In this interview, Jonathan Bortz, MD, highlights new and emerging science on the health benefits of choline. Bortz delves more deeply into the role of choline in cognition across the lifespan. He addresses the unique role that choline plays in lipid metabolism and liver health. Listeners will learn about the physiological implications of choline inadequacies and how clinicians can help close the gap for their patients.
Approximate listening time: 43 minutes
About the Expert
Jonathan Bortz, MD, obtained his medical degree from the University of the Witwatersrand Medical School, Johannesburg, South Africa, and trained in endocrinology and metabolism at Washington University in St. Louis, MO. He was in private practice for 15 years before moving into the pharmaceutical sector, where he developed multiple branded products for the prescriptive nutritional and prenatal markets. Bortz now serves as the senior director of strategic innovation, human nutrition, and pharma for Balchem Corporation and is recognized for his ability to translate complex and intricate physiology into understandable and actionable science.
About the Sponsor
Balchem is the supplier of VitaCholine, the premier source of the essential nutrient choline. Choline plays a crucial role in the body throughout life, yet it’s been well established that most of the population doesn’t get nearly enough from diet alone. Choline is a key component in various molecules that strengthen cell membranes, regulate genetic expression, and transport fats out of the liver for conversion to energy. Choline is essential in the proper development of the fetus, principally the brain and central nervous system, and studies have shown a marked improvement in the cognitive function of children receiving increased amounts of choline. As a precursor of the vital neurotransmitter acetylcholine, choline assists the brain in sending messages throughout the body via the nervous system.
Consumers are about to ask a lot more questions about choline and given the myriad of health benefits it provides, patients will appreciate their health care practitioners being able to answer those questions. For more information, you can download this digital guide and receive 1 full CE credit thanks to an educational grant provided by VitaCholine.
This podcast is brought to you by VitaCholine, the leading manufacturer of quality choline products for foods, supplements and infant nutrition.
Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we're going to be talking about utilizing choline in clinical practice. My expert guest is Dr Jonathan Bortz, but before we begin, I'd like to thank the sponsor of this topic who is VitaCholine. Dr Bortz, thank you so much for joining me.
Jonathan Bortz: You're welcome, Karolyn. It's my pleasure. Thank you.
Gazella: Well I am anxious to dig into today's topic because we have a lot to cover and it's a fascinating topic. So let's start with some of the basics. It seems like choline is getting some additional coverage recently. So tell us a little bit about choline and why suddenly it's in the spotlight.
Bortz: Well Karolyn, it's interesting because choline was really first discovered, if you will, or some of the physiologic aspects teased out in the late 1800s, early 1900s. It really wasn't until 1932 when Charles Best, of Banting and Best fame, the discoverers of insulin if you will, really started describing how, when they looked at their dog model, they found that the animals that had choline deficiency had developed metabolic disease and really what we now know as fatty liver. So from 1932, things were pretty dormant until Dr. Steven Zeisel in the early 1990s really started looking at choline as a rediscovered nutritional ingredient if you will. It wasn't really until 1998 when the Institute of Medicine first established it as an essential nutrient, but then it took literally nearly another 10 years for the USDA to recognize it as one of its shortfall nutrients. This happened in 2015.
In May of 2016, the FDA actually established an RDI for choline for the very first time. I think once that happened, professional organizations like the American Medical Association and the American Academy of Pediatrics in 2017 and '18 respectively started calling for attention to be paid to choline, particularly for the addition of prenatal vitamins. I think along with that and the fact that there have been several high-profile publications in well-respected journals that are beginning to tease out and understand the important role of choline, I think this has really garnered a lot of the attention that really has occasioned this interview for example.
Gazella: Right. And you mention the dietary shortfall so I'm curious. Are there any specific populations that actually face a greater risk from choline inadequacy?
Bortz: So the answer is yes, but I think first it's important to say that because of the source of choline which is really in animal-source foods, a very high presence in liver for example which has got the highest concentration of choline and then eggs and then red meat, these are the sort of food types that have been discouraged over the last 60, 70 years with the whole cholesterol story. So the truth is that actually entire population is at risk for choline deficiency, and in fact NHANES data has described that. So I think that the ... By the way, this is the case in both developing countries and developed countries. So the average intake, and I think NHANES was very instrumental in describing what the recommended intakes should be, and it turns out that about 90% of the population, both men and women, are deficient, again both in developing and developed countries.
