Hello everyone, welcome back to round 8 of the Crowdcast Q&A series. Very excited to be doing these. Before we get started, I just wanted to first of all thank everyone for submitting questions. I've read through all the questions and just as a reminder, I do look at the voting, and I look at, you know, the top-voted questions. But I also go through, just to be— not be, you know, repetitive. Sometimes some of the top-voted questions can be different permutations of questions I've answered in previous Crowdcasts. So I do go through them and pick out ones that may have not have gotten upvoted as much, but are also very interesting. And In addition, some questions require a deeper dive. So I'll give you an example.

This time I was looking into the effects of EMF and possible negative health consequences. And as I started to dive into the literature, I realized that I was gonna need much more time because there was a lot of nuance. So that question I bookmarked and I will get back to next Crowdcast. So things like that, sometimes I, you know, bigger questions that I don't have enough time to really give the attention and detail it requires, I do bookmark them and we'll get back to them at a later Crowdcast date. Additionally, I download all the questions. So if I didn't get to your question, I do go through previous questions and we'll pull out some questions that were not answered. With that said, I'm going to go ahead and get started with the first question.

Aaron asks, pros and cons to daily coffee drinking, specifically as it pertains to ApoE4 carriers, and is there anything specific to look at when choosing a brand of coffee? So this is sort of a big question. I'm going to— I'm going to— there's, there's been lots and lots of epidemiological studies looking at health, potential health benefits, or even risks of drinking coffee. So there's been, there's been quite a few studies looking at the effects of coffee drinking on Alzheimer's disease. And it's been shown that a higher lifetime coffee intake is likely to contribute to a lower Alzheimer's disease risk.

So one study looked at 282 normal cognitive— cognitively normal adults and 129 with mild cognitive impairment and found if they categorized these individuals into people that had no coffee or less than 2 cups a day, versus high coffee intake, which is considered greater than or equal to 2 cups a day, they found that the people that were lifetime coffee drinkers greater than or equal to 2 cups a day had a significant lower Alzheimer's disease risk. They had lower amyloid beta reactivity in their brains as well. And there's also been many different preclinical studies in animals showing that coffee consumption can protect against Alzheimer's disease.

Now, that study I mentioned did not specifically look at the differences between caffeinated and decaffeinated coffee, but I'll get to some of that in a minute. There was another study which I really liked because it was, instead of an epidemiological study, which can never really establish causation, there was a randomized controlled trial that showed consumption of dark roast coffee brew, about 500 mL a day for 1 month, caused a 23% reduction in DNA damage in white blood cells compared to baseline levels. Now, if you remember anything about DNA damage, I've talked quite a bit about it. DNA damage can lead to a variety of different negative health consequences. So if damage is not repaired properly, it can lead to a potentially carcinogenic mutation in DNA.

DNA damage can also, if it's not repaired properly, can lead to dysfunctional cells. So genes may not be working as good as they're supposed to because of a mutation. It's not necessarily gonna lead to cancer, but could just lead to dysfunction in a variety of different genes that acquired a mutation. If this happens in a stem cell, it can possibly lead to depletion of stem cell pools, which can contribute to aging. So the fact that it was able to lower DNA damage by 23% is really, impressive in my mind. And we know that coffee has a variety of polyphenols in it. And for example, there's, there's been other studies by Dr. Guido Kroemer that has shown some of the polyphenols in coffee are able to activate autophagy.

And autophagy is able to, to, to lower, you know, DNA damage burden as well. It can clear away, you know, pieces of damaged um, you know, chromosomes and stuff like that. So, um, it's possible that the polyphenols may be responsible for some of the, the lowering of the DNA damage there through a variety of different mechanisms. Um, coffee consumption's also been linked to a lower risk of certain cancers by up to 20%, and also type 2 diabetes and Parkinson's disease by 30%. So people that drink A lot of coffee have a 30% lower risk of Parkinson's disease. There are certain people that do not benefit from coffee consumption, and those are pregnant women. For example, pregnant women actually was found that it can increase the risk of miscarriage.

And again, many of these polyphenols in coffee, which are also present in decaffeinated coffee, also have anti-inflammatory and antioxidant activities. And autophagy, autophagic activity as well. So I would say that overall, there is a strong body of evidence, a lot of epidemiological studies suggesting that coffee drinking is beneficial for health. And I would say that the cons or the potential risks of coffee drinking can, can occur for people, particularly people that have a very slow caffeine metabolism. So there's a gene polymorphism in the cytochrome P450 1A2 gene.

And that has been associated— people with that specific single nucleotide polymorphism have been associated with a higher risk of heart attack and a higher risk of hypertension, but only people with that with that polymorphism. In addition, there was a really weird study that was published back in the early 2000s in the American Journal of Nutrition showing that people— it was a randomized controlled trial, and I'll tell you some of the problems with this in a minute. But what the randomized controlled trial showed was that drinking a large quantity, so about 6 cups a day of unfiltered coffee, for example, like a French press, was associated with much higher levels of homocysteine. In fact, the levels were increased by close to 10%.

And that was really surprising, particularly because of the polyphenols present in coffee and the anti-inflammatory activity and antioxidant activity, et cetera, right? The problem with that study was that the control group did not consist of either a filtered coffee or even a decaf coffee control. So the problem is, is that 6 cups of coffee a day is a lot of coffee. And caffeine has been shown to— so it has a molecular 3-dimensional structure that is similar to a vitamin B6 antagonist. And there— so it's thought that caffeine at very high doses can basically, um, you know, inhibit vitamin B6. And there has been another study showing that, um, too much— so again, it was a higher dose of coffee— was linked to lower levels of vitamin B6, of riboflavin and also for folate.

And all of those B vitamins are involved in the methylation pathway, specifically involved in the methylation of homocysteine to convert it back into methionine. So, kind of linking it back to that high-dose unfiltered coffee study, the question becomes, was it really the unfilteredness, the fact that the coffee was unfiltered, or was it the fact that there was so much caffeine that was basically inhibiting some of these B vitamins and therefore led to higher homocysteine levels because of the inability to methylate homocysteine. So, not a perfect trial and I haven't seen follow-ups with that as well. So, I'm kind of disappointed that there hasn't been any research kind of following that up.

But kind of In parallel with that, with the polyphenols and things like that, again, those are present also in decaf coffee. And kind of directly trying to— I've been asked about what types of coffee beans or maybe what coffee brands are the best. And to be honest, I don't know for sure. What I do know is I did find that I did look at a couple of studies and found there is a brand. So the coffee robusta beans as opposed to the Arabica beans, the robusta beans have a significantly higher— I would say it was 10% more polyphenols present. Unfortunately, they also have more caffeine per per coffee bean. So, um, it's a little bit of a stronger taste, uh, the, the coffee Robusta beans.

And, uh, the Cafe Lavazza, they have a variety of different— for me, I, I prefer— I like the, the, the taste of the, uh, Arabica, the Arabica, um, coffee beans. It's a little bit milder. But you can find, um, that coffee, this Cafe Lavazza, L-A-V-A-Z-Z-A, coffee has like a mixture of the coffee robusta and arabica. So you can sort of get the best of both worlds if you're like me and you kind of like the flavor more of the, more of the mild flavor, but you also want to get a higher polyphenol content. So I'm going to move on to the next question. And that is— it was a general question from— I think there were a couple of people, so I didn't put the names. But basically, they were asking whether or not I could summarize what the data says on food combining.

So basically combining fats and carbohydrates and proteins, et cetera. In terms of postprandial blood glucose levels, what I will say is that the answer—I'm going to go into the answer to this question—and the answer—I'm actually going to go more into what's called food order, meaning when you eat the different types of food seems to make a difference. In terms of food combining, I would say probably one of the most consistent lines of evidence for lowering postprandial blood glucose levels is the addition of fiber. So, you know, and that's, and that's something that's been shown even for people that have a higher blood glucose response to things like protein or lipids, which I, I myself do not.

Since I wear a continuous glucose monitor, I can measure my postprandial blood glucose response to a variety of different foods. And I do not get elevated blood glucose levels postprandially, meaning after I eat, from protein, eating protein, or even eating fat. But some people do. And that depends a lot on genetics and microbiome composition as well. So what I did find very interesting was food order. And there's there's a growing body of evidence that eating a carbohydrate-rich meal after eating protein and or vegetables with a fiber matrix lowers the postprandial blood glucose response. And this has really been looked at in the context of type two diabetes. So there was a the initial pilot study that was done was in people with type two diabetes, and Yeah.

