Original Research
Effects of Various Forms of Calcium on Body Weight and Bone Turnover Markers in Women Participating in a Weight Loss Program Ginger Wagner, MS, RD, Shirley Kindrick, PhD, RD, Steven Hertzler, PhD, RD, Robert A. DiSilvestro, PhD Human Nutrition, The Ohio State University (G.W., S.H., R.A.D.), The Center for Wellness and Prevention, The Ohio State University Medical Center (S.K.), Columbus, Ohio Key words: calcium, weight loss, fat loss, supplements, milk, women, bone turnover markers Objective: This study examined the effects of calcium intake on body weight, body fat, and markers of bone turnover in pre-menopausal adult women undergoing a 12 week weight loss program of diet and exercise. Methods: Subjects were prescribed a 12 week diet with a 500 Kcal restriction containing about 750 mg calcium/day, exercised 3 times/week, and were given either placebo capsules, capsules of calcium lactate or calcium phosphate (daily dose about 800 mg calcium), or low fat milk (daily dose about 800 mg calcium). Subjects completed and returned daily diet diaries weekly. Results: Daily calcium intake in mg from diet records ⫹ supplement assignment was: 788 ⫾ 175 (placebo), 1698 ⫾ 210 (Ca lactate), 1566 ⫾ 250 (Ca phosphate), 1514 ⫾ 225 (milk)(no significant differences among the calcium and milk groups). Each group had statistically significant changes in body weight (p ⬍ 0.01), but there were no significant differences among groups for the weight loss: 5.8 ⫾ 0.8 kg (placebo), 4.1 ⫾ 0.7 kg (Ca lactate), 5.4 ⫾ 1.3 kg (Ca phosphate), 4.2 ⫾ 0.8 kg (milk). Body fat was changed significantly in each group (p ⬍ 0.01), with milk group showing a little less change than the other groups. Serum bone specific alkaline phophatase activity, a bone synthesis marker, increased similarly in all groups (p ⬍ 0.001 within groups, no significance for changes among groups). In contrast, the Ca lactate group, but not other groups, had a drop in urine values for alpha helical peptide, a bone resorption marker (p ⬍ 0.05). Conclusion: For the conditions of this study, increased calcium intake, by supplement or milk, did not enhance loss of body weight or fat, though calcium lactate supplementation lowered values for a marker of bone degradation.
INTRODUCTION
In some studies of calcium effects on bone health or blood pressure, retrospective analysis shows an apparent effect on body weight [1,6 – 8]. In animal studies, variations in calcium intake can alter body weight [rev in 1,3]. Despite such observations, calcium is not generally accepted as a weight loss aid. One reason is that diet history analysis does not always distinguish cause and effect relationships from coincidental ones. Moreover, not all survey studies have found relationships between calcium or dairy and body weight [9,10], though some of these studies may not have examined a wide enough range of calcium intakes. On the other
Overweight conditions continue to be a major problem in many countries. Some research has suggested that body weight, especially as affected by body fat, can respond to calcium in supplements and dairy products, with the latter possibly being more effective. This contention has been based on the following observations: Calcium has actions in the body that could help with weight loss [1–3]. Certain diet history analysis show an inverse relationship of calcium or dairy intake to body weight and/or fat [1–5].
Address reprint requests to: Robert A DiSilvestro, Human Nutrition, The Ohio State University, 345 Campbell Hall, 1787 Neil Ave, Columbus, OH 43210-1295. E-mail:
[email protected] Presented in part at Experimental Biology 2005, San Diego, CA, April, 2005.
