When it comes to testing, you can always count on a lively debate about how to best identify food sensitivity and intolerance. In this interview we review recent clinical and mechanistic research on the ALCAT test, including studies conducted by Yale School of Medicine and other institutions. In addition, general advice will be given about how food testing can help integrative practitioners create personalized diets for health and performance for their patients.
Approximate listening time: 38 minutes
About the Expert
Roger Deutsch is the CEO of Cell Science Systems, where he oversees research and general management. He has been involved with all aspects of the development of ALCAT technology for 34 years. He previously studied psychology at the State University of New York, Purchase and Chinese medicine at the International College of Oriental Medicine in the United Kingdom. He is coauthor of the book, Your Hidden Food Allergies Are Making You Fat, and has lectured in more than 25 countries on the topics of food, inflammation, and the aging process. He is deeply involved in supporting free education for impoverished girls and free healthcare in rural India.
About the Sponsor
Cell Science Systems, Corp (CSS) is a CLIA licensed lab and an FDA registered medical device establishment that has developed the ALCAT test for food and chemical sensitivities, as well as GI function assays, telomere length assessments, molecular diagnostics, and this month will also be launching cellular tests for the assessment of functional micronutrient deficiencies and antioxidant status. CSS received the company of the year award in 2016 for Food Intolerance Testing, North America, by Frost & Sullivan.
The ALCAT test has been clinically validated in research at the Yale School of Medicine, where mechanistic studies were also conducted. Those studies have led to new discoveries regarding the pathogenic mechanisms underlying food sensitivities.
CSS will continue to participate in industry grant–funded, cross-border, translational research that focuses on the role of food-induced release of DNA and its role in pathology. CSS is located in Deerfield Beach, FL, and also operates a wholly owned subsidiary lab in Potsdam, Germany.
Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, our topic is Identifying Food Sensitivity and Intolerance. I'd like to thank Cell Science Systems, who is the sponsor of this topic. My guest is Roger Deutsch, who is one of the pioneers in the field of food and chemical sensitivity testing. Roger, thank you so much for joining me.
Roger Deutsch: Thank you, Karolyn. Pleasure to be here.
Gazella: Well, historically, it's been kind of challenging to identify food sensitivities and intolerances in patients. Generally speaking, I'm just wondering, why is that? Does the research you've participated in offer any new understandings?
Deutsch: Yeah, the research that I've been involved in certainly does offer a lot of new understandings. Just to put this in context, and just to review, I'm sure most people are very clear on this distinction between allergy and intolerance. Just for sake of brief review, the term allergy was coined by a physician named von Pirquet in 1906 to denote an altered reaction. Then there was quite a bit of debate amongst allergists in Europe during the '20s and '30s as to what should be included in that definition of an altered reaction.
At the end of the day, they settled on including only those types of reactions that induced an immediate symptom onset, because those are more definable. Just through some research in the '30s where they transferred serum from an allergic patient to a non-allergic patient and then scratch test the area where the serum transfer took place, and they would induce the wheal-and-flare. They knew that there was some factor in the serum that caused allergy. They didn't know what it was. They called it reagent. Then, years later, in 1969, they found out reagent was IgE. Then they found out all the events that were preceding the IgE molecule and then how the IgE molecule bound to mast cells and then cross linked, which caused degranulation and release of histamine and immediate symptoms and so forth.
Later, interestingly, they found out that's the same pathway the body uses to protect against infections with worms. So they called that allergen. Of course, worms are large compared to a cell, so when the immune system has to combat such a big pathogen, it's a very dramatic reaction, so there's a very dramatic release of histamine. The symptom onset, then, is very dramatic and very rapid. Then that being as clear as it was, by contrast, intolerances or sensitivities due to an enzyme deficiency or some other part of the immune system, the innate immune system underlying a sensitivity was more difficult because the symptom onset wasn't immediate. The linkage between cause and effect was ambiguous, obscure, and the pathway was unknown, so what do you look for?
