Q&A #14: Berberine for Metabolic Health—Plus Curcumin vs. NSAIDs

Hello everyone. Welcome back to another Crowdcast. This is Crowdcast number 14. Been doing these for a while now. Before we get started, I want to mention that this, this round I ended up having questions much later than usual. So I typically archive all the questions that have been submitted for every single Crowdcast Q&A that I've done in the past. And I will pull from archived questions if, you know, if I— so if I've not addressed your question, chances are that at some point I may address it because I do go back and pull from archived questions. So with that said, this time around we do have a lot of archived questions that I'm gonna— a few, actually quite a few archived questions that are pretty good questions and relevant. I think most people are interested in hearing about.

So it kind of varies from Crowdcast to Crowdcast. In terms of which question, which questions I address. You know, I'm not. I look at the top voted ones, but they don't always get addressed, particularly if it's something I've I've really talked about in the past. So just just keep that in mind. And for people that are live right now watching, and and I do answer questions in the chat, and also. You can find a replay of this video always on crowdcast.io, but we up— we upload replays to YouTube, and we also will upload the audio to your private podcast feed. If you have not downloaded your private podcast feed, you can find that on your dashboard at foundmyfitness.com/dashboard.

That's also where you can find the replay to the video, and we also send out an email newsletter letting you know when the replay is available with links to them as well. So there's lots of ways for you to access this information after the, the live Q&A. So I'm going to start with the first question from James. And James asks, what causes vitamin D, B12, and other vital nutrients under absorption to occur as we get older? In other words, why does absorption become less efficient? What is the absorption difference between age 20 and 40, and what is the mechanism? So a common theme for many nutrients is that they're basically, you know, there is an association between older age and in a deficiency for some micronutrients.

And there's a lot of contributing factors to that, including reduced intake of micronutrients. And in the case of vitamin D, you're, you know, people are inside. We'll talk about vitamin D in a minute, but people being inside also plays a role. But there's also some association that, you know, organs are not functioning as optimally as we age. And so, for example, the stomach, may not produce as much pepsin, or the pancreas may not make as much digestive enzymes, or the skin doesn't produce vitamin D3 as well. The kidneys may not reabsorb many nutrients, and so they're lost in urine. So there's a lot of factors. Most organs are made with enough redundancy that, you know, even a decrease in efficiency in one never leads to an absolute deficiency because there's compensation. Uh-huh.

So, um, let's talk about vitamin B12. It has a unique absorption process and, uh, any problems with this absorption process can actually lead to vitamin B12 deficiency. So first, the stomach has to isolate, you know, it has to isolate it. So if it's attached to a protein, it has to be detached and using, you know, um, pepsin and different digestive enzymes and stuff. So taking proton pump inhibitors or antacids basically can decrease the amount of some of these stomach acids and that can decrease B12 absorption. In addition, the stomach also naturally produces pepsin and as we age, it produces less. So that also contributes to decreased absorption. There's also proteins that are— that bind to B12 that are necessary for absorptions.

Absorption of it, and certain things like autoimmune disorders or even gastric gastric bypass surgery can affect those proteins, and therefore it can decrease the absorption of B12. Also, things like Crohn's and other disorders of the small intestine or even celiac disease, those can also decrease B12 absorption. So basically, there's a lot of different factors that can affect. Vitamin B12 absorption in addition to age. And all these factors are affecting different organs like the intestines, like the stomach. Again, some, some, you know, pharmaceuticals can even affect it like these proton pump inhibitors. So that's all something to keep in mind. And you can get your vitamin B12 levels measured. A sublingual vitamin B12 can help bypass some of the stomach absorption problems.

So that's kind of vitamin B12 in a nutshell. Vitamin D, you guys have heard me talk about a lot. And it's really unique because— and actually, I'm quite surprised how often I'll be talking to very educated people that are not educated in the field of biological sciences, but nonetheless are highly educated. And they are shocked that the main source of vitamin D is from the sun. They think it's something you should get from your food. And so, you know, it's— vitamin D is unique in that you make it from sun. And so it's just— it's so essential for, you know, our biology that you just make it from the sun. And as we age, our skin becomes less efficient at producing vitamin D3 from, you know, upon UVB radiation exposure and turning in, you know, this form of cholesterol into vitamin D3.

So that becomes much, much less efficient. In fact, a 70-year-old makes 1/4 the amount of vitamin D3 from the sun as their former 20-year-old self. So it really becomes less efficient as we age and really suggests, particularly since our modern society is much different than, you know, our ancestral times when most most people, even elderly, used to be outside all the time. Nowadays, people are never outside, and particularly the elderly. Elderly people rarely get outside. So it becomes really essential for elderly people to take a vitamin D3 supplement. There's also, similar to vitamin B12, there's also some intestinal disorders that can affect the absorption of vitamin D3 from a supplement, like Crohn's, as I mentioned before, or celiac disease. Vitamin D3 is fat-soluble.

So people that do have difficulty digesting fats, they also could have decreased absorption of vitamin D3. In some cases, there's conditions like pancreatic insufficiency or chronic pancreatitis or pancreatic cancer. cystic fibrosis, when you get your gallbladder removed, or even certain GI infections, acute infections, those things can also decrease the efficiency in terms of absorbing vitamin D3 from foods or supplements. So that's also something to keep in mind. They're not— I mean, Crohn's disease and celiac are probably some of the most common disorders that I just, um, you know, rattled off.

But generally speaking, some individuals with those disorders certainly would have to routinely measure their vitamin— their 25-hydroxy vitamin D3 levels, which is the major stable circulating precursor of vitamin— of the vitamin D hormone. And they may also have to supplement with a much higher dose. because of the, the malabsorption issues. So the next question has to do with pregnancy, and this question was submitted by Kayla. Kayla says, I have heard chocolate or cacao has benefits in the first trimester but could cause complications in the third trimester of pregnancy. If there's any information on this topic or just a pregnancy book in general that you know about, I would love to know about it. So first of all, I will just say again, I am not a medical doctor.

I am a scientist, so I am not giving any type of medical information. I'm happy to put together information that's published in the scientific literature and communicate it to you guys, but just keep in mind that this is not medical advice. And any of this information that you want to implement, you should absolutely run by your physician, whether that's a primary care physician or your OB-GYN or whomever. So just again, keep in mind what I'm saying here is not at all medical advice. It's just information that's published in the scientific literature. And so what I found is that regarding actually— and this is something that I remember even looking into when I was pregnant as well, and I typically actually avoided most chocolates and stuff like that during pregnancy.

So the first trimester, consuming 1 to 3 servings of chocolate a week is actually associated with a lower risk of getting preeclampsia and gestational hypertension. Compared to women that didn't eat chocolate. But this was not a randomized controlled trial. This is observational studies. And as we know, there's tons of potential confounding factors with observational studies. So it's not something that I think is very, very solid, like you need to eat chocolate during your first trimester. It's just basically, you know, clearly eating 1 to 3 servings of chocolate a week in the first trimester was not associated with negative effects. It was actually associated with positive effects.

And in fact, gestational hypertension is is is something that does arise during pregnancy in some in some women. And preeclampsia is actually a syndrome that during pregnancy, where the circulation between the baby and the mother it becomes compromised, and that causes hypertension, and then leads to a loss of protein in urine and a loss of blood clotting factors and. It can put the mother and a child at risk for seriously pregnancy-related emergency complications and stuff. So it's definitely not something to take lightly. Regarding the third trimester and chocolate intake, there's been some information suggesting that we know that There's many different polyphenols in chocolate, and a lot of these polyphenols have a lot of beneficial effects.

They've been shown in randomized controlled trials. I've talked about them in the past in the brain, the heart. And, you know, in some cases, it also can, you know, be a mild anti-inflammatory in the sense where it can sort of perturb prostaglandin synthesis. And Yeah. Prostaglandins, you know, while they are inflammatory mediators, they do play important roles in biology and in normal development. So it's not something that you're, you know, it's one case where you have someone who's maybe obese and, you know, there's sort of these chronic inflammatory signals and maybe the prostaglandins are kind of chronically being activated. Um, versus, you know, wanting to constantly, you know, get rid of the prostaglandins. Like, that's not something that's good either.

