142: Fueling Fertility: How NAD⁺ Shapes Ovarian Health and Egg Quality with Dr. Mark Ratner

So, NAD serves these two different roles. It's for energy production, and it's also for enzyme activation. Both of those roles play very, very heavily into female fertility, into ovarian health, ovarian aging, and end quality. So, when we talk about female fertility and the OOSI or the N, we really have concerns about two different aspects, quantity and quality. By listening to the Coherence Code podcast, you agree to not use this podcast as medical advice to treat any medical condition, either in yourself or others. Consult your own physician or healthcare provider for any medical issues that you may be having. This entire disclaimer also applies to any guests or contributors to the podcast. Welcome to the Coherence Code podcast, where we explore how the mind and body work together, so you can move from stress and intercomplex to clarity, calm and alignment. My name is Lauren Brown. I'm a Doctor of Traditional Chinese Medicine and a Clinical at the Therapist. And through my work, I've seen that healing happens when we remove what gets in the way, and allow the body and the nervous system to do what they're just trying to do to heal. Welcome to the Coherence Code podcast. I'm your host, Dr. Lauren Brown. And today, we're diving deeper into a topic that's become central in longevity science, and particularly today, what we're talking about fertility reproductive health. NAD. I want to know what it really does, how to raise it, and why it matters for equality and ovarian aging. Now, if you've listened to my past episodes, you know we've explored NAD, in particular, NAD recycling, inflammation, and why precursor supplements may not work optimally in everyone in a past episode. After that conversation, I had some correspondence with our guest today, Dr. Mark Ratner, and he provided detailed response about maybe not dismissing the topic, but actually clarifying several key biochemical points in challenging some of the assumptions that have been popular in the NAD space. So my guest today is Dr. Mark Ratner. He's a chief science officer of the neurologics. And it's a company that is well known for evidence-based fertility and woman's health formulations. Mark is a medical doctor. He has decades of experience in clinical practice, nutritional biochemistry, and supplementation formulations. Now, he did his undergraduate and graduate studies in nutrition at Cornell University, why he's such a good fit for the biochemistry around nutrition and supplement formulations. And as I remind you, he is an MD, and he does residency in training at the Tulane University School of Medicine. And he's someone who does read the primary literature, understands the enzymatic pathways, and builds products that reflect actual human data and not trends. And I've had Mark on the Integrated Facility Supposing twice. He's been in person in Vancouver when we held it as a speaker, and also when we did it online, I think it was back in 2021. Now, the neurologic released a product called OVA NAD+. And it combines nicotinamide riboside NR, and Mark, what's the residual light compound? How do you say it? A lot. Yeah, it's called terastil bean. Terastil bean, okay, which supports NAD production, mitochondrial health, and ovarian function. So this is why I think this conversation is going to matter, and why I wanted Mark here to have this conversation. We're always looking for ways, at least in my clinic, and the people I work with and my colleagues, we want to help our patients try to conceive, and a lot of them are in their mid-30s to mid-40s. And in this demographic, we're constantly talking about egg quality, we're talking about mitochondrial function, we're talking about ovarian reserve, we're talking about biological versus chronological age, and how all that's impacted by inflammation and metabolic health. And it seems like NAD sits at the intersection of all of these. And at the same time, the NAD world has become confusing, and honestly, a little bit of contradictory. Do you use NR NMM and AM? Do you use a recycling formula? Hey, should I do IV NADs, maybe an NAD injection, or is an oral precursor or not? Is there such a thing as a precursor overload? This enzyme, CD38, and inflammation, does it make the precursor useless? What actually matters for egg quality? So as I mentioned, after hearing my previous episode, Mark sent me a thoughtful scientific clarification around which enzymes is truly rate limiting, why some precursors outperform others, what CD38 really does, and why suppressant could be risky, and how NAD and CERT1 specifically influence oocycuality ovarian aging. So, Mark, my aim today for having you on this conversation is to help me not be confused, but also the public. And I kind of want you to clarify the actual biochemistry behind NR, NNM, NAM, and NAD production. We're going to connect it hopefully today to egg quality and ovarian aging, using what we know from current research that you've been sharing. And how do we integrate this with lifestyle and clinical support? Because NAD doesn't operate in isolation. So, all that was my intro to say, Mark, I put a lot of pressure on you today. But maybe can you share a little bit about what is NAD and how this impacts egg quality, and then we can start looking at all the products on the market and what you're offering and all the things people can do at the end to improve the quality and the chances of having healthy pregnancy take home baby. Great. Okay. So, what is NAD? NAD, nicotine, amine, adnein, dinogliotide, very long tongue twister there. It is a compound that is literally found in every cell of our body. It's a derivative of vitamin B3, niacin. And it serves really, really important functions in the cell, both in two different ways. It's got two main roles that it plays. NAD comes in two forms. It comes in an oxidized form, which we call NAD plus, and it comes in a reduced form, NADH. The reduced form, NADH, is actually what we call an electron donor. So, it's involved in a very important step in energy production in the cell. So, NADH, donates an electron and the, what's called the electron transfer chain, which produces ATP. That's the primary energy substrate of the cell. And when it does that, NADH becomes oxidized and it becomes NAD plus. And so, this is what we call a redox pair. And they, they switch back and forth between NAD and NADH, NAD plus and NADH. The other role that NAD plays besides this energy production role is an enzyme activation. NAD plus is what we call it, deacetylase, okay, another time twister, which is very important for activating certain key protective enzymes in ourselves. What are those enzymes? Well, one of them is CD38. CD38 is an enzyme that actually, when activated, it helps to activate the immune response. Another one of the enzymes that NAD plus activates is called, or it's a class of enzyme called the PARP enzymes. PARP is short for an even longer term that's even harder to remember and pronounce. But basically the PARP enzymes, which are activated by NAD plus, repair breaks in our DNA. So they're important for DNA repair. The third class