A lot of different things were proposed. Before too long, people proposed looking at the white blood cell. In the 1950s, an allergist in El Paso named Black reported his usage of looking at white blood cells through a microscope, being challenged with an allergen and seeing morphological changes that then were correlated with clinical symptoms. Then that work got picked by some researchers in St Louis at Washington University named, gosh. I forgot what their name is. I don't know. It will come to me later, but anyway, they gave it the name cytotoxic test. They published about three or four papers, and it became very popular and broadly used. There was a lot of political upheaval because it's something that came on that proposed a solution to a lot of problems. People don't like huge paradigm shifts, so it fell a little bit by the wayside.
We knew that there was a white blood cell component to the thing, which is logical. The immune system would underline an immune reaction. It's no mystery. When we came along, we thought, "Look. The allergists don't like the cytotoxic test." Bryan was the name, William and Marian Bryan brought out the cytotoxic testing. Allergists get upset about it, because it maybe changes the paradigm in ways they were afraid of. It was subjective, because it required a technician to look at cells under a microscope and make a judgment call as to whether or not there was a reaction. We came along in that period of time, in the mid-'80s and applied electronic instrumentation to the measurement of the cells and introduced some other standards, better controls over the allergen presentation and used the computer to interpret the degree of change in the white blood cells. We went along quite a long time observing and making the clear association that when the white blood cells would expand or degranulate or didn't become lysed, now we know undergo apoptosis or necrosis or pyroptosis, there was good clinical correlation.
We did studies in the late '80s with people who were pioneers, and had backgrounds in research and drug companies even that were interested in this field. We found that when you had an ALCAT, the name of our technology was ALCAT. When you had an ALCAT positive and if you challenged the person with the food that was positive under double blind conditions, you would get correlation about 80% of the time. When there was an ALCAT negative, you would get correlation, in other words, no clinical response from a double blind challenge, about 85% of the time. That was good clinical validation. It was building the mechanism. If you fast forward to earlier this year and last year, there had been a number of clinical studies in between, of course, but we gave the technology to be investigated to some very smart people at Yale School of Medicine.
They did a clinical study that they know how to do, a randomized, controlled, double blind, placebo-controlled trial, feeding patients either a diet that was based on the ALCAT test, eliminating positive foods or placebo group, and nobody knew who was in what group except the one coordinator who didn't tell until the end, a placebo diet based on an ALCAT test where they kept the positive foods in. They just looked at change in symptom scores over time. They saw a huge difference between the people following the true experimental diet versus the ones following the placebo. Then they looked at some chemistries. They actually banked serum at the beginning of the study, knowing that retrospectively, they'd see who had done well. Then they could go and evaluate what might have happened amongst that population that had a strong response.
They did find that, out of about 1,200 or so peptides and proteins that they assayed, that neutrophil elastase would drop precipitously in those people. Clearly, the neutrophil seemed to have some effect. They went on and did some look into what's happening inside the cell, and which subtypes of leukocytes were most involved. They did immunological studies using flow cytometry and they found that eosinophils were activated most of the time. Neutrophil elastase was being released, so obviously, there was some orchestration between these two classes of granulocytes, but the other thing they found, which is very interesting, is that there was greater release of DNA from the cells that had reacted in a positive way than there were, excuse me, reacted to a food that was tested as positive versus when there was no food in that sample or an ALCAT-negative food. Somehow, the positive reaction would induce the peripheral leukocytes to undergo some sort of process that would result in the release of toxic mediators like neutrophil elastase and others, but would also cause a release of cellular DNA.
That's an interesting finding, because over the last few years, most people are not familiar with this yet, but common sense tells you DNA doesn't belong outside the cells. It belongs either nicely tucked away in a eukaryotic cell in the nuclei or in the mitochondria. When it gets out, it can cause problems. We could talk all day about how it gets out, but there's some very smart research from Max Planck Institute, which shows that these neutrophils and macrophages and other granulocytes used, as a strategy to kill pathogens, something called ETosis. When it applied to neutrophils, it's called NETosis. Even after this cell has released mediators, generated free radicals, then it's to try and defend against invaders. Even though the cell is dead, a lot of the nuclear material, the histones, the DNA, merge with granules and the toxic mediators inside and the plasma membranes and the internal membranes and strip out, form these nets. That can trap pathogens, and the DNA is toxic, and kills them.
