Vitamin D supplementation for cystic fibrosis.
BACKGROUND
Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis.


OBJECTIVE
To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population.


METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013.


METHODS
Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function.


METHODS
Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events.


RESULTS
Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double-blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two studies for attrition bias. In the studies published as abstracts, assessment of the risks of bias was uncertain in many aspects.


CONCLUSIONS
In patients receiving vitamin D supplementation, 25-hydroxyvitamin D levels are significantly higher. However, there is no evidence of clinical benefit or harm in the limited number of small-sized published studies. Adherence to relevant cystic fibrosis guidelines on vitamin D supplementation should be considered until further evidence is available.
Christchurch Hospital, Canterbury District Health Board, Private Bag 4710, Christchurch, New Zealand, 8140.
Janet H
JH
Ferguson
Anne B
AB
Chang
D000328:Adult; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects; D002136:Calcium, Dietary / Q000008:administration & dosage; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism; D019587:Dietary Supplements; D010188:Exocrine Pancreatic Insufficiency / Q000150:complications; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy
D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D014807:Vitamin D; D002117:Calcitriol; D002112:Calcifediol