Q&A #12: Which Cholesterol Tests Matter—and How Diet Changes LDL Particles

Hi everyone, welcome back to our Crowdcast Q&A monthly. This is round 12, and for those of you that are new, just, um, a little quick reminder. I go through questions, I choose some of the top voted questions, I choose some questions that I think are interesting that more people would like to know about, or I've heard, I've had repeated over multiple different episodes. Maybe I haven't gotten to it, or even people have emailed me. Also, towards the end of this Q&A, I will hit some rapid-fire questions. In other words, questions that I can just sort of answer really quickly without having to dive deep. I did Choose a couple of questions this round, and we're gonna, we're gonna do a little bit of a deep dive because I think they're important topics.

And as usual, just remember that this, the information in this Q&A is not meant to be medical advice. I'm not a medical doctor, I'm a scientist, so please keep that in mind. Also, I will try to be answering questions from time to time in the chat, which is sort of a benefit of attending these Crowdcast Q&As live. So I'm going to start with the first question that was— that's on my list, and this question is from Katya, and she asks, Is it safe for people with hypothyroidism or at least a mild hypothyroidism to eat cruciferous vegetables or supplement with sulforaphane, for example, Prostaphane? So there has been some concern that sulforaphane may compete with iodine for transport into the thyroid and hence could be a goitrogen.

Which is something that can disrupt the production of thyroid hormones, particularly for people who are iodine deficient and have hypothyroidism. But following enzymatic breakdown of what are called glucosinolates in the Brassica family of vegetables like cruciferous vegetables, you can have a variety of different isothiocyanate compounds that are produced. And one is sulforaphane. You can get Phenethyl, you can get indolic isothiocyanates, and these all possess anti-carcinogenic activity. And in contrast, you can also get compounds called progoitrin and indolic glucosinolates that degrade into goitrin and thiocyanate. And those specifically possibly could decrease thyroid hormone production. However, as we'll get to in a minute, it's extremely difficult for that to happen.

Sulforaphane itself is not actually a goitrogen to my knowledge, but progoitrin and the indolic glucosinolates degrade to goitrin and thiocyanate possibly could affect thyroid hormone production theoretically. So I think it is safe, and let's talk a little bit about some of the research. We know that I think where some of this scare, where the sort of fearmongering for eating cruciferous vegetables and thyroid comes from is there are some animal studies that show eating extremely high amounts of cruciferous vegetables can cause hypothyroidism. And that's because of the molecule progoitrin, which can compete for iodine. And so the thyroid uses iodine to make the hormones T4 and T3. But this has not been observed in humans, eating the cruciferous vegetables and it causing hypothyroidism.

So, there was one study that looked at the iodine uptake in human subjects following the administration of recrystallized goitrin. By the way, this is not sulforaphane. This is a completely different compound. This is another compound that can be formed when eating cruciferous vegetables. So, the study looked at recrystallized goitrin and found that the minimal amount, which was about 25 milligrams, that could cause a decrease in iodine uptake, but 10 milligrams had no inhibition on uptake at all.

So in order to get the 25 milligrams of goitrin I just mentioned, which could have some minor competition with binding to iodine, or sorry, with competing with iodine binding to the thyroid, In order to get that, you would have to eat nine pounds of kale in one sitting, or eleven pounds of broccoli in one sitting, or eighteen pounds of Brussels sprouts in one sitting, or twenty-nine pounds of turnips in one sitting. Good luck with that. You get my point. It's really just unreasonable to think that. someone is going to eat that much cruciferous vegetables to get the goitrin, the levels of goitrin that have been shown in humans to start to outcompete iodine binding for the thyroid. So I would say that it is extremely rare for cruciferous vegetables to cause or exacerbate hypothyroidism.

Another study in humans found that consumption of 150 grams per day of cooked Brussels sprouts for 4 weeks had no adverse effect on thyroid function. Also, supplementing with sulforaphane seems to be safe for thyroid because sulforaphane really does not affect the iodine uptake into thyroid. So healthy people that are given an amount of isothiocyanates that's roughly equivalent to what you would find in about 70 grams of broccoli sprouts, Did not experience any negative effects on thyroid hormones after after a week. But that's a short-term study. What about long-term studies in animals? There was a study published in 2018 that took mice and caused the mice to have what's called drug-induced hypothyroidism.

This is a this is a model for trying to look at hyperthyroidism in animals and see how various treatments affect it. So there were 2— actually, this was actually in rats, not mice. There were 2 groups of rats, and one group of rats was fed either an iodine deficient or had the drug-induced hyperthyroidism, and basically found that broccoli sprouts given to these rats in very large quantities had no harmful effects on the thyroid, period. And in terms of their thyroid hormones, the thyroid-stimulating hormone, T3 or T4, no effect. In fact, in the animals that actually had hypothyroidism, sulforaphane improved and had a beneficial influence on the antioxidant balance in their thyroid gland. So, if anything, it was beneficial, sulforaphane was beneficial for the animals with hypothyroidism.

So I hope that really clears up any confusion with sulforaphane and cruciferous vegetables in general. I think that there's a growing community that wants to find any evidence they can to say plants are not good for you, and they just take and extrapolate things from in vitro studies or from animal studies, as I mentioned, that just have no relevance for humans. So, in order to get a level of the goitrin compound, which is an isothiocyanate separate from sulforaphane, that is a metabolite that is formed from cruciferous vegetables, you would have to just eat an insane amount that just no one would ever eat, period.

So I'm going to move on to the next question, and this question is from Emily, and Emily says, when I drink one serving of alcohol, dry wine or vodka, before a meal, it drops my insulin response. I tested it about one hour after eating the exact same meal and with alcohol. It was almost 40 milligrams per deciliter lower than without alcohol. Is this something healthy? Or something that should be avoided. So let's talk a little bit about this briefly. What the literature basically says is that moderate alcohol consumption may cause an increase in insulin sensitivity and a decrease in blood sugar levels or blood glucose levels in non-diabetic people. People.

