Transcription
[Music] What effect does diet have on our immune system? There's some tantalizing new evidence that we're going to get to, but first of all, let's talk about the immune system and why it's important to understand the differences between the innate immune system and the adaptive immune system.
The innate immune system is what you start off with in terms of looking for things that are foreign. So, this is what causes you to have a fever. This is what secretes, as we've talked about before, interferon. This is what's really important in fighting things like COVID-19, but also influenza.
Whereas the adaptive immune system is where antibodies are made, where you have plasma cells that make antibodies against specific antigens. Today, we're going to talk about which types of diets affect these different types of the immune system. This is new data that's come out that's really quite impressive, and it's impressive because of some of the data that's actually happened before.
But before we get to that, I'm Dr. Roger Scheld. I'm the co-founder of medcram.com, where we explain medicine clearly. Please visit us at medcram.com, where we have world-class videos with continuing medical education.
So, let's get back to the topic at hand here. We've talked about the importance of the innate immune system and specifically the product of the innate immune system, which is interferon. We've talked about how just about any virus needs to get around the major barrier for infection in your body, which is the body's ability to secrete interferon. We also talked about it in terms of the severity of COVID-19. We've shown in previous videos how increased levels of interferon were associated with more mild symptoms of COVID-19, and that was pretty dramatic. This study that showed that statistically significantly.
We also talked about SARS-CoV-2 and the Mac-1 gene, which was required for interferon antagonism and for efficient virus replication, as was published in this research article published last year in August. And what it showed was exactly what we had discussed before, which was that SARS-CoV-2 has this gene, specifically Mac-1, which produces a protein that reduces the body's ability to make interferon. In fact, when they tested it specifically in bronchial cells and alveolar cells, when they compared the wild type in blue with the genetic mutation in the Mac-1 gene in orange, notice that when they mutated this gene, Mac-1, that there were higher levels of interferon across the board, and that in this situation, they were able to kick out the virus much more easily.
This, of course, culminated in a human study which was published in the New England Journal of Medicine that showed that pegylated interferon, when given as a randomized control trial in patients who had COVID-19, had about a 50% reduction in hospitalizations or ER visits, and the number needed to treat was pretty low, pretty reasonable, about 35, with an absolute risk reduction of 2.9%. Even in the vaccinated and the unvaccinated population, there was a significant reduction of about 50% in both in terms of hospitalizations. The conclusion was the risk of COVID-19-related hospitalization or an ED visit was approximately 50% lower in the interferon group than in the placebo group. Results were consistent regardless of vaccination status.
It made us think, how can we potentially increase our innate immune system's ability to increase interferon production? And we've talked about this before. This is no surprise. This was a paper that was published a number of years ago that showed that elevated temperatures could increase interferon-gamma, at least substantially, even tenfold, and that was significant. And we talked about previous applications to this, like hydrotherapy, which was used at the turn of the century.
But we've also talked about diets. And up to this point, we didn't know why this was the case. But in this specific study from earlier in the pandemic, where they looked at about 3,000 healthcare providers, mainly physicians and nurses, in six different countries: France, Germany, Italy, Spain, UK, and the United States, who had substantial exposure risk in the early part of 2020. So, this again was prior to any vaccinations. Participants provided in this particular study information on characteristics, dietary information, and COVID-19 outcomes. They used multivariable logistic regression models, both models one, two, and three, which we'll talk about in just a second, to see whether or not there were things that predicted whether or not these physicians, these nurses who were part of a network, developed either mild or moderate to severe COVID-19. There were 568 COVID-19 cases and about 2,300 controls, so almost 3,000.
They asked these participants, physicians and nurses, to self-report about whether or not they were following a plant-based diet, a plant-based diet, or pescatarian diet, or if they were on a low-carbohydrate, high-protein diet. And they found, in conclusion, that in six countries, a plant-based diet or pescatarian diet were associated with lower odds of moderate to severe COVID-19 compared to control groups.
Let's take a look at that study, because why this is important is going to dovetail into a new study that's just come out that looks at the effects of a plant-based diet or vegan diet versus a low-carbohydrate, high-fat diet. Let's look at this study first. They were looking at the control groups. They had 2,300, as we mentioned, and then they had cases, those that were very mild to mild, and those that were moderate to severe, with a P value. If we look at these P values, smoking was actually not statistically significant. Body mass index, in fact, in this group was not statistically significant. But there were a number of things that were statistically significant, and these were the self-reported diets. So, that's pretty interesting. These physicians and nurses who took part in this study would tell you that they had specific plant-based or plant-based or pescatarian diet or low-carbohydrate, high-protein diets, and that these would be statistically significantly related to whether or not they got mild or moderate to severe COVID-19.
