The role of micronutrient deficiencies in nutritional anemia beyond iron: An expert perspective on the scope and strength of the current evidence

There is a tacit assumption that the majority of nutritional anemia is caused by iron deficiency. However, several other key micronutrients are involved in iron and/or erythrocyte metabolism and thus play a role in the development of nutritional anemia. This consensus paper provides an updated review that synthesizes current evidence on the role of individual micronutrients, beyond iron, in the development of nutritional anemia and identifies emerging hypotheses and potential mechanistic links to erythropoiesis and iron metabolism involving nutrients of both established and growing interest. To achieve this, we convened leading experts in micronutrients and nutritional anemia to categorize 10 key micronutrients of interest into a hierarchy based on the scope and strength of evidence for their roles in the development of anemia, erythropoiesis, and iron metabolism. Folate, vitamin B12, and vitamin A were ranked as having strong evidence, meaning data are consistent in describing a causal association between nutrient status and anemia development, and the evidence for the proposed mechanism(s) is well-established. Riboflavin, zinc, vitamin B6, vitamin C, and vitamin E were ranked as having moderate evidence, and vitamin D and copper were ranked as having potential and/or emerging evidence. We also identify critical gaps in the current evidence and propose priority areas for future research for each micronutrient. This perspective paper aims to serve as a comprehensive reference to inform future research priorities and guide global nutrition policy, strategy, and programming related to anemia prevention and control.