Season 2, Episode 7: A Practical Approach to Metabolomics and Organic Acids Testing with Dr. Dan Kalish

Evelyne: I am so excited for today’s conversation, because as a Designs for Health practitioner you have access to the Metabolomics Spotlight test. I’ve tried to learn organic acids for so long and I feel like it always goes in one ear out the other. So, I’m excited to learn from you and to maybe simplify everything and to really understand when to use this test, who it would be best for and how a practitioner can incorporate this into their practice. So, Dr. Dan Kalish is the founder of the Kalish Institute for Functional Medicine. He has trained over 7,000 practitioners on building successful functional medicine practices.

Founded in 2006, the Kalish Institute teaches clinical application and patient communication techniques through a hands-on case-based approach. Dr. Kalish has published a research study on his clinical methods with the Mayo Clinic, has authored three books on functional medicine, and is a notable speaker at integrative medicine conferences. And Dan, I actually remember when you got that paper published, because I saw you at an IFM conference and you gave me a copy and you were so excited. You’re like, “Look at this.” That was awesome.

Dan Kalish: That was a peak moment in my life for sure.

Evelyne: I bet. Congratulations. That’s awesome. Dan, can you give us an overview of how you got into this field and then how you got so passionate about teaching this now to other practitioners?

Dan Kalish: Oh, sure. Yeah. So, when I was in my early twenties I was living in a monastery in Thailand, believe it or not, and I got extremely sick. The hygiene wasn’t so great there. And so, I ended up having a pretty bad, they call it amebic dysentery, problem. And when I came back to the United States a couple of years later and left the monastery, it morphed into a chronic fatigue problem from this parasitic infection I acquired in the jungle there. And so, I spent a long time, like 14 years, trying to figure out what was causing my fatigue and all these symptoms I had.

And then I had a functional medicine analysis, a lab test and treatment and I was better. I was like, oh, this is something I think I want to do. And the directness of the lab testing and the science-based aspect of the work really intrigued me, but using natural treatments at the same time and how effective it was. So, that’s what got me launched. And then once I was into my career just a few years I met Dr. Bill Timmins, and he was one of the more popular teachers at that time. This is early ’90s, and I just was taken under his wing and started training other doctors. And then it took off from there.

Evelyne: What a cool story. I think that’s amazing. And I also think that there are so, so many people suffering in the world right now with chronic fatigue, whether it’s post COVID or whatever it is, and they never get help. So, I think this is so relevant. So, can you tell us, first of all, what is an organic acids or metabolomics test? What are we looking at?

Dan Kalish: Yeah. So, it’s a very simple test. You just do a urine sample, you send it into the lab, and they measure all these different metabolites or breakdown products, and they cover four major areas. It looks at your mitochondrial health, which has to do with longevity and cardiovascular disease prevention, energy levels and those kinds of things. It looks at your neurotransmitter levels, your brain chemistry and how well your brain is working. It looks at detoxification capacity, how your liver is getting rid of potentially dangerous things. And it has a section on GI markers. So, those four areas, energy, brain, detox and GI, they’re all covered on this one test.

Evelyne: And I think the number one question that I get from practitioners is, when should I run a metabolomics test? Who is my ideal patient for this and how do I even determine, do I do a GI test first? And I know different practitioners do that differently. What are your thoughts on that?

Dan Kalish: Yeah. So, if the patient has mitochondria, a brain, liver or a gut, then you have to do the test.

Evelyne: All right.

Dan Kalish: It’s basically you need to test everybody. You have to test everybody. In fact, about an hour ago I was teaching a class at my mentorship program and one of the doctors in the class submitted her own lab. She has absolutely no health problems whatsoever, feels great, and her organic acids test was a mess. So, you don’t have to have symptoms to have problems. That’s the whole thing about functional medicine, we’re not symptom oriented. So, you can use organic acids testing as a wellness, longevity, anti-aging kind of screening test, or you can use it as a test to determine what to do for someone with a chronic health problem. You can use it for kids or older adults.

We basically test everybody on organic acids in my mentorship class, and it’s one of the most informative things you can do. It is not a substitute for a digestive test. There are digestive markers on it, but you couple it in general with a GI test. It doesn’t matter which one you do first, because you have to do both of them eventually anyways. So, one or the other, but making sure that you do both at some point.

Evelyne: Do you think if you run a GI test first, like a stool test, and then work on, quote unquote, fixing the gut for say a couple of months and then run a metabolomics test, you get better results whereas, and I’m just thinking hypothetically, whereas if you run a metabolomics test and work on things, you’re maybe not necessarily working on the gut, but are you still fixing things in the gut? Do you know what I’m saying?

Dan Kalish: Yeah. I think it ultimately doesn’t matter that much.

Evelyne: Okay.

Dan Kalish: Because the metabolomics testing or organic acids, it’s not just looking at whether you’re eating the right nutrients or absorbing the right nutrients, it’s got more nuance to it than that. So, I try to do both tests in the very beginning of a treatment program. That makes the most sense to me, just to run them side by side really.

Evelyne: Yeah, that makes sense. And do you think that, because for the practitioner listening, what are some of the issues that you see, maybe some of the symptoms, especially maybe recently I feel like everybody is so stressed, that would really indicate like, okay, you really need to run a metabolomics test?

Dan Kalish: Well, fatigue for sure, because the test screens for neurotransmitter function, which can be related to fatigue, and it screens for mitochondrial function, which is kind of the heart of fatigue. Depression and anxiety goes back to neurotransmitters. Really need to check on that. If the person wants to do, well, if you’re thinking symptomatically, any kind of chronic inflammatory problem or anything that involves oxidative stress or insulin resistance, which is pretty much all the chronic conditions probably get lumped under there. Anything from autoimmunity, to fibromyalgia, to even things like post-cancer treatment, someone that’s maybe they had breast cancer but now they’re recovered from that, but they want to make sure that their body is okay, it’s not going to come back. So, it has pretty wide applications.