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Calcium and Weight Loss hand, it’s not clear that studies with negative results examine ranges that are very different from those of the positive result studies. To address theses issues further, calcium-weight loss intervention studies have been done. Zemel’s group [11,12] reports that dairy intake and/or calcium supplements enhance body weight and body fat losses, with the dairy intervention having the greater effect. In contrast, two other intervention studies, one using dairy products and one using calcium supplements, do not report a calcium effect [13,14]. The design specifics for the intervention studies differ in a number of ways. For example, in the dairy study with negative results [13], subjects were not necessarily overweight and no intentional energy intake restriction was required. In contrast, other studies [11,12,14] used energy intake restriction in overweight subjects. A new intervention study was done that differs from the previous ones in several ways: An exercise program was incorporated into the weight loss plan. More than one type of calcium supplement was examined. One of the calcium supplements was calcium lactate, a very well absorbed complex [rev in 15]. The dairy intervention for the high calcium intake was strictly low fat milk, which for many health conscious people, is the dairy product chosen most often. Bone turnover markers were used to evaluate the general impact of calcium intake on measures responsive to calcium functional status. The last issue is important both to monitor calcium status and bone metabolism. In the latter regard, there is some evidence that calcium intake can partly counteract the bone loss that can be associated with weight loss [16]. Possibly, the combination of exercise plus heightened calcium intake can further slow or reverse this problem.
MATERIALS AND METHODS Subjects and Treatments This study protocol was approved by the Biomedical Institutional Review Board (IRB) of The Ohio State University. All
subjects signed an IRB approved consent form. Subjects were pre-menopausal adult women, (mean and SD for ages given in Table 1) years who were overweight to severely obese (BMI: 26 – 41 kg/m2). Exclusion criteria included pregnancy (checked by urine pregnancy test kit) and a fasting serum glucose above 100 mg/dl (tested with an ACCU-CHEK® blood glucose monitor from Roche Diagnostics, Indianapolis, IN). Other exclusion criteria, based on a pre-study questionnaire, were smoking, irregular menses, health problems that influenced the tendency to gain or lose weight (i.e. diabetes mellitus, glucose intolerance, and cancer), alcohol consumption over one serving/day, and medications that interfere with bone turnover, nutrient absorption, metabolism, excretion, or gastric motility (ie contraceptives, corticosteroids, hormone replacements, acetaminophen, salicylates, and diuretics). Subjects were not screened for a specific pre-study calcium intake. This study employed a randomized, double-masked controlled intervention lasting 12 weeks. All subjects followed a diet with a 500 Kcal deficit, and were required to exercise at The Ohio State University Medical Center, Center for Wellness & Prevention., three times per week, and were weighed once per week. Target energy intake was calculated for about half the subjects based on resting metabolic rate using a MedGem® device (HealtheTech, Golden, CO). Due to mechanical failure of the device half way through the recruitment process, this procedure was replaced by the Harris Benedict equation for women [17]: 655 ⫹ (9.6 ⫻ body weight in kg) ⫹ (1.8 ⫻ height in cm) ⫺ (4.7 ⫻ age). The resulting energy was multiplied by an activity factor of 1.2, then reduced by 500 Kcal. For diet instruction, each subject consulted individually with a registered dietitian with weekly feedback and followups. The protein, carbohydrate, and fat recommendations were based on the American Heart Association guidelines [18] utilizing the exchange system. Subjects received a “gadget” list to help them with serving sizes (ie common items related to serving sizes). For each day of participation, subjects kept a food diary which they turned in weekly. Diet records were monitored by the dietitian for compliance for total energy, micronutrient distribution, and calcium. Verbal and/or written feedback was given to all subjects with individual counseling
Table 1. Subject Characteristics for Each of the Four Study Treatments
Age mean ⫾ SE range Weight (lbs) mean ⫾ SE range BMI (kg/m2) mean ⫾ SE range
Ca Lactate n ⫽ 12
Ca Phosphate n ⫽ 16
Milk n ⫽ 17
Placebo n ⫽ 13
40.2 ⫾ 1.8 25–47
41.6 ⫾ 1.6 25–48
37.6 ⫾ 2.2 19–53
36.0 ⫾ 2.2 22–46
196.2 ⫾ 5.8 160–231
196.7 ⫾ 8.9 143–261
203.1 ⫾ 7.3 153–255
190.7 ⫾ 11.3 148–298
33.3 ⫾ .75 29.6–37.5
33.4 ⫾ 1.4 25–42.8
33.7 ⫾ 1.0 29–42.5
32.4 ⫾ 1.5 26.4–44.8
No statistical differences were found among the treatment groups for age, height, weight, or BMI (one-way ANOVA, p ⬎ 0.05 for all comparisons).
