But we're also seeing, on a case-by-case basis that, yes, people are also exhibiting low blood levels of vitamin D, which is, again, consistent with the research we see around both COVID and long COVID, low levels of zinc, for example. So we're seeing a lot of those key nutrients that are involved with immunomodulation are both low in the diet and also low in the blood.

Adrian: And so these people are they eating your kind of standard diets and they're obviously, just through your dietary analysis, you're just noticing that they're not eating a sufficient amount of certain vitamins and minerals, or are these people that you're talking about, are they people who are not eating a healthy diet or eating an unhealthy diet?

Cliff: And I'm really glad you asked that, Adrian, because often given the risk factors that we see with obesity and metabolic disorder, let's say, and poor diets in general, we would expect there to be these nutrient interactions. This is why I think the cohort that we've been working with are so interesting, or they're so interesting to me, at least. Because they are typically younger, healthier, fitter people, and also generally eating pretty well. And what I mean by that is if we just look at a rough outline of what they're eating, you get people to jot down what they're eating over a day, for example, at first glance, it looks pretty good. And so when you just eyeball what they're eating, you'd think, "Well, they're eating pretty well," and you might not then take it any further.

But because we are looking specifically at what they're eating and we're getting them to track all their food and supplements, and then we're running it through analysis so we can actually see what those levels of vitamins and minerals they're taking in are, we're seeing striking things. And we're seeing that each and every one of them is low in a number of vitamins and minerals. And so it's a real call to action, I think, for practitioners that we can't always just look at someone's diet and get an overview of it and expect to understand exactly what they're taking in or whether it's sufficient. And so these people, it's really amazing how they've managed to function so well. When we're talking about some of them, for example, being professional athletes, how have they managed to perform so well for so long despite these poor diets? It's only when there's this viral challenge that provokes a number of fairly drastic changes within the body that it becomes evident that they're actually very undernourished.

Adrian: Yeah, because that's what I was thinking. I was thinking people that you're seeing are probably eating a generally...on paper looks like it would be a generally healthy diet, but obviously, then when you go deep into it, you're saying that there's nutrient deficiencies that are occurring.

Cliff: Absolutely. And I think to some degree what we might be seeing is people who are eating a lot of hyper-palatable, ultra-refined food that's fairly low or lower in overall nutrient density. So taking in lots of calories, lots of energy, but lower levels of nutrients. And that's predisposing them to risk for a number of reasons, both through the nutrient interactions themselves, and also because it's predisposing them to metabolic syndrome and being with excess adiposity.

On the other end, if we've got people who are under eating and they're very active, maybe they're also a bit stressed, they're sort of these sort of type two personalities where they're very driven, all that kind of stuff, and they're under eating a little bit, then it's unlikely that they'll be able to consistently take in all the vitamins and minerals they need. So although it's on balance a fairly good diet, it's just insufficient. And so we're seeing different types of people and it's very important for practitioners and researchers to understand that, that we can't just put people into a box of poor eating, older, metabolic syndrome type risk factors because there are other things that predispose us to risk as well.

Adrian: If you're a practitioner, how do you then do the analysis of nutrients? Is there a program that you use, or how do you do it?

Cliff: For our research and my clinical practice and the work we do at the institute, we use an app called Cronometer. I have nothing to do with that company or anything like that, it’s just a very good app. And it's really the only one that allows that level of micronutrient analysis because most food-tracking apps don't really get into the micro’s too much. So it's the one that allows a client or a research participant to easily enter all that they're eating, taking it from supplements, drinking, and then for us to be able to see in real-time what's coming in. And it's automatically basically analysing that for the vitamin and mineral...well, all nutrient content. So we can see very quickly those reports.

Adrian: All right. We'll definitely have a link to that app at the show notes. And so what do they do though? They just enter their food into this app for several days, or how does it work?

Cliff: Yeah, so it's very similar to most of the other food-tracking apps there. So if people are using... People are often used to using MyFitnessPal or MacroFactor, some of those apps out there. And often from the user end apps like MacroFactor are probably the best because they're very user-friendly. Cronometer is very similar. It's a similar sort of technology. And so they just enter the foods that they're eating either manually or they can even scan the barcodes. Very simple to put the food in there. And then it's obviously very simple for us in the back end to see what's coming in and for it to automatically tabulate what their nutrient intake is.