That's a good thing, but if too much of this goes on and the body's mechanism for cleaning up the mess, which is mostly DNA's one, and you have the persistence of this toxic DNA in the circulation, excuse me. It causes all sorts of problems, like metabolic problems, like lupus, like arthritis, and even cancer. It's a new area of medicine, so it's interesting. We've found that the ALCAT test predicts the foods that trigger the release of DNA. Now we have the next step ahead of us, using a grant that we received from one of the larger industry players, we're going to characterize the nature of the DNA that's released, because the nuance here is that if the DNA is methylated, it's not toxic. If the DNA is unmethylated, it is very toxic. We want to look at that. The expectation is that we'll find that it is mostly unmethylated, because the release of DNA is kind of chaotic and not controlled.
Gazella: That is fascinating. I have you tell you, you're talking about the 2018 study that was published in Alternative and Complementary Therapies?
Deutsch: No, this study was, it came out Yale.
Gazella: It was earlier this year?
Deutsch: Yeah, I can't remember the actual name of the journal right off the top of my head.
Deutsch: If people go on to CellScienceSystems.com, there are a couple of papers from Yale. The first one I spoke of was a clinical paper. That was published in BMJ Gastroenterology. The other one was another nice, international journal.
Gazella: Great. I do want to talk about the study that was published in Alternative and Complementary Therapies, but I want to stay on this topic that you just introduced, because honestly, it's fascinating to me. I think our readers will find it fascinating as well. Right now, can we draw clinical conclusions that ALCAT can be used to predict which foods might increase the release of potential unmethylated DNA, or is that down the road? Is that a clinical application right now, or is that something that is down the road?
Deutsch: I think the clinical utility has been established a long time ago from the studies from back in the late '80s where they did these double blind and placebo-controlled oral challenges very carefully and found overall efficacy of the test at 84-plus percent. There's been other studies, one that you just mentioned that also came out in last month's Complementary and Alternative Medicine with some work done at University of Northern Illinois. There, of course, they found some other pathways and some other mechanisms. They found that Serum Amyloid A, which is reflective of overall body inflammation, also drops precipitously in people who have clinical improvement when they alter diet based on ALCAT, much more so than control groups, where you have blinded sham diets being implemented.
Another validation just came out last week. This was on European Society of Clinical Nutrition and Metabolism. There was a group from the University of Pavia, which is northern Italy. The University itself was established in the 900s or the 800s. It's a very old institution, very well-respected in Europe. They found that with respect to gluten, isolated gluten, the 33-mer peptide that you can buy from chemical companies that are used in a lot of tests, some tests, and gluten-containing grains, wheat, oats, barley and rye, that the ALCAT test and double blinded placebo-controlled oral challenges with gluten and gluten-containing grains was also very highly correlated. They proposed, at the University, that ALCAT actually be used as a new diagnostic criterion for non-celiac gluten sensitivity.
Gazella: Yeah. There's a lot of solid research showing the clinical efficacy of using the ALCAT test. That's what I'm hearing from you regarding the research that's been done up to this point.
Deutsch: Yep. It's pretty clear.
Gazella: Great. Good. I want to step back a little bit. How common are sensitivities and intolerances to specific foods?
Deutsch: That's always a challenging question, because we don't have a clear-cut definition. Intolerances are generally induced by a lack of an enzyme to break down some component of a food, and we have an adverse reaction that may not be that severe, so lactase deficiency can induce lactose intolerance. If you bring those in, but then you get into the more nuanced types of intolerances where there's a chemical that is naturally occurring in a food or could be added in processing where the person lacks the enzyme to break down that toxin. Again, keeping in mind that all plants produce natural toxins in order to defend against pests. Nowadays, I think we see the inability of individuals to break down some of those toxins and the innate immune system comes into play, because we're increasingly depleting and compromising our ability to detoxify. Again, because of some overall changes in diet and how food is produced, the industrialization of farming and so forth.
