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Advanced Metabolomics: Identifying the Metabolic Signature for Aging with Betsy Redmond, Ph.D., MMSc, RDN

Advanced Metabolomics: Identifying the Metabolic Signature for Aging with Betsy Redmond, Ph.D., MMSc, RDN

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Email: betsy.redmond@diagnosticsolutionslab.com

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Advanced Metabolomics: Identifying the Metabolic Signature for Aging with Betsy Redmond, Ph.D., MMSc, RDN

New Frontiers in Functional Medicine® with Dr. Kara Fitzgerald

Aging itself stands as the paramount driver of disease. As functional practitioners, the question arises: How can we assess biological age to make precise corrections that foster both healthspan and lifespan? Enter the era of omics, where metabolomics emerges as an exceptional tool with transformative potential. I’m thrilled to welcome back to New Frontiers Dr. Betsy Redmond, longtime friend and the senior education specialist at Diagnostic Solutions Laboratory, to lead us on this discussion. Together, we’ll take a deep dive into specific metabolites and pathways intricately linked to aging, mood, inflammation, and gut health and you’ll hear about equol, a rising star on the postbiotic scene. We’ll even unravel some surprising insights from my own test results!

Be sure to grab a copy of the Sample Report and pull up a seat for this fascinating discussion packed with valuable takeaways for yourself and your practice. ~DrKF

Advanced Metabolomics: Identifying the Metabolic Signature for Aging with Betsy Redmond, Ph.D., MMSc, RDN

In this episode, Dr. Redmond, senior education specialist at Diagnostic Solutions Laboratory (DSL), dives into the fascinating world of metabolomics and its application in functional medicine. Discover why understanding metabolic processes and disease associations through metabolomics testing is crucial for personalized health assessments. Dr. Redmond shares how DSL goes beyond traditional marker-focused reports by providing comprehensive analyses of metabolic pathways. You’ll also learn about the role of metabolomics in unraveling the mysteries of aging and age-related changes, as well as the impact of amino acids on health and longevity.

In this episode of New Frontiers, learn about:

  • Importance of metabolomics in understanding metabolic processes and disease associations [00:03:24]
  • Discussion on specific breakdowns and individual metabolite pathway analysis [00:07:19]
  • The aging phenomena and their relationship to diseases [00:11:00]
  • Correlation between chronological age and biological age [00:11:15]
  • Key markers of aging and protein structure changes [00:13:13]
  • The implications of elevated methionine on aging and methylation [00:32:03]
  • Metabolomics as an assessment for frailty and sarcopenia in the aging [00:45:23]
  • Metabolic issues associated with amino acid imbalances [00:46:02]
  • Key amino acids associated with longevity [00:45:48]
  • The significance of equol in relation to aging and the re-expression of tumor suppressor genes [00:57:35]

Dr. KF SPONSORED CONTENT

I am eternally grateful to our sponsors who, by blogging, podcasting and advertising with us, enable me and my team to devote energy and time to writing and publication. All the companies who sponsor us are companies that I trust for myself and my patients and use regularly in my clinical practice. Please check out their websites! – Dr. KF

The Full Transcript

Dr. Kara Fitzgerald (00:00:03) – Hi, everybody. Welcome to a New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And today I’m talking with one of the best. You can see her here if you’re watching us on YouTube. If not, let me tell you about her, the one and only Dr. Betsy Redmond. She has been a friend and colleague of mine for my entire career, really. We were together at Metametrix Laboratory many years ago. Today Dr. Betsy Redmond is a senior education specialist at Diagnostic Solutions Laboratory (DSL), and she’s also a nutrition consultant. She is conventionally trained; she’s got a master’s degree in clinical nutrition from Emory and has a doctorate in nutrition from the University of Georgia. She has over fifteen years of experience in functional laboratory research and education. She was part of our brain trust at Metametrix. In fact, we all leaned on her brilliance. Welcome, Betsy, to New Frontiers.

Dr. Betsy Redmond (00:01:02) – Oh, you’re going too far.

Dr. Kara Fitzgerald (00:01:04) – It’s always great to be able to hang out with you.

Dr. Kara Fitzgerald (00:01:06) – I’m very excited. So, you know, I’m just thinking about Jeff Bland, he started the Personalized Lifestyle Medicine Institute, sort of the next generation of what we’re thinking about, where we’re headed in in functional medicine. And I have been to many of his conferences and we all wait with bated breath for metabolomics panels, these more robust panels combining organic acids, amino acids, fatty acids, just bringing that knowledge forward. We started back at Metametrix, you and I and the whole team over there, looking at smaller panels. It was the forerunner of being in the omics era. But I’m very excited to be talking to you today about the metabolomics that DSL has gotten into, and bravo, you guys for really taking the bull by the horns and bringing this to functional medicine. Tell me how you got there, how you guys decided to offer this, and what you’re doing. And then we’ll talk about some of the specific markers.

Dr. Betsy Redmond (00:02:16) – Okay, yeah. We decided we wanted to offer organic acids, amino acids. It’s in the functional space. But we wanted to be what’s current, so we looked at it, and organic acids used to be more like, “this is high, it might mean this,” or you might need to take this supplement. But metabolomics really looks at a bigger picture. And metabolomics really started with just small molecules, but they’ve really pulled out. And so, you can see they’ll look at things like aging or metabolic concerns. They’ll look at a group of people who have something and a group of people who don’t, and then they’ll look and see what’s the difference. And oftentimes, when they make these charts with all the bubbles, it’ll be like tryptophan pathway, not necessarily specific markers. Or the phenylalanine pathway. We wanted to look at the whole pathway, and so that’s why we wanted to put them together. So, if you look at our report, it will have branched-chain amino acids right with their alpha-keto acids or tryptophan and the whole pathway. So if you look at a pathway next to it, you can then start to see where the issues may be.

Dr. Kara Fitzgerald (00:03:29) – Right. And we will link to a sample report on the show notes people, so access that. In fact, you may want to pause this and just take a second and grab it because we’re going to refer to it. I got my test done. Betsy and I were going to record this a few weeks ago, and then we stopped midstream and I said, “I might as well get this done so that we can talk about it.”

Dr. Kara Fitzgerald – So on one hand, back in the day we were looking at organic acids. If high give B6. If high maybe you have some yeast or something. We had more simplistic explanations. We were in the research as much as we possibly could be. I know we put tons of energy, but there just wasn’t- But now we’re really truly entering the omics era, to your point, and now we’re able to look at many more compounds and really dance around what’s happening metabolically.

Dr. Kara Fitzgerald (00:04:23) – And also, to your point, what’s very exciting about this is we’re looking at disease associations with imbalances here. We’re looking at what healthy cohorts look like, we’re looking at what aging looks like. So I think it’s just it’s pretty exciting stuff. I mean, are you-

Dr. Betsy Redmond (00:04:41) – No, I think it’s great.

Dr. Kara Fitzgerald (00:04:42) – This has been a passion project for you.

