Q&A #31: Cholesterol Tests, Statins & PCSK9 Inhibitors—Plus Long COVID

Hi everyone, nice to be here today. Welcome to number 31 of our Crowdcast live Q&A series. So we've done this 31 times. Awesome. For those of you that are new, typically the protocol is that questions are submitted in the ask a question section, and questions can be voted upon by other members. Typically, I go through the questions earlier in the month, and I choose questions based on a variety of factors. 1, upvotes. 2, my personal interest. And 3, interest of the audience, how many times I've had this question in one form or another. And so typically we choose a couple of 2 to 3 questions that we do a deep dive on, go sort of in-depth analysis for. And then on top of that, I will answer some other questions that have short answers.

And then I do rapid-fire questions, which are often just sometimes even a word or a sentence answer. And then as we're going through the live Q&A, I also look in the chat and answer questions live. So that's one of the perks of joining these live is that you get to ask a question in real time. And so you can see here in the chat that people are already asking questions. And by the way, if you want to ask a question that I answer and do like an in-depth analysis on, please put it in the Ask a Question section because that's where we look for the questions. So I'm going to go ahead and get started with a few of our deep dives. I will start by saying that there was a question submitted by Gal on berberine and Long-term safety, et cetera. I'll be covering that next month in depth.

So we do have a topic page on berberine and we will be updating it with some newer studies. We also found a relatively long-term study, 16 weeks, which is fairly decent length study. So we'll be covering that next time and also updating our topic page. Okay. So I'm going to start with the first question, which was also the top upvoted question. The question was submitted by Monica. And Monica asks, hi, Rhonda. Are there any supplements or lifestyle modifications one can take or do to help with long COVID symptoms? I had COVID-19 in March of 2021 and have been suffering from neurological symptoms I've been experiencing fatigue, lightheadedness, muscle weakness, tremors, etc., ever since I was diagnosed with long COVID.

My symptoms are occasionally unbearable, and the only treatments I've been offered are SSRIs and breathing exercises. Are you aware of any new research on treating long-haul COVID? Thank you so much. So before I get started on this, I want to remind everyone that that this is not medical advice. These Crowdcasts are literature reviews. Often they reflect my opinions and they are not— I'm not a medical practitioner and so I am not giving medical advice. So please speak with a healthcare professional, speak with your primary care physician for any type of lifestyle changes that you're wanting to make. Before doing so. So with that said, let's talk about the long-haul COVID, which is a really general term. There's a lot of different symptoms that are associated with long-haul COVID.

You know, many people have gut issues that last a while. Some people have breathing issues, lung problems, heart issues, brain issues. So there's a variety of different symptoms that people tend to have, loss of Smell, taste. So there's a few clinical trials that are ongoing right now, about 100 actually, that are investigating a variety of drugs and supplements including complement C5 inhibitors, granulocyte-macrophage colony stimulating factor, CoQ10, and a variety of other drugs. So it'll be interesting to follow those clinical trials and see— Yeah. if there's any exciting data that comes out of them. There are a couple of mechanisms. In fact, there's probably a variety of mechanisms responsible for long-haul COVID.

The top 2 that I've read about have been, one, SARS-CoV-2 virus is able to infect multiple organs, including the brain and heart, for example. As well as other organs as well. And it is thought that in some people, for whatever reason, and it doesn't always seem to get into the brain of everyone. It's not, this isn't something that always happens, but it does happen. And it's possible that the virus lingers around for long periods of time in different organs and is responsible for lingering symptoms. The other mechanism is an autoimmune response mechanism where— and by the way, so this has been shown, you know, in different studies. And so, you know, there are hypotheses, but there are also probably multiple contributing factors at play here.

And so it's also been shown that some people have autoimmune response in response to a SARS-CoV-2 infection, and therefore their autoantibodies are being generated, and these are possibly playing a role in long-haul COVID symptoms. So with that said, I'm going to give you— I'm going to talk a little bit about what some of the literature says and also just some Some of my personal opinion with respect to the brain and with respect to the brain and also the the smell and taste, which is a really really really common long haul COVID symptom. There was a very small randomized controlled trial that was done out of Italy, and it showed that.

Luteolin, which is a polyphenol that's really high in some plants, particularly celery, that luteolin, 300 milligrams a day, along with palmitoylethanolamide, can help improve the recovery of the taste, loss of taste and smell in people that had COVID. It's also the luteolin, there's been some animal studies that have shown that it may be beneficial for brain fog. It's been shown to lower neuroinflammation. And this is where I think that really looking at some of these polyphenols that have been shown in some study, some, you know, in some studies to affect the brain, particularly clinical studies, that it might be, you know, a good idea to try it out. And so I think luteolin, would be one, and I think that resveratrol is another one.

Resveratrol has been shown in a couple of clinical studies to lower neuroinflammation in the brain and improve brain function. The other one would be cocoa via. There's been a variety of studies looking at that, the polyphenols in dark chocolate, and cocoa via is a very, very concentrated form of the flavonols in dark chocolate that basically it's been shown in multiple clinical studies to improve brain function. So I think those are a few of the polyphenols and flavonols that I would probably focus on. In any instance that involves brain function, I always sort of also fall back on omega-3 fatty acids, which have been— that are immensely beneficial for resolving inflammation and also for brain function as well.

So with that said, I think also going back to the mechanisms here, if possible and if accessible, I think intravenous vitamin C, which is very high dose, gives you very high dose plasma levels of vitamin C. And in fact, also the vitamin C is in the oxidized form, the dihydroascorbic acid form, that it's also known as DHA. That it's been shown that that can also increase the killing of pathogens through a hydrogen peroxide-induced mechanism, and it doesn't damage cells. The hydrogen peroxide seems to selectively target pathogens. This is not something that you can achieve from oral doses of vitamin C. It has to be intravenous for this mechanism to occur.