They basically were eating— so their first meal, they were eating carbohydrates, but they would wait 15 minutes and then eat protein and vegetables after the carbohydrates. Or the next visit, they would do the opposite. So they would eat protein and carbohydrates, vegetables, and then they would wait 15 minutes and then eat the carbohydrates, which in this case was more of a refined carbohydrate like rice, something that's a higher glycemic Has a higher glycemic index, and it was found that basically eating the carbohydrates 15 minutes after eating the protein and vegetables led to a dramatically lower postprandial blood glucose response. So it was like almost 30% lower by 30 minutes.

By 60 minutes, it was almost 40% lower, and then towards the end of the curve, by 120 minutes, it was like. you know, 17% lower. So basically, the entire area under the curve was about 73% lower, which is quite significant. And so that was the first pilot study. And then there was a similar study done in people without type 2 diabetes. So this, again, the carbohydrates that were tested in terms of being able to lower the postprandial blood glucose response were more of the refined nature like rice and In this case, it was rice. And so they tested in normal healthy people giving them separate plates of rice, vegetables, and meat, and they were giving them different— 3 different orders.

And so the participants that had vegetables first and then waited 10 to 15 minutes and then had the carbohydrates or had the protein first and waited 10 to 15 minutes and then had the high glycemic index carbohydrate like rice. White rice. Again, the postprandial blood glucose response was much lower. And this is something that I have also noticed, and I'm going to talk a little bit about my own personal experience in a later question. But some of the mechanisms have to do with basically delaying gastric emptying and lowering glucose absorption.

So both of those things seem to be responsible for The lower postprandial blood glucose response, and there's there was another study showing again in type two diabetics that eating the protein and vegetables beforehand either or in fact seemed to to lower the blood glucose response. So I I find this to be a very very interesting data because it really suggests that. You can sort of hack your postprandial blood glucose response by simply eating protein and vegetables 10 to 15 minutes before eating something maybe with a higher glycemic index. For example, the higher glycemic index foods that I typically eat aren't very high, but I'll make a smoothie with kale and avocado and a lot of blueberries. And, and so, you know, that would be something, or maybe a bowl of oatmeal.

Fruit would be the highest, you know, glycemic index thing that I would, that I would actually be able to, to say that I eat. So more on that. I actually do want to do a deeper dive and sort of get some more information on that because I think it's just a really A really, really interesting topic. So I see that there was a question in the chat about DHA and brain function. If Austin could please submit that question for the next Crowdcast, that would be a great question to kind of dive into and answer. So the next question has to do with bioavailability. This was submitted by Sophie. The bioavailability of Meriva versus Novosol curcumin. Also, I am wondering about the dose of PQQ that is useful. Thanks so much. So, let me start off by just talking about the PQQ dose.

I mentioned this, I believe, last Crecast. The PQQ, there was a couple of randomized controlled trials showing that it can improve cognitive function. It can also improve mitochondrial function. This was in humans. The dose in both of those clinical studies was 20 milligrams per day. So on to the curcumin bioavailability question. So curcumin is a hydrophobic molecule. It has low systemic bioavailability due to very poor solubility in aqueous fluid or even digestive fluids. It's rapidly processed by the liver by some of the cytochrome P450 enzymes, and it's excreted in urine. So blood concentration Blood concentrations of curcumin are typically low and the tissue distribution is pretty limited following the oral dosing of curcumin.

So there's been a variety of studies investigating various strategies to improve bioavailability of curcumin. And as I mentioned, it's hydrophobic, meaning that it's more soluble in fats, So there's been, of course, a bunch of studies on that. One another study that's been looked at is inhibiting the the metabolism of curcumin by these cytochrome P450 enzymes in the liver to slow it down, therefore you know elevating the blood levels of curcumin for a a longer duration. And most of you are probably familiar with some of that research involving a compound found in black pepper called piperine. And there's, you know, there's studies showing that it can increase the bioavailability up to, you know, 20-fold.

There's also a novel liquid and an oral delivery system such as like a crystalline curcumin in a microionized form that can increase the bioavailability Quite significantly by 28-fold. NovaSol, which is what Sophie asked about, is incorporated into what's called a biomimetic micelle. And what that is, is it's a liquid micelle that has about 93% tween, which is like a detergent, and 7% curcumin powder. This study, which was, I think, it was funded by the makers of NovaSol, but oftentimes that's what you're going to find with studies like this. It compared different formulations of curcumin and found that the NovaSol was just unbelievably better than normal curcumin. It was 277 or 114 or 185-fold depending on the dose. More bioavailable than normal curcumin.

This was in women and men, um, and, um, but it was only compared to normal curcumin, just regular curcumin. Meriva, which is what's called a phytosome, it's, it's curcumin, soy lecithin, a microcrystalline cellulose, um, and then it's about 18 to 20% curcuminoids. Uh, the phytosome has a patented phospholipid based delivery system that is supposed to disperse these chemicals into phospholipids like phosphatidylcholine. So there's been a few randomized controlled trials looking at the effects of Meriva, but in terms of looking at bioavailability, double-blinded crossover study, meaning each participant had either the treated or the control compound.

So the, the study was measuring plasma concentrations of 3 different curcuminoids, curcumin and then demethoxycurcumin and also another type of curcumin after 2 dosages of either Meriva or the regular unformulated curcumin. And overall, the absorption was about 20— 29-fold higher with the Meriva phytosome you know, formulation. So the thing to note, there's, there's a study, and I will link this in the, the, on SuperCast on the, on the timeline and summary that we post on the personal feed, which you can find on the FoundMyFitness dashboard. That would be foundmyfitness.com/dashboard. When you log in, you'll find you'll find the study, the link to the study there.

The study there was a study that compared many different randomized controlled trials and looked at the bioavailability of the different formulations. And there's a nice graph in the study that shows that the NovaSol is one of the highest curcumin formulations in terms of bioavailability. It's a little bit better than. Than Meriva. However, these were not head-to-head comparisons. These are based on completely separate studies where Novosol was compared to regular curcumin or Meriva was compared to regular curcumin. So the dosing could have been different. There could have been a million different differences in the study design. So I would take that with a grain of salt.

Looking at the figure itself, it seems like they're pretty comparable, honestly, particularly if you consider there could be difference in the study design and doses and stuff. So I wouldn't make a strong statement that Novasol is significantly better in terms of bioavailability compared to Mareva. I think they're both pretty good options. Personally, I don't necessarily wanna have Tween. I don't, I'm not like, I've worked with Tween before. It's something I would use to lyse cells and stuff, but So, you know, it may be fine, but, but personally, I like the, the lecithin in, in my formulation. So I like the Meriva. So Mark is asking in the chat, does curcumin suppress the positive effect of working out such as NSAIDs or metformin?

Which is a great lead into a question that has to do with antioxidants and other compounds, particularly potentially negating the effect of exercise. So I will say, just as a preliminary background for those of you not familiar, there have been some studies looking at either aerobic exercise or even strength training types of exercise And taking high-dose supplemental antioxidants like vitamins C and E along with, you know, during the training regimen. And although it's not necessarily consistent, so for example, with vitamin C, you'll find some studies show that there's no effect on any endpoints for looking at benefits of exercise on a variety of different health parameters.

But you can find some studies showing that a really high dose, particularly the vitamin C when it was in combination with vitamin E and a high dose of vitamin E, you know, we're talking well above, you know, what the RDA. So the RDA for vitamin E is around 25 IUs a day. And we're talking this was like 400 IUs a day. So it's much, much higher than levels you're supposed to be getting from foods. Uh-huh. For example, um, it can blunt some of the positive effects of, of exercise, and that largely has to do with the fact that exercise itself creates a burst of oxidative stress. You know, your mitochondria are working really hard. Mitochondria are one of the primary sources of free radicals, free oxygen radicals, um, superoxide. Yeah.

And the other thing that's happening is, you know, immune inflammation can be generated because immune cells get activated as well from the stress that's caused from exercise. And these immune cells can increase, you know, the production of pro-inflammatory cytokines and they can also increase the production of other things as well that are inflammatory. But as a response, the body activates a variety of genes often referred to as stress response genes. These are genes that have high anti-inflammatory activity. They have high antioxidant activity. It activates genes that are involved in repairing damage, DNA damage. It activates autophagy genes. It activates all these sorts of genes that are also involved in longevity.

And that's because, you know, the stress of the exercise, it happens in this short burst. And the damage isn't— it's, you know, the stress that's induced is not— it's lower than what the response is. So the activation of all these amazing stress response genes not only counters that damage that's potentially, you know, created, but it continues on for a time, a while after that. So you're having, you know, better repair activity, better antioxidant activity, better anti-inflammatory activity, things like that. If you sequester those, you know, that reactive oxidative burst through things like a very high dose of vitamin E, then you will not activate a lot of those stress response genes. And so some, not all, but some of the benefits from exercise may be negated.

