Homocysteine Follow Up with Dr. Deborah Gordon – Episode 60

Do you have high homocysteine or genetic methylation mutations? This week we dive even deeper into these topics with Dr. Deborah Gordon, MD.

In This Episode

Episode Intro … 00:03:36
Dr. Deborah Gordon Bio … 00:04:37
Dr. Gordon’s Observed Flaws in the Clinical Trials on Reducing Homocysteine … 00:07:18
Methylation Genetic Mutations … 00:11:24
The Gut’s Impact on Methylation … 00:18:56
Clinical Approach to High Homocysteine … 00:25:54
Modified Approach When Working with Sensitive Patients with High Homocysteine … 00:33:18
Additional Clinical Testing … 00:35:59
Stress and Emotional Health … 00:46:54
Episode Wrap-up … 00:49:49

Homocysteine Follow Up with Dr. Deborah Gordon - Episode 60 - Podcast300b RuscioRadio

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Dr. Michael Ruscio: Hey, everyone. This is Dr. Ruscio without your Fast Facts, but with a question about the Fast Facts. I’m not really sure if the Fast Facts are something that people find very helpful or just kind of eh.

So if you would really do me a favor and let me know if you think they’re really helpful and we should continue with them, or if they’re something that are not really necessary, I would really appreciate it. They take a fair amount of time to put together. And as my schedule just continues to get tighter and tighter and tighter, I’m trying to consolidate it to the things that are only the most beneficial for everyone.

So happy to keep doing them if they are helpful. If they’re not really something that people are getting much out of it, then I will gladly take one more thing off of my very full plate. So please let me know. Any method of communication is fine. The comments section associated with this post would be fine, or social media, or Twitter, or what have you. So please let me know and we’ll listen on this for a couple of weeks, and then make a decision.

All right, thanks, guys. Bye.

Hey, folks. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. I am here with a good friend of mine. And one of the most happening ladies I know planning a really cool six-leg race up in her neck of the woods right now, Dr. Deborah Gordon.

Dr. Deborah Gordon: Hi, Michael.

DrMR: Hi. How are you?

DrDG: Well, I’m doing great. Keeping busy.

DrMR: It sounds like it. So you’re planning a pretty fun race it sounds like right now. You were just telling me off air. And that’s going to be up in Oregon in April you said.

DrDG: Yeah, it starts in the town of Ashland and goes all around to the lake and up in the mountains. And some legs are pretty forgiving and some legs are pretty grueling. We like athletes to come from all over, so we’ve got a couple of expert cyclists coming from Sacramento, kind of closer to your neck of the woods.

And so my daughter’s coming from Montana. We usually have someone coming from New York. So if any of your listeners want to take on a great challenge, this is your challenge. It’s a lot of fun.

DrMR: And that’s beautiful country up there, I’m assuming. I haven’t been to that specific area, but I know Oregon overall is a pretty beautiful place.

DrDG: It is. We are the mixture of the archetypal Oregon. With my office right now, I’m looking out on Forrest. Where the race happens is more of an open high mountain valley, kind of like Montana where you’ve got big sky and mountains in the distance, and lakes. So we’re a little mixture of what you classically think of as Oregon and what you might think of more as the central part of the United States.

DrMR: Nice. Nice. Well, I’m sure it’ll be a great event. Anybody listening looking to see some beautiful terrain and get some exercise, great event to check out.

Episode Intro

And we’re not actually talking about exercise today. We’re actually talking about homocysteine, following up on the homocysteine podcast that we had. And you had shot me a note a couple of weeks ago saying, “Hey, there’s a few other aspects that you could go into that would be interesting to talk through.” And so you shot me an email. And we, just to give the backstory, we originally met either at Paleo f(x) or at the Ancestral Health Symposium. But we know each other through both of those venues. And we’ve kind of stayed in touch ever since.

DrDG: Yeah, it was Paleo f(x). You very generously gave me a ride to the airport.

DrMR: Right. Okay, yeah now I remember. I wasn’t sure if met you first through AHS or first through Paleo f(x).

DrDG: f(x).

DrMR: Okay, so good to know. Paleo f(x) I guess is kind of like the professional healthcare providers spring break. You go there, drink too much Kombucha, stay up too late.

DrDG: Yeah, that’s a good way to think of it.

Dr. Deborah Gordon Bio

DrMR: So before we jump in, can you tell people just a little bit about your background, and then kind of what you’re doing now?

DrDG: So I’m a traditional—I won’t say traditional—conventionally trained family doc. I did a family practice residency and medical school through the University of California at San Francisco. And I was always interested in preventive medicine or what we would now call functional medicine.