You might find that because the body is not as efficient as it should be, breaking down a toxin the food with which the person has not had, through his ancestry, the development of those detoxification pathways, that if they have a little bit, it's okay. If they have too much, it becomes a problem or if it's the wrong time of year and there's too many other co-factors or they visited Mexico and have a disruption in their diet, then they have more of an issue with it. It's not as clear-cut as, say, an allergy where just a few molecules of the offending substance can trigger a very dramatic response. It actually gets amplified by things like Substance P in the body and spreads out, because it's a whole different pathway and a whole different animal entirely. It depends how you want to try and define these intolerances and sensitivities.
People fluctuate, depending on season, detoxification pathways, intestinal permeability, overall level of health, cofactors and so forth. If you are comfortable with a generalization, I'd say that it's very rare. We have found some, but we've had to look hard. It's very rare to find a person who doesn't have any sensitivities or intolerances. In how many? Again, it depends how you operationally define them, but it's highly relevant. It underlies a lot of inflammatory problems, metabolic syndrome and all the health issues that can come from that. It's extremely common, but I don't want to put a number on it, because we're all guessing.
Gazella: Yeah. That's interesting. It's rare to find someone who doesn't have a sensitivity or an intolerance. That's a pretty big statement. I'd like to talk specifically about celiac disease and non-celiac gluten sensitivity. Tell us about testing regarding those issues.
Deutsch: Celiac disease is an autoimmune disorder where cytotoxic T lymphocytes attack the enterocytes in the small intestine. In order for that to happen, the T lymphocytes have to recognize the allergen or trigger. The trigger, it's not really an allergen. The trigger is gluten. It's presented to the T lymphocyte by an antigen-presenting cell, mostly dendritic cells, which absorb the trigger, break down the peptides internally and lysosomes, transport it by an MHCII molecule to the surface where if there are T cells that recognize that complex, will become activated and may lead to celiac. Celiac depends upon the ability of the T lymphocytes to recognize the combination of that MHCII molecule with the gluten and gliadin peptides. If you're not genetically, if you don't have the genes to produce that specific variation of an MHCII molecule, you can not get celiac disease, so the tests for those genes, which are human leukocyte antigen DQ2.5 and 8. They're very easy to test through PCR. We also do that testing. That test has phenomenal negative predictability. If you don't have those genes, you cannot get celiac.
However, you could still have an adverse reaction to gluten, which is not mediated by the T lymphocytes and that pathway, but it is a function of the innate immune system, which means neutrophils, eosinophils, mostly neutrophils. That's what we call non-celiac gluten sensitivity. That's what they studied in Pavia and found that the ALCAT test is measuring the activation of the granulocytes, which are mostly peripheral granulocytes, mostly neutrophils. The same thing was seen years ago with Fasano and his group, working with the people at NIH in leukocyte biology labs where they challenged with gluten in experimental animals in transgenic mice whose neutrophils would glow when they became activated. They saw all this activation. It's the same pathway, but it goes further in those people who are genetically predisposed. If you go past the first lines of defense of the innate immune system and reach into the specific immune systems, T lymphocyte population becoming active, that causes the real problem.
Gazella: I see. ALCAT is actually effective for both food sensitivity and food allergy.
Deutsch: I wouldn't say it's effective for food allergy, because I wouldn't call celiac disease really a food allergy, because there's no IgE molecule. Again, the allergists only like to use the word allergy when there's IgE involved or there's an immediate symptom onset. Here, you do have other immunological reactions, more like a Type 4 reaction, whereas an allergy, in the Gell and Coombs system, is a Type 1 reaction. ALCAT will let you know whether you're going to have a problem with gluten. Exactly how that problem will manifest will depend upon many factors, your genetics and also your microenvironment, your ecology in your gut. The ALCAT will tell you both those issues, but not what we call a true food allergy with a Type 1 type of reaction.
