In The Media

Dr. Hedberg: Well, welcome everyone to “Functional Medicine Research.” I’m Dr. Hedberg. And I’m really looking forward to today’s conversation with Dr. Bruce Hoffman. He’s a board-certified physician, and he has a Fellowship in Anti-Aging Medicine, as well as a Master’s Degree in Clinical Nutrition. He’s a certified functional medicine practitioner. And, one of the really interesting things about him is that, in addition to his clinical training, he studied with many of the leading mind-body and spiritual healers of our time. People like Deepak Chopra, Paul Lowe, Osho, Ramesh Balsekar, and one of my favorites, Jon Kabat-Zinn.

So, Dr. Hoffman, you shared the stage with Dr. Deepak Chopra and Dr. John Demartini. And he continues to spread his inspiring vision of healing and wellness with audiences and patients around the world. So, Dr. Hoffman, welcome to the show.

Dr. Hoffman: Thanks very much, Nikolas. I’m glad to be here. Thank you.

Dr. Hedberg: Great. So I’m really looking forward to this discussion on mast cell activation syndrome. It’s something I haven’t seen a lot of in my practice. I have heard a number of lectures on this and read quite a bit about it. And it seems to be an area of your expertise. So why don’t we jump right in and just talk about what mast cell activation is, and how is this condition diagnosed?

Dr. Hoffman: Sure. I first got interested in mast cell activation syndrome when I started to work with a cancer patient advocate by the name of Dr. Mark Renneker out of San Francisco. And he alerted me to the connection between cancer and mast cell activation syndrome, particularly in gynecological cancers. And then put me in touch with Dr. Lawrence Afrin, who leads one of the major sort of advocacy groups for mast cell activation syndrome as opposed to systemic mastocytosis, which I’ll explain in a bit.

And so, I’ve been for the last three to four years working with Dr. Lawrence Afrin’s group and learning to understand the implications of mast cell activation syndrome in most of the patients that we see. Which are chronic multisystem, multisymptom patients who, as you know, have been everywhere and remain frustrated with the one disease, one drug paradigm that we learned at medical school. So, what I learned over time was how to separate between two specific conditions, one called systemic mastocytosis and the other called mast cell activation syndrome.

But before I begin with that, I’d like to say that mast cells are part of, they’re produced in our bone marrow, and they’re part of our immune system. And they make up a very small percentage of it. And they act as defense structures against incoming invading pathogens. So, anything that comes into our environment or into our biome, mast cells are often at the first line of defense. And they were actually discovered a long time ago, 1878, I believe, by Paul Ehrlich. And he called them mast cells because they were fat and puffy.

And the word mast in Greek means breast or the German means masticate. So, this is how the name mast cell got generated. Just for your North American readers, I say mast, and most people don’t know what I’m saying. So, it is mast in North America. People often don’t know mast cells, what I’m saying.

So, these were originally discovered by Paul Ehrlich when he developed specific staining for them. And since then, they sort of lingered on in the literature. They were linked early on to cancer, but that sort of faded out of the picture until it was resuscitated by some Italian researchers who now are doing massive amounts of work on mast cell activation syndrome and cancers. And then it really sort of resurfaced in the 1990s and didn’t really gather steam until about 2007, when two, you know, researchers and clinicians put together sort of a consensus statement on what constitutes MCAS.

There are two different schools of thought and they do tend to conflict with each other in terms of the diagnostic criteria. But basically, mast cells being part of the immune system, and regulating many of the incoming so-called antigens or toxins tend to be distributed in almost all tissues, but nowhere quite as much as on mucosal surfaces: so eyes, mouth, skin, GI tract, bladder, etc. They’re also found in other tissues, you know, lungs and heart tissues, and brain, many mast cells are activated in the brain.

And so, when they get triggered, they do tend to release many, many mediators of inflammation. And it was estimated that there were over 200 mediators of inflammation that get released by these mast cells. But Dr. Afrin in a very recent post, as of last night, said that he’s now changing his opinion that he believes there are over 1,000 mediators released by mast cells. All these inflammatory mediators like histamine, like proteases, prostaglandins, leukotrienes, all these inflammatory mediators that then set up this multisystem, inflammatory response, which can confuse diagnosticians particularly if you have been trained in single organ, you know, specialties.

