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The role of vitamins in the prevention and control of anaemia

Published online by Cambridge University Press:  02 January 2007

Steven M Fishman ,
Parul Christian  and
Keith P West Jr
Steven M Fishman
Affiliation:
Division of Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
Parul Christian*
Affiliation:
Division of Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
Keith P West Jr
Affiliation:
Division of Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
*
*Corresponding author: Email pchristi@jhsph.edu
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Abstract

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Objective

While iron deficiency is regarded as the major cause of nutritional anaemia, changes in vitamins A, B12, C and E, folic acid and riboflavin status have also been linked to its development and control. This paper provides a systematic review of vitamin supplementation trials relating to the control of nutritional anaemia.

Methods

A MEDLINE search was used to find reports of vitamin supplementation trials that reported changes in anaemia or iron status.

Results

Vitamin A can improve haematological indicators and enhance the efficacy of iron supplementation. Both folate and vitamin B12 can cure and prevent megaloblastic anaemia. Riboflavin enhances the haematological response to iron, and its deficiency may account for a significant proportion of anaemia in many populations. Vitamin C enhances the absorption of dietary iron, although population-based data showing its efficacy in reducing anaemia or iron deficiency are lacking. Vitamin E supplementation given to preterm infants has not reduced the severity of the anaemia of prematurity. Vitamin B6 effectively treats sideroblastic anaemia. Multivitamin supplementation may raise haemoglobin (Hb) concentration, but few studies have isolated the effect of multivitamins from iron on haematological status.

Conclusions

In general, the public health impact of vitamin supplementation in controlling anaemia is not clear. Neither are the complex interactions involving multiple vitamins in haematopoiesis sufficiently understood to explain the observed variability in haematological responses to vitamins by age, population, vitamin mixture and dosages. Further research is needed to understand the roles of individual and combined vitamin deficiencies on anaemia to design appropriate micronutrient interventions to prevent anaemia.

Keywords

VitaminNutrientSupplementAnaemiaHaemoglobin
Type
Research Article
Information
Public Health Nutrition , Volume 3 , Issue 2 , June 2000 , pp. 125 - 150
Copyright
Copyright © CABI Publishing 2000

References

1ACC/SCN. Second Report on the World Nutrition Situation. Vol. 1. Global and Regional Results. Geneva: Administrative Committee on Coordination/Subcommittee on Nutrition, 1992.Google Scholar
2WHO/UNICEF/UNU. Iron Deficiency: Indicators for Assessment and Strategies for Prevention. Geneva: World Health Organization, 1997.Google Scholar
3Lee, GR. The anemia of chronic disease. Semin. Hematol. 1983; 20: 61–80.Google ScholarPubMed
4Fairbanks, VF. Iron in medicine and nutrition. In: Shils, ME, Olson, JA, Shike, M, eds. Modern Nutrition in Health and Disease. Philadelphia: Lea and Febiger, 1994; 185–213.Google Scholar
5Viteri, FE. Iron supplementation for the control of iron deficiency in populations at risk. Nutr. Rev. 1997; 55: 195–209.CrossRefGoogle ScholarPubMed
6DeMaeyer, E, Adiels-Tegman, M.The prevalence of anaemia in the world. Rapp. Trimest. Statist. Sanit. Mond. 1985; 38: 302–16.Google ScholarPubMed
7International Nutritional Anemia Consultative Group (INACG). Iron Deficiency in Women. Washington, DC: The Nutrition Foundation, 1981.Google Scholar
8Rossiter, CE. Maternal mortality. Br. J. Obstet. Gynaecol. 1985; 5 (Suppl.): 100–15.CrossRefGoogle Scholar
9Dallman, PR. Iron In: Brown, ML, ed. Present Knowledge in Nutrition. Washington, DC: International Life Sciences Institute/Nutrition Foundation, 1990; 241–50.Google Scholar
10Christian, P.Antenatal iron supplementation as a child survival strategy. Am. J. Clin. Nutr. 1998; 68: 403–4.Google ScholarPubMed
11Sommer, A. Nutritional Blindness. New York: Oxford University Press, 1982.Google Scholar