Uh, so, so it's one of those extreme on both ends kind of cases. Um, in the case of pregnancy, it can, it can basically, um, disrupt a connection between the pulmonary artery and the aorta that basically causes, uh, blood to bypass the lungs. and closes during childbirth. So the concern is that, well, if there's anti-inflammatory effects of chocolate during the third trimester, can this cause closure of the infant's— that connection's actually— that connection that I just referred to, the ductus arteriosus. And so if that thing closes prematurely, you can have extra stress on the fetal heart, It can result in a wide range of complications, including a requirement for heart surgery shortly after birth. And it can also lead to mild symptoms and also respiratory insufficiency.

So this is kind of the same reason why anti-inflammatories, which are much more potent at inhibiting prostaglandins than, for example, any of the polyphenols in chocolate, that's why it's not recommended to take NSAIDs, these anti-inflammatories during pregnancy, particularly the third trimester. So there was kind of circling back to the polyphenols. One study found that in the babies of mothers who consumed more than 1,000 milligrams of polyphenols a day had significantly more ductus arteriosus constriction than those who ate less than 127 milligrams a day. Um, however, this include all— this study was including all sources of polyphenols, um, not just, just chocolate, you know. So it was like tea, um, coffee, things like that as well.

So there's definitely, I would say, a lot of potential confounding factors and, and not, you know, you're not really able to pinpoint it to just chocolate. There's been animal studies looking at higher doses of you know, cacao and anti-inflammatories that can cause the premature closure of this ductus arteriosus. But those are really difficult to translate to humans because a lot of those studies are just enormously high dose that would be almost virtually impossible to be relevant to humans. So I personally took— my personal choice was, you know, I think that, you know, eating a little bit of dark chocolate if you have a sweet tooth Maybe, you know, some dark chocolate that's really, you know, high, high, and high dark chocolate, not, not tons of sugar.

You know, a couple times a week is probably not gonna be a really bad thing. But I personally chose to, to take out most of the chocolate. I did eat some dark chocolate, but I wasn't doing the, the cocoa mixes, or I wasn't taking CocoaVia supplements. So I kind of cut out a lot of that stuff. Stuff that I usually would supplement with. And I got most of my polyphenols. I didn't do any tea or caffeine or coffee during my pregnancy at all. And most all my polyphenols came from fruits, which have been shown to be very beneficial during pregnancy. So it's an interesting— it's an interesting point. I'm glad someone asked a question about it because it is something that I did review in the literature. You know, years ago when I, when I was pregnant. So.

And sort of on a related topic in the sense that it's more relevant to women, Emily asks, does hormonal birth control prevent ovarian cancer by not allowing the release of the egg? Are there risks— are there other risks associated with hormonal birth control or the pill that women should really consider before taking it? Is there a type of birth control that is best for longevity or healthspan? So again, this is very much a personal decision, something that needs to be discussed with your OB-GYN and/or primary care physician as well. There is, you know, published scientific literature that women who have been on or have ever been on any type of hormonal type of birth control, they have anywhere between a 30% to 50% decreased risk of ovarian cancer.

And it's thought this is because when the egg is released by the ovaries during ovulation, it causes significant stress and can cause scarring of the ovaries. So, when this occurs just hundreds and hundreds of times over the course of a woman's life, there could be a theoretical increased risk of cells becoming what's called dysplastic or dysfunctional. And, you know, that could potentially in combination probably with other lifestyle factors lead to ovarian cancer. So I think that, you know, anything that does limit the number of ovulations does decrease the risk of ovarian cancer. And this includes pregnancy and also breastfeeding. Both of those also limit ovulation and they're also associated with a decreased risk of ovarian cancer.

And again, I think that it's not sort of a black and white sort of thing. This is one contributing factor. There's also genetic risks and general lifestyle risk, that there are several types of cancer associated with obesity. And the types of cancer that are associated with obesity are actually a lot of cancers that are hormonal related. So breast cancer, ovarian cancer, prostate cancer, these types of cancers are very tightly correlated with obesity. obesity is, you know, people that are obese have a much higher chance of those specific types of cancers as well as others as well. But that's also just something to keep in mind that this is ovarian cancer is not just linked to birth control. The NIH, they have a great article on the associations of oral contraception and cancer.

And it really in short, oral hormonal birth control has been actually associated with an increased risk of breast cancer and cervical cancer and a decreased risk of ovarian, colorectal, and endometrial cancer. So, this data is mostly from oral hormonal things that are affecting estrogen and progesterone, those types of oral contraceptives. And there are other types of contraceptives like the patches or the rings that have different cancer associations, but that research is much less conclusive because those sorts of contraceptives are a little bit newer than the oral contraceptives. So there's a lot larger body of evidence on oral contraceptives. Yeah.

You certainly, I think, anyone, any female that is on hormonal birth control or thinking about going on it should discuss all the potential risks with their physician. So, in addition to breast cancer and endometrial cancer, it also increases the risk of clots. In some studies, so this could be also associated. This has been associated with an increased risk in heart attacks, strokes, deep vein thrombosis, which is a clot in the veins and the legs, pulmonary embolism, which is a clot in the lungs. So the the hormonal birth control can increase the risk of blood pressure, blood pressure, and also or hypertension and. Gallstones anywhere between 15 to 20%.

So there's definitely some risks associated with taking hormonal birth control, particularly the the oral contraceptives, and there's also a small yet statistically significant effect of oral hormonal birth control on lifespan. So according to one study, taking the oral birth control for at least 5 years decreased average life expectancy by up to 22 days if taken over the age of 30, and up to 88 days if taken over the age of 40. So not a huge effect, statistically significant effect, but nonetheless worth mentioning. The authors attribute the decrease in lifespan because of increased heart attacks and strokes. The non-hormonal birth control methods such as condoms have no effect on lifespan.

And getting into other types of very serious types of birth control, it would be a vasectomy or things like that. In fact, Men that get vasectomies have an increase in lifespan. So it's been shown that men that have gotten a vasectomy have about a 15% decrease in all-cause mortality and a 24% decrease in cardiovascular-related mortality. And the reasoning for that is still not known. So again, something to discuss with your OB-GYN. If you're considering hormonal types of birth control and particularly the oral types. So Rohit is asking in the chat, what is one thing a person can do to reduce the chances of cancer? I think that pretty much anyone that's in this group is probably very interested in improving their healthspan, and that's part of the reason why they're here.

And really, I think that, you know, some of the best practices for reducing cancer risk are exercise. A consistent, you know, exercise routine is one of the really big things that's been associated with decreased cancer. Incidence. Avoiding refined sugars. If you're obese, losing weight. Obesity is a big one that's associated with increased cancer risk. Obviously, no smoking. Excessive alcohol consumption also. And with respect to food, there's been a lot of controversy and I've talked about this.

In fact, I think I talked about this in great detail in the last Crowdcast with meat consumption and cancer-related mortality, where you know there's there is an association between increased meat consumption and a higher all-cause mortality specifically for cancer in people that have any any other type of unhealthy lifestyle factor like being overweight, like being sedentary, like being a smoker, or like excess excess alcohol consumption. People that have any of those sort of unhealthy lifestyle factors, if they eat meat on top of those unhealthy lifestyle factors, they have a dramatically higher risk of cancer mortality, which ultimately means getting cancer, right? If you're going to die from cancer, you're obviously getting it. So I think some of the main, main things are to exercise.

So do not remain sedentary and to maintain a healthy BMI. And then some of the obvious things like not smoking and stuff. Of course, things like sleep, stress, those also play a role as well. So I'm going to move on to the next question, which has to do with NSAIDs, which is kind of relevant to what we were talking about with the polyphenols. in terms of the polyphenols are very, very, very mild, have very mild activity on prostaglandins. But NSAIDs, on the other hand, are very much stronger. So Peter asked about ibuprofen. He says, I believe I once heard you on Joe Rogan's podcast discussing that there are dangers to taking ibuprofen. Is this correct? If so, what What are the dangers and what would be safe alternatives?

