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Age-associated B vitamin deficiency as a determinant of chronic diseases

Published online by Cambridge University Press:  14 December 2007

Patrick Brachet*
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Aurélie Chanson
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Christian Demigné
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Frédérique Batifoulier
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Marie-Cécile Alexandre-Gouabau
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Viviane Tyssandier
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
Edmond Rock
Affiliation:
Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès Champanelle, France
*
*Corresponding author: Dr Patrick Brachet, fax +33 4 73 62 47 46, email [email protected]
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Abstract

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The number of elderly individuals is growing rapidly worldwide and degenerative diseases constitute an increasing problem in terms of both public health and cost. Nutrition plays a role in the ageing process and there has been intensive research during the last decade on B vitamin-related risk factors in vascular and neurological diseases and cancers. Data from epidemiological studies indicate that subclinical deficiency in most water-soluble B vitamins may occur gradually during ageing, possibly due to environmental, metabolic, genetic, nutritional and pathological determinants, as well as to lifestyle, gender and drug consumption. Older adults have distinct absorption, cell transport and metabolism characteristics that may alter B vitamin bioavailability. Case–control and longitudinal studies have shown that, concurrent with an insufficient status of certain B vitamins, hyperhomocysteinaemia and impaired methylation reactions may be some of the mechanisms involved before a degenerative pathology becomes evident. The question that arises is whether B vitamin inadequacies contribute to the development of degenerative diseases or result from ageing and disease. The present paper aims to give an overview of these issues at the epidemiological, clinical and molecular levels and to discuss possible strategies to prevent B vitamin deficiency during ageing.

Type
Research Article
Copyright
Copyright © The Authors 2004

References

Achon, M, Alonso-Aperts, E & Varela-Moreiras, G (2002) High dietary folate supplementation: effects on diet utilization and methionine metabolism in aged rats. Journal of Nutrition, Health and Aging 6, 5154.Google ScholarPubMed
AFSSA & CNERNA-CNRS (2001) Apports Nutritionnels Conseillés pour la Population Française, 3rd ed. Paris: Technique & Documentation.Google Scholar
Amorim Cruz, JA, Moreiras, O & Brzozowska, A (1996) Longitudinal changes in the intake of vitamins and minerals of elderly Europeans. SENECA Investigators. European Journal of Clinical Nutrition 50, Suppl. 2, S77S85.Google ScholarPubMed
Baik, HW & Russell, RM (1999) Vitamin B12 deficiency in the elderly. Annual Review of Nutrition 19, 357377.CrossRefGoogle ScholarPubMed
Bailey, LB, Cerda, JJ, Bloch, BS, Busby, MJ, Vargas, L, Chandler, CJ & Halsted, CH (1984) Effect of age on poly– and monoglutamyl folacin absorption in human subjects. Journal of Nutrition 114, 17701776.CrossRefGoogle ScholarPubMed
Bailey, AL, Maisey, S, Southon, S, Wright, AJ, Finglas, PM & Fulcher, RA (1997) Relationships between micronutrient intake and biochemical indicators of nutrient adequacy in a ‘free–living’ elderly UK population. British Journal of Nutrition 77, 225242.CrossRefGoogle Scholar
