A carefully controlled trial finds that magnesium can lower fasting glucose in older adults with magnesium deficiency, but stopping diabetes progression may require more than correcting a single mineral.
Study: Oral magnesium supplementation improves glycemic control in older Chinese adults with pre-diabetes and hypomagnesemia: a randomized controlled trial. Image credit: Pixel-Shot/Shutterstock.com
Prediabetes is a state marked by raised but not diabetes-level blood glucose. A recent study published in the journal Frontiers in Nutrition examines whether magnesium supplementation in prediabetes, particularly in older adults with hypomagnesemia, can improve glycemic control.
Magnesium deficiency emerges as modifiable risk factor
Prediabetes, a condition marked by blood glucose levels that are elevated but not yet in the diabetic range, is a critical window for intervention. Without treatment, prediabetes can progress to type 2 diabetes. It is important to design and test effective community-friendly approaches to prevent this outcome.
One potential target is magnesium status. Magnesium deficiency is relatively common, particularly among older adults, and has been linked to impaired glucose metabolism and insulin resistance. Biologically, magnesium is a cofactor in multiple enzymes regulating glucose metabolism and insulin signaling.
Only two randomized controlled trials (RCTs) have been carried out to assess the effect of magnesium supplementation in prediabetes subjects. Both trials were small and did not select participants based on magnesium deficiency or closely track dietary magnesium intake, which may explain their mixed results.
Older adults are more likely to have prediabetes and magnesium deficiency due to poor nutrient absorption with age. The current study, therefore, targeted this population.
Testing 360 mg magnesium oxide daily
The researchers conducted an exploratory RCT over 16 weeks in 71 older Chinese adults (mean age 69 years) with prediabetes and magnesium deficiency. They were randomized to receive a magnesium oxide supplement (360 mg elemental magnesium per day, taken once daily with a meal) or a placebo. Sixty-five of them completed the trial.
The primary endpoint was the change in fasting plasma glucose (FPG) from baseline to Month 4. Additionally, the researchers assessed insulin levels, C-peptide, and insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR), a proxy often used for hepatic insulin resistance. They also measured glycated hemoglobin (HbA1c), glycated albumin, and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6).
Serum magnesium rises with modest glycemic shift
Dietary magnesium intake was similar in both groups, though calcium intake at baseline was higher in the magnesium group. This group also had higher baseline insulin and HOMA-IR levels. The analysis adjusted for these differences.
Supplementation with magnesium led to a larger increase in magnesium than placebo did. The adjusted mean difference was 0.056 mmol/L.
Fasting glucose was also modestly reduced in the magnesium group, with an adjusted mean difference of -0.5 mmol/L. Other measures, including HbA1c, were not significantly different, suggesting that the reduction in fasting glucose did not translate into evidence of sustained overall glycemic improvement over the 16-week period.
The improvement in fasting glycemia is consistent with an earlier trial using a similar sample, though another study produced conflicting findings. The authors emphasize the fundamental premise of the current study: magnesium supplementation is associated with a noticeable improvement in glucose metabolism only in hypomagnesemic patients.
Notably, nearly 92 % of subjects reported adherence to the intervention protocol, and dietary intake did not change throughout the study period. This strengthens confidence in the observations. The intervention was well tolerated, with no intervention-related adverse events reported. Coupled with the absence of changes in markers such as glycated hemoglobin, the small effect size reduces its clinical relevance, especially over the long term.
A preliminary metabolomics array indicates that magnesium supplementation is associated with changes in 52 metabolites. Metabolomics is a technique that measures small molecules in the blood to provide a snapshot of metabolic processes. These were linked to lipid metabolism and insulin resistance. However, given the nature of this analysis and the fact that metabolite identities were putative and based on mass spectrometry annotation, this is only a hypothesis-generating study.
A well-controlled design but underpowered sample
The study's strengths include the interventional RCT design, monitoring dietary magnesium throughout the study period, and the use of metabolomics to reflect non-glycemic alterations associated with magnesium supplementation.
Despite these strengths, several limitations make these findings strictly hypothesis-generating rather than a confident assertion of a clinically meaningful improvement in glycemic status with magnesium supplementation. The small sample size meant the study was underpowered for most outcomes. Using fasting glucose alone, rather than dynamic glycemic markers such as postprandial glucose and the oral glucose tolerance test (OGTT), could have led to the omission of some effects of the intervention on glucose metabolism.
Baseline differences in insulin and insulin resistance between groups could have introduced residual confounding. The effect size was small, and the relatively low bioavailability of magnesium oxide may also have limited the physiological impact of supplementation.
Magnesium oxide is relatively less bioavailable than the citrate or glycinate salts. This might have reduced the physiological effects of magnesium supplementation by limiting the amount of ionized or intracellular magnesium made available to the body. Future work should compare different formulations to confirm this and elicit a dose-response relationship.
Larger, longer trials needed for clarity
In older Chinese adults with prediabetes and magnesium deficiency, magnesium supplementation was effective in significantly increasing serum magnesium concentrations and correcting magnesium deficiency at the group level, and reducing fasting glucose concentrations. On the other hand, “the overall evidence for a robust, multi-faceted improvement in glucose metabolism from this single trial is limited.”
Future work should confirm these findings, especially the clinical relevance of lowering fasting glucose levels in isolation. This would require larger trials with longer follow-up periods.
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