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Please cite this article in press as: VorugantiVS, et al.Short-term weightloss in overweight/obese low-income women improves plasma

zinc and metabolic syndrome risk factors. J Trace Elem Med Biol (2010), doi:10.1016/j.jtemb.2010.05.001

ARTICLE IN PRESSG Model

JTEMB-25272; No.of Pages6

Journal of Trace Elements in Medicine and Biology xxx (2010) xxx–xxx

Contents lists available at ScienceDirect

Journal of Trace Elements in Medicine and Biology

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . d e / j t e m b

Physiology

Short-term weight loss in overweight/obese low-income women improves

plasma zinc and metabolic syndrome risk factors

Venkata Saroja Voruganti a,∗, Guowen Cai b, Deborah M. Klohe c, Kristine C. Jordan d,Michelle A. Lane e, Jeanne H. Freeland-Graves c

a Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, United Statesb SAS Institute, 100 SAS Campus Drive, Cary, NC 27513-2414, United Statesc Department of Nutritional Sciences, The University of Texas at Austin, Austin 78712, United Statesd Division of Nutrition, University of Utah College of Health, Salt Lake City, UT 84112, United Statese Nutrition and Foods Program, Department of Family and Consumer Sciences, Texas State University, San Marcos, TX 78666, United States

a r t i c l e i n f o

Article history:

Received 2 November 2009

Accepted 19 May 2010

Keywords:

Obesity

Intervention

Body fat

a b s t r a c t

Metabolic syndrome is a group of disorders involvingobesity, insulin resistance, dyslipidemia and hyper-

tension. Obesity is the most crucial risk factor of metabolic syndrome, because it is known to precede

other risk factors. Obesity is also associated with disturbances in the metabolism of the trace mineral,

zinc. The overall purpose of this study was to investigate the effects of short-term weight loss on plasma

zinc andmetabolic syndrome risk factors. An 8-week weightloss interventionstudywas conductedwith

90 low-income overweight/obese mothers, whose youngestchild was1–3 yearsold. Plasma levels of zinc,

glucose, insulin, leptin, triglycerides, total, high-density lipoprotein (HDL) and low-density lipoprotein

(LDL) cholesterol were measured and compared at weeks 0 and 8 of the weight loss program. At pre-

study,plasma zinc was lowin 39%and,within normal valuesin 46%, of obese/overweight mothers. By the

endof intervention, plasma zinc rose by 22%and only 5% of themothers continuedto exhibit low plasma

zinc. At post-study, the metabolic syndrome risk factors of waist circumference, HDL cholesterol, and

diastolic blood pressure ( p < 0.05) showed significant improvements. Plasma zinc increased by a greater

margin (67%) in women with low zinc, as compared to those with normal zinc (18%); weight reductionwas similar in both the groups. Finally, changes in % body fat were related negatively with changes in

plasma zinc (r =− 0.28, p < 0.05). The circulating levels of zinc, as well as the metabolic syndrome com-

ponents, showed significant improvements in overweight/obese low-income women after weight loss.

© 2010 Elsevier GmbH. All rights reserved.

Introduction

Metabolic syndrome is a group of disorders involving obesity,

insulin resistance, dyslipidemia and hypertension [1]. This condi-

tion affects about 35% of adults in the United States (US) [2]. An

earlier study by Ford [3] f ound the prevalence of metabolic syn-

drome in US adults to be approximately 27%, an increase of 16%

since 1994 [3]. This escalation is particularly alarming for women,because they showed a greater increase (23.5%) than men (2.2%)

[3].

According to the National Cholesterol Education Program-Adult

Treatment Panel (NCEP ATP III), metabolic syndrome is charac-

terized by the presence of at least three of the following risk

∗ Corresponding author at: Department of Genetics, Southwest Foundation for

Biomedical Research, PO Box 760549, San Antonio, TX 78245, United States.

Tel.: +1 210 258 9795; fax: +1 210 258 9132.

E-mail address: [email protected] (V.S. Voruganti).

factors; waist circumference > 88cm for women and> 102cm for

men, fasting glucose > 100mg/dl, fasting triglycerides > 150mg/dl,

HDL cholesterol < 50 mg/dl for women and< 40 mg/dl for men, and

blood pressure > 130/85 mm Hg [4]. Although metabolic syndrome

is considered to be the combined effect of all these risk factors,

each individual component is known to independently augment

the risk of associated diseases such as cardiovascular disorders and

type 2 diabetes [5]. The recent escalation in metabolic syndromeincidence has been attributed to obesity [2], the most crucial risk

factor of this syndrome [6].

