RHR: The Effects of Red Meat on a Whole-Foods Diet, with Dr. Stephan van Vliet

In this episode, we discuss:

• Stephan’s background
• The whole-food matrix: not all nutrients are created equal
• Dr. van Vliet’s upcoming research: the effects of red meat in a healthy “whole foods” diet
• Why you should be cautious when it comes to restrictive diets
• The effects of a vegan diet in children
• The role of animal protein in the diet
• Can a diet high in animal protein cause kidney problems?

Show notes:

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Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I’m really excited to welcome Dr. Stephan van Vliet as my guest. Dr. van Vliet earned his PhD in kinesiology and community health as an ESPEN fellow from the University of Illinois at Urbana-Champaign and received postdoctoral training at the Center for Human Nutrition in the School of Medicine at Washington University in St. Louis.

He’s a member of the Duke Molecular Physiology Institute within the School of Medicine at Duke University. Dr. van Vliet’s research has performed at the nexus of food production systems and human health. In his work, Dr. van Vliet links agricultural production systems to the nutrient density of food and their subsequent effects on consumer metabolic health using high-throughput techniques such as metabolomics and proteomics.

Dr. van Vliet routinely performs interdisciplinary clinical and translational studies to evaluate the effects of dietary pattern[s] and food sources on protein and lipid metabolism, inflammation, insulin action, body composition, and intracellular signaling pathways that regulate metabolic health. And his work has been published in the American Journal of Clinical Nutrition, the Journal of Nutrition, and Frontiers in Sustainable Food Systems.

I wanted to talk to Dr. van Vliet because I came across an article he wrote about vegan diets and children, and also became aware that he’s working on a randomized control trial that will study the effects of red meat in the context of a whole-foods diet versus a Standard American Diet. This is a study that I’ve been dreaming would exist at some point, and I was so excited to find out that it’s actually underway because I think that will address some of the major issues with nutritional epidemiology as it concerns red meat. And I want to talk to him about his recent research on plant-based meats, grass-fed meat, dairy, and dairy products and their nutritional profile, calorie restriction, etc. So I think you’re really going to enjoy this. Without further ado, I bring you, Dr. Stephan van Vliet.

Chris Kresser:  Dr. Stephan van Vliet, welcome to the show. It’s a pleasure to have you on.

Stephan van Vliet:  Thank you so much, Chris. I’m happy to be here and thank you for inviting me.

Chris Kresser:  I’ve been looking forward to this conversation. I think we know some of the same people but didn’t know each other. And I originally became aware of your work when I saw some comments that you’d made on a study on vegan diet and children and then also became aware that you, and we’re going to talk more about this, so you can correct me if I’m wrong, are currently working on a randomized controlled trial studying the effects of red meat in the context of a whole-foods diet versus a Standard American Diet. As I expressed when we connected, that’s like my dream study—the study that I wish had been done so many years ago.

But before we dive into all of that, why don’t you give everybody a little bit of an idea of your background and how you became interested in this field.

Stephan van Vliet:  Certainly. I did my undergrad, actually, in business, so I had a little bit of a career switch at some point, but it was really during that time that instead of reading journals regarding economy and management, I was reading physiology and nutrition journals. So then by the time I finished my undergrad and got my degree in business, I decided I should probably make a career switch. So I (audio skips 1:32) shift for a while in a muscle metabolism lab in The Netherlands working with stable isotopes and studying muscle protein metabolism. I got my master’s then in exercise and nutrition science before making my way over to the [United States] where I did a PhD at the University of Illinois, and I graduated as an ESPEN fellow in kinesiology and community health. It was there where my work focused a lot on whole-food protein ingestion and its effects on muscle protein synthesis. And I found an important role for what we call bioactive compounds or nonprotein nutrients and stimulating muscle protein synthesis, meaning that the picture is a little bit more complicated than just amino acids stimulating protein synthesis. But actually, having very nutrient-dense foods can further upregulate protein synthesis. So that was the spiel of my thesis.

Then I did postdoctoral training at Washington University School of Medicine in St Louis. My research was focused on obesity. And over the past two years, I’ve been at Duke University, the Duke University School of Medicine in the Stedman Nutrition and Metabolism Center, and it’s really here that a lot of my work is focused on nutrition and dietary patterns and food metabolomics, and we can talk about what that exactly is. But it’s basically looking at the complexity of the whole-food matrix and how the hundreds to thousands of metabolites in foods can impact human health or really going beyond just the nutrients that only appear on food labels. But really looking at what are all the constituents in food and how do they impact our metabolic health. And indeed, we currently have an ongoing study as you mentioned, where we are looking at the effects of red meat as part of a “whole foods” diet or traditional diet versus a more modern Standard American Diet.

Not all red meat is created equal. In this episode of RHR, I talk with Stephan van Vliet about the effects of red meat as part of a “whole foods” diet versus a more modern, Standard American Diet. #chriskresser

Chris Kresser:  I can’t wait to talk about that, and I want to start maybe a little bit more generally diving into a couple [of] areas that you mentioned in your introduction. One is this concept of food synergy that you were alluding to. I don’t know if you’re familiar with the work of Gyorgy Scrinis who’s a food philosopher. I didn’t even know such a profession or specialization existed until I encountered his work. I think he’s a professor in Australia.