Again, this is something to discuss with your physician, certainly not medical advice, but there are actually many bad effects associated with taking ibuprofen, certainly chronically, but even sort of sporadically. So ibuprofen, Advil, other NSAIDs, they can actually reduce the flow, blood flow to the kidney by blocking the synthesis of prostaglandins. And I was mentioning the cacao and the polyphenols in cacao, that's not going to happen. In fact, a lot of the polyphenols increase blood flow to a lot of organs. So the way these NSAIDs are working are just very, very robust. They're inhibiting an enzyme called COX-2. 2, which is responsible for making prostaglandins.

And inhibiting the blood flow to the kidney can be exacerbated in patients that are dehydrated or taking any type of, you know, medicine that— or pharmaceuticals that also are rough on the kidneys, right? So that can actually, you know, basically lead to acute kidney injury and possibly even death. Uh, so blocking the synthesis of prostaglandins, um, can be very bad for— for the kidneys. It also is really bad, uh, for the stomach. So prostaglandins promote the production of mucin along the stomach lining that protects the stomach from it— from its, uh, acidity. So mucin is really important to basically, you know, protect your stomach from the acidity that's produced in there, um, to di— digest, you know, various foods and stuff.

Uh, so— So ibuprofen blocks those prostaglandins and thus the mucin production gets reduced. And so mucus lining in the stomach can make you really susceptible to stomach ulcers. NSAIDs also have been shown to inhibit muscle hypertrophy after strength training types of exercise. So the inflammation that's generated during exercise is a positive type of inflammation. It acts as a signaling molecule to basically activate a ton of genes that are anti-inflammatory. It also activates genes that are involved in muscle growth. And so inhibiting that inflammation with NSAIDs, inhibit— because NSAIDs will do that. Basically blunts that inflammation that is generated during exercise, and therefore, you miss out on many of the exercise-induced benefits.

The other, and this is probably the thing that James— I'm sorry, Peter was referring to in his question because I did talk about this on Joe's podcast a few years ago, the risk of NSAIDs and different cardiovascular outcomes is just— it's just been growing over the years. There are several FDA black box warnings on NSAIDs regarding this stroke and heart attack risk. So there have been multiple studies that show that NSAIDs can increase the risk of heart attack and stroke anywhere from 40 to 90%. So for example, in a group of adult men who previously had a heart attack, 8% of those not taking NSAIDs had a heart attack over the observed 3-year period, where 11% of those taking an NSAID had a heart attack.

The one NSAID exception has been aspirin, which does not inhibit the COX-2 enzyme that I was referring to earlier. which most NSAIDs do. So aspirin doesn't have that same negative effect on cardiovascular outcomes. It actually is associated in some studies with a reduced heart attack and stroke. The upper limit of safety for ibuprofen for an adult is 3,200 milligrams a day. However, you can have kidney and stomach injury even taking that, you know, taking the recommended dose for too long. So, you know, I personally think the data on heart attacks and strokes has just been growing and growing, and it's bad enough that the FDA has now, you know, put out several warnings, and I just avoid it altogether and really try to not have anyone in my family take it.

At all, but you know I guess once in a while probably isn't isn't isn't going to kill you. There are other options. You know, I think you know acetaminophen is is probably something that that people take for managing pain. You know, particularly like post surgery or something where you actually still want some inflammation. Inflammation is also involved in wound healing, and so you know sometimes when you're having minor surgeries then. you know, you want the wound healing to occur. And so, you know, possibly acetaminophen would be a better alternative. That would be something to discuss with your physician.

Um, it's not an NSAID, so it doesn't have the same risks on the kidneys or stomach or heart, um, or, you know, negative— there's not negative cardiovascular events associated with acetaminophen or Tylenol. But in doses over 4,000 milligrams a day, it can cause liver injury. So Um, you know, it can have negative effects on the liver, and people with liver problems, that may be even more of an issue. Um, there are— personally, uh, I don't really get a lot of pain, um, but in the past, if I, you know, sometimes, you know, during my menstrual cycle, I'll get like a little, you know, minor headache or, you know, something like that. And, um, what really works for me is The liposomal—it's actually phytosomal curcumin that I take.

And so basically, it's curcumin that is encapsulated in in liposomes, but it's encapsulated in such a way where it's like in the center of it. And so they call it this phytosome, and it basically just bypasses some of the bioavailability issues with curcumin and makes it a lot more. Bioavailable. Curcumin does not have the strong anti-inflammatory, doesn't affect these prostaglandin synthesis pathways like the NSAIDs do. So, you know, and there's been studies that show have shown in people that taking two grams of curcumin a day was just as good as eight hundred milligrams of ibuprofen for treating. Knee pain associated with osteoarthritis.

There's been other studies as well, people with different types of osteoarthritis and, you know, their mobility improved, their inflammatory cytokine profile decreased after 1 to 2 grams of specifically the phytosomal curcumin that I mentioned. So that works well for me. So that's something that I occasionally take if I need to. And, um, you know, there's other, I guess, sources out there that people also, you know, turn to depending on what type of, you know, if their pain's something topical, you know, some people put menthol, menthol cream, um, or even capsaicin cream on there. And, um, you know, I don't know too much all about that stuff, but, um, I do know that for me, the, the phytosomal curcumin works.

And The dose I usually take is about 1 to 2 grams depending on, you know, what, what my pain is. I rarely take it, maybe once a month or once every couple of months. So David's asking in the chat, Is this NSAID risk stuff dose-dependent, occasional versus regular use? So yes and yes and no. It definitely is dose-dependent with respect to the kidney issues I was referring to earlier on. The stroke risk and heart attack risks, you know, it certainly seems to be more prevalent in, you know, the regular use, but there has also been an associated risk with even occasional use. And it's unclear if perhaps that's in, particularly in, I believe it was women even had a really high risk.

So it's unclear if there's also other interacting factors that are sort of, you know, they're basically kind of combining together and sort of causing this, this additive effect. But, you know, I think that occasional use probably is, you know, much, much, much safer than people that are, that are, you know, regularly using it. Janet's asking in the chat about Mareva, and yes, Mareva is the sort of name for phytosomal curcumin, which is what I take myself. So that's just the name for it. It's called Meriva. It's phytosomal curcumin. Right, so I'm going to move on to the next question from Kim. And Kim asked, I would love your thoughts on optimal ferritin levels for adults and what the research shows are the factors that inhibit absorption.

I've heard caffeine, polyphenols, tannins, calcium. I'm also curious what you think of organ meats in terms of optimizing nutrition and balancing that against meat consumption and cancer risk. So let's address the ferritin question. And basically within the normal range of ferritin, there's really not an established optimal range within that normal range, and supplementation stuff is not recommended. So ferritin is a molecule that stores iron in the body, and it's one of several factors for determining overall iron status in the body. In general, when iron levels in the body are high, ferritin is high, and when iron levels in the body are low, ferritin is low. However, there are circumstances when this is not true.

Things like liver failure or a systemic infection that a person has, perhaps even iron poisoning or some other type of really chronic illness. could just kind of disrupt that relationship. And the normal, quote unquote, normal levels of ferritin really vary a lot by lab and institutes, physicians. So looking at, for example, the Mayo Clinic, they use a range of 20 to 500 nanograms per milliliter for males. And 20 to 200 nanograms per milliliter for females. So less than 20 suggests a person has iron deficiency or anemia, and you know that can often present with you know fatigue, chronic fatigue, tiredness. On the opposite end of the spectrum, too high levels of ferritin can suggest. Potentially an iron overload, also known as hemochromatosis.

