Q&A #43: Rhonda’s Diet and Supplements—Plus Menopausal Hormone Therapy

Hi everyone. Happy New Year. Nice to be here for, uh, 2023, kicking off our Crowdcast number 43. Got some great stuff today. So for those of you that are new, welcome. Happy that you're here. I typically, um, go through a lot of the questions that were submitted in the submit a question area. And, um, often I like to choose several questions to do a deep dive on. For example, today we'll be going deep on hormone replacement therapy in women, which is something we haven't covered in depth before. We have talked about sort of topically or peripherally, you know, some aspects of estrogen replacement therapy. So I go deep on some questions. I choose the questions based on top votes. I choose questions based on things I haven't talked about in the past.

I choose them on my interest as well, or just what I think generally would be interesting. Generally interesting to the community. I also will answer questions live in the chat here throughout the Q&A, particularly questions that are relevant to a topic we're discussing. And then I also do some rapid-fire questions as well, where these are, you know, answers that I can give you in a sentence or 2 or something short and brief. So with that, I'm excited to get started. I know a lot of people have been asking about my updates on my supplements and sort of sample diet. So we're going to start with that. So Bruce Lee asked, Rhonda, are you open to posting your diet regimen? What's your food routine, preparations, produce type, things like that?

So I'm going to— I'm not listing like every single meal I ever eat, but I'm sort of just going to give you guys some examples. Of my meals. And, you know, I don't skip meals. And we'll talk a little bit about this when we talk about a fasting question. But I generally try to still eat within a time-restricted window. It's usually probably around 9 hours. And so I eat all my meals within those 9 hours. But typically I start off with morning coffee. I add a scoop of Great Lakes collagen powder to my coffee. And I've been sort of recently cutting down on dairy and saturated fat as like things that I don't need, like cream in my coffee. So I've been using oat milk and I like oat milk and I do a little bit of monk fruit as well. And so that's my coffee.

For my eggs, I used to do scrambled eggs in Kerrygold butter. I no longer do that anymore. I now do scrambled eggs in olive oil. And the reason for that is I've just been convinced that— and we'll talk again a little bit more about this, there's a smoke point and oil question. But I've just over— throughout the Crowdcast that we've done, actually, a lot of people have asked questions about various things like how do you lower ApoB, you know, which is a cardiovascular risk biomarker we'll talk about today as well. And olive oil is, you know, therapeutically, like, is lowering ApoB levels. There's so many really good polyphenols in olive oil. And so I'm really convinced that getting more of that in my diet is great, and I'm not concerned about cooking it even at higher temperatures.

So we'll talk a little bit more about that in a minute. So I usually do about 4 eggs. In olive oil, and then I'll add some tomatillo sauce as well. And then sometimes I'll also, just to get some fiber in there, I'll either do some whole oats with oat milk or I'll do a smoothie, kale and blueberry smoothie. And so that's my morning. Mostly trying to get a lot of protein in. For lunch, I'll do a protein like sardines or some salmon that I have leftover and avocado, or sometimes I'll even do a turkey sandwich with uncured turkey meat and I'll do sprouted bread. So a little bit of romaine lettuce on that as well. So sometimes I'll do that. And then for dinner, I'm doing a protein choice. So it's either grilled salmon with olive oil and lemon or grilled chicken thighs.

With chimichurri, or I'll do a grass-fed Wagyu beef like filet mignon for my protein choice. And then I'll have a side of veggies. And so sometimes I'll do grilled veggies. So I'll get organic broccolini, organic carrots and squash, and put some olive oil, a little bit of salt, and put those in the oven. Or I will do a big salad with a variety of romaine lettuce and arugula and carrots and a little bit of tomato, just a variety of different vegetables in the salad. And then I do olive oil with a little— with lemon, fresh lemon, and then I do some salt and oregano for dressing. And the olive oil brands, I talked to you guys about that a couple of Crowdcast to go, but I usually for my olive oil right now I've been doing a lot of Amphora Nueva because the other brand I like is out of stock.

And Amphora Nueva is they have really high polyphenol olive oil, and I usually just get their house blend, but they have a lot of a lot of really good options. So Erin is asking in the chat about my smoothie. She says just kale and blueberries in the smoothie or any protein powder or avocado. Thank you for asking that. So sometimes I will put collagen powder in there depending on if I have it in my coffee or not. And then I do a little bit of oat milk. I don't usually do— I used to do egg white protein powder and I used to get it from a company called Julian Bakery, but their prices have gone up over tenfold because of some kind of avian flu issue with birds or something. So I stopped buying their protein powder. Their protein powder is great, by the way.

It's like, it's egg white, you know, organic egg white protein powder. But I stopped buying it because it's just cost prohibitive. So I switched to— I do add additional protein powder on, let's say, days I'm not getting as much protein and I'm doing weight training. Then I take some Thorn protein powder. They have vanilla or chocolate protein powder that I take as well. So that's kind of what I use for my smoothie. I usually don't put protein powder, although in the past I used to do egg white powder because it was unflavored and it kind of went well with it. And Luis is asking a question about calcium, and so let's talk about my supplements because I have cut out dairy. I sometimes do like a little bit of feta cheese in my salad. I probably should have mentioned that.

It's not like I'm totally avoiding dairy, full stop. I'm just cutting— I've just cut out dairy at points in my diet where I feel like it's extraneous. I don't need cream in my coffee. I can use oat milk. I don't need to cook my eggs in butter. I can use— You know, olive oil, which is actually you know health promoting. So it's not that I don't ever eat, and I also do sometimes eat yogurt. So sometimes I'll have yogurt as well, and I do, and I do also do the you know kefir as well. But that's usually goat milk. So sometimes I do switch out my smoothies with goat milk kefir with like some raspberries or strawberries. So it really depends on like what I have around, like do I have kale and blueberries? If not, then I'll do the kefir. I'll do some kefir and some sort of berry with it as well.

But the olive oil brand that I choose, by the way, they also have data on their polyphenol content, which is another reason why I really like them. They're just— it's a really good brand of olive oil. But let's talk about some of my— My supplement, my recent supplement choices, they do change a little bit. I would say checking back quarterly is kind of a good idea. I still use the one multivitamin by Pure Encapsulations. It's not the— I mean, there are things I wish, you know, it's missing some things like magnesium. It's not like the best ever, but it is one that I still It's not super, super high dose B6. It has, you know, it has a lot of the things that I feel are insurance, like backup insurance for some of the micronutrients.

It also has 2,000 IUs of vitamin D. So, I'm getting a good amount of vitamin D just from the multi, which is nice as well. I also do lutein and zeaxanthin for eye health. And I do a calcium. So, the lutein and zeaxanthin zeaxanthin I also get from Pure Encapsulations. And then I do a calcium, vitamin K2, vitamin D combination. And so, I'm getting like 600 or so milligrams of calcium, and then I'm getting another 1,000 IUs of vitamin D from that as well. So, I'm doing that. And then I do— so, this is in the morning. I should have mentioned that. I do morning and then I do nighttime supplements. So, in the morning, I'm doing the one multivitamin, the lutein, zeaxanthin, the calcium, K, and D. I do CoQvia because it has a little bit of caffeine in it.

