Effects of calcium supplementation on body weight: a meta

Effects of calcium supplementation on body weight: a meta-analysis1,2
Ping Li, Chaonan Fan, Yuanyuan Lu, and Kemin Qi*
Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Beijing, China
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cardiovascular diseases, hypertension, and diabetes (1, 2). Therefore, the prevention and treatment of obesity have been the focus of
many studies from a wide range of countries. In vitro and in vivo
studies have confirmed that calcium, as an essential mineral
component of our bodies, has many biological effects and may
play an important role in hormone secretion (3), glycogen metabolism (4), and adipocyte proliferation and differentiation (5).
More than 30 y ago, McCarron et al. (6) first noted an inverse
relation between calcium intake and body weight. Several crosssectional epidemiology studies have shown that calcium supplementation may increase weight loss that is mediated by
increasing fecal fat excretion and body fat oxidation and improving insulin sensitivity (7), although no correlation between
calcium intake and weight loss has been reported (8).
The results from systematic reviews and meta-analyses have
not reached a consensus regarding the effects of calcium intake on body weight. Trowman et al. (9) showed that calcium
supplementation had no association with reductions in body
weight on the basis of 13 randomized controlled trials in the year
2006. Onakpoya et al. (10) conducted a review of 7 randomized controlled trials, which indicated an unclear correlation
between calcium supplementation and weight loss (10). Chen et al.
(11) proved that calcium supplementation with energy restriction
could reduce body weight and increase fat loss in long-term studies
(.1 y) including 29 randomized controlled trials. Booth et al. (12)
reported that no differences were shown in body weight changes
by increasing dietary calcium through supplements and dairy
food (12). The discrepancies in these outcomes may have been
attributable to many factors in the inclusion criteria such as the
source and amount of calcium supplementation, length of supplementation, and the race, age, sex, and initial weight of the
subjects.
Because of the limitations in these systematic reviews and
meta-analyses, such as the lower number of included references
and inadequate consideration of possible confounding factors, in
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ABSTRACT
Background: Whether calcium supplementation can reduce body
weight and prevent obesity remains unclear because of inconsistent
reports.
Objective: We performed a meta-analysis to investigate the correlations between calcium supplementation and changes in body weight
on the basis of age, sex, body mass index (BMI) of the subjects, and
length of calcium intervention.
Design: PubMed, EMBASE, Web of Knowledge, and China National
Knowledge Infrastructure databases were systematically searched to
select relevant studies that were published from January 1994 to March
2016. Both randomized controlled trials and longitudinal studies of
calcium supplementation were included, and random- or fixed-effects
models in a software program were used for the data analysis.
Results: Thirty-three studies involving a total of 4733 participants
were included in this meta-analysis. No significant differences in
weight changes were shown between calcium intervention and control
groups (mean: 20.01 kg; 95% CI 20.02, 0.00 kg; P = 0.12). However,
negative correlations between calcium supplementation and weight
changes were shown in children and adolescents (mean: 20.26 kg;
95% CI: 20.41, 20.11 kg; P , 0.001) and in adult men and either
premenopausal or old (.60 y of age) women (mean: 20.91 kg; 95%
CI: 21.38, 20.44 kg; P , 0.001) but not in postmenopausal women
(mean: 20.14 kg; 95% CI: 20.54, 0.26 kg; P = 0.50). When BMI was
considered, a negative correlation between calcium supplementation and weight changes was observed in subjects with normal BMI
(mean: 20.53 kg; 95% CI: 20.89, 20.16 kg; P = 0.005) but not in
overweight or obese subjects (mean: 20.35 kg; 95% CI: 20.81, 0.11 kg;
P = 0.14). Compared with the control groups, no differences in weight
changes were shown in the calcium-intervention groups when the
lengths of calcium interventions were ,6 mo (mean: 20.09 kg; 95%
CI: 20.45, 0.26 kg; P = 0.60) or $6 mo (mean: 20.01 kg; 95%
CI: 20.02, 0.01 kg; P = 0.46).
Conclusion: Increasing calcium intake through calcium supplements can reduce body weight in subjects who have a normal
BMI or in children and adolescents, adult men, or premenopausal
women.
Am J Clin Nutr 2016;104:1263–73.
Keywords: body weight, calcium, meta-analysis, obesity, body
mass index
INTRODUCTION
Obesity has become one of the most important public health
problems worldwide and is closely associated with the occurrence of many chronic noncommunicable diseases such as cancers,
1
Supported by the National Natural Science Foundation of China
(81602859), the Beijing Natural Science Foundation of China (S150006),
and Beijing Municipal Science and Technology Commission (Research
Funds of a Professional Quota Budget; 2015-bjsekyjs-2).