But he has argued persuasively that we have this myopic reductionist approach to nutrition where, as you mentioned, we’re only thinking about nutrients on a food label as if a food is just a combination of nutrients and nothing else. And that one of the issues with nutritional research that plagues nutritional research is that it doesn’t consider the synergistic effects of nutrients as they occur in a food. And an example of this is I just did a presentation at [IHH-]UCSF Symposium on [Nutrition and] Functional Medicine on the role of vitamin D in the COVID-19 pandemic.

And it turns out that magnesium is a very important cofactor for vitamin D and is needed for the metabolism of vitamin D. And if you have a magnesium deficiency, even if you’re getting enough vitamin D, you’re going to be biologically vitamin D deficient. There [are] so many other examples of this and yet, in most of the studies that I see, this is never considered as a factor. Do you think that’s a limitation of perspective or of technology? Or both?

Stephan van Vliet:  Yeah, probably a little bit of both. I think it’s also human nature to want to dumb down things into very individual constituents because that’s usually the way that we can better understand things.

Chris Kresser:  Right.

Stephan van Vliet:  But indeed, the nutritional reductionism I agree, it’s a huge issue because we routinely track 150 nutritional compounds in USDA databases. Thirteen of those appear on nutritional labels, which are obviously protein and fat, several vitamins and minerals, and carbohydrates and sugar, and also saturated fat. But it is really when we look at some of these compounds that are in foods, which we sometimes call the human food dome or the food metabolome, it contains an estimated 70,000 unique metabolites that are potentially capable of impacting human health. And it is indeed, in that case where the synergy between those and we see that often, that was also what I saw in my PhD work, where we saw a synergy between various nutrients in the whole-food matrix.

Particularly, for instance, one study that we did was, we compared whole eggs versus egg whites. Now whole eggs and egg whites have a very similar amino acid profile. But obviously, all the bioactive compounds and vitamins and minerals are contained in the yolk portion of the whole egg. So what we saw was that when we gave people an isonitrogenous amount (it means matched for protein), so a similar amount of protein from egg whites versus whole eggs, we saw a higher muscle anabolic response in [the] case of the whole eggs. And this was likely due to the synergy of these compounds within the food matrix, because as previous studies had shown, that if you just provide protein and then the fat as isolated sources, you do not see that effect of an often anabolic response.

So there’s definitely something within the whole-food matrix that it has a beneficial effect. And I think to broaden the point, that is also what we generally see with that calcium-containing foods are protective for health. Carotenoid-containing foods are protective for health. But if you would ingest carotenoids, as for instance beta carotene. There [have] been many field trials in the area of beta carotene, actually sometimes showing an increase in disease risk, right?

Chris Kresser:  Yes.

Stephan van Vliet:  Because carotenoids always occur with 300 other carotenoids in nature. So if we then give an isolated constituent, that usually makes it much less effective. So I agree with you that nutritional reductionism is hard. But then also, the other issue comes back to technology, and we use food metabolomics where we at least are able to get somewhat of an insight [into] the complexity of whole-food sources. But I still cannot say exactly okay, these work together in this way and this is how it works. We’re really scratching the surface on that, too. But it does at least seem that this whole-food matrix effect is crucial. And here we are at the moment, also. Yeah, it is an emerging area of interest.

Chris Kresser:  Right. And the data might be so complex that we’ll need [artificial intelligence] (AI) or machine learning or something to really make sense of it in the end. Do you think that’s the case? Or do you think we’ll be able to parse it with our human brains?

Stephan van Vliet:  No, I think definitely. But even with AI and machine learning, it’s only as good as the inputs, I guess.

Chris Kresser:  Sure.

Stephan van Vliet:  It’s still the human brain. But yes, that’s definitely something that’s coming up now, using machine learning and AI and training based on, it’s still sort of based on the inputs that you get from studies. But that’s definitely helpful to understand these things. And right now, I would say is what we can see is that okay, as far as a whole-food matrix or how you ingest these compounds matters. So the best we can say now is that it’s probably best to get your sources from food as much as possible.

Chris Kresser:  Yeah, that’s fascinating, and I think it’s so important. And I really am hopeful that this greater focus on metabolomics and proteomics, which enables us to see the complexity of what’s going on in the background, will lead us to a change in our perspective on nutrients and the role that they play.

Chris Kresser:  Along those same lines, one of the biggest issues in nutritional epidemiology, which I’ve talked and written about a lot, is the healthy user bias. So for people who are not familiar with that, this is a phenomenon that occurs. Let’s say you do a study and you’re trying to determine the effects of red meat [on] the diet. And you study a general population and you find that people who ate more red meat had [a] higher risk of cancer and heart disease and other diseases. But the problem there is that red meat has been perceived as unhealthy in the [United States], at least for many, many years. So people who eat red meat are also more likely to engage in other behaviors that are unhealthy or perceived as unhealthy.

And so it’s very difficult then to parse out whether the disease effect is due to red meat or due to those other factors. Do you think that, I know you’re, of course, actively working on this with the randomized controlled trial, so we can talk about that now. But do you think that this greater focus on metabolomics and proteomics will also help to address the healthy user bias and research? Or is that going to be more, at least in the short term, related to study design as you’re doing it with the randomized controlled trial?

