Background: The obesity pandemic has been paralleled by a high prevalence of vitamin D deficiency (VDD). There is growing epidemiological evidence linking low vitamin D status with obesity events. In addition, observational studies also show that obesity may increase the risk of VDD. However, there is insufficient knowledge to understand whether there is a causality between the two. Moreover, the impact of vitamin D supplementation on obesity indices has shown inconsistent outcomes. Objective: This meta-analysis aimed to assess whether vitamin D supplementation modified general and central obesity indices in apparently healthy populations. Methods: A systematic retrieval of relevant randomized controlled trials (RCTs) was undertaken using Pubmed, Embase, Web of Knowledge and Chinese National Knowledge Infrastructure databases. The pooled weighted mean difference (WMD) and 95% confidence intervals (CI) were used to assess the changes in body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and 25-hydroxyvitamin D (25[OH]D) from baseline. Results: Twenty RCTs involving 3,153 participants reporting either BMI, WC, WHR or 25(OH)D met the inclusion criteria. When compared with placebo, vitamin D supplementation had no significant decreases in BMI (WMD = –0.09 kg/m2, 95% CI –0.19 to 0.01, p = 0.08), WC (WMD = –0.71 cm, 95% CI –1.58 to 0.16, p = 0.112) or WHR (WMD = 0.00, 95% CI –0.01 to 0.01, p = 0.749). However, in the subgroups of females, Asia region studies and intervention duration ≥6 months, a beneficial and significant reduction in BMI and WC was noted (all p < 0.026). On the other hand, pooled results showed that there was a significant increase in serum 25(OH)D levels (WMD = 13.20 ng/mL, 95% CI 9.83–16.58, p < 0.001) after vitamin D intervention. No publication bias was found in our study. Conclusions: Overall, supplementation with vitamin D produced no significant effect on the BMI, WC or WHR of healthy adults.

Obesity is defined as an abnormal or excessive accumulation of body fat resulting from an imbalance between energy intake and expenditure. The obesity epidemic affected an estimated 650 million adults and 124 million children in 2016 [1], and this condition increases the risk of chronic diseases like diabetes, cardiovascular diseases and cancer [2]. Currently, it is considered to be the fifth greatest risk factor for mortality [1]. A low serum vitamin D level is one of the metabolic disturbances associated with obesity [3]. The serum levels of 25-hydroxyvitamin D (25[OH]D) are commonly used as a biomarker for the long-term vitamin D nutritional status of an individual [4]. The Institute of Medicine defines vitamin D deficiency (VDD) as a medical outcome characterized by rickets and osteomalacia, with a serum 25(OH)D concentration <20 ng/mL (50 nmol/L) [5]. Currently, both obesity and VDD constitute worldwide epidemiological problems.

Obesity and VDD often coexist. Body mass index (BMI) and abdominal fat mass are known determinants of vitamin D status, and VDD is common in individuals with obesity [6]. Observational studies from a recent meta-analysis showed an inverse relationship between 25(OH)D levels and BMI both in diabetic and nondiabetic groups [7]. The first meta-analysis quantifying the association between obesity and VDD showed that the prevalence of VDD was 35% higher in the obesity group than in the control group [8]. However, it is still unclear whether VDD is a cause or an outcome of obesity. One proposed theory posits that vitamin D, being fat soluble, can be sequestered in cutaneous and visceral adiposity depots, resulting in low serum vitamin D levels in obese individuals [9]. An alternative theory proposes that volumetric dilution can explain most of the differences in serum 25(OH)D levels between obese and lean individuals [10]. Different mechanisms may explain why VDD is associated with a higher risk of adiposity. On the one hand, VDD increases parathyroid hormone levels and promotes a greater inflow of calcium (Ca) into adipocytes [11]. On the other hand, VDD might accelerate the differentiation of preadipocytes into adipocytes [12]. Both conditions could influence the obesity risk either directly (e.g., by increasing adipogenesis) or indirectly (by modulating inflammation, oxidative stress, metabolism and gene regulation) [13]. A study on diet-induced obesity in a mouse model showed that a high vitamin D and Ca intake can activate the Ca2+-mediated apoptotic pathway in adipose tissue, which would alleviate obesity by reducing body fat [14]. In addition, the vitamin D receptor and the vitamin D-metabolizing enzymes which produce 25(OH)D and 1,25(OH)2D are expressed in human adipose tissue, strongly suggesting there is a complex relationship between vitamin D and obesity [13, 15].

