Obese individuals are more likely to have either lower blood concentrations or lower bioavailability of minerals and/or vitamins. However, there are limited data on the effects of nutritional supplementation on body weight (BW) control, energy homeostasis and lipid metabolism in obese subjects.
The purpose of this study is to evaluate the effects of supplementation with multivitamin and multimineral on adiposity, energy expenditure and lipid profiles in obese Chinese women.
A total of 96 obese Chinese women (body mass index (BMI) 28 kg m−2) aged 18–55 years participated in a 26-week randomized, double-blind, placebo-controlled intervention study. Subjects were randomized into three groups, receiving either one tablet of multivitamin and mineral supplement (MMS), or calcium 162 mg (Calcium) or identical placebo daily during the study period. BW, BMI, waist circumference (WC), fat mass (FM), fat-free mass, resting energy expenditure (REE), respiratory quotient (RQ), blood pressure, fasting plasma glucose and serum insulin, total cholesterol (TC), low- and high-density lipoprotein-cholesterol (LDL-C and HDL-C) and triglycerides (TGs) were measured at baseline and 26 weeks.
A total of 87 subjects completed the study. After 26 weeks, compared with the placebo group, the MMS group had significantly lower BW, BMI, FM, TC and LDL-C, significantly higher REE and HDL-C, as well as a borderline significant trend of lower RQ (P=0.053) and WC (P=0.071). The calcium group also had significantly higher HDL-C and lower LDL-C levels compared with the placebo group.
The results suggest that, in obese individuals, multivitamin and mineral supplementation could reduce BW and fatness and improve serum lipid profiles, possibly through increased energy expenditure and fat oxidation. Supplementation of calcium alone (162 mg per day) only improved lipid profiles.
The past couple of decades have witnessed a worldwide epidemic of obesity which poses a major threat to human health, especially in Western societies.1 The WHO (World Health Organization) estimated that worldwide there are more than 1 billion overweight adults, and among them 300 million are obese.2 The rapid economic development in China has been accompanied by the adoption of Western style dietary and physical activity behaviors.3 The 2002 Chinese National Nutrition Survey showed that 22.8% of adult Chinese were overweight and 7.1% obese (body mass index (BMI) ⩾24 and ⩾28 kg m−2, respectively) according to the Chinese standard.4 Furthermore, obesity is strongly associated with hyperlipemia, one of the important risk factors of cardiovascular disease.4, 5
Previous studies have shown that vitamins and minerals have an important role in energy and blood lipid metabolism6, 7, 8, 9 through several mechanisms.10, 11, 12, 13 Obese individuals are more likely to have either lower blood concentrations or lower bioavailability of minerals and/or vitamins.14, 15, 16, 17 However, there are limited data on the effect of multivitamin and mineral supplementation on body weight (BW), energy expenditure and lipid profiles in obese subjects. A long-term observational cohort study with 15 655 American men and women showed that overweight or obese subjects (n=4708) who took multivitamin, vitamin B6, vitamin B12 or chromium supplements gained less weight over the 8–12-year follow-up period than did those who did not take these supplements.18 In our previous animal study on obese rats,19 supplementation of multivitamins and minerals led to BW loss and improvement in energy metabolism. The aim of this study is to evaluate the effects of supplementation with multivitamin and mineral on BW, energy expenditure and lipid profiles in obese Chinese women over a 26-week intervention period.
Subjects and methods
Obese Chinese women (n=283), aged 18–55 years, whose BMI was >28.0 kg m−2 recommended by the WGOC (Working Group on Obesity in China) as the cutoff point for obesity,20 were recruited from Harbin, China in 2006. Among them, 96 women who met the inclusion criteria participated in this 26-week randomized, double-blind, placebo-controlled intervention trial. The inclusion criteria were as follows: (1) total cholesterol (TC) ⩾5.2 mmol l−1, or low-density lipoprotein cholesterol (LDL-C) ⩾3.1 mmol l−1, or high-density lipoprotein cholesterol (HDL-C) <0.91 mmol l−1 or triglycerides (TG) ⩾1.7 mmol l−1; (2) stable BW during the past 6 months (change in BMI<0.5 kg m−2); (3) not taking vitamin and mineral supplements in the past 6 months; (4) not taking cholesterol or blood pressure-lowering medications; (5) no history of myocardial infarction, diabetes and not being pregnant; and (6) <2 h per week of regular physical activity.
Informed consent was obtained from all subjects, and the study protocol was approved by the Ethics Committee of the Harbin Medical University.
