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Department of Family Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic
The prevalence of metabolic syndrome (MetS) has been increasing rapidly worldwide. The activities of zinc,
magnesium and chromium have a potential association with MetS; therefore, we investigated the effects of
zinc, magnesium and chromium supplements on metabolic risk factors in adults with MetS. In this double-
blind, placebo controlled randomised study, 32 adults with MetS were included in the zinc, magnesium, and
chromium-administered group (n = 16) or the placebo group (n = 16) and received either 300 mg magnesium,
600 μg chromium and 36 mg zinc per day or placebo over a 24-week period. The primary endpoint was the
change in the MetS components, including serum glucose, triglyceride and high-density lipoprotein
cholesterol levels, blood pressure and waist circumference. Data were analysed using repeated-measures
analysis of variance. The metabolic risk factors did not change post-intervention, but the serum C-reactive
protein level decreased in the mineral-supplemented group compared with that in the placebo group. Further
studies with stricter inclusion criteria are needed to better evaluate the potential for zinc, magnesium and
1. Introduction
atherogenic dyslipidaemia, elevated blood pressure and abdominal obesity, associated with an
increased risk of cardiovascular disease and all-cause mortality [1]. The prevalence of MetS
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has been increasing rapidly worldwide, such that MetS has become a major medical issue [2].
activity in target organs, suggesting that insulin resistance plays a key role in the pathogenesis
of MetS [3]. Potential roles of chronic inflammation have also been reported in patients with
MetS[4], and the presence of chronic inflammation may affect the development of MetS [5].
Zinc, magnesium, and chromium have direct and indirect effects on the secretion and signal
transduction of insulin, and in the development of insulin resistance [6-9]. Therefore, zinc,
insulin resistance and diabetes mellitus. Furthermore, zinc decrease inflammation, which are
primary contributors to the initiation and progression of insulin resistance and diabetes [10,
11]. Magnesium also plays a role as an antioxidant and may reduce chronic inflammation [12].
In several experimental studies, trivalent chromium reduced vascular inflammation [13] and
However, studies evaluating the effects of minerals on MetS in adults are rare, and the results
remain controversial [15-17]. No study has been conducted on the metabolic effects of zinc,
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conducted a randomised, controlled study to investigate the effects of zinc, magnesium and
A 24-week, randomised, controlled trial was conducted to assess the effects of mineral
supplementation on the metabolic risk factors in adults with MetS. Of all patients who visited
a medical centre in South Korea, those who met the revised National Cholesterol Education
Program Adult Treatment Panel III criteria for MetS were selected as the subjects of this study
[18]. MetS was considered present when three or more of the following criteria were met: waist
circumference ≥ 85 cm using the Korean Society for the Study of Obesity cut-off point for
abdominal obesity [19]; triglycerides ≥ 150 mg/dL or on drug treatment for elevated
treatment to reduce HDL-C; systolic blood pressure ≥ 130 mm Hg, diastolic blood pressure ≥
treatment for elevated glucose. The inclusion criteria were (1) an age of 20–70 years and
(2) fulfilment of the criteria for MetS. The exclusion criteria were (1) elevated serum alanine
aminotransferase levels (> 129 IU/L), (2) renal dysfunction (serum creatinine ≥ 1.5 mg/dL),
hospitalisation due to coronary heart disease in the preceding 6 months, (4) presence of a
neurological or psychiatric disorder, (5) mineral supplementation within 3 months prior to the
screening visit, (6) previous or present alcohol or drug abuse, and (7) pregnancy or
breastfeeding. Volunteers who met the study inclusion and exclusion criteria were randomised
into two groups (an allocation ratio = 1:1) using computer-generated random
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numbers: a mineral-administered group and a placebo group. Over a 24-week period, the
groups received either the minerals or placebo three times daily: after breakfast, lunch, and