Evelyne: That’s helpful, thank you. And since you mentioned insulin resistance and we’ve talked about that on a few shows, what are some of the markers that you’re looking at on the test? Because I’m always thinking blood with insulin resistance, like fasting blood glucose, insulin…

Dan Kalish: It’s checking lactate and pyruvic acid. Those are probably the main ones.

Evelyne: And tell me a little bit more about those.

Dan Kalish: Oh, okay. So, when your body’s processing glucose or sugar and you’re trying to get the glucose or sugar to go into the citric acid cycle where you make energy, you’re going to take the glucose molecule, six carbon molecules, split it in half, into two, three carbon pyruvates. And then in a perfect world that pyruvate just goes into the mitochondria and starts to help you make energy. And if that’s not happening, pyruvic acid or pyruvate is going to build up. And if that’s really not happening, then lactic acid is going to build up. So, those markers, pyruvic acid and lactic acid, are like the early warning signs that there’s something major going on with your ability to process glucose.

Evelyne: And do you feel like you see that show up on a test before you see blood markers of glucose and insulin that are off?

Dan Kalish: Absolutely you can. It can be paired with the blood markers, or it can show up earlier because it’s an earlier stage of identifying the problem really.

Evelyne: Interesting. Very cool. And I think that when it comes to nutrient deficiencies, that’s also something we can uncover from this test. So, how do you determine running this one versus an actual micronutrient panel?

Dan Kalish: Yeah. So, this is a tricky one. So, we want to think about this for a long time, because the way that this test… Let’s go back to the origins of this test in the first place. So, what are organic acids? So, organic acids were first started to be run as lab testing in the 1960s. Why did they do them? Exclusively to screen for genetic disorders. Mm. So, Richard Lord, who’s my teacher, was a graduate student at the time in the ’60s at University of Texas at Austin, and he’s like, oh, okay, this is interesting. They’re running these organic acids panels to look for inborn errors of metabolism or genetic defects in newborn babies, which are life-threatening. Urea cycle disorders, PKU, things like this. So, if those genetic disorders are not discovered when that baby is born, then the baby could die, or have a permanent and bad neurological problem.

And so, everyone took this very seriously, extremely high organic acids markers, you hit the panic button, the parents are told immediately this is a problem and we’re going to have to intervene. Then he thought, well, all these inborn errors of metabolism relate to nutrient handling problems. Maybe someday when I grow up and become a real doctor I could use organic acids testing to screen for the same exact genetic disorders in adults. And so, when he created the lab that first ran organic acids testing, which no longer exists, they started to, this is Richard Lord’s idea really in the ’60s and then the ’70s and ’80s, to run organic acids testing, the same exact markers that are used for inborn errors of metabolism or life-threatening genetic disorders, but to change the reference ranges, obviously massively, in order to look for genetic variants or biochemical individuality in adults.

So, when I first met Richard and started to work with him closely about 12 years ago, he told me this and I was like, “Well, Richard, nobody knows that, everybody thinks organic acids are screening for nutrient levels.” And he started laughing. He’s like, “Well, I never really got around to telling anybody, and honestly, the marketing department at the lab wouldn’t let us tell the real story.” So, his brainchild, organic acids, was marketed as a nutrient evaluation screening tool. But what’s really happening here is we’re looking at biochemical individuality between people based on their genetics.

Of course, there’s an interaction with what you’re eating and your nutrient status and your gut absorption. That’s a set of factors also. But what we’re really interested in on this test is how is your individual patient different, biochemically, physiologically, in terms of their cell physiology? And the organic acids test shows you that information in real time because it shows you which enzymes are functioning and which ones aren’t. And then you can extrapolate where the problems are from that. So, you can look at organic acids as just like a simple screening tool for B12 deficiency, but at the deeper level you’re looking for, again, this personalized program that you can develop, or this individualized biochemistry that’s going to vary from person to person based on their genes. That’s what makes the testing so exciting is that depth that you can bring to the work.

Evelyne: Great. Thank you so much for explaining that. So, I want to get into some of these pathways, and I think that one of the things that holds practitioners back is not understanding the intricacies of each pathway. I know for me, I’ve learned them before, multiple times, it just goes in one ear out the other. And I’m not working with clients right now, so maybe if I did see these tests all the time it would maybe start to sink in, but can we run this test without understanding each pathway in detail?

Dan Kalish: Yeah. So, here’s what I would say, is that, that happens 100% of the time. As you run the test in the first year or two you’re doing this you’re just kind of scrambling to figure out what’s going on. And then what I try to do in all the teaching that I do with my boot camps and mentorship is do an image based pathway based education thing. So, we’ll show them an image of beta oxidation, here’s the process, you learn this in school, you forgot it after the exam, so did I. Here are the markers on the test that directly relate to that, that matter.

And if we do it that way, then people memorize, they quote unquote, memorize the pathways simply because they’re looking at the lab, they’re seeing the markers and how they relate to the pathway. So, in other words, you bring the pathway alive and you make it relevant by showing them the markers on a test and tying it back to the pathway. That works 100% of the time with every doctor I’ve ever trained. But if you just learn it in the abstract and it’s not tied back to something that’s clinically relevant, it’s just going to pass through your brain.

Evelyne: Right.

Dan Kalish: So, that’s the goal. An image, the pathway, and then the marker. And then on that same image is the supplement solution for that pathway. That completes the whole package for the doctor. Because they see the pathway, the problem, meaning the lab marker, they see the solution in terms of the supplement, all in one place and then it sticks in their brain forever.

Evelyne: Okay. So, let’s dive a little deeper into some of these areas that we mentioned and some of the pathways. So, what do we need to know about beta oxidation? In a broad overview, how does it actually work and when it doesn’t work efficiently, what do you see and what are you looking at on the metabolomics test?

Dan Kalish: Okay. Well, this is my favorite pathway. I can’t believe you brought this one up out of all the different pathways. It’s my favorite because it’s so important and it’s rarely talked about. So, when you’re at rest, you’re sitting around, sleeping, anything but exercising, or anything but just having eaten a meal, most of the energy that your body’s producing comes from beta oxidation. And depending on who you read, anywhere from 60 to 80% of the energy that powers your heart and your brain comes from beta oxidation when you’re at rest. Now, if you’re exercising it’s different, if you just ate it’s different. But for most of your life, this is the main mechanism that keeps you alive. And basically the process is the burning of fat. So, we have to take fat and get it into the mitochondria to make energy. Completely different set of pathways than for getting glucose into the cell.