And I do feel like a little bit of a nootropic effect when I take the CoQvia as well. So, I take it in the morning. And then, I take about 3 grams or something around 3 grams of higher-dose EPA in the morning as well. And then I take, generally when I'm in stock, I take Brock, which is the prostaglandin that is now in the US. And I take 1 to 2 pills of that with food. The omega-3 supplement I take is still really not available in the US. It's N-Pure 3, but I do like Metagenics. They're high omega-3. It's called OmegaGenics. They have a pretty good omega-3 brand as well. And then some of you also can get prescription Lovaza, which is also a good omega-3 supplement. And it is ethyl ester form though. And so you have to take that with food or it won't really be absorbed well.

But I do think Metagenics is pretty good. So that's a good option. Nighttime supplements I take, magnesium glycinate. It's about 120 milligrams, and that is from Pure Encapsulations. Nighttime, I take Ester-C, and it's about 600 milligrams. I generally take it at nighttime because it's— there's been enough hours after my exercise that I'm not concerned about any blunting of, you know, the inflammatory or oxidative stress that's induced by exercise because, you know, several hours have have gone by. Also, at doses, you know, 500, 600 milligrams of vitamin C, there really hasn't been any substantial evidence that alone blunts the benefits or adaptations to exercise. So, but I still take it at nighttime.

And if I do work out later in the evening, then I'll skip the Ester-C just sort of out of caution. Autophagy Renew is a new one I'm sort of taking. That one is by Life Extension, and I generally take it for their luteolin, which is, you know, it helps with lowering neuroinflammation. But also it's got, you know, it's got some autophagy-instigating components in it, at least according to animal studies. And You know, it's good to take that at night when you're going to be fasting anyways. And then at night, I take my higher DHA omega-3. Take about three grams. If I forget to take the omega-3 in the morning, then I just sort of double up and I'll take five to six grams at once of omega-3. But I do try to. I'm trying to really make an effort to get omega-3 throughout the day.

I think there's an argument to be made to keep. Blood levels sort of more consistent with higher dose for a couple of reasons. One is for the specialized pro-mediating molecules and the resolvins, like having this like little bit of anti-inflammatory effect going on or resolving of inflammation, I guess would be also a better way to put it. So it's not necessarily blunting inflammation, but it's just resolving it more efficiently. Yeah. But also, there's been studies showing that, you know, every time we eat a meal, the postprandial inflammatory response that happens in our gut leads to a little bit of, let's say, you know, endotoxin release. And this is inflammatory. It is atherogenic. That omega-3 blunts that LPS or endotoxin release. Release.

So having higher levels throughout the day, I think, is beneficial for that reason as well. I take the DHA usually in the evening, the higher DHA one in the evening, because there have also been some very sparse— I mean, much more work needs to be done. I would say, you know, take this with a grain of salt, but there is some preliminary clinical evidence that DHA can help with sleep as well. And so I'm like, why not? Why not take that at night? I also take in the evening, I take my ubiquinol, and then I take melatonin. Sorry, no, my ubiquinol is taken in in the morning. Sorry about that. That was a mistake. I take that in the morning. I took 200 milligrams of ubiquinol in the morning, and that is from Pure Encapsulations for mitochondrial health.

And then I take my melatonin in the evening. And I do take high dose, and the reason is that it actually is one of the few things, actually one of the only things, that really seems to help with my night terrors. The other thing that really helps is doing a sauna or a hot tub in the evening as well. So those are my supplements. Spencer's asking to talk about the benefits of ubiquinol. We covered that a couple of Crowdcasts ago. So you should go back and look at that. We do have— we've talked about it more than once as well. We have a master Crowdcast sheet that is available on your dashboard at foundmyfitness.com/dashboard. When you log in, you should be able to have access to that Crowdcast PDF, and then you can just search it for ubiquinol.

But, you know, Most of the benefits, there's been a variety for cardiovascular health clinical studies, and then there have been mitochondrial health as well. So those are some of the reasons I take the ubiquinol. And then we've talked about it in the past that people taking statins actually really need to take it because statins deplete their ubiquinol directly. So that is That is why people that take statins should always be taking ubiquinol. People are asking about the brand melatonin. So right now I'm doing pure encapsulations and I'm doing 10 to 20 milligrams a night, which is pretty high dose. Bar is asking if there's a benefit for slow release. It probably varies from person to person. I personally find slow release makes makes me groggier if I take that.

So I feel like it lasts too long, whereas I'm ready to get up in the morning and then I'm not really— I'm feeling groggy, whereas if I just take regular melatonin, I don't feel that way. But people probably— there's different metabolisms of it and people respond differently. So it's probably— you can experiment and see what works best for you. Like, I know people in my family take slow-release and it really works well for them. So, that would be something to try out. I think Cricket's asking about omega-3 Metagenics for people with ApoE4. So, we're going to even talk a little bit about omega-3 supplement with respect to ApoE4. But, yeah, I think it's a great brand for everyone regardless of ApoE. For status.

John's mentioning that I didn't— the curcumin, I usually was talking about taking Meriva. I don't take it on a daily basis. I do take it if I have, you know, if I'm doing— if I have any sort of soreness with my muscles from a workout, it really helps, or if I have a headache. So I sort of use it like Most people use ibuprofen in a way, and it works for me for that. But who knows, I may go back to circling it back into my daily routine, but for now I'm not. Oh, Stephanie's asking about creatine. Yes. So I did experiment a little bit with creatine in the past. I haven't— there was like a weird study that I came across where creatine interacted with caffeine in a weird way to increase Parkinson's risk, and that runs in my family. So I just held off.

I'm sort of holding off on that because I wanted to dive deeper and I haven't had a chance. I'm not sure that there's really anything there. I mean, so many people use creatine, and I know it is beneficial, particularly for people that are older, and it helps You know, helps give them more muscle energy, essentially. I wouldn't take it during pregnancy. You know, during pregnancy, I was very, very cautious and I sort of stripped down to just the real, real essentials like the prenatal and the vitamin D and the omega-3, you know, just the really important things. And so— So that is, you know, taking anything extra during pregnancy is— it's always a risk because a lot of studies haven't been done and they probably won't be done because of ethical reasons, right?

I mean, anything that's going to potentially put a child at risk, um, isn't— you're not going to get, you know, clearance to do. So, um, we may never really know. And, you know, it's one of those things where you just— you might as well err on the side of caution. I see some people talking in the chat about hair loss, and I will say that I covered this in a Crowdcast, and it's really like this— this is all based off of one study that was done. Go back into that Crowdcast to listen to it because I go into detail about it. There may be a personalized— there's— people always respond differently to things. everything. I mean, there are people that respond poorly to things that people respond great to. So that is always something to keep in mind. There is a personal response there.

