Assessing potential biomarkers of micronutrient status by using a systematic review methodology: methods.

BACKGROUND To explore the relation between micronutrient status and health, it is important to understand which markers of micronutrient status can be relied on and under what circumstances. OBJECTIVE The objective of this article was to develop a common systematic review methodology for use in the assessment of micronutrient status for selenium, iodine, copper, zinc, riboflavin, vitamin B-12, vitamin D, and omega-3 (n-3) long-chain polyunsaturated fatty acids. DESIGN We developed a methodology on the basis of defining studies that clearly altered micronutrient status and then pooled data on the effects of this intervention on each specific biomarker to assess objectively the response of various status markers to changes in intake. RESULTS The generic methodology included defining, and systematically searching for, studies that resulted in a change in micronutrient status. Study inclusion, data extraction, and assessment of validity were conducted with a minimum of 10% independent duplication. For each study and each potential biomarker, the highest dose and longest duration intervention data were selected to assess the statistical significance of any change in intake on the status biomarker. The consistency of biomarker response was explored by subgrouping the studies according to baseline micronutrient status, sex, population group, supplementation type, dose, duration, and analytic method. CONCLUSION This methodology allows systematic assessment of the usefulness of a number of biomarkers for a selection of micronutrients.