Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes

by | Mar 25, 2022 | 2021, Diabetes, Magnesium, Minerals

Written by Marlene Hollick, Ed.D., R.D., Staff Writer. Based on a meta-analysis of the association between magnesium and blood glucose parameters, results suggested that magnesium supplementation presented a favorable role for diabetic patients, as well as those at high risk for diabetes.

magnesiumThe benefits of magnesium, an essential mineral associated with hundreds of enzymatic reactions 1 including metabolic diseases such as diabetes 2, had been discussed in prior systematic reviews and meta-analyses. Higher magnesium intakes were associated with reduced diabetes incidence in a meta-analysis of over 500,000 participants 3. Oral supplementation of magnesium is often indicated for high-risk populations such as the elderly, diabetics, and pregnant women, due to the low percentage of the general population who meet the RDA for this nutrient 4.

However, prior individual randomized controlled trials had included small numbers of participants 5,6. This limitation prompted the researchers to conduct a systematic review of randomized controlled trials to note the effects of oral magnesium supplementation (vs. placebo) on diabetics and high-risk participants regarding blood glucose and insulin-sensitivity parameters. The researchers hypothesized that participants who received the experimental treatment (magnesium) would demonstrate better outcomes compared to those who received the placebo.

A literature search was conducted for the systematic review using multiple databases, including Cochrane Central Register of Controlled Trials and Clinicaltrials.gov, between January 1, 2016, to October 26, 2021. Diabetes was defined based on the inclusion criteria established by the American Diabetes Association. Risk factors for diabetes included obesity, renal failure, and metabolic syndrome. For the meta-analysis, criteria for inclusion included randomized double-blind controlled trials, diabetic or high-risk subjects, oral magnesium supplementation use, glucose metabolism assessments or . sensitivity measures, and quality rankings as per Jadad’s scale ≥ 3/5 points 7.

STATA version 14.0 was used for the analyses, and p-values under 0.05 were regarded as statistically significant. The standard mean differences (SMD) between the means of the treatment and placebo groups with 95% confidence intervals (CIs) were computed, and a random-effect model was utilized 8.

Out of the initial 1060 studies identified, 25 randomized controlled trials met eligibility criteria for meta-analysis and systematic review. Thirteen of the studies included participants with diabetes consisting predominantly of type 2 diabetes with one type 1 diabetes and one gestational diabetes; 361 participants received the magnesium treatment while 359 received the placebo control for a median period of 12 weeks. Participants receiving the magnesium treatment were an average of 56 years, while the average age of the placebo control group participants was 49.9. The mean BMI of these participants indicated overweight status mostly among the women. Magnesium oxide was the predominant supplement used for the treatment groups.

The other 12 of the 25 randomized controlled trials consisted of participants who met the American Diabetes Association criteria for elevated risk of developing diabetes. The conditions of the research subjects included overweight status, metabolic syndrome, elevated fasting plasma glucose between 100-126 ml/dL, and polycystic metabolic syndrome. Magnesium oxide was again the most frequently selected supplement for use in the treatment groups.

This systematic review with meta-analysis examined 25 studies that followed up 477 participants in the treatment groups and 480 participants in the placebo control groups over a span of 4-24 weeks, with a median length of 14 weeks. The participants in the magnesium treatment group, mostly males, had a median age of 42.5 years compared to the placebo control group’s median age of 45.6 years. Both groups had similar BMIs (28.8 kg/m² and 28.9 kg/m², respectively). Magnesium oxide was the major supplement selected for the treatment groups.

Results indicated the following:

  1. People at high risk of diabetes: There was a statistically significant improvement in fasting plasma glucose levels among participants who received the magnesium supplementation compared to participants who received the placebo. In studies that employed oral glucose tolerance tests, there was a statistically significant improvement among participants who received the magnesium supplementation compared to those who received the placebo. No statically significant changes were observed for HbA1c or serum insulin levels among the magnesium treatment groups compared to the placebo control groups.
  2. Meta-regression analysis: There were no significant associations found between differences in serum magnesium and fasting plasma glucose among diabetic participants. Among the participants who are at increased risk for diabetes, greater differences in serum magnesium levels between the magnesium treatment groups and the placebo groups were associated with greater differences in fasting plasma glucose levels.
  3. Compliance and adverse effects: There were no significant differences, among allocated participants who finished the study, between the magnesium treatment groups with diabetes (82%) and the placebo control groups (75%). Results were reported to be similar among participants who were at increased risk for diabetes. No severe side effects were identified among any of the groups, with gastrointestinal issues (mainly diarrhea) the most frequent effect reported.

Previous experimental studies had demonstrated that magnesium plays a role in how well cells utilize glucose 9 such as by reducing insulin resistance among high-risk individuals 5,10. Magnesium was also shown to reduce the inflammatory markers 11 and oxidative stress 12 associated with insulin resistance 13. Further studies noted that magnesium was favorably associated with muscle metabolism 14, and had demonstrated improvements in dyslipidemia 15, adiposity 16, and quality of sleep 17.

This meta-analysis study with systematic review reinforces previous research findings on the role of magnesium and glucose control under conditions of randomized, double-blind controlled trials. Limitations of the study include small samples with short follow-up periods, non-standardized magnesium formulation and dosages, and participant selection preference for type 2 over type 1 diabetes. Recommendations for additional research include the use of larger studies with longer follow-up periods, standardized formulations and dosages, and the increased inclusion of participants with type 1 diabetes.

Source: Veronese, N. Dominguez, L., Pizzol, D., Demurtas, J., Smith, L., & Barbagallo, M. (November 15, 2021). Oral magnesium supplementation for treating glucose metabolism parameters in people with or at risk of diabetes: A systematic review and meta-analysis of double-blind randomized controlled trials. Nutrients 2021, 13(4074). https://doi.org/10.3390/nu13114074

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Posted March 25, 2022.

Marlene Hollick, Ed.D., M.P.H., M.A., R.D, has decades of hands-on experience and academic expertise across a wide range of health and nutrition disciplines, including home care, hospitals, nursing homes, public schools, and higher education. Dr. Hollick earned her Ed.D. in Higher Education Leadership and Health Care Education from Nova Southeastern University, a Master of Public Health from New York University, and a Master of Arts in Food and Nutrition, also from NYU.  She is a Registered Dietitian, a Certified Dietitian/Nutritionist, and is currently enrolled in the post-graduate Science Writing program at Johns Hopkins University.

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