So that leads to the sort of difficulty with the diagnosis as people present with many different symptoms. And unless you have an understanding of mast cell activation syndrome, and a method of sort of sifting through the multiple systems they can present, you can often get very confused and misled. So, the recent, you know, people speaking about mast cell activation syndrome is an attempt to bring some coherence to this somewhat disorganized field. And hence, establishing criteria for the diagnosis, lab tests, and then treatment protocols. So now it’s coming into its own and I think you’re going to hear a lot about it in the years to come.

Dr. Hedberg: Mm-hmm, so we’re talking about illnesses that may be so-called mystery illnesses, and multifactorial presentations like gut issues, skin, brain, and things like that. Can you just let everyone know some of the overlap that you see in various conditions in your practice that would specifically indicate mast cell activation syndrome?

Dr. Hoffman: Yeah. So, mast cells, when they release the inflammatory mediators, can present locally or systemically. So, a local condition would be something like hives, urticaria, or interstitial cystitis. Or it can be systemically like people can present with cognitive symptoms. So, they’ll have fatigue and brain fog, and associated GI symptoms, like GERD. GERD is a potentially very big diagnostic category for mast cell activation syndrome or, you know, the irritable bowel syndrome. Even the autoimmune diseases of Crohn’s disease and ulcerative colitis have been linked to mast cell activation syndrome.

Asthma is another one. Asthma, you know, if you analyze all the triggers of an asthma response, and you identify them, like, for instance, mold, allergy or mold inflammation, which are two different criteria, and you remove the trigger and downregulate the mast cell activation potential, I can’t tell you how many cases of asthma have been absolutely shut down when you treat the mast cell activation. It’s very rewarding. The same goes for GERD, the same goes for irritable bowel syndrome. The same goes for anxiety and cognitive decline. When you target the triggers and downregulate the mast cell activation, it’s very rewarding to treat these patients, and they’re very grateful. Angioedema, another one, canker sores another one, there’s many, many symptoms in all the organs that can present with this syndrome.

Afrin has written a chapter in a book. The book is called “Mast Cells,” the editor is David Murray. The chapter is chapter…I think it’s chapter 6, and it’s called Presentation, Diagnosis and Management of Mast Cell Activation Syndrome. And at the back, he gives a long, long list of every organ that can be affected from ophthalmic, to lymphatic, to pulmonary, to cardiovascular, and just goes through all the systems. Even fibromyalgia, even osteoporosis, headache, all the mood disorders, dysmenorrhea, endometriosis, many of the hematological conditions, the immunological conditions. There’s a huge long list of different organ systems that can be affected that present as isolated diagnoses to specialists, but often they miss the overriding pathophysiological basis to the condition.

And our training as MDs makes us very aware of what is called systemic mastocytosis, which is when the mast cell from a clonal perspective within the bone marrow becomes amplified. There’s actually a mutation of the KIT gene. And the mast cells become very high in numbers. So, there’s increased numbers of mast cells, which is systemic mastocytosis, which is very different from mast cell activation syndrome, which is an abnormal reaction of the mast cells, not an increased number.

So, I can’t tell you how many patients come back to me after having got the diagnosis of mast cell activation syndrome by myself with the criteria I use, go to the specialties, go to the hematologist, go to the gastroenterologist, or pulmonologist, who then does a serum tryptase and even sometimes go as far as do a bone marrow biopsy, and then come back and say, “Oh, that diagnosis is incorrect, he doesn’t or she doesn’t have systemic mastocytosis.” Systemic mastocytosis is a very rare condition, I’ve never seen one in my life. But I see almost twice a day, mast cell activation syndrome. Dr. Afrin believes that probably about 30% of the population gets affected to some degree or the other.

Dr. Hedberg: And are there any theories at this point about why mast cells become so overactive in an individual’s body. Any good research out there on that?

Dr. Hoffman: Well, there’s lots of speculation. And the most common hypothesis is that we do live in a much more sort of, you know…we’re inundated, so to speak, with multiple stressors far more than our capacity to withstand them. Our immune system, it just gets triggered because of multiple stressors. And there are many triggers for mast cell activation. Poor sleep. Stress is one of the biggest triggers. Food, I mean, food is incredible in its ability to trigger the mast cells that are in the mucosal surfaces of the mouth through to the anus.

So, we believe that our ability to…..we can no longer withstand the onslaught of our ongoing multiple stressors, whether they be environmental, emotional, nutritional. We just are in this constant state of over reactivity if you’re genetically predisposed. Now, Dr. Afrin doesn’t believe it’s necessarily a genetic condition that is transmitted through the germline. But he believes there are mutations in some of the mast cell production. And Dr. Molderings, who’s published a lot of papers with Dr. Afrin, has done a lot of research on the so-called KIT mutation, not in the bone marrow, but within the mast cells themselves, and has shown that they are these sporadic and spontaneous mutations that occur. Why those occur? I can’t say. I don’t know the answer to that. Yeah.