Eligible subjects were first sorted according to their BMI, and then randomized into three groups with a block size of three, with random numbers generated by SPSS (version 13.01S; Beijing Stats Data Mining Co. Ltd, Beijing, China). To ensure the homogeneity of outcome variables at baseline across the placebo and treatment groups, the homogeneity of BMI and lipids at baseline among the three groups were tested. If the homogeneity of the outcome variables at baseline was not satisfied, then a new set of random number was generated and subjects were randomized again. This process was repeated until the homogeneity of outcome variables among the three groups was reached. During the 26-week intervention period, subjects in the multivitamin and mineral supplement (MMS) group received one tablet daily containing 29 multivitamins and minerals (Centrum, Wyeth Pharmaceutical Co. Ltd, Harbin, China) as shown in Table 1; subjects in the calcium group received one tablet daily containing 162 mg calcium (Dayu Biochemistry Co. Ltd, Shanghai, China); and subjects in the control group received one tablet of identical placebo made of maize starch daily. The tablets used in the three groups were identical in appearance. Compliance of the study subjects was assessed by conducting scheduled telephone interviews weekly, then monthly after 4 weeks and by counting tablets returned at the last visit to the clinic. The study subjects and the study staff remained blinded to the allocation of the three groups during the entire study period.
Demographic data were collected at baseline using a standardized questionnaire. Information collected included age, ethnicity, education, occupation, smoking history, physical activity at work and leisure, health history, medications and menopause status. The level of physical activity during leisure time was defined as follows: 0=none, 1=1–30 min per week, 2=31–60 min per week, 3=61–90 min per week, 4=91–120 min per week and 5=>120 min per week. On the basis of the definition of physical activity in Chinese women,21 the level of physical activity at work was coded as: 1=sedentary, 2=moderate and 3=heavy.
At baseline and 26 weeks, dietary intakes were determined using a semi-quantitative food-frequency questionnaire. The food-frequency questionnaire was developed according to the method proposed by Willett22 and the dietary patterns of the community. The food-frequency questionnaire contained 103 items, including food intakes, alcohol drinks, as well as multivitamin, mineral and calcium supplements. The dietary energy and nutrients intakes were estimated using the Food Nutrition Calculator (V1.60, Chinese CDC, Beijing, China)
At baseline and 26 weeks, height, waist circumference (WC) and BW were measured twice to ±0.1 cm and to ±0.1 kg, while fasting overnight and wearing only underwear. BMI (calculated as BW in kilograms divided by the square of height in meters) was used as a measure of overall adiposity. Fat mass (FM) was measured using the electric impedance method with a body FM analyzer (TANITA TBF-300, Tanita Corporation, Tokyo, Japan), and the fat-free mass was calculated (as BW−FM).
Blood pressure was measured using a standard mercury sphygmomanometer on the right arm after at least 10 min of rest. Mean values were determined from two independent measurements (by the same researcher) at 2-min intervals.
Assessment of resting energy expenditure
Resting energy expenditure (REE) was measured using the pulmonary function and nutrition metabolism testing system (Quark PFT ergo, Cosmed Corporation, Rome, Italy) early in the morning after 12 h of overnight fasting. Subjects were instructed to refrain from taking medications, heavy meals, alcohol, coffee and other caffeine-containing beverages, smoking and doing heavy physical exercise the night before. Indirect calorimetry was performed over a 30-min period using a metabolic measurement system, which consisted of a facemask, a computer with oxygen and carbon dioxide sensors, a sampling pump, barometric sensors and electronics and a turbine connecting the facemask to the computer. The expired air sample was analyzed by the computer. Oxygen consumption and carbon dioxide production were measured in terms of rate per breath at rest for a total of 30 min. Data obtained from the last 10 min of the measurement period were used for the calculation of respiratory quotient (RQ) and REE. The instruments were calibrated before each test.
At baseline and 26 weeks, antecubital venous blood samples were collected after 12 h of overnight fasting. Plasma glucose was measured using the Kyoto blood sugar test meter (Arkray, Inc. Kyoto, Japan) and test strip. Serum TC, HDL-C and TGs were assayed with standard enzymatic colorimetric techniques using commercial kits (Biosino Biotechnology Ltd, Beijing, China) with an auto-analyzer (AUTOLAB PM 4000, AMS Corporation, Rome, Italy). LDL-C was calculated using the equation by Friedewald et al.23 Serum insulin was measured using radioimmunoassay using commercial kit (Diagnostic Systems Laboratories, TX, USA).