The prevalence of obesity has been escalating rapidly; in

2007–2008 the age adjusted prevalence of obesity was 33.8% [7].

Also, obesity is widespread in women, predominantly in those who

are low-income [8] and minority [9]. Metabolic syndrome and obe-

sity are associated with several metabolic disturbances, one of

them being alterations in the metabolism of trace minerals such

as zinc [10]. Zinc status, particularly circulating level, is known

to be altered in conditions such as obesity and type 2 diabetes,

as observed in animal [11–13] as well as human [14–16] models.

0946-672X/$ – see front matter © 2010 Elsevier GmbH. All rights reserved.

doi:10.1016/j.jtemb.2010.05.001

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2 V.S. Voruganti et al. / Journal of Trace Elements in Medicine and Biology xxx (2010) xxx–xxx

Specifically, plasma zinc has been observed to be low in obese chil-

dren and adolescents [15,16], adult men and women [17–20], and

obese mice [21].

Zinc, a trace element, is required for several cellular functions

and participates in important metabolic pathways related to the

metabolism of proteins, carbohydrates, lipids and nucleic acids

[16,22]. Zincdeficiencyhas several features in common withinsulin

resistance,hyperglycemia,and impairedglucose tolerance [10] and

maylead to the development of diabetes [23]. The influence of zinc

on glucose metabolism may be related to its insulin-like properties.

For example, zinc promotes lipogenesisand glucose transportin rat

adipocytes [24] and glucose uptake in mouse skeletal muscle [25].

Moreover, zinc may be involved in insulin signaling by forming a

complex with insulin and increasing the ability of insulin to bind

to its receptor [16]. Thus, it is conceivable that zinc may play a role

in the metabolic syndrome.

Weight lossis an effective treatmentfor the metabolic syndrome

[26] as it has been shown to improve blood pressure and plasma

concentrations of glucose, insulin and lipids [27]. Additionally,

plasma zinc also increases with weight loss. Specifically, plasma

zinclevels increasedand returned to normal levelsin obesepatients

whowere fedhypocaloricdiets [19,28]. In contrast, morbidly obese

patients undergoing a Roux-en-Y gastric bypass surgery did not

have attenuations in plasma zinc with weight loss [20]. There-fore, the effect of weight loss on circulating zinc levels remains

controversial. In the current study, the primary objective was to

investigate the effect of short-term weight loss on circulating zinc

levels. The secondary aim was to confirm the positive effects of

weight loss on metabolic syndrome risk factors.

Material and methods

Design

An 8-week weight loss intervention study was conducted with

90 overweight or obese, (body mass index (BMI) ≥25kg/m2) low-

income mothers. All participants were administered a 33-item

demographic questionnaire at week 0. Details of the interventionhave been given in Klohe-Lehman et al. [29]. In short, anthropo-

metric variables (body weight, waist circumference, percent body

fat, BMI, blood pressure) were obtained at weeks 0 and 8. Blood

was collectedaftera 12-h fasting period; plasmawas extractedand

stored at−80 ◦C untilfurtheranalysis. Plasma levelsof zinc,glucose,

insulin, leptin, triglycerides, total and high-density lipoprotein

(HDL) and low-density lipoprotein (LDL) cholesterol were mea-

sured at weeks 0 and 8.

Subjects

Selection criteria included: age, 18–45 years; youngest child,

1–3 years; Hispanic, Caucasian or African-American ethnicity;

English literacy; eligibility for WICor Medicaid; and income< 200%of the federal poverty index. The ethnicity of the participants was

63% Hispanic, 19% African-American and 18% Caucasian.The nature

of the risks and benefits of the study were explained to the partic-

ipants, and informed consent was given. The Institutional Review

Board of The University of Texas at Austin approved this study.

Anthropometric measurements

Heightwas measured in inchesusing a stadiometer (Perspective

Enterprises, Portage, MI). Weight was determined with an elec-

tronic scale (Model HS-100-A, Fairbanks Scales, St. Johnsbury, VT).

Waistcircumference was obtained by positioninga measuring tape

around the abdomen at the highest lateral border on the right

ilial crest, as recommended by NHANES III (National Heart Lung

and Blood Institute 1998). Percent body fat was estimated by bio-

electric impedance(Model TBF-300A,Tanita Corporation, Arlington

Heights, IL). Body mass index (BMI, kg/m2) wascalculated by divid-

ing body weight in kilograms by height in meters squared. Systolic

and diastolicblood pressures were measured with sphygmamome-

ter (Model Marshall Medical, Placerville, CA).

