Dr Rupy: I'm delighted to welcome Dr Chris D'Adamo on the show. He is a medical research scientist with expertise in the synergistic effects of healthy lifestyle, environmental exposures and genetics on human health and wellness. His research, clinical and educational network includes leaders in the fields of integrative medicine and lifestyle medicine. And he's also received a PhD in epidemiology from the University of Maryland School of Medicine and is currently an assistant professor with dual appointments in the departments of family and community medicine and epidemiology and public health. He is the perfect person to talk about the pitfalls of nutritional research and where we can and cannot use nutritional research. We do talk about the nuances that specifically impact nutritional research that I think everyone needs to be aware of and understand. We talk about their culinary medicine programme and how that started, which I'm pleased to hear has been running for a number of years now. And the way they introduce it early into their clinical career, I think is exactly the way that we should be doing it here in the UK too. We also talk about sulforaphane, which is a unique phytonutrient that is found in a number of different ingredients, most notably cruciferous vegetables like Brussels sprouts, but particularly in broccoli sprouts. Now, broccoli sprouts, if you've got my first book, you'll know that I mentioned it back then, and the research looking at the impact of sulforaphane on upregulating your innate detoxification systems, the ability of it to remove environmental pollutants, as well as the impact on inflammation pathways is absolutely fascinating. And as Chris has been doing a lot of research in this for a number of years, he was the perfect person to talk about the science of sulforaphane, the properties of sulforaphane, where we find it, and the impact on virality and the host defence response to viruses, in particular influenza. Whether that can be extended to COVID-19 or not, we don't really have the data for that right now. But also on cancer and something that I wasn't aware of, autism spectrum disorder, which is regarded as something that has, well, it's definitely a nuanced topic, but neuroinflammation is one of the defining features that I think needs a bit more attention. And the impact of sulforaphane on that, although it hasn't been borne out in huge clinical trials, is something that definitely warrants a lot more attention. How to incorporate sulforaphane into your diet, as well as the other impacts that it has. The mechanisms behind introducing different phytonutrients into your diet or supplementation regime are quite impactful. And you know, I'm certainly a fan of getting the foundations in order first, so food, lifestyle, sleep, exercise, etc. But certainly these are things that are could be the cherry on top. And I think if people are interested in enhancement or improving lifespan as well as healthspan, then this is something that I would suggest is a good listen to as well. My primary focus with the Doctor's Kitchen is to try and get people into good habits. And this is certainly not a panacea, but certainly something that I think will come into fashion a bit more over the next couple of years as we find out a bit more about how to better our lives. So I really do hope you enjoy this conversation. You can check out the clips on YouTube. Please do check out the show notes at thedoctorskitchen.com/podcasts and you'll find a lot of the links that we discussed on the show there as well. Have a good listen.
Dr Chris D'Adamo: Chris, thank you so much for joining us via Zoom. It's a pleasure to have you here.
Dr Rupy: My pleasure, Rupy. I enjoy your podcast and look forward to the discussion today.
Dr Chris D'Adamo: Brilliant, brilliant. Listen, I've looked through some of your work with culinary medicine. I think it's fabulous. We're going to have a discussion about broccoli and sulforaphane in particular, but I'm sure that will go to a whole bunch of other phytonutrients as we talk. But I thought perhaps we could kick off by perhaps introducing yourself to the audience over here in the UK, well largely in the UK, and we could talk about your background and training in epidemiology and your experience in research.
Dr Rupy: Sure. So I am a nutritional epidemiologist by training, and that's a, that alone could be a fascinating podcast topic. The field's done a lot of good. It's also in some ways done some harm and misled us. So, it's a great tool. And happy to chat about that. And I have taken that background and now direct the Centre for Integrative Medicine at the University of Maryland School of Medicine. So it was the first centre in the US in an academic institution. And we've done work in a lot of your areas of interest. So certainly nutrition and herbal medicine, but also acupuncture, mind body modalities, yoga. And really, as the name implies, integrating these sort of called complementary modalities into conventional care. And it's just been a fascinating journey. We've been doing research, much of which funded by our National Institutes of Health. We've been doing clinical care, so treating patients with a variety of conditions and educating medical students and healthcare professionals and the public at large. And where I am today, I'm actually at a teaching kitchen at the Institute for Integrative Health, which is a community-based nonprofit in Baltimore. And it's founded by the founder of our university centre, Brian Berman, who's a mentor, colleague and friend. And yeah, we've had such a blast with culinary medicine, teaching medical students and other healthcare professionals about nutrition through cooking. And alongside that, with my big passions, I think we'll touch on today too, is dietary supplements. You know, in the US, over half of Americans take a dietary supplement. It's across the world, very common. And there's so much confusion out there. But I've been doing clinical trials on dietary supplements, publishing work on that and educating and giving consumers and clinicians tools to have a differentiating eye towards product quality, how to know what to choose, what to take when, and so on and so forth. So, yeah, I look forward. There's a lot of topics we can we can touch on today and look forward.
Dr Chris D'Adamo: Yeah, I'd love to double click on the integrative health aspect and how that's a facility within the University of Medicine. But perhaps we could dive into the nutrition research stuff. And you mentioned right at the top there that, you know, it's done a lot of good, but there's a lot of misinformation. What are the biggest issues with nutritional research?
Dr Rupy: I think the biggest challenge is, you know, looking for a silver bullet solution to things or frankly demonising a single macronutrient or component of the diet. Whereas I think if you look at commonalities in research, it really comes down to, now nothing sexy here, but it's true, eating whole foods, minimally processed, eating real food. But I think if we look at some of the, I'd say false conclusions we've drawn around dietary fat, for example. You know, if you look at the history, that was born largely out of observational studies. So we'd look at those who ate more dietary fat, there were correlations with higher lipids and correlations then with heart disease. And out of that was born the diet heart hypothesis. But when we did the randomised control trials and we really dove in and adjusted for other factors, we saw that, well, look, dietary fat in and of itself is not a causal risk factor for a disease. We need to look, paint with a finer brush. And we've even moved away from thinking saturated fat. I mean, there's certain types of fats, inflammatory oils, hydrogenated oils are harmful for health, but not all of them, certainly, and even with saturated fat. So I think what we've seen, we've seen the same thing with red meats and the better science now shows that, well, look, different kinds of red meat have different effects, grass-fed versus grain-fed. And now sugar has become a big enemy, but there's quite a bit of a difference between the sugar that's in blueberries and bundled with polyphenols and the sugar that's in a Coke. So I think we've drawn false conclusions in nutritional epi, but it's still a great tool. We just need to to look at it as part of its proper context.
