Effect of Mg Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials, 2022, Nicola Veronese

Abstract

Magnesium (Mg) may have several beneficial effects on human health outcomes. One hypothesized mechanism eliciting such effects is the action of Mg on serum inflammatory parameters. However, studies on this topic to date have several important limitations. Therefore, the present systematic review and meta-analysis aimed to summarize the current state of the art of all randomized control trials (RCTs) investigating the effects of Mg supplementation versus placebo on serum parameters of inflammation.

We searched several databases until 23rd November 2021 for RCTs. Eligible studies were RCTs investigating the effect of oral Mg supplementation vs. placebo and having serum inflammatory markers as an outcome. Among 2484 papers initially screened, 17 randomized controlled trials (889 participants; mean age: 46 years; females: 62.5%) were included.

Generally, a low risk of bias was present. In meta-analysis, Mg supplementation significantly decreased serum C reactive protein (CRP) and increased nitric oxide (NO) levels. In descriptive findings, Mg supplementation significantly reduced plasma fibrinogen, tartrate-resistant acid phosphatase type 5, tumor necrosis factor-ligand superfamily member 13B, ST2 protein, and IL-1.

In conclusion, Mg supplementation may significantly reduce different human inflammatory markers, in particular serum CRP and NO levels.

https://www.mdpi.com/2072-6643/14/3/679

 

So this (the nitric oxide) is why epsom salt baths help.

 

My personal experience with magnesium is that I needed IM injections with taurine to get the full benefit for over one year. Supplementation with capsules didn't do anything for me.

Edit to add:

Taurine increases magnesium absorption into the cells.

 

Effect of magnesium versus placebo on serum nitric oxide.

 

I would like to see an inverted funnel plot on that - although probably not enough data to be useful.
The results look all too much the same. No statistical scatter. A well known tell-tale sign something is not quite right.

 

Didn't another thread mention something being wrong with nitric oxide (NO)? I'm still trying to figure out if magnesium helps me. I'm not certain if it's a coincidence or not, but I've noticed an improvement after prolonged supplementation (2 weeks +). I've noticed this a few times after stopping and then resuming taking it.

 

The studies on NO included were

1. Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients
2. Magnesium supplementation affects metabolic status and pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial (a retracted paper)
3. The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial

The expression of concern for 2. mentions "timing of trial registration, dual publication, ethical approval, participant recruitment, participant data, and supply of placebos."
The retraction notice for 2. mentions "The Editor-in-Chief is retracting this article due to concerns about the validity of participant data in the study."

I don't know how to make a funnel plot.

The three studies were conducted in Iran, with some authors appearing on several papers.

 

I've been taking Epsom salts footbaths for migraines and had a speedy and substantial reduction in migraines since I started, which has been maintained for months as I've continued with them. I previously tried Mg capsules for three months with zero effect. I've read that some people don't absorb oral Mg well and have to have IV Mg but I seem to be doing well with transdermal (though I don't have blood test results to back it up as causative and didn't do an RCT, of course).

 

I took mg capsules for years but was still depleted when tested. I started taking mg sulfate injections twice a week for over one month but didn't feel much benefit. When we combined it with taurine (Dr. Paul Cheney protocol) was when I felt better, the positive effect was instant, so there was no need to guess whether it helped my particular needs.

Epsom salts soaks are helpful too.

I use mg chloride gel twice a week b/c I don't absorb mg very well in the gut and deplete my mg stores quickly.

 

The RBC Mg test don't tell you much until you're at least 1/3 depleted. There is only one lab in U.S that I'm aware of that tests Mg in the cells- (Exatest).

 

From the full paper - my emphasis :

The use of "the majority" in the bolding above is misleading. It isn't a majority of the studies that used 250mg daily of Mg Oxide. It is a majority of the studies that used Mg Oxide that used 250mg daily.

The types of supplement used in each of the 17 studies can be found in Table 1 in the systematic review paper.

Mg Oxide - 7 studies
Mg Citrate - 5 studies
Mg Pidolate - 1 study
Mg Chelate - 1 study
Mg Chloride - 3 studies

From this link : https://www.afibbers.org/magnesium.html

I would have thought in a systematic review that comparing amounts of elemental magnesium taken in the studies, and the absorption possible, would have been important to comment on.

There are several links on the web where the author discusses the best forms of magnesium supplement to take. Mg Oxide is usually derided by the ones I've read because the absorption is so poor - and yet it's so cheap in comparison to other possible supplements that many multivitamins and magnesium supplements will use it as their source of magnesium.

 

Mg Oxide is very poorly absorbed, I remember reading one study where Mg Citrate's effect on blood Mg levels was several times higher than Mg Oxide. Intracellular Mg levels weren't different between the two though. Maybe in order to increase them you would need a prolonged supplementation of weeks or months? Furthermore, if this is the case then a very small fraction of what you take would go where you want (inside the cells), so you would need quite a high dose to make a difference, higher than 250 mg / day for sure.

 

I've only read the few sentences above; however, I'm struck that if magnesium was a common problem in people with ME/CFS then surely it would have turned up in some studies?

The results from the GWAS [Chris Ponting] study should help to test this theory.

I think I vaguely recall a single nucleotide polymorphism turning up in a study of samples from a UK (CureME?) biobank - protein used to transport calcium/divalent ions into cells, or some such?

 

If there are ion channel.issues with calcium would there not be a knock on effect on magnesium as there is a direct cellular relationship ?

 

Magnesium participates in so many processes that it's hard to know why it's helping. To name some: histamine degradation, energy production, electrolyte transport, glutamate receptors, glutathione synthesis.

I read that most of the population in the western world doesn't get enough magnesium. More magnesium would help prevent heart disease, high blood pressure, anxiety and depression which are big problems.

 

Years ago the ME Association did a study on Mg supplements which gave a positive result. The newspaper headlines were "ME patients told to take epsom salts"

 

Many, many years ago (early teens) I thought I was suffering from constipation. I don't know how I found out but I learned that epsom salts was a laxative, and I found some in the house. I don't know what it's purpose was but I took some in water.

I would recommend never, never, never taking epsom salts in water. It was - and I'm not exaggerating or lying - the most vile thing I have ever tasted.

I know now that it can be used in the bath, but I didn't know that as a kid.

 

There is epsom salts for baths and epsom salts for consumption (mg sulfate) that is kept behind the pharmacy counter. You have to ask the pharmacist or get a prescription. I once took the oral supplement and it tasted fine.

 

I was forced to stop breastfeeding and it was very painful. The midwife told me to take a large dose of epsom salts. Let's just say it worked in more ways than one and it tasted absolutely disgusting!

 

You have my sympathies. [rhetorical question] I wonder what the connection is between breast/nipple pain while breastfeeding and epsom salts. Is it an old wives tale or is it grounded in proper research? And did it fix what it was intended to fix?

I took epsom salts all those decades ago in the hope of fixing constipation. It didn't work probably because, as it turned out, I didn't have constipation my problem was something quite different.