The data we presently have for the use of vitamin D for the treatment of inflammatory bowel disease are of very low quality, and we do not know whether it works or if it is safe.
What is inflammatory bowel disease?
Inflammatory bowel disease is a life-long disease that affects the gut. Its two main types are ulcerative colitis and Crohn's disease. Ulcerative colitis only affects the large intestine. Crohn's disease can affect any part of the gut, from mouth to bottom. Common symptoms include bloody poo, diarrhoea, stomach ache, fever, weight loss, and fatigue. We do not know exactly what causes it, but it is probably a mix of genes, problems with the immune system, bacteria in the gut, and something in the environment. There is no known cure, but the symptoms are usually managed with medicines, such as steroids and immune system medications, and sometimes surgery. Most people with inflammatory bowel disease have times when they have symptoms (called active disease) and other times when their symptoms are under control (called remission). When symptoms reappear after being in remission, it is called relapse.
What did we want to find out?
We wanted to find out if vitamin D works for the treatment of inflammatory bowel disease, and whether it is safe to use. Specifically, we looked at improvement of symptoms for people with active disease; relapse for people in remission; quality of life; and withdrawals from the trial because of side effects.
What did we do?
We searched for randomised controlled trials (studies where people are assigned to one of two or more treatment groups using a random method) comparing vitamin D with any other treatment, standard treatment, or different doses of vitamin D.
What did we find?
We found 22 trials with 1874 participants with inflammatory bowel disease. The studies lasted from four to 52 weeks. Ten studies were on Crohn's disease, five on ulcerative colitis, and seven on participants who had either of these. Seventeen studies were on adults, three on children, and two on both. Four included people with active disease, six in remission, and 12 on a mix of both. The studies included doses of vitamin D used to treat deficiency and doses given as supplements.
Thirteen studies compared vitamin D (all doses) against placebo (dummy treatment) or no other treatment. There was low-quality evidence that there may be fewer clinical relapses when using vitamin D compared to placebo or no treatment. We cannot say anything about any of the other measures we looked at because the quality of the evidence was very low.
Five studies compared high-treatment-doses to low-treatment-doses of vitamin D. There were no data on improvement of symptoms. There was low-quality evidence that there may be no difference on relapse in Crohn's disease, but there were no data on ulcerative colitis. We cannot say anything about any of the other measures we looked at because the quality of the evidence was very low.
Four studies compared treatment doses to supplement doses of vitamin D. There were no data on improvement of symptoms, relapses, or quality of life changes. We cannot say anything about any of the other measures we looked at because the quality of the evidence was very low.
What are the limitations of the evidence?
The evidence is mostly of very low and low quality. This is because of problems with the way the studies were carried out, and problems with how the results were reported. Additionally, the individual studies did not make the same measurements, meaning that we did not have enough numbers of people to strengthen the results of the measures we looked for.
How up-to-date is this review?
This review is up-to-date to June 2023.
There may be fewer clinical relapses when comparing vitamin D with placebo, but we cannot draw any conclusions on differences in clinical response, quality of life, or withdrawals, due to very low-certainty evidence. When comparing high and low doses of vitamin D, there were no data for clinical response, but there may be no difference in relapse for CD. We cannot draw conclusions on the other outcomes due to very low certainty evidence. Finally, comparing vitamin D (all doses) to supplemental-dose vitamin D, there were no data on clinical relapse or response, and we could not draw conclusions on other outcomes due to very low certainty evidence or missing data.
It is difficult to make any clear recommendations for future research on the basis of the findings of this review. Future studies must be clear on the baseline populations, the purpose of vitamin D treatment, and, therefore, study an appropriate dosing strategy. Stakeholders in the field may wish to reach consensus on such issues prior to new studies.
Vitamin D possesses immunomodulatory properties and has been implicated in the pathogenesis and severity of inflammatory bowel disease (IBD). Animal studies and emerging epidemiological evidence have demonstrated an association between vitamin D deficiency and worse disease activity. However, the role of vitamin D for the treatment of IBD is unclear.
To evaluate the benefits and harms of vitamin D supplementation as a treatment for IBD.
We used standard, extensive Cochrane search methods. The latest search date was Jun 2023.
We included randomised controlled trials (RCTs) in people of all ages with active or inactive IBD comparing any dose of vitamin D with another dose of vitamin D, another intervention, placebo, or no intervention.
We defined doses as: vitamin D (all doses), any-treatment-dose vitamin D (greater than 400 IU/day), high-treatment-dose vitamin D (greater than 1000 IU/day), low-treatment-dose vitamin D (400 IU/day to 1000 IU/day), and supplemental-dose vitamin D (less than 400 IU/day).
We used standard Cochrane methods. Our primary outcomes were 1. clinical response for people with active disease, 2. clinical relapse for people in remission, 3. quality of life, and 4. withdrawals due to adverse events. Our secondary outcomes were 5. disease activity at end of study, 6. normalisation of vitamin D levels at end of study, and 7. total serious adverse events. We used GRADE to assess certainty of evidence for each outcome.
We included 22 RCTs with 1874 participants. Study duration ranged from four to 52 weeks. Ten studies enroled people with Crohn's disease (CD), five enroled people with ulcerative colitis (UC), and seven enroled people with CD and people with UC. Seventeen studies included adults, three included children, and two included both. Four studies enroled people with active disease, six enroled people in remission, and 12 enroled both.
We assessed each study for risk of bias across seven individual domains. Five studies were at low risk of bias across all seven domains. Ten studies were at unclear risk of bias in at least one domain but with no areas of high risk of bias. Seven studies were at high risk of bias for blinding of participants and assessors.
Vitamin D (all doses) versus placebo or no treatment
Thirteen studies compared vitamin D against placebo or no treatment.
We could not draw any conclusions on clinical response for UC as the certainty of the evidence was very low (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.51 to 10.57; 1 study, 60 participants). There were no data on CD.
There may be fewer clinical relapses for IBD when using vitamin D compared to placebo or no treatment (RR 0.57, 95% CI 0.34 to 0.96; 3 studies, 310 participants). The certainty of the evidence was low.
We could not draw any conclusions on quality of life for IBD (standardised mean difference (SMD) −0.13, 95% CI −3.10 to 2.83 (the SMD value indicates a negligent decrease in quality of life, and the corresponding CIs indicate that the effect can range from a large decrease to a large increase in quality of life); 2 studies, 243 participants) or withdrawals due to adverse events for IBD (RR 1.97, 95% CI 0.18 to 21.27; 12 studies, 1251 participants; note 11 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 12). The certainty of the evidence was very low.
High-treatment-dose vitamin D versus low-treatment-dose vitamin D
Five studies compared high treatment vitamin D doses against low treatment vitamin D doses.
There were no data on clinical response.
There may be no difference in clinical relapse for CD (RR 0.48, 95% CI 0.23 to 1.01; 1 study, 34 participants). The certainty of the evidence was low.
We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 0.89, 95% CI 0.06 to 13.08; 3 studies, 104 participants; note 2 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 3).
The data on quality of life and disease activity could not be meta-analysed, were of very low certainty, and no conclusions could be drawn.
Any-treatment-dose vitamin D versus supplemental-dose vitamin D
Four studies compared treatment doses of vitamin D against supplemental doses.
There were no data on clinical response and relapse.
There were no data on quality of life that could be meta-analysed.
We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 3.09, 95% CI 0.13 to 73.17; 4 studies, 233 participants; note 3 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 4).