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Magnesium: The Forgotten Nutrient

Magnesium is an essential nutrient. It enables key metabolic processes, contributes to bone strength, and acts as a cofactor in hundreds of enzymatic reactions.1 Despite its central role in physiology and health, magnesium is under-consumed by most Americans, leading to chronic magnesium deficiency and increased risk for multiple serious health conditions, such as cardiovascular disease, type 2 diabetes, and depression.2 The main factors underlying reduced magnesium intake are the declining nutrient content of produce and refined grains, and increased consumption of processed foods, both of which are common in the Standard American Diet (SAD). Boosting magnesium intake to recommended levels requires people to improve the quality of their diets by increasing consumption of whole foods, reducing intake of processed foods, and possibly using daily magnesium supplements.

 

This article reviews the central importance of magnesium in the human body, the causes and consequences of magnesium deficiency, and approaches to improve magnesium status and overall health.

Why Is Magnesium Important?

Magnesium is the fourth most abundant cation in the human body. It plays a central role in energy production, glycolysis, and the synthesis of proteins and nucleic acids (DNA and RNA).1 Among other actions, magnesium is a cofactor for more than 300 enzymes and is essential to cell growth and function, energy storage and production, stabilization of cell membranes, nerve conduction, muscle contraction, and the function of ion channels (Figure 1).3-4

Unfortunately, multiple survey studies from the United States, Europe, and other regions have demonstrated that the recommended daily allowance (RDA) of magnesium remains unmet in a large proportion of the population, likely as a result of SAD dietary patterns.5-8 It is estimated that about half of the United States population consumes less than the RDA of magnesium.6,9 The estimated severity of magnesium deficits has led some experts to suggest that many people need greater than 300 milligrams of magnesium per day to replete and maintain body stores.10

How the Body Regulates Magnesium

The average human body contains about 24 grams of magnesium.11 Most magnesium in the body is intracellular, with greater than 90 percent located in bone, muscle, and other soft tissues; serum levels represent only  about one percent of total body magnesium stores.10-11 In humans, magnesium is regulated through three key mechanisms: absorption by the gut; renal filtration, reabsorption, and excretion; and exchange with the reservoir of magnesium in bone.10,11 About 25 percent to 75 percent of magnesium consumed in the diet is absorbed by the gut; the degree of absorption depends on multiple factors, most notably magnesium status.11

The kidneys filter about 2.4 grams of magnesium per day, reabsorbing about 95 percent and excreting any excess in the urine.11 When magnesium levels are low, the kidneys increase reabsorption and urinary concentrations fall; when magnesium intake exceeds requirements, the excess magnesium is excreted in the urine. Because magnesium is tightly regulated by the kidneys, urinary magnesium levels are a fairly good indicator of magnesium intake; levels less than 80 mg/d suggest risk for magnesium deficiency.13

Factors that may contribute to magnesium deficiency include inadequate dietary intake, reduced absorption by the gut, increased losses through the gut or kidney, excessive sweating (e.g., vigorous exercise), increased magnesium needs (e.g., pregnancy, chronic stress), and the effects of certain medications (Figure 2).4,14

When dietary intake and renal reabsorption of magnesium are insufficient to meet physiological needs, magnesium may be mobilized from muscle and bone, potentially contributing to hidden deficits of magnesium.11,12 These hidden or subclinical magnesium deficiencies are especially concerning, as they appear to be common, are difficult to diagnose, and may contribute to a wide range of chronic health problems.15,16 Several sources indicate that up to one-third of the general population has a subclinical magnesium deficiency.9,17 However, the prevalence of subclinical magnesium deficiency may be higher than estimated, as current methods for determining body magnesium levels (e.g., serum, urine, dietary intake) are likely inaccurate.18

Potential Health Consequences of Magnesium Deficiency

Lower magnesium levels have been linked to a broad array of chronic health conditions, ranging from cardiovascular disease to depression (Table 1). Proposed mechanisms through which magnesium may affect risk for chronic diseases include modulation of cellular metabolism and reproduction, systemic inflammation, oxidative stress, thrombosis, and endothelial function, among others.3

Table 1. Studies demonstrating an association between magnesium intake and common diseases.

