1932

Abstract

Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential, and metabolic interactions with other micronutrients, including iron, vitamin B, and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and severe anemia with erythroid hypoplasia. Subclinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the life cycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review considers the available evidence on causes, detection, and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health, and policy priorities.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-061121-084407
2023-08-21
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/nutr/43/1/annurev-nutr-061121-084407.html?itemId=/content/journals/10.1146/annurev-nutr-061121-084407&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Alam MM, Iqbal S, Naseem I. 2015. Ameliorative effect of riboflavin on hyperglycemia, oxidative stress and DNA damage in type-2 diabetic mice: mechanistic and therapeutic strategies. Arch. Biochem. Biophys. 584:10–19
    [Google Scholar]
  2. 2.
    Al-Harbi NO, Imam F, Nadeem A, Al-Harbi MM, Iqbal M, Ahmad SF. 2014. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin. Int. Immunopharmacol. 21:2383–88
    [Google Scholar]
  3. 3.
    Alhazza IM, Hassan I, Ebaid H, Al-Tamimi J, Alwasel SH. 2020. Chemopreventive effect of riboflavin on the potassium bromate-induced renal toxicity in vivo. Naunyn Schmiedebergs Arch. Pharmacol. 393:122355–64
    [Google Scholar]
  4. 4.
    Aljaadi AM, How RE, Loh SP, Hunt SE, Karakochuk CD et al. 2019. Suboptimal biochemical riboflavin status is associated with lower hemoglobin and higher rates of anemia in a sample of Canadian and Malaysian women of reproductive age. J. Nutr. 149:111952–59
    [Google Scholar]
  5. 5.
    Aljaadi AM, Wiedeman AM, Barr SI, Devlin AM, Green TJ. 2021. Dietary riboflavin intake and riboflavin status in young adult women living in metro Vancouver, Canada. Curr. Dev. Nutr. 5:4nzab021
    [Google Scholar]
  6. 6.
    Apeland T, Mansoor MA, Pentieva K, McNulty H, Strandjord RE. 2003. Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin. Chem. 49:61005–8
    [Google Scholar]
  7. 7.
    Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF et al. 2015. Biomarkers of nutrition for development—folate review. J. Nutr. 145:1636S–80S
    [Google Scholar]
  8. 8.
    Bamji MS. 1969. Glutathione reductase activity in red blood cells and riboflavin nutritional status in humans. Clin. Chim. Acta 26:2263–69
    [Google Scholar]
  9. 9.
    Barile M, Brizio C, Valenti D, de Virgilio C, Passarella S. 2000. The riboflavin/FAD cycle in rat liver mitochondria. Eur. J. Biochem. 267:154888–900
    [Google Scholar]
  10. 10.
    Bates B, Lennox A, Prentice A, Bates C, Page P et al., eds. 2014. National Diet and Nutrition Survey Results from Years 1, 2, 3 and 4 (Combined) of the Rolling Programme (2008/2009–2011/2012) London: Public Health Engl.
  11. 11.
    Bates CJ, Evans PH, Allison G, Sonko BJ, Hoare S et al. 1994. Biochemical indices and neuromuscular function tests in rural Gambian schoolchildren given a riboflavin, or multivitamin plus iron, supplement. Br. J. Nutr. 72:4601–10
    [Google Scholar]
  12. 12.
    Bates CJ, Powers HJ. 1985. A simple fluorimetric assay for pyridoxamine phosphate oxidase in erythrocyte haemolysates: effects of riboflavin supplementation and of glucose 6-phosphate dehydrogenase deficiency. Hum. Nutr. Clin. Nutr. 39:2107–15
    [Google Scholar]
  13. 13.
    Bates CJ, Prentice A, Cole TJ, van der Pols JC, Doyle W et al. 1999. Micronutrients: highlights and research challenges from the 1994–5 National Diet and Nutrition Survey of people aged 65 years and over. Br. J. Nutr. 82:17–15
    [Google Scholar]
  14. 14.
    Bates CJ, Prentice AM, Paul AA, Prentice A, Sutcliffe BA et al. 1982. Riboflavin status in infants born in rural Gambia, and the effect of a weaning food supplement. Trans. R. Soc. Trop. Med. Hyg. 76:2253–58
    [Google Scholar]
  15. 15.
