Jill Brook: [00:00:00] Hello, mast cell patients and wonderful people who care about mast cell patients. I'm Jill Brook, and today we have an episode of Mast Cell Matters, Deep Dives into Mast Cell Activation Syndrome or MCAS, with our amazing guest host Dr. Tania Dempsey, world renowned MCAS expert, physician, researcher, educator to other physicians. Dr. Dempsey, thank you for being here today and which of your incredible colleagues did you bring with you today?

Dr. Tania Dempsey: I am excited to introduce Dr. Gregory Plotnikoff. This is gonna be an amazing interview, so I'll give you a little bio on him. Dr. Plotnikoff is the founder and medical director of Minnesota Personalized Medicine and is a board certified internist and pediatrician with more than three decades of patient care experience.

He's the recipient of several national and international awards for medical research and teaching. And he's been called one of Minnesota's [00:01:00] best brains, Minnesota's Dr. House and a super sleuth. I love that. Prior to medical school, Dr. Plotnikoff attended Harvard Divinity School to deepen his understanding of suffering and of human responses to suffering.

After eight years of medical school and residency training, he helped establish the Center for Spirituality and Healing at the University of Minnesota, where he served as its first medical director. From 2002 to 2008 as a US Japan Foundation Leadership Fellow, and with an initial support as a Bush Foundation Leadership Fellow, Dr.

Plotnikoff served as a professor of medicine at Keio University School of Medicine. And he studied their research taught in Japanese, the Kampo herbal medicine tradition. He had an incredible experience there. The national library of medicine lists more than 60 medical journal articles that Dr.

Plotnikoff has published in peer reviewed medical literature. He's a [00:02:00] lead author of more than 25 medical textbook chapters. In 2003, his article on chronic pain and Vitamin D deficiency is the one, one of the most highly cited articles in the history of the Mayo Clinic proceedings. I can just go on.

He's amazing. I'm honored to know him and to, to work with him and collaborate with him and so, so welcome Dr. Plotnikoff.

Dr. Greg Plotnikoff: Oh my gosh. Well, thank you. And I, I hope I can live up to everyone's expectations. But yes, I can be a little bit geeky, so.

Dr. Tania Dempsey: Me too. All of us actually. So we're, we're all good. It's all good. So you were telling us right before we started recording that you just got back from Dysautonomia International where you spoke, you actually presented a couple of different presentations, and you were really excited about some of the stuff that you learned and some of the stuff that you presented. And we would love to discuss that and share with our audience about what you are, what you're excited about.

Please share.

Dr. Greg Plotnikoff: Cool. Well, [00:03:00] well, thank you. Actually, it was a great conference. I guess it's available online as well. Great organization with knowing about for resources and more. I was really deeply moved by a presentation by Dr. Chip Norris at Medical University of South Carolina. Now his lab has 27 researchers. Majority of whom have hypermobile Ehlers Danlos syndrome. They are like really motivated in this topic. And so they've been doing deep dives. One of the things they published fairly recently was a survey of 4,000 people with hypermobile EDS, and what they found was the average number of comorbidities, that is other kind of medical diagnoses, was 25. I don't know of [00:04:00] any other condition on this planet that has 25 on on average, 25 comorbid medical conditions. Think about something severe like diabetes and stuff. We have a couple. You know, congestive heart failure, a couple. Cancer, a couple. But 25 on average. And what was really wowed is number one was pain, not necessarily musculoskeletal pain, not necessarily joint pain, I should say. Number two was dysautonomia. And number three were GI concerns.

Dr. Tania Dempsey: Hmm.

Dr. Greg Plotnikoff: Not on that top of the list were things directly related to joints. And I thought that was kind of really wow.

Now obviously there were a lot of joint issues, et, et cetera, but top of the list were things like dysfunction of the autonomic nervous system, dysfunction of GI and things like that. As one [00:05:00] person said, it was a teenager group, I was chairing, and it was kind of like every time I eat I'm pregnant. And so, so that was quite shocking. Just kind of, I just don't know anything like that. And does that fit to either of your experiences? Is that kind of, that with hEDS, that, that you see so many other things and so if you look through that window, it opens up this whole other world. Just like you look through the mast cell window, it opens up this whole other world.

Dr. Tania Dempsey: The question I have though is, is it because a large majority of those patients have mast cell disorder that then is driving

many of those other disorders.

Dr. Greg Plotnikoff: Isn't that a, isn't that a great question? What you see depends about what window you look through.

