Abstract

Abstract Background

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.

Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions.

To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators.

For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries.

We included studies if they were randomised double‐blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults.

Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events.

We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co‐interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence).

The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.

Author(s)

Sebastian Straube, Sheena Derry, Carmen Straube, R Andrew Moore

Abstract

Plain language summary

Vitamin D for the treatment of chronic painful conditions in adults

Chronic pain is pain of moderate or severe intensity lasting three months or more. It can have a variety of causes, but most comes from musculoskeletal conditions such as arthritis, or pain in muscles. Chronic pain usually affects older people more than younger people. Chronic pain is disabling, and has a large negative impact on quality of life.

Vitamin D has a variety of roles in the body. It is made in the skin through the action of sunlight and can also be obtained from food. A lack of vitamin D has been implicated in a number of conditions, including chronic pain. Additionally, associations of such diverse types of pain as headache, abdominal pain, knee pain, and back pain with season of the year and latitude provide indirect support for a role for vitamin D. The possibility of a link between low levels of vitamin D and chronic pain has attracted interest because ‐ if it were true ‐ vitamin D would be an inexpensive and relatively safe treatment.

We searched scientific databases for studies comparing vitamin D supplementation with placebo (a dummy treatment) or active medicines for the treatment of chronic painful conditions in adults. The evidence is current to February 2015.

There is a small amount of evidence supporting this link but it is not of high quality and may not be reliable. This update of a review sought high quality evidence from randomised controlled trials (studies where participants are randomly allocated to receive one of several treatments) on vitamin D for chronic painful conditions.

We found no consistent pattern that vitamin D treatment was better than placebo for any chronic painful condition, but the studies had methodological shortcomings (low quality evidence).

More research is needed to determine if vitamin D is a useful pain treatment in any particular chronic painful condition. That research should examine whether any effect is restricted to people who are vitamin D deficient. It should also examine how much vitamin D is required, and for how long, before beneficial effects occur.

Author(s)

Sebastian Straube, Sheena Derry, Carmen Straube, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions

Implications for practice For people with chronic pain

The evidence base did not indicate that vitamin D supplementation for chronic painful conditions in adults is beneficial in terms of bringing about pain relief, though the evidence is insufficient to reach a definitive conclusion for clinical practice.

The evidence base did not indicate that vitamin D supplementation for chronic painful conditions in adults is beneficial in terms of bringing about pain relief. Frank vitamin D deficiency or insufficiency may dictate vitamin D treatment, but pain intensity reduction should not be expected.

There is no evidence that vitamin D supplementation reduces pain in people with chronic pain.

Treating chronic pain with vitamin D is unlikely to have any benefits, or be cost‐effective.

Implications for research General

Even though this Cochrane review update now includes more than twice as many studies and participants as the original review (Straube 2010), there is still a need for more work in this area. A number of studies that have been identified by searching online trial registries seem to be ongoing, so that there is the possibility of having more data available to assess the effect of vitamin D in chronic pain in the future. Even though the present evidence does not suggest a beneficial effect, such an effect of vitamin D on chronic pain is theoretically possible, even in the absence of a clearly identifiable mode of action, because of the wide range of effects of vitamin D (Holick 2007), and the many molecular and neural mechanisms involved in the pathogenesis of various chronic pain conditions. While there is little evidence from double‐blind randomised controlled trials, other study types do suggest that there may be a link (Straube 2009). Because vitamin D is inexpensive and relatively safe, a use in chronic pain could be advocated even if the benefit was of modest size.

Large, double‐blind, randomised controlled trials in a variety of chronic pain conditions conducted over long enough periods of time with multiple assessments to capture short, medium, and long term effects are called for. To provide the highest quality evidence, these trials need to be stratified by baseline 25‐hydroxyvitamin D levels, with defined treatments, with clinically relevant pain outcomes (such as the primary outcomes that this review looked for), and ideally with outcomes analysed by post‐treatment 25‐hydroxyvitamin D level. Because it is unclear whether vitamin D has an effect at all, trials need to include a placebo group; and because it is unclear which dose of vitamin D ‐ if any ‐ is effective, different treatment regimens need to be compared. Finally, trials need to report on adverse events and give details of withdrawals and drop‐outs (all‐cause, lack of efficacy, and adverse event withdrawals), as is now established standard in the pain field.

Standard pain outcomes should be used. The ideal outcome is people achieving at least 50% pain intensity reduction, or being in a final pain state of no worse than mild pain.