It was not very well taught when I graduated from medical school in the Dark Ages. Really 1979 that’s quite a while ago. So I’m self-taught really since then. And I’ve had an integrated practice. I’ve done other things around southern Oregon, but I’ve had a private medical practice for 25 years that’s combined lifestyle medicine and classical homeopathy, which I’m doing less now. There’s a much more demand and I’m much more fascinated by all of the advances in functional medicine. And there’s so many more resources than there were 20 years ago.

DrMR: True.

DrDG: So I do that a couple of days a week. And then I have a website that keeps me challenged and interested, learning new things, listening to podcasts like yours. And getting either inspired or riled up, one way or the other.

DrMR: Right. Nice. Well, so you had a few things and you shot me a few things that you kind of wanted to expand on. And I guess before we jump in, in case anyone missed it, we did do an episode on homocysteine and heart disease a few weeks ago. And we outlined what many of the clinical trials show.

And I guess the very short summary on that is that it seems to be fairly consistently documented that homocysteine is an independent predictor for cardiovascular disease. However, the trials that have been done lowering homocysteine with B vitamins haven’t shown a whole lot of change in the way of outcomes.

They have shown successful lowering of the homocysteine. But that doesn’t seem to translate to much of a change in cardiovascular disease outcomes, meaning heart attacks, death from heart disease, things like that. So you had some things that you wanted to add to that conversation. Maybe we can’t make such definitive conclusions to do some of the way the studies are set up, or what have you.

Dr. Gordon’s Observed Flaws in the Clinical Trials on Reducing Homocysteine

So let’s jump in, Deborah, with wherever you wanted to start first. And we’ll just kind of flow from there.

DrDG: Well, what really spurred my interest was cognitive issues. But I also have stuff to say about the cardiovascular issues, which were—your podcast really well covered the clinical evidence as you read it. And I’d say about 10 or 15 years ago I kind of became familiar with this area and got all excited and then kind of backed off really for the same reasons you show caution, which is that the studies to date primarily but not entirely—we won’t go there—did lower homocysteine, but they didn’t lower cardiovascular risk.

DrMR: Right.

DrDG: Well, since that time I’ve been delving into the world of methylation and genetics and realized a couple of things, that they used what I would consider very low quality vitamins in all these studies. They used plain old folic acid. And they used cyanocobalamin.

And if you really understand the mechanics of how homocysteine works and how it’s metabolized in the body, you’d say, “Well, someone’s homocysteine is probably high because they’re not capable of using regular folic acid.” Yes, but the regular folic acid did lower their homocysteine.

The other thing we realize from looking at the genetics is that homocysteine is probably a stand-in for kind of all the other things these B vitamins do. And so just one sort of theoretical idea is that by not using the methylated B vitamins, they’ve lowered the homocysteine, but they haven’t addressed your methylation status. And these B vitamins, the methylfolate and the methyl B12, are really just carriers to bring methyl groups into the body. And methyl groups, you and I know, but for some of your listeners, it’s a carbon group with three hydrogens attached.

Europe uses the euro. The United States uses the dollar. The human body uses methyl. We transport methyl all around our bodies. And if it we’re not getting it in and moving it around efficiently, we can’t generate energy. We can’t produce new tissue. We can’t detoxify. We can’t repair. So it may be that homocysteine is just a stand in. And what properly methylated B vitamins do is, yes, lower homocysteine, but also do 25,000 other things. So that’s one theoretical possibility.

But one much more mechanical flaw with these clinical trials is what is considered normal of homocysteine? And I sort of got onto this track really from the cognitive end of things because, as you know, homocysteine is associated with cardiovascular disease, both heart attack and stroke, and it’s also associated with dementia.

And currently the optimal level for homocysteine to reverse dementia is a much lower level than is accepted as normal in the standard clinical trials. So they might try and lower it to 15 or 13. But for cognitive benefits you have to lower it to between 5 and 8. So maybe those cardiovascular trials didn’t take it low enough. What do you think?

DrMR: Well, yeah, there’s a few things I definitely want to try to expand on there. I guess I’ll start with your first point. And some of these things I ask, not as challenges, but really as honest questions because methylation is something that I’ve done some work in, but I certainly haven’t made it a primary area of my focus. So I have a lot of questions there. Just to clarify these are questions, not challenges.

DrDG: Right.

DrMR: And we have a pretty good rapport.

DrDG: Great.

DrMR: But just to make sure you don’t get angry at me and then send me hate mail or egg my house or not give me a ride from Paleo f(x).

Methylation Genetic Mutations

So coming back to the form of vitamins, I agree with the concept that using the best quality vitamin is usually a good idea. Now, the methylated forms, aren’t those predominately problematic in terms of utilization if people have the genes that don’t lend themselves to the proper breakdown and assimilation?

DrDG: You’re exactly right. But the proportion of people who have defect, either partial or full in that genetic area, ranges between 30% and 70% of the population.

DrMR: Okay, that’s a little different.

DrDG: So it depends a little bit on your ethnic heritage. But, yeah, it could be as high as 70% in some populations.

