Vitamin A supplementation for cystic fibrosis

  • Review
  • Intervention

Authors


Abstract

Background

People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice.

Objectives

To determine if vitamin A supplementation in children and adults with cystic fibrosis:
1. reduces the frequency of vitamin A deficiency disorders;
2. improves general and respiratory health;
3. increases the frequency of vitamin A toxicity.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014.

Selection criteria

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.

Data collection and analysis

No relevant studies for inclusion were identified in the search.

Main results

No studies were included in this review.

Authors' conclusions

As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed.

Résumé scientifique

La supplémentation en vitamine A dans la mucoviscidose

Contexte

Les personnes souffrant de mucoviscidose avec insuffisance pancréatique présentent un risque de carence en vitamines liposolubles car ces vitamines (A, D, E et K) sont co-absorbées avec les graisses. Ainsi, certains centres de prise en charge de la mucoviscidose administrent en routine ces vitamines dans le cadre d'une supplémentation, mais les centres varient dans leur manière d'aborder le développement possible de ces carences en vitamines. La carence en vitamine A entraîne surtout des problèmes oculaires et cutanés tandis que la supplémentation en vitamine A à des niveaux excessifs peut entraîner des effets nocifs sur les systèmes respiratoire et squelettique chez l'enfant. C'est pourquoi une revue systématique de la supplémentation en vitamine A chez les personnes souffrant de mucoviscidose devrait contribuer à orienter la pratique clinique.

Objectifs

Déterminer si la supplémentation en vitamine A chez les enfants et les adultes souffrant de la mucoviscidose :
1. Réduit la fréquence des troubles liés aux carences en vitamine A;
2. Améliore l'état général et la santé respiratoire;
3. Augmente la fréquence d’effets toxiques de la vitamine A.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre d’essais cliniques du groupe Cochrane sur la mucoviscidose et autres maladies génétiques constitué des références identifiées lors de recherches exhaustives dans des bases de données électroniques et de recherches manuelles dans des revues et des résumés d’actes de conférence pertinents.

Date de la recherche la plus récente effectuée dans le registre des essais cliniques du groupe sur la mucoviscidose : 7 avril 2014.

Critères de sélection

Tous les essais contrôlés randomisés ou quasi-randomisés comparant toutes les préparations de vitamine A par voie orale utilisées dans le cadre d'une supplémentation par rapport à l'absence de supplémentation (ou à un placebo) à n'importe quelle dose et pendant n'importe quelle durée, chez des enfants ou des adultes souffrant de mucoviscidose (déterminée par des tests de la sueur ou des tests génétiques) avec et sans insuffisance pancréatique.

Recueil et analyse des données

Aucune étude pouvant être incluse dans la présente revue n'a été identifiée lors de ces recherches.

Résultats principaux

Aucune étude n'a été incluse dans cette revue.

Conclusions des auteurs

Comme aucun essai contrôlé randomisé ou quasi-randomisé n'a été identifié, nous ne pouvons pas tirer de conclusions sur les bénéfices (ou les risques) de l'administration régulière de vitamine A chez les personnes atteintes de mucoviscidose. Nous recommandons, jusqu'à obtention de nouvelles données, de respecter les directives spécifiques locales portant sur l'administration de vitamine A aux personnes atteintes de mucoviscidose.

アブストラクト

嚢胞性線維症に対するビタミンA補充

背景

嚢胞性線維症および膵機能不全患者には脂溶性ビタミン欠乏のリスクがあるが、こうしたビタミン(A、D、E、K)は脂肪と共に吸収されるからである。したがって、嚢胞性線維症治療施設の一部ではこうしたビタミン類を栄養剤として日常的に投与しているが、これらのビタミン類欠乏症の発生に対する取り組み方は施設により異なる。ビタミンA欠乏は主に眼と皮膚障害を引き起こすが、過剰なレベルにまでビタミンAを補充すると小児の呼吸器および骨格系に害を及ぼす可能性がある。以上から、嚢胞性線維症患者に対するビタミンA補充に関するシステマティック・レビューは臨床診療における指針の一助となるだろう。

目的

嚢胞性線維症小児患者および成人患者におけるビタミンA補充により、
1.ビタミンA欠乏障害の頻度が低下するか
2.全身および呼吸器の健康状態を改善するか
3.ビタミンAの有害性の頻度が高まるかどうか
を検討すること。

