Oral Mg2+ Supplementation Reverses Age-Related Neuroendocrine and Sleep EEG Changes in Humans

This seems really interesting… but I’m not familiar with Mg2+. They say its a natural compound - but I can only find two examples of it commercials available (a water filter, and fish tank water test kit). Anyone know anything about it?

The process of normal aging is accompanied by changes in sleep-related endocrine activity. During aging, an increase in cortisol at its nadir and a decrease in renin and aldosterone concentration occur. In aged subjects, more time is spent awake and slow-wave sleep is reduced: there is a loss of sleep spindles and accordingly a loss of power in the sigma frequency range. Previous studies could show a close association between sleep architecture, especially slow-wave sleep, and activity in the glutamatergic and GABAergic system. Furthermore, recent studies could show that the natural N-methyl-D-aspartate (NMDA) antagonist and GABA(A) agonist Mg(2+) seems to play a key role in the regulation of sleep and endocrine systems such as the HPA system and renin-angiotensin-aldosterone system (RAAS). Therefore, we examined the effect of Mg(2+) in 12 elderly subjects (age range 60-80 years) on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. A placebo-controlled, randomised cross-over design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg(2+) was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days. At the end of each interval, a sleep EEG was recorded from 11 p.m. to 7 a.m. after one accommodation night. Blood samples were taken every 30 min between 8 p.m. and 10 p.m. and every 20 min between 10 p.m. and 7 a.m. to estimate ACTH, cortisol, renin and aldosterone plasma concentrations, and every hour for arginine-vasopressin (AVP) and angiotensin 11 (ATII) plasma concentrations. Mg(2+) led to a significant increase in slow wave sleep (16.5 +/- 20.4 min vs. 10.1 +/- 15.4 min, < or =0.05), delta power (47128.7 microV(2) +21417.7 microV(2) vs. 37862.1 microV(2) +/- 23241.7 microV(2), p < or =0.05) and sigma power (1923.0 microV(2) + 1111.3 microV(2) vs. 1541.0 microV(2) + 1134.5 microV(2), p< or =0.05 ). Renin increased (3.7 +/- 2.3 ng/ml x min vs. 2.3 +/- 1.0 ng/ml x min, p < 0.05) during the total night and aldosterone (3.6 +/- 4.7 ng/ml x min vs. 1.1 +/- 0.9 ng/ml x min, p < 0.05) in the second half of the night, whereas cortisol (8.3 +/- 2.4 pg/ml x min vs. 11.8 +/- 3.8 pg/ml x min, p < 0.01) decreased significantly and AVP by trend in the first part of the night. ACTH and ATII were not altered. Our results suggest that Mg(2+) partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging. The similarities of the effect of Mg(2+) and that of the related electrolyte Li+ furthermore supports the possible efficacy of Mg(2+) as a mood stabilizer.


Commercially available products:

Source: https://www.amazon.com/BWT-Cartridge-Filters-120-Liter-Capacity/dp/B00CD229Q6/ref=asc_df_B00CD229Q6/

s-2002-33195.pdf (253.5 KB)

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Related:

In old age long but not short sleep duration was associated with mortality.

Sleep duration in midlife and old age and risk of mortality over a 48-year follow-up: The Helsinki businessmen study (HBS) cohort

Highlights

  • Sleep duration in midlife and old age was related to all-cause mortality.

  • Mortality with short sleep duration in midlife was attributed to unhealthy lifestyle factors.

  • In old age long but not short sleep duration was associated with mortality.

https://www.maturitas.org/article/S0378-5122(24)00059-8/fulltext

This looks worth looking into. I don’t understand all the stats they gave, but they looked like impressive changes. A solid night’s sleep is something I need more of, so I hope we find a source other than filters.

I would assume it is magnesium as a salt ie not the oxide. Something like citrate, malate or threonate. Hence the Mg2+"magnesium ion will disassociate.

OK - John, you’re saying you can achieve the same thing via citrate, malate or threonate? Any idea of dosing?

In the study:

Mg(2+) was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days.

Huberman has a podcast on hydration inwhich he describes an effervescent magnisum tablet added to water which makes the water better able to hydrate at the cellular level. Might be the same as what is described in this research. He made a point that this is not the same as the magnisum you’d take as a supplement.

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It seems the magnesium that Huberman is talking about is different… is this what you are talking about, or perhaps a different podcast (I think he talks about this in more of a sleep-oriented podcast)

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Looking at the paper it is Magnesium Oxide which is poorly soluble in water (but more soluble in acid - think of the stomach) and hence it is unclear as to how well the ions are transferred to blood serum. To be honest I would avoid supplementing with MgO, any of the soluble salts (and I prefer citrate of course) would be better.

Because I take from time to time large amounts of my citrate mix that includes large amounts of Magenesium (as it dissolves easily then it is clearly in the ionic form in solution).

In the end, however, if people are deficient in magnesium they will get more benefit. I don’t think there is any doubt that sufficient Magnesium is essential.

There are people that argue specifically for Threonate. I am not myself persuaded it is particularly good and I think citrate has major advantages.