Gazella: Right, okay. Good point. Good clarification. Let's dig into that 2018 study that was published in the Journal of Alternative and Complementary Therapies. Can you describe the objective, the method, and the outcomes of that study?
Deutsch: Going from memory, I don't have that in front of me. It was basically, again, a double-blinded, randomized trial looking for improvement in symptoms that are typically related to sensitivities, food sensitivities. We were looking at various inflammatory conditions where the control diet was, again, a sham diet where foods were taken out, but they were not ALCAT test positive foods. The test subject didn't know that their new diet instructions were excluding ALCAT test positive foods or ALCAT negative things. Then just looking at the outcomes and some biomarkers, and specifically Serum Amyloid A and body composition. There were differences seen that were pretty distinct between the two groups. There was a much greater improvement in the symptoms in the report, which is also on our website. It was, again, the University of Northern Illinois.
Dr Lukaszuk led the research project, showed that there was much greater reduction in symptoms amongst the people who were following the ALCAT test and the significance was significantly high. It wasn't something that could have happened as a function of genetics. There was a very sharp drop in Serum Amyloid A, which a lot of people are beginning to look at more than high-sensitivity C-reactive proteins as an indicator of total body inflammation. It puts together a nice picture of that. Biochemistry is changing. The immune system is less reactive and people are improving body composition and reducing their symptoms.
Gazella: Yeah. It sounds like you've got some great research going on, but I'd like to talk a little bit about the future. Can you tell us about cellular technology for identification of functional nutritional deficiencies?
Deutsch: One of my favorite topics. I used to live in Austin for 14 years. During that time, there was a lab. There was a charitable organization named the Clayton Foundation that backed a researcher of Experimental Biology Department, University of Texas in Austin named William Shive. William Shive was a protégé of a gentleman who wrote the book in the 1950s called Biochemical Individuality. That book basically explained that we're all quite different, and his experience was that he went in. Prior to the 1950s, he went in for a surgery the night before. They gave him morphine to help him sleep, and it kept him awake all night. That kind of reaction caused him to think over about how we're all a little bit different. A paradoxical reaction like that was quite pronounced. He did a lot of research just in animals and humans, looking at how we're different, and extended that concept to the idea that nutritional needs are also unique.
In the 1970s, a group basically challenged, recognized that we needed, as a profession, to have a test for nutritional deficiencies that took into account individuality. William Shive was proposed as the person to help develop it because of his knowledge in the field. He got backing from the Clayton Foundation. The Clayton Foundation, by the way, was a gentleman named Clayton who was in partnership with MD Anderson there in New Orleans. They would support research in nutrition and cancer. One of the things they did was to try and recycle the funding. As soon as something was developed, they would try and commercialize and monetize it, license it out, and recycle those funds for new things, because philanthropists want to see more and more benefit happen.
I got to know Dr Shive, and he was doing his evaluations in using the classical way of looking at lymphocyte proliferation, using incorporation of radioactive [inaudible 00:29:27] into the DNA and then extracting that after five days and measuring radioactivity and therefore inferring how much new DNA there was, what DNA synthesis levels occurred and being able to infer growth of lymphocytes, which we spoke about before. When they were stimulated by a mitogen, where a mitogen could be a plant lectin like phytohemagglutinin, which would universally induced EMD cells to multiply. Remembering here what I was speaking to you about the difference between gluten sensitivity and celiac disease. Celiac disease is, again, involving T lymphocytes, meaning it's a function of the specific immune system, so only certain T lymphocytes will recognize a pathogen's peptides being presented to it, and others won't, which is why it's not really a great test for looking at particular allergies because there's too much background noise. 99% of lymphocytes don't react to a pathogen, but 1% of them do.
