Subclinical cobalamin deficiency

Current Opinion in Gastroenterology

Volumn 28, Issue 2, 2012, Pages 151-158

  Carmel, Ralph ^a  

^a NEW YORK METHODIST HOSPITAL   (United States)

Author keywords

aging; cobalamin; cobalamin deficiency; cognitive impairment; homocysteine

Indexed keywords

ANTIBIOTIC AGENT; COBALAMIN; FOLIC ACID; HOMOCYSTEINE; METFORMIN; METHYLMALONIC ACID; PEPSIN A; PYRIDOXINE; TRANSCOBALAMIN II;

ALZHEIMER DISEASE; ANEMIA; BRAIN; BRAIN ATROPHY; COBALAMIN DEFICIENCY; COGNITIVE DEFECT; DIET SUPPLEMENTATION; DRUG BIOAVAILABILITY; DRUG MEGADOSE; FOOD BOUND COBALAMIN MALABSORPTION; GERIATRIC DISORDER; HELICOBACTER INFECTION; HUMAN; PROGNOSIS; REVIEW; SUBCLINICAL COBALAMIN DEFICIENCY; VITAMIN DEFICIENCY; VITAMIN SUPPLEMENTATION;

ASYMPTOMATIC DISEASES; COGNITION DISORDERS; DIETARY SUPPLEMENTS; FOLIC ACID; FOOD, FORTIFIED; HUMANS; VITAMIN B 12; VITAMIN B 12 DEFICIENCY; VITAMINS;

EID: 84858073335     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0b013e3283505852     Document Type: Review

References (73)

1. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008; 112:2214-2221.
2. Carmel R, Karnaze DS. The deoxyuridine suppression test identifies subtle cobalamin deficiency in patients without typical megaloblastic anemia. JAMA 1985; 253:1284-1287. (Pubitemid 15127844)
3. Karnaze DS, Carmel R. Low serum cobalamin levels in primary degenerative dementia: Do some patients harbor atypical cobalamin deficiency states? Arch Intern Med 1987; 147:429-431. (Pubitemid 17036577)
4. Carmel R, Sinow RM, Karnaze DS. Atypical cobalamin deficiency: subtle biochemical evidence of deficiency is commonly demonstrable in patients without megaloblastic anemia and is often associated with protein-bound cobalamin malabsorption. J Lab Clin Med 1987; 109:454-463. (Pubitemid 17064448)
5. Stabler SP, Marcell PD, Podell ER, et al. Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography- mass spectrometry. J Clin Invest 1986; 77:1606-1612. (Pubitemid 16047105)
6. Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency. II: Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol 1990; 34:99-107. (Pubitemid 20180101)
7. Lindenbaum L, Rosenberg IH, Wilson PWF, et al. Prevalence of cobalamin deficiency in the Framingham elderly. Am J Clin Nutr 1994; 60:2-11.
8. Carmel R,Green R, Jacobsen DW, et al. Serum cobalamin, homocysteine and methylmalonic acid concentrations in a multiethnic elderly population: Ethnic and sex differences in cobalamin and metabolite abnormalities. Am J Clin Nutr 1999; 70:904-910. (Pubitemid 29512918)
9. Hvas AM, Ellegaard J, Nexo E. Increased plasma methylmalonic acid level does not predict clinical manifestations of vitamin B12 deficiency. Arch Intern Med 2001; 161:1534-1541. (Pubitemid 32679567)
10. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: A critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr 2011; 94:348S-358S.
11. Vogiatzoglou A, Oulhaj A, Smith AD, et al. Determinants of plasma methylmalonic acid in a large population: Implications for assessment of vitamin B12 status. Clin Chem 2009; 55:2198-2206.
12. Bailey RL, Carmel R, Green R, et al. Monitoring of vitamin B12 nutritional status in the Unites States by using plasma methylmalonic acid and serum vitamin B12. Am J Clin Nutr 2011; 94:552-561.
13. Yetley EA, Pfeiffer CM, Phinney KW, et al. Biomarkers of vitamin B-12 status in NHANES: A roundtable summary. Am J Clin Nutr 2011; 94 (Suppl):313S- 321S.
14. Fedosov SN. Metabolic signs of vitamin B12 deficiency in humans: Computational model and its implications for diagnostics. Metab Clin Exp 2010; 59:1124-1138.
15. Carmel R. Ethnic and racial factors in cobalamin metabolism and its disorders. Semin Hematol 1999; 36:88-100. (Pubitemid 29048615)
16. Hazra A, Kraft P, Selhub J, et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat Genet 2008; 40:1160-1162.
17. Tanaka T, Scheet P, Giusti B, et al. Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. Am J HumGenet 2009; 84:477-482.
18. Carmel R. Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations. Clin Chem 2003; 49:1367-1374. (Pubitemid 36900624)
19. Carmel R, Parker J, Kelman Z. Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels. Br J Haematol 2009; 147:386-391.
20. Carmel R, Parker J, Kelman Z. Mutations of TCN1 cause transcobalamin I deficiency with low serum cobalamin levels that are indistinguishable from cobalamin deficiency. Blood 2009; 114 (Suppl):787. (abstract).
21. Carmel R, Parker J, Kelman Z. Nonnutritional modulation of cobalamin levels: TCN1 mutations, polymorphisms, and alternative splicing, and FUT2 polymorphism. FASEB J 2010; 24:lb241. (abstract).
22. Carmel R, Bellevue R, Kelman Z. Low cobalamin levels associated with sickle cell disease: Contrasting origins and clinical meanings in two instructive patients. Am J Hematol 2010; 85:436-439.
23. Chen X, Remacha AF, Sarda MP, Carmel R. Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holotranscobalamin II. Am J Clin Nutr 2005; 81:110-114. (Pubitemid 43073382)
24. Bor MV, Cetin M, Aytac S, et al. Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12. Clin Chem 2005; 51:2151-2155. (Pubitemid 41532633)
25. Carmel R. On measuring and interpreting holotranscobalamin (holotranscobalaminII). Clin Chem 2002; 48:407-409.
26. Riedel BM, Molloy AM, Meyer K, et al. Transcobalamin polymorphism 67A- >G, but not 776C->G, affects serum holotranscobalamin in cohort of healthy middle-aged men and women. J Nutr 2011; 141:1784-1790.
27. Carmel R. Cobalamin, the stomach, and aging. Am J Clin Nutr 1997; 66:750-759.
28. Howard JM, Azen C, Jacobsen DW, et al. Dietary intake of cobalamin in elderly people who have abnormal serum cobalamin, methylmalonic acid and homocysteine levels. Eur J Clin Nutr 1998; 52:582-587. (Pubitemid 28395697)
29. van Asselt DZB, de Groot LCPGM, van Staveren WA, et al. Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. Am J Clin Nutr 1998; 68:328-334. (Pubitemid 28355650)
30. Bor MV, vonCastel-Roberts KM, Kauwell GPA, et al. Daily intake of 4 to 7mg dietary vitamin B12 is associated with steady concentrations of vitamin B12- related biomarkers in a healthy young population. Am J Clin Nutr 2010; 91:571-577.
31. Vogiatzoglu A, Smith AD, Nurk E, et al. Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: The Hordaland Homocysteine Study. Am J Clin Nutr 2009; 89:1078-1087.
32. Carmel R. Food-cobalamin malabsorption. Bailliè re's Clin Haematol 1995; 8:639-655.
33. Cohen H, Weinstein WM, Carmel R. The heterogeneity of gastric histology and function in food cobalamin malabsorption: Absence of atrophic gastritis and achlorhydria in some patients with severe malabsorption. Gut 2000; 47:638-645.
