Magnesium - Beyond Bioavailability: Bioaccumulation in the Brain 1.2-Fold Higher for Mg-Taurate | No Effect on Muscle

Brainiacs listen up: Magnesium + taurine can also be achieved from a (high seafood) diet.
You will remember that the year 2017 saw the publication of the first study to lend credible support to the use of transdermal magnesium. If you go back to my article discussing the results of the study, you will find the following items in the overview of CNS symptoms of magnesium deficiency (48% of the Americans don't get enough Mg | Moshfegh 1997): "Nervousness, increased sensitivity of NMDA receptors to excitatory neurotransmitters, migraine, depression, nystagmus, paraesthesia, poor memory, seizures, tremor, vertigo."

What you will also find is a figure depicting the effects of administering different forms of magnesium (orally) to rodents on plasma, bone, and red blood cell (#RBC) magnesium levels.
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The figure is from another SuppVersity article from 2013, and it is still the most comprehensive comparisons of the oral bioavailability of magnesium compounds I know: What it does not provide, though is data that may explain the previously mentioned central-nervous-system effects of (low) Mg.
Figure 1: Where most of the magnesium in your body is found (based on Swaminathan 2003)
How's that? Well, as Uysal et al. point out, "[f]ollowing absorption from the digestive tract, magnesium enters the bloodstream [and] is then transported at different rate[s] of magnesium transport across cell membranes".

Fact 1: The rate of magnesium transport across cell membranes is higher in the heart, liver, and kidney and lower in the skeleton, red cells, and brain (Rude 1993).

Needless to say that this "penetration" is an important requirement for the previously hinted at (health) effects on the brain and the central nervous system... and guess what: a recent study by scientists from Turkey and the US suggests that previous measures of "bioavailability" may have underestimated the different absorption kinetics of organic and inorganic magnesium salts.

Hence, the aim of this study, which has just been published in "Biological Trace Element Research", was to investigate the bioavailability of different...
  • organic (magnesium citrate, magnesium acetyl taurate, and magnesium malate), and ...
  • inorganic (magnesium oxide and magnesium sulfate) magnesium compounds. 
As you may know, "[m]agnesium citrate and magnesium oxide are the most prescribed Mg compounds as dietary supplements", magnesium acetyl taurate (all about taurine), on the other hand, is something you will have to ask for, specifically -- however, after the publication of Uysal's paper, the number of people doing just that may keep increasing.

Fact 2: Dietary fermentable fiber improves, not impairs, magnesium absorption in the intestines (Coudray 2003) - probably by interacting with the microbiome.

Figure 2: The amount of magnesium in serum is only one parameter that determines its biological effect ... and probably not the most important one (data from Uysal 2018).
People who are less interested in further increasing the transport of Mg from the digestive tract into circulation, as it can be achieved by feeding your microbiome appropriately (fermentable fiber, guys), but rather in its (almost unique) ability to make it from their blood into their eyes and brains, where it stops the development/progress of cataracts (Choudhary 2016), and has been shown to have the very "preventive value in the treatment of migraine" (McCarty 1996b) other forms of magnesium don't seem to have.

As you can see in Figure 2, these effects are not a mere function of bioavailability, as the often derided magnesium sulfate (diarrhea-prone) will increase the level of plasma magnesium to the same extent as the 10-20x more expensive magnesium-taurate or magnesium malate salts (mg sulfate also displays all the beneficial anti-diabetes effects you may have heard about, by the way).
Figure 3: A new study shows that magnesium taurate (MgT) seems to have brain-specific effects (see larger figure) but may be less suitable to increase skeletal muscle magnesium levels (see smaller figure, both from Uysal 2018). What is noteworthy in this context is that Uysal et al. also observed the biological downstream effects on stress/anxiety you would expect to see from the restoration of optimal brain magnesium levels in their hairy rodent subjects.
The obvious question that arises if this is not your first visit to the SuppVersity is, whether you even have to take the taurine-bonded magnesium and/or cannot simply co-supplement with taurine and another form of magnesium like citrate, sulfate or carbonate to have enough taurine your #1 brain osmolyte (Oja 1996). Unfortunately, there's scant evidence to support the notion that a mere co-administration of both agents will have superior effects compared to other forms of magnesium.
DIY - MgTaurate? In theory, McCarty et al. provide you with all the information on how to produce your own magnesium taurate in their 1995 patent specifications, in which the simpler method to end up with MgTau is based on mixing magnesium hydroxide (433 mg, 7.46 mmol; Aldrich) and taurine (1.87 g, 14.9 mmol) in 20 ml water was heated under reflux for seven hours (learn more).
The idea that compounding the two has been first proposed by McCarty et al. more than a decade ago (McCarty 1996a). What the scientists who also own the previously referenced patent (see box) do yet fail to explain why the same 10:1 mix of unbound taurine:magnesium would not yield the same benefits as the compounded molecule.

In fact, studies in bone (Jeon 2007) or the epithelium (Katakawa 2016) seem to suggest that the mere presence of taurine may facilitate significant increases in cellular mg levels. If you take taurine, which is, by the way, one of the few supplements that consistently get a SuppVersity ThumbsUp!, buying MgTau be a waste of valuable dollars (Euros or Bitcoins) you would better spend on taurine- and magnesium-rich foods as they've been found by Yamori et al. (2017) to significantly reduce the risk of cardiometabolic disease in these benefits in Japanese seafood connoisseurs.

Fact 3: Food processing will reduce the magnesium content of your foods by up to 85% - and that's on top of the already declining Mg content of Western produce (Thomas 2007).

