Scientific Nutrition Update 45: Magnesium

This episode was a request from Al Boulley, who was curious about the effect of certain minerals on human health, and in this one I focused in on magnesium.  Magnesium may have benefit for depression, anxiety, insulin sensitivity, glycemic control, and even testosterone.

Script (Remember I ad-lib):

For today’s episode I am going to talk about a request from Al Pouley.  Specifically he was curious about the effect of certain minerals on our health, and today we are focusing specifically on magnesium because it is fascinating.  It may be useful in glycemic control, depression, anxiety, blood pressure, and testosterone. That is a lot of potential uses for a cheap supplement, that is generally well tolerated.

 

Let’s start with the reason I first became interested in it years ago, testosterone.  Back when I was a big shot football player and weightlifter I cared a lot about things that could give me a slight advantage, and I had heard that magnesium supplementation could help with testosterone.  At the time I did not investigate it thoroughly, but now in doing so I find it quite interesting. The first study I found interesting was one that looked at a comparison between tae kwon do practitioners and sedentary people after 4 weeks of magnesium supplementation.  What they found was that in both the exercise group and the supplement group there were significantly increased testosterone levels, but the difference was most noticeable in the group that both exercised and supplemented. The changes in both supplement groups was largest after exhaustion.  They also had a second control that was exercise but no supplement, and this group also had a significant increase in testosterone but less than the exercise group that had the magnesium. This would seem to suggest that magnesium can potentially increase testosterone levels. There is actually an interesting proposed mechanism for this which involves magnesium interacting with a complex of testosterone and sex hormone binding globulin, which lowers the affinity between testosterone and shbg, theoretically raising free testosterone levels.  This might particularly help in aged populations who see testosterone and magnesium levels both decline. These changes may help explain part of the reason that magnesium has been suggested to improve athletic performance, both in strength and submaximal endurance, but it is likely not complete. The likely full mechanism involves it acting as a cofactor for the energy processes including ATP in the muscles. It is also important for me to note in magnesium replete individuals, meaning those who have achieved appropriate magnesium levels, supplementation does not have additional benefit.  It acts more as a limiting factor.

 

What was perhaps even more interesting to me is the potential link to insulin sensitivity and glycemic control.  There is evidence that hypomagnesemia reduces insulin sensitivity and in several different studies it appears that magnesium supplementation can increase insulin sensitivity both in diabetic patients and in non-diabetic insulin resistant patients.  In type 2 diabetics the magnesium supplementation besides improving insulin sensitivity also seemed to improve blood glucose levels and glycemic control. The proposed mechanism for this is improved functioning of the tyrosine kinase enzyme at the insulin receptor level.  These results are promising but the HbA1c levels often are not significantly reduced, however that may be an issue with the length of the studies, and is deserving of more research. Reading the evidence I am relatively optimistic about the potential for magnesium, although it needs more investigation.

 

There is still a couple of other interesting effects of magnesium supplementation that I want to look into.  One of the reasons magnesium supplementation is often recommended online is because people believe that it can help with sleep.  I have personally used it for this purpose before, but I was never good at taking it consistently enough to really get a feel for my personal effect.  However, there was a study done on elderly people with insomnia and what was found was: significant increases in sleep time, sleep efficiency, melatonin, and time to fall asleep.  This would suggest to me that at least for insomniacs magnesium could potentially help with sleep. This is somewhat confounded by the investigation being done on elderly people who tend to be more hypomagnesemic.  Intuitively I think the biggest gain is going to be among those who are deficient in magnesium, but that is a significant number of people as magnesium has been removed from the water supply and many foodstuffs.

 

The singular most fascinating aspect to me is the potential for its use as a treatment for depression and anxiety.  Now before I continue, I am not a psychiatrist. Depression and anxiety are both very serious illnesses, and you should not start, stop, or change any treatment without consulting with the appropriate professionals.  I am just detailing my personal interpretation of the studies. Okay so with that out of the way let’s take at look at what these studies say, and these studies is why this episode is one day late, I really wanted to make sure I understood this well before I talked about it.  Remember I am not suggesting you change your medications or add magnesium, however, you may choose to consult with the appropriate professionals. There is evidence of depressed levels of magnesium in the cerebrospinal fluid of people with major depression, however, plasma levels are generally unaffected.  Furthermore, people with depression tend to have a diet significantly lower in magnesium, though it’s hard to determine in that case which way the causal arrow is pointing. Intuitively I think it could be a feedback loop. Meaning that people who eat less magnesium, are more likely to develop depression, which makes it less likely you eat enough healthy food with magnesium, which makes the depression worse, etc…  It makes sense that magnesium would be important for appropriate functioning, it is an important cofactor for a huge number of enzymatic reactions, and is important for appropriate neuronal membrane fluidity. However, that still doesn’t answer the fundamental question as to whether or not magnesium supplement could help alleviate symptoms. This is where things get interesting. There are several case studies published in the literature of people with severe treatment resistant depression who had symptoms completely disappear after treatment with magnesium.  However, those are case studies, they are not placebo controlled and so I’m very nervous trusting them. Interestingly all the way in 1921 magnesium was the first potential treatment indicated for depression. However, that study despite being almost century old is paywalled everywhere I look and I don’t have enough time before graduation to get it through my school, so I can’t speak too much as to what happens in it. However, there is a more recent double blinded, placebo controlled study, that used IV infusions of magnesium and what they found was a significant improvement on the patient health questionnaire 9 used to assess severity of depression, but no significant improvement on the hamilton rating scale for depression.  However, even just improvement on the PHQ-9 is promising. There was also another study that looked at treatment of depression in people with type 2 diabetes, a condition that tends to lead to low magnesium and this also showed a significant improvement in depressive symptoms. Actually improvement equal to the more commonly used antidepressant. Obviously this is far from conclusive, but it is interesting evidence that needs to be considered. It is promising since it shows significantly fewer side effects than the majority of anti-depressants.

