Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

Gianluca Rizzo, Antonio Simone Laganà, Agnese Maria Chiara Rapisarda, Gioacchina Maria Grazia La Ferrera, Massimo Buscema, Paola Rossetti, Angela Nigro, Vincenzo Muscia, Gaetano Valenti, Fabrizio Sapia, Giuseppe Sarpietro, Micol Zigarelli, Salvatore Giovanni Vitale, Gianluca Rizzo, Antonio Simone Laganà, Agnese Maria Chiara Rapisarda, Gioacchina Maria Grazia La Ferrera, Massimo Buscema, Paola Rossetti, Angela Nigro, Vincenzo Muscia, Gaetano Valenti, Fabrizio Sapia, Giuseppe Sarpietro, Micol Zigarelli, Salvatore Giovanni Vitale

Abstract

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

Keywords: cardiovascular disease; cobalamin; deficiency; diagnostic markers; food sources; neurological symptoms; supplements; vegan; vegetarian; vitamin B12.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. EURISPES 2016. [(accessed on 28 July 2016)]. Available online: .
    1. Larsson C.L., Johansson G.K. Dietary intake and nutritional status of young vegans and omnivores in Sweden. Am. J. Clin. Nutr. 2002;76:100–106.
    1. World Health Organization . Global Status Report on Non Communicable Diseases 2014. WHO; Geneva, Switzerland: 2014.
    1. Ferdowsian H.R., Barnard N.D. Effects of plant-based diets on plasma lipids. Am. J. Cardiol. 2009;104:947–956. doi: 10.1016/j.amjcard.2009.05.032.
    1. Pettersen B.J., Anousheh R., Fan J., Jaceldo-Siegl K., Fraser G.E. Vegetarian diets and blood pressure among white subjects: Results from the Adventist Health Study-2 (AHS-2) Public Health Nutr. 2012;15:1909–1916. doi: 10.1017/S1368980011003454.
    1. Barnard N.D., Katcher H.I., Jenkins D.J., Cohen J., Turner-McGrievy G. Vegetarian and vegan diets in type 2 diabetes management. Nutr. Rev. 2009;67:255–263. doi: 10.1111/j.1753-4887.2009.00198.x.
    1. Tonstad S., Butler T., Yan R., Fraser G.E. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009;32:791–796. doi: 10.2337/dc08-1886.
    1. Waldmann A., Koschizke J.W., Leitzmann C., Hahn A. German vegan study: Diet, life-style factors, and cardiovascular risk profile. Ann. Nutr. Metab. 2005;49:366–372. doi: 10.1159/000088888.
    1. Key T.J., Appleby P.N., Davey G.K., Allen N.E., Spencer E.A., Travis R.C. Mortality in British vegetarians: Review and preliminary results from EPIC-Oxford. Am. J. Clin. Nutr. 2003;78:S533–S538.
    1. Key T.J., Fraser G.E., Thorogood M., Appleby P.N., Bera V., Reeves G., Burr M.L., Chang-Claude J., Frentzel-Beyme R., Kuzma J.W., et al. Mortality in vegetarians and nonvegetarians: Detailed findings from a collaborative analysis of 5 prospective studies. Am. J. Clin. Nutr. 1999;70:S516–S524.
    1. U.S. Department of Agriculture. U.S. Department of Health and Human Services . Dietary Guidelines for Americans 2010. 7th ed. U.S. Government Printing Office; Washington, DC, USA: 2010.
    1. American Dietetic Association Position of the American Dietetic Association: Vegetarian diets. J. Am. Diet. Assoc. 1988;88:351.
    1. Craig W.J., Mangels A.R., American Dietetic Association Position of the American Dietetic Association: Vegetarian diets. J. Am. Diet. Assoc. 2009;109:1266–1282.
    1. Allen L.H. Causes of vitamin B12 and folate deficiency. Food Nutr. Bull. 2008;29:S20–S37. doi: 10.1177/15648265080292S105.
    1. O’Leary F., Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2:299–316. doi: 10.3390/nu2030299.
    1. Stollhoff K., Schulte F.J. Vitamin B12 and brain development. Eur. J. Pediatr. 1987;146:201–205. doi: 10.1007/BF02343237.
    1. Li D. Chemistry behind Vegetarianism. J. Agric. Food Chem. 2011;59:777–784. doi: 10.1021/jf103846u.
    1. Herrmann W., Schorr H., Obeid R., Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am. J. Clin. Nutr. 2003;78:131–136.
    1. Otten J.J., Hellwig J.P., Meyers L.D. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Institute of Medicine of the National Academies; Washington, DC, USA: 2006.
    1. Società Italiana di Nutrizione Umana . LARN: Livelli di Assunzione di Riferimento di Nutrienti ed Energia per la Popolazione Italiana. Società Italiana di Nutrizione Umana; Milano, Italy: 2014.
    1. U.S. Department of Agriculture. Agricultural Research Service. Beltsville Human Nutrition Research Center. Food Surveys Research Group. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for Health Statistics What We Eat in America, NHANES 2009–2010. Nutrient Intakes from Food: Mean Amounts Consumed per Individual, by Gender and Age, in United States, 2009–2010. [(accessed on 28 July 2016)]; Available online: .
    1. Obeid R., Schorr H., Eckert R., Herrmann W. Vitamin B12 status in the elderly as judged by available biochemical markers. Clin. Chem. 2004;50:238–241. doi: 10.1373/clinchem.2003.021717.
    1. Yetley E.A., Pfeiffer C.M., Phinney K.W., Bailey R.L., Blackmore S., Bock J.L., Brody L.C., Carmel R., Curtin L.R., Durazo-Arvizu R.A., et al. Biomarkers of vitamin B-12 status in NHANES: A roundtable summary. Am. J. Clin. Nutr. 2011;94:S313–S321. doi: 10.3945/ajcn.111.013243.
    1. Panel on Dietetic Products, Nutrition, and Allergies Scientific opinion on dietary reference values for cobalamin (Vitamin B12) EFSA J. 2015;13:4150.
    1. Institute of Medicine . A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board. National Academy; Washington, DC, USA: 1998.
    1. Watanabe F. Vitamin B12 sources and bioavailability. Exp. Biol. Med. 2007;232:1266–1274. doi: 10.3181/0703-MR-67.
    1. Bor M.V., Lydeking-Olsen E., Møller J., Nexø E. A daily intake of approximately 6 microg vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am. J. Clin. Nutr. 2006;83:52–58.
