Magnesium Supplements

Magnesium is critical for brain health and is mostly obtained through a healthy diet. Some research has shown lower magnesium levels in patients with Alzheimer’s disease, but there is little evidence that supplementation can prevent or treat dementia. Magnesium supplementation in moderation appears to be safe for most people, with some notable exceptions (including a warning for people with compromised kidney function).

EFFICACY
Possibly
with   Very limited  evidence
SAFETY WHEN
USED AS DIRECTED
Some risks
with   Strong  evidence

Magnesium (Mg2+) is a “trace element,” meaning that it is found in low levels in the human body. Despite its low levels, magnesium is critical for our brain and body. Among other things, magnesium is required for the proper functioning of many enzymes that carry out the biochemical reactions essential for good health, including brain health.

Did you know? The human body contains, on average, only 25 grams of magnesium and yet magnesium is essential to catalyze almost 300 important biological reactions!

Magnesium is available in many foods, as described in our separate report on dietary magnesium. Magnesium is commercially-available as an oral supplement in a variety of forms that fall into three categories: magnesium salts, magnesium-acids and magnesium coupled to an amino acid. The human body uses elemental magnesium (i.e. magnesium that is not coupled to anything). The “carriers” attached to magnesium in supplements help deliver magnesium to our intestines, where it is broken apart and the elemental magnesium is absorbed. Different magnesium carriers break apart from magnesium at different rates, which can affect the “bioavailability” of elemental magnesium after ingestion and, thus, its absorption by our bodies. Although these different types of magnesium supplements offer differing degrees of bioavailable magnesium to our bodies, there is very little evidence that one type is superior to other at increasing brain magnesium levels.

  • Magnesium salts: These include magnesium bicarbonate, magnesium carbonate, magnesium chloride, magnesium hydroxide, magnesium oxide, magnesium phosphate and magnesium sulfate. Of these, magnesium chloride offers the most free (“bioavailable”) magnesium after digestion in the gut. Magnesium sulfate offers somewhat less bioavailable magnesium, while magnesium carbonate, magnesium oxide and magnesium hydroxide (a laxative often called Milk of Magnesia™) offer very low bioavailable magnesium [1-3].
  • Magnesium acids: Supplements containing magnesium acids include magnesium ascorbate, magnesium citrate, magnesium gluconate, magnesium lactate and magnesium fumarate. Of these, magnesium lactate and citrate offer the most bioavailable magnesium while magnesium fumarate and magnesium gluconate offer moderately bioavailable magnesium [1].
  • Magnesium amino acids: Sometimes called “magnesium-amino acid chelates”, these forms of magnesium differ from the magnesium salts and magnesium acids in that they do not rely on absorption of elemental magnesium in the gut, but instead depend on biochemical pathways that break down proteins (since amino acids are the building blocks of proteins). These forms of magnesium include magnesium glycinate, magnesium lysinate, magnesium taurate, magnesium orotate and magnesium threonate. Most of these forms of magnesium offer similar high bioavailability as magnesium citrate and magnesium chloride [1], but because of the way they are manufactured, they also tend to be the most expensive magnesium supplements. Results from a small clinical trial of healthy human volunteers suggest magnesium citrate offers better bioavailability than most amino acid chelates [2].

The US RDA for magnesium is 310 to 320 mg per day for women and 400 to 420 mg per day for men (NIH), although it has been reported that actual daily intakes for U.S. adults are lower than that, typically 278 to 352 mg/day for men and 237 to 326 mg/day for women [4]. Normal blood levels of magnesium for healthy adults range from 0.75 to 0.95 nmoles per liter (nmol/L). Magnesium deficiency is typically defined as serum levels lower than 0.75 nmol/L (NIH). Magnesium deficiency is common in people with type 2 diabetes [5], people with gastrointestinal disorders like Crohn’s disease or celiac disease [6], and in older adults. Not only do older adults in the U.S. typically eat a diet lower in magnesium than younger adults [4], but the body’s ability to absorb magnesium also declines with age [7].

Possibly, based on very limited evidence.

No clinical trials in humans have tested if raising magnesium levels, either through diet or supplement use, can prevent dementia. However, evidence from some preclinical cellular and animal models suggests it may be possible.

Scientists have observed in several studies that low magnesium levels in either the blood [22-24] or the brain [25] are more common in people with Alzheimer’s disease without the disease. Similarly, people who eat high levels of dietary magnesium in foods have been observed in a few studies to have a lower risk of developing dementia or cognitive impairment (see our report on Dietary Magnesium). However, these studies do not prove that low magnesium levels caused Alzheimer’s disease or that high magnesium levels can protect. For example, the people with reduced dementia risk may have shared other dietary or lifestyle factors besides high magnesium intake that accounted for their lower risk.

