Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial.
ABSTRACT The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to receive either Mg-aspartate-hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity, plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic, overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently type 2 diabetes.
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ABSTRACT: Macro elements are the minerals of which the body needs more amounts and are more important than any other elements. Trace elements constitute a minute part of the living tissues and have various metabolic characteristics and functions. Trace elements participate in tissue and cellular and subcellular functions; these include immune regulation by humoral and cellular mechanisms, nerve conduction, muscle contractions, membrane potential regulations, and mitochondrial activity and enzyme reactions. The status of micronutrients such as iron and vanadium is higher in type 2 diabetes. The calcium, magnesium, sodium, chromium, cobalt, iodine, iron, selenium, manganese, and zinc seem to be low in type 2 diabetes while elements such as potassium and copper have no effect. In this review, we emphasized the status of macro and trace elements in type 2 diabetes and its advantages or disadvantages; this helps to understand the mechanism, progression, and prevention of type 2 diabetes due to the lack and deficiency of different macro and trace elements.The Scientific World Journal 01/2014; 2014:461591. · 1.22 Impact Factor
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ABSTRACT: AimsTo estimate quantitatively the association between dietary magnesium intake and risk of metabolic syndrome by combining the relevant published articles using meta-analysis.Methods We reviewed the relevant literature in PubMed and EMBASE published up until August 2013 and obtained additional information through Google or a hand search of the references in relevant articles. A random-effects or fixed-effects model, as appropriate, was used to pool the effect sizes on metabolic syndrome comparing individuals with the highest dietary magnesium intake with those having the lowest intake. The dose–response relationship was assessed for every 100-mg/day increment in magnesium intake and risk of metabolic syndrome.ResultSix cross-sectional studies, including a total of 24 473 individuals and 6311 cases of metabolic syndrome, were identified as eligible for the meta-analysis. A weighted inverse association was found between dietary magnesium intake and the risk of metabolic syndrome (odds ratio 0.69, 95% CI 0.59, 0.81) comparing the highest with the lowest group. For every 100-mg/day increment in magnesium intake, the overall risk of having metabolic syndrome was lowered by 17% (odds ratio 0.83, 95% CI 0. 77, 0.89).Conclusion Findings from the present meta-analysis suggest that dietary magnesium intake is inversely associated with the prevalence of metabolic syndrome. Further studies, in particular well-designed longitudinal cohort studies and randomized placebo-controlled clinical trials, are warranted to provide solid evidence and to establish causal inference.This article is protected by copyright. All rights reserved.Diabetic Medicine 06/2014; · 3.24 Impact Factor
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ABSTRACT: Objective This article presents an overview of metabolic syndrome (MetS), which is a collection of risk factors that can lead to diabetes, stroke, and heart disease. The purposes of this article are to describe the current literature on the etiology and pathophysiology of insulin resistance as it relates to MetS and to suggest strategies for dietary and supplemental management in chiropractic practice. Methods The literature was searched in PubMed, Google Scholar, and the Web site of the American Heart Association, from the earliest date possible to May 2014. Review articles were identified that outlined pathophysiology of MetS and type 2 diabetes mellitus (T2DM) and relationships among diet, supplements, and glycemic regulation, MetS, T2DM, and musculoskeletal pain. Results Metabolic syndrome has been linked to increased risk of developing T2DM and cardiovascular disease and increased risk of stroke and myocardial infarction. Insulin resistance is linked to musculoskeletal complaints both through chronic inflammation and the effects of advanced glycosylation end products. Although diabetes and cardiovascular disease are the most well-known diseases that can result from MetS, an emerging body of evidence demonstrates that common musculoskeletal pain syndromes can be caused by MetS. Conclusions This article provides an overview of lifestyle management of MetS that can be undertaken by doctors of chiropractic by means of dietary modification and nutritional support to promote blood sugar regulation.Journal of chiropractic medicine 09/2014; 13(3).
Diabetes, Obesity and Metabolism 13: 281–284, 2011.
© 2011 Blackwell Publishing Ltd
Oral magnesium supplementation reduces insulin
resistance in non-diabetic subjects – a double-blind,
placebo-controlled, randomized trial
The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of
oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin
resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to
receive either Mg–aspartate–hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity,
plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of
fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant
changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic,
overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently
type 2 diabetes.
