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Histamine, Homocysteine and Health with Joanne Kennedy

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Histamine, Homocysteine and Health with Joanne Kennedy

Gut issues are a major driver of low homocysteine and high histamine in many of our clients. But what other conditions might result in this scenario, and how does it affect our health in other ways?

In this new episode, Naturopath Joanne Kennedy takes us through the ins and outs of the biochemistry of histamine and homocysteine in the body, including how too much or too little of either of these can present in patients, what blood tests she recommends and why it is so important to test homocysteine in anyone who comes into our clinics with an inflammatory condition, and why we need to be cautious in prescribing methylated B vitamins to clients in these cases. 

Covered in this episode

[00:51] Welcoming Joanne Kennedy
[01:18] The role of homocysteine in methylation
[02:25] Implications of low homocysteine 
[07:10] Addressing the root causes of low homocysteine
[12:41] Testing for homocysteine
[16:40] Cautions of using B6 in driving down homocysteine
[22:31] Testing and tracking homoecysteine
[25:45] Signs and symptoms of high oxalates
[27:42] Where to focus treatment
[32:40] Fermented foods
[35:41] Cautions in treatment
[40:54] Additional resources
[46:11] Microbiota testing
[47:27] Thanking Joanne and closing remarks


Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us today is Joanne Kennedy, who's a naturopath specialising in methylation and histamine intolerance. From her Sydney CBD practice she now sees patients both nationally and globally because of her down-to-earth explanation of what's really going on.

Welcome, Joanne. How are you?

Joanne: Hi, Andrew. I'm very well. Thank you for having me on your podcast.

Andrew: Pleasure, an absolute pleasure. Now you're well-renowned for your simple explanations, particularly to do with homocysteine. So let's go first through the role of homocysteine in methylation.

Joanne: Okay. So homocysteine has two really important roles. Firstly, it makes methionine. Which goes on to make S-adenosyl methionine, or SAM-e as we know it, which is a methyl donor. But homocysteine is...we need to also think about homocysteine as a sulphur-based amino acid, so we can think about it as a sulphur storage molecule in the body. And sulphur, as we know, is extremely important for sulfation, it's extremely important for making glutathione, the body's major antioxidant, and it is also important for making taurine.

So there's a lot of really important roles for homocysteine, both for methylation and both when it comes to detoxification, inflammation, and antioxidant support.

Andrew: Okay, so what are the implications of low homocysteine?

Joanne: So when homocysteine is low, what is happening is that the body's requirement for sulphur is upregulated, it's high. And clinically we usually see this with an increased need for glutathione due to inflammation and oxidative stress. And that can be coming from chronic gut issues, heavy metals. I see endometriosis will do it often, girls with endometriosis, because of all the inflammation will drive homocysteine down. And what homocysteine is doing, it's donating the sulphur to cysteine for cysteine to go on to make glutathione to sequester all the free radicals that occur with the inflammation. So what happens is homocysteine starts to become low and you become deficient, because your need for cysteine is so high.

Andrew: Yeah.

Joanne: Okay? Then what happens when homocysteine is low, you don't have enough homocysteine to create methionine to go on to create SAM-e for methylation. So we become sort of deficient in our sulphur-based amino acids as well as having issues with methylation at the same time.

Andrew: Okay, so just an interesting point, I wonder if this has any correlation, but what about things like trauma? Anything from sports injuries to burns, where you've got a massive amount of tissue damage and your body is going to require sulphur at least, certainly amino acids, to help repair the damage and help repair collagen.

Joanne: Yeah.

Andrew: Is there...

Joanne: Yeah, I would say I would always test homocysteine in those people.

Andrew: Right.

Joanne: Definitely. Because their requirements for sulphur and for glutathione are going to be really, really high. I don't see burns victims in my clinic, I don't specialise in sport either. But definitely if you're treating those people, looking at homocysteine levels to really understand what their need for glutathione support is would be really beneficial clinically.

So the thing that can happen when these pathways are upregulated is that the need for sulphur is so high and the sulphur with these pathways runs fast, so these people can sometimes feel like they can't tolerate a lot of sulphur, sulphur foods. Which is really interesting because they really need sulphur, so certain Brassica vegetables, red meat, eggs. But sometimes they can't tolerate the sulphur because it's actually being used in the body so quickly that they can actually feel quite sick from eating it, but they really need it.

So people like this can sometimes benefit from taking a transdermal glutathione, because glutathione is a sulphur-based molecule. So sometimes when people take glutathione, they can feel quite unwell. So people like that would probably really benefit from a transdermal glutathione.

But the other really important thing we need to know about when homocysteine starts to drop is that the enzymes, the cystathionine beta-synthase and the cystathionine lyase enzymes, these enzymes are B6-dependent. So when you start running that pathway, when homocysteine starts to drop, you are churning through your B6.