Bailey, LB, Rampersaud, GC & Kauwell, GP (2003) Folic acid supplements and fortification affect the risk for neural tube defects, vascular disease and cancer: evolving science. Journal of Nutrition 133, 1961S1968S.CrossRefGoogle ScholarPubMed
Benderitter, M, Hadj-Saad, F, Lhuissier, M, Maupoil, V, Guilland, JC & Rochette, L (1996) Effects of exhaustive exercise and vitamin B6 deficiency on free radical oxidative process in male trained rats. Free Radical Biology and Medicine 21, 541549.CrossRefGoogle ScholarPubMed
Bernstein, MA, Tucker, KL, Ryan, ND, O'Neill, EF, Clements, KM, Nelson, ME, Evans, WJ & Fiatarone Singh, MA (2002) Higher dietary variety is associated with better nutritional status in frail elderly people. Journal of the American Dietetic Association 102, 10961104.CrossRefGoogle ScholarPubMed
Bird, CL, Swendseid, ME, Witte, JS, Shikany, JM, Hunt, IF, Frankl, HD, Lee, ER, Longnecker, MP & Haile, RW (1995) Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiology, Biomarkers and Prevention 4, 709714.Google ScholarPubMed
Björkegren, K & Svärdsudd, K (2001) Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes – a population–based study. Journal of Internal Medicine 249, 423432.CrossRefGoogle ScholarPubMed
Boisvert, WA, Castaneda, C, Mendoza, I, Langeloh, G, Solomons, NW, Gershoff, SN & Russell, RM (1993) Prevalence of riboflavin deficiency among Guatemalan elderly people and its relationship to milk intake. American Journal of Clinical Nutrition 58, 8590.CrossRefGoogle ScholarPubMed
Boushey, CJ, Beresford, SA, Omenn, GS & Motulsky, AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. Journal of the American Medical Association 274, 10491057.CrossRefGoogle ScholarPubMed
Broekmans, WM, Klopping-Ketelaars, IA, Schuurman, CR, Verhagen, H, van den Berg, H, Kok, FJ & van Poppel, G (2000) Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans. Journal of Nutrition 130, 15781583.CrossRefGoogle ScholarPubMed
Brouwer, IA, van Dusseldorp, M, West, CE, Meyboom, S, Thomas, CM, Duran, M, van het Hof, KH, Eskes, TK, Hautvast, JG & Steegers-Theunissen, RP (1999) Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. Journal of Nutrition 129, 11351139.CrossRefGoogle Scholar
Brouwer, IA, van Dusseldorp, M, West, CE & Steegers-Theunissen, RPM (2001) Bioavailability and bioefficacy of folate and folic acid in man. Nutrition Research Reviews 14, 267293.CrossRefGoogle ScholarPubMed
Camilo, E, Zimmerman, J, Mason, JB, Golner, B, Russell, R, Selhub, J & Rosenberg, IH (1996) Folate synthesized by bacteria in the human upper small intestine is assimilated by the host. Gastroenterology 110, 991998.CrossRefGoogle ScholarPubMed
Chasan-Taber, L, Selhub, J, Rosenberg, IH, Malinow, MR, Terry, P, Tishler, PV, Willett, W, Hennekens, CH & Stampfer, MJ (1996) A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians. Journal of the American College of Nutrition 15, 136143.CrossRefGoogle ScholarPubMed
Choi, SW & Mason, JB (2002) Folate status: effects on pathways of colorectal carcinogenesis. Journal of Nutrition 132, 2413S2418S.CrossRefGoogle ScholarPubMed
Choumenkovitch, SF, Selhub, J, Wilson, PW, Rader, JI, Rosenberg, IH & Jacques, PF (2002) Folic acid intake from fortification in United States exceeds predictions. Journal of Nutrition 132, 27922798.CrossRefGoogle ScholarPubMed
Clarke, R, Refsum, H, Birks, J, Evans, JG, Johnston, C, Sherliker, P, Ueland, PM, Schneede, J, McPartlin, J, Nexo, E & Scott, JM (2003) Screening for vitamin B–12 and folate deficiency in older individuals. American Journal of Clinical Nutrition 77, 12411247.CrossRefGoogle Scholar
de Bree, A, Verschuren, WM, Bjorke-Monsen, AL, van der Put, NM, Heil, SG, Trijbels, FJ & Blom, HJ (2003) Effect of the methylenetetrahydrofolate reductase 677C—T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. American Journal of Clinical Nutrition 77, 687693.CrossRefGoogle Scholar