Condition Relation to Magnesium Intake
Bone disease
  • low serum Mg levels independently associated with increased risk for fracture in men19
  • lower Mg intake associated with reduced bone mineral density in women20
  • reduced dietary Mg intake led to bone loss in animal studies21
  • reduced Mg intake documented in postmenopausal women with low bone density22
Depression
  • lower serum Mg levels linked to higher risk for depressive symptoms23
  • Mg supplementation led to greater reductions in depressive symptoms compared to placebo24
Heart failure
  • higher Mg intake associated with decreased risk of heart failure admission compared to lower intake in the Jackson Heart Study25
  • risk for heart failure reduced by 22 percent for each 100 mg/d increase in Mg intake in a meta-analysis of prospective studies26
Hypertension
  • lower dietary Mg intake linked to increased risk for hypertension in a meta-analysis; hypertension risk decreases five percent for each 100 mg/day increase in Mg uptake27
  • Mg supplementation significantly reduced systolic (-4.18 mmHg) and diastolic (-2.27 mmHg) blood pressure in a meta-analysis of randomized trials28
  • Mg supplementation (median dose 368 mg/d for median of three months) significantly reduced systolic (-2.0 mmHg) and diastolic (-1.78 mmHg) blood pressure in a meta-analysis of randomized trials29
Kidney disease
  • significant association between lower dietary Mg intake and greater risk for rapid declines in kidney function30
Metabolic syndrome
  • higher Mg intake associated with lower risk of metabolic syndrome in meta-analyses31
  • over 15-year follow-up, highest Mg intake reduced risk for metabolic syndrome by 31 percent (P<0.01) compared to lowest Mg intake in 4637 adult Americans32
  • Reduced risk for impaired glucose tolerance and insulin resistance with higher Mg intake33
  • Long-term Mg supplementation significantly improved insulin sensitivity and fasting glucose in meta-analysis34
Migraines
  • magnesium supplementation significantly improved all migraine indicators in randomized study of 133 people with migraines35
Stroke
  • relative risk for stroke decreased by 7 percent to 13 percent for each 100 mg/d increase in Mg intake in meta-analyses of prospective studies26,36
  • risk for stroke reduce 13 percent with highest vs. lowest Mg intake in a prospective study of 180,864 women36
Type diabetes (T2D)
  • significant, linear dose-response relationship; highest Mg intake associated with 15 percent to 17 percent reduction in risk for type 2 diabetes (T2D) compared to lowest intake in cohort studies and a meta-analysis37,38
  • risk of T2D 8 percent to 13 percent lower per 100 mg/day increase in Mg intake in ameta-analysis37
  • Mg supplementation reduced plasma glucose levels in pre-diabetic adults in a randomized trial39

Health Benefits of Higher Magnesium Intake

In contrast to magnesium deficits, higher dietary magnesium intake has been linked to reduced risk for major diseases, reduced stress and depression, and improved migraine symptoms (see Table 1). Higher dietary intake has also been associated with increased fat-free mass (i.e., skeletal muscle), reduced risk for frailty, improved grip strength and bone density, and reduced risk of mortality due to liver disease.40-43 For example, an analysis of the National Health and Nutrition Examination Survey (NHANES) cohort found a 49 percent reduction in risk for mortality due to liver disease for every 100 mg increase in magnesium intake.43

Aging is associated with higher risk for magnesium deficiency due to age-related changes in diet, intestinal absorption, and renal function.44,45 However, adequate magnesium status may support healthy aging not only by reducing risk for the multiple diseases described above, but by preserving chromosomal function. Telomeres are chromosomal structures that contribute to chromosomal integrity and cell health and longevity; reduced telomere length has been linked to age-associated diseases (such as cancer) and mortality.46-47 One study of 10,568 adults from NHANES found that high mineral and vitamin consumption, including magnesium, was associated with increased telomere length, suggesting better cellular integrity.47 Other studies have also identified a link between magnesium status, telomeres, and healthy aging.48

Substantial and mounting evidence, therefore, implicates magnesium deficits in higher risk for multiple serious chronic health conditions, whereas higher magnesium intake reduces health risks and supports normal physiologic function.