Dr. Betsy Redmond (00:04:43) – It has. And there’s a lot of markers, especially if you’re new, because we also wanted to- Like, if conventional clinicians want to see “What is that?”, I want it to be easy to look up. You can take any of the markers we have or really any organic acid, fatty acid, amino acid and look up HMDB, The Human Metabolome Database. It’s-

Dr. Kara Fitzgerald (00:05:10) – We’ll link to that on the show notes also. Do you happen to know the website off the top of-

Dr. Betsy Redmond (00:05:14) – When I want to do something, like if I wanted to look up citric acid, I would just go to Google or a search engine, put in citric acid and HMDB and it’ll come right up. It gives you what’s currently known, I mean, some of the things they don’t go in maybe as deep as we do. And then they’ll also give you all the synonyms, which is really handy because sometimes things are called so many different-

Dr. Kara Fitzgerald (00:05:40) – That’s exactly right. That’s right. So you go on Wikipedia and you can see one name and then on The Human Metabolome Database, actually they’ll corral them all together.

Dr. Betsy Redmond (00:05:49) – Yeah, they just add the synonyms.

Dr. Kara Fitzgerald (00:05:50) – Wikipedia does that not so bad.

Dr. Betsy Redmond (00:05:52) – Wikipedia doesn’t go as deep for obscure compounds.

Dr. Kara Fitzgerald (00:06:00) – I want to just say too, I’m looking at my report and I’ve given you permission to talk freely about it, and guys, if you pull up the sample report, you’ll see that there’s a down and dirty reference. So, if you don’t want to geek out on metabolomics data, and if you don’t want to go to The Human Metabolome Database, which is where Betsy lives when she’s not in Georgia, you can get a down and dirty- This is where you need support. You need support in toxins, you need support in certain amino acids. We’ll talk about aging because that’s an interest area for me, not just because I’m getting older, but… So for clinicians who are working in a really busy practice and you don’t have time to do the drill down there’s an easy, ready reference front page summary cover that will give you really clear direction. Let’s talk about… Actually, let me just say- Tell me the clear direction that you can get. What can a clinician glean from the report as a whole that’s going to guide what they’re doing with their patients?

Dr. Betsy Redmond (00:07:19) – Right. It goes in like… I’ve always got to use hand motions. So it goes in three steps. The first one, the top of the front page is really broad. It’s going to look at a big overview. And then the bottom of that is a further description. We have six categories that we’re looking at: energy metabolism, and then we look at all these amino acid breakdowns, nutrition, toxins. Then we look at the microbial metabolite stuff. We’re looking at six different areas and we look at all the markers in there and then we just add up how many of those are outside the reference range, so we give a score. The front page is based on the 95th percentile because that’s, by labs, what is going to put us out of range. So that summary score of each category gets put at the top. But then if you look at the bottom half of the front page, it breaks it down. Is it glycolysis? Is it the Krebs cycle? Is it the phenylalanine pathway? It kind of gives you an idea. And then the last layer is to just go through the test and it’ll tell you specifically, because we’re doing it based on the 95th, because that’s proper lab work. but if you go through, you may find other ones that are creeping up that meet the story that you want to tell.

Dr. Kara Fitzgerald (00:09:00) – Yeah. So then you can move into the heart of the laboratory data itself. And you have, which I absolutely love coming from our lab background, you’ve taken the time to divide them into quintile reference ranges so we can see the outliers, the 95th reference interval, so the frank highs, the frank lows. But then we can also see where we fall within the population as a whole. Am I right in the middle? Am I a little bit high? Am I trending down? And then as clinicians, we get to drive the car much more efficiently, I think, and make good, strong clinical decision based on trends and not just frank disease. One of the things that Peter Attia says that I think is very apt, and it’s easy, is he talks about the current medicine model being sort of medicine 2.0.

Dr. Kara Fitzgerald (00:09:50) – Don’t come to me until you have a disease, then we will diagnose the disease. But we know that pathological changes happen earlier. Way, way, way earlier, maybe decades earlier, maybe in utero even. And it’s only with these subtle intervals, it’s only with being able to look at the data much more clearly can we perceive those changes early on and actually make a difference.

Dr. Betsy Redmond (00:10:17) – Yes, and I think that’s everybody with IBS, isn’t it, going to the conventional care? And they’re like, “Oh, we did a colonoscopy. You don’t have cancer.” Thanks.

Dr. Kara Fitzgerald (00:10:27) – Yeah, that’s right. That’s right. Yeah. You haven’t pooped in three days. No big deal. Okay. That’s not constipation. Yeah, that’s right. Let’s talk about some of the aging analytes in here. Longevity has moved into the front and center of our conversation, maybe because those of us who’ve been around functional medicine for a while, we’re all marching into our 40s, 50s and 60s and we care about it.

Dr. Kara Fitzgerald (00:11:00) – But I think we’re getting more and more in our space that the aging phenomena, the changes that happen to the body in the aging journey actually drive the diseases that we’re trying to keep at bay in functional medicine. So how can we assess that?

Dr. Betsy Redmond (00:11:15) – Well, I mean, it’s hard to study chronic disease and not also study aging. They all move along together. When you look at some of those research studies, I think you know I’ve always got a stack of articles. So this one is by Johnson, and I’m assuming it will be in the shownotes, but they have a really great graph and it has chronological age on one side, biological age on the other, and then how much they correlate. It has an R squared value of 0.69. So about 70% of biological age is accounted for with chronological age. But there’s such a huge variation and I think that’s where we want to kind of go.

Dr. Kara Fitzgerald (00:12:02) – That’s where it gets interesting. Yeah, Yeah.

Dr. Betsy Redmond (00:12:04) – They divide it by men and women, but there’s like, two men that are both twenty. One looks like he’s like fifteen and one looks like he’s forty-five. There’s a seventy-year-old woman who looks like she’s forty and another one who looks like they’re ninety-five. And what they also found was that as people age, they tested them five to ten years later, the people who were aging faster were still aging faster.

Dr. Kara Fitzgerald (00:15:07) – So, in this article, which just is extremely cool, not a lot of these biomarkers correlate with the chronological age journey, but certainly some of them do. But the biological age journey seems kind of rich here. Things that we can actually action and make different. Talk to me about some of these markers that are really interesting to you and why.

Dr. Kara Fitzgerald (00:15:34) – And then if you want to, let’s talk about some of the markers you found on my test. So talk to me about this paper. What’s interesting there? And then let’s talk about the test and what you guys have and what we can look at as clinicians.

Dr. Betsy Redmond (00:15:47) – Yeah. So I was saying that, you know, they were looking at markers related to biological age and one of those was homocitrulline. So, you know, homocitrulline was higher in people who had higher biological age.

Dr. Kara Fitzgerald (00:16:04) – Got it. Okay. Okay. All right. And that-

Dr. Betsy Redmond (00:16:07) – So it comes off the urea cycle. So, it maybe it’s also related to really high protein intake, any kind of kidney impairment function, so you can see higher levels. And there are articles talking about protein carbamylation, because that’s what it’s called when you make homocitrulline. It’s carbamylation and it’s been associated with aging.

Dr. Kara Fitzgerald (00:16:36) – So it’s a change to the protein structure.