Speaking of real-food sources of magnesium, it is worth taking a parting look at the often-heard claim that "with the ongoing nutrient-depletion in our produce, it's simply impossible to get enough magnesium with your diet"... well, in short: that's naturopathic bullshit meant to have you spend money on overpriced supplements that are not better than those you could buy for 10% of the price at Walmart. The reason this myth is so diehard, though, is that it contains not one, but two sparks of truth: (1) Over the past decades, the magnesium concentration of US veggies, fruit, meat, dairy, and cheese has in fact declined. And (2) if you don't eat these foods right away, but after processing the magnesium loss can amount to 90%.

Figure 4: It's true, compared to the values from 1940, US veggies, fruits, meats, cheeses, and dairy contained an average 19% less magnesium in a study by Thomas using data from produce from 2002 (Thomas 2007).
It stands out of the question that the latter (2) is the more likely reason why so many Americans are magnesium-deficient (often without correspondingly low serum levels). If you're concerned about these nutrient losses, though, you should be aware that magnesium is by no means the mineral with the highest reduction in US produce in the last 60 years: With average nutrient reductions of -62% and -37%, those are copper and iron, respectively, followed by a still astoundingly high -29% reduction of calcium in the aforementioned food groups.

Fact 4: You can get enough magnesium from the diet... if you consume a whole foods diet. If >50% of the foods you buy are heavily processed, you don't stand a chance.

So, if there's magnesium in your diet, how much do you need on top of it? Well, if you remember the recently published paper about vitamin D and magnesium (re-read it), you'll know that as little as 100mg can be plenty. In conjunction with the 300 mg you may be getting from your diet, you'll end up at the 400mg/d margin that's the RDA (for men, and won't hurt women).

Against that background, the crazy price of magnesium taurate does no longer sound so crazy - after all, it's not necessary to take more than the suggested serving size, which usually contains ~100-200mg elemental magnesium. However, if taken with food (to avoid diarrhea) and in reasonable amounts, magnesium sulfate would yet be a much cheaper alternative for those who don't want to give magnesium taurate a chance, because they suffer from migraines (McCarty 1996b) and those didn't improve from combining 'regular' magnesium supplements with some cheap taurine (buy in bulk for $20 per kg).
Figure 5: Magnesium in brain. Mg2 is an important regulator of glutamate signaling in the brain (de Baaij 2015).
So what should I remember? Different forms of magnesium differ in both, their bioavailability, i.e. the amount of magnesium that makes it into your bloodstream, and their bioaccumulation, i.e. the deposition of magnesium where you want it: in your cells.

In this context, magnesium taurate is of particular interest. In fact, a new study by Uysal et al. (2018) suggests that it delivers the important macromineral right to the brain, where it has been shown to enhance the brain mg levels and actually enhance learning and memory (Slutski 2010 | to elevate young & old rodents' brain levels, the researchers used Threonate, though).

Whether and to which extent the same brain-mg-boosting effects can be achieved by non-complexed (and non-patented) forms of taurine and magnesium (ratio 10:1) wouldn't yield similar effects is something future studies will have to investigate. And let's be honest: In view of the proven health benefits of high(er) dietary intakes of both from experimental and epidemiological studies (Yamori 2010), it seems likely that these studies could yield positive results | Comment!
  • Coudray, Charles, et al. "Two polyol, low digestible carbohydrates improve the apparent absorption of magnesium but not of calcium in healthy young men." The Journal of nutrition 133.1 (2003): 90-93.
  • Choudhary, Rajesh, and Surendra H. Bodakhe. "Magnesium taurate prevents cataractogenesis via restoration of lenticular oxidative damage and ATPase function in cadmium chloride-induced hypertensive experimental animals." Biomedicine & Pharmacotherapy 84 (2016): 836-844.
  • Jeon, Seol-Hee, et al. "Taurine increases cell proliferation and generates an increase in [Mg2+] i accompanied by ERK 1/2 activation in human osteoblast cells." FEBS letters 581.30 (2007): 5929-5934.
  • Katakawa, Mayumi, et al. "Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats." Hypertension Research 39.12 (2016): 848.
  • McCarty, M. F. "Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate." Medical hypotheses 46.2 (1996a): 89-100.
  • McCarty, M. F. "Magnesium taurate and fish oil for prevention of migraine." Medical hypotheses 47.6 (1996)b: 461-466.
  • Moshfegh, A., et al. "Usual nutrient intakes from food and water compared to 1997 Dietary Reference Intakes for vitamin D, calcium, phosphorus, and magnesium." What we eat in America, NHANES 2005-2006 (2009).
  • Oja, Simo S., and Pirjo Saransaari. "Taurine as osmoregulator and neuromodulator in the brain." Metabolic brain disease 11.2 (1996): 153-164.
  • Rude, Robert K. "Magnesium metabolism and deficiency." Endocrinology and metabolism clinics of North America 22.2 (1993): 377-395.
  • Slutsky, Inna, et al. "Enhancement of learning and memory by elevating brain magnesium." Neuron 65.2 (2010): 165-177.
  • Thomas, David. "The mineral depletion of foods available to us as a nation (1940–2002)–a review of the 6th Edition of McCance and Widdowson." Nutrition and health 19.1-2 (2007): 21-55.
  • Uysal, N., Kizildag, S., Yuce, Z. et al. "Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?" Biol Trace Elem Res (2018).
  • Vici, Giorgia, et al. "Gluten free diet and nutrient deficiencies: A review." Clinical nutrition 35.6 (2016): 1236-1241.
  • Yamori, Yukio, et al. "Taurine in health and diseases: consistent evidence from experimental and epidemiological studies." Journal of biomedical science 17.1 (2010): S6.
  • Yamori, Yukio, et al. "Taurine Intake with Magnesium Reduces Cardiometabolic Risks." Taurine 10. Springer, Dordrecht, 2017. 1011-1020.
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