For example, one of them that's been shown is insulin sensitivity. But again, not all studies are consistent with that. Other compounds have been shown to do something similar. Metformin is one. I talked about that in a recent interview with Kevin Rose, and I believe I also talked about it on the last Crowdcast. As well as resveratrol. And again, there's some conflicting data with the resveratrol showing both enhancement as well as blunting some of the benefits. And that may have to do with the dose of resveratrol used. But when it comes to polyphenols, things like EGCG, things that are found in dark chocolate or green tea or or curcumin, these phytochemicals, these are things that also they exhibit what's called xenohormesis.

So very similar to what exercise is doing, exercise is also considered a hormetic stressor because it is a stress that elicits a very strong stress response, activation of stress response genes. Well, certain compounds in plants are able to do that as well. And in fact, they activate many of the same pathways that exercise itself activates. So I haven't seen in the literature polyphenols blunting the effect of exercise. Same goes for curcumin. So, so the question about the NSAIDs and the curcumin. So NSAIDs are, you know, anti-inflammatory drugs that specifically inhibit an enzyme called COX-2.

And COX-2 enzyme is responsible for, among other things, producing leukotrienes and other inflammatory signaling molecules, prostaglandins, that are important for activating that stress response pathway that's involved in exercise. So, if you blunt that, then you're basically— the exercise benefits some of those aren't going to be as powerful or as robust. Curcumin does not act the same way that NSAIDs act. I mean, it's not— I've seen data that it, you know, at worst is a super, super mild inhibitor of COX-2, if at all. In fact, it's not really a COX— it doesn't really inhibit COX-2. You know, it's activating anti-inflammatory pathways. Again, very different than— it inhibits inflammation in a very different way.

Instead of blunting the inflammatory signals, it's activating genes, anti-inflammatory genes. So, again, I'm not as concerned with curcumin or even polyphenols. In fact, there's been a variety of studies looking at polyphenols with respect to exercise. Okay. And I haven't seen that it's blunting the effects. So the next question has to do with lipid biology and particularly how it's related to cardiovascular health. And this question was asked in a number of ways by a couple of people. And the question was, what is the best dietary strategy for lowering LDL particle number? So a good— what's typically used to indicate LDL particle number is ApoB. And ApoB, elevated ApoB is associated with a risk for coronary heart disease.

There's been a variety, and this is a very nuanced question because it gets down again to genetics and phenotypes and stuff, which we'll talk about. So it's not a sort of one-size-fits-all answer, but there have been a series of clinical trials, randomized clinical trials showing that reducing saturated fat intake can lower ApoB, and the opposite, increasing saturated fat intake can increase ApoB. But that's not always the case. So individuals that have an abundance of small dense LDL particles, small dense LDL particles, so LDL comes in a variety of shapes and sizes and the large buoyant LDL particles are in more recent years have been found to not necessarily be associated with heart disease, are not necessarily a high-risk factor for heart disease, although they can be in some people.

LDL particles get modified and when they become small and dense, Those LDL particles are linked to a higher risk for a variety of different cardiovascular diseases, and part of the reason for that is because the in fact the ApoB the ApoB protein gets obscured on these small dense LDL particles, and that sort of prevents them from being recycled and being. trying to, you know, getting out of the circulation, and so they end up being in circulation longer, and a variety of different inflammatory modifications happen to small dense LDL particles.

With that said, there are individuals that tend to have a higher quantity of small dense LDL particles, and these people are categorized in this— in the scientific literature as being LDL phenotype B, whereas individuals that tend to have larger, more buoyant LDL particles and less of the small dense ones, those individuals are often characterized as being or having an LDL phenotype A. So phenotype B is the more risky one because they have the small dense LDL particles, whereas phenotype A tends to have the larger buoyant ones, which if anything actually Can be beneficial in some in some instances.

So the the expression of the LDL phenotype A or B actually is influenced by a variety of factors, one of them being genetics, but also your macronutrient intake and body weight, particularly BMI. So high carbohydrate intake can promote the production of what are called very large LDL particles, VLDL. And actually in people that are phenotype B, that can give rise to small dense LDL particles. So people with the phenotype B actually taking in and particularly taking in more of a refined type of carbohydrate in, um, as opposed to vegetables, for example, um, can, can actually lead to a, a higher conversion of the VLDL into small dense LDL. Um, so, so that's, again, it's very nuanced, um, in terms of, you know, how people respond to different dietary changes.

And, um, one of the best ways to To see what— how you're responding yourself would be to quantify, you know, and measure things. And you can do that. You can get an LDL particle test. You can ask your physician for one. There's a variety of services that, you know, you can do without a physician's prescription to get it, you know, or you can use companies, WellnessFX, for example, or Life Extension also has a variety of blood tests that you can do. I've used both of those services before and like them both. So I would say sort of as a continuance to that question, you know, again, generally speaking, lowering saturated fat intake lowers for most people the particle number, but it doesn't necessarily lower the small dense LDL.

And in fact, you know, sometimes There's been some studies showing, randomized controlled trials showing that increasing saturated fat and lowering carbohydrate intake can— it does increase the large buoyant LDL number, but it decreases the small dense LDL in some people. So again, you know, it really just depends on the phenotype that you are, whether or not you're predisposed to the small dense LDL particles. Avocados interestingly have been shown, and there was a randomized crossover study done recently in people that were overweight or obese, that it seemed to lower cholesterol.

And I don't know exactly what the mechanism is, but, you know, that was another, you know, possible avenue for— I think, you know, avocados are great and possibly even replacing If you're using coconut oil, replacing it with avocado oil, which, which is high in monounsaturated fat. It's not high in polyunsaturated fat. You generally don't want to use oils that are high in polyunsaturated fat to cook with because polyunsaturated fat is really easily oxidized. And vegetable oils, unfortunately, are very high in polyunsaturated fat. Things like canola oil, corn oil, soybean oil— those are, those are high in polyunsaturated fat.

I would avoid those for cooking, and there's been a variety of studies coming out over the years showing that indeed they do lead to oxidized lipids and things like that, and you don't want to consume oxidized lipids. Avocado oil is low in polyunsaturated fat. Monounsaturated fat is not prone to oxidation. So olive oil is not high in polyunsaturated fat. It's high in monounsaturated fat as well. So that would be, you know, I can tell you. So I have one ApoE4 allele, and which doesn't necessarily predispose me to small dense LDL, but it does predispose me to a, you know, overall more LDL cholesterol. Uh-huh. Due to, you know, the recycling— there's a defect in the recycling. So at any certain point, I could have more LDL circulating in my system.

Years and years ago, I used to use coconut oil to cook. And after cutting out the coconut oil and shifting mostly to avocado oil and sometimes olive oil, high polyphenol olive oil, I dramatically dropped my LDL, my total LDL levels. And that was— this was years ago before I started measuring the small dense particle size. So on that note, there was another study that was done. It was a 24-week dietary intervention study that showed E4 carriers, ApoE4 carriers, had greater reductions in APOB and plasma cholesterol compared to E3E3 individuals after replacing saturated fat with either low glycemic carbohydrates like vegetables, high fiber foods, or even with a monounsaturated fat. Okay. So, Marianne is asking a question in the chat. It's a little off topic.

She's asking, do any of you take melatonin every night as Rhonda? I'm in the UK where you can't buy it, but I'm from the Netherlands originally where you can buy 2 to 3 to 5 mgs. Rhonda takes 300 micrograms I think at night. So let me update you guys. I am now taking 3 to 6 milligrams a night. And my, my case is a little special because I am prone to night terrors. And there's— I've done a lot of reading on this, and stress plays a big role in it. So the lower my stress level, my night terrors really seem— it seemed to wax and wane according to my stress. So when stress is high, my night terrors can kind of resurface and vice versa. But I've noticed that at doses 3 milligrams or higher, it really helps prevent the night terrors.

And additionally, once you reach 40, melatonin levels produced in the pineal gland do start to decrease and they sort of continue decreasing with age. So now that I'm 41, I'm I'm taking my melatonin. I didn't know you couldn't buy melatonin in the UK. That's a surprise to me. Scott Reed is asking if I can post a link to the study with ApoE4 carriers and saturated fat. And yes, I will post in the Supercast feed. Make sure you have downloaded that Supercast from your FoundMyFitness dashboard, and it will— it has links. It'll have links to the timeline and studies. So that'll be very useful. And Kevin here, who is Kevin Patrick, who's a part of my, my Super Found My Fitness group, I have once a month, I do a couple-hour hangout on the first Sunday of every month.

