The Cell Danger Response: Restoring Cellular Health with Phospholipids and Bioactive Lipids

I am always eager to learn from other clinicians about how they approach complex patients and layer various healing modalities into the therapeutic encounter. My guest today, Dr. Bruce Hoffman MD, has combined his passion in integrative medicine with psychiatry to explore cellular health to best guide his patient’s health journey. Dr. Hoffman is based in Calgary, Canada at the Hoffman Centre for Integrative Medicine and the Brain Center of Alberta. He’s an IFM-certified functional medicine practitioner, board-certified in anti-aging and regenerative medicine, certified in Shoemaker’s mold protocol, a certified Ayurvedic practitioner, certified in Bredesen’s ReCODE protocol, certified as a family constellation therapy specialist, ILADS trained for Lyme and co-infections, and trained in Chinese medicine, to name just a few of his substantial specialties. He knows his stuff. Tune in for this thought-provoking conversation as we explore the role the psyche plays in disease and healing, including clinical pearls, interventions, and effective supplementation. Listen, share, and leave a starred rating, if you wouldn’t mind! Thanks for listening. ~DrKF

How do psychiatry and chronic illness interact and what are the latest clinical tools to help support complex patients? In this episode of New Frontiers, Dr. Bruce Hoffman discusses the interconnected layers of his Seven Stages of Health and Transformation model and how he combines his training in psychiatry, Ayurveda, functional medicine, and other modalities to guide patients through healing generational family trauma alongside conditions such as autism spectrum disorder, Parkinson’s disease, Lyme disease and co-infections, mast cell activation syndrome, and postural orthostatic tachycardia syndrome. Stay tuned as Dr. Hoffman shares some amazing clinical pearls, his favorite diagnostic tools, and some of his most effective go-to therapeutic interventions.

In this episode of New Frontiers, learn about:

Dr. Bruce Hoffman, MSc, MBChB, FAARM, IFMCP is a Calgary-based Integrative and Functional medicine practitioner. He is the medical director at the Hoffman Centre for Integrative Medicine and The Brain Centre of Alberta specializing in complex medical conditions. He was born in South Africa and obtained his medical degree from the University of Cape Town. He has a master’s degree in Nutrition, is a certified Functional Medicine Practitioner (IFM), is board certified with a fellowship in anti-aging (hormones) and regenerative medicine (A4M), a certified Shoemaker Mold Treatment Protocol Practitioner (CIRS), certified Ayurvedic Practitioner, certified in the Bredesen ReCODE brain treatment program, certified MAPS (autism) practitioner,  certified in Family Constellation therapy, and ILADS trained in the treatment of Lyme disease and co-infections. He is the co-author of a recent paper published by Dr Afrin’s group: Diagnosis of mast cell activation syndrome: a global “consensus-2”. View full Bio.

• Special BodyBio Discount: NFFM listeners receive 25% off using code: NF25
• The Hoffman Centre for Integrative Medicine (podcasts & video)
• BodyBio Fatty Acid Report Information
• IGL Epigenetics Test
• Afrin study: Mast Cell Activation
• Shake recipe on Hoffman website
• PDF: BodyBio PC Full Spectrum Liosomal Phospholipids
• PDF: Balance Oil: Pure, Unrefined ALA + LA Essential Fatty Acids
• PDF: BodyBio Butyrate

Additional Studies:

• https://www.mdpi.com/2079-7737/8/2/27
• https://www.sciencedirect.com/science/article/pii/S1567724919302922
• https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.488.7646&rep=rep1&type=pdf
• https://www.sciencedirect.com/science/article/pii/S1567724918301053
• https://www.sciencedirect.com/science/article/abs/pii/S1388198102003281

• DrKF FxMed Clinic: Patient consults with DrKF physicians
• Clinician Professional Development: DrKF FxMed Clinic Immersion
• DrKF FxMed Nutritional Residency Program

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine, and today is no exception. I am delighted to be with a very longtime colleague, Dr. Bruce Hoffman. We’ve got an exciting sort of depth conversation planned for you today. Let me actually spell out why it’s going to be a deep conversation just listening to his extensive training will suggest where we’re going.

So Dr. Hoffman is a Calgary, Canada-based integrative and functional medicine doctor. He is the director of the Hoffman Centre for Integrative Medicine, also The Brain Center of Alberta, specializing in complex medical conditions. He was born in South Africa and obtained his medical degree from the University of Cape Town. He’s got a master’s in nutrition. He’s a certified functional medicine practitioner through the Institute for Functional Medicine.

He’s board certified with a fellowship in anti-aging and regenerative medicine. He’s trained in the Shoemaker Mold protocol. He’s a certified Ayurvedic practitioner. He’s trained in Bredesen ReCODE brain treatment, in the MAPS autism training. He’s a certified family constellation therapy specialist. He’s trained in ILADS for Lyme and co-infections.

He’s also a contributing author to the recent paper, which is available. In fact, we’ll link to it on our show notes, from Dr. Afrin’s group titled Diagnosis of Mast Cell Activation Syndrome: a Global Consensus-2. So mast cell activation is something that he’s also focused on. I actually also want to bring to your attention more, just kind of the rich depth. I mean, clearly, Bruce, you’re a lifelong learner, but I think you’ve really kind of taken these things in. I just want to give you a little more of his background.

He’s trained in Chinese medicine, and homeopathy, and German biological medicine. You almost went to get board certified in psychiatry. You wanted to be a Jungian analyst. I found that really interesting, Dr. Hoffman, in your history. And so you bring that to your work now with patients. So you did some of that training, even though you didn’t move into psychiatry, but you did some of that training. You worked with Jon Kabat-Zinn, with Deepak Chopra, with Dr. Klinghardt, with Ken Wilber.