12Humphrey, JH, West, KP, Sommer, A.Vitamin A deficiency and attributable mortality among under-5-year-olds. Bull. World Health Org. 1992; 70: 225–32.Google ScholarPubMed
13Sommer, A, West, KP. Vitamin A Deficiency: Health, Survival and Vision. New York: Oxford University Press, 1996.CrossRefGoogle Scholar
14WHO. Indicators for Assessing Vitamin A Deficiency and their Application in Monitoring and Evaluating Intervention Programmes. Geneva: World Health Organization, 1996.Google Scholar
15Beaton, GH, Martorell, R, L'Abbe, KA, et al. Effectiveness of Vitamin A Supplementation in the Control of Young Child Morbidity and Mortality in Developing Countries. Final Report to CIDA. Toronto: University of Toronto, 1992.Google Scholar
16Fawzi, WW, Chameres, TC, Herrera, MG, Mosteller, F.Vitamin A supplementation and child mortality. JAMA 1993; 269: 898–903.CrossRefGoogle ScholarPubMed
17Glasziou, PP, Mackerras, DEM. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ 1993; 306: 366–70.CrossRefGoogle ScholarPubMed
18Findlay, GM, Mackenzie, RD. The bone marrow in deficiency diseases. J. Pathol. 1922; 25: 402–3.Google Scholar
19Wolbach, SB, Howe, PR. Tissue changes following deprivation of fat-soluble A vitamin. J. Exp. Med. 1925; 42: 753–77.CrossRefGoogle ScholarPubMed
20Koessler, KK, Maurer, S, Loughlin, R.The relation of anemia, primary and secondary, to vitamin A deficiency. JAMA 1926; 87: 476–82.CrossRefGoogle Scholar
21Sure, B, Kik, MC, Walker, DJ. The effect of avitaminosis on hematopoietic function. I. Vitamin A deficiency. J. Biol. Chem. 1929; 83: 375–85.CrossRefGoogle Scholar
22Blackfan, KD, Wolbach, SB. Vitamin A deficiency in infants: a clinical and pathological study. J. Pediatr. 1933; 3: 679–706.CrossRefGoogle Scholar
23Mejia, LA, Hodges, RE, Arroyave, G, Viteri, F, Torun, B.Vitamin A deficiency and anemia in Central American children. Am. J. Clin. Nutr. 1977; 30: 1175–84.CrossRefGoogle Scholar
24Wolde-Gebriel, Z, Gebru, H, Fisseha, T, West, CE. Severe vitamin A deficiency in a rural village in the Hararge region of Ethiopia. Eur. J. Clin. Nutr. 1993; 47: 104–14.Google Scholar
25Ahmed, F, Barua, SMohiduzzaman, M, et al. Interactions between growth and nutrient status in school-age children of urban Bangladesh. Am. J. Clin. Nutr. 1993; 58: 334–8.CrossRefGoogle ScholarPubMed
26Bloem, MW, Wedel, MEgger, RJ, et al. Iron metabolism and vitamin A deficiency in children in northeast Thailand. Am. J. Clin. Nutr. 1989; 50: 332–8.CrossRefGoogle ScholarPubMed
27Mohanram, M, Kulkarni, KA, Reddy, V.Hematological studies in vitamin A deficient children. Int. J. Vitam. Nutr. Res. 1977; 47: 389–93.Google ScholarPubMed
28Hodges, RE, Sauberlich, HE, Canham, JE et al. , Hematopoietic studies in vitamin A deficiency. Am. J. Clin. Nutr. 1978; 31: 876–85.CrossRefGoogle ScholarPubMed
29Mejia, LA, Arroyave, G.The effect of vitamin A fortification of sugar on iron metabolism in preschool children in Guatemala. Am. J. Clin. Nutr. 1982; 36: 87–93.CrossRefGoogle ScholarPubMed
30Mejia, LA. Vitamin A deficiency as a factor in nutritional anemia. Int. J. Vitam. Nutr. Res. 1985; 27: 75–84.Google ScholarPubMed
31Muhilal, , 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: 1271–6.CrossRefGoogle ScholarPubMed
32Mejia, LAChew, F.Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am. J. Clin. Nutr. 1988; 48: 595–600.CrossRefGoogle ScholarPubMed
33Smith, JC, Makdani, D, Hegar, A, Rao, DDouglass, LW. Vitamin A and zinc supplementation of preschool children. J. Am. Coll. Nutr. 1999; 18: 213–22.CrossRefGoogle ScholarPubMed
34Panth, M, Shatrugna, V, Yasodhara, PSivakumar, B.Effect of vitamin A supplementation on haemoglobin and vitamin A levels during pregnancy. Br. J. Nutr. 1990; 64: 351–8.CrossRefGoogle ScholarPubMed
35Suharno, D, West, CE, Muhilal, , Karyadi, DHautvast, JGAJ. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 1993; 342: 1325–8.CrossRefGoogle ScholarPubMed
36Shatrugna, V, Raman, L, Uma, KSujatha, T.Interaction between vitamin A and iron: effects of supplements in pregnancy. Int. J. Vitam. Nutr. Res. 1997; 67: 145–8.Google ScholarPubMed
37Fawzi, WW, Msamanga, GI, Spiegelman, D, et al. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 1998; 351: 1477–82.CrossRefGoogle Scholar