DrMR: So is there a particular heritage that seems to be the poorest methylaters, if we can ask that broad of a statement?

DrDG: Ooh. Yes, we an answer that question. But can I answer it off the top of my head, no? So I forget. It’s either Mediterranean or like Scotch Irish that’s really bad at it. And I think it’s Mediterranean, but I’m going to have to go check that. Yes, you can do that somewhat predictively.

So I typically ask people to do complete genetic testing through 23andMe, which is not complete by any means, but it’s the most complete commercially available genetic test. But if you want to find out if you had just this genetic defect, it’s a pretty simple blood test. Medicare even will cover it once in a life of a person.

So you can just test for their MTHFR status. And there’s actually more genes involved than just those, but that’ll cover most of the problems. And so you can get an answer really just on a simple lab test because even if you know your genetic heritage, who wants to guess whether they’re in the two thirds or one third. That’s not specific enough.

DrMR: Sure. Okay, so you recommend a profile to help determine if you’re a poor methylater or not. And I certainly think that makes some sense. However, there’s a couple of other things that I wonder about because the thing I want to try to help people with here is maybe knowing all of these available tests are maybe what you consider the primary tests, the tests that should be done first. And then which ones are maybe better left for secondary, tertiary, quaternary sort of test.

Because I think one of the things that both doctor and patient alike struggle with is, boy, there’s all these tests I can do. Is there a way I can prioritize so as not to have to do several thousand dollars’ worth of lab testing right out of the gate?

So one of the things that I ask to try to help people figure out where a methylation analysis goes in that the first line testing, second line testing, third line testing, and so on. If one is eating a healthy diet, won’t that provide you all the methylated forms of vitamins, like methylfolate and methylcobalamin?

DrDG: Actually, no. So you have a partially methylated form of folate in raw leafy greens. And there is some, I think, methylated B12 in organ meat. But still. So as an example, I eat a really good well-balanced diet. And when I got involved in these genetics, I tested myself.

So one thing is if someone’s homocysteine is perfectly normal, they can even have a genetic defect, but they probably have a complimentary one because some genetic defects actually lower your homocysteine. So if you don’t have a high homocysteine it doesn’t really matter.

But I would argue that if you have a high homocysteine, you should know for exactly the reason you pointed out, that you can lower homocysteine with regular B12 and folate. But when I tested myself I found that we did sort of a family test. My brother had a double compromised MTHFR gene and mine was only singly compromised.

So I personally felt much better. And I was eating that great diet. I ate organ meats once a week. And I ate lots of dark leafy greens. And I had a homocysteine that was above 10. And it would be considered normal by a conventional doctor. But I didn’t consider it normal because I want to optimize my cognitive function. So I want to keep it in that sweet spot, high enough to be over five but low enough to be under eight.

So it certainly is my personal case. But if you look at the food sources I think it’s dihydrofolate that comes from food. So it’s not a fully methylated folate that comes from leafy greens. It’s a quite complicated pathway, which I cannot at all keep in my mind.

DrMR: Got you.

DrDG: But you have a partially methylated folate from dark leafy greens, but if you’ve ever eaten any processed food in your life, you’ve also eaten lots of plain old folic acid. And they’re all heading for the same gate to become fully methylated and become tetrahydrofolate, methyl tetrahydrofolate.

So the more plain old folic acid you’ve eaten, the more I would argue that it would be important to know if you need the methyl version of folate. And some people don’t do well with methyl folate. I have a friend who he’s at risk for Alzheimer’s disease, and his homocysteine was about 20.

And I started him, stupidly, on all the methyl vitamins right at once. And he had an adverse reaction to it, which you can kind of predict from seeing people’s genes. But you can also just commonsensically, which I didn’t use at that point for other reasons, but start people one at a time and see how they tolerate them.

And then there’s a slightly more elegant form of folic acid called folinic acid, which also has an easier time of getting into the real circuitry than conventional folic acid does. It’s the cheapest form. It’s the first form they used. They found out it lowered birth defects. So it’s what’s in all our foods, but it’s not really a very good form of folate.

DrMR: So a couple of follow-ups there kind of racing through my head. I really want to ask you. What’s that? It’s complicated. Yeah, I know.

DrMR: Yep. I want to come back to you in a second asking you what you kind of do with this information? And I understand sometimes that may be complex, but if we can help to give people a basic understanding of what methylation support may look. So I want to work our way to that. But I have one or two questions first that might be a good lead-in and might answer that on the way there.

The Gut’s Impact on Methylation

The gut and the gut’s impact on methylation. I know Ben Lynch is kind of a big methylation guru. And someone shot me an email recently saying he’s recently been discussing how SIBO can lead to an increased production of folate.

