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Magnesium Supplementation

One of the most common questions I get is: what do I think about fill-in-the-blank supplement? I get where patients are coming from. If some major symptom or other problem could be treated with taking a supplement, I’m all in. But how do we wade through all the noise and figure out what might have a benefit, and what is just the latest fad?

Supplements can play a valuable role in our longevity goals. However, there is a potential danger as well, given that all of us have limited time, energy, and other resources. We have to be wise in how we spend those resources. We have to major on the majors, and minor on the minors, and I would place taking supplements firmly in the “minor” camp. An over-emphasis on supplements can be costly if it takes our eye off the ball of more important things (e.g. exercise).

Like any other decision in life, the decision to take a supplement is a cost/benefit analysis, and unfortunately it is a decision we make with less than perfect data. Every individual will have a different cost/benefit threshold for making that decision. And every individual will approach the decision with their own unique biology and medical background.

With all that as a preface, I do think there is a short list of supplements in which the data seems particularly promising. Magnesium is probably at the top of my list for a supplement that you should consider. This article will outline what magnesium is, why it is important, and the best sources of magnesium in our diet. I will summarize what the medical literature has to say about its potential benefits, and lastly will discuss the best ways to take magnesium, especially given how many different options are available.

What is magnesium?

Magnesium acts as a cofactor for more than 300 enzymatic systems that regulate many different chemical reactions in the body. These reactions range from protein synthesis to muscle and nerve transmission, to neuromuscular conduction, as well as blood glucose and blood pressure control.

About 60% of total body magnesium is stored in the bones. Most of the rest of our body’s magnesium is found in muscle and non-muscular soft tissue. Less than 1% of total body magnesium is found in the serum. It is for this reason that the measurement of magnesium with a standard blood test is an unreliable indicator of your total body’s magnesium status, as serum levels have little correlation with total body magnesium levels. In other words, just because your serum magnesium level is normal does not mean you have optimal magnesium stores, and furthermore it is very possible to have symptoms of low magnesium even when your blood test shows you are normal.

Foods high in magnesium content include nuts and seeds, black beans, green vegetables (spinach and broccoli), and dark chocolate. The Recommended Daily Allowance (RDA) for magnesium is 320 mg/day for adult females and 420 mg/day for adult males. Population studies in North America and Europe consistently show that our diets are low in magnesium content, and that most people only consume 30-50% of the RDA for magnesium. The Unites States NHANES 2005-2006 survey reported that nearly one half of all American adults do not consume the appropriate amount of magnesium (Moshfegh et al). It has been suggested that the dietary intake of magnesium for the average American has been declining over the past 100 years, from about 500 mg/day to 175-225 mg/day. This probably reflects an overall poorer dietary quality, with an over-reliance on processed foods. But many experts also argue that the decrease in dietary magnesium intake is due to decreasing levels in our soil, such that even when we eat a reasonable quantity of fruits and vegetables, we are getting less magnesium (and other important nutrients) from them.

What are the consequences of low magnesium?

Early signs of magnesium deficiency include fatigue, weakness, loss of appetite, and nausea. More pronounced magnesium deficiency presents with symptoms of increased neuromuscular excitability such as cramps, muscle fasciculations, tremor, and tetany.

Low levels of magnesium have been associated with a number of chronic diseases, such as Alzheimer's disease, type 2 diabetes, asthma, hypertension, cardiovascular disease, migraine headaches, depression, and attention deficit hyperactivity disorder (ADHD). A large prospective European study (Leone, et al) showed that in middle-aged men, high magnesium values were negatively related to mortality, with a 40% decrease in risk for all-cause mortality (0.6; 0.4-0.8), and a 50% decrease in risk for cancer deaths (0.5; 0.3-0.8).