38Mahomed, K, Hytten, F. Iron and folate supplementation in pregnancy. In: Chalmers, I, ed. Effective Care in Pregnancy and Childbirth. London: Oxford University Press, 1989.Google Scholar
39Bloem, MW, Wedel, M, van Agtmaal, EJ, Speek, AJ, Saowakontha, SSchreurs, WHP. Vitamin A intervention: short-term effects of a single, oral, massive dose on iron metabolism. Am. J. Clin. Nutr. 1990; 51: 76–9.CrossRefGoogle ScholarPubMed
40Semba, RD, Muhilal, , West, KP, et al. Impact of vitamin A supplementation on hematological indicators of iron metabolism and protein status in children. Nutr. Res. 1992; 12: 469–78.CrossRefGoogle Scholar
41Chawla, PK, Puri, R.Impact of nutritional supplements on hematological profile of pregnant women. Indian J. Pediatr. 1995; 32: 876–80.Google ScholarPubMed
42Kolsteren, P, Rahman, SR, Hilderbrand, K, Diniz, A.Treatment for iron deficiency anaemia with a combined supplementation of iron, vitamin A, and zinc in women of Dinajpur, Bangladesh. Eur. J. Clin. Nutr. 1999; 53: 102–6.CrossRefGoogle ScholarPubMed
43Christian, P, West, KP Jr. Interactions between zinc and vitamin A: an update. Am. J. Clin. Nutr. 1998; 68 (Suppl. 2), S435–41.CrossRefGoogle ScholarPubMed
44Stoltzfus, RJ, Dreyfuss, M, Shrestha, JB, Khatry, SK, Schulze, K, West, KP. Effect of maternal vitamin A or carotene supplementation on iron-deficiency anemia in Nepalese pregnant women, post-partum mothers, and infants. In:. Report of the XVIII International Vitamin A Consultative Group Meeting, Cairo, Egypt. Washington, DC: International Life Science Institute Research Foundation, 1997; 86.Google Scholar
45Koeffler, HP, Amatruda, TT. The effect of retinoids on haemopoiesis – clinical and laboratory studies. In: Pitman, , ed. Retinoids, Differentiation, and Disease. London: Ciba Foundation Symposium, 1985; 252–73.Google Scholar
46Amatruda, TT, Koeffler, HP. Retinoids and cells of the hematopoietic system. In: Sherman, MI, ed. Retinoids and Cell Differentiation. Boca Raton, Florida: CRC Press, 1986; 80–103.Google Scholar
47Jelkmann, W, Pagel, H, Hellwig, TFandrey, J.Effects of antioxidant vitamins on renal and hepatic erythropoietin production. Kidney Int. 1997; 51: 497–501.CrossRefGoogle ScholarPubMed
48Mejia, LA, Hodges, RE, Rucker, RB. Role of vitamin A in the absorption, retention, and distribution of iron in the rat. J. Nutr. 1979; 109: 129–37.CrossRefGoogle ScholarPubMed
49Semba, RD. Vitamin A, immunity, and infection. Clin. Infect. Dis. 1994; 19: 489–99.CrossRefGoogle ScholarPubMed
50Bloem, MW. Interdependence of vitamin A and iron: an important association for programmes of anaemia control. Proc. Nutr. Soc. 1995; 54: 501–8.CrossRefGoogle ScholarPubMed
51Garcia-Casal, MN, Layrisse, M, Solano, L, et al. Vitamin A and β-carotene can improve nonheme iron absorption from rice, wheat, and corn by humans. J. Nutr. 1997; 128: 646–50.CrossRefGoogle Scholar
52Layrisse, M, Garcia-Casal, MN, Solano, L, et al. Vitamin A reduces the inhibition of iron absorption by phytates and polyphenols. Food Nutr. Bull. 1998; 19: 3–5.CrossRefGoogle Scholar
53Gallagher, PG, Ehrenkranz, RA. Nutritional anemias in infancy. Clin. Perinatol. 1995; 22: 671–92.CrossRefGoogle ScholarPubMed
54Myhre, E.Studies on megaloblasts in vitro Scand. J. Clin. Lab. Invest. 1964; 16: 307.Google ScholarPubMed
55Rondanelli, EG, Gorini, P, Magliulo, E, Fiori, GP. Differences in proliferative activity between normoblasts and pernicious anemia megaloblasts. Blood 1964; 24: 542.CrossRefGoogle ScholarPubMed
56Steinberg, SE, Fonda, S, Campbell, CL, Hillman, RS. Cellular abnormalities of folate deficiency. Br. J. Haematol. 1983; 54: 605.CrossRefGoogle ScholarPubMed
57Hughes-Jones, NC, Wickramasinghe, SN. Lecture Notes on Haematology. Oxford: Blackwell Science, 1996.Google Scholar
58Strieff, RR, Little, AB. Folic acid deficiency in pregnancy. N. Engl. J. Med. 1967; 276: 776.CrossRefGoogle Scholar
59Blot, I, Papierhik, F, Kaltwasser, JP, et al. Influence of routine administration of folic acid and iron during pregnancy. Gynecol. Obstet. Invest. 1981; 12: 294.CrossRefGoogle ScholarPubMed
60Herbert, V, Das, KC. Folic acid and vitamin B12. In: Shils, ME, Olson, JA, Shike, M, eds. Modern Nutrition in Health and Disease. Philadelphia: Lea and Febiger, 1994; 402–25.Google Scholar