Dr Chris D'Adamo: Definitely. Yeah, I think there's, you know, context and nuance specifically that impact nutritional research that listeners need to understand. And I think one of the biggest things is, like you said, demonising one particular aspect without really truly appreciating that your diet is a collection of multiple different things. Even within a singular food, you have an orchestra of different nutrients. And I wonder through the culinary medicine programme that you have, how do you get across those nuances to early medical students and how do you teach that in the kitchen?
Dr Rupy: Well, you know, it's funny. I had to smile when you said the orchestra. I use that very example. So a carrot is not just beta carotene. And you know, it's there's an orchestra of nutrients there. So I did my doctoral work on vitamin E. And it's an incredibly important nutrient. Without it, you you won't survive, you know. But it's we've seen even that different forms of vitamin E, you know, there are eight forms, there's four tocopherols, four tocotrienols, that lots of alpha tocopherol will actually deplete the others. So I give that same analogy you use of the orchestra. You know, if you go to a concert and you got the cello just jamming out way louder than everything else, it's going to drown out the other instruments. And that's the way it is with food. There's there's, you know, hundreds of different compounds in in foods that work together in synergy. So I think that's been a big part of the when it comes to the culinary medicine. So been engaging around, so we get them, you mentioned early on, we get them the first week. So I really commend the University of Maryland School of Medicine for saying, hey, look, this is important because not just for future patient care, but for the wellness, health and wellness of medical students. It's a, you know, it's a stressful time, you know, when you're in medical school. So we get them very early on and we get them thinking about food and nutrients. You know, nutrients are very important. Nutrients can be used therapeutically, but to think about whole foods and to break down some of these these barriers, I think of of dogma around is it low fat or low carb? Is it, you know, one of the examples I like to use is we show the commonalities between paleo and vegan diets. When done well, you know, there's more in common despite all the bickering like on the blogosphere and and people really getting a trench. It's like, hey, let's look at the commonalities of eating real whole food. And so it's been fun. And then you get to teach it. So I'm in a kitchen here. You get to to teach through something very practical through cooking. So we engage them with fun recipes. We do like zoodles, zucchini noodles, stuff like that, cauliflower rice. We talk about the difference between wild caught salmon and, you know, farm raised these types of things. And we kind of frame it in the context of access too, because we're in Baltimore, Maryland, which is a city that has a lot of, you know, economic challenges and access challenges. So how can we do this in a way that patients can can access it? Not everyone can shop at Whole Foods or these types of places. So how can we do this in a way that's accessible to people? So, but it's a food first philosophy. And then we get into supplements where there's certain cases where that is is very helpful to patient care. But that that's kind of the way we get at it. It's been a lot of fun and and we're just going to be getting started up this week for the next next cohort of medical students.
Dr Chris D'Adamo: That's immense. Yeah. I mean, there's so many things there that mirror what we're trying to do here in the UK. We're currently in two medical schools with our programme. One of which is compulsory for year five. So we get them quite late. And I think there's almost like a sense of scepticism that is sort of ingrained in them at that point. But then we've also been doing a little bit of preliminary work with Imperial College where we deliver lectures to year one. And I think, like you said, getting in there early, so not only are you teaching them about nutrition and the importance to medicine, but you're also instilling self-care practices because, and I'm sure this is the same in the US, over here in the UK, medics, nurses, anyone that works full-time in the healthcare profession are more likely to be obese, more likely to have mental health issues, and more likely to die young, quite frankly, as well. So we really need to start taking care of ourselves as well as our patients.
Dr Rupy: Absolutely. I mean, there was an interesting paper that showed that there is quite a bit of interest for incoming medical students. When they come in, they want to learn about nutrition. As time goes on, you're right, whether it's scepticism or frankly just not getting much exposure to it, to realise that, hey, this is real. It's not, I mean, there's medications, you know, we we need them, but we also need the foundation of food and lifestyle. So, and then that tends to wane over time. So I think getting them early in the training, there's published data on this, is key. And there's in the US, there there's such a scarcity of nutrition education. It's 25 hours is the requirement. And like less than 30 of US medical schools even meet that. And then you get into residency and there's no requirements at all. And the nice thing is, there's papers in the, you know, JAMA, the Lancet that are saying, hey, look, this is something that we need need to resolve. And there is a groundswell of interest in more nutrition education. We're seeing, like again, we're in the compulsory, this is the core curriculum we're getting into now. So I think that's the that's the key and and it's just been fun to see that. It's been fun to see the transition of my faculty colleagues and and, you know, clinicians that are out there that say, hey, look, we want to we want to do some clinical cooking classes even, you know, to obesity, cancer, some of these areas. So it's just really refreshing and has me very encouraged for the future.
Dr Chris D'Adamo: Definitely, yeah. And I'd be interested to know what the trajectory for the integrative centre was. Was it, did it start with nutrition and then broaden to all these other wider applications of interventions such as, like you said, yoga, meditation, or even acupuncture? Is that the way in that it went or were there other sort of interests prior to that?
Dr Rupy: The way in is a really, really great question. So it was founded in 1991, so it's been been around for a while. Again, my, you know, Dr. Brian Berman started it. It actually started predominantly with acupuncture. So there was this big need, there's still a big need when it comes to chronic pain and non-pharmacological treatments for that. But it started with with acupuncture. And this also kind of followed the trajectory of, you know, one of the National Institutes of Health, you know, a centre being, you know, dedicated to to these these modalities. So then it got into things like herbal medicine, you know, meditative therapies. You know, my my background was in nutrition. I've been with the centre for about 10 years now. So I I I brought a big focus of that to our work. But the way in is key. And I think, you know, you you sort of, it sounds very, you know, like warlike, but it's not. But a Trojan horse really, if you can reach people with things like, okay, you know, nutrition's pretty conventional. Uh, you know, stress, sleep, these kinds of things, stress management. And then you say, hey, by the way, there are these other tools too. So we even had really interesting stories too over the years of there was a real sceptic as far as acupuncture went. And he had chronic back pain and Dr. Berman said, hey, we want to look into acupuncture. And he got, and this is a very well-accomplished researcher, written textbooks and so on. He said, my back pain is cured. You know, I want to know more about this. And he became one of our big, you know, collaborators over the years. And the same thing with nutrition and they look at the data, they look at the data. We'll talk about sulforaphane today and say that these are powerful, you know, treatments that can help us with our patients. So that's kind of the way in that we've seen. We've seen, we've heard stories all across the world with that too.