This is also a little more prominent in women for unclear reasons, and it is not true for heavy alcohol consumption, and particularly for alcohol that is high in sugar, sugary drinks, for example. There was a meta-analysis of 20 different studies that found there's a U-shaped relationship for alcohol consumption and the risk of diabetes. So compared with lifetime alcohol abstainers, people who don't drink alcohol, men who consume 22 grams a day of alcohol had a 13%— were 13% less likely to become diabetic. However, men that consumed around 60 grams a day of alcohol had the same risk of becoming diabetic as people that consumed no alcohol. So this is called a U-shaped curve.

Compared with lifetime alcohol abstainers, women who consumed 24 grams a day of alcohol were 40% less likely to become diabetic. But again, just like men, women that consumed amounts higher than that, such as 50 grams a day, had the same risk of becoming diabetic as alcohol abstainers. So there seems to be a U-shaped curve with respect to alcohol consumption and insulin sensitivity. But there are other harmful effects, particularly in women when it comes to alcohol. So for example, consuming 3 alcoholic beverages a week actually has been shown to increase the risk of breast cancer, which is the most common cancer found in women. So I think there's certainly other aspects to weigh in terms of risks and benefits. with alcohol consumption.

Okay, we're going to move on to another question that I have seen repeatedly many, many times on many different, you know, email, social media posts, Crowdcasts. So I'm gonna, I'm gonna talk about this in a little detail. This question came from Dave, and Dave asks, how effective is vitamin K2 in reducing arterial calcification and arterial stiffening? If this works, what dosages have been used to achieve this? And a related question was from Andreas who asks, how much vitamin K2 should be taken daily while taking vitamin D supplements? So I'm going to address both of these questions together. The first question of whether or not high vitamin K intake is protective against arterial calcification was first addressed in what was called the Rotterdam Study.

This was a really large European clinical trial following about 4,807 subjects. And they were over the age of 55 and they were followed for about a 10-year period. And the dietary intake of what's called menaquinone, which is also a form of vitamin K2, also referred to as MK-4 or MK-7. Was inversely correlated with cardiovascular calcification and cardiovascular death. Elderly people in the top third of vitamin K2 intake, so they had intakes of around 41 micrograms per day, they were half as likely to have severe aortic calcification and cardiovascular disease, and they had a 26% decreased risk for all-cause mortality. Compared to people that had the— in the lowest third vitamin K2 intake. So those people will consume around 15 micrograms per day.

Interestingly, vitamin K1, also known as phylloquinone, did not correlate with any of those beneficial outcomes with respect to cardiovascular health in that study. So again, it seemed as though the intake was around 40 micrograms of vitamin K2 per day was— had the most protective effect. There was a second large-scale study, and this was called the PROSPECT-EPIQ study, that really repeated similar findings but for coronary artery disease. So coronary artery disease is a narrowing of the blood vessels that feed the heart, which can break off and cause cardiovascular events such as heart attacks. So cardiovascular events are currently the number one cause of death in the United States.

So this study consisted of around 16,000 women, and they were aged 49 to 70 years old who did not have any cardiovascular events or cardiovascular disease at baseline. Intake of vitamin K and other nutrients was estimated, and they were followed for about 8 years. And they found that basically after adjusting for confounding factors, that there was an inverse association between vitamin K2 and coronary artery disease. For every increase of vitamin K2 of 10 micrograms per day, there was a decrease in the risk of coronary artery disease by 9%. And another study came out actually the same year that the PROSPECT-EPIQ study and found that there was a 20% reduced risk of coronary artery disease In the top quarter of vitamin K2 consumers compared to the bottom quarter of vitamin K2 consumers.

Again, sort of validating and reconfirming all these other studies that had come out. And in this particular study, the average consumption of vitamin K2 who had the 20% decrease in coronary artery disease was about, again, around 50 micrograms per day. Wow. So it seems as though if you look at the meta-analysis studies, there is a dose-dependent decrease in arterial stiffening with respect to coronary artery disease and vitamin K2 intake. And the amounts seems to range between 40 to 60 micrograms per day of vitamin K2. And it is unclear whether or not amounts above 60 micrograms per day have any benefits above that or if they plateau. There are also some studies looking at the benefit of vitamin K2 and bone health.

And there was a systematic review and a meta-analysis of randomized controlled trials. So these are This is different than the studies I just mentioned, which were observational studies just looking at food questionnaires, you know, people, you know, recalling, you know, what their intake of different food components or supplements containing vitamin K2. These were randomized controlled trials, so people actually were given vitamin K2 or a placebo. And the effects on bone density and bone mineral density and bone fracture were evaluated. And it was found that vitamin K2 supplementation does improve bone density and it does reduce the rates of hip and other bone fractures. So these trials use the type of vitamin K2 known as MK-4 either at 15 milligrams per day or 45 milligrams per day.

And there was another clinical trial that used MK-7, which is another form of vitamin K2. MK-7 is thought to have a little bit of a longer half-life, but there are fewer randomized controlled trials that have investigated the effects of MK-7 relative to MK-4. So this— the trial using MK-7 used a dose of 180 micrograms per day. And found again there was improved bone strength and decreased loss of bone mass. Another study found something similar using MK-4 with 45 milligrams per day. Okay. And another meta-analysis of 12 studies found that vitamin D plus vitamin K, and this, in this case, it was vitamin K1 or vitamin K2. So there was 6 of the studies in this meta-analysis used vitamin K1 and 6 of the studies used vitamin K2.

And both of those in combination with vitamin D improved bone health. So a little bit about the differences between vitamin K1 and vitamin K2 because there have, you know, again in the observational studies looking at coronary artery disease and cardiovascular health, the vitamin K2 seemed to be superior. And the bone health studies, it seems as though both vitamin K1 and vitamin K2 improved health. Vitamin K1, one of the main differences between vitamin K1 and vitamin K2 happens to do with where they're distributed in tissues. And where they're distributed in tissues is important because they activate proteins in those tissues. Different proteins are located in different tissues.