And because the cell membrane is made out of fat, the fat that’s outside the cell and outside the mitochondria doesn’t pass through very well. And so, you have to get basically a fat, to burn it up for energy, through a fatty membrane. And in fact, the mitochondria have two membranes, a double membrane, so that’s even more difficult to do. So, there’s a really complex mechanism that makes this work. And because it’s complex, it’s prone to problems. Meaning variations, biochemical variations from person to person that make this thing not work. And the short version of the story is you have to take the fat, you have to break it down to something a little bit smaller, get it through membrane one, through membrane two, and then reassemble it inside the mitochondria, inside the matrix of the mitochondria. And the only thing that can make this happen is a molecule or a nutrient called carnitine.

So, the process is called the carnitine shuttle. So, the carnitine has to go out, grab that fat, manipulate it and change its shape so it can get through the membrane, escort it through the second membrane, disengage and go back out and grab another fat molecule. And there’s enzymes involved, there’s different pathways, it has to go through each of these membranes in different ways. There’s all these complicated terms that they use for it, but any one of those steps that gets disturbed, or a lack of carnitine, is going to cause a big problem.

So, we see problems with beta oxidation all the time, and that’s going to result then in someone feeling fatigued, an athlete, they can’t do their endurance activities as well as they should. It’s going to cause someone to get fat, to have excess body fat on their body. And of course it’s going to put you at risk for cardiovascular disease and other kinds of problems that relate to your overall health. It’s really incredibly important. And it’s such a simple solution. You just give carnitine and vitamin B2, and for everything with metabolic function, you give magnesium. But it’s a pretty straightforward correction. Mostly it’s carnitine.

Evelyne: And so, with the carnitine, what is the underlying reason why it’s usually low? Is it genetic, is it that they’re not eating enough of it in their diet? What’s the underlying issue?

Dan Kalish: Well, carnitine, you can kind of tell by the name, comes from meat. So, if you’re a very strict vegetarian you can be low in carnitine. It’s not inevitable, but it can happen. Honestly, I don’t see that very often, but it can happen. Most of the time the problem with carnitine is a defect in these various enzymes that are working. So, it’s back to our biochemical individuality. It’s not a dietary problem, it’s not a problem with eating the wrong foods, it’s a problem with these pathways not working properly based on your individual biochemistry.

And when you start taking carnitine, fat people lose weight, cyclists can ride their bike harder and faster, people that were tired start to get energy, people who had really a lot of sugar cravings as a secondary fuel source don’t have their sugar cravings anymore because they’re getting their energy from fat like they should be, it makes your heart healthier. There’s all kinds of benefits. It’s really quite incredible. It’s a very simple solution.

Evelyne: Yeah. Super interesting. It makes me think of when I was doing my master’s, Bryan Walsh was one of my professors, and we were learning about this and he used the example of Ryan Hall, the marathon runner. I don’t know if he still holds the U.S. record for the marathon and the half marathon, but he was an endurance athlete and he had to retire in 2016 because he just could not run anymore. Interestingly, he’s now lifting weights. He looks like a completely different person. But Bryan Walsh was saying that maybe he just had some of these mitochondrial issues that we might’ve been able to discover had we run a test like this. And I just think it’s fascinating, and I wonder how many people are walking around struggling, or professional athletes who struggle and have to retire from their sport because of something like this. Is that something you see in your practice as well?

Dan Kalish: Yeah. I’ve tested a lot of professional athletes in sports ranging from basketball, to football, to weightlifting, to golf. A lot of endurance athletes, runners, cyclists. And carnitine deficiencies show up frequently. It may also be in part in athletes because they’re running these energy systems so much harder. So, it would be like if you bought a brand new Porsche and you just let it sit in your driveway or garage for 10 years versus you bought a brand new Porsche and you took it to the racetrack every single day, there’s some accelerated energy production that happens in an athlete’s body that would not happen in a normal human being’s body. And that may bring these carnitine deficiencies more to the front, because you’re running these systems harder, so you’re going to see the defects more obviously.

Evelyne: Yeah. Super interesting. Thank you for explaining the beta oxidation in such a simplified way. I love that. Let’s talk about the Krebs cycle. So, I’d love to know, within the Krebs cycle, are there more important steps than others? And can you talk about whether some of the steps in the Krebs cycle are more relevant when you’re looking at a metabolomics test?

Dan Kalish: Yeah. So, it’s a integrated system. I think of it, when I explain to patients, it’s like a bicycle chain. You are locking up your bike and if one of the links in the bike chain is broken, chain doesn’t work. So, when you’re looking at a cycle, if there’s one enzyme in the cycle that’s not working, then the whole thing is vulnerable to not working at all. If you have five breaks in the cycle, then obviously it’s going to be even a bigger problem. But I think what happens with these citric acid cycle enzymes is some of them are very prone to damage from oxidative stress that’s generated from environmental toxin exposure. And I don’t know honestly why some of them are more prone to damage, it’s maybe their position or their biochemical status in some way. But the succinate dehydrogenase enzyme seems to take the initial hit with environmental toxin damage.

And that’s a very bad place to have a problem, because it’s the one enzyme that’s not only part of the citric acid cycle, but it’s also part of the electron transport gene. So, in the electron transport chain you have these complexes, we all had to memorize complex one, two, three, four. And sometimes they call it complex five, sometimes they have a different name on it, but complex two is succinate dehydrogenase. And it’s one of the key, if not the key enzyme in the citric acid cycle also. Believe it or not, it’s one structure that’s doing both of these things, and it’s the one that seems to get taken out quite easily from toxin exposure.