But with respect to the hair loss thing, it really hasn't— it hasn't panned out to be like a repeatable thing so far as I could tell in the literature as well. But I would say if you're losing hair from creatine, I would stop taking it for sure. Okay. So there was a question— there's a couple of questions, one from Sam and one from Troy, about my thoughts, my updated thoughts on time-restricted eating, on fasting, on prolonged fasting for autophagy, and, you know, whether or not, you know, fasting is— if I've changed my mind on fasting. So I think people are asking me this because of some recent podcast guests like Stuart Phillips and Brad Schoenfeld talking about mostly the muscle loss that can occur when you're not taking in protein.

And a lot of people have sort of— they think that meal skipping is synonymous with fasting. Or meal skipping is synonymous with time-restricted eating, and it's not. Well, I mean, fasting, yes, okay, but time-restricted eating, no. So here's kind of my updated thoughts on this topic. I do think muscle mass is extremely important for aging, and I think that There are 2 important signals for it, protein intake and resistance training. And so I think I've been convinced that you do lose muscle mass when you are not eating. So if you are fasting, if you are not eating for a day, let's say. However, if you are resistance training while you are fasting, you can really, uh, Stop the loss of muscle because you are going to—you're giving your muscles a signal for growth.

You're not going to gain muscle, right? But like you will prevent your body from losing so much muscle. I think that time-restricted eating is an important part of health, and I think it's great to do the right way. I don't think that time-restricted eating means don't eat breakfast and then eat one meal a day. I think time-restricted eating is. Is eating within a circadian pattern, and it is giving your body enough time to digest. And then when you're done digesting, to have a repair mode. Because if you are in— if you're taking in food, if there's digestion occurring, all the— like, repair mode's not happening. And you need repair mode to happen. You need repair mode to happen every night. You need it to be Robust.

And so if you are in repair mode for 15 hours, 16 hours, let's say you do an 8-hour time-restricted eating window or 9 hours, it's more what I do, you know, you're giving your body a repair time. And I think that's important. But you don't have to skip your protein to do that, right? It's easy to eat your meals within 8 hours. That's a lot of time. So I think time-restricted eating is a good daily practice. Now, full-stop fasting, where you're skipping meals, and I think that people that are normal weight, people that don't have fat really, you know, they're not overweight, they're not obese, then there's no reason to do that on a daily basis. In fact, doing it on a daily basis would probably not be beneficial.

But people that are obese and overweight, they actually can skip meals and still preserve some muscle mass because they have so much fat to lose too. They have so much fat to lose. Lifting weights is absolutely 100% essential for anyone that is fasting— normal weight people, obese people, overweight people. That's going to help prevent the muscle loss. But then there's the The okay, well, what about the normal weight person that wants to do the quarterly or the semiannual or annual prolonged fast? I do think there is clinical evidence, certainly preclinical evidence, but even some preliminary clinical evidence that it is beneficial for a reset and.

You know, depending on what that is for you, people that are normal weight probably don't have to do such a long fast to get even some of that reset. We know that autophagy can be measured definitely after 24 hours in people. Does that mean that you're not undergoing autophagy before that? Absolutely not. It just— the types of clinical biomarkers that are used are We haven't found the sensitive enough biomarkers. I think autophagy is absolutely happening. People that are eating, you know, 8, 9 hours like myself and then fasting for 15 or 16 hours. Absolutely, I think that's— it's just, you know, you have to have an assay that you're using that's sensitive enough to detect it.

So if you are doing a 24-hour, you know, fast quarterly or semi-annually, or if you're doing a 48-hour fast, then resistance training during that time is essential to help prevent the muscle loss. And what's the benefit? I mean, there is a resetting of immune cells. There's some, you know, early clinical evidence that some of the hematopoietic stem cells start to self-renew, you know. So there's an argument to be made that a quarterly know, semi-annually or annually fast depending on the person, you know, isn't necessarily bad, particularly if you're doing weight training. Now, like doing a weekly 24-hour fast, like that's a bit much, right? Unless you're obese or overweight, like those people would benefit, I think, from doing that sort of thing.

I mean, caloric restriction is absolutely effective at weight loss, at fat loss. And if you're doing weight training in combination with it, And also taking in higher protein when you are eating your meals, then, you know, you're going to be improving your health. So those are sort of my updated thoughts on fasting. I hope that makes sense to everyone. And there's people asking about like types of resistance training. And I really, from talking to both Brad Schoenfeld and Stuart Phillips, who are both really experts in this arena, They really, I think, hammered home this idea that like anything, your body weight, like anything that— jumping rope is a form of resistance training, right? Your body weight is used as the resistance. Rubber bands.

I mean, there's so many things that can be used for resistance training. You don't have to go to the gym and necessarily lift weights, right? You just have to get fatigued. You have to fatigue your muscles. and have a resistance for them, right? So Alan and Margaret are asking about a 5-day water fast twice a year for, you know, that they used to do it and that muscle loss wasn't worth it at age 74. And I would agree. I would agree. I think that that's a bit much for a 74-year-old. And muscle is extremely important at that age and it's very difficult to put on more muscle as you, you know, You know, get older. So there are other ways of increasing autophagy. Again, exercise is another one that's really good. I mean, autophagy exercise does put you in a caloric deficit, you know, as well.

But I do think that, you know, a 24-hour fast, 48-hour fast, you know, once a year with resistance training, you know, there could be an argument for that. When you're 74 years old, I don't, you know, like maybe 24 hours, maybe you don't want to go too hard, but you have to be doing the resistance training as well. I think that's just the absolute key. But this weekly thing and some people doing the one meal a day, I just don't think that's really good because you're really starving your muscle. Okay. I'll break the longer ones up with a couple rapid-fire questions. So, Farley asked about, as an APOE4 carrier, they were interested in my article, my publication on phospholipid DHA getting into the brain easier for APOE4 carriers.

That's high in, of course, salmon roe, and whether or not I'm still eating salmon roe and how much per day. So since you guys just heard my diet, you hear that I'm really not eating salmon roe anymore, and then I'm taking extremely high dose Triglyceride form omega-3. So there was a new study not long ago from Yasin Hussain's lab who showed that people who were ApoE4 who took omega-3 doses above 2 grams of— took DHA doses above 2 grams were able to convert DHA into phospholipid form. So, and I talk about this in my publication. I say it like that essentially you convert— your body converts DHA when you take in DHA in triglyceride form, your body converts it to phospholipid form. And the more— the higher the dose, the more of it you convert to phospholipid form.

And so that's kind of, I think, a good thing to keep in mind is that really it might just be a lot easier to take a higher dose of omega-3. And that's what I choose to do. We're going to talk a little bit more in depth about EPA and DHA in another answer. Rapid-fire question from Rebecca. She asked what brand of sprouted bread I use. So I mentioned I use— sometimes we'll, you know, have a turkey sandwich. The brands that I use are— I'll use the Ezekiel sprouted bread. A lot or some of the Dave's spread. So Dave's bread, they had Dave's Killer Bread or whatever he calls it. He's got some sprouted forms where there's some of the breads are sprouted. And so I also use that as well. Okay. So let's talk about oils and smoke point. So James asked a question.