    Bates CJ, Prentice AM, Paul AA, Sutcliffe BA, Watkinson M, Whitehead RG. 1981. Riboflavin status in Gambian pregnant and lactating women and its implications for recommended dietary allowances. Am. J. Clin. Nutr. 34:5928–35
    [Google Scholar]
  16. 16.
    Ben S, Du M, Ma G, Qu J, Zhu L et al. 2019. Vitamin B2 intake reduces the risk for colorectal cancer: a dose-response analysis. Eur. J. Nutr. 58:41591–1602
    [Google Scholar]
  17. 17.
    Blanck HM, Bowman BA, Serdula MK, Khan LK, Kohn W, Woodruff BA. 2002. Angular stomatitis and riboflavin status among adolescent Bhutanese refugees living in southeastern Nepal. Am. J. Clin. Nutr. 76:2430–35
    [Google Scholar]
  18. 18.
    Böhles H. 1997. Antioxidative vitamins in prematurely and maturely born infants. Int. J. Vitam. Nutr. Res. 67:5321–28
    [Google Scholar]
  19. 19.
    Boisvert WA, Castaneda C, Mendoza I, Langeloh G, Solomons NW et al. 1993. Prevalence of riboflavin deficiency among Guatemalan elderly people and its relationship to milk intake. Am. J. Clin. Nutr. 58:185–90
    [Google Scholar]
  20. 20.
    Bou-Abdallah F, Paliakkara JJ, Melman G, Melman A. 2018. Reductive mobilization of iron from intact ferritin: mechanisms and physiological implication. Pharmaceuticals 11:4120
    [Google Scholar]
  21. 21.
    Brun TA, Chen J, Campbell TC, Boreham J, Feng Z et al. 1990. Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency. Eur. J. Clin. Nutr. 44:3195–206
    [Google Scholar]
  22. 22.
    Butler BF, Topham RW. 1993. Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. Biochem. Mol. Biol. Int. 30:53–61
    [Google Scholar]
  23. 23.
    Buzina R, Jusic M, Milanovic N, Sapunar J, Brubacher G. 1979. The effects of riboflavin administration on iron metabolism parameters in a school-going population. Int. J. Vitamin Nutr. Res. 49:2136–43
    [Google Scholar]
  24. 24.
    Can. Food Insp. Agency 2009. Prohibition against the sale of unenriched white flour and products containing unenriched flour Section B.13.001 Food and Drug Regul., Gov. Can. Ottawa, Can.:
  25. 25.
    Cardoso DR, Olsen K, Skibsted LH. 2007. Mechanism of deactivation of triplet-excited riboflavin by ascorbate, carotenoids, and tocopherols in homogeneous and heterogeneous aqueous food model systems. J. Agric. Food Chem. 55:156285–91
    [Google Scholar]
  26. 26.
    Charoenlarp P, Pholpothi T, Chatpunyaporn P, Schelp FP. 1980. The effect of riboflavin on the hematologic changes in iron supplementation of schoolchildren. Southeast Asian J. Trop. Med. Public Health 11:197–103
    [Google Scholar]
  27. 27.
    Cimino JA, Jhangiani S, Schwartz E, Cooperman JM. 1987. Riboflavin metabolism in the hypothyroid human adult. Proc. Soc. Exp. Biol. Med. 184:2151–53
    [Google Scholar]
  28. 28.
    Dainty JR, Bullock NR, Hart DJ, Hewson AT, Turner R et al. 2007. Quantification of the bioavailability of riboflavin from foods by use of stable-isotope labels and kinetic modeling. Am. J. Clin. Nutr. 85:61557–64
    [Google Scholar]
  29. 29.
    Das B, Das D, Satpathy R, Patnaik J, Bose TK. 1988. Riboflavin deficiency and severity of malaria. Eur. J. Clin. Nutr. 42:277–83
    [Google Scholar]
  30. 30.
    Decker K, Doris B, Glatzle D, Hinselmann M. 1977. Riboflavin status and anaemia in pregnant women. Ann. Nutr. Metab. 21:17–19
    [Google Scholar]
  31. 31.
    Dutta P, Pinto J, Rivlin R. 1985. Antimalarial effects of riboflavin deficiency. Lancet 2:84631040–43
    [Google Scholar]
  32. 32.
