A Vitamini Eksikliğinin Anemi Üzerindeki Etki Mekanizmaları

Öz

Bu çalışmada mevcut literatür yardımıyla A vitamini eksikliğinin (AVE) kan demir düzeyi ve anemi durumu üzerindeki potansiyel etki mekanizmalarının açıklanması amaçlanmıştır. Öncelikle A vitamini eksikliği ve anemi arasındaki ilişki, çeşitli mekanizmalar aracılığıyla gerçekleşmekte olup karmaşık bir yapıya sahiptir. Eritropoez modülasyonu, enfeksiyona karşı bağışıklık fonksiyonu ve demir metabolizması bu etkileşimlerin anahtar noktalarıdır. Epidemiyolojik çalışmalar, özellikle çocuk ve hamile kadın popülasyonlarında AVE ve anemi arasında güçlü bir ilişki olduğunu göstermektedir. A vitamini, eritropoietin (EPO) geninin transkripsiyonunu aktive ederek eritropoezi etkileyebilir ve enfeksiyon anemisini azaltabilir. Bununla birlikte, AVE sırasında demirin hapsedilmesi ve serbest bırakılmaması, anemi ve demir indekslerinin anormalleşmesine neden olabilir. Yapılan araştırmalarda, A vitamini takviyelerinin kan demir düzeyi ve anemi durumu üzerindeki etkisi hakkında çelişkili bulgular mevcuttur. Bazı çalışmalarda A vitamini takviyesinin kan demir düzeyini ve anemi durumunu iyileştirebileceği rapor edilirken, bazı çalışmalarda ise bu konuda anlamlı bir etki tespit edilmemiştir. Sonuç olarak, A vitamini eksikliğinin anemi üzerinde olumsuz etkileri olabilir ve A vitamini takviyeleri AVE ve anemi gibi sorunların önlenmesi ve tedavisi için önemli bir yöntem olabilir.

Anahtar Kelimeler

• A vitamini
• A vitamini eksikliği
• anemi
• demir

Effect Mechanisms of Vitamin A Deficiency on Anemia

Öz

In this study, it is aimed to explain the potential mechanisms of vitamin A deficiency (VAD) on blood iron levels and anemia status with the help of the existing literature. First of all, the relationship between vitamin A deficiency and anemia is mediated through various mechanisms and has a complex structure. Modulation of erythropoiesis, immune function against infection and iron metabolism are key points of these interactions. Epidemiological studies show a strong association between VAD and anemia, especially in populations of children and pregnant women. Vitamin A may affect erythropoiesis by activating transcription of the erythropoietin (EPO) gene and reduce infection anemia. However, the trapping and non-release of iron during VAD can lead to anemia and abnormalization of iron indices. There are conflicting findings in research on the effect of vitamin A supplements on blood iron levels and anemia status. While some studies have reported that vitamin A supplementation can improve blood iron levels and anemia, some studies have found no significant effect. In conclusion, vitamin A deficiency may have adverse effects on anemia and vitamin A supplements may be an important method for the prevention and treatment of problems such as VAD and anemia.

Anahtar Kelimeler

• Vitamin a
• Vitamin A deficiency
• anemia
• iron

Kaynakça

1. Biswas A, Tripathy I, Basu K. Effects on hematopoiesis in children suffering from iron deficiency anemia with vitamin A supplementation. Int J Med Res Prof. 2016;2(1):155-67.
2. Biswas A. Role of vitamin A supplementation in management of iron deficiency anemia in children. Int J Community Med Public Health. 2018;5(4):1477-80.
3. Villalpando S, Cruz Vde L, Shamah-Levy T, Rebollar R, Contreras-Manzano A. Nutritional status of iron, vitamin B12, folate, retinol and anemia in children 1 to 11 years old: results of the ensanut 2012. Salud Publica Mex. 2015;57(5):372-84.
4. Bondevik G, Eskeland B, Ulvik R, Ulstein M, Lie R, Schneede J, et al. Anaemia in pregnancy: possible causes and risk factors in Nepali women. Eur J Clin Nutr. 2000;54(1):3.
5. Dreyfuss ML, Stoltzfus RJ, Shrestha JB, Pradhan EK, LeClerq SC, Khatry SK, et al. Hookworms, malaria and vitamin A deficiency contribute to anemia and iron deficiency among pregnant women in the plains of Nepal. J Nutr. 2000;130(10):2527-36.
6. Semba RD, Kumwenda N, Hoover D, Taha T, Mtimavalye L, Broadhead R, et al. Assessment of iron status using plasma transferrin receptor in pregnant women with and without human immunodeficiency virus infection in Malawi. Eur J Clin Nutr. 2000;54(12):872.
7. Albalak R, Ramakrishnan U, Stein AD, Van der Haar F, Haber MJ, Schroeder D, et al. Co-occurrence of nutrition problems in Honduran children. J Nutr. 2000;130(9):2271-3.
8. Hodges RE, Sauberlich H, Canham J, Wallace D, Rucker R, Mejia L, et al. Hematopoietic studies in vitamin A deficiency. Am J Clin Nutr. 1978;31(5):876-85.

9. Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI, Van der Meer JW. Redistribution of vitamin A after iron supplementation in Indonesian infants. Am J Clin Nutr. 2003;77(3):651-7.
10. Hinderaker S, Olsen B, Lie R, Bergsjø P, Gasheka P, Bondevik G, et al. Anemia in pregnancy in rural Tanzania: associations with micronutrients status and infections. Eur J Clin Nutr. 2002;56(3):192.
11. Cunha MS, Siqueira EM, Trindade LS, Arruda SF. Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis. J Nutr Biochem. 2014;25(10):1035-44.
12. Gutowska K, Formanowicz D, Formanowicz P. Interrelations between iron and vitamin A-studied using systems approach. Int J Mol Sci. 2022;23(3):223-31.
13. Pagani A, Nai A, Silvestri L, Camaschella C. Hepcidin and anemia: a tight relationship. Front Physiol. 2019;10(2):494-9.
14. Mendes J, Frossard R, Siqueira E, Machado A, Brito e Silva J, Gabriel M, et al. Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels. Genes Nutr. 2016;11(3):1-7.
15. Gernand AD, Xu X, West Jr KP. Vitamin A in nutritional anemia. In: Karakochuk CD, Zimmermann MB, Moretti D, K. Nutritional anemia. 2nd ed. Switzerland: Springer; 2022. 153-71 p.
16. Josefsen D, Blomhoff HK, Lømo J, Blystad AK, Smeland EB. Retinoic acid induces apoptosis of human CD34+ hematopoietic progenitor cells: involvement of retinoic acid receptors and retinoid X receptors depends on lineage commitment of the hematopoietic progenitor cells. Exp Hematol. 1999;27(4):642-53.
17. Kambe T, Tada-Kambe J, Kuge Y, Yamaguchi-Iwai Y, Nagao M, Sasaki R. Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma cells through the direct repeat of a steroid/thyroid hormone receptor response element half-site in the hypoxia-response enhancer. Blood. 2000;96(9):3265-71.
18. Okano M, Masuda S, Narita H, Masushige S, Kato S, Imagawa S, et al. Retinoic acid up‐regulates erythropoietin production in hepatoma cells and in vitamin A‐depleted rats. FEBS Lett. 1994;349(2):229-33.
19. Neumcke I, Schneider B, Fandrey J, Pagel H. Effects of pro-and antioxidative compounds on renal production of erythropoietin. Endocr. 1999;140(2):641-5.
20. Jelkmann W, Pagel H, Hellwig T, Fandrey J. Effects of antioxidant vitamins on renal and hepatic erythropoietin production. Kidney Int. 1997;51(2):497-501.
21. Semba RD, Muhilal M, West Jr KP, Winget M, Natadisastra G, Scott A, et al. Impact of vitamin A supplementation on hematological indicators of iron metabolism and protein status in children. Nutr Res. 1992;12(4):469-78.
22. Cusick SE, Tielsch JM, Ramsan M, Jape JK, Sazawal S, Black RE, et al. Short-term effects of vitamin A and antimalarial treatment on erythropoiesis in severely anemic Zanzibari preschool children. Am J Clin Nutr. 2005;82(2):406-12.
23. Zimmermann MB, Biebinger R, Rohner F, Dib A, Zeder C, Hurrell RF, et al. Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron. Am J Clin Nutr. 2006;84(3):580-6.
24. Cañete A, Cano E, Muñoz-Chápuli R, Carmona R. Role of vitamin A/retinoic acid in regulation of embryonic and adult hematopoiesis. Nutrients. 2017;9(2):159.
25. Thurnham DI. Vitamin A, iron and haemopoiesis. Lancet. 1993;342(8883):1312-3.
26. Mejia LA, Hodges RE, Rucker RB. Role of vitamin A in the absorption, retention and distribution of iron in the rat. J Nutr. 1979;109(1):129-37.
27. Mejia LA, Hodges RE, Rucker RB. Clinical signs of anemia in vitamin A-deficient rats. Am J Clin Nutr. 1979;32(7):1439-44.
28. Gardner R, Hodges R, Rucker R. Fate of erythrocyte iron in vitamin A deficient rats. Fed Proc. 1979;38(3):762-.
29. Roodenburg A, West C, Beguin Y, Van Dijk J, Van Eijk H, Marx J, et al. Indicators of erythrocyte formation and degradation in rats with either vitamin A or iron deficiency. J Nutr Biochem. 2000;11(4):223-30.
30. Sijtsma K, Van den Berg G, Lemmens A, West C, Beynen A. Iron status in rats fed on diets containing marginal amounts of vitamin A. Br J Nutr. 1993;70(3):777-85.
31. Roodenburg AC, West CE, Hovenierl R, Beynen AC. Supplemental vitamin A enhances the recovery from iron deficiency in rats with chronic vitamin A deficiency. Br J Nutr. 1996;75(4):623-36.