dinner (two tablets and one capsule per meal). Therefore, the total mineral dosage was
elemental magnesium 300 mg/day as magnesium oxide, elemental chromium 600 μg/day as
chromium (III) chloride and elemental zinc 36 mg/day as zinc oxide. The placebo tablets and
capsule contained maltodextrin, and the total weight was the same as that of the mineral
supplements. Participants were followed up every 8 weeks (at baseline and at weeks 8, 16, and
24) with clinical evaluations, including a physical examination, laboratory tests, and adverse
event (AE) monitoring; AEs were defined as any unfavourable and unintended sign, including
administration of the minerals or placebo. All participants completed a hair mineral assessment
analysis before and after the intervention. Enrolment began on 27 May 2014, and the final
subject visit took place on 14 January 2016. All subjects signed a written informed consent
form before starting the trial. This study protocol was approved by the Institutional Review
Board of The Catholic University of Korea (IRB approval number: VC13HISE0198). This
2.2. Measures
The primary endpoint was the change in metabolic risk factors. Measurements were conducted
every 8 weeks during the study. Venous blood samples were collected after an 8 h overnight
fast. Serum glucose, triglyceride and HDL-C levels were determined using an auto- analyser
(Hitachi 747; Hitachi, Tokyo, Japan). Blood pressure was taken in the sitting position and waist
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The secondary outcomes were changes in magnesium, zinc and chromium levels in the hair
samples, which were collected at baseline and at week 24. In the subjects with colored hair or
with functional shampooing, the collection of hair samples was delayed and taken after 2 weeks
for the accuracy in the hair mineral analysis. Hair samples were obtained from four points on
the occipital area of the scalp, and only 4 cm of each hair strand close to the scalp Hair samples
were obtained from four points on the occipital area of the scalp, and only 4 cm of each hair
strand. The hair samples were sent to the US branch of Trace Elements, Inc. (TEI, Dallas, TX,
USA), a professional institution specializing in hair mineral analysis. In the trace element
laboratory, the hair specimen was cut into the hair strands less than 3mm in length and mixed
to allow a representative subsampling. The cut hair was weighed to the nearest
USA) and then carefully transferred into a 15 mL uniquely labeled, single-use, acid-washed,
sterile polypropylene centrifuge tube. To each specimen tube containing the hair specimen,
70% nitric acid (UltraPure Grade Acids, Fox Scientific, Alvarado, TX, USA) was added. The
specimen tubes containing the nitric acid and hair were then introduced into a computer-
controlled microwave digestion system (MARS 5, CEM Corporation, Matthews, NC, USA).
Under precise microprocessor control, the hair specimen was subject to the nitric acid and a
uniform high temperature digestion via a two-stage temperature ramping sequence, utilizing a
fiber optic temperature probe placed into a representative specimen tube within the microwave
digestion tray. After digestion, the samples were cooled, uncapped and then accurately diluted
to a set volume with a deionised water/gold solution, recapped and placed on a vortexer for
thorough mixing of each hydrated specimen. Magnesium, zinc and chromium concentrations
in the hair sample were determined by inductively coupled plasma mass spectrometry (Sciex
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calibration was performed with the linear regression method by means of a four-point
calibration curve using certified standard solutions (Spex Certiprep, Metuchen, NJ, USA)
traceable to the National Institute of Standards and Technology. The Accuracy and precision
of the analytical method was verified with standard reference materials (NCS ZC 81002 Human
Hair, China National Analysis Center for Iron and Steel, NCS Testing Technology Co., LTD.,
Beijing, China, and QMHQ1725 Human Hair, Quebec National Institute of Public Health,
Quebec City, Quebec, Canada). The standard deviation index was 0.85 for zinc, 1.57 for
chromium, and 0.4 for magnesium. The coefficients of variation for inter- and intra-assay were
5% and 1% for zinc, 5% and 1% for chromium, and 5% and 0.2% for magnesium. Mineral
concentrations in the hair sample are shown as mg per 100 g of the dry hair (μg/g).