And it's sort of a very intimate group of people. And, you know, they submit questions and we sort of have long discussions about things like that. If you're interested in looking into that, you can find out more on the FoundMyFitness subscribe page. But he's linking to Del Bredesen's study on Alzheimer's disease. And we're actually going to talk a little bit about Alzheimer's because there was a question about that, about ketones specifically. So we will get to that soon. Before I get to the next question, just one more question that I'm going to answer in the chat right now is from Callum. And he's asking, did you personally or did you decide to personally take resveratrol after your recent meta-analysis? If so, what dosages and do you take it on days? That you exercise.

I still, I still haven't started taking it yet. I am, I am heavily leaning towards taking it. And I'm leaning towards not taking it on days that I exercise. But again, I do think dose may be important in that. And I did start giving it to my mother, who is not physically active, and I'm trying to work on that. But, um, but I, but I, but I actually recently started sneaking in her, in her morning yogurt. We will talk about vitamin K2, uh, Richard is asking in the chat, but I'm going to move on to the next question on my list here, which was from Amy. And Amy asks if there are restrictions for women and fasting. I've heard a lot of podcasts Benefits for fasting, but I haven't heard many directed for women. I.e., is the frequency? Is it different? Does it affect women's hormones, their cycle?

Should it be done at a certain part of the cycle or anything else to be aware of? So just as a sort of opener and background, that fasting is not recommended for women that have a history of an eating disorder. It's not recommended for women that are pregnant or thinking of becoming pregnant or breastfeeding. It's also not recommended for women that are extremely lean or underweight. So any of those, you know, any of those criteria would definitely disqualify a woman from— or should disqualify a woman from fasting. I'll start off with— and this is something that can be traced back even to the caloric restriction literature, and it was something that I was very interested in Yeah.

You know, I started reading about it probably when I was in graduate school because, you know, I sort of knew that I was not going to have children immediately and that probably I was going to be having children later in life. And so, I was sort of interested in methods for delaying, you know, the aging of my eggs, delaying, you know, menopause and extending the lifespan of my eggs and, you know, ovaries and things like that. And something that is very consistent in the animal literature is that caloric restriction and even alternate-day fasting, different forms of intermittent fasting, basically can— it can lead to amenorrhea. So menstrual cycles can cease. And ovaries can shrink.

And what's interesting is that when you return to normal feeding, so in the case of either caloric restriction or you stop doing the alternate-day fasting, what happens is— and probably the most interesting literature on this was done with caloric restriction because it was done for a very, very long time, like over the lifespan, close to the lifespan. What was found was that it completely delayed the estrous cycle. So while there was, you know, amenorrhea occurred and, you know, the menstrual cycle sort of halted, it picked right back up when the caloric restriction, you know, fasting kind of was cut out. And so, and it lasted much longer in the female rodents. That were supposed to undergo sort of, you know, a menopause-like thing, and that didn't happen until much later.

And I thought that was always— I always thought that was very interesting for women that, you know, I'm certainly not saying that women should, you know, become amenorrhoeic. I mean, that could even be potentially dangerous. But it is kind of interesting to know about that literature in terms of delaying ovarian aging in a sense. And that is something that also can be induced by very, very intense and heavy exercise so that I actually, again, actually this was when I was in college, when I was an undergrad, I would run just, you know, 8 to 10 miles a day. And I totally became amenorrheic when I was doing that, like my menstrual cycle just stopped. So, you know, and that's— exercise is another form of energy stress, much like caloric restriction and fasting.

So let's talk about human studies. There are a few human studies that have looked at, you know, the effects of fasting in different genders, male and female. There's only two. So there was one study that was a little—I think that was a little more concerning—the study that was done in both men and women, and they was—they were doing alternative day fasting. So they would fast one day and then eat the next day and fast. Next day and eat the next day. And there was a differential effect on glucose tolerance and the response to glucose after a meal in men versus women. So women that were doing this alternate-day fasting seemed to experience a slightly impaired glucose response to a meal that was not found in men. The men in fact had an improved response.

The women, it's not really known what caused that. Insulin was the same. So insulin was unchanged. So it wasn't, you know, due to insulin. It may have something to do with the way glucose was cleared. Maybe, you know, so it's not, it wasn't really known, but that was something that sort of jumped out. There was a lot of, you know, there were other benefits that were found, you know, in terms of, you know, women had activation of You know, great, you know, SIRT1 genes, things like you know longevity genes, and they had a variety of other benefits that happened. But it was just that one impaired glucose response after a meal. So postprandial glucose levels were a bit impaired. That was that was the main thing that I found concerning.

Going back in the literature, far back in the literature, sometimes you have to go go back to the 60s or 70s, you know, to find. Interesting data because some of this stuff just isn't looked at anymore. There was a few— there was a couple of studies that looked at the effects of sex hormones on fasting. And it was interesting. So what was found, and this was done actually in both postmenopausal and premenopausal women that were throughout this trial, they were given exogenous sex hormones. So they were given, for example, oral contraceptives that had estrogen, progesterone. And it was found during a prolonged fast. So this was, you know, longer than, than 48 hours.

It was found that at the 36-hour mark of the prolonged fast, the sex hormones, both estrogen and progesterone, really kicked in and kicked up ketogenesis. And Ketone levels were, and you know, beta hydroxybutyrate levels were much, much higher in after after the the estrogen and progesterone were administered. It's not really known you know why. It's thought that possibly the the estrogen and progesterone may increase the the fatty acids being transported into mitochondria, and you know basically sort of. Increasing the, the production of ketone bodies. So it kind of is interesting because, um, you know, it, it helps if you can make these ketone bodies.

It helps in terms of providing another source of energy, um, for cells that have mitochondria, which are most of your cells with the exception of red blood cells. Um, so that's pretty much all I have, um, on, on The women in fasting. So I'm going to go ahead and move on to the next question, which is what someone had asked about in the chat, which has to do with vitamin K2 supplementation. So the question was, does vitamin K2 supplementation have any positive effect on calcific aortic valve stenosis in people with a higher Lp count or in general? Any thoughts on Lp reduction or mitigation? So, I will start off by saying that obviously is a very specific question. There's no empirical data yet to specifically address that question.

However, there is an ongoing randomized double-blinded placebo-controlled trial that is investigating the effect of menaquinone, actually MK-7, which is one of the forms of vitamin K2 supplementation on the progression of aortic valve calcification. And basically the way the study is designed is people are getting 720 micrograms a day and they're also getting 25 micrograms a day of vitamin D for 2 years. The results are expected to be published— well, actually the results are expected to be completed in 2021. When they'll be published is a different question. But sort of a background here, vitamin K2, there's 2 forms of vitamin K. There's vitamin K1 and then there's vitamin K2 and there's different actually subforms of each of these.

The vitamin K1 is a very important cofactor for activating genes in the liver that are actually activating proteins that are involved in blood clotting and coagulation. And if you look at vitamin K2— sorry, vitamin K1, which is phylloquinone, if you look at its tissue distribution, what you'll find is that after intake of vitamin K1, which is really robustly found in dark leafy greens, It's really, really high in green leafy plants. Vitamin K1 preferentially goes to the liver, which is where these proteins that are involved in coagulation are. And so, it makes sense that since vitamin K1 is so important for blood clotting, that would go to the liver preferentially.

Whereas, the menaquinone, the vitamin K2, seems to preferentially stay in— it stays in circulation and can be transported to things like bone and muscle. And the reason for that is because that form of vitamin K plays a really important role in activating proteins involved in removing calcium from the bloodstream and bringing it to tissues that need it like the bone, like muscle, proteins like matrix Gla, for example. So that, you know, there are differential effects of these different forms of vitamin K. However, there's also been studies showing that once— and there was a human study showing that one, you know, once the vitamin K1 level is saturated in terms of activating coagulation proteins, vitamin K1 stays around in the circulation longer and can perform the same function as vitamin K2.

So with that said, going back to the question which has to do with this aortic valve calcification, the reason this is being looked at is because aortic valve calcification It's a condition where calcium can deposit on the aortic valve in the heart. The other quick thing I wanna briefly mention is that calcium can precipitate very, very quickly and easily precipitate, particularly when it's in the presence of phosphorus. So if it's not being moved to cells and tissues and distributed like it's supposed to be, The concern is that it could form a precipitate, right, and a plaque, which ultimately could potentially form a plaque. Currently, there's no treatment for this aortic valve calcification aside from surgery.

