Welcome to the Evolution of Medicine podcast! On this episode, James sits down with Dr. Tom Guilliams, who had our most-downloaded podcast of the year in 2019. Dr. Guilliams talks about a topic most clinicians have strong opinions on: bioavailability. With a background in molecular immunology and extensive research on nutrition and dietary supplement efficacy, Dr. Guilliams brings a unique and refreshing perspective to functional medicine clinicians of any discipline who are trying to get the best results with their patients. Highlights include:

  • Bioavailability and the new science on what that looks like in the era of the microbiome
  • How traditional herbal preparations can maximize microbiome availability
  • How attempting to replicate the pharmaceutical model for dietary supplements has brought us to opposite conclusions simultaneously, and how this will be a refreshing conversation for the new decade
  • How researchers are devising new ways of thinking about how evidence works in the evaluation of non-drug therapies
  • The questions practitioners who want to maximize dietary supplement effectiveness should be asking
  • And so much more!

Resources mentioned in this episode:
goevomed.com/LMRC
functionalforum.com/podcasts/podcast-phenotypic-flexibility
thecommunitycure.com
Tickets for PLMI Conference in Chicago

James Maskell: Hello and welcome to the podcast. We are kicking off 2020 with Dr. Tom Guilliams. He had the most downloaded podcast of last year. Today, we’re going to talk a little bit about an upcoming conference, but we’re going to focus today on a nice juicy clinical topic that, I’m sure if you’re a practitioner listening to this, will get you all riled up one way or another. We were talking about bioavailability and new thinking, new science on what that looks like in the era of the microbiome. We are joined by a Dr. Tom Guilliams. He has a number of roles, including being vice president for research with [Ortho Molecular Products], and does a lot of his own research. He did a great talk last year at the PLMI conference that stimulated my thinking on this, and I thought this would be something that would be super interesting for practitioners all across the world, that are trying to get the best results with their patients. I hope that this is a great start to 2020, enjoy. A warm welcome back to the podcast. Tom Guilliams, welcome back, Tom.

Dr. Guilliams: Thanks. Good to be back, James.

James Maskell: Really excited to chat with you here today. Your podcast on metabolic flexibility was our number-one downloaded podcast of 2019, super interesting topic. And actually influenced one of the things that we’re doing this year, which 2019 was the Year of the Group for us, group visits and all the things that we’ve done on that end. 2020 is going to be all about the Year of Resilience and talking about a new conversation about resilience. If you haven’t had a chance to go back and listen to that podcast, definitely check it out, but I’m excited to announce that Tom will be one of the speakers at the Personalized Lifestyle Medicine conference that’s happening in Chicago, May 1st and 2nd of 2020. You’ll be talking about that same topic again there, Tom. Again, just a reminder for everyone who’s there, why is this such an important conversation?

Dr. Guilliams: Thanks, James. Yeah, I think this idea behind resilience and just trying to figure out how we can look at patients along the continuum of health rather than just the continuum of disease. We need definitions. We need ways of figuring out how someone moves from what we say is healthy and we can’t detect any disease to a state of some sort of dysfunction. This idea of phenotypic flexibility, which we’re going to have another speaker talking about more specifically, but my talk is going to be about how we use provocation, or ways of stressing out systems that are supposed to be healthy, but then to try to figure out the preclinical areas where we can now see them beginning to fail or fail under pressure. Of course, we do that with the oral glucose tolerance test, but there’s lots of other ways we can do that within, let’s say, the HPA axis or other metabolic functions, memory, these kinds of things. I think it’s really important that we start looking at different definitions along the continuum to be able to measure health and measure people’s early vulnerabilities if we’re going to intervene in preventative medicine.

James Maskell: Perfect. That really sets up everything for that conference. I’ll definitely be there. Other speakers, Dr. Bland, we got Dr. Vojdani, who probably people are familiar with. There’s, as you mentioned, Femke Hovevenaars coming from Netherlands to talk about phenotypic flexibility. We got Dr. Phyllis Zee, and I’m super excited that Jeff Geller is going to be talking about treating isolation. It’s a really incredible program. I hope to see some of the people listening to this there. Now with this topic for today, obviously one of the things that we’re doing is really shifting our thinking away from the old model of thinking to a new model of thinking, whether that’s prevention versus resilience.

But one super interesting thing that you said last year that I thought we should definitely have a whole podcast on this is a topic of bioavailability. I know that’s become a buzzword in the supplement industry over the last 10 years, and particularly over the last couple of years, this concept that forms of products can be more bioavailable in certain ways. You said a couple of things that made me think that perhaps you think the way that we’ve been taught to think about bioavailability is not where we need to go. I’d love for you to share some of those thoughts with our community.

