Literature search and review related to specific preparatory work in the establishment of Dietary Reference Values for Niacin, Biotin and Vitamin B6
Accepted: 7 December 2012
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AbstractNo abstract available
Project developed on the procurement project CT/EFSA/NUTRI/2011/03
The aim of this systematic review is to identify the scientific data published from 1990 onwards upon which Dietary Reference Values (DRVs) for niacin, biotin and vitamin B6 may potentially be based.
Pallas aimed to explore the association between micronutrient intake, status, and health, comprising three main review objectives: 1. to collect and summarize relevant clinical health outcomes or intermediate health markers associated with micronutrient intake, adequacy, or biomarkers of micronutrient intake used to define nutrient requirements; 2. to summarize evidence on (dose-response) associations between micronutrient intake/status or its indicators (e.g. biomarkers of intake or status), and selected health-related outcomes or its indicators (e.g. intermediate predictors or biomarkers of health); 3. to find evidence of factors that influence the bioavailability of the specific nutrient and any relevant interactions between micronutrients affecting their requirement.
In phase 1 of the review, the most relevant biomarkers of intake, status and/or health, and potential health-related outcomes were specified. To achieve this, Pallas performed a desk research of key-reports; an initial general review of existing literature reviews, meta-analyses, and key-publications on intake, biomarkers of intake, status and/or health, and/or health-related outcomes (and associations between these aspects); and consulted experts on vitamins and/or methods. At the end of phase 1 the complex search strings for the research objectives were optimised.
In phase 2 of the review, the systematic literature review was performed. In January 2012 (niacin), March 2012 (biotin) and July 2012 (vitamin B6), the literature was systematically searched for peer-reviewed studies published in the English language from 1990 onwards. Animal studies were excluded from the search. Databases searched were Medline, EMBASE and the Cochrane Library CENTRAL. Additional references were identified by checking reference lists in key reviews, included studies and DRV reports. Search results were imported into EndNote®, duplicates were removed. Data were collected on the identified relevant associations between micronutrient intake, status and health. For this, Pallas applied a three-step literature selection procedure based on established inclusion- and exclusion criteria. In the first step, titles and abstracts were screened and potentially relevant articles were selected. In the second step, the selected articles were read full text and pertinent papers were included for the review. During the data extraction into evidence tables, selection step three was performed by excluding duplicate articles.
Niacin, biotin and vitamin B6 searches were done separately.
For niacin, searches in PubMed, Cochrane Library and EMBASE yielded 5,281 unique articles. Based on title and abstract, a total of 245 articles were selected of which 19 met our inclusion criteria after full text screening. Two additional pertinent articles were found by hand search, resulting in a total of 21 articles that were included into the review. For biotin, searches were also conducted in the databases of PubMed, Cochrane Library and EMBASE, resulting in a yield of 1,783 articles. Based on title and abstract, a total of 62 articles were selected. After full text screening of the articles, nine articles (including one hand search article) were extracted into the evidence tables. For vitamin B6, searches were conducted in the database of PubMed and yielded 9,500 articles. Since the amount of available literature on vitamin B6 is rather large and, as a consequence, selection of pertinent articles would be very time-consuming, Pallas performed a stepwise review of the literature, which was limited to the PubMed database. Based on title and abstract, a total of 423 articles were selected for full text screening. Including one additional article from hand search, a total of 51 articles met our inclusion criteria and were included into the review.
All three nutrients in combination resulted in a total of 75 articles, six of which were included on more than one micronutrient. Studies were classified as systematic review or meta-analysis (n=7), controlled trial (n=14), prospective cohort study (n=30), nested case-control study (n=18) and cross-sectional study (n=6). Data on the study design, methods and results were extracted into evidence tables. All stages in the process were duplicated by researchers at a level of 10% to ensure consistency in data recording. The quality of each study was assessed, with specific quality criteria per study design, including factors like confounding, methods of nutrition assessment, randomisation, the presence of a control group and population size and more. Papers were divided into three groups according to their risk of bias: high risk of bias (n=27); moderate risk of bias (n=42) and low risk of bias (n=6).
The included articles reported on intake and status relation; the association between intake/status and specific health outcomes (e.g. cancer, cardiovascular disease and cognitive decline); maternal intake during pregnancy or lactation and health outcome in the infant; micronutrient bioavailability and factors affecting micronutrient status or metabolism.
Overall, there appeared to be a lack of high quality evidence on which DRVs for niacin or biotin could be based. Higher vitamin B6 intake or plasma PLP levels may be protective against the development of certain types of cancer and cardiovascular diseases. Some studies indicate that currently reported vitamin B6 requirements may be too low; however, more trials are needed to confirm this.