Written by Christopher Kelly
July 9, 2015
Tommy.Wood.on.2015-06-09.at.09.22
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Christopher: Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today, I am joined by Dr. Tommy Wood. Hi, Tommy.
Tommy: Hi, Chris.
Christopher: I've got Tommy back on the show. Tommy is a medical doctor. If you haven't heard any of the previous episodes, we did one on hydration and then we've also done another on oxidative stress. Tommy is a brilliant biochemist. He's currently studying for his Ph.D. in neonatal brain metabolism. And I've got him on today to talk about blood chemistry and then specifically I wanted to talk about anion gap, because it's a very frequently asked question.
People understand that there's some association with metabolic acidosis and they want to know, am I acidic? Am I going to die? I want to answer these questions. I want to know how you, Tommy, use this as a tool when you interpret a blood chemistry. What's the best place to start here? Do you think we should start by defining exactly what the anion gap is?
Tommy: Yeah, absolutely. I think the anion gap is basically the concentration of unmeasured anions in the blood. To take another step back, in order to keep in balance, we have a number of both positive and negative ions in the blood. So positive things would be like sodium and potassium, which you hear a lot about. And something negative might be chloride or albumin, which is the main protein and the blood, tends to have a negative charge. And the way you--
Christopher: Just to introduce some words that people may or may not have heard before, there's the cations and the anions. So the anion gap is the difference between the two.
Tommy: Yes. Cations are the positively charged ones. Anions are the negatively charged ones. The anion gap is basically the unmeasured anions in the blood, so the negative ions in the blood. The way that we tend to calculate it is we add the sodium plus the potassium and then we take away the chloride and the bicarbonate. And then what's left, that number, is the anion gap. It covers all the other negative ions that tend to be in the blood. It's mainly albumin. It's the main one. And then phosphate is another one, which people may have heard in various settings. Those usually make up most of the anion gap, those two.
Christopher: Okay. Excellent. I had my aha moment being an electrical engineer when I realized that a cation was really a cathode and an anion was really an anode and then everything sort of made a little bit sense to me. I've mentioned this before. If you want to understand this better, I highly recommend the Khan Academy Chemistry module. I will link to that in the show notes so you can go and get a better understanding of this. And then look at your own blood chemistry and see if you can see these cations and anions. The anion gap is a calculated number then. It's not something they've measured directly in the blood. Why is it there and when is it useful?
Tommy: It's absolutely just a calculated measure. What the normal range is will depend on where you got your blood chemistry from and how they measured. It's particularly the difference is in the way they measure chloride that change the anion gap. But for most people, the normal range is something like four to 12. Like I said, that's mainly taken up by albumin. But where the anion gap has really been the most useful actually and where, the place that I've used the most is when you're actually looking at the blood chemistry of a sick patient.
You have a patient and they have an acidosis. Basically, the pH of their blood has dropped. The number of protons in the blood is increased. And you're trying to find a cause. And often what you'll see is that if they are producing a lot of another anion, say something like lactate, then that will increase the anion gap and they will have something called a high anion gap metabolic acidosis.
Christopher: Why would someone have a lot of lactate floating around in their blood then when they had the blood drawn for the chemistry?
Tommy: I was just going to quickly say that, basically, anything that ends in "ate" is often an anion, a negative ion, and it's basically that if you have an acid, so like lactic acid, you have the main molecule which determines what acid it is, and then you have the proton which comes off, and that's what makes it an acid.
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And then what names the acid is the whole other molecule and that's the negatively charged anion. And so in lactic acid, it's lactate. Anything, lactate, phosphate, bicarbonate, something that we'll also talk about. They're all negatively charged. Those are anions. You might see a high lactate in a patient that has lost a little blood for his shot and not delivering enough blood to their organs and then they start to get some kind of anaerobic metabolism. They're basically not getting enough oxygen to those muscles, so then they start to create more lactate and that will create, part of that process will create an acidosis. The anion gap will go up because of that lactate.
Christopher: Okay. People know this. They're listening in. If you exercise hard enough, you get to a point where you can't deliver oxygen to the exercising muscle quickly enough. So your body reverts to this less efficient anaerobic metabolism of glucose when you start to see the buildup of lactate. You can feel that for whatever reason that I won't go into here. Know that it's possible to metabolize glucose in more than one way. The without oxygen way can happen even when you're not exercising, right?
