Effects of zinc, magnesium, and chromium supplementation on cardiometabolic risk in adults with

metabolic syndrome: A double-blind, placebo-controlled randomised trial

Ha-Na Kim, Se-Hong Kim, Young-Mi Eun, Sang-Wook Song*

Department of Family Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic

University of Korea, Seoul, Republic of Korea

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

chromium to improve metabolic risk in adults with MetS.

Keywords: Zinc; Magnesium; Chromium; Metabolic syndrome; Insulin resistance; Inflammation

1. Introduction

Metabolic syndrome (MetS) is a cluster of metabolic risk factors, including hyperglycaemia,

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

3
has been increasing rapidly worldwide, such that MetS has become a major medical issue [2].

MetS involves a complex interaction of maladaptive characteristics related to impaired insulin

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,

magnesium, or chromium deficiency may predispose an individual to glucose intolerance,

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

improved insulin signalling and sensitivity [14].

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,

magnesium and trivalent chromium supplementation in adults with MetS. Therefore, we

4
conducted a randomised, controlled study to investigate the effects of zinc, magnesium and

chromium supplementation on cardiometabolic factors in adults with MetS.

2. Materials and methods

2.1. Participants and study design

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

triglycerides; high-density lipoprotein cholesterol (HDL-C) < 50 mg/dL or receiving drug

treatment to reduce HDL-C; systolic blood pressure ≥ 130 mm Hg, diastolic blood pressure ≥

85 mm Hg or on antihypertensive drug treatment; and fasting glucose ≥ 100 mg/dL or on drug

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),

(3) presence of unstable hypertension, arrhythmia, or a coronary heart disease event, or

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

abnormal laboratory findings, symptoms, or diseases temporally associated with the

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

study was registered at the Clinical Research Information Service (CRiS:

https://cris.nih.go.kr/cris/en/) under the identifier code KCT0001552.

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

circumference was measured after a rest period of at least 5 min.

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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

0.001 g on an analytical-grade balance (Ohaus Explorer, Ohaus Corporation, Parsippany, NJ,

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

Elan 6100 or 9000, Perkin Elmer, Shelton CT, USA). Instrument

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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).

2.3. Other measures

Self-reported information on age, sex, smoking status, alcohol consumption, and medical

conditions, including past or current medical problems and operation history, was obtained.

Measurements of insulin levels, homeostasis model assessment insulin resistance (HOMA-IR)

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

index, calculated as follows: [fasting glucose (mg/dL) × fasting insulin (μIU/mL)]/405.

2.4. Statistical analysis

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

t-test) to detect a meaningful difference between groups in serum glucose level

8
(10 ± 9 mg/dL), waist circumference (2.0 ± 1.8 cm, serum triglycerides (20 ± 18 mg/dL), HDL-

C (5 ± 5 mg/dL) and blood pressure (10 ± 9 mm Hg) .

All values are expressed as means ± standard deviation or frequencies (percentage).

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

subsequent measurement time point (intention-to-treat). The Repeated measures ANOVA

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,

9
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

for any metabolic risk factor.

No significant difference between the mineral and placebo groups was observed in magnesium,

zinc or chromium levels in the hair samples (Table 3).

A significant group × time interaction and effect of time were observed for serum CRP levels

(F = 3.78, P = 0.015 and F = 3.39, P = 0.024, respectively) (Table 4).

4. Discussion

We investigated the ameliorative effects of zinc, magnesium and chromium supplementation

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

hyperglycaemia, atherogenic dyslipidaemia, elevated blood pressure, and abdominal obesity

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

10
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

suggested that magnesium supplementation is associated with improved glucose metabolism

and insulin sensitivity, suggesting that magnesium supplementation could be used as a

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

magnesium level [24]. In a randomised controlled trial of normomagnesemic, nondiabetic

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

consideration for studies of chromium supplementation [26, 27], where chromium

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.

11
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

be attenuated compared with subjects in other studies with mineral deficiencies.

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,

12
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

resistance and low mineral status are warranted.

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

chromium supplementation on cardiometabolic risk factors in adults with MetS.

Conflicts of interest: The authors declare no conflicts of interest.

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),

respectively. Umam Fazlurrahman

13
 References
Umam Fazlurrahman
[1] V.L. Murthy, S.A. Abbasi, J. Siddique, L.A. Colangelo, J. Reis, B.A. Venkatesh, J.J. Carr,

J.G. Terry, S.M. Camhi, M. Jerosch-Herold, S. de Ferranti, S. Das, J. Freedman, M.R.