I mean, first of all, welcome to New Frontiers.

Dr. Bruce Hoffman: Thank you, Kara.

Dr. Kara Fitzgerald: And what haven’t you done?

Dr. Bruce Hoffman: It sounds like I don’t have a life.

Dr. Kara Fitzgerald: It’s extraordinary, I want to spell it out. I know that you’re just doing this amazing work with your patients, and you’re fusing this intense training that you’ve undergone, and that you continue to experience into what you described as the Seven Stages of Health and Transformation. So it’s not like you do a weekend course and then the books go away, or the PDFs are put away.

I mean, you’re actually working with these tools and making them into something your own. And it’s called the Seven Stages of Health and Transformation. And I know that you’re working with very complex patients in Canada, and actually beyond Canada. I know people are drawn to your work from all over the place. And so, I want you to talk about the seven stages, and what your approach is to these complex patients that are coming to see you.

Dr. Bruce Hoffman: Yeah, sure. When I was a young teenager, I was exposed to a schoolteacher in South Africa who was very different. And he took us out of our sort of South African apartheid, white, privileged background and sort of threw us into … threw me in particular into an alternative universe whereby I was exposed to the world of psychotherapy, psychoanalysis and eastern thought.

And I had, at a very young age, an experience which they call satori, which is this sense of seeing space-time as a continuous whole and not seeing cause and effect as being linear. And it was a sort of … Many people have these. They are sort of called awakening experiences or high experiences. And that just sort of catapulted me into a different way of looking at things, and then initiated in me a curiosity about all aspects of the human psyche and human development and human potential.

And originally, I sort of got interested in Jungian psychoanalysis and wanted to become an analyst and went to med school only to become an analyst. And I was actually accepted into the psychiatric residency, but actually didn’t go through with it. I worked for two years in psychiatry in the military. I had to go to compulsory military training. But I didn’t actually do my residency.

And I do feel quite privileged in the sense that by not taking that particular route, I was able to keep expanding across all layers and levels of experience. And what I found was when I ended up just being a family doctor in rural Saskatchewan, and seeing the limitations of drug-based, which Majid Ali beautifully named it N2D2 medicine, name of disease, name of drug.

Once you start to see the limitations, and then you start to look at the potential of human achievement and what they can aspire to, one sort of moves out of just treating disease to trying to get your patients to look at optimal potential of their entire existence. And so, what I do now through the seven stage model is view pathology, or the so-called disease states or complex symptomatology, as this entry point into a dialogue with a patient.

But I’m also looking at other aspects of the psyche and the experiences to see what it is that their soul, if you will, is asking to come through. What is it that they’re trying to achieve? Symptoms to me are etiological. They’re sort of pointing towards hidden subjects that need to be brought to the surface. I never see symptoms as linear. I always think of them as what is the body attempting to do by throwing out these particular imbalances?

And with that approach, and using my early exposure to Ayurveda and Advaita, which is a system of Hindu philosophy that I was exposed to by the schoolteacher, and I was able to build a model called the Seven Stages of Health and Transformation, which looks at the human experience as being divided, which is a silly term, because there is no division. But it’s conceptually divided into these layers and levels of experience.

The first level being the outer world, the external environment. And that’s sort of level one in this conceptual field. And from that, we draw everything to do with what’s going on in the chemosphere, outside of ourselves, the toxicology and the infectious load. And we look at that from etiological point of view. That’s level one.

Level two is the physical structure, which is made up of biochemistry and structural aspects. And that is what we do in both traditional medicine and in functional medicine, and in all the structural modalities like chiropractic, and bodywork, et cetera. And then level three is to do with the brain, the peripheral, and the autonomic nervous system, and its electrical effects on physiology and biochemistry. And then what are the manmade EMFs effects on that.

And then level four is to do with the emotional body. And as we know, that many people have these adverse childhood experiences, which then get laid down neurologically in the brain as specific defects particularly in right frontal lobe development, and activation of the amygdala, and the fight-flight response with down regulation of the vagal nerve. And because I have this brain treatment center, you can diagnostically look at this and treat it accordingly.

And then level five is to do with ego development, how people negotiate the slings and arrows of this … The world is a tough place. We’re sort of always somewhat vigilant against the next thing that’s going to arise. And so, we develop in the first half of life a very different set of strategies from in the second half of life in terms of how we develop our ego, which is our sense of how we negotiate the world and our belief systems, our values and our defenses.

People grow up with a way of orientating themselves, but they also remain highly defended to those things which are most traumatic. And depending on early childhood experiences, defenses can be highly helpful or healthy, you could say. But they can also be highly pathological when people suppress anything that comes close to an early experience of trauma, and the so-called PTSD response.

So level five is everything to do with the ego and how it negotiates its way in the world. And the first 30 years are all about ego development and they’re characterized by certain drives, drives of the libido, drives of full power, drives to know oneself. And all the great psychoanalysts of the 19th century were very … They had great insight into these mechanisms.

But they’re now used therapeutically in a system called ISTDP, where psychologists look at different structures that people bring to the therapeutic encounter and work one on one with them in transference and countertransference to try and get behind that which they’re defending against and which is asking to be brought forward. So that level is very important.

And then level six is that what we call the soul. This is the most authentic part of who you are, the most instinctual part of who you are, which never really comes to any sort of conscious assertion until the second half of life, I would say. Carl Jung, the great psychoanalyst wouldn’t look at patients before the age of 40. He said they’ve taken up two drives. There’s no conscious awareness of their deepest self to work with. And so he wouldn’t work with anybody under the age of 40, which is rather strange, but it’s true.