Dr Chris D'Adamo: Yeah, definitely. I I I totally agree with that Trojan horse analogy. I think first you've got to go with something conventional, something that everyone can sort of agree on. And then you kind of introduce other aspects that might be a little bit fringe. And that goes the same with patients as well. I mean, I'm hardly going to start talking about mindfulness meditation with some of my patients who are not privy to that sort of knowledge yet. But at the start, I'm definitely going to be talking about food and and and how that can have an impact first. Let's talk a bit about sulforaphane. Actually, before we do that, I wanted to get your opinion on reference ranges for micronutrients. As you're a supplement person, someone who's done a lot of research in this as well and personal study. How how are they created and why might that not be the most useful tool when it comes to the person sitting in front of you in clinic or the individual?
Dr Rupy: Oh man, that's an incredibly important question. It gets even ties into the food labels when they see this. I mean, first of all, it's incredibly variable. You know, our nutrient needs, yours and mine are going to be likely be different. And you get people at different stages of life, people with different health status, people with different activity levels, all these things impact, even the size of a person impacts that. So, you know, when you look at the reference ranges in particular, those are largely based on means and medians out of populations that aren't necessarily, it's not for optimal health. You know, these are a lot of times people who tend to be kind of sick actually who produce these. And our, you know, the the RDAs are based on preventing nutrient deficiency diseases. So, I don't know about you, but my goal was to more than just not have scurvy, you know, I want to I want to thrive. And I I think a lot of these are, we don't really know what a lot of these optimal thresholds are. So when we look at at the reference values, I mean, vitamin D is one where there's a quite a bit of research has gone into. But when we look at those levels, those aren't necessarily what we want to get to to prevent chronic disease, to thrive and and reach optimal health. And then you get the the complicated factor too of what's in the blood. So let's say we get a blood draw, we look at at plasma or serum B12, for example. Well, there's so much more to it than that. You got to look at at the metabolites really. So things like methylmalonic acid, homocysteine, or magnesium. By the time your magnesium gets low in the serum, you've got some problems. So we'll look at things like red blood cell magnesium sometimes. It's sort of the integrative or functional medicine approach. But I think there can be a false sense of security where someone goes and says, I, look, my B12 levels were normal, they're in the normal range. But they're low in energy, they're maybe not getting very much B12 in the diet. You know, things aren't things are suggestive of B12 deficiency or whatever else it might be. So that's a really fascinating area where we need we need more research. We're getting there a little bit with vitamin D, but we need more research with other things.
Dr Chris D'Adamo: Yeah, I think the public health bodies are sort of in a rock and a hard place when it comes to reference ranges because I think, to your point, you know, they're trying to prevent deficiency. But I think on a personal level, and I think certainly my patients would all agree that they don't just want to be out of the woods when it comes to disease. They actually want to be thriving, as energy as energetic as possible and, you know, to to to really thrive in optimal health. And this brings us nicely to the topic of sulforaphane. So this is something I've known about for a number of years now. It came on my radar probably about four or five years ago when I came across some studies looking at environmental pollutants and the just the impact on inflammation pathways through broccoli. And broccoli sprouts and everything. When did you first come across the impact of sulforaphane? And perhaps we could define exactly what we mean by sulforaphane as well.
Dr Rupy: Sure. Yeah. Well, you know, it's funny because when it comes to nutrition, you hate to play favourites. What's your favourite nutrient? But if there was one favourite micronutrient for me, it'd probably be sulforaphane. It's just an incredibly powerful. And you know, I've done a lot of work with vitamin E, D, carotenoids and so on, other, you know, flavonoids, but but sulforaphane I think has a unique evidence base behind it. So what it is, it's it's an isothiocyanate, which um, we'll talk about some of the science behind it, but these are potent um, activators of the NRF2 pathway, which we can we can talk about, and inhibitors of NF-kappaB. So, we'll get more into the science of that, but in essence, it it uh, turns on a bunch of anti-inflammatory and antioxidant genes and turns off, you know, many of the inflammatory pathways. But where it it comes from, the raw materials for it are called glucosinolates. And this is in cruciferous vegetables in varying amounts. So things like broccoli or broccoli sprouts actually have have quite a bit more than the the mature broccoli. Uh, Brussels sprouts, cabbage, um, moringa, which is one of my my favourites. It's uh, you know, one of these these hot superfoods, which is really interesting. So you get the glucosinolate in that. But then you need uh, myrosinase, which also tends to be in these uh, cruciferous vegetables again in varying amounts. And it converts the glucosinolate, whichever whichever it might be, glucoraphanin in broccoli, glucoraphanin in moringa, uh, into the isothiocyanate, the probably the best studied of which is is sulforaphane. And we can talk about a lot of the the nitty gritty details, but how I got into it actually is I so we're in Baltimore and a lot of the seminal work was done uh, with our our friends across town at at uh, Johns Hopkins University, uh, Paul Talalay, Jed Fahey, um, Tom Kensler, uh, from Hopkins, Brian Cornblatt at at Nutramax Laboratories who trained at Hopkins. You know, they did a lot of this really seminal work and you know, I'm a health and nutrition enthusiast myself. So I started working it into my own my own life uh, before I started studying it. So that's the sort of short history.
Dr Chris D'Adamo: So for people who are completely new to the subject, sulforaphane being anti-inflammatory, there's a number of different key pathways that it works on, the one the two that you mentioned, NRF2 and NF-kappaB. Um, why is this so unique and where do and how what's the dose that we're actually talking about when we when we talk about these different types of ingredients?