    1. Andrès E., Kurtz J.E., Perrin A.E., Maloisel F., Demangeat C., Goichot B., Schlienger J.L. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Am. J. Med. 2001;111:126–129. doi: 10.1016/S0002-9343(01)00792-6.
    1. Peters R., Burch L., Warner J., Beckett N., Poulter R., Bulpitt C. Haemoglobin, anaemia, dementia and cognitive decline in the elderly, a systematic review. BMC Geriatr. 2008;8:18. doi: 10.1186/1471-2318-8-18.
    1. Watanabe F., Yabuta Y., Tanioka Y., Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J. Agric. Food Chem. 2013;61:6769–6775. doi: 10.1021/jf401545z.
    1. Watanabe F., Yabuta Y., Bito T., Teng F. Vitamin B12-containing plant food sources for vegetarians. Nutrients. 2014;6:1861–1873. doi: 10.3390/nu6051861.
    1. Herbert V. Vitamin B-12: Plant sources, requirements, and assay. Am. J. Clin. Nutr. 1988;48:852–858.
    1. Watanabe F., Abe K., Takenaka S., Tamura Y., Maruyama I., Nakano Y. Occurrence of cobalamin coenzymes in the photosynthetic green alga, Chlorella vulgaris. Biosci. Biotechnol. Biochem. 1997;61:896–897. doi: 10.1271/bbb.61.896.
    1. Smith E.L. Purification of anti-pernicious anaemia factors from liver. Nature. 1948;161:638. doi: 10.1038/161638a0.
    1. Randaccio L., Geremia S., Demitri N., Wuerges J. Vitamin B12: Unique metalorganic compounds and the most complex vitamins. Molecules. 2010;15:3228–3259. doi: 10.3390/molecules15053228.
    1. Quadros E.V. Advances in the understanding of cobalamin assimilation and metabolism. Br. J. Haematol. 2010;148:195–204. doi: 10.1111/j.1365-2141.2009.07937.x.
    1. Gherasim C., Lofgren M., Banerjee R. Navigating the B(12) road: Assimilation, delivery, and disorders of cobalamin. J. Biol. Chem. 2013;288:13186–13193. doi: 10.1074/jbc.R113.458810.
    1. Cooper B.A., Rosenblatt D.S. Inherited defects of vitamin B12 metabolism. Annu. Rev. Nutr. 1987;7:291–320. doi: 10.1146/annurev.nu.07.070187.001451.
    1. Fenton W.A., Hack A.M., Willard H.F., Gertler A., Rosenberg L.E. Purification and properties of methylmalonyl coenzyme A mutase from human liver. Arch. Biochem. Biophys. 1982;214:815–823. doi: 10.1016/0003-9861(82)90088-1.
    1. Marsh E.N., Meléndez G.D. Adenosylcobalamin enzymes: Theory and experiment begin to converge. Biochim. Biophys. Acta. 2012;1824:1154–1164. doi: 10.1016/j.bbapap.2012.03.012.
    1. Scalabrino G., Carpo M., Bamonti F., Pizzinelli S., D’Avino C., Bresolin N., Meucci G., Martinelli V., Comi G.C., Peracchi M. High tumor necrosis factor-α in levels in cerebrospinal fluid of cobalamin-deficient patients. Ann. Neurol. 2004;56:886–890. doi: 10.1002/ana.20325.
    1. Lipton S.A., Kim W.K., Choi Y.B., Kumar S., D’Emilia D.M., Rayudu P.V., Arnelle D.R., Stamler J.S. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proc. Natl. Acad. Sci. USA. 1997;94:5923–5928. doi: 10.1073/pnas.94.11.5923.
    1. Hodgkin D.C., Kamper J., Mackay M., Pickworth J., Trueblood K.N., White J.G. Structure of vitamin B12. Nature. 1956;178:64–66. doi: 10.1038/178064a0.
    1. Chaouali N., Gana I., Dorra A., Khelifi F., Nouioui A., Masri W., Belwaer I., Ghorbel H., Hedhili A. Potential Toxic Levels of Cyanide in Almonds (Prunus amygdalus), Apricot Kernels (Prunus armeniaca), and Almond Syrup. ISRN Toxicol. 2013;2013:610648. doi: 10.1155/2013/610648.
    1. Obeid R., Fedosov S.N., Nexo E. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Mol. Nutr. Food Res. 2015;59:1364–1372. doi: 10.1002/mnfr.201500019.
    1. Banerjee R. B12 trafficking in mammals: A for coenzyme escort service. ACS Chem. Biol. 2006;1:149–159. doi: 10.1021/cb6001174.
    1. Hannibal L., Kim J., Brasch N.E., Wang S., Rosenblatt D.S., Banerjee R., Jacobsen D.W. Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Mol. Genet. Metab. 2009;97:260–266. doi: 10.1016/j.ymgme.2009.04.005.
    1. Gimsing P., Hippe E., Helleberg-Rasmussen I., Moesgaard M., Nielsen J.L., Bastrup-Madsen P., Berlin R., Hansen T. Cobalamin forms in plasma and tissue during treatment of vitamin B12 deficiency. Scand. J. Haematol. 1982;29:311–318. doi: 10.1111/j.1600-0609.1982.tb00600.x.
    1. Herbert V., Sullivan L.W. Activity of Coenzyme B12 in Man. Ann. N. Y. Acad. Sci. 1964;112:855–870. doi: 10.1111/j.1749-6632.1964.tb45063.x.
    1. Adams J.F., Ross S.K., Mervyn L., Boddy K., King P. Absorption of cyanocobalamin, coenzyme B 12, methylcobalamin, and hydroxocobalamin at different dose levels. Scand. J. Gastroenterol. 1971;6:249–252. doi: 10.3109/00365527109180702.
    1. Gailus S., Höhne W., Gasnier B., Nürnberg P., Fowler B., Rutsch F. Insights into lysosomal cobalamin trafficking: Lessons learned from cblF disease. J. Mol. Med. 2010;88:459–466. doi: 10.1007/s00109-010-0601-x.
    1. Wuerges J., Geremia S., Randaccio L. Structural study on ligand specificity of human vitamin B12 transporters. Biochem. J. 2007;403:431–440. doi: 10.1042/BJ20061394.
    1. Gruber K., Puffer B., Kräutler B. Vitamin B12-derivatives-enzyme cofactors and ligands of proteins and nucleic acids. Chem. Soc. Rev. 2011;40:4346–4363. doi: 10.1039/c1cs15118e.