Two patterns of obesity, general (peripheral) obesity and central (abdominal) obesity, are often involved in epidemiological anthropometry. The BMI is one of the most commonly used anthropometric indices to determine the presence of general obesity in clinical practice and in population surveys [16]. Most observational studies have confirmed that vitamin D status is inversely correlated with the BMI [7]. However, several randomized controlled trials (RCTs) and a recent meta-analysis on the effects of vitamin D supplementation on BMI did not seem to support this correlation [17-20]. On the other hand, several studies have suggested that central obesity is considered as a better predictor of several adverse health outcomes and mortality [21, 22]. Thus, more attention should be paid to the current prevalence of central obesity. Waist circumference (WC) and waist-to-hip ratio (WHR) are ideal indicators for evaluating central obesity [16]. A recent cross-sectional study of highly educated adults conducted by Mansouri et al. [23] demonstrated that serum 25(OH)D levels were negatively correlated with WC, and that participants with VDD had a 2.04-fold greater risk of central obesity than those with normal levels of 25(OH)D. Several RCTs have investigated the effects of vitamin D supplementation on WC and WHR [24-26]; however, the results are still under debate. Moreover, until now, we have not found any meta-analyses in the worldwide epidemiological literature investigating the quantitative association between vitamin D supplementation and central obesity indices.

Given this background, the aim of this study was to examine whether an improvement in vitamin D status correlated with reduced obesity indices in order to make informed decisions on the administration of vitamin D. Therefore, we conducted a meta-analysis of 20 RCTs involving apparently healthy populations who reportedly did not participate in any weight loss programs.

This systematic review with a meta-analysis was registered, and its protocol was published at the PROSPERO International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/PROSPERO/CRD42019130375). We conducted the study following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [27]. The complete PRISMA checklist is provided in online supplementary Material Table S1 (see www.karger.com/doi/10.1159/000507418 for all online suppl. material).

Data Sources and Literature Search Strategies

The searches were conducted by L.D. and Y.W. from January 1995 to December 2019 using Pubmed, Embase, Web of Knowledge and Chinese National Knowledge Infrastructure databases with the following keywords or MeSH terms: “vitamin D,” “cholecalciferol,” “calcifediol,” “ergocalciferol,” “25(OH)D,” “1,25(OH)2D,” “25-hydroxyvitamin D,” “1,25-dihydroxyvitamin D,” “vitamin D supplementation,” “body mass index,” “BMI,” “waist circumference,” “WC,” “waist to hip ratio,” “WHR,” “obesity,” “abdominal obesity,” “overweight” and “adiposity.” Further, the records were restricted to publications in English or Chinese and human studies. To complement the electronic search, we also perused studies included in relevant systematic reviews and reference lists of pertinent articles. Details on the literature search strategy are described in online supplementary Table S2.

Inclusion and Exclusion Criteria

Two authors (L.D. and Y.W.) independently reviewed the titles and abstracts to identify articles for potentially relevant sources. Full texts of them were requested to evaluate eligibility. Articles were included if they met the following criteria: (1) followed an RCT design; (2) investigated the association between vitamin D supplementation and effect of obesity indices; (3) included a general healthy population rather than specific disease patients; (4) separately reported changes in the BMI, WC or WHR in the intervention and control groups before and after the intervention. We excluded studies if: (1) data were not fully available after contacting the authors by e-mail; (2) they were meta-analyses or systematic reviews; (3) they were duplicate studies; (4) participants were children, pregnant women or subjects diagnosed with a chronic medical illness; (5) participants engaged in special occupations; (6) subjects participated in any kind of weight loss program, including bariatric surgery, weight-reducing drugs or exercise. Discrepancies between 2 authors were solved by discussion and after reaching a consensus with the third author (L.H.).

Data Extraction

Data on the studies’ characteristics and related information were collected in Excel format using a premade checklist by one reviewer (L.D.), and then double-checked by another author (Y.W.). The following information was extracted: (1) information of study (surname of the first author, year of publication, region of study, sample size of each group, intervention type and amount, duration of intervention and intervention combined with calcium or not); (2) characteristics of participants (age, gender, 25[OH]D levels at baseline and health status of participants); (3) changes in the BMI, WC, WHR or 25(OH)D in the intervention and control groups before and after the intervention. Attempts were made to contact the corresponding or first author for unavailable information.

Risk for Bias Assessment

Two authors (L.D. and Y.W.) independently assessed the quality of all included studies by following the Cochrane Collaboration’s tool [28] (online suppl. Table S3). Seven aspects (random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias) were estimated. Summary assessments for studies were assigned as “high,” “low” or “unclear” according to the risk bias in each important outcome. Disagreements were solved through group discussion.

Data Synthesis and Statistical Analysis

The weighted mean difference (WMD) and 95% confidence interval (CI) were used to assess the combined changes in BMI, WC, WHR and 25(OH)D from baseline to follow-up between the randomly assigned intervention and placebo groups. If the SE was reported for the variation in the mean, we calculated the corresponding standard deviation (SD) by multiplying by √n. If the mean and SD for changes in BMI, WC, WHR and 25(OH)D before and after intervention were not reported, we calculated them based on the following formula, described in the Cochrane Handbook for Systematic Reviews of Interventions [28]:

Meanchange = Meanfinal – Meanbaseline

SDchange = √SD2baseline + SD2final – (2 × Corr × SDbaseline × SDfinal).

The correlation coefficient (Corr) was estimated based on calculations of other parameters which provided complete data for SDbaseline, SDfinal, SDchange in both the intervention and placebo groups.