    EFSA Panel Dietet. Prod. Nutr. and Allerg 2017. Scientific opinion on dietary reference values for riboflavin. EFSA J. 15:8e04919
    [Google Scholar]
  33. 33.
    Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD et al. 2011. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478:7367103–9
    [Google Scholar]
  34. 34.
    Fairweather-Tait SJ, Powers HJ, Minski MJ, Whitehead J, Downese R. 1992. Riboflavin deficiency and iron absorption in adult Gambian men. Ann. Nutr. Metab. 36:134–40
    [Google Scholar]
  35. 35.
    Fass S, Rivlin RS. 1969. Regulation of riboflavin-metabolizing enzymes in riboflavin deficiency. Am. J. Physiol. 217:4988–91
    [Google Scholar]
  36. 36.
    Food Nutrit. Board, Inst. Med 2000. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Washington, DC: National Academies Press
  37. 37.
    Fox A, McHugh S, Browne J, Kenny LC, Fitzgerald A et al. 2017. Estimating the cost of preeclampsia in the healthcare system: cross-sectional study using data from SCOPE study (Screening for Pregnancy End Points). Hypertension 70:61243–49
    [Google Scholar]
  38. 38.
    Giancaspero TA, Busco G, Panebianco C, Carmone C, Miccolis A et al. 2013. FAD synthesis and degradation in the nucleus create a local flavin cofactor pool. J. Biol. Chem. 288:4029069–80
    [Google Scholar]
  39. 39.
    Goldenberg RL, Culhane JF, Iams JD, Romero R. 2008. Epidemiology and causes of preterm birth. Lancet 371:960675–84
    [Google Scholar]
  40. 40.
    Graham JM, Peerson JM, Haskell MJ, Shrestha RK, Brown KH, Allen LH. 2005. Erythrocyte riboflavin for the detection of riboflavin deficiency in pregnant Nepali women. Clin. Chem. 51:112162–65
    [Google Scholar]
  41. 41.
    Health Can 2004. Canadian Community Health Survey, Cycle 2.2, Nutrition—Nutrient Intakes from Food, Provincial, Regional and National Summary Data Tables, Vol. 2 Gov. Can. Ottawa, Can.:
  42. 42.
    Hoey L, McNulty H, Askin N, Dunne A, Ward M et al. 2007. Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults. Am. J. Clin. Nutr. 86:51405–13
    [Google Scholar]
  43. 43.
    Hoey L, McNulty H, Strain JJ. 2009. Studies of biomarker responses to intervention with riboflavin: a systematic review. Am. J. Clin. Nutr. 89:61960S–80S
    [Google Scholar]
  44. 44.
    Horigan G, McNulty H, Ward M, Strain J, Purvis J, Scott JM. 2010. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C→T polymorphism in MTHFR. J. Hypertens. 28:3478–86
    [Google Scholar]
  45. 45.
    Hsu DS, Zhao X, Zhao S, Kazantsev A, Wang RP et al. 1996. Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins. Biochemistry 35:4413871–77
    [Google Scholar]
  46. 46.
    Huang R, Choe E, Min DB. 2004. Kinetics for singlet oxygen formation by riboflavin photosensitization and the reaction between riboflavin and singlet oxygen. J. Food Sci. 69:9C726–32
    [Google Scholar]
  47. 47.
    Huang S-N, Swaan PW. 2001. Riboflavin uptake in human trophoblast-derived BeWo cell monolayers: cellular translocation and regulatory mechanisms. J. Pharmacol. Exp. Ther. 298:1264–71
    [Google Scholar]
  48. 48.
    Hustad S, McKinley MC, McNulty H, Schneede J, Strain JJ et al. 2002. Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation. Clin. Chem. 48:91571–77
    [Google Scholar]
  49. 49.
    Huvaere K, Olsen K, Skibsted LH. 2009. Quenching of triplet-excited flavins by flavonoids: structural assessment of antioxidative activity. J. Org. Chem. 74:197283–93
    [Google Scholar]
  50. 50.
    Inst. Med 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Washington, DC: National Academies Press
  51. 51.
    Jaeger B, Corpeleijn W, Dijsselhof M, Goorden S, Haverkamp J et al. 2022. Mind the B2: life-threatening neonatal complications of a strict vegan diet during pregnancy. Neonatology 119:6777–80
    [Google Scholar]
  52. 52.