Dr. Kara Fitzgerald: It’s very interesting in this anti-aging obsession that we have, isn’t it? I mean, clearly, there’s some wisdom, but keep going.

Dr. Bruce Hoffman: Yeah. So, in our personal, when we’re born and we’re born into our experiences, very often when you’re not seen by your parents adequately, and being seen by parent, you don’t have to be perfectly seen but a good parent who will always support and challenge a child accordingly. But if there’s any neglect or abuse and neglect-trauma appears to be even more traumatic to a child, an abuse trauma.

The child will develop a provisional self, an adaptive self to go out into the world in order to achieve what it’s meant to achieve. But the authentic self, the instinctual self will often go underground and then be hidden by these defenses and this comes up. I can’t tell you how many people present to me in sort of midlife … Midlife being anywhere from 35 to 55. It starts at somewhat of a younger age when entropy starts to set in.

And they are being driven to ask deeper questions of themselves and to reclaim those parts of themselves, which they know instinctively, they left behind in their pursuit of safety and being seen. So their provisional selves go out, achieve something in the outer world, but there’s something crippled and something quite damaged, or well preserved. Some innocence, well preserved, but it’s hidden from sight.

And people in midlife generally kind of know that. And they want to often go back and retrieve those hidden parts of themselves that they know are manifesting as symptoms, but they have no conscious connection with them. So part of the work I do is trying to find out what … I don’t ask this question out loud, but I’m asking it while I’m interfacing with a patient is, what are these symptoms telling me, and what does the soul want?

What is the innate wisdom and innate creativity of this patient that needs to be brought to the forefront? And that’s the fundamental question that sits there while I’m looking at all the functional medicine, toxicology, biochemistry, hormones, mitochondria. I’m always having these conversations in my head, what does the soul want? What is being asked of this person? What do they need to manifest in order to bring parts of themselves back home?

And that is the second half of life quest really, how do you gain your creative, instinctual self. And not only that, but there’s also another hidden part and that’s a hidden part of your family system. Family systems carry secrets and carry hidden entanglements that often manifest themselves epigenetically and get expressed through biochemistry as symptoms.

And I’ve done some marvelous work with, or I haven’t. But I’ve partnered with Mark Wolynn, who is an exceptionally gifted functional family constellation practitioner. And we looked at, once a year, we used to do a workshop where we looked at the symptoms of patients who came to my clinic and try to link them to any inner entanglements or the family system two to three generations before the patient is even born.

And it’s extraordinary what entanglements you find and what dynamics you find, which can manifest as symptomatology in the patient. And this research is very well established now to all the major universities, that there’s an epigenetic chapter of trauma through the generations. And then lastly, is spirit. The level seven is the spiritual body. And that’s the part of ourselves that’s transcendent to any ego-based space-time demands. And that’s where you surrender to some intelligence greater than yourself and just sort of stay open to that potential. And that’s sort of the whole realm of what we call the one mind beyond space-time.

So I use that model. So when patients present, I’m just trying to sense, they come … One of the great tragedies that I find, or one of the great challenges, not tragedies so much as challenges, is that when you become well versed in functional medicine, people will present and they’ll write in their entry forms. You ask them, “Why are you here?” And they’ll say, “Well, I’ve got mast cell,” Lyme or mold, and whatever.

And they will sort of have reduced their entire symptomatology to what they believe to be a lab test or a symptom that they’re experiencing. And it’s never the case. It’s never the case. Those are just inquiries as an entry points into a much deeper dialogue, in my experience. And so, I’m always curious. Yes, you may have a trigger called Lyme or a trigger mold and mast cells have gone awry. Yes, that’s true.

But really, what’s the deeper reality that we need to sort of work with? And sometimes I get to it, and sometimes I don’t. Sometimes I just treat mast cell, and Lyme, and mold and be done with it. But other times, not. Yeah, sorry?

Dr. Kara Fitzgerald: I mean, what an extraordinary entry into our conversation, thanks for all of that. I mean, it’s amazing. And I can just tell that you are sitting with all of these levels. And I think that, in functional medicine, they talk about gathering before the patient encounter.

Dr. Bruce Hoffman: Yes, that’s right.

Dr. Kara Fitzgerald: And I can hear that you’re gathering at all of those levels, which creates a possibility in the encounter. It’s been extraordinary. So is this written? Have you written about this? Have you-

Dr. Bruce Hoffman: Yeah, I’ve written. I’ve got podcasts with transcripts, and I’ve written a book, which unfortunately, sits on my laptop.

Dr. Kara Fitzgerald: You can link to it on our show notes then. I’m kidding. But it’s powerful. And, well, we’ll bug you about it so that we can link to what you’ve got available in our show notes. It’s an expansion on functional medicine principles in a very important way. So that was one question. And then the other thought that I was having and you started to touch on is, so the presentation, this phenotypic presentation of mast cell activation, or Lyme, and it’s true that our patients will come to us with pretty rigid ideas on this, and what it means.

And as you said, either you move beyond it or you don’t, and you address it and life goes on. But you alluded to in the beginning of your unpacking the seven stages, you alluded to sort of these as having information in and of themselves, like what kind of a … Is there kind of a personality type or somebody who comes with a certain type of a family constellation structure that might be more vulnerable to Lyme and co-infection or might be more vulnerable to autism or MCAS? And can you speak to that?

Dr. Bruce Hoffman: Well, the interplay is complex as you know, from genetics to diet, to sleep, to rest, to toxicology. And to ever increasingly, obviously, to early developmental experiences. I can’t emphasize how profound those experiences play on auto-expression of biochemistry. It’s unbelievable.