Dr. Guilliams: Yeah, so I think in many ways, my background as you know, is quite a bit in the dietary supplement world and the ingredients that are encased and regulatorily as a dietary supplement. But many of those ingredients are also used in other ways perhaps as drugs or cosmetics or other things. I’ve always said that the way we research natural compounds, or dietary supplement compounds, has been swallowed up by the way that we have studied drugs. We just put them in the same model and assume that they’re going to have the same outcomes. When they fail, we think they’ve failed. I often say we don’t always follow evidence-based medicine. We sometimes follow medicine-based evidence, or maybe I should say drug-based evidence.

In the drug world, obviously if we have some sort of compound, we want to know is it effective, so we do research in cell culture. We look at it in test tubes and in Petri dishes. Then when we find an activity we want to make sure that it gets into the body of a person, hopefully safely, and gets to the cell tissue at a similar dose that we used in the Petri dish, so that we can have our efficacy. There’s so many assumptions about that process, one of which is figuring out the bioavailability of that compound. Of course bioavailability, we don’t want to get too much into the details of that. The pharmaceutical world really depends on very limited amount of metabolism. We take the drug in typically orally, let’s say, and we look at its absorption. How does it get into the blood or into the serum, and then how is it distributed throughout the body and various tissues?

How is it metabolized, and then eventually, how is it excreted out of the body? That’s what we call classic pharmacokinetic research. Of course, we do that with drugs all the time. It really messes things up if the drug is metabolized in 20 different ways, and we have all these other metabolites in the bloodstream that we have to measure. A lot of those ingredients, or a lot of those drugs, never make it to market because they’re just too complicated. We want things very simple. In the dietary supplement world, people aren’t doing unfortunately that kind of studies. We have all kinds of people marketing their products as being 10 times, 100 times more bioavailable than somebody else’s product. When you start looking into that, and of course most of the marketers of those products are saying that not only do we have 10 fold or 100 fold more bioavailability, the assumption is we have 10 fold or 100 fold more efficacy, and it works 10 times better or 100 times better, or it’ll work the same using 10 times less or 100 times less of the raw material.

Those assumptions I can tell you are almost never, if ever, tested or approved in the literature. It’s partly because we really have conflated the idea of bioavailability with absorption. Then also we have conflated the idea of if it absorbs in the body, it must therefore then increase efficacy or increase the therapeutic benefit. As we’ve learned, this is oftentimes not the case. In fact I would say most times not the case and certainly not proven. One area that we can get into would be the whole curcumin story, which I followed very closely recently because curcumin, and other botanicals like curcumin, are quite unavailable, or at least in the traditional sense of the term, have very low bioavailability or low absorption in the body.

Therefore, the assumption was if we could increase its absorption using all kinds of different technologies, we would automatically increase its efficacy. As it’s turned out, that has turned out not to be the case because of all kinds of nuances that are particularly critical for botanicals, or what we call phytochemicals, because of the unique way that the body deals with a lot of phytochemicals. Almost all of them have poor bioavailability, and yet many of them can have great efficacy even when they have low bioavailability. I think the maturity of our industry is that we need to start confronting some of our own marketing claims and our own pseudo-scientific claims, and really get back to efficacy. You’re asking the question, do all of these changes that we’re doing, not only do they improve the product, do they obviously make sure the product is still safe? We can improve the absorption of something that could end up being unsafe.

Then the onus is on us to show that we’ve actually improved efficacy, but not only that, but we’ve improved values. We can get into this, but there are some products that increase the absorption, let’s say, twofold or maybe fourfold. Maybe they even shown that they can have a twofold benefit, but if it costs four times as much because of the technology’s so expensive, have you really improved something that is only twice as good, but it’s four times more expensive? Probably not. You’re probably better off taking the original product based on the cost that you’re going to get. There’s lots of questions that I think marketers of nutrient ingredients don’t ask or they get ahead of themselves. Those are some of the things that I think should be addressed when we think of this whole question about absorption and bioavailability.

James Maskell: Yeah, it’s such an interesting point. One of the things that I remember you said when I heard you talk about this before, was just that no one’s really thinking about the role of the microbiome. Ultimately if there was one thing I think if we look at the last decade that just went by, the microbiome was probably the biggest story in healthcare to a certain degree in new understanding of this macro organ that does so much. I’d love to just talk about it in that context because ultimately if we know that it’s important, as we know that it is now a decade later, then we should probably be thinking in those terms when it comes to creating things that are efficacious.

