Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: A randomised trial

European Journal of Clinical Nutrition

Volumn 57, Issue 11, 2003, Pages 1426-1436

  Lewerin, C ^a   Nilsson Ehle, Herman ^a   Matousek, M ^a   Lindstedt, G ^a   Steen, B ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

Aged; Folic acid; Homocysteine; Methylmalonic acid; Reference values; Vitamin B12

Indexed keywords

CYANOCOBALAMIN; FOLIC ACID; HEMOGLOBIN; HOMOCYSTEINE; METHYLMALONIC ACID; PLACEBO; PYRIDOXINE; TRANSFERRIN;

AGE DISTRIBUTION; AGED; AMINO ACID BLOOD LEVEL; ARTICLE; BLOOD; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORRELATION ANALYSIS; CYANOCOBALAMIN DEFICIENCY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ACTIVITY; DRUG EFFICACY; FEMALE; FOLIC ACID DEFICIENCY; HEMOGLOBIN DETERMINATION; HUMAN; HYPERHOMOCYSTEINEMIA; MALE; MULTIVARIATE ANALYSIS; OUTPATIENT CARE; PREVALENCE; RANDOMIZED CONTROLLED TRIAL; REFERENCE VALUE; SIDE EFFECT;

AGED; AGED, 80 AND OVER; DOUBLE-BLIND METHOD; FEMALE; FOLIC ACID; FOLIC ACID DEFICIENCY; HOMOCYSTEINE; HUMANS; MALE; METHYLMALONIC ACID; REFERENCE VALUES; VITAMIN B 12; VITAMIN B 12 DEFICIENCY; VITAMIN B 6;

EID: 0242693157     PISSN: 09543007     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ejcn.1601707     Document Type: Article

References (67)