Dr. Kara Fitzgerald: I want to just say as an aside that I am with you on that. I mean, we’ve just published a study in looking at DNA methylation, so looking at the epigenome. And one of the things that’s just stopped me in my tracks is this idea of biological embedding, which is exactly what you’re talking about, where the signatures of the psychic experience are laid down on the genome.

Dr. Bruce Hoffman: It’s quite extraordinary. And if people come and they see me, say for mast cell, and then they find themselves doing acute EEG, and the NeuroQuant MRI, and doing neuropsych questionnaires and they go, “Why are you doing all this? I’ve got mast cell.” Well, mast cell is the expression of your, mitochondria undergo the cell danger response. They released ATP, ATP caused the granulation of the mast cell, and the release of a thousand mediators.

So yes, you had mast cell activation syndrome, but what’s underlying, what are all the triggers in functional medicine, the antecedents, mediators and triggers that provoked this mast cell to go crazy? The brain is the interface between one’s epigenetic and early developmental experiences, and one’s outer experiences. The brain is the interface, and if you look at acute EEG, and even a NeuroQuant MRI, you can read biographies of those. They’re so alarmingly informative.

And so, I look at a body-based stress assessment. I look at heart rate variability, as we all do. But then I look at acute EEG, and I look at this sort of juxtaposition of the delta-theta-beta-alpha brainwaves, and you can really see imprints of early developmental trauma. And you can see people who are stuck in fight/flight responses, people who stuck in Porges’ polyvagal, dorsal vagal responses.

You can see it right there in the biochemistry and the physiology. And you know that that person, say, who’s stuck in Porges’ dorsal vagal shutdown response, that’s a whole different patient and somebody who just got a few allergies. You’re dealing with a whole different kettle of fish there. And you can’t just jump right in and just do your normal functional medicine and try a few supplements … It’s a whole another experience, which you have to be sensitized as a practitioner to those layers and levels of complexity. And I use these tools to interpret it.

If you look at it and do a NeuroQuant MRI, you can see the amygdala hypertrophy at like 97 percentile. It’s like twice the size of the standard, the paired match group. You can see amygdala hypertrophy. You can see the thalamus hypertrophy, and the thalamus is rich in mast cells. You can see white matter being decreased, and so forth and so on. You can see all sorts of fingerprints of these complex triggers that can create symptomatology in these complex patients.

Dr. Kara Fitzgerald: Absolutely. It’s just extraordinary. So somebody comes in a typical allergy, seasonal allergy, maybe they’re bad, and so you’ll just treat them accordingly and get them balanced, but it’s relatively straightforward. But you’ve got somebody else also coming in and sneezy, allergic, et cetera, et cetera, but you diagnose this amygdala imbalance. I mean, you go down this whole different direction. Just roughly describe your entry into treatment with these two, with similar phenotypic but very different underlying causes.

Dr. Bruce Hoffman: Well, first of all, I don’t see patients anymore with just simple allergies. I wish I did. But those, I would just treat with H1 or H2 blockers, and Quercetin and vitamin C like all of us know how to do. But people with complex illness who have these multiple layers and levels of imbalances, I throw quite a large diagnostic net. I mean, I do a lot of tests. I’m criticized for it because of costs. But I also know myself well enough to know that without it, I’m going to be just another practitioner along the long chain of practitioners who took a little swipe at something and didn’t get much done, and didn’t look at the complex interface of all the different parameters.

So I do throw a large diagnostic net and do ask for the tests we know so well. Food sensitivities, gut microbiome, histamine levels, zonulin, DAO. I do all the mast cell mediator markers. I do all the ION panels and things like levels in methylation. I do all of that. I look at toxicology.

But I also do quite a lot with the brain, heart rate variability, autonomic nervous system functioning, and often refer for psychometric assessment to look for psychiatric diagnosis, whether they’d be cluster B personality disorders or whether they’d just be mood disorders. So I refer out for those. And I gather all this data. I also refer a lot to dentists and chiropractors particularly NUCCA chiropractors, visceral manipulation therapists.

We do a lot of diagnostics and trying to gather an insight into what hierarchically will be the entry point into this person’s therapeutic experience. I left out the most important, which is I look, apart from food and gut, which of course trumps most things. We look at the mitochondrial functioning and we look at the fatty acids because as you know, the mitochondria, the canaries in the coal mine, and they’re the first thing to sense any danger whether the danger is perceived or real, chemical or imagined.

And we have this credible capacity now through the IGL test in Germany to look at mitochondrial functioning and through BodyBio or the Kennedy Krieger fatty acid test to look at fatty acids. And those are the two tools that have trumped everything else in my practice.

Dr. Kara Fitzgerald: Wow, what is that? Tell me just briefly what the IGL is and then we can link to the … And the Kennedy Krieger and we’ll link to both.

Dr. Bruce Hoffman: So before this test came along, we in functional medicine would look at mitochondrial dysfunction, all we really had was a cheek swab. We had the organic acid test, but now we’ve got this ability to look into about 300 lab parameters that tell us the following: A, mitochondrial numbers, if they’re normal or if they are low in number. And mitochondrion, as you know, when they’re low in number, they must be undergoing some form of autophagy or cell death which ties into Naviaux’s cell danger response theory, that when we’re under threat, perceived or real, mitochondria start to self-destruct and release their ATP extracellularly, that then sends off a whole inflammatory cascade that oxidizes lipid peroxide, cell membranes and leads to this innate immune activation, mast cell activation, et cetera, et cetera.

Dr. Kara Fitzgerald: What’s the specimen? What’s the specimen for that test, sorry?

Dr. Bruce Hoffman: Blood. It’s a blood test.