Dr. Betsy Redmond (00:16:39) – Yeah. So just like proteins can undergo alterations with glucose, the same type of thing, but it’s with the isocyanic acid that comes off when you make urea, it also comes off and you can also get it from cigarette smoke. It binds with the lysine residue and then you make homocitrulline.

Dr. Kara Fitzgerald (00:17:05) – Is it a surrogate marker of some sort of toxic process or is homocitrulline itself toxic? Do you know that? Just out of curiosity.

Dr. Betsy Redmond (00:17:15) – I don’t know that.

Dr. Kara Fitzgerald (00:17:15) – Because it’s a byproduct. So smoking can cause this protein, the structural change to protein, and aging we know causes a structural change to many proteins. And this is one of those markers. That’s so fascinating.

Dr. Betsy Redmond (00:17:31) – So I will say yours was low.

Dr. Kara Fitzgerald (00:17:35) – Woohoo! That’s awesome. And if we’ve got somebody with a high homocitrulline, what do we do about it?

Dr. Betsy Redmond (00:17:44) – Well, it’s going to be related to urea production. Well first if you’re smoking, I would stop that. But look at kidney function overall, and on our test, you could look at creatinine, albumin, look at some of those things. When you go to make homocitrulline it also shoots over and makes orotic acid. So, more orotate would be made, so they’re both elevated. Is it somebody who’s on a high protein diet who maybe needs to pull back a little bit? Maybe they don’t have the full function for that.

Dr. Kara Fitzgerald (00:18:19) – Yeah, that is so fascinating. So, there’s been this trend towards massive consumption of protein in our space. We blogged on it recently. Actually, we did a bit of a dive on it, but there’s a movement towards consuming up to two grams per kilogram body weight or a gram a pound body weight. So high, high protein intake and it makes sense to me that it wouldn’t be ideal for all of us.

Dr. Kara Fitzgerald (00:18:49) – We’re all different. And I know there’s compounds that we make in the gastrointestinal tract from protein or from certain amino acids that aren’t necessarily our friends. So if we’re consuming a lot of protein and we have dysbiosis, we might see some of those jack up and be associated with inflammation, like classically indican.

Dr. Betsy Redmond (00:19:17) – Yeah. So I think that’s one of the things because- I think you’re right. Everybody isn’t going to be the same. So maybe you can’t handle that.

Dr. Kara Fitzgerald (00:19:27) – Right, right. Or at least not with your current metabolic snapshot.

Dr. Betsy Redmond (00:19:33) – Right. So everybody’s going to be a little bit different, so it might help you tailor that.

Dr. Kara Fitzgerald (00:19:38) – Interesting. So homocitrulline would be one of those compounds, where if it’s elevated, we’re thinking about accelerated aging. Specifically, we’re thinking about kidney function. We might see it in somebody with higher protein intake who is not doing as good of a job with it.

Dr. Betsy Redmond (00:19:55) – Right.

Dr. Kara Fitzgerald (00:19:56) – What are some of the other markers associated with it?

Dr. Betsy Redmond (00:20:00) – Overall? There’s a good article because I’m all about the articles. Because I think there’s so there’s so many issues though. You can start looking and you know, what are they doing? Are they looking at people who did age well, who didn’t age well? I think it just depends on what you’re looking at. You don’t want to automatically read a study and say, well, that’s what I want to do. Because centenarians might have that but is that what you wanted? So there’s that study where they look at people who are older in China who live in a town that there are lots of centenarians and they compare it to a regular town where there’s not lots of centenarians. And then they found some things, like they were more likely to have higher tyrosine, higher citric acid, higher lactic acid, and higher valine.

Dr. Betsy Redmond (00:20:59) – And I think the citric acid, that’s also so related to diet. More plant-based diet tends to have higher citric acid. It can also go up if there’s an issue with renal function. But your citric acid was good.

Dr. Kara Fitzgerald (00:21:17) – I’m happy to hear that, you know, especially because just recently my brother went through kidney stones and that’s classically associated with low citric acid and dehydration. Citric acid is one of the interventions, you know, lemon water. We always recommend to our patients to drink, and very seriously, I mean it can absolutely make a difference in the formation of the calcium oxalate stones. So citric acid is evidence of a good diet and it’s seen in people who are living long lives. Are they healthy? Did they look at that group and define that?

Dr. Betsy Redmond (00:21:55) – They didn’t really define that so much. But you see it in other studies where they look at people on more plant-based diets, higher polyphenols, citric acid-

Dr. Kara Fitzgerald (00:22:05) – And it’s associated with health.

Dr. Betsy Redmond (00:22:07) – Yeah. So I think also we say don’t eat a bunch of pectin right before you take the test. We have a list of some foods because that can shoot all those up. One of the other things that we’re looking at in aging is decreased tryptophan. And so that pathway is fascinating because it does a lot. So that’s one of the ones that you had that surprised me, was a lower tryptophan.

Dr. Kara Fitzgerald (00:22:36) – Yeah. And that’s not a great thing. I know it’s kind of… I eat plenty of protein but I have struggled with my albumin, which in circulation is, you know, that’s another longevity metabolite and mine tends to be a little bit on the lower side. I think I actually may be somebody who needs to stay on eating decent protein. We’ll see. I mean, that might be a piece of the puzzle, but my tryptophan was low too. That was interesting to me.

Dr. Betsy Redmond (00:23:07) – I mean overall, you looked great.

Dr. Kara Fitzgerald (00:23:11) – Thank you. Good. I look youthful.

Dr. Betsy Redmond (00:23:11) – Yeah, you look like a 16-year-old.

Dr. Kara Fitzgerald (00:23:16) – So, tryptophan. I want to understand about tryptophan, but what made you determine in general that I had a metabolomic pattern of somebody younger. So first tryptophan, and then give me your pattern analysis.

Dr. Betsy Redmond (00:23:30) – Yeah, You know what? I’ll give you the rundown, and then we can go through the whole tryptophan thing. You had higher citric acid, you had higher alpha-KG

Dr. Kara Fitzgerald (00:23:40) – Alpha ketoglutarate.

Dr. Betsy Redmond (00:23:41) – Yeah. You had branched-chain amino acids that were not high. So you want to have those in the sweet spot. You had lower quinolinic acid, your methionine was lower, and your taurine was good, so those things. The two things that I noticed were that you had a slightly elevated pyroglutamic acid, which might be a glutathione thing, and then lower tryptophan. But you had a slightly different picture.

Dr. Betsy Redmond (00:24:10) – Tryptophan can go on several pathways. Tryptophan can go over to make serotonin, everybody’s pretty familiar with that. And then the breakdown product of that’s going to be 5-hydroxyindoleacetic acid (5-HIAA), and yours was good, so you seem to be making that. But why? Normally when I see a low tryptophan- So tryptophan also goes to kynurenine and then to make indoles in the gut. So, in the kynurenine pathway, normally tryptophan will throw out the TDO enzyme (tryptophan 2,3-dioxygenase) in the liver. It’s making some kynurenine, the kynurenine pathway goes through a lot of steps. It makes quinolinic acid that makes NAD (nicotinamide adenine dinucleotide). That’s what it’s churning out. But if there’s any inflammation, it switches over into that extrahepatic IDO enzyme (Indoleamine-pyrrole 2,3-dioxygenase) . And so, if there’s TNF Alpha, if there’s IL-6, different inflammatory markers, it just pumps up that IDO enzyme and that pulls tryptophan down to kynurenine pathway.

