This week’s historic podcast: “Individualized Diets, ALCAT, and BMJ Gastroenterology” features the results of a brand-new study published in the British Medical Journal, validating food sensitivity testing (the ALCAT Test®) for IBS patients.
The study named, “Efficacy of Individualized Diets in Patients with Irritable Bowel Syndrome: A Randomized Control Trial” was led by the late Dr. Ather Ali, ND a colleague of our co-founder, James Maskell, who sadly passed away this October.
It is our great pleasure to honor Dr. Ali’s legacy by helping spread the word about his incredible research.
In this podcast, James interviews another of the study’s lead researchers: Dr. Wajahat Mehal, professor of medicine at Yale University, for the inside scoop on this ground-breaking study.
Tune in today to get all the details direct from the source, including:
- A high-level overview of the entire randomized, controlled, blinded study from Dr. Mehal
- An inside-look at key outcomes of the study, including significant improvements in the Global Improvement Scale (GIS) at 4 weeks and 8 weeks for IBS patients who specifically removed ALCAT positive food items from their diet
- Dr. Mehal’s take on the most encouraging results of the study
- Insights on the implications of this study to the future of gastroenterology and functional medicine
Resources mentioned in this podcast:
Announcer: Welcome to The Functional Forum Podcast, the place health professionals come to hear from innovators and agitators leading the charge. We cover the latest clinical breakthroughs in health technology, as well as, practical tools to help transform your practice and the health of your community. Now, here’s your host, James Maskell.
James Maskell: Hello and welcome to the podcast. This week we speak with Dr. Wajahat Mehal, professor of medicine at Yale University. He is a specialist in digestive diseases and is one of the authors of a new paper that appeared in the BMJ open gastroenterology in November. The name of the paper is ‘Efficacy of Individualized Diets in Patients with Irritable Bowel Syndrome: A Randomized Control Trial.’
This is not something that we’ve really talked about. We have very rarely talked about any brands of supplements or labs on the show, but this is a significant moment for those of you and those of us that believe in things like the ALCAT test. This is a significant moment for the movement.
In this podcast, we talked about first of all, the legacy of Dr. Arthur Ally, who is one of the lead on this paper. We talked about the mechanism of the ALCAT, the test and what it says about what’s happening in the digestion. Then, we just talked about the implications of a study like this appearing in such a journal and what it could mean to bring more and more gastroenterologists into the fold. It was a very interesting half an hour. I hope you enjoy.
A warm welcome to the podcast, Dr. Wajahat Mehal. Welcome doctor.
Dr. Mehal: Thank you so much, James.
James Maskell: Doctor, it’s such a pleasure to have you here on the podcast. Before we get into the subject that we’re here to talk about, I know we’re here to talk about a study that you were are significant part of there, one of the other contributors was Dr. Arthur Ally. Maybe we could just start there. I’m sure the two of you had a close working relationship through the development there. Sadly, I know he passed away a month or so ago and it was very sad moment for the naturopathic profession, the integrated medicine profession and everyone associated. I’m hoping and I’m sure you are that a lot of the legacy that he’ll leave behind will be from this study and other words. What was your experience in working with him?
Dr. Mehal: Yes. Thank you for remembering that. Arthur actually was the lead in this study. I provided a lot of laboratory and scientific support to this study, but this was very much Arthur’s study. As you know from your experience, he was wonderful to interact with as a colleague and as a friend. We’re just all still very slowly coming to terms with this great tragedy of him passing away so, so very early.
James Maskell: Absolutely. I know that doing this podcast and the visibility that we can give to this study can help to honor his legacy and support it. Maybe listeners of this podcast aren’t aware of this, but from 2007 to 2009, I lived in New Haven, Connecticut and had an opportunity to meet Dr. Ally right at the beginning of my career when I was just really getting to understand what was going on in the space. It was really amazing to see obviously the integrated medicine clinic there and then obviously what had happened since. I hope that’s, if you’re listing to this and you care about the naturopathic profession or you care about truth in medicine, that here’s an opportunity to honor his work and his legacy.
