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Literature search and review related to specific preparatory work in the establishment of Dietary References Values for Thiamin, Pantothenic Acid and Choline


The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.


A comprehensive search of the literature was performed to collate scientific data from which Dietary Reference Values could be derived for thiamin, pantothenic acid, and choline. In December 2011, June 2012 and August 2012, literature searches were run for thiamin, pantothenic acid and choline, respectively, according to individual search strategies. Databases searched were PubMed, EMBASE, Foodline, BIOSIS, FSTA and the Cochrane Library CENTRAL databases. The search results were imported into an Endnote library (version X5) and duplicates were removed. Literature quality appraisal was performed. Quality appraisal tools for intervention trials, observational studies and systematic reviews were completed and used as the base for scientific report writing. Study details are provided in tables for each of the three micronutrients. Relevant details of the study design and outcomes are summarised individually in the Results sections.

A total of 8357 articles (thiamin, n=221; pantothenic acid, n=192 and choline, n=7944) were screened based on key words in the title and abstract resulting in 183 full-text articles that were analysed and 96 publications (thiamin, n=28; pantothenic acid, n=16 and choline, n=52) included in the report.

For thiamin, health outcomes included Alzheimer’s disease, cardiovascular disease, cataract and colon cancer, as well as biomarkers of exposure (4 randomized controlled trials, 4 controlled trials, 1 cohort, 1 case-control, 16 cross-sectional, 2 case studies). The majority of the studies (n=23) were deemed to have a high risk of bias with the remaining (n=5) studies having a moderate risk of bias.

Of the 16 articles included for pantothenic acid, 3 were randomized controlled trials, 2 were uncontrolled trials, 3 were cohorts, 7 were cross-sectional studies and 1 was a systematic review. Studies examined the association between pantothenic acid intake and biomarkers of intake (n=6), genomic instability (n=1), birth outcomes (n=2), growth (n=1), cardiovascular disease (n=3), Parkinson’s disease (n=2) and tooth loss (n=1). Half of the studies reviewed were graded as having a high risk of bias (n=8), while the rest were graded as moderate (n=7) and low (n=1) risk of bias.

In addition to biomarkers of exposure and status, health outcomes related to choline intake included carnitine interactions, inflammation, homocysteine concentration, cardiovascular disease, cancer, birth defects, and cognitive function (26 trials, 9 cohort, 9 case-control, 7 cross-sectional and 1 systematic review). The majority of the studies (n=44) were deemed to have a high risk of bias with 6 studies having a moderate risk of bias and 2 having a low risk of bias. A number of studies have examined the role of common (>5%) genetic polymorphisms in modifying the response to choline intake, but all such studies were deemed to have a high risk of bias.

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