Introduction and background

Nutritional anemia is a multifactorial hematological disorder characterized by reduced hemoglobin concentration or impaired oxygen-carrying capacity resulting from deficiencies of essential nutrients required for erythropoiesis [1,2]. It continues to represent a major global public health challenge, affecting almost one-fourth of the world's population, with the highest burden observed among pregnant women, children, adolescents, and socioeconomically vulnerable populations. The prevalence remains disproportionately high in low- and middle-income countries, where inadequate dietary intake, recurrent infections, chronic inflammation, and poor healthcare accessibility coexist.

Historically, nutritional anemia has been predominantly associated with iron deficiency [2,3]. Consequently, most clinical and public health interventions have focused primarily on iron supplementation and food fortification. However, increasing evidence indicates that anemia frequently develops due to concurrent deficiencies of multiple micronutrients, including folate, zinc, copper, selenium, vitamin B12, A, and C [4-7]. These micronutrients are involved in diverse yet interconnected physiological pathways regulating erythropoiesis, DNA synthesis, heme production, iron transport, mitochondrial metabolism, and oxidative stress regulation.

Recent studies further suggest that micronutrient deficiencies rarely occur independently [8,9]. Instead, overlapping interactions among nutrients significantly influence their absorption, transport, and biological utilization. For example, excessive zinc intake may impair copper absorption, while vitamin C enhances non-heme iron bioavailability. Similarly, chronic inflammation and infection alter iron homeostasis through hepcidin-mediated sequestration, thereby contributing to functional iron deficiency even though adequate iron reserves are present.

Although iron deficiency anemia (IDA) has been widely studied, the combined contribution of other micronutrients to anemia remains less clearly addressed [10,11]. Most conventional diagnostic and therapeutic approaches continue to rely on isolated nutrient assessment, often overlooking mixed deficiency states and subclinical micronutrient imbalances. This limitation contributes to underdiagnosis, poor treatment response, and persistent disease burden.

Therefore, this review aims to provide an exhaustive and mechanistic outline of micronutrient-associated nutritional anemia by integrating current knowledge on erythropoiesis, iron metabolism, oxidative stress, nutrient interactions, diagnostic challenges, therapeutic strategies, and precision nutrition. Unlike conventional discussions that focus mainly on iron deficiency, this review highlights the broader network of micronutrients involved in anemia, including their interactions with inflammation, gut absorption, oxidative stress, and mixed-deficiency states. Such an approach may help clinicians recognize mixed deficiencies more effectively and avoid relying solely on iron replacement.

Methodology/literature search strategy

This narrative review was prepared by examining published literature related to nutritional anemia, micronutrient deficiencies, erythropoiesis, iron metabolism, diagnostic biomarkers, and anemia management. Appropriate articles were explored through PubMed, Scopus, Web of Science, Google Scholar, and official public health sources, such as the World Health Organization and national health program documents.

The search terms included “nutritional anemia”, “iron deficiency anemia”, “micronutrient deficiency”, “vitamin B12 deficiency”, “folate deficiency”, “vitamin A and anemia”, “zinc and anemia”, “copper deficiency anemia”, “selenium and erythropoiesis”, “vitamin C and iron absorption”, “hepcidin”, “functional iron deficiency”, “micronutrient interactions”, and “multi-micronutrient supplementation”. Original research articles, review articles, clinical studies, meta-analyses, and public health reports were considered. Greater emphasis was given to studies discussing the biological role of micronutrients in red blood cell formation, iron transport, oxidative stress, inflammation, diagnosis, and therapeutic strategies.

Articles not directly related to nutritional anemia, micronutrient-associated hematological changes, or anemia-related public health interventions were excluded. Since this is a narrative review, formal meta-analysis or quantitative evidence grading was not performed. Instead, the available literature was synthesized to provide a broad mechanistic and clinical understanding of nutritional anemia beyond iron deficiency.