2
Supplemental Figure 1 is available from the “Online Supporting Material”
link in the online posting of the article and from the same link in the online
table of contents at http://ajcn.nutrition.org.
*To whom correspondence should be addressed. E-mail: [email protected].
Received April 7, 2016. Accepted for publication September 2, 2016.
First published online October 12, 2016; doi: 10.3945/ajcn.116.136242.
Am J Clin Nutr 2016;104:1263–73. Printed in USA. Ó 2016 American Society for Nutrition
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this article we updated the evidence on the role of calcium intake
in body weight and obesity; specifically, we aimed to determine
whether calcium intake could reduce body weight with a longer
length of supplementation (.12 wk) with the use of calcium
intake in the calcium-intervention groups that met the Dietary
Reference Intake (DRI) of calcium (1000 mg/d) to avoid insufficient calcium supplementation. Moreover, several subgroups were separated for analyses to determine the correlations
between calcium supplementation and body weight on the basis
of subject age, sex, and initial body weight and the length of the
calcium-intervention trials.
Inclusion and exclusion criteria
To ensure the quality of the research, all references that were
included had to be randomized controlled trials from cohort
studies and longitudinal studies on calcium supplementation with
lengths of calcium interventions .12 wk. The references of
literature reviews, studies on animals or cell lines, and studies
with subjects who were pregnant or in patients with severe wasting
diseases such as cancer were excluded.
In the retrieval process, 2 reviewers were asked to independently screen all the references and citations to identify potentially eligible studies that were provided by the searching
index terms. Any disputes were resolved by another reviewer.
Moreover, all possible publication biases were assessed with the
use of funnel plots of the outcome comparisons by the same
person.
Data extraction and processing
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IB
Correlations between calcium supplementation and body
weight were calculated according to the Cochrane standards and
meta-analyses guidelines (Preferred Reporting Items for Systematic
Reviews and Meta-Analyses). The data were screened from
PubMed (http://www.ncbi.nlm.nih.gov/pubmed), EMBASE (https://
www.elsevier.com/solutions/embase-biomedical-research), Web of
Knowledge (http://www.cnki.net/), and China National Knowledge
Infrastructure databases (http://kns.chkd.cnki.net/kns55/brief/
single_default.aspx?dbprefix=chkd) from January 1994 to March
2016 without limitations regarding language and authors. The
searching index terms that were used alone or in combination in
this study included “calcium” or “Ca2+” or “dairy products” or
“calcium supplementation” and “body weight” or “obesity” or “body
fat” or “obese” or “overweight” or “body composition” or “body
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Data search
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METHODS
mass index (BMI)” or “fat mass index (FMI)”. Moreover, additional
articles were included by reviewing the references of the relevant
studies that were identified. All final selections were full-length,
original, published articles.
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After reading the full references, relevant data were extracted to
retain the study characteristics, calcium intervention, and main
outcomes. Study characteristics primarily included the titles, authors, date of publication, publication journals, and basic information of the subjects such as age, sex, country, BMI, education,
economic status, calcium intake, and energy intake. The
FIGURE 1
Flowchart of included studies.