検索戦略

Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Registerを検索したが、それは総合的電子データベース検索と関連雑誌および学会紀要の抄録集のハンドサーチにより同定された参考文献からなる。

Group’s Cystic Fibrosis Trials Registerの最新検索日:2014年4月7日。

選択基準

膵機能不全を有する、または有さない嚢胞性線維症(汗の検査または遺伝子検査により確定する)小児患者または成人患者を対象とした、栄養剤としてのあらゆる経口ビタミンA製剤を投与量および使用期間にかかわらず、無補充またはプラセボと比較するランダム化または準ランダム化比較試験すべて。

データ収集と分析

検索により、選択すべき関連性のある研究を同定できなかった。 本レビューに含める研究はなかった。

主な結果

本レビューに含める研究はなかった。

著者の結論

同定できたランダム化または準ランダム化比較試験はなかったため、嚢胞性線維症患者に対するビタミンAの定期的投与の利益(またはそれ以外の場合)に関する結論は導き出すことはできない。さらなるデータが得られるまで、嚢胞性線維症患者におけるビタミンA使用に関する国または地域固有のガイドラインに従うべきである。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.1.1]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

The use of regular vitamin A preparations for children and adults with cystic fibrosis

Cystic fibrosis can lead to certain vitamins, such as vitamin A, not being properly absorbed by the body. This can result in problems caused by vitamin deficiency. A lack of vitamin A (vitamin A deficiency) can cause specific problems such as eye and skin problems. It can also be associated with poorer general and respiratory health. Therefore people with cystic fibrosis are usually given regular vitamin A preparations from a very young age. However, too much vitamin A can also cause respiratory and bone problems. The review aimed to show whether giving vitamin A regularly to people with cystic fibrosis is beneficial or not. However, the authors did not find any relevant trials to include in the review. They are therefore unable to draw any conclusions regarding the routine administration of vitamin A supplements and recommend that until further evidence is available, local guidelines are followed regarding this practice.

Résumé simplifié

L'utilisation régulière de préparations de vitamine A par les enfants et les adultes souffrant de mucoviscidose

La mucoviscidose peut conduire à la mauvaise absorption par l’organisme de certaines vitamines telles que la vitamine A. Cela peut entraîner des problèmes causés par des carences vitaminiques. Un manque en vitamine A (carence) peut entraîner des problèmes spécifiques tels que des problèmes oculaires ou cutanés. Il peut également être associé à une détérioration de l'état général et de l’état respiratoire. Par conséquent, les personnes souffrant de mucoviscidose reçoivent généralement des préparations régulières de vitamine A dès leur plus jeune âge. Cependant, des excès de vitamine A peuvent également entraîner des problèmes respiratoires et osseux. La présente revue avait pour objectif de déterminer s'il est bénéfique ou non de donner régulièrement de la vitamine A aux personnes souffrant de mucoviscidose. Cependant, les auteurs n'ont pas trouvé d'essais pertinents à inclure dans la revue. Ils ne sont donc pas en mesure de tirer de conclusions sur l'administration en routine de suppléments de vitamine A et nous recommandons, jusqu'à obtention de nouvelles données, de respecter les directives locales portant sur cette pratique.

Notes de traduction

Traduit par: French Cochrane Centre 22nd August, 2014
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français

平易な要約

嚢胞性線維症の小児および成人に対するビタミンA製剤の定期的使用

嚢胞性線維症により、ビタミンAなどの特定のビタミン類が体内で適正に吸収されなくなる場合がある。これにより、ビタミン欠乏による障害が生じ得る。ビタミンAが欠けていること(ビタミンA欠乏)が原因で目や皮膚障害など特定の問題が生じることがある。全身および呼吸器の健康状態不良にも関連し得る。そのため、嚢胞性線維症患者には、通常非常に若年からビタミンA製剤を定期投与する。しかし、ビタミンAが多すぎると、呼吸器や骨障害が起こることもある。本レビューは、嚢胞性線維症患者に定期的にビタミンAを投与することは有益なのか否かを示すことを目的とした。しかし、著者らは本レビューに含めるべき関連性のある試験を見出さなかった。そのため、ビタミンA製剤の日常的投与に関する結論を導き出すことはできず、この慣行に関してはさらなるエビデンスが得られるまで地域のガイドラインに従うことを推奨する。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.1.1]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Background