And they were asking me if it’s folic acid or is it folate because, “I have SIBO and you’re treating me for SIBO, and I also have MTHFR. And I’m wondering if the SIBO is producing folic acid, or is it producing folate?” And the response I gave them was I really don’t know. I haven’t seen anything published about that. It has been documented, of course, that SIBO bacteria can cause an increased production of either folate or folate acid.

The challenge is that folate and folic acid are used so interchangeably in the literature, it’s hard to determine what specifically was actually produced. It may count as folic acid as used, but it may actually be folate.

DrDG: Right.

DrMR: So I would assume folate, but I don’t really know. Do you know, first anything about that specifically? And then I want to circle back to how you feel the gut interfaces into all of this? So the first part of the question, do you know if SIBO produces folate or folic acid?

DrDG: I don’t completely know. But I will say I’ve been reviewing Ben Lynch’s material recently. And I believe how SIBO would generate more folate is by creating oxidative stress. And if you create oxidative stress at a slightly different part, not the homocysteine part, but at a different part of the complex interlocking circles, you generate a lot of folate and can generate nitric oxide, and stuff like that.

So I was looking at his diagram about oxidative stress. And that generates folate. So if that’s at all relevant, but it’s not specific to SIBO. But SIBO obviously generates a lot of oxidative stress. And in general about gut health, the point that I think Ben Lynch and other people…Because I’ve looked at others, like the Functional Medicine Institute’s presentation on methylation.

So when I say, “Oh, I have a heterozygous defect, and my brother had a homozygous defect,” so I should have a 30% compromise in methylation and he should have a 70% compromise in his methylation. And it did make a bigger difference in his life. But that is so vulnerable to epigenetics.

So if somebody’s following your recommendations… And I do think every time I have a complex patient in, the two things I end up really focusing on are the gut and sleep. And then, “Okay, we’re going to do this for your gut. But if that doesn’t work, then we need to go into the secondary and tertiary testing levels.”

So restoring gut health and addressing stress and eating a nutrient dense diet and getting enough sleep and exercise and sunlight, I think they all intersect because they all affect different… So if you look at these homocysteine pathways you’ll see places where you need vitamin B2 or where you need zinc. And if you have SIBO, you’re not absorbing zinc very well. Anything you need to absorb in the small intestine, it’s just highly variable at that point.

So all of the cofactors you need for these methylated B vitamins to perform their desirable effect on homocysteine depends on you having a good diet and absorbing those nutrients.

DrMR: Totally, totally agree to them. I’m glad to hear you say that because, yeah, I think that’ll be helpful for both doctor and patient alike because it can be challenging, especially from what I see many patients walking through the door coming in. They have done maybe an MTHFR test. And they come in with chronic constipation or chronic bloating and maybe diarrhea, or whatever it is, and ulcers. And they’re wondering, Do we need to start treating the methylation problems right out of the gate?

And I always remain open on these things, but my general position is let’s start with, as you said most foundationally, diet and lifestyle, including sleep. Focus on the gut after that and then reevaluate. And I think it’s really important to mention that, because I think if you do a good job with those foundational pieces, many cases will correct themselves.

Many people will feel very well, and there won’t be a need to do much more. But then if someone’s not fully improved, maybe they’ve only improved 20%, 30%, 40%, then I think looking at this as a secondary sort of screening. It makes a whole heck of a lot of sense.

DrDG: Well, the other area to look at it is your cohost for the homocysteine podcast. She was describing her boyfriend, who was in the picture of perfect health, but has a high homocysteine. So in his case, you’ve done diet and lifestyle, and he’s got a high homocysteine.

And what I would recommend to someone like that. And this is sort of because I believe that lowering homocysteine wisely reduces actually cardiovascular risk…And there is that one study which I sent to you, the Swiss Study, where they really took the homocysteine down farther and then lower cardiovascular risk. It lowers stroke risk. And it’s part of Bredesen’s protocol. And there’s good research behind it for addressing dementia.

So if somebody has high homocysteine, then I would suggest clear up for something like getting the 23andMe, which now costs $200 dollars instead of $100. And they can do some analysis themselves, or I do some for them. And I think it’s worth finding out why you have a high homocysteine because this young man may be 30 and optimally healthy, but some day he’s going to be older. And these ravages of high homocysteine probably take effect sequentially over time, or they’re a marker for other problems that take effect over time.

So I might be biased by my patient population, which is largely 45, 50, and up to 96, I think is my oldest patient. So even a healthy person, you work with that person, he’s constipated and sluggish and has brain fog, and they feel better and their homocysteine’s still high, I would suggest those people figure out why their homocysteine’s high.

Clinical Approach to High Homocysteine

DrMR: So that’s a really good lead-in to the question I want to come back to, which was what do you then do with this information? Of course, we’ve talked about the methylated vitamins as an option. And, of course, we always start with the foundation of diet and lifestyle, sleep, gut. But then what do you do next?