Stephan van Vliet:  Yeah, I think there’s going to be related to the study design. But I do want to point out that, indeed in epidemiology, you generally see that individuals that are on the Standard American Diet also consume more red meat, and a regional survey on the Standard American Diet being rich in all the (inaudible 11:42) food, sugar, lower in fruits and vegetables. But there are several large-scale population-based studies in individuals with healthy lifestyles, such as the Oxford EPIC cohort that has 65,000 people. The 45 and Up Study in Australia, which had I think about 270,000. Then also more recently in Alberta’s Tomorrow Project, also an epidemiological study. And what the authors found there is that in the context of high fruit and vegetable intake, high red meat intake actually was protective.

And there, I won’t say it was not nonsignificant, but the relative risk in the people that ate the most fruits and vegetables versus the lowest fruits and vegetables, despite having high red meat intake, which was over a pound a week, still showed that the relative risk of cancer went from, I think, 1.2 to about 0.8. So I must say that you do indeed see this healthy user bias, but at the same time, you see when people do eat red meat, and also in epidemiological studies, you see that when people eat red meat as part of a “healthy whole foods” diet, the risk becomes more or less benign. And that is also what we’re interested in testing in a randomized controlled trial is that if you consume red meat as part of a Standard American Diet, or you consume it as part of a more traditional diet, which is, think about how maybe our grandparents used to eat meat as part of a whole foods diet that’s also rich in fruits and vegetables, unprocessed plant foods, low in added sugars, and super sweetened beverages and things like that. So think of it low as in low in ultra-processed foods.

So we were interested in testing that, and that is currently an ongoing randomized controlled trial that we have. And even though we are about halfway through, what we see now is that people that consume high amounts of red meats on “whole food” diets tend to improve. This is a four-week study, so it’s short-term, but in these four weeks, we see a reduction in triglycerides, a reduction in [low-density lipoprotein] (LDL) cholesterol, maintenance in [high-density lipoprotein] (HDL) cholesterol, [and] reduction in total cholesterol. We see some inflammatory markers improving like [interleukin-6] and C-reactive protein.

Again, not the full data set yet. So I don’t know if it’s all up at, when we have the full data set. But these are at least some of our preliminary findings where we see that if you, and we’re validating the epidemiological study. So we’re actually not that different from the epidemiological studies, but most of what you hear in nutritional epidemiology is because most of it is performed in people on the Standard American Diet. So I think that that is important to point out.

Chris Kresser:  Yeah, that’s a great point. And I covered several of those studies in a few of my Joe Rogan appearances and debates with Joel Kahn. And it’s a good reminder that you can design an observational study to answer these questions if you design it with that intent, and if you design it well, right?

The first study, I think, that I’m aware of that attempted to do that was the Health Food Shoppers study out of the UK where they were aware of the healthy user bias and they thought, “Well, how can we take at least one simple step toward trying to identify a population of people who are making healthier choices than the general public and then differentiate between eating meat or not eating meat within that population?” So they basically just studied people who shopped at health food stores thinking that that was probably a decent although somewhat crude way of identifying people who have a generally higher awareness of health.

And then they found that there was a huge difference in overall mortality and morbidity between the entire Health Food Shoppers group and the general population, but there was no difference in morbidity and mortality between the people who ate meat and didn’t eat meat within the Health Food [Shoppers] group. So, that still, of course, doesn’t prove, it’s still observation, [and] all the caveats apply. But it’s at least an attempt to control for some of those potentially confounding factors.

Stephan van Vliet:  Yes, exactly. Based on some of that data we’re trying to objectively test the hypothesis what it is will hold up in the randomized controlled trial. And I do want to add though is that there’s some mechanistic insight in this, too. Because the findings of extensive in vitro and in vivo data mostly in animal models, but they do suggest that plant compounds can antagonize the deleterious effects of harmful compounds in red meat. So think of adverse (inaudible 16:48), nitrogen compounds, (inaudible 16:51) proteins.

Chris Kresser:  Yes. TMAO.

Stephan van Vliet:  Yeah, exactly. So if you marinate your meats or use a lot of spices or have it with red wine or coffee or [an] otherwise plant-rich diet, you do see that the formation of these compounds is reduced by sometimes to 70 to 80 percent. So it’s really that complementary nature of plant and animal foods and I think combining one food with another to offset the bad of one food to reap the benefits. So let’s say obviously red meats, let’s take that as an example. Rich in bioavailable protein, rich in a variety of vitamins and minerals, but it may come with some deleterious compounds, too. But we can offset those, potentially, by consuming them as part of a phytochemically rich diet or combining this with bland foods.

And I think that is as old as humanity because one example I always like to use is that in more traditional groups within Latin America and at least historically, for instance, is [to] use clay with their potatoes. The reason that they would do that is they would reap the benefits of the potato, get the starch, get vitamins, minerals, but the clay would bind to the toxins and the toxins would pass out of them. So this is another classic example of how humans have been ingenious in the past to combine one food with another to make sure that you get the benefits of one food but offset the potential negative compounds of the other. So, in that case, there’s also that potential with red meats, for instance.