of enzymes that are so important that NAD plus activates are what we call, cert-2ins. And the cert-2ins are seven different enzymes. We call them cert-1, cert-2, SiRT is the abbreviation. So cert-1, cert-2 all the way up through cert-7. These enzymes are the master metabolic regulators in ourselves. So NAD serves these two different roles. It's for energy production and it's also for enzyme activation. Both of those roles play very, very heavily into female fertility, into ovarian health, ovarian aging, and egg quality. So when we talk about female fertility and the OOSI or the N, we really have concerns about two different aspects, quantity and quality. We know that as women age, they have fewer and fewer eggs left. We can get into that discussion a little bit more deeply. We also know that as women age, the quality of those eggs, by which we mean the chromosomal quality, whether not the proper number of chromosomes or present in the egg that they produce that month, that goes down as they age as well. And so there is a really growing body of evidence that by enhancing NAD activity in the ovary and Certuin I activity, the first Certuin enzyme, by improving both of those, we can improve both equality and equality. And so some people will use the term that it can rescue ovarian aging. There is one paper that said it reverses ovarian aging, but I think that's an overstatement, okay, to say that it actually reverses ovarian aging, meaning it produces new eggs that aren't already there in the resting, in the follicular state. That's never been shown, but can it slow the process of ovarian aging? I think there's a good reason to think that that is the case. Do you think though, this is just in the topic in general about this ovarian rejuvenation that you shared? If there's a lot of noise in the system, inflammation, metabolic disorders, is there an increased chance when the chromosomes, the eggs split and then when they get disseminated by the sperm and they start to divide, that if there's noise in the system, mitochondria health isn't great that you have errors in these chromosomes dividing. And if you can clean up that noise like NAD, for example, then there's the energy requirement and the ability to repair so you have less chance of those errors. So I'm not saying you're making more eggs, but can you change the equality of the egg then if you give it the materials it needs so there's less chance of those errors? So this is the same principle that underlies the use of co-Q10, co-ansite Q10 in terms of improving egg quality. Each of the cells in our body contains 46 chromosomes, actually 23 pairs of chromosomes, total of 46. That four is sperm and the egg. They each have 23. And obviously when they come together, you end up with an embryo that has 46 chromosomes in each cell. The process by which sperm and egg end up with 23 instead of 46, we call that meiosis and let's focus on the egg for a second. Let's step where it divides from 46 down to 23 that last step of meiosis requires those pairs of chromosomes. Let's think of the pair as being two copies of chromosome one and two copies of chromosome two and two copies of chromosome three. Those two chromosomes need to split and they get pulled into one side as it comes the egg and the other side becomes what we call the polar body and it gets discarded. That process of splitting the chromosomes and dividing them so you get 23 and 23 requires a huge amount of energy. Where does that energy get produced in the mitochondria? And the mitochondria uses this electron transfer chain to produce energy. One of the steps in that electron transfer chain is co-Q10. The transfer electrons is done by co-Q10. If you have reduced levels of co-Q10, you've got less energy being produced by the mitochondria and so that process of chromosome will splitting does it happen with the same assurance. Instead of the chromosomes going one this way and one that way, you can end up with both chromosomes going this way. Now you're going to end up with an egg that's got an extra chromosome in it and we call that aneuploidy. An egg that's got the correct number of chromosomes, we call that an aeuploid egg or oocyte. It's got 23 chromosomes. But if the pair doesn't split, if one of those pairs doesn't split and you get, because there isn't enough energy being produced in the egg, then you end up with an egg that's got the wrong number of chromosomes. Now co-Q10 is important for that because it's in the middle of that electron transfer chain, but the actual start of that chain, that process of electron transfer, is begun by NADH. If you have lower levels of NADH in the egg, in the ovary, you're not going to have that same energy production. And it's been very clearly shown in mouse models that as the female ovary ages, the level of co-Q, I'm sorry, of NADH is diminished with aging. And if you can restore levels of NAD to better levels, to younger levels, you can end up with better quality eggs, less aneuploidy. The right number of chromosomes, those eggs will fertilize. Now you might say, so this concept of aneuploidy, most people are familiar with Down syndrome. Down syndrome is an extra copy of chromosome 21. It's trisomy 21, meaning that embryo ends up with three copies of 21 instead of just two. So you might say, well, why does that happen just with chromosome 21? The answer is it happens with every chromosome that failure to divide properly can end up happening with any chromosome. But with the other chromosomes, you just end up with an egg that won't fertilize. Chromosome 21 happens to have the fewest genes. It's only got like six or seven genes on it. And so an egg that's got an extra copy of chromosome 21, it can fertilize and you end up with a baby that has Down syndrome. So infertility as women get older is primarily due to the fact that they've got abnormal chromosome content in their eggs. And so by improving energy production, not only with NAD supplementation, or I should say NAD boosting, but also something like coans on Q10, you're going to reduce the risk of aneuploidy and improve egg quality in the aging ovary. Thank you for that. And we're going to get into supplementation. First I want to stick with the biochemistry that you're sharing on Pactis. So as you shared, the aging ovary, just with aging, we have a reduction in NAD. And this can be part of the risk of infertility or egg quality, more aneuploid abnormal embryos. And things that can accelerate the NAD loss, my understanding is it gets drained, not just by aging, but it gets drained by chronic inflammation, oxidative stress, and metabolic dysregulation, right? So lifestyle and diet will, this is where CD38 comes in. Okay. So the process by which NAD plus activates those enzymes, okay. CD38, the part enzymes, the SirTuins, when it activates those enzymes, it actually destroys the NAD plus. It breaks it down, okay. And it turns out that there's a pathway in ourselves as a chemical pathway to then regenerate NAD from those breakdown products. But it's been very clearly shown that the greatest loss of NAD at the cellular level is from activation of CD38. So CD38 is a very interesting enzyme, okay. It's present on the