61Burland, WL, Simpson, K, Lord, J.Response of low birthweight infants to treatment with folic acid. Arch. Dis. Child. 1971; 46: 189–94.CrossRefGoogle ScholarPubMed
62Strelling, MK, Blackledge, DG, Goodall, HB. Diagnosis and management of folate deficiency in low birthweight infants. Arch. Dis. Child. 1979; 54: 271–7.CrossRefGoogle ScholarPubMed
63Ehrenkranz, RA. Iron, folic acid, and vitamin B12. In: Tsang, RC, Lucas, A, Uauy, R, et al. , eds. Nutritional Needs of the Preterm Infant: Scientific Basis and Practical Guidelines. Baltimore: Williams and Williams, 1993; 177–94.Google Scholar
64Fleming, AF. The aetiology of severe anaemia in pregnancy in Ndola, Zambia. Ann. Trop. Med. Parasitol. 1989; 83: 37–49.CrossRefGoogle ScholarPubMed
65Batu, AT, Toe, T, Pe, H, Nyunt, KK. A prophylactic trial of iron and folic acid supplements in pregnant Burmese women. Isr. J. Med. Sci. 1976; 12: 1410–17.Google ScholarPubMed
66Srisupandit, S, Pootrakul, P, Areekul, S, et al. A prophylactic supplementation of iron and folate in pregnancy. Southeast Asian J. Trop. Med. Public Health. 1983; 14: 317–23.Google ScholarPubMed
67Charoenlarp, P, Dhanamitta, S, Kaewvichit, R, et al. A WHO collaborative study on iron supplementation in Burma and Thailand. Am. J. Clin. Nutr. 1988; 47: 280–97.CrossRefGoogle Scholar
68Basu, RN, Sood, SK, Ramachandran, K, Mathur, M, Ramalingaswami, V.Etiopathogenesis of nutritional anemia in pregnancy: a therapeutic approach. Am. J. Clin. Nutr. 1973; 26: 591–4.CrossRefGoogle ScholarPubMed
69Sood, SK, Ramachandran, K, Mathur, M, et al. WHO sponsored collaborative studies on nutritional anaemia in India: 1. The effects of supplemental oral iron administration to pregnant women. Q. J. Med. 1975; 44: 241–58.Google ScholarPubMed
70Iyengar, L, Rajalakshmi, K.Effect of folic acid supplement on birth weights of infants. Am. J. Obstet. Gynaecol. 1975; 122: 332–6.CrossRefGoogle ScholarPubMed
71Iyengar, L, Apte, SV. Prophylaxis of anemia of pregnancy. Am. J. Clin. Nutr. 1970; 23: 725–30.CrossRefGoogle Scholar
72Osifo, B.The effect of folic acid and iron in the prevention of nutritional anaemias in pregnancy in Nigeria. Br. J. Nutr. 1970; 24: 689–94.CrossRefGoogle ScholarPubMed
73Jackson, RT, Latham, MC. Anemia of pregnancy in Liberia, West Africa: a therapeutic trial. Am. J. Clin. Nutr. 1982; 35: 710–14.CrossRefGoogle ScholarPubMed
74Fleming, AF, Martin, JD, Hahnel, R, Westlake, AJ. Effects of iron and folic acid antenatal supplements on maternal haematology and fetal wellbeing. Med. J. Aust. 1974; 2: 429–36.CrossRefGoogle ScholarPubMed
75Colman, N, Larsen, JV, Barker, M, Barker, EA, Green, R, Metz, J.Prevention of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid. Am. J. Clin. Nutr. 1975; 28: 465–70.CrossRefGoogle ScholarPubMed
76Fleming, AF, Ghatoura, GBS, Harrison, KA, Briggs, ND, Dunn, DT. The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria. Ann. Trop. Med. Parasitol. 1986; 80: 211–33.CrossRefGoogle ScholarPubMed
77Mackey, AD, Picciano, MF. Maternal folate status during extended lactation and the effect of supplemental folic acid. Am. J. Clin. Nutr. 1999; 69: 285–92.CrossRefGoogle ScholarPubMed
78Tee, ES, Kandiah, M, Awin, N, et al. School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls. Am. J. Clin. Nutr. 1999; 69: 1249–56.CrossRefGoogle ScholarPubMed
79Areekul, S, Subcharoen, A, Cheeramakara, C, Srisukawat, K, Limsuwan, S.Studies on the effect of folic acid supplement on folate and vitamin B12 status in children. Southeast Asian J. Trop. Med. Public Health 1980; 11: 81–6.Google ScholarPubMed
80Hoffbrand, AV. Folate deficiency in premature infants. Arch. Dis. Child. 1970; 45: 441–4.CrossRefGoogle ScholarPubMed
81Kendall, AC, Jones, EE, Wilson, CID, Shinton, NK, Elwood, PC. Folic acid in low birthweight infants. Arch. Dis. Child. 1974; 49: 736–8.CrossRefGoogle ScholarPubMed
82Roberts, PMM, Arrowsmith, DE, Lloyd, AVC, Monk-Jones, ME. Effect of folic acid treatment on premature infants. Arch. Dis. Child. 1972; 47: 631–4.CrossRefGoogle ScholarPubMed
83Stevens, D, Burman, D, Strelling, MK, Morris, A.Folic acid supplementation in low birth weight infants. Pediatrics 1979; 64: 333–5.CrossRefGoogle ScholarPubMed