Dr Rupy: So the um, it depends on the this is dosing can be a little bit tough with this because it varies so much from plant to plant unless you're talking about a supplement or an extract of some sort. Um, but uh, so that that varies quite a bit and it varies based on what the what we're looking at. If we're looking at a, you know, a patient with autism, for example, and the size of that patient or or cancer, some of these other other fascinating um, areas that we can uh, discuss today. Um, but I I think what makes it so unique is just the multiple mechanisms and the fact that it's an indirect antioxidant. So this your your your viewers and listeners may find this of interest. You have direct antioxidants like vitamin C, uh, vitamin E, um, that uh have, you know, really important properties. Hey, I spent uh, five years studying vitamin E. It it's it's important. But then you get the issue with some of those is that you can get actually pro-oxidant or you can throw things out of balance when something is coming in with with direct antioxidant uh, capacity. What's interesting with um, compounds like uh, sulforaphane is they they are indirect, so they turn on these genes, uh, you know, that that have, you know, those that express glutathione, for example, um, that have this this uh, indirect effect that indirect sounds less powerful, but it's actually better, you know, um, uh, because it's more controlled. You don't run into that pro-oxidant, you know, uh, effect that you may get if you take too much vitamin C or or whatever else the case may be. And just the variety of mechanisms. We'll talk a little about heat shock proteins today too, which is really fascinating on a lot of levels. So it's just it's it's a it's a nutrient that seems to have so many health-promoting properties. I think why why it sort of elevates in my status above a lot of the others.
Dr Chris D'Adamo: Yeah, that's that's fascinating. And do they have any sort of similarities with other agents that we might have heard of already, like resveratrol from uh, grapes and dry peanuts and stuff like that? Or is it a different indirect mechanism? Because and perhaps we could talk about like hormesis and and the differences between those.
Dr Rupy: Yeah, well, you know, I know you had David Sinclair on uh, recently. I think um, I think resveratrol is fascinating and uh, it it works through there are some similarities with this. You look at at curcumin, for example, is another one. That's an NF-kappaB uh, you know, inhibitor to a lot of a lot of um, uh, phytonutrients are. Um, there are are different pathways. Um, you know, some of those are more on the uh, NAD uh, pathway. Um, when you look at sirtuins and so on with resveratrol. So that's again why it's great to get a lot of these different things in one's diet or supplement uh, regimen. So I'd say some of the overlap would probably be in the the NF-kappaB. The NRF2 of all of the um, uh, natural compounds uh, that have been looked at, uh, sulforaphane is is is probably the the strongest at activating that that that pathway. They've they've done some interesting comparisons. You know, curcumin does it somewhat, uh, some other other uh, compounds do too, but um, uh, sulforaphane seems to be uh, the most powerful in that respect.
Dr Chris D'Adamo: Yeah, that's that's fascinating. And let's talk a bit about the applications of this. So from some of the research that you sent over to myself and uh, some that I've seen in the past, so sulforaphane, like you said, appears to have a multi-modal effects across different uh, conditions or disease states, whether it be increasing detoxification pathways to remove environmental pollutants, improving host cell response when it comes to uh, the the the response to viruses. And one that I haven't come across before, which is the impact on autism spectrum disorder. Um, why don't we why don't we start off with the viral one? Because that's as we're in a pandemic at the moment, it's probably the most the most applicable.
Dr Rupy: That's on everybody's mind these days. So one of the ways that sulforaphane increases the um, you know, immune defence against viruses and other other uh, pathogens is uh, natural killer cells. So it increases the, you know, that innate immune response with natural killer cells. As such, uh, we've seen, there's actually quite potent antibacterial and antibiotic uh, uh, effects like with H. pylori. It's sort of selective. So there's been a lot of work, uh, you know, again, a lot of it at Hopkins, uh, with with H. pylori. But if we look at viral, because again, that's on everyone's minds now, antiviral properties. Um, yeah, it's been shown to uh, you know, uh, with H1N1 flu, you know, have activity against that, against uh, HIV, uh, even. So it's it's shown to have some pretty potent uh, antiviral properties again owed uh, largely to the natural killer cell, but also heat shock protein and NRF2 uh, activation that itself has been shown to increase the immune response. Um, and then you, you know, you combine this with other actives like maitake mushroom, one of one of my favourites too. You know, you come in there with a multi-pronged approach that can really uh, enhance our immunity, which is it's really never been more important than it is now. It's important all the time, uh, because even cancer and things like that, these are really essentially immune dysregulation. We're not attacking the cancer cells, the immune system's not doing its job. But uh, again, now it's on everyone's mind even more prominently.
Dr Chris D'Adamo: Yeah. So so one of the impacts of the sulforaphane is to heighten the innate immune response by increasing natural killer cell activity. Are there other mechanisms by which it increases the host cell response to viruses? And I I should make it clear to the listener, we're probably not talking about COVID-19 at this point, but this has certainly been shown in vitro, to my knowledge, um, with with other influenza viruses or different influenza viruses.
Dr Rupy: Well, most definitely. I think I think one of the things that that uh, you know, when we talk about COVID, and obviously the the big problem is when there's a cytokine storm. So I think when when something has the impact that sulforaphane does on that NRF2 pathway and that can controlling the expression of a lot of these these uh, uh, inflammatory genes, you know, that we're going to have a more appropriate immune response where there's not going to be, you know, uh, an overproduction of of cytokines that can lead to to problems. And of course, this is not so simple. I know in the very early stages of of um, uh, uh, COVID, everyone was talking about, was elderberry increasing cytokines? Is it going to cause a cytokine storm? No, it's it's not that simple. But um, with sulforaphane again, since it's controlling the expression of those genes, um, uh, it it it will help attenuate, you know, the an over-inflammatory response that that is really the the big problem when it comes to COVID and other infections like that.
Dr Chris D'Adamo: Yeah, it's it's almost like food has this chameleon-like response. I remember speaking to Dr. Lee about uh, different types of food and it's not as if just because one food appears to have a pro-angiogenic effect that it's going to have an angiogenic effect that's going to increase tumour burden in everyone because food has this like uh, incredible response that, you know, adapts to the surroundings. So it doesn't have a binary effect like a pharmaceutical would.