Dr. Guilliams: Yeah. The idea of bioavailability, the way I describe the traditional way of thinking of bioavailability, is having the bioactive ingredient at the target tissue at a dose that’s efficacious. We think of getting something into the body. Every time we do a bioavailability study, we’re talking about initially looking at the absorption. You give somebody something orally and then you start taking serum samples and you start saying, “Is it there? Can I measure it? Did it go up?” Typically you see this area. The curve is over, let’s say, a couple of hours or maybe 24 hours, but we’ve forgotten the fact that a lot of target tissue, let’s say, target cells are not even human. They’re the bacteria living in the GI tract. We now know that there are, let’s say, thousands, probably tens or hundreds of thousands of interactions that have now been published between a variety of phytonutrients and their ability to influence the metabolism, let’s say, of the gut bacteria, the types of bacteria.

Of course, we know fiber and these kinds of things up-regulate or change the growth conditions for bacteria. We know the target tissue, if we want to use that term, may initially be the gut first, and in the case of phytonutrients, it may be even one of the primary targets of metabolism, not only in the sense that these phytonutrients influence the metabolic capacity or the growth conditions of the bacteria, which then can influence that the human activity, which we know a lot about, but that the bacteria within the gut are actually the first step in transforming these phytonutrients into their bioactive compounds. Then those compounds are absorbed. The compound that may be in the blood of the human may not even be the same compound that was ingested because those have been metabolized by the gut bacteria. Then those secondary metabolites are then absorbed and then perhaps modified again by human enzymes. Then we might not even be looking for the right compounds.

There was a great paper published just a few years ago, 2016, which I started lecturing on this topic about three, four, five years ago, but this paper was great. It’s called, “Could the Gut Microbiota Reconcile the Oral Bioavailability Conundrum of Traditional Herbs?” It was a review article that basically stated we have all of these highly bioactive herbal compounds, but most of them have extremely low traditional bioavailability, meaning you don’t find them in high doses in the blood. We can talk about curcumin, resveratrol, of course, continue to go down the list, and almost every one of these highly active compounds that we find in test tubes and cell culture experiments have extremely low bioavailability, some almost undetectable.

Yet they still have efficacy in many cases. The idea behind this paper was to explore the whole idea that the microbiota themselves could help explain why it is that the traditional way of thinking about these compounds just doesn’t add up. It doesn’t take much, and you can go on to PubMed in 10 minutes and type in a couple of search parameters and you can find literally thousands of articles of phytochemicals compounds interacting or interfacing with gut microbiota or gut microbes that are common to the human GI tract. One that I often mention beyond curcumin is berberine. Berberine is a phytochemical alkaloid that we know has a lot of effects on microbes. It’s was always thought to be antimicrobial or antibacterial, but lots of data have now shown it to be very effective as a metabolic regulator, so regulating lipids, regulating blood sugar, regulating a lot of the enzymes and proteins that modulate what we call cardiometabolic risk.

As it turns out, not only does berberine get modified by the gut bacteria actually to improve its bioavailability, interestingly enough, but berberine itself modulates and changes the gut bacteria, the type of gut bacteria that are active creating a metabolically favorable profile. Interestingly, metformin, which is a drug, is also known to modify the gut microbes in a way that also influences metabolism. This is not really that surprising, although interestingly, we ignore this big factor sometimes when we’re eager to just talk about, let’s say, a new “fancy new bioavailable form of a raw material.”

James Maskell: Yeah, that’s super interesting. I guess the question that I want to know is if you look at the way that herbs were prepared traditionally in traditional herbology of all the different disciplines, obviously all across the world there are different herbal disciplines. There’s Native American herbal disciplines. There’s European herbal disciplines. There’s modern herbal disciplines in naturopathic medicine. Is there anything in the way that those herbs were prepared traditionally that might maximize microbiome availability?

Dr. Guilliams: I think the biggest difference between the traditional use of herbs and the more modern, let’s say, phytopharmaceutical way of thinking about them, almost all of these were whole plant or at least whole plant parts. They were typically using the whole plant or the whole root or the whole leaf and you had multiple compounds. Obviously in some plants you have thousands of different phytochemicals, but certainly you have major components, and you have dozens of these in those preparations. Some of them were just macerations where you just chop things up, or you can extract them. Oftentimes, obviously water extracts are probably the most common and easiest.