1. Adams JF, Clark JS, Ireland JT, Kesson CM & Watson WS (1983): Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 24, 16-18.
2. Alpert JE & Fava M (1997): Nutrition and depression: the role of folate. Nutr. Rev. 55, 145-149.
3. Apeland T, Mansoor MA, Strandjord RE, Vefring H & Kristensen O (2001): Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol. Scand. 103, 294-299.
4. Augustsson O, Eriksson BG, Rosenhall U, Rothenberg E, Warne B & Steen B (1994): The Johanneberg study - a sociomedical survey in an urban elderly population. I. General presentation of the study including an analysis of non-response and identification of risk groups. Scand. J. Soc. Med. 22, 283-292.
5. Bailey LB & Gregory JF (1999): Polymorphisms of methylenetetrahy-drofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J. Nutr. 129, 919-922.
6. Bald E & Sypniewski S (1994): Ion-pair high-performance liquid chromatography of cysteine and metabolically related compounds in the form of their S-pyridinium derivates. J. Chromatogr. A 676, 321-330.
7. Bates CJ, Pentieva KD, Prentice A, Mansoor MA & Finch S (1999): Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over. Br. J. Nutr. 81, 191-201.
8. Belaiche J, Zittoun J, Marquet J, Nurit Y & Yvart J (1983): Effet de la ranitidine sur la secretion de facteur intrinseque gastrique et sur l'absorption de la vitamine B12. Gastroenterol. Clin. Biol. 7, 381-384.
9. Berg MJ (1999): The importance of folic acid. J. Gend. Specif. Med. 2, 24-28.
10. Bostom AG, Bausserman L, Jacques PF, Liaugaudas G, Selhub J & Rosenberg IH (1999): Cystatin c as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler. Thromb. Vasc. Biol. 19, 2241-2244.
11. Bottiglieri T (1996): Folate, vitamin B-12, and neuropsychiatric disorders. Nutr. Rev. 54, 382-390.
12. Brattström L & Wilcken DE (2000): Homocysteine and cardiovascular disease: cause or effect? Am. J. Clin. Nutr. 72, 315-323.
13. Brouwer DAJ, Welten HTME, Reijngoud DJ, Vandoormaal JJ & Muskiet FAJ (1998): Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine. Clin. Chem. 44, 1545-1550.
14. Carmel R, Sinow RM & Karnaze DS (1987): 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. 109, 454-463.
15. Chanarin I & Metz J (1998): Diagnosis of cobalamin deficiency: a reply. Br. J. Haematol. 100, 617-618.
16. Clarke R (1998): Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ 316, 894-898.
17. de Bree A, van Dusseldorp M, Brouwer IA, van bet Hof KH & Steegers-Theunissen RP (1997): Folate intake in europe: recommended, actual and desired intake. Eur. J. Clin. Nutr. 51, 643-660.
18. de Bree A, Verschuren WM, Blom HJ & Kromhout D (2001): Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am. J. Epidemiol. 154, 150-154.
19. Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF & Bottiglieri T (1997): Folate, vitamin B12, and homocysteine in major depressive disorder. Am. J. Psychiatry 154, 426-428.
20. Fioravanti M, Ferrario E, Massaia M, Cappa G, Rivolta G, Grossi E & Buckley AE (1997): Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch. Gerontol. Geriatr. 26, 1-13.
21. Haller J, Lowik MR, Ferry M & Ferro Luzzi A (1991): Nutritional status: blood vitamins A, E, B6, B12, folic acid and carotene. Euronut SENECA investigators. Eur. J. Clin. Nutr. 45(Suppl 3), 63-82.
22. Hathcock JN & Troendle GJ (1991): Oral cobalamin for treatment of pernicious anemia? JAMA 265, 96-97.
23. Healton EB, Savage DG, Brust JC, Garrett TJ & Lindenbaum J (1991): Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 70, 229-245.
24. Herrmann W, Quast S, Ullrich M, Schultze H, Bodis M & Geisel J (1999): Hyperhomocysteinemia in high-aged subjects: relation of b-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation. Atherosclerosis 144, 91-101.
25. Hussein WI, Green R, Jacobsen DW & Faiman C (1999): Normalization of hyperhomocysteinemia with l-thyroxine in hypothyroidism. Ann. Intern. Med. 131, 348-351.
26. Hvas AM, Ellegaard J & Nexo E (2001): Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study. Clin. Chem. 47, 1396-1404.
27. Hvas AM, Juul S, Gerdes LU & Nexo E (2000): The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine. J. Intern. Med. 247, 507-512.
28. Ihamäki T, Varis K & Siurala M (1979): Morphological, functional and immunological state of the gastric mucosa in gastric carcinoma families. Comparison with a computer-matched family sample. Scand. J. Gastroenterol. 11, 817-822.
29. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J & Rozen R (1996): Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7-9.
30. Jones BP, Broomhead AF, Kwan YL & Grace CS (1987): Incidence and clinical significance of protein-bound vitamin B12 malabsorption. Eur. J. Haematol. 38, 131-136.
31. Joosten E, van den Berg A, Riezler R, Naurath HJ, Lindenbaum J, Stabler SP & Allen RH (1993): Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate, and vitamin B-6 occur commonly in elderly people. Am. J. Clin. Nutr. 58, 468-476.
32. Kittang E & Schjönsby H (1987): Effect of gastric anacidity on the release of cobalamins from food and their subsequent binding to R-protein. Scand. J. Gastroenterol. 22, 1031-1037.
33. Krasinski SD, Russell RM, Samloff IM, Jacob RA, Dallal GE, McGandy RB & Hartz SC (1986): Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators. J. Am. Geriatr. Soc. 34, 800-806.