surface of cells, okay. And it's primarily present on the surface of immune cells. And what happens is when there's an initial immune reaction and cytokines are released, those are messages that come out of certain immune cells, they basically upregulate the amount of CD38 that's present on these other immune cells. And the NAD then activates the CD38. Activation of CD38 then sends messages out to the rest of the immune system that says, let's get going here, okay. And it upregulates the inflammatory response. So CD38's not a bad guy, okay. I mean, there's this notion that somehow CD38 is a bad actor in our tissues, in ourselves, okay. It's really really important, especially in an acute immune response. If we're exposed to a virus, if we're exposed to a bacterial infection, in those initial stages of the immune response, CD38 is absolutely critical. Where it gets into trouble, okay, is chronic inflammation. And as we get older, there's more and more inflammatory changes in our tissues. They call it inflammation, okay. There's this term that has been coined. I'm not sure you'll find it in the dictionary, but I'll share with the audience. We often say in my clinic, inflammation, in the play around definition, we say is it leads to accelerated biological aging, which leads to premature degenerative diseases. And I say premature fertility decline. So it's. It's a sort of a, what do you call it? It's a, it's a, you know, it's self perpetuating. It gets sort of, it starts to get worse and worse. At the more inflammation, the more aging, the more inflammation, it gets worse and worse. - That's why chronologically, all 40-year-old aren't equal, 'cause chronologically, you have the same number of times the earth is going around the sun per se, but somebody may be biologically 48, although they're chronologically 40, and this is that inflammation. So, a couple of things I wanted to hear again, hear myself say it for my audience and for my, my, my, my, my, so see CD38, it's in a part of that inflammatory response, but it's not necessarily a bad actor. It's the body self preservation. It's, Mark, I think it the same way when we see cholesterol and people freak out, or you have high cholesterol, it's the body self preservation for the inflammation in the cardiovascular system. It's trying to deal with the poor, the poor lifestyle, everything else. It's a self preservation, and if you don't deal with that problem over time, it becomes its own problem, the cholesterol, right? But it came from the, the, a way of survival. Hey, you're inflamed, you're vessels are inflamed, we need to protect. And it sounds like CD38 is the same thing, it's a protection thing, but if it's going on for years and years, this, the body basically is not getting the support it needs to deal with inflammation. And so I'm wondering if is it the CD38 is the issue, or it's the chronic inflammation, and there's just that the body can't handle it. And so all these breakdowns happen. So CD38, it's funny, because in a sense, it's both partly a response to inflammation, but it's also a cause of further inflammation, okay? And so it's when inflammation becomes chronic, that the approach of saying, let's downregulate CD38 a little bit, let's tamp down how much CD38 is being expressed in our tissues becomes a potential approach. Unfortunately, the only, I mean, look, there are monoclonal antibodies, these are drugs that are used, that target CD38 carrying cells, and they were used for cancer treatment and things like that. But they end up causing immunosuppression. And so using a supplemental approach to try and reduce CD38, that's been shown to be potentially effective in mouth studies. There are no human studies showing that that approach works in human tissues as well. So it's, but then again, if we go to the NAD literature, that's also primarily mouth studies, okay? - Only our patients were mice. - You were right. - At least in the fertility world. There's no question that the precursors, NR, NMN, the sum degree, NAM, which is nicotinamide or nicotinamide. Those are capable of increasing NAD levels in human tissues. That's been very clearly shown. The only problem is there's no study that has looked at ovarian tissue in humans, okay? They've looked at muscle, they've looked at fat, they've looked at the liver, and they've shown that you can take NR, you can take NMN. Those are the two best ones. There's no question that they're more effective than say NAM, which is nicotinamide or nicotinic acid, which is actually the, you know, nicotinamide in itself. But there's no study that has yet looked at ovarian tissue levels. That's still waiting to happen. And we're extrapolated to some degree from mouth models. And you might say, well, is that appropriate? Can we study female mice and see a benefit there in terms of preserving ovarian health and improving ed quality in mice? And then say, well, this is gonna work in people too. And it's a very important question. You should understand though, that there are some real interesting similarities between mice and human ovaries, okay? Mousin, Eurasian human ovaries. The benefit of using mice is that mice live for two years. Okay, that's it. They become fertile after a month. Okay, they're like four weeks old and mice can start having babies, right? But just like women and, you know, women's ovaries, they basically lose ovarian reserve very steadily. By 18 months, mice are no longer ovulating, okay? They also have increasing levels of aneuploidy. Those are the abnormal, the abnormal chromosomes, right? The abnormal egg chromosomes, okay? Just like people do, just like women do, okay? So, and they also have NAD, and NAD, you know, both NAD plus NADH, they also have the same sertoine enzymes. And we haven't even talked about how sertoine, how sertoine one improves ovarian health and preserves ovarian reserve, okay? So there are some real parallels between mouse ovarian physiology at the cellular level and human ovarian physiology. So there's good reasons to think that. - Yeah, and we do a lot of the non-invasive stuff, supplements people will often start to do, although there's not human trials yet on them. But that we would love to see those. So NAD, in general, we're talking about the mitochondria, the battery of the cell, every cell has the mitochondria. Most of our audience is very familiar with COQ10. People are hearing about NAD, and NAD for one, we shared so far, helps with the energy production and DNA repair. Two important things that cells need. They need energy to function. We talked about the egg cell needs a lot of energy for that myosis, for those chromosomes, to go to either side. And then the embryo, which comes from the female line, those mitochondria are what allows the embryo to divide on its own energy in the fallopian tube or in the IVF lab, growing out to blastasis, and requires that energy for implantation. And many embryologists I've spoken to share that the embryo early on, cleans up stuff. Like when there's spurs up so great, it does some repair. So all that part of the mitochondria function. So NAD is, the mitochondria is important for this, and NAD is shown to help with that energy