If you start with the mast cell window, suddenly you see all these people with hypermobility. You start with a [00:06:00] hypermobility window, suddenly you see all these people with mast cell.

And, and you start with a dysautonomia window and like long COVID or something like that, you're gonna see suddenly, oh my gosh, there's hypermobility, there's mast cell activation. Oh

my goodness. So

in some sense, I had this image that we're kind of like blind people feeling this elephant, and we're all trying

to make sense of something which up to this moment in world history has never really been very clear, never even seen. It's been, I have you know, outta sight.

So the second thing that he shared was something that is going to come out in publication in the next couple weeks, but they've been doing deep dives into the genetics behind hypermobile EDS.

Dr. Tania Dempsey: Oh, that's interesting.

Dr. Greg Plotnikoff: So we know yes, that there are multiple forms of Ehlers Danlos, where it's very clear

[00:07:00] what the genetic issue is, and it's very clear, it has to do with connective tissue issues.

And and if one does connective tissue disorder panels, one can find other things. But what he's been doing is, is doing whole genome sequencing for just in hEDS and what is popping out as unique and uniquely different, and the shocking thing here is nothing to do with joints or collagen or like, has everything to do with autoinflammatory states and, and kind of, and different inflammatory pathways. So it kind of opens up a whole new window to look through of kind of autoinflammatory syndromes and, and as maybe that hEDS is something very different from genetic EDS.

Dr. Tania Dempsey: Right. Wow, that's [00:08:00] fascinating.

Dr. Greg Plotnikoff: Yes, and so, so now then of course, of course all in our mind now is, okay, how do these things relate to mast cell? And, and oh, it was this kind of, so can have the wait for, for those things. But I know when this publication comes out and, and the actual SNPs and the genes are mentioned, I know all of us are going kind of be up at night thinking about what does this,

what is this going to mean. And how, what might this open up in terms of new approaches and that may be helpful for people.

Dr. Tania Dempsey: Absolutely. I can almost get into Dr. Larry Afrin's brain. I can almost think about what he would say. And we've had conversations about autoinflammatory syndrome actually, because a fair number of, of our MCAS patients, when we do let's say Invitae testing, which is a genetic test, and even [00:09:00] whole genome sequencing, we have

been finding sometimes more common autoinflammatory syndrome conditions like the NOD2 and sometimes less common mutations or polymorphisms. And, and so the question is, are those conditions a driver of Mast Cell Activation Syndrome? Are they somehow the start of an inflammatory process that then brings in the mast cell and, and or are they predictors of Mast Cell Activation Syndrome?

Right. So this is this is really exciting.

Dr. Greg Plotnikoff: Yes. So, so he went, he refused to share what genes they were,

but, but the NOD2 of course was on my mind.

Dr. Tania Dempsey: Yeah.

Dr. Greg Plotnikoff: Which, which reminds me actually a related presentation by Tae Chung from Johns Hopkins

about looking at the genetics of long COVID. He [00:10:00] said they're, they found some unique, using proteomics and other things,

they found some unique pathways. One of them was TCN2, which I'm really curious because the Brigham and Women's Group, at their long COVID chronic fatigue syndrome clinic, they did a fairly sizable study on 7,000, a proteomic study of, of 7,000 proteins, they found three that were exceptionally elevated. One of them had to do with B12 transport. And I think and so I think there may be kind of a lot of things coming together.

And so kind of my take from this is, boy is there hope. There are some, these are kinda real exciting things which can lend themselves to actionable

interventions that may be really deeply meaningful for our patients.

Jill Brook: For those of us that are less familiar with some of the stuff you're talking about, do you mind just maybe explaining a little bit more where your hope comes [00:11:00] from, and when you talk about B12 transport, how would that tie in? Can you, can you just maybe flesh out that idea a little more?

Dr. Greg Plotnikoff: Well, it's an interesting question. What is normal and who is normal? Think about it. They're both, they're very political questions. They're, they're full of value judgments. And for, for something like B12, is it a bell curve for the population and that that normal is the 90, you know, you know, kind of the middle part the, or has to do with physiological function. Is there an index disease associated with it? And, and that, that type of thinking you know, we think about for scurvy, you know, we think, well, vitamin C, you know, scurvy is the index disease for setting vitamin C standards. 60 milligrams a day or one orange.