Biochemical measurements

Plasmazinc was determined by a flame atomic absorption spec-

trophotometer (5100PC, Perkin Elmer Corporation, Shelton, CT)

[30]. Plasma glucose was analyzed by a glucometer (Glucome-

ter Elite, Bayer Corporation, Elkhart, IN). Plasma concentrations

of insulin and leptin were measured using a commercial enzyme-

linked immunoabsorbent assay kit (ALPCO, Windham, NH). Lipids,

including triglycerides, total and HDL cholesterol were obtained

enzymatically (Sigma Diagnostics Inc., St. Louis, MO). The Freid-

wald formula was used to estimate LDL cholesterol [31]. Insulin

sensitivity was calculated by the Quicki method [32] and insulin

resistance was computed by the homoeostatic model assessment

method (HOMA) [33]. The prevalence of metabolic syndrome was

evaluated in these mothers, based on the criteria given in the NCEP

ATP III panel [4].

Statistical analyses

Statistical package for social sciences (SPSS, version 10.0; SPSS

Inc., Chicago, USA) was used for all statistical analyses. Descrip-

tives (means, standard deviation and range) were computed for

both anthropometric and biochemical parameters. Relationships

between zinc and other metabolic syndrome risk factors were

tested using Pearson’s correlation between anthropometric and

biochemical measurements. Analysis of variance (ANOVA) with

post hoc Scheffe analysis was used to determine significant differ-

ences between three or more subject groups. All differences were

considered to be significant at p < 0.05.

Results

At pre-study, all mothers were premenopausal and their ages

ranged from 18 to 42 years (mean 27.6±0.6 years). Based on

BMI, 22% were overweight (BMI 25–29.99 kg/m2), 56% obese (BMI

30–39.99kg/m2) and 22% were morbidly obese (BMI≥40kg/m2).

At baseline, plasma zinc was low in 39% (<0.8 mg/l) and within

normal values in 46% (0.8–1.2 mg/l) of mothers. Mothers in both

groups(lowvs. normalzinc) hadcomparableBMIsat thestart ofthe

study. For metabolic syndrome risk factors, 88%had elevated waist

circumference; 67%, high fasting glucose; 29%, enhanced triglyc-

erides; and 88%, low HDL cholesterol.

Moderate weight loss increased plasma zinc following

intervention in low-income women

At the start of this study, 39% of mothers had low plasma zinc

(<0.8mg/dl).After the 8-week intervention period, plasma zincrose

by 22% during the intervention. At the end of the study, only 5%

of the mothers continued to exhibit low plasma zinc. Weight loss

was similar in mothers with low zinc at baseline versus those who

exhibited normal zinc at baseline.

Moderate weight loss improved metabolic syndrome risk factors

following intervention in low-income women

A moderate weight loss of ∼2.3kg (2.5%) was observed in moth-

ers after an 8-week intervention program. This weight loss ranged

from 0 to 11.5 kg. Pre- and post-study characteristics (Table 1)









V.S. Voruganti et al. / Journal of Trace Elements in Medicine and Biology xxx (2010) xxx–xxx 3

Table 1

Pre- and post-study descriptive characteristics of participating mothers.

Characteristics Pre-studya Post-studya P -value

BMIb (kg/m2) 35.4 ± 0.8a 34.6 ± 0.8a <0.001

Body fat (%) 43.2 ± 0.7 42.1 ± 0.7 <0.001

Leptin (ng/ml) 18.3 ± 1.09 18.9 ± 1.1 NS

Insulin (IU/l) 13.0 ± 1.2 14.7 ± 01.6 NS

HOMAc IR 4.0 ± 0.7 3.6 ± 0.42 NS

Cholesterol (mg/dl)

Total 166 ± 4.1 158 ± 3.3 <0.05LDLd 103 ± 4.1 87.2 ± 4.4 <0.01

Zinc (mg/l) 0.85 ± 0.04 1.04 ± 0.02 <0.001

Metabolic syndrome risk factors

Waist circumference (cm) 107 ± 2.0 104.7 ± 1.9 <0.001

Glucose (mg/dl) 112 ± 4.8 106.8 ± 4.9 NS

Triglycerides (mg/dl) 123.7 ± 7.0 115.8 ± 3.3 NS

HDLe cholesterol (mg/dl) 38.7 ± 1.2 52.3 ± 3.4 <0.0001

Blood pressure (mmHg)