and repair, which is excellent to hear. Can we just highlight one thing for our listeners? Because we're going to talk about supplementation. That's the focus today, because people are looking at NAD and what's the best form of it to support this energy production repair. But let's remind people that it is inflammation, chronic inflammation, oxidative stress, and metabolic dysregulation that accelerates the draining of it. Unnecessarily, we're going to have it with aging, but we're accelerating. So NAD precursors, which is what OVA NAD is, that you guys have created a their logic. It's a precursor. We should let people know that nobody's getting the actual NAD molecule. They're getting precursors to it. Because it's not something we need. Like cookie tin, we can get from our diet. But NAD is made inside. Not we don't get it from food sources, my understanding, but you'll correct that. But I think I want to highlight is NAD precursors, like your supplement OVA NAD, I'm assuming work much more effectively when inflammation, sleep disruption, stress, and high blood sugars aren't constantly draining the NAD toward damage control. I think that's a valid assumption. Yeah. You know, does this have the studies been done to absolutely prove that? No, but mechanistically, it's absolutely what you would expect to be the case. Because we're not just because you wasn't a study. I just want to because people go, some people shut off. No study. I'm out. There's never been a study that says if you jump from a 30,000 plane without a parachute that you will survive or die on the ground, there's never been a study. But I think it's a pretty good assumption. No, exactly right. So because of the mechanism of inflammation and sleep disruption, poor diet, stress, toxins, all that's creating unnecessary inflammation, your body's needing to deal with that, and that will cause a loss of NAD. So basically what we're saying is rather than NAD going towards that great energy production that it needs to give energy to the cell and repair the cell, it's off putting out inflammation fires. So it's distracted. So let's just help the body, the cell, do what it needs to do. And let's also, let's supplement it. But I guess my point is, Mark, you can't out supplement bad diet, lifestyle, abusive relationships, smoking, et cetera. You can't out supplement it in my opinion. It's pretty hard. You have basically, it's kind of like a sink that you're trying to keep filled up. And if the drain is open and the NAD is just pouring out of you because it's being chewed up by all that inflammation, you're going to have a hard time keeping that NAD level at a proper good level. No question about that. So supplementation, couple of questions. So I've had a guest on in the past and the theory went, which I thought sounded great. And then I'd done a deeper dive because of your email. There's this idea that you don't want to give necessarily the building blocks, the raw materials, like there's a few on the market, like yours that have NR in it. You also have that, what's special about yours is you have a form of-- The tear still be. Yeah, which is a cousin to Reds Veritrol, minus standing for looking at. it's a better cousin, seems to be more absorbable and stable and stuff. But in that discussion, I had on that episode, they're saying, you got this recycling plant and you got this conveyor belt and you're putting all these raw materials in. But if the recycling plant isn't working, eventually you have a build up in the conveyor belt and it makes a mess out of everything. The pathways get blocked and it actually causes a problem. And so work on the recycling. I've always thought when people ask me, so should I take the supplement that works on the recycling, or should I take the raw materials? And I'll say, I guess both. I'm curious, so you're thought on the recycling pathways because that's what some people say. Just you don't need so much the precursors. I don't know if that's exactly how they said it, but they definitely said you got to work on the recycling. That's the issue. And that's where you thought differently. So and the research wasn't there necessarily to support it. Okay, getting back to one thing that you said a moment ago, and that is you're right, you cannot take NAD as a supplement itself. Okay, there are companies out there that will sell that sell it. Okay, you can find it on Amazon. Actual NAD, but the problem is it's a molecule that gets broken down in the GI tract. Okay, into its components. Okay, it gets broken down. You're not going to absorb it as NAD. The second thing is even if you can get it into your bloodstream, if you can absorb it, okay, and get it into your bloodstream. And there are places out there that will give you an infusion of NAD. Okay, so the absorption issue is sort of bypassed. It's just getting directly infused into you intravenously. Okay, the problem is NAD is what we call a hydrophilic molecule. Very large hydrophilic molecule, meaning it's water loving. So to get through a cell membrane, which is lipid-based, okay, it's water, what we call hydrophobic. Okay, NAD can't get into the cells. Okay, only the precursors could get it. And so you can't really supplement with NAD and have any kind of significant benefit. You need to use a precursor. The two big precursors that are being that are in use now are NMN, nicotinamide mononucleotide, NR, which is nicotinamide right aside. Okay, up until about three months ago, nicotinamide mononucleotide was not allowed for sale in the United States. Okay, I'm not sure about Canada. But that wasn't because it wasn't effective or it was dangerous. It was because of a regulatory issue that a pharmaceutical company had that they sued the FDA to stop the sale of NMN. And at first the FDA said, okay, fine, we're not going to allow it to be sold. But they reversed that. So now you can get either one or both in the United States. The immediate precursor of NAD is NMN. Okay, if you give NR, okay, nicotinamide riboside, it has to first be converted to NMN, which is then converted into NAD. But the enzymes that do those conversions are not rate limiting. There is no rate limitation on either of those enzymes. There's plenty of them of those enzymes available. Now, the other precursor that some people will suggest using is what's called NAM, which is niacinamide or nicotinamide, okay. That is actually also one step away. I'm sorry, two steps away. It gets converted to NMN, which then gets converted to NAD. The problem is that NAMN requires an enzyme that is rate limiting, okay. And so you have to basically pick your precursor to make sure that you're not going to require the presence of a limited quantity enzyme to make it active. That's the first issue. The second issue is this. There's already some data that in some tissues, NR does a better job. And in other tissues, NMN does a better job. Why would that possibly be? It's because in order, and when I say does a better job, I mean of raising NAD levels in those tissues. So it's like NR does a better job in carton, the kidneys, and NMN seems to do a better job in the liver and muscle. Why couldn't that possibly be? It's because to get