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How to Measure Immune Balance Using Blood Testing [transcript]

Written by Christopher Kelly

July 24, 2018


Christopher:    Tommy, thank you so much for joining me this morning.

Tommy:    Thanks for having me.

Christopher:    Tell me about some of your recent life changes. There's been quite a lot of things going on for you since last April.

Tommy:    Yeah. Probably the biggest one is I got married at the end of May. Also, since the end of March I moved out of my post doc job at the University of Washington although I will continue to do a little bit of research with them. Hopefully, I continue some academic stuff. But I also now do some academic stuff with the IHMC, which people may have heard of when you had Ken Ford on the podcast or listened to his STEM Talk.

    It's an awesome research institute based in Florida. Ken offered me an academic position with them, which is great, and I can do some research on human performance in extreme environments, which is their thing. But other than that, spending more time working with Nourish Balance Thrive and then, of course, the blood calculator which we'll hopefully talk about today.

    We are very keen to publish what we do and make sure that what we're doing is peer reviewed and people can read about it and it's freely available. We just wrote a paper about our predicted age score. It's been submitted. It's under peer review now. We'll see how that goes. And either they'll like it but we'll have to make some changes and it will get published or we'll have to submit it to a different journal. That's the life of an academic writing paper.

    I'm very excited about that and everything else that's coming up with the blood calculator. We're getting a lot of interest with continuing to make it better, which is obviously what we need to do.

Christopher:    That's what I'm most excited about in the peer review process. You've got, for free, we didn't have to pay any money to have these people look at our work and then, hopefully, they're going to tell us what's wrong with it and so we can make it better. How cool is that?

Tommy:    Yeah, it is great. People sometimes slam the peer review process and that's often people who have been on the negative side of it. And if you're reviewed by people who are biased against your work or don't like what you're saying, of course, then that can cause a lot of issues. But equally it's a chance for people who should be usually are experts in the field that you're writing in can give you feedback and tell you what you need to do to improve.

    Certainly, a couple of the papers for my PhD were much better for having been peer reviewed and even some ideas came up in peer review that I then implemented and allowed me to add to the paper because they suggested other ways that I could analyze my data and then the paper was much better for it. Hopefully, we'll get some of that kind of input in the work that we're doing a produce a better result because of it.

Christopher:    I will go into the predicted age feature of the blood chemistry calculator in a future episode. In this episode, we're going to focus on the immune balance score. Perhaps we need to take a step back and just explain for people that may not know the blood chemistry calculator exactly what it is and why they should care.

Tommy:    The blood calculator is a tool that we essentially wanted as part of our practice to help us better understand what to do or how to understand blood test results. In the whole spectrum of available testing, blood test, definitely the best understood and the most robust, even though all tests have errors, at least with the basic blood test results, things that most people can get from their doctor, you could even, direct to consumer, you can usually order them in many places now.

    Those are the tests that we have the longest history and we understand really well but there's a lot of potential information that you can extract from that but people are not necessarily that good are doing it just because it requires pattern recognition or it can easily become quite subjective so people just decide what might be good, might be bad or the other end of the scale, they might just create a standard reference range based on the average person who takes that test in that lab and then try and use that to say that something is normal or not when there's a lot more information that could be gathered.

    That's why I built the tool. It includes our optimal reference ranges. Our reference range is based on the research in terms of actual health outcomes. And then you built the models to predict a whole load of issues based on all the test data that we have access to. In combining those things, we built these different scores.

    It allows you to get one number in one area of the data that you can then use to dig down into other problems. We have things like the predicted age, which is based on the algorithm, then we have things like the immune balance score which is based mainly on the input data. So, the actual data that you can take is taken from the blood test that you got at your doctor or you ordered through us or elsewhere.

    And then based on the research, I have multiple references for each scoring system. We can then assign an overall score in terms of how your immune system is balanced. This is something that started off as what we called an inflammation score. But in reality, a lot of the things that come out and are important don't necessarily tell you just about inflammation. They tell you about how things are maybe set up within the immune system and then any potential issues that might be associated with that.

    That's kind of a bigger picture thing and if you notice that you have a poor score on your immune balance then you can start to dig down into the causes. That's why we want to produce it. It's not just that you have a score and then that's what you get. You can dig down into where you're picking up those scores based on input markers and then start to figure out what you might want to do about that to try and improve it. You can really dig down into each different aspect and figure out where your score is coming from.


Christopher:    And who is this for? This is something that we built for ourselves and we're using it in our practice with the clients of our elite performance program on a daily basis. I just had two client calls before this podcast and I made heavy use of the blood chemistry calculator in both of those calls. What do you think the chances of somebody who is just a regular person, not necessarily gotten -- I mean, do I have any credentials? That's a really good question. Someone who has not had a formal education, shall we say, being able to make use of this report and do something meaningful with it?    

Tommy:    I guess, it depends on how interested that person is in digging into stuff. As a super user, somebody who's supposed to understand their own data better, you can certainly make good use of this. Every output, every score is heavily referenced with ranges. You can go and dig down into the research. You can try and figure out what's going on there.

    But equally we're starting to build out some coaches who we know, who we respect who are doing great work with clients. We will also have an opportunity for people who, if they come to this or interested in knowing more about their blood chemistry but they don't necessarily understand all the outputs, and it is quite data intensive tool, there's a lot of output to understand, and sifting through all of that is nuanced and takes a little bit of practice. We will have some coaches who could help people do that.

