Daily Value

Magnesium: The ‘Best’ Form Isn’t What You Think Part 1.

• Dr. William Wallace • Episode 71

Share episode

Magnesium supplements are marketed like different compounds with different biological targets - i.e., “for sleep,” “for the brain,” “for stress,” “for energy.” But the foundation of these claims depends on chemistry: how magnesium salts dissolve, how they release Mg²⁺ in the gut, and how much actually reaches circulation.

Part 1 breaks down the first half of the magnesium story: why magnesium must be paired with a counter-ion, how dissolution determines real absorption, and what modern data show when common salts like citrate, glycinate, and oxide are compared head-to-head.

The goal: separating marketing myths from measurable differences in solubility, acute bioavailability, and baseline magnesium status

00:00 Introduction to Magnesium Forms

00:30 Magnesium's Chemical Nature

01:11 Absorption Differences Among Magnesium Forms

01:35 Clinical Studies on Magnesium Absorption

04:24 Magnesium in Animal Studies

06:05 Human Studies on Magnesium

08:47 Conclusion and Preview of Part Two

  • Doi: 10.1186/s40795-016-0121-3
  • PMID: 11550076
  • PMID: 31330811
  • PMID: 39252819
  • PMID: 26519439
  • PMID: 34111673
  • PMID: 23853635
  • doi: 10.3390/nu9050429
  • PMID: 39009081
SPEAKER_00:

Magnesium comes in more forms than any mineral on the shelf, citrate, glycinate, three and eight oxide, all marketed like they do completely different things. Today I'm going to show you what the science actually says about these forms, where the differences matter, and where they really don't. This is part one of a two-part series. I'm William Wallace, and you're listening to Daily Value. Magnesium never exists on its own because it naturally carries a double positive charge written as Mg2. That notation just means the magnesium atom has lost two electrons, making it highly reactive. A charged particle like that can't sit by itself in a capsule or in your bloodstream. It will immediately grab onto something negatively charged to balance the plus two charge. So every magnesium supplement has to pair ionic magnesium, that's Mg2, with what's called a counterion, like citrate, glycinate, malate, chloride, or oxide, that pairing stabilizes it as a solid compound and also shapes how it dissolves, absorbs, and behaves in your body. And the form you choose changes one thing more than anything else, how well it dissolves. And this is important. Your intestine can only absorb magnesium that's dissolved into its ionic form, Mg2. If a magnesium salt dissolves easily in stomach acid, more of it becomes available for absorption. If it dissolves poorly, more of it passes through unchanged. This is the first place where the form of magnesium starts to look different. A good example is a clinical pharmacokinetic study by Capeller and colleagues in 2017, comparing magnesium citrate to magnesium oxide, two of the most common forms on the market. In that study, citrate form produced significantly larger rises in serum magnesium and significantly higher urinary magnesium, meaning more was actually absorbed. And this is exactly what you'd predict from chemistry. Citrate dissolves well in acidic environments. Oxide dissolves poorly unless the pH is extremely low. But here's where things get interesting. If you've ever seen older charts claiming citrate absorbs 30 to 40%, while oxide absorbs only 4% to 18%, those numbers come from older tracer studies done in people who are not magnesium replete. When your body is low on magnesium, it pulls in as much as it can, and the differences between forms can look huge, especially when you're comparing magnesium forms from different studies in populations that have various starting levels of magnesium. However, in newer studies where researchers saturate magnesium stores first, those differences shrink dramatically. That's why in the 2017 head-to-head trial, citrate only absorbed a bit better than oxide. Citrate form was only absorbed 2% to 3% more compared to magnesium oxide. That's a real difference, but nowhere near the dramatic spread you see when looking at studies that don't begin with magnesium repletion in people. Modern lab testing reinforces that message. In 2019, researchers took 15 different magnesium supplements and ran them through a standardized digestion model, basically a lab setup that mimics the acidity and enzymes of the human stomach and small intestine. What they found was a little surprising. Some products released almost none of their magnesium into solution, while others released nearly all of it. That's a tenfold difference coming from products sold side by side in the same stores. And things get even more interesting here. These differences had nothing to do with the milligrams printed on the label. A product with high elemental magnesium sometimes dissolved poorly, while one with lower magnesium content dissolved extremely well. In other words, the number on the front doesn't always tell how much will actually become available to your body. It's the chemistry of dissolution, not necessarily the magnesium count that determines how much you can absorb. These acute absorption differences, that's short term, help explain why forms get reputations. Citrate for gentler digestion, glycinate for fewer GI issues, oxide for cheap bulk magnesium, but absorption is just the first step. It tells you how much magnesium reaches the bloodstream in the first few hours, not what happens inside the tissues that actually store, use, and regulate magnesium. Once magnesium is absorbed, the next question is whether different forms behave differently inside the body. This is where the conversation gets slightly more complicated because the best tissue level data we have comes from animals and not humans. One of the best known animal studies on magnesium forms comes from a 2010 study by Slutsky and colleagues when researchers gave rats magnesium L3 and 8 for 24 days and saw about a 15% increase in brain magnesium. Something magnesium chloride, citrate, and gluconate did not do under the same conditions in that study. Brain magnesium rose. The rat showed improvements in learning and memory. Now, there have been a few studies since then in humans showing that magnesium L3 and 8 does improve some parameters of cognitive function and sleep in older adults with working memory problems and middle-aged adults, respectively. The combination of these things is the reason you hear people saying things like 3 and 8 is the only form that can readily make its way into the brain. But again, that claim came from rodent data. And if we're going to use rodent data, well, magnesium 3 and 8 isn't the only form that does this in animals. In a 2021 systematic review summarizing these studies, forms such as magnesium torate and magnesium acetyl torate showed some of the highest brain magnesium accumulation among the salts tested in rodents. These comparisons did not include magnesium L3N8, so we can't say how well torate-based salts compare to 3-8, only that they perform strongly within the specific animal models examined. Other salts in the same review, like glycinate and citrate, showed greater uptake in tissue, such as muscle or bone. When you move to humans, the picture changes a little bit. Human studies almost never measure magnesium in the brain, and long-term trials rarely measure magnesium in bone or muscle. Almost all human data rely on serum magnesium, red blood cell magnesium, or clinical outcomes. And because less than 1% of total body magnesium is found in blood, these markers tell us very little about tissue distribution. So instead of tissue levels, we have to look at what actually changes in people's sleep, cognition, and symptoms. Let's start with L3N8. It's not because it's better than other forms across the board, but because it produced a very specific finding in animals, an increase in magnesium inside the brain that conventional salts couldn't achieve under the same experimental conditions, again in that same study that we referenced earlier. That observation led to human testing. In a 2015 trial by Lou et L, adults age 50 to 70 with measurable cognitive impairments were given 1.5 to 2 grams per day of magnesium 3 and 8 for 12 weeks. That gives approximately 144 milligrams of magnesium from that dose. Across that period, researchers weren't measuring brain magnesium directly, because we can't safely do that in humans, but they did measure intracellular magnesium in red blood cells and found that it increased in the treatment group while decreasing in placebo. More importantly, the 3N8 group showed significant improvements in work and memory, executive function, and overall cognitive ability compared to placebo. But here's the part people miss. If raising brain magnesium were the only reason these benefits occur, then you'd expect low absorption forms to do nothing in humans. But that's not what the data shows. In a 2012 randomized controlled trial of older adults with insomnia, magnesium oxide, a form that every influencer tells you doesn't work at all, significantly improved sleep time, sleep efficiency, melatonin levels, and morine alertness over the course of eight weeks. These adults began the study with below optimal baseline magnesium and received 500 milligrams of magnesium per day taken in divided doses to reduce any potential GI distress. And despite oxides' lower solubility, their post-intervention serum magnesium still rose and clinical sleep outcomes improved. On paper, magnesium oxide looks like a poor choice. It dissolves slowly, it doesn't shine in bioavailability charts, and it's the form everyone loves to hate. But in real people who are actually low in magnesium, this bad form still moved hormones, still improved sleep, and still made a difference. That tells us something important. The way we talk about magnesium forms online, as if one is magic and the others are useless, doesn't match how biology behaves in real humans. In this first part, we stayed mostly at the surface, how magnesium is packaged as different salts, how those salts dissolve, and how a few key studies show differences in short-term absorption and in specific situations, like insomnia. In part two, we're going to zoom out, we'll look at the bigger human picture, how different salts perform across many trials, what the meta-analyses actually say, whether any form truly stands out for the brain, and how much of the hype comes from the magnesium versus the other molecule that it's attached to. I'm William Wallace. This is Daily Value, and that is the end of part one. Till next time. Stay healthy.

Head Shot

Dr. William Wallace

Host