And so vitamin K1 has a very strong preference of, you know, after it's in the bloodstream, it goes to the liver. And in the liver, it's responsible for activating proteins involved in coagulation. And so It plays a very important role in blood clotting. But vitamin K2, on the other hand, seems to stay in the periphery, in the bloodstream where it's involved in activating proteins that are involved in moving calcium out of the bloodstream and bringing it to other tissues like the bones, like muscle tissue.

So it's really important in moving and shuttling calcium out of the bloodstream, which is important because calcium can easily form precipitates in particularly in the presence of phosphorus in in in the bloodstream if it's not being you know properly shuttled to where it's supposed to go like the bones so it seems as though in conclusion vitamin K2 in doses of around 40 to 60 micrograms per day seems to be what the science says is most beneficial I personally take 50 50 micrograms A supplement with 50 micrograms of vitamin K2. So that's sort of wraps up that vitamin K2 section. I see some people asking about omega-3 in the chat. We will be getting to that topic soon.

The next question was from Kenny, and Kenny said— says, for common cold prevention, looks like both zinc and vitamin C have good studies behind them. So should we take both? Does that modify the dosage recommendation of 80 milligrams of zinc and 2 grams of vitamin C? I read the vitamin C topic page you guys put out and the dosage wasn't clear and there was no mentioning of combination with zinc. So first of all, I will say that there's a lot of information on the vitamin C topic page. And doses do change based on the studies, and there's a lot of differences in terms of what endpoints are being looked at. So that's important. And I think that anyone wanting to look at the common cold can, can go to our topic page.

You can find that at foundmyfitness.com, and in the navigation bar, just click on the topics, and you'll see you can scroll down and click on vitamin C and find that topic page. Uh-huh. Lots of information there. Table of contents lets you kind of click on whatever you know subtopic vitamin C that you're interested in. We also are almost we're wrapping up a topic page on zinc, so you'll have a lot of information on that. There's not a lot of studies looking at the combination of vitamin C and zinc. So there is I did there is you know one study that did look at. The combination of vitamin C and zinc with respect to immune defense and maintenance of health.

And it seems as though from 2 double-blind randomized placebo-controlled trials, a combination of 1,000 milligrams of zinc— sorry, 1,000 milligrams of vitamin C plus 10 milligrams of zinc In people that had the common cold, there was a trend but a non-significant reduction in the duration of common cold. When the analysis was pooled from both of these studies, then there was a significant decrease in the duration of the common cold, meaning typically when you see a trend in a decrease from a randomized controlled trial, but you don't see statistical significance, it could mean a variety of things. One of the main things it could mean is that the study was underpowered, meaning there weren't enough people in the study to show statistical significance.

So sometimes when you pool together 2 studies or more, then you will find that you have more statistical significance because there's a greater sample size to power the study. But it would still be nice to see statistical significance within that individual study. But again, this was a dose of 1,000 milligrams of vitamin C plus 10 milligrams of zinc combined. And that's really the only study I could find that showed a beneficial effect of combining the two. There just hasn't been a lot of research looking into that. And I'm gonna— there's another topic that we're gonna dive really deep into, but there was another sort of related question with vitamin C that I'm gonna just hit right now since we're talking about vitamin C. And this question was from Koa.

And Koa says, oral vitamin C administration is typically less effective than intravenous due to bioavailability. So for those who don't have access to intravenous vitamin C, is it worth looking into liposomal vitamin C? Studies suggest that liposomal vitamin C is more bioavailable than non-liposomal. So I think I'm glad this question was asked because I know there, there are a lot of people that really think that liposomal vitamin C is superior to just regular oral administration of vitamin C. And if you look at the higher quality scientific literature, really it seems as though— so first of all, typically people that are eating a lot of like between 5 and 9 servings of vegetables and fruits that are pretty high in vitamin C, those individuals typically have what are called steady-state plasma concentrations of vitamin C. So just, you know, sort of like their baseline, what their steady state is at any given moment is around 80 micromoles per liter.

And you can't Yeah. You can't achieve a plasma level of vitamin C above— it's diffi— I mean, it's very difficult to achieve plasma levels above 220 micromoles per liter from oral administration. And there have been studies showing that 3 grams of oral vitamin C ascorbic acid, just regular old ascorbic acid, can get you to around 220 micromoles. per liter. Uh, if you wanna maintain that throughout the day, those have to be taken 6 times throughout the day because of the short half-life of vitamin C. And so, you know, over the course of 24 hours, if you only take 3 grams once, you go back to your baseline. Uh, comparing liposomal vitamin C to just the regular old ascorbic acid or even the buffered vitamin C calcium ascorbate, Yeah.

It seems as though liposomal vitamin C in doses less than 5 grams achieves similar plasma levels. And so, it's not until you really get into multi-gram, like multi-multi-gram, we're talking like 20 grams or 30 grams of liposomal vitamin C, that has been shown to get you above or get a person above the peak plasma levels of 220. And it's been shown to get people to 320 or even up to 400 micromoles per liter. So that's really the highest that I've seen liposomal vitamin C increase plasma levels of vitamin C is up to around 400 micromoles. That's in contrast to what intravenous vitamin C can get you up to, which is around 15,000. Yeah. Just really not— it's really comparing apples to oranges.

It's just not even comparable even with liposomal vitamin C. So I would say, you know, I don't see really any reason to take liposomal vitamin C unless there's a therapeutic reason, you have a common cold and you're taking very large doses like in the 20 to 30 gram range, you know. that may, that might be. But, you know, if you can take 3 grams of just regular old oral, you know, ascorbic acid or calcium ascorbate, you know, that's, that's going to get you to a similar level that 3 grams of liposomal would get you. So I think, I think that's kind of important to keep in mind. There's a— there was a start— a study that showed a single 10-gram dose of liposomal vitamin C could increase the plasma levels to 300 micromoles.