Dr. Kara Fitzgerald: Both are blood tests, okay.

Dr. Bruce Hoffman: Yeah. So, it goes off and then they measure ATP production. They measure percentage of ATP that’s blocked. They measure cell free DNA. I mean, DNA that’s outside the cell shouldn’t be there.

Dr. Kara Fitzgerald: Where it shouldn’t be here.

Dr. Bruce Hoffman: They look at DNA adducts, toxins sitting on the DNA interfering with protein expression, interfering with the DNA expression of all the factors that go to make up messenger RNA and enzymes, et cetera, et cetera. It looks at phospholipid production. Phospholipids, phosphatidylcholine genome, most potent of all the cellular membrane ingredients.

It measures phosphatidylethanolamine, the phospholipid on the inner membrane which transfers electrons and the electron transport chain. It looks at outer phosphatidylcholine. It looks at cardiolipin synthase enzymes to see if they are making cardiolipin which is part of the inner membrane. It looks at whether you have what your amount of cardiolipin is so you’re looking at your phospholipids content.

It also looks at mold markers, markers for fungal metabolites. It looks at microtoxin metabolites. It looks at superoxide dismutase level. It looks at occupation of cell membranes. It looks at glutathione peroxidase, glutathione transferase. It looks at cell membrane voltage, incredibly helpful. When you’re looking at membrane voltage below 170 millivolts, it’s like 150.

And you’re looking at intracellular calcium excess or magnesium-potassium deficiencies. It looks at methylthionine levels. It’s incredible insight into toxicology and mitochondrial homeostasis. And from that, combined with the Kennedy Krieger fatty acid panel, which looks at your polyunsaturated omega 3, omega 6 levels, and it looks at renegade in very long chain fats and it looks to see if you’re myelinating adequately, et cetera, et cetera.

You can really transform a person’s biochemistry into something that ships them from this so-called cell-doubt, cell-danger response into a healthy response. And it takes an average four to six months of hard-work. But if you address the mental, the mind-body, the defense, the psyche and the biochemistry and toxicology in a hierarchical manner, and sometimes you got to stop biochemical work and you got to go work psychologically or even spiritually sometimes.

But if you start working with complex patients in this way, you’ll very soon know when to stop by a chemical work and to work at another level. If you’re sitting behind a desk and the patient is in front of you, and you’ve done beautiful biochemical work and you know that your work is impeccable and the patient is still sick, you know you’ve addressed the wrong level and it’s time to look at another level.

Dr. Kara Fitzgerald: I would imagine that you’re not … I mean, you said hierarchical, and I think that is true. But you’re doing it concurrently as well. I mean, you must be.

Dr. Bruce Hoffman: You always are. You always do it concurrently, but you learn to sense when it’s time to address, say, amygdala overactivity and vagal nerve shutdown as opposed to doing intravenous lipids and butyrate. Sometimes you’re doing all these beautiful biochemical interventions repeating the nutrition, food, gut and hormones and the patient stays resistant and/or hyperreactive.

And then you know they got an overactive amygdala and/or underactive vagal nerve. And so, you’ve got to shift focus and go down a different path. And just having done this for a long time, I’m sure you have experiences. You get to know when you probably are working at the wrong level.

Dr. Kara Fitzgerald: Yes, it does. This is such a simple thing, but in my residency, we don’t do IV therapy in my clinic here in Connecticut. We mostly do telemedicine these days. But in my residency, back when you and I used to talk, that was also in a clinic setting as well. And just that IV experience, I thought about it because I know you’re doing IV. We set up the environment to bring the energy down and so, even for those individuals who don’t want to hear it, that there’s a psychological component to their presentation.

There’s sort of backdoor ways to enter into that healing relationship or that healing, meeting the needs for healing in that space even when patients don’t want it.

Dr. Bruce Hoffman: It’s such a dance that goes on in this complex relationship between the so-called healer and the one who’s coming for your help. That if you’re not cognizant of the complexities that may arise, one can attempt to impose therapeutics onto a patient when the psyche is not intending to cooperate. It has no intent to allow that vulnerability.

And if you don’t know sort of the trauma of that person, the defenses, the fragility, the resistances, you can often rarely get into a difficult therapeutic encounter. And so it behooves us as healers, whatever the word may be, to stay very conscious of our own projections and our own inabilities and our own blind spots when we’re interfacing with patients.

And yes, they may have amygdala upregulation. They may be fragile and highly resistant. But does that mean that we get rid of them and say, I can’t help you anymore? Does that mean that we have to dig deeper into our consciousness to try and meet them where they are. And if we can unlock the door that’s previously been not open to them, we can assist in unlocking that door, there’s an incredible flood of therapeutic material and healing material that gets unleashed.

So I don’t like to do neuro biofeedback and amygdala training. If the psyche of that patient isn’t receptive to it, so it-

Dr. Kara Fitzgerald: Absolutely.

Dr. Bruce Hoffman: … a lot of conversation and a lot of negotiation sometimes around some of these issues. And people can remain hyper reactive and highly fragile and resistant. And that behooves us to just stay with that patient if we can until something shifts in the psyche and so often it does. Often it does.

Dr. Kara Fitzgerald: Yes, that been my experience as well that when they don’t achieve what they came to me to achieve or they get through some but not all, then perhaps they are open to a broader inquiry. I want to just ask, so I want to talk about, I want to get to your interventions. I know people will be very interested in how you’re addressing some of the mitochondrial issues that you’re seeing. But I just wanted to ask in your time and practice …

I mean, your practice now is self-selecting for challenging cases because you’ve been doing this for a long time and you’re just recognized as an expert, but are you also seeing sort of uptick in these kind of complex patient presentations?

