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of folate to cause adverse effects, efforts are needed to improve methods to detect and correct vitamin B12 deficiency before adverse hematological or neurological changes occur and to determine the prevalence of vitamin B12 deficiency.


The Standing Committee on the Scientific Evaluation of Dietary Reference Intakes agreed to assign highest priority to research that has potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. The following five areas for research were assigned the highest priority:

  • Studies to provide the basic data for constructing risk curves and benefit curves across the exposures to food folate and to folate added to foods and taken as a supplement. Such studies would provide estimates of the risk of developing neural tube defects, vascular disease, and neurological complications in susceptible individuals consuming different levels of folate.

  • Studies of the magnitude of effect of folate, vitamin B6, vitamin B12, and related nutrients for the prevention of vascular disease and of possible mechanisms for the influence of genetic variation.

  • Studies to overcome the methodological problems in the analysis of folate. This includes the development of sensitive and specific indicators of deficiency and the development of practical, improved methods for analyzing the folate content of foods and determining its bioavailability.

  • Studies to develop economical, sensitive, and specific methods for assessing the prevalence, causes, and consequences of vitamin B12 malabsorption and deficiency and for preventing and treating these conditions.

  • Studies of how folate and related nutrients influence normal cellular differentiation and development, including embryogenesis and neoplastic transformation.

Although data are not sufficient for deriving a Tolerable Upper Intake Level (UL) for most of the B vitamins and additional research is required on the adverse effects of B vitamins and choline, it was concluded that higher priority should be given to the areas listed above because of relatively low expectation of adverse effects or toxicity.

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