Chris Kresser:  I couldn’t agree more, and I have to admit my personal bias here that I’ve always been a little bit skeptical of really extreme dietary approaches that are followed for a long period of time for that reason. So the carnivore diet being the latest example, I think, where there’s no doubt that anecdotally, I’ve seen this as a clinician, some people are getting phenomenal results from following a carnivore diet. People with severe autoimmune diseases that have been intractable and have not been able to address them any other way [are] becoming essentially symptom-free and going into remission after some period of time on a carnivore diet.

And so I completely understand the appeal, and yet for all of the reasons that you just mentioned, including no historical example that we know of, of a population that exclusively consumed animal products at all times during the year for a long period of time and based on some of the mechanisms that you just mentioned of what we know about how phytochemicals can tend to offset some of the potentially harmful compounds that are formed when you eat meat or when meat is digested, it gives me pause (let’s just put it that way) and makes me feel a little bit cautious or nervous about people doing that for a long period of time. I’m just curious, what’s your perspective on that, based on your research?

Stephan van Vliet:  I fully agree with everything that you mentioned, especially, that’s also my reservation regarding the carnivore diet. And I think, if we draw a parallel to maybe a vegan diet, you see the improvement in health could potentially be because of the foods that you’re not eating, right?

Chris Kresser:  Right.

Stephan van Vliet:  It’s a good elimination diet if you have issues with certain bland compounds or you have leaky gut and you have problems with digestion, then an elimination diet could definitely help by taking away the source. So you initially, of course, feel better. And the same, for instance, with potentially a vegan diet where if you improve your diet quality, that may improve, or let’s say if you had sensitivity to dairy or something and you remove that, then obviously, you can see a health benefit. And of course, I must also admit that eating a lot of phytochemicals in part of a vegan diet is beneficial. And we should jump into a study later on that came out a few days ago in the American Journal of Clinical Nutrition, which was in children. But we can talk about that in a little bit.

But that showed that the increase in phytochemicals might be a good thing, but that in some animal foods as part of that might also be a good thing. But not to go off too far at the moment. But yeah, I agree. That’s also my long-term reservation, is that yes, initially, you may feel better because you eliminate some foods. But what about some of these phytochemicals that you’re missing over the long term? Well, they have an impact on your health, and sometimes disease risk over the long term, particularly with things such as cancer.

Chris Kresser:  It’s such a critical point. I’m glad you brought it up. It can be a good segue into talking about vegan diets and kids, which is the way I originally was exposed to your work. I often ask that same question. Someone says, “I felt amazing when I switched to a vegan diet.” And some of the follow-up questions would be, “What were you eating before?” And often the answer is a Standard American Diet. So, of course, if you switch from eating ultra-processed foods and sugar and flour, and industrialized seed oils, and all that crap, and then you move to eating whole foods, you’re going to feel a lot better almost across the board.

But then the next question is, “How long have you been on the vegan diet?” And if the answer is a few months, then I’m still going to be skeptical that it’s the best choice because, we can talk about this if it comes up, in the study of vegan diets, we know that some of the nutrient deficiencies that can develop on a vegan diet don’t happen overnight, right? They take months, in some cases, years, and it depends a lot on the nutrient status of the person before they adopted the vegan diet. It also depends probably on genetic factors that affect conversion of precursor nutrients, like beta carotene to active forms of the nutrient like retinol.

So yeah, let’s use this as a segue to talk about this study that looked at the effects of vegan diets and kids. I believe you weren’t the author of that study, but I recall reading a tweet that you did about the study. Am I remembering that correctly?

Stephan van Vliet:  Yes, that’s correct. The study was out of Finland. I do want to highlight, I’m coming back to your point first before I move into the vegan diet. I would say the same could be true for a carnivore diet, too, where initially, you will feel better on that. So that I think is a (crosstalk 23:52).

Chris Kresser:  Absolutely.

Stephan van Vliet:  If you go from a Standard American Diet to a carnivore diet or a vegan diet, or a whole-foods carnivore diet.

Chris Kresser:  Or a ketogenic diet. I want to mention that, too, because [the] ketogenic diet can be [an] incredibly powerful therapeutic tool for so many conditions like epilepsy and type 2 diabetes and type 1 diabetes and cognitive decline, dementia, Alzheimer’s [disease], Parkinson’s [disease], etc. But that doesn’t necessarily mean by extension that it’s a sustainable, or optimal long-term option. I think that’s where we need to make the distinction, right?

Stephan van Vliet:  I agree. And also, the individual differences between humans is so great that what may work for [one] person might not work for the other person. And that’s why also when you have (inaudible 24:41) of people being on a carnivore diet for 20 years or being on a vegan diet for 20 years, and it being in good health based on their (inaudible 24:50) at least, I certainly believe that is possible. But I don’t think it is possible across the board, right?

So indeed, we do know the individual differences exist, and as you mentioned, the beta carotene to retinol conversion varies wildly between people and with some of these other conversions, too.

Chris Kresser:  [Vitamin] K1 to K2.

Stephan van Vliet:  Yeah, exactly. So those are all important nuances. When someone says, “Oh, this works for me, and I feel great,” that can be the case. But another person says, “Well, I tried the vegan diet for 10 years and my health fell apart,” it may not be because they didn’t do it right. But it could just be that, due to genetic differences, [they] are not able to sustain that.