from the precursor to NAD requires two things. It requires transport proteins to bring the precursor into the cell. And then it requires those enzymes to do the conversion. And there's evidence that different tissues have different levels of those transport proteins and different levels of those enzymes. So the question is, since we're really focusing back on ovarian benefits, right, which of those NMN or NR, okay, is better for the ovary and the answer is we don't know. All right, not in humans. In mice, it doesn't seem to matter, okay. There are studies both with NMN and NR. And both of them in the mouse models do the same good job of raising NAD levels in mouse over is. So he's done the studies yet in people. So with NMN, it seems to be one step closer, pre-cursor to NAD. If I know it used to not be available, but now it is. If you could reformulate, would you use NMN over NR? Like is one more expensive than the other? Is one more stable in a supplement form? Since we don't know tissue wise, one is one step closer as a pre-cursor. So let me say that we are in the process of evaluating the changes that we want to make. But I think the best approach at this point, until there's a study or studies that clarify which of those pre-cursors does a better job in the ovary, I would say that if I was to start from scratch, I might want to go with both. I want to just highlight something because I've known Mark for several years now. We met pre-COVID. It's funny how we date things now, right? So pre-COVID. And that was one thing at our conference. We have many what I think are excellent. We always vet excellent supplement companies. We're always looking for good supplement companies that would sponsor. When I met you guys, your line wasn't huge like a selection wise like all the other ones. And I remember our discussion. I got to have research. We do science out of hype here. So until there's science, we won't do it. So I appreciate your answer and saying that right now you're using NR. And you're looking at the idea of maybe having both in there, NMNNR. Yeah, yeah. I mean, look, we are what we call a practitioner line. In the supplement world, we're a practitioner line. And we've been around 23 years. We started this couple of days, 23 years ago. But after 23 years, we only have 40 products. Now that might sound like a lot. But you know, other companies like Medogenics and Ford and Pure encapsulations, these other practitioner lines, they've got 300 products. Well, more. So our process is slow and our processes. We set the bar relatively high, just like you said, unless there's good science, we're not going to chase these products. And we're constantly looking at our products to reformulate as the science evolves. I got some rapid-fire questions here that some we've answered. We'll go through them again and get some yes and no's. But I had one other thing. I've more we're not done here by the way, everybody. So the other ingredient, because there's other NAD supplementation supplements. And again, they're not NAD by the way, everybody. Again, like Mark, Dr. Mark Wrenner said, they're precursors because you can't get NAD outside the body. But you did add another serocidling. Is that how you say it? Peristyl being is an analog of the reservoir at all. And the reason we added that is because we want to both increase NAD levels and SirTuyn one levels. The SirTuyns play a really crucial role in ovarian reserve. And this is a significant issue. As more and more women have delayed starting a family, whether it's for professional reasons or whatever, the whole egg freezing world has taken off. Okay. Many, many women come in and they have consultations about egg freezing. But interestingly, only 20% of women, this is a survey that was done and looked at women across the the United States, only about 20% of women who go through a consultation actually then follow through and do the actual egg freezing. So there's a lot more women out there that are concerned about preserving their fertility than actually are ending up doing egg freezing. And so the point is that if there are steps that can be taken to help slow the loss of ovarian reserve, then we think that's a great backup strategy for those women who are concerned about about future fertility. And so that's where we added the terrestrial being. By the way, terrestrial being is it's P-T-E-R-O or still being. The stillbeens are a classic of polyphenols that are found in peanuts and blueberries, they're found in certain plant foods and grapes. And the most well-known of the still beans is reservoir atrol, which is something that was first isolated from grape skins. And it's been the source of a ton of research that's been studied extensively. The problem with reservoir atrol as a supplement is that it is poorly absorbed. It's got very low bioavailability. Why are we interested in reservoir atrol because it seems to improve sertoin levels? It increases sertoin levels, especially sertoin 1. Remember, there's seven sertoins. And sertoin 1 is the sertoin that's intimately involved in ovarian aging. How does that work? So I think everybody is familiar, at least people who are focused on fertility are familiar with the fact that women are born with all of their eggs that they're ever going to be able to make already in their ovaries. And it birthed, it's been estimated to be like between 1.5 and 2 million eggs. Now, as soon as the baby's born, those eggs start to degenerate. Sorry, and they're not really eggs at that point. They're what we call follicles, primordial follicles. And then once a woman goes through puberty and starts to have monthly cycles, what happens is, each month, about 1,000 of those resting primordial follicles, these are sort of hibernating follicles, about 1,000 of those get recruited each month and become what we call primary follicles. And then over the course of the following year, those follicles gradually develop. And they develop under the influence of hormones, FSH and LH, which are familiar hormones that anybody in the fertility world, until gradually at the end of that one year, you're left with one follicle that spits out an egg. So you go from 1,000 primordial follicles that are recruited to become primary follicles. And then those primary follicles, gradually, over the course of the year, they mature, but you lose 99.99% of them. So you'll end up with just that one. And so what happens? Just except if you do an IVF, they'll rescue, in a sense, several of those follicles versus one, because you'll have a group of them. And we always talk about the 100 days before ovulation or IVF retrieval, because we talked about that one year, but it seems like that was last 100 days, 120 days, seemed to be the most impactful of the environment, that the follicle is maturing and containing that all the same. That was exactly right. And so what happens is the in that one year process towards the last two or three months, you end up with what we call pre-antral follicles and then antral follicles as they're getting larger and larger. And when they do IVF, under normal circumstances, non IVF, only one follicle becomes what we call the dominant follicle and it