I’m honored to be joined by Dr. Mark Ratner, Chief Science Officer at Theralogix. We’re diving deep into the science of NAD+ – what it is, why it matters for fertility, and how it might help improve egg quality and outcomes for those pursuing IVF or egg freezing. Dr. Ratner, a board certified urologist, brings a wealth of expertise in nutritional supplements and reproductive health, and I’ve been looking forward to sharing this conversation with you.
Throughout our interview, we explore the fascinating roles of NAD+ and sirtuins in ovarian health, discuss the latest research (from mice to humans!), and break down what these findings could mean for anyone hoping to preserve or boost their fertility. We also touch on practical strategies, from supplements to lifestyle changes, and address common questions about safety, effectiveness, and the future of this exciting area of reproductive science.
In this episode, we cover:
- What NAD+ is and why it’s crucial for egg health and fertility
- The role of sirtuins as “master regulators” in our cells and their connection to ovarian reserve
- How age-related declines in NAD+ and sirtuins impact egg quality
- Insights from animal and human studies on NAD+ supplementation and fertility outcomes
- The difference between NAD+ supplements and precursors like nicotinamide riboside
- Dietary and lifestyle approaches to boosting NAD+ (and why caloric restriction isn’t for everyone)
- The growing awareness among fertility specialists and what’s next for research in this field
Resources:
Theralogix OvaNAD+ supplement: theralogix.com (use code EGG for a discount)
Dr. Aimee’s Fertility Essentials
Join The IVF Class with Dr. Aimee
Full Transcript:
Dr. Aimee: Today, I’m joined by Dr. Mark Ratner, the chief science officer at Theralogix. If you’ve ever wondered what NAD+ is, why it matters for your fertility, and whether boosting it could help improve your chances of success with IVF or egg freezing, you’re in the right place. The topic of today’s episode is Boosting Egg Quality: What We Know About NAD+ and Fertility.
Dr. Ratner has dedicated much of his career to understanding the science behind nutritional supplements and their role in reproductive health. In this conversation, we’re diving into the fascinating world of NAD+, sirtuins, and how these molecules may influence egg health, ovarian reserve, and fertility as we age.
Welcome to the show, Dr. Ratner. Thank you so much for joining me today. I’ve been looking forward to this conversation for a long time.
Dr. Mark Ratner: Thank you for having me.
Dr. Aimee: We talk a lot about NAD+. That’s a lot of letters and then a symbol. Can you explain in simple terms what NAD+ is and why it’s so important when it comes to our eggs and fertility?
Dr. Mark Ratner: Sure. NAD is a molecule that’s present in every cell of our body. People think of this as a supplement, but it’s not really a supplement, it’s something that we naturally have in our cells. NAD stands for nicotinamide adenine dinucleotide, but you don’t have to worry about that long-winded name. We make NAD in our cells from Niacin, which is Vitamin B3.
NAD in our cells has two main important functions. It actually stands right in the center of literally hundreds of important chemical reactions in our cells. All of those reactions break down into two big categories. One is energy production. NAD is important for producing energy in our cells, and that happens in the mitochondria. You may remember from high school biology, that’s where energy is produced in our cells, in the mitochondria.
The other thing that NAD does is it activates certain very key enzymes in our cells. What do the enzymes in our cells do? Enzymes are like the work horses in our cells. Enzymes basically make all the different reactions happen. It turns out that NAD is required for certain very important enzymes to be activated. What happens, though, is as we get older, the amount of NAD in our cells gradually declines.
All of the interest for the past several years has been in can we boost the amount of NAD in our cells and restore youthful levels of NAD.
Dr. Aimee: NAD cells in our brain, cells in our ovaries, cells in our uterus, a very important topic.
Dr. Mark Ratner: Absolutely.
Dr. Aimee: Let’s talk about sirtuins. I think for a lot of listeners this might be the first time that they’re hearing this word. That’s a new word for so many of us. What are they and how do they play a role in egg supply and egg quality?
Dr. Mark Ratner: Sirtuins are a group of seven enzymes, seven sirtuins. The sirtuins are the master regulators of cellular metabolism. Each of those seven perform different jobs, different functions. We call them SIRT1, SIRT2, that’s their abbreviation. There’s SIRT1, SIRT2, SIRT3, all the way up through SIRT7. Those enzymes, which are critical for all kinds of functions in the cell, are activated by NAD. NAD and sirtuins work together.
Dr. Aimee: They’re friends.