So, if that enzyme goes, your citric acid cycle is going to break down and your electron transport chain is not going to work either, and you’re in a pretty big problem. But I think the main issue when you’re thinking about the different individual steps in the citric acid cycle is to think about why would they not be working in the first place? Is it environmental toxin exposure, which would be the number one cause, or is there something else going on? Maybe there’s a gut problem or something else. But I would always think first about, does this person have a heavy metal or a chemical burden that’s a problem?

Evelyne: Interesting. And I know there is a section on the test where we are looking at some of those exposures. I was actually going to ask about this at the end, but might as well ask now. So, I was looking at my own Metabolomics Spotlight test and my mandelic acid was high. And so, it says it’s related to styrene exposure. And so, I know it’s in plastics and in the air, I didn’t have other elevated markers. And of course I try to live a relatively healthy lifestyle. But I’m curious, is that something that you commonly see in the tests that you’re looking at?

Dan Kalish: Yeah. So, I think the broader subject really is chemical and heavy metal exposure, and how does the body process or handle all that? And so, with individual markers, it could be a high mercury level, high lead, benzene, toluene, a problem with styrene, it almost doesn’t matter. What you’re seeing is that for whatever exposure there is, the liver and the body in general isn’t able to bind up and remove these environmental toxins, whether they’re chemicals or heavy metals. So, I think it’s easier for clinicians to focus on the mechanism that clears them than to worry too much about the individual marker. But of course, you want to coach people. So, for example, if they work in a factory and they touch lead all the time because they’re welding or something, then you want to coach them to not touch the lead. Or if they’re an artist and they’re around cobalt all the time.

So, if they have some obvious chemical or heavy metal exposure, and I’ve seen this a lot, I have patients who work in the Navy and they’re building submarines, that’s a problem. I’ve had a lot of artists who handle really toxic substances. They don’t even really know that the paint that they’re using is toxic. It could be a car mechanic. So, you want to rule out all the environmental exposure. But most of the time, I would say 95% of the time when you see high levels of any kind of heavy metal or chemical, the person doesn’t have a history of working in a factory that had a ton of styrene or something. But what’s really happening is that there is a global problem, at least on this planet, I’ve never been to any other planet so I don’t know, it may be happening on other planets too. But our planet has got tens and tens and tens of thousands of environmental toxins that human beings have produced and distributed widely so that they’re in our food, and air, and water, and our bodies as well.

And so, the only real question is, is not are you exposed to styrene, or toluene, or benzene, is can your body clear it or not? And those people that are biochemically inclined to not clear environmental toxins very well are at a big disadvantage in the current planet that we have created here. I think 1,000 years ago it didn’t matter. Once in a while maybe the tribe on the other side of the river shot you in the butt with a poison dart and you had to clear some toxin, or you ate a mushroom that was toxic. But the body wasn’t really designed for a constant daily exposure from the time that you’re conceived in utero all the way through whatever your present day moment is, with chemicals and heavy metals. So, a lot of us don’t clear them very well and you’ll see them building up. So, then you want to jump on it and of course reduce exposure and eat clean food and all those things, stay away from chemicals, but more importantly, figure out which liver detox pathways you need to stimulate so the person can dump these toxins out.

Evelyne: So, I do know that I have some snips related to detoxification that are not optimal, but in my case, why would just one of them then be high and not all of them if that is the issue, if the liver clearance is the issue?

Dan Kalish: You mean one chemical marker?

Evelyne: Yeah. Like the styrene.

Dan Kalish: That’s just going to be based on your exposure.

Evelyne: Okay.

Dan Kalish: It doesn’t really matter though because the solution is going to be the same, assuming that you don’t have some horrible history of working in a factory or something where you’re exposed to all this.

Evelyne: I do not.

Dan Kalish: Yeah. So, it doesn’t matter because the correction is going to come from understanding which pathway is blocked and then clearing that. And then there could be another, there’s like 80,000 plus of these substances in the environment and we’re not measuring all but if few of them.

Evelyne: Right.

Dan Kalish: And so, it could be there’s another 2,017 chemicals in your body right now that just weren’t measured. And you can actually test for this stuff. If you spend 5 or $10,000, you can measure with enough blood work exactly which chemicals and metals are in your body. And I think the last study I saw, the average American had anywhere from 70 to maybe 6 or 700 environmental toxins in their tissues at any one time. And it impacts babies who are still in the womb as well. It’s not just after you’re born that this starts, because you get…

So, the average baby, the last stats I saw was maybe a little bit under 100 environmental toxins the day they’re born. So, we’re all super saturated with these. And so, I think the only way you can really deal with it, rather than measuring which hundreds or thousands of these you may have in your tissues, is look at the way that you get rid of them and clear them because that’s a very practical thing that you can apply rather than just accumulating a list of which flame retardants are actually in your cells. And it just gets to be really depressing, to be honest, for people.

Evelyne: Right. I know. We try to do what we can and not worry so much about the rest because that’s toxic in and of itself. And I think it also speaks to the importance of taking supplements that help support liver detoxification, but not just liver specific herbs, but making sure that we have all of those things that are part of phase one and phase two detox, and B vitamins, and protein and all those things. So, with B vitamins, I know those play critical roles, certain B vitamins in certain steps of the Krebs cycle. Can you talk a little bit more about that, and do you find that just supplementing everybody with a B complex is helpful? When do you supplement with single B vitamins? Tell me a little bit more about that.

Dan Kalish: I have a whole, many months long course on this. Because B vitamins have sort of been lost in the shuffle of functional medicine. You don’t see conferences where they talk about B vitamins. But without any of the key B vitamins being present you would be dead before you hit the floor. So, these are not optional nutrients, these are must haves for cellular function. And we could talk about these for months, but just to keep it simple, there are markers on organic acids that show a general need for B complex. They’re not specific to the individual B vitamin. But then there are markers that will tell you very specifically, do you need biotin, folate, B12, B6, there’s a bunch of them, B2 can also be measured. And so, in general, when you’re supplementing with B vitamins, you’re always going to use a B complex. You’re getting some of each of the B vitamins. And then add to that the individual Bs that may be showing deficiencies on the testing.