Dr. Bruce Hoffman: It’s all I see now and sometimes, I wish it wasn’t.

Dr. Kara Fitzgerald: Right, I want to go back to insulin resistance case there.

Dr. Bruce Hoffman: Hormone replacement therapy, sure. But I am excited by the challenge. As you know, there’s no rest. I’m in my 60s and I don’t think I’ve studied more now. I mean, when I was a young medical student, that is nothing. This is boot camp all over again. You better stay ahead of all the research and all the latest series and all the latest issues that come across us.

But yes, am I seeing more complex cases? Absolutely.

Dr. Kara Fitzgerald: And there’s a change though, would you just say there’s sort of a change in the challenge of cases? I mean again, just going back to when you and I talked a lot, SIBO might be a challenging case. But those days seem …

Dr. Bruce Hoffman: SIBO is like one of 24 things that need to be looked at. As we’ve expanded our diagnostic possibilities and as new researchers have come up, Afrin and his mast cell activation syndrome along with the other writers and the other researchers, that’s thrown a huge level of insight into a certain presentation that we didn’t have 10 years ago. So, we have that and Naviaux’s mitochondrial cell danger response, unbelievable what that’s done to our consciousness as practitioners.

It just opened up … Now, before when we did functional medicine training, we learned about food, gut, hormones and nutrition. But now, that’s a subset within a subset of complexity. And that stuff, we have to know backwards, otherwise, we can’t get to anywhere. But what else do you bring to the table? And now, we’ve got to bring in all these other things, all these other factors into the healing relationship.

And it is far more complex. There are a lot more sicker people. And they are still looking for N2D2 solution. Even the ones who are educated, they will come and say, “I’ve got mold, Lyme, as I said in the beginning, and can you treat it?” I say, “Sure. But is that what you really have, or is that just what’s showing up as a presenting feature?” People come with false positive antibodies on Lyme test, and they say, “I got Lyme.” “Oh, it’s three on the Armin Lyme EliSpot. Is that really Lyme disease? Is that a false positive?”

And so you got to know all these subtleties. You got to constantly be in touch with the researchers and the lab directors and you got to listen to all the experts in our fields. You got to shine the light of the single aspect. And you got to know how to incorporate that clinically in patient because patients are smart now. They come with all their research.

Dr. Kara Fitzgerald: Yeah, they are.

Dr. Bruce Hoffman: And they know stuff and sometimes, it’s misguided. Sometimes, it’s spot on and they intuitively can often sort of guide a path that is previously hidden from you. They were often uncovered and helped shine a light down a certain pathway. People are smart.

Dr. Kara Fitzgerald: I want to talk a little bit about your approach. I mean we could look at mast cell activation or I mean, the mitochondria. The conversation I think is pretty provocative and one that’s interesting. I mean, are there core biochemical imbalances that you’re looking for?

Dr. Bruce Hoffman: Absolutely, yeah.

Dr. Kara Fitzgerald: Can you just talk about some of these? Let’s pull together somebody with mitochondrial dysfunction, like I want to just kind of pull together how you’re going to address it and maybe what you’re looking for in laboratory and other tools of evidence and then how you’re actually addressing it clinically?

Dr. Bruce Hoffman: Yeah. When people present their history, two, three-hour history, you do your biochemical workup. Take a very extensive dietary history. Usually get dental workup, get sleep studies, NeuroQuant MRIs, brain studies, et cetera. And once you have those in front of you, what do you do first of all? The first thing I do is always look, I use my traditional medical insight and I look at straightforward pathology.

Free T3 is low and the TSH is high, B12 is low. I’d look at straight biochemistry and I never bypass it. I pay very close attention to traditional medicine’s biochemical imbalances, and look at nutrition in great detail. And it behooves us now with all these complex illnesses to know all those approaches to nutrition that are out there whether it’d be GAPS or paleo autoimmune low histamine, et cetera, et cetera.

So, I look at traditional biochemistry. I look at nutrition and then I use nutritionist chef health coach, Justine Stenger, on our staff to take a dietary history and start to introduce a dietary approach which is commensurate with their presentation. And most of the time, it’s a paleo autoimmune low histamine diet, sometimes low FODMAPs, sometimes low oxalate. But generally, I find getting people off some of those major foods that are inflammatory and getting onto paleo autoimmune low histamine diet quietens the microbiome to an extent that we can begin to repair.

So, traditional biochemistry, nutrition, dietary approaches and then start to look at all the things that most functional medicine doctors look at. The food sensitivities, status of a gut, nutritional levels, macro and micronutrients, antioxidants, toxicology, heavy metals, chemicals, mold, fungi, mast cell activation in great detail, and look at hormone levels.

And I look at hormones in three distinct compartments. I don’t just look blood levels. I look at blood, saliva and urine all on the same day to look at the different compartments of how hormones are attached to transport proteins, how they show up at the cell surface and how they get metabolized through the methylation pathways. I’ll look at all three to start with.

And then I look at infectious agents, and I tend to do quite extensive infectious disease workups, both B cell and T cell assessments. I find if you just do T cell, do ELISpots, it’s not enough. And if you don’t do B cell, you often get very confused and go down the wrong pathways.

Dr. Kara Fitzgerald: What tests are you using? Tell me what tests are you using?

Dr. Bruce Hoffman: I’m using the ArminLabs. I do the ELISpot, and I use IGeneX. I do the IGeneX ImmunoBlots and I do the co-infection panels. I use Galaxy labs for the Bartonella. And I do also use MDL labs for some of the other infections, Garth Nicholson’s lab. Those labs are usually used to look at infectious load. And then, so once I had that diagnostic roadmap, and then therapeutically as I said, I’d correct any traditional metabolic imbalances, thyroid, hormone, whatever.