    1. Obersby D., Chappell D.C., Dunnett A., Tsiami A.A. Plasma total homocysteine status of vegetarians compared with omnivores: A systematic review and meta-analysis. Br. J. Nutr. 2013;109:785–794. doi: 10.1017/S000711451200520X.
    1. Mathews F.S., Gordon M.M., Chen Z., Rajashankar K.R., Ealick S.E., Alpers D.H., Sukumar N. Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-A resolution. Proc. Natl. Acad. Sci. USA. 2007;104:17311–17316. doi: 10.1073/pnas.0703228104.
    1. Muir M., Chanarin I. Separation of cobalamin analogues in human sera binding to intrinsic factor and to R-type vitamin B12 binders. Br. J. Haematol. 1983;54:613–621. doi: 10.1111/j.1365-2141.1983.tb02141.x.
    1. Fyfe J.C., Madsen M., Højrup P., Christensen E.I., Tanner S.M., de la Chapelle A., He Q., Moestrup S.K. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004;103:1573–1579. doi: 10.1182/blood-2003-08-2852.
    1. Beedholm-Ebsen R., van de Wetering K., Hardlei T., Nexø E., Borst P., Moestrup S.K. Identification of multidrug resistance protein 1 (MRP1/ABCC1) as a molecular gate for cellular export of cobalamin. Blood. 2010;115:1632–1639. doi: 10.1182/blood-2009-07-232587.
    1. Hippe E., Olesen H. Nature of vitamin B 12 binding. 3. Thermodynamics of binding to human intrinsic factor and transcobalamins. Biochim. Biophys. Acta. 1971;243:83–88. doi: 10.1016/0005-2795(71)90039-0.
    1. Quadros E.V., Rothenberg S.P., Jaffe E.A. Endothelial cells from human umbilical vein secrete functional transcobalamin II. Am. J. Physiol. 1989;256:C296–C303.
    1. Herzlich B., Herbert V. Depletion of serum holotranscobalamin II. An early sign of negative vitamin B12 balance. Lab. Investig. 1988;58:332–337.
    1. Ashwell G., Morell A. The dual role of sialic acid in the hepatic recognition and catabolism of serum glycoproteins. Biochem. Soc. Symp. 1974;40:117–124.
    1. Moestrup S.K., Birn H., Fischer P.B., Petersen C.M., Verroust P.J., Sim R.B., Christensen E.I., Nexø E. Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis. Proc. Natl. Acad. Sci. USA. 1996;93:8612–8617. doi: 10.1073/pnas.93.16.8612.
    1. Nielsen M.J., Rasmussen M.R., Andersen C.B., Nexø E., Moestrup S.K. Vitamin B12 transport from food to the body’s cells—A sophisticated, multistep pathway. Nat. Rev. Gastroenterol. Hepatol. 2012;9:345–354. doi: 10.1038/nrgastro.2012.76.
    1. Rutsch F., Gailus S., Miousse I.R., Suormala T., Sagné C., Toliat M.R., Nürnberg G., Wittkampf T., Buers I., Sharifi A., et al. Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nat. Genet. 2009;41:234–239. doi: 10.1038/ng.294.
    1. Li Z., Gherasim C., Lesniak N.A., Banerjee R. Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein. J. Biol. Chem. 2014;289:16487–16497. doi: 10.1074/jbc.M114.567339.
    1. Koutmos M., Gherasim C., Smith J.L., Banerjee R. Structural basis of multifunctionality in a vitamin B12-processing enzyme. J. Biol. Chem. 2011;286:29780–29787. doi: 10.1074/jbc.M111.261370.
    1. Scott J.M. Bioavailability of vitamin B12. Eur. J. Clin. Nutr. 1997;51:S49–S53.
    1. Baik H.W., Russell R.M. Vitamin B12 deficiency in the elderly. Annu. Rev. Nutr. 1999;19:357–377. doi: 10.1146/annurev.nutr.19.1.357.
    1. Berlin H., Berlin R., Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med. Scand. 1968;184:247–258. doi: 10.1111/j.0954-6820.1968.tb02452.x.
    1. Elia M. Oral or parenteral therapy for B12 deficiency. Lancet. 1998;352:1721–1722. doi: 10.1016/S0140-6736(05)79821-4.
    1. Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am. J. Clin. Nutr. 1994;59:S1213–S1222.
    1. McPhee A.J., Davidson G.P., Leahy M., Beare T. Vitamin B12 deficiency in a breast fed infant. Arch. Dis. Child. 1988;63:921–923. doi: 10.1136/adc.63.8.921.
    1. Dror D.K., Allen L.H. Effect of vitamin B12 deficiency on neurodevelopment in infants: Current knowledge and possible mechanisms. Nutr. Rev. 2008;66:250–255. doi: 10.1111/j.1753-4887.2008.00031.x.
    1. Schneede J., Ueland P.M. Novel and established markers of cobalamin deficiency: Complementary or exclusive diagnostic strategies. Semin. Vasc. Med. 2005;5:140–155. doi: 10.1055/s-2005-872399.
    1. Elmadfa I., Singer I. Vitamin B-12 and homocysteine status among vegetarians: A global perspective. Am. J. Clin. Nutr. 2009;89:S1693–S1698. doi: 10.3945/ajcn.2009.26736Y.
    1. Majchrzak D., Singer I., Männer M., Rust P., Genser D., Wagner K.H., Elmadfa I. B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans. Ann. Nutr. Metab. 2006;50:485–491. doi: 10.1159/000095828.
    1. Bissoli L., Di Francesco V., Ballarin A., Mandragona R., Trespidi R., Brocco G., Caruso B., Bosello O., Zamboni M. Effect of vegetarian diet on homocysteine levels. Ann. Nutr. Metab. 2002;46:73–79. doi: 10.1159/000057644.
    1. Green R., Miller J.W. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population. Clin. Chem. Lab. Med. 2005;43:1048–1051. doi: 10.1515/CCLM.2005.183.
    1. Naik S., Bhide V., Babhulkar A., Mahalle N., Parab S., Thakre R., Kulkarni M. Daily milk intake improves vitamin B-12 status in young vegetarian Indians: An intervention trial. Nutr. J. 2013;12:136. doi: 10.1186/1475-2891-12-136.
    1. Refsum H., Yajnik C.S., Gadkari M., Schneede J., Vollset S.E., Orning L., Guttormsen A.B., Joglekar A., Sayyad M.G., Ulvik A., et al. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am. J. Clin. Nutr. 2001;74:233–241.