And that's about the extent of the science. But what if vitamin [00:12:00] C has other roles for things? And, and now that we think about, it's not just the vitamin B12 level,

but how is it functioning in the body? So what's the methylmalonic acid, what's the homocysteine? And that still may not tell us what's going on, like in the central nervous system at a, a more distinctly cellular level. And so if people don't have good transporters, you can have normal B12 levels, but be functionally insufficient at key areas in the body. So the excitement about that is maybe that fits with what some of our colleagues have been saying, that some people require rather massive doses, like intramuscular B12 three times a week,

which seems insane. It doesn't make any sense, unless maybe there's a you have to overcome a certain barrier to reach that. And so, so if in fact some issues with chronic fatigue or long [00:13:00] COVID actually have it like a B12 component to it. While we've got lots of B12, more B12 on the planet than there is suffering, and maybe we just need to get it to the right spot. So, which reminds me, okay, as we go in a nonlinear fashion,

the fascinating article in Nature last week about CoQ10 deficiency. And the

reason I share this with both you and our audience today, is it kind of highlights a way of thinking. So the researchers looked at at a genetic deficiency of CoQ10. And we know the pathways in producing it, and what they were able to do was go through a pathway and identify one intermediate gene enzyme that was disrupted. They could figure out what was immediately downstream to that, produce it, then they introduced it into this child who is severely disabled and the child is [00:14:00] walking again. Wow. Well, what a happy story. But here is a combination of genetics, is a combination of being able to produce, produce the right supplement. And this is kind of an affirmation of kind of what has been considered functional medicine way of thinking. That it's actually in is that, yeah, you can identify barriers and then identify strategies for going around those barriers that often can be non-pharmaceutical in nature, or in this case, semi pharmaceutical in nature. Then we, you know, we can have good, good outcomes. And and so I think we're gonna be seeing more and more of this type of thinking come through.

Dr. Tania Dempsey: Which, which I think is amazing. And I think that it really, sort of, I think it sort of speaks to the, the fact that, at least from my perspective, I, I tell my patients there's an answer. There's a [00:15:00] reason why you're, why you're sick. I'm gonna do everything in my power to figure this out.

Right. But there are, and I do, right? I'm relentless. I will try to figure it out. But we don't have the tools for e figuring out everything. Right? But the answers are there, right? We just need to understand how to, how to ask the question and what tools to use. Right? And here's an example where they found a tool.

They found the solution and they were able to help a child. And, and so I say all the time, the, the answers are there, right? We, we just don't, we don't always know all of them yet, but we're getting there, right? This is, this is hope that, that there's progress in, in the medical world.

Dr. Greg Plotnikoff: Yes. And, and the relentlessness that you and I bring to patient care is paralleled by people who are [00:16:00] able to persevere, persist. Stubborn in the best sense of the word. And that is refusing to accept things as they are and know that, wow, a lot of good thoughts going into this, and people are recognizing the importance of looking through as many windows as possible. I think that's the kind of big thing is you look through a window, everything you see through that window is, is true and can be quite beautiful. And that can come right back around and kind of validate the validity of that window for looking at the world.

Dr. Tania Dempsey: That's true.

Dr. Greg Plotnikoff: But every window's defined by walls and what's behind that wall might be as important or even more important than what's highlighted by the window. And so part of the relentlessness that we bring to, to patient care is to look through as many windows as possible. MCAS being a great window. Hypermobility being a great window. Dysautonomia being a great window, microbiome, [00:17:00] I mean, there's many multiple windows to be looking through.

And I think one window I want to share with you all is window from Japan. Now you mentioned that kind of, I spent six years as a

professor of medicine in Japan, and I have to say, fascinating because we read the same journals, the same textbooks, and yet the practice is, is different and reflection of culture and history

and the like. So recently, courtesy American College of Physicians, we hosted a physician from Japan as part of the Global Physician Scholar program.

And I called him up the other day and I said, okay, here's a challenge. I am seeing so many people with gastroparesis, so many people

with GI motility disorders and nausea and vomiting and, and all kinds of things, and the gastroenterologists are kind of feel like they're over their head and so they, they're not able to really address this.