Dr. Mark Ratner: They are absolutely friends. Although, as sirtuins get activated, they gobble up NAD. They are one of the reasons, as we get older and we have more and more sirtuin activity in our cells, that NAD levels start to go down, because the activation process breaks down NAD.
The reason we’re super interested in sirtuins, specifically SIRT1, the first sirtuin, is because it appears to be in charge of ovarian reserve. Just like NAD, as we get older, the amount of sirtuins in our cells goes down. Because the sirtuins require NAD for activation, as NAD goes down, it’s sort of a double whammy. Sirtuin levels are dropping, but then they’re activation partner NAD is also dropping. This is why there is so much interest now in whether we can boost NAD levels in our cells and sirtuin levels in our cells. Specifically, in terms of ovarian health, we’re looking at SIRT1, the first sirtuin.
Dr. Aimee: Age is damaging to eggs, there’s no doubt about it. I wish there was a way that we could make it reversible and not inevitable that as a woman grows older, her eggs get damaged by age. I think that I want everyone to know about this, and I think it’s so important that patients learn about this so that they can start supplementation even if they’re not considering fertility treatment or IVF. There is a possibility, I think, that women who take NAD supplements, like OvaNAD+ for example, that their menopause might be later, they might have less miscarriages later, and their eggs might be healthier at an older age. I hate to use the word older, because a 37-year-old is not old by any means, but we know that her eggs can behave older.
How does the natural decline in NAD+ as we get older connect to the decline in egg quality and ovarian reserve? You mentioned that it goes down, but can you be more specific about how it’s connected?
Dr. Mark Ratner: Sure. For an egg to develop properly, it requires a huge amount of cellular energy. There’s a concept, and I don’t want to get too deep into the weeds here, but one of the things that makes egg quality decline as women get older is that the number of chromosomes in the egg can become abnormal.
We normally are supposed to have in our regular body cells, 46 chromosomes, 23 pairs. When sperm and egg come together, they each are supposed to have 23. You put 23 and 23 together, and you end up with a baby that has 46. In order for those eggs to end up with 23 chromosomes, it requires a huge amount of energy. In fact, remember, I said mitochondria is where the energy production occurs in our cells. The single cell in the human body that has more mitochondria than any other cell is the egg. The egg has more energy production requirements than any other cell in our body.
What happens is as those eggs get older and older, the ability to produce that energy decreases. Why does it decrease? We know one of the things that we can do to help improve energy production in that developing egg is we can supplement Coenzyme Q10 because that’s part of the energy production process. The molecule that actually starts the energy production process is NAD. If NAD is declining as those eggs get older, energy production is suffering.
If we can restore better energy production in these older eggs, we’re going to end up with better eggs. The way that we do that is by raising NAD levels in the egg, in the follicle where the egg is developing, inside of the ovary.
Dr. Aimee: I learned about NAD from a patient of mine. She had been through several cycles of IVF and came to me for another cycle. She had this incredible cycle, and it just didn’t make sense. She had several cycles unsuccessfully, and then all of a sudden, this beautiful cycle that, had I not known that they were her own eggs, I would have thought that she had used donor eggs. It just knocked my socks off. I asked her. She’s a PhD scientist. I said, “What did you do differently? I need to know. What did you do?” She said, “I read an animal study showing that NAD+ supplements can improve egg health.”
Can you talk a little bit more about what we know so far about whether this could be true for women trying to conceive?
Dr. Mark Ratner: The studies that were initially published, that have been the bulk of what has been published, have been mouse studies. Why do they use mice for these studies? The mouse is a terrific model for doing reproductive research, especially ovarian aging research, and the reason is because mice only live for two years. That’s it. They are fertile at eight weeks. A mouse can start having babies at eight weeks. But there are some real similarities between mice and human women in terms of ovarian function. Such as women are born with all of the eggs that they’re ever going to be able to make already in their ovaries. That’s what we call the ovarian reserve. It’s kind of what’s in the bank. Same thing with mice.
As women get older, the number of remaining eggs starts to decline. It gets lower and lower, and we say that we’re losing ovarian reserve. Diminished ovarian reserve. Mice experience the exact same thing. The other thing is this concept of chromosomal abnormalities. What we call it, the name is aneuploidy. That means that if enough energy is not present as that egg is developing, it’s going to end up with the wrong number of chromosomes. Instead of 23, it might have an extra one for 24, or it might be short one and only have 22. That happens to women past the age of 36, 37, 38, that risk of abnormal chromosome content in the egg really starts to go up. Same exact thing with mice. It starts at about eight months with mice. So, there are all of these parallels.