It's part of the mechanism by which intravenous vitamin C is thought to be beneficial for killing cancer cells as well, because, because the hydrogen peroxide levels are low enough such that normal cells— it's kind of like a hormetic effect where normal cells are activating their antioxidant pathways, and so you end up having an antioxidant response, whereas cancer cells are unable to, to engage in that sort of hormetic response. They're very kind of screwed up types of cells, and so the, the low levels of hydrogen peroxide end up actually killing the cancer cell. So, um, I, I do know several people that have had long COVID that have done multiple rounds of intravenous vitamin C and had beneficial effects. So that's one another option. There's a lot of places that do it.

And then another option for the autoimmune mechanism focuses a lot on gut health and potentially on doing a long fast. So the gut is actually a major regulator of T regulatory cells, which are the major type of immune cell that helps prevent autoimmune responses. Regulatory T cells, or Tregs for short as they're called, basically prevent your immune cells from attacking its own tissue. So they help your immune cells differentiate between self and non-self. And there's been a variety of studies that have shown that the bacteria in the gut that produce a lot of these short-chain fatty acids like butyrate, for example, are— these short-chain fatty acids act as signaling molecules in the circulation for immune cells to activate T regulatory cells so that you have a nice repertoire of T regulatory cells being active at any given time.

This is where I would focus on consuming fermented foods, kefir, you know, even just yogurt, you know, probiotic yogurt, A good one is Bio-K. Bio-K is really high in probiotics. And then there's other fermented foods like sauerkraut and kimchi, and there's some kombuchas as well. But I think the fermented foods have really been shown in multiple studies now to help with T regulatory cell regulation as well as lower inflammatory biomarkers. That would be one potential approach as well. Now, the long fast is something to do, you know, under a clinician's care because they can, you know, it is something that is potentially dangerous.

And so a lot of work with the long fast has come out of Dr. Valter Longo's lab, animal research as well as some clinical studies showing that there's like a reset with with more of a prolonged fast, something more like a 48 or 72-hour water fast or even a fasting-mimicking diet, a 5-day fasting-mimicking diet by ProLon, can help with that resetting. And it's been shown to really help get rid of dysfunctional autoimmune cells in the body. It seems like they selectively die during a prolonged fast and there's a resetting that happens. and a replenishing and rejuvenation of the immune system with functional non-autoimmune cells.

And so this is something, again, to try under a clinician's care, but it would be something I personally would probably try if I were experiencing some long COVID symptoms. So Factor 8 is asking in the chat regarding CocoaVia, would just eating 100% dark chocolate get some similar benefits? It's hard to say for sure without a clinical study. I mean, 100% dark chocolate should have, you know, a high concentration of these flavonols. The CocoaVia, I mean, what they're doing is really concentrating these flavonols. So I'm not sure it would have the exact same benefit, but it might still be beneficial. So, you know, personally, I just think CoQ10 is pretty awesome just because of the multiple clinical studies that have shown benefits in both younger and older individuals in the brain.

So that would be something to consider. Rayanne is asking in the chat if I will give my thoughts on vaccines for young children age 5 to 11. I will. I'm continuing to follow that data. There's still— it's still sort of scant, and until there there's more data. I'm not speaking on it today, but we'll see how next month goes. If there's more data at that point, then I will speak on it. Anti-Aging Girl brought up a really good point in the chat. She says, would the keto diet potentially calm down the overactivated immune system in long COVID and decrease autoimmune symptoms? Thanks for bringing that up, Anti-Aging Girl, because yes, there has been also some preliminary data that ketogenic diets Yeah.

Can sort of mimic in a way the fast and potentially through the production of beta-hydroxybutyrate, which may be part of the signaling for resetting the immune system. So that would potentially be another thing to try would be the ketogenic diet. So thanks for bringing that up. I completely forgot to mention that. Okay, so there's another question in the chat about— from Duncan about Robert Malone talking about suppression of T cells from vaccines and boosters. In fact, that's— or sorry, Daniel. Daniel is mentioning it and Duncan mentioned Robert Malone as well. I just want to say that's extremely the opposite of what data has shown. I'm not even sure where that's coming from, if it's like a fear-inducing kind of panic type of tactic, but there have been unbelievable amounts of studies.

I mean, study after study after study in very, very high-impact journals that have shown that vaccines cause a massive T-cell response, and that in fact the T-cell response is what is keeping people that are vaccinated out of the hospitals, because even though antibody levels wane over time, the vaccine-induced T-cell responses are robust. And it just— there continues to be studies coming out. In fact, there was just like a study a couple of weeks ago that just came out on that as well. So I would say the opposite, and overwhelming evidence shows the opposite. Okay, so the next question I'm going to address that's more of a deep dive question was submitted by Marina, and the question has to do with statins. Marina says, hi Rhonda, what are your thoughts on familial hypercholesterolemia?

High genetic cholesterol levels. Is it really necessary to take statins forever? Or are there other ways to maintain our health with this genetic condition? So familial hypercholesterolemia is inherited. It's an inherited form of elevated LDL cholesterol, and it affects roughly 1 out of 500 people. While normal LDL levels are usually below 100, people with this type of genetic disorder have anywhere between 200 to 1,000 LDL levels. And so people with this are at a really high risk, really high risk for heart attacks and strokes and sudden death and actually heart disease at any age.

