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Arquivos de Medicina

versão On-line ISSN 2183-2447

Arq Med v.19 n.1-2 Porto jan. 2005

 

Putative Role of Riboflavin in Disease Prevention

 

Nélson Tavares

 

The Center for Human Nutrition, The University of Sheffield, United Kingdon; The Faculty of Nutrition and Food Sciences of the University of Porto, Portugal

 

In the early part of the twentieth century, pioneering studies on the deficiency state of pellagra in experimental animals showed that water-soluble tissue extracts could be effective in treating diseases. Further studies showed that one part of the heat-stable fraction from the mentioned extract, called yellow growth factor, had fluorescent properties. This was later purified and named riboflavin. Until 1932, when the landmark discovery of the ‘’yellow enzyme’’ containing an isoalloxazine ring and a phosphate group was made, the physiological role of the yellow growth factor remained obscure. The synthesis of riboflavin, accomplished in 1935, was followed by the identification of the two active coenzyme forms, flavin mononucleotide (FMN) in 1937 and the clarification of the structure of flavin adenine dinucleotide in 1938, this formed from FMN. As a water-soluble vitamin, riboflavin plays a part in a variety of oxidation-reduction reactions. Flavin mononucleotide and flavin dinucleotide act as active coenzyme forms of riboflavin that participate in a variety of reactions in the human body. Riboflavin has an important role in the fat metabolism disturbances. Through deficiency and supplementation studies and effects on the structure and function of the small intestine, riboflavin has a role in iron handling. Riboflavin is associated with compromised oxidant defense. Flavin adenine dinucleotide acts as the co-factor for 5,10 Methylenetetrahydrofolate reductase, an important enzyme, which participates in the remethylation pathway for homocysteine metabolism. Homocysteine is located at a critical metabolic crossroad and therefore both pathways, remethylation and transsulfuration; and directly and indirectly impacts all methyl and sulphur group metabolism occurring in the body. Poor vitamin status could promote higher homocysteine levels. In addition, high levels of homocysteine could be considered conditional risk factors for cardiovascular diseases. Riboflavin has also been ascribed a role in the protection against certain cancers and cataracts.

Key-words: Riboflavin, homocysteine, iron handling

 

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REFERENCES

1 - Rucker R, Suttie J, McCormick D, Machlin L. Handbook of Vitamins. Third Edition. Published by; Marcel Dekker, INC. New York; 2001.         [ Links ]

2 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994.

3 - McCormick DB, Greene HL. Vitamins In: Burtis CA, Ashwood Er, eds.Tielz Textbook of Clinical Chemistry. Saunders; Philadelphia.1994.

4 - Merril AH Jr, Lambeth JD, Edmondson DE, McCormick DB. Formation and mode of action of flavoproteins. Annu Rev Nutr1981;1:281-317.

5 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994

6 - Dietary reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Panthothenic Acid, Biotin and Choline,(1998) http://www.iom.edu/Object.File/Master/7/296/0.pdf

7 - US Dept of Health Education & Welfare, N.I.H. Bethesda. Leung, Woot.-T.W. Food composition table for use in S.E. Asia.I. Proximate composition, mineral and vitamin contents of E. Asian foods. 1972

8 - Hughes J, Sanders TAB. Riboflavin levels in the diet and brest milk of vegans and omnivores. Proc.Nutr.Soc. 1979;38:95A.

9 - 64 - Zempleni J, Galloway JR, McCormick DB. Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. Am J Clin Nutr1996;63:54.

10 - Boisvert WA, Mendonza I, Castañeda C, Portocarrero L, Solomons NW, Gershoff SN, Russel RM. Riboflavin requirement of healthy elderly humans and its relationship to macronutrient composition of the diet. J Nutr 1993;123:915-25.

11 - Chia CP, Addison R, McCormick DB. Absorption, metabolism, and excretion of 8a-(amino acid) riboflavins in the rat. J Nutr 1978;108:373-381.