Andrew: Right.

Joanne: And you become deficient in B6. And that's going to have huge implications for mood, as we know that B6 is important for the synthesis of all neurotransmitters.

Andrew: Yeah.

Joanne: It's also very important for the synthesis of progesterone. So huge mood issues. But what we also see is that people can start to build up oxalates because you really need B6 to break down oxalate. Okay? And then what happens is when the oxalates get high, they actually start dumping sulphur in the urine and you become even more deficient.

Andrew: Even worse.

Joanne: Even worse. So these patients are tricky. Because their requirement for sulphur is so high and they can't tolerate sulphur, so you need to sort of try and unravel what is causing the need for these sulphur amino acids. So why do they need a lot of glutathione in particular.

Andrew: Yeah. Can I just...

Joanne: So clinically a lot of people with low homocysteine don't necessarily have issues with sulphur and tolerating sulphur, it just...it can happen. And when it does happen, it's tricky.

Andrew: Yeah. Can I go back to what you said about transdermal glutathione? Does that really stink?

Joanne: That's a good question, I actually haven't smelt any. It probably does.

Andrew: Because oral glutathione certainly has a sulphurous smell to it.

Joanne: Yeah, it’s squalid. It's not nice at all. People don't...people generally don't...well, generally they don't like it. But if they need it, they feel so good on it that they don't care.

Andrew: Yeah, right. Right. There are so many things going around my mind when you spoke about this low… Forgive me, this increased need for sulphur and a drop in homocysteine. And I was wondering about even the ongoing depression of after a heart attack or autoimmune diseases and things like that, that I'm not saying it's the cause of, but certainly a component of. Would you agree with that?

Joanne: Anyone that's got a sort of inflammatory condition, which is most of the patients that are going to come to your clinic, you should be testing homocysteine. Because if it's really low, that's where you start. This is where you start looking at trying to reduce the inflammation, supporting them with some N-acetylcysteine if they can tolerate it, glutathione if they can tolerate it. You need to actually start working on that pathway to free up homocysteine.

So you can do that by treating inflammation, oxidative stress, providing with some N-acetylcysteine and zinc and selenium to help regenerate glutathiones. And glutathione, as well, if that's what you would like to do. Supporting that can actually help take the load off of homocysteine. 

So you're giving cysteine, the sulphur amino acid, that will convert into sulphur, as well. Right? For sulfation. And then you can see the homocysteine will start to come up. So if you retest it, hopefully the homocysteine will start to come up. And that's sort of a marker of how well you're doing at reducing the inflammation and oxidative stress and saving the sulphur and conserving the sulphur.

Andrew: Yeah.

Joanne: Because the sulphur you also need to make taurine and for sulfation and all these pathways. So you need to be able to make sure you've got enough sulphur for all the important roles that it does, so looking at homocysteine levels is a good place to start. And you need, before you even start treating methylation, giving methylfolate, methyl B12, SAM-e, you really need to understand what your homocysteine levels are. Because if you start giving methyls, particularly SAM-e, it's going to start dropping your homocysteine even lower because SAM-e will promote that pathway. So it's a bit tricky, but you need to test so that you understand high, low, and what's actually going on before you start treating methylation.

Andrew: Yeah. And when we talk about homocysteine, what's the lowest that you'll allow? Like a six?

Joanne: If someone comes in at six, I'm not that worried about it.

Andrew: Okay.

Joanne: Six to... But when it starts dropping, 5.5, 5, 4. The autistic children will have homocysteine down at like 3. They've got huge problems with oxalates and yeast. Yeast actually contains its own oxalate. So they have huge problems with that pathway, oxalates, and sulphur and sulphur dumping, and they've got huge problems.

So you don't often see it at three, but the autistic kids will have it at three. But if I've got someone that comes in with a homocysteine at five, I'm like, "That's not good." And you see it in endometriosis all the time, all the time.

Andrew: Low homocysteine?

Joanne: Yeah, low homocysteine. Because they just...the inflammation is huge and they're just trying to sequester all the inflammation and oxidative stress that occurs in endometriosis. And so many of these women do feel so much better on glutathione. It's hard to get...I don't really focus on getting it up in these girls because it's just there's other things to look at. But this is why they often feel so much better on glutathione, is because their need for this sulphur-based amino acid. And the sulphur to support glutathione is really high in these girls.

Andrew: And what percentage of patients do you see that have low homocysteine compared to high homocysteine? Because we're all sort of caught up on high homocysteine and bringing it down.

Joanne: That's right. I probably see more low, to be honest.

Andrew: Really?

Joanne: Yeah. I often do because people are coming to me with huge gut issues.

Andrew: Yeah.