Dr. Kara Fitzgerald (00:25:17) – And so we’ll see evidence of inflammation. That’s the pattern you usually see. So when you see a low tryptophan, you’re flipping the page to look at inflammation?

Dr. Betsy Redmond (00:25:26) – Well, I’m looking on the pathway because we also report kynurenine itself. Not kynurenic acid, but kynurenine in that first step. So you can look at the  kynurenine to tryptophan ratio, the K/T ratio, and that’s been associated with chronic disease, it’s been associated with aging. It’s considered-

Dr. Kara Fitzgerald (00:25:46) – So a high K and a low T.

Dr. Betsy Redmond (00:25:49) – Right. The other low T. So yeah, you’re going to be pulling that down. Normally we see it get pulled down and when you pull down so much of it, there’s so much inflammation, sometimes people will essentially run out of tryptophan to make serotonin and they might be associated with depression. Yours didn’t really have that pattern, but looking for inflammation – why is the tryptophan getting pulled down that way?

Dr. Kara Fitzgerald (00:26:21) – Yeah. Yeah. And inflammaging, you know, unless we’re very actively working against it the volume on inflammation is going to turn up on the aging journey. So I can work on increasing my tryptophan with tryptophan foods and you know, my gut microbiome, but I’m glad to hear that inflammation is a non-issue via the kynurenine pathway. That’s awesome. Can you infer from this that I’m making adequate NAD from this information? Because that’s another sort of a hot compound that I’ve been thinking a lot about.

Dr. Betsy Redmond (00:27:00) –So what you see in research, what I’ve read is that looking at that pathway you’ll end up making more kynurenine and you’ll have, in aging, a higher K/T ratio. But then it goes down the pathway but you have elevated quinolinic acid. Elevated because you’re not going all the way. So quinolinic acid has a specific enzyme, the QPRT (Quinolinic acid phosphoribosyltransferase), that’s very sensitive to inflammation. So then you end up pushing down the pathway, you end up with higher K/T, higher quinolinic acid, but you’re not going to make more NAD. So, you end up with low NAD. You’re not making it because inflammation is stopping quinolinic acid and then you end up with higher quinolinic acid.

Dr. Betsy Redmond (00:27:52) – So you want to check out all the spots of that pathway. And then the pathway is really heavily dependent on (vitamin) B6, so that’s also something to look at. There are some good studies looking at mathematical modeling and when B6 is going to come up, so trying to look at it- I mean we’ve always looked at it based on tryptophan load studies, but most people aren’t doing a tryptophan load. But in the mathematical modeling they find xanthurenic acid can become elevated first. Even though there’s lots of enzymes that require B6 in the pathways, xanthurenic acid generally comes up first. Yours was a little bit elevated.

Dr. Kara Fitzgerald (00:28:32) – It was, yeah, I’m looking at it now. I’m going to say that I don’t have a lot of inflammation. So the kynurenine pathway probably is going on to make NAD. But there’s not a whole lot of action here and I don’t have that much tryptophan, so I could probably use some tryptophan to support NAD synthesis.

Dr. Kara Fitzgerald (00:28:53) – And then to your point. My xanthurenic acid is a little bit high and so I could use some B6 and that could help in driving tryptophan down to NAD?

Dr. Betsy Redmond (00:29:06) – Yeah, I think it’s always good to make sure you support that whole pathway. There was a study and I just thought it was so interesting. There were people who lost weight, and they checked their actual B6 blood level, (PLP, pyridoxal 5-phosphate) and then they had them lose weight and they had less inflammation. And so, with that, they weren’t chugging through this pathway, but their actual B6 blood level went up. And they were saying, well, probably because they didn’t need so much B6 to chug through this inflammatory pathway, because pretty much everything requires B6.

Dr. Kara Fitzgerald (00:29:47) – Right. Right. So by losing weight, they in effect turn the volume down on some of the metabolic damage that was happening, turned inflammation down and preserved B6 status? Is that what they were suggesting? That’s pretty cool.

Dr. Kara Fitzgerald (00:30:01) – Yeah, that’s a really interesting. All right. What else did you want to talk about on some of the markers associated with aging? And then I want to spend some time talking about why my pyroglutamate might have been up, because you had a really compelling reason that made sense in the context of my life. So other markers and then-

Dr. Betsy Redmond (00:30:23) – Yeah, well, and the pyroglutamate, you know, one of the markers that goes down with aging is glutathione.

Dr. Kara Fitzgerald (00:30:31) – Right. So pyroglutamate indicates the glutathione pathway is sort of being taxed. It’s being used, it’s being taxed, it needs support. Is pyroglutamate in the literature? Does it rise in aging?

Dr. Betsy Redmond (00:30:49) – You know, I don’t know if it specifically rises in aging. They talk about glutathione itself. When pyroglutamic acid goes up, it can identify that you have inadequate amounts of sulfur amino acids like cysteine, or you need some additional glycine. So you need cysteine, glutamic acid and glycine to make glutathione.

Dr. Kara Fitzgerald (00:31:16) – So we want to be thinking about that with a rise in pyroglutamate.

Dr. Betsy Redmond (00:31:22) – Right.

Dr. Kara Fitzgerald (00:31:23) – All of them. We just want to think about glutathione. But all of those individuals. I want to just say that pyroglutamate has cool research on rising with Tylenol toxicity.

Dr. Betsy Redmond (00:31:34) – So yeah, that’s it’s big. I think that’s its claim to fame.

Dr. Kara Fitzgerald (00:31:36) – Yeah.

Dr. Betsy Redmond (00:31:37) – I mean that’s where they realized it’s hepatically induced. Yeah.

Dr. Kara Fitzgerald (00:31:41) – It’s associated with glutathione. Yeah. Tylenol steals glutathione pretty efficiently.

Dr. Betsy Redmond (00:31:46) – I think there’s that old classic article about the young doctor who you know, somebody has acetaminophen poison toxicity and he gives them a bunch of glycine and stuff.

Dr. Kara Fitzgerald (00:31:59) – And NAC (N-acetyl cysteine). NAC is the standard of care.

Dr. Betsy Redmond (00:32:03) – Yeah. When you go to your methionine pathway, your methionine is lower, which is great, because you see that in research like, all sorts of animals in research have lower methionine. Methionine restriction is a big thing. It’s obviously not a solved issue. It’s that sometimes methionine restriction is a little easier than caloric restriction in some of those research studies. But-

Dr. Kara Fitzgerald (00:32:33) – Do you know why is an elevated methionine associated with aging? Do you know? I mean that’s like a classic amino acid in meat, again, right? Maybe would it be high in… Would it be another thing that we want to maybe- Like we just don’t necessarily want to be consuming three steaks a day if we’re paying attention to the literature on methionine, but do-

Dr. Betsy Redmond (00:33:03) – Right. Yeah.

Dr. Kara Fitzgerald (00:33:03) – I mean, do you know why we want it lower? What do they say? What do they speculate about in the literature?