And the common ones that we see are all related to methylation, which is a very well known process that people have studied, which would be B6 deficiency, B12, and folate. Sometimes you see all three, sometimes you might see one. And if you see, let’s say a B6 marker that’s positive, you would give B complex plus additional B6 to solve that problem. And we have, even in my mentorship students who are in their second month of doing this stuff, we’ve seen people reverse some really serious health problems simply by using B6. It can be that simple. We had a case just recently, the doctor gave the patient thiamin in a high dose and it was this miracle. And I asked the doctor, “Where did you learn that?” She said, “That’s in the class. I just learned this a few…” I was like, “Oh, yeah, that’s right.”

That’s organic acids testing. So, this doesn’t have to be super complicated. And sometimes I hear these stories I can’t even believe what’s happening. B vitamins, if you learn how to use them really well, will probably be either number one or number two tool that you use to the greatest clinical effect. So, if you’re not using individual B vitamins on a regular basis, you’re missing out on what could be argued as the number one or number two most important treatment option in our field. Pretty important.

Evelyne: Wow, very interesting. I have a bunch of follow-up questions on that. So, with the B vitamins, when you see a need for them as indicated on, say, Metabolomics Spotlight test, how quickly can patients expect a shift after treatment? You just shared some stories, but are we talking days, weeks, and then how long should somebody stay on this? Because are we shifting these pathways in that then they work more efficiently, but then as soon as you stop taking the B vitamins they don’t work as well anymore, because just genetically you’re not doing that as efficiently?

Dan Kalish: Yeah. So, a patient should notice a difference typically within three or four weeks. I’d say that’s sort of average. Sometimes sooner, sometimes later. But that’s sort of typical for using B vitamins. They’re so important that you don’t want to stop them prematurely before the levels are normalized. They’re water-soluble, so if the person takes them a little too long they’re not particularly dangerous, maybe a little bit of a waste of money to buy them. But the definitive way to know that you’ve solved the potential problem there is to do a retest. So, you take them off the supplements for three days, maybe for a week, and then you retest their levels and see if they’re normal. And with organic acids testing you will learn two or three times more information on the retest than you did on the original test.

Evelyne: Interesting.

Dan Kalish: Because you have to think about it, it’s a process in movement. So, the first test is just like, hmm, this is what’s happening now. And you have very little insight into the dynamics of cellular physiology. Then you intervene, let’s say with B vitamins and some extra biotin as an example. We had a great biotin case this morning. It was a young woman with really bad skin problems and her biotin markers were crazy off. So, the biotin is going to obviously help improve some of her issues. And then on the retest on her in six months we’re going to see, has the biotin marker normalized? Then you don’t have to keep taking biotin. Is it still a problem? Well, then we didn’t give her enough, did we? Or for long enough. And so, you might also see that you gave her biotin and that changed her pyruvate and lactate markers, pyruvic acid and lactic acid markers, because biotin is also involved very strongly in blood sugar controls. As the audience knows.

So, the second test that you do shows you what moved around and how did things move around based on your intervention. That’s when you start to get real data about what? That person’s biochemical individuality. If you gave 100 people biotin that were deficient in biotin, they’re all going to react differently because they all have different genes that are going to handle the situation differently. And so, each follow-up test that you do, you learn more and more about that particular person’s physiology and you’re able to make better and better decisions. So, I strongly encourage anyone who’s doing this to order tests every six months and analyze them very carefully because what you see shifting on test number two is where you really start to understand what you’re actually doing, and how much you’re helping, and what’s going on for that person.

Evelyne: And then do you feel like there is a point where they don’t need to supplement with those anymore until maybe you do the test again and then it indicates that there’s a need for it?

Dan Kalish: Yeah. The better you get at this job, the fewer products you do and the faster you get people off of them. So, if they’re deficient in B6 and you nail it and you give them just the right amount of B6, and six months later their B6 marker is clear, they’re done.

Evelyne: Okay, interesting. And I think one thing that you are so good with in teaching practitioners is how to structure a supplement program. And I think that a lot of times, especially when you get back, say six or seven supplement recommendations, how do you teach practitioners you work with how to sequentially recommend those? Do you tell the patients that, hey, we’re going to start with a little bit more and then taper off? Can you share any tips with us?

Dan Kalish: Yeah. This really undermines a lot of practitioner’s programs. And I see these programs coming in because we’ll have a brand new student and they’ll be like, “Oh, I’m doing this program.” I’m like, “Whoa, where did you get the idea?” So, number one is that there’s not equal priority to all these different problems. You’re not supposed to fix all of this at the same time. Imagine, I don’t know, imagine any other situation where you’re in where you’re trying to fix something, you’re going to sequence it and start with a priority item and then work your way down the list. And if you do the prioritization well, you might fix your first high level problem and in the process of doing that, fix two or three other problems down the road.

As a simple example that I just used. Let’s say the person is deficient in biotin and they have a skin problem and you give them an adequate amount of biotin, you might also correct, to a certain extent, or help rebalance their pyruvic acid and lactic acid, which is going to improve their insulin handling capacity. So, then you don’t have to separately work on insulin because that was corrected with that initial protocol. And so, in terms of prioritizing, we try to think about it in terms of body systems, so the person’s treating body systems, and we look at it as neuroendocrine being first, then GI being second, and then detoxification and nutrient replacement being third. And trying to focus programs on those three different systems in that particular sequence seems to yield the best results.

Evelyne: That’s very helpful, thank you. So, I want to jump back to some of the different categories, especially neurotransmitters. I know when I speak with practitioners on a daily basis in the field, everybody is stressed and a lot of people have a lot of anxiety and depression, and I think that the organic acid slash metabolomics test can be really helpful in seeing what’s going on there. Can you talk a little bit more about what are some of the markers that you’re looking at on a metabolomics test?