Dr Rupy: Right, right. Well, it's a broad, there's a broad bunch of, you know, pharmaceuticals are very targeted to often to single pathways. And of course, the there's downstream effects that we're, you know, that where other things come in. But yeah, food has much broader uh, effects across the board. And yeah, where things occur, where is the inflammation occurring? You know, I'm interested in autophagy, where is that occurring and and some of these types of things. So yeah, it's it's a it's a fascinating, again, orchestra of activity.
Dr Chris D'Adamo: Yeah, definitely. And so so sulforaphane, has that been used at all in um, human clinical trials to demonstrate sort of an antiviral impact?
Dr Rupy: Well, it's been used uh, in clinical trials for a lot of other things. Um, so cancer, uh, again, cancer, you know, I don't even know where where we start with this, but if we look at, let's let's actually first start the detoxification. So that's one of the things that got me into this. So I, you know, I've I've um, uh, looked at my genetic, you know, snips. I've done a 23andMe test and run through a bunch of of of uh, filters and I don't detoxify very well. You know, I've got some methylation issues and so on. And that manifested with something long before I knew about snips, that if I was out, uh, you know, we're on a main road here, if I was out in traffic or if I was travelling or if I was around cigarette smoke or mould, I had a real hard time bouncing back with that. Um, so the phase two detoxification pathway that sulforaphane has been shown in human studies to help to dramatically reduce benzene, for example. So benzene is a carcinogen that we find in vehicle exhaust and and uh, you know, uh, other things like that. Acrolein, which you might have heard about that one, uh, similar. That also can be produced in food, you know, when we heat things too much and so on. Um, the sulforaphane has been shown to detoxify that. That's why I started taking uh, Avmacol, which is the um, uh, sulforaphane supporting product that has the most clinical trials. And I found myself feeling quite a bit better. You know, I'd walk in, walk in the streets of Baltimore, walk in the office and I wouldn't have this this sort of sluggish feeling anymore. But they've shown in in clinical studies that it helps get rid of those carcinogens. So how does that then, so let's look at how that would play an effect in cancer. So we already talked about how sulforaphane um, you know, increases the NRF2 activity, decreases NF-kappaB. Um, and collectively from getting rid of those carcinogens that we all get exposed to, you know, we all breathe the air, there's no way around it, uh, that has these these carcinogens. We, you know, upregulate the expression of a bunch of these genes, including, you know, histone deacetylase, uh, you know, that inhibiting that can help with certain cancers. P53 protects that. So you get this sort of multi-modal um, uh, approach that's happening. So for something that cancer is as complex as that, uh, we start to see that um, you know, like in human studies with prostate, with PSA, lower PSA levels, it reaches breast cancer, reaches the breast tissue, uh, in breast cancer patients. There's a lot, a lot there. There's cardiovascular disease studies and and autism is probably the one that that has piqued my interest the most because we've just seen these, it's such a challenging condition and there's so much sort of, I'd say, almost uh, predatory, you know, uh, marketing that goes on with a lot of these parents who are desperate because it's almost as if they've lost their their their ability to communicate and connect with their child. And the clinical studies with autism are just are are fascinating to me. And a lot of that we believe comes down to neuroinflammation and heat shock response. And I can talk about that if you like.
Dr Chris D'Adamo: Yeah, yeah. Let's talk about heat shock proteins because you mentioned that a couple of times now. I've only talked to, I've only sort of considered heat shock proteins in the literal sense of uh, when you go to the sauna and you upregulate your HSPs and that appears to have some association with lower rates of dementia, lower rates of cardiovascular disease amongst men, uh, who have used the sauna. I think it was a Finnish study, um, as part of like, you know, cultural uh, reasons. Um, and I and I think it's fascinating the mechanism behind that. How does sulforaphane that we get from broccoli sprouts and all the other ingredients that you mentioned, how does that interact with the HSP uh, mechanism?
Dr Rupy: Yeah, it's really fascinating. So the heat shock uh, protein response for for your viewers that may not know, essentially it helps protect against uh, protein misfolding that occurs when there's, surprise, surprise, heat. That's one of them. That's where the name comes from, but other stressors too. And uh, these provide some resilience to stress. So it's again, it's this hormesis you mentioned before too. You know, that which doesn't kill you tends to make you stronger. So you get these these bursts of whether it's heat, um, you know, I I'm a big sauna fan myself and and uh, not just because of the data, it tends to make me feel good. I think a lot of people feel the same way. But there are ways to induce that that don't uh, require that. So let's take a look at at uh, autism, for example. So, um, that's uh, a condition that, you know, leading uh, clinicians like Andrew Zimmerman, um, in Massachusetts who's been treating autism patients for decades, um, and was involved in a recent biomarker uh, study, uh, showed, you know, they knew that, hey, when when uh, patients would get a fever, the parents reported that they their symptoms were gone. So they would be less agitated, less irritable, they'd communicate more effectively, they'd have fewer tics. And this is pretty consistent, you know, over over many years and many clinicians. But good luck getting, you know, a child with autism to go into a sauna. It's not really accessible. So many clinicians were looking at ways, how can we safely induce the heat shock response? Um, and uh, sulforaphane was shown to do that. And uh, there was a clinical research uh, portfolio that was launched looking at uh, sulforaphane supporting supplements, uh, you know, either broccoli sprout extract and shown really impressive um, uh, changes in behaviours. So again, less irritable, better communication. And even getting into the biomarkers, you know, we always want to know what's the mechanism? Is there a mechanism? And uh, where increased, you know, expression of these antioxidant genes, um, and uh, lower neuroinflammation and, you know, these heat shock proteins. So that's kind of how it works. I mean, it's a it's a pretty fascinating story just to the the value of how a clinician's observation and the parents who know their their children the best, that they would notice this and then we find a mechanism and then we find a potential solution. It's just a beautiful uh, demonstration of the the the medical and scientific process intertwining and helping solve a big problem.
Dr Chris D'Adamo: Yeah, I mean, that's the fact that I haven't heard about that before is astounding. I mean, it sounds like it should be on everyone's sort of playbook when it comes to primary care because I'm I'm trained as a primary physician. I obviously see uh, parents of children with ASD and I think it, you know, it's one of these issues that is uh, increasing in its prevalence. What I'm fascinated to know about is how long do, with that particular study, how many people were used and is it significant enough of an effect? And how many more studies do you think it will require to to almost become, you know, gold standard to to have this supplemental regime? And how do you personalise that as well?