Power calculation and statistical analysis
Power calculations were performed before the commencement of the study. A sample size of 28 in each group will be sufficient to detect a difference of 1.8 kg m−2 in BMI between the treatment and the placebo groups assuming a s.d. of 2.4 kg m−2 as reported in this population, at 80% power and 5% level of significance. This number has been increased to 32 per group (total of 96) to allow for a predicted dropout of ∼10%. Statistical analyses were carried out using SPSS. Data were presented as mean±s.d. or percentage as appropriate. Paired samples t-test was used to evaluate the changes in outcome variables before and after intervention in each group. The χ2 test was used to compare categorical variables. Mean levels of continuous study variables at baseline and follow-up among the three groups were compared using ANOVA (analysis of variance) and ANCOVA (analysis of covariance), respectively. In the model of ANCOVA, the covariates included baseline values, age, alcohol consumption, smoking, total physical activity and menopause. The percentage differences between the treatment and the placebo groups in outcome variables at 26 weeks were calculated using covariates-adjusted values as 100 × (treatment group−placebo group)/placebo group for each study variable. All P-values are two-tailed, and a P-value <0.05 was considered significant for all statistical analyses in this study.
Subject retention and compliance
Figure 1 shows the study design and flow of subjects. Among the 96 eligible individuals who participated in the study at baseline, 87 subjects completed the study and 9 participants withdrew because of employment commitments. There were no significant differences in the overall compliance rates among the three groups (92.6% in the placebo group, 93.4% in the MMS group and 93.7% in the calcium group, P=0.85).
Characteristics of subjects in the three groups
At baseline, there were no significant differences between the three groups in age, BW, BMI, daily physical activity level at leisure time and work, as well as the percentage of women who currently smoked, consumed alcohol or reached menopause (Table 2). Dietary nutrient intakes did not differ significantly across the three groups at either baseline or 26 weeks, and the changes in dietary nutrient intakes during the intervention period were not significantly different among the three groups (Table 3).
Effects on BW, WC, fatness, fat-free mass, energy expenditure, blood pressure, fasting plasma glucose, insulin and lipid profiles
The mean levels (±s.d.) of outcome variables at baseline and 26 weeks in the three groups are presented in Table 4. There were no significant differences in baseline values of the outcome variables among the three groups. At 26 weeks, BW, BMI, WC, FM, RQ, TC and LDL-C decreased significantly, and REE and HDL-C increased significantly in the MMS group compared with baseline. The calcium group had significantly lower FM and significantly higher serum HDL-C at 26 weeks compared with baseline. In the placebo group, there were no significant changes in all outcome variables measured over the intervention period.
Figure 2 shows the percentage differences between the treatment and placebo groups at 26 weeks adjusted for baseline values, age, alcohol consumption, smoking history, physical activity and menopause status. At 26 weeks, BW, BMI, FM, systolic blood pressure, diastolic blood pressure, TC and LDL-C were significantly lower, and REE and HDL-C were significantly higher in the MMS group compared with the placebo group. The MMS group also had a borderline significant trend of lower RQ and WC at 26 weeks compared with the placebo group (RQ, P=0.053; WC, P=0.071). The calcium group had significantly higher HDL-C and significantly lower LDL-C compared with the placebo group at 26 weeks.
There were no significant changes in TG, fasting plasma glucose, insulin and fat-free mass in all groups over the intervention period.
Our study showed that the 29-ingredient multivitamin and mineral supplementation over 26 weeks could reduce BW, WC, blood pressure and FM, decrease RQ and increase REE, and had a beneficial effect on lipid profiles, whereas calcium supplementation (162 mg per day) alone could improve lipid profiles only.
Our previous studies on rats12, 24 have shown that dietary calcium could reduce the levels of serum cholesterol, TGs, BW and body fat. The purpose of having the calcium group in this study is to examine whether vitamins and minerals besides calcium also have important roles in reducing BW and improving lipid profile in obese women. Our results showed that supplementation with multivitamin and mineral was more effective than calcium alone in improving these outcomes. It is well recognized that energy intake in obese individuals is higher than in those with normal weight, and vitamins and minerals influence the balance of energy metabolism.10, 11, 12, 13 In addition, obese individuals have been shown to have low blood concentrations or low bioavailability of minerals and/or vitamins.14, 15, 16, 17 Therefore, obese individuals may need greater amounts of vitamins and minerals to cope with the increased burden of energy intake. The findings of this study support the notion that besides calcium, obese individuals need other vitamins and minerals for balancing energy metabolism, controlling BW and for improving lipid profiles.