This is an impressive list of associations, but it is important to note that they are merely correlations. The cardinal rule of statistics is that correlation does not prove causation. There are many potential confounders that may be causing the associations, and in the case of magnesium levels, the so-called “healthy user” bias may be particularly important. If you remember all the dietary foods that are rich in magnesium – nuts and seeds, green vegetables, black beans – these are things that healthy people tend to eat more of. So it may be that higher magnesium levels are simply a marker of an overall healthy diet, and that the healthier diet and not the magnesium itself is what is producing the decreased risk of all the above disorders, including all-cause mortality.

But with those important caveats in place, it is still very easy to be seduced by correlations, and a 40% decrease in all-cause mortality does get your attention. The real question is whether the correlations hold up when randomized controlled trials (RCTs) are performed, which is how the question of causation is really answered.

In many cases we do not have RCTs available that test a specific outcome. And note there will probably never be an RCT that looks at all-cause mortality as an outcome of magnesium supplementation. But in my review of the literature I was actually surprised at how many RCTs existed that look at magnesium supplementation in the areas of insulin resistance, type 2 diabetes, cholesterol, and blood pressure, not to mention a number of other areas ranging from migraine headaches, inflammation, depression, and sleep. Let’s take a brief look at 3 of those areas: type 2 diabetes, hypertension, and sleep.

Magnesium and Type 2 Diabetes

Magnesium plays a crucial role in glucose and insulin metabolism, which is demonstrated by the large amount of data supporting the use of magnesium for lowering glucose levels and improving insulin resistance in individuals with prediabetes and type 2 diabetes. In a randomized controlled trial of 116 men and women aged 30-65 years with low magnesium levels and newly diagnosed prediabetes, a dose of magnesium 382 mg daily vs. placebo for 4 months significantly lowered fasting glucose, 2-hour glucose, markers of insulin resistance, triglycerides, and significantly increased HDL levels (Guerero-Romero et al). A meta-analysis of 18 RTCs in individuals with type 2 diabetes and prediabetes showed that magnesium supplementation resulted in a statistically significant reduction in fasting blood glucose and markers of insulin sensitivity (Veronese et al).

Magnesium and Hypertension

Magnesium is often touted for having positive effects on blood pressure. Numerous observational studies show an inverse relationship between magnesium levels and blood pressure, as well as low dietary intake of magnesium and risk for hypertension. A surprisingly high number of RCTs have been performed testing magnesium’s effects on blood pressure. Unfortunately the results of the RTCs are inconsistent. But the most recent meta-analysis I found (Zhang et al) concluded that magnesium supplementation resulted in a modest improvement in blood pressure, with average reductions in both systolic and diastolic blood pressure of about 2 mm Hg.

Magnesium and Sleep

Magnesium is currently quite popular as a sleep aid. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction, and functions in a protective role against excessive excitation. Magnesium has an essential role in ion channel conductivity, such as the N-Methyl-D-aspartic acid (NMDA) receptor. Magnesium acts as a natural antagonist of NMDA, which may mediate its role in sleep regulation.

I could only find two small RCTs in this area, but both studies showed positive impacts on sleep with magnesium supplementation. The first study (Abbasi et al) was conducted in 46 subjects and compared magnesium 500 mg daily vs. placebo for 8 weeks. The second study (Breus et al) was conducted in 31 adults and compared magnesium 1 gram daily vs. placebo for 2 weeks. Both studies showed a statistically significant improvement in sleep duration and sleep efficiency in the magnesium group, and the latter study showed an improvement in deep sleep as well.

How Much Should I Take, and What is the Right Form of Supplement?

If you have ever shopped for magnesium supplements, you know that there is an overwhelming amount of options available.

Magnesium salts are often divided into two categories: organic and inorganic. The two most common inorganic forms of magnesium are magnesium oxide and magnesium chloride. Magnesium chloride is very highly absorbed in the gut, however magnesium oxide is poorly absorbed. For this reason magnesium oxide is highly effective as a laxative, but it is much less effective in increasing your body’s magnesium levels.