Statistical heterogeneity between different studies was measured using χ2-based Q and I2 statistics. Depending on the heterogeneity, either a fixed-effect model or a random-effect model was adopted (if the heterogeneity I2 was above 50%, the random-effect model was used; otherwise, the fixed-effect model was applied). Separate meta-analyses were carried out for different subgroups including gender, region, duration of intervention, dose of intervention, vitamin D status at baseline (VDD or not), baseline BMI (≥30 or not), risk of bias (high, low or unclear) and whether it was combined with Ca administration (yes or no).

Sensitivity analyses were performed to assess the robustness of the summary estimates by omitting 1 study at a time and repeating the meta-analysis with the rest. Publication bias was assessed through visual inspection of Begg’s funnel plots and by Egger’s linear regression tests. If some publication bias was detected, the trim-and-fill method was used to adjust the meta-analysis results by adding data from potential missing studies [29]. p values <0.05 were considered statistically significant. Analyses were performed using the Stata 12.0 statistical software package.

Study Selection and Characteristics

Of the 1,412 studies identified, 20 studies were selected for the present meta-analysis. They included 24 intervention groups with 3,153 participants (n = 1,768 in the intervention group and n = 1,385 in the placebo group). Of these, 20 articles investigated vitamin D supplementation and BMI changes [17-19, 24-26, 30-43], 12 articles studied vitamin D supplementation and WC changes [17, 18, 24-26, 32, 36, 37, 40-43], 6 articles investigated vitamin D supplementation and WHR changes [19, 24-26, 31, 42], and 7 articles studied vitamin D supplementation and serum 25(OH)D changes [19, 24, 30-32, 36, 37] (Table 1). A list of the excluded articles and the reasons for exclusion is shown in the flow chart (Fig. 1).

Table 1.

Characteristics of included RCT studies

Characteristics of included RCT studies
Characteristics of included RCT studies
Fig. 1.

Flow chart showing the article selection process.

Fig. 1.

Flow chart showing the article selection process.

Close modal

All participants were considered healthy, except for the fact that part of them suffered from simple obesity. The majority of studies were conducted with female or mixed (male/female) participants; only 2 studies included male subjects only [17, 24] (Table 2). The daily doses of vitamin D supplementation varied from 100 to 8,571 IU/day. The duration of supplementation ranged from 1.5 to 36 months (Table 1). Assessments of bias risk for included trials are shown in online supplementary Table S3. All studies had low risk of bias for incomplete outcome data and selective reporting. There was insufficient information about random sequence generation in 4 studies [24, 25, 38, 43] and high risk of bias in one study [34]. Three studies had high risk of bias for blinding of participants and personnel and outcome assessment [34, 38, 41]. In 2 studies, risk of allocation concealment was unclear [41], and one was high [34].

Table 2.

Characteristics of participants

Characteristics of participants
Characteristics of participants

Meta-Analysis of General Obesity

A forest plot showing the effects of vitamin D supplementation on the BMI changes was constructed, including data from 20 RCTs. Overall, no effect of vitamin D supplementation on BMI change was found (pooled WMD –0.09 kg/m2; 95% CI –0.19 to 0.01; p = 0.08; I2 = 63.1%, pheterogeneity <0.001; Fig. 2). Considering this borderline significance and the moderate heterogeneity, subgroup meta-analysis was conducted to investigate interactions based on the characteristics of the participants and intervention. These results suggested that variables including gender, region where the study was conducted, intervention duration, baseline BMI and risk of bias could be the potential source of the heterogeneity. Notable findings from the subgroup analysis included beneficial effects of supplementing vitamin D on the BMI decline when participants were female, when the study was conducted in Asia, and when the intervention duration was ≥6 months (p < 0.026; Table 3).

Table 3.

Subgroup analysis of vitamin D supplementation on BMI and WC

Subgroup analysis of vitamin D supplementation on BMI and WC
Subgroup analysis of vitamin D supplementation on BMI and WC
Fig. 2.

Forest plot of the effects of vitamin D supplementation on BMI [17-19, 24-26, 30-43].

Fig. 2.

Forest plot of the effects of vitamin D supplementation on BMI [17-19, 24-26, 30-43].

Close modal

Meta-Analysis of Central Obesity

A forest plot showing the effects of vitamin D supplementation on the WC changes was constructed, including data from 11 RCTs. There was no statistically significant difference between the intervention and placebo groups for WC changes (pooled WMD –0.71 cm; 95% CI –1.58 to 0.16; p = 0.112; I2 = 68.0%, pheterogeneity <0.001; Fig. 3a). Subgroup analysis demonstrated that heterogeneity decreased in the following subgroups: male, European region, BMI ≥30 at baseline, non-VDD at baseline, duration of intervention ≥6 months, and bias at high risk (Table 3). Similarly, notable findings from the subgroup analysis included beneficial effects of vitamin D supplementation on the WC reduction when participants were female, when the study was conducted in Asia, and when the duration of the intervention was ≥6 months (p < 0.003; Table 3). When compared with the placebo group, however, the pooled meta-analysis and subgroup analysis all indicated that there was no effect of vitamin D supplementation on WHR changes (pooled WMD 0.00; 95% CI –0.01 to 0.01; p = 0.749; Fig. 3b; online suppl. Table S4). In addition, no heterogeneity was detected (I2 = 41.1%; pheterogeneity = 0.131; Fig. 3b).