How Much Magnesium is Enough?

The proposed normal range for serum magnesium is approximately 1.7 to 2.2 mg/dL.49 The recommended daily allowance (RDA) and estimated average requirement (EAR) to maintain healthy levels of magnesium vary based on age, sex, and reproductive status (Table 2).50-52

Table 2. Estimated average requirements (EAR) and recommended daily allowances (RDA) for magnesium intake in adults.50-52

Age (years) EAR (mg/day) RDA (mg/day)
19-30 (males/females) 330/255 400/310
>30 (males/females) 350/265 420/320
Pregnancy (14-18/19-20/31-50) 335/290/300 400/350/360

The Problem: Insufficient Dietary Magnesium Intake

With declining nutrient content in foods and broad consumption of SAD-style diets, deficiencies in essential nutrients such as magnesium have become extremely common. An analysis of 2005-2006 NHANES data identified dietary magnesium intake below EAR in 48 percent of 8437 participants.6 In this study, about 60 percent of surveyed adults did not consume the established RDA for magnesium. A diet-modeling study based on 8944 participants in NHANES (2007-2010) revealed that the percentage of individuals consuming below the EAR for magnesium ranged from 51.7 percent to 88.5 percent for adult males and 34.5 percent to 75.8 percent for adult women.5 Accordingly, the 2015-2020 Dietary Guidelines for Americans designate magnesium as an under-consumed nutrient relative to the EAR in the diets of both males and females two years of age and older.52

Improving Dietary Magnesium Intake: Whole Foods

Dietary sources of magnesium include many whole foods, such as nuts, seeds, legumes, whole-grain cereals, and many vegetables (Table 3).53-57 Conversely, consumption of processed foods, sugars, saturated fats, and refined grains – all of which are common in the SAD – is associated with reduced intake of magnesium and other essential nutrients.58

Table 3. Dietary sources of magnesium.53-57

Food group Examples Mg content (mg/100g)
Nuts and seeds Pumpkin seeds 592
Flaxseed 392
Sesame seeds 356
Almonds 270
Cashews 260
Walnuts 158
Pistachios 109
Legumes Peanuts 178
Soybeans 86
Chickpeas 48
Kidney beans 45
Lentils 36
Produce Sun-dried tomatoes 194
Spinach 87
Kale 57
Dates 54
Fresh parsley 50
Potatoes with skin 43
Whole grains Buckwheat flour 251
Amaranth grain 248
Quinoa grain 197
Oats 177
Spelt 136
Barley 133
Dairy Parmesan cheese 44
Feta cheese 19
Whole-fat milk 13
Whole-fat yogurt 12
Egg 12
Seafood Cod
Salmon
Meat Chicken breast 34
Turkey 32

In a worrying trend, studies have described declining concentrations of micronutrients in food since the first half of the 20th century. For example, investigators have identified magnesium reductions of four percent to eight percent in beef, four percent in chicken, 38 percent in cheddar cheese, 70 percent in parmesan cheese, 21 percent in whole milk, and 24 percent in vegetables over decades.59 The magnesium content of wheat has dropped almost 20 percent since the 1960s, likely due to changes in the soil (e.g., acidification, mineral depletion) and modern cultivation practices (e.g., selective breeding, chemical fertilizers).60 The processing and refinement of food leads to further substantial losses of magnesium. In fact, most processed foods and highly refined grains (e.g., white flour, sugar) are essentially devoid of magnesium.