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Calcium and Weight Loss also given to subjects having trouble following the dietary guidelines. If a subject was unable to comply with any of the requirements within approximately 3 weeks from beginning the study, she was excluded from the study. Dietary calcium intake from the diet alone was designed to contain approximately 750 mg/day, which is about the average calcium intake reported in one diet survey report [19]. All groups, except the milk group, consumed enough dairy to produce a dietary intake 750 mg of daily calcium. The dairy choices were 1% milk, light yogurt and/or cheese. The milk intervention group had that same dairy intake with the same choices, but also added extra dairy servings of 1% milk. These extra servings provided additional calcium equal to that obtained by the calcium supplement groups. To compensate for the extra dairy (about 215 Kcal), there was the removal of 1 fruit, 1 medium fat meat, and 1 starch exchange. All subjects were instructed to abstain from calcium supplements not provided as part of the study, and to avoid calcium fortified foods such as fortified orange juice or certain breakfast cereals. Subjects were randomly assigned to one of four treatments: calcium lactate (supplied by Purac of America Inc, Lincolnshire, IL), calcium phosphate (also supplied by Purac), placebo (cellulose), or milk. Assignment was by a blind drawing of a treatment for each subject. Initially, 20 –22 subjects were recruited per treatment group, though exclusions and drop outs during the study reduced the numbers (see Results section). For the first three treatments, subjects consumed 6 capsules 2 times per day, with the calcium supplements supplying about 800 mg of calcium per day (which combined with diet, should have produced a daily calcium intake of about 1550 mg). For the milk treatment, subjects consumed 10 oz of 1% fat milk twice per day for a total of 800 mg calcium. The subjects in the milk group were told that they would be given either milk or a non-dairy milk-like placebo beverage, though all received the milk (provided weekly in a non-labeled plastic container). For those in the milk group, energy intake was decreased by approximately 215 Kcals to account for the additional energy provided by the beverage. The original diet prescription was therefore lessened by 1 fruit, 1 medium fat meat, and 1 starch exchange. Exercise sessions were of 45 min to 1 h duration and were a combination of resistance and aerobic exercise. Each session was supervised by project personnel. Before the diet and exercise intervention commenced, baseline blood and urine samples were taken, and body weight and percent body fat was measured. The samplings and measurements were repeated after the 12 week intervention. Blood and urine samples were taken in the morning following an overnight fast, with the pre- and post-treatment samples taken at about the same time of day for each individual subject.
Analytical Methods Body weight was taken weekly from week 0 through the end of week 12. Body composition was determined via use of bioelectrical impedance (BIA) and the RJL Systems online
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body composition assessment software (RJL Systems, Inc, Clinton Twp, MI). The bone metabolism markers serum bone alkaline phosphatase, and urinary helical peptide were measured pre- and post-treatment by Metra assay kits from Quidel Inc. (San Diego, CA). Urine values were expressed per mg creatinine, which was determined using a Metra assay kit from Quidel.
Statistical Analysis Statistical analysis was done using NCSS 2001 (NCSS Computing, Kayesville, UT) with significance set at p ⬍ 0.05. For starting general subject characteristics (ie age), comparison among groups were done by ANOVA. For most other measures, pre-treatment to post-treatment changes were compared by paired t-test. If significant changes were found, the changes for each group were compared to the others by ANOVA, and if appropriate, followed by Tukey-Kramer test. For helical peptide, where the data was not distributed normally, data was square route transformed, then pre-treatment to post-treatment changes compared by paired t-test, and changes for each group compared to the others by ANCOVA and Fisher’s LSD
RESULTS A total of 58 women completed participation. Some baseline characteristics are given in Table 1. According to one-way ANOVA, no statistical differences were found among treatment groups for age, height, weight, or BMI. Compliance to the exercise program was confirmed by each workout being observed by study personnel. Compliance was about 90% or better by all project finishers. Based on diet records, mean weekly Kcal intakes were acceptable in all finishers. Kcal intake did not differ significantly among groups by two-way ANOVA: 1372 ⫾ 154 (placebo), 1452 ⫾ 301 (Ca lactate), 1360 ⫾ 270 (Ca phosphate), 1477 ⫾ 229 mg (milk). Daily calcium intake from diet records ⫹ supplement assignment was; 788 ⫾ 175 mg (placebo), 1698 ⫾ 210 mg (Ca lactate), 1566 ⫾ 250 mg (Ca phosphate), 1514 ⫾ 225 mg (milk). There were no significant differences among the calcium and milk groups, though each of these groups differed from the placebo group (one-way ANOVA ⫹ LSD). Based on unused supplement return, no finishers showed indication of more than 2 day’s noncompliance. All groups, including placebo, displayed significant body weight loss from pre- to post-treatment by paired t-test (Fig. 1). The mean changes in body weight from pre- to post-treatment did not differ significantly between groups by one-way ANOVA (Fig. 2). After a re-analysis of the data to account for pre-treatment body weight values, there was still no significant difference among the treatment groups by ANCOVA (p⬎ 0.05). The before and after 12 week trends for body fat (Figs. 3
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Fig. 1. Changes in body weight (BW) from pre- to post treatment with SE bars. *Statistically significant change from pre-values by paired t-test (p ⬍ 0.01).