Self-reported information on age, sex, smoking status, alcohol consumption, and medical
conditions, including past or current medical problems and operation history, was obtained.
index, and C-reactive protein (CRP) levels were conducted every 8 weeks during the study
period. Plasma insulin levels were determined by radioimmunoassay (Immulite 2000 XPi
system, Siemens, Erlangen, Germany). Insulin resistance was assessed using the HOMA-IR
The required sample size was calculated as a total of 32 subjects (16/group) assuming a 20%
dropout rate, with 80% statistical power and a significance level of 0.05 (two-sided independent
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(10 ± 9 mg/dL), waist circumference (2.0 ± 1.8 cm, serum triglycerides (20 ± 18 mg/dL), HDL-
Demographic characteristics were compared using the independent t-test for continuous
variables and the chi-square test for dichotomous variables. Repeated measures analysis of
variance (ANOVA) was used to compared serum glucose, triglycerides, HDL-C, waist
circumference, and blood pressure data between the two groups at baseline and at each
models included group (mineral- or placebo-administered), and time (of measurement) as fixed
factors; the group × time interaction effect was also evaluated. In addition, a post-hoc analysis
was conducted for multiple comparisons between groups at weeks 8, 12, and 16 using Scheffe’s
analysis. Within-group comparisons in magnesium, zinc and chromium levels in the hair
samples were analysed using paired t-tests, and independent t-tests were used for between-
group comparisons of scores before and after the intervention. A P-value < 0.05 was considered
significant.
3. Results
The disposition of the participants is shown in Fig. 1. A total of 40 participants were screened,
of whom 32 were randomised into the mineral- or placebo-administered group (both n = 16). A
total of 24 subjects (11 and 13 in the mineral and placebo group, respectively) completed the
study. The reasons for the eight dropouts were as follows: withdrawal of consent (n = 1), lost to
follow-up (n = 4), and AEs (n = 3: two subjects in the mineral group [dizziness and itching
sensation] and one subject in the placebo group [urinary retention]). The compliance rate for
taking the minerals or placebo was 92.9 and 89.6% in the mineral and placebo group,
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respectively. No subject was excluded due to treatment compliance ≤ 70%. Demographic and
baseline characteristics did not differ between the groups (Table 1).
Changes in metabolic risk factors in the mineral and placebo groups are shown in Table 2. No
significant effect of group or time, and no significant group × time interaction, was observed
No significant difference between the mineral and placebo groups was observed in magnesium,
A significant group × time interaction and effect of time were observed for serum CRP levels
4. Discussion
on metabolic risk factors in Korean adults with MetS. A daily mineral intake of 300 mg
elemental magnesium, 600 μg elemental chromium, and 36 mg elemental zinc for 24 weeks
was associated with no significant difference in any metabolic risk factor, including
compared with daily intake of the placebo. Additionally, no differences in zinc, magnesium or
chromium levels in the hair samples were observed between the mineral and placebo groups
during the study, but mineral intake for 24 weeks improved serum CRP levels.