84Worthington-White, DA, Behnke, M, Gross, S.Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity. Am. J. Clin. Nutr. 1994; 60: 930–5.CrossRefGoogle ScholarPubMed
85Herbert, V. Vitamin B12. In: Olsen, RE, Broquist, HP, Chichester, CO, et al. , eds Nutrition Reviews' Present Knowledge in Nutrition, 5th edn.Washington, DC: The Nutrition Foundation, 1984; 347–64.Google Scholar
86Herbert, V. Vitamin B12. In: Brown, ML, ed. Present Knowledge in Nutrition. 6th edn.Washington, DC: International Life Sciences Institute/Nutrition Foundation, 1990; 170–8.Google Scholar
87Antony, AC. Megaloblastic anemias. In: Hoffman, R, Benz, EJ, Shattil, SJ, et al. , eds. Hematology: Basic Principles and Practice. New York: Churchill Livingstone, 1991; 392–422.Google Scholar
88Allen, LH, Backstrand, JR, Chavez, A, Pelto, GH. Functional Implications of Malnutrition. Mexico Project Final Report. Storrs, CT: University of Connecticut, 1992.Google Scholar
89Allen, LH. Vitamin B12 metabolism and status during pregnancy, lactation and infancy. In: Allen, LH, Lonnerdal, B, eds. Nutrient Regulation During Pregnancy, Lactation, and Infant Growth. New York: Plenum Press, 1994; 173–86.CrossRefGoogle Scholar
90Levy, S, Rachmilewitz, EZ, Izak, G, Salomonowitz, A, Rachmilewitz, M.A therapeutic trial in anemia of pregnancy. Isr. J. Med. Sci. 1968; 4: 218–22.Google ScholarPubMed
91Lane, M, Alfrey, P.The anemia of human riboflavin deficiency. Blood 1965; 25: 432–42.CrossRefGoogle ScholarPubMed
92Alfrey, CP, Lane, M.The effect of riboflavin deficiency on erythropoiesis. Semin. Hematol. 1970; 7: 49–54.Google ScholarPubMed
93Bates, CJ. Human riboflavin requirements and metabolic consequences of deficiency in man and animals. World Rev. Nutr. Diet. 1987; 50: 215–65.CrossRefGoogle Scholar
94Sirivech, S, Driskell, J, Frieden, E.NADH-FMN oxidoreductase activity and iron content of organs from riboflavin and iron-deficient rats. J. Nutr. 1977. 107: 739–45.CrossRefGoogle ScholarPubMed
95Ulvik, RJ. Ferritin iron as a substrate for synthesis of protoheme in intact rat liver mitochondria. FEBS Lett. 1981; 132: 281–4.CrossRefGoogle ScholarPubMed
96Perry, GM, Anderson, BB, Dodd, N.The effect of riboflavin on red-cell vitamin B6 metabolism and globin synthesis. Biomedicine 1980; 33: 36–8.Google ScholarPubMed
97Fairweather-Tait, SJ, Powers, HJ, Minski, MJ, Whitehead, J, Downes, R.Riboflavin deficiency and iron absorption in adult Gambian men. Ann. Nutr. Metab. 1992; 36: 34–40.CrossRefGoogle ScholarPubMed
98Powers, HJ. Riboflavin–iron interactions with particular emphasis on the gastrointestinal tract. Proc. Nutr. Soc. 1995; 54: 509–17.CrossRefGoogle ScholarPubMed
99Decker, K, Dotis, B, Glatzle, D, Hinselmann, M.Riboflavin status and anaemia in pregnant women. Nutr. Metab. 1977; 21 (Suppl. 1), 17–19.CrossRefGoogle ScholarPubMed
100Powers, HJ, Bates, CJ, Lamb, WH. Haematological response to supplements of iron and riboflavin to pregnant and lactating women in rural Gambia. Hum. Nutr. Clin. Nutr. 1985; 39C: 117–29.Google Scholar
101Buzina, R, Jusic, M, Milanovic, N, Sapunar, J, Brubacher, G.The effects of riboflavin administration on iron metabolism parameters in a school-going population. Int. J. Vitam. Nutr. Res. 1979; 49: 136–43.Google Scholar
102Charoenlarp, P, Pholpothi, T, Chatpunyaporn, P, Schelp, FP. Effect of riboflavin on the hematologic changes in iron supplementation of schoolchildren. Southeast Asian J. Trop. Med. Public Health 1980; 11: 97–103.Google ScholarPubMed
103Powers, HJ, Bates, CJ, Prentice, AM, Lamb, WH, Jepson, M, Bowman, H.The relative effectiveness of iron and iron with riboflavin in correcting a microcytic anaemia in men and children in rural Gambia. Hum. Nutr. Clin. Nutr. 1983; 37C: 413–25.Google Scholar
104Suboticanec, K, Stavljenic, A, Schalch, W, Buzina, R.Effects of pyridoxine and riboflavin supplementation on physical fitness in young adolescents. Int. J. Vitam. Nutr. Res. 1990; 60: 81–8.Google ScholarPubMed
105Ajayi, OA, Okike, OC, Yusuf, Y.Haematological response to supplements of riboflavin and ascorbic acid in Nigerian young adults. Eur. J. Haematol. 1990; 44: 209–12.CrossRefGoogle ScholarPubMed
106Oski, FA. Anemia due to other nutritional deficiencies. In: Williams, WJ, Beutler, E, eds. Hematology. New York: McGraw-Hill, 1995; 511–15.Google Scholar
