Hey everyone, welcome to a sneak peek ask me anything or AMA episode of the Drive podcast. I'm your host, Peter Atia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peteratiamd.com. Subscribe so without further delay, here's today's sneak peek of the Askme anything episode. Welcome to AskMe anything AMA number 54. I'm once again joined by my co host, Nick Stenson. In today's episode, we focus mainly on one thing, which is magnesium and magnesium supplementation. This is a supplement we get asked about a lot. In fact, it's certainly among the most asked about supplements, and I think that's because it exists in so many forms. There seems to be no limit to the amount of confusion surrounding this, and for that reason, we decided we probably need to do a dedicated podcast on this. It's also one of the most common supplements that my patients take. In fact, I take three or four different forms of magnesium every day, and I get asked about it a lot. So I finally decided, let's have a deep discussion about it so people can understand it, because obviously, if I'm taking that much of it, I must think it's pretty important.

In today's AMA, we speak about the role of magnesium in the body. It plays a very important role in so many processes. We talk about the three or four most important, and then of course, that leads to a very clear extension of, well, what are the negative aspects or the harms of magnesium deficiency? How do you know if somebody's magnesium deficient? We then talk about the various ways you can increase your magnesium levels, including through diet, but also through supplementation. From there, we dive deeper into the different types of magnesium supplements. And again, this might be the most important part of the discussion for people who don't really want to understand the physiology. They just want to know what to do. We end the discussion looking at the potential cognitive and sleep benefits of magnesium as well. We then end the AMA with a quick discussion on a few new benchmarks I've been thinking about as it relates to exercise and age. In particular. I've become really interested in understanding, now that I'm 50, what I think I should be able to do relative to what I did when I was 40 or 30, and perhaps more importantly, how much longer I'll be able to do those things as I turn 55, 60, et cetera.

This is just me musing on some things that I've been thinking a lot about has nothing to do with magnesium. As always, if you're a subscriber and want to watch the full video of the podcast, you can find it on the show notes page. If you're not a subscriber, you can watch the sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy AMA number 54.

Peter, welcome to another AMA. How you doing?

Good, man.

How are you doing? Good. I think we have a good one today. We get asked a lot about supplements, and I know it's not always your favorite subject to talk about, but we are actually dedicating this AMA to one type of supplement in particular, magnesium, which we get a lot of questions about. I think there's a lot of confusion around. There's all these different types, there's all the different benefits. When do you use it? How much do you use it? How much is through food? How much is through an actual supplement? And so we decided to compile all of those together and really hit them today. And I think the reason, if you're wondering why we're spending an entire AMA on it, is it's one of the most common supplements for patients in your practice. You place a lot of emphasis on it for yourself and for your patients. And because of that, we decided to talk about it in detail today. And I think what might be helpful as we start this process for people is at the simplest level, what is the role of magnesium in the body? And why does low magnesium matter?

Why should people really care about this and listen to this full thing?

Yeah, everybody's heard of magnesium. As we'll talk about, there's no shortage of magnesium supplements out there, but in order to, I think, talk about this subject intelligently, it does help to set the stage and get into all the things magnesium does. Now, the reality of it is, magnesium is a cofactor in at least 300 enzymatic systems in the body. It is very important as a co transporter for the movement of potassium and calcium across membranes. I guess maybe I'll say a little bit about that in a moment. But first, let me just give the high level, the three big systems where I think magnesium matters the most is with respect to bone health, with respect to nerve transmission, and with respect to glucose control and insulin metabolism. So again, there are lots of things we could spend easily two or 3 hours just talking about what magnesium does. We are not going to do that. We're going to spend three minutes talking about that. But those would be the big three. So again, what is magnesium? Right. So magnesium is a cation. That means it's a positively charged ion. So it has two positive charges.

And just like potassium is a cation with one positive charge and calcium is a cation with two positive charges, these things often have to move in opposition to each other. We'll talk about that in a moment. With respect to nerve transmission, let's start with bone health. The bones basically reflect the largest total body pool of magnesium. So 60% of the magnesium in your body resides within your bones. Not surprisingly, therefore, magnesium deficiency is a significant problem when it comes to bone health. So I want to keep this a little bit simple so that we don't get lost in the weeds. But bones are basically in a constant state of building and breaking. The building cells are called osteoblasts. In med school, we remembered that b for building and the breaking cells are osteoclasts. And I don't know why I remembered that, but it seemed somehow easier. So there's a balance between the osteoblasts and the osteoclasts. Obviously, if that balance moves too far in the direction of bone breakdown, you get osteopenia and ultimately osteoporosis. It turns out that magnesium plays a very important role into that, both directly and indirectly. It plays a role in that directly through the upregulation and down regulation of osteoblast and osteoclass.