de Jong, N, Paw, MJ, de Groot, LC, Rutten, RA, Swinkels, DW, Kok, FJ & van Staveren, WA (2001) Nutrient–dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning. American Journal of Clinical Nutrition 73, 338346.CrossRefGoogle Scholar
Desouza, C, Keebler, M, McNamara, DB & Fonseca, V (2002) Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs 62, 605616.CrossRefGoogle ScholarPubMed
Doshi, SN, McDowell, IF, Moat, SJ, Payne, N, Durrant, HJ, Lewis, MJ & Goodfellow, J (2002) Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation 105, 2226.CrossRefGoogle ScholarPubMed
Duan, W, Ladenheim, B, Cutler, RG, Kruman, II, Cadet, JL & Mattson, MP (2002) Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. Journal of Neurochemistry 80, 101110.CrossRefGoogle ScholarPubMed
Duell, PB & Malinow, MR (1997) Homocyst(e)ine: an important risk factor for atherosclerotic vascular disease. Current Opinion in Lipidology 8, 2834.CrossRefGoogle ScholarPubMed
Duthie, SJ, Narayanan, S, Brand, GM, Pirie, L & Grant, G (2002) Impact of folate deficiency on DNA stability. Journal of Nutrition 132, 2444S2449SCrossRefGoogle ScholarPubMed
Ervin, RB, Wright, JD & Kennedy-Stephenson, J (1999) Use of dietary supplements in the United States, 1988–94. Vital and Health Statistics. Series 11, iiii, 114.Google Scholar
Essama-Tjani, JC, Guilland, JC, Potier de Courcy, G, Fuchs, F & Richard, D (2000) Folate status worsens in recently institutionalized elderly people without evidence of functional deterioration. Journal of the American College of Nutrition 19, 392404.CrossRefGoogle ScholarPubMed
Eussen, SJ, Ferry, M, Hininger, I, Haller, J, Matthys, C & Dirren, H (2002) Five year changes in mental health and associations with vitamin B12/folate status of elderly Europeans. Journal of Nutrition, Health and Aging 6, 4350.Google ScholarPubMed
Expert Group on Vitamins and Minerals (2003) Safe upper levels for vitamins and minerals: report. www.foodstandards.gov.uk/science/ouradvisors/vitandmin/Google Scholar
Fenech, M (2002) Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food and Chemical Toxicology 40, 11131117.CrossRefGoogle ScholarPubMed
Feskanich, D, Singh, V, Willett, WC & Colditz, GA (2002) Vitamin A intake and hip fractures among postmenopausal women. Journal of the American Medical Association 287, 4754.CrossRefGoogle ScholarPubMed
Finkelstein, JD (1998) The metabolism of homocysteine: pathways and regulation. European Journal of Pediatrics 157, Suppl. 2, S40S44.CrossRefGoogle Scholar
Flood, VM, Webb, KL, Smith, W, Mitchell, P, Bantick, JM, Macintyre, R, Sindhusake, D & Rubin, GL (2001) Folate fortification: potential impact on folate intake in an older population. European Journal of Clinical Nutrition 55, 793800.CrossRefGoogle Scholar
Folsom, AR, Nieto, FJ, McGovern, PG, Tsai, MY, Malinow, MR, Eckfeldt, JH, Hess, DL & Davis, CE (1998) Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 98, 204210.CrossRefGoogle Scholar
Fuchs, CS, Willett, WC, Colditz, GA, Hunter, DJ, Stampfer, MJ, Speizer, FE & Giovannucci, EL (2002) The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiology, Biomarkers and Prevention 11, 227234.Google ScholarPubMed
Gastaldi, G, Laforenza, U, Ferrari, G, Casasco, A & Rindi, G (1992) Age–related thiamin transport by small intestinal microvillous vesicles of rat. Biochimica Biophysica Acta 1105, 271277.CrossRefGoogle ScholarPubMed
Ghandour, H, Lin, BF, Choi, SW, Mason, JB & Selhub, J (2002) Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins. Journal of Nutrition 132, 13571360.CrossRefGoogle ScholarPubMed
Giles, WH, Kittner, SJ, Croft, JB, Anda, RF, Casper, ML & Ford, ES (1998) Serum folate and risk for coronary heart disease: results from a cohort of US adults. Annals of Epidemiology 8, 490496.CrossRefGoogle ScholarPubMed