Systolic 118 ± 1.4 116 ± 1.4 NS

Diastolic 77.6 ± 1.1 75.7 ± 0.9 <0.05

a Mean±SEM.b Body mass index.c Homeostatic model assessment method (Mathews et al. [33]).d Low-density lipoprotein.e High-density lipoprotein.

show significant decreases in BMI, percent body fat, BMI, total, and

LDL cholesterol, waist circumference and diastolic blood pressure

and increase in HDL cholesterol and plasma zinc. No change was

observed in plasma leptin, insulin or systolic blood pressure. The

decreases in plasma glucose and triglyceride following intervention

were not statistically significant. At the pre-intervention stage, 53%

of the participants had metabolic syndrome; whereas, only 19% of

the mothers exhibited this syndrome at post-intervention.

Changes in body fat were associated negatively with changes in

plasma zinc

The relationship between changesin % body fatand plasma zinc

is depicted in Fig. 1. These data show a decrease of 2.4% in body fat,

which was associated with an increase in circulating zinc (r 2 =−

0.28, p < 0.05).

Fig. 1. Relationship of changes in % body fat and changes in plasma zinc.

Fig. 2. Relationship of changes in dietary intakes of energy and zinc.

Changes in dietary zinc were positively associated with reduction

in energy intake

Energy and zinc intakes were evaluated pre- and post-

intervention. Mean (SE) energy intake declined from 2007 (49 kcal

at week 0 to 1465 [46] kcal, p < 0.001) at week 8. Concomitantly,

dietary zinc decreased by ∼20% during the 8-week period [mean

(SE) at week 0 = 9.22 (0.3) mg] as compared to week 8 [mean

(SE) = 7.43 (0.3)mg] p < 0.0001. The reduction in energy intake

was significantly correlated with change in dietary zinc (r 2 =0.42,

p < 0.0001) (Fig. 2).

Mothers differed in their response to weight loss based on their

baseline plasma zinc status

Fig. 3 depicts the prevalence of metabolic syndrome risk factors

at pre- and post-study, in mothers with low and normal zinc lev-

elsat baseline. At baseline, mothers with lowzinc exhibitedgreater

waist circumference andpercent body fat, andhigher plasmalevels

of glucose, insulin, triglycerides and LDL cholesterol as compared

to those with normalzinc; howeverthese differences were not sta-

tistically significant ( p > 0.05). Although weight loss was similar in

both groups, mothers with lowzincat baseline showeda significant

decrease in waist circumference and plasma glucose than mothers

who had normal zinc at baseline. Plasma zinc levels increased in

both groups; interestingly the increase was more pronounced in

mothers with low baseline zinc than others. Percent body fat, body

mass index and HDL cholesterol showed similar improvements inboth groups (Fig. 3).

Discussion

A modest reduction in weight and metabolic risk factors is

knownto dramatically enhance well-beingand improve health sta-

tus [34]. In addition, moderate weight loss can improve glycemic

control and insulin sensitivity in type 2 diabetic patients and pre-

vent the progression to diabetes in patients who are at high risk.

In the current study, small weight loss normalized plasma zinc and

diminished risk factors for metabolic syndrome. Specifically, lower

zinc levels at pre-intervention were associated with greater post-

intervention decreases in plasma glucose and blood pressure, as

well as increased HDL and plasma zinc. This response is encourag-










Fig. 3. Metabolic risk factors at pre-and post-study in mothers withbaselinelow and normal plasma zinc.Black and whitebars indicate pre-and post-study measurements,

respectively.

ing, as many individuals findit difficult to lose substantial amounts

of weight.

Metabolic syndrome is a complex, multifactorial disorder, with

obesity being the primary risk factor. Thus weight loss is the first

and foremost therapy that should be adopted for treating this

condition, followed by treatment of individual components of the

syndrome [35]. In the present study a modest weight loss of 2.5%

occurred. However, this minimal weightloss reduced the incidence









V.S. Voruganti et al. / Journal of Trace Elements in Medicine and Biology xxx (2010) xxx–xxx 5

of metabolic syndrome by one-third. Beneficial changes also were

observed in individual risk factors such as waist circumference, cir-

culating glucose, triglycerides and HDL cholesterol. For comparison

the prevalence of metabolic syndrome was decreased by 59% after

a weight loss of 8.2 kg (∼8%) in older obese adults [36]. However,

more modest weight losses also have been reported to improve

metabolic risk factors. A study conducted by Lofgren et al. [37]

found that a 5% weight loss reversed metabolic syndrome in seven

out of eight premenopausal women.