Description of the condition

Cystic fibrosis (CF) is a genetic disorder that affects multiple organs. Pancreatic insufficiency affects up to 90% of people with CF, whereby fat malabsorption occurs and pancreatic enzyme replacement is required to prevent steatorrhoea and malnutrition (Dodge 2006). Fat soluble vitamins (A, D, E and K) are co-absorbed with fat and thus deficiency of these vitamins may occur (Dodge 2006). Some CF centres routinely administer these vitamins as supplements from the neonatal period, whilst others (few) administer them only later in life or when deficiencies are detected clinically or on routine monitoring. While deficiencies may occur from the disease process of CF and insufficient supplementation, vitamin toxicity may also occur from excess supplementation. Both deficiency and excess of these vitamins may lead to specific medical problems (Dodge 2006; Sethuraman 2006).

Vitamin A is an essential nutrient for epithelial cell maintenance and repair in the respiratory, urinary and intestinal tract, immune response, and bone growth (DAA 2006). Dietary vitamin A (retinol or retinol esters) is found in liver, beef, eggs, fish, the fat of dairy products and vitamin A fortified margarine. Beta- and alpha-carotene can act as precursors for the synthesis of vitamin A. The dietary carotenoid (beta-carotene) is found in red, orange, yellow and leafy green vegetables (e.g. carrots, sweet potato, silverbeet) and red and orange fruit (e.g. mangos, oranges).

Vitamin A deficiency can be defined as serum retinol (SROL) concentration less than 0.70 µmol/L (less than 20 µg/dl) (West 2003). However, SROL levels may be influenced by albumin and retinol binding protein (RBP) as well as acute illnesses with infection and inflammation (Napoli 1996; Stephensen 1994). SROL levels should be measured during clinical stability (DAA 2006).

The major consequence of vitamin A deficiency is ocular (eye) with abnormal dark adaptation (night blindness), conjunctival and corneal xerosis (thickening) which can lead to blindness (DAA 2006; West 2003). Another consequence of vitamin A deficiency is the skin condition phrynoderma (a form of follicular hyperkeratosis associated with some micronutrient deficiencies). Vitamin A deficiency has also been linked to impaired mechanisms of host resistance to infection, poor growth and increased mortality in a study of mothers and children (West 2003).

On the other hand, hypervitaminosis A (excess levels of vitamin A) is associated with hepatotoxicity and bone problems (Brei 2013). Also, cross-sectional studies have reported that up to 25% of children with CF do not require vitamin A supplementation as sufficient amounts were already available though their diet (Brei 2013; Graham-Maar 2006).

Description of the intervention

Vitamin A is available as a sole supplement as well as in combination form with other vitamins as multi-vitamins (either as a liquid or a tablet). The availability of different formulations differ in different health services (Graham-Maar 2006). Vitamin A is usually administered as a daily dose, but the recommended doses vary in different guidelines. For example, the Royal Brompton Hospital guidelines recommend 4000 IU for children aged under one year, then 4000 to 10,000 IU for all other age groups (Royal Brompton Hospital 2011); and the USA guidelines recommend 3000 μg retinol activity equivalents (approximately 10,000 IU) (Graham-Maar 2006).

How the intervention might work

Normalisation of vitamin A levels may avoid the afore-mentioned problems. However supplementation of these vitamins to excessive levels may cause harm to the respiratory system, the skeletal system (osteoporosis and fractures) and liver abnormality (Penniston 2006) in children with and without CF (Graham-Maar 2006; Sethuraman 2006).

Why it is important to do this review

The approach of addressing the possibility of the development deficiency of these fat-soluble vitamins is variable among CF centres. While vitamin A deficiency maybe a problem, excess supplementation causing chronic hypervitaminosis A may also occur. Thus a systematic review on the efficacy of vitamins A, D, E and K supplementation in children and adults with CF in preventing effects of the deficiency of these vitamins would help guide clinical practice. Supplementation of vitamins D, E and K will be addressed in other Cochrane Systematic Reviews (Ferguson 2012; Jagannath 2013; Okebukola 2011; Shamseer 2010). This review will evaluate vitamin A supplementation in children and adults with CF. This version of the review is an update of previous versions (Bonifant 2012; O'Neil 2008).

Objectives

To determine if vitamin A supplementation in children and adults with CF:

  1. reduces the frequency of vitamin A deficiency disorders;

  2. improves general and respiratory health;

  3. increases the frequency of vitamin A toxicity.