Dr. Betsy Redmond (00:33:08) – When we see it higher, the first thing I think of is impaired methylation just because it’s involved in methylation. And that’s not something like, “Oh, methylation is great, let’s turn up the volume all the way.” So, you kind of want to pull back from that. Yours was a little bit lower, which was good.

Dr. Betsy Redmond (00:33:32) – I’m always looking for a balance. I don’t want really high, really low. You had some of the markers after it, cystathionine… that were higher and some of those are, cystathionine itself can become elevated if there’s a need for B6, B12, folate. Those kinds of markers can impact it.

Dr. Kara Fitzgerald (00:33:55) – Yes. And I do think I need support in methylation, even as people know me, you know, researching specifically DNA methylation. But I need to tend to my methylation cycle. I mean, my homocysteine will definitely trend up if I’m not being mindful about consuming adequate methyl donors for sure. So that does make sense to me. You know, I want to, actually, going to your point of high methionine negatively influencing the methylation cycle, that really famous Jill James study it’s looking at the methylation cycle in individuals with autism. It’s a super old study but it was impactful on me. It was in 2004 and so methionine was high in this population, homocysteine was low in this population and they opened to the whole methylation cycle with methyl donors.

Dr. Kara Fitzgerald (00:34:49) – So with B12 and folate and betaine. They normalized homocysteine levels, they actually increased homocysteine because homocysteine was low, but they also dropped the elevated methionine and glutathione synthesis. So, glutathione, being produced from the sulfur in homocysteine, improved. It was really cool. By addressing the methylation cycle, it just had these far-reaching effects.

Dr. Betsy Redmond (00:35:16) – Yeah. Didn’t she have sibling control in that study?

Dr. Kara Fitzgerald (00:35:21) – I think she did.

Dr. Betsy Redmond (00:35:22) – Yeah, and then one of the siblings had Down syndrome, so she found a similar methylation impairment in Down syndrome.

Dr. Kara Fitzgerald (00:35:31) – Oh that’s fascinating. Which has been identified elsewhere, it’s been published on elsewhere. That’s very interesting. Okay. So, that higher methionine we’re thinking about maybe protein consumption, animal protein consumption, but perhaps more likely just methylation.

Dr. Betsy Redmond (00:35:47) – Yeah. Looking at those things. Because you have the methylation cycle and then goes to cystathionine and then cystathionine goes down to that transulfuration pathway.

Dr. Betsy Redmond (00:35:58) – So what we’re looking at there is cystine, which, you know, plasma cystine can be rate limiting for glutathione.

Dr. Kara Fitzgerald (00:36:06) – And how was mine? What was my cystine?

Dr. Betsy Redmond (00:36:08) – Yours was on the lower end. Yeah. So there’s some good research I think. I think there’s a whole blog on that on your side. So that low cystine, which you know, when I saw the article on that, I actually contacted the author from the Netherlands and I’m like, “Didn’t you mean cysteine?” And he’s like, “No, I meant cystine.” So, that’s on the lower end, and you don’t want it super high either. But it’s going to help feed into there.

Dr. Kara Fitzgerald (00:36:40) – So earlier, the reason cystine is important, you know, everybody is aware of cysteine, homocysteine, cysteine, and glutathione, but cystine is actually two cysteines complexed and that is how it gets intracellular. So that’s basically how glutathione is produced intracellularly?

Dr. Betsy Redmond (00:37:01) – Yeah. So it’s going to come in and then the glutamic acid is going to come out and cystine is going to come in, it’s going to feed the cysteine, cystine, cysteine, and that’s going to go get together with glutamic acid and glycine.

Dr. Kara Fitzgerald (00:37:19) – And make glutathione intracellularly.

Dr. Betsy Redmond (00:37:22) – Yeah. So you have a low cystine, you have a higher pyroglutamic acid. So, do you maybe need some support there?

Dr. Kara Fitzgerald (00:37:34) – Some detox support. And when we were talking about this- So actually so we could jump into that, and then I had a really high- What was really high that we puzzled over for a minute?

Dr. Betsy Redmond (00:37:45) – Yeah. So we look in some toxic markers. We look at mandelic acid and benzoylformate. We also looked at different xylene markers, two, three and four. Your mandelic acid was on the high side. It was over the 95th reference.

Dr. Kara Fitzgerald (00:38:05) – It was high, frankly high. Yeah.

Dr. Betsy Redmond (00:38:07) – So, that seemed a little bit puzzling because only once have I seen somebody with less than DL (less than detectable limit) on all of them.

Dr. Betsy Redmond (00:38:18) – Most people just get exposure to, you know- Mandelic acid is going to come from tar production, from petroleum byproducts that they make, things you can get car exhaust, you can get contamination in food packaging. Yours was a little bit higher, and then you realized that you have been getting-

Dr. Kara Fitzgerald (00:38:42) – Yeah. So it turns out that we have had just massive construction, roadwork going on out just outside of our house for… it’s only just wrapping up now. It’s been going on for over a year. There has been a ton- So recently, paving is the last thing that they do, so recently they did all of the paving, including a chunk of my driveway. They expanded, they put sidewalks in, it was a massive project. And it seems obvious, right? Like, of course that’s your exposure. But because it’s been just in our lives for this chunk of time, it wasn’t top of mind, but of course I’ve got evidence of exposure to petroleum compounds.

Dr. Kara Fitzgerald (00:39:33) – I mean, tar has just been in the air. It’s interesting, even though we’ve got air purifiers in the house and I keep the windows close to the construction closed, of course, I’ve got some of that background exposure. I mean, I need to do this on my daughter as well and suggest it to my neighbors. There’s three of us, three houses sort of together in kind of the heart of what’s been this project. And it’s thankfully coming to a close and it has made everything better there. But yeah. I’ve been under this lasting toxic exposure that you’ve picked up exquisitely and we can see that it’s influenced my glutathione. And when I first looked at these labs, I was like, What? You know-

Dr. Betsy Redmond (00:40:21) – That can’t be me.

Dr. Kara Fitzgerald (00:40:24) – Yeah, What? Where am I getting this? And as you and I sort of teased apart the pathway and I thought about it, I’m like, Oh, my God! It’s huge, You know? And this is I don’t know…

Dr. Kara Fitzgerald (00:40:32) – This is not information that I was getting anywhere else with this level of clarity, this level of sort of granular detail. A, what I need to do, what’s happening, what the exposure source is, how it’s influencing my detox battery, but also how it’s negatively influencing the aging journey. I mean you can see where it starts, you know, and if I continue to have these exposures-

Dr. Betsy Redmond (00:40:56) – Yeah. Bit by bit.

Dr. Kara Fitzgerald (00:40:57) – Yeah, yeah, it’s true. I know it’s true. We’re like going back to the, the Peter Attia idea of medicine 2.0. This is medicine 3.0, where I where I get to correct this.

Dr. Betsy Redmond (00:41:08) – Right. And I will say, if you want to test your daughter, this was the urine part. You can do just the organic acids so you don’t have to you don’t have to do the blood draw.

Dr. Kara Fitzgerald (00:41:21) – Yeah, I absolutely want to test her and my intervention is going to be, like in your opinion, what is the best approach? Do I use preformed glutathione or am I using NAC plus some glycine?