    1. Haddad E.H., Berk L.S., Kettering J.D., Hubbard R.W., Peters W.R. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am. J. Clin. Nutr. 1999;70:S586–S593.
    1. Karabudak E., Kiziltan G., Cigerim N. A comparison of some of the cardiovascular risk factors in vegetarian and omnivorous Turkish females. J. Hum. Nutr. Diet. 2008;21:13–22. doi: 10.1111/j.1365-277X.2007.00831.x.
    1. Herrmann W., Obeid R., Schorr H., Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin. Chem. Lab. Med. 2003;41:1478–1488. doi: 10.1515/CCLM.2003.227.
    1. Herrmann W., Schorr H., Purschwitz K., Rassoul F., Richter V. Total homocysteine, vitamin B(12), and total antioxidant status in vegetarians. Clin. Chem. 2001;47:1094–1101.
    1. Krivosíková Z., Krajcovicová-Kudlácková M., Spustová V., Stefíková K., Valachovicová M., Blazícek P., Nĕmcová T. The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: The impact of vegetarian diet. Eur. J. Nutr. 2010;49:147–153. doi: 10.1007/s00394-009-0059-1.
    1. Herrmann W., Geisel J. Vegetarian lifestyle and monitoring of vitamin B-12 status. Clin. Chim. Acta. 2002;326:47–59. doi: 10.1016/S0009-8981(02)00307-8.
    1. Lindenbaum J., Healton E.B., Savage D.G., Brust J.C., Garrett T.J., Podell E.R., Marcell P.D., Stabler S.P., Allen R.H. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N. Engl. J. Med. 1988;318:1720–1728. doi: 10.1056/NEJM198806303182604.
    1. Riedel B., Bjørke Monsen A.L., Ueland P.M., Schneede J. Effects of oral contraceptives and hormone replacement therapy on markers of cobalamin status. Clin. Chem. 2005;51:778–781. doi: 10.1373/clinchem.2004.043828.
    1. Carmel R. Measuring and interpreting holo-transcobalamin (holo-transcobalamin II) Clin. Chem. 2002;48:407–409.
    1. Herrmann W., Obeid R., Schorr H., Geisel J. The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Curr. Drug Metab. 2005;6:47–53. doi: 10.2174/1389200052997384.
    1. Huang Y.C., Chang S.J., Chiu Y.T., Chang H.H., Cheng C.H. The status of plasma homocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians. Eur. J. Nutr. 2003;42:84–90. doi: 10.1007/s00394-003-0387-5.
    1. Geisel J., Schorr H., Bodis M., Isber S., Hübner U., Knapp J.P., Obeid R., Herrmann W. The vegetarian lifestyle and DNA methylation. Clin. Chem. Lab. Med. 2005;43:1164–1169. doi: 10.1515/CCLM.2005.202.
    1. Obeid R., Geisel J., Schorr H., Hübner U., Herrmann W. The impact of vegetarianism on some haematological parameters. Eur. J. Haematol. 2002;69:275–279. doi: 10.1034/j.1600-0609.2002.02798.x.
    1. Herrmann W., Obeid R., Schorr H., Hübner U., Geisel J., Sand-Hill M., Ali N., Herrmann M. Enhanced bone metabolism in vegetarians—The role of vitamin B12 deficiency. Clin. Chem. Lab. Med. 2009;47:1381–1387. doi: 10.1515/CCLM.2009.302.
    1. Stabler S.P., Lindenbaum J., Allen R.H. The use of homocysteine and other metabolites in the specific diagnosis of vitamin B-12 deficiency. J. Nutr. 1996;126:S1266–S1272.
    1. Donaldson M.S. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann. Nutr. Metab. 2000;44:229–234. doi: 10.1159/000046689.
    1. Kwok T., Cheng G., Lai W.K., Poon P., Woo J., Pang C.P. Use of fasting urinary methylmalonic acid to screen for metabolic vitamin B12 deficiency in older persons. Nutrition. 2004;20:764–768. doi: 10.1016/j.nut.2004.06.001.
    1. Miller D.R., Specker B.L., Ho M.L., Norman E.J. Vitamin B-12 status in a macrobiotic community. Am. J. Clin. Nutr. 1991;53:524–529.
    1. Lindenbaum J., Savage D.G., Stabler S.P., Allen R.H. Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am. J. Hematol. 1990;34:99–107. doi: 10.1002/ajh.2830340205.
    1. Selhub J., Jacques P.F., Rosenberg I.H., Rogers G., Bowman B.A., Gunter E.W., Wright J.D., Johnson C.L. Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991–1994): Population reference ranges and contribution of vitamin status to high serum concentrations. Ann. Intern. Med. 1999;131:331–339. doi: 10.7326/0003-4819-131-5-199909070-00003.
    1. Bessman J.D., Gilmer P.R., Jr., Gardner F.H. Improved classification of anemias by MCV and RDW. Am. J. Clin. Pathol. 1983;80:322–326. doi: 10.1093/ajcp/80.3.322.
    1. Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians? Am. J. Prev. Med. 2015;48:e11–e26. doi: 10.1016/j.amepre.2015.02.009.
    1. Schilling R.F. Intrinsic factor studies II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B12. J. Lab. Clin. Med. 1953;42:860–866. doi: 10.1016/j.lab.2004.09.001.
    1. Chanarin I. Historical review: A history of pernicious anaemia. Br. J. Haematol. 2000;111:407–415. doi: 10.1046/j.1365-2141.2000.02238.x.
    1. Herrmann W., Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch. Arztebl. Int. 2008;105:680–685.
    1. Headstrom P.D., Rulyak S.J., Lee S.D. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn’s disease. Inflamm. Bowel Dis. 2008;14:217–223. doi: 10.1002/ibd.20282.
    1. Banerjee D.K., Chatterjea J.B. Serum vitamin B12 in vegetarians. Br. Med. J. 1960;2:992–994. doi: 10.1136/bmj.2.5204.992.
    1. Armstrong B.K., Davis R.E., Nicol D.J., van Merwyk A.J., Larwood C.J. Hematological, vitamin B 12, and folate studies on Seventh-day Adventist vegetarians. Am. J. Clin. Nutr. 1974;27:712–718.
    1. Pawlak R., Parrott S.J., Raj S., Cullum-Dugan D., Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr. Rev. 2013;71:110–117. doi: 10.1111/nure.12001.
    1. Pawlak R., Lester S.E., Babatunde T. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: A review of literature. Eur. J. Clin. Nutr. 2014;68:541–548. doi: 10.1038/ejcn.2014.46.