Tommy: Yeah. Absolutely. It could be because you have some problem with mitochondrial function then we might see lactate go up. Or it could be because you're not delivering enough glucose to the cells so we often see a lactic acidosis or we can see lactate go up. In diabetic ketoacidosis, lactate will also go up. So that's if you're not getting enough insulin in patients that have type one diabetes, say you're not getting enough insulin.
Part of that will be because they start to become dehydrated and then they can't get enough blood to the tissues and then they start to generate lactate as well. So there's kind of intermixed. Usually, dehydration or shock are usually the times that we'd see, in a patient in the hospital, we'd see lactate go up.
Christopher: Okay. Do you think it's possible to achieve the kind of acidosis that you'd see measured on the blood chemistry with nutritional ketosis? If you just had a sort of an 0.5 to 3 millimolars of blood ketones measured with a hand-held meter, would that affect your anion gap? Would you see the acidosis in the blood chemistry?
Tommy: It's actually unlikely that you'd see that much of a change. So when you generate ketone bodies, you absolutely generate an acid. That has the potential to make the pH of your blood go down. The problem is that when you're doing a basic blood chemistry on a healthy person or a relatively healthy person who's up and walking around, you'll measure sodium, potassium chloride and bicarbonate so you can calculate an anion gap. But you haven't got that PH. You don't actually know if they have an acidosis or not.
And if somebody is in nutritional ketosis, it's very, very unlikely that you'll see an actual acidosis, that you'll actually see the pH of their blood change. And the reason that is, is because your body compensates. You have bicarbonate, that is sort of the main way that you buffer acid in the body. If you start to increase your production of something like beta hydroxybutyrate and acetoacetate, if you're in nutritional ketosis, your body will compensate by dropping your bicarbonate a little bit potentially.
So you adjust. Your kidneys will make less of it or you'll reabsorb less of it, and that will sort of level out your anion gap. The pH of the blood doesn't change and the anion gap doesn't really change. They kind of talk about in nutritional ketosis maybe your anion gap will increase by one or two or three but it won't cause a huge -- It's very unlikely to cause a really big increase in the anion gap.
Christopher: Okay. Super interesting. I'd been looking at all this stuff. It seems like this buffering mechanism, it happens inside red bloods. Is that right?
Tommy: That's absolutely parts of it. What happens there is that -- Say, if you suddenly create a lot of acid, then what will happen is that the hemoglobin and the red blood cells can actually bind the acid and then they'll actually be part of the buffering mechanism. They're part of a shorter term buffering mechanism.
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One of the ways that you regulate acid or you have two main ways that you regulate acid. If you create more acid in the body, so you have more protons hanging around, what happens is they will tend to bind to bicarbonate using an enzyme called carbonic anhydrase. And you create CO2 and then you breathe that out. That's one way to sort of breathe out acid essentially. But if you were to suddenly start retaining CO2, and this happens in people with COPDs or if they have problems with smoking or if they have obstructive sleep apnea, then they will have a high level of CO2 in the blood.
Then what happens is the protons will increase in the blood, so you have potential to create an acidosis. But then the other way the body compensates is by increasing bicarbonate. So the kidneys then respond. So you can either breathe out acid basically via CO2, so you have respiratory compensation we call it, or you have renal compensation where the body regulates the amount of bicarbonate it makes in order to deal with the amount of acid in the body.
Christopher: Okay. This is good stuff. I wonder whether it might be useful to look at an example and since Jimmy Moore has made his blood work public, maybe that would be a good one. I've never actually mentioned it on the podcast before or wrote about it or said anything about it but I'd been working with Jimmy Moore. Most people would know Jimmy Moore. He's an author, podcast host, blogger. If you haven't checked out the Livin' La Vida Low-Carb Show, he has interviewed very nearly -- I think he's doing this thousandth episode this summer. He's had all kinds of amazing experts on his show. You're probably the only one that hasn't been on his show, Tommy. You should get in touch with him and get on there. Fantastic podcast.
I was really honored to be able to work with Jimmy and to run some of the tests that we do at Nourish Balance Thrive on him and try and figure out why he's not losing weight in the way that he once was. He lost a tremendous amount of weight. He was once over 400 pounds, I believe, and he lost 180, I think. Then he made the mistake of writing a book, a ton of stress and maybe wasn't sleeping as well and some other things that we go into in the interview. There's actually an interview on his podcast that you can listen to.