    Jarrett H, McNulty H, Hughes CF, Pentieva K, Strain JJ et al. 2022. Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18–102 years. Am. J. Clin. Nutr. 116:61767–78
    [Google Scholar]
  53. 53.
    Jiang W-D, Chen L, Liu Y, Feng L, Wu P et al. 2019. Impact and consequences of dietary riboflavin deficiency treatment on flesh quality loss in on-growing grass carp (Ctenopharyngodon idella). Food Funct. 10:63396–409
    [Google Scholar]
  54. 54.
    Jungert A, McNulty H, Hoey L, Ward M, Strain JJ et al. 2020. Riboflavin is an important determinant of vitamin B-6 status in healthy adults. J. Nutr. 150:102699–706
    [Google Scholar]
  55. 55.
    Karakochuk CD, Barker MK, Whitfield KC, Barr SI, Vercauteren SM et al. 2017. The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial. Am. J. Clin. Nutr. 106:233–77
    [Google Scholar]
  56. 56.
    Kehoe L, Walton J, Hopkins SM, McNulty BA, Nugent AP et al. 2018. Intake, status and dietary sources of riboflavin in a representative sample of Irish adults aged 18–90 years. Proc. Nutr. Soc. 77:OCE3E66
    [Google Scholar]
  57. 57.
    Kerr MA, Livingstone B, Bates CJ, Bradbury I, Scott JM et al. 2009. Folate, related B vitamins, and homocysteine in childhood and adolescence: potential implications for disease risk in later life. Pediatrics 123:2627–35
    [Google Scholar]
  58. 58.
    Khan S, Rayis MP, Rizvi A, Alam MM, Rizvi M, Naseem I. 2019. ROS mediated antibacterial activity of photoilluminated riboflavin: a photodynamic mechanism against nosocomial infections. Toxicol Rep. 6:136–42
    [Google Scholar]
  59. 59.
    Khaydukov EV, Mironova KE, Semchishen VA, Generalova AN, Nechaev AV et al. 2016. Riboflavin photoactivation by upconversion nanoparticles for cancer treatment. Sci. Rep. 6:35103
    [Google Scholar]
  60. 60.
    Kutta RJ, Archipowa N, Johannissen LO, Jones AR, Scrutton NS. 2017. Vertebrate cryptochromes are vestigial flavoproteins. Sci. Rep. 7:44906
    [Google Scholar]
  61. 61.
    Lee SS, McCormick DB. 1985. Thyroid hormone regulation of flavocoenzyme biosynthesis. Arch. Biochem. Biophys. 237:1197–201
    [Google Scholar]
  62. 62.
    Lienhart WD, Gudipati V, MacHeroux P. 2013. The human flavoproteome. Arch. Biochem. Biophys. 535:2150–62
    [Google Scholar]
  63. 63.
    Ma AG, Schouten EG, Zhang FZ, Kok FJ, Yang F et al. 2008. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic acid supplements. J. Nutr. 138:101946–50
    [Google Scholar]
  64. 64.
    MacHeroux P, Kappes B, Ealick SE. 2011. Flavogenomics: a genomic and structural view of flavin-dependent proteins. FEBS J. 278:152625–34
    [Google Scholar]
  65. 65.
    Madigan SM, Tracey F, McNulty H, Eaton-Evans J, Coulter J et al. 1998. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people. Am. J. Clin. Nutr. 68:2389–95
    [Google Scholar]
  66. 66.
    Martínez-Limón A, Alriquet M, Lang WH, Calloni G, Wittig I, Vabulas RM. 2016. Recognition of enzymes lacking bound cofactor by protein quality control. PNAS 113:4312156–61
    [Google Scholar]
  67. 67.
    McCormick D 1994. Riboflavin. Modern Nutrition in Health and Disease M Shils, J Olsen, M Shike 366–75 Philadelphia: Lea & Febiger. , 8th ed..
    [Google Scholar]
  68. 68.
    McCormick D, Greene H 1994. Vitamins. Tietz Textbook of Clinical Chemistry C Burtis, E Ashwood Philadelphia: Saunders
    [Google Scholar]
  69. 69.
    McNulty H, Dowey LRC, Strain JJ, Dunne A, Ward M et al. 2006. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C→T polymorphism. Circulation 113:174–80
    [Google Scholar]
  70. 70.
