Q&A #42: How to Lower ApoB—and Can Hyperbaric Oxygen Improve Health?

Hello everyone. Welcome to Crowdcast number 42. December. This is the last Crowdcast of 2022. Really good questions going around on both last month's podcast and this month. Last month I didn't get to a few questions, so we're going to start off this Crowdcast with Hypobaric oxygen treatment, digestive enzymes, and ApoB. Those were 3 important questions that over the last couple of months we answered but hadn't had time to get to. So we're going to start off with those. And for those of you that are new, typically we do a few deep dive answers to questions that I've chosen that were either top voted or are questions that I think are interest to the broader community or questions that I haven't answered before, questions that I'm interested in learning more about.

So a sort of a variety of factors go into choosing the questions. I also do a variety of rapid-fire answers. So these typically come at the end of the Crowdcast. They're answers that I, you know, can do in a sentence or 2 or even less than that sometimes. So we'll get to those as well. And for those of you that your question has not been answered, you may have noticed my team and I are trying to go through unanswered questions and email people with at least some information, some sort of, you know, direction, a reference, maybe a couple of sentences. So, um, that's a new thing and I hope you guys have enjoyed that. We're really trying to get back to, to most of you guys in some shape or form. With that said, I also answer questions in the chat live.

So, um, I'll, I'll pause after, after, you know, answering a question and look at the, the live chat as well. So that's kind of the benefit of attending these live. Um, they are recorded so you can— we send out a replay video. That you can watch on YouTube along with a timeline with, you know, clickable links. And you also can listen to this Crowdcast episode on the Alaquat, which is our members-only podcast. Most of you have probably downloaded that private podcast feed, but if you have not, you can find that on your dashboard at foundmyfitness.com/dashboard. You can also just listen to it on the dashboard if you don't want to download a private podcast feed player. So many options for you guys to re-listen to these Q&As, as well as listen to our aliquots that we post almost weekly.

Those are also packed full of information. So I really suggest you guys are getting your private podcast feed, or at the very least listening to the podcast, the aliquot podcast on your Dashboard. So I'm looking here at my my my Google Doc sheet. I have 21 pages of information. So I think as I go through, you know, when I say deep dive, like we really kind of go deep. And so I'm gonna I'm gonna probably just summarize instead of like going through every single detail. Otherwise, I'll never we'll be in the situation where we never get to any any other questions again. So bear with me here. Dwight asked the question about hyperbaric oxygen therapy or treatment. So he says, have you done any more research on the health benefits of hyperbaric oxygen therapy?

So just general background, hyperbaric oxygen therapy, it's used in the treatment of a variety of conditions, medical conditions, and there are certain ones that are really the treatments like, you know, used for. So these include carbon monoxide poisoning or air embolism, poor wound healing. So I've known someone that has used it for wound healing aspects. And the wounds that respond best to hyperbaric oxygen treatment are those in which the oxygen is a limiting factor for healing. So these would be things like infections that have anaerobic bacteria. You could have something like a traumatic crushing injury, a diabetic ulcer. Bone infections, necrosis from radiation treatment from cancer, also skin grafts that are not getting enough blood flow.

So those are all really good examples of wounds that hyperbaric oxygen therapy would be useful for. The mechanism of action is— so normally the air that we, you know, breathe in is about 78% nitrogen, it's 21% oxygen, and 1% other gases. So hyperbaric oxygen therapy is useful in conditions where you actually want more oxygen or less of another gas. So for example, less nitrogen. And it, you know, it can increase the pressure 3 times to that of normal atmospheric pressure. So in cases like an air embolism or carbon monoxide poisoning or driver sickness, there's actually too much nitrogen or too much carbon monoxide gas. And so high O2 content really helps replace the high nitrogen or carbon monoxide in those cases.

But in other cases like infection, you're actually just actually wanting to kill microorganisms with the oxygen. And in cases like the skin grafts or traumatic injuries, The hyperbaric oxygen is actually—it's actually providing oxygen for cellular metabolism. So there's a lot of different ways that hyperbaric oxygen therapy can work. It's not just one way. There's been a variety of animal studies, and you know, you know, it's helped with, for example, a skeletal muscle injury in a rat model. I would say this is not. Held true for human studies that are related to injury, like exercise-induced injury, for example. I'm not going to get into all the details of this particular animal study, but essentially, it changed the immune phenotype and it helped satellite cells.

So, you know, these are stem cells in skeletal muscle. It helped make more of those. And so, you know, there was a lot of beneficial effects, but it is an animal study. And I think that you really have to take those with a grain of salt because, you know, until there's human studies on it, it's really not known whether or not it's going to translate. Again, there's really no reliable evidence that hyperbaric oxygen therapy can increase healing or recovery from sports injuries. Or recovery from exercise. Athletes kind of already have really good blood perfusion that can bring oxygen to you know the the wound or to tissues that need more oxygen.

So you know it's it's it's really hard to make an argument that hyperbaric oxygen therapy in that context is going to be even more beneficial than what you're. what you're getting from exercise. There have been some studies looking at hyperbaric oxygen therapy in the context of COVID-19. I would say, you know, it's not really been shown to improve mortality. It's not been shown to improve the need for ventilation with COVID-19 infections. So it's looked— it's currently being investigated whether or not hyperbaric oxygen therapy is beneficial for long COVID. Heart attacks or strokes and traumatic brain injury related to COVID. So that's sort of in progress. There has been a prospective randomized sham-controlled trial looking at hyperbaric oxygen treatment.

So this is 40 daily sessions in a row, so 5 days per week and over a 2-month period, and they're getting 100% oxygen. for 90 minutes with a 5-minute air break every 20 minutes. That has been showed— shown to significantly improve some aspects of post-COVID-19 condition, or sometimes called long COVID. So it was shown to improve some sexual dysfunction. It was shown to improve psychiatric symptoms. So depression, anxiety, those improved. It also helped with pain interference and some symptoms of fatigue. And, um, the, the, the beneficial effects were attributed to improved brain perfusion and neuroplasticity.

So this was a sham-controlled double-blind trial, which is good because anytime you're looking at psychiatric symptoms, things like depression, anxiety, if you think you're getting a treatment, the, you know, the placebo effect is very, very strong. And so you need a sham control. for people, you know, people that think they're getting a treatment because of the placebo effect. So in this case, there was a sham treatment. So it does strengthen the data somewhat. It was a small study. There were 37 people in the treatment group and 36 people in the control group. There's another prospective randomized sham-controlled double-blind trial looking at hyperbaric oxygen for the treatment of pediatric persistent post-concussion syndrome. This was 60 one-day sessions.

So they were— most of these are 5 sessions consecutive. So it's usually Monday through Friday. They're getting 100% oxygen. And this— in this case, it was 60 minutes for these kids and it was no air breaks. And so it was over a 3-month period. So it, it was a small study again. It was 15 people in the control group or the sham control group and about 10 people, 10 children that had mild traumatic brain injury. And their age was 6 months to 10 years old. So the hyperbaric oxygen therapy significantly improved cognitive function. It improved memory, executive function, a variety of emotional behavioral symptoms, hyperactivity. And things like that. This also correlated with improvements in brain MRI, looking at microstructural changes in certain cortical brain regions.

So the cognitive and behavioral improvements also correlated with the MRI physical, like what you're actually seeing in the MRI as well. And the mechanisms of the hyperbaric oxygen therapy in these children that had what's called persistent post-concussion syndrome. Again, this is— this occurs from a variety of different types of traumatic brain injuries. It's thought to be neuroplasticity is, is improved by increasing cell proliferation, promoting neurogenesis, the growth of new neurons, promoting neurostem cell regeneration, and regenerating axon white matter. So a lot of these studies have been done in animals. Obviously, you're not going to be looking at this sort of thing in children.

But so again, these are proposed mechanisms based on what's been shown in animal studies and based on the clinical evidence that was shown to improve by MRI, and then also the cognitive and behavioral improvements as well. I would say, like, you know, again, there's not a ton of evidence. And in fact, I'm going to talk about another study that probably is the one most people think about. And when they're, when they're thinking about hyperbaric oxygen therapy, this was a study that was a prospective clinical trial. So it was not— there was no sham control, but it was 30 healthy adults. They were, they were aged 64 and older. They, they underwent 60 days of hyperbaric oxygen therapy. Again, it was 5 days a week, 100% oxygen.