Joanne: Histamine, they've got histamine issues. So what's going on with histamine? It's mainly gut. It's a dysbiotic gut microbiome, and all the inflammation that that causes, a lot of huge histamine release. Whether they know that they've got a histamine problem or not.

So it's the histamine stuff, gut, I see a lot of women with endometriosis. So a lot of inflammatory conditions you'll see a low homocysteine. Interestingly enough, sort of I'd say slightly more low than high, yeah.

Andrew: Right, right. And the other question I have about homocysteine is is homocysteine tested alone or do you test with methylmalonic acid, MMA, anything like that? Do you ever use it in combination with other tests?

Joanne: Yeah. So if you're going to do a workup with someone, if you're going to start looking at methylation and what you need to do, you would definitely be testing active B12, red blood cell folate levels. Plasma zinc/serum copper is really important because zinc is a cofactor in the methylation pathways.

Andrew: You use plasma zinc?

Joanne: Plasma zinc/serum copper, yeah.

Andrew: Might want to get consensus on that one.

Joanne: Oh, okay. It's just what I've been taught.

Andrew: Oh, no.

Joanne: And fasting homocysteine. So there's no point in giving people methyls, methylfolate, methyl B12, when their homocysteine is low because it makes these people feel worse. Because it starts stimulating the production of SAM-e, SAM-e upregulates CBS enzyme, it can start dropping your homocysteine even lower. Plus, if your homocysteine is low, you're highly likely to have gut issues, right? Really. And histamine issues because of all the inflammation. 

You give methyls, it breaks down histamine. And it will break it down, quick, smart, but you're not treating the cause of the histamine. So it breaks it down. And it often breaks it down in the central nervous system in the brain. So this is why people can get headaches and migraines and insomnia and irritability, anxiety, from methyls. Because it's breaking down histamine.

Andrew: Yeah, this really explains the... Not "contra." What's the word? The flipped expected outcomes to using the activated Bs, which we're all taught is the best forms of the Bs to use.

Joanne: Yeah. Oh, absolutely. It's not great for everybody. And I am pulling my patients off methyls that they've been prescribed more than I'm giving them. Because they're prescribed willy-nilly, they're prescribed without testing homocysteine. Anyone with inflammation and signs of high histamine, definitely don't give the methyls, at least straight away. Because it will just make them feel worse most of the time. 
Because with histamine it's the DAO enzyme in the gut that really is taking the brunt of what's going on with histamine. And if you don't fix that, histamine gets into the brain, you break it down with methyls, and it comes out as adverse reaction.

Andrew: Right. But of course the activated B vitamins are those which are found in food. So has it got to do with dose, or other combinations they use?

Joanne: Oh, yeah, yeah. Yeah, it would have to do with dose. It's not happening from food. No, it's not happening from food. It would have to be dose.

Andrew: Got you.

Joanne: And the other thing is these people need, they need, the methyls, they need them, but you need to go in slowly. So with folinic acid instead of methylfolate and hydroxycobalamin instead of methyl converts slowly and it will start sort of providing the methylation support until you fix the inflammation and oxidative stress that's driving down homocysteine.

And I'll see people will come into my clinic, they don't have any sort of gut symptoms or histamine symptoms at all. And they'll just take some activated Bs. No methyls, just folinic acid and hydroxy. And they'll e-mail me, "Jo, I've got a headache." And I'm like, "You've got a histamine problem."

Andrew: Right.

Joanne: You do. I always go through my questions with them, "No, no, no, no, no," nothing. And then bang, they do, they have a big problem with histamine. As soon as you start methylating, pushing methylation, and you break it down, the symptoms can sometimes be hidden and they'll come out.

Andrew: Okay, so I want to get on to where do you start a little bit later, because you've given us a big clue along the way that's sort of a naturopathic axiom. But you've said that B6 is a cofactor for cystathionine beta-synthase. And then you've got serine in there, as well, haven't you?

Joanne: Oh, yeah, serine.

Andrew: Is that right?

Joanne: Yes.

Andrew: Or am I thinking about the transsulfuration pathway?

Joanne: No, serine is part of that pathway. But I can't remember what it does.

Andrew: No, that's okay, my brain going off.

Joanne: No, but it is, it is part of that pathway.

Andrew: Let's go back to B6 then. Implications of taking high dose B6? And how high is good? How high is safe? And when do you call it?

Joanne: Well, the thing with B6 is when you...the typical pyrrole formulas. And this is where I really learnt about this, right? 250 milligrams or more a day. Right? Especially when this is being prescribed without even testing homocysteine in the first place. This will start driving the homocysteine down because it just stimulates CBS so, so much. Okay? The B6, and then it starts dropping homocysteine.