Carnethon, C.E. Lewis, J.A. Lima, R.V. Shah, Transitions in Metabolic Risk and Long-Term

Cardiovascular Health: Coronary Artery Risk Development in Young Adults (CARDIA)

Study, J. Am. Heart Assoc. 5(10) (2016).

Umam Fazlurrahman

[2] S. O'Neill, L. O'Driscoll, Metabolic syndrome: a closer look at the growing epidemic and

its associated pathologies, Obes. Rev. 16(1) (2015) 1-12.

[3] E.J. Gallagher, D. Leroith, E. Karnieli, The metabolic syndrome--from insulin resistance to

obesity and diabetes, Med. Clin. North Am. 95(5) (2011) 855-73.

[4] N. Esser, S. Legrand-Poels, J. Piette, A.J. Scheen, N. Paquot, Inflammation as a link

between obesity, metabolic syndrome and type 2 diabetes, Diabetes Res. Clin. Pract. 105(2)

(2014) 141-50.

14
[5] G. Grandl, C. Wolfrum, Hemostasis, endothelial stress, inflammation, and the metabolic

syndrome, Semin. Immunopathol. (2017).

[6] T. Gunther, The biochemical function of Mg(2)+ in insulin secretion, insulin signal

transduction and insulin resistance, Magnes. Res. 23(1) (2010) 5-18.

[7] Y. Hua, S. Clark, J. Ren, N. Sreejayan, Molecular mechanisms of chromium in alleviating

insulin resistance, J. Nutr. Biochem. 23(4) (2012) 313-9.

[8] F. Chimienti, Zinc, pancreatic islet cell function and diabetes: new insights into an old story,

Nutr. Res. Rev. 26(1) (2013) 1-11.

[9] J.B.S. Morais, J.S. Severo, G.R.R. de Alencar, A.R.S. de Oliveira, K.J.C. Cruz, D.D.N.

Marreiro, B. Freitas, C.M.R. de Carvalho, M. Martins, K.M.G. Frota, Effect of magnesium

supplementation on insulin resistance in humans: A systematic review, Nutrition 38 (2017) 54-

60.

[10] R. Kelishadi, M. Hashemipour, K. Adeli, N. Tavakoli, A. Movahedian-Attar, J. Shapouri,

P. Poursafa, A. Rouzbahani, Effect of zinc supplementation on markers of insulin resistance,

oxidative stress, and inflammation among prepubescent children with metabolic syndrome,

Metab. Syndr. Relat. Disord. 8(6) (2010) 505-10.

[11] O.P. Garcia, D. Ronquillo, M. del Carmen Caamano, G. Martinez, M. Camacho, V. Lopez,

J.L. Rosado, Zinc, iron and vitamins A, C and e are associated with obesity, inflammation, lipid

profile and insulin resistance in Mexican school-aged children, Nutrients 5(12) (2013) 5012-

30.

[12] L.E. Simental-Mendia, A. Sahebkar, M. Rodriguez-Moran, G. Zambrano-Galvan, F.

Guerrero-Romero, Effect of Magnesium Supplementation on Plasma C-reactive Protein

Concentrations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,

Curr. Pharm. Des. 23(31) (2017) 4678-4686.

15
[13] M. Jamilian, F. Bahmani, M.A. Siavashani, M. Mazloomi, Z. Asemi, A. Esmaillzadeh,

The Effects of Chromium Supplementation on Endocrine Profiles, Biomarkers of

Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a

Randomized, Double-Blind, Placebo-Controlled Trial, Biol. Trace Elem. Res. 172(1) (2016)

72-8.

[14] R. Ganguly, S. Sahu, R.J. Chavez, P. Raman, Trivalent chromium inhibits TSP-1

expression, proliferation, and O-GlcNAc signaling in vascular smooth muscle cells in response

to high glucose in vitro, Am. J. Physiol. Cell Physiol. 308(2) (2015) C111-22.

[15] A. Pizent, M. Pavlovic, J. Jurasovic, S. Dodig, D. Pasalic, R. Mujagic, Antioxidants, trace

elements and metabolic syndrome in elderly subjects, J. Nutr. Health Aging 14(10) (2010) 866-

71.

[16] N. Iqbal, S. Cardillo, S. Volger, L.T. Bloedon, R.A. Anderson, R. Boston, P.O. Szapary,

Chromium picolinate does not improve key features of metabolic syndrome in obese

nondiabetic adults, Metab. Syndr. Relat. Disord. 7(2) (2009) 143-50.