34. Carmel R. The disappearance of cobalamin absorption testing: A critical diagnostic loss. J Nutr 2007; 137:2481-2484. (Pubitemid 350058720)
35. Andres E, Affenberger S, Vinzio S, et al. Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment. Am J Med 2005; 118:1154-1159. (Pubitemid 41363768)
36. Carmel R, Aurangzeb I, Qian D. Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gatsritis. Am J Gastroenterol 2001; 96:63-70. (Pubitemid 32104809)
37. Leung S, Mattman A, Snyder F, et al. Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem 2010; 43:759-760.
38. Hvas AM, Morkbak AL, Hardlei TF, Nexo E. The vitamin B12 absorption test, CobaSorb, identifies patients not requiring vitamin B12 injection therapy. Scand J Clin Lab Invest 2011; 71:432-438.
39. Smith DA. The worldwide challenge of the dementias: A role for B vitamins and homocysteine? Food Nutr Bull 2008; 29 (Suppl):143-172.
40. Selhub J, Troen A, Rosenberg IH. B vitamins and the aging brain. Nutr Rev 2010; 68 (Suppl 2):S112-S118.
41. Ho RCM, Cheung MWL, Fu E, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and metaregression. Am J Geriatr Psychiatry 2011; 19:607-617.
42. Balk EM, Raman G, Tatsioni A, et al. Vitamin B6, B12, and folic acid supplementation and cognitive function. A systematic review of randomized trials. Arch Intern Med 2007; 167:21-30. (Pubitemid 46072403)
43. Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med 2010; 123:522-527.
44. Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database of Syst Rev 2003:CD004394. doi: 10.1002/14651858.CD004394.
45. Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease. A randomized controlled trial. JAMA 2008; 300:1774-1783.
46. McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006; 354:2764-2772. (Pubitemid 43974194)
47. Clarke RJ, Bennett DA. B vitamins for prevention of cognitive decline. Insufficient evidence to justify treatment. JAMA 2008; 300:1819-1821.
48. de Lau LML, Smith AD, Refsum H, et al. Plasma vitamin B12 status and cerebral white-matter. J Neurol Neurosurg Psychiatr 2009; 80:149-157.
49. Vogiatzoglou A, Refsum H, Johnston C, et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology 2008; 71:826-832.
50. Tangney CC, Aggarwal NT, Li H, et al. Vitamin B12, cognition, and brain MRI measures. A cross sectional examination. Neurology 2011; 77:1276-1282.
51. Hooshmand B, Solomon A, Kareholt I, et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease. A longitudinal study. Neurology 2010; 75:1408-1414.
52. Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: A randomised, double blind, controlled trial. Lancet 2007; 369:208-216. (Pubitemid 46107683)
53. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS One 2010; 5:e12244.
54. de Jager CA, Oulhaj A, Jacoby R, et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: A randomized controlled trial. Int J Geriatr Psychiatry 2011. http:// onlinelibrary. wiley.com/doi/10.1002/gps.2758.pdf [Accessed 21 July 2011] This important companion to reference [53 ]
55. Selhub J, Morris MS, Jacques PF. In vitamin deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci U S A 2007; 104:19995-20000.
56. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 2007; 85:193-200. (Pubitemid 46067634)
57. Clarke R, Sherliker P, Hin H, et al. Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK. Br J Nutr 2008; 100:1054-1059.
58. Miller JW, Garrod MG, Allen LH, et al. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate. Am J Clin Nutr 2009; 90:1586-1592.
59. Carmel R. Does high folic acid intake affect unrecognized cobalamin deficiency and how will we know it if we see it? Am J Clin Nutr 2009; 90:1449-1450.
60. Mills JL, Carter TC, Scott JM, et al. Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status? Am J Clin Nutr 2011; 94:495-500.
61. Morris MC, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr 2010; 91:1733-1744.
62. Bucca CB, Culla B, Guida G, et al. Unexplained chronic cough and vitamin B- 12 deficiency. Am J Clin Nutr 2011; 93:542-548.
63. Li F, Watkins D, Rosenblatt DS. Vitamin B12 and birth defects. Mol Genet Metab 2009; 98:166-172.
64. Thompson MD, Cole DEC, Ray JG. Vitamin B-12 and neural tube defects: The Canadian experience. Am J Clin Nutr 2009; 89 (Suppl):697S- 701S.
65. Carmel R. Efficacy and safety of fortification and supplementation with vitamin B12: biochemical and physiological effects. Food Nutr Bull 2008; 29 (Suppl):S177-S187.
66. Green R. Is it time for vitamin B-12 fortification? What are the questions? Am J Clin Nutr 2009; 89 (Suppl):712S-716S.
67. Carmel R. Mandatory fortification of the food supply with cobalamin: An idea whose time has not yet come. J Inherit Metab Dis 2011; 34:67-73.
68. Winkels RM, Brouwer IA, Clarke R, et al. Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: A randomized controlled trial. Am J Clin Nutr 2008; 88:348-355.
69. Carmel R, Sarrai M. Diagnosis and management of clinical and subclinical cobalamin deficiency: Advances and controversies. Curr Hematol Rep 2006; 5:23-33.
70. Favret B, Vaucher P, Herzig L, et al. Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: A multicentre pragmatic randomised controlled trial. BMC Fam Pract 2011; 12:2.
71. 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.
72. Gimsing P, Hippe E, Helleberg-Rasmussen I, et al. Cobalamin forms in plasma and tissue during treatment of vitamin B12 deficiency. Scand J Haematol 1982; 29:311-318. (Pubitemid 12037579)
73. House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy. A randomized controlled trial. JAMA 2010; 303:1603-1609.