Adrian: Oh, that'd be great. All right. So we've got then, from what you are saying is that there's some nutrient deficiencies potentially occurring and that increases the risk of long COVID. And so basically, would your treatment involve dietary interventions, or do you also use supplements as part of your treatment?

Cliff: Yeah, I sort of take a hierarchy approach. So diet and lifestyle are always at the base of that pyramid. So we always want to be giving nutritional advice in a broader sense to get people eating healthier. There are obviously other things that we do within our lifestyle that also affect nutrient-influence factors within the body. For example, glutathione. Glutathione is the key antioxidant within the body. But glutathione production relies on having good nutrition overall, getting all those essential nutrients, making sure that we're not over-stressed, that we're sleeping well, that we're moving well, that we're breathing well all those things play into it. So we'll always work on that as the baseline.

But supplementation I think is critical. Particularly because in the modern world, it's very difficult for people to not only get consistently what they need each and every day, but we live in a very unique environment. We live in an environment that is...or a food environment that's typically a little bit lower in nutrient density. It trends towards obesogenic foods. Our other psychosocial environment trends towards higher stress, lower movement, more sitting, poorer breathing, all those types of things. And so nutrient supplementation can certainly help to support health in the presence of all those factors that are potentially depleting us.

Adrian: Okay. So I'm just trying to think, then, as a practitioner, you have somebody coming in with long COVID, you could potentially then do a dietary assessment, getting them to record their food and then that will then allow you to identify any particular nutrients that they may be kind of not consuming enough of. Then obviously, you could do your blood tests for things like iron and vitamin D and so forth, and treat accordingly. And then it sounds like certainly, stress and other lifestyle-based approaches are really going to be really important for somebody presenting with long COVID.

Cliff: Yeah. And I think once you've done that, once you've covered off some of the key immune regulating nutrients like vitamin D and zinc, which you can test very easily for in the blood, other nutrients are not so easy to necessarily test for. But if you're getting some of those fairly basic and standard tests done, all your standard blood markers plus zinc, vitamin D, maybe folate, B12, those types of things, iron as you suggested, you get a pretty good idea of what's happening and you can dose supplementation accordingly.

On top of that, there are some additional supplements that are going to be a benefit too. And these are really based mostly on, number one, supporting glutathione, which I mentioned before. And for that, a lot of people nowadays are taking glutathione supplements. I'm not really a big fan of that because glutathione is not absorbed well into the cell. It's typically not absorbed intact. And so it becomes a very roundabout and expensive way of providing glutathione because it can eventually be that the metabolites that are from the breakdown of glutathione can be converted to glutathione at some point. But it's a very roundabout and expensive way to do it, like I said.

There is a supplement called N-Acetyl Cysteine or NAC, which is a very bioavailable efficient donor of the amino acid cysteine, which is the limiting substrate for glutathione production. So as a target for glutathione, N-Acetyl Cysteine is probably a much better bet. It's got pretty good evidence behind it for other conditions. And given the now fairly large body of evidence showing that glutathione depletion is probably a really big factor for COVID and long COVID, it really makes sense to take things like N-Acetyl Cysteine to help support glutathione. And we typically prescribe that in doses of about 1200 to 2400 mg per day. On top of that...

Adrian: And can you take that as a preventative too?

Cliff: You certainly can do. I’m loath to say people should take a supplement like that, which is pretty specific for the long-term. There are a lot of studies showing fairly long-term use. It's not particularly toxic at those relatively low levels. So it appears to be a very safe supplement generally. But I think when people are looking at taking something like that, they should probably just check in with their health practitioner and make sure that it's appropriate for them. But in those types of doses, 1,200 to 2,400 mg per day, it's shown really positive benefits for things like Crohn's disease, systemic lupus. So it has been used previously for other conditions and it's a pretty good bet I think for boosting glutathione.

Adrian: Any others you recommend?

Cliff: A couple of the others are more involved with mitochondrial energy dynamics, so they're really about providing fuel on that cellular level. And that doesn't really seem to a lot of people to be a good target for treating something like long COVID. But obviously, there is a lot of fatigue associated with long COVID. But there's also a lot of depletion of energy, mitochondrial energy and modulation, or manipulation of mitochondrial energy dynamics by the virus itself. Because obviously, the virus doesn't produce its own energy. It's using cellular machinery to provide it with energy for replication. And so if someone is already on the cusp of depletion, the virus is going to further deplete that mitochondrial energy production. And so there is pretty strong evidence that things like coenzyme Q10 and NAD are depleted in COVID and long COVID patients and they might be fairly good predictors of the severity of outcomes.