So number one, there's a general global vulnerability. In terms of specific populations, I think that because of the nature of animal-source food origin of choline and the fact that the animal-source foods were associated with hyperlipidemia and the whole cholesterol heart model, the populations I think at particular risk are vegetarians and actually more particularly vegans. So I think I would identify those as clearly at-risk populations.
Gazella: So what ... Oh, go ahead.
Bortz: No, no, no. Go ahead, Karolyn.
Gazella: Well I was going to ask about the role of choline in early childhood development because I've been reading a lot about that. So I'm wondering if you can touch on ... You were probably going there next.
Bortz: Well where I was going is that there's the dietary intake side, but then there's also the metabolic side. It turns out that one of the reasons that choline, which by the way used to be referred to as Vitamin B4 and really doesn't quite get categorized as a vitamin and the reason for that is that the body does have the ability to synthesize choline in small amounts. This synthetic pathway is particularly well-developed in women, and the reason for that is that the requirements, and this is exactly where your question was leading, the requirements for choline are particularly high in the third trimester as well as the fact that they are, choline is prevalent in breast milk.
For example, there isn't an infant formula on the market that doesn't have choline. It is required to be in that formulation because of the high concentration in milk. As well as in breast milk, as well as the fact that in their third trimester, there is a ramping up of choline requirements. The reason for that is that choline is critical in both neurogenesis, both the development of neuronal cells as well as the myelin development, and we can discuss the reasons for that in a bit. But it turns out that this ramp-up is really very estrogen-dependent because the pathway that generates phosphatidylcholine, the phospholipid that actually carries DHA across the placenta into the fetus, is carried by the phosphatidylcholine that is made through 1 of 2 important, only one of the 2 important metabolic pathways for choline.
It's called the oxidative pathway or the betaine methionine pathway or otherwise known as the PEMT pathway. The PEMT stands for phosphatidylethanolamine methyltransferase. So it's actually making phosphatidylcholine from phosphatidylethanolamine, and that enzyme is called the PEMT enzyme, is very sensitive to estrogen. So it gets switched on by estrogen. So as the third trimester advances, estrogen levels climb and that's what turns up or revs the engine so to speak. By the way, that's the reason that, if you look at the NHANES data as well as the recommended dietary intake, women require about 425 milligrams of choline in the nonpregnant states and about 450 in the pregnant states whereas men require about 550 milligrams. It's not a body size issue. It's the fact that women can actually synthesize the phosphatidylcholine more effectively because of this estrogen-responsive PEMT enzyme.
Why does that tie into the earlier question that you asked about vulnerability? That is that it's been identified again by Dr. Steven Zeisel and others that the enzyme responsible for this is subject to a significant prevalence of misspellings in the gene that codes for the enzyme, and in his hands and certainly Caucasian, North European Caucasian in the United States, it's about 50 to 75%. So there's a huge number of women, particularly of Caucasian descent, who have an ineffective, not a nonfunctional but a less functional PEMT enzyme. So I would categorize folks particularly of that Northern European origin as being particularly vulnerable to choline deficiency.
Gazella: I see. So it's clear that choline is actually a critical nutrient for fetal and early childhood development, and you describe, you did a great job with describing why. I'm wondering if there are any other reasons why choline is so important to pregnant women.
Bortz: Sure. Okay. So 2 things. I think it's important to understand when I was first introduced to choline, I understood it as being the part of acetylcholine which is an important neurotransmitter, but didn't really appreciate that choline has got 2 very different but very important functions. That's one of the reasons why they are so impactful in a variety of different conditions. The key issue is that choline, which really is a derivative of glycine and a mono-acid, has got 3 separate methyl groups, 3 CH3s. So it's a trimethylamine. What this means is that it is able to donate its methyl group and is the key nutritional methyl donor to the body.
What are other methyl responsive vitamins? Well folic acid and vitamin B12. Those are methyl carriers. Choline is the donor and B12 and folate are the carriers. So those 3 really constitute the sort of 3 legs of the stool, if you will, that constitute 1 carbon metabolism. What is that responsive for or responsible for? That is methylating mainly genes in order to actually stimulate the appropriate production of various proteins and other factors. So methylation is a key component and it turns out that methylation is required by the neuronal progenitor cells. These are the cells that become the neurons in the brain and in the peripheral nervous system. So the actual differentiation of these neuronal progenitor cells requires methylation.