12 - Yagi K, Nakagawa Y, Suzuki, and Oshishi. Incorporporation of riboflavin into covalently bound flavins in rat liver. J. Biochem 1976;79:841.

13 - Komindr S, Nichoalds GE. Clinical significance of riboflavin deficiency. In: Brewster MA, Naito HK, eds. Nutritional Elements in Clinical Biochemistry. New York: Plenum Press.p15-68, 1980.

14 - Nichoalds GE. Riboflavin. Symposium in Laboratory Medicine. In:Labbae RF, ed. Symposium on Laboratory Assessment of Nutritional Status. Clinics in Laboratory Medicine Series. Vol.1. Philadelphia: WB Saunders. p685-698,1981.

15 - McCormick DB. Two interconected B vitamins: Riboflavin and pyridoxine. Physiol Rev 1989;69:1170-1198.

16 - Prager MD, Hill JM, Speer RJ. Whole blood riboflavin levels in healthy individuals ans in patientys manifesting various blood dyscrasias. J Lab Clin Med 1958;52:206.

17 - Cole HS, Lopez R, Cooperman JM. Riboflavin deficiency in children with diabetes mellitus. Acta Diabetol Lat 1976;13:25-29

18 - Rivlin RS. Riboflavin and cancer. In: Rivlin RS, ed. Riboflavin. New York: Plenum Press. p. 369-391.1975.

19 - Steier M, Lopez R, Cooperman JM. Riboflavin deficiency in infants and children with heart disease. Am Heart J 1976;92:139-143.

20 - Bessey OA, Lowry OH, Love RH. Fluorometric measure of the nucleotides of riboflavin and their concentration in tissues.J.Biol.Chem.1949;180:755

21 - Fazekas AG, Menendez CE, Rivlin RS. A competitive protein binding assay for urinary riboflavin. Biochem.Med. 1974;9:167.

22 - Chastain JL, McCormick DB. Flavin catabolites: Identification and quantitation in human urine. Am J Clin Nutr 1987;46:830-4.

23 - Sauberlich HE, Judd JH, Nichoalds GE, Broquist HP, Darby WJ. Application of the erythrocyte gluthathione reductase assay in evaluating riboflavin nutritional status in a high school student population. Am.J.Cli.Nutr. 1972;25:756.

24 -Chastain JL, McCormick DB. Flavin catabolites: Identification and quantitation in human urine. Am J Clin Nutr 1987;46:830-4.

25 - Roughead ZK, McCormick DB. Urinary riboflavin and its metabolites: Effects of riboflavin supplementation in healthy residents of rural Georgia (USA). Eur J Clin Nutr 1991;15:299-307.

26 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994

27 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994

28 - Rivlin RS. Riboflavin in the Present Knowledge. In: Ziegler EE, Filer LJJr.,eds. Nutrition, Washington, DC. Ziegler EE, Filer LJ,Jr.,eds. ILSI Press, Washington, DC, p.167, 1996.

29 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994

30 - Belko AZ, Obarzanek E, Roach R, et al. Effects of aerobic exercise and weight loss on riboflavin requirements of moderately obese, marginally deficient young woman. Am J Clin Nutr 1984;40:553-61.

31 - Soares MJ, Satyanarayana K, Bamji MS et al. The effect of exercise on the riboflavin status of adult men. Br J Nutr 1993;69:541-51.

32 - Sauberlich HE, Judd JH, Nichoalds GE, Broquist HP, Darby WJ. Application of the erythrocyte gluthathione reductase assay in evaluating riboflavin nutritional status in a high school student population. Am.J.Cli.Nutr. 1972;25:756.

33 - Sadowski JA. Riboflavin. In : Hartz SC, Russel RM, Rosenberg IH, eds. Nutrition in the Elderly. The Boston Nutritional Status Survey. London: Smith-Gordon. p. 119-125,1992.