One study followed individuals with familial hypercholesterolemia for 14 years and found that 27% developed new coronary artery disease and 12% developed a new aortic valve So doing everything possible to reduce LDL levels with this condition is really important. So unfortunately, statins may be necessary for people with this type of conditions because it is— the risk for sudden cardiac death is so high. I would say, and this kind of gets into another— into a follow-up question next that was submitted by Chad on the PCSK9 inhibitors, which are, I think, better than statins because they have fewer side effects. The problem is that it's hard to get them because they're so expensive.

And so you really, like, in order for your physician to prescribe them, you have to really have, you know, a negative reaction to statins. And then also they go to other drugs as well before even going to the PCSK9 inhibitors, unfortunately. So let's talk a little bit about the PCSK9 inhibitors. So Chad asks, for those with high LDL and small particle LDL that haven't resolved with diet or exercise. What are your thoughts about the monoclonal antibody PCSK9 inhibitors versus starting a statin? So for background, the PCSK9 inhibitors are a new monoclonal antibody medication that's used to lower LDL. They increase the liver's clearance of LDL cholesterol from the blood.

Meta-analyses of 14 different— sorry, 24 different clinical trials shows that it reduces LDL cholesterol on average by about 53%. And it reduces all-cause mortality by 55%. When used in combination with a statin, the PCSK9 inhibitors had a 15% decreased risk of cardiovascular death, heart attack, stroke, and a variety of other heart problems over 2 years. Now, as I mentioned, statins are usually used first before PCSK9 inhibitors, mainly because of the price. And so statins cost around $10 to $20 a month, and the PCSK9 inhibitors cost $500 per month. So they're usually not prescribed unless the patient cannot tolerate statins. And again, I said, even at that, there'll be other drugs that are tried before the PCSK9 inhibitors just because of the price.

It's really kind of unfortunate because it seems like there's a really small amount of side effects with these drugs. And so the hope is that in the future, the price of these drugs are brought down because, in my opinion, you know, there are a lot of terrible side effects with statins. People that have the familial hypercholesterolemia, though, can be at really high risk for heart attack, stroke, and, like I said, sudden cardiac death. And so it's really— it's not the kind of case that you'd want to sort of gamble around with, you know. But generally speaking, people without that condition, and, you know, a lot of people are sort of overprescribed statins. Unfortunately.

And so, you know, it— I'm just hoping that one day the PCSK9 inhibitors do make their way into being the first treatment because it seems as though they're a really great option. Okay, so I'm going into these related questions here. Gal asks about cholesterol tests. There are so many different kinds. I'm wondering if you ever have gone through explaining them all, or if you could. My husband's LDL is high and his LDL-P, which is LDL particle test, came back very high. Is this concerning? Should he get another kind of test? Would you say the small dense LDL is more important than the particle? Thank you so much. Okay. A little background. Cholesterol and triglycerides are fat soluble, and they need lipoproteins to be transported throughout the blood.

So there are 5 major lipoproteins in blood. There's chylomicrons, there's very low density lipoprotein, or VLDL, there's intermediate density lipoproteins, or IDL, and there's low density lipoproteins, or LDL, and then high, high density lipoproteins, HDL. Each of these classes of lipoproteins carries cholesterol and triglycerides to a varying degree, with LDL carrying the majority of cholesterol and VLDL carrying the majority of triglycerides. There are 2 different tests for measuring blood lipids. So the traditional lipid panel works by discriminating by the density of lipoproteins. So the test will give you the total cholesterol, so HDL, LDL, and triglycerides. The downside of this traditional lipid panel is that LDL is not directly measured.

It's estimated based on total cholesterol, HDL, and triglycerides, which are directly measured. So this is really unfortunate because LDL is crucial for making medical decisions such as starting statin therapy, and And oftentimes those decisions will be made without actually directly measuring LDL, which to me is kind of mind-blowing. So to get to the particle number, that would be a way of directly measuring LDL levels. So that is what the LDL-P test or the LDL particle Number is, it's basically a more accurate way of determining a person's LDL concentrations because they're actually measuring the particle numbers of LDL particles rather than making an estimation indirectly, you know, by measuring other things. There's also the particle size test. So we just talked about particle number.

So there's also particle size, which distinguishes— distinguishes the lipoproteins based on their size. And so, you know, we've talked a lot about this, that, you know, there's different sizes of LDL particles. There's large buoyant LDL, and then there are small dense LDL. The large buoyant LDL is thought to be the actually healthy type of LDL that you need. Obviously, every cell in your body has cholesterol. It needs cholesterol. Anytime you have you know, damage to a cell or something needs to be repaired, or anytime you're making a new cell, your body transports cholesterol through lipoproteins to get to that cell to give it cholesterol. And so you really need the large buoyant LDL because that's helping repair damage, it's helping to make new cells, it's important.

Small dense LDL is a modified type of LDL, and it's been modified in such a way that some of the proteins like ApoB have become obscured and have therefore trouble being recycled back into the liver. And so like, you're much more likely to have a small dense LDL particle stay in the circulation, stay in your vascular system, in some cases indefinitely, compared to a large buoyant LDL which is being recycled back to the liver and it sort of has a transient half-life in your circulation. And so the small dense LDL particles also are very prone to To bringing in inflammatory responses. And so the small dense LDL particle will stay in circulation, it elicits an inflammatory response, and so you end up then having more inflammation, and this is sort of the beginnings of atherosclerosis.

So small dense LDL particles are not good, and they are thought to be Okay. And LDL-C is thought to be one of the major types of LDL that is associated with heart disease. So I would say personally, the data to me suggests that LDL particle number and particle size are the 2 important lipid tests that are a more accurate measure of heart health compared to the traditional lipid test. So that's kind of the bottom line with the LDL lipid panels and, you know, what they mean basically. I'm scrolling down to another question that was actually relevant to this whole topic as well. Lanise is asking if high LDL is always— it's basically always a bad thing. And the answer is no. You know, some people do live a really long time with high LDL levels.