They're going through 14 medications, aren't [00:18:00] any better. What are you guys doing in Japan? He said, oh, that's very easy. We give IV thiamin and pantothenic acid and it's like, oh. So I was thinking pantothenic acid, vitamin B5 derived from valine is a thiamin dependent reaction,

and and processing of valine and sister keto acids are all thiamin dependent. So, so last couple months in preparing for this talk, I did a deep dive into Japanese literature on thiamin deficiency, what we in the west called beriberi, they call kakke. And in med school I was taught either you get it if you're like severely alcoholic or some kind of severe malnourishment. And by the way, it's a 19th century issue and it's an Asian issue, nothing to do with North America. [00:19:00] And said, well, okay, yes, I'll accept that as the truth. And now I know, well, maybe that's not quite the case. Here's why he says it's not quite the case. Going and reading Japanese physician reports from the early 1900s where they had no technologies or limited technologies. They're very good observers. And the signs of early beriberi or thiamin deficiency are gastrointestinal. They are epigastric fullness, nausea, abdominal pain, followed later by vomiting, anorexia related concerns. I'm just like, well, isn't that interesting? And then you can almost get paresthesias and it's go, goes on on it gets worse and worse. But the early observations were predominantly, all GI, the very ones that [00:20:00] are kind of befuddling and betwixing today. It turns out in 1940 the Archives of Internal Medicine had an article from North America where there was intentional induction of thiamin deficiency. And what did the patients first experience? Anorexia, nausea, abdominal pain, vomiting, early satiety, low motility, constipation. Huh? How many people do we see with that? Does that sound like your practice at all? Tania?

Dr. Tania Dempsey: Just a few patients.

Dr. Greg Plotnikoff: Yes. So you say, well, but this is North America and it's 21st century. No one gets beriberi. But in the Annals of Internal Medicine just a few years ago, Harvard reported on a series of cases of people with severe nausea, vomiting, abdominal pain, and lactic [00:21:00] acidosis

presenting to the ER. The picture is you rush these people into surgery. There's something catastrophic going on in the gut. You get into surgery. They go into surgery.

Nothing. But because pyruvate was elevated, they're given IV thiamin, and it resolves. So there's a gastrointestinal beriberi, huh?

Jill Brook: Wow.

Dr. Greg Plotnikoff: Yeah. Wow is exactly right. So it turns out that in 21st century North America, it's been well described now in people with gastric bypasses, and there's been a whole series of malpractice cases because no one thought of beriberi after a gastric bypass and people suffered horrible adverse effects and, whoops. So part of our mission now is to say, well, you know, maybe we ought spend more time with thiamin. But the question is, well okay, [00:22:00] who might be at risk? You know, it's just kind, it doesn't take much thiamin to to, to do things. So the question is, I don't know, just raise some, some thoughts. What would make sense of who might be at risk?

Dr. Tania Dempsey: Right.

Well, I mean our patient population generally, you know, limited diets because of reactivity, right?

Dr. Greg Plotnikoff: Number one. Yes.

Dr. Tania Dempsey: Chicken or egg, you know, but they're, you know, limited with what they're able to eat. There are some sort of absorption issues, so they have dysbiosis or some other issue in their gut, so they're not absorbing. I'll go so far as to say that if thiamin deficiency happens in alcoholics, you know, there's a condition where there's an overgrowth of certain bacteria in the gut that produces like a, like, almost like a alcohol reaction. I forgot the name of it. Do you remember what the name of it?

Dr. Greg Plotnikoff: Yes. Well, It's it's sometimes called [00:23:00] Brewery.

Auto Brewery Syndrome.

Dr. Tania Dempsey: Yeah, Brewery Syndrome. Yeah. Yeah. So maybe, you know, maybe that those patients are at risk for, for thiamin deficiency I, I have measured thymine levels in my patients. I see a lot of low thiamin in my, my patient population.

So I think this is really interesting and riboflavin.

Dr. Greg Plotnikoff: Yes.

Dr. Tania Dempsey: I have some theories about riboflavin that we could talk about.

Dr. Greg Plotnikoff: Yes, yes. You identify that kind of restricted diets can be very low and things. And a gluten-free diet is very low. I had no idea that it would take 27 slices of gluten-free bread to, to come approach the RDA for thiamin. Well, I don't know anyone doing 27 slices.

Dr. Tania Dempsey: Is it because thiamin is fortified in regular bread?

Dr. Greg Plotnikoff: Well, yes, because it turns out baking anything above 120 degrees centigrade, roughly, say 250. And most [00:24:00] things you bake at what,

400 or something? And that, breaks it down, no matter if it's gluten-free or not

gluten-free. If you use baking soda, that breaks it down. If you wash your rice, it washes it away.

So it's a lot about how one prepares one's food and then how one stores one's food. Ultraviolet light, and refrigerators at the grocery stores. If you've got a clear plastic, it's going to destroy the thiamin in the product. The the use of sulfite based preservatives so that bisulfides breakdown thiamin. And Tania, I know you're gonna go wild over this, so we need a little drumroll for this.