And they had it for— they were at 2 ATA for 90 minutes with 5-minute air breaks every 20 minutes. So that's sort of a pretty common protocol that you'll see throughout the literature. And in these older adults, after, you know, the 60 days of hyperbaric oxygen therapy, their white blood cells were isolated and telomere length was measured. And telomere length increased about 20%, and markers of immunosenescence decrease anywhere between 10% to 37%. So telomere length is sometimes used as a biomarker for aging, although I think nowadays, it's much less of a biomarker for aging than it was 20 years ago, 15 years ago. We know much more about telomere length. It's sort of a funny biomarker for aging because You know, things that are bad for you can increase it.

Things that are good for you can increase it. Things that are bad for you can decrease, you know, or accelerate telomere attrition. So telomere length, as we— each year as we get older, our telomeres become shorter and shorter. When they become too short within a cell, it sort of stresses the cell out, and a cell will either die or it will undergo senescence. So it's no longer really functional. But still sort of somewhat metabolically active and secreting pro-inflammatory cytokines and essentially can be, you know, accelerating the aging of nearby cells or nearby tissues, for example. So, you know, telomere length, it's one of those, in my opinion, it's one of those biomarkers in isolation doesn't mean much. It's like, huh, well, interesting, but could be not so interesting.

The immunosenescence, you know, as we age, our immune cells, Immunosenescence is also sort of very intimately linked with telomere length because, again, you know, when telomeres become critically short in cells, including immune cells, stem cells, fill-in-the-blank cell type, one of the things that happens is they do undergo senescence. And when your immune cells senesce as we age, it sort of makes us more susceptible to infection. It makes... It just— our immune system isn't working properly. And so it does sort of lead to this concept of what's called, you know, inflammaging, immunoaging. And so it's an interesting study. You know, I don't know what to make of it.

So the authors sort of speculate that the hyperbaric oxygen basically is acting as a hormetic sort of stimulus in that, you know, kind of similar to what you get from exercise or polyphenols, or in some cases intermittent fasting, where you're, you're inducing a stress and then the stress response pathways become active, and they're active to a much higher degree than what's needed to negate, you know, the, for example, reactive oxygen species that are generated from hyperbaric oxygen, which is you know, reactive oxygen species are generated from exercise, and they're also generated from hyperbaric oxygen treatment.

So they basically not only, you know, counter the reactive oxygen species generated from hyperbaric oxygen therapy, but they also are active for a longer period of time and have beneficial effects. And there's a variety of other proposed mechanisms. So... My sort of understanding looking at the literature really is, I think it's very— the hyperbaric oxygen therapy is interesting, and I'm definitely interested in continuing to follow new data that comes out. I would certainly love to see— I found the traumatic brain injury data very interesting in the children with the post-pediatric persistent concussion syndrome. I would love to see some brain data in healthy adults and healthy adults, elder adults, for example. I will say that with that said, there are risks to hyperbaric oxygen therapy.

Overall, it's generally pretty safe. But I would say that there The, the, there's a, the common side effect. So if you look in the literature, you'll see, um, middle ear barotrauma as the most common side effect. Um, it's been reported at an incidence of approximately 2% in a retrospective review. Um, and that included about 1,500 patients that were from the military population. they received a total of like 31,000 hyperbaric oxygen therapies. However, if you continue looking, you'll find other studies like a prospective study found actually the sensitivity for detection of what's called the Eustachian tube dysfunction was actually much higher than 2%.

And after hyperbaric oxygen therapy, 15 out of 33 patients, so it's 45% of the treatment group, actually had evidence of some type of this eustachian tube dysfunction. So, um, I, I do, and again, that's prob— that's because of the pressure changes. I mentioned it like, you know, 3 times, the pressure. Um, so I, I do think there's, there is a concern for ear health. And, and, and whether or not that's, you know, the studies that are looking at side effects are using sensitive assays, you know, like it all, you know, you're going to find whatever your sensitivity of the assay is. And so if you're not really using something very sensitive, then you're going to say, oh, it's not as common.

But if you're using something more sensitive that detects even maybe the slightest damage that wouldn't even be manifested, maybe that person wouldn't even know there's any sort of ear problem. But, but the damage is still, if you're, if you're measuring it with an assay that's sensitive enough, you'll, you'll see it. And that concerns me. So I think, um, for now, I don't think that normal healthy people should go out and seek hyperbaric oxygen therapy because of the potential trade-off. And we don't really know what, you know, what that risk, you know, now for someone that has a TBI, now that obviously I see the, the risk to benefit ratio would be in favor of the benefit, right?

I mean, if you have cognitive problems and, you know, problems with structural abnormalities in the brain from a traumatic brain injury, then it seems, you know, obviously beneficial. But for someone that doesn't have that, I'm not sure what, you know, if the risks to benefits are there yet. I think we just really need a lot more data on that. But Nonetheless, super interesting stuff. Okay, so the next question was submitted by KRD, and it has to do with digestive enzymes. And I have to say that this was very illuminating for me.

You know, I've always kind of been— I've sort of gravitated towards the digestive enzyme supplement being a little, you know, if you had a Venn diagram into like, you clinically relevant or really beneficial and like woo, I was sort of more like, oh, it's kind of woo, more woo. Like, I don't know if it's really that important. And I will say that my thoughts on that have somewhat changed after sort of reading some of the science out there. So the question was, hi, Rhonda, what are your thoughts on supplementing with digestive enzymes? Oxbile, betaine HCl, are they worth taking? Do they cause any issues with natural functioning of the GI system?

So digestive enzymes are produced and secreted by the GI system to degrade fats, proteins, and carbohydrates to help accomplish digestion afterwards and to help absorb nutrients. So there was a multicenter randomized placebo double-blind controlled study looking at certain digestive enzymes. So in this case, it was urusodeoxycholic acid and 6 kinds of digestive enzymes. So pepsin, papain, diastase, cellulase, pancrelipase, and pancreatin. So lots of different types of digestive enzymes. And so this is sort of a multiple digestive enzyme treatment group. The total rate of their effectiveness for dyspeptic symptoms. So this is caused by a variety of— there was a variety of different origins for the cause of this.

But basically, the digestive enzymes helped with those symptoms compared to placebo quite dramatically. In fact, 92% of the treatment group had improvements in their digestion compared to 53% in the placebo group. So when each symptom was compared, you know, there's the— so there was look at— they looked at satiety, for example, abdominal discomfort, abdominal distension. I mean, all of these were pretty significantly improved, you know, 80% in the treatment group versus 50% in the placebo group, you know, on average for most of those symptoms. So I think that Yeah. Is a pretty— and this was pretty strong evidence that digestive enzymes help with abdominal discomfort, distension, and satiety, and even anorexia as well.

A lot of people don't eat because they don't want to experience the abdominal discomfort and distension and stuff after eating. After eating. There was another randomized placebo-controlled trial, and this was in children with autism spectrum disorder, and they received a variety of different digestive enzymes, and it also significantly improved a variety of tests that are— a battery of tests that are used to, you know, for autistic spectrum disorder. So it improved their scores anywhere between 3 to 8 points. So people with autism, children with autism spectrum disorder often have a lot of GI problems, abdominal pain, distension, in some cases even like vomiting and stuff.

So again, that was a placebo-controlled trial, very important for these sorts of trials looking at placebo because placebo very much does affect, you know, the perceived outcome. Another study found that this was also— this was a double-blind crossover study. So people both got— people in this study got both treatments. So one treatment had to do with comparing the digestibility of animal protein versus plant protein with and without digestive enzymes. So it was a double-blind crossover design. And the animal protein was whey protein, which is a very fast, you know, digesting, very easily absorbable protein. And the plant protein was a combination of pea and rice protein.