And again, it just comes down to a variety of things like I just talked about. So you'll have these talks of, oh, people have high cholesterol, and it's like, well, how is that measured? Okay, it was just, you know, an inaccurate indirect way of measuring it. So perhaps they have, you know, a lot of large buoyant— Cholesterol particles. LDL cholesterol and they don't have a lot of small dense LDL cholesterol. And so this small dense LDL cholesterol, that's really the telling, you know, bad part of the LDL. And so you can have someone with high LDL but low small dense LDL and, you know, and still live a long healthy life. So yet again, it's just another reason why it's important to to not have medical decisions based on one indirect test or measurement of LDL.

And unfortunately, a lot of medical professionals do still do that. So getting the particle test, getting the particle size test done in addition, and doing them multiple times. I mean, there's a variety of things that can affect— Your LDL levels. Inflammation, one, stress, anything that causes stress, like psychological stress, can transiently make your LDL levels go through the roof. And so if you're like getting your blood panel done and you happen to have something stressful happen in your life, or you happen to have been sick recently, your LDL could be really, really high. But if you would wait and, you know, waited a month or two later and done it again, you might see that it goes back to normal.

So it's really not a good idea to ever make a medical decision based off of one test either, an N of 1. And Ed and Twila are mentioning in the chat as well, of course, the triglycerides are important as well and your HDL. I mean, there's a variety. There's a variety of factors to look at when trying to ascertain cardiovascular health, not just LDL. But I did— the question was very specific to LDL, and I did want people to understand the different types of tests. And along that line, since we were talking about small dense LDL, Chad was asking, is someone— if someone is consistently showing LDL pattern B. Pattern B. So there's, there's 2 types of LDL patterns. There's pattern A, which means people have more of the large buoyant LDL.

And there's pattern B, which is where people have more of the small dense LDL. So pattern B is— you definitely do not want to be pattern B. So chat is asking, if someone is consistently showing LDL pattern B on their lipid test, but they are seemingly healthy, have a great BMI, eating a mostly Mediterranean diet and exercising, how would they go about converting to a normal LDL pattern A and get back those large fluffy LDL cholesterol particles? So we're going to talk a little bit about a few different randomized controlled dietary studies that have been done. So the first one followed about 105 men that were following a high-fat, so 46% of their energy from fat, or a low-fat diet, so 24% of their energy from fat for 6 weeks. And then they switched. to the alternative diet.

So this was a crossover study. So after the high-fat diet, individuals were classified as either phenotype A or phenotype B. Following the low-fat diet, all phenotype B individuals remained phenotype B. So in other words, phenotype B being the bad one where you have more small dense LDL particles, Following that low-fat diet, people in that category with high small dense LDL phenotype B stayed phenotype B. So the low-fat diet did not shift them to a better phenotype. However, 36 individuals shifted from a good phenotype, phenotype A, having more of the large buoyant LDL, to phenotype B after following a low-fat diet. So in other words, a low-fat diet may not be good for people that have a good large buoyant LDL because it shifted them to the bad small dense LDL type.

And people that already had that small dense LDL phenotype didn't do any better with low-fat diet. So really, to be honest, I'm not seeing the low-fat diet as— Yeah. So that's a big selling point here. Now, people that were phenotype B that did go on the low-fat diet, although they still stayed phenotype B, they did have some favorable improvements in some biomarkers like ApoB, which was lowered. And so that's one benefit for potentially being on a low-fat diet if you're phenotype B. Let's talk a little bit about another study. So this was another study that was involving 510 men and 72 premenopausal women.

On a low-fat, high-carbohydrate diet, 35% of the phenotype A shifted to phenotype B, whereas 6% changed from phenotype B to A. So in other words, again, a low-fat diet, it seems as though people on— people that already have a good LDL profile, it shifts them to a bad one. So it seems like low-fat diets are not beneficial for people that already have a good LDL profile and maybe even very, very negligibly beneficial for people that have small dense LDL phenotype. It seems as though they're still not doing much. Excuse me. Okay. I'm gonna pause for a brief minute, and I'll be right back. Okay. So in another study, this study, people with phenotype B that were put on a high saturated fat diet resulted in significantly greater increases from baseline in ApoB levels. Medium and small LDL.

So it seems as though people with phenotype B going on a high saturated fat diet may not be beneficial. It seems to shift them into having even more of the small dense LDL particles and and more and higher levels of ApoB, which is not good either. In another study, people with phenotype B that reduced their carbohydrate content without changing their fat content significantly, it did seem to be beneficial for them. So I think in conclusion, people that have A small dense LDL type of profile, the phenotype B, may be better on doing a more, you know, trying and experimenting with a more low carbohydrate diet, but without like significantly increasing their fat, but potentially increasing protein.

So, and perhaps their fat sources, instead of being from saturated fat, you may want to try monounsaturated and polyunsaturated fats, so like avocados, nuts, salmon, olive oil, things like that. Maybe something to experiment with and try, at least according to some of this data. And Kenny is mentioning in the chat the quality of the carbohydrates are important, and I 100% agree. So cutting out, obviously, anything that's refined, processed would be beneficial, and sticking to vegetables, vegetable sources, you know, vegetables and some fruits as well. Danny's asking if omega-3— if omegas are effective at switching from pattern to pattern A? I haven't seen that study done yet, but I know that omega-3s do— I have seen some evidence that they can lower small dense LDL as well as ApoB.