So the homocysteine will start to drop, the pathway is upregulated, you're just pushing sulphur down that pathway. And the thing with sulphur, the symptoms are very similar to histamine, headaches and nausea and bladder pain, stuff like that, really similar. So when you're taking all this B6, it will just start dropping homocysteine. And then you've got all these histamine reactions happening, right? And then you don't have enough homocysteine for methylation. So the B6 is problematic.

And the other thing is with B6 you should only really start with a really small dose, like 15 milligrams, because it's just enough to get methylation pathways moving whilst you fix what's causing the low homocysteine. Even people with oxalate. So when B6 becomes deficient, you build up endogenous oxalate, your own body will start making more oxalate.

And so sometimes when you take all this B6 without understanding there's an oxalate problem, right? Which does...is... Great Plains Laboratory talk about this, oxalate is an underlying cause of pyrroles. Right? So if you don't fix the oxalate problem in the gut first, you've got all this B6, well it's going to break down oxalate.

Andrew: Right.

Joanne: And it's going to come out as bladder pain and gut pain. Yeah, so I see a lot of women with bladder pain and gut pain, recurrent urinary tract infections from taking all these high-dose-based B6 because it just keeps breaking down oxalate. Breaking it down, and they don't have enough calcium to bind the oxalate for excretion.

Andrew: Yeah.

Joanne: It binds it up so that it doesn't cause damage. And then they take all this B6 and they have a worsening of the oxalate problems that were never identified in the first place.

Andrew: Then you've also got a risk of, like long term, you've got a risk of renal stones, haven't you? With high oxalate.

Joanne: That’s right, kidney stones, oxalate causes kidney stones, definitely, yeah. Renal stones, it does. In fact, it's so interesting, there's so often a family history.

Andrew: Okay, so would you advocate then, instead of calcium to bind the oxalates, would you advocate magnesium and B6?

Joanne: What you do for oxalates is you give calcium citrate and magnesium citrate.

Andrew: Ah, right.

Joanne: Because... To help break down...help bind up the oxalate.

Andrew: Right.

Joanne: The real interesting thing with the calcium though is if you've got issues with fat malabsorption, right? Which can actually happen if you don't have enough taurine because that makes bile acids. Methylation is also important for making bile acids. You have fat malabsorption, and fats bind up your calcium. Okay? 

People with SIBO often have dysregulated bile acids, right? It binds up your calcium so you don't have enough calcium available to bind the oxalate. And I love treating oxalates because it's really tricky but clinically not that hard to treat. So calcium magnesium citrate to help break down and bind up the oxalates can work really, really, really well for these people. And you've just got to take them off all the B6, if they're on too much B6. Just a little bit, like 15 to 20 milligrams is usually enough.

So with B6 you've got to think about, “Why are you low on B6? Why do you need so much B6?” Because it's widely spread out in food. It's not like B12 where you need animal protein and really good amounts of hydrochloric acid. The reason B6 is low is usually due to an upregulation of CBS pathway, requirement for glutathione, or oxalates, which are really increasing your need for B6.

Andrew: Do you find the... Sorry, forgive me. Say again?

Joanne: It's fixing that pathway to free up your B6.

Andrew: Yeah, I think the temptation is always to use something as a target rather than a marker. So if you see it low, hit it.

Joanne: Yeah.

Andrew: Can I ask a question about the testing laboratories? Do you find that they give adequate explanations of the clinical implications of low and high homocysteine or even low or high B6, for instance? Or do we need to be really on our game ourselves about the implications of high and low B6? Not just you see low, you hit it, give it B6, rather than delve into why.

Joanne: Oh, absolutely. Because a lot of the labs will just look at results and sort of say, "You need to take this supplement, this dosage." And you really need to sit down with your patient and understand why they've got a deficiency in these nutrients. One of the classic things I see is organic acids tests which will bring up low oxalate, but it will bring up low vitamin C. And the reason you've got low vitamin C if you've got low oxalate is because all the vitamin C is going in to make oxalate. So vitamin C will increase oxalate.

Andrew: Right.

Joanne: So you've got high oxalate on the test and you've got low vitamin C.

Andrew: Yeah.

Joanne: If you don't see a good physician that can help you, you just get that test result yourself, I see patients do it, they supplement with vitamin C. And all that's doing is increasing oxalate.
So yeah, you do, you need to delve into all of this stuff. Great Plains do really great educationals around their testing organic acids. You need to sit down and really do them thoroughly because they're brilliant, there's so much information in there to actually learn. But yeah, you've got to go and do your own research and learning. You can't just rely on what the labs say about test results.

Andrew: Now you've said that you test for homocysteine very frequently. Do you track the tests during the patient's therapy?