    McNulty H, Strain JJ, Hughes CF, Pentieva K, Ward M. 2020. Evidence of a role for one-carbon metabolism in blood pressure: Can B vitamin intervention address the genetic risk of hypertension owing to a common folate polymorphism?. Curr. Dev. Nutr. 4:1nzz102
    [Google Scholar]
  71. 71.
    McNulty H, Strain JJ, Hughes CF, Ward M. 2017. Riboflavin, MTHFR genotype and blood pressure: a personalized approach to prevention and treatment of hypertension. Mol. Aspects Med. 53:2–9
    [Google Scholar]
  72. 72.
    McNulty H, Ward M, Hoey L, Hughes CF, Pentieva K. 2019. Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges. Proc. Nutr. Soc. 78:3449–62
    [Google Scholar]
  73. 73.
    Merrill AH, Henderson JM, Wang E, McDonald BW, Millikan WJ. 1984. Metabolism of vitamin B-6 by human liver. J. Nutr. 114:91664–74
    [Google Scholar]
  74. 74.
    Merrill AH, Lambeth JD, Edmondson DE, McCormick DB. 1981. Formation and mode of action of flavoproteins. Annu. Rev. Nutr. 1:281–317
    [Google Scholar]
  75. 75.
    Natl. Inst. Health Care Excell. (NICE) 2019. Hypertension in pregnancy: diagnosis and management NICE Guidel. 133 NICE London:
  76. 76.
    Northrop-Clewes CA, Thurnham DI. 2012. The discovery and characterization of riboflavin. Ann. Nutr. Metab. 61:3224–30
    [Google Scholar]
  77. 77.
    Olfat N, Ashoori M, Saedisomeolia A. 2022. Riboflavin is an antioxidant: a review update. Br. J. Nutr. 128:101887–95
    [Google Scholar]
  78. 78.
    Olpin SE, Bates CJ. 1982. Lipid metabolism in riboflavin-deficient rats II. Mitochondrial fatty acid oxidation and the microsomal desaturation pathway. Br. J. Nutr. 47:3589–96
    [Google Scholar]
  79. 79.
    Pentieva K. 2021. Riboflavin. Principles of Nutritional Assessment R Gibson New York: Oxford University Press. , 3rd ed. https://nutritionalassessment.org/riboflavin/
    [Google Scholar]
  80. 80.
    Pinto J, Huang YP, Pelliccione N, Rivlin RS. 1982. Cardiac sensitivity to the inhibitory effects of chlorpromazine, imipramine and amitriptyline upon formation of flavins. Biochem. Pharmacol. 31:213495–99
    [Google Scholar]
  81. 81.
    Pinto J, Huang YP, Rivlin RS. 1987. Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide. J. Clin. Investig. 79:51343–48
    [Google Scholar]
  82. 82.
    Pinto J, Rivlin RS. 1979. Regulation of formation of covalently bound flavins in liver and cerebrum by thyroid hormones. Arch. Biochem. Biophys. 194:2313–20
    [Google Scholar]
  83. 83.
    Powers HJ. 1986. Investigation into the relative effects of riboflavin deprivation on iron economy in the weanling rat and the adult. Ann. Nutr. Metab. 30:5308–15
    [Google Scholar]
  84. 84.
    Powers HJ. 1999. Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc. Nutr. Soc. 58:2435–40
    [Google Scholar]
  85. 85.
    Powers HJ. 2003. Riboflavin (vitamin B-2) and health. Am. J. Clin. Nutr. 77:61352–60
    [Google Scholar]
  86. 86.
    Powers HJ, Bates CJ, Lamb WH. 1985. Haematological response to supplements of iron and riboflavin to pregnant and lactating women in rural Gambia. Hum. Nutr. Clin. Nutr. 39:2117–29
    [Google Scholar]
  87. 87.
    Powers HJ, Hill MH, Mushtaq S, Dainty JR, Majsak-Newman G, Williams EA. 2011. Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). Am. J. Clin. Nutr. 93:61274–84
    [Google Scholar]
  88. 88.
    Powers HJ, Weaver LT, Austin S, Wright AJA, Fairweather-Tait SJ. 1991. Riboflavin deficiency in the rat: effects on iron utilization and loss. Br. J. Nutr. 65:3487–96
    [Google Scholar]
  89. 89.
