European Journal of Clinical Nutrition

https://doi.org/10.1038/s41430-017-0059-9

ARTICLE

Vitamin D supplementation for the prevention of vitamin D

deficiency after bariatric surgery: a systematic review and
meta-analysis
Zhifei Li1 Xin Zhou1 Wei Fu1
● ●

Received: 21 June 2017 / Revised: 17 August 2017 / Accepted: 21 September 2017

© Macmillan Publishers Limited, part of Springer Nature 2017

Abstract
Objective To evaluate the efficacy of vitamin D supplementation on the prevention of postoperative vitamin D deficiency.
Methods PubMed, Embase, Web of Science, and Cochrane library were searched. Prospective studies evaluating the effects
of vitamin D supplementation in patients who had undergone bariatric surgery were included. Meta-regression was per-
formed to explore heterogeneity, and assess the relationship between dosage of vitamin D supplementation, study design,
and prevalence of vitamin D depletion.
1234567890

Results Twelve studies enrolling 1285 patients met the inclusion criteria, and were included. Vitamin D supplementation
was associated with significant improvements in 1-year Vitamin D depletion and 1-year 25-OHD level. A daily supplement
of more than 800 IU vitamin D significantly reduced the prevalence of 1-year Vitamin D depletion, but the dosage of less
than 800 IU did not. Significant decrease in prevalence of 1-year Vitamin D depletion was observed in randomized
controlled trials (RCTs), but not in non-RCTs. For the 1-year 25-OHD level, significant elevation was found in the studies
irrespective of the study design and dosage of vitamin D supplementation. Meta-regression showed that there was significant
relationship between vitamin D depletion and study design, but not between vitamin D depletion and the dosage of vitamin
D supplementation.
Conclusion Vitamin D supplementation with a daily dosage of more than 800 IU is effective in preventing postoperative
vitamin D deficiency and improving the 25-OHD level. However, the results should be interpreted cautiously since there was
significant heterogeneity among the studies.

Introduction year [4]. Obesity accounts for several non-communicable

Vitamin D is a steroid hormone and a nutrient. There are
two forms: vitamin D2 (ergocalciferol) and vitamin D3
(cholecalciferol). The former is a product of ultraviolet
irradiation on ergosterol, primarily found in mushrooms,
while the latter is naturally synthesized in human skin upon
exposure to sunlight [1]. Vitamin D3 is the endogenous
form of vitamin D. It will be activated in the form of 1a, 25-
dihydroxyvitamin D when it is exposed to UVB rays and is
hydroxylated in the liver and kidney. The obesity epidemic
is a public problem around the world [2, 3]. It is estimated
to account for more than 2.8 million deaths in adults every
* Wei Fu
13911098483@163.com
1 vitamin D (20–51%), and calcium (±10%) [14–16]. In order
Department of General Surgery, Peking University Third Hospital,
Beijing, China
diseases, such as cardiovascular, metabolic, pulmonary, and
psychological complications [5]. Thus, obesity imposes a
heavy economic and social burden for the populations [2].
Medical therapy and surgical intervention are two approa-
ches that have been used in the treatment of obese patients.
While there is limited effectiveness of medical therapy [6],
amounts of studies support the efficacy of bariatric surgery
in obese patients [7–9]. Moreover, bariatric surgery leads to
the weight loss [7–9], as well as a substantial reduction in
the obesity-related comorbidities [9, 10].
The Roux-en-Y gastric bypass (RYGB) is one of the
widely used surgical procedures to reduce weight loss in the
world [11]. However, due to the limitation of intake, RYGB
is also associated with the increased risk of various nutri-
tional and vitamin deficiencies [12, 13], including iron
(47–66%), vitamin B12 (37–50%), folic acid (15–38%),
to prevent the postsurgical vitamin D deficiency, an oral