And it, you know, that's something that can definitely be very dangerous. There's a lot of genes that test for that. Many people that have done like 23andMe or AncestryDNA genetic tests and have used our genetic report probably have seen whether or not they have those genes. But one of the really best and significant ways of getting rid of excess iron is actually donating blood. You know that, you know that's basically probably one of the best ways, which is really interesting because it relates to another question we're going to address later about aging lifespan and. Donating blood and/or plasma, reducing or diluting the plasma concentration. Anyways, that's— we'll get to that in a little bit.

So people that actually do have iron deficiency, you know, or anemia, supplementing with iron is recommended. And, you know, there are some tips and tricks to improve the absorption. If we're talking about iron coming from food, red meat, you know, contains iron and hemoglobin, it really has the highest bioavailability of iron. Um, supplementing with iron, you know, without eating meat is also very possible as well. Um, the, the bioavailability of iron in hemoglobin, so in red meat, is between 20 to 30%, whereas taking a supplement, um, the bioavailability is only 1 to 10%. But vitamin C is probably one of the major things that increases the absorption of iron.

So, so basically you can take a non-absorbable type of iron, which is ferric iron, and you can convert that to what's called ferrous iron, which is the absorbable kind. And that happens with vitamin C. So, you know, taking a vitamin C supplement with iron dramatically increases the bioavailability, or eating it with vitamin C, you know, foods that are really high in vitamin C like, you know, red bell peppers. I think guava and papaya are really high also. Many different fruits are pretty high in vitamin C. Iron's also better absorbed when the stomach is more acidic. So people taking again antacids or proton pump inhibitors, they're probably gonna have more of an issue absorbing iron, particularly if they're taking an iron supplement.

Caffeine also decreases the bioavailability of iron due to a molecule in in coffee. I guess it's not caffeine; it's coffee itself, not caffeine. Coffee decreases the bioavailability because of a molecule in in iron called chlorogenic acid, which has some benefits as well, but it does. It does decrease the bioavailability of iron anywhere, you know, up to, you know, 60 to 90%. So it really can be quite bad to be drinking coffee and then taking your supplements. And if you're, you know, anemic, for example, and you're taking your iron supplements, um, phytic acid, tannins, oxalates, those things also decrease iron bioavailability. Um, you know, so, so people that are on a plant-based diet, their iron is bound to, to phytic acid or phytates, which, um, you know, limit the bioavailability.

And so people need to eat, um, you know, up to 3 times the serving of what the RDA is for iron, um, to, to get, uh, that actual amount, um, if they're only getting it from plants. Yet again, vitamin C does increase the absorption and Um, you know, spinach is pretty high in iron. Um, again, it's not as bioavailable as red meat, but if you're eating spinach salad with some red peppers, that helps because red pep— red bell peppers are very high in vitamin C. So now the next question has to do with exercise, and it was submitted by Brett. And Brett asks, hello, I frequently exercise and have been doing mostly aerobic exercises for years. Recently, I have added resistance training to maintain muscle mass and have read not to combine weight training and cardio in the same session.

He says, I would be interested in your thoughts regarding this issue. So let's talk about the research. It's really difficult to generalize because exercise, you know, there's so many benefits to exercise, and there's also a lot of benefits that are also dependent on people's fitness level, their age, types of exercise, which muscles are, you know, working out and things like that. Um, but, you know, when there is conflicting data, it's really important to kind of look at all the studies and sort of meta-analyses and look at the methods and sort of see You know, what, what the, what, what the body of evidence seems to suggest. And, um, it really seems as though some people do suggest that there should be, you know, a 6-hour separation between aerobic and strength training exercises.

Um, But I'm not sure it's really that important, to be honest. You know, I think I really like— I personally don't do that. And I do think also getting in the sauna or any type of heat stress, it has— it's affecting a lot of the molecular pathways involved in maintaining muscle mass and in muscle growth. And I think that, you know, combining the cardio with the sauna and the strength training, I think there's a really great, you know, sort of synergy between all of those things. So, I mean, people that are super concerned, you know, maybe you can separate 6 hours between your aerobic and strength training. If you— if that's something that you can do, like I personally, time-wise, like, I need to kind of like, you know, I try to like get stuff done.

And, you know, sometimes I'll like lift some weights 10 minutes after I finish a cardio, like, I'm not going to stop doing that. And it's certainly, I think stopping doing that would be, you know, less beneficial for me. So I just don't think that's something people should be super concerned about, honestly. That's, that's the bottom line. I think there's just too many, too many confounding factors in, in some of these studies and methodologies and things like that to give a definitive answer that it really is best, in my opinion. So Joanne's asking, does running in the hottest part of the day confer some of the benefits of sauna use? So there have been some studies looking at endurance exercise in hot and humid environments and heat, how, you know, being heat acclimated helps with that.

But yeah, there is, there is, you know, an effect of of, um, you know, activating the, the heat shock proteins, which are already activated from exercise alone. But, you know, sort of doing that in the hot environment, um, may do that more robustly. Um, and you may get, you know, the sweating happens and all that, you know. It can be dangerous as well. So that's something to, to really keep in mind. You don't want to, you know, dehydrate. Um, but I mean, that's also kind of like hot yoga, right? Hot yoga sort of Uh-huh. Tapping into that as well where you're— where you're doing the yoga which already can be quite challenging, um, and then you're adding the heat on top of that.

So, um, you know, it— it— definitely something to keep in— in mind is— is the, you know, exhaustion and, uh, particularly if you're not heat acclimated. So heat acclimation is something that I would say is important. So doing a little bit of that. You don't just start out— don't just start out running out in the hottest day and like you know, Arizona in the summer. So you might want to like go out and do something like for 5 minutes, you know, and then work your way up to 10 and then maybe work your way to 15 and so on. Also, you would probably get— make more vitamin D, but also you'd be exposing yourself to more, you know, potential DNA damage as well. So that is— that's also something to keep in mind. So, the next question was interesting.

I learned something from— I didn't— I remember looking into this compound years ago when I was a graduate student. In fact, I think I even supplemented with it. And so it was kind of nice to kind of refresh my memory. This question was submitted by Christina, and Christina asked, what are your thoughts on pycnogenol, a standardized extract from the bark of the French maritime pine, which consists of phenolic compounds, condensed flavonoids, and phenolic acids? Do you think the scientific evidence for this supposed antioxidant and anti-inflammatory effects are strong? Studies have reported improvements in conditions, a wide range of conditions. So let's talk a little bit about pycnogenol.

So the mechanism underlying most of its health benefits seems to be mediated through its antioxidant, you know, its activation of antioxidant pathways and its ability to increase circulation via nitric oxide. So, surprisingly, there've been several clinical studies looking at pycnogenol, but the problem is these studies are mostly small and many of them are open-labeled and not randomized placebo-controlled studies, which really opens Pandora's box to placebo effect. We can talk about some of these studies, but I think in general, my overall review is that these studies need to really be confirmed in placebo-controlled studies that are randomized to really know if there is a significant effect.

So there was a small clinical trial found that pycnogenol could lower fasting blood glucose level and could also improve eyesight in people with type 2 diabetes that had retinopathy. There's a handful of studies that have looked at pycnogenol and cardiovascular risk. So it's been shown to decrease the risk of clots and blood pressure and also improve cholesterol in some small clinical studies. There's been some meta-analyses of clinical trials where patients had decreased blood pressure, both systolic and diastolic blood pressure. And if you look at those meta-analyses and only look at the randomized double-blinded placebo-controlled studies, there really wasn't actually a significant effect on blood pressure. Again, sort of just highlighting the importance of placebo-controlled trials.

Pycnogenol was also found to reduce serum levels of leukotrienes, which are some inflammatory mediators that are associated with asthma. Leukotrienes are also really significantly reduced with omega-3 fatty acids. In fact, omega-3 fatty acid supplementation in placebo-controlled trials in children have been shown to reduce um, a variety of, of, uh, asthma symptoms. There was a placebo-controlled trial with osteoarthritis showing that pycnogenol could, um, reduce pain. It reduced the C-reactive protein levels better than placebo, and it also decreased the amount of NSAIDs that people had to take. Which sort of nicely overlaps with the NSAID question we had earlier with people asking about other alternatives.