    Definitely applicable to pretty much anybody because a lot of what we're trying to look at is long term health rather than specific diseases. So, anybody who is interested in being healthier for longer as well as trying to figure out what might be underlying any issues that they have, chronic health issues, it's certainly applicable to both. But if the outputs are complex or people who don't quite understand then coaching will be on hand to help them if want it. So, certainly applicable to almost anybody who is interested in long term health.

Christopher:    My suggested approach is have a go yourself. I've said that before about other tests that we use in our practice. For example, when I interviewed Mark Newman about the DUTCH test, I said the same thing. Order one and see what it says. Try and understand what it says. If you get stuck or if you think you found a problem that you can't fix then either keep investigating or go get a coach if you really get stuck. I think it's really helpful to try and understand what's going on inside your body for yourself before you go get help.

Tommy:    It's also worth pointing out that many of the interventions that we would recommend are the basics. It always come back to sleep and stress and nutrition and movement and other aspects of the environment that are going to be affecting your physiology. There are certainly other issues that might be coming into play. But if some things pop up on the calculator and the answer, well, the simple answer might be improving your diet or other aspects of your environment, other aspects of your lifestyle, and then you can track how your body responds using this tool, we often see things dramatically improve just by implementing some of those changes.

    So, the scores give you a really nice way to track how things are improved over time as you implement various changes and then can maybe get you to a point where you fixed everything and things look much better and that's great or you get to a point when maybe you need more help. But doing the basics, doing that yourself, using something like this, some data to track that, I think is great. Everybody should be their own main health advocate. You don't always need a huge bunch of fancy tests or fancy coach to help you do that.

Christopher:    And I should point out that I have now implemented the ability to combine two or more blood chemistry calculator reports into a time series so that you can track changes over time. I think that's really, really important. I wouldn't like to say that you have to do that. If you're considering altering your diet in some way or doing something with your sleep or stress management or something else, I wouldn't like to say that you have to track changes in blood chemistry in order to know that that's working. But for someone like me who has a history in engineering and computer science then I really like to do that. It's fun as well as helpful.

Tommy:    If you do something and it makes you feel better you can't really argue with that.

Christopher:    Yeah, absolutely. Well, let's get stuck into this immune balance score. What exactly is it? What does it comprise of?

Tommy:    Sure. So, there are multiple different inputs that come from the data itself, things like albumin and something called the gamma gap which is basically the difference between total protein and then the number of immunoglobulins that you have floating in the blood. Those are mainly the antibodies, but some other proteins that bind to various fats in the blood. Ferritin, people might have heard of, which is an iron storage molecule, also increases in the setting of chronic inflammation.

    Hemoglobin levels, RDW, the red cell distribution width, which is basically how variable the size of your red blood cells are, liver enzymes, and then lots of things that come from the white blood cells. So, the number of many of the white blood cells, so eosinophils, neutrophils, lymphocytes. And then some ratios between different white blood cells can also be very informative.


    So, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and the lymphocyte to monocyte ratio are associated with outcomes and issues in various diseases. We include those especially in the setting of cancers, for instance, something like the neutrophil to lymphocyte ratio or the lymphocyte to monocyte ratio can be informative. And if somebody were to have one of those things, that might be something that's worth tracking because it's associated with various outcomes.

    Those are the inputs that go in and then there's one prediction from the machine learning models, so predicted elevated CRP. We predict whether somebody has a CRP, a C-reactive protein, which is one of the commonest markers of systemic inflammation. We predict whether CRP is above an 0.5 and this has a 92% sensitivity and 86% specificity in men and slightly higher in women.

    The model is pretty good at predicting people who have high CRP. And because we're measuring it directly there's some other ways that we can extract more data from very cheap and easy to get blood test. That's the one thing that we're using which isn't direct output from the blood test.

Christopher:    I think it's worth reiterating here that we know how good all of these predictions are because when I train the models I don't train them on all of the data. I hold 20% of it out for testing purposes. So, the models never seen this 20% of the data and the I run the testing process where the model attempts to predict the C-reactive protein of the held out data and then we compare the predicted result with the actual result that the model never saw in the training process and then we compare the two.

    You can plot one against the other in a simple plot and then you know how good it is. That allows us to calculate the specificity and the sensitivity which is published on the blood chemistry calculator website. None of the models are perfect but, Tommy, as you said earlier, no blood test is perfect, right?

Tommy:    The same for every test. We've certainly come up talking to people about how maybe something's been predicted but then the actual test has been performed and showed that the prediction was incorrect. There's lots of ways to think about it. I think it's nice to think about why you might look like somebody who has that issue, why do you look like somebody who has high CRP even if you don't have high CRP? Is there something else that might be going on that fits into that picture?

    But equally, literally every test that's done in the medical sphere has some degree of sensitivity and specificity which means that you might get a false positive or a false negative where you require a further test to figure out what might be going on there. It's like any other test that you get. If you are getting tests, and that could be stool test, urine test, blood test, it's always worth bearing in mind that there's some errors, some variability and those things can certainly change over time or change during the day or change from day to day. That's just the nature of testing and we just always need to be aware of that.

Christopher:    And so why is it important to score well on immune balance score?