So there are supplements that can obviously help to boost coenzyme Q10. And for NAD levels, supplements like Nicotinamide Riboside can really help to boost NAD as well. So there are some really interesting supplements that can really help with that mitochondrial energy side of things as well. Now they also help to reduce viral replication as well. So there are some cool ancillary properties to those.

Cliff: I tend to, in the first instance, really focus on the nutrient side of things to really bring up glutathione to work on that sort of cellular energy side of things. But there is good research around Quercetin for addressing viral replication as well. So we often include that because often Quercetin and some other things like Resveratrol are often bundled up with say Nicotinamide, Riboside and various supplements. So it makes it very easy to prescribe that as well. Because obviously, with clients and with our research participants, we don't want them taking 20 different supplements either.

Adrian: Yeah.

Cliff: Because we still want to make things as easy as we can for them. But, yeah, some of those things like Quercetin are showing really good research as well. There's some decent research I think around curcumin, turmeric.

Adrian: Mm-hmm.

Cliff: Obviously for the anti-inflammatory effects mostly.

Adrian: Yeah. Are there any herbal ingredients that you use from an immune perspective that might be helpful?

Cliff: One of the areas that I'm very interested in is medicinal mushrooms. And there's just now beginning to be a little bit of research on mushrooms like Reishi or Ganoderma species, Shiitake, Cordyceps. But I know I'm going on here a little bit, Adrian, but my favourite for the treatment of long COVID is lion's mane mushroom or Hericium Erinaceus, or there are other local species like Hericium Novae-Zealandiae or Hericium Australis. And the reason is that it crosses over a lot of different dynamics.

Typically, the medicinal mushrooms as a family of supplements tend to help reduce oxidation and inflammation, which is obviously critical for long COVID, but lion's mane particularly is very effective for improving cognition, reducing depression and anxiety. It's one of the few things that we can take as a supplement that can help to boost neuro-repair, neurogenesis. So for those fatigue and neuro-cognitive effects of long COVID, it covers a lot of bases. And to be completely honest, I think if there's one supplement that I've, or one thing, so it's not always a supplement, of course, some people are eating it, some people are taking powder, some are taking extracts. If there's one thing that I've prescribed to people that has given them very profound effects very quickly, it's lion's mane mushroom.

Adrian: Wow, okay. So you've got then...

Cliff: You should give it a crack, Adrian, get on the lion's mane.

Adrian: Yeah, it sounds like it's worth a shot for sure. I mean, I know that there's a lot more interest in medicinal mushrooms and the impact on the immune system, and, yeah, it sounds like a really good option for people. 

And I know a lot of people are probably using vitamin C and things like that. What's your thoughts on vitamin C?

Cliff: Yeah, I should have mentioned that. Vitamin C is one of those first-line supplements. Now there is some good evidence from IV vitamin C, particularly for reducing fatigue. And specifically, for long COVID. So, if people can get that in that long COVID scenario, then that's really beneficial. But I don't see any reason why taking high doses of oral vitamin C wouldn't give a similar effect. We see that anecdotally, there just hasn't been enough research on it yet, but we typically recommend that our participants and clients are taking at least 1000 mg a day or more, getting up really close to their threshold of what they can take for at least a time.

Adrian: And just from a lifestyle perspective, what about if they're fatigued? What do they do with regards to exercise? Do they kind of need to back off a little bit or what are your recommendations around exercise?

Cliff: That's a great question. Obviously, exercise is to some degree it's tonic for the immune system. And so my approach is always that we want people moving and we want to get them back moving sooner rather than later. Now, the challenge, of course, is that in the post-COVID scenario, people will be... It's very similar to chronic fatigue syndrome. People will be in a situation where if they go too hard too soon, they tend to have a pretty big collapse afterwards. And so this is why I think it's really important to focus on the biggest bang for buck with exercise. And that tends to be from strength training, rather than say high-intensity interval training or moderate-intensity cardio done for long periods of time. Those tend to tax the central nervous system more and have a greater effect negatively on the immune system in people who are already compromised.