Although there is no experimental proof from human studies that either adequate dietary intake of magnesium or magnesium supplements can prevent Alzheimer’s disease or related dementias, evidence from preclinical cellular and animal studies suggest it may be possible. Several recent studies in rodent models of Alzheimer’s suggest that raising magnesium levels, either by oral supplementation or direct brain injection, can prevent disease-related problems with learning and behavior and improve brain health [11,26]. Additionally, although it has been speculated that some neurodegenerative diseases like Alzheimer’s might arise from magnesium deficiency [27,28], there is no experimental evidence in humans to suggest that magnesium supplementation can prevent or treat Alzheimer’s disease. There is some evidence, though inconclusive, that increasing dietary intake of magnesium may lower dementia risk (see our report on Dietary Magnesium).

Possibly, based on very limited evidence.

While it has been hypothesized that magnesium supplementation may benefit patients with dementia [28] and some evidence from preclinical animal model studies suggests that magnesium may disrupt some Alzheimer’s disease pathways [10-13], there is little direct evidence from humans to support this. Also, as mentioned earlier, low blood and brain levels of magnesium have been reported in patients with Alzheimer’s disease. A small clinical trial (NCT02210286) is currently recruiting patients to test if magnesium supplementation for 60 days can benefit patients with mild-to-moderate Alzheimer’s disease and should report results sometime in 2015.

APOE4 Carriers: There is currently no evidence to suggest that APOE genotype will affect how the brain responds to magnesium from supplements or diet. To learn more about what the APOE genotype means for your health, read our APOE information page.

Unknown, given there is no evidence.

There is no evidence to suggest that magnesium supplements of any form can increase lifespan or slow aging. However, there is some indirect evidence that increased dietary magnesium intake may extend lifespan by reducing the risk of death by various diseases (see our report on Dietary Magnesium).

Magnesium is critical for brain health and required for the metabolism of many other trace metals important for the brain, including selenium and vitamins B6 and D [8]. Unfortunately, it can be difficult to determine if someone has low levels of magnesium in their brain. Magnesium levels in the brain can either be estimated from brain tissue at autopsy or by a specific type of brain scan called a MRI (magnetic resonance imaging) [9], but neither are available for routine diagnostics. Magnesium levels can be measured in the blood but do not correlate well with magnesium levels in other tissues, meaning that low or high blood magnesium levels may not represent an imbalance in specific organs like the brain [1]. That said, measuring blood magnesium levels is the best available method to get a snapshot of whole-body magnesium levels.

Evidence from experiments in test tubes, cells and animals suggests many ways that magnesium may play a part in the Alzheimer’s disease process and ways that elevating brain magnesium may alter the disease process (see following sections). In test tubes and cells, some studies report that magnesium may block one of the key enzymes responsible for producing toxic, “hyperphosphorylated” tau protein [10, 11] while also playing a role in the elimination of toxic tau from diseased cells [12]. Other experiments on isolated cells suggest that magnesium also may reduce production of toxic beta-amyloid protein fragments [13]. Oral magnesium threonate supplementation may also improve short- and long-term memory performance in healthy and aged rats [14], although this study has not been replicated.

Two things are important to note when considering the results of these studies. First, these experiments were performed in isolated cells and animal models and have not been replicated in humans. Second, the types of magnesium administered to the cells or animals varied widely and can be considered a type of magnesium supplementation, in which magnesium is coupled to aid digestion. As mentioned above, dietary magnesium consists mainly of elemental magnesium and magnesium chloride, which are absorbed to different degrees by the human body than other forms of magnesium commonly found in supplements.

Previous laboratory studies in animals have suggested that magnesium supplementation can protect or treat  [15-17] [18, 19] traumatic brain injury (which may have disease pathways in common with Alzheimer’s) but, unfortunately, a meta-analysis of two clinical trials with magnesium supplementation in humans with similar brain injuries suggested little or no benefit [20].

A small clinical trial in 46 elderly adults with insomnia, a potential risk factor for Alzheimer’s disease, found that those treated for 8 weeks with 500 mg magnesium sulfate daily reported improved sleep duration, lower cortisol levels and decreased early-morning waking [21].

Some risks, based on strong evidence.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Moderate use of magnesium supplements is considered safe for most people, although caution should be taken by people with kidney disease or otherwise compromised kidney function. Very high doses or a build-up of magnesium in the body may result in kidney damage. Excess magnesium from supplement use can be toxic, and it is recommended that healthy people limit magnesium supplements to 350 mg per day or less [29]. Common side effects, especially for magnesium carbonate, magnesium citrate, magnesium chloride, magnesium gluconate, magnesium oxide and magnesium hydroxide, include nausea, vomiting and diarrhea. Magnesium sulfate should be avoided when using antibiotics of the aminoglycoside class, such as neomycin, gentamicin and streptomycin because of an increased risk of muscle paralysis (Drugs.com). Many magnesium supplements, including magnesium citrate, magnesium chloride, and magnesium gluconate may decrease the effectiveness of dolutegravir (Tivicay™), a drug commonly prescribed to patients with HIV. Some magnesium supplements, including magnesium citrate, also should be used with caution if you are on a sodium-restricted diet. However, there is very little danger in obtaining too much magnesium from the diet (see our report on Dietary Magnesium). To determine if magnesium supplementation is safe for you, consult your health care provider.