The first studies that have been done looking at NAD boosting have used mice. They’ve typically given them anywhere from four weeks to four months of supplementation. They start it usually at about eight months, because in an average normal mouse, by 18 months, they’re not ovulating anymore, they’ve gone through mouse menopause. But with these studies, what they’ve discovered is that if you boost their NAD content in the ovaries, they keep ovulating past 18 months and the egg quality is much better. You don’t get that aneuploidy, you don’t get those abnormal chromosome numbers to the same degree if you can boost NAD levels in mice.
Now, there has finally been a human study published. Actually, it was presented as what we call an abstract presentation at a big European fertility meeting back in June. They looked at 50 women who were going through IVF. These were women who had diminished ovarian reserve. They either had very low AMH, under one, or what we call their antral follicle count was under five. Many of your listeners, I’m sure, are very familiar with those kinds of tests.
Half of those 50 women got NAD boosting, they took a supplement to boost their NAD. The other 25 were controls. It turns out that the group that got NAD boosting had a doubling of their fertilization rates and a doubling of their clinical pregnancy rates. This was a small study and it was just presented as an abstract, but there’s a lot of information in that abstract that we’re hoping to still get when they publish the full study. It’s an indication, this is a short-term benefit of NAD boosting.
What that tells us is if you do NAD boosting, if you take a supplement to boost your NAD for maybe four, five, six weeks prior to an egg retrieval, that may be enough to improve the quality of that egg.
Dr. Aimee: That’s what I tell my patients, to take it at least 30 days before you start stimulation. I wonder if the mice have menopause. Do you know, do those little mice have hot flashes?
Dr. Mark Ratner: And they get very grouchy. That’s right.
Dr. Aimee: Very grouchy, very spicy. There are people who don’t like to take pills or they want to avoid supplements. Is there anything that women can do with diet and lifestyle that will boost NAD without taking a supplement?
Dr. Mark Ratner: That’s a great question. What we are focused on is not just NAD, but boosting NAD and sirtuins. It turns out that the studies that have shown the most consistent elevation of NAD levels and sirtuin levels without taking pills are what we caloric restriction studies. They started off doing these things in mice and worms, and now they’ve actually done it in primates and mammals.
Remember, I said the typical mouse lives two years, 24 months. If you restrict their caloric intake for their whole life, and you do it to about 30 to 40 percent of caloric restriction, they’ll live to 36 months. You will actually extend their lifespan by about one-third. The way that’s happening is because NAD levels and sirtuin levels are going up.
Caloric restriction is a way to do it, but not an easy thing to do. To try to severely restrict somebody’s caloric intake for a long period of time is just not fun, and not really feasible.
What we use in OvaNAD+ to try to raise sirtuins and raise NAD are two different supplements. I should mention, and this is an important thing, there are products out there which are actually NAD in supplement form. The problem is that you can’t absorb it. NAD as a supplement cannot be absorbed from the stomach. Even if you do absorb a little bit of it, it won’t get into your cells very well. What you have to take instead is a precursor, you have to take one of the compounds that the body then converts into NAD. This is what is in OvaNAD+ the product, it’s called nicotinamide riboside. It has been shown to be extremely effective in raising tissue NAD levels. In just six to eight weeks, those levels will jump up.
In terms of sirtuins, we use something called pterostilbene, which is what’s in OvaNAD+. Pterostilbene is an analog of Resveratrol. Some people have heard of Resveratrol, you can get it from grape skins. Resveratrol in the lab boosts sirtuin production. Again, the problem with Resveratrol is it’s tough to absorb, the bioavailability is not good. Pterostilbene is sort of Resveratrol with one extra little molecule, and it works just like Resveratrol, except it’s well-absorbed and highly bioavailable, and it boosts SIRT1. Remember, that’s the one that functions in the ovary, SIRT1.
Dr. Aimee: I imagine that the word is out, doctors know about this. Are you seeing more fertility specialists recommending NAD to their patients?
Dr. Mark Ratner: Yes. We actually work with probably somewhere near 70% of the IVF practices in the country, they use at least one or more of our products with patients. We have the ability to reach out and survey the specialty, and we did that earlier this year. We surveyed about 400 IVF docs around the country. We asked them, “Are you familiar with the science behind NAD and sirtuins for female fertility?” One-third of them said yes. We were surprised because it’s not universally understood yet, but it’s growing.
Of the one-third that we got yeses from, we said, “Are you using this with patients?” Half of them were. I think there is a growing awareness, and that’s part of our job is to get the science out there and let people understand how it works, why it works, and what the situations are that it might be best used in.