So choline is responsible and that's why it's such a key element in this rapidly expanding neural development phase of the third trimester. The fetal brain is sort of doubling in size in the last month or so. So there's tremendous, tremendous neuronal activity going on. The biggest growth that actually starts laying down the infrastructure of neuronal tissue is choline-dependent.
Bortz: Number 2 is that choline's other significant attribute besides being a methylator or methylation stimulator of genes is that it also lends ... Methylating is one of the mechanisms for the closure of neural tubes. It's thought to be methylation of that neuronal tissue. So it turns out that while everybody knows and insists that their patients take folic acid because that has been demonstrated to reduce neural tube defects, it turns out that really only about 50% of neural tube defects, which is really the very distressing malformations, spina bifida and other more severe manifestations with anencephaly, but only about 50% or there about are folate-responsive. So there is a very high residual risk, if you will, if you're only giving folic acid in your prenatal vitamin.
In fact, that's what the American Medical Association and the Pediatric Academy called out. They said, "You know what? This is important for neural tube defects." It turns out, Karolyn, that when you stabilize both B12 and folic acid, it's been demonstrated and been published, Shaw et al showed, that as you decrease your choline intake and your choline levels drop, you virtually double the incidents of neural tube defects. So choline itself is a very critical part of preventing these awful malformations. So that's on the sort of genetic and epigenetic side.
On the flip side, choline is also very, very water-soluble. That's why it is such an important component of phospholipids. How else do you carry lipid-soluble long-chain fatty acids in an aqueous environment like blood? You have to have a molecule that is water-soluble on the one end and lipid-soluble on the other. That is a phospholipid. That's by definition this polar molecule. Choline is one of several of these polar heads that makes phospholipids very water-soluble. Well that in itself ends up being responsible for the construction of phospholipids oriented in a certain way to create these double, these sort of membranes with 2 layers of phospholipids. So choline is very critical for membrane creation. Those membranes affect myelin.
So therefore, myelination or white matter production also in that third trimester and first probably 1,000 days of postnatal development of the infant is very, very choline-dependent as well. Myelin has a 30, 40% phosphatidylcholine content. White matter or myelination is what ends up being demonstrated to increase neural processing speed. So that's the sort of thumbnail as to why choline is so critical for neurologic development.
Gazella: Yeah. I think that you've given us a lot of great information and a lot that I personally had not known especially about the folate responders and the other information that you provided us with. I'd like to talk a little bit about research because I know that there's been some newer research. So what are some of the latest findings from clinical studies involving choline?
Bortz: Sure. So first of all, they recognize that over the last probably 30 years or so a lot of animal research has focused on a part of the brain called the hippocampus which is responsible for a lot of relational processing in the brain. Well it turns out that the hippocampus has been so critical to just different aspects of neurocognitive development and stress and visual-spatial memory for example. That is why by virtue of the fact that there is methylation that is taking place at these hippocampal areas and actually affecting the way these cells get laid down and then interact in their environment in relationship to cerebral cortex and what have you.
It's also been shown that, in really a pivotal study that comes out of Cornell, Dr. Marie Caudill and her colleagues, where they gave pregnant women in the third trimester either 100 milligrams or 550 milligrams of choline and then were able to look at their offspring and do neurologic tests on 4-month-olds, 7-month-olds, 10 months, and 13-month-old infants. They used a standardized test where you show a peripheral image to an infant and then you can measure their reaction speed as to how quickly they look at that particular alternating peripheral image. What they found is that ... By the way, these mothers all had a standardized diet of 380 milligrams of choline. So in other words, they were either getting 480 or 930 milligrams of choline. What they found is that, in the offspring of mothers who had the 930 during that third trimester, their infants had a significantly shorter reaction time indicating increased neural processing, again confirming the fact that this myelination was taking place much more effectively with a higher choline intake.
So the question that the group had was, "Well if we can ..." By the way, this was the first study that actually showed this impact in a human study on their infants. The next question was is this enduring. What is fascinating is that ... And this has not been published yet but is in the process. It is in the process of being submitted but has been presented as abstracts at a few international meetings. But the question was, "Well what if we follow up on those kids and see whether there is some lasting impact of the fact that their mothers had recommended choline or a higher than recommended choline intake?" These kids were brought back from all over the world and there were about 20 of them who were studied and shown that, at age 7 when subjected to various sustained attention tasks and all the other data, neurologic and neurodevelopmental tests, the offspring of the kids whose mothers had 930 milligram had a significant better performance.
