So naturally, the next question on people's minds is, what about magnesium supplements? Where do they fit in? What if I don't get enough magnesium from dietary sources? Can I supplement? So let's start with supplemental magnesium doses. So how much is too much? The US Institute of Medicine's Food and Nutrition Board has set the upper safe limit for daily supplemental magnesium intake at 350 milligrams per day. So this is the level considered, you know, that it's unlikely to cause diarrhea or gastrointestinal issues for most people. Diarrhea is the first sign of excessive magnesium supplementation. It's often used therapeutically as a laxative, but this is a bit of a conservative dose. It does not include magnesium from dietary sources.

So in other words, there's no evidence that going above the RDA for magnesium is harmful. In fact, some evidence suggests that it may even be beneficial, particularly if the magnesium is mostly coming from dietary sources. For optimal bioavailability of magnesium supplements, it's also generally more effective to take the total daily dose in divided smaller amounts rather than a single large dose. So this approach allows for more efficient absorption by the body. It can also minimize the potential GI discomfort. So smaller spaced out doses, they're processed better by the digestive system. And this also ensures maximum absorption and utilization of the magnesium. The bioavailability of different magnesium supplements does vary, and it's not fully standardized in studies.

Clinical research on organic magnesium salts—including magnesium citrate, magnesium glycinate, magnesium tartrate, and magnesium malate—indicates that these forms are generally more bioavailable and effectively raise plasma magnesium levels compared with inorganic forms such as magnesium oxide, magnesium chloride, and magnesium sulfate. They can lead to more significant increases in magnesium levels in the blood. For this reason, I think they are more effective choices for supplementing magnesium and also, of course, addressing deficiencies.

But just to eliminate any confusion, the term organic in this context refers to the presence of carbon being in the acid molecule. So we're not talking about agricultural standard of being organically grown here. It's a different term. Magnesium sulfate is an inorganic form that can be taken orally, although it is more commonly used as Epsom salt for applications through the skin. When taken orally, it can act as a laxative and is used therapeutically for that purpose. The effectiveness of Epsom salt, particularly in baths, is unclear. We'll talk about this a little bit later because the transdermal absorption of magnesium through Epsom salt baths really hasn't been conclusively proven. But let's talk about another form of magnesium called magnesium L-threonate.

Magnesium threonate is a form of magnesium that has garnered a lot of attention because of its potential impact on brain function. So generally, only a small portion of the magnesium ingested in a supplement form reaches the brain, and this is due to the intricate active transport systems that control the progression of magnesium from the digestive tract into the bloodstream, and then subsequently from the bloodstream across the blood-brain barrier. The body establishes and manages a very tight concentration gradient. It creates a higher magnesium level in the blood compared to the cerebrospinal fluid, and that allows a very controlled quantity of magnesium that can actually get transported into the brain.

This precise regulation is really important to maintaining this equilibrium of magnesium necessary for optimal brain function. So in humans, it's been found that even an increase up to 300% in blood magnesium results in less than 19% change in the cerebrospinal fluid magnesium content. And I think this really highlights the significant role that physiological processes in maintaining magnesium balance play, which then influence the brain health and function. So some animal evidence suggests that magnesium L-threonate can easily get across the blood-brain barrier. And at a human-equivalent dose of 8.1 milligrams per kilogram of body weight, which would be around 662 milligrams for a 180-pound person, it can improve cognition and decrease amyloid beta plaques.

Now, this is in the brains of mice, and it's thought that the magnesium L-threonate is uniquely effective in crossing the blood-brain barrier due to its specific molecular structure. So this form of magnesium is chelated to threonic acid, and that is a metabolite of vitamin C. So this chelation enhances its ability to pass through the blood-brain barrier, or so it's thought. The precise mechanism by which magnesium L-threonate bypasses this tightly regulated concentration gradient between the blood and the brain is not fully understood. It is believed, though, that its molecular structure does somehow facilitate easier entry into the brain, thereby increasing concentration of magnesium in the brain more effectively than other forms of magnesium.