Because one of the things that I am challenged with is there seems to be so many different opinions and so much discordance in terms of how to test, what to test, what the results mean, how to treat. And I’ve seen many different changes in what was recommended for supporting MTHFR two years ago, six months after the recommendation changed almost a complete 180.

And so it made me take a little bit of pause thinking that, Boy, there may be so much that we don’t know here. That this may be a little bit of a crapshoot. But I say that as someone who hasn’t been following this for a year and a half, and a lot can change in a year and a half. And a lot can change with just clinical experience, which I know you have here. So what do you do?

DrDG: So I like having their 23andMe. So I have some suggested guesses about which way they might respond to the methylated B vitamins. But I say they have a high homocysteine. And they do have a methylation defect.

I think the two big schools of thought about what to do at this point…No, there’s three. There’s conventional medicine, which just gives you the conventionally prepared combo products called Metanx. I think that’s primarily the one they use. And they use it for diabetics, and they use it for peripheral neuropathy. And it has been shown in clinical studies to help with all those things. And it’s all methylated Bs.

But here’s the dichotomy that I think you and I are more faced with. In my experience, functional medicine docs largely…And I come from Ashland, Oregon, which is one of the homes of functional medicine because David Jones started. He was one of the founders of the IFM. And he’s from my town here. They use very high dose of methylated Bs. And I think they do tend to combine them.

And the important thing about the methylated Bs is it’s methyl folate and methyl B12. And then it’s B6, which is not methylated. But it’s called Pyridoxal 5 Phosphate. So it’s a phosphorylated version of pyridoxine, which is what conventional B6 is. So they use really high dose and they just start people.

And then Ben Lynch starts people one at a time. Then he’ll start with methyl folate and he’ll start with really low dose methyl folate. So then you start looking at your other genes. So if you have the gene that is COMT and you have SNPs or variants or abnormal genes in that region, abnormal findings in that gene in its regions, you might be vulnerable and get more anxious and even maniac or panic attacks from taking too many methylated Bs.

So if you have abnormalities in that area I’ll start people really low. If I’ve known somebody for ages, they’re 50 years old, they’re 60 years old, they’re really healthy, they’re really vital, they have had no mental and emotional issues over their life, I kind of don’t care what their genes are. I’m a lot more generous with my dosing.

I have a patient who I say, “This is really funny. I look at your genes. And I’d expect you to be the most anxious person in the world. And I don’t think you have an anxious bone in your body. But perhaps it’s because you’re a Buddhist monk and you meditate for hours every day for the last 30 years.”

DrMR: Right.

DrDG: All my prognostications go out the window. So I start people when it is time, methyl folate. And then I add in methyl B12 and pyridoxal 5 phosphate. And I give them separately because I think they work better at different times of the day. Pyridoxal 5 phosphate really helps people sleep better and remember their dreams. B12 for some people it’s energizing, for some people it puts them to sleep, and for most people it doesn’t make a difference. And I like to give methyl folate in the morning because it is a little energizing for most people.

But, say, you do all of that and their homocysteine is still high or they have that COMT gene and they can’t take the methyl folate, that’s when just that simple blood test for MTHFR won’t help because there are two or three other exits for homocysteine out of this. So it normally recycles with methenamine.

We eat muscle meat and we get methionine. And then it hands off a methyl group. And then homocysteine is formed. And homocysteine gets a methyl group and forms methionine again. And homocysteine, if it accumulates there, it needs to be removed. And it has really three exit pathways. And one of them is to just become methionine again.

But there are two other exit pathways and you have to look at what those genes are. And one of them is BHMT, which is Betaine Homocysteine S-Methyltransferases. And that’s when it’s modified by things like phosphatidylcholine and phosphatidylserine, which are also in Dr. Bredesen’s program for optimizing cognitive function.

So this is really my sort of pet interest at the moment, is trying to take people who are risk for Alzheimer’s. And that would be people who have it in their family or who they have the APOE4 gene, either heterozygous or homozygous. And there’s millions of us in the country who have one of those genes, slightly abnormal.

But I like to take people at risk or even with the early signs of dementia. And these are the people where it really is important. It’s part of his program. And it’s not one leg. You know how you say three legs of a stool? Well, he says treating cognitive decline is like fixing a leaky roof with 36 holes.

DrMR: I noticed that, yeah.

DrDG: You have to address 25 or 30 of those holes before you’re going to have a fairly dry place to sleep at night. So there are these two other genes. And one of them is you can address with phosphatidylcholine or serine. And one of them you’ve addressed in a different way. It’s the CBS gene. And that requires a diet modification and some supplementation.

But you look at the other exit pathways for homocysteine and see how they’re affecting you, and if you can use those other pathways to lower your homocysteine. So it’s that multistep thing again, always starting with what you said, which is the diet and lifestyle stuff.