And what researchers have noticed is that patients that are taking vitamin K antagonists, so for example, warfarin, you know, things that are involved in like blood thinners, these patients have a worse vascular calcification than people that are not taking those vitamin K antagonists. So it's thought potentially that maybe vitamin K2 could slow the calcification process. Now that is something if a person is taking a vitamin K1 antagonist, um, like warfarin, I would— or, you know, Coumadin— I, I would act, you know, don't start taking vitamin K2. Like, you should definitely talk to your doctor because you don't want to inhibit— you don't want to, um, have any sort of contraindication with your, with your medication.

But there is an ongoing trial that will be investigating that, and, and that we have to wait for the results. Um, there's another study that's, uh, referred to as the Rotterdam study where researchers looked at the dietary intake of phylloquinone, which is vitamin K1, and menaquinone, which is vitamin K2, and the incidence of coronary heart disease on— and also on all-cause mortality and aortic calcification. And it was found that the relative risk of coronary heart disease mortality was reduced in the mid and also the upper tertiles, so, you know, the people that had the highest and close to the highest dietary intake of menaquinone, which vitamin K2 is really high in fermented soybeans. This is referred to as natto in Japan. So that's probably the highest source of vitamin K2.

And to a lesser degree, you can find it in some fermented cheeses as well. So I would say that, you know, generally speaking, I think there's a lot of promise for vitamin K2 being a potential treatment for, or even prevention for vascular calcification, particularly in high-risk people with, you know, that are high-risk for calcification. It seems to be something that I think that has a lot of potential. And I do take vitamin K2. I tend to take, um, 50 micrograms of— I think it's MK-4 I take, and I take that a couple times a week. So Justin Edwards was asking, in the chat about a website for information on supplement quality, like fish oil quality. So, so one of the, one of the websites would be, as Mark has mentioned here in the chat, labdoor.com.

They, they do third-party testing on a variety of supplements. And that is called the International Fish Oil Standards, IFSO. If you just Google IFSO fish oil, you'll find the International Fish Oil Standards website pull up. And that you can enter in any brand of your choice or even use a batch number or things like that and pull up some information if that company is compliant with the International Fish Oil Standards site. And I'm gonna move on. Oh, one thing I didn't mention that was part of this question was the LPA. And they were asking about reducing the LPA. It's kind of somewhat refractory to a lot of lifestyle, unfortunately, and drug interventions. I'm not going to really get into the drug interventions. That's something that you can discuss with your physician.

I will say there was one study that showed a minor but still statistically significant reduction in Lp So this was L-carnitine, 2 grams a day, significantly reduced Lp numbers. So for example, baseline was— it reduced it. So it started from -7.7% to -11.7% compared to placebo treatment. There's also a study looking at the interaction between certain genes, people that have certain polymorphisms, and aspirin. Not everyone benefits from aspirin in terms of reducing Lp, but there is a SNP which is the rs3798220 that was shown to have a, again, a minor effect, but still significant in reducing Lp levels with aspirin. All right, let's move on to the next question from Janice. And Janice is an ApoE4 carrier. She has one allele, and she's got chronic borderline high total and LDL cholesterol.

which we already talked about, and also borderline high LDL particle number, which we also talked about. And she's got no other cardiovascular risk factors, and she's asking about studies. They seem to be sort of mixed on— in terms of raising LDL and what the effects of lowering LDL, raising LDL are on the brain, and if there's any— if you don't have any concerns with cardiovascular disease, Is it important to take a statin for brain health? And of course, I'm not, you know, able to give any medical advice here, but I am going to talk about some literature that is something that I think is— it's not been talked about much, and it's an important topic that is near and dear to my heart, and for personal reasons.

And it has to do with the literature connecting serum cholesterol level, statin use, and Parkinson's disease risk. So it's been shown that actually higher serum total cholesterol is associated with a reduced Parkinson's disease risk in a dose-dependent manner. Actually, that's been shown. So the higher the total cholesterol, the lower the Parkinson's disease risk. And this association still remains significant after adjusting for multiple different potential confounding factors. Again, it's a prospective study. As I always like to say, you can't establish causation. But in line with that, another study showed that higher serum cholesterol, total cholesterol again, is protective against Parkinson's disease.

This was a case-controlled study with 140 sorry, 124 Parkinson's disease patients that showed lower serum LDL cholesterol is associated with an increased risk for Parkinson's disease. It's not as clear-cut as it seems. So low cholesterol and Parkinson's disease is not clear-cut. So while low LDL cholesterol levels were associated with an increased Parkinson's disease risk. Genetic variants that lower LDL cholesterol are not associated with a higher Parkinson's disease risk, which sort of led some researchers to look at drugs that lower cholesterol because some of these people were actually taking statins.

And it could be that it's not necessarily because statins lower cholesterol, um, you know, that could be the potential link between the increased risk of Parkinson's disease, uh, and, you know, vice versa. You know, people that have higher total cholesterol often aren't, aren't taking statins, and so, um, that may be the protective factor, so they're not taking the statins. So, um, Statin use, particularly the lipophilic form or versions, I should say plural, is— and the lipophilic statins include things like Ator or atorvastatin, lovastatin, and simvastatin. Those are all the lipophilic ones which have a higher probability of crossing the blood-brain barrier. they're associated with an increased risk for Parkinson's disease.

And this is also in line with FDA databases that have found neurological disease is reported more often for lipophilic statins than for the hydrophobic statins. What about statins? So there's a couple of studies that have looked at the statin use and increased risk for Parkinson's disease. And the thing about statins is that they, in addition to inhibiting the LDL cholesterol, one of the enzymes involved in the production of cholesterol, HMG-CoA. They also directly— this is not just a side effect, there's a direct effect on blocking the production of what's called mevalonate, and that is a precursor for coenzyme Q10, which is a fat-soluble substance found in the mitochondria that is essential for the production of energy in the form of ATP.

And CoQ10 also protects against oxidative stress in the mitochondria as well, and it helps recycle antioxidants. But what's really interesting is that mitochondrial dysfunction is a hallmark of Parkinson's disease. In fact, There are genetic links to the Parkin pathway, which is involved in what's called mitophagy, which is a lot— many of you are familiar with autophagy, being able to recycle damaged— a lot of damaged components inside cells, including organelles, which mitochondria is. Well, there's this specific type of autophagy that, you know, specifically refers to the recycling of mitochondria and damaged mitochondria, and it's called mitophagy.

And mitophagy is important for getting rid of dysfunctional mitochondria and to eliminate them from the pool of mitochondria so that you're basically, you know, getting rid of things that could be potentially more damaging. that is linked to a higher risk for actually Parkinson's disease, and you can even cause Parkinson's disease in animals by inhibiting that pathway. So I would like to do some more research and talking to experts on this because I think it's certainly something I haven't heard anyone talking about. There's been a couple of very small placebo-controlled trials showing that CoQ10 administration can improve, you know, some Parkinson's disease symptoms, but this evidence is very preliminary. Animal studies have shown the same thing. So I hope that that answered the question.

Now, there are, again, there are some mixed There's some mixed literature on some of these statins and neurological diseases. In fact, with the Parkinson's disease risk, at first it was thought that statins may be protective, and then, and then it was later found that actually they, they seem to increase the risk. So I'm gonna move on to the next question. Caleb asks, how can someone who is pregnant or looking to become pregnant ensure they are obtaining enough omega-3 for proper brain development or nervous system development if they have a seafood allergy and cannot eat fish? Are there supplements or interventions that are likely to be safe to increase omega-3 EPA and DHA.

So there have been some studies that have looked at, for example, increasing the EPA and DHA content from non-marine sources, or for people that cannot eat marine sources of omega-3, and also for people that don't convert alpha-linolenic acid very well. So alpha-linolenic acid is the plant, um, or the non-marine form of omega-3 that can be converted into EPA and DHA, but the conversion depends on gene and on a certain enzyme that's produced by a gene. And there are different single nucleotide polymorphisms in that gene that completely change the efficiency of that conversion. Some people do it well, some people do it terribly. Estrogen, interestingly, dramatically increases the efficiency, which makes sense because during pregnancy, estrogen levels just skyrocket.

So, it seems like it's nature's way of making sure that DHA is formed because ALA, the conversion of ALA efficiency dramatically skyrockets in the presence of estrogen. With that said, there have been some open-label studies, which typically they're randomized pilot studies that show that algae oil supplements— so algae is another source that wouldn't necessarily be, I don't think at least, something that someone with a seafood allergy should be Necessarily allergic to, but algae oil has been shown to increase DHA in in both fish and non-fish eaters. And you know, so I would I if it were me, I would certainly try out the the algae oil. The there was another question. And I'll just answer the question now. And it had to do with the best source of algae oil.