Joanne: Yeah, I do. Especially when they're coming in under six. So it's really, really good to see, and the patients really like to see, an improvement in results. So when homocysteine is low, it's say, 4, 4.5, and they've got chronic gut issues, you can actually see the results move up, you can see the homocysteine come back up to a healthy level of like 7. It's hard to do it with endometriosis because just the chronic nature of that inflammation. It's hard, but, yeah, you can often see improvement. You can get up from like four to six. You can do that. And especially if you're providing N-acetyl cysteine or glutathione to these patients to take the load off homocysteine. And then they’ll methylate better, too.

Andrew: And is six the sweet spot? Between...

Joanne: Between six and eight.

Andrew: Between six and eight? Okay.

Joanne: Yeah. Seven is ideal. But if someone has got a homocysteine and it's six, I'm not going to be that focused on it.

Andrew: Got you. And oxalates, what about the levels?

Joanne: The levels in testing?

Andrew: Testing and levels.

Joanne: Oh, okay. It's signs and symptoms, and if oxalate.

Andrew: Got you.

Joanne: But I don't even worry about that, I've got so many...

Andrew: Let's go through a few of them, the signs and symptoms of high oxalates.

Joanne: Okay. So it's definitely things got to do with the bladder, and then urethra. So it will cause bladder pain, bladder burning, recurrent urinary tract infections, vulvodynia. Because of the yeast component, it will also cause recurrent thrush.

Andrew: Right.

Joanne: Okay? It causes pain which is sharp in the gut usually, gut pain that's sharp. And it will cause joint pain. Widespread pain. Also, classic, really, really interesting, oxalate dumping. So these people don't even know they've got oxalate dumping because they're just...everyone is eating nuts and seeds all the time because they're on a paleo diet and they're good snacks. But they start eating a lot of oxalates, and then their body will try and dump them. And it will cause flu-like symptoms. Just the glands are up, feeling of malaise is absolute classic sign of oxalate dumping.

Clinically I see this a lot. So someone will come in with SIBO histamine problems, definitely test it, we know for sure all the symptoms. They might not have oxalate symptoms. I'll go through it, they don't really have it. But they'll go and they'll put themselves on a SIBO low-histamine diet, but then they'll just start eating way more nuts than they normally do. And then they will present with the malaise symptoms and the joint pain because they're actually having oxalate dumping. It's like, "Wow, this person has an oxalate problem, as well."

Andrew: Right.

Joanne: And it's hard because it's SIBO and histamine and oxalate and all of it. So, but classic is that...is pain.

Andrew: Yeah.

Joanne: Oxalate is sharp, tiny crystals and they cause a lot of pain.

Andrew: Okay, so we've spoken about it time and time again, now is the time to open up the Pandora's box. Where do we start with therapy, gut? How do you...

Joanne: Yeah, we should always start with gut. So low homocysteine. Identifying the cause. Most of the time my patients, they've just got some gut issues that need to be identified, or sort of an inflammatory condition like endometriosis. So, and the endo girls, often they've always got gut issues, too, right?

So we start with gut, whether it's SIBO or large bowel dysbiosis. We need to start working on the protocols that all clinicians have to help with gut. If there are oxalates, you need to make sure you do a stool test rather than just testing for oxalates because it's signs and symptoms, and yeast definitely do that. Combined with low homocysteine, so you've got not enough B6. Okay? So you need to start working on gut. If they can tolerate sulphur, which most people can. The not tolerating sulphur thing is clinically you don't see it that often. Well, I don't, anyway. Okay?

So you would get these patients on some N-acetylcysteine or some glutathione. Right? So whilst you're working on the gut to reduce inflammation, oxidative stress, support glutathione production so that homocysteine is not...you've got the cysteine to free up homocysteine.

Andrew: Yeah.

Joanne: So the cysteine will then go on to start supporting production of SAM-e as long as you've got B12. Right? Because we need B12 to take homocysteine around to methionine with folate. And, lo and behold, what do you need to have good B12 levels? You need good gut.

Andrew: Yeah, yeah.

Joanne: So things like hydrochloric acid, betaine hydrochloride, to help break down protein and get some more B12, that will help sort of start bringing your homocysteine around for methylation. But gently. It's gentle because when these gut...even oxalates cause huge histamine problems. Of course, they're damaging the gut, they're causing a lot of inflammation en masse, they're releasing histamine. Right? So if you just start pushing methylation too quickly before you fix these issues, then that's when you get a lot of side effects from giving the methyls.

So I usually just start with some activated Bs, just a small dose. Except I'll go high on B12 if they really need, like a liposome or hydroxycobalamin, to help get the B12 levels up.

Andrew: And speaking of sulphur, do you give things like MSM? Which is renowned for if people take the full dose first day, they'll get nauseous.

Joanne: Yeah. The sulphur is... You've got to fix the oxalates, right? Go get calcium magnesium citrate, really, and just get the very high oxalate foods out of the diet, fix the gut, that's really good for getting on top of oxalate issues. So then you're not dumping your sulphur.