I think this study is interesting and very relevant for vegetarians and vegans that are trying to aim for their I would say 1.6 grams of protein per kilogram of body weight, bare minimum 1.2 to basically prevent muscle atrophy. But if you're building muscle, more 1.6 to 1.8 grams of protein per kilogram of body weight. The digestive enzymes were protease, they were peptidases, they were bromelain, alpha-galactosidase, and it improved the digestibility of the plant proteins. And so basically, people were actually absorbing more of the amino acids from the plant proteins than they otherwise would have. And so it was a lot more comparable to animal protein. So I think that's really interesting and sort of has an immediate take-home for vegetarians and vegans.

There was another study looking at digestive enzymes for malabsorption malabsorption disorders. And there was a variety of different studies showing that there are beneficial effects from the bile acids, you know, and some of the other digestive enzymes as well. So I think overall, the evidence, at least for the clinical application, people that have You know, whatever the digestive issue is that is leading— and there's a lot of people that are undiagnosed that, like, you know, they may have something going on that leads them to distension, to, you know, abdominal discomfort, you know, which is a pretty general, I would say, symptom. But it seems as though digestive enzymes seem to help with that.

Now, with respect to the biotin or biotin HCl, that's sort of used for acid replacement in the stomach. It dissociates in the stomach into the amino acid biotin and HCl. Interestingly, it was sort of banned in 1993 by the FDA because of insufficient evidence. Banned in the sense where it's not—it's not—it wasn't, you know, being being recommended to for you know therapeutic reasons to do that to replace stomach acid. It's still like it's still widely recommended, but there's really limited evidence on it because a variety of factors. But essentially, it's it's sort of got. Side effects. Um, but it seems as though the, the, the biotin HCl may be— it may be helpful for people that are on proton pump inhibitors, so PPI therapy.

So that the side effect with, with the proton pump inhibitors is they have protein, micronutrient, or drug malabsorption. They also have slow gastric emptying, and they are— they're more prone to microbial infections in the GI tract. So it does seem to help with people on protein pump inhibitor therapy. Whether or not, like, just, you know, regular people should be taking it, I don't know that there's a lot of evidence to suggest it's that beneficial. Now, there's some other studies looking at, you know, taking the Biotin, the Biotin in, you know, independent of HDL, and it is a methyl— it is a methylation precursor, and so it has been shown in some studies to effectively reduce homocysteine levels.

So there's a meta-analysis that have shown that betaine supplementation decreases plasma homocysteine, and it can help with cardiovascular markers. So there was a systematic review and meta-analysis Okay. Showing that it— that at lower doses, so less than 4 grams per day, it can improve lipid markers, but at doses higher than 4 grams per day, it actually has the opposite effect and it can increase LDL cholesterol and total cholesterol. So it seems as though sort of a sweet spot for Biotin supplementation is more like 2 grams per day. Okay. On the lowering of homocysteine. So staying below the 4 grams per day seems to be kind of a sweet spot for that.

So overall, I think that the evidence on digestive enzymes seems to be pretty sufficient, and I haven't seen evidence— so barring the the Biotin HCl, you know, when you're just talking about like pepsin, papain, you know, pancrelipase, pancreatin, like those sorts of digestive enzymes, there's not a lot of evidence that it's really disrupting natural function of the GI system. So it seems like a, you know, a possibility for people having digestive enzymes to try and certainly finding a reliable supplement, you know, source. So, you know, that, that's obviously always the issue. But, um, I think it's pretty interesting. Some people in the chat like Steve asking about controversial studies like nicotinamide riboside. We're actually going to get into that today as well a little bit.

And I did cover it a few months ago as well in, um, in a previous Crowdcast. That I believe was, um, that was a Crowdcast. Let's see, it was in the summer, I think. But, um, I, I did cover it previously as well, but we are going to talk about it again today. All right, so the next deep dive question was ApoB. I know a lot of you guys are interested in looking at, you know— so the question was submitted by Adriana and it was, what are the best ways to lower ApoB? And then as a follow-up question, Adriana asked, how do you check for soft plaque in the arteries? And we've talked quite a bit about ApoB. For those of you wanting to look back at previous Crowdcasts, we do have on the dashboard a Crowdcast master document that has a summary of all the topics covered in our previous Crowdcasts.

I think we still need to update it for the last few, but you can search— it's searchable, so you can search ApoB, or you can search nicotinamide riboside, and you can find links to the sections where I have previously addressed or talked about that topic. So use that as a resource as well. I try not to be too repetitive. We have talked about ApoB in the past as well. But ApoB is, you know, also, you know, it's sort of a way to also measure lipoprotein particle number. It's, you know, high levels of ApoB are associated with a higher risk for, you cardiovascular disease and particular ones, you know, certain particular cardiovascular diseases. So it's really beneficial to try to lower ApoB.

Because I know Adriana was really interested in lifestyle ways to lower ApoB, we're going to cover that in more detail, but I just want to start off by saying, you know, The most, I would say, robust ways of lowering ApoB are pharmacological interventions. And so looking, probably the 2 main, I would say, common ApoB-lowering drugs are statins and PCSK9 inhibitors, with PCSK9 inhibitors lowering ApoB more significantly than statins. So statins, I think, lower ApoB. If you look at meta-analyses of trials, statins lower ApoB at about 25 mg/dL, which is quite significant, especially if you compare it to what we're going to talk about today, which is dietary ways. I mean, just, you know, you'll never get something like that. PCSK9 inhibitors lower ApoB.

ApoB by almost up to like 40 mgs per deciliter. So, um, and, um, statins of course have a lot of terrible side effects, the main one being the direct effect on mitochondria and therefore muscle, um, you know, strength, muscle myopathy basically. Um, so, uh, definitely a lot of side effects with statins. So we're going to talk about first plant-based diets. Now, it all, like, you know, you always have to look at the quality of the diet because you could have something, and this is the perfect example, this first one I'm going to talk about. If you just go, okay, animal versus plant-based diet, and you just talk about what the results are, it's important to know, well, this particular plant-based diet was mostly soy. So you're basically just substituting soy protein with animal protein.

And in this case, the effect on ApoB, the substituting of soy protein for animal protein, it lowered ApoB by about 4%. The— again, Soy, when I think of a plant-based diet, I think of a whole foods sort of based diet where they're, you know, you're getting your lots of vegetables and you're getting protein from a lot of different sources, not just soy. Another study, this was, you know, more of a plant-based diet that was raw fruits, vegetables, seeds, avocado, buckwheat, oats, legumes. So it was a lot more of the broad-spectrum vegetarian type of diet where it's a whole foods-based diet. So people on that diet lowered their ApoB anywhere— so it was about 13 mgs per deciliter.

So if you compare that to the statins, which I mentioned a moment ago, which is about 25 mgs per deciliter, Not too bad, you know, of a lowering effect. Now, do I think that that's because the saturated fat or, you know, animal protein is increasing ApoB, or is there something going on with the polyphenols and getting a lot of flavonoids, bioflavonoids, polyphenols, all these different things from just— Yeah. It's the balance between, okay, you're eating a lot of raw fruits and vegetables and you're getting a wide variety of colors. You're eating oats, you're getting beta-glucans, and we're going to talk about this all in a minute. All these different flavonoids and stuff actually do affect ApoB.

So, you know, there might be some very, very, very minimal effect of lowering saturated fat, affecting your ApoB, but there's also an effect from just taking in a variety of compounds from foods that are actually beneficial. So if you look at another study, this was a traditional Mediterranean diet, and this was a lot— very large. This was a, you know, these were— there were 551 participants in this study. It was multi-center, so across many different centers. It was a randomized controlled trial. And there were a variety of diets. So it was a traditional Mediterranean diet. So Mediterranean diets, they're typically— you're eating a lot of vegetables and fruits, and you're getting a lot of fish and poultry and a little bit of red meat.

