Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis
PP Hujoel. Review published: 2013.
Most of the trials in this meta-analysis were from 1920 to 1950 and used 800 IU of Vitamin D on children
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CRD summary
This review of controlled clinical trials found the data suggested that vitamin D was a promising preventative agent against tooth cavities and decay (dental caries), which lead to a low-certainty conclusion that vitamin D may reduce the incidence of dental caries. The author's cautious conclusions reflect the limitations of the data and appear to be appropriate.
Authors' objectives: To assess the effectiveness of vitamin D in dental caries prevention.
Searching
The following databases were searched up to January 2011: JSTOR, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). Search strategies were reported in a separate online appendix. Three reference works on dental caries and relevant text books were also searched.
Study selection
Controlled clinical trials that evaluated supplemental dietary vitamin D or ultraviolet radiation and included a concurrent control group were eligible for inclusion. Eligible trials had to report the incident caries counts and follow-up time; they also had to assign vitamin D under control of the investigators for the purpose of prevention. Trials of salivary or microbiological surrogates of caries were excluded, as were retrospective studies and cross-sectional studies. Trials where vitamin D assignment was based on medical need were also excluded. The outcome of interest was the incidence of dental caries.
Most included trials evaluated vitamin D3 with a median dose of 800 IU or vitamin D2 with a median dose of 3,750 IU; detailed information on the calculation of vitamin D doses was reported in the paper. A small number of trials evaluated ultraviolet radiation. The included trials recruited either children or young adults; most trials were conducted between the first and the second world wars. The age of participants ranged from two to 16 years. Trials usually recruited both girls and boys, but four trials only recruited either girls or boys. Participants had either an unspecified diet or a mineralising diet, which complemented the vitamin D supplementation. Most caries counts were reported at a tooth level or a surface level, with caries data primarily based on permanent teeth or permanent teeth combined with primary teeth. Most trials were conducted in institutional-based or school-based settings; some were conducted in practice-based or hospital-based settings. Included trials were conducted in the USA, UK, Canada, Austria, New Zealand and Sweden.
The authors did not report how many reviewers assessed studies for inclusion.
Assessment of study quality
The quality of trials was assessed using the 21-item Downs and Black instrument. The assessed items included method of treatment assignment, blinding, use of placebo, baseline comparability and loss to follow-up. A summary quality score was assigned to each trial.
The authors did not state how many reviewers performed quality assessment.
Data extraction
Data were extracted on event rates to calculate relative risks with 95% confidence intervals. For crossover trials, caries data were limited to the period prior to cross-over.
The authors did not state how many reviewers performed data extraction.
Methods of synthesis
Random-effects models were used to calculate the pooled relative risks with 95% confidence intervals. Statistical heterogeneity was assessed using the Q statistic and I2. Meta-regressions were used to assess the impact of risk of bias on the overall results.
Subgroup analyses were performed on the basis of different types of supplemental vitamin D. Sensitivity analyses were performed to assess the impact of individual trials on overall results.
Publication bias was assessed using funnel plots and Egger’s test.
Results of the review
Twenty-four controlled clinical trials were included in the review (2,827 participants). The quality score ranged from 6 to 21 (mean 14.8). Three trials used random assignment. Eleven trials were cluster-randomised. Non-comparability in baseline caries score between intervention and control groups was present in four trials. There was a lack of outcome assessor blinding in nineteen trials. Fourteen trials did not use placebo as control. The median drop-out rate was 47% (where reported).The median duration of follow-up was 12 months.
Supplemental vitamin D was associated with a significant reduction in the incidence of dental caries compared with no supplement (RR 0.53, 95% CI 0.43 to 0.65; 38 comparisons). Significant heterogeneity was observed for this outcome (p<0.0001).
Subgroup analyses showed that compared with no supplement,
- supplemental ultraviolet radiation (RR 0.36, 95% CI 0.17 to 0.78),
- vitamin D3 (RR 0.51, 95% CI 0.40 to 0.65) and
- vitamin D2 (RR 0.64, 95% CI 0.48 to 0.86)
were associated with a significant reduction in dental caries.
Sensitivity analysis showed that no individual trial had a large impact on the summary estimate. Results of meta-regressions were also reported.
There was evidence of publication bias.
Authors' conclusions
The analysis of data from controlled clinical trials suggested that vitamin D was a promising caries-preventive agent, which lead to a low-certainty conclusion that vitamin D may reduce the incidence of caries.
CRD commentary
The review question was clear and was supported by appropriate inclusion criteria. A number of relevant databases were searched. Efforts were made to find unpublished studies, but assessment of publication bias indicated that this bias was present. No language restrictions were applied to the search, which minimised the risk of language bias. It was unclear whether sufficient attempts were made to minimise errors and biases during the review process.
Appropriate criteria were used to assess trial quality; most trials were subject to risk of bias (particularly the high risk for attrition bias). Statistical heterogeneity was assessed; it indicated a highly significant heterogeneity for the pooled outcomes. Appropriate methods were used to pool the trials, but the value of the pooled outcomes may have been compromised by the high degree of heterogeneity. The authors acknowledged the limited generalisability of the evidence to available populations, since most data were from populations growing up between the first and the second world wars.
Overall, the author's cautious conclusions reflect the limitations of the data and appear to be appropriate.
Implications of the review for practice and research
Practice: The authors stated that the result of this systematic review suggested that vitamin D exposure in early life may play a role in caries prevention.
Research: The author stated that ongoing trials that investigated the role of vitamin D intake should assess both dental caries and periodontal disease as part of overall research aims.
Funding: No external funding.
Bibliographic details
Hujoel PP. Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis. Nutrition Reviews 2013; 71(2): 88-97. 10.1111/j.1753-4887.2012.00544.x
Abstract
Vitamin D has been used to prevent and treat dental caries. The objective of this study was to conduct a systematic review of controlled clinical trials (CCTs) assessing the impact of vitamin D on dental caries prevention. Random-effects and meta-regression models were used to evaluate overall and subgroup-specific relative-rate estimates. Twenty-four CCTs encompassing 2,827 children met the inclusion criteria. Twenty-two of the 24 CCTs predated modern clinical trial design, some of which nonetheless reported characteristics such as pseudo-randomization (n = 2), blinding (n = 4), or use of placebos (n = 8). The relative-rate estimates of the 24 CCTs exhibited significant heterogeneity (P < 0.0001), and there was evidence of significant publication bias (P < 0.001). The pooled relative-rate estimate of supplemental vitamin D was 0.53 (95% CI, 0.43-0.65). No robust differences were identified between the caries-preventive effects of vitamin D(2) , vitamin D(3) , and ultraviolet radiation (Prob > F = 0.22). The analysis of CCT data identified vitamin D as a promising caries-preventive agent, leading to a low-certainty conclusion that vitamin D may reduce the incidence of caries.