34 - Nichoalds GE. Riboflavin. Symposium in Laboratory Medicine. In:Labbae RF, ed. Symposium on Laboratory Assessment of Nutritional Status. Clinics in Laboratory Medicine Series. Vol.1. Philadelphia: WB Saunders. p685-698,1981.

35 - Rivlin RS. 1990. Medical aspects of vitamin B2. In: F. Muller,ed. Chemistry and Biochemistry of Flavins. Boca Raton, FL, CRC Press, p.201,1990.

36 - McCormick DB. 1994. Riboflavin. In: M.E. Shils, J.A. Olson, and Shike M. (eds), Modern Nutrition in Health and Disease, 8th ed., Philadelphia, Lea and Febiger. p.366. 1994

37 - Bender K, Blattner C, Knebel A et al. UV-induced signal transduction. J Photochem and Photobio 1997;B37:1-17.

38 - Ogunleye AJ, Odutuga AA. The effect of riboflavin deficiency on cerebrum and cerebellum of developing rat brain. J Nutr Sci Vitaminol (Tokyo)1989;35:193-7.

39 - Triggs WJ, Roe CR, Rhead WJ, Hanson SK, Lin SN, Willmore LJ. Neuropsychiatric manifestations of defect in mitochondrial beta oxidation response to riboflavin. J Neurol Neurosurg Psychiatry 1992;55:209-11.

40 - Vergani L, Barile M, Angelini C et al. Riboflavin therapy. Brain,1999;122:2401-11.

41 - Bersen P.L.J.A., Gabreels F. J.M., Ruitenbeek W., and Hamburger H.L. Treatment complex I deficiency with riboflavin. J.Neurol. Sci. 1993;118:181.

42 - Powers HJ, Thurnham DI. Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages. Br J Nutr 1981;46:257-66.

43 - Powers HJ. Riboflavin-iron interactions with particular emphasis on the gastrointestinal tract. Proceddings of the Nutrition Society 1995;54:509-17.

44 - Powers HJ, Weaver LT, Austin S et al. Riboflavin deficiency in the rat: effects on iron utilization and loss. B J Nutr 1991;65:487-96.

45 - Adelekan DA, Thurnham DI. TA longitudinal study on the effect of riboflavin status on aspects of iron storage in the liver of growing rats. Proc. Nutr. Soc. 1981;40:101A.

46 - Powers HJ, Bates CJ, Duerden JM. Effects of riboflavin deficiency in rats on some aspects of iron metabolism. Int J Vitam Nutr Res 1983;53:371-6.

47 - Powers HJ. Experiment to determine the effect of riboflavin deficiency at weaning on iron economy and heme synthesis. Ann Nutr Metab 1985;29:261-6.

48 - Powers 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 1983;37:413-25.

49 - Powers HJ, Bates CJ. Effects of pregnancy and riboflavin deficiency on some aspects of iron metabolism in rats. Int J Vitam Nutr Res 1984;54:179-83.

50 - Powers 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;39:117-29.

51 - Powers HJ, Bates CJ, Lamb WH, Singh J, Gelman W, Webb E. Effects of multivitamin and iron suplement on runningperformance in Gambian children. Hum Nutr Clin 1985;39:427-37.

52 - Powers HJ. Riboflavin-iron interactions with particular emphasis on the gastrointestinal tract. Proceddings of the Nutrition Society 1995;54:509-17.

53 - Adelekan DA, Thurnham DI. The influence of riboflavin deficiency on absorption and liver storage of iron in the growing rat. Br J Nutr 1986;56:171-9.

54 - Powers HJ. Investigation into the relative effects of riboflavin deprivation on iron economy in the weanling rat and the adult. Ann Nutr Metab 1986;30:308-15.

55 - Powers HJ, Bates CJ. Micronutrient deficiencies in the aetiology of anaemia in a rural area in the Gambia. Trans R Soc Trop Med Hyg 1987;81:421-5.