Not only that. When they were doing different blocks of tests that were repetitive and were taking up time, these kids actually were able to sustain their retention and get things right so to speak with the testing versus the 480 milligram group whose sort of performance was flagging with the time and the intensity and the degree of difficulty. In addition, executive function was looked at, and this is really what I think is the most exciting. They were given very, very ...
In fact when I show adult audiences what the tests were—one of them is called a Tower of London test where you've got beads on different size pegs and you have to move them within a very limited number of moves to a pattern that the kid has been shown in a flashcard or something and they're told, "Don't do it. It's not trial and error. You've got to figure out all the steps you have to do. No more than 4 steps and figure it out and then get to it"—what they found is that the kids who are offspring of the 930 group just knocked it out of the park. They were 2 and a half times more likely to solve a problem on the first attempt and get it right versus their 480 counterparts. Not only that, they actually were able to demonstrate that when they were told to plan it, their planning time ... Instead of going from about 14 to 16 seconds in the 480 group, they went from about 12 to 29 seconds.
In other words, the kids had better inhibitory control, made better planning, and this is a well-validated executive function test. It's also been shown that when you look at processing speeds that other researchers in Boston demonstrated earlier than that, that if you've got good processing speed, this will translate into better attention and working memory at age 11 years. Now for the first time, we're able to demonstrate that actually if you give choline, you can actually increase infant reaction time, processing speed, and that can translate into these benefits in early to mid-childhood.
Gazella: I mean that is fascinating.
Bortz: That's very—
Gazella: Yeah. I mean that's fascinating. I have a couple of clarification questions for you. So the Cornell findings that you're describing, is this the same group that did the 7-year followup study that you're describing showing that—
Bortz: That is correct.
Gazella: Okay. So now, we know that it has lasting effect. I just want to clarify. So this was 930 milligrams that the mother took during the third trimester in just a daily dose of choline?
Bortz: Good clarification. No.
Bortz: The mother, the average diet was ... Not average. The controlled diet. This was a controlled diet study that wasn't some people have more eggs or less or chopped liver, whatever, right? They had a controlled diet of 380 milligrams, and then they were supplemented either 100 or 550.
Gazella: Got it. Okay.
Bortz: So the supplemental dose ... By the way, the folks who were given 550 didn't end up spilling more choline in the urine. In other words, they used it. Here's another important point, Karolyn. The 550, that being the FDA use that number from a study that Steve Zeisel did in healthy males. What he did was ... And I think this is very important. What he did was he looked at normal, healthy diet and he then put males on a very low choline diet. Within 2 weeks, their choline levels had dropped and their liver function tests had gone up. Their aminases, their transaminases had gone up higher even at the third week and when he gave them 550 milligrams—again, these are men—within a week, their transaminase levels came down and their choline improved.
In other words, what he showed was that 550 milligrams was the minimum choline needed to actually protect the liver. Why the liver? Remember I said to you that choline is important for membranes. Well particularly the phosphatidylcholine is particularly high in liver membranes, muscle membranes, mitochondria, and myelin as well as VLDL by the way, very low-density lipoprotein. So if you don't have enough choline, you're going to start pulling choline from the reserve which is going to be membranes which is why you start getting leaky CPKs in muscle and leaky transaminases in liver. So in other words, the 550 that the FDA said is your daily recommended intake, actually that is the minimum amount to prevent, in healthy males, liver dysfunction. So what Marie Caudill's group showed is that when they gave the 550 over and above the 380 diet, there was not any wastage. In other words, it's used. It is used.
Gazella: Yeah. I want to kind of stay on this topic of choline across an entire lifespan. So we know that it's relevant during infant cognition and now you're describing how it can impact the liver. So how else does it help across an entire lifespan from infancy through adulthood?
Bortz: Well let me ... Let's go back into the neurologic realm for a minute. I presented this information to boardrooms and to adults. While they are fascinated by the prenatal and the early childhood and neurologic development, I heard this about a year ago to say, "Well what about us? It doesn't make any difference for us to be taking choline." I would say to you that a study came out, an animal study nevertheless, but a critical study came out where they looked, they had mice who were 2 and a half months old. They were dams. They fed them either a controlled diet for a choline diet. They had offspring. The offspring of the choline cohort were nursed for 21 days and then weaned. So those offspring went on a controlled diet, and then those offspring had offspring.