    Powers HJ, Wright AJA, Fairweather-Tait SJ. 1988. The effect of riboflavin deficiency in rats on the absorption and distribution of iron. Br. J. Nutr. 59:3381–87
    [Google Scholar]
  90. 90.
    Psara E, Pentieva K, Ward M, McNulty H. 2020. Critical review of nutrition, blood pressure and risk of hypertension through the lifecycle: Do B vitamins play a role?. Biochimie 173:76–90
    [Google Scholar]
  91. 91.
    Public Health Engl 2016. National Diet and Nutrition Survey. Results from Years 5 and 6 (Combined) of the Rolling Programme (2012/2013–2013/14) London: Public Health Engl.
  92. 92.
    Qian X, Lu Z, Tan M, Liu H, Lu D. 2007. A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension. Eur. J. Hum. Genet. 15:121239–45
    [Google Scholar]
  93. 93.
    Rivlin RS. 1970. Medical progress: riboflavin metabolism. New Engl. J. Med. 283:9463–72
    [Google Scholar]
  94. 94.
    Rivlin RS 1991. Disorders of vitamin metabolism: deficiencies, metabolic abnormalities and excesses. Cecil Textbook of Medicine JH Wyngaarden, LH Smith Jr., JC Bennett, F Plum 1170 Philadelphia: W.B. Saunders. , 19th ed..
    [Google Scholar]
  95. 95.
    Rivlin RS 2007. Riboflavin. Handbook of Vitamins J Zempleni, R Rucker, D McCormick, J Suttie 233–52. Boca Raton, FL: CRC Press. , 4th ed..
    [Google Scholar]
  96. 96.
    Rohner F, Zimmermann MB, Wegmueller R, Tschannen AB, Hurrell RF. 2007. Mild riboflavin deficiency is highly prevalent in school-age children but does not increase risk for anaemia in Côte d'Ivoire. Br. J. Nutr. 97:5970–76
    [Google Scholar]
  97. 97.
    Ross NS, Hansen TP. 1992. Riboflavin deficiency is associated with selective preservation of critical flavoenzyme-dependent metabolic pathways. Biofactors 3:3185–90
    [Google Scholar]
  98. 98.
    Santhiago MR, Randleman JB. 2021. The biology of corneal cross-linking derived from ultraviolet light and riboflavin. Exp. Eye Res. 202:108355
    [Google Scholar]
  99. 99.
    Sauberlich H. 1999. Laboratory Tests for the Assessment of Nutritional Status Boca Raton, FL: CRC Press. , 2nd ed..
  100. 100.
    Sauberlich H, Skala J, Dowdy R. 1974. Laboratory Tests for the Assessment of Nutritional Status Boca Raton, FL: CRC Press
  101. 101.
    Sauberlich HE. 1985. Bioavailability of vitamins. Prog. Food Nutr. Sci. 9:1–21–33
    [Google Scholar]
  102. 102.
    Seely EW, Ecker J. 2014. Chronic hypertension in pregnancy. Circulation 129:111254–61
    [Google Scholar]
  103. 103.
    Shi Z, Zhen S, Wittert GA, Yuan B, Zuo H, Taylor AW. 2014. Inadequate riboflavin intake and anemia risk in a Chinese population: five-year follow up of the Jiangsu nutrition study. PLOS ONE 9:2e88862
    [Google Scholar]
  104. 104.
    Sirivech S, Frieden E, Osaki S. 1974. The release of iron from horse spleen ferritin by reduced flavins. Biochem. J. 143:2311–15
    [Google Scholar]
  105. 105.
    Sisson TRC. 1987. Photodegradation of riboflavin in neonates. Fed. Proc. 46:51883–85
    [Google Scholar]
  106. 106.
    Slattery MM, Geary M, Morrison JJ. 2008. Obstetric antecedents for preterm delivery. J. Perinat. Med. 36:4306–9
    [Google Scholar]
  107. 107.
    Stevens W, Shih T, Incerti D, Ton TGN, Lee HC et al. 2017. Short-term costs of preeclampsia to the United States health care system. Am. J. Obstet. Gynecol. 217:3237–48.e16
    [Google Scholar]
  108. 108.
    Subramanian VS, Subramanya SB, Ghosal A, Said HM. 2013. Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport. Am. J. Physiol. Cell Physiol. 305:5C539–46
    [Google Scholar]
  109. 109.