Dan Kalish: Yeah. So, the main markers for neurotransmitter function, there’s many, we could go on for hours, relate to catecholamines. So, there’s homovanillic acid and vanillylmandelic acid, and those relate to dopamine metabolites, or the breakdown products of dopamine and the breakdown products of epinephrine and norepinephrine. Then there’s another marker that’s called 5-HIAA, and that’s a marker for serotonin metabolites, or serotonin production. So, when you look at those collectively, you can see the catecholamines, dopamine, epinephrine, norepinephrine, and serotonin. And you want to think of that as an integrated system, because it’s all one brain. It’s not like you have two brains. And so, if you’re stressed the obvious thing is that your adrenaline or epinephrine would go high, but you will also see stressed out people with big serotonin problems or dopamine problems. So, it’s very much an integrated system. People that don’t sleep well might be more prone to serotonin problems, people with energy, focus, mood problems, memory issues, may be more oriented around dopamine related crisis. And in general you want to fix this as an integrated system.

And so, there are these amazing amino acids that are out there, tyrosine and 5-HTP, there’s something called tryptophan. There’s another product called Mucuna. So, between combining the 5-HTP, and tyrosine, and Mucuna, and tryptophan in different ways, depending on what the lab says, you can really help normalize brain chemistry in someone who’s extremely stressed. And then the goals are to help them sleep through the night really well, to keep them relaxed and balanced during the day, to eliminate or reduce sugar cravings that can happen from brain chemistry issues. And the neurotransmitter programs are probably some of my favorite, because they can kick in and start to impact people in a matter of hours or days, quite a bit faster than most of the other programs that we use. And the impact can be quite significant for a lot of people. So, even if the person is severe and they’ve been under stress for a long period of time, you can still get a correction relatively quickly compared to the other things that we do in functional medicine.

Evelyne: Yeah. So, with the metabolomics markers, the metabolites, so like the homovanillic acid, and I can’t say it, I said it differently than you, the vanillylmandelic, that one.

Dan Kalish: Vanillylmandelic. The van one.

Evelyne: Yeah, that one. So, can you tell, based on where those are, if somebody is more, say, stressed and wired versus stressed and tired and whether you’d recommend maybe more calming or more stimulating adaptogens, or kind of a mix? Is that something that you could tell from this test also?

Dan Kalish: Yeah. You kind of can because the markers can be quite high or quite low. So, it definitely gives you an idea if they are overproducing and burning through and just breaking down these brain chemicals at a super high rate, or if they’re just incapacitated and the markers are really low and they’re not even able to keep pace with the amount of stress that they’re under. But it doesn’t necessarily change the treatment so much.

Evelyne: Okay.

Dan Kalish: The treatments are similar either way, but you do get a sense of how extensive or how longstanding the problem is from that. It’s very similar to what you see with cortisol testing where you can have really high cortisol, which is bad, but you can have really low cortisol, which is also bad. It’s similar to that.

Evelyne: Yeah. Tell me a little bit more about cortisol. And I’m thinking specifically a lot of people use a salivary cortisol index to look at a cortisol rhythm, four point cortisol rhythm. When would you use that, or do you feel like you get enough information from this cortisol metabolite measurement on the metabolomics test?

Dan Kalish: No. So, I definitely would recommend the full salivary adrenal panel. And the three tests that we do, and I teach this in all the different courses, three tests, three body systems. So, it would be the HPA analysis, salivary cortisol testing, GI testing, and then organic acids. So, those three in my mind are the essential workup that you would do on every new patient. And there’s some overlap. Okay, yeah. So, there’s some GI markers on organic acids, but you still need the GI test to really know. And there’s some stress markers that relate to cortisol on the organic acids, but you really need the HPA axis analysis to understand the depth of what’s going on there.

Evelyne: Gotcha. Thank you. That’s helpful. And you said something interesting before. So, if a marker like a neurotransmitter metabolite shows up high, does that just mean that the body is clearing it faster? Maybe it’s not as high in the brain. How do you know whether it’s a clearance issue or an issue of too much?

Dan Kalish: The problem with organic acids is it’s complicated. So, some of these markers mean something, some of these markers mean something really bad is happening when they’re high and something even worse is happening when they’re low. Some of these markers, when they’re low, it doesn’t mean anything is wrong. And you have to learn it marker by marker. That is the problem. And it takes, honestly, it takes me at least a year to train someone in organic acids, which is amazing. It took me almost 20 years to learn how to do it. Maybe I’m a slow learner or something. But what I try to do with all the educational programs I design is an immersion experience. So, when you’re learning a language, they say you can learn a language, like I did in eighth grade, I had to learn French but I don’t remember anything.

Or you can acquire a language. So, acquiring a language would be like, you’re in France, you’re sitting around, you’re an infant, and you’re just hearing all these French people speak French. And you don’t have a checklist at the end of the day, did I learn my word? No, you’re just absorbing it. So, I think the way that clinicians’ brains work, I’ve learned this finally after 30 years of teaching, is they need to acquire organic acids. They need to hear it. We just did a two-hour class this morning on this. They need to hear that week after week after week. And then it’s like listening to your parents speak French every day. Now you’re five years old and you can speak fluent French. We want to teach it that way because it’s such a complex subject, if you try to learn, oh, homovanillic means this if there’s there, and you just try to learn it in a linear memorized kind of way, it would just drive you crazy because there’s so many variables. It’s almost impossible to learn that way.

Evelyne: Yeah. And I don’t want anyone listening to feel discouraged, because you have great classes on it. With the Designs for Health Metabolomic Spotlight test, it does algorithmically make supplement recommendations. So, it makes it easier to learn and you can connect with a clinician to review the test. And we also have trainings. So, I don’t want to scare anyone from learning this, but I think it’s-

Dan Kalish: Let me back up a bit. This calculator I’m holding in my hand right here, if you’re just listening you don’t know this, but I’m holding a calculator in my hand. Can I use this calculator every day? Yeah, I can. Do I know how this thing works? Absolutely not. I don’t know what kind of chip is in here. I have no idea how this thing works. So, if you’re doing the Designs for Health Spotlight version of this thing, and they’re telling you what stuff to use, you don’t have to understand how these mechanisms work and why they work. So, you can help people at a very profound level with no knowledge of what these markers are all about. And that is how everybody starts. You run your first, if you wait until you learn the test it’s going to be 20 years from now, you run your test, you look at your algorithm, you recommend those products, you see what the results are, you run another one. And you’re going to just start with that.