Fig. 3.

Forest plots of the effects of vitamin D supplementation on WC [17, 18, 24-26, 32, 36, 37, 40-43] (a) and WHR [19, 24-26, 31, 42] (b).

Fig. 3.

Forest plots of the effects of vitamin D supplementation on WC [17, 18, 24-26, 32, 36, 37, 40-43] (a) and WHR [19, 24-26, 31, 42] (b).

Close modal

Meta-Analysis of Serum 25(OH)D

A forest plot showing the effects of vitamin D supplementation on serum 25(OH)D changes was constructed, including data from 7 RCTs. Following vitamin D supplementation, there was a significant beneficial effect on serum 25(OH)D levels (pooled WMD 13.20 ng/mL; 95% CI 9.83–16.58; p < 0.001; I2 = 75.7%, pheterogeneity <0.001; Fig. 4). Subgroup analysis demonstrated that heterogeneity decreased in the subgroups of studies conducted in European and Asian regions, and those with BMI <30 at baseline (Table 4).

Table 4.

Subgroup analysis of vitamin D supplementation on 25(OH)D (ng/mL)

Subgroup analysis of vitamin D supplementation on 25(OH)D (ng/mL)
Subgroup analysis of vitamin D supplementation on 25(OH)D (ng/mL)
Fig. 4.

Forest plots of the effects of vitamin D supplementation on serum 25(OH)D [19, 24, 30-32, 36, 37].

Fig. 4.

Forest plots of the effects of vitamin D supplementation on serum 25(OH)D [19, 24, 30-32, 36, 37].

Close modal

Sensitivity and Publication Bias Analyses

Sensitivity analysis utilizing the leave-one-out method did not show any major change on primary outcomes, an indication of the good stability of the results. Neither Begg’s test nor Egger’s test showed significant publication bias with respect to the effects of vitamin D supplementation on BMI (t = –0.19, p = 0.852), WHR (t = –0.60, p = 0.582) and 25(OH)D (t = –1.29, p = 0.245; online suppl. Table S5 and Fig. S1). Considering the borderline significance for the publication bias in WC (t = 2.20, p = 0.050), the trim-and-fill method was applied to adjust the results. However, this methodology indicated that after 2-step iterations, the number of missing studies was 0. No alterations were found in the adjusted WMD and 95% CI (–0.71 cm, [–1.58 to 0.17]). Therefore, the outcome was stable in terms of WC.

There is great interest in investigating possible preventive effects of vitamin D beyond its traditional role in maintaining skeletal health. The possible role of vitamin D in the pathogenesis of obesity is an important topic for public health and for issuing clinical guidelines. However, based on the literature published to date in apparently healthy populations, our pooled results indicate nonperceptible effects of vitamin D supplementation in terms of reducing the BMI, WC and WHR.

These 3 obese indices (BMI, WC and WHR) are readily available, noninvasive and inexpensive, which can frequently be applied in epidemiological surveys and clinical practice. The most widely used anthropometric index, the BMI, reflects both fat and muscle mass, but it does not accurately represent the distribution of body fat, especially abdominal fat [44]. Therefore, several studies suggested that the additional measurement of WC and WHR is better than the BMI alone to identify individuals with obesity, distinguishing the types of obesity and examining the prevalence of various types of obesity [16, 45]. To our knowledge, this is the first meta-analysis for the effects of vitamin D supplementation on general and central obesity indices in apparently healthy populations. Statistically, a potential reduction in BMI following vitamin D supplementation (p = 0.08) was noted as the sample size expands. However, such a small point estimate and narrow CI (–0.09, 95% CI –0.19 to 0.01), these puny effects would not be expected to have a clinical benefit. These results were consistent with previous studies that showed no significant effect on BMI change by use of vitamin D supplementation [46, 47]. The WC measures adipose tissue accumulation around the organs of the abdominal cavity. Abdominal fat is a good storage site for vitamin D, inhibiting its release into the blood and reducing its bioavailability, which is the main explanation offered for VDD in individuals with obesity [9]. Nevertheless, in the present meta-analysis of 11 RCTs for WC and 6 RCTs for WHR, vitamin D treatment did not decrease the WC and WHR, with the WMD and 95% CI (–0.71 cm [–1.58 to 0.16], p = 0.112; and 0 [–0.01 to 0.01], p = 0.749, respectively). Although no obvious benefits of vitamin D supplementation were seen based on these 3 obesity indices, we found notable improvements in serum 25(OH)D levels after vitamin D supplementation, with a WMD of 13.20 ng/mL and 95% CI of 9.83–16.58 (p < 0.001). In agreement with our results, previous meta-analysis also showed a significant effect of vitamin D supplementation on serum 25(OH)D concentrations [48].