So again, that's higher than the 220 peak that usually you can get from oral consumption. So again, for everyday use, I don't think that liposomal vitamin C really makes sense, and it certainly is not comparable to the benefit— the therapeutic effects that you see with intravenous vitamin C, particularly with respect to potentially being an adjunctive treatment for cancer, some of the really robust effects on viral, basically killing or inactivating viruses as well. So I'm gonna, I'm gonna really do a, a pretty big deep dive on this next question because it's been submitted in so many different shapes and forms. I mean, it's, it's almost a question that I get every single Crowdcast in, in some form or another, and it has to do with cholesterol.

And a lot of people ask, what can I do to lower my cholesterol? And it's kind of a general question. And I think that there are a lot of different nuances and important, very important nuances to to cholesterol and to this whole topic that, that needs to be addressed because it's, it's a lot more than just cholesterol. So people are talking about lowering their cholesterol, they usually mean LDL cholesterol, low-density lipoprotein cholesterol. And if you're getting a blood test, that typically shows up on a blood test. It's referred to as LDL-C. And that's— it's typically just a marker of the total LDL cholesterol. And it's really not the best indicator of really, you know, cardiovascular risk.

And it really just stands for the portion of cholesterol in the blood that is carried around by particles which are called LDL particles. These are the particles that are transporting the cholesterol, the LDL cholesterol throughout the body into different tissues. LDL cholesterol, the total LDL cholesterol is potentially a marker for the number of LDL particles But it doesn't really reflect the numbers for those particles. And it's the numbers of the LDL particles that are a little more indicative of atherosclerosis risk. So traditionally over the years, LDL cholesterol or LDL-C, again, as it's demarked on a blood lipid test, traditionally it's served, it's basically easily measured.

And that's why it's something that's You know, typically what you— if you're getting a blood lipid test, you'll see your LDL-C or your LDL cholesterol measured. But the numbers of LDL particles is a— it's a more desirable metric for heart disease risk when the particle number is elevated in general. That tends to correlate with increased levels of what are called small dense LDL particles. And the number of individuals in the population who have high LDL particles, typically they also have a high number of what are called small dense LDL particles. So LDL comes in many sizes and shapes, and if you want to learn more about this, please go back and listen to the episode I did with Dr. Ronald Krauss.

Uh, you can find that on the episode page at foundmyfitness.com/episodes and just scroll around the, the different episodes and you'll find the episode with Dr. Ronald Krauss. It's also— you can find that on iTunes as well as the private podcast feed, um, which by the way, if you haven't downloaded, that's, uh, present on your dashboard at foundmyfitness.com/dashboard. But the particle sizes are really important because LDL is found in different sizes. It's found in large buoyant particles, sorry, large buoyant particles, and it's found in medium size, and it's found in small dense sizes. And the small dense sizes are what are really, have been associated with atherosclerosis risk and risk in general for a cardiovascular event.

And that is because those particles in particular are very prone to getting stuck and basically inserting themselves into the arterial wall and where they become basically stuck and they can't be recycled back to the liver where typically after these particles which are carrying cholesterol, they're carrying fatty acids, triglycerides, they're carrying a variety of things that are important and they're transporting it to various tissues so that, you know, your tissues can have, you know, these important components for all cell cells in general. But after they transport them, you know, the LDL particles go back to the liver and they're recycled so they don't stay in the circulation for the long periods of time.

But the small dense LDL particles unfortunately are much more prone to getting stuck in the arterial walls. And once they get stuck, it's hard to get them out. And that's partially because a protein that's present, which we're gonna go into great detail about, called ApoB, is sort of obscured. And so that protein's important for being recycled back to the liver, and when it becomes obscured, then that doesn't really happen as readily. So particle size is really important, particle number is really important. And I wanna just talk about particle number, which also is oftentimes on a blood lipid test is ApoB is a marker for that, and again, we're gonna go into some detail about that why that is.

But in fact, why don't I just— why don't we just skip to that and talk a little bit about why ApoB is a marker. So ApoB is a protein that is produced in the liver and it provides structural support for lipoproteins, particularly very low-density LDL, so VLDL. And It's basically a marker of cardiovascular risk because a couple of reasons. One, it's a more direct way to measure LDL particle number because you can have cholesterol and actually the large buoyant cholesterol I was mentioning is actually considered a good type of LDL cholesterol because that type of cholesterol is transporting You know, the cholesterol, it's— it's— it's— it— to— you know, it's— it's— it's being used by cells. You need— every cell in your body needs cholesterol.

You know, it's made— you know, the cholesterol is part of the cell membrane. And so every time you're making new cells, any type— anytime you're repairing a damaged cell, it needs cholesterol. And that LDL is what provides the cell with, uh— with that, you know, cholesterol. Um, so the large buoyant LDL is nice because It's less likely to get stuck in the, again, in the arterial walls and stuff. So ApoB is a marker for particle number. The lipoprotein itself contains the cholesterol. And so it's the lipoprotein particle number. Sometimes you can have more cholesterol because you've got more of this large, large buoyant cholesterol. Sometimes you can have more of that, but you can still have a small particle number.

Now that's usually the exception rather than the usual case, and that's because most people aren't eating— they're eating a standard American diet, which we're gonna go into in a minute. But basically ApoB is constantly being made by the liver. And it is the backbone of these LDL particles, not the cholesterol itself, the particles. And it's the ApoB that is more likely to insert into the arterial wall, and that can then allow particles to build up in the arteries. And then again, that's, you know, increases your risk for atherosclerosis. ApoB is present on small dense LDL, and it's actually those particles that are more likely to insert into the arterial wall. Also, ApoB is regulated.

So people that have elevated ApoB can often, you know, that is again a direct marker of particle number, which could mean increased risk of, you know, atherosclerosis or, you know, cardiovascular problems. Generally, it does mean that, but again, it's not always the case because some people can have an elevated particle number, but those particles can contain more of the large buoyant and not the small dense. That's the exception again. ApoB typically is regulated at the level of degradation because your liver is constantly making this stuff, and usually you don't find a lot of regulation of ApoB at the level of making it, producing it, synthesizing it.