Zinc, magnesium and chromium are minerals known to alleviate insulin resistance, which plays
a key role in the pathogenesis of MetS. Zinc is important in insulin activity and carbohydrate
metabolism, and zinc supplementation showed a beneficial effect on glucose metabolism and
insulin resistance in numerous, but not all study [20, 21]. A randomised
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controlled trial in healthy individuals showed no significant effect of zinc supplementation (20
mg of elemental zinc) on serum glucose levels, suggesting that the metabolic effects of zinc in
individuals without insulin resistance or diabetes might be not clear [22]. Many studies have
complementary treatment to prevent or control diabetes and MetS. However, other studies
showed opposing or negative results. One clinical trial reported that magnesium
supplementation improved glucose levels and insulin resistance in patients with type 2 diabetes
and hypomagnesemia [23]. Another study showed that magnesium had a relatively small
positive effect on insulin sensitivity in non-diabetics with insulin resistance and a low serum
adults, the HOMA-IR index did not differ significantly between subjects who were versus were
not taking a magnesium supplement [25]. Numerous randomised controlled trials and
systematic reviews have suggested that participant selection according to certain clinical
criteria, such as the presence of insulin resistance or glycaemic control status, is an important
supplementation does not affect glucose metabolism or insulin action in subjects without
insulin resistance or diabetes, producing more consistent effects in subjects with poor insulin
resistance or glycaemic control. In this study, the mean fasting glucose level at baseline was
118.0 ± 3.4 mg/dL, suggesting that our subjects might not have been severely glucose-
intolerant. Additionally, the HOMA-IR index and fasting insulin values were 2.94 ± 0.55 and
9.85 ± 1.68 μU/mL, respectively, indicating that the insulin resistance status of the subjects
was mild. In summary, the clinical characteristics of the subjects in this study, i.e. mildly
elevated glucose levels and insulin resistance, may have affected the results.
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The appropriateness of the mineral dosage should also be considered when evaluating possible
reasons for the negative results. In this study, the dosages of elemental zinc (36 mg), elemental
magnesium (300 mg) and elemental chromium (600 μg) were appropriate compared with those
in other studies [20, 28-30]. The compliance rate in both the mineral and placebo group was
also high, and similar between the groups. However, despite the appropriate dosages and high
level of compliance with the mineral supplementation, magnesium, zinc and chromium levels
in hair samples were not different between the mineral and placebo groups after the
intervention. Mineral concentration analysis via hair samples might be inappropriate for
evaluating mineral status, especially magnesium status. However, magnesium, zinc and
chromium levels in hair samples at baseline were in the reference range, suggesting that the
results regarding the metabolic effects of magnesium, zinc and chromium over-
supplementation in adults with MetS and within the reference range of hair mineral levels might
The critical roles of chronic inflammation in the initiation and progression of insulin
resistance, which in turn plays a key role in the pathogenesis of MetS, are well known [4, 5].
In this study, zinc, magnesium and chromium supplementation for 24 weeks decreased serum
CRP levels relative to those in the control group, and where serum CRP constitutes a precise
index of inflammatory activity. The result whereby inflammation was decreased in the mineral
group compared with the control group could expect the positive effects of the minerals
supplementation on metabolic risk factor in further trials designed with subject selection
considering the severity of insulin resistance and glucose intolerance, and the body mineral
status.
This is the first randomised, placebo-controlled trial to examine the effects of zinc,
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magnesium and chromium supplementation on metabolic risk factors in adults with MetS.
However, this study had some limitations. First, the sample size was relatively small; however,
the study had sufficient statistical power to detect meaningful changes in the variables. Second,
we did not include other indicators of body mineral status in addition to the hair mineral
analysis. Other indicators measured in serum or plasma, different types of blood cell, or urine
could be more helpful in evaluating the effects of mineral supplementation on MetS. Third, we
did not consider dietary intake that could affect metabolic risk factors or the hair mineral levels.
Additionally, more stringent subject inclusion criteria are needed to demonstrate the effects of
mineral supplementation. Further studies of adults with MetS who have elevated insulin
In conclusion, metabolic risk factors, assessed according to serum glucose, triglyceride, and
HDL-C levels, blood pressure and waist circumference did not improve over the 24-week
intervention period, whereas the serum CRP level decreased after supplementing with zinc,
magnesium and chromium in Korean adults with MetS. Further studies with more specific
participant inclusion criteria are needed to better evaluate the effects of zinc, magnesium and
Umam Fazlurrahman
Acknowledgements: The study materials and hair mineral analysis were provided by TEI
KOREA Co., Ltd. (Seoul, Korea) and Trace Elements, Inc. (TEI, Dallas, TX, USA),
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