It also plays a role in that indirectly through the metabolism of calcium, ptH, parathyroid hormone and vitamin D. I'm not going to say much more about that at the moment because that's not really the purpose of what we want to do. I just want to point out that magnesium deficiency is very bad for bones.

Peter, real quick before you continue on beyond bone health, for anyone who hasn't listened yet, AMA 37 was an AMA dedicated fully to bone health, its importance, all the different factors. So if you want to learn more about that, that's another great resource for people to have. Yeah.

So let's go on to the second point, which is magnesium helps with glucose control and insulin metabolism. So magnesium is involved in the regulation of insulin secretion in the pancreatic beta cells in addition to the phosphorylation of the insulin receptor in the target cells. So if you recall, and we discussed this in great detail in the podcast with Jerry Schulman, when insulin hits the insulin receptor, that leads to an intracellular kinase that phosphorylates and ultimately leads to the movement of the glute transporters that move across the cell membrane and allow glucose to flow in. And so metabolism obviously therefore heavily impacted by that. And so, in addition to increasing glucose movement into the cell and facilitating the effects of insulin, I. E. Driving insulin sensitivity, it's also a cofactor in carbohydrate oxidation. There are a number of clinical studies, though not all of them, that suggest that supplementing with magnesium and a magnesium rich diet can improve insulin sensitivity and fasting glucose. This is going to be a common theme in this podcast, which is that the extent to which magnesium can help in a given area, whether it be bone health or as we're talking about here with respect to metabolism, is largely a function of magnesium deficiency.

In other words, the more deficient you are in magnesium, the more you will be helped by supplementing magnesium. We're going to talk a lot about how to supplement magnesium and all of the different ways. And I will tell you it's way more complicated than I think most of us would realize. We'll also obviously talk about how do you know if you're magnesium deficient? And there's good news on the first question, not so great news on the second question. But just to round out, why should we care about magnesium? I would say the third big bucket here is the effect that magnesium plays in nerve transmission and muscle function. So, magnesium is an antagonist of the NMDA receptor and a GABA agonist. So if you think about how nerve transduction works, imagine a couple of big proteins that sit spanning across the membrane of a cell, and they create a pore. And the pore is what allows the ions that participate in the action potential to move. So again, these things are like kind of taking stored energy in the form of the charges of the ion. And as they move one way across the channel, that creates a polarization of the cell.

And it's the serial or sequential firing of those action potentials that leads to signal transduction down a cell. Well, it turns out that magnesium sits right smack in the middle of that receptor, and it must be removed for the excitatory signal to occur. So when magnesium is deficient, this is a contributing factor to things like mood and other neurologic conditions, even potentially a contributor to migraines. Again, we'll talk more about some of these applications later, but the point here, again is that magnesium sits very much in the center, both literally and figuratively, for a lot of the action. As we think about signal transduction across nerves, across muscles, and various other cells, again, it all kind of factors into the movement of these other cations I spoke about earlier, sodium, potassium, calcium, et cetera.

You hinted at it a second ago, but I think now is a really good time to get to this question, which is for people who have listened to that and are now worried they have low magnesium. Are there certain symptoms or things that they can do to kind of know where they're at?

I'll just tell you a funny story. When I was in residency, there are certain things that you're measuring on hospitalized patients relentlessly. One of them is potassium. Potassium. You measure that in the plasma. We cared greatly about what our patient's potassium level was. If it was too low or too high, it was problematic. If it was too high, it could be fatal. And just to give you a sense of the narrow range in which we're looking at here, we're talking about a normal physiologic potassium level might be between three and a half and five milli equivalents per liter. Don't worry about what the units mean. But the point is somewhere between 3.5 and five units per liter. And it's not uncommon in hospitalized patients that you have to replace potassium. If, God forbid, you ever replaced too much potassium, you got somebody up to five and a half or six milli equivalents per liter. The risk that you could throw them into a fatal heart rhythm was so significant that if you ever saw that value, even if you thought the lab made a mistake, you were immediately rechecking it and taking corrective actions. Similarly, if the levels are too low, you're going to see all sorts of typically not as problematic and not necessarily fatal, but other sorts of changes in heart rhythm won't get into the whys of that, because we're not really here to talk about potassium.