Stephan van Vliet:  But coming back to the study on the vegan diet and children, and I think this is where it gets a little bit more tricky, because obviously, as an adult, I would not question that someone can be healthy on a vegan diet. But what the study found in feeding children is they didn’t have a distinct metabolome profile and included lower DHA, which is omega-three fatty acids. Also considerably lower levels of total cholesterol, HDL cholesterol, LDL cholesterol, alterations [in] circulating amino acids, lower levels of vitamin[s] A [and] D, lower levels of zinc. And if you zoom in on the cholesterol for a little bit, what’s particularly interesting about that is that what the authors also saw, alongside the lower levels of HDL and LDL cholesterol, also intermediaries in cholesterol. So this [cholestenol] was lower.

So what that basically means is that the endogenous compensatory cholesterol biosynthesis that you typically see in vegan adults, where the endogenous production takes over and provides the necessary cholesterol, this was not so much the case in children. So that’s maybe somewhat concerning, because especially when children are obviously growing, and we know cholesterol is essential for cellular growth, for cell division, for development of many physiological substances, because it’s a major role in the synthesis of cell membranes. Especially in a rapid growth period as a child, that might be an issue. It’s a precursor to steroid hormones and also the brain myelin.

Chris Kresser:  The myelin. Myelin sheath, yep.

Stephan van Vliet:  Yeah, exactly. So that is important. And then also, what they all just did was a metabolomics analysis similar to what we use in my lab, too. And that’s why I particularly was interested in the study, and it was quite unique and hats off to the authors for the study. But they also showed that bile acid biosynthesis was the largest pathway that was altered in vegan children. So the metabolomics data. And we know the main route of cholesterol excretion is through bile acids. And so these direct measurements revealed that higher primary bile acid and cholic acid and a lower taurine to glycine ratio, showed that there was a large difference in a pathway in bile acid biosynthesis.

So I think that’s where a little bit of the caution should come in. And even though there [are] no clearly defined efficiency levels based on blood cholesterol, the fact that these cholesterol levels in vegan infants and children were so low, and that cholesterol within the body was not upregulated or did not take over, yeah, that would be my big concern for the long term. And then rolling into a study that just came out in the American Journal of Clinical Nutrition. And this was a study where also [there was a] cross-sectional comparison between vegan kids, vegetarian kids, and omnivorous kids. So they were between five [and] 10 years old. And here, it also showed many of the same things. Lower total cholesterol, lower HDL, also lower [vitamin] B12, and 25-hydroxyvitamin D unless they were supplemented. But what was important is the bone mineral density was lower, and the vegan children were shorter than [the other children]. So there was a suggestion at least that it stunts growth a little bit. And what was interesting about that, and perhaps somewhat paradoxically, is that they did have sort of a metabolic profile that was suggestive of better cardiovascular health. So they had issues with growth, with something (growth? 29:21), but they did show with a healthier cardiometabolic profile. For instance, a lower C-reactive protein.

Chris Kresser:  [I have] a question about that, though. Was there any context control of the omnivorous diet, or was it just a Standard American omnivorous diet?

Stephan van Vliet:  Yes. So let’s go into that because the findings are relatively easy to explain in that case. It’s almost speculative, I must admit that. But what the study found was that the children that were consuming the omnivorous diet were consuming more of a Standard American Diet. So that means that their sugar intake or sucrose intake was 50 grams whereas [for] the vegan children, it was 38 grams. The fiber intake of the omnivorous children was 15 grams, [and] vegan children had a fiber intake that was double of that. And also if you look at some other indicators like beta carotene, 2500 micrograms in omnivores, over 5000 in the vegan diet.

So what that suggests is that the vegan children were on a healthy diet whereas the omnivorous children were on more of a Standard American Diet. So I could not help [but] think that what if the vegan children ate a little bit of animal foods with their diet as part of their whole-foods diet? They probably would still have low C-reactive protein, [and] they would have a good cardiovascular [cardiovascular disease] risk metabolic profile. But they would probably also be thriving and be just as, of the same bone mineral density and probably also the same growth as the omnivorous children. So, in other words, what was tricky about the study is that the vegan children were clearly on a healthier diet. But I would imagine if the omnivorous children were on an equally healthy diet, they would also would have presented with a low C-reactive protein.

Chris Kresser:  I would imagine that, as well, and that’s why I’m so excited about your RCT, your controlled trial that you’re doing with red meat, because I think it will help to answer that question.

Chris Kresser:  I know there was another paper published by Ty Beal on nutrient gaps in low-income countries, and the diets of people in low-income countries and animal proteins potentially being able to fill that gap. That’s somewhat related to what we’re talking about now. So maybe we could talk a little bit about the role of animal protein in the diet, the things that animal proteins can uniquely provide, or if not uniquely, are substantial sources that are not found in plant proteins. And we could maybe start with Ty Beal’s paper, and then we can segue into a discussion of the difference between plant and animal proteins in terms of anabolic response and amino acid profile, which is, I know, a specialization of yours and you’ve done some work on that, as well.

Stephan van Vliet:  Absolutely. We can also talk about a recent paper where we actually compared beef with a novel plant-based meat alternative. So plant protein that was matched.

Chris Kresser:  Yes.