 

Since it seems at least somewhat efficacious in treatment of depression I was curious about anxiety since they often respond to similar treatments.  There was a study that looked at magnesium supplementation combined with vitamin b for the treatment of premenstrual anxiety, and they found a significant reduction in the group receiving the magnesium with vitamin b.  Which again is obviously a promising result. There is a couple of other studies, but they are poorly done or badly confounded so even though they report positive results I am going to ignore them. This is all obviously needing more research, but they are promising results.

 

The mechanism for these actions are likely mediated by magnesiums ability to interact with both the N-Methyl D-Aspartate (NMDA) and Gamma Amino Butyric Acid (GABA) receptors as an essential cofactor.  This would be supported by animals study that suggest NMDA antagonists enhance the antidepressant effects of magnesium. This is very speculative though and needs significantly more research.

 

There is some additional support for the idea that magnesium supplementation is worthwhile.  Namely dietary and water levels have been falling rapidly and as such people now have significantly lower levels than in the past. Especially with magnesium being removed from the water supply and the small amount of magnesium that exists in refined flour it becomes a compelling idea that supplementation could be valuable.  However, this is still somewhat speculative and inconclusive.

 

In conclusion, there is interesting evidence that a significant number of people may unwittingly be magnesium deficient, and that supplementation of magnesium may help with testosterone levels, depression, anxiety, insulin sensitivity, and glycemic control.  However, it is important to remember I am not a doctor and you should always consult with a physician before adding or changing a supplement. If you learned something interesting today please consider sharing this episode with a friend and thank you for tuning in.   

Bibliography (I may not directly address these studies in the episode but I looked at them and thought they might be valuable):

 

Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. 2012. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci 17(12):1161-9.

Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. 2008. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: A randomized, equivalent trial. Magnesium Research 21(4):218.

Cinar V, Polat Y, Baltaci A, Mogulkoc R. 2011. Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biol Trace Elem Res 140(1):18-23.

De Souza MC, Walker AF, Robinson PA, Bolland K. 2000. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6for the relief of anxiety-related premenstrual symptoms: A randomized, double-blind, crossover study. Journal of Women’s Health & Gender-Based Medicine 9(2):131-9.

Eby GA and Eby KL. 2010. Magnesium for treatment-resistant depression: A review and hypothesis. Medical Hypotheses 74(4):649-60.

Eby GA and Eby KL. 2006. Rapid recovery from major depression using magnesium treatment. Medical Hypotheses 67(2):362-70.

Excoffon L, Guillaume YC, Woronoff-Lemsi MC, André C. 2009. Magnesium effect on testosterone–SHBG association studied by a novel molecular chromatography approach. Journal of Pharmaceutical and Biomedical Analysis 49(2):175-80.

Guerrero-Romero F, Tamez-Perez H, González-González G, Salinas-Martínez A, Montes-Villarreal J, Treviño-Ortiz J, Rodríguez-Morán M. 2004. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes and Metabolism 30(3):253-8.

Maggio M, Ceda GP, Lauretani F, Cattabiani C, Avantaggiato E, Morganti S, Ablondi F, Bandinelli S, Dominguez LJ, Barbagallo M, et al. 2011. Magnesium and anabolic hormones in older men. International Journal of Andrology 34(6pt2):e600.

Maggio M, De Vita F, Lauretani F, Nouvenne A, Meschi T, Ticinesi A, Dominguez LJ, Barbagallo M, Dall’Aglio E, Ceda GP. 2014. The interplay between magnesium and testosterone in modulating physical function in men. International Journal of Endocrinology 2014:1-9.

Mehdi SMA, Atlas SE, Qadir S, Musselman D, Goldberg S, Woolger JM, Corredor R, Abbas MH, Arosemena L, Caccamo S, et al. 2017. Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression. Psychiatry Clin Neurosci 71(3):204-11.

Murck H. 2002. Magnesium and affective disorders. Nutritional Neuroscience 5(6):375-89.

Rodríguez-Morán M and Guerrero-Romero F. 2003. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: A randomized double-blind controlled trial. Diabetes Care 26(4):1147-52.

Serefko A, Szopa A, Wlaź P, Nowak G, Radziwoń-Zaleska M, Skalski M, Poleszak E. 2013. Magnesium in depression. Pharmacological Reports 65(3):547-54.

Song Y, He K, Levitan EB, Manson JE, Liu S. 2006. Effects of oral magnesium supplementation on glycaemic control in type 2 diabetes: A meta-analysis of randomized double-blind controlled trials. Diabetic Medicine : A Journal of the British Diabetic Association 23(10):1050.

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