No that’s what he recommends for brain function. This is for hydration. He values it not for the nutrition but for its ability to facilitate hydration, especially if your drinking water is soft. I’ll dig it up and post-it.

FWIW

In my view

IV magnesium chloride{not sulfate)

One of many published papers.

“Protective Effects of Magnesium Chloride on Liver Enzymes and Biomarkers of Oxidative Stress in high fat diet fed Rats”

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Almost any magnesium will be Mg2+. Unless you eat the metal.

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Podcast is Huberman Lab’s “How to Optimize Your Water Quality & Intake for Health
The section of interest is summarized here:
(02:03:26) Hydrogen-Enriched Water, Magnesium, Optimize Hydration

  • Hydrogen-enriched water can be created by dissolving magnesium tablets in water
  • Drinking hydrogen-enriched water has been linked to reduced inflammation and improved health metrics
  • Hydrogen-enriched water is more efficiently absorbed and leads to better hydration
  • Tap water with sufficient magnesium can be filtered and consumed without hydrogen-enrichment
  • Hydrogen-enrichment can make water more palatable and more effective in hydrating cells and tissues

It contains this US Amazon link to the type of magnesium he’s talking about. Although they are called “Molecular Hydrogen Tablets” they contain magnesium.

The only thing that makes me think that these two supplements are connected is the description that they fizz and contain magnesium. It would be great to have access the full text, maybe it contains the details on the type of magnesium used. Since the original paper is more than 20 years old, you’d think it would be available somewhere!

I’ve added the paper in the first post now so we can all review it.

Mg2+ is just the way scientists write magnesium found in its cation form, which is in salts like magnesium glycinate and magnesium citrate. You can’t buy it alone, its part of the package.

So, in other words you’re saying that buying either of these two forms (which are easily available) would be equivalent to what they used in the study?

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Your original question was about how to obtain Mg2+ as if it was rare thing you could only find in fish tank cleaner. I’m just saying that Mg2+ is easily available as part of any magnesium salt, also including magnesium malate. How much Mg2+ would be bioavailable to match the study’s formulation is way above my pay grade.

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All the different salts of Mg that are available relate to their bioavailability and their ability to cross the BBB. Mg L-Threonate is best for crossing blood brain barrier (I use the “MagMind” product made by Jarro. The other salts vary in their ability to be absorbed by the gut. A lack of absorption will result in diarrhea. In fact bottles of Mg citrate are used prior to (the night before) GI surgery to clean out the bowel. I have MgCl2, Mg Glycinate, Mg L-Threonate and “Slow Mg” which is a mixture of MgCl2 and CaCl2 that aids in gut absorption (recommended by Peter Attia). The Glycinate, L-Threonate, and the Slow Mg affect my GI tract the least. When I get a bit constipated from too much protein I throw in a little MgCl2. I take 4 capsules of the Mg threonate (190 mg Mg2+) and 4 tablets of the slow mg (286 mg Mg2+) for a total of ~475 mg Mg2+ prior to bed each day without significant GI disturbance.

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From my pharmacy background…Magnesium oxide does not dissociate well in aqueous solutions into its doubly charged magnesium cations (++) and oxide anions. To enhance dissociation, ligands (eg:glycine) and weak acids (citric and malic) can be used. “Biolectra Ingredients: Simethicone, Rice starch, Citric acid, Potassium bicarbonate, Cyclamate, Magnesium oxide, Sodium chloride, Malic acid, Lemon Aroma, Sodium saccharin, Sodium hydrogen carbonate, Mannitol”.
The reaction between the numerous acids and bases produces carbon dioxide and the "effervescent " effect as well as a lower pH to support magnesium as Mg++. As well, citric acid can act as a ligand to enhance dissolution.
Magnesium oxide and magnesium hydroxide (milk of magnesia) are notorious for causing laxative effects at higher dosages because they are poorly absorbed from the GI tract and osmotically draw fluid into the bowel.
Magnesium bisglycinate and other salts of magnesium are generally considered better compounds for oral bioavailability. From oral ingestion to intracellular penetration is almost certainly a long and indirect pathway, likely best optimised by ensuring ingestion of magnesium rich foods (almost everyone cannot obtain sufficient magnesium this way) and supplementing with a broad sampling of magnesium chelates and salts… thus letting the body and biome “decide” which and how much enters.
Hope this is helpful.

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This Mg2+ ingredient is nothing special. Calling it Mg2+ rather than calling it magnesium or Mg is mostly a matter of nomenclature. Fact is, basically all the magnesium supplements you will find (glycinate, citrate, oxide, threonate etc.) contain magnesium salts. When dissolved in water they will dissociate into their respective ions, one of the ions being Mg2+. As an example, magnesium citrate is made from magnesium bound to citrate and will dissociate mostly into Mg2+ ions and citrate ions. All of the magnesium supplement will give you magnesium mostly as Mg2+.

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Oddly enough, however, they were using MgO. Ordinarily it does not disassociate into ions in water that well. Hence it is one of the worst Magnesium based substances to describe as Mg2+.

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