In setting reference values for avoiding deficiency or insufficiency in the Dietary Reference Intakes, defining outcomes specifically targeting each nutrient is required such as clinical manifestations that can occur with deficiency or insufficiency, or biomarkers specifically representing the nutritional status, which, however, has not been adequately performed. Therefore, the present study reviewed the clinical manifestations and biomarkers of fat-soluble vitamins, focusing on the reports from the Scientific Opinion of the Dietary Reference Values of the European Food Safety Authority. There was a certain consensus among countries regarding the biomarkers for vitamin A and vitamin D. The basis for vitamin A was the intake level that maintains the minimum vitamin A storage in the liver based on a compartmental modeling approach, and the basis for vitamin D was the intake level based on serum 25-hydroxyvitamin D concentration. On the other hand, for vitamin E and K, there are no appropriate outcomes that reflect their intakes over a wide range yet. Therefore, their intake standards are mostly determined based on the current intake of each vitamin in most countries. This implies the need for biomarkers that accurately reflect the nutritional status of vitamins E and K.
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