makes the egg one egg a month. Right. But when they do IVF, by giving all of these extra hormone injections, they rescue, as you said, all of the pre-antral and antral follicles, so that instead of just making one egg that month, you might make 15 or 20, because all of those antral follicles are pushed to mature and become full-dominated follicles. Anyway, so the point here is that that process by which primordial follicles get recruited each month to become primary follicles is controlled by certain one, certain one. And if we can, so theoretically, can we pull out, you know how we prime to get more follicles in an IVF stem? Can we not that we make more eggs, but pull more out out of that pool? Because of this that's exactly what the goal of Sir 2 and 1 is. And when they do this in mice, okay, and they elevate Sir 2 in levels in mice, they end up with doubling the number of follicles, the antral follicles, and eggs that get retrieved. So, is there still being, has this resveratial cousin, the ster- uh, tarot still being shown to do that as well in the mice studies? Well, it raises certain one. Okay. So, and then, and by doing that, you pull, you get more out of the pool exactly. So, so the point is that you're looking for a synergistic benefit here between NAD levels going up and Sir 1 levels going up. And you have both a short term benefit in that the chromosomal separation is done in a better way and you end up with a healthier egg that's got the right number of chromosomes. So, that's a short term benefit and that really only takes maybe six or eight weeks of NAD boosting prior to the egg retrieval or conception, okay, to improve that eggs quality. Okay. But if you want the long term benefit, it's potentially possible to start slowing down the loss of those follicles and keeping more in reserve by using supplementation that will improve NAD and Sir 1 levels chronically. So, okay. That's the goal. So, with, so in the literature, with patients, we hear it, we've looked into it, resveratial in general. So, first of all, as you mentioned, tarot, tarot still being, right? It's a cousin of resveratial, but my understanding, first of all, it's stronger, you know, as in it's more bio-available, so which is why you want this, right? And it seems to stay a little bit active longer. So, you're going to get more benefit compared to resveratial. People talk about resveratial and it could interfere in plantation. Have you seen anything that in the literature on that? Because a lot of times, because it's out there, people have discussed it, that we just tell people take it, but they stop close to if they're doing a frozen embryo transfer or they're trying to concede around ovulation, we would stop it. So, you have a product that has that in there. Have you done any literature review on, on resveratial and plantation? Because that is definitely. Actually, it's a great question. There's actually a paper that was published a year ago, maybe. Looking at women who have a condition that's called recurrent implantation failure, okay? So, this is something that's seen in IVF practices and fertility practices, where women who have good quality embryos, you know, they've tested the embryos, they know that they're chromosomeally healthy and yet, every time they implant one of these good embryos, it fails to implant. So, they call this recurrent implantation failure. So, they studied 100 women with recurrent implantation failure and they actually biopsy their endometrium and what they found was that. And they compared them to women who had normal implantation and what they found was that women who had recurrent implantation failure had certain one levels that were 40% lower. And so, if your certain one levels are too low, it appears that it impairs what's called desigualization, okay? Now, that's a real tongue twister, but desigualization is basically the process by which the embryo and the endometrion, the lining of the uterus, attach themselves. And so, you potentially, by raising certain one levels, can improve implantation rather than happy to send to the articles, an interesting study. So, it's actually. I'm not sure whether there's a difference with gene resveratrol and terrestrial being in terms of that benefit. You wouldn't expect it because the difference between terrestrial being and resveratrol is almost the same molecule. It's just that the terrestrial being substitutes a couple of methyl groups for hydroxyl groups on resveratrol, which makes it easier to absorb and less readily broken down by the body. So, it's more bioavailable. It's basically doing the same thing as resveratrol. I'll do a little. As we're chatting, I'm going to do a little search, and if anything comes up, I'll ask you about it. I know that. So, you're. But basically, from what you've come across, it's the opposite. You're not seeing it as a interfere with implantation. You're actually saying that if cert ones are low, we see implantation failure and this product, this supplementation, will increase it, which in theory should help with implantation. Yeah, I mean, here's the thing, just improving NAD levels will increase the activation of cert one. But for cert one activity to be optimized, to be increased, you need to do two things. First, you need the transcription. Cert one is an enzyme. It's a protein. How do proteins get made through DNA transcription? So, you want to increase the transcription of DNA to lead to more certain one being produced. And then you need the NAD to activate the cert one. And so the terrestrial being is there to help improve transcription and what we would say, expression of certain one, how much, certain one the cell is expressing, and then the NAD is there to help activate it. All right, here's in real time everybody. Here's what I think where's the guy? Resveratrol appears to have anti-decydualization effects on the uterine line in endometrium. It can inhibit the transformation of endometrial stromal cells into the decidua and specialize uterine tissue that support endometrial implantation. That was in a nature article. A clinical study of embryo transfer cycles in vitro IVF found that women who took 200 milligrams per day of a viral troll continuously had lower clinical pregnancy rates and higher miscurricular rates compared to controls that's in a pub med. Because decidualization and endometrial receptivity are critical for endometrial implantation, the anti-decision effect of residual trolls is strong, biological concern, even if it improves egg quality. That's what I've seen. The consensus research, if used before ovulation, stimulation to increase egg quality, especially if there's diminishing of very reserve or even PCUS, is probably wise to start residual troll at least before embryo transfer ovulation and avoid it during the luteil phase. All right, some more real time research being done here. So this is a paper that was published in biological reproduction, 2022, out of, I believe this is China. Yeah. Actually, no, Michigan State University. And basically, here's what it says, "Sert one plays an important role in implantation and decidualization during mouse in early pregnancy." That was the mouse