The overall results may be explained by several reasons. First, clinical trials that assess the effects of vitamin D on obesity vary with different study designs. Therefore, the published studies are distinguished by methodologies, including participant characteristics, intervention times, intervention doses, as well as vitamin D formulations, making it difficult to pool the results. It is also a potential reason for the high heterogeneity of the present meta-analysis. Second, the utilization of vitamin D undergoes a series of physiological and biochemical processes, making it difficult to evaluate the ultimate bioavailability of participants [49]. Third, BMI, WC and WHR are all indirect indicators of obesity, making it hard to quantify amounts of fat accurately, and thus the direct effect of vitamin D supplementation on adipose tissue is hard to describe. Finally, 25(OH)D is an intermediate product of vitamin D metabolism which reflects circulating vitamin D levels in blood over a period of time. Production of 1,25(OH)2D3, an active form of vitamin D, depends on the enzyme 1α-hydroxylase, which catalyzes the synthesis of 1,25(OH)2D3 from 25(OH)D [15]. Following vitamin D supplementation, the likelihood that 25(OH)D will be used as a substrate in the catalytic reaction is reduced, so the levels of 25(OH)D in circulating blood will increase. This may be a reasonable explanation for the elevated serum 25(OH)D levels.

In any meta-analysis, the heterogeneous nature of the pooled results presents a challenge for the interpretation of any quantitative outcomes [47]. Subgroup analysis, a common method of exploring sources of heterogeneity, was performed in this study. Interestingly, when conducting a subgroup analysis in BMI and WC, beneficial and more significant effects were found in the subgroup of females, Asia region studies, and duration of intervention ≥6 months (all p < 0.026). Reasonable explanations for the increased effect of vitamin D treatment in special groups may be the fact that obesity prevalence among women and Asians is higher than that in men and other areas [50, 51]. In particular, Asians are more likely to have central fat deposition despite having a lower BMI [52, 53]. Therefore, those participants have a more sensitive response to vitamin D supplementation and more easily display the beneficial effects. In addition, vitamin D must be administered for a certain period of time before changes in the BMI and WC become evident [54].

Some limitations of this analysis deserve consideration, including the inability to completely collect all related published papers. Moreover, the sample size of most included RCTs was low. Additionally, the effects of seasonality, vitamin D formulations and sun exposure were not evaluated. However, there are 2 important advantages that differentiate it from previous studies. All participants were reported to be in good health (except for the simple obesity), therefore the results can be generalized to the general population. In addition, none of the subjects participated in any type of weight loss program (including exercise, weight loss medications or weight loss surgery). This maximizes the observed separate effect of vitamin D supplementation on obesity indicators.

In summary, this study is the first meta-analysis quantifying the effects of vitamin D supplementation on general and central obesity indices. Despite increased serum 25(OH)D levels, the obesity indices (BMI, WC and WHR) did not improve significantly. Therefore, the management and clinical application of vitamin D should be made with caution. However, it does not rule out that it may have potential clinical implication along with other weight loss programs.

We thank all the investigators in this study.

The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.

The authors have no conflicts of interest to declare.

No funding supports this work.

Y.W. and L.H. contributed to the study conception and design. L.D. and Y.W. contributed to the acquisition of data, the development of the protocol and the drafting of the manuscript. L.D. and Y.Z. contributed to the analysis and interpretation of the quantitative data. L.D. and Q.L. contributed to the critical revising of the final draft. L.D. and L.W. contributed to the analysis and interpretation of the descriptive data and the revision of the final draft. All authors approved the final version.