Also a lot of olives and olive oil as well in the Mediterranean diet. Whole grains as well are included in the Mediterranean diet. So the diets were traditional Mediterranean diet supplemented with olive oil, or a traditional Mediterranean diet supplemented with mixed nuts, so getting the fats either from olive oil or mixed nuts, or a low-fat diet. And so those were the 3 types of dietary interventions. the only diet that really changed the ApoB or decreased ApoB was the traditional Mediterranean diet supplemented with olive oil. The other ones were sort of trending, but they didn't reach statistical significance. So the Mediterranean diet supplemented with virgin olive oil decreased ApoB.

by, by around 4.4%, and it also decreased the ApoB to ApoA-1 ratio by 6.2%. And there's been other studies that have found that olive oil itself, even just supplementing with 4 grams of virgin olive oil, can decrease ApoB to ApoA-1 A1 ratio, but the olive oil had to have— had to be 4 grams per day. 2 grams per day did not decrease the ApoB. So I think that, and, you know, the fact that you can just essentially supplement, like you're taking 4 grams of virgin olive oil on top of whatever your diet is, that lowers ApoB. And, you know, that in and of itself is lowering ApoB. I would say that it seems as though something in the polyphenols in olive oil are affecting ApoB. And we're going to talk about olive oil later in the Crowdcast as well. Oat beta-glucans.

So again, oats are something that are included. They were included in the vegetarian diet I mentioned earlier. They're part of a Mediterranean diet. Beta-glucans are found in oats. They're also found in mushrooms. There's some evidence that they themselves can lower ApoB by about 3.5. So taking about 3.5 grams per day of the oat beta-glucans can lower ApoB and also lower LDL cholesterol as well. So the ApoB is about 2.5% compared to control diets without the beta-glucan— oat beta-glucans. beta-glucans. So again, it's just another— and as I continue down, actually, let me just talk about the next thing before I interject my thoughts here. So I just mentioned the oat beta-glucans. There's also evidence that there's a bioflavonoid that's very high in a variety of citrus fruits.

It's called hesperidin, and it's a sugar-bound form of the flavonoid hesperidin. Hesperidin. And it's basically in oranges, it's in limes and lemons and grapefruits and in mandarins. I mean, it's just in a variety of citrus. In fact, 200 to 600— there's 200 to 600 milligrams per liter of hesperidin in in clementine, in clementines. In fact, sweet orange juice as well, like just orange juice contains it. So it's high in the citrus peel as well, like in the pie then stuff. But it really just kind of highlights that, you know, avoiding foods like oranges because you think your glucose is going to go up, I don't know that that's necessarily beneficial.

I think, and I've sort of gone all around, like I've tried, you know, I've done the continuous glucose meters for, you know, a couple of years and I avoided eating oranges and this and that. And I've kind of come full circle to realize that actually even eating the oranges seems to benefit my lipids and seems to have, you know, benefit even fasting blood glucose. And, you know, so I don't, I don't know that avoiding oats and oatmeal and oranges— I actually think that trying to eat a variety of whole foods, healthy foods that are containing things like bioflavonoids and polyphenols and these beta-glucans, and I'm coming back to that, that is beneficial for overall health. And so there have been randomized placebo-controlled trials looking at this bioflavonoid found in citrus.

Improving ApoB, improving triglycerides, improving LDL, you know. So, and there's more than one, you know, randomized controlled trial and even things, even looking at things like, you know, juice doing it. So it's just kind of, I think, there's been a really big push to, oh, we got to look low glycemic. We don't ever want our blood glucose to go up. And I get it. I think it's, you know, okay to cycle that in. And in fact, it's something that I personally, I think is— I'm leaning more towards cycling a sort of Mediterranean type of keto. But I also do eat oranges and I'm not scared of them. And I think that— and I do eat oatmeal. And, you know, so I think that— I think there's a lot of beneficial compounds in these foods.

And clearly, the randomized controlled trials are showing that is the case as well. Interestingly, zinc also seems to lower ApoB. This was a randomized controlled trial, 20 milligrams. And in this case, it was actually elemental zinc for 8 weeks. Lowered compared to placebo, it lowered ApoB and LDL. It also lowered the ApoB to ApoA-1 ratio as well. And it was sort of a, you know, so the ApoB, for example, went from 72.4 mg/dL to 67.5 mg/dL. So kind of a, you know, mild to modest effect. The effect of exercise, so there's been a variety of randomized controlled trials that have found that after a few months of aerobic exercise, the concentration of ApoB in men with hypercholesterolemia decreased.

There's a variety of controversies sort of over this as well, you know, because not all studies have shown a reduction in ApoB after exercise. So, but, you know, again, you know, exercise is— Like you're not going to go wrong with exercise. So my conclusion is, you know, ApoB, there's also been some studies showing that omega-3 fatty acids lower ApoB as well. ApoB is not easy to lower. It's really not an easy thing to lower with diet and lifestyle, but it seems as though there might be some compounding effects with a Mediterranean diet, with olive oil, with taking 4 grams of olive oil a day, with the oat beta-glucans, 500 milligrams, with the hesperidin found in— the bioflavonoid found in citrus, hesperidin.

So it just kind of goes to show you, and what else is there in these other fruits and vegetables that are doing it that we don't know? Probably other things as well. So it just kind of goes to show that all these compounds, these bioflavonoids and polyphenols and Flavanols, and I mean, these things are benefiting us in ways that we haven't even discovered yet. So I don't know that it's great to just full stop avoid them because you're afraid that eating a piece of fruit is, you know, got a little bit of sugar in it. I just— I haven't seen a study where eating fruit gives you heart disease or gives you diabetes or gives you like Alzheimer's disease. In fact, everything I've seen epidemiological study-wise is the opposite.

Of course, the epidemiological studies are riddled with problems, but, you know, you'd think that, like, if it was so bad for you, that data would show up. So the second part of this question was, how do you measure soft plaque in the arteries? So normally, the coronary arteries do not contain calcium. So a standard measure of, you know, your calcium score or CAD, Soft plaque does not contain the calcium. So it's kind of like you'd be measuring your calcium score and accumulating a bunch of soft plaque and thinking you're doing great, when actually it's like a silent killer. In fact, soft plaque is often referred to as the silent or hidden killer. It's inside the artery walls and it can cause sudden death if it ruptured.

Soft plaque rupture is responsible for up to 75% of acute coronary events. So traditionally, a cardiologist would perform a coronary angiogram. It's also known as a cardiac catheterization or catheter angiogram to check for blockages. So coronary catheter angiograms are useful in identifying plaques that cause stenosis, but they often miss soft plaque. So a CT coronary angiogram uses advanced CT technology to obtain high-resolution 3-dimensional images of the heart and coronary arteries. These images show both hard and soft plaque in the arteries. And, you know, there's specially trained radiologists that can, you know, interpret and look at the images and look at it. So I would say the answer to that question is a CT coronary angiogram. That is the way to actually measure soft plaque.

So D Lever is asking in the chat about avoiding fruit and carbs for a keto— like, that's mostly what a ketogenic diet is. Yes, that is true. That is— so, you know, there's a lot of modified versions of a ketogenic diet, but I think— and I am convinced that there are many benefits to ketogenic diets. I am leaning towards ketogenic diets that are not full of tons of saturated fat, like butter and dairy, for example. In fact, there's a question about butter, which I'm also going to get to, which— so I think the question was submitted by Isabelle and asked me if I include butter in my, you know, butter and dairy in my diet. And I have to say that it's of pretty recent that I have cut out most butter. I used to cook with butter and now I cook with olive oil.

And this was another question about brands, which I'm going to answer as well. So olive oil, I have now— I think there's just overwhelming evidence that the polyphenols in olive oil are beneficial. And I just, I think that more olive oil is better. And I used to cook my eggs with butter because it tastes better. And now I've totally switched over to olive oil. And the olive oil, I use 2 brands of olive oil. I use Amphora Nueva. And so A-M-P-H-O-R-A. N-U-E-V-A, I think it is. And they have a variety of very high polyphenol-containing olive oils. I use them. I use their amphora blend and I cook with that. It's particularly good for high-heat cooking as well. So I cook with that olive oil. And then For like salads, I mean you can use that that on salads and stuff as well.

But I do kind of like to get a variety of you know of olive oils as well. And so I use DeCarlo Arcamone organic DOP extra virgin olive oil for my salad. So that's D E C A R L O DiCarlo A R C A M O N E Arcamone and their organic DOP extra virgin olive oil. I mean, it's like you just open it up and taste it. I mean, it's chock-full of polyphenols. I mean, you can taste it. It's great. So I use those 2 olive oils and some— like, again, you can just choose one and use them, but I like to kind of get a variety of them. So I'm using less and less butter. There's some, you know, I would say some exceptions. I haven't 100% cut it out, but I use very little butter these days. I also have cut down on my dairy. Those are the 2 things that really seem to raise my LDL and my particle number.