You know, I mentioned for myself, I take the Meriva, which is the phytosomal curcumin, but there have been other studies. For example, this pycnogenol seems to be something that have worked in at least one placebo-controlled study in people with osteoarthritis. Um, there's been some— I mentioned that the, um, the pycnogenol does affect nitric oxide, um, and there have been some studies showing that it can help men improve erectile dysfunction, um, quite, quite a significant effect with erectile dysfunction. In fact, men taking pycnogenol had 80% improvement compared to 5% of men that were just taking the control, placebo control. So there seems to be an effect on erectile dysfunction, which suggests blood flow may be improved.

With respect to the blood pressure studies, it could be, you know, that there is still an effect, but just we need larger randomized controlled studies to really kind of tease that out. So in general, I think that you know there's there's a handful of double-blind randomized controlled studies that show improvements for some some things. It seems very interesting overall, but I think much more research is needed before I start to supplement with it. You know, but it's something that. Something to kind of keep, keep our eyes on, or I'll keep my eyes on. You know, hopefully some more studies will come out on that. So, Eman was asking in the chat, any tips for heat acclimation?

So, heat acclimation, you know, being, being acclimated to higher, you know, ambient temperatures and higher elevated, you know, core body temperature can happen through a variety of different modalities. Probably one of the most ubiquitous ones is exercise. The more a person, particularly cardiovascular exercise, but also strength training, the more person's elevating their core body temperature, the more frequently they're doing it, the more they sweat, the more you're, you're elevating your core body temperature, the better you become at handling that elevation in core body temperature. And that in itself is what heat adaptation or heat acclimation is. So sauna also induces, you know, heat adaptation.

So, so like, for example, if you take a person that's never been in the sauna, the first time they go into 180 degrees Fahrenheit sauna, they're not going to be able to stay in more than 5 minutes, probably, particularly if they're not someone that's physically active. Someone that's physically active may be able to stay in longer the first time. But the second time you take them in the sauna, they may be able to stay in there for, you know, 7 or 8 minutes. And then the third time they can stay in 10 or 11 minutes because they become acclimated to the heat, they're adapting.

And so what happens with these adaptations is that you get into the hot environment or your core body temperature starts to elevate regardless of the ways, either because ambient temperature being hot or because you are physically active and making your— you're elevating your core body temperature. You're starting— when you're acclimated, you start to sweat at a lower core body temperature. So you start to cool off quicker. You know, you have all sorts of increased blood flow, things like that start to happen earlier. Your heart is able to deal with the stress of it, you know, earlier and better as well. So I I think that the adaptations happen with the more exposures you have.

And certainly, frequent physical activity is a really good one, frequent sauna use, hot baths, and perhaps even training in more of a hot sort of environment, whether that's Bikram yoga or running outside in the South or Arizona or wherever. wherever you are that's hot in the summer, um, or whether it's running or training indoors with a sauna suit, um, all sorts of things like that can help. Mindy Wallace is saying in the chat, Rhonda and her team are awesome. I'm so grateful for their research and interpretation for us. Thank you, Mindy. I'm glad you're enjoying the answers to this question that me and the team have put together. So let's move on to the next question, which will be a very short question. It's more of a rapid-fire question.

The question was from Marianne, and Marianne asked, does taking melatonin supplement stop the pineal gland from naturally producing melatonin? To the best of my knowledge, no. Taking a melatonin supplement does not affect the pineal gland for producing melatonin. I can't find anything in the literature to suggest this. And another reason why I really don't think that even the fact that the literature— there's nothing in the literature to suggest it, Just knowing that you know food itself, tryptophan, which is in a variety of foods, it's an amino acid, and tryptophan gets metabolized in the gut. It gets metabolized. So tryptophan, lots of things happen to tryptophan when you when you eat. You know, for example, like meat or something that has you know a higher concentration of tryptophan.

The tryptophan can be transported, go across the blood-brain barrier and be transported in the brain. That's one thing. And in the brain, it gets converted into serotonin, a neurotransmitter. The majority of tryptophan is actually metabolized to serotonin in the gut. And in the gut, the serotonin then can be metabolized into melatonin. So in fact, the largest pool of melatonin in the body is not in the pineal gland, it's actually in the gut. So you're constantly making melatonin in your gut, which is also like if you're taking a melatonin supplement, you know, that sort of same thing is happening as well. You know, so I don't think that makes sense from an evolutionary perspective.

If you are already naturally making a lot of melatonin from, you know, precursors like tryptophan from ingesting it. Uh, you know, I don't, I don't know why your body, why evolution would have, you know, biology would be made in such a way that would stop your pineal gland from making, uh, melatonin because you'll be, you'd be eating these foods, you know, forever. So it just wouldn't make any sense. Nonetheless, it's definitely a question that many people have. So Lance is asking in the chat, if I have eaten a few hours before the sauna, I find it harder to stay in the sauna for 20 minutes. But when I have eaten, when I sort of go in there more fasted, it's easier to stay in there. Yeah, I think everyone's sort of different.

I personally, I certainly don't like to eat like right before getting in the sauna as well. So, you know, and that's the same goes for exercise. Like, you know, the sauna is mimicking moderate aerobic activity. So in a sense, you know, I think most people have figured out that eating right before going for a run or something is just like terrible. And the same kind of goes for the sauna, I think. So I'm gonna move on to the next question, which was submitted by Alex. And Alex asked about erythritol, which is a non-caloric sweetener that's found in many different foods and drinks, beverages, treats, things like that. Mm-hmm. And Alex wants to know, are there any side effects long-term or to the gut microbiome in taking erythritol?

So I know we've talked about a variety of non-caloric sweeteners and the effects on the microbiome in the past on our Crowdcast chats. Many of these no-calorie sweeteners are not absorbed in Yeah. The small intestine. And so, they basically travel intact through the intestines and they make their way to the large intestine and the colon where the microbiome, majority of the microbiome is. And, that is why some non-caloric sweeteners can have effects on the gut microbiome. One in particular is sucralose that's been shown to actually have negative effects on the gut microbiome. I think the brand name for that is Splenda. I mean, I don't even know why that's still found. I mean, we've, we've moved on to like better non-caloric sweeteners, you know, with stevia and monk fruit extract.

I just don't know why we still find Like if you go into a diner and you see like the packets, you know, they've got like the yellow, which is the sucralose, and they've got the blue, which is Equal, which is like, I mean, it's just awful. You know, the, the, and then the pink one, which is aspartame. So those things, you know, they should just go away, honestly. But anyways, back to erythritol. It's unique in with respect to these not no-calorie sweeteners because erythritol is 90% absorbed in the small Uh-huh. Small intestines. So most of the erythritol will not make its way to the gut microbiome. And basically, that 90% that's absorbed basically is excreted unchanged in the urine before your body has time to metabolize it.

So about 90% of erythritol is just being excreted through the urine without any metabolism happening or absorption or any of that. I mean, it's being absorbed by the small intestines, but it's not being metabolized. So there's no effect on, you know, generally no effect on blood glucose levels or insulin levels. The 10% that does go into the small intestine, or sorry, that is not absorbed by the small intestine seems to go unmodified into the stool. That means that even though the microbiome is, uh, you know, exposed to a small amount of it, uh, in the large intestine, it's pretty likely to not have a very significant interaction. Um, so that's the, the story with the erythritol.

All right, the next question kind of takes us back to the iron question when we were talking about people with high iron. high ferritin, potentially people that have hemochromatosis, that donating blood is like one of the best ways to, to lower iron and ferritin levels in those individuals. This question was submitted from Roy, and Roy asked, could donating blood plasma also dilute your plasma In a similar manner as replacing the blood plasma like the mouse study that found diluting plasma could reverse the aging process. So, I shared this study, I don't know, about a month and a half ago. It's, in my opinion, groundbreaking and very exciting even though it's preclinical, meaning it was an animal study. Yeah. So let's kind of take a step back and talk about it.

