Vitamin E supplementation in people with cystic fibrosis

Review question

We wanted to know what effects, if any, vitamin E supplementation (at any dose) has on how often people with cystic fibrosis have health problems due to vitamin E deficiency.

Background

Approximately 85% to 90% of people with cystic fibrosis do not produce enough enzymes in their pancreas and are not able to absorb fat when digesting food; they are also likely to have problems absorbing the fat-soluble vitamins A, D, E and K. If levels of vitamin E are too low, this may cause blood disorders and problems with the nervous system, with memory and with thinking skills.

Search date

We last searched for evidence on 20 July 2020.

Study characteristics

We identified four studies including 141 participants; two of these were in children (aged six months to 14.5 years) and two did not specify the age of the participants. Those taking part in the studies received different forms of vitamin E supplements (either water-soluble or fat-soluble), placebo (a substance containing no medication) or no supplements. Three studies stated that the treatment for each person was chosen at random, but one study only said the people were split into different groups.

Key results

Water-soluble vitamin E

Evidence from one study (45 participants) showed that supplementation may increase vitamin E levels in the blood after six months. Similar results were seen at the earlier time points of one month (two studies, 32 participants) and three three months (one study, 45 participants). Only one study (45 participants) reported weight at one and six months, but showed no difference between supplementation and placebo at either time point.

Fat-soluble vitamin E

Two studies (36 participants) reported higher levels of serum vitamin E after one month of fat-soluble vitamin E supplements compared with no treatment, but a different study (36 participants) did not find any difference between supplementation and no treatment after three months.

None of the studies in either comparison reported results for our planned outcomes of vitamin E total lipid ratio, the incidence of vitamin E-specific deficiency disorders, lung function or quality of life.

As the studies used different forms of supplements and different doses, it was difficult to combine the results and apply them to the wider cystic fibrosis population. The results showed that vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, but the quality of the evidence was low.

Future studies should look at more specific outcomes such as vitamin E status, lung function and nutritional status, especially in people already receiving treatment with pancreatic enzymes and vitamin E supplements. They could also look at the best level of vitamin E supplements needed to be most clinically effective.

Quality of the evidence

We judged the evidence to be low quality for the following reasons. We do not think that any of the people taking part in the studies could tell whether they received the supplements or the placebo, so that would not have affected the results; although they would have known if they were taking supplements or not taking anything. We could not tell from the information we have whether most of the studies were designed so all people had an equal chance of being in any of the groups. We also could not tell if anyone would have been able to guess in advance which group they would be in. It was also not clear if there were results reported for everyone taking part in the studies and the reasons why anyone might have dropped out of the studies. We do not know if these facts will affect our confidence in the results.

Authors' conclusions: 

Vitamin E supplementation may lead to an improvement in vitamin E levels in people with cystic fibrosis, although evidence we assessed was low quality. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.

In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Read the full abstract...
Background: 

People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency, including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended for people with cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review.

Objectives: 

To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis.

Search strategy: 

We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international online trial registries for any ongoing clinical trials that were not identified during our register search.

Date of last search of the Register: 11 August 2020.
Date of last search of international online trial registries: 20 July 2020.

Selection criteria: 

Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration.

Data collection and analysis: 

Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. They assessed the quality of the evidence using GRADE.

Main results: 

Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and two did not specify participants’ age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.

There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population.

None of the studies in either comparison report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life.

Water-soluble vitamin E

Water-soluble vitamin E may improve serum vitamin E levels compared with control at six months, one study (45 participants), mean difference (MD) 19.74 umol/L (95% confidence interval (CI) 13.48 to 26.00) (low-quality evidence). Similar results were also seen at one month, two studies (32 participants), MD 17.66 umol/L (95% CI 10.59 to 24.74) and at three months, one study (45 participants), MD 11.61 umol/L (95% CI 4.77 to 18.45). Only one study (45 participants) reported weight (secondary outcome of growth and nutritional status) at one and six months, but showed no difference between treatment and control at either time point.

Fat-soluble vitamin E

Two studies (36 participants) reported higher levels of serum vitamin E at one month with fat-soluble vitamin E compared with control, MD 13.59 umol/L (95% CI 9.52 to 17.66); however, at three months one study (36 participants) showed no difference between treatment and control. No studies in this comparison reported on growth or nutritional status.

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