A Pilot Study of Vitamin D Repletion Shows Improvement in Pain and Vascular Endothelial Function in Adult Patients with Sickle Cell Disease

Vitamin D deficiency (VDD), defined as 25(OH)D<30 mg/mL, is highly prevalent (as high as 98%) in patients with sickle cell disease (1, 2). It is hypothesized that patients with SCD are predisposed to VDD due to decreased cutaneous vitamin D synthesis, compromised intestinal absorption, inadequate dietary intake, and possibly spending less time outdoors (1). Two defining phenotypes of SCD are chronic pain and endothelial dysfunction, both of which may be impacted by vitamin D (3-6). Many centers are active in treating VDD in SCD patients and recently patients in acute pain have been found to have improvement with replacement of their vitamin D. Thus, the purpose of the present study is to evaluate how vitamin D repletion effects inflammation, pain and endothelial function with SCD patients with VDD.

Patients in the adult sickle cell clinic at Georgia Regents University were screened for vitamin D (serum 25-hydroxycholecaciferol levels). Once the inclusion criteria were met, patients were given 8 weeks of high-dose vitamin D repletion (100,000 units oral ergocalciferol weekly) and vitamin D levels (serum 25-hydroxycholecalciferol levels), endothelial function (pulse wave velocity (PWV), flow-mediated dilation (FMD), and endothelial-independent dilation), inflammatory markers (IL6, IL10, TNF-α, ROS, and SVCAM), bone health (bone mineral density using DXA scan), and pain (pain algometer at mandible, neck, and forearm and pain diaries) were evaluated at baseline, week 4 and week 8. All outcomes were again evaluated at week 16 to determine the impact of 8 weeks without treatment.

Thus far, out of 127 SCD patients screened, as expected, we found 95.2% of patients to be VDD. To date, nine patients with SCD who are VDD (<24 mg/ml) have been enrolled. Within the pilot study, 8 patients have completed 16 weeks with the mean vitamin D levels at 14.0mg/ml, 30.3 mg/ml, 67.7 mg/ml, and 52.0mg/ml mg/ml at week 0, week 4, week 8 and week 16, respectively. Pre-liminary we have found that FMD improved from a baseline mean of (8.4% + 4.3) to 4 weeks (11.0% + 4.4; p=0.004) and 8 weeks (11.1% + 4.5) following treatment and began to decrease at week 16 (10.1% + 4.6). The pain algometer readings at week 4, week 8 and 16 are generally lower than the baseline readings. However, this is a general trend, and only one comparison (week 4 vs. baseline at Neck) reaches statistical significance (p=0.010). Most of the comparisons do not reach statistical significance, which could be due to the limited sample size. Our data shows a slight negative relationship between mandibular pain, neck and forearm pain and vitamin D level, all of which were not statistically significant (p=0.88), (p=0.72), and (p=0.52), respectively.

This study has resulted in a sustained significant 5 fold increase in patient vitamin D levels from baseline at only week 4. We see a slight negative relationship between pain and vitamin D level. In addition, an improvement in endothelial function is observed following 8 weeks of Vitamin D supplementation. A reflection of benefit of high dose vitamin D repletion in improving endothelial function in sickle cell patients is noted. More longitudinal and comprehensive studies are needed to further investigate the extensive role vitamin D may play in the overall health in sickle cell disease.