[17] J. Wang, G. Persuitte, B.C. Olendzki, N.M. Wedick, Z. Zhang, P.A. Merriam, H. Fang, J.

Carmody, G.F. Olendzki, Y. Ma, Dietary magnesium intake improves insulin resistance among

non-diabetic individuals with metabolic syndrome participating in a dietary trial, Nutrients

5(10) (2013) 3910-9.

[18] D.L. Watts, Trace Elements & Other Essential Nutrients: Clinical Application of Tissue

Mineral Anlaysis, Meltdown Intl 1995.

[19] S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J.

Gordon, R.M. Krauss, P.J. Savage, S.C. Smith, Jr., J.A. Spertus, F. Costa, Diagnosis and

management of the metabolic syndrome: an American Heart Association/National Heart, Lung,

and Blood Institute scientific statement, Curr. Opin. Cardiol. 21(1) (2006) 1-6.

16
[20] S.Y. Lee, H.S. Park, D.J. Kim, J.H. Han, S.M. Kim, G.J. Cho, D.Y. Kim, H.S. Kwon,

S.R. Kim, C.B. Lee, S.J. Oh, C.Y. Park, H.J. Yoo, Appropriate waist circumference cutoff

points for central obesity in Korean adults, Diabetes Res. Clin. Pract. 75(1) (2007) 72-80.

[21] J. Capdor, M. Foster, P. Petocz, S. Samman, Zinc and glycemic control: a meta-analysis of

randomised placebo controlled supplementation trials in humans, J. Trace Elem. Med. Biol.

27(2) (2013) 137-42.

[22] P. Ranasinghe, W.S. Wathurapatha, P. Galappatthy, P. Katulanda, R. Jayawardena, G.R.

Constantine, Zinc supplementation in prediabetes: A randomized double-blind placebo-

controlled clinical trial, J. Diabetes (2017).

[23] S. Czernichow, A. Couthouis, S. Bertrais, A.C. Vergnaud, L. Dauchet, P. Galan, S.

Hercberg, Antioxidant supplementation does not affect fasting plasma glucose in the

Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France:

association with dietary intake and plasma concentrations, Am. J. Clin. Nutr. 84(2) (2006) 395-

9.

[24] F. Guerrero-Romero, M. Rodriguez-Moran, Complementary therapies for diabetes: the

case for chromium, magnesium, and antioxidants, Arch. Med. Res. 36(3) (2005) 250-7.

[25] F. Guerrero-Romero, H.E. Tamez-Perez, G. Gonzalez-Gonzalez, A.M. Salinas-Martinez,

J. Montes-Villarreal, J.H. Trevino-Ortiz, M. Rodriguez-Moran, Oral magnesium

supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance.

A double-blind placebo-controlled randomized trial, Diabetes Metab. 30(3) (2004) 253-8.

[26] S. Lee, H.K. Park, S.P. Son, C.W. Lee, I.J. Kim, H.J. Kim, Effects of oral magnesium

supplementation on insulin sensitivity and blood pressure in normo-magnesemic nondiabetic

overweight Korean adults, Nutr. Metab. Cardiovasc. Dis. 19(11) (2009) 781-8.

[27] W.T. Cefalu, J. Rood, P. Pinsonat, J. Qin, O. Sereda, L. Levitan, R.A. Anderson, X.H.

17
 Table 4. Changes in insulin resistance and C-reactive protein levels between baseline and follow-up time points.

Zhang, J.M. Martin, C.K. Martin, Z.Q. Wang, B. Newcomer, Characterization of the metabolic

and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus,

Metabolism 59(5) (2010) 755-62.

[28] E.M. Balk, A. Tatsioni, A.H. Lichtenstein, J. Lau, A.G. Pittas, Effect of chromium

supplementation on glucose metabolism and lipids: a systematic review of randomized

controlled trials, Diabetes Care 30(8) (2007) 2154-63.

[29] R. Jayawardena, P. Ranasinghe, P. Galappatthy, R. Malkanthi, G. Constantine, P.

Katulanda, Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-

analysis, Diabetol. Metab. Syndr. 4(1) (2012) 13.

[30] M. Rodriguez-Moran, F. Guerrero-Romero, Oral magnesium supplementation improves the

metabolic profile of metabolically obese, normal-weight individuals: a randomized double-blind

placebo-controlled trial, Arch. Med. Res. 45(5) (2014) 388-93.

[31] R.V. Yin, O.J. Phung, Effect of chromium supplementation on glycated hemoglobin and

fasting plasma glucose in patients with diabetes mellitus, Nutr. J. 14 (2015) 14.

Umam Fazlurrahman

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