56 - Powers HJ, Wright AJ, Fairweather-Tait SJ. The effect of riboflavin deficiency in rats on the absorption and distribution of iron. Br J Nutr 1988;59:381-7.

57 - Fairweather-Tait SJ, Powers HJ, Minski MJ, Whitehead J, Dowes R. Riboflavin deficiency and iron absorption in adult Gambian men. Ann Nutr Metab 1992;36:34-40.

58 - Powers HJ, Weaver LT, Austin S, Beresford JK. A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. Br J Nutr 1993;69:553-61.

59 - Williams EA, Powers HJ, Rumsey RD. Morphological changes in the rat small intestine in response to riboflavin depletion. Br J Nutr 1995;73:141-6.

60 - Williams EA, Rumsey RD, Powers HJ. Cytokinetic and structural responses of the rat small intestine to riboflavin depletion. Br J Nutr 1996;75:315-24.

61 - Williams EA, Rumsey RD, Powers HJ. An investigation into the reversibility of the morphological and cytokinetic seen in the small intestine of riboflavin deficient rats. Gut. 1996;39:220-5.

62 - Yates CA, Evans GS, Powers HJ. Riboflavin deficiency: early effects on post-weaning development of the duodenum in rats. Br J Nutr 2001;86:593-9.

63 - Dutta P. Disturbances in glutathione metabolism and resistance to malaria: current understanding and new concepts. J Soc Pharm Chem 1993;2:11.

65 - Rivlin RS, Dutta P. Vitamin B2 (riboflavin). Relevance to malaria and antioxidant activity. Nutr. Today 1995;30:62.

66 - Akompong T, Ghori N, Haldar K. In vitro activity of riboflavin against the human malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother 2000;44:88-96.

67 - Akompong T, Eksi S, Williamson K, Haldan K. Gametocytocidal activity and synergistic interactions of riboflavin with standard antimalarial drugs against growth of Plasmodium falciparum in vitro. Antimicrob Agents Chemother 2000;44:3107-11.

68 - Graham IA, Daly LE, Refsum HM et al. Plasma homocysteine as a risk factor for vascular disease. The European concerted project. JAMA 1997;277:1775.

69 - Shelhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217-246.

70 - Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001;73:613-21.

71 - Day PL, Langston WC, O´Brian CS. Cataract and other ocular changes in vitamin G deficiency.Am.J.Ophthal 1931;14:1005-9.

72 - Cumming RG, Mitchel P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107:450-456.

73 - Perlman JA, Klein BE, Klein R, Ritter LL. Relation between lens opacities and vitamin and mineral supplement use. Ophtalmology 1994;101:315-25.

74 - Leske MC, ChylacK LT Jr, Wu SY. The Lens Opacities Case-Control Study. Risk factors for cataract. Arch Ophtalmol 1991;109:244-51

75 - Leske MC, Wu SY, Hyman L, Sperduto R, Underwood B, Chylack LT, Milton RC, Srivastava S, Ansary N. Biochemical factors in the lens opacities. Case-control study. The Lens Opacities Case-Control Study Group. Arch Ophtalmol 1995;113:1113-9.

76 - Kuzniarz M, Mitchell P, Cumming R, Flood V. Use of Vitamin Supplements and Cataract: The Blue Mountains Eye Study.American Journal of Ophthalmology 2001;132:19-26.

77 - Sperduto RD, Hu TS, Milton RC, et al. The Lixian cataract studies. Two nutrition intervention trials.Arch Ophthalmol 1993;111:1246-53.

78 - Li JY. Vitamins and Minerals in Cancer: the Nutrition Intervention Trials in Lixian, China. In Cancer and Nutrition. Prasad K.N., Cole W.C. (eds) The Netherlands. IOS Press. 1998.

79 - Pullin CH, Wilson JF, Ashfield-Watt PA, Clark ZE, Whiting JM, Lewis MJ, McDowell IF. Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals. Clin Sci (Lond) 2002;10245-50.