United States
United States
United States
Denmark
United States
United States
United States
China
Chan et al.,
1995 (14)
Hanks et al.,
2010 (15)
Lappe et al.,
2004 (16)
Lorenzen et al.,
2006 (17)
Merrilees et al.,
2000 (18)
Skinner et al.,
2003 (19)
Venti et al.,
2005 (20)
Zhu et al.,
2013 (21)
N
Population
characteristic
22 (21)
88 (88)
25 (27)
45 (46)
60 (50)
27 (32)
167 (148)
48 (48)
22 (23)
T
1656 6 191 (961 6 268)
9.5 6 0.4 (9.5 6 0.3)
Healthy students
Health children
Healthy white
children
Postpubertal
teenage girls
Healthy young
girls
R
1020–1028 (770–876)
1500 (500)
1027 6 152 (392 6 141)
4.0 6 0.6 (3.9 6 0.5)
10.1 6 1.1 (10.3 6 0.8)
1y
6y
2y
1y
2y
12 wk
Yes
No
No
Yes
No
Yes
Yes
Yes
Yes
Energy
restricted2
Calcium
supplement1
N
Diet food and
calcium
supplement
(diet food)
Daily diet food
(daily diet food)
Diet food and
calcium
supplement
(diet food)
Dairy food
supplementation
(daily diet food)
Dairy food
supplementation
(daily diet food)
Dairy food
supplementation
(daily diet food)
Dairy food
supplementation
(daily diet food)
High-calcium food
(diet food)
Daily diet food
(daily diet food)
TI
O
U
TR
IB
IS
1160 (765)
2.0–8.0 (2.0–8.0)
15.0–18.0 (15.0–18.0)
13.1 6 0.06 (13.2 6 0.08)
D
1073 6 330 (844 6 339)
9.8 6 1.6 (9.3 6 1.5)
1000–1304 (,713)
1y
1437 6 366 (728 6 321)
9.0–13.0 (9.0–13.0)5
4y
2y
831 6 352 (650 6 351)
10.5 6 0.6 (10.6 6 0.8)4
Study
length
Calcium dose,1 mg/d
Age,1 y
FO
Healthy pubertal
girls
Healthy children
Healthy, white,
pubertal girls
Healthy
premenarchal
girls
O
Sample,1 n
Less
Height, body weight,
dietary intake,
body fat, and
related variables
Height, body weight,
body fat, and other
nutrition
Body weight, BMI,
body composition,
waist,
circumference,
and blood
pressures
Less
Less
Less
Less
ND
Less
Less
Less
Weight
gain3
Body composition
and bone density
Height, body weight,
pubertal status,
and fat mass
Height, body weight,
body fat, and
calcium intake
Height and body
weight
Height, body weight,
maturational
stage, and eating
attitudes
Body composition
and bone density
Main outcome
Data in calcium-intervention groups and control groups are shown outside and inside parentheses, respectively.
2
Whether the energy intake of subjects was restricted during the study. Yes denotes that there were similar energy intakes between the calcium-intervention group and the control group. No denotes that
calcium supplementation or dietary intake was adjusted for energy intake.
3
Less denotes that there was less weight gain in the calcium-intervention group than in the control group. ND denotes no significant differences in weight gain between the calcium intervention groups and
the control groups.
4
Mean 6 SD (mean 6 SE) of the variables.
5
Range (all such values).
1
Canada
Country
Barr, 2007 (13)
Study
TABLE 1
Characteristics of studies with children and adolescents
CALCIUM SUPPLEMENTATION ON BODY WEIGHT
1265
Mexico
United
States
NA6
United
States
United
States
Rosado et al.,
2011 (28)
Shapses et al.,
2004 (29)
Thomas et al.,
2010 (30)
Wagner et al.,
2007 (31)
Zhou et al.,
2010 (32)
328 (206)
12 (46)
14 (15)
46 (54)
46 (93)
732 (739)
Postmenopausal
women
Overweight
postmenopausal
women
Overweight or
obese
postmenopausal
women
Postmenopausal
women
Obese
postmenopausal
women
Postmenopausal
women
1600 (600)
$1200 (#500)
1550 (750)
1500–1600 (671 6 406)
58.0 6 5.5 (61.6 6 8.6)
38–60 (38–60)
40–60 (40–60)
65.2 6 6.5 (66.0 6 6.6)
1215 (500)
4y
12 wk
16 wk
Calcium supplement and
diet food (diet food)
Diet food (diet food)
Calcium supplement
and diet food (diet
food)
Low-fat milk and diet
food (diet food)
Calcium supplement
and diet food (diet
food)
Milk and diet food
(diet food)
Calcium carbonate and
diet food (diet food)
Low-fat milk and diet
food (diet food)
Calcium supplement,
milk, and diet food
(diet food)
Calcium supplement1
No
Yes
N
Calcium supplement and
diet food (diet food)
Calcium supplement,
milk, and diet food
(diet food)
TI
O
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
Energy
restricted2
U
25 wk
16 wk
30 mo
15 wk
3 mo
6 mo
8 wk
16 wk
Study
length
TR
IB
IS
44.9 6 5.6 (44.1 6 5.9)
74.2 (74.3)
1861 (853)
1400 (,800)
43.6 6 5.0 (41.6 6 6.1)
D
1000 (500)
1500 (500)
45–55 (45–55)
R
45–50 (45–50)
FO
Overweight or
obese women
Obese
postmenopausal
women
Overweight or
obese,
postmenopausal
women
T
40–59 (40–59)4
800 (500–600)
1500 (500)
Age, y
45.8 6 8.7 (48.3 6 9.5)5
Calcium dose,1
mg/d
1
BMI, trunk fat, trunk
lean, and percentage
of trunk fat
Height, body weight,
and body fat
Height, body weight,
BMI, waist
circumference, and
waist-to-hip ratio
Body weight and fat
mass
Height, weight, body
fat
Body weight and fat
mass
Height, body weight,
waist and hip
circumferences,
and dietary and
physical activity
records
Height, weight, and
appetite
Body weight, height,
BMI, and body
composition
Body weight, height,
plasma
lipoproteins, and
glucose
concentration
Body weight and
blood pressure
Main outcome
Yes
No
No
No
Yes
No
Yes
No
No
Yes
Yes
Weight
change3
2
Data in calcium-intervention groups and control groups are shown outside and inside parentheses, respectively.