However, there are some things that have been shown to regulate it at that level, and that has actually been omega-3 fatty acids, interestingly. There's been some studies looking at fish oil supplementation, about 1,500 milligrams of EPA and 1,000 milligrams of DHA. That's been shown to actually decrease ApoB levels in people with dyslipidemia, so people that have high levels of LDL particle numbers, they have high levels of triglycerides, all sorts of different elevated lipid markers in general.

Another study found that fish oil intake, and this study was about 1.8 grams of EPA and 1.2 grams of DHA, lowered ApoB production by 29% in people with normal blood lipids, which is a really exciting finding because oftentimes you'll find that therapeutic treatments work a lot better on people that have a problem, you know, have a dysregulation in something to begin with. In this case, we're trying to look at ApoB, lowering ApoB. And so, having it lowered in people that don't have dysregulated blood lipids is nice to find. There was also a decrease in the VLDL pool by around 43%. Interestingly, and this is something that was a very new study just published, I believe, last month, and the study was not a randomized controlled trial, it was an observational study.

So it was looking at fish intake or dietary intake of omega-3 fatty acids from supplements and also from not just from marine sources but also from plant sources, ALA, which is found in like walnuts and flaxseeds, for example. So what that study found was an association. Again, I mentioned that fish oil was shown to lower ApoB levels in both people with dyslipidemia and people with normal blood lipids. But fish intake, on the other hand, actually was not associated with lowering ApoB. And in fact, fish intake was associated with a higher ApoB level. And it's unclear why that is. It possibly could be due to other fatty acids present in the fish.

And again, it's an association, so it could be also, there could be a confounding factor where people eating fish are also taking in something else. It's just not, observational studies are a good start, but it's hard to know what it all means until there is a randomized controlled trial. So that's pretty interesting. And again, I think the fish oil finding on lowering ApoB is I would like to see more research on that because there's only been a couple of studies and some of them were done quite a long time ago. So it'd be nice to see some more studies looking at fish oil and ApoB.

But sort of returning to this whole lowering cholesterol and lipid particle number and lipid particle size, really, The main factors with elevated cardiovascular risk and atherosclerosis seem to be particle number, and in particular, the small dense LDL particle. And particle number is often measured by ApoB. That's why we were talking about ApoB, because ApoB is a proxy for particle number, LDL particle number. Whereas ApoA-1 is a proxy marker for high-density lipoprotein, HDL, because those are found in the HDL particles. How diet affects, you know, these different lipids is also something that's on a lot of people's minds.

And it's— I think it's really important to understand that there are differential effects At least this is what's been shown so you know so far in in the scientific literature that have you know that have done randomized controlled trials or crossover trials looking at how various diets whether we're talking about a high saturated fat diet or a low carbohydrate diet we're talking about high protein low carbohydrate diets they can affect people's blood lipids differently depending on what their baseline blood lipid. category is. Generally speaking, so people that have a high number of LDL particles and particularly a high number of small dense LDL particles, they're often called phenotype B, whereas phenotype A is— typically people that have a higher number of the large buoyant LDL.

And what's interesting is there is a strong genetic component for phenotype B, so which is really unfortunate. So people, there are some genes that do play a role in predisposing people to have more of the small dense LDL particles. regardless of their diet. We do know, generally speaking, also that the small dense LDL particles are generated from, you can form them, and they do form from the larger particles, typically in the presence of a very high refined sugar diet. So for example, healthy men, that were given like a sugar-sweetened beverage, like you would get a Coke, one of those every day. Basically, these were normal healthy men with normal blood lipid levels.

After, I don't remember the time, I think it was like, it was either a week or a couple of weeks, they increased their small dense LDL particles by pretty high percentage. And all they did was basically add in sugar-sweetened beverages to their diet, which for a variety of reasons can form small dense LDL particles. So let's talk a little bit about the basically different effects of diets on these LDL particles. We know that there's been some studies, a lot of these studies have been done by Dr. Ronald Krauss, who's a friend of mine, and others looking at the effects of dietary fat and carbohydrate on the LDL particle size. And particularly looking at people that are phenotype A or phenotype B. So phenotype A again is the large LDL, phenotype B is the small dense LDL.

And so men, about 100 men that were given a high-fat a diet, so it was about 46% of their energy was coming from fat, or they were given a low-fat diet. In this case, it was about 24% of their energy were coming from— was coming from fat. And they were given that diet for 6 weeks, and then they were switched to the other diet. So this is, this is called a crossover study. So each, each person got both diets, the high-fat or the low-fat diet. And Before they were given this diet, they were classified as either being phenotype A or phenotype B. Phenotype B being, of course, having an increased risk for cardiovascular disease and atherosclerosis because they have higher percentage of small dense LDL particles.

So following the low-fat diet, the almost all of the people on a phenotype B remained phenotype B. So the low-fat diet really didn't do anything. Beneficial in terms of making a phenotype B person a phenotype A, but it didn't seem to do anything really worse. Most people remained phenotype B. However, about 36 people in that 105 group of men that started out good phenotype A, when they were shifted to a low-fat diet, actually changed to phenotype B. So some— so basically, it seemed as though some of these phenotype A people had a negative effect of a low-fat diet on their blood lipids.

Some of the people in the phenotype B group, again, they remained phenotype B, but they did see decreases in their total LDL cholesterol, which again doesn't mean much, but they did see also decreases in their ApoB, which is beneficial. That is a little bit more of a favorable lipid profile. Those were people that started off with phenotype B. So the authors of that study concluded that a low-fat diet may be a little more beneficial for people that have phenotype B but not people with phenotype A, particularly because some of the people with phenotype A actually had a worse outcome. They shifted to phenotype B. Notes about that diet though, the fat content. Again, the high fat was 46% of energy and the low fat was 24% of energy.

That was, that was That was done by decreasing saturated fat from 18% to 5%, and polyunsaturated fat from 13% to 4%. The diet that was high in fat had about 38% of their calories from carbohydrates, and the low-fat diet had about 60% of calories from carbohydrates. So a separate Looking at those same 105 individuals, they actually— looking at the LDL subfractions, it was found that the phenotype A individuals that were on the low-fat diet, they basically had a decrease in their large buoyant LDL and an increase in their small dense LDL, and that's what shifted them to the phenotype B. So again, a low-fat diet may be detrimental to some people that are phenotype A, and it may be beneficial for some people that are phenotype B. This was confirmed in a similar study involving about 500 men and 72 premenopausal women.