34. Lehmann M, Gottfries CG & Regland B (1999): Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dementia Geriatr. Cognitive Disorders 10, 12-20.
35. Lindenbaum J, Healton EB, Savage DG, Brust JCM, Garrett TJ, Podell ER, Marcell PD, Stabler SP & Allen RH (1988): Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N. Engl. J. Med. 318, 1720-1728.
36. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP & Allen RH (1994): Prevalence of cobalamin deficiency in the Framingham elderly population. Am. J. Clin. Nutr. 60, 2-11.
37. Lindenbaum J, Savage DG, Stabler SP & Allen RH (1990): Diagnosis of cobalamin deficiency II: relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am. J. Hematol. 34, 99-107.
38. Lindstedt G (1999): Nitrous oxide may cause cobalamin deficiency syndrome; vitamin B12 a simple and inexpensive remedy. Lakartidningen 96, 4801-4805.
39. Matthews JH (1995): Cobalamin and folate deficiency in the elderly. Baillieres. Clin. Haematol. 8, 679-697.
40. McKinley MC, McNulty H, McPartlin J, Strain JJ, Pentieva K, Ward M, Weir DG & Scott JM (2001): Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am. J. Clin. Nutr. 73, 759-764.
41. Molloy AM, Daly S, Mills JL, Kirke PN, Whitehead AS, Ramsbottom D, Conley MR, Weir DG & Scott JM (1997): Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349, 1591-1593.
42. Morgan SL, Baggott JE, Lee JY & Alarcon GS (1998): Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J. Rheumatol. 25, 441-446.
43. Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH & Lindenbaum J (1995): Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 346, 85-89.
44. Nilsson-Ehle H (1998): Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy. Drugs Aging 12, 277-292.
45. Nilsson-Ehle H, Jagenburg R, Landahl S, Lindstedt S, Svanborg A & Westin J (1991): Serum cobalamins in the elderly: a longitudinal study of a representative population sample from age 70 to 81. Eur. J. Haematol. 47, 10-16.
46. Nilsson-Ehle H, Landahl S, Lindstedt G, Netterblad L, Stockbruegger R, Westin J & Åhren C (1989): Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects. Dig. Dis. Sci. 34, 716-723.
47. Norlund L, Grubb A, Fex G, Leksell H, Nilsson JE, Schenck H & Hultberg B (1998): The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin. Chem. Lab. Med. 36, 175-178.
48. Nygård O, Refsum H, Ueland PM & Vollset SE (1998): Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland homocysteine study. Am. J. Clin. Nutr. 67, 263-270.
49. Olsson KS, Vaisanen M, Konar J & Bruce A (1997): The effect of withdrawal of food iron fortification in Sweden as studied with phlebotomy in subjects with genetic hemochromatosis. Eur. J. Clin. Nutr. 51, 782-786.
50. Rasmussen K (1989): Solid-phase sample extraction for rapid determination of methylmalonic acid in serum and urine by a stable-isotope-dilution method. Clin. Chem. 35, 260-264.
51. Rasmussen K & Möller J (2000): Total homocysteine measurement in clinical practice. Ann. Clin. Biochem. 37, 627-648.
52. Rasmussen K, Moller J, Lyngbak M, Pedersen AM & Dybkjaer L (1996): Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation [see comments]. Clin. Chem. 42, 630-636.
53. Rothenberg SP (1999): Increasing the dietary intake of folate: Pros and cons. Semin. Hematol. 36, 65-74.
54. Russell RM & Suter PM (1993): Vitamin requirements of elderly people: an update. Am. J. Clin. Nutr. 58, 4-14.
55. Schumann K (1999): Interactions between drugs and vitamins at advanced age. Int. J. Vitam. Nutr Res 69, 173-178.
56. Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW, Wright JD & Johnson CL (1999): 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. 131, 331-339.
57. Solberg HE (1983): The theory of reference values Part 5. Statistical treatment of collected reference values. Determination of reference limits. J. Clin. Chem. Clin. Biochem. 21, 749-760.
58. Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG & Lindenbaum J (1988): Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J. Clin. Invest. 81, 466-474.
59. Stolzenberg-Solomon RZ, Miller ER, Maguire MG, Selhub J & Appel LJ (1999): Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am. J. Clin. Nutr. 69, 467-475.
60. Streeter AM, Shum H-Y, Duncombe VM, Hewson JW & Thorpe MEC (1976): Vitamin B12 malabsorption associated with a normal Schilling test result. Med. J. Aust. 1, 54-55.
61. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R & Vermaak WJ (1996): The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J. Clin. Invest. 98, 177-184.
62. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, McPartlin J & Scott J (2001): Randomized trial of folic acid supplementation and serum homocysteine levels. Arch. Intern. Med. 161, 695-700.
63. Watanabe F, Abe K, Fujita T, Goto M, Hiemori M & Nakano Y (1998): Effects of microwave heating on the loss of vitamin B-12 in foods. J. Agric. Food Chem. 46, 206-210.
64. Webster SGP & Leeming JT (1979): Erythrocyte folate levels in young and old. J. Am. Geriatr. Soc. 27, 451-454.
65. Wharton B & Booth I (2001): Fortification of flour with folic acid. BMJ 323, 1198-1199.
66. Yao Y, Yao SL, Yao SS, Yao G & Lou W (1992): Prevalence of vitamin B12 deficiency among geriatric outpatients. J. Fam. Pract. 35, 524-528.
67. Zimmerman J, Selhub J & Rosenberg IH (1987): Competitive inhibition of folate absorption by dihydrofolate reductase inhibitors, trimethoprim and pyrimethamine. Am. J. Clin. Nutr. 46, 518-522.