So one would assume that would be beneficial for someone that's already starting off with a high level of small dense LDL particles. And part of the reason for that also is because inflammation itself is something that can increase small dense LDL particle size— sorry, can increase the number of small dense LDL particles. And so omega-3s are extremely good at lowering inflammation and resolving inflammation. And so it makes sense that you would see omega-3 fatty acids affecting the small dense LDL particle number.

Another question in the chat is asking whether or not there are studies looking at monounsaturated and polyunsaturated fat and pattern A versus B or phenotype A versus phenotype B. I haven't specifically seen The mono and polyunsaturated fat, but again, sort of just by process of elimination here, knowing that increasing the saturated fat does not seem to help with people that are pattern B, and that basically going on a more low-carb diet but not changing the fat helps, makes me think that perhaps the mono and polyunsaturated fat would be the way to change it. So hopefully those studies will be done, but that would be my guess, and I think that that would be easily testable.

Yeah, so more protein, cut out the refined carbohydrates, and try to increase the mono and polyunsaturated fat and decrease the saturated fat. That would be an experiment I would personally try. Okay, that's pretty much it for the lipid stuff. I'm going to go Back to another question that was submitted by Bob and has to do with micronutrients. So Bob asks, thoughts on— it was a study that he linked to on micronutrient supplementation and acute respiratory infection. And it was a systematic review and meta-analysis. Okay. So let's talk a little bit about what the data showed. So vitamin D supplementation overall reduced the risk of respiratory infections by 3% and shortened the duration of symptoms by 6%. However, the dosing that was the— it was the dosing that was the most effective.

So, from the study, it basically showed that vitamin D was only 3% protective in the general population, but it was 10% protective if the daily dose was greater than 2,000 IUs a day. So, basically, they're just aggregating all these studies together, and a lot of studies were using a low dose of vitamin D. And so, that sort of skews the data to have a lower protective effect. The study also said that they found that a monthly loading dose was beneficial if it was 60,000 IUs, if it was less than 60,000 IUs a day, but if it was greater than that, it was not beneficial. And they hypothesized potentially because such a large dose may inhibit or disrupt the enzyme metabolism of vitamin D. They also found that weekly dosing 10,000 IUs or 20,000 IUs was 30% protective. So, that was quite high.

In fact, it seems as though that was one of the best or the most robust effects with this study with respect to vitamin D dosing was that a 10,000 or 20,000 IU weekly dosing was Yeah. So let's move on to vitamin C. So vitamin C supplementation reduced the risk of respiratory infections by 4% and shortened the duration of symptoms by 9%. Zinc supplementation did not reduce the risk of respiratory infections, but it did shorten the duration of symptoms by 50%. One of the strengths of this study is that they used 80 different randomized controlled trials and zero observational or retrospective data. So it's really trying to establish causation and they're using randomized controlled trials. The limitations would be, one, the data does not include COVID.

The analyzed data was only on adults and not children. And also about a quarter of the studies did have a high risk of bias. So, you know, there's always— that's always an issue with any study. But nonetheless, I think that the results were interesting. And on a related note, G asked in a question about vitamin D and covering vitamin D doses by body weight, because it was something I had previously mentioned. And I think the most interesting thing that came out of this study is really, honestly, that your body weight is important for dosing, and that people that are overweight even slightly overweight and/or obese need 2 to 3 times more vitamin D than— so people that are obese need 2 to 3 times more vitamin D, and people that are overweight need 1.5 times vitamin D to achieve the same blood levels, vitamin D blood levels, as people that are normal weight.

So for example, let's say you're trying to Achieve a concentration of like 50 nanograms per milliliter, um, a normal weight person would need to take around 5,000 IUs a day to achieve that, but an overweight person would need about 1.5 times that, and an obese person would need 2 to 3 times that. So, really, a lot of people that are overweight and obese are probably not getting adequate levels of vitamin D because they're taking a dose based on a normal weight person. And, you know, the other thing that this study showed really was, again, you know, it takes about 1,000 IUs to raise blood levels by like 5 nanograms per mL. So yeah, so for a normal weight person, 50 nanograms per mL takes them 5,000 IUs a day normal.

And it takes a Actually, a normal weight person may need even— if you look at the graph here, it looks like they need even 10,000 per day for overweight and up to 20,000 per day for a very obese person to get 50 nanograms per mL blood levels of 25-hydroxy vitamin D. So, that's quite shocking. Howard's asking in the chat about high-dose omega-3 and prostate cancer risk. I recommend that you listen to the end of the podcast I did with Dr. Bill Harris because we addressed this. And it's like the data is so bad that it's laughable. The data that sparked this whole controversy is data from another trial. It's called the SELECT trial where men were given high-dose vitamin E, alpha-tocopherol, And they were given high-dose selenium.

We now know high-dose alpha-tocopherol, so high-dose being like 400 IUs a day, way over what the RDA is, which is about 35 IUs, is actually— taking high-dose alpha-tocopherol is actually not good for many reasons. One, it's not allowing adaptive responses to be activated because it's sequestering any reactive oxygen species that activates our own endogenous antioxidant pathways. 2, it seems to increase inflammation because it's somehow— it's affecting the gamma-tocopherol. And so it's really bad to take high-dose alpha-tocopherol. Anyways, this was the study. Blood samples were taken from these men that were taking high-dose vitamin E and selenium. And they found that those men with high omega-3 were more likely to have an aggressive prostate cancer.

Well, I mean, you realize these are blood samples from people that were taking high-dose alpha-tocopherol. There's no telling, you know, it's so terribly confounded. And in fact, other studies have shown that men taking omega-3 supplements have a lower prostate cancer incidence. So go back to that podcast with Dr. Bill Harris and listen to the very end. At the very end of it is when, like the last 30 minutes or so, we address it and he brings up some really good points as well. So that would be my recommendation. Thoughts on vitamin E tocotrienols? Some people say they're better than the tocopherols. I personally like to get my vitamin E from foods like nuts. Nuts are a great source of all the tocopherols and tocotrienols.