    1. Schüpbach R., Wegmüller R., Berguerand C., Bui M., Herter-Aeberli I. Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland. Eur. J. Nutr. 2015 doi: 10.1007/s00394-015-1079-7.
    1. Mądry E., Lisowska A., Grebowiec P., Walkowiak J. The impact of vegan diet on B-12 status in healthy omnivores: Five-year prospective study. Acta Sci. Pol. Technol. Aliment. 2012;11:209–212.
    1. Rappazzo M.E., Salmi H.A., Hall C.A. The content of vitamin B12 in adult and foetal tissue: A comparative study. Br. J. Haematol. 1970;18:425–433. doi: 10.1111/j.1365-2141.1970.tb01456.x.
    1. Rizzo N.S., Jaceldo-Siegl K., Sabate J., Fraser G.E. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. J. Acad. Nutr. Diet. 2013;113:1610–1619. doi: 10.1016/j.jand.2013.06.349.
    1. Van Dusseldorp M., Schneede J., Refsum H., Ueland P.M., Thomas C.M., de Boer E., van Staveren W.A. Risk of persistent cobalamin deficiency in adolescents fed a macrobiotic diet in early life. Am. J. Clin. Nutr. 1999;69:664–671.
    1. Van Guldener C., Stehouwer C.D. Diabetes mellitus and hyperhomocysteinemia. Semin. Vasc. Med. 2002;2:87–95. doi: 10.1055/s-2002-23099.
    1. Homocysteine Studies Collaboration Homocysteine and risk of ischemic heart disease and stroke: A meta-analysis. JAMA. 2002;288:2015–2022.
    1. Humphrey L.L., Fu R., Rogers K., Freeman M., Helfand M. Homocysteine level and coronary heart disease incidence: A systematic review and meta-analysis. Mayo Clin. Proc. 2008;83:1203–1212. doi: 10.4065/83.11.1203.
    1. Werder S.F. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr. Dis. Treat. 2010;6:159–195. doi: 10.2147/NDT.S6564.
    1. Welch G.N., Loscalzo J. Homocysteine and atherothrombosis. N. Engl. J. Med. 1998;338:1042–1050.
    1. Shargorodsky M., Boaz M., Pasternak S., Hanah R., Matas Z., Fux A., Beigel Y., Mashavi M. Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: Which of them is really important in atherogenesis? Diabetes Metab. Res. Rev. 2009;25:70–75. doi: 10.1002/dmrr.902.
    1. Mahalle N., Kulkarni M.V., Garg M.K., Naik S.S. Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease. J. Cardiol. 2013;61:289–294. doi: 10.1016/j.jjcc.2012.11.009.
    1. Van Meurs J.B., Pare G., Schwartz S.M., Hazra A., Tanaka T., Vermeulen S.H., Cotlarciuc I., Yuan X., Mälarstig A., Bandinelli S., et al. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. Am. J. Clin. Nutr. 2013;98:668–676. doi: 10.3945/ajcn.112.044545.
    1. Allen L.H. How common is vitamin B-12 deficiency? Am. J. Clin. Nutr. 2009;89:S693–S696. doi: 10.3945/ajcn.2008.26947A.
    1. Stabler S.P., Allen R.H. Vitamin B12 deficiency as a worldwide problem. Annu. Rev. Nutr. 2004;24:299–326. doi: 10.1146/annurev.nutr.24.012003.132440.
    1. Antony A.C. Vegetarianism and vitamin B-12 (cobalamin) deficiency. Am. J. Clin. Nutr. 2003;78:3–6.
    1. Tonelli M., Sacks F., Arnold M., Moye L., Davis B., Pfeffer M., for the Cholesterol and Recurrent Events (CARE) Trial Investigators Relation between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People with Coronary Disease. Circulation. 2008;117:163–168. doi: 10.1161/CIRCULATIONAHA.107.727545.
    1. Dabbah S., Hammerman H., Markiewicz W., Aronson D. Relation between red cell distribution width and clinical outcomes after acute myocardial infarction. Am. J. Cardiol. 2010;105:312–317. doi: 10.1016/j.amjcard.2009.09.027.
    1. Ralapanawa D.M., Jayawickreme K.P., Ekanayake E.M., Jayalath W.A. B12 deficiency with neurological manifestations in the absence of anaemia. BMC Res. Notes. 2015;8:458. doi: 10.1186/s13104-015-1437-9.
    1. Brocadello F., Levedianos G., Piccione F., Manara R., Pesenti F.F. Irreversible subacute sclerotic combined degeneration of the spinal cord in a vegan subject. Nutrition. 2007;23:622–624. doi: 10.1016/j.nut.2007.05.006.
    1. Rusher D.R., Pawlak R. A Review of 89 Published Case Studies of Vitamin B12 Deficiency. J. Hum. Nutr. Food Sci. 2013;1:1008.
    1. Koebnick C., Hoffmann I., Dagnelie P.C., Heins U.A., Wickramasinghe S.N., Ratnayaka I.D., Gruendel S., Lindemans J., Leitzmann C. Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women. J. Nutr. 2004;134:3319–3326.
    1. Yajnik C.S., Deshmukh U.S. Maternal nutrition, intrauterine programming and consequential risks in the offspring. Rev. Endocr. Metab. Disord. 2008;9:203–211. doi: 10.1007/s11154-008-9087-z.
    1. Knight B.A., Shields B.M., Brook A., Hill A., Bhat D.S., Hattersley A.T., Yajnik C.S. Lower Circulating B12 Is Associated with Higher Obesity and Insulin Resistance during Pregnancy in a Non-Diabetic White British Population. PLoS ONE. 2015;10:e0135268. doi: 10.1371/journal.pone.0135268.
    1. Yajnik C.S., Deshmukh U.S. Fetal programming: Maternal nutrition and role of one-carbon metabolism. Rev. Endocr. Metab. Disord. 2012;13:121–127. doi: 10.1007/s11154-012-9214-8.
    1. Rosenblatt D.S., Whitehead V.M. Cobalamin and folate deficiency: Acquired and hereditary disorders in children. Semin. Hematol. 1999;36:19–34.
    1. Evatt M.L., Terry P.D., Ziegler T.R., Oakley G.P. Association between vitamin B12-containing supplement consumption and prevalence of biochemically defined B12 deficiency in adults in NHANES III (third national health and nutrition examination survey) Public Health Nutr. 2010;13:25–31. doi: 10.1017/S1368980009990279.
    1. USDA Food Composition Database; [(accessed on 28 July 2016)]. USDA National Nutrient Database for Standard Reference. Available online: .