You’re going to start with preset protocols that you’re learning in a cookie cutter kind of way. And as the years roll by you’re going to learn individual markers in more and more depth. If you get super into this, you’re going to take a class with me, a one-month class or a one-year class or whatever, and just immerse yourself in it and get more familiar. But what we don’t want is people being scared of the test, or ordering the test when they feel like they understand it, because that day will never happen. So, you want to jump in, order 10 of these and try the protocols on patients and get some clinical experience doing that. You’re not going to hurt anyone doing it, and you’re going to get some amazing results even at that level.

That is super important. I’m glad you brought that up, because it’s an intimidating test but if you’re just doing these basic protocols and they’re given to you when you do the Spotlight thing, you don’t even have to worry about what they are, you don’t have to look them up, they’re literally presented to you on a piece of paper. That’s how you get started. We want that. We want you getting started and then backfilling the information as you go. Otherwise, you’re going to wait for too long and there’s all these people that you could help. They’re just going to slip by. It’s not good.

Evelyne: Yeah, that’s a great point. And I think even with those recommendations, I was just with a colleague of mine who came from a different industry, she wasn’t in our natural medicine world before, and she had a Metabolomics Spotlight run, and she just started, she was taking a multivitamin and magnesium, some basics, but she started supplementing what was recommended based on the Metabolomics Spotlight and felt a huge difference in a very short amount of time. So, I do think that even just using the basic recommendations we can really make a huge difference in a short amount of time.

Dan Kalish: Yeah. Honestly, I did these tests for over a decade before I understood any of the pathways or how any of this worked. You can get results without knowing why it’s working. So, it’s like you can use your cell phone, you don’t understand how the phone works, you just know you pick it up and you hit some button on there and it calls somebody. You don’t really understand how the cell towers are connecting.

Evelyne: Yeah, good point. I want to talk about one more area of the organic acids. Tell me a little bit more about kynurenic acid and quinolinic acid, and their relationship. What do we need to know about those?

Dan Kalish: Okay. So, kynurenic, it’s hard to say that one. It’s easier to say ky-urinate, but it’s kynurenic acid. Kynurenic acid… And oh, this is something to define. So, lactic acid is the same thing as lactate. Pyruvic acid is the same thing as pyruvate. Homovanillate is the same thing as homovanillic acid. So, some lab companies and some research studies will say homovanillic acid, and some will say homovanillate.

Evelyne: Okay.

Dan Kalish: Homovanillic acid or homovanillate. And some reports you read are going to say pyruvic acid and some reports, research studies and labs, are going to say pyruvate. They’re the same thing, same exact molecule pretty much. It’s just people use different nomenclature. And so, kynurenic acid converting to quinolinic acid. So, when your brain is inflamed it’s not happy and it does some really necessary things, but they’re a little not so great. One of the things that it does is it takes a molecule called tryptophan and it converts it into what we call an inflammatory cytokine. That is your body’s way of just adapting.

And so, as your quinolinic acid goes up, it means that your levels of neuroinflammation are going up. And then this is really interesting is many of these organic acid markers, they’re just what they are, they’re chemical and they’re a marker. But with quinolinic acid, the actual quinolinic acid itself acts as a neurotoxin. So, as quinolinic acid goes up, it not only means that this pathway is demonstrating an increase in neuroinflammation, it also means that there’s a buildup of a neurotoxin in your brain. And as the quinolinic acid goes higher and higher, it’s going to cause a problem with something called your NMDA receptors. But the bottom line of that whole pathway is that your brain starts to get agitated and excited, the cells get excited but not excited like I’m happy to be at this Rolling Stones concert, excited like I’m going to blow up and bad things are going to happen.

And so, when these excitatory reactions start to happen, people get anxious, and nervous, and depressed, and don’t feel great. And that’s the end result of this neuroinflammation. So, if quinolinic acid is high, you need to figure out what’s driving this inflammation? Is it a gut problem? And you do a gut test. Is it a toxin? And you look at environmental toxin markers on the test. And you can use a very simple treatment of magnesium to calm down the quinolinic acid while you’re getting around to figuring out what’s driving this inflammatory response. That’s a really important set of pathways. And for a lot of people you’re also going to see that there’s deficiencies or problems with things like serotonin in relation to this because part of quinolinic going up is that your tryptophan levels are dropping and it’s harder for you to make melatonin. So, it’s harder to sleep and it’s harder to make serotonin. So, people tend to get a little anxious and depressed.

Evelyne: Thank you. I just love your passion and excitement around all of this. And also it seems like magnesium is always one of the answers.

Dan Kalish: Yeah. So, I just said this in class today, this morning, I was like, “Look guys, just every single patient that comes in, don’t even analyze it, everybody gets magnesium.” Almost everyone’s deficient in it, nobody eats green leafy vegetables five times a day and just need magnesium for, I think it’s over 300 enzymes, just think if you just give someone magnesium, you’re literally correcting for one of the most common deficiencies in the world, and you’re fixing like 300 different enzymes or more at the same time.

Every single pathway that we’ve talked about today, magnesium dependent. Beta oxidation, magnesium dependent. Citric acid cycle, magnesium dependent. Electron transport chain, that’s the very definition of a magnesium dependent. You’d die if you didn’t have magnesium in that, you would die in a millisecond. The neurotransmitter cell, all of this is magnesium dependent. Because the twice daily multipack has a ton of magnesium in it. So, if you’re worried about magnesium and all these other nutrients, just give them the twice daily pack. One in the morning, one at night with meals, and then all that mineral concern will be taken out. You don’t have to worry about it.

Evelyne: Yeah. I love that. So, I want to switch gears here and ask you some questions that we ask everybody on the show, and thank you so much for sharing such valuable information. Actually, Dan, where can practitioners learn more from you?

Dan Kalish: Yeah. Kalishinstitute.com. K-A-L-I-S-H institute.com. Just go to the website and you can sign up for a newsletter, or just send us an email and ask questions and see all the classes that we offer, et cetera.

Evelyne: Great. And I know you offer classes all the time. I get your emails and I need to be attending more of those because I know they’re wonderful. And you also have them on YouTube.