LAB TESTS

Dr. Hedberg: So, there’s a number of functional medicine practitioners listening to this, so let’s just talk a little bit about lab tests, and some of the ones that you’re using and the ones that are beneficial. Obviously, CBC might be beneficial with elevated eosinophils, basophil, or possibly those are normal, histamine testing and things like that. What are some of the top tests you’re doing in your practice to identify this?

Dr. Hoffman: So yes, we do all the normal standard CBC and electrolytes, and liver function, etc., but those don’t usually yield what you’re looking for. And one of the challenges is that the lab testing positive results fluctuate depending on whether the symptoms are being expressed or not.

So, the first thing is you want to try and catch a person in a flare. Well, that’s difficult you know. So that’s the first challenge. And many of these tests need to be repeated over and over again until you get what Dr. Afrin likes to identify as two positive lab tests, which I’ll explain in a second. The second challenge is that you have to process a lot of these labs on ice. You have to have a refrigerated centrifuge to get accurate results. And it took me two years to get a refrigerated centrifuge. And as soon as I was able to, the positive rate of my lab has skyrocketed. Many of these lab specimens are very poorly handled. And, you know, they sit around for days and you’ll get these false positives for sure, false negatives, I mean. Sorry.

And also, a lot of the mast cell activation syndrome people or patients, they don’t always cause these abnormalities in the lab tests. Positive lab work is only obtained around 20% of the time. So, it’s quite frustrating, you know. But if you want to get lab work tests, I use sort of the minor and the major criteria. There are 10 major lab tests that we do. And then depending on the budget, we do the top 5 or 10, if we can.

And the tests that I recommend are plasma histamine, has to be chilled. And you should catch a person who’s in a flare. If they’re not in a flare, it will very often be negative. And you’ve also got to stop some of the inhibitors of histamine for five days prior to the test. Otherwise, you will get suppression of the histamine response. If people are on, you know, H1 or H2 blockers, you won’t get a positive test. And many people do take them intermittently you know.

Then we look for N-methylhistamine, which is a 24-hour urine also needs to be chilled. And then probably the one test that I get the most positives out of is the prostaglandin D2 plasma test, also must be chilled. And for that test, patients need to be off of all nonsteroidal anti-inflammatories, Motrin, Advil, or aspirin, or salicylate-containing foods. They can’t have a high salicylate diet. Anything containing aspirin for up to five days.

And then the one that is also done is the prostaglandin D2, 24-hour urine, also must be chilled with the same criteria of having to be off of all these medications. And then the last one is chromogranin A, and for that test you have to be off proton pump inhibitors and H2 blockers like famotidine. So, if you do go on proton pump inhibitors and so forth, they can falsely elevate chromogranin A.

And then after that, we’ve got prostaglandins 11 beta F2 alpha, a 24-hour urine, also must be chilled. And then the one that most MDs know about, which is serum tryptase. But this is rarely elevated in mast cell activation syndrome. It’s very important that every doctor who wishes to sort of work with mast cell patients knows this to be true. Because if the tryptase comes back normal, very often, the entire sort of clinical diagnostic differential gets thrown out, “Oh, they don’t have mast cell activation syndrome.” Big mistake, big, big, big mistake.

One of the criteria, one of the two different schools of the consensus criteria, they say that you have to have the serum tryptase elevated over 20% of baseline, or have a baseline greater than 15 nanograms per mil. But Dr. Afrin, who’s somewhat opposed to the consensus statement put out by Aiken and others, he highly disputes this finding and he doesn’t agree entirely that this is one of the main criteria to make the diagnosis. And I tend to agree with him.

Leukotriene E4, a 24-hour urine. Plasma heparin because heparin gets secreted by mast cells. And then a blood clotting profile, thrombin, PTT and INR is often done. And those are the top 10 and then after that, there’s many others; anti-IgE receptor antibodies, pheochromocytoma workup. We often do factor VIII deficiency workup, we do urinary metanephrines often. We almost always get an immunoglobulin profile IgG, IgA, IgE, and IgM. You might see IgE elevated or not. Often you won’t have an elevated IgE. So many people think “Oh, if a high IgE, then it can’t be this.” But that’s not true you can get a non-IgE-mediated mast cell activation. People then do bone marrow biopsies. People can do gastrin, serum gastrin levels. And then as you mentioned, the CBC with eosinophils and basophils can sometimes are elevated. Antiphospholipid antibodies are also often done.

