Magnesium is a necessary co-factor in over 300 enzyme reactions and has an important role in glucose metabolism and insulin sensitivity. Magnesium and insulin have a reciprocal relationship. Insulin helps regulate the transport of magnesium cation from the extracellular to intracellular space for use in glucose metabolism. As part of glucose metabolism, magnesium promotes many of the enzymatic reactions in glycolysis. Magnesium deficiency causes insulin resistance—that is, more insulin than normal is required to metabolize glucose. As a result, the presence of hypomagnesemia and glucose intolerance can feed a comorbid cycle of insulin resistance caused by hypomagnesemia and reduced serum magnesium caused by insulin resistance. Hypomagnesemia is a common laboratory abnormality in patients with type 2 diabetes, suggesting that increasing magnesium intake could be beneficial for glucose control.
A Beneficial Effect?
Several small-scale studies suggest that magnesium may have a beneficial effect on preventing diabetes in patients with normal or impaired glucose tolerance.
In a prospective cohort study by Hruby and colleagues, the dietary magnesium intake and progression to metabolic impairment of 2586 patients aged 21-81 years were followed for 7 years. Magnesium intake was measured by a food-frequency questionnaire and included both dietary and supplemental sources. Higher magnesium intake was associated with beneficial effects in both patients with prediabetes and euglycemic patients. In patients with metabolic impairment, high intake of magnesium (approximately 400 mg/day) was associated with a 38% lower risk of developing diabetes. In the total population, which included euglycemic patients, high magnesium intake was associated with a 51% lower risk of developing diabetes.
In another prospective cohort study, by Hata and colleagues, 1999 patients aged 40-79 years without diabetes were followed for 15.6 years. Magnesium intake was measured by a food-frequency questionnaire and included only dietary magnesium. Patients consuming higher amounts of magnesium (171.6-195.6 mg/day) had a decreased risk of developing diabetes in comparison with patients consuming the lowest amount of magnesium (multivariable-adjusted hazard ratio, 0.86; 95% confidence interval, 0.75-0.99; P = .04).
In a randomized controlled trial by Guerrero-Romero and colleagues, 116 patients aged 30-65 years with hypomagnesemia (ie, magnesium level ≤ 1.8 mg/dL) and newly diagnosed prediabetes were randomized to receive 30 mL of magnesium chloride 2% solution (containing about 382 mg of magnesium) or placebo. After 4 months of magnesium supplementation, fasting glucose, postload glucose, and the homeostasis model for insulin resistance (HOMA-IR) all significantly decreased in comparison with placebo. The glucose tolerance of approximately 50% of the patients receiving magnesium supplementation improved from impaired to normal, compared with 7% in the placebo group.
A cross-sectional study also associates hypomagnesemia with an increased risk for diabetic complications, including retinopathy, nephropathy, and foot ulcers.
Magnesium intake in clinical studies has been around 400 mg/day, which is the recommended dietary allowance of magnesium for men. For women, 300-310 mg/day is the recommended dietary allowance. Only about 50% of Americans aged 1 year or older receive the recommended amount of dietary magnesium. Thus, it may be reasonable to advise patients who are at risk for diabetes to increase magnesium intake. Foods that have high amounts of magnesium include nuts (eg, almonds, cashews, and peanuts), vegetables (eg, spinach, avocado, and edamame), and whole grains.
For patients who cannot meet magnesium requirements through foods, supplemental magnesium not exceeding 350 mg/day could be used. Supplemental magnesium may cause diarrhea, nausea, and cramping. Patients with renal impairment should avoid magnesium supplements unless prescribed by a healthcare provider. Products containing magnesium may interact with other medications and should be separated by at least 2 hours to prevent drug interactions.
The American Diabetes Association does not support the routine use of magnesium supplementation in patients with diabetes but does recommend intake of vegetables, whole grains, and legumes. Larger studies are needed to determine the role of magnesium supplementation in preventing prediabetes, type 2 diabetes, or complications of diabetes.