Tommy:    That's a good question. It's worth mentioning a couple of things about how we set it up. So, the immune balance score is created such that all of the different things that I mentioned earlier as a number increases or decreases outside of what we'd like to see as ideal, you'll generate a number of points. And then the total number of points are inverted and turned into a score of a hundred so that higher is better. But in reality, you pick up points for having certain issues.

    Say, an elevated or predicted elevation of CRP or high ferritin. The way that we created these points is based on the research. Each one has at least three or four references to go with it. How we've done it is that the number of points that you get is based on all-cause mortality usually adjusted for all the other factors that could be playing a role.

    You get one point, whatever it is, say it's a hemoglobin that's slightly less than optimal, so for men, say 13 to 14.5 or 12 to 13 for women, you get one point. In the research, those levels are associated with an increase in all-cause mortality of maybe 25%. There's a small increase but it's enough that there's a bit of a signal there.

    The points go up as the risk of all-cause mortality increases. If we stick with hemoglobin, hemoglobin is 12 to 13 in men or ten to 12 in women, is associated with maybe 50% to 70% increase in all-cause mortality. If you start then getting below hemoglobins at 12 in men or below in ten in women then you're starting to get something like a three times increase in all-cause mortality and your score goes up appropriately in line with that.

    That's the case for all of the different things that we included in the immune balance score. What you can probably figure out as I talk through it is that you're getting an individual score for each marker. But it doesn't necessarily mean that they're additive. So, if you have somebody who has an immune balanced score of 80 and somebody else who has an immune balanced score of 40, that doesn't mean that one of them is twice as bad as the other. I would argue that they're probably synergistic. So, as all these things stock up, that probably becomes increasingly worse rather than linearly worse, if that makes sense.


Christopher:    Did you think that some of the markers there move in lockstep, right? If you see one go up, you're probably going to see the other go up too.

Tommy:    If you have chronic inflammation, elevated CRP, it's very possible that you're going to see a decrease in hemoglobin, an increase in ferritin, an increase in RDW potentially especially if you have some other issues, maybe nutritional. Fasting glucose starts to go up. All this other stuff starts to come together. As things get worse and worse, your score is probably going to dramatically increase. A lot of those are going to move together.

    It's definitely not a case of this is a linear thing but as more of the factors stock up and you can see all those below your score, that increases the likelihood that there's something going on that you really want to look at. The way it's set up is such that you can go in, look at why you're getting that score, so it could be that there's something else going on.

    We talked about hemoglobin and RDW, red cell distribution width, which is the variability in your red blood cell size, and both of those could be affected by something nutritional. So, if you have an iron deficiency or a mixed deficiency, iron and B12 or iron and folate, B6 and copper can also play a role, then you might see an elevated RDW and you might be anemic. You might have a low hemoglobin.

    Actually, maybe none of that has to do with inflammation but if nothing else seems to be increased, you don't have predicted increase in CRP, you don't have elevated ferritin or some other things, then you can say, okay, this is probably a nutritional cause but at least you've seen trigger which has allowed you to think about that. The most important thing is triggering somebody to think about what might be going on and then you could maybe dig down further and look out whether it's likely to be a cause of chronic inflammation and then you could look at some of the white blood cell stuff or whether it might be something else. The nutritional things certainly overlap with the immune balance score quite readily because there's a lot, a big role that nutrition plays in terms of the immune system too, so that makes sense.

Christopher:    Can you say something about how you go about finding these scientific references on which you use to make these optimal reference ranges? Because you say like, oh, it's just there in the scientific literature, you can go look. That may be true for you but it's not true for me. I could thrash around on PubMed for years and not find some of these references. Can you say something about how you go about finding them?

Tommy:    If it's a marker that I know well and may just be things that I've seen previously and that's cheating, I read a lot of stuff so I just go dig up a paper that I know I saw before. But if it's something where I'm less familiar with what might be going on or the level of a certain marker might be associated with, then it really is a case of going through PubMed or actually, if you're searching for an association between two things but you want it to be in a published literature, I would often start with a Google search but might put in something that might put PubMed at the end.

    If you're searching in PubMed, say RDW all-cause mortality, you might find a whole host of other stuff. And the way it's arranged might be what PubMed thinks is the right order. It's arranged by date of publication which you don't really care about. Google is just a better search engine. We know it's a very good search engine.

    If you put PubMed at the end of your search then it's likely to give you a link from PubMed but RDW and all-cause mortality are likely to pop up and be more relevant. Often it's a combination of searching through PubMed, traditional searching through Google, various other factors. But in reality, it sometimes requires shifting through some noise and sifting through some papers which aren't very helpful before you get the stuff that is really is useful.

    The reason why we focused on something like all-cause mortality as our endpoint is because it's very objective. Did you die or not? And before you died, what did your blood test look like and how long before that did your blood test look like that? When we get into other aspects of this, and that's certainly the case for some of the ratios that are in some of the white blood cell ratios which have mainly been looked at in outcomes usually after heart disease or heart attack or in certain types of cancer.

    Thinks get slightly murkier and they're not really as strong in terms of their prediction so you actually get fewer points for that, if you like, within the score because it doesn't necessarily tell you exactly what your long term outcome is like. But it gives you some ideas. That's why we kept them in there. Yes, sometimes it just requires some digging. I'm a big fan of actually reading the paper rather than just reading the abstract.