Dr Rupy: Right. Well, it it's uh, fairly typical of the scientific process. There've been a number of uh, of studies of this now, ranging, the studies are all relatively small, um, but the effect size has been quite strong. So the studies range anywhere from 10 to, I believe 50 or so, uh, kids, um, with this and they've been pretty uh, consistent in in finding um, you know, both the clinical improvements, there's an ABC checklist, there's a a uh, social um, uh, sort of expressiveness. Um, and then looking at these these um, mechanisms that are underlying too with the biomarkers. So the biomarker study was was published, I believe in one of the nature journals, nature scientific reports, um, uh, with uh, you know, Dr. Zimmerman and Dr. Fahey who I mentioned before. Um, that was a relatively small study. Um, uh, that was really focused on the biomarkers, but there's some uh, data that are forthcoming from that. They're going to look also at the at the symptoms. So,
Dr Chris D'Adamo: Yeah, it's amazing. I mean, as an epidemiologist, how how how many more trials or how big because those are quite small numbers just to put into context for the listener. How big a number do we need to, you know, start thinking about when it comes to, okay, we're going to have a supplemental regime with patients within reason across the board when it comes to treating uh, things like ASD and other uh, conditions that are associated with neuroinflammation.
Dr Rupy: Sure. Well, I promise I won't get too nerdy here for your uh, your your viewers, but you know, the the statistical significance comes down both to the sample size and the effect size. So if you see a really strong effect size in a small sample, that is in a lot of ways probably more encouraging than you see this tiny effect size, but since you have 100,000 patients. And we've seen this a fair amount in the the epi literature that will show that there's a reduced risk of cancer that was statistically significant, but it was like a a 2% reduction, but there were 500,000 participants, so it's statistically significant versus something that might have, like I mentioned, 10 uh, patients. You have to have a big effect to see statistical significance there. So what I would like to see, I mean, there are, you know, bigger studies that that are underway now. You like to see replication in, you know, different types of, because not everyone's the same. There's different types of exposures, different types of populations across different uh, age spectrums. I think right now that the data for uh, sulforaphane for autism, uh, for ASD is pretty compelling. You know, based on what we've got because given in the grand landscape with with very few, uh, no serious side effects, that I feel like we're we're kind of there. How to get that on, I think the more studies that go out, the more nuanced the research question gets, the more information we have. Um, but uh, you know, I think waiting for the randomised double blind placebo control multi-site studies with, it's just those take so long to do and they're hard to get funded. Um, that uh, you know, at this stage, you know, I'm I I would confidently, we have a clinical practice to say this is something that people should consider.
Dr Chris D'Adamo: Yeah, well, I mean, coming from an epidemiologist, that's uh, that's quite reassuring. And I think the listeners will definitely appreciate the little snippet of epidemiology there to just contextualise exactly what we're talking about. Because like you said, you know, with a smaller amount of people, you really have to see something quite dramatic um, for it to be statistically significant. Um, the other question kind of pertains to that, I guess, is when it comes to uh, a determined anti-cancer effect, yes, we can have the mechanistic studies, yes, we can see things in vitro. Um, how long are we going to, let's say we had a whole cohort of people who are more at risk of breast cancer for a number of different reasons or other types of cancer. How long would you have to follow those people up for taking a supplement, something like sulforaphane, to actually demonstrate whether this is going to have a positive effect or not?
Dr Rupy: This is the big challenge uh, is cancer prevention research, uh, especially interventional cancer prevention research because these things can take, you know, these cancers can take decades, you know, to to manifest when there's been, you know, some of these uh, predispositions, whether it's genetic, you know, the BRCA1 and 2 type of variants or poor lifestyle. This is the the challenge. So if you look at most of the cancer prevention studies, they've been um, uh, either in animal models or they've been epidemiological studies that look retrospectively at risk. But it can take a long time. I mean, there there have not been a whole lot of for anything. This is certainly for medications as well as for exposures. It's tough if you just get a cohort of healthy people, you're going to have to follow them for decades, you know, if you're an intervention. So that would be really costly to do. So I I think for a lot of these types of things, we look at a combination of, you know, we work with the samples that are there, we look at mechanisms, you know, does it make sense? So let's take a look at sulforaphane. It's a potent HDAC inhibitor. We know a lot of the medications that are used to treat cancers are HDAC inhibitors. So we look at it sort of a resonance in terms of the mechanisms and those those types of things. So, but cancer prevention, the other chronic disease prevention, it's tough to do interventional prevention studies because they're so expensive and it takes so long, you know, for the events to develop, even for those that are at risk.
Dr Chris D'Adamo: Yeah, absolutely. I was listening to a podcast actually quite recently about just the um, lack of success in cancer research and cancer treatment and really where we need to be focusing a lot of our monetary resources is prevention as much as treatment because, you know, slash burning using chemicals, etc. You know, as that's a standard of care and it definitely needs to be, we really need to start putting more effort into diet, lifestyle, but also entertaining other means like, you know, uh, supplementation as I'm, you know, finding out a little bit more about. Um, we had a a colleague of mine who's an oncologist uh, talking about a concoction that they're making with um, I believe broccoli extract is definitely in there, but also mushrooms, which you mentioned a bit earlier, and a few other things like camomile tea, looking at research that um, demonstrated some impact on COVID-19 in cells, giving it to patients in a double blind randomised control trial. If there was a selection of ingredients that you could pick out, and I'm not trying to suggest that, you know, this is definitely going to be a treatment for COVID or anything that can improve it, but what kind of things would you be telling patients or are you telling patients in order to keep healthy on top of the foundation being good sleep habits, good nutritional habits, and good exercise habits?