Stephan van Vliet:  So that also will highlight a lot of these things that we talk about. But yes, coming back to, and indeed that obviously changes things when you start looking at more developing nations or low-income countries [where people] were eating small amounts, even small amounts. Think of it like an egg a day or a few ounces of meat would go a very long way in providing nutrient adequacy. So that is important, and yes, can we potentially eat a little bit less animal-sourced foods? Can some people in the west do that? Yes, I certainly believe that we can and without any issues to our health. Exceptions may be when you’re older. We know you need more protein, especially due to anabolic resistance. Animal proteins are important. Also maybe when you’re younger but throughout in a healthy adult, and yes, that’s potentially the case.

But then if you look at low-income countries, clearly, the protein intake needs to increase. And if we just go beyond protein, obviously we’re also talking about common things that we think of, [like] zinc, [vitamin] B12, [and] iron. But also, some of these what we call secondary compounds, and I don’t really like using that word too much because it makes it seem like they’re not important.

Chris Kresser:  Right.

Stephan van Vliet:  But if you look at things like anserine, carnosine metabolite, or cystamine, I mean, creatine, hydroxyproline, you name it. Taurine. These nutrients have important physiological and anti-inflammatory immunomodulatory roles. And deficiencies are associated with cardiovascular deficits, neurocognitive deficits, skeletal muscle issues, [and] connective tissue dysfunction. So we know from randomized controlled trials that creatine and anserine, which are both amino acid metabolites found in animal-sourced foods exclusively, provide neurocognitive production in older adults. And also cystamine, also found mostly [in] animal foods, is a potent antioxidant that has neuroprotective effects and is a precursor of glutathione, which is one of the most potent intracellular antioxidants.

So if we, and this is again sort of go beyond this nutritional reductionism and we start peeling back the onion layer, or in this case, I don’t know, whatever commerce.

Chris Kresser:  Egg shell?

Stephan van Vliet:  Yes exactly. It’s like pulling back the, cracking the egg shell, is that we see that the complexity of foods is, the whole-food matrix is very complex and provides a plethora of nutrients that may not be found in certain other sources. So that’s why I also don’t like, and I started to get away from this, too, using the term “animal and plant protein” because that somehow means that they’re interrelated, that they are interchangeable. But they’re not because animal and plant foods provide so much more than protein. They provide a wide variety of nutrients that can impact human health. And so the aforementioned one that people may not think of immediately, but those can be potentially important for human health. And that is one of the things that we’re also investigating right now. And for instance, squalene is another one, which has antioxidant or anti-tumor activity in animal models. So it’d be interesting to see how that pans out in humans, too.

Chris Kresser:  Yeah, I’m glad you brought this up because one of the examples of this that I often think of is EPA and DHA. So historically, the precursor omega three, alpha-linolenic acid was considered essential. Essential having a very specific meaning in the nutritional context, meaning the body cannot synthesize it on its own, and we need to obtain it from the diet or else bad things will happen, right? And over time, some scientists have argued that DHA and EPA should actually be considered essential because in some cases, even when someone is getting theoretically adequate amounts of alpha-linolenic acid from things like flaxseed or walnuts or other plant foods that contain it, that may not be sufficient for them to convert that into adequate amounts of EPA and DHA which are actually very important nutrients for a number of processes in the body. The brain, anti-inflammatory effects, etc.

Especially when people are consuming large amounts of omega-six fats that can interfere with that conversion, or if they’re deficient in nutrients that are important for that conversion, which many people who are following an exclusively plant-based diet are. So it starts to get pretty complex, and maybe today’s secondary nutrient might become tomorrow’s primary or essential nutrient when we understand more about them.

Stephan van Vliet:  I agree. And to your point about the omega-three fatty acids, that is indeed true. And it’s likely that that conversion, which is generally less than 5 percent, or in many cases, less than 1 percent of ALA to EPA and DHA, sort of plant version to the animal version, I see that as like a fallback mechanism. In the case that we don’t have it, we can produce enough to sustain, keep us going.

Chris Kresser:  Right.

Stephan van Vliet:  But what we do see in many randomized controlled trials is that intakes of 200 to 300 milligrams, and sometimes even higher than that depending on the clinical state of combined EPA and DHA per day, provide neurocognitive benefits. So while you may hit the minimum on a vegan diet because you ingest ALA, it doesn’t mean that you optimize the potential benefits that you would get from omega-three fatty acids. So I think that is important to know the difference between deficiency versus optimization. I think that is one of the things that you miss out on.

And at the same time, it could be true, too, for some of the other things as we mentioned, just taking the other extreme, again. Taking a carnivore diet. Yes, you may provide yourself with plenty of typically fat-soluble vitamins that are (recommendable? 38:58) sources, plenty of protein, but you may not optimize the amount of phytochemicals in your diet, which indeed are probably only conditionally essential or nonessential. But it doesn’t mean that they are not important or do not have benefits. So I think those are two important things, deficiency versus optimization of the diet.

Chris Kresser:  Yeah, that’s a really critical point, too. And I think that this whole discussion gets back to what we really started talking about in the beginning of the podcast; it’s this idea of moving away from just understanding a nutrient like protein in a kind of macro sense. And really having a better sense of what the nuances are under that umbrella category of protein because not all proteins have the same effects. And we know that from the considerable amount of research that’s been done in terms of the response of the body to the amino acid profile of protein.