vitamin D supplementation of 800 IU daily is generally
recommended by the American Association of Clinical
Endocrinologists (AACE), and The Obesity Society (TOS)
[17]. Despite this could increase the 25-hydroxyvitamin D
(25-OHD) levels by 20%, almost one half of the patients
still have vitamin D depletion [18]. This has been supported
by several studies, which demonstrated that these dosages
are not adequate to reach the recommended serum 25-OHD
levels [19–21]. However, in some other studies [22, 23],
low doses of vitamin D supplementation were also effective
in achieving sufficient levels. Given that the multiple stu-
dies observed controversial clinical outcomes, it is vital to
understand the full impact of vitamin D supplementation
with different dosages on the vitamin D depletion and the
25-OHD levels. Therefore, this meta-analysis was con-
ducted to assess the effects of vitamin D supplementation in
obesity patients who had undergone the bariatric surgery.
Materials and methods
Search strategy and selection criteria
This meta-analysis was performed in accordance with Pre-
ferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) guidelines [24]. Two independent
investigators performed the literature search. Electronic
databases, including PubMed, Web of Science, Embase,
and Cochrane library were systematically searched until
December 2016, with no language restrictions. The search
terms used combinations of bariatric surgery, Roux-en-Y,
gastroenterostomy, gastrectomy, gastric bypass, and vita-
min. Details of the search strategy are shown in Appendix 1.
Related systematic reviews and meta-analysis were also
identified from these databases, and the reference lists of
included studies were checked until we could not find any
other potential articles. Discrepancies between the two
investigators were resolved by discussion and consensus.
The following selection criteria were applied [1]: study
design: prospective study [2]; population: obesity patients
who had undergone bariatric surgery [3]; intervention:
vitamin D supplementation [4]; outcome measures: 1-year
vitamin D deletion, and 1-year 25-OHD level. Since there
was low number of randomized controlled trials (RCTs) on
this subjective, we had no predefined limitations on the
study design or study quality. RCTs, case-control studies, or
cohort studies were all included.
Data extraction and methodological quality
assessment
Data extraction was conducted by two independent inves-
tigators. A standardized Excel file was used to extract the
Z. Li et al.
data. The following information was extracted from each
study: first author’s name, year of publication, study design,
number of patients in each group, patient characteristics
(age, race, weight, and BMI), and outcomes (1-year vitamin
D deletion, 1-year 25-OHD level).
RCTs were appraised for risk of bias using the method
recommended by Cochrane Collaboration [25]. This
method consists of seven quality items to report the quality
of a RCT. Each study was classified as being at low,
unclear, or high risk of bias.
We used the modified Newcastle-Ottawa (NOS) scale to
evaluate the methodological quality of non-RCTs [26]. The
quality scale ranged from zero to nine points. Studies are
regarded as high quality when the NOS scale was greater
than five points.
Statistical analysis
Risk ratio (RR) with 95% confidence intervals (95% CIs)
was calculated for dichotomous outcomes, and weight mean
difference (WMD) with 95% CIs was calculated for con-
tinuous outcomes. Before the data were synthesized, I2
statistic was used to test the heterogeneity among the
included studies, in which I2 4 50% was considered as
statistically significant heterogeneity [27]. A random-effects
model (DerSimonian-Laird method, Inverse variance) was
used to pool the data [28]. Sensitivity analysis was con-
ducted to explore the potential sources of heterogeneity
when significant heterogeneity was present. Meta-
regression was performed to explore heterogeneity and
assess the relationship between dosage of vitamin D sup-
plementation, study design, and the prevalence of vitamin D
depletion. Subgroup analysis was performed based on the
administration dosage of vitamin D supplementation, study
design, surgical type, and study region. Begg’s [29] and
Egger’s test [30] were used to evaluate the publication bias.
P o 0.05 was considered statistically significant. We car-
ried out the statistical analyses by using Stata 12.0 (Stata
Corporation, 4905 Lakeway Drive College Station, TX,
77845, USA).
Results
Study selection
The detailed flowchart of the search process is shown in
Fig. 1. The initial database search yielded 2039 publica-
tions, of which 794 were deleted because of duplicate
records. Then 1245 were left for title and abstract review,
and 1223 of them were excluded because of various reasons
(reviews, letters, case reports, editorial, conference
abstracts, or irrelevance to our topics). The remaining 22
Vitamin D supplementation after bariatric surgery: meta-analysis
Fig. 1 Eligibility of studies for
inclusion in meta-analysis
were scrutinized for full-text information, and ten of them
were also excluded because seven reported the data in
vitamin A rather than vitamin D [16, 31–36], one focused
on liver fibrotic patients [37], one reported data that
were not available [38], and one presented data that were
out of our interest [39]. Finally, 12 studies [18, 34, 40–49]
which involved 1285 patients were included in this meta-
analysis.
Study characteristics
The main characteristics of the included studies are pre-
sented in Table 1. These studies were published between
2006 and 2016. Among these studies, five were published in
USA [18, 41, 43, 45, 48], two in Spain [44, 49], and one
each in Norway [42], Netherlands [34], Germany [40], Italy
[46], and Brazil [47]. The sample size ranged from 41 to
 Z. Li et al.