One of the tests we did was the basic blood chemistry and it shows an elevation of the anion gap but not necessarily acidosis. I know that you can see this blood chemistry. I'll link to Jimmy's website so that people can see the blood chemistry there. Tommy, how do you even start when you look at this chemistry and try to figure out whether this guy is acidic? Is that even possible?
Tommy: So, yeah, if we just focus on his anion gap, let's say. So, measures that we have and, like you say, he's published them on his website, so his sodium is 142. His potassium is 4.8. His total cations or positive ions for the calculation of the anion gap will make 146.8, if you add those together. And then his chloride is 102 and his CO2, which is actually a measure of bicarbonate, is 25. That's 127. And if you take 127 from 146.8, you get 19.8.
Just briefly, it's important to mention that the CO2 on this kind of blood chemistry is a measure of bicarbonate and it's not a measure of the actual CO2 that's in the blood that I was talking about earlier. That's actually the other side of the equation. If you have a high CO2, you actually have more acid in the blood by the way that it's buffered.
Christopher: Right. That's what makes this super confusing, when you look at your blood chemistry. It says CO2 but it doesn't mean CO2.
Tommy: Absolutely. It means it's a measure of bicarbonate. I think that's to do with the way that they -- Basically, if you have bicarbonate and then you treat it with electrode in the blood, then it generates CO2 and it's the CO2 that they measure. So it has to do with the way that they analyze the blood, I think. But the important thing to remember here is that, I think, a lot of people when they look to this chemistry they said he's lost pH balance or he could no longer regulate pH or he can't regulate acid-base.
And that's because this anion gap is high. It's 19.8. The normal, the optimal range that they give here is seven to 12. The standard range is six to 16 because the normal range will include some outliers who are completely healthy. He's obviously outside of both of those ranges.
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Christopher: When people saw this chemistry on his website, the people, like telling me on Facebook, "You know, this guy is acidic. He's going to die." And all this kind of stuff. Maybe that's not true.
Tommy: People have said he has an acidosis because his anion gap is high. We cannot tell that. It's impossible to tell that on this for a number of reasons, mainly because we haven't measured the pH of his blood. And you can't do that on this kind of test where you get it done in the lab and then it ships somewhere and then they test it. If you want to measure the CO2 and the pH of the blood, which I would do -- So, say, if he was sick, in hospital, I'd take something called an arterial blood gas. That's basically the blood that comes straight from the lungs. I take it from a small artery and then I'll run it through a machine.
You need to do that within minutes to get an accurate measure of pH and CO2 because those would change because you have some cells in there that are going to metabolize and change the pH and change the oxygen, change the CO2. We have no measure of his PH. So it is impossible for us to say if he has acidosis or not. And that's the first thing to mention. What we generally say is that if you have an anion gap above 30, then it's very likely you have acidosis.
But, obviously, his anion gap is just below 20. They've sort of done some studies and they've looked at a huge, thousands of people, and looked at their anion gap. If your anion gap is below 24, you have a 50-50 chance of having acidosis. So below 20, we just don't know. It's six of one and half a dozen of the other. So he may have an acidosis. But we cannot tell that from the blood work that we have. There were some interesting things that I think are worth mentioning.
If you look at his albumin, I told you before that the albumin makes up a lot of the anion gap. But his albumin is actually quite low. So what that would do is that would tend to increase the anion -- No, sorry. That would decrease the anion gap because you have less albumin, which is negatively charged. Then if you bump up his albumin, then his anion gap would probably increase even further.
And the same thing with phosphate. His phosphate is also a little low. If his phosphate was in a normal range, then his anion gap might increase further. It's very difficult to tell what's going on because we can't measure the pH of his blood. We can see that he's accumulating a lot of anions. And that doesn't necessarily mean that he has an acidosis but in a lot of people, it happens because or you get an acidosis because of those anions you generated. Sorry?
Christopher: I was just going to say I was curious because he did have an elevation of D-lactate on the -- L meant L-lactate, on the organic acids test. It did show that, we were talking about before, in the critically or chronically ill, that you would not be able to deliver oxygen appropriately to perform mitochondrial respiration. And he does have that but there's not an obvious -- The CO2 is not low. It's not obvious that he is acidic.