After an infection or during an infection, a small number of lymphocytes that recognize the pathogen will divide in the circulation and in the lymphatics and multiply themselves, which is obviously not something that granulocytes to. He's stimulating lymphocytes with a mitogen. You want them to divide, because the ability of these cells to divide and clone rapidly enables you to produce the antibodies and the lymphocytes that will kill the pathogens. What they need to divide are nutrients. If you stimulate them, and they divide very slowly, you might look at adding nutrients into the culture. There was research done on that in the 1930s where people would take mold spores and radiate them and see that they no longer would divide. Then they one by one added back specific nutrients to see what would restore metabolic machinery. In fact, a group from the University of Chicago got a Nobel prize for that in 1958, so the idea was out there that lymphocyte proliferation could be a good marker for measuring a functional response to changing nutrients in a culture.
My early discussions with Dr Shive were, "Dr Shive, the concept is great, but why are you using this old-fashioned method that involves radioactivity if you want to count cells?" Use a cell counter. He agreed. We started to do some work together. Unfortunately, Dr. Shive passed away, but I always was fascinated by that area, and continued to work on it for maybe 15 or 20 years, looking at using cell counters to measure lymphocyte response when stimulated with a mitogen when you alter the culture medium to add another nutrient, one by one. If you found that the adding of the nutrient induced a more robust lymphocyte proliferative response, you can infer that for whatever reason functionally, that nutrient was not at optimal levels, and there should be repletion of that nutrient through foods that contain it or even supplementation.
After many years, we kind of looked at that, but we thought that even a cell counter, we're in the cell counter manufacturing business. Some people don't know it, but we're a CLIA lab, and we do these tests, but we also build cell counters and sizers that are used in our tests, because we want them to do very specific things. We found that there were other methods that we looked at that could be done more rapidly and more simply, and correlated with the cell counts. We've been validating that over the last couple of years, and we're actually going to release that testing this month, in January, to look at the levels of improvement of specific immune function when you add specific micronutrients to cell cultures. We're also looking at doing the same kind of testing under conditions of oxidative stress to see which antioxidants improve the survival of the cells when there is an oxidative stress situation going on.
Gazella: That's awesome. There's a lot of integrative practitioners who are interested in that type of personalized medicine. When you say it's available in January, is it clinically available to practitioners in January?
Gazella: Awesome. That's great.
Deutsch: Yeah, we're making it available.
Gazella: I have one final question. I've been researching Cell Science Systems, and it seems like it's not just about delivering a test for your company. It's about helping clinicians personalize the diet for their patients, but then providing support regarding compliance and sustainability. Why is that so important to your company?
Deutsch: Our company is here to help. I've done this for coming on 34 years now, and I had health problems in my earlier years. I worked through it. I was an athlete as a kid and all that, played on teams and all that, but I had bad allergies. Finally, when I was in my 20s, with the help of some naturopaths in Australia, figured out that my issues were basically diet-driven. I got interested in this field. I know how, from firsthand experience, what a problem it can be if you don't know that you're eating something which causes your eczema, your respiratory problems, your fatigue, your arthritis, your migraines, so on and so forth. I want to do everything possible to have an impact. I know that's the way most people in the naturopathic community are as well. We've created some tools to help educate patients, to help them comply, to help them understand how to substitute certain things, to be able to take an ALCAT test result and have it reflect into a several-hundred-page personalized book of recipes, and then just make this all available.
We created an educational course, which actually, we'll have to go to the Naturopathic Societies and see if they'll accredit it, but we have accreditation for this from the dietitians and nurse practitioners, so it's a course that we offer. Again, we're going to present this to the naturopaths. It costs $199. Then when people go through that, then they can purchase from us these meal planning tools and other things for their patients. We're going to put a lot of this online, so it'll be very convenient, at our website for this purpose, called GutHealthPartners.org, and just make compliance a lot easier so people stick with it and get the benefits. That's what we're doing.
Gazella: That's great. We also have a lot of dietitian and nurse practitioners who are readers of the Natural Medicine Journal, so I'm sure that they'll appreciate that. That sounds like a wonderful mission for your company. This has been very interesting. Thank you again, Roger, for joining me today. Once again, I'd also like to thank our sponsor, of course, Cell Science Systems. Have a great day, Roger.
Deutsch: Thanks. Thanks for having me, Karolyn.