107Bothwell, TH, Bradlow, BA, Jacobs, P, et al. Iron metabolism in scurvy with special reference to erythropoiesis. Br. J. Haematol. 1964; 10: 50–8.CrossRefGoogle ScholarPubMed
108Lynch, SR, Cook, JD. Interaction of vitamin C and iron. Ann. NY Acad. Sci. 1980; 355: 32–44.CrossRefGoogle ScholarPubMed
109Hallberg, L, Brune, M, Rossander-Hulthen, L.Is there a physiological role of vitamin C in iron absorption?. Ann. NY Acad. Sci. 1987; 498: 324–32.CrossRefGoogle Scholar
110Clark, NG, Sheard, NF, Kelleher, JF. Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency. Nutr. Rev. 1992; 50: 134–7.Google ScholarPubMed
111Cook, JD, Monsen, ER. Vitamin C, the common cold, and iron absorption. Am. J. Clin. Nutr. 1977; 30: 235–41.CrossRefGoogle ScholarPubMed
112Stokes, PL, Melikian, V, Leeming, RL, Portman-Graham, H, Blair, JA, Cooke, WT. Folate metabolism in scurvy. Am. J. Clin. Nutr. 1975; 28: 126–9.CrossRefGoogle ScholarPubMed
113Chow, CK. Nutritional influence on cellular antioxidant defense systems. Am. J. Clin. Nutr. 1979; 32: 1066.CrossRefGoogle ScholarPubMed
114Hodges, RE, Baker, EM, Hood, J, Sauberlich, HE, March, SC. Experimental scurvy in man. Am. J. Clin. Nutr. 1969; 22: 535–48.CrossRefGoogle ScholarPubMed
115Hodges, RE, Hood, J, Canham, JE, Sauberlich, HE, Baker, EM. Clinical manifestations of ascorbic acid deficiency in man. Am. J. Clin. Nutr. 1971; 24: 432–43.CrossRefGoogle ScholarPubMed
116Sauberlich, HE. Ascorbic acid. In: Brown, ML, ed. Present Knowledge in Nutrition, 6th edn.Washington, DC: International Life Sciences Institute/Nutrition Foundation, 1990; 132–41.Google Scholar
117Garry, PJ, Vanderjagt, DJ, Hunt, WC. Ascorbic acid intakes and plasma levels in healthy elderly. Ann. NY Acad. Sci. 1987; 498: 90–9.CrossRefGoogle ScholarPubMed
118National Research Council (NRC). Recommended Dietary Allowances. Washington, DC: National Academy Press, 1989.Google Scholar
119Seshadri, S, Shah, A, Bhade, S.Haematologic response of anaemic preschool children to ascorbic acid supplementation. Hum. Nutr. Appl. Nutr. 1985; 39: 151–4.Google ScholarPubMed
120Mao, X, Yao, G.Effect of vitamin C supplementation on iron deficiency anemia in Chinese children. Biomed. Environ. Sci. 1992; 5: 125–9.Google ScholarPubMed
121Angeles, IT, Schultink, WJ, Matulessi, P, Gross, R, Sastroamidjojo, S.Decreased rate of stunting among anemic Indonesian preschool children through iron supplementation. Am. J. Clin. Nutr. 1993; 58: 339–42.CrossRefGoogle ScholarPubMed
122Suboticanec-Buzina, K, Buzina, R, Brubacher, G, Sapunar, J, Christeller, S.Vitamin C status and physical working capacity in adolescents. Int. J. Vitam. Nutr. Res. 1984; 54: 55–60.Google ScholarPubMed
123Ajayi, OA, Nnaji, UR. Effect of ascorbic acid supplementation on haematological response and ascorbic acid status of young female adults. Ann. Nutr. Metab. 1990; 34: 32–6.CrossRefGoogle ScholarPubMed
124Hunt, JR, Mullen, LM, Lykken, GI, Gallagher, SK, Nielsen, FH. Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. Am. J. Clin. Nutr. 1990; 51: 649–55.CrossRefGoogle ScholarPubMed
125Garcia, OP, Diaz, M, Rosado, JL, Allen, LH. Community trial of the efficacy of lime juice for improving iron status of iron deficient Mexican women. FASEB J. 1998; 12: A647(abstract).Google Scholar
126Kuizon, MD, Platon, TP, Ancheta, LP, Angeles, JC, Nunez, CB, Macapinlac, MP. Iron supplementation studies among pregnant women. Southeast Asian J. Trop. Med. Public Health 1979; 10: 520–7.Google ScholarPubMed
127Sharma, DC, Mathur, R.Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid. Indian J. Physiol. Pharmacol. 1995; 39: 403–6.Google ScholarPubMed
128Pekiner, B, Nebioglu, S.Effect of vitamin C on copper and iron status in men and guinea pigs. J. Nutr. Sci. Vitaminol. 1994; 40: 401–10.CrossRefGoogle ScholarPubMed
129Farrell, PM, Roberts, RJ. Vitamin E. In: Shils, ME, Olson, JA, Shike, M, eds. Modern Nutrition in Health and Disease. Philadelphia: Lea and Febiger, 1994; 326–41.Google Scholar
130Dinning, JS, Day, PL. Vitamin E deficiency in the monkey. I. Muscular dystrophy, hematologic changes and the excretion of urinary nitrogenous constituents. J. Exp. Med. 1957; 105: 395.CrossRefGoogle ScholarPubMed