But suffice it to say you would not be replacing potassium in a patient without having measured the level first. Let's talk about magnesium. Most chief residents, when I was a junior resident would scream at you if you ever measured a magnesium level in a patient with normal kidneys before giving them magnesium. The reason for it is twofold. One, it costs more. It's not altering management, but more importantly, because we now understand, and probably understood then if we were paying attention, that the measurement of serum magnesium is not really indicative of total body magnesium, and you have an enormous buffer for overshooting. So it's also true, by the way, that most of the potassium in a person is not in the extracellular space in the plasma. Most of it is in the cells. But because potassium and the difference between what's in the cell and out of the cell is a very important electrical gradient. If you overshoot what's out of the cell a little too much, it can be fatal. That's not the case with magnesium because magnesium is not used to set the charge across the cell. Okay, if you're sitting here listening to this saying, peter, what the hell are you talking about?

My only point here is, one, we don't have great ways to measure magnesium. I will talk about how it's done. But two, we don't tend to care about it very much clinically because unless a person's kidneys are really compromised and the kidneys become the acute place in where magnesium regulation happens, we don't care about overdoing it. So with that said, there are basically a few ways to do this. You can measure plasma levels, and by the way, that's a test that's commercially available. I can honestly say, I don't know the last time I've ordered it on myself or any of my patients. But you can go to labcore or quest or wherever and request that. I think if you're really concerned about magnesium deficiency, though, you have to do these other types of tests. So one of them is a urinary test. So this is a test where you collect the urine that is made over a period of time, say 24 hours, and you look at the amount of magnesium in the urine and that gives you a sense of magnesium deficiency. In other words, the less magnesium in the urine, the more likely the person is to be deficient.

Why? Because it tells you, boy, those kidneys are really holding on to magnesium. We have a sense of how much magnesium should come out of a person in a day state of quote unquote equilibrium. And if the amount of magnesium that's coming out is really low, you would surmise that that person truly has total body deficiency. The other way you do it is a more elaborate version of that test where you load the patient with magnesium. So you give them a huge iv bolus of magnesium and then you also measure the urinary excretion. That's just a more involved test to do that. And to be honest with you, I've never done either of those. It's possible that an endocrinologist might look to something like that. But again, it begs the point, which is, in a person with normal renal function, you tend to err on the side of assuming people are magnesium deficient. And if you have any reason to believe it based on symptoms or signs, so low bone density preventricular contractions. So relatively benign, skipped heartbeats, things of that nature, cramps, that would be a very common thing that would give you reason to believe a person is magnesium deficient.

We just go ahead and replace the magnesium.

Anyway, just to double click, you mentioned migraines a bit ago. Can you talk a little bit more about migraines and low magnesium? Because I think anyone who has had migraines is willing to look at anything to help alleviate those.

Yeah, earlier I stated, I hope I stated it correctly, that magnesium plays an important role in inhibiting the glutamate excitatory pathway of the NMDA receptor in the brain. And not surprisingly, migraines are associated with more excitation. So the thinking would be that if you are deficient in magnesium, you have less inhibition of an incitatory neurotransmission pathway, and therefore you might see more migraines in people who are susceptible. So looking back, we were able to find a 2016 metaanalysis of all the rcts that were done for acute migraines that found that intravenous magnesium provided significant short term relief, I. E. Within 15 to 45 minutes and up to 24 hours post administration. Now, again, that's intravenous magnesium. We're going to talk in a minute about oral magnesium, which is the way most people are going to get magnesium. It's unlikely that oral magnesium is going to be able to provide relief acutely for this, but intravenously, and we're talking somewhere in the neighborhood of two to 4 grams intravenously. Again, I want you to keep that number in the back of your mind. Two to 4 grams of intravenous magnesium. When we start talking about how much oral magnesium you need to take to get that oral magnesium treatments may reduce the frequency and the severity of attacks, but really provides very little relief in the acute setting.

What do we know about how common magnesium deficiency is? Because I think anyone who's listening is kind of curious. What are the Ods this is going on with them?

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