So can you talk a little bit about some, you several years ago hypothesized that perhaps a blending of plant proteins with a complete amino acid profile would improve the anabolic response. And you could maybe define that for listeners who are not familiar with what that means. But the recent work suggests that even when you recreate that same complete amino acid profile, it does not have the same anabolic response that a complete animal source like whey has. Were you surprised by that? And what do you think explains that difference?

Stephan van Vliet:  Yeah, I certainly hypothesized wrong, Chris. That’s for sure. I did think that if, and going back to what complete amino acids profile, generally a plant source is deficient in either methionine or cysteine. So if you combined, for instance, legumes with rice, you might make for a complete amino acid profile.

And so what the recent study showed was they didn’t study the muscle anabolic response, but they did study post brand-new amino acids level. So after eating amino acids, a protein gets digested, absorbed, the amino acids become absorbed, and they get put out through the portal vein into systemic circulation (inaudible 41:31) where (they can then use them 41:32) for muscles. So they didn’t study muscle protein synthesis, but they did study the availability of amino acids in the blood. And what they showed was that despite creating a complete amino acid profile, it was also matched for leucine to the whey protein. And leucine [is] also [a] very important amino acid for main anabolic trigger. So they matched the amino acid contents, but it still showed that the amount of amino acids that became available in the blood after eating the complete plant protein was lower than when compared to eating the dairy protein.

And yeah, that was somewhat surprising, because I would have expected that the amounts would be similar. Because the idea was and what we hypothesized in that paper a few years back was based on the current available literature at that time, was that if you present the (splancing? 42:31) tissue. So the liver with an unbalanced amino acid profile, you upregulate ureagenesis, so the wasting of protein. But you also upregulate protein synthesis in the liver and in the gut tissue. So our hypothesis was is that if you present the liver with an unbalanced amino acid profile, it is sort of a signal that a famine is coming or an amino acid deficiency is coming, so that it upregulates protein synthesis in vital tissues such as the liver and the (inaudible 43:03) organs, and potentially even the heart.

You upregulate protein synthesis in the vital organs at the expense of skeletal muscle so that you at least will survive until you get more of a complete amino acid profile. So I figured if you didn’t ingest the complete amino acid profile, even if it comes from plants, you would still see a similar response to the animal protein. But that wasn’t the case. But what we were right about, I guess, or hypothesized correctly also based on current data, while this was recently confirmed by a study is that if your intake is high enough, let’s say over 1.6 grams per kilogram body weight per day, it doesn’t matter whether you’re consuming plant protein or animal protein. Because at that point, you’re providing so many amino acids, that any difference[s] in amino acid profiles are being overwritten just because you provide so much.

Chris Kresser:  Yeah, that’s really interesting. And it makes me wonder, too, what do we still not understand about the differences and the components. It makes me think of, as a clinician, like, with immunity. The immune system is so vastly complex and there’s so much we still don’t understand. And in the case of viral infections, it’s often, I mean, you think of things like vaccination, the primary goal there is to stimulate our natural innate immune response, despite decades and decades of research on antivirals that are designed to actually kill the pathogen. Still, the best option is to provoke our natural immune response. Right?

And because it’s just so sophisticated and complex, we don’t have an easy way of replicating it other than to stimulate it. And I wonder if there’s something similar happening within the context of whole foods versus trying to isolate certain nutrients or parts of the food and recreate the effect that there’s just this kind of meta effect that the whole food has that we don’t even fully understand.

Stephan van Vliet:  Yeah, and you’re missing out on it. It also considerably underestimates the complexity. I mean, [let’s] touch upon this quickly. What we did was a study, hopefully, it will come out this year, that kept us busy during [the COVID-19 pandemic] when we had to shut down our randomized controlled trials. What we did was we looked at the novel plant-based meat alternative that was matched to design the nutrition label of beef. So [a] similar amount of protein, similar amount of fats, vitamins, minerals, the nutrition facts panels looked fairly identical. At least 50 percent of the consumers cannot really see the difference based on the food survey. So what we looked at was, and this is also what’s generally touted for plant-based meat alternatives, right? Because the mantra is a little bit plant-based meat contains or animal meats are made out of protein, lipids, vitamins, and minerals. And we can create all of these things using plant products using plant material.

So what we did was we [ran] it through our [mass spectrometer] that gave it a metabolomics profiling and then indeed showed that 90 percent of these small molecule metabolites, many of which can have important health implications, and those were the ones we talked about, like taurine and cysteamine and anserine and a variety of other phenols. And also, the (inaudible 46:28) role is phytosterols. We saw a 90 percent difference between the beef and the plant-based meat alternative. And you could glean this from the nutrition facts panel. So that comes back to the fact that we just highlighted, that the complexity of things, and in this case, all food matrix, but also to your point, your example of vaccines is yes, the complexity of metabolism, physiology, and foods indeed show that there’s still much much to learn. And that simply us thinking that we can sort of recreate something like that easily is not the case. It sort of overestimates our ability.

Chris Kresser:  Yeah, exactly. And we’ll probably look back in the future. If not, I’m sure people like you already are looking at it this way. But at the idea of being able to capture the full complexity and effects of a food on a small two-inch by one-inch food label that’s printed on a package that contains that food or somewhere else. It’s kind of silly when you start to understand the complexity of what we’re dealing with.

