Study design (if review, criteria of inclusion for studies)
All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.
Participants
Children or adults with CF (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.
Interventions
Vitamin A supplementation
Outcome measures
Primary outcomes 1. Vitamin A deficiency disorders (visual impairment and other ocular dysfunction; skin manifestations, e.g. phrynoderma) 2. Growth and nutritional status (e.g. weight, height, body mass index, z score for weight, etc.) 3. Mortality
Main results
No studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (β)âcarotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive βâcarotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the lowâdose supplementation period should be interpreted with caution, due to the lack of a washâout period after the highâdose supplementation. The included study did not report on two of the review's primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD) â0.23 (95% confidence interval (CI) â0.89 to 0.43) (lowâquality evidence). With regards to secondary outcomes, supplementation with highâdose βâcarotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD â15 days (95% CI â27.60 to â2.40); however, this was not maintained in the second threeâmonth section of the study when the level of βâcarotene supplementation was reduced, MD â8 days (95% CI â18.80 to 2.80) (lowâquality evidence). There were no statistically significant effects between groups in lung function (lowâquality evidence) and no adverse events were observed (lowâquality evidence). Supplementation affected levels of βâcarotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity.
Authors' conclusions
Since no randomised or quasiârandomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the lowâquality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on βâcarotene supplementation can be drawn. Until further data are available, countryâ or regionâspecific guidelines regarding these practices should be followed.