Dr Rupy: Well, the foundation I think is the key, all those things you just mentioned there. Um, yeah, I'd love to hear more about that that uh, concoction that's coming up because I think the the combination of uh, sulforaphane and mushrooms, particularly maitake mushroom, that's in the Avmacol extra strength that my we're we're doing a clinical trial at my centre on that, uh, is is fascinating. So, I worked with the Institute for Functional Medicine, um, and we developed a list of nutrients, uh, I can provide the link uh, for you, nutraceuticals that can be helpful for this. And uh, you know, we've talked about some of them, sulforaphane, maitake mushroom, um, uh, quercetin, another one that's on the list uh, for sure. That's another one. You know, vitamin C, vitamin D, a lot of the data, and we've seen those with uh, uh, the mortality and vitamin D levels are inversely associated. So keep the vitamin D levels up. Um, you know, elderberry is another one. Uh, curcumin, melatonin. So there's a bunch of these different nutraceuticals that um, we think can be helpful in uh, in this in this uh, process. Just again, to to give ourselves that boost in innate immunity, um, so that we're we can fight off the uh, pathogens that we come across. And then, you know, to manage our inflammatory response with some of the more anti-inflammatory um, uh, components. So, um, I would suggest checking out that list. It's it was very thoughtfully conceived and and uh, a lot of good evidence behind it.
Dr Chris D'Adamo: Yeah, definitely. I'll I'll definitely link to that for sure if you send it over. Uh, my uh, my colleague who I was just talking about, he was also one of the lead authors on the Pomi-T trial that observed uh, patients with slow-growing prostate cancer being given in a placebo-controlled trial, um, a concoction of broccoli, pomegranate, and a few other things like green tea, I think. And a similar sort of list has gone in. And I think those things that you just mentioned, quercetin, um, uh, vitamin E and a couple of other, sorry, melatonin and a couple of others might be in that concoction as well. But it's it's still a trial that's undergoing right now. But it's interesting because it's in a cohort of COVID-19 patients. So,
Dr Rupy: Oh, that's fascinating. Yeah, I'll have to, yeah, send me the link. I'd love to take a look at it. And you mentioned pomegranate's another great one too with the ellagic acid and there's just, I think this is the the the benefit of getting a variety of these different um, uh, plant, you know, the phytonutrients into our our diets because they they all operate on slightly different mechanisms and there's a lot of great synergies, you know, that are between them. Um, you know, uh, sulforaphane and maitake is just one, but yeah, you look at getting curcumin into the mix potentially, pomegranate, uh, a lot of these other polyphenols, dark chocolate, cocoa polyphenols, EGCG. I mean, there's there's a lot there and I think this is uh, the value of getting um, a bunch of these into our diets.
Dr Chris D'Adamo: Definitely. Yeah. Um, I know you've done a lecture that's available online about uh, healthy ageing where you give recommendations about maintaining protein intake, but also looking at magnesium, vitamin D3. I'd love to know what's in your concoction. Uh, not to suggest that, you know, everyone should be taking exactly the same one. Everyone's an individual, you know, your needs are different to mine, but I'd love to know uh, what's in your armoury right now.
Dr Rupy: I'll give you a very long list. No, it's you know, it's funny, what motivated me to get into this subject was uh, my uh, grandfather lived to be almost 101, but he was lifting weights and uh, up into his upper 90s, playing tennis. And I got fascinated by uh, you know, longevity and thriving into into older age. And I was actually trained on epidemiology of ageing fellowship from the National Institute of Ageing here in the United States. And all this about compression of morbidity so that we can thrive, not just to live to be, you know, you look at some of the radical life extensionists, they say they want to be 180 and Dave Asprey and some of these, who knows, maybe we get there. But I think the main thing is to uh, not be sick. You know, so there's a lot that we can do with that. I mean, I think the foundations that you mentioned before, you know, sleep, minimising environmental uh, toxins, physical activity, maintaining lean body mass, all the foundational stuff. But I think you get into a lot of the things. I mean, again, I think sulforaphane uh, for the NRF2 pathway. I think you get into some of the NAD uh, uh, you know, the sirtuins. I mean, I I find that fascinating. Um, so if you look at, you know, NAD uh, uh, resveratrol, a lot of these types of things, I think are fascinating. Um, you know, I think autophagy. So I think that uh, I didn't talk about this in that in that talk, I think that you found, but I think uh, intermittent fasting, you know, time-restricted eating is really important. I think hot and cold exposure, you know, and I'm doing all these things too. And I got an Oura ring, I quantify all this this type of stuff. I think, me too. Yeah, I got one as well. There you go. High five. But but it's uh, there's there's a lot there. And I, you know, I think I think there's a we're going to see a whole new cohort of people who are living very healthy. You know, we see it now in in uh, a lot of parts of the world where people tend to live long. I think social connection and purpose are very big with this too. Um, so these are some of the things, those are just some of the things that that I do. You know, I think there's the the, you know, minimising blue light exposure to help us get better sleep, a lot of these types of things. But I think molecularly, there's a lot, there's a lot there. I think when you look at the sirtuins and NAD, NRF2, keeping inflammation low, keeping blood sugar regulated. So things like berberine, you know, can help with that. Just, you know, eating a good diet, of course. But there's there's a lot there. I love it. I mean, it's, you know, we're really blessed to be in professions where we get to, it's our job and we get to learn and apply it to ourselves. So it's it's a lot of fun.
Dr Chris D'Adamo: Yeah, absolutely. And I think there's a bit of self-experimentation going on as well with myself. I mean, I I certainly see patients of the future being privy to a number of different wearables, of which, you know, an Oura ring is one. But continuous glucose monitoring, uh, nutrigenomic testing, um, to to make sure that we're actually putting together modifiable genetic snips that we can actually have some impact on, whether it be with a B12 supplement or or otherwise. Um, because right now, we're kind of playing a bit of a guessing game. Um, I mean, I primarily work in emergency medicine, so a lot of what we do is diagnosis and we have a lot of investigations. But in the primary care sphere, we're quite limited, uh, unless we go into, you know, functional medicine, which is something that us in the UK are quite behind on. Um, so, yeah, no, I I I'm definitely a fan of entertaining all these different uh, um, modes of of of intervention, whether it be with food and and otherwise.
Dr Rupy: Well, you know, you raised a an interesting fascinating subject of of nutrigenomics and nutrigenetics. So we've our centre has done some work with that. We looked at uh, genetic associations of carotenoids. Um, lycopene, alpha-carotene, published a couple of papers on that. I think there's a tremendous amount of potential there. There's, you know, more and more labs are coming out with with good good assessments. I think we look at clusters of snips. So we look at clusters of the variants because any single variant, we see this a fair amount with, you know, the MTHFR variants. There's actually many variants on MTHFR. The C677T is the one that probably has the strongest impact on human health. But you you'll a lot of times just see people say, oh, I have I have MTHFR. Well, we all have the gene, but you know, they'll have the variant and then they take high levels of methylfolate, which can be helpful, but there's a bigger picture there. And I think the better technologies that I've seen will actually look at clusters of the snips and say, look, you've got these different uh, snips, you may want to consider supplementation or diet or being more aware of detoxifying or, you know, getting certain things in the diet and so on and so forth. I think that it's really fascinating and we're getting farther and farther along and people are using some of these tools in clinical practice with with great success.