He said, is there any relationship between an oil's smoke point and how healthy it is? I personally would like to make pizza with olive oil, but pizza generally cooks above 450 degrees Fahrenheit, and olive oil smoke point is approximately 400 degrees Fahrenheit. And then he lists a bunch of other smoke points for different oils. All right, so let's talk about what determines the smoke point. The oxidative stability of oils depends on their composition, and it's mainly associated with the content of mono and polyunsaturated fatty acids or chains in the triglyceride. The higher level of unsaturation, the higher the oxidative degradation promoted by heating. That has nothing to do with the smoke point and everything to do with the unsaturated, polyunsaturated content of the the oil, right?

There are other compounds in the oil that influence heat stability. So, there was a study assessing the thermal stability of vegetable oils. So, oil stability presented a high correlation to their smoke point, but just a fair correlation with the content of unsaturated compounds. And so, but when you're talking about heat stability, yes, some— so what happens is some of the compounds in the oils can be broken down with high heat. And the higher the smoke point, the less that happens. But a lot of those compounds that get broken down aren't necessarily bad for human health, whereas the oxidation of polyunsaturated fatty acids is. Like, eating oxidized fatty acids is, like, you know, not necessarily good.

So although coconut oil presents a high percentage of saturated compounds, it is not possible to sustain its stability as well as its organoleptic properties. So this is due to the fact that it has minor compounds that degrade. So refined oil has a higher smoke point, but it's devoid of, you know, vitamins, polyphenols, phytosterols, and other low molecular weight natural ingredients. So if you look at some of the studies, done, I mean, what you'll see is better stability is found in sunflower, cotton, and canola oil, which are all high in polyunsaturated fatty acids, but they do have a higher smoke point. And so those are considered— I mean, corn and soybean oil also, they change, their spectral changes slightly after Cooking at like 165 degrees Celsius.

Same with coconut extra virgin olive oil and olive oils. But again, so smoke point, you know, versus the polyunsaturated content is really what I'm more interested in. And, you know, like I've I've come to the conclusion that cooking with olive oil— so olive oil does break down. There are components in it that do break down, and I forgot all the names of them, but there's been studies done where they give people— like they cook olive oil and they feed people these, you know, breakdown components, and they look at like a variety of clinical endpoints, and there's just nothing that changes. Like, it's not harmful. And so that is why I now cook my scrambled eggs with olive oil. I bake my salmon in olive oil.

Like, I'm not scared even though the smoke point is a bit lower, you know, than, for example, like avocado oil, which is also low in polyunsaturated fat. I still— there's— the polyphenols in the olive oil are beneficial. enough that I— and that I just haven't seen evidence that cooked olive oil is harmful. So I'm— that's what I use for cooking. You know, there's a lot of lipid oxidation products, peroxides and hydroperoxides that are unstable. And, you know, I honestly think that cooking with the polyunsaturated fatty acids is where you get more of the risk because those are unsaturated, polyunsaturated. And so, in fact, there's studies showing if you cook with, you know, soybean oil, for example, you get, you know, much higher levels of, you know, these oxidized fats.

And so, really, I think what it comes down to is that, yes, smoke point Does determine the stability of the oil. However, it isn't necessarily correlated with health, in my opinion. I think what I find more correlative with health-promoting or being, you know, not good for health is the polyunsaturated content in the oil. Because that is what leads to peroxide levels, to p-anisene levels, total oxidation, thiobarbutyric acid, all these things called TBARS, all these things that have been shown to be increased in oils like high in polyunsaturated fatty acids like soybean oil. Now, acrolein is something that can be formed from heating cooking oils and fats above 300 degrees Celsius. And acrolein is a carcinogen.

Sulforaphane has been shown to increase acrolein excretion within 24 hours by— it was like anywhere, I think it was something like 50 or 60%. So similar to what benzene— to benzene. So acrolein is something that's also very potently excreted through urine when you are taking in sulforaphane. Which is also good to know. Barbara is asking about avocado oil. Yeah, avocado oil has a high smoke point. It's low in polyunsaturated fatty acids, and therefore it's considered a really good cooking oil. I've— that is what I used to use in the past. I recently switched to olive oil because I've just found overwhelming evidence that olive oil is It is like therapeutically beneficial. It's lowering ApoB. It's doing things that are beneficial.

And I have not seen evidence that cooking olive oil is health— like is bad for health, even though it does lead to some breakdown products and stuff. So for that reason, I do cook with olive oil, but avocado oil is great to cook with. I mean, you're just— it's more of a neutral oil, right? It's not like you're, you're going to be getting a health benefit from avocado oil, but it's not going to be harming you, which is essentially what a lot of people are looking for because they don't want their cooking oils to be harmful, right? So avocado oil is great in that sense. LP is asking my olive oil brand, which I just mentioned, which is Amphora Nueva, and I like their house blend.

So the next question submitted had to do with biomarkers and some of the cardiovascular biomarkers, what I think some of the best cardiovascular biomarkers to look at are. I forgot who submitted this question. Sorry, I don't have the name here. But so the list I'm going to give you, this is what, if, you know, what I personally would go and tell my cardiologist about. So, you know, it's just— It's just from my reading of the literature and from over the years experts I've interviewed. It's sort of, you know, my thoughts on some of the best cardiovascular biomarkers to measure and something that I would go and ask my cardiologist to go and look at or my, you know, my internal medicine physician to look at. to look at if, you know, when I do my lipid panel.

You know, there was the traditional lipid panel for years that American Heart Association recommended, recommends, you know, lipid panels every 4 to 6 years in people over 20, or, you know, patients at high risk for cardiovascular disease should do it more frequently. But the traditional panel was always total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. HDL cholesterol, LDL cholesterol, and triglycerides along with the ratios. So traditionally LDL cholesterol has been used to assess the risk associated with cardiovascular disease. Many clinicians use it as a surrogate for cardiovascular risk as well, but it's been shown in many studies to be an imperfect predictor, and many people people with normal LDL cholesterol go on to develop cardiovascular disease.

So, in addition to just traditional lipid panel, which most people get anyways, you know, when they go for a— when they're looking for cardiovascular biomarkers, LDL particle number and size. So, as we've talked about quite A lot. The small dense LDL particle is the particle size that is the most atherogenic. It's problematic because it can't be recycled back up into the liver and therefore it stays in circulation where it reacts with, you know, the artery vessel, the vessels, you know, in the artery and basically sticks there. So particle size is another one that I always look at. ApoB. ApoB is another one.

So recent studies have shown that both ApoB and non-HDL cholesterol levels may even be better indicators of cardiovascular disease and risk of major cardiovascular events compared to just total LDL cholesterol. So non-HDL cholesterol is the sum of the cholesterol in atherogenic particles, while ApoB is found as a single molecule in each atherogenic particle. And ApoB is actually what sort of gets obscured in a small dense LDL particle, and so it can't— and for that reason, that small dense LDL particle with the ApoB doesn't get, you know, can't bind to the LDL receptor and sort of get taken back up into the liver and recycled. And so ApoB— may be a, you know, better predictor of cardiovascular disease even than non-HDL cholesterol. There's also the ApoB to ApoA-1 ratio as well.