And I just don't, I mean, I just don't find them that beneficial. You know, the calcium is one thing from the dairy that I did do enjoy. I do get a little bit of dairy. So like when I make a salad, I put a little bit of feta cheese, just a little. I may cut it out altogether. So I'm getting a blood draw in a couple of days. And again, just experimenting and see like what works best for you with your your genes and looking at your lipid profile. So I would say that, yeah, there is, you know, and Isabel submitted this question about conflicting evidence on saturated fat, and yes, there is definitely conflicting evidence. But I also just don't know that I'm so convinced that you should just eat tons and tons of butter and ghee and dairy and coconut oil and all these things.

Measure your lipids and if they look great, well, good for you. You hit the genetic jackpot. But I don't know that most people can do that. So I do think there is a benefit to substituting some of the butter and stuff with particularly olive oil. And I've shifted even— like I've talked about avocado oil in the past and that's like good. Sort of substitute for cooking oil. It is great if you're making baby foods and you don't like olive oil, especially high polyphenol olive oil has a very pungent taste that I'm not sure babies are going to enjoy. So I do— like if you're making some sweet potato fries or something, you might want to use avocado oil. But I've now sort of shifted away from avocado oil and not because I don't think avocado oil is a good cooking oil.

I just think olive oil is— I think the polyphenols in the olive oil are pharmacologically active. I think they're beneficial. There's enough evidence that has convinced me of that, that I need to get that 4 grams. I need to increase that, you know, the polyphenols from the olive oil. And so I'm just trying to use it every way I can. So the ketogenic diet question, I think there might just be good evidence also to cycle these sorts of things because I do think that's sort of how humans— I mean, before we had access to grocery stores and Instacart and everything, I mean, we did— it was the seasons, right? It was like, you know, and there is a time when you're eating more fruits and there is a time when you're eating You know, more vegetables and stuff.

And in wintertime, there's a time where you're probably eating more like a ketogenic-ish-like of diet, right? So I'm sort of coming into this idea that it doesn't have to be all or nothing, like there's a blend, because there are benefits to ketogenic diets, but there's benefits to eating fruit, and there's benefits to getting compounds that we have identified from these fruits and vegetables and oats, for example, and compounds that we haven't identified. I mean, they're little pharmacological factories. So I do think there's also an argument to be made for not limiting those types of foods and getting them as well. And so the way I reconcile it for me is, okay, Rhonda, maybe I need to just cycle. I need to do— and whatever works best for you.

Maybe it's best, you know, wintertime, like you do a ketogenic diet and then as you start to hit spring, summer, you do more of the colorful diet where you're eating a variety of whole foods that are not processed and, you know, that you're getting a wide range of flavonoids and bioflavonoids and flavonols and polyphenols. I mean, there's so many of these compounds that are beneficial. So that's kind of what I'm leaning towards. I'm going to quickly touch on the nicotinamide riboside question. So this question was submitted actually by Jazong and Mellowsteel. And essentially what they're saying is, hi Rhonda, I read that nicotinamide riboside has been implicated in some cancers, especially brain. I wonder what your thoughts are on this.

Again, I covered this in a previous Crowdcast a few months ago, and you can search the Crowdcast master document on the dashboard to kind of look at what I've said in the past on this. But nicotinamide riboside is essentially a precursor for NAD. You know, it's really important for making energy. It's important for repairing DNA damage. So one of the enzymes called PARP, PARP, essentially requires tons of it. And, you know, there often can be this competition between PARP and just mitochondria because, you know, they both require it. And so it's very important for normal aging, for normal, you know, cellular function, for repairing damage. But like anything, anything that's great for energy, cancer cells find a way to sort of hijack it and say, I'm going to use this for my benefit as well.

And so, you know, it's again one of those instances where, you know, you can't make this blanket statement and say, oh, NAD precursors are going to give you cancer. That is just— there's just not evidence of that. But I will say There have been a variety of animal studies that have come out, and a new one even, you know, more recently came out, and this was a brain cancer one. But it's not the only study that has come out linking NAD, like nicotinamide riboside, and nicotinamide mononucleotide. Both of these are NAD precursors. They're both found as supplements. They've both been hyped quite a bit. By a variety of influencers. They have been shown in animal studies to improve aging in doses that are totally irrelevant to humans.

I mean, you'd have to be mega-dosing just like bottles of this stuff to get to the same dose that you see in these animal studies where aging is improved. Human studies have shown that you can increase NAD levels in in the blood after taking particularly higher doses, but even some moderate doses of nicotinamide riboside, and also nicotinamide mononucleotide. Again, I've covered that in great detail in previous Crowdcasts, so go back and search the document, and you'll find the time points it'll take. You can listen to those— me talking about those studies in detail. The recent studies that have come out have been very specific types of cancers. And there's been some evidence that certain types of cancers like NAD+ more than other types of cancers.

Again, cancers are all like— they're all very different. And when you take an animal study and you inject them with a certain type of cancer that likes NAD+, and then you also give it you know, IV nicotinamide riboside at a dose that is just insane, it's not so shocking that would promote the cancer growth and help metastasis as well. Like metastasis, you know, cancer metastasis, NAD+ is used for that process as well. I don't necessarily think that, you know, this new study is showing that taking nicotinamide riboside is going to give you cancer. It doesn't show anything about causing cancer. Again, these animals were injected with a very aggressive type of brain cancer that likes NAD, that uses NAD to metastasize.

And so I think in that very, you know, in that specific context, you know, that taking nicotinamide riboside probably is not a good idea. There's really no clear evidence that nicotinamide riboside is carcinogenic. In other words, that it causes cancer. Things that are carcinogenic are things that typically cause DNA damage, cause damage to mitochondria, damage to mitochondrial DNA even in some cases. So, you know, these are ionizing radiation, you know, reactive oxygen species over time, you know, like— Yeah. And even at that, that's sort of carcinogenic. I mean, mutagens, when you're standing in the sun at peak hour UV with no sunscreen and you have fair skin every day, right? Like, and you're in somewhere close to the equator, right? That's carcinogenic.

UVB radiation can be carcinogenic. It can cause mutations that lead to cancer. Nicotinamide riboside is not shown to do that. Nicotinamide riboside increases NAD, and the NAD can be used as an energy source by already existing cancer cells. And so then you might make the argument, well, we don't ever know if we have cancer. And yeah, that's true. Like, to some degree, our immune system is taking care of little cancer cells that are cropping up all the time, and that's sort of one of the important roles our immune system plays, you know, but I still don't think there's evidence that taking nicotinamide riboside is going to give you cancer. With that said, I'm still cautious with nicotinamide riboside, nicotinamide mononucleotide supplements. I personally do not supplement with them.

I don't I don't like it. I think that these studies, and there's been more than one, it's not just this brain cancer one. You can poke holes in the brain cancer one. There's all sorts of, again, like I said, it's a very aggressive brain cancer. You know, it's only done in a certain number of mice and this and that. But at the end of the day, there's been other studies in animals, other types of cancers. There's been a pancreatic cancer. There's been a breast cancer type. You know, so there's, it's not just this one There's been other studies. But again, it's one of those things where it should take people that are super gung-ho about supplementing with nicotinamide riboside or nicotinamide mononucleotide, even because there's been studies with that as well.

I think it should make— it should give you pause and go, okay, well, you know, there's been a lot of hype based on animal data. Based on animal data. Okay. And here's some other animal data that is warranting caution. And so, at the end of the day, the only real clinical data that we have, most of it is just affecting NAD+. It's increasing NAD+ levels. Like, you know, there's been, like, one study where I think there was some improvements in some parameters of perhaps— I think it was metabolic function or something. Very mild, and it was people with, you know, that had some sort of metabolic dysfunction. So at the end of the day, we don't really have clinical evidence that supplementing with nicotinamide riboside is beneficial for aging or for health at all. It's based on animal studies.