DrMR: Gotcha. Gotcha. Okay.

Modified Approach When Working with Sensitive Patients with High Homocysteine

And that’s maybe a good transition to another question, which may not have a simple answer. But for people who seem to be sensitive to everything, and I’m sure there’s some patients listening that note that they seem to have a reaction to almost anything they take or they use. And there’s some doctors that probably notice some of their patients react to 80% of the treatments that they try. Do you have any recommendations for that?

DrDG: I do. So that’s when you’d start with a really low dose.

So again you’d start with the methyl folate first. And you’d start with what I consider really low dose—400 micrograms. And when you go to a conventional doctor, say you’re just at your wit’s end, and you’ve got peripheral neuropathy, and you’ve got high homocysteine and you go to your local neurologist, he’s going to blast you with 15 to 30 milligrams of methyl folate. So we’re talking at 1/100th the dose practically when you get down to 400 micrograms.

So you start with that and then you know that you have as an alternative to that folinic acid, which is much less likely to cause anyone to have a reaction to it. And similarly and then when you add a couple of weeks later methyl B12, I’d have to start with a low dose. And the age which I work with I usually chewable or sublingual. So I start with 1 milligram. And if someone’s really sensitive they can break that in half and just chew on half of the tablet. And so 500 micrograms.

And the P5P, well, yes, I have had people have reactions to that. I think it typically does come in about a 33 milligram capsule, which is equivalent to 50 milligrams of regular B6. But I think that adverse reaction to pyridoxal 5 phosphate is mitigated if they don’t take it every night. So if someone takes it and they say, “Oh, I slept better. I feel great. I had great dreams. But now it’s all gone to hell in a hand basket,” I would tell that person to take it twice a week instead of to take it seven days a week.

So it’s all just dose modulation and then knowing the alternatives. And the alternative to methyl folic is folinic acid, not folic acid. And the alternative to methyl B12 is hydroxy or adenosyl B12. And so the typical conventional B12 is cyanocobalamin. And that cyano group just adds to your toxic load. It can’t be easily recycled into constituent physiological, recognizable, components. So it’s a challenge to get rid of that. So folic acid and cyanocobalamin should be off the shelves.

Additional Clinical Testing

DrMR: Now, let’s say someone does come back high with homocysteine. Are you looking at other markers to know if this might just be a simple vitamin deficiency looking at their folate, their methylmalonic acid, their serine or B12? Are you looking at that kind of initially, to seeing if some basic vitamin support will work, and leading the more depth methylation analysis as a secondary?

DrDG: You’re right, actually. We skipped that step, but I do. So when I order a homocysteine, I always order it with just a simple B12 and folic. And then if there was any question, I’d go onto the more metabolized methylmalonic acid or the 4-amino folate. There’s another way to measure more absorbed folic. And I think the thing that I do then.

So say their vitamins has low, but they may not need methyl B vitamins. But for most people, unless it’s one of those highly sensitive patients. And we all have them and they know who they are, and we know who they are. And if I have somebody who’s a pretty sturdy person, if you walked into my office and you had high homocysteine and you had low vitamin levels, I’d give you pretty full doses of both of those vitamins and just have you take them. And see if bringing them up brought down your homocysteine.

But if somebody came in who had chronic fatigue and was recovering from Lyme disease and had a high homocysteine and low B vitamins, I’d start them very carefully with low doses. And probably maybe really want to know if they needed the methyl B vitamins or not. But if you’re really healthy and you don’t have any methyl genetic defects, you’re probably also going to be really good at recycling that methyl group.

I’ve only had really one patient, and he had the methylation defects, who had a really hard time taking them when I used my normal precautions. So someone like you, you’re vigorous. You’re healthy. You could take them. Somebody who’s obviously more sensitive or not so vigorous, then you better be careful, or know why you’re giving what you’re giving.

DrMR: And just for people listening if they’re not familiar with some of those markers that we just mentioned, there’s kind of a family of markers I guess you could see to put it simply, that may go out of balance along with homocysteine that indicate status of some of these B vitamins. So you can test for B12 directly. You can test for folate directly.

There’s another compound known as methylmalonic acid. It’s a marker of functional B12 status. And so ordering these together gives you a little bit better of an idea as to what the whole family is doing, to put it loosely. And there’s also another marker that’s pretty routinely run on bloodwork known as the CBC with differential. It’s known as MCV. And this is more of a classical marker for diagnosing a vitamin B deficiency that can lead to a large volume in the size of the red blood cells.

So there’s a number of markers that can be ordered together. So if you’re a patient listening to this trying to sort through it, it may not be the best idea just to order homocysteine on its own. It’s a better idea to kind of order this family that’s fairly inexpensive and can be ordered through the most conventional blood labs.