Dr Chris D'Adamo: Yeah, yeah. I mean, it's all very fascinating to me. I can't let you go without asking your opinion as an epidemiologist on the arguments between organic and conventional produce. Granted, it's very different between the UK and the US. I think our conventional produce tends to have less pesticides in general. But I wondered what your opinion on that and and perhaps what you what you talk about with regards to culinary medicine because we certainly get asked by our our medical students quite a lot about this subject.
Dr Rupy: So do I. So that's actually a part of my, this is actually a part of my uh, lecture for them as we get into some of these these topics. I am very much in favour of organically grown uh, produce uh, for both human health and the health of the planet. Um, and uh, you know, I think the conversation of whether there's more micronutrients in an organic blueberry versus a conventional is somewhat interesting, but it's it's it's I think tangential to to the bigger thing. I think cumulative uh, pesticide exposure, uh, I think over a lifetime is is going to be a problem. It's hard to quantify that. You know, you mentioned how how do you do the long-term studies? How do you do the long-term studies on this where it's these tiny amounts over a long period of time? It's tough to do them. You know, um, but uh, you know, I think you look at some of the data that shows that that conventional uh, produce has more pesticide residue than organic. And and that to me is is good enough. And I eat almost exclusively um, organic. But here's the thing, not everyone can afford to do that. So a lot of the patients that we serve and our medical students always talk about that. So I use the, you know, the the good, better, best type of philosophy and not letting perfect be the enemy of good. So if you got a patient who's eating uh, you know, not to I was going to drop a couple of fast food, but say fast food, you know, fast food, and then they go to eating canned green beans. That's a good step forward. You know, it doesn't necessarily need to be uh, organic, uh, you know, locally grown and these kind of these types of things. Um, but for those who do have the means, I think it it's good for the health of the of the planet, you know, uh, among our own personal health uh, to do that. But I think we try to encourage uh, people to get the the uh, the uh, you know, fruits and vegetables where they where they can. Um, if they're really starting out at a lower level. Um, and then same thing to prioritise if they're going to be eating fish and meat to prioritise getting bulk, you know, wild caught salmon or bulk grass-fed beef and then it becomes the price point becomes a little more accessible to people. But yeah, I I'm very much in in support of of uh, organic agriculture and and uh, uh, animal products when when uh, when available.
Dr Chris D'Adamo: Yeah, no, I feel like high-fiving you uh, virtually right now because it's almost like mirrors exactly how I spiel it as well. Like I I employ like a precautionary principle when it comes to organic eating for myself because I'm privileged enough to be able to afford it. And I think there are some environmental reasons as well. Um, but I also, as with your culinary medicine programme, we teach our um, students about food insecurity. Uh, there's over 4 million people in the UK alone who are reliant on food banks and they won't have the uh, opportunity or the luxury of choosing exactly where their produce comes from. And that transition from fast food to canned vegetables is actually a huge shift, um, which, you know, is something that we have to celebrate every step of the way when we're dealing with patients uh, in in our healthcare system. So I appreciate that.
Dr Rupy: I can give you an Oura ring wearing high five virtually because we're on the same page with that one. But yeah, definitely. And I would point uh, your viewers if they haven't seen the environmental working group, they've got a nice list too. Again, when you're making that priority, and I teach the medical students about this, it's the dirty dozen, clean 15. Are you familiar with that?
Dr Chris D'Adamo: Yes, yeah, yeah, I'm come across that before.
Dr Rupy: Yeah, it's a nice list. So for those that can't afford uh, organic, you know, exclusively to to make priorities in certain areas. And largely it's those, you know, foods where we don't eat the skin or the uh, uh, you know, the the outer covering, you know, are the ones probably where it's most important. But but the list, it's a good a good list for people that can be helpful. Environmental working group has a lot of good stuff, I think. You know, when it comes to other, you know, we talked about detoxification, sulforaphane, um, but also some of the personal care products that people use, they're just loading themselves up with uh, carcinogens and our endocrine disruptors. And they've got a good resources on how to minimise those exposures.
Dr Chris D'Adamo: Yeah, I mean, that's like another podcast in itself. I think I need to speak to someone about um, this new term clean beauty, um, which sounds quite scary, but I think it's quite an important uh, you know, conversation to have given that there are like something like 3,000 new personal care products every year that come into our system, which don't undergo testing as to, you know, what the long-term environmental impacts are. And these are things that we put on our skin, on our faces, in the most sensitive parts of our body without, you know, giving due diligence to the impact of that over a long period of time.
Dr Rupy: I think it's hugely important. I mean, I I transitioned, I did it very uh, carefully away from using um, aluminium-based uh, antiperspirants. You know, and it was I because I I would sweat so much before. And I said, how am I going to do this? But it's amazing how when you can transition into some of the the better, you know, there's a lot of these at least in the US, these um, they're kind of baking soda, coconut oil and other natural uh, essential oil deodorants. It's just amazing how much less you sweat with that. So, and then you're not getting the aluminium so close to your brain. There's a lot of these things. You know, you talk about clean beauty. I think that that are really important when it comes to skin products, shampoo, fragrances. You know, a lot of this stuff too, people are are doing themselves uh, you know, a disservice with a lot of that. It's good to see some awareness coming up about it.
Dr Chris D'Adamo: Definitely. Yeah. Chris, honestly, this is so lovely to connect with you. Uh, I'd love to when all this is over, come and visit the kitchen at some point. Uh, I think it'd be brilliant. And I'd love to collaborate on stuff going forward as well with our culinary medicine programme here in the UK.
Dr Rupy: We'll do a multi-continent collaboration somehow. Yeah, definitely. You're always welcome to come and and uh, look forward to connecting with you again sometime soon.
Dr Chris D'Adamo: Brilliant. Thank you, buddy.