Previous studies have found that basically what's called parabiosis or plasma exchange where you basically take 2 different organisms and you join them up so that they share a common blood supply. Basically, if you have a younger organ— a younger, for example, rodent in this case, a younger rodent and an older rodent and you hook them up so that their blood plasma and blood systems are conjoined, basically, there are effects where older— the older mice have this rejuvenation effect. And there's also been similar studies that have now shown that if you take blood from old and young organisms and transfuse them, transfuse the blood. Like, you can, you can actually reverse aging if you put young blood in old mice.

And if you put old blood in young mice, in some cases, you can even accelerate the aging. So this was very, very interesting. And it was kind of, you know, the question remained, well, what's causing this rejuvenation effect in the old mice? Like, why is there— are there factors in young blood that are responsible for the rejuvenation effect, or are there factors in old blood that are accelerating the aging? And, if you get rid of those factors from the old blood, will aging become reversed? And, I think the studies, the early studies kind of hinted that might be the case because transplanting old blood into young mice accelerates the aging.

This new study, basically, there was over a period of about 30 minutes, the plasma, what's referred to as the platelet-rich plasma, in old and young mice was replaced with saline albumin solution. This was basically to dilute the plasma and compensate for any albumin losses. That's why the albumin was added back in. So about 6 days later, the effects on muscle, brain, liver health were assessed. And what was found was that basically muscle repair was enhanced in old mice where their plasma was diluted. There was an increase in neurogenesis or the growth of new brain cells in the old mice in the hippocampus region of the brain. There was reduced fat stores and fibrosis was reduced in the liver of these old mice.

And basically, overall, the blood, the composition of the blood proteins were really more favorable. There was more tissue maintenance and improved immune responses. Basically, you know, these old mice were resembling mice that were much, much younger. And so, that is super interesting. There was no effect on the younger mice. So, diluting the plasma of the younger mice had no effect. They were just the same. So, the really— the authors of this study The Conboys, they're at UC Berkeley. They're really sort of suggesting that there's something in— something or some things plural, there may be many factors in older blood that are responsible for pro-aging effects.

And that basically essentially diluting those factors out, which is what they did by diluting the plasma, diluted those aging factors out. And so, they weren't able to have their negative effects because they were sort of diluted out, or their negative effects were dramatically reduced. And this resulted in a whole host of beneficial effects for the older mice. So, the question is, how do we do this in humans? And I mean, obviously, those are the next questions that researchers are trying to answer. And a lot of people have asked the question of whether or not donating blood plasma could or could not provide any of these rejuvenating effects seen with patient— with these mice that had their plasma diluted.

I would say first and foremost, there we have, you know, There is no evidence that diluting blood will have the same effect. You know, so it's you could theorize that it it could be possible. You know, basically, if donating plasma does reduce some of those factors that are responsible for aging, then in theory you could have potentially a rejuvenating effect effect for how long that lasts. It's not known. I think. know, there's some sort of, you know, 10% dilution of plasma with a donation of blood, and— but that's like a transient effect, you know. And so I think that it's a really good question that will be addressed, um, because it's been raised many, many times in many— you know, I've seen it, I've seen people have asked me, I've seen it online.

I know the authors are familiar with this question, and so they're probably going to address that question first in a preclinical study. But, you know, definitely very exciting research, and I will be following this research closely for sure. So, the next question was submitted by Chuck, and Chuck asked, what are your thoughts on berberine supplementation? So, before I get started on that, I will remind everyone that my team and I have recently within the past month released a comprehensive topic page article on berberine on the FoundMyFitness website. You can find that at foundmyfitness.com. You can go on the navigation bar at the top under topics and click on topics and scroll down to see the whole list of topics that we have. And berberine will be there.

So very excited about our topics pages. We have a team of scientists that work together to write these topic articles, and we also submit them. So there's an internal peer review between scientists, including myself, and we also submit it to peer review, quote unquote peer review, from experts in the field. Where we email them and they read our articles and give us any comments, suggestions. And so, our topics pages have really been— are really a great resource and we're continuing to build them and I'm very excited about them. So, if you haven't checked out the berberine topic page, please check it out.

Just because we cover a topic, by the way, doesn't mean there's any endorsement on taking a supplement if it happens to be a topic that is potentially a dietary supplement or there's any endorsement on it at all. These topic pages are meant to be unbiased reviews of the literature where people can find reliable sources of information where if someone is interested in berberine, they can find the information that they need to make a decision, you know, whether or not they want to, you know, supplement with berberine or not. You know, that, you know, so that, that's the, the goal of these topic pages is to really provide an unbiased source of information on topics. So berberine is, you know, it's an interesting compound. It's found in a variety of plants.

It's been used in a lot of Eastern medicine. Research in this compound is relatively new. I'd say a lot still needs to be learned. There's really still a lot unknown about berberine. Most of the research has been done in animals. There has also been research in there have been clinical studies as well showing that berberine could possibly affect the potentially blood glucose levels, dyslipidemia, which is abnormal blood cholesterol, and type 2 diabetes, as I mentioned, and also possibly even irritable bowel syndrome. There's been a variety of animal studies in addition looking at hypertension, neurodegeneration, and potentially effects on longevity as well. So, I'm not going to talk about all that.

Again, the topic page is very comprehensive, but I do want to kind of just talk about some of the key studies, particularly ones that have been done in humans. But before we get there, people should know that berberine A lot of people have become interested in berberine because it has similar effects to metformin, the drug that's used to treat type 2 diabetes. It activates the AMP kinase pathway, AMPK as it's known. And the AMP kinase pathway is a pathway that's typically activated under conditions of energy stress. So, for example, fasting, caloric restriction activates AMP kinase. Exercise activates AMP kinase. So, energy stress is a major signal for AMP kinase activation. Metformin activates it, and as does berberine. Berberine sort of differs a little bit from metformin.

It also Activates an enzyme called p38, which is involved in stress response. So it activates a variety of pathways that are anti-inflammatory, antioxidant, like NRF2 pathway is activated. So, so that's just a little bit of the similarity and differences between metformin and berberine with respect to mechanism of action. I kind of wanted people to kind of just be familiar with. Let's talk a little bit about dyslipidemia. So, there's been— dyslipidemia has been looked at in a randomized placebo-controlled trial where people were given 500 milligrams of berberine twice a day versus a placebo. And, the participants that were given the berberine Had lost they had lost weight.

There was improvements in their total cholesterol and their triglycerides, their LDL cholesterol, HDL cholesterol compared to placebo group. There was a separate study done involving about 228 people that had high cholesterol, but were basically unwilling to take statins, and so. The study looked at the effects of berberine and also another cholesterol-lowering drug and whether or not the 2 compounds together could modulate cholesterol levels. And so, the berberine was given in a nutraceutical compound that contained other nutraceuticals including red yeast rice extract and some other compounds as well. And that nutraceutical extract reduced LDL cholesterol by like 32%. Very, very robust reduction in LDL cholesterol while the cholesterol-lowering drug reduced it by 25%.

So in fact, the berberine and red rice, red yeast rice extract had a more robust reducing effect on LDL cholesterol than the actual drug ezetimibe. I'm not exactly sure how to pronounce that, but it's a drug that's used to lower cholesterol. So, that's kind of a— I think some of the most profound effects with berberine and most convincing effects so far have been with dyslipidemia. And also with blood glucose regulation and diabetes. So berberine's like been used in traditional Chinese medicine to treat diabetes for quite some time.

There's been— there was a meta-analysis of about 14 studies that compared lifestyle modification with or without Berberine, so the lifestyle medic lifestyle modifications with a placebo or with berberine, and basically the you know the berberine seemed to to have an effect, particularly with lifestyle modifications in terms of lowering blood glucose levels. Not You know, if you compare it to like other drugs like metformin or other drugs used to treat type 2 diabetes, there wasn't any— berberine didn't have a better effect than those drugs. But, you know, berberine did seem to have a very similar effect, particularly if done in combination with lifestyle factors. So lifestyle factors with berberine compared to just diabetic drugs alone like metformin or glipizide or rosiglitazone.