Then later we started seeing alcohol concentrate, ways of extracting using various solvents, like alcohol, that allows different constituents. But still we’re talking hundreds potentially of these constituents being used. The example that I give is curcumin. Curcumin, actually it’s, let’s say, three very closely related compounds that come from turmeric root. But in the root itself, curcumin only makes up about 5% of the phytochemicals. However, because of its extraction, because of the activity that was discovered mostly in vitro, people got enamored with that compound, and they figured out a way to extract it at almost-pure pure compounds. Ninety-five, 96% of a powder can be curcumin, and that of course is not natural. As it turns out, there’s some actually recently published data to show that maybe concentrating curcumin at that level actually created some of its low bioavailability.

When you deliver curcumin within turmeric root, when you just take the turmeric root extract or the whole turmeric plant, you actually have on a gram-per-gram basis a higher absorption of the curcumin levels, than if you were to purify the curcumin as a single compound, which is what’s typically done. Interestingly, rather than the industry saying, “Wait a minute, maybe we got ahead of ourselves, and over-concentrated this more as idea. Why don’t we go back to the plant and maybe look at the other compounds?” Maybe those other compounds are beneficial, act synergistically, and maybe you can increase the bioavailability of these compounds. We chose instead to say, “No, no, we want the 95% pure material. We’ll just use nanotechnology or liposomes or other technologies to be able to jam this in.”

As it turns out, the body sees curcumin like it sees a lot of these phytochemicals, as potentially toxic compounds. It seems like the body immediately conjugates them and puts them into inactive forms. It turns out that most of these products that have been used to increase curcumin’s bioavailability, sure, they actually do increase the amount of compounds of curcumin that get into the serum, but almost all of them become immediately conjugated, either in the gut or in the liver to what we call sulfates and glycuronide compounds. These conjugates, which are inactivated, are actually protecting the body from too much curcumin. We can put as much as we want in there, and the body’s going to continue to remove it because it doesn’t want these high doses. We need to understand phytochemical therapies in a much different way.

These products have always been in the diet at low concentrations, and the body seems to like them and they function at low concentrations, not only because they may be affecting the microbiota, but also because they may be triggering very subtle changes in cell function. We think of those, we talk about those as genomic functions or epigenetic functions, these very small tweakings that occur by taking low doses over a long period of time rather than trying to use it in a pharmacological sense where we use high doses to try to push the body to do something, let’s say, that it may not want to do.

James Maskell: Yeah. It’s so interesting that we’ve focused on replicating the pharmaceutical model in the pharmaceutical way of thinking. In my book that comes out on January 14th, one of the things I talk about in there was that I’m sure you’ve seen because you’ve been to enough lectures with Jeff Bland in the last few years, but you’ve seen that slide on the Nature article about the top 10 selling or the top 10 grossing drugs in America, and that if you actually look at the number needed to treat numbers and the absolute numbers of who gets benefit compared to who doesn’t, the numbers are staggeringly low. People are shocked to understand that one in three to one in 24 people are actually getting help from these things. Yet we, because of that way of thinking still pervading, the traditional way of using some of these herbal preparations, we’ve gone to a pharmaceutical model even though at the same time we’re working out that the pharmaceutical model doesn’t work well for most people. It seems like we’re coming to opposite conclusions at the same time. I think this is quite a refreshing conversation to start the new decade.

Dr. Guilliams: Yeah, and the cost of that, if you think about what we call the number needed to treat, the number needed to treat for some of these drugs is so high, and the cost of some of these drugs are so high, when you multiply that out, the amount of dollars you’re spending in order to treat the few people that are likely to benefit from that, and the ability to approve a drug based on that, is quite a shocking in some ways. It’s any wonder that are our costs of healthcare is so high and yet the outcomes for most of those people aren’t there. They’re paying for the drug; they’re taking the drug. They’re getting the side effects of the drug, but only a handful of people are actually seeing a meaningful benefit in the disease progression of whatever disease that drug is treating.

But like I said, if you try to take that model, and we have unfortunately tried to take that model, and apply it to natural products or lifestyle therapies or some of these things, we also are disappointed because we’re trying to make these products, which are really not designed as drugs or don’t function in the drug model, we’re trying to make them perform in a system that is designed to replicate how a drug would work.

Really one of the things I think Jeff and others are doing, along with the whole personalized lifestyle medicine idea, is to rethink about how clinical trials work, or I should say think about how evidence works in the evaluation of non-drug entities or non-drug therapies, and really devise a new way of thinking about how we can gather evidence because if we don’t, not only are we going to waste money on trials that are not going to help us know anything, but we are really going to miss out on the opportunity of understanding how exactly we can personalize these therapies, so that we can find out who is going to benefit from this set of herbs or this outcome rather than another.