And if you look at the Labdoor site, for example, the Nordic Naturals algae oil ranks as number 2 in terms of the concentration of EPA and DHA, and as well as the quality of not having contaminants and the lipid peroxidation is really good. That is not true for all Nordic Naturals supplements. So if you look at their fish oil supplement, by contrast, it actually is not one of the best in terms of their— it seems to have a much higher oxidation level. So I personally do not use Nordic Naturals for fish oil, but it seems as though their algae oil is pretty good, at least according to that third-party data. I think the other thing to do for people that have fish allergies or even people that are vegetarians, you want to increase your omega-3 intake.

And again, that if you're getting just plant sources like flaxseed or walnuts, which are pretty high in alpha-linolenic acid, You're sort of beholden to your genes in that sense with how well they're converting to EPA and DHA. But you can take— take algae oil supplements. And the other thing to do would be to decrease your— your source of omega-6, particularly omega-6 that are found in vegetable oils. Omega-6 is important. I mean, you do wanna— you know, you— omega-6 is also found in nuts and seeds, and it's a— it's an extremely important component of all cell membranes like arachidonate. arachidonic acid, while it can be a precursor for, um, pro-inflammatory molecules, um, it also is a very important component in cell membrane structure, and this is of all cells including neurons.

Um, much like DHA, which is also an important component of the cell membrane structure, um, the ratio of DHA to, uh, arachidonic acid is important, um, in, in terms of Yeah. You know, if you're not getting enough, it's also— it can change the fluidity of a cell membrane, and that can in turn affect the way things are transported into the cell, like minerals, for example. It can affect the way receptors are embedded in that cell membrane, so it can affect the structure and the function of a receptor, which then could have, you know, depending on what is what ligand is binding to that receptor could have a variety of effects, whether that's a neurotransmitter like dopamine or, um, a growth hormone or insulin, you know, things like that.

So, so, um, you know, I, I don't want to downplay the importance of getting omega-6 from your diet, but I do want to emphasize the importance of cutting out, uh, the sources of omega-6 that can be detrimental. And those sources typically are— polyunsaturated fats like vegetable oil, which are high in omega-6, that are, that are cooked at a high temperature and essentially end up oxidizing quite easily. And so you're ingesting, you know, oxidized lipids. So that would be something to, to cut down on— sunflower oils, corn oils, Vegetable oil, canola oil, all of those things. Just limiting limiting the intake of that and and getting your your omega six from healthy food sources like walnuts and you know seeds and things like that and other types of nuts as well.

So Janet Cole is saying that N-Pure 3, which is the fish oil that I take from Norway, is out of stock. So other options for fish oil would be useful. That Labdoor site, Labdoor, they list a variety of fish oil supplements that are high quality in terms of high EPA, high DHA, low mercury, low PCBs and other contaminants, and also low oxidation levels. So I would check their site out for that information. And there will be another question on the phospholipids we'll get to. Let's see, how am I doing on time? All right. So, I did mostly answer this question. It had to do with the exercise. And this question was submitted by Callum. And he says, you've stated that compounds such as metformin, resveratrol, and vitamin E counteract exercise-induced hormesis or benefits.

Would this also be true for other stressors like the sauna, fasting, broccoli sprouts, other food supplements, polyphenols, flavonoids, things like that? I did talk about the polyphenols and flavonoids and curcumin, but I didn't mention the sauna, broccoli sprouts, and things like that. So I would say that, again, these are— the sauna is another type of— it's a heat stress. It's doing a very similar thing. In fact, many of the physiological mechanisms that are activated with exercise are also with heat stress because exercise elevates core body temperature. So a lot of these same mechanisms kick into play.

There's been studies showing that in fact sauna, you know, not only mimics cardio— moderate cardiovascular exercise in terms of, you know, elevated heart rate, you know, during the activity, lowering the blood pressure afterwards, but also in terms of improving cardiorespiratory fitness. And, um, sauna alone improves cardiorespiratory fitness. Exercise alone improves it even better. Sauna plus exercise improves it even more than either alone, meaning there's a, um, a synergy between the two. So it's even more than, than, than either of the others. So, uh, alone, um, you know, there's other animals, and that was a human study.

And other animal studies have been showing things like BDNF, brain-derived neurotrophic factor, can be also is released even more from the combination of exercise and heat stress. Fasting obviously is another type of hormesis and you have to really just listen to your body. I like to do my exercise fasted. In fact, doing exercise fasted has been shown to lead to better adaptations in terms of mitochondrial ability to oxidize fatty acids And, and, and to do that even, even when you're not exercising. So, so I prefer to do my exercise fasted or with a low glycemic index meal, which also has been shown to, to be more beneficial than, than doing a higher glycemic index meal in terms of some of these adaptations that occur. Broccoli sprouts are very similar in terms of they activate NRF2.

Exercise activates that pathway again. So these what these things are doing are very similar as opposed to a supplemental antioxidant, which is not activating those pathways. It's sequestering the production of reactive oxygen species and even sometimes anti-inflammatory compounds. Excuse me. So I'm going to move on to the next question, which is from Marilyn. And Marilyn asks, I would love to know how you utilize the data you receive from your continuous glucose monitor, which is a Dexcom G6. She says, like you, I don't have type 2 diabetes. But I find the data very helpful. Any benchmarks that you strive for? And in addition to that, there was a very similar question. I think I'm going to combine the answer to these questions.

Chris asked, Do all the negative effects of refined sugar show up through high glucose, high glucose levels as reported by your CGM? If exercising after eating refined sugar or carbs in general is able to keep these levels low, would that be protective against all or most of the negative effects? So I'm kind of going to just talk for a bit about— excuse me. My continuous glucose monitor and what I've sort of learned and benchmarks and things like that. So typically I strive to have my postprandial blood glucose levels below 120, and that's even at 120 being the peak at the highest point. And preferably, I would— I love my— the best is having my fasting blood glucose levels in, you know, the 80s. So there are a lot of things that seem to affect this for me.

I'll tell you that, as I mentioned earlier, what I have found for myself, eating protein or eating like nuts, for example, which are high in fat, Do not lead to significant spikes in my postprandial blood glucose levels. Leafy greens don't lead to spikes much much spike in my my blood glucose levels. Legumes, depending on the quantity that I eat. So for example, if I'm eating lentils, if I eat a large quantity of lentils, then it can lead to a a higher spike in my blood glucose levels, in some cases higher than 120 than I would like. So quantity, you know, also plays a role in addition to quantity— sorry, quality. So like if you were to— like I've done some testing with white rice, for example, and white rice seems to really like to spike my blood glucose levels pretty high.

But it really all depends on In how high that it spikes, it depends on the quantity. You know, so if I eat three or four bites or big tablespoons full, it's significantly less than if I were to eat you know eight to ten tablespoons full. But I prefer not to eat rice for that reason, and also for the reason that rice is in many instances heavily contaminated with arsenic. So I just, I don't find much, you know, micronutrient quality in rice in general. I just don't find a reason that I really need to eat it. So other things, other benchmarks, I noticed that exercise while I'm fasted or exercise with a low glycemic meal beforehand, like, you know, some, some nuts or this coconut yogurt I eat, it's called CocoYo. It's, it's got 1 gram of sugar in the entire— I think it's just 1 gram.

It's got 1 gram of serving. I think there's 1 serving. At most, it has 2 grams. And, and it's, it's, it's— that's a high-fat meal. Or avocado. Any of those things don't, don't really— the exercise will improve my postprandial blood glucose levels, um, you know, within, within a 24-hour period. And also it improves my fasting blood glucose levels within, I would say, a 48-hour, 48 to 72-hour period, the best being the first 24 to 48 hours. Um, so that's another thing, uh, you know, if I for whatever reason, um, do not get a chance to exercise within 72 hours, I will notice that my postprandial and my fasting blood glucose levels aren't as great. I mean, they're still good, but they're not like, you know, I seem to do the best when I include exercise.

I've really got my sleep down great, but, you know, I've been wearing my CGM for quite a while now, and, you know, over a year ago, My son, a year and a half ago, my son there was some you know I don't know he was getting some new teeth in or something and all the sleeping issues kind of resurfaced and it absolutely if I if my sleep was fragmented that would just wreak havoc on my fasting blood glucose levels and postprandial and exercise seemed to help a little bit but it didn't exercise didn't completely negate that so sleep is extremely important. For me in terms of regulating my blood glucose levels. The other thing that I've noticed very recently, in fact, in the past, I would say 2 weeks, I started taking moringa powder.

