Research on the association of vitamin D status with pain conditions continues to accumulate. In this latest study, a multinational European group of researchers found in a large sample of men that having musculoskeletal pain, particularly chronic widespread pain, was significantly influenced by low levels of vitamin D.

As part of the extensive European Male Ageing Study (EMAS), men 40 to 79 years of age completed a mailed pain assessment questionnaire and attended a clinical assessment that included measurement of vitamin D status signified by 25-hydroxyvitamin D3, or 25(OH)D, levels [McBeth et al. 2010]. Subjects were classified according to 25(OH)D levels as “normal” (≥15 ng/ml) or “low” (<15 ng/ml). Of 3,075 male participants included in the analysis (mean age 60 years, primarily Caucasian), 1,262 (41.0%) were pain-free, 1,550 (50.4%) reported “other pain” that did not satisfy criteria for chronic widespread pain (CWP), and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with “other pain” and those with CWP had significantly lower 25(OH)D levels (p<0.05).

After adjusting for age, men having “other pain” were 30% more likely to have low 25(OH)D, and having CWP was associated with a 50% greater likelihood of low 25(OH)D. These relationships persisted after adjusting for physical activity levels as a surrogate marker for sunshine exposure; however, after adjusting for additional lifestyle factors (such as smoking and alcohol use) the relationship of pain and low 25(OH)D was somewhat decreased — although, those with low vitamin D levels were still 20% more likely to also have pain.

COMMENTARY: In this large study, “other pain” was defined as any pain lasting one day or more in the past month and CWP was based on established criteria for diagnosing fibromyalgia. The total sample mean 25(OH)D level was 25 ng/mL, which could be considered overall as somewhat inadequate, and using a cut-off level of 15 ng/mL to separate “normal” versus “low” values is unusual, since many of those classified as normal still would have deficient levels (<20 ng/mL). It is interesting to note that the significant prevalence of CWP in this population of men was fairly equally distributed across 25(OH)D levels extending from <10 ng/mL to 30+ ng/mL. This suggests that there is a wide range of vitamin D deficiency and insufficiency that might influence CWP, including higher levels that many would otherwise consider as quite adequate 25(OH)D (ie, >30 ng/mL).

In the study population, men who were depressed, smoked cigarettes, and/or reported more frequent alcohol use were more likely to have low 25(OH)D levels. We have previously reported on the negative effects of tobacco and alcohol on 25(OH)D status in our review of vitamin D and pain [see PDF of paper here, page 25]. The investigators also examined levels of serum calcium and parathyroid hormone and found no significant differences between men with or without pain; therefore, clinically evident osteomalacia due to insufficient vitamin D may not have been a major influence (however, there also can be subclinical manifestations of difficult-to-detect osteomalacia).

Of further interest, an earlier published study, from the UK, similarly examined a large but mixed-gender population with and without CWP [reported in our blogpost 8/1/09]. In this study, 11% of men and 12.5% of women had CWP; however, an association of low 25(OH)D levels and pain was found in the women but not the men, and this was not accounted for by differences in lifestyle, anxiety, depression, or diet (although, persons with either high or low body mass index were more adversely affected by deficient vitamin D status). The present study, covering a larger and more diverse European population of men, supports the likelihood that CWP may be equally influenced by vitamin D status in both men and women.

As usual, however, we must caution that cross-sectional studies such as these from Europe and the UK do not confirm a direct cause-effect relationship between pain and low vitamin D status, and there appear to be certain potentially confounding factors. Furthermore, none of the researchers reported on clinical outcomes achieved via vitamin D supplementation in their subjects with pain, and this is a common shortcoming of much research in this field of inquiry that needs to be corrected.

REFERENCE: McBeth J, Pye SR, O’Neill TW, et al. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis. 2010;69:1448-1452 [abstract here].