And I think getting them in the right concentrations and the right ratios The best way you're going to do that is by getting them from whole foods. So that's typically what I like to do rather than trying to supplement with them. Sue was asking about collagen supplements in the chat. We have a topic page. On our— on the website, on foundmyfitness.com. If you go to foundmyfitness.com and you click on topics in the toolbar, and we have one on hydrolyzed collagen. So you can scroll down on search topics or click on the H and you'll see the hydrolyzed collagen topic page. We really go into— here's a link to it in the chat. We really go into great detail on all the different types of hydrolyzed collagen, what the research says, and, um, you know, what the studies show.

So it's a really, really good topic page. I personally take Great Lakes collagen powder. I put it in my— I've been, I've been doing, um, kefir smoothies in the morning recently, and so I've been putting them in my kefir smoothies. And I also like to put it in my coffee. Put them in my regular smoothies as well. Okay. So Kenny asked a question. Hi, Rhonda. If I want to grow muscle in just my upper body, I would assume I don't have to consume as many calories as if I was trying to build up my entire body. But then some friends at the gym said that your body will grow all muscles more if you work your entire body. I hope it's not true since consuming twice as many calories is difficult and it's a lot to eat. Do you know of any evidence of this being true?

I could not find any studies that support the notion that working out your entire body improves upper body muscle hypertrophy. However, it is important not to neglect lower body strength because it correlates more with health than upper body strength. Lower body muscle mass correlates with longevity and functional independence in the elderly more than upper body mass does. So it is important to gain lower body mass when you're young because it's actually more and more difficult to gain muscle mass as you age. Additionally, after the age of 50, most people lose about 1 to 2% muscle mass per year due to a process called sarcopenia. But if you are worried about not being able to consume enough calories, you may be You may be eating more than you need.

So you shouldn't need to double your daily calories. You just need to make sure that you're eating enough protein. So increasing protein in your diet increases your muscle gains up to a certain point. And like a meta-analysis, about 50 studies showed that the more protein in the diet, there was an increase in muscle mass gains by up to 1.6 grams per kilogram body weight. So for a 180-pound person, this comes out to about 130 grams of protein per day. And interestingly, and particularly important for elderly who are not exercising quite as much, a high-protein diet, even without exercise, preserves muscle protein more than a low-protein diet in elderly people.

So a randomized study showed that elderly men who went 10 weeks without working out and they were randomized to eat either high-protein or low-protein diet, Those who ate a high-protein diet, which was defined as 1.6 grams of protein per kilogram body weight, gained about 3.3 pounds of muscle. And those who ate a low-protein diet, defined as 0.8 grams of protein per kilogram body weight, lost 1.2 pounds of muscle over the same time period. So again, I think that, especially if you're older, you know, even— Even without exercise, like it's important to have a high protein diet. Danny's asking about we're worrying about overacting mTOR when we're building muscle. No, I think the problem.

To worry about mTOR is if you're, if you're, you know, never activating your muscle and you're just, you're, I mean, if you're never working your muscle, which is when you want mTOR to be active, it plays a role in helping build muscle. The problem is if you're constantly activating mTOR and never exercising, right? Because then you're, you're basically, you know, allowing potential precancerous cells to then start to, you know, grow when they otherwise would be killed. Kenny's asking about protein deficiency outside of developing countries. A lot of elderly people do are, you know, do not have adequate protein.

Um, yeah, it's a big, it's a big problem for elderly people not, not getting enough protein for sure, but not, not particularly in young healthy people living in a developed nation. Ernest is mentioning in the chat about a couple of studies showing that it's better to have, at least in the elderly, to have the vast majority of dietary protein early in the morning compared to distributing among, you know, 3 meals. And yeah, there was a study, we talked about this before, that has shown that it is better For building muscle mass to have it earlier in the morning. And there's a circadian component to that likely, where some of these enzymes and stuff that are involved in building muscle are on a circadian clock. And so having that in the morning seems to be beneficial in that regard.

There's a question about whey protein and whether or not to avoid whey protein. So there's not too much protein in whey. Consuming increased protein does not negatively affect the kidneys or the liver in healthy individuals, particularly those that are active. Whey protein does not affect the absorption of micronutrients. There is a concern that casein protein, which is commonly found in milk and dairy products, may nullify antioxidants, but there is a negligible amount of casein in whey protein powder. Whey protein does not raise cholesterol. And it is a good source of protein. It has high concentrations of essential amino acids like leucine. Proteins containing high proportions of essential amino acids are rapidly digested and effective at stimulating muscle protein synthesis.

So I think in conclusion, I'm not sure that whey protein is necessarily bad. Yeah. Again, this is all in the context of exercising, making sure that you are exercising. Whey protein is high in branched-chain amino acids, which if you're not exercising and you're just taking a bunch of whey protein, the branched-chain amino acids can outcompete tryptophan for transport into your brain. And that can have negative effects on serotonin production. It can affect mood, it can affect impulsive behavior, a variety of different cognitive functions. And so it's not good to just, you know, take in a bunch of whey protein without exercise because exercise alleviates that competition.

The branched-chain amino acids get taken up into muscle instead of competing with tryptophan to be transported in the brain. Now, you do need branched-chain amino acids in your brain as well, and, you know, you're getting those there, but— You just, again, if you're just drinking high amounts of, you know, branched-chain amino acids but not exercising, there could be a problem with serotonin production. So that's something to keep in mind. Mike asked a question about vitamin D. Mike says, if I have adequate vitamin D levels in my blood and stop taking a vitamin If I take a vitamin D daily supplement and I don't get adequate sunshine, how long will it take for my vitamin D blood levels to become deficient? So vitamin D is a fat-soluble vitamin.