But this is probably something you want to check in with your doctor with because this is, of course, not the easiest thing to navigate. So it may not be something that you would want to try to tinker with and muddle through on your own.

DrDG: Yeah, I think that’s a good point. The other thing I’d like to sort of throw in again, or stepping back a little bit from the details, is I know you and I were going to talk about this. So I thought, Well, what else is there known about homocysteine? And I was just curious since I think of it as such an evil compound.

And cardiovascular disease and dementia, it’s also linked to congestive heart failure, migraines, macular degeneration, and hearing loss. And macular degeneration and hearing loss are epidemic in our senior citizens. Migraines are more common than we would like them.

And then the other place, I have a patient where she had repeated miscarriages. And she’s young, doesn’t have any of these problems. And I said “Well, let’s look at your homocysteine.” Because she’s been supplementing with conventional prenatal vitamins for all these pregnancies that she’d lost.

And she had the MTHFR gene, which is what was leading to her miscarriages. And the clue that convinced me—well, it enabled me to convince her to get some genetic testing—was that her homocysteine was high.

So she had migraines and pregnancy loss, high homocysteine. And I think she has a repeat C-section. I think she’s having her full term baby this week. And so starting her methylated vitamins both took down her migraine frequency. I actually haven’t rechecked her homocysteine now that I’m thinking of her talking about it. I think it’s also something to do with her keeping her pregnancy.

DrMR: Well, there you have it, far-reaching effects of the potential here. And like we’ve been discussing, it’s certainly something that I’m opened to. And I’m hoping that this conversation will help people kind of contextualize where this fits in with the overall scheme of things. And it’s nice to hear what you’re observing because many of these things I see through my own lens, which admittedly is a bit biased by my focus and what I think a lot of patients seek me out for, which is predominately gut and thyroid.

And, of course, those also have tie-ins with infertility, especially something like subclinical hypothyroid, which we’ve talked about in subsequent episodes. But this is another thing for people to consider, should they go through diet, lifestyle, gut health, maybe have a thyroid evaluation, especially if infertility is the question.

And if all those boxes are checked, then one of the next things to look into or as you’re looking into these things, look at your homocysteine. See if that’s high. And then maybe something will prompt you to get to a clinician, like Deborah who has this stuff pretty dialed in, and see if that can help get you the rest of the way there.

DrDG: And love your ability to step back and take the eagle’s eye view, Michael. That’s great.

DrMR: Well, thank you. And why I think that’s so important is because patients come to me so confused. So confused with this wealth of information that’s on the internet. And I try to keep bringing it back to a hierarchy for people because the thing that I find really—I’ll just put it bluntly—that really sucks is when someone comes in and they’ve spent a few thousand dollars, chasing their tail with stuff that I would consider a tertiary intervention. And they’ve tried to do that first. And they still have a raging gastrointestinal problem and a few major points in their diet that are way off.

And we fix those things in just a few months, maybe spending a couple of thousand dollars for everything over the course of a few months, and they’re feeling so much better. And it’s disheartening when someone has inadvertently wasted a lot of time, money, and energy, because there’s just too much information on the internet. And they weren’t sure what to do first and what to do second.

So that’s why this is something I’m so passionate about because I’ve seen these patients come in. And sometimes they’re really in dire straits. It may be a woman who is trying to get healthy and now she has this chronic fight with her husband because her husband says “You better not spend another damn dollar because you’ve already blown $5,000 grand and you’ve gotten no better. And I’m tired of these kooky things that I’m not familiar with.”

And it creates a lot of stress in that person’s life, in that couple’s relationship. And so I don’t say these things lightly. These things have a lot of ramifications for real people. Yeah, so I am really kind of passionate about it.

DrDG: Right. Absolutely. And I think the other part that you said, so one of the things I’ve learned from when I did homeopathy when you really have to really hone your observational and listening skills, is developing a fine awareness, if I can, of people’s blind spots.

I think that’s what a lot of times when you chase from practitioner to practitioner, which you’ve urged against—I know talking about gut problems—that you should find someone that’s good and stay with them because no matter who you work with, it might be four different approaches to SIBO before you solve it. But not only does staying with the same practitioner enable you to really be ultimately more efficient, but somebody then can see…

So I had this new patient yesterday who had just been all over with naturopaths and the internet. And he knew tons of stuff, but he’d never really followed good sleep hygiene. So he’s a hardworking, hard driving, successful guy who hasn’t had an effective night sleep since probably before his first child was born three children ago, so between children and getting on the computer when he wakes up at night. And it was sort of hard to get to that because we had all this data in front of us. But I try never to leave a first consultation without finding what somebody’s eating and how they’re sleeping.

And in this case I think it opened our eyes to what has been a blind spot in the thousands of dollars he spent so far, chasing a pretty interesting set of symptoms. Yeah, that all is really interesting. Nobody really knuckled him down on his sleeping. Got to get that iPhone and that computer out of your bed.