So ApoB acts as the major transporter for all the atherogenic particles. ApoA-1 is an anti-atherogenic lipoprotein responsible for transporting cholesterol within HDL cholesterol. So there's been a lot of studies that have looked at apolipoprotein and, you know, the association with cardiovascular events. And so with an increasing ApoB to ApoA-1 ratio, there's a positive linear association between any risk of cardiovascular events. But I'm not sure that it's any better than just looking at ApoB alone, because there have been some studies comparing that as well. So lipoprotein, or Lp, is an atherogenic cardiovascular risk marker as well, mostly genetically determined. It's an ApoB-containing lipoprotein, but the number of circulating particles is much lower.

So Lp has pro-inflammatory and pro-atherogenic properties. Which may partly relate to the oxidized phospholipids carried by Lp. It has different cell signaling effects that contribute to atherogenicity. High Lp induces the expression of inflammatory and calcification genes in vascular and valvar cells, and it's associated with increased incidence and progression of aortic valve stenosis. There's strong evidence for a causal association between Lp concentration and cardiovascular outcomes. The association continues on even when there's low levels of low-density lipoprotein cholesterol. So it's a risk factor for aortic valve stenosis, but evidence does not support Lp as a risk factor for venous thromboembolism or impaired fibrinolysis. VLDL is another one.

So VLDL contributes to the development of atherosclerotic cardiovascular disease, and it's associated with, you know, the thickness and vascular thickness of the part of the carotid intima-media thickness, I guess that's what it's called. Studies have shown that it's associated— high VLDL concentration is linked to coronary heart disease and may contribute to coronary heart disease as well. It's associated with increased mortality in patients with cardiovascular disease, and it's also associated with major adverse limb events for peripheral arterial occlusive diseases. And it does promote thromboembolism and hypercoagulability. So, so VLDL is another another one to measure. And then there's the omega three index.

And I think that that you know a lot a lot of Bill Harris's studies have found that people with a low omega three index lower than four percent have a higher risk for coronary heart disease, in particular fatal coronary heart disease, and people with an omega-3 index of 8% or greater can reduce that dramatically. So that is another thing to measure, and OmegaQuant is the best company to measure the omega-3 index. And then there's also inflammatory biomarkers. you know, looking at oxidized LDL, looking at myeloperoxidase, looking at the LPL— sorry, Lp-PLA2, and then C-reactive protein high sensitivity, fibrinogen, and TNF-alpha. Those are some of the inflammatory biomarkers.

And then actually looking at testing or determining the damage of arteries, a coronary artery calcium score, and a CT angiogram are the types of tests. And then, of course, there's, you know, metabolic health is also really intimately linked with cardiovascular health. So HbA1c, glucose levels, measuring insulin levels, and, of course, triglycerides as well. Those are some of the cardiovascular biomarkers that I'm interested in. And Cindy's asking about companies. I mean, you know, much of this gets covered from health insurance. So just asking your physician to do the test would be probably cheaper in many cases.

But, you know, a lot of physicians kind of also go out and use like Boston Heart or, you know, there's a variety of companies that are that are often used, um, you know, lab-wise. And, um, Quest is another one that's used. But, um, I, you know, going, asking your physician to do these. If you want to not have a physician involved, um, WellnessFX is a company that'll order a lot of these, will do a lot of these, um, blood tests. And they do personalized— you can choose like personalized, um, blood tests to do from them. Also, Life Extension does a lot of personalized blood tests you can go on and choose, and then you just go to like, I think it's Quest, um, or no, LabCorp.

I think it's LabCorp from Life Extension, but they'll, they'll send you to a, to a LabCorp, and then you'll, um, just get your, your blood drawn and you'll get the, the results back. Nicole's asking in the chat if I think hydrolyzed collagen is beneficial for people in general. We have a topic page on the website, on foundmyfitness.com. If you go to topics in the toolbar, I think it's the top left, and then they're alphabetically listed. We have one on hydrolyzed collagen powder, and it goes through all the— what the literature shows on the benefits of hydrolyzed collagen powder, and I do think it's beneficial.

So, of course, that's my opinion, but— Read through the topic page and you'll see a variety of different studies listing, you know, what the clinical benefits have been shown for hydrolyzed collagen powder. D2Row is asking about a DEXA scan for visceral fat. And yeah, that's great. DEXA scans for visceral fat would be great. There was a question from Colleen about— and I chose this question because I was very interested in it because I take melatonin. So Colleen asked about melatonin supplementation, phyto-melatonin versus synthetic melatonin, and if there's differences, is one better than the other? Structurally, synthetic melatonin and phyto-melatonin are the same molecule.

There is no evidence yet that either supplement works better than the other, but research is really in the initial stages. So I think You know, it's not that we have ample overwhelming evidence to have a scientific consensus on this. I would say just as the literature is, you know, in its current state, there's really no evidence that one is better than the other. The difference really is in the components that are present in the supplements along with melatonin. So phytomelatonin is a plant source of melatonin. So in theory, it would contain Substances like antioxidants or vitamins maybe, you know, along with it. Synthetic melatonins, due to the production process, in theory, could be contaminated with substances that could be harmful at high doses.

So, but the substances occur in such small quantities that there's— the risk is like so small, if even at all. Phytomelatonin is extracted from plants, and it doesn't contain contaminants necessarily, but it could contain residues of solvents and pesticides. So phytomelatonin extracted by CO2 from organically produced plants could be preferred. However, phytomelatonin may also be produced in bioreactors, and the same risk of contamination is present then that you get with synthetic melatonin. The real problem is that phyto-melatonin, with phyto-melatonin, is the low availability of supplements. So there's low doses. There's dubious products on the market. There's nothing reliable.

Like, there's a product on the market that claims, according to the manufacturer, that it's entirely— it's obtained entirely from rice and plant— rice plant and rice grain. But that would mean for one package of the product, which has like 120 capsules in it, 0.3 mgs per capsule of phytomelatonin, that you would need 36,000 kilograms of rice for that one bottle. This just— it's absolutely BS. There's no way. So, um, I wouldn't— I would not supplement. I, I think that it's, it's the, the phytomelatonin mark consumer market is extremely dubious, and I would not supplement with that because there's just, there's nothing trustworthy or reliable out there that I could find, in my opinion, for myself. So it's interesting to know about this, but I don't know that it's a battle worth fighting.

I think there's other important things to focus on. So I'm going to continue taking my synthetic melatonin and not, I'm not really worried about it. Okay, so the next question is a deep dive, and it was submitted by Alyssa. And Alyssa says, Dr. Ron, I'm excited to renew my subscription to your community. And thank you, we're excited to have you. But I'd also love to hear your thoughts about hormone replacement therapy for menopause. Lots of misinformation out there. This is an interesting one because we haven't really done a deep dive for hormone replacement therapy in women. Some of the controversy surrounding hormone replacement therapy were from the first results of the Women's Health Initiative. So this was in 2002.