The LDL cholesterol reduction was greater. With a low-fat diet in subjects, 165 subjects that were classified as phenotype B on a high-fat diet. So they were classified as phenotype B when they were on a high-fat diet. So again, it seems as though the low-fat diet could be negative, have a negative effect again on a minority of people that are phenotype A to begin with. And there could be potentially some benefit with the phenotype B than those with phenotype A. I'm going to talk about another study where people again with phenotype B were put on a high saturated fat diet. They actually had increases in their Apo and their ApoB and increases in medium and small. Dense LDL particles with no differences in large or very small LDL.

So because medium and small LDL particles are more highly associated with cardiovascular disease than the larger ones, it seems as though a very high saturated fat diet may actually not be beneficial for being a phenotype B individuals. In this study, the saturated fat, the high saturated fat diet was 39% of the energy, which is quite high. And in another study, in 178 overweight men who were phenotype B, if they lowered their dietary carbohydrate from 54 to 39% and increased their protein intake, and this was important, They increased their protein intake from 15 to 29% without changing their fat or calories. They were actually able to to have a beneficial effect on their lipids. So I think the bottom line that I'm trying to get to is that you know the low carb high fat diet. Uh-huh.

It may be beneficial for some people, but it may be detrimental for other people, and vice versa. The low-fat, high-carb diet may be beneficial for some people and may be detrimental for other people. And really, the only way to know if it's going to be beneficial or detrimental is to get blood lipid— blood lipids measured, and not just a total cholesterol and LDL cholesterol, HDL, but particle size, particle number, you know, finding out if you're phenotype B or phenotype A, you know, before, you know, before changing your diet is very important. And also just doing the lipid test before and after changing your diet seems to be extremely important. So that was sort of a really long deep dive into some of that.

I think that it's, it's, uh, uh, an important topic and it's a very nuanced topic and a lot of people sort of want to claim one diet over another and I think that there's really, there's really a personalized diet option that's important because these diets do affect people differently depending on their their blood lipid, baseline blood lipid and their phenotype to begin with. Anne's asking in the chat about Lp, and Lp actually unfortunately is really regulated by genetics, and high Lp is also associated with an increased risk for cardiovascular disease. There are some interesting treatments that I really— the only— I know statins have not been shown to lower Lp, but there have been some interesting studies looking at niacin.

So if someone wants to ask that question next time, we can go into that a little bit deeper. So for people mentioning the connection issues, I apologize. Just remember that this, this episode will be Uh, available on your dashboard, uh, both as a YouTube video. You can find that at foundmyfitness.com/dashboard. Uh, it also will be available on your private podcast feed. And if you haven't downloaded that podcast feed yet, you'll find that also on your dashboard. So the next question comes from Michael, and Michael is asking about PQQ. He says, PQQ is claimed to help create more mitochondria within each cell. Wouldn't taking PQQ alone also give rise to much more NAD within each cell and be superior to taking supplements that should increase the generation of NAD?

That don't actually increase mitochondrial density. I have talked about PQQ in a previous Crowdcast. That was Crowdcast number 7. So you can go back and listen to that on your private podcast feed or watch it on YouTube if you want to go into more details about that. Sort of as a quick general overview, it is a cofactor. It's made by several species of bacteria. It's a cofactor for some of their metabolic enzymes. It's so it's made in bacteria in the soil, so plants often take it up, and that's how PQQ actually enters the human diet. It is something that humans do get from their diet. It's found in few— it's found in foods like kiwi, green peppers, parsley. They all have pretty modest amounts of PQQ. Interestingly, it's also very highly concentrated in breast milk.

It has very unusual antioxidant activity. It goes through many, many thousands of catalytic cycles, about 20,000 catalytic cycles, so it can, you know, be reused quite a few times, so to speak. I have not seen any direct evidence that PQQ raises NAD levels, but it has been shown to increase the activity of sirtuins, which are dependent on NAD levels. So that's sort of an indirect, potentially an indirect way, you know, perhaps it is raising NAD or perhaps it's directly acting on sirtuins themselves. It's sort of unclear. There have been sort of dozens and dozens of preclinical animal studies looking at the effects of PQQ on mitochondrial function. And then there's just huge benefits that have been shown. There have been a couple of clinical studies looking at PQQ supplementation.

Typically, those studies use a dose of around 20 milligrams of PQQ per day. And there's one looking at cognitive function. PQQ was taken for 12 weeks and cognitive function was improved as well as blood flow to the brain was increased. There was another study, 20 milligrams a day again for PQQ, and it decreased biomarkers of inflammation. Inflammation and oxidation in people, and also it increased markers of mitochondrial activation. So this sort of was a preliminary— some preliminary data that PQQ can potentially improve mitochondrial function in humans. So that is all, I think, you know, great preliminary work. It'd be nice to see some more human studies done.

I would say that I have not seen any human studies with significant benefits of taking NAD precursors like nicotinamide riboside other than raising— it definitely raises plasma NAD levels and also raises NAD levels in white blood cells. There's no published human data on NMN yet. NMN is another precursor for NAD, nicotinamide mononucleotide. So there was actually very recently a new study published, and it was a study, a very small study. I think there was about 10 people. They were obese adults, and they were given 1,000 milligrams of nicotinamide riboside for 6 weeks. There was no effect on insulin sensitivity. There was no effect on mitochondrial function.

There was no effect on hepatic or intramyocellular lipid accumulation, no effect on cardiac energy status, no effect on cardiac ejection fraction or blood pressure, plasma markers of inflammation, no effect on energy metabolism. Pretty much everything that nicotinamide riboside has shown to improve in animal studies, there was no effect in the clinical studies with 1,000 milligrams a day, which is The highest dose I've seen yet with nicotinamide riboside clinical studies. But this study, that study that had no effect on anything did find that NAD levels were elevated in muscle tissue. That's the first time I've seen that in a human study.