A study by Major et al.25 assessed the effects of supplementation with multiple vitamins and minerals on BW in obese men and women during a 15-week energy restriction period. After 15 weeks, BW reduced significantly in both the intervention and the placebo groups. However, there were no significant differences between the two groups in changes in BW. In contrast, our study showed that multivitamin and mineral supplementation for 26 weeks could reduce BW and fatness in obese women. The differences in findings could be due to the fact that energy intakes were restricted in the study by Major et al. (prescribed daily energy intake was determined by subtracting 700 kcal from the daily energy expenditure), whereas subjects in our study maintained their usual dietary intakes. As reduced energy intake has a crucial role in controlling BW, it is possible that energy restriction masked the effect of micronutrient-induced weight reduction in the study by Major et al. Our findings are consistent with the results of a 10-year longitudinal study with 15 655 individuals, that is the VITAL (VITamins And Lifestyle) cohort study, which showed that the long-term use of multivitamins, vitamins B6 and B12 and chromium was significantly associated with lower levels of weight gain among overweight or obese men and women (n=4708) over the 10-year follow-up period.18
Obesity is a condition resulting from a chronic imbalance between energy intake and energy expenditure. In addition, other factors that are involved in energy metabolism may also contribute to the development of obesity. These factors include genetic susceptibility (for example, leptin and POMC genes, etc.), hormones (leptin, insulin, FT3, cholecystokinin, etc.), protein (UCP1-UCP3, NPY, lipoprotein lipase, etc.) and mitochondrial function. Previous studies,10 including ours,11 have shown that a number of minerals and vitamins could promote the expressions of UCP1−3 mRNA and improve mitochondrial function.13 The changes in these indexes can upregulate thermogenesis, promote lipolysis and increase energy consumption,26, 27 which contributes to the improvement in energy homeostasis. Therefore, the increased energy expenditure in the MMS group in this study could have resulted from improved energy homeostasis with increased vitamin and mineral intakes from the supplement. In our study, the reduced RQ in the MMS group suggests that MMSs could lead to a higher level of fat oxidation and to a greater use of fat as an energy substrate. This observation along with the findings on increased REE could explain the significant reduction in BW and fatness in the MMS group.
Many in vitro studies and studies in the general population have shown that vitamins and minerals have important roles in improving lipid and lipoprotein metabolism.6, 7, 8, 9 To our knowledge, this study is the first to evaluate the effects of multivitamin and mineral supplementation on lipid profile in obese subjects. Previous studies have shown that calcium,6 chromium and biotin,7 niacin,8 folate, vitamins B6 and B129 could improve lipid metabolism, and that vitamin B1,28 vitamin B6,29 vitamin C,30 calcium,31 magnesium,32 and zinc33 also have important roles in improving hypertension. The beneficial effects on lipid profile and blood pressure observed in this study may be partly attributed to the actions of these micronutrients in conjunction. In addition, weight loss could reduce insulin hypersecretion and increase insulin sensitivity and β-cell function,34 and decrease blood pressure, and thus, improve hyperlipedemia35 and hypertension. Therefore, weight loss in the MMS group during the study period may also partly explain the beneficial effect of nutrition-based intervention on lipids, lipoproteins and blood pressure.
In summary, this randomized, double-blind, placebo-controlled intervention trial showed that the 29-ingredient multivitamin and mineral supplementation has beneficial effects on BW, blood pressure, energy metabolism and lipid profiles in obese Chinese women. These findings have implications for the development of intervention strategies for the prevention of cardiovascular disease and other obesity-related disorders.
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This study was supported by a grant from the Natural Science Foundation of China (30771804). We thank the researchers and medical personnel of Harbin Medical University for their efforts and collaboration in this study. Professor Chang-Hao Sun was responsible for the conception, design and data interpretation of the study and is the principal investigator of the grant for the study; Ying Li and Cheng Wang were responsible for data collection, data analysis, data interpretation and writing of this paper; Kun Zhu was responsible for data interpretation and writing of this paper; Ren-Nan Feng was responsible for performing clinical procedures, data collection and writing of this paper.
The authors declare no conflict of interest.
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Li, Y., Wang, C., Zhu, K. et al. Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women. Int J Obes 34, 1070–1077 (2010). https://doi.org/10.1038/ijo.2010.14
- multivitamin and mineral supplement
- energy expenditure
- lipid profiles
- Chinese women
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