DrMR: I completely agree. And that’s why we have, of course, a diet and lifestyle section on our new patient intake paperwork. And I look at that and I touch on those things during our exam.

Stress and Emotional Health

And someone recently asked me “How do you know how deep to go into things like stress or emotional health?” Because I’m not a therapist, but I’ve always been pretty good at being able to read people. I think they call it being empathetic. I think I’ve always been pretty good at that.

DrDG: Well, you have the empathy gene.

DrMR: Yeah, well, maybe. But it can be pretty apparent sometimes when you ask someone, “Do you feel like you have adequate time for yourself?” Just the way people answer that question can give you a whole lot of data. I know someone says, “No, I don’t. I feel stressed. I feel overwhelmed. I’m working two jobs.” Just sometimes when you ask a person a question that is pointed to an area of their life that’s neglected, that’s the first time, kind of as you said, the spotlight has been shown on that area.

And sometimes when you get that light on that spot for the first time it’s pretty apparent to see, “Wow, there is a big gaping hole here that needs to be addressed. And before we go too deep into lab testing and treatment, and what have you, let’s take a little bit of time to look into this. Because this may be an easy thing that may yield us a whole lot of dividends and essentially do it for free.”

So I think, yeah, I think you’re making a great point. And to bring us back to the foundational piece that it’s really easy to gloss over—and I myself can be guilty of this—sometimes overworking and overreaching. It’s important to dial those things back in this morning. And just as a great example. I felt myself getting a little anxious, a little angst, because I have a lot on my schedule today and I’m saying, “Goddammit. I wish I didn’t have this booked. I wish I didn’t have that booked. It’s too much.”

And so I just got up and I went for a walk outside. And sometimes it’s paradoxical to think the cure to feeling like you have too much to do is to do nothing, but sometimes it is. Sometimes it really is.

DrDG: Have you heard that quote that everybody should meditate 15 minutes a day, unless they’re really busy and then they should do it twice a day.

DrMR: I love that, yes. Exactly. So, yes, without getting too far afield here, I completely agree. I think these lifestyle things are so important. I’m glad that you brought that patient example because sometimes the missing link is not something super sexy, exotic, and scientific. It’s something pretty simple.

DrDG: Exactly. That’s a good way of putting it. Yeah. I like that question you ask people: “Do you feel you have enough time for yourself?” I’m going to have to lift that from you and start introducing it into my patient intake.

DrMR: Yeah, please do it. It’s a nice way just to hear what people think about their own lives. Because it’s a big problem I think, especially in the United States is that people just don’t have enough self-time. And that’s important.

DrDG: I agree. Yeah.

Episode Wrap-up

DrMR: So, Deborah, to kind of bring this to a close, is there any areas or points of thoughts regarding this whole methylation and homocysteine piece that you haven’t mentioned yet that you’d like to mention?

DrDG: Well, I think the only thing I would say is that where I apply this most often really is in cognitive areas. And somebody listening to your podcast may really be thinking of a family member. But, yeah, homocysteine look like it really has a role in the creation of amyloid, and blah, blah, blah.

But I think the point I want to say about cognitive issues is that they’re much easier to identify the problems and prevent than they are to treat. By the time you need attention for cognitive problems, you need a buddy. You need a health coach. You need somebody who can take responsibility for fixing those, helping you stay on top of fixing those 36 leaky holes in your brain.

And if any of your listeners, either themselves or somebody else, has cognitive problems or looks like they’re getting that way, or they have a family member with Alzheimer’s or dementia, earlier is better.

DrMR: Yeah, it makes a lot of sense.

DrDG: Yeah.

DrMR: It’s the old saying, “An ounce of prevention is worth a pound of cure,” right?

DrDG: Exactly. And everything you do for this Alzheimer’s stuff relates to other things. So you identify heavy metals. And you detox if necessary. And you make sure your zinc and copper ratios are good. So it’s not as if you’re stretching yourself in any disadvantageous way to address it. So, yeah, it’s an ounce of prevention that has far reaching benefits. And it’s so much easier than the cure. Yeah.

DrMR: Absolutely. Well, this has been a great conversation, Deborah. Thanks so much for speaking with us. And I will see you at AAHS. And hopefully we’ll both be giving the talks that we wanted. I know we both had submitted two topics this year. Maybe we’re getting a little bit greedy. But hopefully we’ll get what we want. And maybe as a bonus we’ll be doing two spotlights each.

DrDG: Yeah, we’ll see. Probably not two.

DrMR: Fingers crossed, right.

DrDG: Great, Michael. Thanks very much. I really enjoyed this conversation.

DrMR: Absolutely. Have a good rest of your day, and good luck with everything at the race.

DrDG: Okay. Thanks, Michael. You too. Bye-bye.

DrMR: Thanks. Take care. Bye.

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