Doc, you’re a professor of medicine for digestive diseases at Yale. What was it that sort of struck you as this study being something that you’d like to be involved with?
Dr. Mehal: There were a number of things. Firstly, this is a very common and very intractable medical problem from which many, many people are suffering. That obviously made it important. Then, unfortunately, there are really no well recognized affective therapies for Irritable Bowel Syndrome. Both of those things are incredibly important, and of course, it’s within my area of gastroenterology. All of that made this come to my attention. Then, on top of that, the study design was very rigorous. The baseline assumption that was made was that there will be no differences in patient symptoms depending on the results of the ALCAT test and food alterations.
We went into this with a very, with an entirely open mind and with what’s called a ‘Null hypothesis’, that the assumption is that there will be no differences. Then, it was really for the data to demonstrate if there were any differences. For all those reasons, it struck me as an important study to do. Then, of course, the chance to work with Arthur was an added bonus.
James Maskell: Absolutely. One of the reasons why we had to cover this in the podcast and why I felt compelled to share this content is that it’s not every day that this kind of study makes it into the BMJ Open Gastroenterology Journal. What sort of a coup is it from that end to be able to be published in this journal?
Dr. Mehal: It’s a highly respected independently peer reviewed journal. On that basis, it’s very prestigious and gives everything that’s published in there a significant amount of recognition. It was great to see our peers in gastroenterology reviewing this independently and coming to the same conclusions as we did basically, that there was significant improvement in subjects who followed guidance based on the lymphocyte activation essay.
James Maskell: Absolutely. Listening to this podcast, Doc, you have gastroenterologists, you have functional integrated medicine doctors, naturopathic doctors. You also have nutritionists and dieticians and other people that are all prescribing, one way or another, individual diets. Let’s just get into the science. Could you give us a high level overview of the study, what you set out and what the results were and share with our audience?
Dr. Mehal: Sure, sure. I’ll be happy to. The study deals with the condition of Irritable Bowel Syndrome, which is a very prevalent condition affecting somewhere in the region of 8 to 20% of the US population. This is a condition where patients have tremendous amounts of discomfort and pain and bowel irregularities. It has major mobility associated with it. Apart from just the patient symptoms, loss of working time, et cetera.
Currently, patients are treated by dietary manipulations, but that’s done in a very general blanket fashion, which is to say that everybody is pretty much advised to avoid a certain range of foods. Then, at one extreme, people are put on diets that are very limited. One example would be the food map diet.
That’s a situation where we felt, and other people, I think, would agree that a personalized approach really is much better than treating everybody in exactly the same way. That’s why we were interested to test if the lymphocytes active essay or the ALACT test, which provides results demonstrating whether certain food items are positive or would be considered intolerant for the subject or negative or tolerant, whether individualized guidance based on these tests could allow for a more individual or personalized dietary approach. That was the idea behind it. As I said before, it was structured with a null hypothesis, which is to assume that any guidance from the ALCAT test would not be helpful. That was the baseline assumption when we went into this. If you like, I can describe the general structure of the study.
James Maskell: Yeah, absolutely. For the diet, what was the control group diet?
Dr. Mehal: The way it was structured was very rigorous. What I mean by that is that first of all, participants were randomized to a four week diet. The randomization and the participants were blinded and all the staff interacting with the participants or subjects were also blinded. The subjects didn’t know whether they were on the control diet or whether they were on the ALCAT guided diet. Also, all the clinical trials people interacting with the subjects and the nutritionists advising the subjects didn’t know. It was very rigorously blinded in that sense.
Now, the way that the patients were managed were that, after randomization, the intervention group, everybody had blood taken and sent off for ALCAT testing. On all patients we had results on which food items were positive or intolerant or negative, tolerant under normal circumstances. Then, the intervention group were asked to remove the positive items from their diet. They did that and that was for four weeks.