Table 1 Baseline characteristics of obese patients undergoing bariatric surgery who received vitamin D supplementation in the trials included in
the meta-analysis
Study Country Mean 25-OHD (ng/ml) Treatment regimen No. of Age (mean Preoperative BMI Surgery
preoperatively patients ± SD, y) (mean ± SD, kg/m2)

Carlin AM1 [8] USA 20.3 ± 9 800 IU VitD daily 108 46 ± 9 47 ± 5 RYGB
Dogan K [34] Netherlands 22.5 160 IU VitD daily 74 43.4 ± 10.0 44.8 ± 4.8 RYGB
24.5 500 IU VitD daily 74 45.3 ± 10.2 44.8 ± 6.4 RYGB
Wolf E [40] Germany 25.4 ± 10 3200 IU VitD daily 47 43 ± 11 46.7(44.6, 57.4) RYGB
18.6 ± 4.9 Placebo 47 43 ± 10 50.0(46.3, 58.8) RYGB
Carlin AM [41] USA 19.7 ± 8.5 50,000 IU VitD 30 43 ± 11.9 50.3 ± 4.9 RYGB
weekly
18.5 ± 9.4 800 IU VitD daily 30 42.9 ± 11.3 50.9 ± 6.6 RYGB
Aasheim ET [42] Norway 19.5 1,000 IU VitD daily 27 NR 46 (42–50) RYGB
20.2 None 23 NR 40 (39–44) Lifestyle
Goldner WS [43] USA 19.1 ± 9.9 800 IU VitD daily 13 48.2 ± 11.8 52.5 ± 9 RYGB
15 ± 9.3 2000 IU VitD daily 13 48.3 ± 6.6 60.4 ± 14.2 RYGB
22.9 ± 10.3 5000 IU VitD daily 15 44.6 ± 10.9 56.2 ± 13 RYGB
Flores L [44] Spain 19.6 ± 17 800 IU VitD daily 176 44 ± 11 46 ± 6 RYGB
Boyce SG [45] USA o 30 1600 IU VitD daily 309 47.5 ± 11.4 50.5 ± 30.8 RYGB
Capoccia D [46] Italy 20.9 ± 7.7 800 IU VitD daily 138 NR 46.8 ± 1.5 LGS
da Rosa CL [47] Brazil 14.47 ± 5.6 400 IU VitD daily 83 35 ± 8.86 46 ± 7.56 RYGB
Mahlay NF [48] USA 15.94 800 IU VitD daily 34 47.63 47 RYGB
Lanzarini E [49] Spain 15.2 ± 7.0 16,000 IU VitD 96 45.7 ± 8.9 43 ± 5.5 LSG
every 2 weeks
14.8 ± 2.8 16,000 IU VitD 68 42.5 ± 8.5 44.9 ± 2.8 RYGB
every 2 weeks
BMI body mass index, VitD vitamin D, RYGB Roux-en-Y gastric bypass, LGS laparoscopic gastric bypass, NR not reported