Then Epsom salt baths with sulphate. Because sulphate is the end product. So if people need support with the sulfation pathway, the end product with the sulphur gets converted into sulphite, and then into sulphate. Yeah. If you give Epsom salt baths, like you just start with a little foot bath, nothing too high, not in a high dose. And just for like, it depends how long, 20 minutes. And that will give the sulphate, so it bypasses the entire pathway. Often people will feel good having those Epsom salt baths to support sulfation whilst you're trying to fix that pathway.

Andrew: Right.

Joanne: Yeah.

Andrew: And so mentioned MSM, you've also got, of course, broccoli sprout extracts, and indeed broccoli. And your sulphur-containing, or Brassica, group of vegetables. And then, of course, eggs. And other meats, as well.

Joanne: Of course. Yeah, yeah. Well, you need... It's methionine creates homocysteine. And methionine is a sulphur-based amino acid and it's in meat.

Andrew: Right.

Joanne: But you've got to get these people eating meat, you've got to get the hydrochloric acid up. Because it's, "Oh, I can't eat red meat, I don't feel good on it." It's like, well, maybe it's a bit of sulphur, but it's usually because they don't have enough hydrochloric acid.

Andrew: Right.

Joanne: So they stopped eating meat. Like they didn't tolerate it because their hydrochloric acid is so low because the gut, they're so stressed and their gut is so stressed out that they reduce the hydrochloric acid.

Andrew: Well, there you've got vagal stuff in there, as well.

Joanne: Pardon?

Andrew: Well, you've got vagal nerve stimulation in there, as well, now.

Joanne: Yeah.

Andrew: Can I ask though, you mention betaine hydrochloride to stimulate stomach acid, but of course betaine is involved in the homocysteine cycle, as well. Can that be playing a function in running it too fast or helping?

Joanne: Well, no, it helps. I find it helps. The only sort of side effect I've seen from giving hydrochloric acid will be a flare-up of gastritis, if it's there. Or if histamines are too high, it will cause a lot of reflux. Because histamine stimulates hydrochloric acid.

Andrew: Got you.

Joanne: Big cause of reflux, massive cause of reflux and heartburn. So if you... You need to get the histamines down first.

Andrew: Yeah.

Joanne: And then you can go in with betaine hydrochloride. But that's right, the betaine helps convert homocysteine to methionine through the short route.

Andrew: Yeah.

Joanne: So it's usually really helpful for...so killing two birds with one stone. Supporting homocysteine to methionine to make SAM-e, as well as providing the hydrochloric acid needed to break down the protein.

Andrew: We all think that the fermented foods are totally healthy, but of course they're high in histamines. So sauerkraut.

Joanne: Yeah, honestly. Yeah, they are. And everyone has to go...the more the better. So absolutely, fermented foods for most people with gut issues initially are just a disaster. Because if you've got SIBO, you're very likely to have problems with histamine. If you've got oxalates, you've got problems with histamine. Any sort of large bowel dysbiosis is inflammation, it's going to cause reduction in DAO enzyme and you're going to eat all these foods that are super high in histamine and it just overloads your system with histamine. And these people feel terrible, banging migraines, they feel very irritable, they've got severe insomnia. Histamine increases oestrogen, they have horrendous PMS.

And people, what they'll do, they'll have kombucha, they'll have bone broth, they'll have fermented foods breakfast, lunch, and dinner, and they just really overdo it. So these foods are lovely and helpful once all of the inflammation and histamine is down, bone broth in particular. I just do a two-hour broth once people's histamine levels are low to help sort of gut repair. But yeah, clinically I see it all the time. It's really prevalent in Sydney, people are doing it all the time and it's making them a hell of a lot worse.

Andrew: Yeah. It's amazing stuff because it's really flipping my mind. The things that we thought were all good are questionable. But indeed I've seen it with things like fermented foods where we expect a healthy outcome and indeed you get the reverse happening. What's really interesting to me is how it can quite quickly impact on things like migraines and bladder issues. I think there are these...I don't know if they're pathognomonic, but certainly they'd be hallmarks that I'd be watching out for.

What about caveats? Caveats and cautions? What are the worst things that you see happen, what do we need to be aware of?

Joanne: Okay, so high dose B6. Or these pyrrole compounds.

Andrew: Right.

Joanne: Quite frankly, I question my patients. If they're on them, "Is it helping? Is it helping with their mood?” I question about oxalates so much. The other thing is B6 takes histidine and converts it into histamine.

Andrew: Right.

Joanne: Right. Then you need DAO, or histamine methyltransferase, to get rid of it. So I think a lot of people think the cofactor for DAO is B6, but it's not, it makes histamine a hell of a lot worse.

Andrew: Right.

Joanne: So yeah. Yeah. Everyone keeps saying the cofactor for DAO is B6, I can't find the research on it. Absolutely histidine is converted into histamine with B6.