Methods

Criteria for considering studies for this review

Types of studies

Randomised (RCTs) and quasi-randomised trials (controlled clinical trials).

Types of participants

Children or adults with CF (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.

Types of interventions

All preparations of oral vitamin A used as a supplement compared to either no supplementation or placebo at any dose for at least three months.

Types of outcome measures

We planned to obtain data on at least one of the following outcome measures:

Primary outcomes
  1. Vitamin A deficiency disorders

    1. visual impairment

    2. any other ocular dysfunction

    3. skin manifestations (e.g. phrynoderma)

  2. Growth and nutritional status (e.g. weight, height, body mass index, z score for weight, etc.)

  3. Mortality

Secondary outcomes
  1. Respiratory outcomes

    1. bronchiectasis severity control (e.g. Likert scale, visual analogue scale or radiological score (Marchant 2001))

    2. lung function indices (spirometry e.g. FEV1 and FVC)

    3. proportions of participants who had respiratory exacerbations or hospitalisations or both

    4. total number of hospitalised days or days off work or school

  2. Quality of life

  3. Adverse events (e.g. vomiting, loss of appetite, osteoporosis, fractures or any other adverse event noted)

  4. Possible toxicity events (e.g. liver dysfunction)

  5. Measured levels of vitamin A

We planned to evaluate outcomes based on

  1. short term (12 months or less), and

  2. medium to long term (longer than one year)

Search methods for identification of studies

Electronic searches

We attempted to identify relevant studies from the Group's Cystic Fibrosis Trials Register using the term 'vitamin A'.

The Cystic Fibrosis Trials Register is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library), quarterly searches of MEDLINE, a search of Embase to 1995 and the prospective handsearching of two journals - Pediatric Pulmonology and the Journal of Cystic Fibrosis. Unpublished work is identified by searching through the abstract books of three major cystic fibrosis conferences: the International Cystic Fibrosis Conference; the European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference. For full details of all searching activities for the register, please see the relevant sections of the Cystic Fibrosis and Genetic Disorders Group Module.

Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014.

Searching other resources

Searches of bibliographies and texts of selected studies were also conducted to identify additional studies.

Data collection and analysis

The authors did not apply the process described below since no studies were identified. In future updates of this review, the authors will apply the following methods if studies are identified:

Selection of studies

From the title, abstract, or descriptors, two authors will independently review results of the literature searches to identify studies potentially relevant to the review according to our inclusion criteria for further assessment. From these studies, the same two authors will independently examine the papers in further detail in order to select studies for inclusion using the criteria stated before. The authors will resolve disagreement by consensus.

Data extraction and management

The authors will review studies that satisfy the inclusion criteria for the review and independently extract data on the outcomes described as follows: study setting; year of study; source of funding; participant recruitment details (including number of eligible participants); inclusion and exclusion criteria; randomisation and allocation concealment method; numbers of participants randomised; blinding (masking) of participants, care providers and outcome assessors; dose and type of intervention; duration of therapy; co-interventions; numbers of participants not followed up; reasons for withdrawals from study protocol (clinical, side effects, refusal and other); side effects of therapy; and whether intention-to-treat analyses were possible.

Assessment of risk of bias in included studies

In order to assess the risk of bias, two review authors will independently assess the quality of the studies included in the review according to the criteria described by Jüni (Jüni 2001):

Allocation concealment

The authors will assess allocation concealment in each study as follows:

  1. adequate, if the allocation of participants involved a central independent unit, on-site locked computer, identically appearing numbered drug bottles or containers prepared by an independent pharmacist or investigator, or sealed opaque envelopes;

  2. unclear, if the method used to conceal the allocation was not described;

  3. inadequate, if the allocation sequence was known to the investigators who assigned participants or if the study was quasi-randomised.

Generation of the allocation sequence

The authors will grade each study for allocation concealment as follows:

  1. adequate, if methods of randomisation include using a random number table, computer-generated lists or similar methods;

  2. unclear, if the study is described as randomised, but no description of the methods used to allocate participants to treatment group was described;

  3. inadequate, if methods of randomisation include alternation; the use of case record numbers, dates of birth or day of the week, and any procedure that is entirely transparent before allocation.

Blinding (or masking)

The authors will grade each study for blinding as follows:

  1. blinding of clinician (person delivering treatment) to treatment allocation;

  2. blinding of participant to treatment allocation;

  3. blinding of outcome assessor to treatment allocation.