    There are a number of people who claim to be science or evidence based but then just quote what it says in the abstract when in reality the paper might not really say that. It requires a bit of work but with some practice it becomes fairly efficient.

Christopher:    Can we dive into some of the individual markers? Where would you like to start?

Tommy:    The one that we have talked is the one prediction, probably one the people are most familiar with in terms of chronic inflammation which is CRP. So, the level that we chose to predict from the data set was 0.5, like I mentioned.


    And so I don't really have a graded score from there so I just have either CRP is elevated or not. And, again, from the research we think that CRP above 0.5 is associated with about 75% increased risk of all-cause mortality. But that increase is with increasing CRP. By the time you get to a CRP above three after you adjust for everything else, you get maybe 50% to 100% in all-cause mortality and, as you go increasingly above 0.5, your risk of mortality might quadruple, say, if your CRP goes above four.     So, each step above CRP, as CRP increases linearly, then increase in all-cause mortality also increases linearly. I think that's an important aspect to have and that's why we included it.

Christopher:    Those numbers are really low, don't you think, compared to what you see around the blogosphere when I read people writing about their C-reactive protein result, they'll say something like, "Oh, mine was two point something. That's really good." And I'm thinking I don't think so. Or sometimes you'll hear athletes saying, "Well, I'm an athlete so there's going to be some inflammation and so three point something is normal." And I'm thinking I've seen Jeremy Powers' C-reactive protein. He rides his bike 20 plus hours a week and his is 0.2. I don't know about that.

Tommy:    There's always ways to, I guess, convince yourself that something is good or bad. There's a lot of aspects to that. If your CRP previously was ten and now it's two then you definitely move in the right direction. That might be part of it. But equally, telling yourself that you're an athlete and, therefore, you can go around with the CRP of three or something, I think that's not true. There's something else going on and the healthiest athletes we work with have CRPs below 0.5.

    If you had a really heavy session in the gym, lifting some heavy weights or circuit training and then everything goes off and you see elevated liver enzymes, maybe you'd see some other things like creatine kinase going up, all of that can be associated with a single hard workout. But if this is something that with your standard workouts you're always seeing an elevated CRP, I mean, it's almost certain that something else is going on.

    It is worth pointing out that if your CRP is only slightly elevated, in the big picture, it's only associated with a very small increase risk of all-cause mortality. But again, this is one of those things where everything sort of starts to stock up then it's definitely worth looking at. On its own, it's not the one marker you should look out but definitely it's part of the bigger picture. It certainly is important.

Christopher:    We had Bryan talk about in recent blood chemistry calculator members webinar when you should do a blood test. I thought his answer was really interesting. We've seen some data that shows that transaminase enzymes ALT and AST may stay elevated for up to ten days after a heavy workout. And so I might conclude from that that maybe you want to wait for ten days before doing a blood test else you might get a false positive when it comes to the immune balance score. Bryan was of the opinion that I just want to see the bare naked you. I want you see you on a normal day. If that means a heavy workout one or two days prior then so be it. But how would you approach that problem?

Tommy:    I think both are very informative because if your base line is always just after a heavy workout and you look like that all the time then that's probably going to be a suggestion that something needs to change. Again, if we go back to our predicted age score, which we'd dig into more in the future, we have a lot of endurance athletes who are predicted to be older than they actually are.

    There's something about that lifestyle of the high volume endurance athlete that just makes your blood test look older than you really are. And my suggestion is probably that's not a good thing. There's certainly a lot of benefits to aerobic exercise but when you're working out 20 hours a week for years at a time, that's probably going to be taxing. Some people can certainly survive that and those tend to be the people who really perform very well at those sports.

    But just for the more average person who's training that hard on top of everything else that's going on in their life, probably the fact that you look older than you really are is telling you something. Capturing that and not gaming the blood test by waiting ten, not doing any exercise for ten days is definitely important. I think you can get a lot of information from both. I'd certainly would agree with Bryan that, yes, if something is increased you could look back and say, "Oh, well, that's probably because I did such and such workout two days ago." But if you do that such and such workout every two days and that's what you look like all the time then that's definitely something you need to think about.

Christopher:    My experience has been you're never going to get a hard charging athlete to stop for ten days anyway. It's irrelevant. Just go do the blood test. Well, let's talk about albumin.

Tommy:    Yeah. I know that this is one of Bryan's favorite markers to look at. Again, important for a number of reasons. Albumin to be made, it requires healthy liver function and enough protein to be taken in.


    You need a little bit of insulin bump. You need some protein. You need a working liver. And if you have low albumin, it's usually because you have a problem in the liver, the kidney or the gut. These are often associated with some kind of chronic inflammation, something that's causing these issues. It could be autoimmune or something nutritional preventing you from absorbing things properly or that you're losing stuff through the gut because it's inflamed, something like inflammatory bowel disease.

    Again, this is borne out in the research. If you have an albumin above four, that's great. If it goes below four, then you start to see something like a 50% increase, 25% increase in all-cause mortality, and that gets closer to like a doubling of all-cause mortality, if not more, once your albumin goes below 3.5. Again, it could be nutritional but often associated with chronic inflammation.

    When people are looking at markers of sort of people have produced chronic inflammation scores in the literature, again, cancer is a field where they've looked at this quite frequently, an albumin always seems to be a really good marker that pops up. As your albumin goes below 3.5 or below three, that's really pretty bad and there's a high likelihood that there's something quite serious going on.