Dr. Betsy Redmond (00:41:38) – There’s not one great study that has done a comparison. Which reminds me, the lottery. The big lotto is up to a billion, and that’s what I always say, “I’m going to enter that lottery and I’m going to win a billion and I’m going to do so much functional medicine research. I’m just going to answer all these questions that I have.”

Dr. Kara Fitzgerald (00:41:57) – And you will. I love it.

Dr. Betsy Redmond (00:42:00) – But yeah, so I think that I would think about glycine and NAC because you also had a slightly elevated benzoate, benzoic acid. Which, you know-

Dr. Kara Fitzgerald (00:42:14) – Same. It’s probably from this same exposure that’s been happening.

Dr. Betsy Redmond (00:42:18) – Right So you can get it, you know, we look at it in the microbe section, microbial metabolites. You can get it from diet, you can get it from microbes, but you can get it other places. But it should conjugate with glycine and become hippuric acid. And yours-

Dr. Kara Fitzgerald (00:42:36) – Oh but my I’m not making that conversion.

Dr. Betsy Redmond (00:42:38) – Yeah. So you’re not doing that. So is there not enough-

Dr. Kara Fitzgerald (00:42:42) – Is that because I’m stealing my glycine for this toxic burden? Is that what you’re thinking?

Dr. Betsy Redmond (00:42:47) – I’m not even sure why you’re doing that. I think there’s other things. Glycine does a lot of conjugation stuff, but just looking at that- So your benzoic acid isn’t over the 95th, it’s at the 90th, but most people are less than DL because it just gets cleared out all the time. So, I think that just another reason that I would think of glycine. And then it should go over to your hippuric acid. So generally, you’ll see hippuric acid higher and benzoic acid all the way low and I’m not seeing that in you. Elevated hippuric acid has been associated with a more Mediterranean style diet, it’s been associated with better gut diversity, so looking at that. But I was going to say with that mandelic acid you also had glucaric acid which was elevated.

Dr. Kara Fitzgerald (00:43:44) – My Mediterranean diet. I’m gnoshing on this all day. I actually ran out of salad dressing.

Dr. Betsy Redmond (00:43:51) – Yeah, I mean and the mandelic acid and the benzoylform, those have been collected by NHANES data for a long time so you can actually break it down. NHANES, where they look at 5000 Americans, I think it’s every five years or ten years and they just look at everything. So, you can break it down by gender, by age, by location if you’re interested in all that. But I think that was one of the things that I would think of with your detox. Thinking about that you have an elevated pyroglutamic acid which can identify glycine need. And then you have that benzoic acid that’s elevated, so more on glycine, the cystine that’s a little bit lower, the somewhat toxic exposure. I think those are the things that I think stood out.

Dr. Kara Fitzgerald (00:44:44) – Okay.

Dr. Betsy Redmond (00:44:44) – On your otherwise really good-looking report.

Dr. Kara Fitzgerald (00:44:49) – You’ve inferred it’s more glycine because you’re pulling in a handful of other analytes, so pyroglutamic acid could indicate cysteine as well. But my cysteine numbers-

Dr. Betsy Redmond (00:45:03) – Right and your cysteine was low.

Dr. Kara Fitzgerald (00:45:05) – So I do need some cystine support.

Dr. Betsy Redmond (00:45:03) – Yeah. So I would do both of them.

Dr. Kara Fitzgerald (00:45:05) – We can also clearly see glycine support. So those are two of the three amino acids and I need both of them. Glutamic acid? Do I need glutamic? You looked at my glutamic. Wasn’t that a little bit on the lower side?

Dr. Betsy Redmond (00:45:19) – I think your glutamic acid was actually, yeah, it was on the lower side.

Dr. Kara Fitzgerald (00:45:23) – So I need all three aminos. So pre-formed glutathione wouldn’t be a bad idea.

Dr. Betsy Redmond (00:45:28) – It wouldn’t be a bad.

Dr. Kara Fitzgerald (00:45:38) – Plus another kick of glycine.

Dr. Betsy Redmond (00:45:31) – Yeah. And there’s some research that specifically, and I’m not putting you in this category, specifically looks at frail, older people that glutamic acid tends to become low in people who are frail.

Dr. Kara Fitzgerald (00:45:48) – Interesting. Glycine is a longevity amino acid. I know it’s sort of moving up the ranks of getting attention these days, so we want to have enough of it and-

Dr. Betsy Redmond (00:46:02) – Yeah, I mean, I think there’s some really good long-term research when you look at metabolomics and metabolic concerns. The research that they’ve looked at, the Framingham study, the Prime Med study that they’ve looked at for a long time, you know, decades. And they’ve associated higher risk of metabolic issues, diabetes, obesity, in people who have elevated aromatic amino acids. That’s going to be phenylalanine, tyrosine, the branched-chain amino acids, higher glutamic acid and higher lactic acid, higher alanine, those and then lower glutamine and lower glycine. So those-

Dr. Kara Fitzgerald (00:46:47) – Interesting. So that pattern.

Dr. Betsy Redmond (00:46:48) – Yeah. And so that’s another one that branched-chain amino acids can become lower as you age. The assumption is that they become lower because as people get older, they have less muscle mass, so it might be related to sarcopenia.

Dr. Betsy Redmond (00:47:07) – Some research has noticed that it starts to decline when people are in their 30s. There’s a really interesting article, and they put people in categories of 20 to 30, 30 to 40, 40 to 50, 50 to 60, 60 plus. They also looked at branched-chain amino acids and they looked at cardiorespiratory fitness and then some other things. And they have it in a real nice- I mean, if you’ve got a nice pathway or a nice diagram, I’m all for it. And really everybody was maintaining it until they got to 60. And at 60 it just kind of dropped, the branched-chain, amino acids dropped and the cardiorespiratory fitness went up. So it can have a big job. So when I’m looking at-

Dr. Kara Fitzgerald (00:47:56) – Cardiorespiratory fitness, their fitness increased or declined?

Dr. Betsy Redmond (00:48:01) – Decreased. Their cardio fitness declined and their branched-chain amino acids declined. Yeah. So you’re thinking of it, I’m going to look at I have your report on another computer.

Dr. Kara Fitzgerald (00:48:14) – I do, by the way, I just got my VO2 Max done recently.

Dr. Betsy Redmond (00:48:21) – And it was excellent?

Dr. Kara Fitzgerald (00:48:22) – I was in the 90th percentile for my age. I went at UConn, I’m here in Connecticut. There’s the Corey Stringer Institute, where they do, it’s an incredible place. It was so fun; it was really fun to hang out with the PhD students and get tested. It was exciting. I brought my bike up there; we hooked it up and we did my lactate threshold. They took a bunch of blood specimen and it was neat to see that even with this busy world that I live in, I do put attention into exercise. I put attention into muscle mass. I put attention into cardiovascular fitness. And I’m doing pretty good.

Dr. Betsy Redmond (00:49:02) – Yeah, I think exercise- I know you’re a big proponent of that. One of the other things mentioned with exercise is it can clear kynurenine, so that’s what was one of the other things. Your kynurenine was low, but maybe the exercise kind of helps bring that down.