study, but let me see if I could find the other one, which is the human study. Yeah. I mean, the human study, which I'm happy to share with you, basically showed exactly the opposite, that women with recurrent implantation failure had certain one levels that were significantly lower. And when was that published? Here, certain one levels in recurrent implantation failure. Yeah. So this was in the European Journal several years back. All right. And I just emailed you the 2019 study for the other one. Yeah. I may get you to send me more information. Maybe we'll add it before we put it out. Just let's look at some of the research out there so we can let people know. For now, still in our clinic, we're telling people like for your OVNAD, which we like and recommend now as well, because you're on the podcast, I think your company's given us a discount to give to our patients as well. So we'll put that in the show notes. So you guys can order directly from their logics and save some money. But we're still telling patients take it up to ovulation or close to ovulation and then stop until, but that may change based on our discussion, Mark, that we may do post this post recording. And also, we tell them not to do it the days before or after the transfer. So at this stage, when we're working on a quality, we want them to take it while we're working on a quality. I got some rapid-fire questions and some of the issues we can say we've covered it because I think we have covered everything. So this is what I wanted to talk to you about. And I think we've covered mostly with, let's see if I missed anything. How does NAD decline impact mitochondrial function inside the O site, the egg and what downstream effect does that have on egg quality, OVN reserve? You nailed that. You did that at the beginning. Okay. Precursors compare NAM versus NIR versus NMM. And yours has the NR in it from a biochemical standpoint. How do NAM NR and NNM differ from once inside the cell and why does NIR bypass rate limiting steps that NAM based products depend on? You discuss that too. Right. You talked about NR and NM both being those precursors NAM takes a little bit more work and it becomes rate limiting. So no, you had no recycling concern with NR or NNN as your precursors. Some argue that precursors hit a wall because the recycling pathways become saturated and you said that isn't supported by the literature. And what do actual one of the questions had what do human studies say now? And I think you cleared that up as well with the other question we had. But it's nothing to add to that that I missed the rate limiting steps. That's the big thing out there now. There's some saying there's recycling issues. And pathways get gunked up. And I think you said there's no real literature science on that when it comes to NR or NNN. Yeah. So there basically there's three different ways that the cells can make NAD. It can start with nicotinic acid which is the vitamin form that that you know niacin which is actually you know that's the one that causes facial flush and it can actually start even for that with trigotaphane. Okay. Then there's another way of making it which is called the price handler pathway. And the third way is the salvage pathway which is by far the most important. The salvage pathway is a way remember we said that when NAD plus activates any of those enzymes, PARP enzymes, SirTuins, CD38 and others whenever it activates one of those enzymes the NAD plus gets broken down. And so the salvage pathway takes those breakdown products and reconstitutes them into NAD. So that's what and that's by far the the most important way of keeping NAD levels high in ourselves. So what you're doing when you use a precursor is you're basically feeding the salvage pathway. Okay. With more raw material. And the rate limiting steps are potentially tissue based like I said, it may be that that those that either one of the one of those precursors is better in in the ovary than the other. We still don't know. So it's not only getting into the tissues by the transport proteins that have to bring them into the cells the pre cursors, but it's also those enzymes that then do the conversion. And although we pretty much know that the only one that's that's generally rate limiting is the one that converts NAM into NAM. The one the enzymes that convert NR into NMN not rate limited. The ones that convert NMN into NAD not rate limited. Not a problem with either of those. And can we revisit the IV NAD injections? Because that's another popular thing. I know it's quite expensive and time consuming. You have to sit sometimes for four hours to receive one of those. Some people find them uncomfortable as well. Can it have any benefit? And is in the because they're bypassing the gut as you talked about. There's a lot of breakdown going into the blood. But whether it's a large molecule. Is there benefit to it? Because some people claim there's benefit. I just don't know if there's research about the benefit. Yeah. So you're getting blood levels of NAD. Okay. By doing an infusion. But the question is, are you getting intracellular NAD? Is the NAD that you get by infusion getting into the cells? It may not. Okay. Because there's a lot of evidence to show that because it's a large hydrophilic molecule, it has it has trouble getting across cell membranes. There's no specific transport or protein to bring actual NAD from an extracellular to an intracellular location. Okay. So what does that mean? What's the implication there from a purely theoretical perspective? CD38 is extracellular. It's on the outside of the cell memory. So it's quite possible that some of the benefits of NAD, just being in the blood level being up, could be realized. Because some of the benefits you don't necessarily need the NAD to be intracellular. But the energy benefits in order to improve mitochondrial energy production and ATP production, you clearly need the NAD to be intracellular. And if it has trouble getting intracellular, it has NAD as opposed to being a precursor, which can be transported into the cells easily. Then there are theoretical reasons why NAD infusions might have some benefits, but not the ones that people are looking for in terms of energy production. Okay. Thank you. And then since inflammation, I call this noise, you know, since inflammation can accelerate NAD consumption, do you have lifestyles or clinical interventions you believe would help reduce that metabolic noise? So the NAD support like the OVA NAD that you offer at their logics can work optimally. Do I have lifestyle interventions? I mean, generally speaking, the things that are considered to be heart healthy and metabolically healthy are going to reduce inflammation. And so keeping your insulin levels down, you know, more and more people using continuous glucose monitors to monitor their metabolic health, you know, the kinds of things that the typical pillars in like we always go diet, anti-inflammatory, low glycemic indexing. No question. Shout out for that. By the way, free acubalance diet with 21 days of recipes. You guys can download for the acubalance website. Movement, sleep, stress reduction. - Straight away from