Andrew: Yeah. This is something that I've never understood. Because previously, a long while ago, you used to be able to get histidine in these garlic, vitamin C, and horseradish supplements for sinus.

Joanne: Yeah, yeah.

Andrew: And they seemed to work quite well.

Joanne: Why is that?

Andrew: I have no idea.

Joanne: I don't know either. I'll have to think about that.

Andrew: Yeah, that's a funny one.

Joanne: Yeah, I don't know. I do remember working at the health food shop seeing that. I don't know, I have to think about that.

Andrew: Yeah.

Joanne: But be careful with B6. Test homocysteine before even starting with methylation. So often I see people, "Oh, you've got MTHFR, take Methyl-Guard." Right? It's designed to lower homocysteine, that's what that supplement is designed for. And there's a lot of other supplements that are the same. And it's just dropping your homocysteine even lower.

So don't start even looking at methylation and supporting your patients with methyls, methyl B12, methylfolate, SAM-e, before you know what your homocysteine levels are because it just can make them feel so much worse. 

But suicidal thoughts and tendencies, and really paranoia, it can be really quite a serious adverse reaction, and so you just want to be really careful.

Andrew: So that's something to be really aware, I guess, changes in mental state of our patients.

Joanne: Anyone that comes in sort of, "I'm feeling a bit melancholy, a little bit anxious. Just a little bit. I'm having a fight with my boyfriend, I don't know, but I'm normally not this anxious." It's like, "Are you taking methyls?" "Yes." "When did you start them?" "Oh, two weeks ago." "When did you start feeling anxious?" "Oh, two weeks ago."

Andrew: Right, okay.

Joanne: Just I'm so hyper-aware of it, Andrew, because of the adverse reactions that I've seen.

Andrew: And time lag between starting a supplement and symptom presentation?

Joanne: The time?

Andrew: Time lag between starting a supplement.

Joanne: Oh, it can be instantaneous.

Andrew: Right.

Joanne: Especially with methyls.

Andrew: Right.

Joanne: With SAM-e I never... Well, I never give methyls without niacin. So niacin will stop an over...not over-methylation, but a methylation pathway that's been stimulated too much when it shouldn't be.

Andrew: Yeah.

Joanne: Or it should be, it needs to be, but not...they've got blockages. Right? Niacin will stop the methylation reaction and it will stop the anxiety, the insomnia, the nausea, the heart palpitations, the headache, the mood changes. So you really need to look at providing your patients with niacin, which will help stop methylation if it goes too quickly, too fast.

Andrew: Do you give niacin as in nicotinic acid, nicotinamide, or niacinamide? The acid form, the itchy form?

Joanne: No, not the itchy form.

Andrew: Right.

Joanne: It's nicotinamide. Yeah. Yeah, yeah. You can see that works just as well. That works just as well. But I always get them to take it with food anyway.

Andrew: Right.

Joanne: Yeah. That's the thing with methylation, is niacin will stop it and you need to support your patients with starting a really low dose. Low dose methylfolate. Maybe you can get... Like the 100 micrograms, you can start on 100 micrograms and pulse it up. SAM-e is the same, you start on 200 micrograms, that's the smallest dose you can buy, I think.

Andrew: Yeah.

Joanne: It’s enteric coated so you can't cut it. You just start on low dose SAM-e and pulse it up. Because if you go in too hard, too quickly, people are highly likely to have an adverse reaction, a serious one. They feel terrible, they feel confused, they're scared, they don't trust you. So it's just slowly, slowly, slowly is a lot better approach, yeah.

Andrew: Where can naturopaths learn more about what to do properly? Have you ever thought about writing a course, or do you have any resources?

Joanne: Well, I'm writing a book on histamine at the moment.

Andrew: Right.

Joanne: I'm writing a book.

Andrew: Okay.

Joanne: So I've started doing that, it's a big project.

Andrew: Page one.

Joanne: I've done... Yeah, I don't know. I've done a lot of... I'm doing a lot of research.

Andrew: Right.

Joanne: Histamine is so fascinating, it's the most researched molecule in science and it's just not well-known outside of pharmaceuticals.

Andrew: Yeah.

Joanne: They're looking for receptors and drugs to treat things. So it's a lot of information on histamine, so I'm going through that. But I want to just...but this is a book not for clinicians, it's a book for patients, for people that really need help.

So I'm dumbing it down. Well, not dumbing it down, I'm just putting in layman's terms and I'm looking at all the things that clinically I find really helpful for treating histamine, which is absolutely gut stuff. The SIBO stuff is huge when it comes to histamine, dysbiosis, the fermental carbohydrates. There's no point in getting someone on a low histamine diet when they're just eating FODMAPs and starch, resistant starch, feeding the bugs. That causes histamine big time.