I ordered some, I got it from Whole Foods and it's the Kuli Kuli. I got it after speaking with Jed and Dr. Jed Fahey, who I will be having another podcast with at some point in the near future. And I will absolutely be talking about Moringa with him. But Moringa, so without getting into too much of that since I'm actually not an expert on it and don't know much about it, but I really trust Jed. You know, it according to him, he he says it seems to have very similar effects in terms of activating the same genetic pathway that sulforaphane does, and it's very you know it's it's an isothiocyanate very similar which sulforaphane is as well.

So I started taking the moringa powder because just to experiment with it, and it's also got you know a variety of other micronutrients in it as well: magnesium and some calcium and potassium and things like that. It's also much much cheaper than you know, buying supplements, for example, or even easier than doing broccoli sprouts. So I started adding it to my smoothie, which my smoothie typically is kale and avocado and some blueberries and some coconut milk and unsweetened coconut milk. And I started adding about 3 heaping tablespoons of this kuli kuli moringa powder to it. And what I've noticed is that While the smoothie itself, I drink about, oh, I don't know, I would say 12 fluid ounces of it. The smoothie itself doesn't raise my blood glucose levels.

Certainly, it's somewhere around maybe like 115. I get up to 115 postprandial. Adding the moringa powder seemed to lower my postprandial blood glucose response, um, I would say 8, 8 or so units. Um, so, and it's been very consistent, uh, in the past couple of weeks. Um, I don't know if that's something, and I, I certainly want to talk to Dr. Jed Fahey about this, but, um, there have been some studies with sulforaphane. Um, interestingly, the sulforaphane was able to to improve blood glucose, fasting blood glucose levels, as well as HbA1c, which is a marker for long-term blood glucose levels. But it was only able to do that in people with type 2 diabetes that have dysregulated type 2 diabetes, not people that didn't have dysregulated type 2 diabetes.

But the caveat is, is that all those people in that trial were taking metformin, which Lowers blood glucose levels. So, you know, the question is, would the sulforaphane have done lowered the blood glucose levels and HbA1c? You know, in those people, if they weren't taking metformin. So, with the moringa powder, it's it's consistent. You know, it's something that you know for the past couple of weeks it's done. So I I tend to think that there's definitely something going on there. I mean, I'm excited to. The other thing is that I do, if there are times, I mentioned I try to have a low glycemic meal before my exercise. Sometimes I do end up having the smoothie, which is not necessary. It's not a high glycemic meal by any means, but it's higher.

It raises my postprandial levels higher than an avocado would, for example, right? Essentially almost do nothing to my blood glucose levels. But what I will say is that I go for a run and I dip down into the 70s quite quickly. So it's not, you know, getting my postprandial levels to, you know, 105 doesn't seem to really do much in terms of— it doesn't seem to have a huge negative effect on my blood glucose regulation during exercise and even my fasting blood glucose levels the next day. So with that said, I will kind of continue on to this, the next part of this question, which Chris had asked about, you know, if you can, you know, lower the postprandial blood glucose You know, response with something like exercise, would that negate any of the the negative effects that may may show up right with eating eating particularly with eating refined sugar, but with even having just a constant you know high glucose response.

So I will say that, and this even there was another question that I didn't mention from Alma, and she had mentioned also related to this: Why did I choose one? 120 as my postprandial, and as opposed to like 100 or 110. And, you know, so, you know, basically I would say that 120 is— I usually don't get to 120. It's not like I, you know, 120 is my every— 120 is my— is what I prefer when I'm intaking things that are like a fruit. that would potentially increase my blood glucose levels postprandial, right? Like, so if I were to eat some raspberries or blueberries or things like that, like 120 is my max on that. I typically, for my meals, you know, I typically don't like to get above 110 or even 105, you know, and my meals are typically like a piece of protein and a lot of vegetables.

Some vegetables can raise my levels higher, and again, quantity. So like if I have butternut squash, I'm making that for my son, sometimes I'll eat some, that'll raise my levels higher, or cooked carrots will as well. But, but, but not much higher. I mean, it doesn't get above 120, but it raises my levels higher than, for example, my, my kale or spinach. What I will say in terms of the glucose response, it's been shown. So there's a there's a something happens with them. You know, after you eat a meal and and and what's what's referred to as the post postprandial inflammatory response that is dependent on postprandial blood glucose levels. As well as postprandial triglyceride levels, and it generates inflammation, and that happens in even healthy people.

And this can trigger a whole biological cascade resulting inflammation and endothelial dysfunction. You can get sympathetic hyperactivity. Uh-huh. And so, I like to keep my levels low, both triglyceride and my postprandial triglyceride and postprandial glucose because I'm certainly not wanting to have a very high postprandial inflammatory response. Certainly, high postprandial blood glucose can lead to a much more exaggerated postprandial inflammatory response. And that's another reason why I don't eat multiple meals a day either. You know, like just each time if you're repeatedly doing this multiple times a day, you know, that is leading to— you're getting this postprandial inflammatory response and that can kind of exaggerate some of those biochemical effects I just mentioned earlier.

With a triglyceride Um, post— lowering postprandial triglyceride, there's been quite a few interesting studies showing that actually fish oil can lower postprandial triglyceride levels between 16 to 40% in a dose-dependent fashion. And in part does this by upregulating lipoprotein lipase activity and sort of accelerates the clearance of chylomicrons which then— Mm-hmm. Effects to the triglyceride levels. So, you know, there are a variety of things that are responsible for lowering the postprandial blood glucose that we, that we mentioned. The fiber, the food order, we talked about that earlier in the Crowdcast, eating protein and vegetables before eating the carbohydrate, and exercise is another one. So those— that's kind of been my experience in terms of my continuous glucose monitor.

So Laisha is mentioning that she suffers from migraines and has found that high-dose EPA reduces the intensity and helps them go away. There's some research that suggests there's a relationship which reduces inflammation. And not all migraines are related to inflammation, but I just as an anecdote will say that my mother, I've been giving her high-dose EPA and she's noticed the— she's experienced the same thing. It dramatically helps with her migraines, and I'm particularly thrilled about that. I think there's also been some evidence that ketosis and ketogenic diet and potentially even exogenous ketones may help with migraines as well. But certainly, a ketogenic diet, I think there's been some growing evidence that can help with migraines.

Which kind of leads me to the next question, which was from Michael. And Michael asks what my take on using exogenous ketone esters as an adjunct to standard of care treatment for neurodegenerative diseases like Parkinson's and Alzheimer's disease. Sort of along the same lines, As I just mentioned with the migraines, there's been— I would say there's been a definite growing body of evidence that has suggested a ketogenic diet may actually be useful for Alzheimer's disease and beneficial. And for those of you interested, you should go back and listen to the podcast I did with Dr. Dale Bredesen. We also have some clips on our clip channel, FMF Clips. You can find a clip there specifically on the ketogenic diet and Alzheimer's disease.

He has a protocol that has been quite successful that he's been using. I personally think there's a lot of potential there and much more to be explored when it comes to exogenous ketone esters. You know, there's just so— it's such a new field and really just limited evidence. Yeah. I personally would love to see more data, and I think there is a cert— certainly there is a potential there. You know, there's a few things to keep in mind. One is that the ketone elevation is very short-lived, you know, a couple of hours. And the second thing to consider is that, you know, during those couple of hours, it can lead to a quite significant lowering of blood glucose levels.

Which, you know, again, when you're talking about people that, you know, have a disease and certainly a disease that they forget to eat sometimes, I mean, there's a lot of things that need to be considered. But I am certainly excited about the possibility for ketone esters to be at some point potentially used as an adjunct therapy to help with neurodegenerative diseases. So Andrew was asking about taking supplemental vitamin E because he has a SNP, a single nucleotide polymorphism, in his GSTP1 gene, which is a glutathione-related gene, glutathione synthase. And that particular SNP is associated with more inflammation and harm if vitamin E is taken. And so I will say Andrew's mentioning there's a lot of you know supplements and fish oil they all use.

They all use alpha tocopherol vitamin E as a natural antioxidant to prevent oxidation of the polyunsaturated omega three fatty acids, which you actually definitely want in a fish oil supplement. But I will say that the levels of the vitamin E in in these supplements, in most of these fish oil supplements, are well below what levels that have been shown to be harmful in— not harmful, but can be possibly not good for people with that SNP because getting something below what the RDA is, 25 IUs a day, is, you know, I think that There's no harm in that at all. It's like when you start to get the really high dose vitamin E, when you start to get into, you know, the hundreds of IUs, a couple of hundred, you know, up to 400 IUs, then you start to have negative— potentially have negative effects.