And one test I like to do in the functional world is the Dunwoody Lab test for zonulin, histamine, and the DAO enzyme activity because that’s the diamine oxidase enzyme that sits on the villi that can be genetically compromised. Or because the villi are compromised, you cannot produce enough diamine oxidase. And that’s when you start to put people on low histamine diets and use the HistDAO enzyme to help break down any remaining histamine in food.

But I can tell you the one test that I tend to rely on more than any other right now, apart from the serum and urine test, is to get restaining of any gastric biopsies people have done. This has been overwhelmingly sort of helpful to some of my chronic GI tract patients in particular. So they would have gone, you know, to a GI specialist, they would have had the normal Giemsa tissue stain, and they comment on lymphocytosis. But they don’t actually comment on mast cell activation. And unless they get what’s called the CD117 stain, you won’t isolate the mast cells.

And almost 90% of people that I’ve clinically suspected of having mast cell activation syndrome turn up once they have their biopsies restained of having over 20 cells per high-power field being positive for mast cells. Which is the cut-off criteria that’s been agreed upon by numerous researchers, highly contested, by the way, by some pathologists and gastroenterologists. But we use a cut-off point of greater than 20 mast cells per high-power field to make a diagnosis of mast cell activation syndrome, particularly in the GI tract. The mast cells are very rich in the GI tract, particularly in the duodenum, not so much in the gastric tissue, but particularly in the duodenum.

So, if they ever had a biopsy in the duodenum, phone up the pathologist or write a letter and say, “Please will you restain for the CD117 stain.” And as I said, probably 9 out of 10 come back positive, very helpful. And then the patient sees that and the penny drops then they start reading up all the literature. And then they get on board for the treatment protocols which are, you know, quite…it can be onerous, and they can be extensive. But they’re very clearly delineated with multiple challenges along the way. Because people react to the medications and/or the supplements that you give them because that’s the nature of the condition.

EXCIPIENTS

So, they’ll come back and say, “I can’t take the H1 blocker because I got worse.” Well, most of the time, it’s because it’s the excipient, the additive, the filler, or dye inside the medication that triggered the mast cell syndrome and it’s not the actual problem. You know, they’re not reactive to the supplement, they’re reactive to the excipient within the supplement or the drug. So those are some thoughts.

TREATMENTS

Dr. Hedberg: Right. So once you’ve identified that someone has this syndrome, let’s talk about some of the natural treatments. You just mentioned that some of them are very difficult to follow. And some of these patients are…there’s probably a fair amount of trial and error with some of these patients figuring out what works for them. So, can you just talk a little bit about some of the treatments you’re using?

Dr. Hoffman: Sure. One of the hallmarks of this condition and one of the setups in my interaction with patients is a description of the complexity of the diagnosis and the challenges. And if you don’t have that conversation, you’ll often get a frustrated patient because they’ll come back with flare-ups and they understand it. So, I encourage that all your practitioners who wish to dive into this field really wont understand how patients can flare and how they

may have multiple triggers at any given time. And that the treatment may need to change, and that they mustn’t become frustrated, they must just stay for the long course. And they are sort of part of the team of trying to work out these multiple moving targets.

So the education is number one. I have two handouts, where I’ve described mast cell activation syndrome and mast cell activation syndrome treatment. I make sure they’ve read that. If they’re more interested, I give them Dr. Afrin’s book, “Never Bet Against Occam.” There are many patients who love to read because it’s filled with case histories. So once they get sort of an insight into other cases of complex presentation, they get encouraged to push on. So, education is first.

Second is to try and identify the triggers that trigger their mast cell activation. And this is one of the greatest challenges because there are many triggers from, you know, hot, too much heat, too much cold, stress, poor sleep, as mentioned. And then we get into the more obvious triggers, chemicals, heavy metals, dietary antigens, and then infections or inflammatory triggers like mold.

So, part of the process of working up mast cell patient is not just diagnosing the syndrome, but also trying to work up the triggers. So, in most patients, I do multiple food sensitivity profiles. I don’t just do IgG. I do IgG, IgG4, I do the so-called LEAP test. I do…am I allowed to mentioned lab names on your podcast?

Dr. Hedberg: Yes, definitely.