The control group weren’t simply asked to continue as they were, but they were actually asked to remove some of the negative items or items that were considered to be acceptable from their diet. Then, the diet was continued for four weeks and there was a subsequent follow up of eight weeks. Then, during that time, the patients were given a number of clinical scores.
Prior to starting the study, a primary outcome was identified. There was no post hoc analysis. Everything was done perspectively. The primary outcome was a difference between the groups and something called ‘IBS Global Improvement Scale’. Then there were additional secondary outcomes on different scales. One was an IBS symptom severity scale and one was an IBS adequate relief scale. All of that was predetermined. Then, of course, information, data was collected prospectively and then analyzed at the end of the eight weeks of follow up.
James Maskell: Beautiful. Yeah. Obviously in order to get, I guess, into the BMJ journal, it has to be very rigorously tested. I know clearly there’s probably people listening to this who, in their own experience of running their own practice have seen good results, but it’s one thing to do that in practice, it’s another thing to control the variables and try and get to a point where you really see what the effect is, independent of many variables.
Dr. Mehal: Right. Exactly. Obviously we didn’t know what the reality was, whether patients would improve if they were asked to not eat ALCAT positive food items. The only way we would know ourselves was to really make sure it was very carefully controlled.
James Maskell: Beautiful. What were some things that came out of the data that either surprised you or that were interesting? What are some of the key findings that you think will resonate with physicians and with organizations from the study?
Dr. Mehal: Of course, the most important thing, important clinical data sets are of course, clinical. Are the patients feeling better? Are they doing better? Those are the most important things, as one might expect. As I said, before starting the study we’d identified changes or improvement in the global improvement in the Global Improvement Scale, or GIS, as the primary outcome. That demonstrated that four weeks into the intervention and also eight weeks into the intervention that there was significant improvement in this GIS scale in subjects in whom ALCAT positive items had been removed from their diet. Again, keeping in mind subjects and their dietitians didn’t know if they were removing positive or negative items, but after the randomization was broken, not the randomization, but after the blinding was broken, there was a significant improvement in subjects who had had, as compared to the subjects who’d had control food items removed, but the subjects who had ALCAT positive removed felt better at four weeks and even more so at eight weeks.
James Maskell: That’s great. Yeah, that’s obviously the key thing. We’re there anything that surprised you as someone who is been involved in digestive diseases for decades, I would imagine? Are there things that came out of it?
Dr. Mehal: I think the main, a very pleasant and encouraging, if you like … Maybe ‘Surprise’ is too strong a word, but considering the numbers of subjects that we had, there were 29 in the intervention arm and 20, actually 29 in both arms, which are not very large numbers, but even with those relatively small numbers, it was encouraging to see that we can demonstrate a positive improvement. The concern, of course, with numbers of 29, 30, would be that an intervention is effective, but it’s just that the sample size wasn’t large enough to demonstrate it. I think that was really very reassuring and it makes it very believable.
Additional things that were done were … Blood samples were collected. We were, of course, very interested also to see if, in addition to symptomatic improvement, if there were any biological readouts that could be obtained from patients who were responding. What we did was, in six individuals, samples pre-removal of positive items and samples post-removal from positive items were actually sent for a very detailed and very sophisticated form of proteomic analysis, which is based on technology that comes under the heading of APSMA technology, but essentially what it does is it provides about 1,100 protein readouts from a plasma sample. It does have to be analyzed very carefully because obviously when you obtain large amounts of data, things can appear significant just simply because large amounts of data has been obtained. After all the various statistical corrections, neutrophil elastase was found to, or plasma neutrophil elastase concentrations were found to be reduced in the individuals who had significant symptom improvement in the post sample compared to the pre sample.