Whether the energy intake of subjects was restricted during the study. Yes denotes that there were similar energy intakes between the calcium-intervention group and the control group. No denotes that
calcium supplementation or dietary intake was adjusted for energy intake.
3
Yes denotes that there was a significant weight reduction in the calcium-intervention group compared with in the control group. No denotes that there were no differences in body weight changes between
the calcium-intervention group and the control group.
4
Range (all such values).
5
Mean 6 SD (mean 6 SE) of the variables (all such values).
6
NA, not available.
1
New
Zealand
Reid et al.,
2005 (27)
30 (33)
20 (20)
Poland
Canada
13 (28)
22 (20)
Iran
Canada
30 (30)
Postmenopausal
women
Healthy
overweight
(obese) women
O
N
Sample, n
Philippines
Country
Major et al.,
2007 (26)
Gilbert et al.,
2011 (24)
Holecki et al.,
2008 (25)
Angeles-Agdeppa
et al., 2010 (22)
Faghih et al.,
2011 (23)
Study
1
Population
characteristic
TABLE 2
Characteristics of studies with postmenopausal women
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United
States
United
States
United
States
Zemel et al.,
2004 (43)
Zemel et al.,
2005 (44)
Zemel et al.,
2009 (45)
36 (70)
17 (17)
16 (16)
170 (170)
Obese African
American
adults
Overweight
and obese
adults
Overweight
and obese
adults
Overweight
and obese
adults
Obese adults
1200 6 370 (668 6 273)
39..5 6 2.2 (35.3.6 2.2)
R
1200–1300 (,500)
37.9 6 2.0 (42.9 6 2.0)
1200–1300 (400-500)
1200 (500)
1400 (600)
42.5 6 2.6 (41.3 6 2.7)
25.6 6 5.0 (25.4 6 4.9)
2100 (,600)
38.9 (38.7)
49.0 6 6.0 (48.0 6 8.0)
1288.4 6 94.6 (434.6 6 56.6)
20–50 (20-45)
12 wk
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
No
Yes
Yes
No
Calcium
supplement1
Main outcome
N
High-calcium diet food
Height, weight, fat
(low-calcium diet food)
mass, glucose, and
insulin
Calcium supplement and Body weight and fat
diet food (diet food)
mass
High-calcium diet food
Body weight and fat
(low-calcium diet food)
mass
Skim or 1% milk and diet Height, weight, and
food (diet food)
food intake
High-calcium diet food
Height and body
(low-calcium diet food)
weight
High-calcium diet food Body composition,
plasma hormones,
(low-calcium diet
and glycemic
food)
response
Calcium supplement and Height, weight, and
diet food (diet food)
body composition
Calcium and vitamin D– BMI and body
composition
supplemented orange
juice and diet food
(diet food)
Calcium carbonate and
Height, weight, and
diet food (diet food)
body composition
Low-fat milk and diet
Height, weight, and fat
food (diet food)
mass
High-calcium diet food Height, weight, fat
mass, blood
(low-calcium diet
pressure, glucose,
food)
and insulin
concentration
High-calcium diet food
Height, body weight,
(low-calcium diet food)
and body
composition
Calcium carbonate and
Height and body weight
diet food (diet food)
TI
O
U
24 wk
24 wk
24 mo
12 wk
16 wk
48 wk
24 wk
TR
IB
1100–1300 (550)
IS
1000 (500)
42.0 6 8.8 (41.2.6 9.3)
36.6 6 7.8 (36.6 6 8.0)
D
39.0 6 13.0 (41.0 6 12.0)
21 wk
12 wk
12 mo
12 wk
Study
Energy
length restricted2
+350 (unknown in diet) 16 wk
1400 (700)
52.1 6 1.5 (50.1 6 2.7)
FO
1200–1400 (500)6
1556 6 400 (690 6 234)
Calcium dose,1
mg/d
45.2 6 7.0 (45.1 6 6.5)
65.3 6 6.6 (65.1 6 6.7)5
Age, y
1
Yes
Yes
Yes
No
No
Yes
No
No
Yes
No
No
No
No
Weight
change3
2
Data in calcium-intervention groups and control groups are shown outside and inside parentheses, respectively.