Dr. Hoffman: Okay. I do the lymphocyte sensitivity tests, the LEAP test. I do, as I said, IgE testing, IgG, IgG4. And I do Cyrex Lab food, I do the 10x, I think it is, with all three panels looking for dietary antigens. So, the Cyrex panel is different from the Meridian Valley food panel. Meridian Valley says it’s an IgG, IgE panel, but I disputed that once, and I’m not too sure there’s much IgE in the Meridian Valley panel. I think it’s more IgG. Whereas the Cyrex panel is more IgG and IgA. And you’ll often get contradictory findings. They’re very frustrating. That’s part of why allergists like to just throw them out, they say, “Don’t bring me this nonsense.”

But once you’ve been doing functional medicine for a long time and you have an understanding of the different complexities of dietary triggers, you can look at these profiles and you can sort of pull out the relevant data. And I encourage those of you who may be new practitioners is not to take each test literally. So, if they have a high say a banana on the one test and it’s not on the other, you want to look at the general profile of the dietary antigen testing. You don’t want to be too specific because if you get too specific, most people will have nothing left to eat. So, I’d look at the dietary antigens and most of the time, but not all the time, controversially or not, I tend to put people on the Paleo, autoimmune, low histamine diet for the first month or two. And I can’t tell you how many people immediately settle down just on that one intervention.

And I take out the high histaminic foods, and that is a very important part of it. And one of the great crazes right now is to use all these fermented foods to heal gut permeability, but it’s a disaster for the mast cell person. So, I’m always pulling people off sauerkraut, and kombuchas, and bone broth, it’s a huge trigger. So, all the fermented foods, and then all the leftover foods. As foods break down, then the proteins, the histamine gets broken down by bacteria that releases histamine. So, leftovers are no, no. We also ask people to, once they’ve cooked a meal, to put in the freezer and then to take it out and unfreeze it, but not to leave it sitting in the fridge for days.

And then things like tuna fish, huge triggers, the nightshades (tomato, potato, eggplant, peppers), huge triggers in many people. And even amongst, you know, some of the vegetable kingdom, you know, peas and beans can be triggers of mast cell activation. And so, you have to be careful when you look at the testing, you’re going to sort of see… when I look at particularly the Meridian Valley test, you can often see a mast cell patient, they’ll show up, all the legumes will be positive, all the histaminic fruits will be positive. Candida will often be positive.

And there’s like a trend you can see it and then immediately, you know this is a mast cell activation profile for food antigens. So, we remove the foods, we always treat gut dysbiosis as you know. I use two different labs for gut analysis. I use the Genova GI Effects, and I use the Diagnostic Laboratory Solution’s GI-MAPs. They contradict each other all the time, you know, one will have a zonulin of 700, the other one has zonulin as normal.

But then you just got to use your clinical acumen and your experience and correlate the labs against the symptom profile of the patient and do the best thing. I do tend to use Dunwoody Labs for the zonulin, the DAO, and histamine, as I mentioned. And then the second page of that test is all the LPS, the lipopolysaccharides, to see if there’s been any endotoxemia. And if there’s been any bacterial endotoxemia, you start entering into a whole new world of immune upregulation, which, you know, you have to down regulate in your treatment protocols and heal the leaky gut, etc. which I’m sure your listeners are very well aware of.

PHARMACEUTICALS

So A. is education, B. is testing, C. is removing the histaminic foods and downregulating inflammation in general. And then we get to specific treatments. And I differentiate between pharmaceuticals and botanicals. I tend to preferentially go to the pharmaceuticals to start with because they work quickly, if they’re going to work. And I tend to secondly, add botanicals. But I tend to be an MD, you know, it’s just my preference. I’m sure many naturopaths would go the other way. And many patients refuse to do pharmaceuticals and then I just have to use botanicals.

Pharmaceutical perspective, they must be compounded, you can’t get over-the-counter. Although paradoxically, some people do better on the over-the-counter than they do on the compounded. This is one of the challenges is what you think is going to work doesn’t work. This is why try, try, and try again, you know.

So, first thing, H1 blockers. Histamine 1 blockers, and I tend to use levocetirizine in a dose of 5 milligrams going up to 7.5, even 10 milligrams. And I think the trick to using H1 blockers is you have to dose it round the clock. You know on the box it will say “24-hour relief” that’s not true. You need to dose it at least 12 hourly and sometimes 8 hourly to create full round the clock mast cell blockade. And you’ve got your H1 blockers, you’ve got your first-generation and your second-generation. The first-generation H1 blockers like Benadryl, or ketotifen, cross the blood-brain barrier and have a sedating effect so those are often given at night.