Keywords: diabetes mellitus, glycaemic control, insulin resistance, insulin sensitivity index, magnesium, metabolic syndrome, randomized trial
Date submitted 20 July 2010; date of first decision 22 August 2010; date of final acceptance 2 November 2010
Increasing evidence suggests a crucial role for Mg in insulin
action and sensitivity and allows the hypothesis that a
well-balanced Mg status is useful in improving insulin
resistance and metabolic syndrome and hence for preventing
type 2 diabetes . Less is known about prophylactic or
therapeutic effects of Mg on early alterations of glucose
homeostasis. Some studies indicated a beneficial effect of Mg
supplementation on reducing plasma fasting glucose levels
in patients with type 2 diabetes and on reversing insulin
resistance in hypomagnesaemia, non-diabetic and apparently
healthy subjects . Therefore, the aim of the present study
was to investigate whether Mg supplementation is able to
affect glucose homeostasis and insulin sensitivity not only in
normomagnesemic, overweight, insulin resistant subjects but
also in otherwise healthy subjects.
Study Design and Population
The study was a single-centre, double-blind, randomized,
placebo-controlled trial and performed according to the prin-
ciples contained in the Declaration of Helsinki. Subjects
were included after providing written informed consent if
they fulfilled the following inclusion criteria: (i) body mass
index (BMI) ≥25 kg/m2; (ii) age between 30 and 70 years
and (iii) decreased insulin sensitivity as indicated by fasting
venous plasma glucose level of ≤6.94 mmol/l, venous plasma
Correspondence to: Prof. Dr. Frank Christoph Mooren, Department of Sports Medicine,
Institute of Sport Sciences, Justus-Liebig-University, Kugelberg 62, Giessen 35394,
glucose levels and serum insulin 2 h after an oral glucose load
of <11.11 mmol/l and >60 μU/ml (434.78 pmol/l), respec-
tively. Subjects were randomized to receive either magne-
sium(Mg)–aspartate–hydrochloride(15 mmol(365 mg)/day;
Magnesiocard®) or placebo for 6 months.
Insulin Sensitivity Indices
Insulin sensitivity indices (ISIs) according to Matsuda &
(HOMA)] were calculated from the oral glucose tolerance
test (OGTT) as recently described and served as study end-
points [3–5]. In contrast to the initial description of the
Matsuda formula, the mean plasma glucose concentrations
were calculated only for the 30- and 120-min time points after
time points were used.
Energy expenditure and blood pressure were regularly
determined. For biochemical measures, the total cholesterol,
high-density lipoprotein (HDL) cholesterol, triglycerides, total
extracellular and intracellular Mg concentration as well as the
free (ionized) Mg concentration was determined.
Metricvariablesweregivenasmean ± standarddeviation(SD).
For indices, non-parametric confidence intervals according
to Noether, and categorical variables absolute and relative
frequencies were given. Group comparisons of all indices were
variables Student’s t-test was applied. Explorative stratified
analysis was carried out with the Cochran–Mantel–Haenszel
test with modified ridits and ANOVA respectively, ANCOVA GLM
DIABETES, OBESITY AND METABOLISM
models with SAS 9.1. The critical significance level was a
Finally, 52 of 98 screened subjects were randomized, 5 sub-
jects (2 verum, 3 placebo) dropped out because of personal
reasons. There were no differences between treatment groups
withrespect todemographic, anthropometricand biochemical
characteristics at baseline. Especially, serum Mg levels were in
the normal range. Treatment compliance was similar in both
Verum and placebo groups did not show any significant
difference with respect to BMI and physical activity during the
intervention (Table 1). At the end of the study, ionized Mg of
the verum group significantly differed from the placebo group.
Likewise, the total serum Mg levels showed a trend for higher
Mg levels showed no significant changes (Table 1).
Fasting plasma glucose was significantly lower in the Mg
group (Table 2). Fasting serum insulin displayed a non-
significanttrendforimprovementbyMg(p = 0.0875).Plasma
glucoseand serum insulinconcentrations120 minafterOGTT
showed no differences between groups. The ISI Gutt improved
during the trial, but the difference between verum and placebo
was not significant. However, the other indices for insulin
resistance, ISI Matsuda and ISI–HOMA were significantly
improved by Mg intake. Furthermore, there was a trend for
a reduction of diastolic blood pressure in the Mg group
(p = 0.0561). The lipid profiles did not change after Mg
Mg supplementation ameliorates insulin resistance in obese,
insulin-resistant subjects. Two out of three ISIs improved after
Mg supplementation for about 6 months. The ISI–HOMA
and ISI Matsuda showed significant improvement, while ISI
Gutt did not. Moreover, glucose handling seemed to be
improved as the fasting plasma glucose significantly decreased
after intervention. The heterogeneous responses of the ISIs
might have various reasons. One reason might be that the
increase of physical activity in the placebo group probably
made it more difficult to reach a significant difference.