It showed that hormone replacement therapy had more detrimental effects than beneficial effects. But the Women's Health Initiative study actually had a lot of important limitations. So it tested only oral conjugated equine estrogens either alone or in combination with a single progestin, and that was medroxyprogesterone acetate. It did not answer doubts about the safety and effectiveness of other hormone replacement formulations, regimens, or delivery methods. So conjugated equine estrogen from horse or synthetic versus bioidentical estradiol that is used today. So that would be the one thing to look at. So there was a review paper of randomized controlled trials, there were meta-analyses, observational studies.

Most of the studies revealed similar or lower risk for breast cancer, venous thromboembolism, cardiovascular outcomes, and cognitive parameters for estradiol compared with the conjugated equine estrogen that was used in that original study. So again, there was either similar or lower risk for breast cancer and venous thromboembolism and cardiovascular outcomes. So synthetic progesterone equals progestin versus bioidentical progesterone that is now used in the, you know, US today. So meta-analyses have found, and also population-based observational studies have found, that among women using opposed oral estrogen, there was higher venous thromboembolism risk in women using medroxyprogesterone acetate, which is what was used in that original 2002 study, the Women's Health Initiative, compared to those using other progestogens.

So, you know, again, that original study could have been skewed towards the negative because it was using a certain form of progestin. A review paper of randomized controlled trials and meta-analyses, observational studies, found that most of the studies found a similar or lower risk for breast cancer, veno— thromboembolism, cardiovascular outcomes, cognitive parameters. Again, for progesterone compared to progestin, right? So progesterone is now what is more commonly used compared to that original study in 2002. And then there's also transdermal administration, which is often used today as well.

There have been meta-analysis and population-based observational studies among women using estrogen-only preparations So oral, but not transdermal preparations increased venous thromboembolism risk. So transdermal administration was safer with respect to the venous thromboembolism risk. Some other limitations of, you know, this Women's Health Initiative study and the controversy surrounding it. Come from other factors. So most of the participants in that study were more than a decade past their final menstrual period.

So I think the key lesson for the Women's Health Initiative study was, you know, was not given much attention to, was the risk-to-benefit ratio and the safety profile of hormone replacement therapy and how it differed among, you know, different clinical characteristics of the participants as well. So age, time since menopause, their comorbidity status, all those things as well. So I would say, you know, if you look at some of these clinical— if you look at their age, a lot of, you know, the majority of the participants in that study were 60 to 69 years old. I mean, they were way past menopause. You know, 33% were 50 to 59, and then another 21% were 70 to 79, again, way past menopause. You know, there was 10.5% were current smokers, where 40% were past smokers.

You know, 35.7% of these women were treated for hypertension. So there's a lot of other factors going on in that study population where there was— you know, all these negative outcomes. And so a reanalysis of the Women's Health Initiative trial was performed, and new studies showed that the use of hormone replacement therapy in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, on reducing coronary disease and all-cause mortality. But again, the key is this was younger women early in their postmenopause. So, like, you know, we're talking you're getting right into menopause and postmenopause. You're not waiting 10 years after you've been in menopause, right?

There was a large open-label randomized controlled trial from Denmark that found Healthy women taking combined hormone replacement therapy for 10 years immediately after menopause had a reduced risk of heart disease and death from heart disease. Epidemiological modification in the incidence of hormone-related cancers, cardiovascular disease, and bone fractures in post-Women's Health Initiative era, which is characterized by a massive reduction in use. So breast cancer incidence was decreased or unchanged. Endometrial cancer was increased. Cardiovascular disease was increased or unchanged. And bone fractures was increased or unchanged. So that was from the Women's Health Initiative study. So I think the take-homes here are, it seems as though the type of hormone replacement therapy Yeah.

Plays a role in risk-to-benefit ratio. It seems as though the time, so around menopause, so earlier in menopause seems to have more of a benefit than risk ratio in women versus women that are taking it much later, 5, 10 years after their they've already gone through menopause. And then there are other health and comorbidity factors that also play a role as well. There are, for women, you know, again, these are— this is analysis of some of the studies published, but like for women that are interested in possibly doing hormone replacement therapy, talking about these things with your endocrinologist, I mean, that is what I plan to do when I'm there at, you know, one day in the future.

So, you know, talking about these, you know, the original Women's Health Initiative studies and the problems with it and the, you know, types of estrogen, the bioidentical estrogen versus what was used in the original, the equine estrogen that was used, and then bioidentical progesterone versus this Yeah. This progestin that was used, the medroxyprogesterone acetate, you know, like talking about the different types and then transdermal versus oral with your endocrinologist as well would be, you know, what I would do. There are, you know, some things to know before, you know, starting hormone replacement therapy, obviously talking with your physician about that as well.

But there's a lot of examinations that are, you know, for someone that decides to start them, you know, looking at physical— doing the physical exam, liver function, kidney function, anemia, fasting blood sugar, blood tests, serum lipid profile, followed by a mammogram, a bone mineral density test, Pap smear, like screening, all of that stuff. And then, you know, perhaps even thyroid function, breast ultrasonography, endometrial biopsy, and then measuring these things depending on what your physician decides, you know, 1 to 2 year interval, like doing— going back and actually measuring these things just to kind of monitor, you know, things like endometrial hyperplasia, cancer screening, things like that.

I haven't seen any large randomized controlled trials that have assessed the effect of long-duration hormone therapy use. So again, that's another consideration. Most of the time, the hormone replacement therapy is used for certain indications like vasomotor symptoms, so night sweats or hot flashes, or prevention of osteoporosis in postmenopausal women, Or also the treatment of hypoestrogenism. So that's caused by hypogonadism or ovarian insufficiency. So I think that kind of covers the controversy of the hormone replacement therapy really coming down to that original study with the Women's Health Initiative, coming down to types of estrogen, coming down to use of the hormone replacement therapy, the timeframe with respect to menopause, right? That's important.

So earlier seems to have beneficial effects, where later not so much, and it increases more of the risks. And then also just comorbidities, like anything, right? Comorbidities always play a role in treatments of things. So, Lots of things to consider there. And, you know, whereas, you know, there was this general statements of, oh, hormone replacement therapy is going to give you a heart attack or give you breast cancer. I mean, it's not necessarily true, right? There's lots of nuance here, and there are lots of factors in those original studies that came to that conclusion. There's also a related question from Pooja about hormone replacement therapy after the age of 40 to increase muscle mass and energy. So, I mean, I haven't seen any clinical studies on that.

There's some preclinical evidence on animals suggesting a possible benefit when combined with exercise. But, I mean, you know, I think the main thing to prevent muscle loss is to get your protein and to do resistance training, and that's the thing to focus on. Oh, I see Bill Harris is here in the feed. And he answered some questions about pro-inflammatory concerns of too high omega-3, which I haven't seen any concerns about, but I do really recommend the Omega-3 Quant test. I usually use their advanced one as well. Okay, so the next question was submitted from Rebecca, and this question was about ApoE4 and omega-3. So Rebecca says, as an ApoE4 carrier, I try to get 3.45 grams of DHA a day. Should I balance that with a certain amount of EPA? Does EPA to DHA ratio matter?