I love to use ketotifen, I use lots of it on a dose ranging from 0.25mg, which is a homeopathic dose almost, right up 2 to 3 milligrams at night. And if there’s any issues with insomnia, it works like a dream. It’s absolutely spectacular for sedation. The problem is sometimes they over sedate when you have to lower the dose. But it also downregulates mast cell activity at night. So first-generation H1 blockers, I prefer ketotifen over Benadryl. Second-generation H1 blockers, I use levocetirizine as my preferred go-to H1 blocker.

And then I use H2 blockers, and I use famotidine in a dose of 20 milligrams twice a day, sometimes going up to three times a day. And this tends to downregulate all the mast cell activation activity in the GI tract.

One of the little tricks of the trade I’ve picked up over time is if you do the Genova GI Effects, you’ll often see that eosinophil protein X marker a little high, that’s almost a slam dunk for mast cell activation…not always because there’s other things that trigger that. But if you see that with a constellation of other positives, you follow that marker closely because when that starts to downregulate, you know, you’ve got your mast cell activity under control. So those are my first two go-to medications H1 and H2 blockers.

Probably my next is cromolyn. Cromolyn is a mast cell stabilizer particularly for people who are very food sensitive. You take it before meals. I give it along with the HistDAO enzyme. And that dose you can take it from 100 to 300 milligrams, and that can also be a major game-changer in many people’s lives. You have to play with the dose, you have to play with the different companies that make it. It’s a bit of a tricky thing, but it can really have a huge effect on downregulation of mast cell activation.

And then the fourth drug that I use, and many patients have come back to me with this fourth drug, Singulair, montelukast. This downregulates leukotrienes, which are one of the thousand mediators of inflammation. One of the things that we’ve noticed in mast cell syndrome is that when you think a patient has an upregulated leukotriene pathway, which is typical for asthma, you give the montelukast or the Singulair and the asthma is managed.

Well, it so happens that one can’t predict which class of drugs is going to work on which mediator. So, if you give a mast cell stabilizer for food sensitivities, guess what? The asthma may go away. Or if you give Singulair for asthma symptoms, the hives go away. So, thereis crosstalk amongst many of the mediators. And it’s a great mystery as to why that occurs, nobody’s worked it out yet. Dr. Afrin said he doesn’t know. He doesn’t know why this happens and he’s going to keep researching till he works it out. So those are the four drugs I use, probably the top four drugs I use over and over again.

SUPPLEMENTS

Nutraceuticals, of course, Quercetin, tops the list, no question about it. There’s a product called Natural D-Hist made by Ortho Molecular, that’s my go-to supplement over and over again. Two, three times a day seems to be the magic dose. And then using HistDAO one to two before each meal that seems to be the number one nutraceutical.

Number two would be vitamin C, either orally or intravenously, sometimes can have a huge benefit as well. Green tea has an effect. Turmeric or curcumin can have an effect but some people react to it. If you see on the food sensitivity profile, if you see that it’s positive in at least one or two tests, you can use it, but you want to be cautious because it can sometimes activate mast cell activation. You got to be careful with turmeric. Resveratrol is another one. And chamomile tea has some calming effects. So those are my sort of…they’re called the A team of my nutraceutical approach.

And the B team is sort of…there are many others like luteolin, Ginkgo biloba, Pycnogenol. Pycnogenol is a great one too I use quite a lot of Pycnogenol. Feverfew works. There are many things that can work. So, I pick and choose and go through them and change them. I ask everybody to first identify the triggers, if they can, and then to start rotating the pharmaceuticals and/or nutraceuticals and see which has the biggest blockade effect. And people soon work it out, you know. You’ve got to get a good compounding pharmacist on your side. And you got to make sure that they don’t fill the compounded pharmaceuticals with lots of fillers and dyes because some people react to that.

And then one of the other challenges…I just had a very seriously ill patient present to a hospital with anaphylaxis and she was on polypharmacy. She was on 10 different drugs. And many of the drugs she was on were triggers for her mast cell activation. And those were never identified as triggers by her medical team. And so, we asked the pharmacist to go through each drug and look for the additives. Many of them had iodine in them, many of them, there was soy extract base, and those had to be changed accordingly. And she settled down. So those are some of the challenges I have.

Dr. Hedberg: And one of the drugs that wasn’t mentioned was LDN, low-dose naltrexone, I know some practitioners are using that for this. Have you tried that or used it?