That is solely based on a very small and limited number of animal studies. When we turn to human studies, only a couple have explored the effects of magnesium L-threonate. So these studies are, I want to point out, industry-funded, which does invite us to consider a potential conflict of interest. So the initial study that I think garnered a lot of attention was published in 2016. It was a small-scale study that only had 44 participants total. Those in the treatment group took daily doses of about 1,500 to 2,000 milligrams of magnesium L-threonate. So this is marketed as Magtein, and they took it for over 12 weeks based on— so this was based on their body weight. That's why there's a range in dose. The findings of this study, I personally think, are underwhelming.

So the treatment group only achieved a marginal increase in plasma magnesium levels with no elevation noted in red blood cell magnesium levels compared to the placebo group. Additionally, there was a significant increase in urinary magnesium, which suggests that most of the supplemented magnesium L-threonate was actually being excreted through urine. There were some cognitive tests that were also done. There was no significant difference observed when each of these 4 different measured cognitive tests were looked at in isolation compared to the placebo group. But if the data was all pooled together, so all 4 cognitive tests were then pooled together, then there was a statistically significant difference in cognitive function compared to the placebo group.

Obviously, this suggests a degree of statistical uncertainty in the study's conclusions, whether or not it was just due to a small sample size. I said there's only 44 people in this study. Perhaps if there were 444 people, there would have been a stronger signal, and the data wouldn't have had to have been pooled together. Or maybe there really isn't much of an effect. There's no telling. The second study was also industry-funded, which I think is important to keep in mind. This study was published in 2022, and it involved 100 participants. And the treatment group was given 400 milligrams of magnesium L-threonate along with vitamins C, D, B6, and phosphatidylserine. In contrast, the placebo group received only 2 grams of a starch capsule.

So despite the absence of any elevation of serum or brain magnesium levels, the treatment group did have improved cognitive test performance compared to the placebo group. I would say this study raises pretty significant questions around causation because the treatment group was not just given magnesium L-threonate. They were given a variety of vitamins. They were given vitamin C, B vitamins, vitamin D, and vitamin B6, but they were also given phosphatidylserine. So I think to be able to establish a solid conclusion that magnesium L-threonate is responsible for improving cognitive function, the placebo group should have gotten all those other vitamins and the phosphatidylserine, but not the magnesium L-threonate. However, that was not the way the study was done.

So in my opinion, I think it's an interesting study, but really no conclusions can be stated directly about magnesium L-threonate. So I think a concluding statement with respect to supplemental magnesium, there are a few concluding statements. One, to enhance bioavailability, it's advisable to take smaller frequent doses of magnesium supplements. Organic magnesium salts like magnesium glycinate or magnesium tartrate are generally more readily absorbed than inorganic forms like magnesium oxide. I also think there are some added benefits of these organic salts. For example, taking magnesium glycinate also gives you some accompanying compounds like glycine. So glycine could potentially be beneficial, at least according to some studies.

Also, magnesium taurate would give you taurine, which also may have some health advantages, but that's the subject of another podcast. Some caution is warranted to avoid excessively high magnesium doses. So 350 milligrams per day is the safe upper limit, and that is for either organic or inorganic magnesium supplements. If you go above that, you may get GI side effects. So that's something to keep in mind. I would say a really important takeaway from this section is magnesium L-threonate is not the best option for meeting daily magnesium needs, as outlined by the RDA. It shouldn't be included as contributing to your recommended daily allowance of magnesium.

And that is because magnesium L-threonate contains a very low amount of elemental magnesium. So if you are considering supplementing with magnesium L-threonate for its potential brain health benefits, which I would say have not been established, do not count that magnesium dose towards your RDA goal. So to ensure you're getting enough magnesium, you know, you need to calculate what you're getting from your foods, but also consider supplementing with other organic magnesium forms like magnesium glycinate, which does have a higher amount of elemental magnesium content. As you can tell, there are many different forms of magnesium available. A natural question is, what do I take? The answer is I hedge my bets.

I take a supplement that has many different forms of magnesium salts, which seems logical to me. There are not many products I have found that offer that. One of them is Magnesi-Om by Moon Juice. The other one I sometimes take at night is magnesium glycinate by Pure Encapsulations. There are many different brands. I'm not affiliated with either of those, but I know many of you want to know what I take, so there you have it.