What they then did at the end of 14 months, by the way, in the 2 generations of offspring which is pretty old for a mouse is they looked at their brain and they found that there was a significant, statistically significant reduction in the amount of beta amyloid that was deposited in their brains. In other words ... And then they looked at the offspring's offspring and found that that was the case as well. So they then looked at the genes that were affected and what they found, which is really fascinating, is that the choline group landed up through methylation impacting genes, methylating the genes, and these became trans-generational. In other words, the impact of the mother went to the offspring and then was genetically passed on to their offspring. Again, the second generation and the third generation mice were all on controlled diets.
So a paper has just come out a couple months ago that actually looks also at a mouse model with Alzheimer's disease, and this found improvement in the impact on various aspects of the pathogenesis of Alzheimer's and in fact function of these animal models. Now, remember up until the first Caudill study, all this stuff was done in mice. In other words, there is a precedent that the choline effects are shown in the animal model does translate into the human. We still have to do that, but there is an interesting cohort that was looked at in the Framingham offspring cohort in which it was shown that following folks from that Framingham study, they found that those who had a higher choline intake had less degeneration of their cognitive faculties.
So there's strong evidence to suggest that not only is choline important in the neurodevelopment side, in verbal acuity, visual-spatial acuity, fine motor, now the executive function that we spoke about in these 7-year studies, but also in neuro maintenance and preventing neurologic decay.
Gazella: Well that's pretty exciting. I'm curious because you mentioned the connection with estrogen in the pregnant woman.
Gazella: I'm wondering if there's any connection ... When we think about estrogen, we also think about postmenopausal women who frankly can struggle with a wide variety of issues including brain function, et cetera. Is there a connection in that population?
Bortz: So there appears to be. Okay. I'm going to wrap this into ... Sorry. I'm going to try and wrap this into one-size-fits-all in this transition from pre- to postmenopausal. That is that it turns out that women are definitely protected from a lot of different metabolic aspects and facets here, but those who have the single nucleotide polymorphism in which their estrogen-responsive PEMT gene is less functional, they are more likely to get, to develop a fatty liver for example and also more likely to develop cognitive effects.
So what about the premenopausal woman who actually is producing choline gangbusters during childbearing up until menopause? It turns out that postmenopausal, there's a definite decrease in both the vulnerability to fatty liver and it's also been at least hypothesized in looking this a little bit more carefully that this may be playing a significant role in, as you said, Karolyn, having an impact on some of the cognitive changes that may occur in and around menopausal period. Now, you may not notice it as much with women who have got these SNPs because they may not see this change so to speak as dramatically as those who don't have the SNPs, but I think that women certainly do catch up to men in the expression of both cardiovascular disease, fatty liver, and a variety of other conditions as well. This may be part of the answer.
Gazella: Yeah. That makes a lot of sense actually. I want to stay with fatty liver because you've mentioned the liver a few times and I am curious about what is shown specific to fatty liver in terms of choline's impact. I mean we now know that nonalcoholic fatty liver disease is quite prevalent so we want to be able to do everything we can to prevent it. So what's the connection there and what role can choline play?
Bortz: Yeah. So the interesting thing is that ... Well first of all just to put it into context, everyone talks about diabetes and prediabetes as being of pandemic proportions. Well they're estimated to be about 80 million plus fatty liver cases, many undiagnosed in the United States. I do try and get my CME credits in every year and what I've noticed in the last year is that I'm being bombarded as an endocrinologist with fatty liver seminars from various sources. I actually looked into it to see what is it, what's been happening in the last few years. Number one, what has been demonstrated is that there is a dramatic increase in the number of discharge diagnoses, and the [inaudible 00:34:52] are very poor and not specific enough.
But fatty liver is definitely becoming not just substantial, but is also being targeted to endocrinologists that say you should be looking at this as a risk factor because a diabetic patient who's got more advanced fatty liver, so NASH for example, there's a direct correlation with actually cardiovascular endpoints, end causes of mortality. So mortality goes up in a diabetic patient with more advanced [inaudible 00:35:33] hepatitis. What's happening though is that big pharma has taken notice of this. In fact, there are about 20 different pipeline products that are sort of advancing. No one really talks about nutrition. Even though there's data that shows that if you go on a low-calorie diet for a week, a very short period of time, the actual amount of the way in which we can measure fatty liver whether it's elastography or fibrous scan or biopsy, whatever it is decreases.