Fig. 4. Average changes in percent body fat (pBF) with SE bars. *Significant difference between groups with Tukey-Kramer test (p ⬍ 0.05).
post-treatment, within group change (Fig. 6). Similarly, for inter-group changes in helical peptide values, only the calcium lactate group was significantly different from the other groups (Fig. 7).
DISCUSSION Fig. 2. Mean change in body weight (BW) post treatment with SE bars. No statistically significant difference was noted for change in BW for any treatment group versus the others (one-way ANOVA).
Fig. 3. Pre- and Post-percent body fat (pBF) with SE bars. *Statistically significant change from pre-values by paired t-test (p ⬍ 0.01).
and 4) were mostly similar to those of body weight in that all groups lost fat, and there were generally no differences in the losses between groups. The one exception to this pattern was that the milk group lost significantly less fat than the placebo group. For serum bone alkaline phosphatase, a marker of bone synthesis [15], all groups showed a significant increase (Fig. 5). For group comparisons of pre-treatment to post-treatment changes, there were no significant differences between treatment groups (one-way ANOVA, data not shown). For urinary alpha helical peptide, which is a marker of bone resorption [20], there was not a consistent pattern between treatment groups. Also, data was not normally distributed based on any of several tests for normality including Shapiro-Wilk. Transformation of helical peptide data using square route created normally distributed data. For normalized data, only the calcium lactate group showed a statistically significant pre-treatment to
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This study is the third intervention that has not shown an effect of manipulated calcium intake on weight loss [13,14]. Unlike one of the previous studies [13], which examined people with normal weights and self selected energy intakes, the present study used an energy intake restriction in overweight to obese individuals. In addition, unlike either of the previous two studies [13,14], the present study used an exercise intervention. Exercise training not only directly affects Calorie expenditure, but may also make calcium balance more positive [21,22]. However, information on the extent to which calcium absorption responds to different training intensities and durations is still very limited. In another deviation from the previous two studies [13,14], the present work showed that a calcium treatment could affect a measure related to a calcium function (a bone degradation marker) without affecting weight loss. This implies that changing calcium functional status does not guarantee an effect on weight loss. Furthermore, this effect on functional status, which related to bone health, raised the possibility that calcium plus exercise can have beneficial effects on bone health during weight loss. The lack of effect of any groups versus placebo for weight loss was not likely due to insufficient subject number. Prior to the present study, a power calculation was done based on the intervention study of Zemel et al [11]. In that study, the percent weight loss and variation for the diary intervention ⫹ moderate Kcal restriction was compared to the results for the placebo ⫹ moderate Kcal restriction. A power value of 0.999 was calculated for 12 subjects per group, which is slightly above the mean number per group from the Zemel et al study [11], and below the number of finishers per group in the present study. For the present study, if the minimal desired change is designated as the biggest mean difference found between the placebo
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Fig. 5. Pre- and post-treatment levels of BAP with SE bars. *Statistically significant increase in BAP from pre values with paired t-test (p ⬍ 0.001).
Fig. 6. Pre and post (square route transformed) levels of helical peptide (HP). *Statistically significant change from pre value by paired t-test (p ⫽ 0.02).
