Magnesium L-Threonate

And one of the places where you and I converge is in terms of our interest in the nervous system and supplementation is uh viv magnesium. Now I've talked at you know endlessly uh on the podcast and elsewhere about magnesium for sake of sleep and improving trans transitions to sleep and so forth but you have a somewhat different interest in magnesium as it relates to cognitive function and durability of cognitive function. would you mind just sharing with us a little bit about what that interest is where where it stems from and because it's this because it's the human lab podcast and we often talk about supplementation what um what you do with that information. Okay. So I need to disclose that I am a scientific advisor to a company called North Centaur which my graduate student Guanglu was CEO. Um so that said I can give you some background. Guung uh although he when he was in my lab worked on breathing had a deep interest in learning and memory and he left my lab he went to work for with a renowned learning of memory guy at Stanford Dick Chen and when he um finished there he was hired by Susuma Tonagawa at MIT who also knows a thing or two about memory I'm teasing Susuma has a nobel for his work on immunogloabbulins but then is a worldclass memory researcher Yeah. Um and more. Um he's many things. And and Guung had very curious, very bright guy. And he was interested in how signals between neurons get strengthened which is called long-term potentiation or LTP. And one of the the questions that arose was if I have inputs to a neuron and I get LTP is the LTP bigger if the signal is bigger or the noise is less. So we can imagine that uh when we're listening to something if it's louder we can hear it better or if there's less noise we can hear it better. And he wanted to investigate this. So he did this in tissue culture of hippo hippocample neurons and what he found was that if he lowered the background activity in all of the neurons that the LTP he elicited got stronger and the way he did that was increasing the level of magnesium in the bathing solution. So he played around with the magnesium and he found out that when the magnesium was elevated, there was more LTP. All right, that's an observation in a tissue culture. Right? And I should just mention that more LTP essentially translates to more neuroplasticity, more rewiring of connections in essence. So he um tested this in mice and basically he offered them a um uh he had control mice which got a normal diet and one that had more enriched to magnesium and the ones that lived uh enriched with magnesium had higher cognitive function uh live longer everything you'd want in some magic pill. those mice did that, excuse me, rats. Um, the problem was that you couldn't imagine taking this into humans because most magnesium salts don't passively get from the gut into the bloodstream into the brain. They pass via a what's called a transporter. transport something in a membrane that grabs a uh magnesium molecule or atom and pulls it into the other side. So if you imagine you have magnesium in your gut, you have transporters that pull the magnesium into the gut into the bloodstream. Well, if you had take a normal magnesium supplement that you can buy at the pharmacy, it doesn't cross the gut very easily. And if you would take enough of it to get it in your bloodstream, you start getting diarrhea. So, it's not a a good way to go. Oh, it is a good way to go. So, couldn't help myself. Uh, well said. Um so he worked with this brilliant chemist Fay Mau and um Fay looked at a whole range of magnesium compounds and he found the magnesium 3 and8 was much more effective in crossing this the uh gut blood barrier. Now they didn't realize at the time but threeenate is a metabolite of vitamin C and there's lots of 3en8ate in your body. So magnesium 3 and8ate would appear to be safe and maybe part of the role or the now they believe it's part the role of the 3en8ate is that it supercharges the transporter to get the magnesium in. And remember you need a transporter at the gut into the brain and into cells. They did a study in humans. They hired a um a company to do a test. It was a hands-off test. It's one of these companies that gets hired by the big pharma to do their test for them. And they got patients who had were diagnosed as mild cognitive decline. These are people who had cognitive disorder which was age inappropriate. And the the metric that they use for determining how far off they were is Spearman's G factor, which is a me generalized measure of intelligence that most psychologists accept. And the biological age of the subjects was I think 51 and the cognitive age was 61 based on the spearmman g test. Oh I should say the spearmman g factor starts at a particular uh level in the population at age 20 and declines about 1% a year. So sorry to say we're not 20 year olds anymore. Um, but when you get a number from that, you can put on the curve and see whether you're it's about your age or not. These people were about 10 years older according to that metric. And long story short, after three months, this is a placebo control double blind study, the people who were in the placebo arm improved two years, which is common for human studies because of placebo effect. The people who got the compound improved eight years on average and some improved more than eight years. They didn't do any further diagnosis as to what caused the mild coal decline, but it was pretty it was extraordinarily impressive. So, it moved their cognition closer to their biological age. Biological age. Um, do you recall what the doses of magnesium 3 and it's in the it's in the paper and it's basically what they have in the compound which is sold commercially. So the compound which is sold commercially is uh handled by a neutrautical wholesaler who sells it to the retailers and they make whatever formulation they want. Um but um it's it's a dosage which uh is my understanding is readily tolerable. I take half a dose. The reason I take half a dose is that I had my magnesium blood magnesium measured and um it was low normal for my age. I took half a dose it became high normal and I felt comfortable staying in the normal range. Um but you know a lot of people are taking the full dose and uh and um for at my age I'm not looking to get smarter. I'm looking to decline more slowly and it's hard as you know it's hard for me to tell you whether or not it's effective or not. When I've recommended it to my friends, academics who are not by nature skeptical, if not cynical, and I insist that they try it, they usually don't report a major change in their cognitive function. Although sometimes they do report, well, I feel a little bit more alert and my move my physical movements are better, but many of them report they sleep better. Yeah. And and that makes sense. I think uh there's good evidence that 3 and8 can uh accelerate the transition into sleep and maybe even uh access to deeper u modes of sleep. But this that's very interesting because I uh until you and I had the discussion about 3 and 8 I wasn't um aware of the uh cognitive enhancing effects. But the story makes sense from a mechanistic perspective and it brings it you around to a bigger and more important statement which is that I so appreciate your attention to mechanism.