In terms of the controls, those that were on a plant-based diet, very mild, 8.6% versus the 99.2% in the control group. And from moderate to severe, it actually went down even lower to 2.9%. Similar to those that either had plant-based or pescatarian. Pescatarian, by the way, includes fish, compared to the control, 10.7% of the total had that type of diet. It was less represented for in mild to moderate, and even less represented in the moderate to severe. However, in the group that self-identified as low-carbohydrate, high-protein diet, in the control, that was about 16.9%. There were less in the very mild to mild group, but there was statistically significantly more in the moderate to severe.
So, the question that you might have is, how much can we trust self-reporting of diet? And that's a very good question. Let's take a look at those that followed a plant-based diet and those that followed plant-based or a pescatarian, and specifically let's look at those P values. After going through a 47-item dietary review on all of these subjects, which were physicians and nurses, there was a statistically significant difference between total vegetable intake between those that followed plant-based or pescatarian and those that did not. That seems to go along with an accurate representation of a self-reported diet. Some other things that were statistically significant was there was more legumes in the plant-based pescatarian diet, more nuts in the plant-based pescatarian diet. There was less poultry in the plant-based pescatarian diet than there were in the one that was not, and of course, significantly less red and processed meats in those that followed a plant-based or pescatarian diet.
Now, you may say that this could be simply a marker of a healthy user effect. We're going to talk more about that, especially in the next study that we're going to talk about. But in this study, if we saw that there was a healthy user effect, then in things, for instance, like refined grains, we would have expected to be a statistically significant difference between these groups. There was not. In terms of sweets and desserts, we would have expected there to be a statistically significant difference in these groups. There was not. In terms of sugar-sweetened beverages, we would have expected there to be a statistically significant difference between these groups. There was not. There was also not for fruit juices, for vegetable oil use, or for alcohol. And for many of these other differences.
Here we have the results, and this is a graph that's looking at adjusted odds ratios and 95% confidence intervals for the association between self-reported dietary patterns and moderate to severe COVID-19. We're looking at how likely were they to get moderate to severe COVID-19. Now, this will become important as we talk about later. What did we say was an important mitigating factor in terms of whether or not someone could get COVID-19 severely? Interferon. And what we're going to find out here is whether or not these dietary patterns promote elevation of interferon.
In terms of model one, and model one was adjusted for age, sex, race, ethnicity, and country, notice here with unity being at one, we had plant-based diets that were statistically significantly less likely to get moderate to severe COVID-19. Even those for a combination of plant-based diets or pescatarian diets, as opposed to a non-statistical significant difference here because the 95% interval crosses unity, so P equals 0.13. We see very similar results for model two, which takes into consideration everything that we took in model one, but also medical specialty, smoking status, and physical activity. Even taking those into consideration, we're not seeing any real change in terms of these values. Finally, with model three, which takes in all of these things, everything that we took into model two, plus body mass index, plus medical conditions: diabetes, pre-diabetes, cholesterol, hypertension, CAD, heart attack, heart failure, cancer, prior lung disease, prior lung infection, being overweight, having asthma or autoimmune disease. Taking all of those things into consideration, once again, really, we're not seeing much of a difference. And those that self-report having a plant-based diet, which we already showed actually does have some differences when we do a 47-item list, it shows that there is a statistically significant less risk of moderate to severe COVID-19.
Could it be possible that taking in a plant-based or plant-based pescatarian diet might improve interferon? Now, that's a far-fetched question, but in fact, there's been a paper that's actually looked at just that. And this was a paper that was published in the journal Nature Medicine titled "Differential Peripheral Immune Signatures Elicited by Vegan Versus Ketogenic Diets in Humans." First of all, the thing I want to make sure that we're clear on is that a vegan diet is not necessarily mutually exclusive to a ketogenic diet, although that's what they have here listed. They defined that the vegan diet, which was actually made up for these groups of people that we can see here, there were four women here in group A along with six men, and then in group B, there were five women and five men. And this was a randomized control trial where they defined the vegan diet as being 10.3% fat and 75.2% carbohydrate, with the ketogenic diet being 75.8% fat and only 10% carbohydrate.