Dr. Kara Fitzgerald (00:49:20) – Interesting. Yeah. And we saw that my lactate was high, and I said to you that it’s certainly possible that I had done a more intense event before I gave the specimen and perhaps should have controlled- So, the day before I might have done a more intense resistance training or high intensity intervals on my bike or something like that.

Dr. Betsy Redmond (00:49:45) – I think just knowing what you’ve done before is, you know, otherwise you don’t need to make it perfect for the test.

Dr. Kara Fitzgerald (00:49:52) – But if you’re not, if your lactate is up, if you’re in anaerobic metabolism and you’re sedentary that doesn’t bode well. That’s a strongly pro-aging pattern.

Dr. Betsy Redmond (00:50:07) – Yeah, and there’s some good population studies looking at that.

Dr. Betsy Redmond (00:50:11) – I think there’s a big Dutch civil service study and they just looked at urine lactic acid, and alanine. They looked at you know, they found a lot of things, but those were two that really stood out with the whole kind of glycolysis process that when those are elevated at baseline, five years later those people are more likely to have metabolic issues.

Dr. Kara Fitzgerald (00:50:32) – That makes sense. It just makes sense.

Dr. Betsy Redmond (00:50:35) – Yeah. Following the pathway. You know, follow the pathways. Just pull them up and you can kind of see where they’re going. With your branched-chain amino acids, they were fine. They were a little- Valine was a little bit higher, but overall, they were great, your alpha-keto acids, so looking at them all together. I don’t want them too high because that’s going to be associated with metabolic conditions, I don’t want them too low because that’s going to be associated with aging.

Dr. Betsy Redmond (00:51:08) – Aging. Sarcopenia Yeah.

Dr. Kara Fitzgerald (00:51:10) – Yeah. So you just want the sweet spot. This has been great. I can see the areas that I need to work on. I’ve got a really clear action plan. I know why I need to work on these areas based on exposures. I’m grateful that the construction is done. We’re not going to have any more tar being dropped in our neighborhood I certainly hope, so I can start doing this cleanup. I want to evaluate my daughter and I’ll talk to my neighbors about it to see if they’re interested, because we all have this.

Dr. Betsy Redmond (00:51:46) – Yeah, Yeah.

Dr. Kara Fitzgerald (00:51:47) – We all have it. what else, Betsy? What else on this report do you want to bring out? We talked about toxins. We talked about some of the really cool patterns associated with aging and what we might do about it.

Dr. Kara Fitzgerald (00:52:02) – Yeah, there’s a lot here. And in fact, I would just suggest, and then I’ll shut up, is for anybody diving into metabolomics, it’s fun, it’s powerful, there’s a lot of action, and you could certainly start by using the ready reference page one, but also consulting. You’re available. People can talk-

Dr. Betsy Redmond (00:52:22) – Yeah, we’re available. And you know, we have stuff on our website. You don’t have to even sign up on our website, you can just go to the learning center. I have a webinar that’s on aging and metabolomics, that’s on the metabolic function of metabolomics, that’s on mood disorder and metabolomics. There’s one that correlates gut function and metabolomics because that’s so closely put together.

Dr. Kara Fitzgerald (00:52:51) – And you and I have a previous conversation when you were first launching the panel, so think it’s going on two years now that we’ll link on the show notes as well. So we talked about some pattern analysis there. All right, so just in the final minutes, what else? Tell me what else you want to talk about.

Dr. Betsy Redmond (00:53:08) – Well, the other one that I think that I briefly mentioned was alpha-ketoglutarate, (AKG), or alpha-ketoglutaric acid. And that one has been around a long time but people don’t always pay attention to it. And yours is good. Yeah. Yeah, higher. Certainly, they have supplementation with AKG and that’s been shown to be successful but-

Dr. Kara Fitzgerald (00:53:33) – Well it’s actually been shown to lower biological age by one clock measurement, and it’s also known to drop with age.

Dr. Betsy Redmond (00:53:44) – Right? Well, from 40 to 80, there’s a tenfold drop.

Dr. Kara Fitzgerald (00:53:51) – Wow. So, it really drops.

Dr. Betsy Redmond (00:53:52) – Yeah, right. I know. I’m smack in the middle of that, so it’s like-

Dr. Kara Fitzgerald (00:53:56) – And it’s sort of the heart and soul of the Krebs cycle. So, it’s right in the mitochondria. It’s a key player in generating energy.

Dr. Kara Fitzgerald (00:54:05) – It also happens to be a cofactor in demethylation on DNA. So, we need it to take methyl groups off of the DNA. We need alpha-ketoglutarate to be able to do that. So, if you’re hypermethylated, you know, if you have a good gene turned off with excess methylation on it, then you need AKG to do that clean up. But it plays some very important roles in the body.

Dr. Betsy Redmond (00:54:33) – Yeah, yeah. And with a more acidic situation it can go down.

Dr. Kara Fitzgerald (00:54:41) – Oh, so that would be like inflammation?

Dr. Betsy Redmond (00:54:44) – Yeah, yeah. Or people who maybe shouldn’t- I think some of the research they’ve done, like people who are getting a more plant-based diet, and I don’t think they’re necessarily looking at vegans, but just making sure you’re getting all those plants, you know, that was associated with a better level.

Dr. Kara Fitzgerald (00:55:01) – Interesting. And why? Because they were more alkaline. What do you mean?

Dr. Betsy Redmond (00:55:08) – I think when it’s more acidic, it gets absorbed. So under more acidic conditions it just it gets absorbed and results in a drop in urinary excretion.

Dr. Kara Fitzgerald (00:55:22) – Oh, okay.

Dr. Betsy Redmond (00:55:25) – So we’re looking at urinary. I think that the Krebs cycle- It’s so fascinating. I think years ago it was like, well, this is high, so let’s do that, because there are a lot of nutrient cofactors there. But everybody flows into there. Fats flow in, glycolysis comes in, all the amino acids flow in there, it’s connected with the urea cycle. So, everything’s happening there.

Dr. Kara Fitzgerald (00:55:53) – In the mitochondria, in the Krebs cycle.

Dr. Betsy Redmond (00:55:55) – Right.

Dr. Kara Fitzgerald (00:55:56) – Yeah. So cellular respiration. It’s metabolism, right? It’s the soul of metabolism. Okay, cool. Yeah. So of course, everything would go there. Protein, fat, carbs, it all ends up there.

Dr. Betsy Redmond (00:56:12) – Yeah. And then thinking of last words, some of the things that in researching all this and getting it started and looking at it, researchers are putting it out there that it may be, you know, it’s going to become one of those things that you just do every year. You’re going to look at certain markers every year. And this is really going to tell you- It’s good to compare against yourself because there aren’t necessarily standards. There’s a healthy reference range. Yeah, we have that. But for you yourself, what pathways are impaired and you know, so you know, oh, that’s so you can address it differently. But just getting it every year.

Dr. Kara Fitzgerald (00:56:58) – Well especially, You know, as we’ve been talking about aging a lot, we’re both interested as we march…

Dr. Betsy Redmond (00:56:12) – As agers.