1.
World Health Organization
.
Fact sheet obesity and overweight
.
2016
.
2.
Nansseu
JR
,
Noubiap
JJ
,
Bigna
JJ
.
Epidemiology of overweight and obesity in adults living in cameroon: A systematic review and meta-analysis
.
Obesity (Silver Spring)
.
2019
Oct
;
27
(
10
):
1682
92
.
[PubMed]
1930-7381
3.
Gangloff
A
,
Bergeron
J
,
Lemieux
I
,
Després
JP
.
Changes in circulating vitamin D levels with loss of adipose tissue
.
Curr Opin Clin Nutr Metab Care
.
2016
Nov
;
19
(
6
):
464
70
.
[PubMed]
1363-1950
4.
Asghari
G
,
Farhadnejad
H
,
Hosseinpanah
F
,
Moslehi
N
,
Mirmiran
P
,
Azizi
F
.
Effect of vitamin D supplementation on serum 25-hydroxyvitamin D concentration in children and adolescents: a systematic review and meta-analysis protocol
.
BMJ Open
.
2018
Sep
;
8
(
9
):
e021636
.
[PubMed]
2044-6055
5.
Ross
AC
,
Manson
JE
,
Abrams
SA
,
Aloia
JF
,
Brannon
PM
,
Clinton
SK
, et al
The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know
.
J Clin Endocrinol Metab
.
2011
Jan
;
96
(
1
):
53
8
.
[PubMed]
0021-972X
6.
Bassatne
A
,
Chakhtoura
M
,
Saad
R
,
Fuleihan
GE
.
Vitamin D supplementation in obesity and during weight loss: A review of randomized controlled trials
.
Metabolism
.
2019
Mar
;
92
:
193
205
.
[PubMed]
0026-0495
7.
Rafiq
S
,
Jeppesen
PB
.
Body mass index, vitamin d, and type 2 diabetes: A systematic review and meta-analysis
.
Nutrients
.
2018
Aug
;
10
(
9
):
E1182
.
[PubMed]
2072-6643
8.
Pereira-Santos
M
,
Costa
PR
,
Assis
AM
,
Santos
CA
,
Santos
DB
.
Obesity and vitamin D deficiency: a systematic review and meta-analysis
.
Obes Rev
.
2015
Apr
;
16
(
4
):
341
9
.
[PubMed]
1467-7881
9.
Wortsman
J
,
Matsuoka
LY
,
Chen
TC
,
Lu
Z
,
Holick
MF
.
Decreased bioavailability of vitamin D in obesity
.
Am J Clin Nutr
.
2000
Sep
;
72
(
3
):
690
3
.
[PubMed]
0002-9165
10.
Drincic
AT
,
Armas
LA
,
Van Diest
EE
,
Heaney
RP
.
Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity
.
Obesity (Silver Spring)
.
2012
Jul
;
20
(
7
):
1444
8
.
[PubMed]
1930-7381
11.
Sergeev
IN
.
Vitamin D-Cellular Ca2+ link to obesity and diabetes
.
J Steroid Biochem Mol Biol
.
2016
Nov
;
164
:
326
30
.
[PubMed]
0960-0760
12.
Wen
J
,
Hong
Q
,
Wang
X
,
Zhu
L
,
Wu
T
,
Xu
P
, et al
The effect of maternal vitamin D deficiency during pregnancy on body fat and adipogenesis in rat offspring
.
Sci Rep
.
2018
Jan
;
8
(
1
):
365
.
[PubMed]
2045-2322
13.
Ruiz-Ojeda
FJ
,
Anguita-Ruiz
A
,
Leis
R
,
Aguilera
CM
.
Genetic factors and molecular mechanisms of vitamin d and obesity relationship
.
Ann Nutr Metab
.
2018
;
73
(
2
):
89
99
.
[PubMed]
0250-6807
14.
Sergeev
IN
,
Song
Q
.
High vitamin D and calcium intakes reduce diet-induced obesity in mice by increasing adipose tissue apoptosis
.
Mol Nutr Food Res
.
2014
Jun
;
58
(
6
):
1342
8
.
[PubMed]
1613-4125
15.
Wamberg
L
,
Christiansen
T
,
Paulsen
SK
,
Fisker
S
,
Rask
P
,
Rejnmark
L
, et al
Expression of vitamin D-metabolizing enzymes in human adipose tissue— the effect of obesity and diet-induced weight loss
.
Int J Obes
.
2013
May
;
37
(
5
):
651
7
.
[PubMed]
0307-0565
16.
Zhang
YX
,
Wang
ZX
,
Zhao
JS
,
Chu
ZH
.
The current prevalence and regional disparities in general and central obesity among children and adolescents in Shandong, China
.
Int J Cardiol
.
2017
Jan
;
227
:
89
93
.
[PubMed]
0167-5273
17.
Tepper
S
,
Shahar
DR
,
Geva
D
,
Ish-Shalom
S
.
Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial
.
Diabetes Obes Metab
.
2016
Jun
;
18
(
6
):
633
7
.
[PubMed]
1462-8902
18.
Sun
X
,
Cao
ZB
,
Tanisawa
K
,
Ito
T
,
Oshima
S
,
Higuchi
M
.
Vitamin D supplementation reduces insulin resistance in Japanese adults: a secondary analysis of a double-blind, randomized, placebo-controlled trial
.
Nutr Res
.
2016
Oct
;
36
(
10
):
1121
9
.
[PubMed]
0271-5317
19.
Mousa
A
,
Naderpoor
N
,
de Courten
MP
,
Teede
H
,
Kellow
N
,
Walker
K
, et al
Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial
.
Am J Clin Nutr
.
2017
Jun
;
105
(
6
):
1372
81
.
[PubMed]
0002-9165
20.
Tabrizi
R
,
Moosazadeh
M
,
Lankarani
KB
,
Akbari
M
,
Heydari
ST
,
Kolahdooz
F
, et al
The effects of vitamin D supplementation on metabolic profiles and liver function in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials
.
Diabetes Metab Syndr
.
2017
Dec
;
11
Suppl 2
:
S975
82
.
[PubMed]
1871-4021
21.
Sangrós
FJ
,
Torrecilla
J
,
Giráldez-García
C
,
Carrillo
L
,
Mancera
J
,
Mur
T
, et al
Association of general and abdominal obesity with hypertension, dyslipidemia and prediabetes in the predaps study
.
Rev Esp Cardiol (Engl Ed)
.
2018
Mar
;
71
(
3
):
170
7
.
[PubMed]
1885-5857
22.
Traissac
P
,
El Ati
J
.
Trends in obesity, NHANES 2003-2004 to 2013-2014: is waist circumference increasing independently of bmi?
Obesity (Silver Spring)
.
2019
Jul
;
27
(
7
):
1043
.
[PubMed]
1930-7381
23.
Mansouri
M
,
Miri
A
,
Varmaghani
M
,
Abbasi
R
,
Taha
P
,
Ramezani
S
, et al
Vitamin D deficiency in relation to general and abdominal obesity among high educated adults
.
Eat Weight Disord
.
2019
Feb
;
24
(
1
):
83
90
.
[PubMed]
1124-4909
24.
Nagpal
J
,
Pande
JN
,
Bhartia
A
.
A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men
.
Diabet Med
.
2009
Jan
;
26
(
1
):
19
27
.
[PubMed]
0742-3071
25.
Khosravi
ZS
,
Kafeshani
M
,
Tavasoli
P
,
Zadeh
AH
,
Entezari
MH
.
Effect of vitamin D supplementation on weight loss, glycemic indices, and lipid profile in obese and overweight women: A clinical trial study
.
Int J Prev Med
.
2018
Jul
;
9
(
1
):
63
.
[PubMed]
2008-7802
26.
Al-Bayyari
N
,
Al-Zeidaneen
S
,
Hailat
R
,
Hamadneh
J
.
Vitamin D3 prevents cardiovascular diseases by lowering serum total homocysteine concentrations in overweight reproductive women: A randomized, placebo-controlled clinical trial
.
Nutr Res
.
2018
Nov
;
59
:
65
71
.
[PubMed]
0271-5317
27.
Moher
D
,
Liberati
A
,
Tetzlaff
J
,
Altman
DG
;
PRISMA Group
.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
.
BMJ
.
2009
Jul
;
339
jul21 1
:
b2535
.
[PubMed]
0959-8138
28.
Higgins
JP
,
Green
S
. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration
2011
. www.handbook.cochrane.org
29.
Duval
S
,
Tweedie
R
.
Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis
.
Biometrics
.
2000
Jun
;
56
(
2
):
455
63
.
[PubMed]
0006-341X
30.
Pittas
AG
,
Harris
SS
,
Stark
PC
,
Dawson-Hughes
B
.
The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults
.
Diabetes Care
.
2007
Apr
;
30
(
4
):
980
6
.
[PubMed]
0149-5992
31.
Sneve
M
,
Figenschau
Y
,
Jorde
R
.
Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects
.
Eur J Endocrinol
.
2008
Dec
;
159
(
6
):
675
84
.
[PubMed]
0804-4643
32.
Zittermann
A
,
Frisch
S
,
Berthold
HK
,
Götting
C
,
Kuhn
J
,
Kleesiek
K
, et al
Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers
.
Am J Clin Nutr
.
2009
May
;
89
(
5
):
1321
7
.
[PubMed]
0002-9165
33.
Zhou
J
,
Zhao
LJ
,
Watson
P
,
Zhang
Q
,
Lappe
JM
.
The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial
.
Nutr Metab (Lond)
.
2010
Jul
;
7
(
1
):
62
.
[PubMed]
1743-7075
34.
Kjærgaard
M
,
Waterloo
K
,
Wang
CE
,
Almås
B
,
Figenschau
Y
,
Hutchinson
MS
, et al
Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial
.
Br J Psychiatry
.
2012
Nov
;
201
(
5
):
360
8
.
[PubMed]
0007-1250
35.
Zhu
H
,
Guo
D
,
Li
K
,
Pedersen-White
J
,
Stallmann-Jorgensen
IS
,
Huang
Y
, et al
Increased telomerase activity and vitamin D supplementation in overweight African Americans
.
Int J Obes
.
2012
Jun
;
36
(
6
):
805
9
.
[PubMed]
0307-0565
36.
Salehpour
A
,
Hosseinpanah
F
,
Shidfar
F
,
Vafa
M
,
Razaghi
M
,
Dehghani
S
, et al
A 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese women
.
Nutr J
.
2012
Sep
;
11
(
1
):
78
.
[PubMed]
1475-2891
37.
Rosenblum
JL
,
Castro
VM
,
Moore
CE
,
Kaplan
LM
.
Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults
.
Am J Clin Nutr
.
2012
Jan
;
95
(
1
):
101
8
.