And so, you know, it might be, you know, it might be one of those things where it could be beneficial or it could not be. Yeah. Yeah. It could not be beneficial, or it could just be sort of placebo. It's not doing anything. So again, I don't think that it's like— oh, I wouldn't say, oh, you definitely need to avoid it. It's going to cause cancer. There's no evidence it causes cancer at all. It's just, I think it's just more food for thought for we don't understand everything when it comes to particularly high-dosing this supplement. You may think high-dosing is great because animal studies showed it was, but, you know, perhaps there is some caution that's warranted. So those are my thoughts. Nick is asking about a few biomarkers like HbA1c.

So that's sort of a long-term biomarker for your your blood glucose levels. And what do I find a concern for myself? Mine has never really been high. So, you know, I think looking within the normal range, like if you're on the high end of the normal range, then— and honestly, I think one of the best ways to improve that is Honestly, through exercise, because it really increases the amount of glucose transporters on a variety of tissues, muscle, and even other tissues, we're learning. And so it really, like eating the fruits, eating, like it even forgives like some of the bad stuff. And so I think people that are really physically active, instead of avoiding fruits, I mean, the best thing you could do is just become physically active, right?

So if you're not physically active, Becoming physically active, I think, is one of the best things. In fact, exercise has been shown to reverse type 2 diabetes. So when you're avoiding fruits, I don't think you're solving the problem. Exercise is increasing transporters, glucose transporters, so that you're taking glucose into your muscle where it's then having an anabolic— it's having a beneficial effect. It's getting in, it's getting out of your vascular system, right? So it's actually changing your biology, the exercise, whereas avoiding fruits, I mean, maybe it's going to— I don't like— is it— maybe it's going to help your fasting blood glucose levels. Maybe it's kind of going to help.

I don't even know if it's really going to help much HbA1c, to be honest, because I think there's so many benefits of eating like flavonoids and polyphenols and things like that. Now, maybe if you're just drinking tons of fruit juice, like stopping that would benefit your HbA1c. But I just don't see a place for— if someone says, how do I improve my HbA1c? I wouldn't first and foremost go avoid fruits. Like, that is not like the thing that I think is going to move the needle. And Nick's also asking about DHA and EPA in blood. So again, Long-term omega-3 levels would be the omega-3 index, and that was developed by Bill Harris and his colleague, Von Schacke, back in 2004. And OmegaQuant is the best company to measure the omega-3 index.

And if you look at all the data published, having an omega-3 index of 8% at bare minimum or more, 8% is the minimum, is associated with a 5-year increased life expectancy compared to having an omega-3 index of 4%. So I think that, you know, you want to at least be above 8% for the omega-3 index. And that is, again, the omega-3 index is measuring your EPA and DHA in your red blood cell membranes. And so if you are starting a new supplement, If you started eating more fish, salmon, for example, then you need to wait at least 120 days before doing that omega-3 index if you want it to be reflected there, because it takes about 120 days for your red blood cells to turn over.

And so, if you did an omega-3 index and you felt— and you were, let's say you were at 6%, and you say, hey, that's not good enough. I want to be higher. then, and you increase your supplementation, you have to wait. I would wait at the bare minimum 120 days because it's not going to be reflective on your omega-3 index test. Steve is asking about the fish oil brand that I take now. I'm still taking a brand that's really only available in Norway, N-Pure 3, because I've got a big supply of it from a friend who really just is supplying it locally. But what I have looked at, so I think a really good brand is, it's by Metagenics, M-E-T-A-G-E-N-I-C-S. And this is kind of what I recommend for all my like close friends and family and stuff too. It's called OmegaGenics EPA DHA 1000.

That's a pretty good brand of omega-3, and it's in triglyceride form, which I think is a really important form to get as well. So, if you guys are looking to get a high-quality fish oil supplement, I think that would be my top choice right now, would be the Metagenics. Omega-3 EPA/DHA 1000, OmegaGenics by Metagenics. Okay. I am going to hit up some more of the rapid-fire questions. Okay. So Liz asked— Liz says, in the last Q&A, you emphasized the importance of slow-wave sleep for clearance of amyloid from the brain. I recently read people over the age of 60 get very little slow-wave sleep or stage 3 and 4 sleep.

Are we doomed to accumulate toxic compounds as a result, or can glymphatic processes be like— can, can, um, can basically you improve glymphatic clearance through other ways other than sleep? So the glymphatic system is primarily active during sleep, and so basically cerebral spinal fluid is pushed up And it gets in through the brain, into the brain. And while you're sleeping, the brain actually swells a little bit. And it really, it's literally like use like a pressure washer. You know, it's like cleaning out toxic compounds that have accumulated over the day in the brain. This could be cellular debris. It could be amyloid beta-42 fragments that do accumulate and form plaques. So it can be a variety of different toxic waste products.

And then, you know, it's a very important process for just cleaning out the brain. And sleep is the main way that that happens. And particularly during slow-wave, so deep slow-wave sleep, and that is when you're getting most of your glymphatic, you know, activation. There are animal studies that have looked at physical exercise, so forced running on an exercise wheel. This was shown to enhance glymphatic clearance and actually protected mice that were engineered to have a high amyloid beta 42 plaque burden. So exercise was essentially boosting glymphatic clearance. It was doing what the slow-wave sleep does, not as much. Slow-wave sleep is by far the best way to do it, but exercise is probably one of the best second, I would say, I would put that second to getting your slow-wave sleep.

So, and the thing is, is that actually accumulation of amyloid beta-42 inhibits slow-wave sleep. So there's like this feed-forward negative loop where the less you clear out your amyloid-beta-42, you know, peptides and plaques, then you actually— it helps you, then it inhibits you from getting And so as we age, our amyloid burden does go up, and that's partly why slow-wave sleep goes down. So exercise is really important to compensate there because it also clears out amyloid beta-42, which is known to inhibit slow-wave sleep. Omega-3 fatty acids have also shown to increase glymphatic system clearance. So I would say— Interesting. That would be number 3. So sleep, exercise, omega-3, those have all been shown to impact the glymphatic system.

So Roman asks, how does eating one meal a day, for example, dinner only like Dr. David Sinclair, affect the microbiome and circadian rhythm, or would you recommend against this? So obviously, I'm not a medical doctor, so I can't recommend anything. But I would say that outside of the context of like an obese person, perhaps overweight, using one meal a day as a strategy to lose weight, to lose fat with resistance exercise combined. Because, in fact, the podcast we're releasing on Monday with Dr. Brad Schoenfeld, we talk about body recomposition. And he says that basically, if you are in a caloric deficit, which is what 1 meal a day is, right? 1 meal a day is a great strategy for losing weight.

But if you're in a caloric deficit and you do not resistance train, up to 30% of the weight you lose comes from muscle. Like, that is really bad. That is really bad. And so people doing this one meal a day and not exercising, not doing resistance training, are really creating a big, big problem that they're not aware of, basically. I mean, it is great to lose the fat too. I mean, like, really important. But you do not want to lose all that muscle. Particularly when you're older, particularly when you're older and doing that. So I think that doing one meal a day, if you're obese and you're resistance training and you're trying to lose weight, is a good strategy to lose weight. Caloric restriction will do it.

However, I don't think that one meal a day is a good strategy for just normal people trying to improve aging. I think that's a terrible thing to do. I don't think, you know, I mean, once in a while, you can do a 24, 48-hour fast, you know, get a little bit of stress in there to clear out while you're resistance training, of course. But you want to, you know, you want to activate autophagy and perhaps even a stronger stressor where you're actually killing off some immune cells, like that's been shown with Valter Longo's, like, early clinical research that some markers of apoptosis and even markers of stem cell proliferation are active after, you know, a prolonged fast. But it's not like, you know, it's something to do occasionally and, you know, while you're resistance training.

So I don't think that doing a one meal a day is, in my opinion, a healthy aging strategy to use. I think it's a weight loss strategy combined with resistance training that can help obese people lose weight. And outside of that, I actually think that it's detrimental. It's a very big stress to be constantly starving yourself like that. Greg is asking in the chat what the second olive oil was that I mentioned that I use. So I used one, Amphora Nueva, And 2, I use DeCarlo, D-E-C-A-R-L-O, Arcamone, A-R-C-A-M-O-N-E, DeCarlo Arcamone, and it's organic. I use their extra virgin olive oil and I use that for my salad and it's really good. But again, you can just use— the Amphora Nueva is also great because you can buy their house blend, which is what I typically buy.