    1. Banca Dati Di Composizione Degli Alimenti per Gli Studi Epidemiologici in Italia (BDA) [(accessed on 28 July 2016)]. Available online: .
    1. Doscherholmen A., McMahon J., Ripley D. Vitamin B12 absorption from eggs. Proc. Soc. Exp. Biol. Med. 1975;149:987–990. doi: 10.3181/00379727-149-38940.
    1. Dubey R.C., Maheshwari D.K. A Textbook of Microbiology. S Chand & Company Ltd.; New Delhi, India: 2013.
    1. Allen L., de Benoist B., Dary O., Hurrell R. Guidelines on Food Fortification with Micronutrients. World Health Organization; Food and Agriculture Organization; Geneva, Switzerland: 2006.
    1. Green R. Is it time for vitamin B-12 fortification? What are the questions? Am. J. Clin. Nutr. 2009;89:S712–S716. doi: 10.3945/ajcn.2008.26947E.
    1. Allen L.H., Rosenberg I.H., Oakley G.P., Omenn G.S. Considering the case for vitamin B12 fortification of flour. Food Nutr. Bull. 2010;31:S36–S46. doi: 10.1177/15648265100311S104.
    1. Stover P.J. Physiology of folate and vitamin B12 in health and disease. Nutr. Rev. 2004;62:S3–S13. doi: 10.1111/j.1753-4887.2004.tb00070.x.
    1. Bhuiyan A., Dash S., Shahriar S., Nahid F., Arefin S. A case of sub-acute combined degeneration of the spinal cord with associated pernicious anaemia. Pulse. 2011;5:57–60. doi: 10.3329/pulse.v5i1.20193.
    1. Tan L.T.H., Ho K.K.F., Fong G.C.Y., Ong K.L. Subacute combined degeneration of the spinal cord. Hong Kong J. Emerg. Med. 2010;17:79–81.
    1. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) Tolerable Upper Intake Levels for Vitamins and Minerals. EFSA; Parma, Italy: 2016.
    1. Shibuya K., Misawa S., Nasu S., Sekiguchi Y., Beppu M., Iwai Y., Mitsuma S., Isose S., Arimura K., Kaji R., et al. Safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy: A phase I/II open label clinical trial. Intern. Med. 2014;53:1927–1931. doi: 10.2169/internalmedicine.53.1951.
    1. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112:2214–2221. doi: 10.1182/blood-2008-03-040253.
    1. Sharabi A., Cohen E., Sulkes J., Garty M. Replacement therapy for vitamin B12 deficiency: Comparison between the sublingual and oral route. Br. J. Clin. Pharmacol. 2003;56:635–638. doi: 10.1046/j.1365-2125.2003.01907.x.
    1. Van Walraven C., Austin P., Naylor C.D. Vitamin B12 injections versus oral supplements. How much money could be saved by switching from injections to pills? Can. Fam. Physician. 2001;47:79–86.
    1. Thakkar K., Billa G. Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur. J. Clin. Nutr. 2015;69:1–2. doi: 10.1038/ejcn.2014.165.
    1. Zhang Y.F., Ning G. Mecobalamin. Expert Opin. Investig. Drugs. 2008;17:953–964. doi: 10.1517/13543784.17.6.953.
    1. Institute of Medicine . Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) National Academies; Washington, DC, USA: 2005.
    1. Doi K., Matsuura M., Kawara A., Tanaka T., Baba S. Influence of dietary fiber (konjac mannan) on absorption of vitamin B12 and vitamin E. Tohoku J. Exp. Med. 1983;141:677–681. doi: 10.1620/tjem.141.Suppl_677.
    1. Alexander D., Ball M.J., Mann J. Nutrient intake and haematological status of vegetarians and age-sex matched omnivores. Eur. J. Clin. Nutr. 1994;48:538–546.
    1. Herbert V. Everyone should be tested for iron disorders. J. Am. Diet. Assoc. 1992;92:1502–1509.
    1. Appleby P., Roddam A., Allen N., Key T. Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford. Eur. J. Clin. Nutr. 2007;61:1400–1406. doi: 10.1038/sj.ejcn.1602659.
    1. Herzlich B., Herbert V. The role of the pancreas in cobalamin (vitamin B12) absorption. Am. J. Gastroenterol. 1984;79:489–493.
    1. Bauman W.A., Shaw S., Jayatilleke E., Spungen A.M., Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23:1227–1231. doi: 10.2337/diacare.23.9.1227.
    1. Li D., Yu X.M., Xie H.B., Zhang Y.H., Wang Q., Zhou X.Q., Yu P., Wang L.J. Platelet phospholipid n-3 PUFA negatively associated with plasma homocysteine in middle-aged and geriatric hyperlipaemia patients. Prostaglandins Leukot. Essent. Fat. Acids. 2007;76:293–297. doi: 10.1016/j.plefa.2007.02.003.
    1. Kulkarni A., Mehendale S., Pisal H., Kilari A., Dangat K., Salunkhe S., Taralekar V., Joshi S. Association of omega-3 fatty acids and homocysteine concentrations in pre-eclampsia. Clin. Nutr. 2011;30:60–64. doi: 10.1016/j.clnu.2010.07.007.
    1. Grundt H., Nilsen D.W., Mansoor M.A., Hetland Ø., Nordøy A. Reduction in homocysteine by n-3 polyunsaturated fatty acids after 1 year in a randomised double-blind study following an acute myocardial infarction: No effect on endothelial adhesion properties. Pathophysiol. Haemost. Thromb. 2003;33:88–95. doi: 10.1159/000073852.
    1. Pooya S.H., Jalali M.D., Jazayery A.D., Saedisomeolia A., Eshraghian M.R., Toorang F. The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Nutr. Metab. Cardiovasc. Dis. 2010;20:326–331. doi: 10.1016/j.numecd.2009.04.002.
    1. Zeman M., Zák A., Vecka M., Tvrzická E., Písaríková A., Stanková B. N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fibrate combination. J. Nutr. Biochem. 2006;17:379–384. doi: 10.1016/j.jnutbio.2005.08.007.
    1. Rosell M.S., Lloyd-Wright Z., Appleby P.N., Sanders T.A., Allen N.E., Key T.J. Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men. Am. J. Clin. Nutr. 2005;82:327–334.
    1. Li D., Turner A., Sinclair A.J. Relationship between platelet phospholipid FA and mean platelet volume in healthy men. Lipids. 2002;37:901–906. doi: 10.1007/s11745-002-0977-0.