I think those are 2 other drugs that are used to treat type 2 diabetes. So, in other words, berberine with lifestyle modifications was able to effectively lower blood glucose levels similar to conventional medications. Although maybe the conventional medications were a little bit better, so I think that's that's also something interesting. I think a lot more research needs to be done in that area with respect to berberine. There's a potential effect on irritable bowel syndrome, but this is really just one study randomized double-blind placebo-controlled trial involving about 132 people with irritable bowel syndrome that took. 400 milligrams of berberine or placebo twice daily for 8 weeks. And the IBS patients basically experienced reduced diarrhea frequency.

They had reduced abdominal pain and they had a reduced urgency for having to go, you know, have a bowel movement. So interestingly, the patients, IBS patients also improved, had improved quality of life. So they had reduced levels of depression, which is very common in people with IBS. So I think that this sort of pilot study lays some good groundwork for future clinical trials with berberine for IBS. There really needs to be more research done, but certainly there's a good start there in my opinion. I think a lot of questions about, because there's some overlap in mechanism or mechanistic action between berberine and metformin, a lot of them have to do with activating AMP kinase and other cellular pathways that reduce oxidative damage and stress.

People are concerned whether or not Berberine inhibits exercise-induced benefits, exercise-induced adaptations that are beneficial, like metformin. So evidence suggests that metformin inhibits mitochondrial adaptations and improvements in cardiorespiratory fitness after exercise. It diminishes whole-body insulin sensitivity after exercise, aerobic exercise. There's also been some studies showing that metformin inhibits adaptations of strength training in terms of mitochondrial adaptations after strength training. So really kind of a downer for people that are physically active. And in my opinion, you know, I think, I think that people that are physically active, being physically active is a better You know, modality for healthspan improvement than taking metformin is.

And in fact, the ideal would have been oh if metformin enhances the benefits of exercise, well that would be a no-brainer. But it doesn't. In fact, it inhibits them. So not really good news for people that are physically active and healthy in terms of you know metformin being some kind of miracle longevity drug, which it's often referred to in popular media. I think that is very misleading. Anyways, the question is, does berberine also inhibit these exercise-induced benefits? And really, I think there needs to be more investigation into this area. There's just been very little. There's been one intervention study that looked at the effects of berberine on men that were sedentary but then were engaging in circuit training.

And, it actually found in these men, these men were sedentary and overweight. The men that were sedentary, overweight, doing circuit training and taking berberine, they actually had improvements in the effects of exercise. And similarly in rats, the aerobic exercise with berberine combined has been shown to actually improve, and these were actually in diabetic rats, it's been shown to improve the levels of antioxidant enzymes, improve glucose regulation as well. So, exercise to exhaustion can induce heart damage if you do this in animals, and berberine seems to attenuate those harmful effects of exercise-induced heart damage in animals. So, it's really not known whether or not berberine is going to inhibit beneficial adaptations of exercise.

I would say so far the literature suggests it's not. But it would, you know, it'd be nice to see more data on that before a, you know, a conclusion can be made, in my opinion. So Bobby is asking in the chat about side effects. Generally speaking, you know, high, high doses of, you know, berberine, you know, above, above a gram a day, you know, it's not really known whether or not super, super high doses like that, you know, are going to have a bad effect. It's possible that it could have a bad effect on the liver. It does impair the activity of enzymes that metabolize a variety of drugs, so a variety of cytochrome P450 enzymes. And so, you know, that could be something that could be considered a negative effect, but, you know, a variety of compounds can do that. Resveratrol does as well.

It certainly, it certainly, you know, is something to consider for people that are, that are taking pharmaceuticals because these, these, the, the CYP, these, these enzymes in the liver that are basically metabolizing what are called xenobiotics. So these compounds that are foreign to our bodies, not, not a vitamin or a mineral or a trace element or something, they're, they're metabolized by, you know, these, these these cytochrome P450 enzymes so that that can change the activity of them. And, you know, piperine does that, for example, and that's why people like to take piperine with curcumin because they want to increase the bioavailability of curcumin. And so, so berberine does that as well, and it could increase the bioavailability of a variety of pharmaceuticals people are taking.

So certainly is something to keep in mind. But other than that, it seems to be relatively, you know, generally safe. Some people do have GI distress if they're taking doses like 1,000 milligrams a day, even if they're spread apart like, you know, 300 milligrams 3 times a day. It still seems to can give people some GI distress. But I think the major real concern is the effect on these enzymes in the liver. And, you know, whether or not that's something to really be concerned about long-term or not, you know, it still needs to be addressed in my opinion. So the next question actually has a lot of overlap with a new topic article we're going to be releasing this coming week. On a compound called quercetin. And the question, uh, was, can you talk about quercetin as a senolytic?

Um, I think most people have heard me of recent talk about quercetin in the context of it being a zinc ionophore. Zinc requires an ionophore to transport zinc into the cell. And quercetin is a zinc ionophore and is something that can help increase intracellular zinc levels. I've also talked about quercetin recently in the context of it having antiviral activity in addition to being a zinc ionophore. There have been some in vitro studies showing specifically quercetin can inhibit the activity of certain coronaviruses, specifically SARS-CoV-1, the coronavirus that was responsible for causing the original SARS outbreak back in 2002, 2003. So quercetin is something I have talked about in the past.

It is a flavonoid that, you know, is found in foods, particularly foods that are commonly eaten are onions and apples. But a food that probably has the highest amount of quercetin is actually pickled capers, which I love to put on like my tomato caprese if I'm making, you know, some, you know, tomato caprese or, you know, smoked salmon. So, so the pickled capers are really high in quercetin. So let's talk about senolytic compound, and let's define senolytic. And you know, because some of you may not even be aware what that is, but research does indicate that quercetin may actually help treat many age-related diseases. And the topic article that we're going to release is going to cover— I'm not going to go into all that detail. I'm just going to focus on some of the senolytic research.

I'm not even going to focus on all of it. I'm going to focus on some of the senolytic research that's been done in humans because I find that to be, you know, more compelling if research has taken the next step to actually translating preclinical findings into humans. And so, senolytic compounds are compounds that can actually clear away senescent cells that accumulate with age in the body. Senescent cells have properties that distinguish them from normal cells. For example, they basically stop replicating so they can't make any new cells. So basically, they just— rather than dying, rather than dying, getting rid of the cell, the cell stays there in the tissue.

And unfortunately, it's still alive and secretes harmful compounds including pro-inflammatory cytokines that basically damage or even kill nearby neighboring cells in a tissue, you know, so within an organ. And basically, what this is known as is senescence-associated secretory phenotype, or SASP, S-A-S-P. I did a podcast a couple of years ago with the cellular senescence queen, Dr. Judy Campisi from the Buck Institute. and, um, for aging. And I really, I recommend you go back and listen to that podcast, uh, or, or view that podcast video, uh, if you haven't already, because she talks a lot about it. But, um, so senescent cells are basically, they're accelerating the aging of nearby tissues. We have fewer senescent cells when we're younger. As we get older, we accumulate more and more.

And so what ends up happening is the aging process it becomes more accelerated, right? So your aging process becomes quicker, more faster, like rapidly. It's like happening more rapidly and rapidly as you get older. And part of that is because of senescent cells, which are, in addition to other things that are going wrong, actually accelerating aging. They're actually doing something negative. So Researchers have hypothesized, you know, because senescent cells accelerate aging, that if you could clear them out of a tissue, that you, in theory, would be able to basically, you know, increase lifespan. You'd be able to reverse aging in a sense.

And so, there have been a variety of studies that have found that you You know, can if you do clear out senescent cells, you actually can increase healthspan and lifespan by up to 32%. And so that those were some some early proof of principle studies in animals that have been done. The quercetin research has been done in combination with a drug known as dasatinib, which is. An antimalarial drug that's actually often used to treat cancer. And it's been shown that quercetin in combination with dasatinib can reduce senescent cells without affecting healthy cells. So these compounds that can selectively basically clear out and get rid of senescent cells, which usually don't die, they are referred to as senolytics. So, that's why quercetin is referred to as senolytic.