It's present in a, you know, it's a very negligible amount in some foods, particularly the fortified foods, but it's most reliably obtained through sun exposure. When vitamin D is consumed or manufactured through sun exposure, it must be converted into its active form known as calcitriol. Before it can be converted into calcitriol, it is converted into calcidiol, which has a relatively long half-life of about 15 days. So calcidiol provides the most accurate indication of the body's vitamin D levels. Calcidiol is also known as 25-hydroxyvitamin D. Calcitriol is the active vitamin D hormone, and it's really not a good indication of the body's vitamin D levels. Its half-life is only 15 hours. So let's talk about the time to depletion.

There's really no simple answer, but the amount of time it takes vitamin D to leave the body. We know that calcidiol, again, provides the best indication of vitamin D levels, and that's a 15-day half-life. So the body will deplete half of its supply of vitamin D In 15 days. But this does not take into account the body's stored vitamin D. So vitamin D3 is fat soluble. It's stored in fat. And so it can be released into the bloodstream from fat stores. And this is a very regulated process. So like when your vitamin D levels start to fall lower, you know, you will release some of your stored vitamin D. So, it's really kind of hard to say how long it would take for a person's vitamin D levels to become deficient because, again, it all depends on how much has been stored in your fat and all these other factors.

And so, you know, taking any kind of guess, it probably would take a few months, I would say, before the deficiency would start. In most people. Okay, the next question has to do with pregnancy. It was submitted by Gossia says, I wonder if you're aware of any research suggesting what to do to avoid chromosomal abnormalities in pregnancy. I read the research suggesting that most of the cases might be caused by a failure to effectively replace cohesion proteins that are lost from chromosomes during the aging of eggs. But I can't find anything suggesting any even remote promise of what I can do to help strengthen centromere cohesion. Is there anything that might suggest how to lower the risk? Yeah, this is a tough question.

I can tell you what I do know about micronutrients and chromosome stability. And these are kind of the factors that I personally considered pre-pregnancy, actually. Big ones are folate, vitamin B12, and riboflavin. Under folate-deficient conditions, the DNA nucleotide uracil is incorporated into DNA instead of thymidine, and this leads to chromosome breakage. In addition, folate and vitamin B12 play a critical role in the maintenance of DNA methylation, which apart from its importance for transcriptional control of gene expression, epigenetics. It also determines the structural stability of important regions of the chromosome. This is where the MTHFR polymorphism comes into play.

There are significant interactions between people, particularly people that are homozygous for the MTHFR polymorphism, the C677T, And its cofactor riboflavin and folic acid. So, high riboflavin concentration increases instability under low folic acid conditions. And this is particularly with people that have the MTHFR. And so, if you have someone that's getting high amounts of riboflavin but not getting enough folic acid, that could lead to chromosomal instability. Studies on the interactive effects of folic acid deficiency and inherited mutations in the MTHFR gene indicate that moderate deficiency in folic acid can have a strong impact on genome instability. So basically, it's really, really important to get enough folate, also methylfolate for people with the MTHFR.

Making sure you're also getting enough B12 along with that. So those are really, really, really crucial factors. And then again, having too much of the riboflavin when you're deficient in folate can be problematic as well. Nicotinic acid or niacin is another dietary micronutrient that's known to play a fundamental role in chromosome integrity. Zinc is also important for chromosome stability. Most of these can be found in, in a standard prenatal vitamin, and that's something to start doing, I would say, probably like a year before conception. Okay. The next question was submitted by Rebecca and has to do with coffee oils. Rebecca says, I use reusable coffee filters that don't filter out coffee oils. Do coffee oils have positive or negative health impacts?

Should coffee oils be avoided during intermittent fasting or time-restricted eating? Okay, let's talk about— let's address that last part of the question first because that's the easiest. I don't think that coffee oils need to be avoided during a fast or time-restricted eating or anything like that. So the oils in coffee are known as diterpenes. They include kahweol and cafestol. There's really pros and cons of these coffee oils. So both of these compounds have some beneficial effects, like they have anti-carcinogenic activity, although those studies are really limited to in vitro studies that are done, you know, in cells in a petri dish. So you kind of have to take it with a grain of salt. So on the flip side of that, these coffee oils have also been shown to raise LDL cholesterol.

Unfiltered brew coffee can contain around 30 times the concentration of these diterpenes compared to filtered coffee. Filtered coffee filters out most of these compounds. Although drinking unfiltered coffee is not necessarily bad for most people, it is associated with elevated cardiovascular mortality in older men. Specifically. This could be due to the link between unfiltered coffee and the LDL cholesterol, or it could be something else that's unknown. Filtered coffee has been shown to be linked to a 15% lower all-cause mortality, a 12% lower heart disease risk in men, and a 20% lower heart disease risk in women. So it's, again, I'm not necessarily convinced that drinking unfiltered coffee is bad for absolutely everyone, and I still think the studies are preliminary.

Unfiltered coffee usually refers to Turkish coffee or coffee that's made in a French press or boiled coffee. Espresso also would technically be unfiltered coffee, but Yeah. It contains such small amounts of these compounds, mostly because people are drinking a very small volume. So they're drinking like 30 mL of the espresso versus drinking a full cup of coffee. And there was a study that was done out of Italy that showed Italians that drank 3 to 4 espresso cups had 28% lower all-cause mortality than non-espresso drinkers, and they had 15% lower all-cause mortality than non-espresso drinkers. So I think that there's a lot more data that really we need in order to make any definitive conclusions about these coffee oils and what their effects are on health.