    1. Adams J.F. The urinary excretion and tissue retention of Cyanocobalamin by subjects given repeated parenteral doses. J. Clin. Pathol. 1964;17:31–38. doi: 10.1136/jcp.17.1.31.
    1. Allen R.H., Stabler S.P. Identification and quantitation of cobalamin and cobalamin analogues in human feces. Am. J. Clin. Nutr. 2008;87:1324–1335.
    1. Kondo H., Binder M.J., Kolhouse J.F., Smythe W.R., Podell E.R., Allen R.H. Presence and formation of cobalamin analogues in multivitamin-mineral pills. J. Clin. Investig. 1982;70:889–898. doi: 10.1172/JCI110685.
    1. Takenaka S., Sugiyama S., Watanabe F., Abe K., Tamura Y., Nakano Y. Effects of Carnosine and Anserine on the Destruction of Vitamin B12 with Vitamin C in the Presence of Copper. Biosci. Biotechnol. Biochem. 1997;61:2137–2139. doi: 10.1271/bbb.61.2137.
    1. Miyamoto E., Kittaka-Katsura H., Adachi S., Watanabe F. Assay of vitamin B12 in edible bamboo shoots. Vitamins. 2005;79:329–332.
    1. Kittaka-Katsura H., Watanabe F., Nakano Y. Occurrence of vitamin B12 in green, blue, red, and black tea leaves. J. Nutr. Sci. Vitaminol. 2004;50:438–440. doi: 10.3177/jnsv.50.438.
    1. La Guardia M., Venturella G., Venturella F. On the chemical composition and nutritional value of pleurotus taxa growing on umbelliferous plants (Apiaceae) J. Agric. Food Chem. 2005;53:5997–6002. doi: 10.1021/jf0307696.
    1. Watanabe F., Schwarz J., Takenaka S., Miyamoto E., Ohishi N., Nelle E., Hochstrasser R., Yabuta Y. Characterization of vitamin B12compounds in the wild edible mushrooms black trumpet (Craterellus cornucopioides) and golden chanterelle (Cantharellus cibarius) J. Nutr. Sci. Vitaminol. 2012;58:438–441. doi: 10.3177/jnsv.58.438.
    1. Bito T., Teng F., Ohishi N., Takenaka S., Miyamoto E., Sakuno E., Terashima K., Yabuta Y., Watanabe F. Characterization of vitamin B12 compounds in the fruiting bodies of shiitake mushroom (Lentinula edodes) and bed logs after fruiting of the mushroom. Mycoscience. 2014;55:462–468. doi: 10.1016/j.myc.2014.01.008.
    1. Watanabe F., Takenaka S., Katsura H., Masumder S.A., Abe K., Tamura Y., Nakano Y. Dried green and purple lavers (Nori) contain substantial amounts of biologically active vitamin B(12) but less of dietary iodine relative to other edible seaweeds. J. Agric. Food Chem. 1999;47:2341–2343. doi: 10.1021/jf981065c.
    1. Miyamoto E., Yabuta Y., Kwak C.S., Enomoto T., Watanabe F. Characterization of vitamin B12 compounds from Korean purple laver (Porphyra sp.) products. J. Agric. Food Chem. 2009;57:2793–2796. doi: 10.1021/jf803755s.
    1. Yamada S., Shibata Y., Takayama M., Narita Y., Sugawara K., Fukuda M. Content and characteristics of vitamin B12 in some seaweeds. J. Nutr. Sci. Vitaminol. 1996;42:497–505. doi: 10.3177/jnsv.42.497.
    1. Suzuki H. Serum vitamin B12 levels in young vegans who eat brown rice. J. Nutr. Sci. Vitaminol. 1995;41:587–594. doi: 10.3177/jnsv.41.587.
    1. Dagnelie P.C., van Staveren W.A., van den Berg H. Vitamin B-12 from algae appears not to be bioavailable. Am. J. Clin. Nutr. 1991;53:695–697.
    1. Watanabe F., Takenaka S., Kittaka-Katsura H., Ebara S., Miyamoto E. Characterization and bioavailability of vitamin B12-compounds from edible algae. J. Nutr. Sci. Vitaminol. 2002;48:325–331. doi: 10.3177/jnsv.48.325.
    1. Baroni L., Scoglio S., Benedetti S., Bonetto C., Pagliarani S., Benedetti Y., Rocchi M., Canestrari F. Effect of a Klamath algae product (“AFA-B12”) on blood levels of vitamin B12 and homocysteine in vegan subjects: A pilot study. Int. J. Vitam. Nutr. Res. 2009;79:117–123. doi: 10.1024/0300-9831.79.2.117.
    1. Miyamoto E., Tanioka Y., Nakao T., Barla F., Inui H., Fujita T., Watanabe F., Nakano Y. Purification and characterization of a corrinoid-compound in an edible cyanobacterium Aphanizomenon flos-aquae as a nutritional supplementary food. J. Agric. Food Chem. 2006;54:9604–9607. doi: 10.1021/jf062300r.
    1. Pulz O., Gross W. Valuable products from biotechnology of microalgae. Appl. Microbiol. Biotechnol. 2004;65:635–648. doi: 10.1007/s00253-004-1647-x.
    1. Merchant R.E., Phillips T.W., Udani J. Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12 Deficiency. J. Med. Food. 2015;18:1357–1362. doi: 10.1089/jmf.2015.0056.
    1. Kittaka-Katsura H., Fujita T., Watanabe F., Nakano Y. Purification and characterization of a corrinoid compound from Chlorella tablets as an algal health food. J. Agric. Food Chem. 2002;50:4994–4997. doi: 10.1021/jf020345w.
    1. Watanabe F., Tanioka Y., Miyamoto E., Fujita T., Takenaka H., Nakano Y. Purification and characterization of corrinoid-compounds from the dried powder of an edible cyanobacterium, Nostoc commune (Ishikurage) J. Nutr. Sci. Vitaminol. 2007;53:183–186. doi: 10.3177/jnsv.53.183.
    1. Watanabe F., Katsura H., Takenaka S., Fujita T., Abe K., Tamura Y., Nakatsuka T., Nakano Y. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J. Agric. Food Chem. 1999;47:4736–4741. doi: 10.1021/jf990541b.
    1. Herbert V., Drivas G. Spirulina and vitamin B 12. JAMA. 1982;248:3096–3097. doi: 10.1001/jama.1982.03330230018017.
    1. Tanioka Y., Yabuta Y., Miyamoto E., Inui H., Watanabe F. Analysis of vitamin B12 in food by silica gel 60 TLC and bioautography with vitamin B12-dependent Escherichia coli 215. J. Liq. Chromatogr. Relat. Technol. 2008;31:1977–1985. doi: 10.1080/10826070802197453.