So, what they did was a randomized controlled crossover trial where they did this type of diet for two weeks, and they looked at blood samples at both points. And I'll just tell you here as a spoiler, it didn't matter if they did the vegan diet first or the ketogenic diet first. In both cases, there was statistical significance, and we're going to go over those. What was really interesting is that this was a very diverse group of people, but the results were very consistent and standard.
So, let's go over the results of what they found. This is a very confusing chart, but I'm going to try to explain it to you here very carefully. The change in relative amounts of these things that they have listed here is given in terms of red and blue. Red means that there was an increase, blue means that there was a decrease, and the magnitude of that increase or decrease is given by the size of the circle. You'll see here that K is ketogenic and V is vegan. We're going to split this table down the middle, and we're going to look here at something called innate immunity. And what they found was all of these things related to innate immunity went up dramatically when they were on a vegan diet as compared to the baseline or ketogenic diet. In this category, there was an enrichment in monocytes, enrichment in neutrophils, immune activation, monocyte signature, and TLR signaling. But here's the key point, and that's this: interferon signature was greatly increased in all of these where they were put on the vegan diet. However, when they were put on the ketogenic diet, notice that there was a reduction. That's blue, that means there was a statistically significant reduction in those points, and notice how big the circles are.
There also notice that it's not all bad for the ketogenic diet. Remember, the ketogenic diet is simply a diet that stimulates ketones. You don't have to be on a high-fat diet to have a ketogenic diet. You could have time-restricted eating, and that could also lead to a ketogenic diet. Having a vegan meal, for instance, in the morning and in the afternoon, and then going on intermittent fasting could potentially give you not only the benefits of a vegan diet but also the benefits of a ketogenic diet. Which were what, in this case, on the ketogenic side? What did we have an increase on? On this side, notice it was T-cell activation, B-cell activation, enrichment in B cells, etc. So, in other words, what we're talking about here is adaptive immunity. So, what it seems is that there is an improvement in adaptive immunity with ketogenic diets, but an improvement in innate immunity in vegan diets.
The same thing happens over here. Notice we're looking at the vegan side. We're going to split this down. We do a hallmark analysis of things that we know. And again, looking at innate immunity, what are we seeing that's increasing with vegan? TNF signaling, that interferon response, that interferon response. We're even seeing androgen response is much higher in vegans. This kind of goes against the narrative that we often see with high-protein, high-fat diets. There's an androgen response that's actually higher in vegans and actually lower in the ketogenic diets. Protein secretion is actually higher in the vegan diet. Here's something that really goes against the narrative that was really interesting in this study: heme metabolism. What they noticed in the study was that heme metabolism, the production of hematopoietic cells, red blood cells, was statistically significantly higher in the vegan diet than there was in the ketogenic diet. And again, remember, we're not looking at people who are vegan or who are ketogenic. We're looking at people who were placed on these diets for two weeks, and it was a randomized crossover trial, and these results were very consistent and standard. There's really no role here for the healthy user effect. These are actual biomarkers. And I would highly recommend that you look at this study because there's more results and findings in the study.
The key here that I want you to look at is interferon response. And what you're noticing in the vegan group, and again, tie that into what we're seeing here with type 1 interferon activity in COVID-19. The higher the immune response, the higher the interferon response, the more mild the case of COVID-19. And the question is, is whether or not that would explain what we're seeing here?
And here we've talked about things that could improve your health. And the mnemonic that I often like to use is that of NEWSTART. N stands for nutrition, E stands for exercise, W stands for water, S stands for sunshine, T stands for temperance, A stands for air, fresh air, R stands for rest, and T stands for trust, relationships, even spiritual relationships. What we've talked about today is nutrition. We've talked before about exercise. We've certainly talked about hydrotherapy with water. You know that we've talked about sunshine. We haven't talked too much about temperance, but I can tell you that if you look at alcohol, there really isn't a threshold for where damage starts to occur in the liver. And we've talked about air and the fighting sides that are given off by trees in the environment. We've shown how that actually affects the innate immune system. Rest is also very important. We've talked specifically about sleep, getting at least seven hours of sleep per night, and what things like obstructive sleep apnea and insomnia can do to that and why that's important. I think these are things that are very important in terms of your health and lifestyle, especially important as we're coming out of the winter season where a lot of us have had to deal with respiratory issues. And if you want to be able to do things that will improve your immunity, these are some places that you can start.
Thanks for joining [Music] us.