Dr. Kara Fitzgerald (00:56:58) – We are, we’re both agers. I mean, there’s a lot. I want to make sure that I’m as dialed in as I can be here, you know, just like I took the time to do my VO2 max and take the time to exercise and work on living, eating well, et cetera. I want to know these are dialed in.

Dr. Betsy Redmond (00:57:24) – Yeah, this is just going to be at a much smaller level.

Dr. Kara Fitzgerald (00:57:31) – It’s essential.

Dr. Betsy Redmond (00:57:32) – Yeah, I’ve got good muscle tone. How’s it all functioning?

Dr. Kara Fitzgerald (00:57:35) – Yeah. One of the things we were going to talk about and we forgot to, so I want to bring it up because I think it’s really, really cool is that you look at equol. Let’s talk a little bit about it because it’s an awesome compound in my opinion. It’s an essential important player. So, what is it?

Dr. Betsy Redmond (00:57:54) – Right. So, we have our section six, which is microbial metabolites. So, it’s a combination, just the markers on the page, that’s where indoleacetic acid is listed too. It’s looking at what bacteria do you have in your gut,  what are they getting, what’s coming into the gut, and what those bacteria are making. So looking at all those metabolites. So, you had good indoleacetic acid, you have some polyphenols there, but one that you had was equol. So, that is going to be, you know, it gets made, and it’s got certain health benefits, and it’s made from isoflavones. So certainly, everybody’s thinking of soy, but it turns out the nut that’s highest in that is pistachios, and you’re a big pistachio eater.

Dr. Kara Fitzgerald (00:58:48) – We always have a ton of them in the house. It’s just sort of a background item in our lives. Pistachios. I mean I probably have a handful of pistachios, maybe two, most days. You know, for me, in my research, we’re looking at… So in the aging process, you start to hypermethylate and turn off incredibly important genes, genes that keep us healthy. So another angle of looking at aging being the biggest driver of disease are these hypermethylation patterns. We start shutting down protective genes and turning on pro-inflammatory genes.

Dr. Kara Fitzgerald (00:59:31) – There’s a lot of research looking at the tumor suppressor genes getting hypermethylated as we age. It’s like we’re just shooing in cancer, you know, it’s crazy. And equol, so there’s a whole table in the book that I authored, Younger You, and looking at these tumor suppressor genes, and equol is a key player in supporting the re-expression of these genes. And I want to say that most of this research is done in vitro. There are some animal studies, actually. Sulforaphane is badass for helping turn back on these tumor suppressor genes and being effective in animal models. But in our research in humans, we can see now, and this will be published in the not-so-distant future, that we’ve had a favorable influence in our diet and lifestyle intervention on tumor suppressor genes as well. So it’s incredibly exciting. But equol just shows up over and over and over again, equol. But we need to be able to make it, you know, we need to be able to make it in our GI.

Dr. Kara Fitzgerald (01:00:41) – So I was absolutely thrilled. And I know a lot of people are anxious about eating soy. I’m not if we eat good quality soy and we can tolerate it, you know, if it’s organic. But yeah, pistachios. I mean, I don’t eat a lot of soy. You know, every once in a while, I will, but it’s not a big player in our lives. So, as you and I were brainstorming, like, why do I have equol, I had to look it up in my own book. Oh, pistachios. Wow. I didn’t realize.

Dr. Betsy Redmond (01:01:04) – The number one nut. So yeah, get cracking.

Dr. Kara Fitzgerald (01:01:06) – I’m yeah, I’m absolutely thrilled that I’ve got background equol.

Dr. Betsy Redmond (01:01:11) – Yeah. It’s a nice little thing to have. I think when they look at population studies, probably 25% of Western countries-

Dr. Kara Fitzgerald (01:01:17) – Make it? Have the correct- Wow.

Dr. Betsy Redmond (01:01:21) – Yeah. So you’re ahead of the curve.

Dr. Kara Fitzgerald (01:01:21) – Yeah, it’s nice. So, it may be a little bit of a surrogate suggestion that I’ve got some diversity happening with my microbiome that I’m able to make it.

Dr. Kara Fitzgerald (01:01:29) – I think people in Asia, soy consuming countries have way more equol and this is associated with lower risk of breast cancer, less transition to menopause, you know, just less symptomology with menopause. I mean, just a really important player. I mean, yeah, yeah, I’m a fan.

Dr. Betsy Redmond (01:01:50) – It’s a nice little bonus to have.

Dr. Kara Fitzgerald (01:01:52) – It’s a nice little bonus. I was pretty psyched. I was A, really excited to see that you were measuring it because I was just waiting for a lab to make it available to us. But then, B, yeah, I didn’t anticipate being a producer, so I was pretty happy to see that. Dr. Redmond It was just great. This was a really fun conversation.

Dr. Betsy Redmond (01:02:11) – Yeah. I like confirming that your health is good. Yeah, you’re going to make it another year.

Dr. Kara Fitzgerald (01:02:16) – Yeah, I have some actions though. Yeah, I’ve got my marching orders. Thanks for joining me. We’re going to gather all of your papers. I will be downloading some of those papers myself. We’ll get a sample report so people can walk along with us as we take this journey. And I look forward to seeing you in the not-so-distant future and having another conversation on New Frontiers.

Dr. Betsy Redmond (01:02:45) – Yeah. I would like it. Yeah. We’ll do a follow up.

Dr. Kara Fitzgerald (01:02:47) – We’ll do a follow up.

Betsy Redmond, Ph.D., MMSc, RDN

Dr. Betsy Redmond is a senior education specialist at DSL and a nutrition consultant. She is both conventionally trained with a Masters’ degree in clinical nutrition from Emory University and a doctorate in nutrition from the University of Georgia. Dr. Redmond has over 15 years’ experience in functional laboratory research and education.

Show Notes

Diagnostic Solutions Laboratory

Dr. Betsy Redmond

OMX Organic Metabolomics Profile

OMX Organic Metabolomics Sample Report

The Human Metabolome Database

Study: The plasma metabolome as a predictor of biological aging in humans (nih.gov)

Study: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism

Review: The metabolomics of human aging: Advances, challenges, and opportunities

Review: Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target

Study: The Aging Process: A Metabolomics Perspective

Study: Integrative perspective of the healthy aging process considering the metabolome, cardiac autonomic modulation and cardiorespiratory fitness evaluated in age groups

Study: Protein carbamylation is a hallmark of aging

Study: Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies

Study: Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation

Hallmarks of Aging: An expanding universe

Article:  The Use of Dietary Supplements and Amino Acid Restriction Interventions to Reduce Frailty in Pre-Clinical Models

Study: Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis

Study: Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery

The Disposal of Reactive Carbonyl Species through Carnosine Conjugation: What We Know Now

Blog: The Protein Magic Formula: How Much Should We Eat For Optimal Health & Longevity?

VO2 Max

Korey Stringer Institute at University of Connecticut

Dr. Jeffrey Bland

Peter Attia

Younger You

 

Previously on New Frontiers: Using Metabolomic Analysis for Clinical Insight with Betsy Redmond, PhD, MMSc, RDN

DrKF Resources

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