[PubMed]
0002-9165
38.
Forsythe
LK
,
Livingstone
MB
,
Barnes
MS
,
Horigan
G
,
McSorley
EM
,
Bonham
MP
, et al
Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults
.
Br J Nutr
.
2012
Jan
;
107
(
1
):
126
34
.
[PubMed]
0007-1145
39.
Wood
AD
,
Secombes
KR
,
Thies
F
,
Aucott
L
,
Black
AJ
,
Mavroeidi
A
, et al
Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT
.
J Clin Endocrinol Metab
.
2012
Oct
;
97
(
10
):
3557
68
.
[PubMed]
0021-972X
40.
Wamberg
L
,
Kampmann
U
,
Stødkilde-Jørgensen
H
,
Rejnmark
L
,
Pedersen
SB
,
Richelsen
B
.
Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels - results from a randomized trial
.
Eur J Intern Med
.
2013
Oct
;
24
(
7
):
644
9
.
[PubMed]
0953-6205
41.
Zhu
W
,
Cai
D
,
Wang
Y
,
Lin
N
,
Hu
Q
,
Qi
Y
, et al
Calcium plus vitamin D3 supplementation facilitated fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial
.
Nutr J
.
2013
Jan
;
12
(
1
):
8
.
[PubMed]
1475-2891
42.
Mitchell
DM
,
Leder
BZ
,
Cagliero
E
,
Mendoza
N
,
Henao
MP
,
Hayden
DL
, et al
Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial
.
Am J Clin Nutr
.
2015
Aug
;
102
(
2
):
385
92
.
[PubMed]
0002-9165
43.
Major
GC
,
Alarie
F
,
Doré
J
,
Phouttama
S
,
Tremblay
A
.
Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations
.
Am J Clin Nutr
.
2007
Jan
;
85
(
1
):
54
9
.
[PubMed]
0002-9165
44.
Gao
W
,
Qiao
X
,
Wang
Y
,
Wan
L
,
Wang
Z
,
Wang
X
, et al
The interactive association of general obesity and central obesity with prevalent hypertension in rural lanzhou, China
.
PLoS One
.
2016
Oct
;
11
(
10
):
e0164409
.
[PubMed]
1932-6203
45.
Wu
PS
,
Jordan
SW
,
Hodson
T
,
Chao
AH
.
Waist-to-hip ratio is a better predictor than body mass index for morbidity in abdominally based breast reconstruction
.
Microsurgery
.
2018
Oct
;
38
(
7
):
731
7
.
[PubMed]
0738-1085
46.
Mora
N
,
Rieke
K
,
Plitcha
J
,
Segura
A
,
Leehey
D
,
DeShong
K
, et al
25-Hydroxyvitamin D supplementation and BMI change: A meta-analysis of randomized controlled trials
.
J Obes Weight Loss Ther
.
2013
Jul
;
3
(
4
):
181
.
[PubMed]
2165-7904
47.
Chandler
PD
,
Wang
L
,
Zhang
X
,
Sesso
HD
,
Moorthy
MV
,
Obi
O
, et al
Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials
.
Nutr Rev
.
2015
Sep
;
73
(
9
):
577
93
.
[PubMed]
0029-6643
48.
Farrokhyar
F
,
Sivakumar
G
,
Savage
K
,
Koziarz
A
,
Jamshidi
S
,
Ayeni
OR
, et al
Effects of vitamin d supplementation on serum 25-hydroxyvitamin d concentrations and physical performance in athletes: A systematic review and meta-analysis of randomized controlled trials
.
Sports Med
.
2017
Nov
;
47
(
11
):
2323
39
.
[PubMed]
0112-1642
49.
Christakos
S
,
Dhawan
P
,
Verstuyf
A
,
Verlinden
L
,
Carmeliet
G
.
Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects
.
Physiol Rev
.
2016
Jan
;
96
(
1
):
365
408
.
[PubMed]
0031-9333
50.
Hales
CM
,
Fryar
CD
,
Carroll
MD
,
Freedman
DS
,
Ogden
CL
.
Trends in obesity and severe obesity prevalence in us youth and adults by sex and age, 2007-2008 to 2015-2016
.
JAMA
.
2018
Apr
;
319
(
16
):
1723
5
.
[PubMed]
0098-7484
51.
Zhang
L
,
Wang
Z
,
Wang
X
,
Chen
Z
,
Shao
L
,
Tian
Y
, et al;
China Hypertension Survey investigators
.
Prevalence of abdominal obesity in China: results from a cross-sectional study of nearly half a million participants
.
Obesity (Silver Spring)
.
2019
Nov
;
27
(
11
):
1898
905
.
[PubMed]
1930-7381
52.
Chan
JC
,
Malik
V
,
Jia
W
,
Kadowaki
T
,
Yajnik
CS
,
Yoon
KH
, et al
Diabetes in Asia: epidemiology, risk factors, and pathophysiology
.
JAMA
.
2009
May
;
301
(
20
):
2129
40
.
[PubMed]
0098-7484
53.
Fan
JG
,
Kim
SU
,
Wong
VW
.
New trends on obesity and NAFLD in Asia
.
J Hepatol
.
2017
Oct
;
67
(
4
):
862
73
.
[PubMed]
0168-8278
54.
Padwal
R
,
Li
SK
,
Lau
DC
.
Long-term pharmacotherapy for obesity and overweight
.
Cochrane Database Syst Rev
.
2003
;(
4
):
CD004094
.
[PubMed]
1469-493X
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