Christopher:    Can you say something about what albumin is, what it does, where it comes from? Because I think that's how Bryan got into. That's Bryan's fantastic story. He graduated naturopathic medical school and went to interpret blood chemistry and he's like, "What the hell is albumin? Where does it come from? What does it do?" He couldn't answer these basic questions. And so began his journey of investigating and researching blood chemistry analysis. Can you just fill us in? What exactly is albumin? Where does it come from? What does it do?

Tommy:    Albumin is the main protein in the blood made by the liver. It has a number of functions. One is just part of creating oncotic pressure, keeping water within the blood. Having protein within the blood stops then the movement of water out of the blood into the tissues because of diffusion or difference in protein gradient from one side to the other. So creating oncotic pressure, we call it, within the capillaries, within the blood vessels. And then it also binds to a lot of stuff. It binds to a lot of minerals. Some of the hormones, drugs within the body are bound to albumin and circulate that way. It has both passive and slightly more active roles in terms of transport.

Christopher:    Talk about the gamma gap. That's not a name that I was terribly familiar with before you started researching that immune balance score but I had seen some of the names that define it.

Tommy:    Gamma gap is a fancy term for just the number of globulins that you have in your blood. So, again, if you think about the research, adjusted for other factors, if you have a gamma gap above three, that increases your all-cause mortality by about 40%. And if you measure two things in the blood, the total amount of protein in the blood and you take away albumin, so [0:27:49] [Indiscernible] albumin, that is either globulins or gamma gap. That's the same thing.

    The globulins include the immunoglobulins. That's largely antibodies, things that are going to be binding to various fats in the blood, antigens, bacteria, viruses, other protein things that we might be allergic to or sensitive to. There is also all the binding globulins. So, people might have heard of sex hormone binding globulin, thyroid binding globulin, all these other proteins that are basically made and designed to transport hormones particularly around the body, particularly fat soluble hormones, to get them to where they need to go.

    If you think about an elevated gamma gap which is associated with increased all-cause mortality, that's either going to be for two reasons because you have more globulins and that's usually immunoglobulins. You have a lot of immunoglobulins being produced. This happens in certain, can happen in certain blood cancers, and then will definitely happen in the case of some kind of infection or if your body is producing a lot of antibodies in response to something.

    But in the other end, it could be because you have low albumin. That's just artificially almost increase in your gamma gap because just more of your total protein is made up of globulins rather than albumin. You might see those go in lockstep if albumin is low or you might see them increased in one [0:29:10] [Indiscernible] other things, again, most of which associated with some kind of chronic inflammatory picture.

Christopher:    At this point, I think it might be worth mentioning that we're going to make really comprehensive show notes for this episode that you can find over at nourishbalancethrive.com/podcasts. You don't need to order a blood chemistry calculator report to compare your blood chemistry with some of the reference ranges and references that Tommy's been talking about here. I'll make sure all of those are in the show notes so that you can do it by hand if you want.

    Actually, I would encourage you to do it by hand. I feel it's a bit like writing code. If all you ever do is run somebody else's then you don't really learn much about how to write code. But if you try and calculate these things by hand first then you end up understanding more about what's actually going on.

Tommy:    Yes. I have a table for all of these things, gives the ranges that we use, gives the scores that we assign, gives the risks, particularly on all-cause mortality, or if not all-cause mortality, something else that I'm using to give the score and all of the references that we used to make that. We'll make all of that available.


    So, people might have other papers they want to send us or other things where they want dig into these themselves, we'll make all of that available so that that can -- that's part of our peer review process, as it were.

Christopher:    Yeah. And I love the idea of it being [0:30:22] [Indiscernible] because they're not going to just push changes. If new evidence emerges, then we can just change our worldview. I can push a software update and then everybody's blood chemistry calculator report gets updated. I really like the ability to be able to do that. Talk about ferritin, our favorite protein.

Tommy:    Ferritin, like I mentioned earlier, is an iron binding protein and it's kind of the long term storage for iron. It's something that, I think, two or three years ago now we started looking at iron overload which would be associated usually with a high ferritin in our athletes and then all of a sudden loads of particularly middle aged endurance athletes male especially came out of the wood work and they all seemed to have iron overload.

    I think that's very common in the successful male endurance athlete because you're sort of almost pre selected to be somebody good at storing iron so you make a good amount of hemoglobin and that's going to make you a good performer endurance sports. There's a number of reasons both dietary and genetic why that might be the case.

    However, in the setting of inflammation, your ferritin goes up. It's called an acute phase protein for that reason and that at the most basic level it's because if something is causing an inflammatory response, so say it's a bacteria, and we know that for bacteria to survive or for many bacteria to survive, they like iron. What the body does is it says, "Well, as part of my inflammatory response, they try and clear whatever this bug is. I'm going to squirrel away my iron so that the bug doesn't get access to it." That's part of the reason why ferritin increases. That's something that we can track.

    Again, if you have an elevated ferritin but nothing else looks inflammatory, hemoglobin looks good, or even looks slightly high, then you might be going down the nutritional, the iron overload kind of pathway. But if you have other issues and it looks like there might be some chronic inflammation and ferritin is elevated then that's the reason why it's part of the immune balance score.