unnecessary chemicals. That's the pillars of life, right? - Absolutely, yeah. - And then any ideal candidates for this NAD support, like that would wanna focus on foundational changes for this, like, you know, is it anybody? - With fertility, you was saying from fertility perspective, we're generally speaking. I mean, look, the whole, all of the buzz and the reason why there are dozens and dozens of NAD boosters being sold on Amazon and elsewhere, really started with lifespan, with the concept that, you know, somehow this is gonna extend lifespan. And the data just doesn't really support that at this point. I mean, not in people. If you're a fruit fly or a roundworm, yes, increasing your NAD levels will have you live longer, but it just hasn't been shown in vertebrates, in higher or not even in mice. However, there's a concept of health span. And I think there's an accumulating body of evidence that improving your NAD and answer to in levels can improve health span, meaning you're gonna stay healthier longer. That's, I think, if not, as sexy as lifespan, it's certainly as important. - You know, I always enjoy meeting with you and talking with you. And, you know, there's a lot of information out there, and we want to offer what we think will help our patients, the best at acu-balancing for my listeners. I want them to get educated so they can go talk to their healthcare provider. And I like that, you know, you're there and you've got the science behind your supplements. In our clinic, we're always doing things, you know, from the Chinese proverb, Mike, it's nourished the soul before you plant the seed. We're looking at this environment. You were talking about these, you know, the one year, 100 days, we're looking for that environment to support that myosis, to support the mitochondria health. And so we just mentioned the pillars, everybody. There's diet, download that diet for free from our website. There's movement and sleep and stress reduction. We use low-level laser therapy in our practice to help with blood flow and regulate inflammation. And it's been shown to help mitochondria function, acupuncture for blood flow, stress reduction, herb supplements. And just to share, this is the supplement now that we've added also is one of the recommendations. We do coq10 and there's, you know, the fish oil. You have a really good, an acetal de-kyro product, which is great for the metabolic risk factors and issues. And I'm so happy that you've created this NAD product because there's lots out there. And as I started this sentence, run on sentence, their logic puts the science behind it. And that's why I wanted to have this conversation. And once I saw that you put out the product, we started having this conversation. I wanted to bring it publicly. Is there anything you want to share? Otherwise, I kind of want to just summarize a little bit what we talked about today. - No, I think this has been great. We kind of like covered the whole gamut of topics here. It's a fascinating area. It's one that, listen, there are, at this point, there are studies ongoing in China, in Australia. And there's a couple of, I'm gearing up here in the States, looking at specifically different precursors in fertility outcomes. And so I think over the next several years, we're gonna have more and more certainty about what the best approach is. But those studies are hard to do. They're tough to do, especially in fertility patients 'cause nobody wants to get placebo. - Okay. - Right. So I just think that it's an exciting area. And it's certainly one that is gonna be evolving in the next several years. - Perfect. So everybody, today's conversation, hopefully with Dr. Mark Ratner, helped clarify several key points about NAD biology and how it relates to a quality or very reserve and just basically overall reproductive aging. First, NAD isn't a wellness fat. It's a central molecule for mitochondrial function, DNA repair, and the enzymes that protect cellular longevity, including the Oocyte A. Second, how you raise NAD matters. So we've explored why N.R., nicotinamide, riboside, N.R. is a highly efficient precursor. And why claims about precursor overload aren't backed by human studies. And why suppressant enzymes like CD38 may carry unintended consequences. Thirdly, supplements work best 'cause they're supplements. They're there to supplement work best when the foundations are strong. And so my clinic at Accubance, before we layer in anything advanced, we always start with just lowering systemic inflammation, reducing that internal noise. So anti-inflammatory eating, check of the diet, movement, exercise, restorative sleep, stress reduction. We offer also provide acupuncture, low-level laser therapy, herbal medicine, and targeted nutritional support, including the OVA NAD biothereologics. So once these pillars are in place, NAD support can be a meaningful tool for improving mitochondrial health and optimizing aid quality. Now, obviously, if you haven't put those tools in the place, you really want those supplements to counter as much of the negative lifestyles you can. So in today's episode, or I should say, if today's episode brought up questions about how NAD fits into your fertility plan, you can reach out to us at Accubance, or message me on Instagram @LorneBrownOfficial or @ our Accubalance Instagram channel, or a podcast channel. Mark, I want to thank you again for bringing clarity to this complex topic. I really do. And thank you to all of our listeners for tuning in. And remember, your biology is adaptable. And when you create the right environment, the body often responds in remarkable ways. So thank you, Mark, and thank you to-- - My pleasure, Lauren. Thank you for having me. - I want to let you know that this is several weeks after I recorded this episode with Dr. Mark Ratner on NAD. And what we've done is we recorded another episode just on Resveratrol, because in this episode on NAD, we had that discussion about, is it safe or not based on the papers that are out there to take Resveratrol after ovulation, or leading up to a transfer, like a frozen embryo transfer, or even a fresh transfer. So he sent me several papers that I got to review, and I brought him back, and we recorded a whole other episode on Resveratrol, on the research, whether it can be used not just for egg quality, but for implantation failure, and leading up to a transfer or post-obulation. And he went through all the research, right up to the most recent paper at the time of our recording of 2025 paper. We recorded it in early 2026, but the last research he could find was in 2025. So inviting you to go look for that next episode with Dr. Mark Ratner, where we talk about Resveratrol on our podcast. Thank you for spending this time with us on the Coherence Code of Podcasts. I'm Dr. Lauren Brown, and I will see you next week for another conversation on Coherence and Healing. If this conversation resonated with you, please like, subscribe, or follow the show, and also share it with someone who might benefit from it as well. Remember to take a moment to breathe, reflect, and stay connected. Welcome. (upbeat music) - Welcome to Coherence Coat of La Calla. (gentle music)