An analysis of NHANES data (2007-2010) suggested that even with adequate dairy intake (a common source of magnesium), magnesium deficiencies would remain highly prevalent in Americans (34 percent to 75 percent of males, 17 percent to 51 percent of females).5

Variety Matters

Magnesium levels vary by type of plant, cultivar, and plant anatomy. Magnesium is mobile in the phloem and can be found in high concentrations in rapidly growing structures with good access to phloem, such as roots, seeds, tubers, and fruit. Some species with higher concentrations of magnesium in the leaves include beets, chard, and spinach.61 Magnesium concentrations also vary by cultivar. One review identified magnesium levels ranging from 45.8 to 69.3 mg/100 g across varieties of kale and 8.7 to 12.3 mg/100 g among types of carrots.61

Given the wide range of magnesium levels within and between plants, consuming a variety of plants may be the best strategy to optimize dietary magnesium intake.

The Benefits of Magnesium Supplementation

With the declining levels of magnesium in available foods, many people may be challenged to maintain adequate magnesium levels through diet alone. Magnesium supplements are another option to support healthy magnesium status. Compared to food alone, the addition of dietary supplements significantly increases intake of nutrients, including magnesium, and reduces nutrient inadequacies in adults.62 The benefits of magnesium supplementation have been widely demonstrated. Several such studies are illustrated in Table 1. Additional studies have linked magnesium supplementation to reduced stress and depressive symptoms. For example, a study from France evaluated the effect of supplementation with magnesium, probiotics, and vitamins in 242 subjects with psychological stress.63 Following one month of supplementation, measures of subjects’ psychological stress decreased significantly (P<0.0001); fatigue scores also decreased significantly (P<0.0001). An open-label, randomized study evaluated the effect of magnesium supplementation in 126 adults with mild-to-moderate depression.64 After six weeks of magnesium chloride supplementation, depressive symptoms improved significantly over baseline (6.0 point improvement in Patient Health Questionnaire-9 scores, P<0.001). Anxiety scores also improved significantly. The supplement was well tolerated, and 61 percent of participants said they would use magnesium in the future.

Many people are in need of some level of magnesium supplementation. These deficits are illustrated in Table 4, which shows the mean daily intake of magnesium in the 2011-2012 NHANES survey compared to RDA.65 The addition of a supplement containing 100mg dietary magnesium would bring the mean magnesium intake to within the RDA values for both genders, for all age brackets.

Table 4. Magnesium intake from food and beverages compared to RDA and the impact of a 100 mg/day magnesium supplement. Data from the 2011-2012 NHANES survey.65

Gender Age (years) Daily intake (mg/day) RDA (mg/day) Mg deficit (mg) Difference with 100 mg/day supplement (mg)
Male 20-29 346 400 -54 +46
30-39 388 420 -32 +68
40-49 375 420 -45 +55
50-59 348 420 -72 +28
60-69 360 420 -60 +40
≥70 301 420 -119 -19
Female 20-29 266 310 -44 +66
30-39 299 320 -21 +79
40-49 275 320 -45 +55
50-59 278 320 -42 +58
60-69 272 320 -48 +52
≥70 249 320 -71 +29

 

Magnesium is an essential nutrient for human health. Deficiencies in magnesium increase risk for serious chronic diseases, whereas increased intake through improved diet and/or supplementation can improve health status and reduce disease risk. Unfortunately, current evidence indicates that half or more of Americans currently have some degree of subclinical magnesium deficiency. Increasing magnesium intake requires greater consumption of whole foods (unrefined grains, vegetables, fruits, nuts) and reduced intake of refined or processed foods. For many people, the addition of a magnesium supplement may be required to replete magnesium stores and maintain healthy magnesium levels over the long term.