Fig. 7. Mean changes (square route transformed) in HP with SE bars. *Statistically different mean change compared to the milk or placebo groups by ANCOVA and Fisher’s LSD (p ⫽ 0.025).
and any calcium group, and the larger of the two deviations is used, and the smaller subject number is used, a power value of 1.00 is obtained even for p ⫽ 0.01. A still unresolved issue is why there are conflicting results concerning calcium and weight loss. A simple explanation may be that an effect on weight loss requires a swing from a very low calcium intake, such as 400 –500 mg/day, to a considerably higher calcium intake. In support of this concept, 400 –500 mg calcium/day is the lower intake range for the intervention studies reporting a calcium or dairy intervention effect on weight loss [11,12]. In contrast, the current study and the other two intervention studies [13,14] not showing a calcium-weight loss effect set the low calcium intake at over 700 mg/day during the intervention stage. On the other hand, in the present study, even without limiting the low calcium intake to under 500 mg/day, calcium lactate supplementation changed values for an indicator of calcium functional status without impacting weight loss. Even so, one could argue that an even bigger impact on
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calcium status is needed to affect weight loss (such as what happens when intake is increased from a starting level of only 400 –500 mg of calcium per day). This conclusion, though interesting, cannot be made yet as no single study has directly compared graded levels of calcium intakes. Currently, one research team accounts for all the calciumweight loss intervention studies that include a low calcium intake group at 400 –500 mg/day [11,12]. Thus, other variations in subject traits or practices could distinguish these studies from others done so far. If calcium intakes have to be increased from 400 –500 mg/day to a much higher intake to see an effect on body weight, then this limits how many people may benefit weight-wise by increasing their calcium intake. Another possible source of study design variations could be calcium intake of the subjects prior to enrollment into the studies. In the present study, there was no screening for a specific pre-treatment calcium intake. Despite this fact, there were no significant differences between groups for the pretreatment bone specific alkaline phosphatase activities or helical peptide values (one-way ANOVA). Although calcium intake is not the only factor in bone metabolism, the similarity in starting values for bone metabolism markers suggests that none of the treatment groups had an unusually large mean calcium intake. On the other hand, this does not rule out that previous calcium intake was too high in all groups to see an effect of a 12 week calcium intervention. In the present study, subjects in each group lost about the amount of weight predicted from the diet-exercise intervention alone. Thus, compliance to the weight loss program appeared good. It has been speculated [23] that compliance variance may contribute to some observed enhancement of weight loss by a dairy intervention. It is not clear why in the present study, the milk group lost less fat than the placebo group. Possibly, food substitutions employed by the milk group in the present study impacted the diet in some way that slowed fat loss. Another unresolved issue is why calcium lactate but not milk or calcium phosphate affected values for a marker of bone resorption. Calcium lactate does have excellent absorption properties, though calcium phosphate and milk calcium are also supposed to be well absorbed [rev in 15]. It is possible that calcium lactate has the best absorption and/or utilization of the three calcium sources used here. Along these lines, in a rat study [15], calcium lactate shows better bone stimulating activity than calcium carbonate or citrate. Although this rat study does not include milk or calcium phosphate, it does raise the possibility that calcium lactate may be especially good at producing bone metabolism benefits. It can also be noted that giving calcium lactate to infants produces high body calcium retention [24]. In contrast, in a study of weight loss in overweight people, a high dairy diet shows some difference versus a low dairy diet for markers of bone turnover [16]. However, in this study, the calcium intakes in the low and high dairy groups are lower and higher, respectively, versus the present study’s
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10.
11.
CONCLUSION None of the calcium sources tested here accelerated loss of body weight or of fat. Despite this lack of effect, it is possible that calcium may enhance weight loss in certain, as of yet undefined circumstances. The present study did show that an intervention with calcium lactate, but not three other calcium sources, had a beneficial effect on a marker for bone resorption in women participating in a weight loss program.
12.
ACKNOWLEDGEMENTS
15.
This work was supported by a grant from Purac of America Inc. The authors thank Ellis Hogetoorn of Purac for help with several practical aspects of the project design. The authors also thank Elizabeth Joseph for excellent technical assistance, and thank the following for assistance with subject exercise monitoring: Nicole Wood, Rachelle Basalla, Emily Dy, and Bethany Crawford.
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Received July 25, 2005; Revision accepted August 17, 2006.
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