Optimising micronutrient status globally is a major health priority. Nutritional biomarkers are critical for the identification of nutrient inadequacies in light of the limitations of dietary assessment methods. Early diagnosis and prevention of nutrient inadequacies require sensitive, validated and harmonised methods to determine and monitor micronutrient status in individual healthcare and population-based surveys. Important criteria in the identification, validation and implementation of nutritional biomarkers include the testing of biomarker specificity and sensitivity, and their response to dietary as well as physiologic changes, e.g. age or pregnancy. Nutritional status can be categorised into deficient, suboptimal, adequate and excess status, where appropriate, and provided cut-offs are available. Cut-offs are quantitative measures to reflect health outcomes and are important in validating nutritional surveys, interventions and monitoring of populations. For many biomarkers, available cut-offs have limited interpretability and are most commonly derived in adult populations only. For the comparison of studies from across the globe, the harmonisation of analytical methods is essential and can be realised with the use of internationally available reference material and interlaboratory comparison studies. This narrative review describes current efforts on identifying and validating existing and new biomarkers, the derivation of biomarker cut-offs, and international efforts on harmonisation of laboratory methods for biomarker quantitation and their interpretation, in the example of B-vitamins. Establishing sensitive, reliable and cost-efficient biomarkers and related cut-offs for use in populations across the globe are critical to facilitating the early diagnosis of micronutrient inadequacies on the clinical and community-based level for timely intervention and disease prevention.
Keywords: MMA methylmalonic acid; NHANES National Adult Health and Nutrition Survey; PLP pyridoxal 5’-phosphate; tHcy total homocysteine; Biomarker; Micronutrients; Nutritional status; Vitamins.