Andrew: Right.

Joanne: So, well, it's a lot of my...it's going to be a lot of my clinical knowledge and along with the research, and it's going to be more for patients, just try to get an understanding on how to get on top of this stuff. Because histamine is a huge problem globally. I have patients all around the world, in Egypt, in Abu Dhabi, Canada, all over the place, the U.S., with huge histamine problems and it's just a lot of physicians don't know a lot about it. And anyone with gut issues and inflammation, you're very likely to have a histamine problem. And this is...these are the people we see, this is chronic inflammation. This is what naturopaths are good at, is treating chronic inflammation. So mast cells are released as part of the inflammation cascade and they release histamine. So we need to be looking at it.

Andrew: Two things. Firstly, you really need to develop a clinician's course to go alongside the book.

Joanne: I know.

Andrew: Second one is what you've done is quite amazing. Because normally we think about, or we assume our local environ for our patients, which are usually near to us. You're dealing with people globally that have vastly different cultural and dietary intakes. So that's no mean feat, what you're doing. This is huge.

Joanne: Yeah, no, I do. But I really love it because I learn so much from these patients. And I guess I've got patients in Abu Dhabi and Egypt, but they are so into natural medicine.

Andrew: Right.

Joanne: And they listen to podcasts, they know so much, they know all about all the different functional medicine testing that needs to be done, they know all about products. They're really, really well-educated on this stuff. So it's just really interesting to talk to them and understand that globally the need for naturopathic medicine is really, really in demand.

Andrew: Yeah. How can they embrace their cultural or historical use of herbs.

Joanne: They really like it, especially the women. It's part of their...they're proud to provide that for their family. So yeah, it's really, really interesting. But I just...just a story, I had a patient in New York and she had huge histamine issues, but neurological histamine. She'd get the dizziness and the vertigo, and which comes with nausea. It's coming from the brain, right? Can't regulate a body temperature. That's a really interesting, that’s a big histamine symptom, people that can't control body temperature.

Living in New York in the middle of winter, and she would go from hot to cold. Right? So she'd walk out, she’d be in the bus all warm in a puffer jacket, and then she'd go outside in the freezing cold in New York. And then she just couldn't regulate, her body temperature would just throw out, the dizziness, the vertigo would start, and she'd nearly pass out.

Andrew: Wow.

Joanne: And she looked at histamine a lot and she was kind of doing a low histamine diet, but what she was eating was rice and rice noodles. And all that starch was feeding the SIBO. Right? And it was just stimulating histamine, it was getting into her brain. And because of the New York temperature changes, it's extreme there, hot to cold, cold to hot, she would just nearly pass out every time she did that.

Andrew: Really?

Joanne: So it's just fascinating to see. And it's like, "That is...you've got to get that rice out of your diet because that's driving that." And it fixed it really, really quickly. So it's just interesting to see in different environments how histamine is going to actually manifest its quite extreme symptoms.

Andrew: There are so many questions, I have to ask one last one though. And that is do you ever test microbiota?

Joanne: Oh, yeah, I always do a microbiome test.

Andrew: And do you find variations or modulation of the microbiota with dietary intercedence?

Joanne: In different countries?

Andrew: In different countries and, indeed, in Australia, yeah. I would so love to see that.

Joanne: I think that would...I can't answer that because I just think it's too...that's a database, you have to do a spreadsheet on that.

Andrew: Yeah, all right. Until tomorrow.

Joanne: I don't know. But I'm definitely looking at the gut microbiome and I'm really looking for all those histamine-releasing bacteria. When we're looking at histamine, that bifidobacteria is so important for breaking it down.

Andrew: Yeah.

Joanne: And oxalates. So I'm looking a lot at what's going on with dysbiosis. And I look at SIBO all the time because the DAO enzyme that breaks down histamine, it's in the gut, but a lot of it is in the small intestine. So I'm looking at that all the time when it comes to histamine.

Andrew: So much more to learn. Joanne Kennedy, thank you so much for giving us just... It's like I'm just opening my eyes. It’s a whole new world.

But thanks so much for giving us an insight into your work. Because it's not just locally groundbreaking, this is globally groundbreaking, what you're doing. Because you're helping people around the world and jumping that cultural barrier, if you like, because you're helping these people in Egypt and New York that have vastly different diets, even the availability of food. 

So what you're doing quite amazing, thanks so much for taking us through some of it today on FX Medicine.

Joanne: You're welcome. Thanks, Andrew.

Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.



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FX Medicine is at the forefront of ensuring functional and integrative medicine gains the recognition it deserves and ultimately establishes itself as an integral part of standard medical practice. Hosted by Andrew Whitfield-Cook, our podcasts are designed to promote research and evidence-based therapeutic practises, acting as a progressive force for change and improvement in patient health and wellbeing.