Dr. Aimee: I think that it took a while for doctors to recommend CoQ10, and I feel like everyone tells their patients to take CoQ10. I’m hoping that they’ll also include NAD. That’s my hope, because I’ve been using it for years and I think the results are phenomenal.
Dr. Mark Ratner: I think the analogy is perfect. What was a big challenge with CoQ10 was that when they first started doing CoQ10 studies in female fertility, it was in mice. They used mice in the same way that they’re using mice in NAD research. Then when they turned around and said let’s do some studies in women, it was really hard to get those studies done. The reason is because when you do a clinical trial like that and it’s what we call placebo controlled, which means let’s say you’re going to enroll 100 couples in your study, 50 are going to get NAD boosting or NAD and sirtuin boosting, and the other 50 are going to get a sugar pill placebo. You have to disclose that to them. You have to tell them there’s a 50% chance that they’re not going to get the real thing.
If you’re going into a clinical trial for a new drug that’s being developed, there’s no way you can get that drug except in that clinical trial. If it’s a 50% chance of getting the placebo, you might be willing to take that chance. But with supplements, if I say CoQ10, 50% chance you’re going to get a placebo, most people are going to say, “I can buy this online or I can go to the drugstore and buy it. I don’t want to be in your study. Thanks anyway.”
It’s very hard to enroll clinical trials and get subjects into clinical trials in the fertility world, but they are succeeding at it in China. There are now six placebo-controlled clinical trials that have been done in China with CoQ10. When you put the data all together, this was actually published last year, when you combine the data from all six of those trials, you basically get an 84% increase in clinical pregnancy rate with CoQ10 supplementation.
Dr. Aimee: Wow. That’s impressive.
Dr. Mark Ratner: I think it’s a similar story. We are actually working to try to get a clinical trial going in Australia looking at NAD and sirtuin boosting. We’re going to be looking at trying to slow the loss of ovarian reserve. This gets back to what I was saying at the outset, that there are really two ways this product can be employed.
The first is if you’re going through an IVF cycle, if you’re planning to freeze your eggs, six weeks before you’re going to have the egg retrieval, get started on this. Energy production can be boosted in the ovary, egg quality can be boosted in that short of a period of time.
However, there’s also a long-term way to use this type of product. That is for women who maybe are not prepared to freeze their eggs, they can take something like this, and by raising their sirtuin levels on an ongoing basis, they may be slowing down the loss of eggs from that supply, that ovarian reserve.
Dr. Aimee: That’s my theory. All the 20-year-olds, I’ve told them when you’re 50, I should still be here, I want you to let me know if you’re in menopause yet. I told them take your NAD and take your CoQ10, until you’re done having babies, and maybe beyond, and I’d be super curious to see if my theory is right.
Safety is a big thing. People want to make sure that the supplements they’re taking are safe, that the side effect profile is good. Can you speak on that?
Dr. Mark Ratner: Both components in this particular product (nicotinamide riboside, which boosts the NAD, and pterostilbene, which boosts sirtuins) have a terrific track record of safety and tolerability. In fact, they have been used in human clinical trials at doses far higher than what we’ve included in the product with total safety. Side effects are pretty minimal. I think the safety question is we’re pretty comfortable with that, absolutely.
Dr. Aimee: I even tell my patients to take it in the first trimester. Listening to my podcast is not a replacement or substitute for advice from your own physician. But I do tell my patients to take it until at least their heartbeat ultrasound, because I think there might be a benefit in terms of reducing miscarriage risk. That’s just another theory of mine.
There’s a lot of exciting research we’ve talked about. What else do you think we might learn in the next few years that could help people grow their families related to NAD and fertility?
Dr. Mark Ratner: That’s a good question. I’m not sure. You really don’t know what’s around the corner. I think that part of the challenge in these kinds of studies is that they take a long time to do. When you’re talking about human couples and women…a mouse is only going two years, but in a woman, it’s going to be a 40 or 50 year process to go through their reproductive lifespan.
I think what we need to do is come up with some clever ways of measuring these things with what we would call substitute end points. Most of the clinical trials that are done in fertility, what’s the outcome, what’s the measurement that you want to make at the end of that clinical trial? You want pregnancy rates. You want live birth rates. Those trials take a long time to do, they’re very expensive to do because you need to enroll many, sometimes hundreds of couples. Given the way NIH funding has essentially come under fire, trying to get those kinds of studies done has become even more difficult.