So I tend to have people start back with very simple, very low volume, but relatively high load strength training. Now by relatively high load, I mean doing relatively low rep numbers, but also still keeping a number of reps in reserve. So what I mean by reps in reserve is let's say we are looking at a very simple protocol of one set of squats, one set of pushups, and one set of pull-ups per day. And that's it. That will only take someone a couple of minutes. But doing, let's say, up to six repetitions, but at a nine repetition max, so that would be three reps in reserve. So the idea is that people aren't pushing themselves to max, but they are consistently strength training to build their tolerance and to build their resiliency. 

Now, this is also important in the post-COVID situation because there is anabolic resistance that occurs in long COVID. It's not something a lot of people talk about, but there's this anabolic resistance and insulin resistance that occurs. So this means people are more prone to those symptoms of metabolic syndrome, their glucose disposal is poorer, but they're also because of the anabolic resistance, more likely to lose muscle tissue as well. So as you and I both know one of the best ways to mitigate that muscle loss is to put the muscles under load, to put the body under load, to be doing some strength training, and, of course, to make sure our protein intake's optimised. So along with this low volume, relatively high load, but not to max training schedule, we'll also have people taking in fairly high protein intakes around two grams per kilo of body weight per day.

Adrian: Okay. And that's through any sources of protein or is it do you also, again, use supplementation to get those protein levels up?

Cliff: Where necessary. If people can eat their protein, that's great. I'm a big fan of protein powders, but I only see them as necessary where people aren't getting enough protein in. Now, I drink protein shakes every day, and that's just purely because I know that if I don't, I won't get to that optimal protein level for me. So it really just comes down to the person. But the real idea is that most people end up taking a protein shake just because it makes life easier.

Adrian: Okay. Brilliant. All right, so I'll just go through... I've just take mainly been taking some notes as you mentioned all this stuff. So certainly, if somebody comes in with long COVID then certainly doing a dietary assessment, it would be useful, and you mentioned the app that we'll have a link to in the show notes. Obviously, then doing some blood testing, testing for your standard bloods and your iron and your vitamin D and your zinc levels and your B vitamins and your folate and things like that. Then obviously, implementing dietary interventions and supplementation to replete levels that are low in the blood or through the dietary assessments that you've done. And then you've mentioned a whole bunch of different supplements including medicinal mushroom, lion's mane mushroom, and you've got your zinc, and you've got your vitamin C, and your quercetin, and all those different options that you have for people. And then finally, just kind of being mindful about the aerobic exercise and maybe looking more about using resistance exercise to help people kind of recover. Have I missed anything there?

Cliff: No, that's a good summary. And really it is about...it's kind of like return to play. It's that idea that we use with top-level athletes when they've overtrained. It's about going back to basics, getting all the foundations of health sorted, and then starting to build their work tolerance again. That's very much the same situation with post-COVID syndrome or in fact any sort of post-viral fatigue.

Adrian: Well, thanks, Cliff. I think you've really provided some useful clinical advice on how to deal with people who are coming in with post-viral COVID. And I think that's really important rather than just kind of talking about it in a generic way. I think there's some really great tools and strategies that we can use with our clients that you've mentioned that will help them recover, hopefully, a lot quicker and reduce some of the severity of their symptoms. So thank you very much for that and I think it's some great advice you've given today.

Cliff: Thanks, Adrian. Well, I hope it will help people out there. That's our whole intention with this research and we're getting a lot more information out there just to help people who are currently feeling like they're a bit stuck. And a lot of the participants in our research and a lot of the clients that I've seen, they really feel like they've hit a brick wall because they just can't see a way forward. And to be honest, I think a lot of that is because if you just get online and Google, there will be a lot of different supplements recommended or a lot of various things that people will try. But if you're not taking that graduated approach to health where you're taking care of the foundations first, you can take any supplement in the world, but if you're not replete with zinc and vitamin A and vitamin D and all those other things that are really critical for immune function, it's still not going to have the effect you want. So when people begin to get on a process where they can build up their health and resiliency, then they can really move forward and start to see pretty pronounced and profound results.

Adrian: All right. Well, thank you very much, Cliff. I mean, certainly, if people want to find out more about your work, there'll be links in our show notes to your websites. And I know that you do a lot of education and training in the area, so I think that would be really useful for a lot of practitioners. So, yeah, thank you very much for joining us today.

Cliff: Awesome. Thanks, Adrian. It's been great.

Adrian: All right. Thank you everyone for listening today. Don't forget you can find all the show notes, transcripts, and other resources from today's episode on the FX Medicine website. I'm Dr. Adrian Lopresti, and thanks for joining us. We'll see you next time.


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