131Marvin, HN, Dinning, JS, Day, PL. Erythrocyte survival in vitamins E-deficient monkeys. Proc. Soc. Exp. Biol. Med. 1960;105: 473–5.CrossRefGoogle ScholarPubMed
132Porter, FS, Fitch, CD, Dinning, JS. Vitamin E deficiency in the monkey. IV. Further studies of the anemia with emphasis on bone marrow morphology. Blood 1962; 20: 471.CrossRefGoogle ScholarPubMed
133Marvin, HN. Erythrocyte survival of rats deficient in vitamin E on vitamin B6.. J. Nutr. 1963; 80: 185–90.CrossRefGoogle Scholar
134Chou, AC, Broun, GO, Fitch, CD. Abnormalities of iron metabolism and erythropoiesis in vitamin E-deficient rabbits. Blood 1978; 52: 187–95.CrossRefGoogle ScholarPubMed
135Horwitt, MK, Century, B, Zeman, AA. Erythrocyte survival time and reticulocyte levels after tocopherol depletion in man. Am. J. Clin. Nutr. 1963; 12: 99–106.CrossRefGoogle ScholarPubMed
136Ehrenkranz, RA. Vitamin E and the neonate. Am. J. Dis. Child. 1980; 134: 1157–66.Google ScholarPubMed
137Oski, FA, Barness, LA. Vitamin E deficiency: a previously unrecognized cause of hemolytic anemia in the premature infant. J. Pediatr. 1967; 70: 211–20.CrossRefGoogle ScholarPubMed
138Ritchie, JH, Fish, MB, McMasters, V, Grossman, M.Edema and hemolytic anemia in premature infants. N. Engl. J. Med. 1968; 279: 1185–90.CrossRefGoogle ScholarPubMed
139Lo, SS, Frank, D, Hitzig, WH. Vitamin E and haemolytic anaemia in premature infants. Arch. Dis. Child. 1973; 48: 360–5.CrossRefGoogle ScholarPubMed
140Williams, ML, Shott, RJ, O'Neal, PL, Oski, FA. Role of dietary iron and fat on vitamin E deficiency anemia of infancy. N. Engl. J. Med. 1975; 292: 887–90.CrossRefGoogle ScholarPubMed
141Gross, SJ, Landaw, SA, Oski, FA. Vitamin E and neonatal hemolysis. Pediatrics 1977; 59: 995–7.CrossRefGoogle ScholarPubMed
142Melhorn, DK, Gross, S.Vitamin E-dependent anemia in the premature infant. I. Effects of large doses of medicinal iron. J. Pediatr. 1971; 79: 569–80.CrossRefGoogle ScholarPubMed
143Gross, S, Melhorn, DK. Vitamin E-dependent anemia in the premature infant. J. Pediatr. 1974; 85: 753–9.CrossRefGoogle ScholarPubMed
144Fermanian, J, Salmon, D, Olive, G, Zambrowski, S, Rossier, A, Caldera, R.Double blind study of vitamin E compared to placebo in the prevention of anemia in the low birth weight infant during the 7th week of life: therapeutic study [in French]. Nouv. Rev. Fr. Hematol. Blood Cells 1976; 16: 245–54.Google ScholarPubMed
145Blanchette, V, Doyle, J, Schmidt, B, Zipursky, A. Hematology. In: Avery, GB, Fletcher, MA, MacDonald, MG, eds. Neonatology: Pathophysiology and Management of the Newborn. Philadelphia: JB Lipincott, 1994; 952–99.Google Scholar
146Blanchette, V, Bell, E, Nahmias, C, Garnett, S, Milner, R, Zipursky, A.A randomized control trial of vitamin E therapy in the prevention of anemia in low birth weight (LBW) infants. Pediatr. Res. 1980; 14: 591.Google Scholar
147Zipursky, A.Vitamin E deficiency anemia in newborn infants. Clin. Perinatol. 1984; 11: 393–402.CrossRefGoogle ScholarPubMed
148Zipursky, A, Brown, EJ, Watts, J, et al. Oral vitamin E supplementation for the prevention of anemia in premature infants: a controlled trial. Pediatrics 1987; 79: 61–8.CrossRefGoogle ScholarPubMed
149Conway, SP, Rawson, I, Dear, PRF, Shires, SE, Kelleher, J.The early anaemia of the premature infant: is there a place for vitamin E supplementation?. Br. J. Nutr. 1986; 56: 105–14.CrossRefGoogle Scholar
150Ferlin, MLS, Chuan, LS, Jorge, SM, Vannucchi, H.Early anemia of prematurity. Nutr. Res. 1998; 18: 1161–73.CrossRefGoogle Scholar
151Majaj, AS. Vitamin E-responsive megaloblastic anemia in infants with protein-calorie malnutrition. Am. J. Clin. Nutr. 1963; 12: 374–9.CrossRefGoogle Scholar
152Whitaker, JA, Fort, EG, Vimokesant, S, Dinning, JS. Hematologic response to vitamin E in the anemia associated with protein-calorie malnutrition. Am. J. Clin. Nutr. 1967; 20: 783–9.CrossRefGoogle ScholarPubMed
153Asfour, RY, Firzli, S.Hematologic studies in undernourished children with low serum vitamin E levels. Am. J. Clin. Nutr. 1965; 17: 158–63.CrossRefGoogle ScholarPubMed
154Baker, SJ, Pereira, SM, Begum, A.Failure of vitamin E therapy in the treatment of anemia of protein-calorie malnutrition. Blood 1968; 32: 717–25.CrossRefGoogle ScholarPubMed