Dr. Hoffman: I do use low-dose naltrexone. It’s part of the many other…there’s many other alpha-lipoic, and so forth. And LDN is definitely part of it. And LDN has an effect particularly on autoimmune responses and downregulation of an inflammatory response. It’s not my first drug though, I don’t go to LDN as my first line. I use it if there’s autoimmunity and lots of gut permeability then I bring in LDN. And LDN is challenging because people give it at night but it can be very activating. Just yesterday, I saw a patient who since she started LDN hasn’t slept a wink. We changed it to morning.

Dr. Hedberg: Right. So how do you deal with the psychoneuroimmunology aspects of this condition? You know, some people, they develop a deep identification with their illness, and then they develop a lot of beliefs about things that they’re sensitive to. And we’re not saying that it’s all in their head, but we do know from the PNI research that what we believe, and what we emphasize, and think about, and focus on can affect the immune system and our biochemistry. So, are you using any kind of cognitive behavioral therapy or things like that, that could help some of these patients who are so focused on their condition and their hypersensitivities?

Dr. Hoffman: Yeah, because this opens up a huge area of the work that I’ve been forced to look at over time and for which I use quite a complex algorithm to sort of diagnose and treat. I’ve studied Ayurveda for years and I use the Ayurvedic model of layers and levels of healing. And when a person presents with specific belief systems around their condition, I have to sort of look through the layers and levels of what may be playing a role in that belief system.

Just very briefly, I tend to look at these diagnostic criteria. I look at the family system to see what family system they were born into and what beliefs the family system carried. Because I can’t tell you how many cases get resolved when we do what’s called family constellation therapy and look at the entanglements of the forefathers and ancestors, and how those epigenetically got transferred down to the offspring. Very profound piece of work, I cannot emphasize it enough. And I encourage all functional medicine practitioners to get a very sound footing on the epigenetic transfer of family system trauma and the entanglements that can be inherited, completely silently, unknown consciously to the patient, only uncovered through work in family constellation therapy whereby certain methodology is employed to determine what these factors may be. So that’s number one.

Number two, I look at early developmental trauma patterns, and ego strength, and defense systems of a patient. And I employ a number of ways to identify that. The number one system that I look at is looking at defense structures of the patient and the ego strength. And you can tell after, you know, half an hour, is this person…do they have good ego strength? Are they resilient or they do have a fragile ego structure? And I send people for quite a lot of psychometric testing to establish some of these criteria.

I have a psychologist I work with who is able to help me with some of the psychometrics. And we even do, you know, some of the simple psychometrics testing, and even the Burns Inventory, the ACE Questionnaire. When we do qEEGs, we do the in-depth psychological assessment that’s provided by the CNS Vital Signs software to look at which of their psychological profiles are most dominant. Is it anxiety, OCD, is it depression, etc.?

So we look at that level of their development, the ego strength and their defenses. And then we look at early developmental trauma. And as you know from literature, people who have early developmental trauma have very different brain structures. They have, you know, very often this hugely enlarged anterior cingulate gyrus. They have in their beta, their fast brainwaves, there’s two to three standard deviations above normal. Their capacity to inhibit the sort of reptilian, limbic brain is diminished. And those are challenging patients, very challenging, and you have to address that level of healing.

This is not a biological intervention. There’s not much you can do biologically unless you identify what the core ego strength resilience of the patient is. How much projection of will the patient has? Many patients will sit in front of you, project the will to heal on you. And that’s a slippery slope. If they are not invested in sort of figuring it out on their own with you, you have a problem on your hands, you know. And patients will often project their early developmental trauma of parents on to you, whether it’s positive or negative. Best to have a positive projection in the beginning. But if you are the evil father that you get projected onto you, you’re in trouble.

So it behooves all of us as functional medicine practitioners to kind of try and identify, who is this person sitting in front of me, what did they inherit, how was the early developmental life? And then what defenses are they employing to keep away feelings they don’t want to feel? And I use a psychological technique called ISTDP. And I refer that out to somebody who’s specialized in it. That person I use is also very well versed in CBT. But CBT, without the underpinnings of the complexity of the presentation, can sometimes not stick. It can be very helpful to some, but for those who are fragile with projection of will, CBT will not hold. You can’t use CBT, it washes off them, you know, they won’t be able to hold that.