Whether the energy intake of subjects was restricted during the study. Yes denotes that there were similar energy intakes between the calcium-intervention group and the control group. No denotes that
calcium supplementation or dietary intake was adjusted for energy intake.
3
Yes denotes that there was a significant weight reduction in the calcium-intervention group compared with in the control group. No denotes that there were no differences in body weight changes between
the calcium-intervention group and the control group.
4
Subjects in this study were old adults who were aged .60 y.
5
Mean 6 SD (mean 6 SE) of the variables.
6
Range (all such values).
1
United
States
Yanovski et al.,
2009 (42)
35 (36)
Obese adults
19 (20)
United
States
Obese adults
30 (29)
United
States
Brazil
Obese adults
Overweight
and obese
adults
20 (20)
66 (65)
United
States
T
Obese adults
Adults
Health men
and women
Healthy adults
Iran
17 (8)
Argentina
Van Loan et al.,
2011 (41)
Shalileh et al.,
2010 (38)
Thompson et al.,
2005 (39)
Torres et al.,
2010 (40)
Palacios et al.,
2011 (36)
Rosenblum
et al.,
2012 (37)
20 (18)
25 (29)
98 (102)
Barr et al.,
United
2000 (33)4
States
Harvey-Berino
United
et al., 2005 (34)
States
Jones et al.,
Canada
2013 (35)
O
N
Sample, n
Country
Study
1
Population
characteristic
TABLE 3
Characteristics of studies with adult men and either premenopausal or old women
CALCIUM SUPPLEMENTATION ON BODY WEIGHT
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Study characteristics
N
Calcium intake in all calcium-intervention groups met the DRI
of calcium (1000 mg/d) with different sources such as calciumrich food, milk, and calcium supplements, whereas calcium intake through diet foods in control groups was below the DRI of
calcium. As regards the potential influences of energy intake, 10
studies confirmed that calcium supplementation or intake had
been adjusted for energy intake, and the remaining 23 studies
indicated that there were no differences in energy intake between
experimental groups and control groups.
N
O
T
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A random-effects model in Review Manager Software (RevMan version 5.3, International Cochrane collaboration) was used
to perform the meta-analysis on the effectiveness and correlations
between calcium supplementation and body weight changes
between calcium intervention and control groups. Continuous
outcomes were presented as means 6 SDs with 95% CIs. The
subgroup analysis was performed by age, BMI, and length of
the calcium intervention. The I2 statistic was used to evaluate the
heterogeneity between all the studies that were included in this
research. The random-effects model was used when I2 was .50%,
whereas the fixed-effects model was used when I2 was #50%. A
funnel plot was used to detect the possibility of bias. Statistical
significance for 2-sided P values was defined as a , 0.05.
As shown in Figure 1, a total of 1524 citations that met the
inclusion criteria were initially identified from PubMed, EMBASE,
Web of Knowledge, and China National Knowledge Infrastructure
databases. After screening the titles and abstracts, 366 articles
were retrieved, and 7 additional articles were also included by
reviewing the references of these relevant studies. Finally, 33
eligible articles were included in this meta-analysis after examination of the full texts.
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Statistical analysis
RESULTS
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information on the calcium intervention that was extracted mainly
included the quantity and length of calcium supplementation. The
main outcomes included body weight, body composition, BMI,
and fat mass index, which were also converted as differences in the
changes in body weight or BMI between baseline and after the
calcium intervention.
FIGURE 2 Effects of calcium supplementation on body weight. No significant differences in weight loss were shown between calcium-intervention
groups and control groups (mean: 20.01 kg; 95% CI: 20.02, 0.00 kg; P = 0.12). The line in the figure denotes the 95% CI of each reference, the symbol
denotes the mean of each reference, and IV denotes the method of inverse-variance.