    1. Denter J., Bisping B. Formation of B-vitamins by bacteria during the soaking process of soybeans for tempe fermentation. Int. J. Food Microbiol. 1994;22:23–31. doi: 10.1016/0168-1605(94)90004-3.
    1. Nout M.J.R., Rombouts F.M. Recent developments in tempe research. J. Appl. Bacteriol. 1990;69:609–633. doi: 10.1111/j.1365-2672.1990.tb01555.x.
    1. Okada N., Hadioetomo P.S., Nikkuni S., Katoh K., Ohta T. Vitamin B12 content of fermented foods in the tropics. Rep. Natl. Food Res. Inst. 1983;43:126–129.
    1. Kwak C.S., Hwang J.Y., Watanabe F., Park S.C. Vitamin B12 contents in some Korean fermented foods and edible seaweeds. Korean Nutr. 2008;41:439–447.
    1. Babuchowski A., Laniewska-Moroz L., Warminska-Radyko I. Propionibacteria in fermented vegetables. Lait. 1999;79:113–124. doi: 10.1051/lait:199919.
    1. Mozafar A. Enrichment of some B-vitamins in plants with application of organic fertilizers. Plant Soil. 1994;167:305–311. doi: 10.1007/BF00007957.
    1. Sato K., Kudo Y., Muramatsu K. Incorporation of a high level of vitamin B12 into a vegetable, kaiware daikon (Japanese radish sprout), by the absorption from its seeds. Biochim. Biophys. Acta. 2004;1672:135–137. doi: 10.1016/j.bbagen.2004.03.011.
    1. Bito T., Ohishi N., Hatanaka Y., Takenaka S., Nishihara E., Yabuta Y., Watanabe F. Production and characterization of cyanocobalamin-enriched lettuce (Lactuca sativa L.) grown using hydroponics. J. Agric. Food Chem. 2013;61:3852–3858. doi: 10.1021/jf305033s.
    1. Gu Q., Zhang C., Song D., Li P., Zhu X. Enhancing vitamin B12 content in soy-yogurt by Lactobacillus reuteri. Int. J. Food Microbiol. 2015;206:56–59. doi: 10.1016/j.ijfoodmicro.2015.04.033.
    1. Rizzo G., Baroni L. Health and ecological implications of fish consumption: A deeper insight. Med. J. Nutr. Metab. 2016;9:7–22. doi: 10.3233/MNM-160054.
    1. Craig W.J. Nutrition concerns and health effects of vegetarian diets. Nutr. Clin. Pract. 2010;25:613–620. doi: 10.1177/0884533610385707.
    1. Clinical Trials NCT02679833. [(accessed on 28 July 2016)]; Available online: .
    1. Yazaki Y., Chow G., Mattie M. A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels. J. Altern. Complement. Med. 2006;12:881–885. doi: 10.1089/acm.2006.12.881.
    1. Vidal-Alaball J., Butler C.C., Cannings-John R., Goringe A., Hood K., McCaddon A., McDowell I., Papaioannou A. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst. Rev. 2005;3:CD004655.
    1. Oladipo O., Rosenblatt D.S., Watkins D., Miousse I.R., Sprietsma L., Dietzen D.J., Shinawi M. Cobalamin F disease detected by newborn screening and follow-up on a 14-year-old patient. Pediatrics. 2011;128:e1636–e1640. doi: 10.1542/peds.2010-3518.
    1. Waggoner D.J., Ueda K., Mantia C., Dowton S.B. Methylmalonic aciduria (cblF): Case report and response to therapy. Am. J. Med. Genet. 1998;79:373–375. doi: 10.1002/(SICI)1096-8628(19981012)79:5<373::AID-AJMG8>;2-K.
    1. Andersson H.C., Shapira E. Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC) J. Pediatr. 1998;132:121–124. doi: 10.1016/S0022-3476(98)70496-2.
    1. Linnell J.C., Smith A.D., Smith C.L., Wilson J., Matthews D.M. Effects of smoking on metabolism and excretion of vitamin B12. Br. Med. J. 1968;2:215–216. doi: 10.1136/bmj.2.5599.215.
    1. Shepherd G., Velez L.I. Role of hydroxocobalamin in acute cyanide poisoning. Ann. Pharmacother. 2008;42:661–669. doi: 10.1345/aph.1K559.
    1. Freeman A.G. Cyanocobalamin—A case for withdrawal: Discussion paper. J. R. Soc. Med. 1992;85:686–687.
    1. Freeman A.G. Hydroxocobalamin versus cyanocobalamin. J. R. Soc. Med. 1996;89:659.
    1. Balta I., Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan. Ocul. Toxicol. 2014;33:94–95. doi: 10.3109/15569527.2013.808657.
    1. Cianci A., Colacurci N., Paoletti A.M., Perino A., Cicinelli E., Maffei S., Di Martino M., Daguati R., Stomati M., Pilloni M., et al. Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: An observational study. Clin. Exp. Obstet. Gynecol. 2015;42:743–745.
    1. Cignini P., Mangiafico L., Padula F., D’Emidio L., Dugo N., Aloisi A., Giorlandino C., Vitale S.G. Supplementation with a dietary multicomponent (Lafergin®) based on Ferric Sodium EDTA (Ferrazone®): Results of an observational study. J. Prenat. Med. 2015;9:1–7. doi: 10.11138/jpm/2015.9.1.001.
    1. Colonese F., Laganà A.S., Colonese E., Sofo V., Salmeri F.M., Granese R., Triolo O. The pleiotropic effects of vitamin D in gynaecological and obstetric diseases: An overview on a hot topic. Biomed. Res. Int. 2015;2015:986281. doi: 10.1155/2015/986281.
    1. Laganà A.S., Vitale S.G., Nigro A., Sofo V., Salmeri F.M., Rossetti P., Rapisarda A.M., La Vignera S., Condorelli R.A., Rizzo G., et al. Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives. Int. J. Mol. Sci. 2016;17:E999. doi: 10.3390/ijms17070999.
    1. Misra U.K., Kalita J., Singh S.K., Rahi S.K. Oxidative stress markers in vitamin B12 deficiency. Mol. Neurobiol. 2016:1–7. doi: 10.1007/s12035-016-9736-2.

Source: PubMed

3
구독하다