    Looking at the literature, if you take a population of healthy people, in those that have a ferritin above 200, the all cause mortality is increased by about 50%. So, we know that when ferritin gets much, much higher, it might be associated with genetic causes like hemachromatosis. You're going to get organ failure and all those kinds of things down the line if it's not dealt with. There's sort of like a lower lying elevation of ferritin definitely is associated with an increase in all-cause mortality and that's certainly for two reasons.

    It could be because of high iron or it could be because of the chronic inflammatory process which is certainly going to be associated with an increase of dying eventually. Both roots are important to figure out why that ferritin is elevated.

Christopher:    Can you explain why the reference range, you just mentioned is different from the optimal reference range? When I looked at the raw data from my blood chemistry calculator report I see that the optimal reference range for ferritin for men is 30 to 70. Can you explain why you just said 200?

Tommy:    That's a great question. It's something that we discuss a lot behind the scenes. It's how to set these things up. The way that I set up the immune balance score, in order to be able to compare all the different markers and assign points appropriately, I use an outcome that's easy to find in the literature and is very objective. That is all-cause mortality.

    To see an increase in all-cause mortality, ferritin probably needs to be and for it to be independently, after adjustment for factors, be independently associated with increase in mortality, needs to be over 200. That's why I pick that level. However, there is some evidence to suggest that once you get above a ferritin of maybe 70 or 100, you do start to see associations with other diseases, with other issues. It's worth looking into at least. So, that's why we have an optimal reference range that's lower because it's just tricky to think about it and look into other factors. But the reason why I have it higher in the immune balance score is just because of the stringent criteria that I use to make sure that I could compare all the different markers and could give points appropriately in the score.

Christopher:    We've talked about this in detail before in the podcast, the issue of iron overload. I can link to that in the show notes. I mean, if the problem is just straightforward iron overload, has been my problem in the past, then most straightforward solution is to just go donate blood, right?

Tommy:    Yeah. Unless you're a Brit in the US then that makes it tricky.

Christopher:    It does make it a little bit tricky. I went into some of the details in my interview with Gabriele Oettingen and I don't think I mentioned, actually, on the podcast that I did successfully donate blood in the UK to blood.co.uk and everything went great. Obviously, I was not going to do anything else after that. That interview, how she made me describe it, it's really interesting that she said, "What do you want to do?" I said I wanted to lower my ferritin and she said, "No. You don't want to lower your ferritin. What do you really want?" And she's absolutely right. What I really want, like the other day for the first time in I don't even know how many years, I went out kiteboarding and I rode my mountain bike in the same day.


    I spent time with my in-laws who live locally in Scotts Valley and I see how much energy they have and how much they're enjoying playing with their grandchildren. That's what I really want. Ferritin is more of a proximal goal rather than a distal goal but important nonetheless. My ferritin has dropped really well. It's not quite into our optimal reference range. My ferritin as of June of this year is now 98 but at one point it was 227. It seems to drop 170 before I did this last blood donation. Mine dropped to over 70 points just with one blood donation. You may not get it in one go but it's just a nice thing to do. Probably everybody should be donating blood if they're able.

Tommy:    I can't think of any reason why -- I mean, if you have low hemoglobin or maybe you faint or issues with needles, I can understand all that. It's super important. Your life was saved by people who donated blood. You needed a lot of blood transfusions when you had an accident a long time ago. There's a lot of people who needs your blood and if you don't need your blood or you'd even benefit from losing some of your blood then it's a win-win situation.

Christopher:    Yeah, absolutely. Contributing to a cause that's greater than you. Yeah, you're absolutely right. I was involved in a motorcycle accident when I was 19 and I wouldn't be here giving this interview if it wasn't for all the generous people who went and donated blood. On a similar note, let's talk about hemoglobin then. You mentioned that earlier. Is there anything else you wanted to add about hemoglobin?

Tommy:    Hemoglobin, again, it's something that we look out a lot. It's something that, obviously, our athletes really care about because, basically, the high the hemoglobin the faster you go, the more aerobic power you have. And it could be low for two reasons mainly. It can be the chronic inflammation again, that's what's in the immune balance score or nutritional. I mentioned that earlier.

    When you have low hemoglobin in the setting of chronic inflammation, it's often called anemia of chronic disease, and in that scenario you see a lot of other things that we have in the score. You'd see maybe an elevated CRP, you'd see an elevated ferritin. You might have a microcytosis, we call it, which is a low MCV, or you might see an increase in RDW which I also mentioned, the red cell distribution width. It would be the combination of inflammation plus maybe some nutritional deficiencies which can increase the size of your red blood cells, things like our B12 and folate, for instance.

    It's worth bearing in mind that hemoglobin does have a U-shaped curve. Our optimal range which actually fit very similarly with what we have in the immune balance score. So you want a hemoglobin above 14.5 grams per deciliter, if you're male, or above 13 if you're female. And then below those, basically, again, you get a stepwise increase in risk of all -cause mortality as hemoglobin decreases.

    But if your hemoglobin is two or three points higher than that, so you're talking about like 16, 17 plus in males and females, then you start to see an increase in all-cause mortality risk. That could be severe iron overload. Sleep apnea is a reason why we see elevated hemoglobin in some of the people we work with or some hematological or blood diseases, something called polycythemia is sort of like a pathological elevation of red blood cell. That can certainly be a problem too. Above 14.5, above 13, then one half to two points above that is probably our optimal range.