So there was a question on My thoughts on magnesium threonate. Let's see who submitted this question. I don't have a name, but the question was, what are your thoughts on magnesium L-threonate, which most effectively crosses the blood-brain barrier? Would too much magnesium disrupt neuroelectrolyte balances? Some people have mentioned withdrawal symptoms. Would that be the case? Yes. So I talked about this magnesium L-threonate on the— when I was a guest on— recently a guest on the Kevin Rose Show. And so you can listen to that episode if you want to hear my in-depth thoughts on that and our conversation surrounding it. I believe we're gonna be releasing a clip on the FMF clip channel on that as well. But Yeah.

Generally speaking, um, I will say that there've been, um, there's been a few animal studies that really got my excitement in terms of magnesium L-threonate being a potential nootropic where, um, you know, was— it was able to cross the blood-brain barrier, um, better than just magnesium, um, in other forms. And, and it appeared to, um, you know, basically prevent synapse loss and it seemed to be beneficial for cognitive function. There was a— one single clinical study that was done. And the study, of course, was sponsored by the people that make the magnesium threonate, which isn't necessarily a bad thing, but it's always something to keep in mind.

And the study involved 1,500 to 2,000 milligrams a day of, um, depending on the body weight of the person, um, of the, of the magnesium L-threonate. And this was a 12-week study. Um, and at first, you know, that if you just read the results, it improved cognitive function compared to placebo. And so it seems quite exciting. However, if you dive into the actual data and read the entire study, There's a few things that'll jump out. First, you'll see that there was barely any increase at all in plasma magnesium levels in the L3 magnesium L-threonate group compared to the placebo group. There was no increase in red blood cell magnesium at all compared to placebo.

So, and red blood cell is a better marker of magnesium status than Plasma, so that so basically what that the other thing they did show in that study was that there was a significant elevation in magnesium in the urine in the people taking magnesium L three and eight compared to placebo, which basically saying a lot of this almost is being excreted in urine. There were four cognitive tests. that were measured. And none of those tests actually showed any difference compared to placebo if you look at the test alone. So, if you compared each test alone to placebo, there was no difference. But what the authors of this study did was they pooled all the 4 tests together and then compared it to placebo pooled together. And then, they were able to achieve a statistical significance.

So, it's kind of like if they manipulated the data a certain way, they were able to get a statistical significance. So, I mean, personally, I don't think that data is strong enough to really make the statement that magnesium L-threonate is going to improve cognitive function. I think that you would want to see the individual cognitive tests alone. performing better than placebo rather than having, having to pool all 4 tests together. With that said, you know, maybe we need more research, you know. So, so those are my thoughts on the magnesium L-threonate. I really— I'm gonna have to get going, but just a couple of rapid-fire questions. Or maybe Lydia, have I tried Viome microbiome test and what are my thoughts?

So you'll have— you know that I have not tried it, but I am in the process of ordering it to try it. I've been wanting to try it for a while and this kind of refreshed my memory to go ahead and order the test. So I will be trying that. There was another question that people upvoted about, do I offer or have any plans to offer an individual service where I would review people's DNA data and biomarkers and sort of give recommendations based off of that? Right now, no, I do not have any plans on doing that. VC is asking in the chat what brand of probiotic I recommend. I don't necessarily recommend any probiotics for people, but I will say that VisBiome is the probiotic that I and my family take.

I don't take it every day, but even these days, I sometimes have been forgetting to take it weekly, but that's the one with, I would say, VisBiome is made by the same inventor that made VSL number three. He left VSL number three and moved to Visbiome. There's been, so it's the same formulation that he made when he was doing VSL number three. VSL number three modified their formulation a little bit, and I don't know exactly what they did. But there's been a lot of randomized controlled trials and just lots and lots of preclinical evidence showing that VSL number three is is beneficial for a variety of different. Gut-related issues, IBS, colitis, any type of inflammatory bowel thing. So that is the probiotic.

And there was another question from Dan who is— said another podcast mentioned higher DHA in men could be affiliated with prostate cancer. Should men be cautious with fish oil supplements? So, I'll say that particular paper was a terrible study in my opinion. And, the reason it was a terrible study is because blood samples were taken from men that were a part of a large clinical trial called the SELECT trial. Which is a trial that involved men with prostate cancer. And they were given high-dose alpha-tocopherol vitamin E supplements. They were given 400 IUs a day. And they were also given selenium. And I believe it was 200 micrograms. I don't remember the exact dose of the selenium they were given a day. And this was over the course of a couple of years.

And so Blood samples were taken from these men and omega-3 fatty acids were measured in those samples and correlated with prostate cancer risk. Here's the thing that, I mean, for one, the study didn't ascertain or didn't differentiate between omega-3 from diet or supplements. It was just we measured the levels. We don't know if they were from people taking supplements or from from their diet. So there's no telling what was going on. The fact of the matter is that the high-dose vitamin E, the 400 IUs a day, was shown to actually deplete or decrease the levels of another form of vitamin E, gamma-tocopherol. And gamma-tocopherol has a very unique and specific role, although it's less— it's found in— it's less abundant in plasma than alpha-tocopherol is.

Alpha-tocopherol is a very potent antioxidant. Gamma-tocopherol, on the other hand, has a very specific function in inflammation. And in fact, it's important to have anti-inflammatory processes in it. It's involved in negating a variety of inflammatory processes involved in like nitrous reactive nitrogen species that are produced from immune cells. So the alpha-tocopherol depleted the gamma-tocopherol and actually increased the prostate cancer growth in those men. And it could be as a consequence of them having higher inflammation that wasn't measured. But like again, their gamma-tocopherol was depleted in the men taking the alpha-tocopherol, high-dose alpha-tocopherol compared to men giving placebo. And it is known that it does, you know, deplete— can— high dose can deplete it.

So here you have a study where you're— all sorts of crazy things are happening and all of a sudden you add this other variable and you're like, I'm going to measure omega-3 and and see how that affects— I mean, the correlation there, there's just— to me, it's just complete and utter crap. Like, that data means nothing. Um, in fact, there have been many other studies showing that omega-3 fatty acids are, uh, associated with a reduction, uh, in prostate cancer risk largely because inflammation plays a major role in prostate cancer, uh, progression and omega-3 lowers inflammation. So, That one study, you know, the news always likes to have anything that's sort of, you know, sensational sounding.

And if you have something that's supposed to be good for you, all of a sudden bad for you, like the media just takes that and runs. And so that study sort of made a lot of headlines despite the fact that it was not very good data at all. Yeah. So, I'm going to just answer another question from the chat and then I'm going to— this Crowdcast is going to end. But people have been asking in the chat about a resveratrol and NMN brand I recommend. So, I don't recommend really any brands at all. And in fact, NMN, I don't I personally don't take it, and I'm not sure there's been any— there hasn't been any clinical studies in humans yet, and certainly there hasn't been any validation on any of the brands that are selling it. So I just can't speak to the NMN at all.

The resveratrol that I am possibly going to take and the resveratrol that I do have and did give my mom is the microionized M99 resveratrol powder from RevGenetics. And I don't have any affiliation with them. I just— that's the one that I got from other scientists recommending the quality of that specific product, not necessarily all of their products. So another question in the chat. Callum is asking, say, or saying, that David Sinclair says amino acids can decrease longevity. Do you still take collagen powder? Um, so I do like collagen powder. Excuse me, I'm gonna sneeze. Oh, it went away. Um, I do like to put collagen powder in, uh, in my, in my smoothies or, you know, other, other, uh, you know, hot beverages or things like that.

Um, the, the, the amino acid profile I, I would imagine that David is talking about or have to do with leucine and methionine and largely due to the fact that those activate IGF-1 and mTOR, which are chronic activation of those are associated with decreased longevity. That could be something we could save for another Crowdcast if someone wants to submit that question 'cause it would require more than 2 minutes, which is all I have to go into detail. The amino acid profile in collagen is really high in glycine, arginine, So it's proline. These are amino acids that, in fact, glycine has been shown to be, at least in lower organisms, to increase lifespan. So having the opposite effect, in fact, as something like leucine or methionine has been shown in lower organisms as well.

So again, if you wanna hear more about that sort of question, please submit it for next round. And thank you again for all the, the wonderful questions in both the questions you submitted earlier as well as the chat. I really enjoy doing these, and I look forward to next month's. So you guys have a fantastic rest of your Saturday and a great weekend, and I will talk to you soon. Thank you.