Prior research has found that adequate vitamin D levels may play an important role in the moderation of painful conditions, and this can be of special consequence in elderly patients. A newly reported prospective, randomized, double-blind, placebo-controlled trial examined benefits of vitamin D supplementation on quality of life, functional mobility, and pain relief in the elderly. While the outcomes were favorable the conclusions to be drawn from this study are disappointing.
Researchers at the Training and Research Hospital in Adana, Turkey, enrolled 120 community-dwelling elderly subjects aged 70 years, on average, who were attending an outpatient rheumatology pain clinic for various ailments (excluding fibromyalgia but not otherwise specified) [Sakalli et al. 2011]. Subjects were randomly assigned to 4 groups of 30 subjects each; there were no differences in age or gender between the groups and one-time treatments were administered as follows (both investigators and subjects were blinded as to the actual ingredient):
> Group 1 — 300,000 IU vitamin D via intramuscular (IM) injection.
> Group 2 — Placebo IM injection.
> Group 3 — 300,000 IU oral vitamin D tablet.
> Group 4 — Placebo oral tablet.
A battery of biochemical assessments performed pretreatment and at 4-weeks followup included: serum vitamin D, parathyroid hormone (PTH), creatinine, calcium, phosphorous, ALT, ALP, and 24-hour urine calcium excretion. Additionally, before and 4 weeks following vitamin D or placebo administration, pain was assessed via a 10 cm visual analog scale (0-10 VAS), functional mobility with a TUG (Timed Up-and-Go) test, and quality of life with the Short Form (SF)–36 questionnaire. The following outcomes were observed:
- Group 1 (vitamin D injection) — the PTH level was decreased and the vitamin D level increased significantly. VAS scores and the TUG test times decreased significantly. On SF-36 measures, there were statistically significant improvements in physical functioning, bodily pain, general health, social functioning, and mental health. [In all cases significance denotes P <0.05.]
- Group 2 (placebo injection) — there were significant decreases in VAS scores and improvements in emotional functioning, but no changes in biochemical or other parameters.
- Group 3 (vitamin D oral tablet) — similar to group 1, the PTH level was decreased and the vitamin D level increased significantly, and there also was a significant increase in 24-hour calcium excretion. VAS scores and TUG times were decreased significantly, whereas physical function was increased significantly.
- Group 4 (placebo tablet) — VAS scores decreased significantly. There were no significant changes in other parameters.
Of interest, significant increases in parathyroid hormone, but not vitamin D levels themselves, had the strongest correlation with improvements in pain and quality of life factors. Overall, the authors conclude that single, megadose administration of vitamin D — via IM or orally — decreases pain, increases quality of life, and improves functional mobility in the elderly. However, there were some irregular findings that may cause some critics to misclassify this research as a failed trial of vitamin D.
COMMENTARY: Vitamin D for pain has been extensively discussed in our evidence-based report [here] and a series of Pain-Topics UPDATES [here]. In this present study, roughly 63% of elderly patients had vitamin D insufficiencies (<25 ng/mL) at baseline; however, the single megadose supplements had only moderate effect sizes — 0.47 and 0.53 — in elevating vitamin D levels in Groups 1 and 3, respectively, to approximately 26.5 ± 12 ng/mL (mean ± SD). [Note: effect sizes were calculated by us using data in the report and not provided by the study authors.]
The decrease in parathyroid hormone was greatest in Group 3 (oral vitamin D). However, the effect sizes of PTH decreases in Group 1 (IM vitamin D) and Group 4 (placebo tablet) were nearly equivalent, which is unexpected and unexplained. Elevations of PTH, often triggered by inadequate vitamin D, can lead to painful osteomalacia, along with osteopenia and osteoporosis. In this study, there was an unusually high level of PTH in Group 1 at the outset compared with other groups, with significant reductions stimulated by vitamin D supplementation but with high variability — 98.1 ± 61.0 pg/mL pretreatment vs. 69.3 ± 323.0 pg/mL post-treatment — so something was awry in this group.
It makes sense that reductions in PTH correlated with VAS score decreases in pain, especially if there was osteomalacic involvement; however, reductions in VAS scores were small, albeit statistically significant, and occurred across all groups (including placebo) from pre- to post-treatment assessments. In fact, the VAS improvement effect size with IM-placebo in Group 2 was 20% greater than in the vitamin D tablet Group 3. The authors concede that IM injection may exert a strong placebo effect, but there also is a possibility that the VAS as a measure of pain among elderly subjects may produce false or distorted outcomes due to cognitive-deficit factors.
It is essential that more prospective, randomized controlled trials of this nature be performed to truly assess benefits of vitamin D supplementation for pain relief in the elderly. However, this present investigation exemplifies several research deficiencies of concern:
- A single, megadose administration of vitamin D (300,000 IU in this case) is probably an inadequate test for assessing longer-term benefits. In fact, some research has suggested that such megadoses in the elderly may do more harm than good [see UPDATE here]. Also, the human body, even with full sun exposure, naturally produces no more than about 15,000 IU of vitamin D3 per day; so, the value of one-time megadoses far in excess of that needs further elaboration.
- A short-term followup — 4-weeks in this study — is probably inadequate to fully assess vitamin D effects, which could take months to be fully realized (assuming adequate vitamin D is available throughout the period of assessment).
- The vitamin D levels attained by most subjects in this study (26.5 ng/mL on average) were most likely grossly inadequate to produce strongly beneficial effects. Most authorities agree that vitamin D (ie, 25[OH]D3 levels) significantly in excess of 30 ng/mL are necessary for optimal outcomes in relieving pain.
- The group sizes in this study were barely adequate to provide statistically valid results (although the authors do not report having done a statistical power analysis) and the mix of pain disorders (not fully defined) makes it impossible to know if vitamin D was beneficial for some pain conditions more than others.
Overall, the evidence appears to support benefits of vitamin D supplementation in elderly patients with nonspecific pain, but the outcomes were not robust in this particular study and there are certain factors needing further exploration and definition.
REFERENCE: Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int. 2011; Epub ahead of print [abstract here].