After doing some, you know, literature searches, this is kind of some information that I've put together with my team. So to my knowledge, there are no trials comparing the effects of different ratios of EPA and DHA on ApoE4 carriers. So I couldn't find any science, you know, directly speaking to that. For DHA, mechanisms that link ApoE4 with reduced brain DHA metabolism are as follows. So you can find evidence that there's accelerated liver catabolism of DHA in ApoE4 carriers. Possibly defective DHA transfer across the blood-brain barrier in non-lysophosphatidylcholine form. And then there's hypolipidated or decreased ApoE particle numbers resulting in less efficient DHA transport. Supplementation with DHA has been shown to reduce amyloid beta plaque production, aggregation, and toxicity.

and can promote plaque clearance in individuals with moderate dementia and Alzheimer's disease, not necessarily looking at ApoE4 status though. DHA supplementation also has been shown to decrease tau tangles. So patients with Alzheimer's disease who received approximately 2 grams of supplemental DHA for 6 months exhibited decreased amounts of phosphorylated tau protein in cerebral spinal fluid. And non-human primates given DHA supplementation demonstrated decreased tau pathology. Of course, DHA is really important for cell membranes. It facilitates the transport of many nutrients, including glucose, by regulating the GLUT1 transporters. So DHA is important for getting glucose into the brain as well.

There was a meta-analysis of 21 different epidemiological studies with over 180,000 participants that identified A greater intake and blood levels of EPA and DHA were associated with lower Alzheimer's disease risk, but systemic reviews of randomized clinical trials using lower doses, less than 1 gram of omega-3, have been negative. So there was— they have not shown any effect on dementia prevention with doses less than 1 gram per day. So there's a lot of speculation as to why that is. It's not, you know, could be several reasons. So with respect to EPA, ApoE4 carriers have faster EPA clearance from plasma compared to non-carriers. And ApoE4 appears to limit the conversion of DHA to EPA. So after DHA supplementation by promoting EPA's mitochondrial oxidation of it.

So the delivery of EPA after DHA supplementation in ApoE4 carriers, EPAs, mitochondria, it promotes the mitochondrial oxidation of EPA. And so the delivery of EPA to the cerebral spinal fluid as well. So EPA levels are disproportionately lower in the brain when compared to, let's say, you know, DHA or arachidonic acid, for example. But it doesn't necessarily equate to lesser biological significance. So EPA does play fundamental roles in neuroinflammation, neural proliferation processes as well. EPA can work to attenuate the effects of inflammatory mediators. So it also serves as a source of eicosanoids— gosh, my— eicosanoids and resolvins. They're involved in mitigating inflammation and excitotoxicity in the brain.

So I think this finding can contribute to our understanding as to why ApoE4 carriers with limited omega-3 intake might be at a greater risk for neuroinflammation and Alzheimer's disease progression. In general, Alzheimer's disease, not specific to ApoE4, there's been findings from, you know, preclinical studies in Alzheimer's disease models that suggest EPA plus DHA may be better than— may be a better combination treatment for cognitive decline compared to a single fatty acid. Recent studies further directly support that EPA plus DHA combination synergistically attenuate cognitive impairment in animal models of Alzheimer's disease compared to just pure EPA. Again, these are animal studies, so it's still inconclusive. If that translates to humans, but it is a start.

The authors conclude that EPA or EPA in a higher dose plus DHA seem to be more effective to treat major depressive disorder, while DHA or higher dose DHA plus EPA is more effective in improving cognitive decline. But again, you can't draw a conclusion because clinical data is lacking. On treating Alzheimer's disease patients with pure EPA or a higher ratio of EPA. The only thing that I could really find where the EPA/DHA ratio made a difference was— is really with depression. And there was something about a better 2:1 ratio of EPA to DHA for treating depression. And there's some hypotheses that were, you know, generated from that, but I just don't know that there's any conclusions that that's the case for cognitive decline or Alzheimer's disease or ApoE4 as well.

So I think to come back to the question about does EPA or DHA ratio matter, we don't really know. So, I still think it's beneficial to get both EPA and DHA at this moment. That's where the literature has taken me to my own personal conclusion. And, you know, I do try to get both EPA and DHA into my— I supplement with both EPA and DHA. So, you know, that's pretty much my summary of that. that scientific evidence. Okay. So there were some leftover questions that I did not get to last time. This question was submitted by Bill. And Bill says, it was the July 28th, 2022 edition of the New England Journal of Medicine that published a study showing that neither vitamin D supplementation nor serum levels significantly affected bone mineral density or fractures. Could you comment on this? Yeah.

So first of all, the study didn't show that. Technically, they concluded in this randomized controlled trial, supplemental vitamin D3 did not result in a lower risk of incidental— incident total nonvertebral or hip fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. Very different conclusion than what you'll find in the media. So the trial wanted to see if vitamin D levels of 40 nanograms per mL would have any benefit over 30 nanograms per mL for bone health. It is already well known that vitamin D levels less than 30 nanograms per mL cause a decrease in bone mineral density and fractures.

The vast majority of participants already had sufficient vitamin D levels at baseline with an average vitamin D level of 30 nanograms per milliliter. These people were not deficient in vitamin D. They were sufficient in vitamin D. By the end of the study, the intervention group had a vitamin D level of 40 nanograms per milliliter. So they went from 30 to 40, which is not a huge difference, while the placebo group stayed at 30. And they found there was no real difference in bone mineral density or fracture in the group with 40 versus the group with 30. So I think the accurate conclusion of this study is that vitamin D levels of 30 nanograms per milliliter is sufficient for optimal bone health.

The way this study was sort of portrayed in the popular media was that vitamin D supplements are useless. And really, that is not at all what the study showed. In fact, most people to get levels of 30 nanograms per milliliter most often are taking a supplement because— Yeah. Of our modern-day society. We're most of the time indoors. We're not out in the sun as much. And so people are not making vitamin D. And there's a variety of factors that regulate it, age being one, body fat another, regulates the bioavailability, also where you live, latitude, right? So that is actually what the study showed. And previous studies have found that those who are at the highest risk of fractures fractures are those with vitamin D levels that are extremely deficient.

So we're talking like 12 nanograms per milliliter. In this particular New England Journal of Medicine study, only 2.4% of individuals had vitamin D levels around 12 nanograms per milliliter. And basically, they found— they did a sub-analysis and found that those individuals There was nothing they could do because it was underpowered. The study was underpowered for the low vitamin D group. There was only 15 fractures in that group, and so they just couldn't conclude anything. So ideally, to show the effect that vitamin D has on bones, you would want the study on the 2.4% of individuals with vitamin D levels of 12 nanograms per mL, you know, to— you'd have to power the study correctly. Basically, they said it wouldn't have been feasible to do that study.