309. Six studies were RCTs [34, 40–43, 49], six were
single-arm studies [18, 44–48]. Among the six RCTs, one
compared the effects of vitamin D supplementation between
patients who had undergone Roux-en-Y gastric bypass
(RYGB) and laparoscopy sleeve gastrectomy (LSG) [49],
one compared that between patients undergoing RYGB and
lifestyle [42], and the remaining studies compared that in
different dosages of vitamin D supplementation [34, 40, 41,
43]. The mean 25-OHD level for patients in each study was
around 20 ng/ml preoperatively. The dosage of vitamin D
supplementation varied greatly among the included studies,
which ranged from 160 IU/day to 50,000 IU/week.
Quality assessment of the included studies
The details of risk bias for RCTs are summarized in Fig. 2.
Overall, two studies were classified as being at low risk of
bias [34, 40], three at unclear risk of bias [41, 43, 49], and
one at high risk of bias [42]. In the trial of Aasheim [42], the
blinding was not performed to participants, personnel, and
outcome assessors. Thus, it was regarded as being at high
risk of bias. The other three studies did not adequately
describe the methods for randomized sequence and
allocation sequence concealment, [43, 49] or the methods
for blinding [41]. Thus, they were regarded as being at
unclear risk of bias. The NOS scale for non-RCTs ranged
from six to eight (median scale seven), which indicated high
quality.
1-year vitamin D depletion
Nine studies reported the data on the 1-year vitamin D
depletion [18, 34, 40–42, 45, 47–49]. Preoperatively and at
1 year postoperatively, the prevalence of vitamin D deple-
tion was 54.0 and 31.0%, respectively. Pooled results
showed that, vitamin D supplementation was associated
with a significant reduction in the prevalence of vitamin D
depletion (RR = 2.28, 95% CI:1.48, 3.50; P = 0.001) (Fig.
3a). Evidence of substantial heterogeneity was observed
across the included trials (I2 = 93.4%, P o 0.001).
Thus, we conducted sensitivity analysis. When the trial
conducted by da Rosa et al. [47] was excluded, the overall
estimate did not change largely (RR = 2.64, 95% CI: 1.76,
3.96; P o 0.001), but heterogeneity was still present (I2 =
90.7%, P o 0.001). We also further excluded one single
study at a time, the overall combined RR did not alter
Vitamin D supplementation after bariatric surgery: meta-analysis
Fig. 2 Risk of bias summary
materially, which ranged from 2.11 (95% CI: 1.35, 3.28; P
= 0.001) to 2.64 (95% CI: 1.76, 3.96; P o 0.001), how-
ever, significant heterogeneity was still observed among the
remaining studies.
Subgroup analysis was conducted according to the
dosage of vitamin D, study design and the study region.
Pooled results showed that, vitamin D supplementation
significantly reduced the prevalence of vitamin D depletion
when it was administrated with a dosage of more than 800
IU/day (RR = 2.08, 95% CI: 1.42, 3.04; P = 0.001), but not
with a dosage of less than 800 IU/day (RR = 2.54, 95%
CI:0.47, 13.77; P = 0.280) (Fig. 3a). Pooled data from
RCTs showed that, vitamin D supplementation was asso-
ciated with a significant lower prevalence of vitamin D
depletion (RR = 3.82, 95% CI: 1.70, 8.57; P = 0.001);
however, this effect was not observed in the pooled data
from non-RCTs (RR = 1.18, 95% CI: 0.60, 2.31; P =
0.629) (Fig. 3b). Subgroup analysis based on the study
region showed that, vitamin D supplementation was
associated with a significant lower prevalence of vitamin D
depletion (RR = 1.76, 95% CI: 1.16, 2.69; P = 0.008) in
American patients.
1-year 25-OHD level
Eleven studies reported data in the 1-year 25-OHD level.
[18, 34, 40–44, 46–49] Pooled results showed that, vitamin
D supplementation significantly improved the 25-OHD
level in patients who had undergone bariatric surgery
(WMD = −19.01 ng/ml, 95% CI: −25.71, −12.31; P o
0.001) (Fig. 4a). Significant heterogeneity was observed
across the studies (I2 = 98.4%, P o 0.001).
Subsequently, we performed sensitivity analysis. When
we excluded the trial with the smallest sample size [43], the
overall estimate changes substantially (WMD = −1.27 ng/
ml, 95% CI: −2.87, −0.32; P = 0.018); however, sig-
nificant heterogeneity was still present (I2 = 87.2%, P o
0.001). When we further excluded any single trial once at a
time, the overall estimate did not change substantially, but
still there was significant heterogeneity (data not shown).
Subgroup analysis was performed according to the
dosage of vitamin D, surgery type, 25(OH)D level at the
baseline, weight loss, study design, and study region.
Pooled estimates showed that, vitamin D supplementation
significantly increased the 25-OHD level no matter it was
administered with a dosage of more than 800 IU/day
(WMD = −21.43 ng/ml, 95% CI: −29.22, −13.64; P o
0.001) or less than 800 IU/day (WMD = −12.13 ng/ml,
95% CI: −23.76, −0.50; P = 0.041) (Fig. 4a). Subgroup
analysis based on surgery type showed that, vitamin D
supplementation significantly increased 25-OHD level in
patients who had undergone RYGB (WMD = −21.20 ng/
ml, 95% CI: −29.32, −13.08; P o 0.001), but not in those
who had undergone LSG (WMD = −5.87ng/ml, 95% CI:
−18.51, 6.77; P = 0.363) (Fig. 4b). Subgroup analysis
based on 25(OH)D level at the baseline demonstrated that
vitamin D supplementation significantly improved the 25-
OHD levels in bariatric surgery patients no matter they had
normal 25(OH)D levels (WMD = −27.9 ng/ml, 95% CI:
−38.4, −17.4; P o 0.001) or vitamin D deficiency (WMD
= −8.63 ng/ml, 95% CI: −14.97, −2.29; P = 0.008), and
patients with normal 25(OH)D levels seemed to have a
greater improvement in 25-OHD levels than those with
vitamin D deficiency. Subgroup analysis based on the
weight loss suggested that, vitamin D supplementation
significantly improved the 25-OHD level in bariatric sur-
gery patients no matter their weight loss was greater than
40 kg (WMD = −16.40 ng/ml, 95% CI: −23.43, −9.36; P
o 0.001), or between 30 and 39 kg (WMD = −19.70 ng/
ml, 95% CI: −30.23, −9.17; P o 0.001). Subgroup ana-
lysis based on the study design demonstrated that, vitamin
D supplementation significantly improved the 25-OHD
 Z. Li et al.