Dr. Tania Dempsey: I'm ready. I'm ready.

Dr. Greg Plotnikoff: Mycotoxins. Particularly fumonisins. 30 species of fumonisins are potent thiamin breakers. thiamin is two things connected by a little methyl

bridge, which is very fragile, [00:25:00] and,

and fumonisin mycotoxins and one form of a penicillium mycotoxin are very potent breakers of thiamin. That's whether it's in the grains itself, in the storage, or whether it's coming from a wet, moldy house. Huh. And then the microbiome itself.

Dr. Tania Dempsey: Yeah.

Dr. Greg Plotnikoff: So there are a number of, of agents, or I guess we were saying microbes in the intestine, which are either thiaminases, or thiamin blockers. Of the  thiaminases, it includes bacillus subtilis, which is often promoted as a good probiotic. And one that, you know, if you give it for more than a couple months, it never goes away. Oh, yikes. Candida, H. pylori, Staph aureus. There's kinda a whole series of different things which will break [00:26:00] down thiamin. Huh. And then there are medications, omeprazole, antibiotics, metformin and diuretics. Diuretics just flush thiamin out of the body, particularly Furosemide, but the thiazide diuretics as well. So, so for dietary reasons we might not be getting enough and, and how we actually cook the food, how we prepare it, how we serve it, how we store it, and then what's going on in our gut and what medications. We could have a whole, an incredible number of people out there with unrecognized gastrointestinal issues due to low thiamin. So, question is then well is there enough thiamin in a multivitamin? And turns out most multivitamins have thiamin hydrochloride or thiamin mononitrate.

Dr. Tania Dempsey: Right.

Dr. Greg Plotnikoff: And the [00:27:00] absorption efficiency of those is around 3%, maybe 5%. So you can have, quote, getting the RDA can still be low, because you're only absorbing 5% of it, if you're absorbing. One thing I think is really important for everyone to know who has anything to do with a GJ tube, a gastric jejun al tube for tube feeds, thiamin is absorbed in the duodenum and proximal part of the jejunum, so is bypassed by a GJ tube. And this may be one of the reasons why the RDA for people on tube feeds is like, you know, five to tenfold higher than for oral. And for people on TPN, it's, it's significantly higher than that. And people in a medical crisis, it's like a hundred milligrams IV or higher to for [00:28:00] that. But I don't know of anyone I've seen with the GJ tube where there's been attention to to, thiamin.

So you're gonna say, well, okay, so I, my patient has these risks, I'll just go measure it. And Tania mentioned it, you've got patients who you've been able to

document that it's low. But what's so shocking to me is that only 0.8% of the body's thiamin is found of the blood.

It's mostly found in cells, including red blood cells. But there's no commercially available measure at this time for that and so, so blood measurements apparently appeared to be a poor approximation

of actual functional status. So people with Wernicke's encephalopathy have demonstrated normal thiamin levels.

Dr. Tania Dempsey: Hmm. So you can't test it?[00:29:00]

Dr. Greg Plotnikoff: You can't test it directly. So indirectly. I use a lot of you know, fatty acid profiling, and so high phytanic acid to pristanic acid ratios or high branch chain fatty acids or high branch chain amino acids. The sister keto acids, isovaleric, et cetera are all decent measures.

High pyruvate, number one on the list, my mind now is, is, thiamin. But there are probably gonna be a, a whole bunch of functional measures we can think

of, where it's, its block is. And there are 11 different places where thiamin acts in the body, three of them directly related to the Krebs cycle,

and including upstream from GABA, the calming neurotransmitter. So you can see why I am kind of going

gaga. I apologize for going gaga.

Dr. Tania Dempsey: No, no. I'm gonna go with you. I'm [00:30:00] gaga with you.

Jill Brook: So in 2017 Svetlana Blitshteyn published a paper about Vitamin B1 deficiency in POTS patients. And she looked at 64 consecutive patients and she measured their thiamin blood levels, and she found that four of them were low, not truly deficient, but low.

And she had them all all supplement with 100 milligrams of thiamin, I'm not sure which form, per day. And one of those four got quite a bit better. But what I'm hearing you say is that probably was not a blood test that really did justice to what you're talking about and that we need to find better ways to get at where the thiamin matters in the red blood cells and such.

Dr. Greg Plotnikoff: Yes, we have to say that at this point in time, I think the blood tests are probably not, if you come back with a normal thiamin levels coming back, like with normal magnesium level, I'm not quite sure if it means anything.