So in other words, it's not ethical to do the study because it's already known that vitamin D deficiency causes poor bone health. And so they couldn't not treat someone who has vitamin D deficiency as a placebo group because it would be unethical. So I'd say in conclusion, the study did not find a difference in the rates of fracture with vitamin D supplementation because the participants in the study already had sufficient vitamin D levels for optimal bone health. I think that would be a way to state the conclusion of the study. James is asking if I have any comments on the football player who was young and collapsed on the field. I mean, you know, that's a common thing for young athletes that have undiagnosed heart conditions.

Um, I mean, it's not like, you know, it's, it's, it's— this isn't the first time that, that this has happened to a young athlete. Uh, so my comments would be that it's, it's, it is scary. The un— the undiagnosed health conditions, um, there are certain, certain ones, and I can't recall what they're called off the top of my head, but, um, that, that go undiagnosed, and you can pass a variety of physical exams And without doing this specific type of heart test, you won't know that you have this condition. And it is very scary. Okay. So there was another question about histamine intolerance and long COVID. So KRG said, hi, Rhonda, do you have any information on histamine intolerance or mast cell activation syndrome?

Lately, I've seen more and more people report they've developed one or both post-COVID, relating it to their long COVID status. So background information here. Histamine is a bioactive amine which is synthesized and stored in high concentrations in secretory granules, mainly in the innate immune cells, basophils and mast cells. It's also found in, in the gut, in the gastric enterochromaffin cells. It's in the lymph nodes and the thymus. Histamine release can be activated by a lot of different signals, exogenous triggers like allergens, toxins, and viruses. It's involved in various immune and physiological mechanisms stimulating gastric acid secretion, inflammation, smooth muscle cell contraction, vasodilation, cytokine production, lots of things. It also can function as a neurotransmitter.

So, you know, the gateway for dietary histamine is the body— for the body is the intestinal epithelium. And the enzyme diamine oxidase plays a role in protecting the body against exogenous histamine, so that would be ingested from food or maybe generated from the microbiome. Foods that are high in histamine are, you know, some examples, some vegetables, spinach or tomatoes, red wine, canned fish, processed meat, raw unpasteurized milk, cheese. So histamine intolerance is the clinical condition that describes the inability of certain individuals to degrade histamine, and so it leads to the accumulation in plasma, and it results in the onset of symptoms like abdominal distension, postprandial fullness, diarrhea, abdominal pain, and constipation, but also symptoms like dizziness and headaches and palpitations.

The clinical management is carried out mainly through a follow-up of a low histamine diet and oral supplementation with exogenous diamine oxidase. But, you know, even though histamine is often regarded as the cause of health complaints, scientific evidence supporting this clinical claim is pretty limited, and actually there's a lot of contradiction as well. So I would say robust scientific evidence and reliable analytical methods are are really needed to help define the role and impact of ingested histamine in human health and disease. So I don't know that there's a lot of real good evidence with that, even though you may hear it in the blogosphere. So COVID and histamines. There's a growing body of evidence that has implicated histamine and mast cells in COVID-19.

You know, the SARS-CoV-2 infection or virus has been shown to activate mast cells. leads to histamine release, increases IL-1 levels, causes, you know, hyperinflammation, cytokine storms, things like that. Studies suggest that the prevalence of mast cell activation syndrome in long COVID patients, suggesting that, you know, there is— this might be going on in some people that have what's popularly called long COVID. There's immune disturbance from SARS-CoV-2 infection that may lead to this aberrant mast cell activation and then, you know, contribute to allergic flare-ups and things like that. I couldn't find a study that examined, you know, it in the context of COVID but this is interesting.

So the enzyme that breaks up the histamine, the DAO deficiency, may be caused by various factors such as genetics. But also decreased DAO excretion was reported in diseases, viral hepatitis being one, which, you know, it damages the intestines. The intestinal tract with high expression of ACE2 is also a site for COVID-19, right? So SARS-CoV-2 virus infects the intestinal tract as well. There are uncontrolled viral infections that can induce cytokine storms and promote a hypercoagulable state, which can lead to, you know, things like the microthrombi and stuff. But the microthrombi can actually damage the gut barrier, and that can result in a variety of things.

So there was a report from, from a lab in 2021 that found much more histamine intolerance in patients Relating to SARS-CoV-2 virus in the first 3 months, basically, of 2021, 63% of all tests showed low DAO values compared to 54% measured in the previous year. Statistical analysis showed that there was a significant difference in the third wave of COVID-19 pandemic 2021 for the DAO levels as well. You know, that's— take that with a grain of salt. There's really not much. I don't I don't know there's much conclusions that can be made from that. Vitamin D has been shown to inhibit histamine release from mast cells. In vitro studies of vitamin E have been shown to release it as well.

I wouldn't supplement with high-dose vitamin E, but— and especially with— based on an in vitro study, but you can get vitamin E from dietary sources like, you know, nuts, for example, are a great source of vitamin E. Vitamin C also has been shown in a clinical study to help with mast cell histamine release Uh-huh. Intravenous vitamin C has also been shown in a recent study in about 89 patients to help with histamine as well. Zinc is another thing that's been shown to help with histamine release. I mean, getting your proper micronutrients. There's some animal studies with omega-3 suggesting an inhibitory effect of omega-3 on the IgE-mediated activation of mast cells. Flavonoids like quercetin inhibit mast cell activation and release histamine.

So quercetin has been shown to help basically inhibit the release of histamines. A lot of that is animal work as well, so you can only say so much from that. But I think, again, bottom line is making sure you're getting enough of the good micronutrients, your omega-3, your zinc, your vitamin C, vitamin D as well. But other than that, I don't know what else to say other than there's, again, there's just, there has been some evidence that it has been associated with post-COVID syndrome. Adriana is asking what type of zinc. And I don't have it listed here, the type of zinc, but I I don't know that it really makes a huge difference, like zinc acetate. Gluconate is a good one. Those 2 have been shown, I think, in clinical studies to help. Okay, I think that's going to wrap up this Q&A.

I got through my leftover questions. I did a bunch of deep dives, got a couple of rapid-fire questions in as well. So thank you guys so much for all your support and for submitting these questions. I learn I just learn a great deal from doing these Q&As. I really, really enjoy them. Some pro tips to get your questions answered: always kind of be the early bird gets the worm. I do like to go through the questions earlier because it takes time to kind of do some of these deep dives. So when you're the first to submit questions, then more people will see them, more people will upvote them. And so That's one way to get your questions seen. We've also been going through, my team and I have been going through and trying to send you guys emails on unanswered questions.

So, you know, things that are a sentence or two, or maybe we'll just give you a couple of study links if I didn't get to your question. So I hope you guys have gotten some responses for those of you that I haven't answered your questions on these Q&As. If I didn't get to your question on the Q&A, you can also resubmit the question as well. I did make a note of a question that I was going to dive into next month from HC about N-acetylcysteine supplements and liposomal glutathione as well. So I do want to kind of look into the— I've done a literature search on that, but it's been a few years. And so I want to kind of do an update and see what's new in the literature before talking about that. So thank you guys so much, and we'll talk to you next month. Look forward to your questions and to speaking with you guys soon. So have a good rest of your month, the first month of 2023. Make it a good one. Bye.