Follow-up

The authors will grade each study as to whether numbers of and reasons for dropouts and withdrawals in all intervention groups were described; or if it was specified that there were no dropouts or withdrawals.

They will also report on whether the investigators had performed a sample-size calculation and if they used an intention-to-treat (ITT) analysis.

Measures of treatment effect

The authors will include the results from studies that meet the inclusion criteria and report any of the outcomes of interest in the subsequent meta-analyses if any data are applicable.

For the dichotomous outcome variables of each individual study, they will calculate the odds ratio (OR) using a modified ITT analysis, i.e. if the original investigators did not use ITT analysis, they will consider dropouts to be failures. They will also calculate the summary weighted odds ratios and 95% confidence intervals (CIs) (fixed-effect model) using RevMan (RevMan 2011). The authors will calculate numbers-needed-to-treat (NNT) and their 95% CIs from the pooled OR and its 95% CI for a specific baseline risk, which is the sum of all the events in the control groups (in all studies) divided by the total participant numbers in control groups in all studies using an online calculator (Cates 2003).

For continuous outcomes, they will record the mean relative change from baseline for each group or mean post-treatment or post-intervention values and standard deviation. If standard errors are reported, they will calculate the standard deviations. The authors will then calculate a pooled estimate of treatment effect by the weighted mean difference and 95% confidence interval (fixed-effect model) again using RevMan (RevMan 2011).

Unit of analysis issues

For cross-over studies, the authors will calculate the mean treatment differences where possible and enter these using the fixed-effect generic inverse variance (GIV) analysis in RevMan, to provide summary weighted differences and 95% CIs (RevMan 2011). In cross-over studies, if they believe there is a carryover effect which will outlast any washout period included in the study, they will include only data from the first arm in the meta-analysis (Elbourne 2002).

If studies report outcomes using different measurement scales, the authors will estimate the standardised mean difference and 95% CIs.

Dealing with missing data

The authors will request further information from the primary investigators where required.

Assessment of heterogeneity

They will describe any heterogeneity between the study results and test this to see if it reached statistical significance using the chi-squared test. They will consider heterogeneity to be significant when the P value is less than 0.10 (Higgins 2011). The authors also plan to use the I2 statistic where heterogeneity is categorised such that a value of under 25% is considered low, around 50% is considered moderate and over 75% is considered a high degree of heterogeneity (Higgins 2003).

Data synthesis

The authors will include the 95% CI, estimated using a fixed-effect model. However, they will utilise the random-effects model whenever there are concerns about statistical heterogeneity.

Subgroup analysis and investigation of heterogeneity

The authors plan to perform the following a priori subgroup analyses to investigate any heterogeneity which they identify.

  1. children (aged 18 years or less) and adults (over 18 years);

  2. formulations of the vitamin (single or multivitamin);

  3. presence of significant liver synthetic dysfunction (low baseline albumin);

  4. presence of previous bowel resections;

  5. presence of pancreatic insufficiency;

  6. method of CF diagnosis (i.e. screening versus symptomatic diagnosis).

Sensitivity analysis

Sensitivity analyses are also planned to assess the impact of the potentially important factors on the overall outcomes:

  1. analysis using a random-effects model;

  2. analysis by "treatment received" (as opposed to ITT analysis).

Results

Description of studies

Results of the search

The authors identified a single study in our searches (Wood 2003).

Excluded studies

The only study identified was excluded because it was not placebo controlled (see Characteristics of excluded studies).

Risk of bias in included studies

The authors did not find any eligible studies that fulfilled the inclusion criteria.

Effects of interventions

The authors did not find any eligible studies that fulfilled the inclusion criteria.

Discussion

Daily vitamin A supplementation is almost universally recommended for people with CF who are pancreatic insufficient. However, it is unfortunate that there are no controlled studies that have examined this. The appropriate dose and frequency of vitamin A supplementation is also unknown. Furthermore while vitamin A deficiency causes eye and skin disorders, excess vitamin A can also cause problems (Griffiths 2000; Penniston 2006). Indeed, increasingly data on micronutrients have shown that micronutrient supplementation is only beneficial in states of deficiency and harmful when no deficiency exists (Chang 2006; Shenkin 2006). For vitamin A, Griffiths has termed this the 'vitamin A paradox' as vitamin A supplementation is likely to be "protective against pneumonia in malnourished children (who are likely to be vitamin A-deficient) and is paradoxically detrimental for adequately nourished children" (Griffiths 2000).