The next thing I do, I do NeuroQuant MRIs on everybody as well as a qEEG. And I look at the brain patterns and I can’t tell you how helpful that is. If you’ve got this high beta brainwave, and you’ve got maybe high theta brainwaves with not enough alpha, you’ve got work to do. And then you correlate that with the NeuroQuant MRI, and we look particularly for the amygdala upregulation. Many of these people with anxiety, OCD, and belief systems around the illness, who are multiple chemically sensitive and environmentally sensitive and are triggered by everything, will have a very…..the amygdala will be 2 standard deviations above normal, being like in the 97th percentile. The thalamus will be in the 97th percentile.

And the thalamus is rich in mast cells. So, when the thalamus is high, the amygdala is high, you want to ask about mast cell activation, and you want to ask about early developmental trauma. Because the amygdala gets increased in size when there’s repeated stresses on the fear-based part of the limbic brain. And if I see that, I often start inquiring about other techniques to downregulate the amygdala. And that we use DNRS, as you’re probably aware of the Dynamic Neural Retraining System.

We do refer people to that, we do neurofeedback, we do biofeedback, we do vagal tone stimulation. And we start to bring in the Porges polyvagal theory of, you know, sympathetic, parasympathetic dorsal vagal shutdown. And we try to work out where in this constellation of symptoms is this patient presenting? Are they in dorsal vagal shutdown with a rigid defense and sort of no will to get better? Are they getting secondary gain? That’s a very different patient from the one who’s, you know, loved by the parents, no developmental trauma, is loved and seen by a mother, develop appropriate right prefrontal cortex to self-regulate, has financial resources, is loved by the husband, the kids are doing well, they have a home to go to. This is how it works.

And we have to work out who are we sitting in front of when it comes to addressing some of these complex beliefs about, you know, is this a biological overreactive reactive mast cell syndrome, or is this a psychologically overreactive amygdala? Or is this person highly defended? Do they have the ego structure to take on what I’m about to tell them? It’s complex, as you know. I think that…

Dr. Hedberg: Right. And it’s a difficult situation for everyone because, you know, we don’t really get a lot of training, if at all, in all these things you just mentioned. So, we have to learn these things on our own, learn how to incorporate them. And then at the same time, present these to the patient in a way that isn’t telling them that you know, “This is just all in your head” or helping them understand that some of this could be due to your childhood and the way that your parents treated you, and all these kinds of things that happen. And I have done a few podcasts with some experts on adverse childhood experiences and things like that.

So, it’s refreshing to hear you talk about all these things, and it just creates a very complex picture on how to put it all together. And you know, like you said, they come to see you and they put all the burden on you for the healing. And then, you know, you come back with recommendations that, “Well, we need to work on your childhood trauma or your relationships,” and things like that. So, this is a very difficult, you know, condition to take on as a practitioner. I mean its massive amount of mental and emotional output that you have to take on.

Dr. Hoffman: Yes, one of the commonest words I see in the referrals back from specialists is this so-called, awful term, somatization disorder. And it’s just not true 90% of one of the most stressful diagnoses for one of these patients to get is the so-called somatization disorder but it’s often handed out. You know, and, “Yeah, it’s all in your head,” this is so awful. There may be a component that is filtered through the neurological pathways and then synapses. And they may tend to have an upregulated sensory system that processes things somatically. But it doesn’t mean to say that we have to discard this as all psychological, which is very often the insurance companies like to do things like that and some of the specialties too.

I recently referred a patient to a psychiatrist for insurance purposes and I sent five articles plus a written response. “Please do not diagnose this patient as being psychiatric, he has the following conditions.” And then we listed the mast cell activation, the mold sensitivities, electromagnetic sensitivities, etc. And I sent him five papers in support of the validity of this diagnosis. I haven’t heard back yet; I’m waiting to see what the response is. We often have to advocate for our patients in this way because they do present with neuropsychiatric manifestations, but it’s as a consequence, it’s not the cause. Although there may be some issues which provoked, you know, an expression of a mast cell disorder, but you can’t separate you know, mind-body, you’ve got to work with the whole continuum.

Dr. Hedberg: Exactly. Well, this has been really excellent. How would you like people to find you online, what’s your website and contact information?

Dr. Hoffman: The website is hoffmancentre.com. And the phone number here is 403-206-2333. That’s the phone number for my clinic. I do have a number of blogs on my website, and I post to Facebook and Instagram. But my website has a lot of the histaminic articles as blogs, so they can access them on there.

Dr. Hedberg: Excellent. So, to all the listeners, I have created a transcript of this conversation, which will be on drhedberg.com. So just search for Dr. Hoffman and you’ll be able to get the entire transcript there in case you missed anything. Well, thanks for tuning in, everyone. Talk to you next time. This is Dr. Hedberg, and take care.