Alternatively, ISI Gutt might be too insensitive for detecting
changes in insulin resistance and may require larger sample
sizes for achieving significant results . Finally, it can be
hypothesized that Mg predominantly influences hepatic rather
than peripheral insulin resistance. Likewise, both ISI–HOMA,
which mainly reflects hepatic insulin resistance, and fasting
plasma glucose, in the post-absorptive state is an indicator of
hepatic glucose production, significantly improved with Mg
The present findings are consistent with the results of pre-
vious Mg intervention trials on subjects with type 2 diabetes
and insulin-resistant subjects without diabetes. However, it
is worth emphasizing that in both trials only subjects with
Table 1. Main confounding variables and measures for magnesium (Mg) status at baseline and after administration of magnesium Mg–aspartate–hydrochloride or placebo for more than 6 months.
Verum (Mg–aspartate–hydrochloride) n = 25
Placebo (n = 22)
Difference (95% CI)∗
30.90 ± 3.23
30.82 ± 3.63
29.98 ± 2.30
29.86 ± 2.54
−0.04 ( −0.64 to 0.56)
Energy expenditure by physical activity (kcal/week)‡
4369 (3054, 6917)
3315 (2070, 4752)
2467 (1932, 3750)
4513 (3062, 6741)
863.32 (–2911.59 to 4638.23)
Total Mg in serum (mmol/l)
0.898 ± 0.083
0.922 ± 0.068
0.891 ± 0.085
0.890 ± 0.085
(p = 0.07)¶
Total Mg in erythrocytes (mmol/l)
1.872 ± 0.246
1.920 ± 0.359
1.979 ± 0.411
1.955 ± 0.557
Ionized Mg in whole blood (mmol/l)
0.600 ± 0.047
0.608 ± 0.034
0.610 ± 0.046
0.595 ± 0.039
Values are expressed as mean ± SD. CI, confidence interval; BMI, body mass index.
∗Mean of the difference between groups after 6 months of intervention with 95% CI.
†p-values for difference between groups after 6 months of intervention.
‡Expressed as median (first and third quartiles).
§Not done because non-parametric CIs are generally not computed.
¶Indicates trend between baseline and end values either within the verum or the placebo group.
282 Mooren et al.Volume 13 No. 3 March 2011
DIABETES, OBESITY AND METABOLISM
Table 2. Findings at baseline and results after administration of magnesium (Mg)–aspartate–hydrochloride or placebo for more than 6 months.
Verum (Mg–aspartate–hydrochloride), n = 25
Placebo (n = 22)
Difference (95% CI)∗
63.055 ± 17.427
75.981 ± 33.524§
61.321 ± 16.120
64.570 ± 24.669
−5.64 (−16.70 to 5.62)
3.430 ± 1.552
4.037 ± 2.040§
3.535 ± 1.341
3.150 ± 1.288
−1.14 (−1.80 to −0.39)
3.488 ± 1.983
2.974 ± 1.682
2.900 ± 1.489
3.713 ± 2.517
0.91 (0.21 to 1.57)
Fasting plasma glucose (mmol/l)
5.07 ± 0.68
4.75 ± 1.04 (p = 0.07)
4.81 ± 0.48
4.97 ± 0.87
120-min plasma glucose after oral glucose load (mmol/l)
6.24 ± 2.02
5.99 ± 2.41
6.39 ± 1.92
6.55 ± 2.23
Fasting serum insulin (pmol/l)
109.42 ± 55.80
100.00 ± 46.38
97.10 ± 44.93
117.39 ± 58.70
120 min serum insulin after oral glucose load (pmol/l)
854.3 ± 459.4
785.5 ± 622.5
841.3 ± 292.0
789.1 ± 444.9
Systolic blood pressure (mm Hg)
137.7 ± 14.9
131.4 ± 16.4§
134.8 ± 15.0
133.1 ± 21.9
4.74 (−2.63 to 12.11)
Diastolic blood pressure (mm Hg)
85.3 ± 9.4
81.6 ± 9.8§
82.5 ± 9.6
83.2 ± 12.1
4.41 (−0.12 to 8.94)
Total cholesterol (mmol/l)
5.84 ± 1.21
5.79 ± 1.25
5.55 ± 0.79
5.61 ± 0.97
HDL cholesterol (mmol/l)
1.36 ± 0.31
1.28 ± 0.27§
1.32 ± 0.36
1.23 ± 0.28§
LDL cholesterol (mmol/l)
3.57 ± 1.04
3.67 ± 1.04
3.26 ± 0.73
3.37 ± 0.86
2.17 ± 1.13
2.14 ± 1.37
2.26 ± 1.35
2.33 ± 1.51
Values are expressed as mean ± standard deviation (SD). CI, confidence interval; ISI, insulin sensitivity indices; HOMA, homeostatic model assessment; HDL, high-density lipoprotein; LDL, low-density
∗Median (for insulin indices) respective mean (for blood pressure) of the difference between groups after 6 months of intervention with 95% CI.