155Kulapongs, P. The effect of vitamin E on the anemia of protein-calorie malnutrition in northern Thai children. In: Olsen, RE, ed. Protein-Calorie Malnutrition. New York: Academic Press, 1975; 263–8.CrossRefGoogle Scholar
156Neufeld, EJ, Mandel, H, Raz, T, et al. Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. Am. J. Hum. Genet. 1997; 61: 1335–41.CrossRefGoogle Scholar
157Handler, P, Featherston, WP. The biochemical defect in nicotinic acid deficiency. J. Biol. Chem. 1943; 151: 395.CrossRefGoogle Scholar
158Spivak, JL, Jackson, DL. Pellagra: an analysis of 18 patients and a review of the literature. Johns Hopkins Med. J. 1977; 140: 295–309.Google Scholar
159Wintrobe, MM, Follis, RH Jr, Alcayaga, R, Paulson, M, Humphreys, S.Pantothenic acid deficiency in swine. Bull. Johns Hopkins Hosp. 1943; 73: 313.Google Scholar
160Richert, DA, Schulman, MP. Vitamin interrelationships in heme synthesis. Am. J. Clin. Nutr. 1959; 7: 416–25.CrossRefGoogle Scholar
161McCurdy, PR. Is there an anemia responsive to pantothenic acid?. J. Am. Geriatr. Soc. 1973; 21: 88–91.CrossRefGoogle ScholarPubMed
162Ofori-Nkansah, N, Weissenfels, I, Pribilla, W.Vitamin B6 deficiency anemia [in German]. Schweiz. Med. Wochenschr. 1975; 105: 1319–24.Google Scholar
163Meier, PJ, Giger, U, Brandli, O, Fehr, J.Acquired, vitamin B6-responsive, primary sideroblastic anemia, an enzyme deficiency in heme synthesis [in German]. Schweiz. Med. Wochenschr. 1981; 111: 1533–5.Google ScholarPubMed
164Reinken, L, Kurz, R.Activity studies of an iron–vitamin B6 preparation for euteral treatment of iron deficiency anemia [in German]. Int. J. Vitam. Nutr. Res. 1975; 44: 411–18.Google Scholar
165Natta, CL, Reynolds, RD. Apparent vitamin B6 deficiency in sickle cell anemia. Am. J. Clin. Nutr. 1984; 40: 235–9.CrossRefGoogle ScholarPubMed
166Bradfield, RB, Jensen, MV, Gonzales, L, Garrayar, C.Effect of low-level iron and vitamin supplementation on a tropical anemia. Am. J. Clin. Nutr. 1968; 21: 57–67.CrossRefGoogle ScholarPubMed
167Reinken, L, Kurz, R.The treatment of anaemia due to iron-deficiency with iron combined with vitamins [in German]. Klin. Padiatr. 1978; 190: 163–7.Google ScholarPubMed
168Tell'mann, Akh, Saava, ME, Aasvee, KE. Effects of prophylactic vitamin administration to Tallin's schoolchildren on their health and physical development [in Russian]. Vopr. Pitan. 1992; 05–06 36–40.Google ScholarPubMed
169Buzina, R, Grgic, Z, Jusic, M, Sapunar, J, Milanovic, N, Brubacher, G.Nutritional status and physical working capacity. Hum. Nutr. Clin. Nutr. 1982; 36C: 429–38.Google Scholar
170Das, BK, Bal, MS, Tripathi, AM, Singla, PN, Agarwal, DK, Agarwal, KN. Evaluation of frequency and dose of iron and other hematinics – an alternative strategy for anemia prophylaxis in rural preschoolers. Indian J. Pediatr. 1984; 21: 933–8.Google ScholarPubMed
171Powers, HJ, Bates, CJ, Lamb, WH, Singh, J, Gelman, W, Webb, E.Effects of a multivitamin and iron supplement on running performance in Gambian children. Hum. Nutr. Clin. Nutr. 1985; 39: 427–37.Google ScholarPubMed
172Liu, DS, Bates, CJ, Yin, TA, Wang, XB, Lu, CQ. Nutritional efficacy of a fortified weaning rusk in a rural area near Beijing. Am. J. Clin. Nutr. 1993; 57: 506–11.CrossRefGoogle Scholar
173Van Stuijvenberg, ME, Kvalsvig, JD, Faber, M, Kruger, M, Kenoyer, DG, Benade, AJ. Effect of iron-, iodine-, and beta-carotene-fortified biscuits on the micronutrient status of primary school children: a randomized controlled trial. Am. J. Clin. Nutr. 1999; 69: 497–503.CrossRefGoogle ScholarPubMed
174Thu, BD, Schultink, W, Dillon, D, Gross, R, Leswara, ND, Khoi, HH. Effect of daily and weekly micronutrient supplementation on micronutrient deficiencies and growth in young Vietnamese children. Am. J. Clin. Nutr. 1999; 69: 80–6.CrossRefGoogle ScholarPubMed
175Angeles-Agdeppa, I, Schultink, W, Sastroamidjojo, S, Gross, R, Karyadi, D.Weekly micronutrient supplementation to build iron stores in female Indonesian adolescents. Am. J. Clin. Nutr. 1997; 66: 177–83.CrossRefGoogle ScholarPubMed
176Scholl, TO, Hediger, ML, Bendich, A, Schall, JI, Smith, WK, Krueger, PM. Use of multivitamin/mineral prenatal supplements: influence on the outcome of pregnancy. Am. J. Epidemiol. 1997; 146: 134–41.CrossRefGoogle ScholarPubMed