Dr. Kara Fitzgerald: So, you’ll start … So, you’ve got diet. And then you’re going to start them on some thyroid if they need it, some magnesium, some B12, et cetera. So, you’ll do those foundational first step?

Dr. Bruce Hoffman: Yes. And often if there’s great dysregulation in the qEEGs and/or in the stress assessments, and/or in the MoCA cognitive assessment or the CNS vital signs or TOVA, I’ll often start them in neurobiofeedback. I’ll start them on biofeedback programs and start them on neuromodulation techniques using different devices that we use from traditional feedback to Vielight to photomodulation. We’ll use different techniques.

So I often start those concurrent with food and traditional interventions whether it’d be hormones or nutrition. And if the toxic burden is extremely high, I never go ahead and start to detoxify them day one. And I never treat infections in the beginning. Even though Naviaux is very clear that unless you get rid of the threat, you’re not going to change the cell danger response.

So, I usually start out by using oral and intravenous lipid therapy or membrane therapy to try and provoke a mitochondria backing to more of a healing response. And I found that profoundly influential and help in patient outcomes.

Dr. Kara Fitzgerald: What is that?

Dr. Bruce Hoffman: I do a power drink or a membrane stabilizing shake, if you will, where we put into a blender phosphatidylcholine from BodyBio. BodyBio is the only phospholipid I use because of its very high phosphatidylcholine content, which doesn’t break down in the gut. And it contains the phosphatidylethanolamine. It contains all the subfractionations of phospholipids.

So, I use BodyBio phospholipids and BodyBio balanced oils, usually the 6:3 ratio and 4:1 ratio. You put that in the shake along with minerals and electrolytes and then any other ingredient that has shown up in the test that could be instrumental at restoring some homeostatic imbalance. So for instance, if they have low aminos on the ION panel, we use amino acids. If they have low glutathione, we use liquid glutathione as well as oral glutathione as well as oral NAC, all the standard things we learn as functional medicine doctors.

We put in tons of Resveratrol if we can. People tolerate it. And we use usually half a cup or quarter cup of blueberries. We found most people don’t seem to react adversely to blueberries. And then learning from Dr. Kharrazian, we chop up … On a Sunday, I advise patients to go and get every vegetable they like provided it’s not histaminic or oxalates or something on their testing shows they shouldn’t. Organic, chop it up, put it into the freezer. Every day in your shake, you take a couple of tablespoons or half a cup and you put that into the shake with the phospholipids.

And then that becomes a liposomal polyphenolic compound that then crosses the blood brain barrier and exhibits this antioxidant effect intracellularly. So, that’s been a gamechanger for my practice along with intravenous therapies. I start with very, very low dose phospholipids, sometimes vitamins and minerals just to provide the micronutrients for the enzyme systems, sometimes with intravenous amino acids.

But generally, I move over slowly but surely into phosphatidylcholine and glutathione intravenously, not to provoke a massive detoxification response but to try and repair cell membranes. Cell membrane repair is better done with oral phosphatidylcholine, but the IV phosphatidylcholine conjointly with the oral not only helps the cell membrane repair but it also starts to gently sweep adducts off the toxins that are sitting on the DNA of the mitochondria.

But it’s not aggressive. It’s very gentle. Later on, we start to use butyrate and other short-chain fatty acids to further the removal of adducts in toxins.

Dr. Kara Fitzgerald: How are you introducing those?

Dr. Bruce Hoffman: Intravenously and orally. I use them quite a lot. I use oral butyrate and IV butyrate quite a lot.

Dr. Kara Fitzgerald: What’s the oral butyrate? I mean, it’s kind of smelly, but in a capsule like in an enteric-coated capsule? What do you-

Dr. Bruce Hoffman: You can get different kinds. There’s the cal-mag butyrate. There’s the sodium butyrate. There’s sodium potassium butyrate. So, you got to look at the electrolyte balance of the patient and then introduce the specific butyrate formulation that is going to be most helpful for that person’s biochemistry.

So, if they’ve got intracellular calcium deficiency, you’re going to use the calcium one. If they have POTS syndrome … By the way, that’s one of the greatest. One thing I learned 10, 15 years ago was to make sure every patient does the 10-minute, cheap, lying standing test. If you misdiagnosed POTS, that patient is never going to get better.

And I know you’re familiar with it but I do suggest that any young or new practitioner, just get yourself an Omron blood pressure cuff. Every patient that comes in your door, lie them down, do their blood pressure and their pulse after they’ve laid down for a minute or two. Stand them up one minute, three minutes, five minutes, 10 minutes, look at their blood pressure and pulse and look for drops in systolic blood pressures and look at rises in pulse rates.

And those patients don’t perfuse the mitochondria or the brain and they won’t improve until you get increased perfusion to their cellular structures into their brains. They just won’t. You have to treat that first.

Dr. Kara Fitzgerald: And are you addressing it with this protocol?

Dr. Bruce Hoffman: I address that with the standard POTS approaches with increased fluids with salt, a lot of salt, two to three teaspoons of salt. Salt sticks compression stockings and I liberally use Florinef and Midodrin and other medications. And it’s a gamechanger. It’s absolutely a gamechanger in certain patients.

And many people are misdiagnosed. There’s a combination of sort of different … You can get orthostatic hypertension. You can get postural orthostatic tachycardia syndrome, and you can just get pure tachycardias. And they’re different and if I need to differentiate, I send them to cardiologists.