†p-values for difference between groups after 6 months of intervention.
‡Not done as non-parametric CIs are generally not computed.
§Indicates significance (p ≤ 0.05) between baseline and end values either within the verum or the placebo groups.
Volume 13 No. 3 March 2011doi:10.1111/j.1463-1326.2010.01332.x 283
DIABETES, OBESITY AND METABOLISM
hypomagnesaemia were enrolled . This might also explain
why the decrease in the present study (20% vs. placebo) was
quite moderate compared to the 51% reduction with Mg sup-
effect of Mg on insulin sensitivity is much more pronounced
under conditions of hypomagnesaemia . Interestingly, in
Mg concentrations, thereby confirming recent trials about
the Mg effects on glucose handling in both diabetic and non-
and extracellular pools were within the 95% reference range
published recently, a severe Mg deficiency can be excluded .
is already compromised in the state of marginal Mg deficiency,
status.Alternatively,itcanbe speculatedthatMginexcess may
act as a natural insulin sensitizer even under conditions of a
well-balanced Mg status. Several mechanisms may be respon-
sible for the beneficial effect of Mg on insulin resistance. These
include direct effects of Mg on the insulin receptor and its
downstream signalling processes, enhanced enzyme activities
involved in glucose utilization, prevention of an intracellular
calcium overload supposed to negatively affect insulin sensi-
tivity,and finally, anti-inflammatoryeffects known to improve
The clinical relevance of the observed ISI changes after Mg
supplementation is supported by a comparison with other
studies using alternative interventional approaches. Mg sup-
plementation seems to be more effective in improving insulin
resistance than a strict lifestyle modification . The effects
of a 16-week therapy with metformin on ISIs were in the same
range as that in the current study . Only a recent ran-
domized controlled trial with the synthetic insulin sensitizer
after a 4-month intervention .
In conclusion, the results of the present trial in connection
with data from previous intervention trials and epidemiologi-
calstudies provide convincingevidence forapositiveinfluence
of Mg supplementation on insulin resistance. The efficacy of
Mg supplementation—even in subjects with normal serum
Mg concentrations—addresses the question of a prophylactic
administration for people at risk for metabolic syndrome and
highlights the need of sufficient Mg intake by food.
F.C. Mooren1,K.Kr¨ uger1, K.V¨ olker2,S. W.Golf3,
M. Wadepuhl4& A. Kraus5
1Department of Sports Medicine, Institute of Sports Sciences,
Justus-Liebig-University, Kugelberg, Giessen, Germany
2Department of Sports Medicine, M¨ unster-University Hospital,
M¨ unster, Germany
3Department of Laboratory Medicine, Justus-Liebig-University,
4VSA Versuchsplanung und Statistische Auswertung, Ulm,
5Verla-Pharm Arzneimittel, Hauptstraße, Tutzing, Germany
This study was sponsored by Verla-Pharm Arzneimittel. Data
Meeting on Magnesium in Paris, 2008. The corresponding
abstract was published in Magnesium Research (Mooren FC,
Fromme A, V¨ olker K, Golf S. Oral magnesium supplemen-
tation reduces insulin resistance in non-diabetic subjects. A
Research 2008; 21: 137).
Conflict of Interest
F. C. M., K. K., K. V., S. W. G. and M. W. do not declare any
conflict of interest relevant to this manuscript.
A. K. is an employee of Verla-Pharm Arzneimittel.
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