Abstract:
Background: Pain-related conditions can seriously influence quality of life, lead to work disability, and are major contributors to the burden of morbidity and disability worldwide. Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. Objective: The aim of this thesis is to compare the effect of monthly high-dose vitamin D supplementation on pain levels and the prescription of analgesics in general population. In addition, the relationship between vitamin D supplementation and the adherence and persistence of statin utilisation is explored in long-term statin users. Methods: A population-based randomised controlled trial (RCT) of 5108 participants aged 50- 84 years recruited from the community, randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. Pain levels were assessed at baseline, year one, and final follow-up. Analgesic and statin prescription data were collected from New Zealand Ministry of Health databases. Results: There was no difference in mean pain impact questionnaire (PIQ-6) scores in the past 4 weeks at the end of follow-up (mean difference = 0.06, P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants (primary outcome). The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%) – adjusted relative risk (RR) was 0.94 (P = 0.24) (primary outcome). Similar results were observed in the risk of dispensing Nonsteroidal antiinflammatory drugs (NSAIDs) (adjusted RR = 0.94; P = 0.24) and other non-opioids (adjusted RR = 0.98, P = 0.34) (primary outcomes). However, in 2462 participants on long-term statins, compared with the placebo group, vitamin D supplementation improved the persistence (nondiscontinuation of statin therapy following an allowed gap between refills) probability of all statins during a 24-month measurement period (hazard ratio = 1.15, P = 0.02). Conclusion: Long-term monthly high-dose vitamin D supplementation (100,000-IU) did not improve pain levels in the past 4 weeks, or reduce opioid, NSAID or other non-opioid dispensing in the general population. However, among participants with long-term statin therapy, monthly vitamin D supplementation improved persistence with taking statins over a 24-month measurement period.