There are many different organic forms of magnesium, including magnesium glycinate, magnesium citrate, magnesium lactate, and others. These forms of magnesium are generally much better absorbed than inorganic forms, with average bioavailability of about 80%. This means that if you take a dose of 500 mg of magnesium glycinate, you will absorb about 400 mg.

Just as there is no consensus on the right form of magnesium to use, there is no consensus on the right dose. The research studies I reviewed often used a dose ranging from 400 mg to 1000 mg daily, usually in divided doses. Assuming normal kidney function, your body has effective mechanisms to prevent your magnesium levels from getting too high when it is taken in standard doses. The most common dose-limiting side effect from magnesium supplementation is GI upset, in particular diarrhea. Diarrhea is more common with magnesium oxide than the other forms.

I recommend a dose of magnesium between 400-600 mg per day, divided twice a day. Typically this is taken at breakfast and dinner, however it is also worth a trial of taking the second dose 30 minutes before bedtime as a sleep aid.

The Bottom Line

According to U.S. epidemiologic studies, there is a good chance your dietary magnesium intake is too low. Magnesium supplementation is a fairly inexpensive and low risk move that stands a reasonably good chance of benefit. In particular, if you have type 2 diabetes, prediabetes, or even insulin resistance, if you suffer from muscle cramps, or if you would like to give it a trial to see if it helps your sleep quality, these are all highly justifiable reasons to start supplementing.

References

Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci. 2012 Dec;17(12):1161-9. PMID: 23853635;

Alawi, A.; Majoni, A.M.; Falhammar, S.W. Magnesium and Human Health: Perspectives and Research Directions. Int. J. Endocrinol. 2018, 2018, 9041694.

Breus M, Hooper S, Lynch T, Hausenblas H. Effectiveness of Magnesium Supplementation on Sleep Quality and Related Health Outcomes for Adults with Poor Sleep Quality: A Randomized Double-Blind Placebo-Controlled Crossover Trial. Sleep Science and Practice, 2024

Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015 Sep 23;7(9):8199-226. doi: 10.3390/nu7095388. PMID: 26404370

Guerrero-Romero, F.; Simental-Mendía , L.E.; Hernández-Ronquillo, G.; Rodriguez-Morán, M.

Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and

hypomagnesaemia: A double-blind placebo-controlled randomized trial. Diabetes Metab. 2015,

41, 202–207

Leone N, Courbon D, Ducimetiere P, Zureik M. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality. Epidemiology. 2006 May;17(3):308-14. doi: 10.1097/01.ede.0000209454.41466.b7. PMID: 16570028.

Moshfegh, A.; Goldman, J.; Ahuja, J.; Rhodes, D.; LaComb, R. What We Eat in America,

NHANES 2005–2006: Usual Nutrient Intakes from Food and Water Compared to 1997 Dietary

Reference Intakes for Vitamin D, Calcium, Phosphorus, and Magnesium; U.S. Department of

Agriculture, Agricultural Research Service: Washington, DC, USA, 2009.

Peeri NC, Egan KM, Chai W, Tao MH. Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. Eur J Nutr. 2021 Feb;60(1):465-474. doi: 10.1007/s00394-020-02267-4. Epub 2020 May 9.

Pelczyńska, M.; Moszak, M.; Bogdański, P. The Role of Magnesium in the Pathogenesis of Metabolic Disorders. Nutrients 2022, 14, 1714.

Veronese, N.; Watutantrige-Fernando, S.; Luchini, C.; Solmi, M.; Sartore, G.; Sergi, G.; Manzato, E.; Barbagallo, M.; Maggi, S.; Stubbs, B. Effect of Magnesium Supplementation on Glucose Metabolism in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Eur. J. Clin. Nutr. 2016, 70, 1354–1359.

Zhang, X.; Li, Y.; Del Gobbo, L.C.; Rosanoff, A.; Wang, J.; Zhang, W.; Song, Y. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension 2016, 68, 324–333.