I will say that, you know, a majority of these animal studies, most of them being mice, done in mice, the oral amount of nicotinamide riboside used was just astronomically high. It was 400 milligrams per kilogram body weight. And, if you're translating that to a human, if you want to do the human equivalent dose, for a 180-pound person, that would be about 2.6 grams a day, much higher than 1,000 1,000 milligrams, which is 1 gram. So, I, you know, it's just, it's yet to be determined, you know, while these high— this high-dose nicotinamide riboside can elevate plasma levels of NAD, it can elevate some NAD in white blood cells. And with this new study, at least in this, in obese adults, very, very small study, it seems to also elevate NAD in muscle tissue.

There was no really effect on you know, anything really beneficial. Although, although this study did find something interesting, which was that there was an effect on body composition. So these people were obese and their body weight remained stable, but the nicotinamide riboside did seem to decrease the amount of fat mass and increase the amount of fat-free mass. So there was basically 1.3% higher fat-free mass in the nicotinamide riboside group compared to the placebo group. So, you know, that is interesting. But again, all the other benefits that have been seen in animal studies have not been seen even on mitochondrial function and everything have not been seen in humans yet.

The reason I kind of went into that is because there were a few study— a few questions on nicotinamide riboside. as well. So I really just, I wanted to kind of address that all in one. Andrea is saying in the chat, fish oil raises my LDL. I guess it's because the particles get bigger, which would be good, right? So what's been shown is that in that study that I mentioned that was published last month, it was shown that specifically DHA but not EPA can raise LDL cholesterol, large buoyant. It does not raise the small dense LDL particle. And that, and that was, that, that does seem to be something that's been shown in other studies as well. Speaking of omega-3, Lewis asks, any evidence that there's supplementation for children that's been shown to be beneficial.

And I will say that basically, if you were to ask, you know, is there one supplement that's been shown— like, if you could only, you know, if I could only give my son one supplement, what would it be? And I would say hands down, it would be fish oil. It would be the marine omega-3 fatty acids, DHA and EPA, particularly DHA. So, there has been studies showing that omega-3 fatty acids may have long-term neurodevelopmental effects in children that ultimately can reduce antisocial and aggressive behavior. So, omega-3 fatty acids influence cell membrane integrity. They influence the receptors that are bound to cells, which which, you know, in neurons, this is basically affecting how neurotransmitters are, you know, communicating and binding to those receptors. It affects blood clotting.

It affects, you know, biosynthesis of hormones, all sorts of things. And so, there have been randomized double-blinded placebo-controlled trials, one that involved 200 school-aged children, 8 16 years old. They were randomized either into a placebo or a treatment group, and the children that were given, they were given 1 gram of mixed omega-3 fatty acids every day for 6 months. And the placebo group had a drink that was sort of similar tasting to that, the drink that was, you know, had the omega-3 fatty acids. And at the end of the 6-month period, both parents and children completed you know, a variety of personality assessments and reports about behavior, externalizing behavior such as fighting or lying, internalizing behaviors such as depression or anxiety or withdrawal.

Those were all assessed. The children who took the omega-3 fatty acid beverage had significant reductions in negative behaviors that actually persisted 12 months after, or it persisted to the 12-month point. The externalizing behaviors were reduced by 42%, and the internalizing behaviors were reduced by almost 70%. And so that's really kind of very significant. And it was— it's thought that this may be a consequence of the effects on DHA and EPA on neuronal health, neurotransmitter production, neurotransmitter function, inflammation, and in the brain as well. Another study has showed that basically blood levels of omega-3 fatty acids can affect children's behavior and their ability to learn.

So higher levels of omega-3 fatty acids, particularly DHA, have been associated with better reading, memory, fewer behavior problems, particularly when DHA supplementation was was done in these children, there was improved reading and behavior, particularly in the children that were underperforming. So children that were not reading very well at baseline, they had seen the biggest improvement. More double-blind randomized placebo-controlled trials finding that omega-3 supplementation reduces disruptive behavior, just You know, in this, in this study, vitamin D was also given along with omega-3. This was 300 milligrams of DHA, 200 milligrams of EPA, and 400 milligrams of alpha-linolenic acid.

Um, and again, the children in the, in the omega-3 and vitamin D group had improved, um, their behavior. They're less aggressive behavior, less disruptive. Just a really recurring theme with many different randomized controlled trials showing that omega-3 seems to really affect behavior in a positive way in children. Another small clinical trial showed that eating fatty fish such as salmon twice a week for 6 months reduced asthma symptoms and reduced bronchial inflammation by 14 units in children. So children in the omega-3 group that were eating fish twice a week also had a significant reduction in their medication use compared to children in the control group.

It's known that EPA and DHA can inhibit the cyclooxygenases, which are— and the lipoxygenase enzyme activity, which basically can affect inflammation. and particularly pro-inflammatory mediators in that play a role in asthma. So it's thought that that may be how omega-3 is helping with asthma. And another study that's really interesting was this, this study was done a few years ago, basically showed that omega-3 can prevent the— may prevent the onset of schizophrenia and other psychotic disorders long after being consumed, actually up to 7 years later. So there was a study that was done in young people that were at a high risk for schizophrenia, genetic— for genetic reasons, or there was, you know, a family member that had, you know, psychosis or schizophrenia.

And so these young people were given the omega-3 supplements for 12 weeks. And throughout that time, they basically had less psychotic episodes. But a follow-up study was done almost 7 years later, and it found that basically while only 10% of the young people that were in the omega-3 group developed psychosis 7 years later, 40% of people in the placebo group developed psychosis. 7 years later. So, you know, schizophrenia is something that really emerges in young adulthood, particularly during adolescence, and it can kind of happen quickly or sort of gradually. So I just think that's a really important study, particularly for, you know, families that do have, you know, a rel— that there is a relative that has psychosis or schizophrenia, or there's a genetic risk.