Dr. Tania Dempsey: Right.

Dr. Greg Plotnikoff: If it comes back low, then it's really meaningful. [00:31:00] If it comes back normal people could probably still be low. So functional markers may be the best way to go for that.

So, but for one person made a big difference and we say, okay, there's some signal there. So it's in hypothesis, maybe not ready for prime time but, why is this biologically plausible for POTS and for GI and other concerns? And that is because thiamin is critical for making acetyl-CoA. Acetyl-CoA is critical component of acetylcholine. Acetylcholine is the agent, the neurotransmitter in the autonomic nervous system. And so low thiamin, low acetyl-CoA, low acetylcholine, low functioning.

And there's more. Actually if you do have acetylcholine, thiamin actually [00:32:00] augments its effect, so much so that, in experimental animals, if you cut all the mesenteric nerves, enteric nerves, and, and, and give IV thiamin, you get peristalsis. And the other thing is that like pyridostigmine, thiamin is an acetylcholinesterase inhibitor, so it, so not only augments the function of acetylcholine is, and it's necessary for making acetylcholine, but it's also supports acetylcholine levels. So one of the things I was thinking about is kinda like, okay, I've seen people who I thought would respond to pyridostigmine and did not. And I think some of our colleagues are pushing as high as 180 milligrams three times a day.

I'm thinking maybe that's indication for more thiamin and and support.

Dr. Tania Dempsey: How do you supplement?

Dr. Greg Plotnikoff: Well, I'm thinking, you know, we know a [00:33:00] lot of people who give Myers Cocktails

and Myers Cocktail has a hundred milligrams of thiamin in it. So maybe that's one of the things and oh, there's a lot of magnesium in it, and you need magnesium to activate thiamin.

So, so a Myers Cocktail might be kind of a, kind of a nice thing for people who have access and for whom there's kind of more of an urgency issue. Because thiamin hydrochloride is not well absorbed and thiamin mononitrate is not well absorbed, and those are things which are generally found in multivitamins, going to a specific thiamin product could be important. Now, just reminds me of a case from earlier this week. An out of state patient had very, documented in 2018, low thiamin. Never really addressed, but described recently going on AlliMax, which is a, a garlic product and [00:34:00] start feeling so much better, incredibly better. Well, it turns out some of the best sources of thiamin on the planet are the allium vegetables, garlic, onions, and leeks. And unfortunately they're FODMAPs. So if people want a low FODMAP diet might not be getting them. And there may be other reasons people might not be getting them.

Dr. Tania Dempsey: AlliMax is a garlic supplement?

Dr. Greg Plotnikoff: Yes. Yes. And I'm just thinking, just thinking about, you know, the different aged garlic products out there promoted for cholesterol and other reasons, but just thinking about the allium vegetables. And so there's Allithiamin which is a type of thiamin commercially available that can be combined with lipoic acid as Lipothiamin. Or there's an artificial thiamin, which also is fat soluble and, and readily and well absorbed called benfotiamine, which has been has been subject to two randomized controlled [00:35:00] trials for Alzheimer's disease in small populations, but with positive signal. The dosing for that for benfotiamine was either 300 milligrams once a day or 300 milligrams twice a day.

And I don't know how they chose those numbers, but my, what my current hypothesis is, is start small and slowly increase with people to see what's, what's a dose that we appear to get a signal in. And if we go, you know, up to 300 milligrams and no signal, then that's, I don't think that's going to be the issue.

But but this is still early on and and so, all I can say is that in Asia there's a much greater awareness of thiamin and gastrointestinal issues, and at least it's part of the standard of care in Japan, it appears, for either ileus or slowed motility and with enough signal there that [00:36:00] people were very comfortable ordering that.

Dr. Tania Dempsey: I think this is really, really critical and I, I'll bring up the riboflavin thing because as we're talking about B vitamins, I think it just, we have to be aware of, low vitamin or, or nutrient levels in our patients in general, right? thiamin is fascinating and what you bring up I think is something that we all need to start paying attention to.

And I, you know, clearly I will be paying even more attention to it. What I have found with riboflavin is that, so, you know, all the B vitamins, right, have some some interaction. Riboflavin is a mast cell stabilizer, and so I see a tremendous amount of riboflavin deficiency. Now, I've not done the type of deep dive that you've done on thiamin.

I will. But I measure and I find quite frequently low thiamin and low riboflavin often together, [00:37:00] but sometimes not, sometimes independently one or one or the other. And again, I'm not gonna rely on lab tests alone, but it's just interesting that in my population I am seeing very low thiamin and/or riboflavin or riboflavin and/or thiamin.