It is well accepted that people with CF and pancreatic insufficiency are at risk of vitamin A deficiency. However, this is now a rare occurrence (Brei 2013); and it is also biologically plausible that currently, with improved pancreatic replacement therapies and attention to macro-nutrition and caloric supplements, the majority of people with CF are vitamin A sufficient and may not require daily vitamin A supplementation. Daily supplementation in these situations may cause no harm, but it adds a further burden to the daily medical regimen of people with CF, and it is possible that it may be biologically harmful. Thus, some have called for individualised supplementation based on annual measurements rather than a fixed dosage as is currently recommended in most CF guidelines (Brei 2013). Furthermore, current guidelines "do not take into account the specific formulation of vitamin A supplementation, such as water-soluble or fat-soluble retinol and beta-carotene. Water-soluble preparations pose more risks to CF patients than fat-soluble preparations, because they are more easily absorbed in patients with pancreatic insufficiency" (Brei 2013).

Authors' conclusions

Implications for practice

As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with CF. Until further data are available, country or region specific guidelines (e.g. UK CF Trust Nutrition Guidelines (CF Trust 2002)) on the use and monitoring of vitamin A in people with CF should be followed.

Implications for research

The need for a well-designed, parallel, adequately-powered, multi-centre, randomised controlled trial to assess if vitamin A supplementation in children and adults with CF is beneficial or otherwise, is obvious. The study should examine if vitamin A supplementation positively or negatively influences the frequency of symptoms of vitamin A deficiency or general and respiratory outcomes. The possible negative effects should be examined in light of recent data showing possible harm when micronutrients are used in people who are not micronutrient-deficient. Safety monitoring during such a study would be important as the current practice is to use supplementation of vitamin A in people with CF. Vitamin A levels should be measured before and during the studies when clinically stable and related to serum albumin and retinol binding protein. Studies involving both children and adults are required and results should be related to nutritional status and pancreatic status. Data relating to appropriate dose, frequency of supplementation and type of formulation of vitamin A (water-soluble, fat-soluble, beta carotene) are also needed.

Acknowledgements

We thank Nikki Jahnke and Dr Gerard Ryan from the Cochrane Cystic Fibrosis & Genetic Disorders Group for their advice, supportive role and comments to the protocol and review and to Natalie Hall for help with the searches.

Data and analyses

Download statistical data

This review has no analyses.

What's new

Last assessed as up-to-date: 6 May 2014.

DateEventDescription
6 May 2014New citation required but conclusions have not changedNo new studies were included so the conclusions of the review have not changed.
6 May 2014New search has been performedA search of the Group's Cystic Fibrosis Trials Register did not identify any new studies potentially eligible for inclusion in this review.

History

Protocol first published: Issue 4, 2007
Review first published: Issue 1, 2008

DateEventDescription
7 June 2012New search has been performedA search of the Group's Cystic Fibrosis Trials Register did not identify any new references potentially eligible for inclusion in this review.
7 June 2012New citation required but conclusions have not changedNo new studies were included so the conclusions of the review have not changed.
1 December 2009New search has been performedA search of the Group's Cystic Fibrosis Trials Register identified a single reference which was excluded (Wood 2003).
12 August 2009AmendedContact details updated.
10 April 2008New search has been performedA search of the Group's Cystic Fibrosis Trials Register did not identify any trials which might be eligible for inclusion in this review.
10 April 2008AmendedConverted to new review format.

Contributions of authors

Protocol: CB and AC wrote the protocol. ES reviewed the protocol.

Original review: When any studies are identified, CB and AC will select relevant studies, perform data extraction and analysis and write the review. ES will contribute to writing of the review.

Updated reviews: AC updated the reviews with the help of Nikki Jahnke.

Declarations of interest

Catherine Bonifant has no potential conflict of interest.

Anne Chang declares the receipt of a grant provided by GSK, which is however unrelated to this topic.

Elizabeth Shevill has no potential conflict of interest.

Sources of support

Internal sources

  • Royal Children's Hospital Foundation, Brisbane, Australia.

External sources

  • National Health and Medical Research Council, Australia.

Characteristics of studies

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    CF: cystic fibrosis

Wood 2003Non-placebo controlled trial. This trial examined outcomes of 46 CF patients randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)].