I've used a variety of their olive oils. Great. But their house oil blend, you can buy like half a gallon of it, and it's nice to have, like to be able to cook with it, you know, and stuff like that. So it's a little more cost-effective as well. A few more of the rapid-fire questions. So Tom asks, he says, Plants are trying to kill you, which was cited as a cited paper by Dr. Bruce Ames saying that vegetables are bad for you. I believe that you worked with Dr. Ames. Do you know why Dr. Ames would might have suggested avoiding eating plants raw and or cooked? I'm a you know and he goes on talking about potentially a carnivore diet. Let me okay. So let me just say here that first of all everything stated in that question was wrong.

So So Bruce, Dr. Ames, Dr. Bruce Ames, he was— he is my mentor. He was my postdoctoral mentor officially. He's one of my closest friends. And in fact, he's actually turning 95 in like a few days, like 2 weeks. Amazing guy. He published a paper back in, oh gosh, it was the '80s. The paper was about the reason the paper wasn't about plants are bad for you or vegetable. Like Bruce eats not like he eats like like I would say eighty percent like eighty percent of his food is coming from vegetables and fruits, and I told him that carnivore community was using his paper as as you know a resource or a reference that plants are bad for you. And he was appalled. He was mortified. I mean, he couldn't believe how it could be turned like that.

The paper that he wrote was basically showing that plants are making things like polyphenols. These are often referred to as natural insecticides by the plants because they ward off fungus. And resveratrol is an example of one. They ward off fungus and they ward off insects. So sulforaphane is another example of a plant insecticide. You know, these are compounds that are produced by plants that are warding off insects. And his whole basis of writing that paper was for people to not be so terrified of pesticides that were being used to that were being put on plants to ward off insects and fungus and stuff.

His argument was that basically, if you take a plant that is organically produced and you compare it to a plant that is not organically produced, the organically produced plant will have higher levels of resveratrol, for example, or whatever natural insecticide it uses to ward off fungus and insects. And in fact, there's an argument that would be beneficial for us because we are trying to get higher doses of resveratrol in our grapes, for example. But his point was that actually, if you look at the pesticides that are put on the plants, In most instances, if you're not the farmer applying the pesticide, then you're just getting such a small amount of it that it's actually— it's not as harmful as you think.

He was basically saying, look, plants make their own natural pesticides, and you're not scared of those. That was what he was trying to say, is that, look, you're not scared of— people at the time, back in the '80s, they didn't know that plants were making their own pesticides. They didn't know what resveratrol was or sulforaphane. They didn't know that it was actually a natural insecticide produced by the plant. In fact, I don't even know that they even knew that it was a beneficial compound for humans. His whole argument was basically that, look, plants are making their own natural insecticides and you're not scared of those. And so that was the whole premise of that paper. And it was nothing about plants are bad for you. In fact, the paper didn't say plants were bad for you at all.

They were saying— the paper was saying, look, plants are good for you. You eat these natural insecticides and they're good for you. And you're not scared of those natural insecticides. That was basically what the paper was. L is asking in the live chat, do you need a practitioner to order Metagenics? If you are ordering Metagenics direct from their website, I believe you do. If you are ordering— there are a variety of like, you know, iHerb and all these like, you know, there's so many different places that sell the Metagenics as well that do not require a practitioner code. So also Metagenics is a very common, like in your local area, if you have any sort of, you know, there's those places that do IV drips or they do like, you know, they kind of sell vitamins and stuff.

Like a lot of those stores will have Metagenics there. So you can just like walk into your local, you know, like, store that does, you know, they do vitamin IV drips. They usually sell Metagenics in stores like that as well. Gal asked a question about ketone salts. Can you share thoughts on the best way to incorporate beta-hydroxybutyrate ketones? I've been wanting to try them, but I fast in the morning and then I eat a non-keto diet, so I don't know when to have them. If I consume them in the morning, I break my fast, and throughout the day, I don't know if the carbs I eat ruin the health benefits. So great question. I think that I don't— I think they can be used in both contexts. I don't— I wouldn't necessarily call them breaking a fast, to be honest.

I, you know, so the brand that I do or that I use, I think I've talked about it before, Ketone. I've tried I've tried the ketone esters and I just, you know, I feel like the dose was just really high for me and there might be some problems with like taking a really, really high dose ketone ester all the time. Keto nutrition. Also has a lot of great info on you know ketogenic diets and resources, and you know things different types of ketone salts and stuff like that. I'm trying to remember the I can't believe I'm like blanking because you know I haven't been taking it in a while, so. For some reason, it's I'm just blanking on on the actual ketone salt that I take. It's it's the one that's Dom's wife.

I have a bunch of them I ordered, but I usually when I when I have been taking them and I actually need to get back to taking it, but I usually do it in the morning or even throughout the day. And in fact, Dom says that he kind of eats a Okay. A really sort of modified low-carb type of, you know, diet, and he supplements with these ketones, these beta-hydroxybutyrate ketone salts to, you know, to basically help elevate his beta-hydroxybutyrate. So I think you can take them in the morning and throughout the day. They're a little sweet. That's kind of— I think that's kind of why I've not been taking them as much. So, you know, take it with whatever works best for you. But like, I think taking it in the morning fasted would elevate it even more.

But even like if you're eating your foods and stuff, I think that it also helps as well. I think it's Audacious Nutrition is the company that sells the ketone salt. Yeah, it's Audacious Nutrition. Keto Start is the name of the actual ketone salt. So that's the one that I've been taking. I haven't taken it for like 2 months. I know I need to actually get back to taking it. You chose to get the Tdap vaccine right after birth. What are your thoughts on getting the Tdap vaccine and maybe the flu shot as well Preconception, or maybe even before periconception. So the the Tdap vaccine—the reason I got it—the whole point of OB-GYNs recommending it during pregnancy is that the baby gets some of the antibodies and essentially is highly protected from.

You know, getting pertussis or whooping cough during infancy, which can be extremely dangerous for a newborn to get. And so the reason I took it after birth was because I knew that I was going to be breastfeeding and that you, you do, you do trans— you basically transmit antibodies from your breast milk. to the baby. And so the baby is getting antibodies from the Tdap vaccine and is also protected somewhat, moderately protected against getting pertussis as well. Getting it preconception or periconception would have no effect on the baby essentially. When I chose to get the Tdap vaccine, After birth, I also made it required for any family member or friend that was going to see my baby, they had to have updated their Tdap vaccine, which is not hard to do.

You just go and get the shot, 2 shots. And so all our family members had to get that. And I really didn't have any friends. One friend did see the baby at like 1 month old, But she had gotten the Tdap vaccine as well. So that was my choice because I wanted to avoid getting it during pregnancy, mostly because I'm familiar with the literature showing that a strong immune response during pregnancy is associated with an increased risk of having a child with autism, particularly with boys. And I was carrying a boy. So I just didn't want to take that risk for me personally. And I'm sure many women get the Tdap vaccine during pregnancy and everything's fine.

But I just, again, was one of those, if I can eliminate the risk, and in my mind, getting the Tdap vaccine postpartum and then making all the relatives get it as well, to me felt like a safe— Alternative, my infant was not going to be in daycare as a baby either. That's another consideration. Is your child— because the breastfeeding, I would say the drawback to transmitting antibodies to your baby through breast milk is that they're only trans— it's only protecting them for a short period of time, like 1 to 2 months max. Whereas if you get the vaccine while you are pregnant, they're protected for a much longer period of time.

So for someone that knows they have to— a mother that's going to go to work and they're going to put their infant at 3 months of age into a daycare or even at 6 months of age into a daycare, I would say that— or nursery, I would say that getting a whooping cough or pertussis is a dangerous thing. And so that would be I would— the benefit-to-risk ratio might be different than what I was calculating when I was pregnant. Okay. Here's a scientific rapid-fire question from James. He said, you said epigenetic noise might not be the actual cause of aging. I was under the impression that when the Yamanaka factors are turned on, they only remove the noise that accumulates with aging, but doesn't touch epigenetic information carried down through generations.