Christopher:    My experience with hemoglobin has been the more I donate blood the higher my hemoglobin goes.

Tommy:    And you're not--

Christopher:    Isn't that strange?

Tommy:    Yeah. And you're not alone with that, actually. We have quite a few guys where that's been the case. I think it's removing that inflammatory burden. If it was a case of iron overload and other issues, you're actually offloading some stuff that's maybe inhibiting some hemoglobin [0:38:43] [Indiscernible]. I think it does make sense. It's very interesting to see because it's counterintuitive.

Christopher:    It is counterintuitive. But, yeah, the same time my mean corpuscular volume has come down. The size of the cell is normalized. And then also the RDW has come down. And interestingly that's only happened recently.

Tommy:    All of which are great.

Christopher:    I can link to my report, actually, if anyone wants to see my report. I've got a combined report that shows three different blood tests that I can link to in the show notes. Was there any other markers that you wanted to add on at this time, Tommy?

Tommy:    There's a couple of things that I think are interesting. Before we get to the white blood cell count I wanted to briefly mention fasting blood glucose which is also in the score. It's interesting because in the spheres that we operate it, fasting blood glucose is considered very important and it's almost the one thing that people often focus on.

    It's something that they should focus on. However, it's very easy to get caught up in that when lots of other things could be important. The reason why I think these scores could be beneficial is because they're much more objective. I could tell you this is the cutoff, this is what it's associated with. And for glucose, I think somebody mentioned on one of our scores that if you had an elevated fasting blood glucose then it doesn't really matter what everything else because we know that that glucose is bad. But if we look at it compared to some of the other markers, if you have a fasting blood glucose below 100, in terms of all-cause mortality, that's roughly where the best spot is.


    We have other evidences just that it's probably the best is going to be between 80 and 90, something like that. But in terms of all-cause mortality then below 100 is probably enough. If your fasting blood glucose goes to 100 to 110, all-cause mortality risk increases by about 25% to 50%. If it's at 110 to 130, which is getting on truly diabetic ranges, your risk of all-cause mortality once you adjusted for everything else, only increases by about 50% to 75%.

    And then it only starts to double once your fasting blood glucose is above 130. When people are thinking that blood glucose is the be all and end all, actually, you need really high blood glucose, like over 250 milligrams per deciliter before you start seeing a tripling or more of all-cause mortality which might surprise people. They might expect to see bigger increases in that.

    Compare that to a red cell distribution width of above 16 or 17, and by that point your risk of all-cause mortality is like five to eight times. So, a really elevated RDW is a lot worse than a really elevated blood glucose, if that makes sense. It's just worth bearing that in mind when we're looking at outcomes. Glucose is very important but there are a lot of other things that are important too.

    And then when it comes to the white blood cells, one thing that I thought is really interesting, one of the most interesting papers that I picked up was one on eosinophils which is a type of white blood cell that's associated with both parasitic infections and then also allergic reactions and sometimes with some autoimmunity because it's associated with all those things that are bind to antibodies.

    In people who had eosinophils above 0.275, which is actually well within the normal range, and I think is even lower than we have at the top of our optimal range, the 30-year all-cause mortality is increased by almost 50% which I thought was really interesting, suggesting that if right now I have slightly elevated eosinophils, which could be because I have allergic reactions to stuff, hay fever, again, it could be an infection or it could be some degree of autoimmunity, long in the future that's going to be causing problems. They have this really nice long follow-up.

    It's just one of those things which people might not really think about but actually it's going to be important and why it's really worth digging into what might be causing just a small elevation in that type of white blood cell. I thought that was really interesting paper.

Christopher:    It is, yeah.

Tommy:    The other thing is that we have other ratios between the different white blood cells. The absolute numbers, like if you see an increase, a big increase in neutrophils -- Traditionally we think that neutrophils increase with a bacterial infection and lymphocytes increase with a viral infection, that's not necessarily 100% true but it gives you it's going to cause a triggering on the scores just so you can look at where the cause might come from.

    Something like an increase in lymphocytes doesn't really increase your all-cause mortality but I have it in there because if you do have a big increase in lymphocytes then it's worth looking into what else might be going on. If you have other symptoms of chronic inflammation or some kind of obvious viral infection, that's just worth thinking about.

    Then the opposite is also true. If your numbers are dramatically decreased, and that could be neutrophils or lymphocytes or other white blood cells, then that could be nutritional, could be a chronic infection. That's also worth looking it. That's where you can pick up in some of the ratios as well as elevated platelets. So, we have the platelet to lymphocyte ratio. Having high platelets is associated with an increase risk of mortality after heart attacks. Usually our worse outcome, if you have cancer, or maybe an increased risk of cancer, if you sort of find it before you're diagnosed with cancer you have high platelets, that's an emerging potential marker of cancer risk. That's why we have that in the score.

    Something else I didn't mention. Monocytes. We have the lymphocyte to monocyte ratio. If that's low, that causes [0:43:42] [Indiscernible]. That could be low because you have low lymphocytes. Again, could be chronic viral infections, some other things going on, all because you have high monocytes and monocytes are some of the biggest cells in the immune system which go around basically gobbling stuff up to try and present it to other cells in the immune system so that they can then be attacked and whatever it is that you're trying to get rid of can be eliminated.