As mentioned earlier, magnesium supplements are commercially available from a variety of manufacturers and in a variety of conjugated forms (see above, Sources of Magnesium). You should consult with your health care provider to determine if magnesium supplementation is safe for you and if so, which magnesium supplements would be best. As mentioned above, it is suggested that healthy adults limit their use of magnesium supplements to 350 mg per day or less [29].

As mentioned earlier, there is a small clinical trial currently recruiting patients with mild-to-moderate Alzheimer’s disease that will test magnesium threonate supplementation for 60 days and should be reporting results sometime in 2015 (NCT02210286). The evidence for magnesium supplementation could be improved with clinical trials in patients with mild cognitive impairment, to determine if the potential progression to Alzheimer’s disease could be slowed. 

To guide future trials of magnesium supplementation for brain health and dementia prevention/treatment, it would be useful to know which type of supplement is best at raising magnesium levels in the brain. A small clinical trial in healthy volunteers using MRI to detect brain magnesium could improve our knowledge of brain magnesium and supplementation and potentially improve the outcomes of future magnesium clinical trials in patients with Alzheimer’s disease and related dementias.

1. Ranade, V.V. and J.C. Somberg, Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther, 2001. 8(5): p. 345-57.

2. Walker, A.F., et al., Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res, 2003. 16(3): p. 183-91.

3. Firoz, M. and M. Graber, Bioavailability of US commercial magnesium preparations. Magnes Res, 2001. 14(4): p. 257-62.

4. Ford, E.S. and A.H. Mokdad, Dietary magnesium intake in a national sample of US adults. J Nutr, 2003. 133(9): p. 2879-82.

5. Chaudhary, D.P., R. Sharma, and D.D. Bansal, Implications of magnesium deficiency in type 2 diabetes: a review. Biol Trace Elem Res, 2010. 134(2): p. 119-29.

6. Coates, P.M., Encyclopedia of dietary supplements. 2010, Informa Healthcare,: New York. p. 1 online resource (xix, 898 p.).

7. Barbagallo, M., M. Belvedere, and L.J. Dominguez, Magnesium homeostasis and aging. Magnes Res, 2009. 22(4): p. 235-46.

8. Johnson, S., The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses, 2001. 56(2): p. 163-70.

9. Barker, P.B., et al., Magnesium and pH imaging of the human brain at 3.0 Tesla. Magn Reson Med, 1999. 41(2): p. 400-6.

10. Gomez-Ramos, A., et al., Inhibition of GSK3 dependent tau phosphorylation by metals. Curr Alzheimer Res, 2006. 3(2): p. 123-7.

11. Xu, Z.P., et al., Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model. PLoS One, 2014. 9(9): p. e108645.

12. Zhang, J.Y., et al., Microtubule-associated protein tau is a substrate of ATP/Mg(2+)-dependent proteasome protease system. J Neural Transm, 2005. 112(4): p. 547-55.

13. Yu, J., et al., Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimers Dis, 2010. 20(4): p. 1091-106.

14. Slutsky, I., et al., Enhancement of learning and memory by elevating brain magnesium. Neuron, 2010. 65(2): p. 165-77.

15. Enomoto, T., et al., Pre-Injury magnesium treatment prevents traumatic brain injury-induced hippocampal ERK activation, neuronal loss, and cognitive dysfunction in the radial-arm maze test. J Neurotrauma, 2005. 22(7): p. 783-92.

16. Hoane, M.R., et al., Magnesium dietary manipulation and recovery of function following controlled cortical damage in the rat. Magnes Res, 2008. 21(1): p. 29-37.

17. Uysal, N., et al., Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats. Turk Neurosurg, 2013. 23(2): p. 129-37.

18. Fromm, L., et al., Magnesium attenuates post-traumatic depression/anxiety following diffuse traumatic brain injury in rats. J Am Coll Nutr, 2004. 23(5): p. 529S-533S.

19. Turner, R.J., et al., Magnesium gluconate offers no more protection than magnesium sulphate following diffuse traumatic brain injury in rats. J Am Coll Nutr, 2004. 23(5): p. 541S-544S.

20. Arango, M.F. and J.H. Mejia-Mantilla, Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev, 2006(4): p. CD005400.

21. Abbasi, B., et al., The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci, 2012. 17(12): p. 1161-9.

22. Barbagallo, M., et al., Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease. Magnes Res, 2011. 24(3): p. S115-21.

23. Cilliler, A.E., S. Ozturk, and S. Ozbakir, Serum magnesium level and clinical deterioration in Alzheimer's disease. Gerontology, 2007. 53(6): p. 419-22.

24. Vural, H., et al., Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer's disease. J Trace Elem Med Biol, 2010. 24(3): p. 169-73.

25. Andrasi, E., et al., Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis, 2005. 7(4): p. 273-84.

26. Li, W., et al., Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer inverted question marks disease mouse model. Mol Brain, 2014. 7(1): p. 65.

27. Durlach, J., Magnesium depletion and pathogenesis of Alzheimer's disease. Magnes Res, 1990. 3(3): p. 217-8.

28. Ozturk, S. and A.E. Cillier, Magnesium supplementation in the treatment of dementia patients. Med Hypotheses, 2006. 67(5): p. 1223-5.

29. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. 1997: Washington (DC).

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