Tommy: Yeah. So what you'd expect is that if he was -- We know he's accumulating lactate because we've seen that on his organic acid profile. And we know that he's in nutritional ketosis most of the time. Then he will accumulate beta hydroxybutyrate, which we've also measured on the organics. It's there but it's not particularly high.
Christopher: No.
Tommy: But he will also increase acetoacetate. And the balance between acetoacetate and beta hydroxybutyrate tends to depend on the redox state of the cell. Again, that's something we don't have any information on. So maybe his acetoacetate is also high. So between them, those three could potentially be bumping up his anion gap. And not necessarily generating an acidosis. What is interesting is the fact that if you generate, in the long term, if you increase the number of anions in the blood, so lactate, beta hydroxybutyrate, then your CO2, your bicarbonate, your CO2 on this measure, your bicarbonate would tend to drop. You tend to compensate.
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And so that would tend to go down. But his hasn't. So what you'd want to do, I think, first of all, if you're actually worried that he has an acidosis, then actually a real blood gas would be a starting point. But you would also maybe look for a reason why he's maybe retaining or having more bicarbonate for another reason. I don't know directly his medical history but somebody of his size then obstructive sleep apnea is something I definitely think about.
And if you have obstructive sleep apnea, then you tend to retain bicarbonate because your CO2 goes up. So I wonder if that's potentially one reason why his bicarbonate is higher than we'd expect. But again, this is all conjecture because I don't have a really solid blood gas on him.
Christopher: Yeah. I think a lot of this work works that way. It's kind of like detective work. You kind of have to sort of put clues together. But certainly here, you don't look at the anion gap and say to someone, "Well, there's some nutritional thing going on here. You're not eating enough vegetable," or something like that. There's certainly no recommendation like that you can make.
Tommy: No. No, absolutely not. I think we have some solid reasons for why his anion gap is increased. There are some things not quite what we'd expect and we maybe need to go and hunt those down. Maybe one of the reasons why his lactate is high is because we know that his iron is low and that's something that I know he's getting investigated. That could be so why we talked about before, if you're not delivering enough oxygen to the tissues then you start to accumulate lactate. Obviously, you need to iron to make hemoglobin to let oxygen to those issues. That might be one of those. That might be part of the reason.
Christopher: Right.
Tommy: I would never look at an anion gap and say, "You definitely need to take this supplement." I think it can be informative in the absence of an acidosis. It probably isn't that useful on a day to day basis.
Christopher: Right. I understand. Without repeating the whole interview that I did with Jimmy, you can go listen to that one. That seems to me like the thing that pops out the most of this blood chemistry is very low hemoglobin and iron deficiency. And as a result, you can see that the mean corpuscular volume is greatly reduced. He has pale small red blood cells that are not very good at delivering oxygen. There's a nutritional step here with iron which, for whatever reason, is missing. We need to figure out whether he's not eating it or whether the blood has been lost somewhere and that's why he's deficient in iron.
Now he knows about this. Now that he's done this test, he is going to figure this out and he will get to the bottom of it. I think this can be useful information for either an athlete looking to improve their performance. Oxygen deliverability is a deal breaker for everyone. But certainly for an athlete, if I was trying to race up a big mountain, with only 11 points of hemoglobin, I think I'd be pretty winded by the time I go even a couple of hundred meters.
Tommy: Absolutely.
Christopher: Definitely worth the $26 to do this test. I keep saying it's $26. I should probably stop saying that because it's on my website for more money than that but it includes the time for me to run it through the software and provide you with a written report and spend 30 minutes on the phone with you. So it's a bit more expensive. But it's still pretty cheap. It's the cost of a pair of running shoes. If you buy a new pair of running shoes every quarter, then I think you can afford to do this blood chemistry.
I'm pretty sure I can make you run faster with a chemistry than any new pair of running shoes. I can guarantee that. We'll keep this one short and sweet, Tommy, because it's pretty dense. Again, I can't recommend highly enough Bryan Walsh's Metabolic Fitness Pro and the Khan Academy Chemistry module, if you want to understand this stuff a bit more deeply. I think that's the key. It's like once you have our own blood chemistry in front of you, you're like, "What the hell is a cation, anyway?"
That's the kind of motivation that I need anyway in order to learn. It gets really fun. Okay, Tommy. Thanks so much for your time. And we'll speak to you again soon.
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