You know, just the fact that, you know, supplementing with omega-3 supplements for 12 weeks had such a profound effect on reducing the risk of psychosis years and years later is very compelling. Another study recently found that basically it was an observational study looking at omega-3 fatty acid levels, EPA and DHA, in the blood of children and adolescents. And those children and adolescents that had higher levels of omega-3 EPA and DHA had lower levels of DNA damage. So DNA damage is something that accumulates with age. It's involved with cancer and aging in general. And if you can— if you're having high levels of DNA damage early on in childhood, what does that say for the way you're going to age?

It's really not a good indicator that you're going to age well if that DNA damage is already happening early in childhood. And so, and that was also shown that people, the children and adolescents with low levels of omega-3 fatty acids were, had higher levels of DNA damage. You know, so, so I think that hands down omega-3, particularly DHA and EPA, are extremely beneficial for children and adolescents and generally for young people on many levels. Particularly, I focused a lot on the brain, behavior, reading, and then also for other reasons, reducing inflammation, particularly with respect to asthma. But inflammation in general can have consequences that affect many different processes, including cognitive function. Vitamin D is another one that I think is important.

Not all children are going outside and spending a lot of time outside, and they're certainly not out in regions that UVB radiation is being generated in the atmosphere. So like northern latitude places, Washington State, you know, the entire like East Coast of the United States, for example. So I think that's also another beneficial one, but definitely omega-3. Rachel Swanson is asking in the chat if I noticed a difference in your lip— if I noticed a difference in my lip When I increased my EPA levels, really. So my last lipid test I did was in March of this year, sort of right before the the pandemic, and my triglycerides were lowered. But also, you know, triglycerides are really affected by aerobic exercise, which I do a lot of.

So EPA is is has been shown to really have a profound lowering effect on triglycerides. But I'm doing a lot more tests and I'm going to be experimenting a lot more, but I think I'm pretty convinced that I like both DHA and EPA in terms of my supplementation. So I've got one more sort of longer Deep dive, and then I'm going to do some rapid-fire questions. The last deep dive question was submitted by Candace, who says, you had mentioned on Joe Rogan's recent podcast that certain blood types may have different reactions to COVID-19. That should read probably different reactions to the SARS-CoV-2 virus, which causes COVID-19. Yeah. Can you talk a little bit more about how different blood types affect this virus?

And she also— or they also ask, is taking 4,000 IUs of vitamin D every 2 days equivalent to taking 2,000 IUs every day? I'll start— I'll answer that quickly, that question. That's more or less equivalent. Taking 4,000 every 2 days is more or less equivalent to taking 2,000 every 2 days. But the best way to know if you're supplementing with an adequate amount of vitamin D is to get a vitamin D blood test. Very important. So let's talk about the blood type. Based on— and in fact, a really new study just kind of came out confirming some of this.

There've been some studies looking at people with blood type A having a higher risk of acquiring COVID-19 compared to people that do not have blood type A. And actually, people that have blood type O seem to have a significantly lower risk of acquiring COVID-19 compared to non-blood O type. And it's actually been thought that because there was some research on SARS-CoV-1 virus looking at blood type and You know, SARS-CoV-1, and it was found that basically type A antibodies, which are found in people that have blood type O and blood type B, that those type A antibodies can provide some protection by inhibiting the interaction between the SARS-CoV-1 virus and the ACE2 receptor. The ACE2 receptor is how the SARS-CoV-1 and the SARS-CoV-2 virus enter the cell.

So the type A antibodies that are produced in blood types O or blood types B are thought to basically inhibit that SARS-CoV-2 virus from getting into the cell. And that's why people with blood type O seem to have a lower risk of contracting COVID-19. And so that was shown, that has been shown in a couple of preliminary studies that basically people with blood type O have a lower risk of actually getting COVID-19. But what's interesting is there's, there was a new study that showed people with blood type A are actually more likely to, like 50% more likely to require oxygen when they have COVID-19. So this is separate from contracting the disease. This is the severity of the disease, right?

So that's a completely different topic, which the reason I think that's very interesting is because People with type O blood have low levels of a factor that it's involved in the aggregation of blood cells. It's called von Willebrand factor. And basically, people with type O blood have lower levels of that aggregation factor and they have lower risk, a reduced risk of thromboembolism. Compared to other blood types. And the von Willebrand factor plays a role in coagulation. And it's basically, you know, there's increasing evidence that inflammation can cause, you know, inflammation causes thrombosis, it causes, you know, coagulation things happen. And that can also affect, you know, needing You know oxygen and stuff.

So it's I just find it interesting that this new study that just just was published very recently showed that that that people with type A blood, which again they don't have lower levels of the von Willebrand factor that's found in type O. They also have a the type A blood also people type A blood have a higher risk of actually requiring oxygen when they have COVID-19. I went into detail about type O, type A, type O, type B blood, and COVID-19 in the first Q&A that I did on COVID-19, and you can find that on the episode page on foundmyfitness.com. You can find that in your private podcast feed as well as on iTunes. So Make sure to check that out.

If you go to the episode page, you'll find a timeline, and on the timeline you can click the specific time point where blood type is mentioned, and then you can, you know, sort of skip to that without having to listen to the whole podcast. Paul is asking in the chat about taking cold and flu tablets when you're sick and whether or not it makes your body, you know, basically if it messes up your natural healing process. I would say that it really depends on what's in those cold and flu tablets. And also, you know, I think it depends on if you have the flu, obviously you should, you should probably listen to what your, your doctor, you know, advises.

But, but there are some studies, for example, looking at ibuprofen and how ibuprofen can lower You know, inflammation and important inflammatory processes that are also important for healing. And I think there's also been some studies done with ibuprofen and looking at the immune response to vaccines. That's really a proxy oftentimes for measuring immune response is basically your body's response to a vaccine, and the anti-inflammatories, ibuprofen, have been shown to dampen that immune response to the vaccine. That's it for this Q&A, but never fear, Q&As happen monthly, which means the next one is happening imminently. Check your member dashboard for the next event link and access code.