32. Strube YNJ, Beard JL, Ross AC. Iron deficiency and marginal vitamin A deficiency affect growth, hematological indices and the regulation of iron metabolism genes in rats. J Nutr. 2002;132(12):3607-15.
33. Jang J-T, Green JB, Beard JL, Green MH. Kinetic analysis shows that iron deficiency decreases liver vitamin A mobilization in rats. J Nutr. 2000;130(5):1291-6.
34. Rosales FJ, Jang J-T, Piñero DJ, Erikson KM, Beard JL, Ross AC. Iron deficiency in young rats alters the distribution of vitamin A between plasma and liver and between hepatic retinol and retinyl esters. J Nutr. 1999;129(6):1223-8.
35. Ma G, Chen Y, Liu X, Gao Y, Deavila JM, Zhu M-J, et al. Vitamin a supplementation during pregnancy in shaping child growth outcomes: a meta-analysis. Crit Rev Food Sci Nutr. 2023;63(33):122-5.
36. Brownell JN, Schall JI, Mcanlis CR, Smith-Whitley K, Norris CF, Stallings VA. Effect of high-dose vitamin A supplementation in children with sickle cell disease: a randomized, double-blind, dose-finding pilot study. J Pediatr Hematol Oncol. 2020;42(2):83-91.
37. Silva AP, Pereira AdS, Simões BFT, Omena J, Cople-Rodrigues CdS, de Castro IRR, et al. Association of vitamin A with anemia and serum hepcidin levels in children aged 6 to 59 month. Nutr. 2021;91(2):111-4.
38. Tan PY, Loganathan R, Teng K-T, Mohd Johari SN, Lee SC, Selvaduray KR, et al. Supplementation of red palm olein-enriched biscuits improves levels of provitamin A carotenes, iron, and erythropoiesis in vitamin A-deficient primary schoolchildren: a double-blinded randomised controlled trial. Eur J Nutr. 2024;63(3):905-18.
39. Aggarwal S, Verma A, Tiwari S, Kaushik S, Garg S, Kumar S. Assessment of vitamin A status in patients with iron deficiency anemia. MAMC J Med Sci. 2023;9(1):50-6.
40. Kumar R, Oruna-Concha MJ, Niranjan K, Vimaleswaran KS. A review on vitamin A deficiency and depleted immunity in South Asia: from deficiency to resilience. Nutr. 2024;8(3):112-25.
41. Khan JR, Karim ME. A propensity score analysis of the effect of a single dose vitamin A supplementation on child hemoglobin status in Bangladesh. Child Care Pract. 2023;29(2):166-80.
42. McCauley ME, van den Broek N, Dou L, Othman M. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev. 2015;23(10):314-22.
43. Rai RK. Estimated effect of vitamin A supplementation on anaemia and anthropometric failure of Indian children. Pediatr Res. 2022;91(5):1263-71.
44. Ribaudo I, Aramburú-Duclos CB, Blitchtein D. Is vitamin A supplementation associated with anemia in children under 5 years of age in peru: secondary analysis of the “demographic health survey” 2015-2018? Glob Pediatr Health. 2021;8(1):233-7.
45. Suharno D, Karyadi D, West C, Hautvast JG. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet. 1993;34(8):132-8.
46. Tanumihardjo SA. Vitamin A and iron status are improved by vitamin A and iron supplementation in pregnant Indonesian women. J Nutr. 2002;132(7):1909-12.
47. Chawla P, Puri R. Impact of nutritional supplements on hematological profile of pregnant women. Indian Pediatr. 1995;32(7):876-80.
48. Muslimatun S, Schmidt MK, Schultink W, West CE, Hautvast JG, Gross R. Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women. J Nutr. 2001;131(1):85-90.
49. Muslimatun S, Schmidt MK, West CE, Schultink W, Hautvast JG, Karyadi D. Weekly vitamin A and iron supplementation during pregnancy increases vitamin A concentration of breast milk but not iron status in Indonesian lactating women. J Nutr. 2001;131(10):2664-9.
50. Ncube T, Malaba L, Greiner T, Gebre-Medhin M. Evidence of grave vitamin A deficiency among lactating women in the semi-arid rural area of Makhaza in Zimbabwe. A population-based study. Eur J Clin Nutr. 2001;55(4):229.
51. Muhilal, Permeisih D, Idjradinata YR, Muherdiyantiningsih, Karyadi D. Vitamin A-fortified monosodium glutamate and health, growth, and survival of children: a controlled field trial. Am J Clin Nutr. 1988;48(5):1271-6.
52. Mwanri L, Worsley A, Ryan P, Masika J. Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania. J Nutr. 2000;130(11):2691-6.
53. Van Den Broek N, White S, Flowers C, Cook J, Letsky E, Tanumihardjo S, et al. Maternal medicine: Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue. BJOG. 2006;113(5):569-76.