    Suprapto B, Widardo Suhanantyo 2002. Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women. Asia Pac. J. Clin. Nutr. 11:4263–67
    [Google Scholar]
  110. 110.
    US Food Drug Admin. (FDA) 2019. Nutritional quality guidelines for foods: subpart B—fortification policy 21CFR104.20. FDA Silver Spring, MD:
  111. 111.
    van Vranken JG, Na U, Winge DR, Rutter J 2015. Protein-mediated assembly of succinate dehydrogenase and its cofactors. Crit. Rev. Biochem. Mol. Biol. 50:2168–80
    [Google Scholar]
  112. 112.
    Walton J 2011. National Adult Nutrition Survey (NANS) 2008–2010. Summary Report Irish Univ. Nutr Alliance, Cork/Dublin, Ireland:
  113. 113.
    Wang J, Guo G, Li A, Cai W-Q, Wang X. 2021. Challenges of phototherapy for neonatal hyperbilirubinemia. Exp. Ther/Med. 21:3231
    [Google Scholar]
  114. 114.
    Ward M, Hughes CF, Strain JJ, Reilly R, Cunningham C et al. 2020. Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 18:318
    [Google Scholar]
  115. 115.
    Waterstone M, Bewley S, Wolfe C. 2001. Incidence and predictors of severe obstetric morbidity: case-control study. BMJ 322:72941089–93
    [Google Scholar]
  116. 116.
    Whitfield KC, Karakochuk CD, Liu Y, McCann A, Talukder A et al. 2015. Poor thiamin and riboflavin status is common among women of childbearing age in rural and urban Cambodia. J. Nutr. 145:3628–33
    [Google Scholar]
  117. 117.
    Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A et al. 2003. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J. Med. Genet. 40:8619–25
    [Google Scholar]
  118. 118.
    Wilson CP, McNulty H, Ward M, Strain JJ, Trouton TG et al. 2013. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial. Hypertension 61:61302–8
    [Google Scholar]
  119. 119.
    Wolf G. 2002. Three vitamins are involved in regulation of the circadian rhythm. Nutr. Rev. 60:8257–60
    [Google Scholar]
  120. 120.
    Wolthers KR, Scrutton NS. 2009. Cobalamin uptake and reactivation occurs through specific protein interactions in the methionine synthase-methionine synthase reductase complex. FEBS J. 276:71942–51
    [Google Scholar]
  121. 121.
    Yamada K, Chen Z, Rozen R, Matthews RG. 2001. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. PNAS 98:2614853–58
    [Google Scholar]
  122. 122.
    Yamada Y, Merrill AH, McCormick DB. 1990. Probable reaction mechanisms of flavokinase and FAD synthetase from rat liver. Arch. Biochem. Biophys. 278:1125–30
    [Google Scholar]
  123. 123.
    Yang KM, Jia J, Mao L-NN, Men C, Tang K-TT et al. 2014. Methylenetetrahydrofolate reductase C677T gene polymorphism and essential hypertension: a metaanalysis of 10,415 subjects. Biomed. Rep. 2:5699–708
    [Google Scholar]
  124. 124.
    Yoon YS, Jung S, Zhang X, Ogino S, Giovannucci EL, Cho E. 2016. Vitamin B2 intake and colorectal cancer risk: results from the Nurses’ Health Study and the Health Professionals Follow-Up Study cohort. Int. J. Cancer. 139:5996–1008
    [Google Scholar]
  125. 125.
    Yu L, Tan Y, Zhu L. 2017. Dietary vitamin B2 intake and breast cancer risk: a systematic review and meta-analysis. Arch. Gynecol. Obstet. 295:3721–29
    [Google Scholar]
  126. 126.
    Zempleni J, Galloway JR, McCormick DB. 1996. Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. Am. J. Clin. Nutr. 63:154–66
    [Google Scholar]
  127. 127.
    Zeng J, Gu Y, Fu H, Liu C, Zou Y, Chang H. 2020. Association between one-carbon metabolism-related vitamins and risk of breast cancer: a systematic review and meta-analysis of prospective studies. Clin. Breast Cancer 20:4e469–80
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-061121-084407
Loading
/content/journals/10.1146/annurev-nutr-061121-084407
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error