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CALCIUM SUPPLEMENTATION ON BODY WEIGHT
FO
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FIGURE 3 Effects of calcium supplementation on body weight in the following subjects of different ages: children and adolescents (A), postmenopausal
women (B), and adult men and either premenopausal or old women (C). Negative correlations between calcium supplementation and body weight changes
were shown in children and adolescents (mean: 20.26 kg; 95% CI: 20.41, 20.11 kg; P , 0.001) and adult men and either premenopausal or old women
(mean: 20.91 kg; 95% CI: 21.38, 20.44 kg; P , 0.001) but were not evident in postmenopausal women (mean: 20.14 kg; 95% CI: 20.54, 0.26 kg;
P = 0.50) with the use of a random-effects model. The line in the figure denotes the 95% CI of each reference, the symbol denotes the mean of each reference,
and IV denotes the method of inverse-variance.
N
O
T
On the basis of the age and sex characteristics of all subjects,
the studies were divided into 3 subgroups in which the subjects were children and adolescents (Table 1), postmenopausal
women (Table 2), and adult men and either premenopausal or
old women, respectively (Table 3). The main outcomes of these
studies were body weight and body composition (BMI or fat
mass index). There were 9 eligible studies on children and adolescents that discussed the correlations between weight loss
and calcium supplementation with a varied duration of followup treatment from 12 wk to 6 y. In these studies, calcium intake
in the control groups ranged from 314 to 700 mg/d, whereas in
the intervention groups, it ranged from 1000 to 1656 mg/d.
Eleven eligible studies reported the effects of calcium supplementation on body weight in postmenopausal women with
a varying duration of follow-up treatment from 12 wk to 4 y.
Calcium intake in the control groups ranged from 400 to
876 mg/d, whereas that in the calcium-intervention groups
ranged from 1000 to 2100 mg/d. Thirteen eligible cohort or
longitudinal studies used adult men and either premenopausal
or old women as subjects with durations of follow-up treatments from 12 wk to 24 mo. In these articles, calcium intake in
the control groups ranged from 500 to 800 mg/d, whereas in
the calcium-intervention groups, calcium intake ranged from
1000 to 1861 mg/d.
On the basis of body weight, studies were divided into
2 subgroups of overweight or obese subjects and normal-weight
subjects. There were 20 eligible studies on overweight and obese
subjects that were used to analyze the correlations between
calcium supplementation and weight loss; 3 studies included
adolescent participants, 7 studies were on postmenopausal
women, and 10 studies were on adults including both adult men
and women. Subjects with normal body weight were investigated
in the other 13 eligible studies; 6 studies were on adolescents,
4 studies were on postmenopausal women, and 3 studies were on
both male and female adults. Finally, on the basis of the duration
of the calcium intervention, studies were divided into 2 subgroups
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FIGURE 4 Effects of calcium supplementation on body weight in the following subjects with different BMI: subjects with normal BMI (A) and subjects
who were overweight or obese (B). A negative correlation between calcium supplementation and body weight changes was observed in subjects with normal
BMI (mean: 20.53 kg; 95% CI: 20.89, 20.16 kg; P = 0.005) but not in overweight or obese subjects (mean: 20.35 kg; 95% CI: 20.81, 0.11 kg; P = 0.14)
with the use of a random-effects model. The line in the figure denotes the 95% CI of each reference, the symbol denotes the mean of each reference, and IV
denotes the method of inverse-variance.
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with lengths of calcium interventions ,6 mo (15 references)
and $6 mo (18 references).
Meta-analysis
Effects of calcium supplementation on body weight
N
O
T
We combined a total of 33 studies, which, in total, included
4733 subjects, to analyze the association between calcium
supplementation and body weight changes. The results of the
forest plot (Figure 2) showed that there were no significant
differences in weight loss between calcium-intervention groups
and control groups (mean: 20.01 kg; 95% CI: 20.02, 0.00 kg;
P = 0.12) with the use of a fixed-effects model.
Effects of calcium supplementation on body weight in subjects
of different ages
There were 9 studies that included children and adolescents
for a combined total of 987 participants. The results of the forest
plot (Figure 3A) showed that there was a negative correlation between calcium supplementation and body weight gain
(mean: 20.26 kg; 95% CI: 20.41, 20.11 kg) with the use of
a random-effects model (P , 0.001). The analysis of the 11
studies with a combined total of 2577 postmenopausal women
showed no significant differences in body weight changes between calcium intervention groups who received calcium
supplementation and the control groups (mean: 20.14 kg; 95%
CI: 20.54, 0.26 kg) as was shown in a random-effects model
(P = 0.50) (Figure 3B). These 13 studies that included both
adult men and either premenopausal or old women as subjects
included a combined total of 1169 participants and showed a negative correlation between calcium supplementation and values of
body weight changes in calcium-intervention groups compared
with control groups (mean: 20.91 kg; 95% CI: 21.38, 20.44 kg;
P , 0.001) (Figure 3C). This result indicated that calcium supplementation resulted in a reduction in body weight in adult men
and either premenopausal or old women.