Unfortunately, quercetin by itself is not able to act as a senolytic. It has to be given in combination with dasatinib. So, there's preclinical evidence showing that quercetin in combination with dasatinib can selectively clear out senescent cells, and it can improve a variety of age-related diseases in animals. And in fact, it can possibly be a way to extend healthy lifespan as well. So, based on evidence from these preclinical and preliminary clinical trials, these quercetin and dasatinib, or senolytic agents, basically can affect the body in clinically important ways.

Despite the fact that there's a relatively short half-life of these compounds like quercetin and dasatinib, you know, they basically can affect— the good thing is that senescent cells don't divide, so they're affecting the senescent cells without actually affecting healthy cells. And that's important because, you know, you're talking about dasatinib, which isn't something that I would even consider taking because it, you know, it can be toxic for sure. So basically, there's some data from a mouse study where it improved the lifespan by 36%, quercetin in combination with dasatinib. And it increased the lifespan without actually extending the period of disease or physical dysfunction. So the mice were living longer, but they weren't more decrepit as they were living longer.

So they were healthy. That's important. So let's talk about Alzheimer's disease. There have been some studies showing that, you know, the pathological hallmarks of Alzheimer's disease include amyloid beta plaques, tau tangles, reduced glucose uptake into the brain. Senescent cells have also been found in the brains of people with Alzheimer's disease. And there have been some animal studies looking at the buildup of senescent cells in the brain and how that is associated with neurodegeneration. And mice that have been given an intermittent treatment of dasatinib along with quercetin, basically it decreases neuroinflammation and can partially reverse the brain shrinkage found in these animals.

Something similar found in another animal study where the amyloid beta plaque burden was lowered and cognitive decline was slowed in animals. There's a phase 1 clinical trial underway in humans Currently trying to assess the safety of quercetin in combination with dasatinib in humans with early Alzheimer's disease. So, that's underway right now. No results on that right now. There has been a study on pulmonary fibrosis, specifically idiopathic pulmonary fibrosis, which is an age-related chronic lung disease. Where you actually have accumulation of senescent cells in the lung. And so, there's been animal studies that have found that quercetin and dasatinib can basically improve lung function because they clear the senescent cells out of the lung.

There was an open-label pilot study in humans where dasatinib and quercetin was given to a small number of participants. There were 14 participants. They were given 100 milligrams of dasatinib combined with 1,250 milligrams of quercetin, and they were given this intermittently for 3 days a week over 3 weeks. And all the participants completed the study and experienced some clinical improvements without any adverse effects. So, the participants had improved physical function so they could actually like walk far farther in their 6-minute walk test. And really, it's kind of the first study that revealed administering quercetin in combination with dasatinib in humans is feasible, safe, and actually may even have a beneficial effect on this specific age-related disease.

So, the problem is that was an open-label trial. There was no placebo control. So that that still needs to be done. There's been some studies on kidney disease, which also there's senescent cells that can accumulate in kidneys and lead to dysfunction. A variety of animal studies have shown that quercetin and desatinib can benefit you know the you know diet-related kidney disease. So this could be things including you know related to diabetes and hypertension, obesity. And that, that there's an open— another open-label study that was done in 9 adults with diabetic kidney disease. They were given 1,000 milligrams of quercetin and 100 milligrams of dasatinib for 3 days. And it did reduce the senescent cell burden in their adipose tissue. compared to baseline.

So that was, that was a, you know, a good indicator that there was an effect. Presumably, if it's reducing it in the adipose tissue, it could be reducing the senescent cells in other tissues as well, including the kidneys. The participants in it also did reduce the senescent cells in blood and skin. So again, just a good marker that the Dasatinib and Quercetin combination is having a systemic effect in multiple tissues in terms of reducing the senescent cell burden, at least in tissues that are easy to biopsy. So, and that was pretty much it for that study.

They didn't really look at much else, but I still think, you know, the preliminary findings do suggest, particularly in this case, even though it was an open-label study, the fact that, you know, biochemical biomarkers were measured, rather than, you know, feeling a certain way or changes in the way you feel, which is very, very subject to placebo. It does suggest there may be an effect, particularly since senescent cells were lower in multiple tissues, blood, fat, and skin. So, I think that there definitely are more phase— there's like a phase 2 trial specifically for the diabetic kidney disease that's that's underway. But many more phase 1 trials also have been approved for the combination of quercetin and dasatinib.

And I think it's a really, really interesting area, you know, area to investigate in terms of aging, right? I mean, specifically, you know, these studies are looking at diseases because you're always going to get a more robust effect If you have a person that has a disease, they're typically going to have a more accelerated aging type of phenotype. And so, it's good to start off when you're doing a pilot study to start off with a population of people that you might actually see a result in rather than a healthy population. But I don't think that— I mean, I think that for me, I'm excited for the possibility of it really just, you know, extending healthspan and basically, you know, reversing aging in general and affecting the aging process in general, which would have relevance to everyone.

So, I'm definitely extremely excited to follow the quercetin-dasatinib field. I've always been a little hesitant about the dasatinib because it is You know, it's something that can be toxic. It's given to treat cancer as an antimalarial, but it does seem that the intermittent you know treatment where it's given you know at a lower dose and you know it's not something that's given every single day could reduce the potential negative side effects of of you know of the desatib. So that's, uh, that's all for the questions today. Um, Roman's asking in the chat, any chance to get a topic page on pregnancy and all the supplements and nutritional measures you took yourself, as well as exercise and sauna use, um, and things that you've learned since then?

Uh, Roman, you'll be happy to know a surprise is coming very soon, um, uh, that, that addresses that topic. sort of on pregnancy. And I do have a breastfeeding— we have a breastfeeding article topic page that's live on our website now. I haven't announced it yet because I'm co-releasing— I'm going to co-announce it with a breastfeeding— basically, the biology of breast milk is a video that— a 30-minute video that I'll be releasing in a couple of weeks. It's almost done with post-production. And It's sort of the first, you know, video on mommy stuff that I'm— that we're, you know, Found My Fitness is releasing. I plan on doing some more, and I'm not going to turn into a mommy blog, I promise. But, but I, you know, I do think that child development is an important topic.

I've become more interested in it since becoming a parent, and I think that increasingly more people that are either thinking or planning on having children or that, you know, have recently had children or that are pregnant are also really interested in sort of optimizing all the conditions, you know, through dietary and lifestyle factors that are possible. So I think that, you know, those are going to— those actually are going to be future topics that we're addressing. And in fact, they're coming out, starting to come out In the next couple of weeks. And with that, I'm going to say goodbye and thank you so much for all the questions. And again, you can find the replay to this video on your dashboard, foundmyfitness.com/dashboard.

And also for people that want to listen to the audio, you can do that on your private podcast feed. And if you haven't downloaded that, again, that's also on your dashboard, foundmyfitness.com/dashboard. We'll be sending out a newsletter within the coming week with a timeline to this episode, links to some references, as well as links to the replay video. So check your inbox for that as well. And also when I send out a summary of the Crowdcast, I also submit a link to the new Crowdcast where you can sign up to submit questions. So please, please sign up and submit the questions early because me and the FoundMyFitness team like some time to go over these questions, particularly questions that are, you know, require— that are not something that I'm very familiar with.

or require a little more, you know, digging. So, so please sign up early and submit your questions. And the questions are archived. So I will be addressing questions that have not been addressed. I do address them in future episodes as I did today. So just keep that in mind that I do read the questions. And just because they aren't addressed doesn't mean that they won't be addressed in the future. Sometimes I'll read the questions and I don't have enough time to address them. And so I make a note and they're addressed, you know, in a future Crowdcast. So thanks so much, everyone. And, you know, please, please share, you know, this, the information with anyone, you know, that, you know, share the fact that we have our membership and that people can join and get these Q&As once a month, anyone that doesn't know about it. Please pass it along if you enjoy them. Thanks so much, everyone, and I will talk to you guys soon.