James Maskell: What should be the buying behavior of practitioners that want to maximize the efficacy of their herbal inputs?

Dr. Guilliams: Obviously, I think a clinician should be asking more questions. I think when somebody comes in and says, “Hey, our product absorbs this,” and interestingly they’ll say it absorbs more; it’ll absorbs faster. They’ll use all kinds of different things. We can go into the pharmacokinetic reason why they choose one terminal over the other, but they should really be asking what is the evidence that this works better? Just because it’s newer, just because it absorbed supposedly at a higher rate or more, have you guys done the evidence, the comparison between what I used to use and what this is, not just in absorption but in an outcome that’s meaningful. As it turns out, almost nobody wants to do that because it turns out that a lot of these products don’t increase efficacy.

What we want to do is really begin asking those questions and forcing the people that are coming up with these technologies to actually do that research before we start purchasing it. Then they will do the due diligence, but if we buy the material and we don’t ask questions, of course, they’re going to come out and say, “Okay, we’ve got another shiny penny for you. We’ve increased the absorption of resveratrol.” They’ll just go down everything, and if the clinicians aren’t asking for the efficacy data, they will never produce it.

James Maskell: Beautiful. Look, I think that makes a lot of sense. I think it’s part of a biggest shift, which is really in the last year, we talked about the shift from one-on-one patient care to group care as a more appropriate way of looking at lifestyle driven chronic disease, and learning what actually works. How do people get better? How do people get empowered and move beyond these chronic illnesses? They need that kind of support network. I think as we start to see the efficacy of that, it’s obvious, and I love the fact that we’re looking to realign thinking for this next decade around what really works and no, not being trapped in the pharmaceutical or the current way of thinking, even when we’re trying to do very different medicine. That’s why we’re committed to transforming the practice of medicine. I’m really excited to share that.

I’m also looking forward to the year of resilience, tom. It seems like this is a year with your name written all over it. I know you’d be talking about these kinds of concepts for a long time. I know one of the talks you gave a couple of years ago that I really liked is here you went off on myths of the world that we live in. If you had to give a prediction for one other myth or one other thing that is held sacred by our community right now that you think will fizzle in the year 2020 and beyond, bioavailability is one thing you shared. Is there one other topic that you think we might be hearing from you on later this year?

Dr. Guilliams: I don’t know of a myth per se, but I think we’re going to be grounded a little bit more on the CBD one. I think now that we have more opportunities to research CBD that we didn’t have in the past, I think we will find clear applications for it, but I think a lot of the myth around CBD affecting everything, I think will probably fade away a little bit. We’ll have a rational discussion about that. I think the other thing that’s coming in the next year or two is a recalibration of our understanding of the microbiome, the gut microbiota in humans. What is normal? What is it adaption? How can we influence it? I think we’ve got really ahead of ourselves even a few years ago thinking that we could figure it out, we could do stool analysis and figure everybody’s gut out. Now we’re realizing it’s much more complicated. It’s much more of a fluid dynamic environment and it’s not as simple as we thought it was.

Those are just two things I think that are coming and we’ll continue to see over the next couple of years. I think we’ll look back on the CBD thing and say, like we did with DHEA and like we did with CoQ-10 and many of the other ingredients that took up the whole world by storm. They have their place but they didn’t solve everything.

James Maskell: Beautiful. All right, Tom, thanks so much for coming and sharing your wisdom. If you want to hear more from Tom, we may do another podcast later this year depending on this one. Also as I mentioned at the beginning, we’ll all be at the Personalized Lifestyle Medicine conference. It’s in Chicago, May 1st and 2nd. Dr. Geller, who you heard on our podcast last year and is one of the heroes of my book, The Community Cure, will be there, as well as Cheng Ruan and a bunch of other very interesting people be at that conference. But Tom, thanks so much for leading the charge on these kinds of conversations. Always fascinating to get inside your head for half an hour, and really appreciate you being a part of the evolution of medicine content to kick off this new decade.

Dr. Guilliams: It was my pleasure, James. I can’t wait for the PLMI conference as well.

James Maskell: Awesome. All right, this has been the Evolution of Medicine podcast. I’ve been here with Tom Guilliams. We’ll have all the notes of everything we spoke about, the conference and some of the references to what we spoke about here today in the show notes, but in the meantime, thanks so much for being part of our community. If this resonated with you, please share with a colleague that needs to hear it, and hope to see you in Chicago. In the meantime, thanks so much for listening and we’ll see you next time.

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