James Maskell: Was there improvement amongst the group that were taking out non-ALCAT related things? Most people in this space, nutritionists and dieticians are recommending to lose certain foods that may be inflammatory or otherwise for people and some using this basis of testing and some just doing sort of like their own philosophy on food or trying to do it based on signs and symptoms. Outside of that, are healthier diets or removing foods a net benefit to gastrointestinal diseases or this in the study, or was it only through following the directions of the test?
Dr. Mehal: The study was designed specifically to address the question as to whether following the directions of the ALCAT test would result in improvement. It really wasn’t designed to address the question you’re asking in terms of removal of food items based on some other rationale. I really couldn’t speak to that based on the study because that’s not really what the study dealt with. Broadly speaking, there is data that removal of large groups of food items and being on a relatively restrictive diet can help with symptoms of IBS, but the problem one runs into then is compliance. Obviously, none of us like to be on a very restricted simple diet for obvious reasons. That data is out there, but this study wasn’t designed to address that question.
James Maskell: Absolutely. I really appreciate that. I could see how this study could be obviously useful in our community for practitioners who are interested in this kind of content and have maybe tried the ALCAT test and have used it or maybe tried other types of food sensitivity testing. Obviously, this is a big moment in that world. What are your thoughts as to how the general digestive diseases, gastroenterology community will react to the study or have been reacting to this study since it came out?
Dr. Mehal: I’ve had some correspondences from people who’ve read the study and asked me about it, which is always good to see. I think a couple of things.
Firstly, I think the effects of the study will be somewhat cumulative. I think it will take a little bit of time for, if you like, the data to get broader notice. As it’s presented at meetings, et cetera, I think it will start to get noticed.
Secondly, the conventional medical community is, as you probably know, very conservative. Irrespective of whether one is dealing with a test, which previously has not been tested in a controlled fashion or with something more conventional like a pharmaceutical that a big pharma is bringing out, the community is very conservative. For example, with a big pharma pill of whatever curing X, Y, Z there are phase two studies that are relatively small and show a benefit. Then, there’s a large phase three study and hundreds of thousands of people. Then, often, that has to be replicated. It’s a process, but I think I would say this is an important first step in that process.
James Maskell: Yeah, absolutely. Yeah, it’s certainly one of our goals here at The Functional Forum, has been to prepare doctors for this next era of preventive predictive personalized medicine. This seems to run right into that because what we’re really talking about is individualizing diets. Is there any understanding that you had from it that, what is it about the mechanism of the ALCAT test that is effective in driving the right data?
Dr. Mehal: The mechanistic aspects … Again, I’m going to restrict my comments as much based on data as possible. The mechanistic aspects were explored through the proteomic work that was done here, which showed that neutrophil elastase was lower, plasma neutrophil elastase was lower in individuals that had an improvement. In some studies, neutrophil infiltration into the intestine has been recorded in patients with IBS.
One possible explanation for this would be that once patients are following a diet based on ALCAT testing, that’s associated with reduced infiltration of neutrophils into the intestine and perhaps reduced inflammation. That’s speculative based on the data, but that’s one possible reason. If the proteomic data had shown that some protein that was completely unrelated to inflammation was less, then that would be a little bit more difficult to explain, but I think it’s significant that the protein that did come up is well known to be an inflammation associated protein.
James Maskell: Yeah, absolutely. Yeah, that’s super interesting. What are some of the implications? I guess this is outside of the realms of the study, but certainly at the same time that this is happening, you have more understanding of the important role of the gut in dealing with or being a factor in diseases that go beyond the gut. Is there any knowledge that we can glean from this?
Dr. Mehal: No, sure. Obviously, the gut is incredibly important for human health really at every respect. The gut has many, many functions with nutrition, of course, being the most important one, but there are also many consequences of changes in the microbiome in the gut, for example. I think that’s a whole extremely important question, because changes in the microbiome have been found related to a whole range of medical conditions. Everything from just malaise to allergies to ability to concentrate, a whole range of conditions including liver health, et cetera.