No one talks about diet. No one talks about choline. Yet choline, one of the reasons why choline deficiency is associated with fatty liver is that VLDL is primarily phosphatidylcholine-built and in choline deficiency, you'll decrease your VLDL. VLDL carries triglycerides and you'll start trapping triglycerides in the liver. That is what one of the early pathogenetic features of fatty liver along with mitochondrial dysfunction. It's a multifactorial condition. There's no doubt about it, but there's evidence to suggest that high-dose or higher dose choline would land up decreasing the progression although most of pharma is focusing on the more advanced stages of fibrosis, inflammation, and many other sophisticated sort of mechanisms of action.
I think the answer is that it's a fairly simple intervention particularly early on to actually put folks on choline. By the way, just ... Yeah, I was just going to finish up that point. That is that the FDA says that you shouldn't be getting more than about 3,000 milligrams of choline per day, and yet the toxic dose so to speak, and that's usually associated with a sort of fishy odor, is anywhere in the nine to 10 gram range. So in other words, giving 1,000 milligrams or 500 milligrams of choline is certainly well within normal dietary intakes.
Gazella: Yeah. I mean that's actually the question I was going to ask because you mentioned higher dose. I mean we already talked about 550 milligrams as being the minimum amount to prevent liver dysfunction, but when you're talking about fatty liver and you mention higher dose, what dose are you recommending?
Bortz: Yeah. I mean if it was me, I would be ... In fact, I'm taking choline. I'm taking 750 milligrams assuming I'm on about a 350 to 400 milligram diet, maybe a bit higher than that. I'm quite comfortable in the 1,000 milligram choline intake and would happily take more if I was told I had fatty liver.
Bortz: I think that 1,000 milligram is a decent place to start.
Gazella: I see. I'd like to end with talking about the forms of choline because obviously now that we know how effective this nutrient can be, there are several different forms that are available on the market today. So what are—
Gazella: ... the key differences between the forms and probably more importantly, which form do you prefer and why?
Bortz: Sure. So I think that it's important to understand that there are phospholipases that are very active enzymes that break down the various aspects of a phospholipid when it's ingested. So what takes place regardless of whether you're getting phosphatidylcholine or alpha-GPC or CDP choline, what happens is the molecule ends up breaking down to choline, to free choline. That's free choline that is absorbed. So to me, the biggest issue is what is the amount of choline that I could get. The phospholipid approaches, phosphatidylcholine and the other forms that I've mentioned, really have got a limited payload of choline. So you might be paying for the phospholipids part, the glycerol part, the [inaudible 00:40:27] part, et cetera, et cetera, but you end up decreasing on the choline payload.
I think that it all comes down to free choline. That is what is absorbed. Yes, the other ingredients may be absorbed if there's breakdown and then there might be reassembly. So I think the key aspect here is, take enough choline. I think those really are delivered into the highest extent by some of the choline salts.
Gazella: So the ones that you recommend, free choline salts are what you recommend?
Bortz: Yeah, correct. There is the choline bitartrate, choline chloride, and I think these are not expensive ingredients and yet they deliver the choline for absorption. I think that it's important to recognize that some of the more let's say designer forms of choline have got definitely a premium pricing associated and not necessarily the payload.
Gazella: Got it. Well this has been ... As I anticipated in the beginning, we had a lot to cover. I'm wondering if there's anything else you want to add before we close, Dr. Bortz.
Bortz: No, I just think that this is a very, very exciting nutrient and the truth is that it's astonishing to me that this is sort of like a galaxy close to Earth that we haven't spotted before. I want to give credit to the researchers in the field and particularly Dr. Zeisel, Dr. Caudill, and others who have really advanced our understanding of this substantially. The truth is that I would encourage my colleagues to look at this more carefully. It has very interesting physiologic and sort of developmental impact both for our pregnant moms, throughout childhood, adulthood, and senescence. So thanks for giving me the opportunity to talk about this which has become a passion.
Gazella: Yeah. Well great. Well I can see why. It's very exciting and we'll definitely stay on top of the research as it continues to unfold. I want to once again thank you, Dr Bortz, for joining me today. It's been very informational, and I'd also like to once again thank our sponsor, VitaCholine. So everyone, have a great day and I hope you enjoyed this information.