Iron Deficiency Anemia: Efficacy and Limitations of Nutritional and Comprehensive Mitigation Strategies

Abstract

Iron deficiency anemia (IDA) has reached epidemic proportions in developing countries and has become a major global public health problem, affecting mainly 0-5-year-old children and young women of childbearing age, especially during pregnancy. Iron deficiency can lead to life-threatening loss of red blood cells, muscle function, and energy production. Therefore, the pathogenic features associated with IDA are weakness and impaired growth, motor, and cognitive performance. IDA affects the well-being of the young generation and the economic advancement of developing countries, such as India. The imbalance between iron intake/absorption/storage and iron utilization/loss culminates into IDA. However, numerous strategic programs aimed to increase iron intake have shown that improvement of iron intake alone has not been sufficient to mitigate IDA. Emerging critical risk factors for IDA include a composition of cultural diets, infections, genetics, inflammatory conditions, metabolic diseases, dysbiosis, and socioeconomic parameters. In this review, we discuss numerous IDA mitigation programs in India and their limitations. The new multifactorial mechanism of IDA pathogenesis opens perspectives for the improvement of mitigation programs and relief of IDA in India and worldwide.

Keywords: C-reactive protein; RDA; ferritin; iron deficiency anemia.

Figure 1

Prevalence of IDA is higher in Gujarat compared to Kerala despite higher iron intake in Gujarat state. (A) Gujarat has a higher prevalence of vitamin A deficiency than Kerala. Kerala presents a lower iron intake than Gujarat. (B) Prevalence of IDA in Gujarat in all population subsets compared to Kerala. Data are from 2019–2021 [17].

Figure 2

The pathogenesis mechanism of IDA depends on both accessibility of nutrients and their absorption. Socioeconomic and cultural factors influence the dietary amount and its composition. Diet and other environmental factors impact both accessibility and absorption, which increase RDA and pose risks of inadequate intake. Gastrointestinal (GI) inflammation and dysbiosis caused by metabolic and genetic diseases, parasites, and infections lead to inadequate intake of iron and other critical nutrients and, consequently, IDA. The mild and moderate characteristic features associated with IDA are fatigue, weakness, koilonychia, pica, and pallor, ultimately resulting in the major impairments of growth, motor, and cognitive performance.

Figure 3

Crosstalk between mechanisms participating in IDA. Pathogenesis of IDA involves iron (Fe)-dependent mechanisms and other factors regulating iron metabolism and erythropoiesis (e.g., essential nutrients, minerals and their metabolites). Iron deficiency, a contributing factor of IDA, can be caused by defective intake, absorption, and transport of iron and/or be a result of iron loss. Digestive, inflammatory, and blood-loss associated pathologies (Table 2) as well as sickle cell anemia and other genetic diseases involve these pathways. Iron deficiency compromises the function of iron-dependent co-factors leading to defective energy production, nervous system, and hormonal regulation dysregulating Hb synthesis and erythropoiesis leading to IDA. Inflammation, infectious diseases, and oxidative stress increase demand for iron and energy production as well as impair absorption of iron and other nutrients, thereby promoting IDA. ETC, electron transfer chain.

Figure 4

Increased prevalence of IDA from 2015 to 2021 in adolescent and adult men (A) and women (B) as well as in pregnant women (C) and infants (D) in India based on NFHS IV and V surveys. NFHS, National Family Health Survey.