Some of the questions here would be: Which other medical conditions might be shown to have improvement if patients make nutritional adjustments based on the ALCAT test? I think that’s a very, it’s a broad, but an important question. Then mechanistically, what does the ALCAT test do, for example, to the microbiome, I think would be important, but there are many questions. If we address, ask the question of, “How, what are the broader implications?”, there are really many, many areas one could go into.
James Maskell: Yeah, absolutely. I can certainly see that. Certainly, my feeling was when I saw the microbiome research four years or five years ago when it came out, the Human Microbiome Project, that this was going to sort of shake the foundations of, nevermind gastroenterology, but also internal medicine or otherwise. Do you feel like this study has the potential to bring these ideas to a wider audience?
Dr. Mehal: I think so because what it does. A lot of the microbiome research and data that’s out there is experimental as you know. It’s very powerful data, but it is testing hypotheses and it’s experimental. I think the power of this study and this approach would be that individuals or the setting of clinical trials could actually make real world changes in their diet, which would be maybe beneficial without it being just a laboratory based experimental system.
James Maskell: Yeah, absolutely. Good. It’s very, very exciting and I really appreciate what it takes to pull of something like this. It’s certainly a multi-year, tons of thought, resources, pitching and all of that. When I was New Haven, my cousin was a graduate student, so I would see what was involved in the creation of any research. Then, also for those people on behalf of our community that has been using things like the Alcat test and other tests without this research, I hope that it’s going to go a long way to just giving a sense of confidence to our community, that by using this kind of testing and individualizing the diets, you’re actually doing something that’s not fringe, but now hopefully a little bit more respected and mainstream. Where do you see the next phase of credibility coming for these kind of … Is there more work in the horizon? Is there a natural next step to come from this research?
Dr. Mehal: The simplest natural step, what I guess, would be a repeat or a replication, which is always a good idea in any sort of a objective enterprise. Then, a different approach would be broadening it out and asking the question, “Which other medical conditions are most likely to benefit from ALCAT test based nutritional guidance?” The second question is very broad and we could speak about that for a long time.
James Maskell: Great. I look forward to seeing that. Are there plans in the works or are we just dealing with this for now?
Dr. Mehal: No, no. There are definitely discussions and plans and discussions. Absolutely, absolutely.
James Maskell: Beautiful. I really appreciate you coming to be part of The Functional Forum Podcast. To me, this is part of the evolution of medicine. We are retooling the medical system for today’s diseases. Obviously, the digestive diseases are really … I think there is data to show that the digestive diseases are actually the most popular reason for people to come into a functional integrated medicine provider’s office. It’s exciting to see some of the ideas that they’ve been using for a while validated. We will have the link to the study in the show notes. We look forward to continuing the conversation and looking for ways to get the word out. My appreciation for yourself and all the other members who completed the study.
To come back to where we started, I hope that if you’re listening to this and you either knew Dr. Ally or you’re excited about this work, that perhaps one of the reasons why we started our meetup groups around the functional forum was that we would be able to create a safe place to be able to invite gastroenterologists, local gastroenterologists to have these kind of conversations. If a gastroenterologist saw this research and thought, “This is interesting”, he might be able to partner with or hire a dietician who was schooled in this kind of testing for this office and really try and find local opportunity to do that.
If you’re inspired by this podcast, please share it with some people who maybe it could help to help them think differently about the future of how we deal with these kind of things. It’s exciting, I know, ultimately for those patients who have had significant gastrointestinal distress because as you started of by saying, this is not a disease where there’s been a lot of good news.
Dr. Mehal: Yeah, absolutely. I’m thrilled that we could take this step and independently show that dietary changes with the ALCAT test were helpful.
James Maskell: Beautiful.
Thanks so much for being part of The Functional Forum podcast. We’ve been talking with Dr. Wajahat Mehal. He’s the professor of medicine for digestive diseases at Yale University in Connecticut. This has been The Functional Forum podcast. I’m your host, James Maskell. Thanks so much for listening and we’ll see you next time.