Fig. 3 a Forest plot showing the effect of vitamin D supplementation on the 1-year vitamin D depletion. b Subgroup analysis based on the study
design for the effect of vitamin D supplementation on the 1-year vitamin D depletion

Fig. 4 a Forest plot showing the effect of vitamin D supplementation on the 1-year 25-OHD level. b Subgroup analysis based on the surgery type
for the effect of vitamin D supplementation on the 1-year 25-OHD level

level in both RCTs and non-RCTs (for RCTs, WMD =

−24.56 ng/ml, 95% CI: −33.86, −15.12, P o 0.001; for
non-RCTs, WMD = −11.56 ng/ml, 95% CI: −21.56,
−1.56, P = 0.021). Subgroup analysis based on the study
region showed that, vitamin D supplementation was asso-
ciated with an improvement in 25-OHD level in American
patients (WMD = −26.85ng/ml, 95% CI: −39.96, −13.74;
P o 0.001).

Meta-regression

Meta-regression was performed to investigate the potential

effects of dosage of vitamin D supplementation, and the
study design on the prevalence of vitamin D depletion. And Fig. 5 Funnel plots for risk of publication bias
Vitamin D supplementation after bariatric surgery: meta-analysis
results showed that there was significant relationship
between vitamin D depletion and the study design (P =
0.042), but not between vitamin D depletion and the dosage
of vitamin D supplementation (P = 0.283).
Publication bias
Assessment of publication bias using Begg’s and Egger’s
tests suggested that no potential publication bias was found
across the included studies (Begg’s test: P = 0.373; Egger’s
test: P = 0.489) (Fig. 5).
Discussion
The present study was a systematic review and meta-
analysis with the objective of assessing the efficacy of
vitamin D supplementation in preventing postoperative
vitamin D deficiency. This study demonstrated that vitamin
D supplementation significantly reduced the prevalence of
vitamin D depletion and improved the 25-OHD level fol-
lowing 1-year surgery. Subgroup analysis based on study
design and dosage of vitamin D supplementation suggested
that, a significant decrease in the prevalence of vitamin D
depletion was only found in the RCTs, or the studies that
used vitamin D supplementation with a daily dosage of
more than 800 IU. Elevations in 25-OHD level were
observed in patients who received vitamin D supple-
mentation, irrespective of the dosage of supplementation
and the study design.
There have been three systematic reviews that assessed
the 25-OHD status, or evaluated the effect of vitamin D
supplementation in obese patients undergoing bariatric
surgery [50–52]. Our study expends on these earlier
systematic reviews to provide a better characterization of
the evidence base for vitamin D supplementation in
preventing postoperative vitamin D deficiency. First, in this
meta-analysis, patients receiving vitamin D supplementa-
tion suspended in oil or extra supplements were excluded
because this is more likely to enhance the absorption of
the supplement, and influence the treatment effect,
eventhough in the previous systematic reviews, these
patients were included. Second, this study is a systematic
review and meta-analysis, and we used a random-effects
model to pool the data of the included studies. With the
method of meta-analysis, we are able to systematically
summarize the current original studies on a specific topic,
and provide some implications for future researches and
decision making, especially controversial topics, whereas,
the previous studies were systematic reviews, in which
the data were not quantitatively synthesized. Thus, we are
still uncertain about whether vitamin D supplementation
was effective in the preventing postoperative vitamin D
deficiency, or what was the optimal dosage. Third, in
this study, we also were more able to conduct subgroup
analysis based on administration dosage, study design, and
surgical type, which has not been investigated in the pre-
vious systematic reviews. Fourth, in this study, we con-
ducted sensitivity analysis based on various exclusion
criteria to explore the potential sources of heterogeneity.
And when we excluded any single study, the pooled results
did not change substantially, which adds robustness to our
findings.
There was significant heterogeneity among the included
studies, which was not surprising given there were
differences in characteristics of patients, vitamin D sup-
plementation, study design, and surgical type. Our sensi-
tivity analyses by excluding one study in each turn showed
that, the summarized results did not alter substantially.
However, results from meta-regression suggested that,
vitamin D depletion had a significant relationship with the
study design, indicating that study design might be attrib-
uted to the heterogeneity. In this meta-analysis, vitamin D
supplementation significantly reduced the prevalence of
vitamin depletion; however, this effect was only observed in
RCTs, but not in non-RCTs. da Rosa et al. [47] reported a
lower vitamin D depletion after the bariatric surgery. In that
study [47], 56 women and 27 men undergoing RYGB were
provided daily dietary supplementation of 400 IU vitamin
D. During the preoperative period, the prevalence of ade-
quate vitamin D was 55% for women and 63% for men,
respectively. However, during the postoperative period, the
corresponding values were only 15 and 9%, respectively
[47]. The results suggest that dosage of 400 IU vitamin D
was not sufficient to prevent the worsening of the
deficiency.
Contrary to the negative results of da Rosa CL, some
other studies suggested that vitamin D supplementation
resulted in fewer deficiencies in vitamin D. In the trial of
Dogan et al. [34], a standard multivitamin supplement with
160 IU vitamin D and customized multivitamin supplement
containing 500 IU vitamin D were administered before the
RYGB. The prevalence of preoperative deficiencies in the
two groups was 63 and 67.6%, respectively, compared with
that of 10.1 and 18.5% after the surgery, respectively [34].
These results suggest that both dosage of vitamin D sig-
nificantly reduced the development of vitamin D defi-
ciencies after RYGB. Similar results were found in another
study, in which patients received a daily dosage of 1600 IU
vitamin D [45]. In that study, the prevalence of vitamin
deficiency in preoperative patients was 43.4% (134/309),
compared with that of 23.6% (73/309) in postoperative
patients [45]. The authors concluded that the decreased
prevalence of vitamin D deficiency in their study may be
explained by the increased dosage of vitamin D (1600 IU/
day).