Chris Kresser:  I want to ask another question about protein before we finish up here. And we’ll have to have you back because I want to also talk to you in the future about, I know you focus on farm practices and the effects that different types of farming have on yields and a whole bunch of other topics that I know my listeners [and I] are really interested in. But one of the biggest concerns or critiques of animal protein diets, particularly those that are higher in protein than the average intake, is that they can cause kidney problems. I’ve addressed this before, but I’d love to hear your take on it. Because this is, of course, anytime I’ve ever talked to an advocate of a vegan diet or vegetarian diet, this inevitably comes up as one of the downsides of an animal protein-based diet.

Stephan van Vliet:  Yeah, I guess (inaudible 48:44). So here’s the best way of saying it. In the absence of any pre-existing kidney condition, a high-protein diet does not cause kidney disease. That’s about as clear as I can say it.

Chris Kresser:  Yeah. And I found the same in my research, but it’s just one of those memes that like you said, it doesn’t go away easily in spite of overwhelming evidence to the contrary, right?

Stephan van Vliet:  Yeah. No protein researcher in the field thinks that this is the case. So yeah, it’s interesting. But it always seems to keep coming back. And I guess these myths die hard. But within, there’s not a lot of things that I should say that we’re very sure, always completely sure about. I won’t say that we’re completely sure about this, but the overwhelming amount of evidence points to the idea that in the absence of any pre-existing kidney condition, a high-protein diet is not detrimental. And we actually did a study in dialysis patients, which are people that have to undergo (Crosstalk 49:51).

Chris Kresser:  Definitely is a pre-existing condition, yeah.

Stephan van Vliet:  It is a pre-existing condition, but there it also becomes even more complicated because in that case, once your kidneys [have] failed and you need to undergo dialysis and then potentially get, hopefully, get a kidney transplant, at that point, you actually benefit from higher protein index because you’re so incredibly catabolic. And in that case, higher protein intakes are recommended to prevent muscle loss. So it becomes complicated very quickly. But when you’re in sort of the in-between where you have a pre-existing kidney condition, absolutely it is important to see a nephrologist and potentially limit your protein intake.

My guess would be that maybe not the protein, but some of the other things that you are eating might be also something to look at. But yeah, high-protein diets in healthy individuals is not of concern.

Chris Kresser:  Fantastic. I’ve really enjoyed this conversation, Stephan. And I follow you on Twitter. What’s your Twitter handle for those who would like to follow your work there?

Stephan van Vliet:  It is @vanVlietPhD. So my last name, van Vliet. And then if you just Google me and type in Stephan van Vliet, Duke, then I think all my Google Scholar profile on social media and other professional profiles will come up.

Chris Kresser:  Great. That’s v-a-n V-l-i-e-t, correct?

Stephan van Vliet:  That’s right.

Chris Kresser:  Okay. For those of us crude Americans who aren’t very good at spelling Dutch names. So thank you so much for coming on the show. I definitely want to have you back and talk a little bit more about farming and ranching and regenerative agriculture, and some of the impacts that industrialized agriculture can have on not only production, but nutrient density, right?

Stephan van Vliet:  Yeah, exactly. That is mostly the part that I focus on. So that is interdisciplinary work that we started a few years ago, and we’re really working at the agriculture human health nexus. So does the way that we produce food impact the nutrient density, and how does that impact our health? And then what we’re doing is indeed overlaying plant metabolomes with beef metabolomes with human metabolomes and see if there’s this final nutrient transfer.

Chris Kresser:  Right. And you would think that would be a rhetorical question, but it hasn’t been. Historically, the assumption has been that it doesn’t matter, I would say, just based on how things are set up. But we absolutely know that it does, which is not surprising given our conversation today.

Stephan van Vliet:  Yeah. A farmer told me the other day that my job is simply to, or that what I do is verifying common sense. But I don’t want to think of it that way because I don’t want to think that all my work is kicking in open doors. But yeah, it does.

Chris Kresser:  No, I mean, unfortunately, common sense does not prevail in the way that things are set up. So we need this work to verify that common sense is actually rooted in verifiable scientific evidence, not just folklore, or the way that things have been done for a long time.

Stephan van Vliet:  No, no. I agree.

Chris Kresser:  And that’s what’s so interesting about this ancestral lens that we look through sometimes, and you pointed this out earlier, where somehow our ancestors knew about the importance of food synergy and combining some foods with other foods or fermenting a food to reduce the levels of toxins. Or like with, you mentioned, potatoes and clay and people in Africa who consume cassava, which is highly toxic in its raw form. They have extensive methods for preparing it. They didn’t know anything about the biochemistry. They somehow learned this over time through trial and error. But that doesn’t mean that just because they didn’t use science to get to the answer that the answer is incorrect scientifically.

Stephan van Vliet:  I agree. Though I’d hate to be the first person who would ever try a potato and I wonder how many people lost their lives.

Chris Kresser:  Yes, we can thank our ancestors who died eating raw cassava and potatoes for the benefit of humanity.

Stephan van Vliet:  Exactly. Yeah.

Chris Kresser:  All right. Well, thanks again. [I] appreciate it. And we look forward to having you back on the show next time. And thanks, everybody, for listening. Keep sending your questions in to ChrisKresser.com/podcastquestion, and we’ll talk to you next time.