Effects of calcium supplementation on body weight in subjects
with different BMI
There were thirteen studies whose subjects had normal BMI for
a total of 3214 participants. The results of the forest plot indicated
a negative correlation between calcium supplementation and values
of body weight changes in calcium-intervention groups compared
with control groups (mean: 20.53 kg; 95% CI: 20.89, 20.16 kg) with
the use of a random-effects model (P = 0.005) (Figure 4A), which
indicated that calcium supplementation caused a reduction of body
weight. An analysis of the 20 studies with a combined total of 1519
overweight and obese participants indicated no significant differences
in body weight changes between calcium-intervention groups and
control groups (mean: 20.35 kg; 95% CI: 20.81, 0.11 kg) with the
use of a random-effects model (P = 0.14) (Figure 4B).
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CALCIUM SUPPLEMENTATION ON BODY WEIGHT
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FIGURE 5 Effects of calcium supplementation on body weight with different intervention lengths as follows: ,6 mo (A) and .6 mo (B). Compared with
the control groups, no significant changes in weight loss were shown in the calcium-intervention groups with a length of calcium intervention ,6 mo (mean: 20.09 kg;
95% CI: 20.45, 0.26 kg; P = 0.60) or .6 mo (mean: 20.01 kg; 95% CI: 20.02, 0.01 kg; P = 0.46). The line in the figure denotes the 95% CI of each reference. The
symbol in the figure denotes the mean of each reference. IV denotes the method of inverse-variance.
Effects of calcium supplementation on body weight with
different intervention lengths
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We analyzed the 15 studies, which included a combined total
of 1114 participants, with lengths of calcium interventions ,6 mo
and showed no significant differences in body weight changes between calcium-intervention groups and control groups (mean:
20.09 kg; 95% CI: 20.45, 0.26 kg; P = 0.60) (Figure 5A). In
addition, in the 18 studies with lengths of calcium interventions
$6 mo, which included a combined total of 3619 participants,
there were no significant differences in body weight changes
between calcium-intervention groups and control groups (mean:
20.01 kg; 95% CI: 20.02, 0.01 kg; P = 0.46) with the use of a
fixed-effects model (Figure 5B).
Tests for publication bias
With the use of Egger’s regression test, there was no significant evidence of publication bias in any of the references in this
meta-analysis (P = 0.17) (Supplemental Figure 1).
DISCUSSION
This meta-analysis of 33 randomized controlled trials determined
whether increasing calcium supplementation with different sources
such as calcium-rich foods and calcium supplements could reduce
body weight with the use of a random-effects model. The results
showed that increasing calcium intake by supplementation did not
lead to weight loss in the intervention groups compared with the
control groups. This result is consistent with the conclusion of
a meta-analysis by Booth et al. (12) that body weight did not change
by increasing intake of calcium from different sources. However,
another meta-analysis from Onakpoya et al. (10), including only 7
calcium supplementation studies, showed that calcium supplementation resulted in a small but significant reduction in body weight.
The sources of calcium supplementation and energy intake are
2 important factors that contribute to the discrepancy in the
effects of calcium intake on body weight. It has been suggested
that dairy sources of calcium markedly attenuate weight and
fat gain and accelerate fat loss to a greater degree than do
supplemental sources of calcium. This augmented effect of dairy
products relative to supplemental calcium is likely due to the
additional bioactive compounds including angiotensin-converting
enzyme inhibitors and the rich concentration of branched-chain
amino acids in whey, which act synergistically with calcium to
attenuate adiposity (46). However, recent reports have shown that
dairy products have a high protein-quality score and contain a high
proportion of branched-chain amino acids, which cause enhanced
growth by stimulating the production of insulin and insulin-like
growth factor I, thereby increasing the susceptibility to overweight
and obesity (47). In addition, in 2015, Booth et al. (12) showed that
body weight was not changed by increasing calcium intake from
dairy foods, calcium supplements, medicine, or other sources.
Thus, the effects of calcium from different sources on body weight
are still uncertain and need to be elucidated in the future. Furthermore, it is known that calcium intake most likely increases with
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the duration of the calcium intervention, were established to assess
the correlations between calcium supplementation and body weight.