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  10. Orchard, TS., Larson, JC., Alghothani, N., et al. (2014). Magnesium intake, bone mineral density, and fractures: results from the women’s health initiative observational study. Am J Clin Nutr; 99(4):926-933.
  11. Rude, RK., Singer, FR., Gruber, HE. (2009). Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr.;28(2):131-141.
  12. Mahdavi-Roshan, M., Ebrahimi, M., Ebrahimi, A. (2015). Copper, magnesium, zinc and calcium status in osteopenic and osteoporotic post-menopausal women. Clin Cases Miner Bone Metab.12(1):18-21.
  13. Szkup, M., Jurczak, A., Brodowska, A., et al. (2017). Analysis of relations between the level of Mg, Zn, Ca, Cu, and Fe and depressiveness in postmenopausal women. Biol Trace Elem Res;176(1):56-63.
  14. Rajizadeh, A., Mozaffari-Khosravi, H., Yassini-Ardakani, M., Dehghani, A. (2017). Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition; 35:56-60.
  15. Taveira, TH., Ouellette, D., Gulum, A., et al. (2016). Relation of Magnesium intake with cardiac function and heart failure hospitalizations in black adults: the jackson heart study. Circ Heart Fail;9(4):e002698.
  16. Fang, X., Wang, K., Han, D., et al. (2018).Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med; 14(1):210.
  17. Han, H., Fang, X., Wei, X., et al. (2017). Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies. Nutr J; 16(1):26.
  18. Dibaba, DT., Xun, P., Song, Y., Rosanoff, A., Shechter, M., He, K. (2017). The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. Am J Clin Nutr; 106(3):921-929.
  19. Zhang, X., Li, Y., Del Gobbo, LC., et al. (2016). Effects of magnesium supplementation on blood pressure: A meta-analysis of randomized double-blind placebo-controlled trials. Hypertension; 68(2):324-333.
  20. Rebholz, CM. Tin, A., Liu, Y., et al.(2016). Dietary magnesium and kidney function decline: the healthy aging in neighborhoods of diversity across the life span study. Am J Nephrol;44(5):381-387.
  21. Sarrafzadegan, N., Khosravi-Boroujeni, H., Lotfizadeh, M., Pourmogaddas, A., Salehi-Abargouei, A. (2016). Magnesium status and the metabolic syndrome: A systematic review and meta-analysis. Nutrition; 32(4):409-417.
  22. He, K., Liu, K., Daviglus, ML., et al. (2006). Magnesium intake and incidence of metabolic syndrome among young adults. Circulation; 113(13):1675-1682.
  23. Hruby, A., Meigs, JB., O’Donnell, CJ., Jacques, PF., McKeown, NM. (2014). Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans. Diabetes Care; 37(2):419-427.
  24. Simental-Mendia, LE., Sahebkar, A., Rodriguez-Moran, M., Guerrero-Romero, F. (2016). A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res; 111:272-282.
  25. Tarighat Esfanjani, A., Mahdavi, R., Ebrahimi Mameghani, M., Talebi, M., Nikniaz, Z., Safaiyan, A. (2012). The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol Trace Elem Res; 150(1-3):42-48.
  26. Adebamowo, SN., Spiegelman, D., Willett, WC., Rexrode, KM. (2015). Association between intakes of magnesium, potassium, and calcium and risk of stroke: 2 cohorts of US women and updated meta-analyses. Am J Clin Nutr.; 101(6):1269-1277.
  27. Fang, X., Han, H., Li, M., et al. (2016). Dose-response relationship between dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and meta-regression analysis of prospective cohort studies. Nutrients; 8(11).
  28. Hruby, A., Guasch-Ferre, M., Bhupathiraju, SN., et al. (2017). Magnesium intake, quality of carbohydrates, and risk of type 2 diabetes: results from three U.S. cohorts. Diabetes Care; 40(12):1695-1702.