Apart from the adequate dosage, the duration of treat-
ment can also influence the effects of vitamin D supple-
mentation. In the study of Mahlay et al. [48], 72 patients
who had undergone RYGB received postoperatively 800 IU
vitamin D3 daily for a period of 6 weeks. The prevalence of
vitamin D deficiency was 83% in preoperative patients, and
then reduced to 47% in postoperative patients [48].
Although the prevalence was reduced by more than 30%,
there were still almost half of the patients who continued to
have low vitamin D levels. The authors postulated that the
length of treatment might account for the negative results.
In addition, their results were supported by another study,
which suggested that obese patients need treatment in the
length of 8–12 weeks [53]. In that study, the authors argued
that, patients with a level of 25-OH vitamin D less than 30
ng/ml need course repetition. In order to maintain the nor-
mal levels and prevent further vitamin deficiency, patients
should be treated with higher dosages of 50,000 vitamin
D2 weekly for 8 weeks, and repeated for another 8 weeks if
the 25-OH vitamin D is less than 30 ng/ml [53].
Seasonal variation and sunlight exposure were potential
factors that might impact the effects of vitamin D supple-
mentation. However, we did not consider these factors in
this study. Among the included studies, the potential sea-
sonal variation in 25-OHD levels was minimized by com-
paring the levels at 12 months after baseline. Thus, the
seasonal variation would not influence the effects of vitamin
D supplementation.
There were several limitations in this study. First, there
was considerable heterogeneity among the included studies.
Large heterogeneity is the norm in a meta-analysis. Putting
too much trust in homogeneity of effect may give a false
sense of reassurance that one size fits all. Lack of evidence
of heterogeneity is not an evidence of homogeneity [54].
Heterogeneity in this meta-analysis might be caused by the
high variability in vitamin D supplementation regimens,
lack of standard definition of vitamin D depletion, differ-
ences in the study design and surgical type. These factors
may have potential impact on our results. Second, among
the 12 studies, only six were RCTs, and the other six were
observation studies. Compared with RCTs, observational
studies were more likely to result in selection bias and
confounding by indication. Third, we were unable to per-
form the dose–response meta-analysis, due to the sparse
data across the studies.
Conclusions
This study suggests that, vitamin D supplementation with a
daily dosage of more than 800 IU is effective in the pre-
venting postoperative vitamin D deficiency and improving
the 25-OHD level. However, considering the limitations,
Z. Li et al.
more detailed research with well-performed, larger sample-
size are warranted.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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