Dan Kalish: Thank you.

Evelyne: Yeah. And then we also have the Designs for Health Spotlight training, and we’ll link both Dan’s training and our training in the show notes. So, my first question to you is, what is something that you’ve changed your mind about through all of your years in practice?

Dan Kalish: Oh, probably the most important one is the microbiome. And for most of my practice time I’ve really been focused on antimicrobial programs to kill GI pathogens. And now I’m realizing, and some of this is just a result of the testing, well, a lot of it is a result of the testing, now because we have accurate commensal bacterial markers, meaning we can accurately test because of PCR testing. We can actually accurately test the good bacteria in the gut, which wasn’t possible in the past. When I started my career this technology hadn’t been invented yet. In fact, my brother-in-law worked with the scientists that developed PCR. That’s a whole other story, but it’s a pretty cool technology.

And so, now we can see the commensal bacteria, and what we see is that low commensal bacteria is the precursor and probably the underlying reason why pathogens become a problem anyways. So, I’ve really flipped on that and I’m super into using polyphenols and fiber to support the commensal bacteria as prebiotics, rather than just killing everything all the time. That’s been a complete reversal. And for a lot of chronically ill patients it works better to do the polyphenols and fiber, support the good bacteria and let them sort out the bad guys.

Evelyne: Yeah, that makes sense. And do you do fiber, or do you do butyrate sometimes? Even a step further.

Dan Kalish: Well, butyrate… Oh, my gosh, okay, we don’t have another hour, but butyrate is hands down the most impactful supplement I’ve ever seen. So, butyrate, it is almost like cheating it’s so powerful. Because butyrate is going to just instantly in a pill supply all, not all, but some of the main reasons why you have a microbiome in the first place. It’s a pretty important product. So, for anyone who’s got commensal bacterial problems, giving butyrate gets around the whole problem that their microbiome is screwed up. And it buys you some time to correct the microbiome with prebiotics and probiotics, fiber polyphenols and probiotics. So, butyrate is, yeah, it’s like cheating because it’s just so powerful in its effect. And I wouldn’t use it forever because you eventually want people to eat properly and get off of the butyrate, but it’s a good short-term intervention if you just need something quick.

Evelyne: Yeah. Great. I love that. So, what are your three favorite supplements? I know we’ve mentioned some, but what do you not live without?

Dan Kalish: And I’m going to just throw some out there. These are actually my favorite.

Evelyne: Okay.

Dan Kalish: Yeah. Because I can’t take these all really. Just massive impact on my practice, pregnenolone for sure number one.

Evelyne: Really?

Dan Kalish: If you’re not using pregnenolone, you’re not really living. Yeah. Because pregnenolone helps with all the stress stuff. Anyone who’s stressed and has a problem with cortisol needs pregnenolone. Everybody buy pregnenolone, take it, take it, take it. So, pregnenolone is for sure number one. It’s kind of a sleeper product, but most impactful. Then number two would be DopaBoost™. That stuff is amazing and a lot of people have dopamine problems. And then my third one, when we did this analysis like 15 years ago, which shows I’m not a very great business person, but I’ve been in practice for 15 years and I never ran the numbers on what’s our number one seller in our practice. And somehow this report came across my desk and I was like, “Oh, that’s interesting.” Number one seller for that year, saccharomyces boulardii.

Evelyne: Ah.

Dan Kalish: It’s a great product for all kinds of digestive problems. And then it’s not only that I prescribe it all the time, I wasn’t really even thinking about it, but it’s that people stay on it because it helps so much. That’s why it was our number one seller. It wasn’t that I prescribed it to a gazillion people. It’s just people love it so much they just stay on it. So, what a great way to fix your gut. Just a powerful and well-tolerated probiotic. So, those three, I’ll put those three.

Evelyne: Awesome. And final question for you. What are your favorite health practices that keep you balanced and resilient and sane?

Dan Kalish: Yeah. So, I have a Daoist meditation practice that I do. I have a Daoist master that I study with every week. And we do a lot of different stuff. Right now he’s got me doing saunas, so I had to build a sauna, and cold plunges, so I had to buy a cold plunge. So, I’m doing the sauna at like 200 to 220. And the cold plunge is in the mid forties. And that is a daily practice, anywhere from an hour to an hour and a half. Heat, cold, heat, cold, heat, cold. And at first I really couldn’t do it because it is three minutes in the heat and three minutes in the cold. But now it’s not a big deal. I can do it for an hour, hour and a half, no problem. And if we get done with that, that’s a major physical adjustment to your system, and you combine that with the Daoist breathing practices and you’re just in another place.

Evelyne: Have you noticed since you started that?

Dan Kalish: Yeah. What does it really change? Well, it takes all the inflammation out of your body. It is a massive cardiovascular workout, but you’re not exercising. It completely changes your dopamine, testosterone levels, just to a degree which are hard to represent. Nitric oxide is impacted. Obviously it’s just ringing out your vasculature and making it completely different. Yeah, it’s quite impressive. It also changes you cognitively. I think that’s one of the stronger effects. It makes the spiritual practice easier to access the spiritual realm, and it really gets you out of your head. When you’re in 220 degrees, or you’re in 42 degrees, there’s not a lot of thinking going on. You’re not worrying about your grocery list or whatever people think about, or what’s going to happen with the next election or whatever. You’re just in the present moment because you’re so damn cold or damn so hot. So, it changes your brain function.

Evelyne: Yeah. Amazing. Well, Dan, thank you so much. I really appreciate you coming here and sharing with us and just sharing your expertise with thousands of practitioners all over the world. It’s really appreciated.

Dan Kalish: Yeah, thank you very much. Appreciate it.

Evelyne: Thank you for tuning into Conversations for Health. Check out the show notes for resources from today’s show. Please share this podcast with your colleagues. Follow, rate or leave a review wherever listened or watched. And thank you for designing a well world with us.

Voiceover: This is Conversations for Health with Evelyne Lambrecht, dedicated to engaging discussions with industry experts, exploring evidence-based, cutting edge research and practical tips.