  29. Guerrero-Romero, F., Simental-Mendia, LE., Hernandez-Ronquillo, G., Rodriguez-Moran, M. (2015). Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial. Diabetes Metab; 41(3):202-207.
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  38. Shah, NC., Shah, GJ., Li, Z., Jiang, XC., Altura, BT., Altura, BM. (2014). Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging. Int J Clin Exp Med; 7(3):497-514.
  39. Kunutsor, SK., Whitehouse, MR., Blom, AW., Laukkanen, JA. (2017). Low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study. Eur J Epidemiol; 32(7):593-603.
  40. Orchard, TS., Larson, JC., Alghothani, N., et al. (2014). Magnesium intake, bone mineral density, and fractures: results from the women’s health initiative observational study. Am J Clin Nutr; 99(4):926-933.
  41. Rude, RK., Singer, FR., Gruber, HE. (2009). Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr.;28(2):131-141.
  42. Mahdavi-Roshan, M., Ebrahimi, M., Ebrahimi, A. (2015). Copper, magnesium, zinc and calcium status in osteopenic and osteoporotic post-menopausal women. Clin Cases Miner Bone Metab.12(1):18-21.
  43. Szkup, M., Jurczak, A., Brodowska, A., et al. (2017). Analysis of relations between the level of Mg, Zn, Ca, Cu, and Fe and depressiveness in postmenopausal women. Biol Trace Elem Res;176(1):56-63.
  44. Rajizadeh, A., Mozaffari-Khosravi, H., Yassini-Ardakani, M., Dehghani, A. (2017). Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition; 35:56-60.
  45. Taveira, TH., Ouellette, D., Gulum, A., et al. (2016). Relation of Magnesium intake with cardiac function and heart failure hospitalizations in black adults: the jackson heart study. Circ Heart Fail;9(4):e002698.
  46. Fang, X., Wang, K., Han, D., et al. (2018).Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med; 14(1):210.
  47. Han, H., Fang, X., Wei, X., et al. (2017). Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies. Nutr J; 16(1):26.
  48. Dibaba, DT., Xun, P., Song, Y., Rosanoff, A., Shechter, M., He, K. (2017). The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. Am J Clin Nutr; 106(3):921-929.
  49. Zhang, X., Li, Y., Del Gobbo, LC., et al. (2016). Effects of magnesium supplementation on blood pressure: A meta-analysis of randomized double-blind placebo-controlled trials. Hypertension; 68(2):324-333.
  50. Rebholz, CM. Tin, A., Liu, Y., et al.(2016). Dietary magnesium and kidney function decline: the healthy aging in neighborhoods of diversity across the life span study. Am J Nephrol;44(5):381-387.
  51. Sarrafzadegan, N., Khosravi-Boroujeni, H., Lotfizadeh, M., Pourmogaddas, A., Salehi-Abargouei, A. (2016). Magnesium status and the metabolic syndrome: A systematic review and meta-analysis. Nutrition; 32(4):409-417.
  52. He, K., Liu, K., Daviglus, ML., et al. (2006). Magnesium intake and incidence of metabolic syndrome among young adults. Circulation; 113(13):1675-1682.
  53. Hruby, A., Meigs, JB., O’Donnell, CJ., Jacques, PF., McKeown, NM. (2014). Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans. Diabetes Care; 37(2):419-427.
  54. Simental-Mendia, LE., Sahebkar, A., Rodriguez-Moran, M., Guerrero-Romero, F. (2016). A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res; 111:272-282.
  55. Tarighat Esfanjani, A., Mahdavi, R., Ebrahimi Mameghani, M., Talebi, M., Nikniaz, Z., Safaiyan, A. (2012). The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol Trace Elem Res; 150(1-3):42-48.
  56. Adebamowo, SN., Spiegelman, D., Willett, WC., Rexrode, KM. (2015). Association between intakes of magnesium, potassium, and calcium and risk of stroke: 2 cohorts of US women and updated meta-analyses. Am J Clin Nutr.; 101(6):1269-1277.
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