Dr. Aimee: I’d be curious to see studies on NAD and male fertility, potentially. That’s an interesting topic for me.
Dr. Mark Ratner: That’s a great question. The data is somewhat mixed, and I think that is an easier thing to measure.
Dr. Aimee: Right. For so many reasons.
Dr. Mark Ratner: Yes. To get a woman’s egg and see how that egg looks genetically and chromosomally is not easy. You have to do an egg retrieval if you want to actually examine the egg. Sperm is a lot easier. We didn’t mention this at the outset, but by training, I’m a urologist. When I was in my fertility practice, I was working very closely with IVF practices. I used to basically be doing the male part of it, but because it’s a couples issue, over the course of 25 years of practice, you basically have to become an expert in every aspect of it.
Why is the data mixed on male? There are a couple of studies that seem to show that sperm quality improves if you increase NAD levels in the semen, but there was a study published just last year, and this was a strange study that looked at men who had normal semen analyses. In other words, these were guys who weren’t coming in because they had a problem. They took guys who had normal semen analyses and ranked them in terms of the quality. They were all normal, but some were better than others.
Then they measured NAD content. What they found was that the guys who had the best quality sperm had the lowest levels of NAD in their specimen, which seems to be not what you would expect. Right? Conversely, the guys who had the least good quality sperm had the highest levels of NAD. It raises the possibility that maybe the increase in NAD is the body’s response to poor quality sperm. In other words, the body is saying sperm quality is not good here, let’s make some more NAD and get some more NAD going in the semen.
We’re still working on that question. I think there’s still more data to be looked at.
Dr. Aimee: Also, longevity. I want to live until I’m 120.
Dr. Mark Ratner: All of the excitement about NAD boosting really was focused on anti-aging and lifespan extension. The first studies that were ever done were done in yeast. They found that if you boosted yeast’s NAD levels, they lived 30% longer. Then they moved up to roundworms, and they found that it was only a 20% gain in lifespan. Then they moved to fruit flies. In fruit flies, it was only 15%.
What we’re seeing is that the more complicated the organism, the more complex the organism, the less the lifespan benefit appeared to be. When they got to mice and they gave mice NAD to see if they would live longer, they didn’t.
Dr. Aimee: How interesting.
Dr. Mark Ratner: But there’s a different concept, and it’s an important concept to focus on. There’s lifespan, which means the whole organism is living longer. Then we also have to think about what we call healthspan. Healthspan means you’re staying healthier longer. That’s slightly different than lifespan. You may not live longer, but the years that you have, you’ll be healthier during those years.
There’s terrific data in human trials on the ability of NAD boosting to improve human healthspan. It reduces blood pressure, it improves peripheral vascular disease, it reduces inflammation, one study after another. The concept of its use in female fertility can be viewed as improving ovarian healthspan. Your ovaries are going to stay healthier longer.
Dr. Aimee: I’ll be taking my NAD until I am 120 so that I can be doing egg retrievals until then. That is my new goal. I had a goal about the age that I’m going to be at when I can retire. Now it’s going to be extended.
Where can people find OvaNAD+, can you tell us where they can get it?
Dr. Mark Ratner: Sure. You can buy it online. It’s not in drug stores. You buy it online at either our website, Theralogix.com, and I think it’s actually now for sale on Amazon. Although, I think the pricing on Amazon is higher. Those are the places. It gets shipped to you in the mail. It’s a 90-count bottle, one capsule per day, so it’s a three-month supply.
Dr. Aimee: Is there a discount code that listeners can use to maybe get a discount from the Theralogix website?
Dr. Mark Ratner: When you’re checking out, if you use the discount count EGG, I think it drops the price by about 15%.
Dr. Aimee: Cool. Thank you for that. You guys heard it here first. Thank you, Dr. Ratner, for joining us. Is there anything that you want to add before we sign off?
Dr. Mark Ratner: No. I think we explored lots of good stuff. Thank you for having me. It was great talking to you.
Dr. Aimee: Thank you. Thank you so much for joining me today and for sharing your expertise on NAD+, sirtuins, and fertility. This is a very exciting area of research, and I know our listeners will appreciate learning more about how science is continuing to move forward in ways that may one day help improve egg quality and fertility outcomes.
If you enjoyed this conversation, don’t forget to subscribe to The Egg Whisperer Show wherever you listen to podcasts and follow along for more expert interviews and fertility education. If you’d like to ask me your IVF questions or egg freezing questions, or questions about fertility in general, join me at my next IVF class at EggWhispererSchool.com.