    They can differentiate into a number of different things. Microphages and macrophages have different names in different parts of the body. So, the microglia in the brain. That's kind of, with monocytes, is the main initiating cell. It could also become dendritic cells which have a similar function, continuously gobbling stuff up and presenting it is this a foreign thing, do we need to be dealing with that?

    When you have an elevation in monocyte, which we call a monocytosis, that's associated with all those kind of stuff that we're interested in, so chronic inflammation, stress. It's seen in things like atherosclerosis, some other stuff. In that kind of chronic inflammatory picture we might see an elevation in monocytes which is going to decrease your lymphocyte to monocyte ratio. Again, that's associated with increased mortality after heart attacks, stroke and in some cancer but that's why we include it.

    Again, this is just a process of trying to figure out what's going on. If you're scoring high on the inflammation score and then you see some of the general stuff like ferritin or CRP but then it's also you see that there's a change in one of the white blood cell ratios, then that's going to help you narrow things down in terms of what you might need to do.


Christopher:    It's a huge question but people are going to be asking it. What do you do? If you think that you might have an infection, where do you go from here?

Tommy:    That's a good question. It depends on what the setting is. If you have an obvious injury and you have a potential source for a bacterial infection then dealing with that, do you need to see a doctor, do you need to get antibiotics? I would always encourage people to do that if they have an acute injury and what looks like an infection.

    I think when people are doing this test, I imagine it ruled that out. If you have signs of a chronic infection, which we often do in our clients, then you maybe go digging into places where you might have an infection lurking but you haven't really thought about it. The gut is something that we talk about a lot but then things like previous surgical implants or dental health is another big one.

    Is there a tooth that's slowly rotting its way out of your head? Do you have previous fillings? Do you have problems under there? That's a very common cause of chronic inflammation. Anything like that where you think, "Oh, hang on a second. I've had this niggle around this place where I had surgery previously and is it possible that you've developed an infection there?" That's certainly something that we've seen occasionally.

    If it's more likely to be viral, is it just an acute thing? Is it just a flu or cold? You're getting over it and part of almost all of these things that we're measuring on the immune balance score, perfectly normal part of the process of dealing with an infection. You have an increase in the appropriate white blood cell. You might have an increase in fasting glucose because, actually, the body is trying to shift where the nutrients are going. It's trying to feed the immune system.

    All of that is perfectly normal and maybe things just resolve naturally over time. If there's some other kind of chronic infection, viral, perhaps you need to just deal with some lifestyle factor stuff that then allows your body to take care of it. Again, sleep, stress, nutrition, all of that becomes important. There are some antimicrobials that can help things like Monolaurin, Lauricidin, Selenomethionine maybe in certain viral infection.

    It would just depend on where it's coming from. You can certainly test for some of them if you need to. There is an antibody test. But again, they can be tricky to interpret whether it's previous infection or a current infection. And so having a doctor or somebody help you do that is probably going to be important. So, knowing what the potential causes, how long you've had it, where you are in the process of dealing with it, are all worth thinking about before you start then worrying about testing or anything else.

Christopher:    It just reminded me that Malcolm Kendrick said something really interesting on my podcast. That was inflammation is healing. But when I talked to you about that afterwards, you wanted to add an important caveat. Can you restate that here?

Tommy:    The caveat is that inflammation is healing but if you don't get rid of the source of the inflammation then the chronic inflammation can itself be damaging. That's certainly the case -- So, for instance, in a number of cancers. They often turn up in places where there's been a chronic inflammatory stimulus where something has been constantly triggering the immune system, constantly triggering the death or damage to cells and repair and then over time that can actually become a place where cancer develops. Actually, the mouth is a good example of that too.

    Yes, inflammation is healing. It's like all of the stuff that we see is happening as the body tries to deal with what it causes. But if you haven't removed the cause then the chronic inflammation can be part of the problem itself. Again, you need to think about where you are in that process before you decide whether it's a good thing or a bad thing.

Christopher:    I think that's a great place to wrap up.

Tommy:    Yeah.

Christopher:    Okay. If you're interested in doing further investigation with blood chemistry and you are in the US, you can come to bloodcalculator.com and we can order a blood chemistry for you. You will receive a PDF requisition form that you can take directly to Quest Laboratories, really easy. I do it quite a lot. It's super easy for me to just walk into Quest. Make an appointment online before you go in and you'll literally just walk straight in.

    If you're in the UK, you can order a blood chemistry through [0:49:13] [Indiscernible]. If you're in Australia, I forget the name of the lab, but Steve Anderson, he was on my podcast recently, he's been ordering blood chemistry in Australia and he can also help you with the interpretation. You can listen to my podcast I'll link to in the show notes with Steve Anderson if you're in Australia and you're interested in doing that.

    If you order a report and you get so far and then you get stuck then please do get in touch with us. Our email address is support@nourishbalancethrive.com. Don't think that this is just an automatic funnel that leads you to our $10,000 program. It's absolutely not. As Tommy mentioned earlier, we do have a number of practitioners that we're working with and our goal is just to help people get better. If that means redirecting those people to someone else that can help them better then absolutely we will do that.

    Find the show notes over at nourishbalancethrive.com/podcast. Tommy, this has been great. Thank you so much for your time. I really appreciate you.

Tommy:    Thank you.

[0:50:04]    End of Audio

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