And we have one particular one in our city who does tilt table testing. He’s written lots of papers, very experienced. And so we refer to him to sort of introduce further medications if need be. And patients always know about the triad of dysautonomia and mast cell and gastric motility issues. Many patients present with mast cell activation, POTS, and Ehlers-Danlos syndrome with dysautonomias and gastric motility issues. And they’re called triad or pentad patients as per Afrin’s group.

Dr. Kara Fitzgerald: Why are we seeing more of these people?

Dr. Bruce Hoffman: I think the stresses imposed upon our modern society are overwhelming our defenses. We just become extremely vulnerable to this incoming toxic load. We’re not genetically resilient enough to withstand this onslaught, whether it’d be electromagnetic fields or chemicals or foods. Even the fact that we could open the fridge five times a day, eat what we want, I mean that’s a stressor on our system, it’s unbelievable.

We’ve got out of sync with our innate biorhythms and there’s been a huge movement in the functional medicine community through biodiversity and regenerative agriculture. And we’re paying lip service to this need, but I don’t know. I think our DNA and I think microbiomes will eventually adjust to these incoming onslaughts. I don’t think we’ll be extinguished. It always appears that stresses on the system create greater resilience down the line and barring a sort of huge six apocalypse. I think we will become more resilient as we sort of evolve through this toxic phase that we’re going through.

But right now, I think we’re very vulnerable and we are under a lot of stress, under a lot of toxic load.

Dr. Kara Fitzgerald: Well, we’re kind of heading towards the end of the podcast. This is to clinicians, and so this is going to create a lot of interests in your approach to care. I guess I have two questions. One is, where do people learn more about this model that you’re working from? This sounds so powerful, and I certainly appreciate you’re casting a very wide net and people are coming to you because of that and so forth.

But as you described such a careful start to the journey … By the way, we’re going to try to piece together that shake recipe. That was so awesome. We’ll put it on the show notes, people. It’s just the most sophisticated shake yet, so I want to see if we can pull that together and put something on the show notes.

But I mean you must be seeing some pretty good outcome just after this evaluation and you’re pushing the ship from the shore. I mean you must be seeing some good change. And if not, I’m sure you’re just really going back to rethinking.

Dr. Bruce Hoffman: I don’t have a research assistant in my office, so it’s hard to know outcomes. One believes that one’s practice is achieving remarkable outcomes, but I think unless you have a statistician in there, a hardcore research, we’ll never really know. But what I’ve noticed … By the way, a lecture I did is on my website. I lectured to the ICI Conference and it’s on my website. We are doing one and a half hour synopsis of the seven stages.

Dr. Kara Fitzgerald: Okay, perfect.

Dr. Bruce Hoffman: I think it’s the most insightful sort of snapshot of the levels and layers and complexity that’s possible. So, the outcomes we have from what I can tell, because one never really knows the drop-off rate. I don’t think it’s very large. When patients present with complex illness and you do your due diligence and you throw the net far and wide and the patients can keep up with it, and many patients can because they’re so educated and so driven, they’re so sick and tired of seeing hundreds of people and not getting any better.

And you’re looking at your data and you’re looking at mitochondrial function and fatty acids function and ION panels and things and you do repeat them from time to time. It has been my experience that within six months on average, on average, the test itself reverts from highly problematic to restored function, the IGL test. You will see mitochondrial numbers go from low to normal. You will see phosphatidylcholine go from extremely low to normal. You will see glutathione levels come back. You will see microbial toxins disappear. You will see mercury, lead, cadmium, glyphosate levels disappear.

But concurrent with that, the patient will tell you, “I feel completely different.” And we keep objective, we do different score systems. But I use the old MSQ from IFM. And patient’s levels drop from 180 to 20 once you start working from the mitochondria outwards into the whole complexity of the mind-body and familial inherited system. If you start using a broad map and you just don’t run down too many rabbit holes, and you keep your head above you and you just work it through. And if you hit the blank wall, you just ask more questions. You don’t give up.

Somewhere along in that experience, the patients, they feel better, their symptoms improve and they move through that cell danger 1, 2, 3, into the cell danger 3 response, the healing response. And they feel amazing. We have a large amount of patients who do experience that once they’d gone through their process, but we always preface it with, “Look, this is only as successful as the amount of effort you put in. If you stay passive, there’s nothing we can do. You have to be a cooperative partner in this experience. If you have side effects, you don’t throw baby out with the bathwater. You come to the table. We find out what happened, and you work through this process. And if you can’t, you get yourself somebody, an advocate, who can help you.”

In that sort of dynamic and with the staff, the great staff I have and the support systems and the ability to rerun lab tests from time to time, I would hazard a guess that the majority of our patients get better, the majority. I wish I had the statistic to tell you, but I don’t.

Dr. Kara Fitzgerald: Maybe now is the time to get a PhD student in your practice. It would be really nice to gather. I know you’ve been at this for a long time. It’d be nice to maybe get some data.

Dr. Bruce Hoffman: I think I should, yeah.

Dr. Kara Fitzgerald: Yeah, get a student, that good PhD work. Well, Dr. Hoffman. It was just really lovely to connect with you and talk about this. Folks, we will gather as much as we can for the show notes and link over to the site to some of the content that he’s referencing. And if you think of anything else, just let us know. Thanks for joining me today, for this really nice dive into what you’re doing.

Dr. Bruce Hoffman: Thanks, Kara, and nice to speak to you again after all these years.

Dr. Kara Fitzgerald: Right, absolutely. And hopefully, I’ll see you in person at AIC, not this year but next year.

Dr. Bruce Hoffman: Yeah, maybe, who knows? I quite enjoyed this sort of remote telemedicine, teleconference …

Dr. Kara Fitzgerald:  Thank you kindly, for your time. Much appreciated.