And when I started seeing all this riboflavin, and when I say riboflavin deficiency, I'm, it's like zero.

Dr. Greg Plotnikoff: Yes. Less than five on the Quest test. Any predictors for that?

Any predictors, for example, are they in plant-based diets or are they have SIBO?

Dr. Tania Dempsey: Yeah, well, I think, I think it's restricted eating. I think it's all the same factors that you mentioned with, with thiamin, to be honest with you. But because of riboflavin's role in the immune system and, and as it acts as a mast cell stabilizer, that's my theory as to why riboflavin actually helps migraines.

I think it's through the mast cell pathway, but I, I can't [00:38:00] prove it because there's not enough research, but I just wonder about that.

But I have patients where I've supplemented with riboflavin and have seen some improvements. You know, it's almost like I'm using a trial of a mast cell stabilizer. You know, sometimes it works, sometimes it doesn't. There may be a signal in some patients and no signal in others, but I think it's a promising avenue, and so now it just reminds me of like that really we need to be paying attention probably to all B vitamins

in their, in their own way. Right. B12 is problematic. Obviously thiamin, if it's low is problematic, riboflavin is problematic. Right. You can just go through down the line.

Dr. Greg Plotnikoff: Yeah, we're just thinking of B1 thiamin, all the things in methylation, B2, B3, B6, B9, B12, and oh, and here's B5 we were talking about earlier and just like, wow.

But actually it was, it was less than a hundred years ago that the Nobel [00:39:00] Prize was given out for the, for the for the discovery of a thing called a vitamin. thiamin was that first vitamin. And that was 1929 Nobel Prize in Medicine. So here it is less than a hundred years

later and it says like, you know, sometime a hundred years from now, people are gonna go, oh boy, it is like Dr. Dempsey was right, it was right there in front of them. They just didn't have the eyes to see it.

Dr. Tania Dempsey: But that's, but that's an amazing story. And I, I'm, so, so you presented that your research on thiamin at the at DI?

Dr. Greg Plotnikoff: Yeah, so really it was just, you know, a literature search type

idea. But you know, it is, you come across these articles like a 2014 article on laboratory animals where the induction of thiamin deficiency and how did it present in the animals? Anorexia and GI dysmotility.

That seems like so many people we see. And, and so, [00:40:00] so I'm thinking even though there aren't randomized controlled trial data

to demonstrate safety and efficacy, well, we can say safety because thiamin is like, it just, you just pee it out. So

if it's everyone's argument about expensive urine. thiamin's cheap. And and efficacy.

Well, this is one of these times where maybe looser criteria because low cost, low toxicity, easy self-care intervention may have a big bang for the buck. And just like I have a low threshold for that. And so fundamentals first, then pharmaceuticals.

Dr. Tania Dempsey: Right. So, have you, do you have experience yet with patients overcoming with the gastroparesis, with treatment yourself? Like, do, have you had a case yet?

Dr. Greg Plotnikoff: I have, have not, this is really all very, very new.

So, so all I can do is I can cite the fact that there are, are [00:41:00] people self-reporting on social media about thiamin.

Dr. Tania Dempsey: Yeah. I have people reporting on my social media about thiamin.

Dr. Greg Plotnikoff: Okay. Yeah. And and actually and this recent patient who had described the experience of the, the garlic and there was one other person, but it made me kind of say there's something here and, and we need to know more about, and but as you know, as we've all seen, except for some reason vitamins appear to be important for health, but not very important for medicine.

Dr. Tania Dempsey: Right.

I like how you phrase that, appear to be important for health. Yeah. More than that. No, I think it's really underappreciated for sure. You know, that it's the hallmarks, the foundation, right, of the body and if the foundation isn't there. Right. And that, and the foundation and the, and the body's breaking down.

We're trying to stop, right, mast cell reactions we're, we're trying to stop, you know, the, the disease processes that are happening in our [00:42:00] patients. It's a reminder that you have to sometimes start with the basics. And I, and I tell that to patients you know, as an example, you know, I had a patient the other day who tested positive for Lyme and Bartonella and all that stuff, right?

And the first question is, okay, so how are we gonna treat the infection? But at the same time, she has all those, all those infections. She also has B12 deficiency, vitamin D deficiency. She has dysbiosis, right? She has all this other stuff, right? And I said I can't, I can't deal with the, I can't even think about the Lyme right now.