Low plasma zinc levels have been observed in obese [19,28],

type 2 diabetic [22] and obese-type 2 diabetic individuals [14,38].

Similarly, low plasma zinc (<0.8 mg/dl) was observed in 39% of the

overweight/obese women in the current study. Ninety percent of

these values returned to normal with weight loss. Woodhouse et

al. [19] also found a rise in plasma zinc (7%), with a 5.9% decrease

in weight of men and women fed a high dairy hypocaloric diet for

12 weeks. Similarly, Di Martino et al. [17] reported elevated plasma

zinc of 16% in men and 33% in women whose BMI had declined by

an average of 15%decline. In a Japanese weight loss program based

on hypocaloric diets, weight loss was associated with increased

plasma zinc [28]. The same response has been observed in obese

children and adolescents; plasma zinc escalated by 12% after 10

weeks of consuming a very low calorie diet [15]. In contrast, one

1987 study by Brighenti et al. did not show any improvement inplasma zinc status with weight loss in obese subjects [39]. In the

present study, plasma zinc was elevated by about 9% for every 1%

of the body weightlost.Whether or notplasma zinc levels returnto

low baseline concentrations with time merits further investigation.

In this paper, an increase in plasma zinc was associated with a

decrease in % body fat. This increase was not reflective of diet, as

dietary levels of zinc declined by 20%; this decline presumably was

due to the reduction in calories that occurred as a consequence of

dieting. In another study, women judo athletes undergoing physi-

cal training, plasma zinc was inversely associated with % body fat

as also observed in our research [40]. In a cross-sectional study

in Indian men, higher body fat percent was associated with lower

concentrations of plasma zinc [41]. In normal weight humans, zinc

deficiency also was observed in conjunction with low concentra-tions of leptin, a hormone produced in adipose tissue. In obese men

(n =5), Chen et al. [42] reported an inverse relationship between

levels of zinc and leptin. In contrast, a positive relationship was

reported between plasma zinc and leptin in male athletes [43].

However, no association was observed between plasma levelof lep-

tin and zinc in the current study. These conflicting results may be

due to differences in sample size, age, sex and type of adiposityand

physical activity.

Disturbances in zincconcentrations(both circulating and tissue)

have been reported in obesity and insulin resistance. In a random-

ized placebo-controlled, cross-over studyin 60 obese children, zinc

supplementation significantly attenuated plasma levels of glucose

and insulin and HOMA [44]. Assiri et al. observed that women with

metabolic syndrome had lower levels of plasma zinc, as comparedto women without metabolic syndrome [45]. On the other hand,

men and women with metabolic syndrome were found to be at a

higher risk for zinc deficiency, although no statistical correlation

was found between plasma zinc and metabolic syndrome compo-

nents [46].

In the current study women with low plasma zinc had higher

body weight, waist circumference, plasma glucose and % body

fat than those with normal levels of this trace mineral. This is

notable since all these traits are directly or indirectly related to

metabolic syndrome. Improvements in these metabolic risk fac-

tors were more pronounced in women with low zinc than those

with normal zinc, despite similar reductions in weight. In addition,

womenwith lower plasma zinc concentration at baseline exhibited

greater increases in plasmazinc. This outcome suggests that differ-

ent homeostatic adjustments in zinc metabolism maybe dependent

on initial zinc status or related factors, rather than just weight loss

alone.

A limitation is the short duration of the present research. In a

more extended period of time, it would have been advantageous

to confirm the research findings but this was precluded by cost

and subject availability. Although studies reported here have used

plasma zinc to assess body zinc status, its reliability as an indicator

of zinc status is subject to debate. Nonetheless, a systematic review

of methods of zinc assessment in humans concluded that plasma

zinc, if collected and stored properly, could be a reliable indicator

of body zinc status [47]. Thus the changes observed in plasma zinc

might be a reflection of changes in body zinc status [48].

In summary, at pre-study 53% of the overweight or obese low-

income women exhibited risk factors for metabolic syndrome, and

39%had lowconcentrations of plasmazinc.The circulating levelsof

zinc, as well as the metabolic syndrome components, showed sig-

nificant improvements in overweightor obeselow-income women.

These results suggest that even a moderate weight loss can confer

health benefits, irrespective of the initial weight status.

Acknowledgement

This research is supported by a grant from the Texas Higher

Education Coordinating Board, Austin, TX (UTA #00-377).

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