Are there distinct layers in our epigenome? So the Yamanaka factors would have to affect the epigenetic, the epigenome in sperm cells or in the egg cells. And, you know, that is not everything that affects you know, changes our gene epigenome in our blood cells, does it at the level of sperm and egg DNA. So, I would say there's tissue-specific, you know, effects there. And so, that's the question of whether or not the Yamanaka factors are changing you know, the sperm and egg DNA. I don't think that's been shown. I think that would be something— you would have to deliver those Yamanaka factors to those tissues. And that's sort of an interesting but yet, you know, different question.

And also, like, the egg and sperm DNA, like, that's a very— I mean, that's containing all the, you know, the genetic information that's going to be used to make... You know, a zygote. It's going to be used to then, you know, form a person. And so, um, it's a lot, you know, it's definitely a tricky thing, um, because, uh, you know, the question is, can you, can you add the Yamanaka factors long enough to just make it like a young egg cell versus an old egg cell, right? Without, um, without, you know, messing things up. So James is asking a follow-up question. How is sperm and egg DNA determined? Other tissues first? I'm not sure I understand the question that much.

I think, you know, like for women, you know, for example, women, when they are in the uterus in their mother, they have all of their eggs. So essentially, when— it's really interesting because your grandmother, this is how your grandmother affects your DNA essentially. So when I was an egg in my mom's uterus, she was in her mom's uterus. It's really kind of wacky to think about, but, you know, so like exercise and all those things, those sorts of factors. Yeah. Did they smoke, for example? That affects, you know, that can affect the granddaughter essentially. For males, for boys, I mean, they're continually making sperm, right? So they're like, they've got new DNA and stuff.

That's, you know, being, you know, you're making new sperm cells like, you know, throughout adulthood and— So for a long time, actually. So yeah, it's a little different. Stephanie asked if I covered the supplements I take, that she came in late. Yeah. So I just put on the next Crowdcast. And in fact, we emailed a couple of people that asked that question last time, or we're in the process of emailing everyone that asked that question. I thought that was a really great question to cover for the first of the new year. So next month I will be covering the supplements that I currently take, particularly because a couple of those might be changing by the time we get to next month. So you guys will have an update on that next month as well. So those were the rapid-fire questions.

Very interesting questions that were submitted. I think this was a really nice and comprehensive sort of podcast episode that covered a variety of topics as well. Sandra's asking about my skincare, what I use. So I've also covered this in some previous Crowdcasts, but my main brand for skincare that I use is called Cellbone, C-E-L-L-B-O-N-E. Like a cell, like biology cell bone. They're really sort of a reasonable price, but they they use a lot of science to sort of guide their product development. I don't have any affiliate. I've been using them since 2011, so over ten years. And the main what I mainly use from them is I use their I use their face wash. I use their collagen face wash, but I also use Their their their collagen.

It's called the neutralizer, skin neutralizer, and I use a serum, and I use it as a serum on my face. They recommend you use it after you do a like a peel, and then you put it on and then take it off. But like I all the ingredients in it are so amazing that I was like this is a great you know this is a great serum to use. So it's the neutralizer. That's what I use. But I also recently started using their blue light serum. So there's a lot of new evidence now that just like the light from our— the blue light coming from our screens and stuff does affect— it's sort of like skin aging. And so sometimes I don't always put on a sunscreen when I'm in— if I'm not going outside or I'll wait to put on the sunscreen to like right before I go outside. So that's more, you know, biologically active.

And so, so I'm using this blue light serum that they make as well. And I think they're, they're, they're a great company. I really like their products as well. M. Talmadge is asking a question about mTOR, about protein and mTOR. So I did cover this in a crowdcast a couple of months ago about why I don't think protein restriction studies really translate well to humans and why I think that getting dietary protein is one of the best things you can do combined with resistance training and aerobic exercise for aging. And in fact, I'm actually going to be going on Peter Attia's podcast in February, and I'm— we're going to be discussing this topic.

So, it's one of, I would say, and actually, I think last month, if you want to go back and listen to the beginning of the podcast, I talked about this. I talked about how one of the biggest paradigm changes in science that I've had over the years has been— I really was sort of trained in the dogma that, you know, protein restriction was like best for aging and it inhibited mTOR and this was like the best way to age. But it was all based on animal studies. And I talked about this, so go back and check that podcast out if you want to listen to my thoughts on it. But again, I will be also discussing this with Peter in February because, you know, I told him it was an area that I wanted to discuss.

And I think that it's one of those areas where you hear a lot of influencers talking about low protein, let's inhibit mTOR, let's— But the reality is that human aging, so much of it has to do, you know, with maintaining adequate muscle mass. And protein is like one of the strongest signals for that. And so I just, I don't think that it's very translatable. So we will cover that. And Brian is asking if exercise is efficient to activate mTOR if you don't consume high levels of leucine. I don't think that it is. It's effective to help prevent the attrition, but I think that you really need both.

And, you know, I just— you guys are going to love this podcast that I'm releasing on Monday with Brad Schoenfeld, all about resistance training, all about the types of resistance training to do to maximize : Yeah. Adaptations. But I'm pretty convinced that the combination of protein intake plus resistance training is what's key for aging. And, in fact, there's been some human studies that have given people rapamycin analogs in the dose of, like, 1 milligram per day. And this, and they were doing resistance training. And this not only inhibited the mTOR, like the mTOR, you know, 1 arm that's sensitive to leucine, it inhibited the resistance training mTOR 2, which, you know, was a little concerning because— now, that might just be dose-dependent, right?

So, if, like, you take a much lower dose, maybe it's not the same. But, so, I'm also not convinced that rapamycin is, like, the most beneficial way for human aging either, based on all the animal studies. And I think I'm not not convinced, but I'm not convinced for sure either. So, I'm, you know, I'm going to continue following particularly the data from Matt Kaeberlein. I think the dog model is a lot more relevant for human aging. Than, you know, this mouse in a sterile environment that's not getting infectious diseases. It's not, you know, they mostly are dying of cancer. They're not, you know, falling and breaking, you know, a bone. They're not, like, being hospitalized and losing, you know, so much muscle mass that they never recover, right? I mean, all these things.

This is what takes humans down. This is what accelerates the aging process in humans is that one hospital visit, right? And muscle mass is what really protects against that. So a lot of interesting stuff coming out. So that podcast is being released on Monday. And please— oh, you guys will be happy to know that I did really appreciate and I used a lot of the questions you guys submitted. And I think I'm going to start doing that more frequently. My next podcast in January is going to be with an expert on Alzheimer's disease, dementia, the blood-brain barrier, and also ApoE4. And so I'd love to get your guys' questions. So I will send an email out to you guys as well as that approaches a little bit, you know, a little bit later.

But getting your guys' feedback on that, I think, is really— it's nice to have, you know, questions from you guys to know what you're interested in and like You know, that's something that's a little more applied. And so, so that, that really does help. Okay, you guys. Well, thank you so much for all your questions and for attending these live. I mean, this is so cool that you guys like take time to, to come to these Crowdcast Q&As. And also, thank you so much for your support, the support for the podcast and for everything that we're doing. Greatly, greatly appreciative for, for all you guys. And I really hope you guys enjoy All the podcasts and all the aliquots and Q&As and the Science Digest. The Science Digest we sent out yesterday was really good.

It covered a lot of resistance training stuff as well. So make sure you guys check that out if you haven't checked your email. We send that out every other Friday, so you get it 2 Fridays a month. And make sure you submit your questions for next month. And I look forward to answering all of them and talking about my supplement routine, among other things as well. All right, you guys, talk to you soon. Bye. Oh, have a great holiday as well. For those of you that celebrate Christmas, Merry, Merry Christmas and Happy New Year. The Crowdcast will— I think it will be on January It's usually the first Saturday of the month, but go ahead and check on the Crowdcast dashboard to see when it is. But it's coming up soon. So we'll talk to you guys in 2023. Bye. Bye.