Because the Lyme is bad, the infections will be worse when the immune system in the body is breaking down. So let's set the foundation, let's help the terrain,

which will help us eventually get, you know, get a, get a hold of the infections. Because the reality is, I don't know if these infections could be fully eradicated, but I know that you can get people [00:43:00] better by helping to build them, you know, their, their, their foundation and build their health back.

Then you work on, you know, other stuff. So I, I emphasize that a lot with patients. We have to remember the basics.

Dr. Greg Plotnikoff: Yes, yes.

Fundamentals first, then the pharmaceuticals. So, can I make a little pitch for something along this line? So we put together an article published about a year or two ago that we paid a lot of money for it to be open access on nutritional issues in plant-based diets. We call it the Seven Questions for Symptomatic Patients on a Plant-based Diet. And what made me think about this was riboflavin. Riboflavin was not one of the seven questions to be asking. But it is something that is at high risk. It's really difficult to get riboflavin on a plant-based diet. One has to be really intentional, almost [00:44:00] as intentional as with B12 and, and long chain Omega-3 fatty acids, et cetera, et cetera. But I put this out there as a pitch.

If people go to pubmed.gov, the PDF is free. It's everything I wish we were being taught in medical school. And, and, and this is, it's written for both health professionals and patients, so the patients can know as much or more than their health professional on these topics and for, for self-care. And and, and, I think, you know, kind of as as we delve more and more into things, is it kind of like, you know, riboflavin is one of those things that, such a good thing but really hard to find in a plant-based diet. And a little riff off that is a gluten-free plant-based diet has no methionine in it, as does Orgain plant-based kind of [00:45:00] protein drinks or Kate Farms 1.4 or multiple other plant-based protein, you know, kind of shake type supplements. No methionine. No methionine means no methylation. No methylation means things related to, you know, neurotransmitter production, mood, memory,

energy, sleep, estrogen clearance, histamine clearance all depends upon this. And yet people can be very intentionally going on a, a healthy focus and, you know, and setting aside those Twinkies and Ho Hos and having, you know, a good plant-based diet, but especially a gluten-free plant-based diet, or some of these protein things based on pea protein, no methionine, which means things can actually worsen. And, it's a whole series, long, long list of things that methylation is important [00:46:00] for. And for mast cell, obviously it's critical to clear histamine, so we don't have that feed forward loop. And no methylation, no histamine clearance means, oh, things are gonna spin in the wrong direction, so...

Jill Brook: That's great. We'll put a link to that paper in the show notes so everybody can just go there and click on it right now if they want to.

Dr. Greg Plotnikoff: Yeah. It's a PDF. Just share it, share it, share it. I shared it with, with colleagues across the country who are in position of teaching medical students. They said, medical students don't have the time for this, and there are more important subjects they have to learn first. And so I think it takes us experienced health professionals who, who now have the time to actually go back and learn these things that we can, but maybe our patients can learn it even better.

Dr. Tania Dempsey: Absolutely. Absolutely. Well, this has been amazing. Greg, thank you so much for [00:47:00] joining us today. I mean, we could, I mean, there's so many other things we wanna talk about. We'll have to do a part two. Do you, I don't know if you, you have a social media or a, a website, but if you wanna share that, we'll also put links to it.

Where can people find you?

Dr. Greg Plotnikoff: Okay. Well, Minnesota Personalized Medicine is where I hangout and yes, there we put on things on Instagram and other places. I really enjoy dialogue and I really enjoy learning and I, I know both of you do as well and so I invite people, send me cool things because none of us can read 4,000 journals a month.

And, and some days it's just enough just to even finish notes for the day, much less do other things. I really welcome insights, love hypotheses.

And then as you heard me say before, yes, a hypothesis without the data is, is [00:48:00] empty and data without a hypothesis is blind. And so there's this kind of iteration going back and forth and get a good hypothesis, a good question, then we can find the best data and, and it's been said, don't get mad, get data. We'll be moving ahead with that as well.

Jill Brook: Well, you two are amazing. Thank you so much for continuing to learn so much about everything and deep diving and I, I know it's not easy to find the time to educate yourselves so much. I know in the beginning, I think you said you're, you're both geeks and I just wanna thank you for being geeks on our behalf. You're just amazing.

Dr. Greg Plotnikoff: Well, thank you for inviting me to this geek fest.

Jill Brook: Okay, listeners, that's all for today. We'll be back soon with another episode, but until then, thank you for listening, remember you're not alone, and please join us again soon.