Patients with cystic fibrosis (CF) are deficient in vitamin D, which at higher levels can help prevent exacerbation. A new study examines current guidelines and future recommendations.
Yasmeen Abu-Fraiha, MD
While it’s long been established that vitamin D deficiency is a common problem in patients with cystic fibrosis (CF), there has been little success following implementation of a number of recommended protocols for supplementation. A new study examines existing guidelines and what else can be done to improve treatment of vitamin D deficiency in these patients and reduce respiratory exacerbations.
The study, published in the Journal of Pediatric Gastroenterology and Nutrition, reviewed guidelines for vitamin D supplementation published by the North American Cystic Fibrosis Foundation (NACFF) in 2012 and found they were still insufficient to increase vitamin D to clinically beneficial levels in CF patients.1 Yasmeen Abu-Fraiha, MD, lead author of the report and cofounder of the nongovernmental organization GENESIS, says vitamin D deficiency is undertreated in patients with CF, even with current guidelines that already recommend high doses of supplementation.
“Our study demonstrates that the new NACFF guidelines for supplementing vitamin D in patients with CF succeed in raising serum levels of 25-hydroxyvitamiin D (25[OH]D) but are still not sufficient in raising it in all the patients above the cutoff of 30 ng/mL (75 nmol/L),” Abu-Fraiha and her team write in the report. “Monitoring serum vitamin D levels while adjusting the dose according to the levels may lead to normalization of the levels in most patients. More research is needed to test the protocol over longer periods with a larger sample size and higher compliance rate to draw reliable conclusions. This study, however, suggests that increasing serum vitamin D levels in patients with CF leads to a decrease in the number of respiratory exacerbations.”
The study evaluated 90 patients for nearly 17 months using the NACFF recommendations for vitamin D supplementation. Whereas the number of patients with normal vitamin D levels increased over the study period from 20 to 27, the study authors conclude that progress was not enough to significantly improve outcomes for these patients because desired serum levels still were not achieved in most patients.
Benefits of vitamin D in CF
The study is the first to test the efficacy of the NACFF protocol and supports previous research suggesting much higher doses of vitamin D are needed for a clinical benefit in CF patients. Increased serum vitamin D levels are associated with fewer pulmonary exacerbations-a change that both improves quality of life for patients and reduces costs from treatments and hospital stays.
This report is unique in that it shows the benefit of administering active vitamin D over inactive vitamin D, and correlates serum vitamin D levels to the number of days a CF patient may stay in the hospital. Researchers note that the role of vitamin D in preventing autoimmune disease, enhancing antimicrobial protection, and fighting viral infections has opened the door to more research that could further help CF patients avoid exacerbations.
Abu-Fraiha explains the role of vitamin D in reducing pulmonary exacerbations in CF patients.
“First, the respiratory epithelium is able to convert inactive 25(OH)D to active 1,25(OH)2D and this function is impaired in CF. For that reason, giving CF patients active vitamin D3 may overcome this impairment. Second, the presence of vitamin D receptors in respiratory epithelium may indicate an important role for vitamin D in the lungs and the correlation between vitamin D deficiency and respiratory viral infections,” she says. “Finally, it is known that vitamin D has a role in the systemic immune system-it inhibits the activity of antigen presenting cells, the expression of inflammatory cytokines, and the differentiation of T lymphocytes. It is also suggested that vitamin D has independent antimicrobial activity.”
Abu-Fraiha notes that the relationship between vitamin D levels and fewer exacerbations may not be causal, and merely a sign of better overall compliance in treatment regimens, although the subjects in this study did not report any changes in compliance with treatment regimens over the study period.
“Our patients were treated according to the NACFF guidelines published in 2012 and they were insufficient. It is probable that CF patients may need higher doses of vitamin D3, or closer follow-up for better compliance to treatment,” she says. “Because even with very high doses of vitamin D supplementation it was difficult to achieve normal vitamin D levels, we believe that it is extremely hard to reach vitamin D toxicity in CF patients, and this should not be a concern.”
Vitamin D deficiency is underdiagnosed
The study suggests that malabsorption and a need for megadoses of vitamin D could be partly to blame for the lack of clinical efficacy of the NACFF protocol, as well as a lack of data on patterns of vitamin D metabolism in patients with CF compared with control groups. More research is needed to measure other vitamin D metabolites, the study concludes.
Abu-Fraiha says she hopes the study will help increase awareness of vitamin D deficiencies in patients with CF and other pulmonary diseases.
“Vitamin D deficiency is an underdiagnosed entity, especially in sunny countries like Israel. We should pay attention to it more and treat it more aggressively than previously thought. If there is really a causal association between vitamin D deficiency and respiratory infection, treatment will become more cost effective,” she notes. “However, we need more research to understand fully the vitamin role in the respiratory system and in the immune system.”
1. Abu-Fraiha Y, Elyashar-Earon H, Shoseyov D, et al. Increasing vitamin D serum levels is associated with reduced pulmonary exacerbations in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2019; 68(1):110-115.