However, there were still several limitations. First, the heterogeneity
between all of the included references meant that only a randomeffects model could be used, which affected the efficiency of the
study. Second, some other confounding factors were unable to
be taken into consideration, such as physical activities and
other dietary factors. Third, when we analyzed the effects of
calcium with the total subjects included and with calcium
interventions .6 mo, the randomized controlled trial with the
larger sample size (27) had a .90% contribution. Whether this
contribution resulted in a lack of significant effects on body
weight needs to be investigated further. Finally, cohort studies with
larger samples are still needed to confirm the relation between
calcium supplementation and body weight.
In conclusion, the references published to date have not clearly
shown that increasing calcium supplementation reduces body
weight. However, after considering age, sex, BMI, and length of
calcium supplementation, the effects of calcium intake on weight
loss were evident. Increasing calcium supplements can reduce
body weight in subjects with normal BMI or in children, adolescents, adult men, and either premenopausal or old women.
TR
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the increasing caloric intake, and a positive energy balance is
known to have an effect on body fat. In the current study, calcium
supplementation or intake was adjusted for energy intake in most of
the included studies, and no differences in energy intake were
indicated between the calcium intervention groups and control
groups in the remaining studies.
Because there were too-few studies that used a meta-analysis to
assess the effects of confounding factors of calcium supplementation
on body weight, the current meta-analysis was further divided into
subgroups according to the ages and sexes of the subjects, their
initial body weights, and the lengths of calcium supplementation.
The results showed that calcium supplementation could reduce body
weight gain in children and adolescents and increase body weight
loss in adult men and either premenopausal or old women but not in
postmenopausal women. The reasons that calcium supplementation
did not increase weight loss in postmenopausal women were as
follows. First, more-severe calcium deficiencies may exist in this
group because of the increased calcium loss in the postmenopausal
stage, and more calcium supplementation is needed to maintain
physiologic functions (48, 49). Second, calcium supplementation
may mostly be used for the establishment of bone in conditions of
osteoporosis rather than for adipocyte regulation (49). Finally, many
elements, including hormone changes in postmenopausal women,
can also affect body weight, and these factors may lessen the effects
of calcium supplementation on body weight (50).
In this study, we also showed that initial body weight and BMI
played important roles in the effects of calcium supplementation on
body weight. Calcium supplementation led to significant weight
loss in subjects with normal BMI, which was not shown in subjects who were overweight or obese. There has been evidence
that calcium intake affects the expression and activities of
many enzymes involved in energy metabolism and body fat (51).
In overweight and obesity, many metabolic processes in the
body are greatly altered, and the role of calcium has become
less pronounced. In addition, the lack of an association between
reported calcium intake and body weight in obese subjects may
have been caused by the high-fat, high-energy diet consumed by
this population, which overwhelmed the anti-obesity effects of
calcium (52). Thus, the effects of calcium supplementation on
body weight were more likely to be realized in lean subjects than in
overweight or obese subjects. These findings indicate that sufficient calcium intake may play a more important role in obesity
prevention than in its treatment and, thus, may be helpful in
directing obesity-prevention efforts by increasing calcium intake.
The possible mechanisms by which calcium intake affects body
weight have been considered to be related to several aspects. First,
calcium combines with fatty acids and forms insoluble calcium soap
in the intestine, thereby increasing fecal fat excretion (53). Second,
calcium regulates the intestinal flora and maintains their stability,
which could reduce the incidence of obesity. Third, calcium intake
increases the concentrations of calcium in intracellular compartments to regulate the activity of fatty acid synthetic and hormonesensitive lipases, which results in a reduction in fat storage and
increases in fat decomposition and oxidation (51). Finally, increased
resting energy expenditure is associated with calcium intake and
mediates the relation between calcium intake and total body fat (16).
In this meta-analysis, calcium intake in the intervention groups
had to meet the DRI of calcium (1000 mg/d) to avoid negative
conclusions because of insufficient calcium intake. The corresponding subgroups, on the basis of subject age, sex, and BMI and
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The authors’ responsibilities were as follows—PL: conceived and conducted the investigation, analyzed the data, and wrote the manuscript; CF
and YL: supported the investigation by extracting useful data from the
literature; KQ: was responsible for the entire implementation of the study
and the overall content of the manuscript; and all authors: read and approved
the final manuscript. None of the authors reported a conflict of interest
related to the study.
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