80 - Kitazawa M, Sugiyama S, Ozawa T, Miyazaki Y, Kotaka K. Mechanism of chlorpromazine-induced arrhythmia-arrhyth-mia and mitochondrial dysfunction. J Electrocardiol 1981;14:219-24.

81 - Mack CP, Hultquist DE, Shlafer M. Myocardial flavin reductase and riboflavin: a potential role in decreasing reoxygenation injury. Biochem Biophys Res Commun 1995;6;212:35-40.

82 - Tutel’ian VA, Pogozheva AV, Rumiantseva OI et al. Effects of biologically active supplements on the antioxidant and vitamin status of patients with hypertension and ischemic heart disease. Vopr Pitan 2001;70:12-4.

83 - McKinley MC. Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease. Proc Nutr Soc 2000;59:221-37.

84 - Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. Oxford University Press, New York. 1989.

85 - Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM. Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinaemia. Euro. J. Clin. Invest 1995;25:149-54.

86 - Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine.J Clin Invest 1986;77:1370-6.

87 - Stamler J, Osborne J, Jaraki O. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993;91:308-18.

88 - Higashi O, Ishigaki W, Hashimoto T. Effects of riboflavin-2',3',4', 5'-tetrabutyrate and flavin adenine dinucleotide on the platelet aggregation induced by hydrogen peroxide.Tohoku J Exp Med 1978;124:323-9.

89 - Ralevic V, Hoyle CH, Burnstock G. Pivotal role of phosphate chain length in vasoconstrictor versus vasodilator actions of adenine dinucleotides in rat mesenteric arteries.J Physiol 1995;15;483:703-13.

90 - Stamler J, Slivka A. Biological Chemistry of thiols in the vasculature-related diseases. Nutr Rev 1996;54:1-30.

91 - Moat SJ, Bonham JR, Powers HJ. Role of aminothiols as a component of the plasma antioxidant system and relevance to homocysteine-mediated vascular disease. Clin Sci (Lond) 2001;100:73-9.

92 - Pullin CH, Wilson JF, Ashfield-Watt PA, Clark ZE, Whiting JM, Lewis MJ, McDowell IF. Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals. Clin Sci (Lond) 2002;10245-50.

93 - Krajcovica-Kudlackova M, Blaziek P. Nutritional determinants of homocysteinemia. Cas Lek Cesk 2002;141:417-20.

94 - Lang D, Kredan MB, Moat Sj, Hussain SA, Powell CA, Bellamy MF, Powers HJ, Lewis MJ. Homocysteine-induced inhibition of endothelium-dependent relaxation in rabit aorta: role for superoxide anions. Arteroscler Thromb Vasc Biol 2000;20:422-7.

95 - Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001;73:613-21.

96 - Vollset Stein Emil, Refsum Helga, Tverdal Aage et al. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study Am J Clin Nutr 2001;74:130-6.

97 - De Bree A, WM Monique, Blom H, Kromhout D. Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y. Am J Clin Nutr 2001; 73:1027-33.

98 - McKinley MC, McNultry H, McPartlin J, Strain JJ, Scoot JM. Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status. Eur J Clin Nutr 2002;56,850-6.

99 - Madigan Sm, Tracey F, McNulty H et al. Dietary intake and status of riboflavin and vitamin B-6 and biochemical response to riboflavin supplementation in free-living elderly people. Am J Clin Nutr 1998;68:389-95.

100 - Webster RP, Gawde MD, Bhattacharya. Modulation of carcinogen-induced DNA damage and repair enzyme activity by dietary riboflavin. Cancer Lett 1996;98:129.

101 - Rivlin RS. 1973. Riboflavin and cancer: a review.Cancer Res 1973;33:1997.

 

Correspondência:

Dr. Nélson Tavares

Faculdade de Nutrição e Alimentação da Universidade do Porto

Rua Dr. Roberto Frias

4200-465 Porto

e-mail: nelsontavares@natiris.pt

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