We do know they can raise LDL cholesterol, but I mean, You know, in the grand scheme of things, is that, is that what's really raising it to a level that's like unhealthy? Probably not. So there's some rapid-fire questions. Elisa was asking, this is particularly for people living near conventional agriculture. What can we do to support our detoxification? Unfortunately, we live near fields that are regularly treated with different phytochemicals. What supplements are particularly relevant? Is it very worrisome? And we will move, but in the meantime, and also for other people in this situation, what can we do? I would say probably one of the main supplements that I've seen that does the detoxification obviously would be sulforaphane.

The major detoxification pathway in the body is regulated by the NRF2 system, and sulforaphane is the major activator, dietary activator of NRF2. And there's been studies showing, again, that, you know, people taking sulforaphane can increase their benzene excretion by up to 60% and their acrolein excretion by like, you know, 40%. So I would say that broccoli sprouts would be one way. Moringa powder also activates the NRF2 pathway, you know, or taking a supplement like the Avocall, Prostafane, which have been shown in studies to enhance or to activate the NRF2 system. The other thing would be sweat. Sweat does get rid of some exogenous chemicals as well. And so, of course, sauna would be a way to do that. Exercise would be a way to do that as well. What about heavy metals?

A related question had to do with heavy metals and arsenic and how to support arsenic heavy metal excretion through urine. So some heavy metals are excreted through urine and others are excreted more through sweat. So for example, So, mercury is— the major source of excretion of mercury is through urine. And one way to facilitate the excretion of mercury would be by taking in beta-mercaptans from garlic. This has been shown to increase the excretion of mercury via urine. So, garlic is a great source of the beta-mercaptans. Other heavy metals like aluminum and cadmium, they are predominantly excreted through sweat. So again, that would be exercise and sauna. Arsenic is predominantly excreted through urine, but also somewhat you can excrete some arsenic through sweat as well.

So I think one of the best things to do would be exercise. Exercise is one of the best ways to do that. As well as, you know, again, activating the NRF2 system is a really great way, and moringa powder is probably one of the most cost-effective and robust ways to do that. Broccoli sprouts are a little more of a commitment, but also a very, very great way that's cost-effective as well to activate NRF2. James is asking about getting some of the— how to get omega-3s for someone that has a fish allergy. I would say the best way would be algae, microalgae oil. That would be the best way to get omega-3s for someone that has a fish allergy. Michael's asking, can you talk about caffeine found in matcha green tea and how it affects adenosine receptors?

Caffeine from any source inhibits adenosine receptors. Kenny asks, Hi, Rhonda. You mentioned in Aliquot 45 that people can have long-term symptoms from COVID even if they don't get sick or hospitalized. Does this mean that if we are vaccinated, get back to normal, and then still catch COVID that we could have long-term symptoms? There was a study that showed people who were vaccinated, fully vaccinated, and had a breakthrough— this was before boosters— and had a breakthrough infection, are 50% less likely to get long-haul COVID. Hi, Dr. Patrick. What are your thoughts on smoked fish such as salmon or mackerel? Do you think it's helpful to get additional omega-3 in your diet, or are they something that you avoid? I think they're great, and I actually eat them all the time.

I like the mackerel from from Patagonia. Terry is asking in the chat, my omega-3 test came back high at 8.7. I take a lot of EPA and DHA. Would you be concerned? No, that's not as high as— my husband just did his and he was 16, which is the level that dolphins are. No. So in Japan, they typically have an omega-3— I presume that you're talking about the omega-3 index here, which is a measure of omega-3 in red blood cells. Yes. Japanese typically have anywhere between like 10 or 11, 11 to like, you know, 13. And they're some of the longest-lived cultures, you know, that we know about. Their life expectancy is on average 5 years longer than people in the US who have an average omega-3 index of about 4 to 5. Moby's asking if Vascepa has any heavy metals.

Vascepa is the purified EPA that is prescription, can be— is prescription available through a physician. I would be surprised. It's a highly purified form of EPA. I'd be really surprised if it had any heavy metals in it. Most fish oil supplements purify away heavy metal contaminants and stuff like that. That's pretty standard. Ernest is asking if exposing fish like salmon to high heat Does cooking destroy omega-3? It does to some degree. It does to some degree. So that's one reason to take a fish oil supplement in addition to eating fish. Well, that wraps up this Crowdcast. Thank you so much for all your wonderful questions this time around. And please submit your questions in the Ask a Question section for next time.

I will kick off the Crowdcast with cover— starting with that Berberine question that I mentioned I did not get to this time around. And for those of you that want to re-listen, rewatch this Crowdcast, we will be sending out an email summary with the link to the video. You can always rewatch it right here on the Crowdcast as well, but we'll have links to the time points, which is always nice. We also have this, you can listen to the audio only. You can find that on your dashboard. You can listen to it directly on your dashboard. You can find that at foundmyfitness.com/dashboard. You can also download your private podcast feed player to listen to that as well, where we also release our aliquots. So we'll be releasing this audio Q&A number 31 this coming week.

And then we have a special aliquot 2-part series on New Year's New Year's resolutions coming out on the Aliquot soon, so make sure you listen to that on your dashboard either or your private podcast player. Thank you so much for all your support. I really, really appreciate all you guys. I really enjoy doing these Crowdcasts. They're so much fun. I learn a lot, and I just can't thank you guys enough for all your support. I look forward to seeing you guys next month. I hope everyone has a nice healthy month and I look forward to all the questions that we're going to get for next time around. So I'll talk to you guys soon. Bye.