Giovannucci, E (2002) Epidemiologic studies of folate and colorectal neoplasia: a review. Journal of Nutrition 132, 2350S2355S.CrossRefGoogle ScholarPubMed
Gold, M, Chen, MF & Johnson, K (1995) Plasma and red blood cell thiamine deficiency in patients with dementia of the Alzheimer's type. Archives of Neurology 52, 10811086.CrossRefGoogle ScholarPubMed
Gonzalez-Gross, M, Marcos, A & Pietrzik, K (2001) Nutrition and cognitive impairment in the elderly. British Journal of Nutrition 86, 313321.CrossRefGoogle ScholarPubMed
Gregory, JF III (1998) Nutritional properties and significance of vitamin glycosides. Annual Review of Nutrition 18, 277296.CrossRefGoogle ScholarPubMed
Gregory, JF III & Quinlivan, EP (2002) In vivo kinetics of folate metabolism. Annual Review of Nutrition 22, 199220.CrossRefGoogle ScholarPubMed
Haller, J (1999) The vitamin status and its adequacy in the elderly: an international overview. International Journal for Vitamin and Nutrition Research 69, 160168.CrossRefGoogle ScholarPubMed
Hartman, TJ, Woodson, K, Stolzenberg-Solomon, R, Virtamo, J, Selhub, J, Barrett, MJ & Albanes, D (2001) Association of the B-vitamins pyridoxal 5′–phosphate (B(6)), B(12), and folate with lung cancer risk in older men. American Journal of Epidemiology 153, 688694.CrossRefGoogle Scholar
Heijmans, BT, Boer, JM, Suchiman, HE, Cornelisse, CJ, Westendorp, RG, Kromhout, D, Feskens, EJ & Slagboom, PE (2003) A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Research 63, 12491253.Google ScholarPubMed
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, 91101.CrossRefGoogle ScholarPubMed
Hirsch, S, de la Maza, P, Barrera, G, Gattas, V, Petermann, M & Bunout, D (2002 a) The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people. Journal of Nutrition 132, 289291.CrossRefGoogle ScholarPubMed
Hirsch, S, de la Maza, P, Mendoza, L, Petermann, M, Glasinovic, A, Paulinelli, P, Barrera, G, Rosenberg, IH & Bunout, D (2002 b) Endothelial function in healthy younger and older hyperhomocysteinemic subjects. Journal of the American Geriatrics Society 50, 10191023.CrossRefGoogle ScholarPubMed
Homocysteine Lowering Trialists' Collaboration (1998) Lowering blood homocysteine with folic acid based supplements: meta–analysis of randomised trials. British Medical Journal 316, 894898.CrossRefGoogle Scholar
Howard, JM, Azen, C, Jacobsen, DW, Green, R & Carmel, R (1998) Dietary intake of cobalamin in elderly people who have abnormal serum cobalamin, methylmalonic acid and homocysteine levels. European Journal of Clinical Nutrition 52, 582587.CrossRefGoogle ScholarPubMed
Huang, RF, Hsu, YC, Lin, HL & Yang, FL (2001) Folate depletion and elevated plasma homocysteine promote oxidative stress in rat livers. Journal of Nutrition 131, 3338.CrossRefGoogle ScholarPubMed
Institute of Medicine National Academy of Sciences (1998) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline Washington, DC: National Academy Press. www.iom.edu/Google Scholar
Jacques, PF, Bostom, AG, Wilson, PW, Rich, S, Rosenberg, IH & Selhub, J (2001) Determinants of plasma total homocysteine concentration in the Framingham offspring cohort. American Journal of Clinical Nutrition 73, 613621.CrossRefGoogle ScholarPubMed
Jacques, PF, Rosenberg, IH, Rogers, G, Selhub, J, Bowman, BA, Gunter, EW, Wright, JD & Johnson, CL (1999 a) Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. American Journal of Clinical Nutrition 69, 482489.CrossRefGoogle ScholarPubMed
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PW & Rosenberg, IH (1999 b) The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New England Journal of Medicine 340, 14491454.CrossRefGoogle ScholarPubMed
James, SJ, Melnyk, S, Pogribna, M, Pogribny, IP & Caudill, MA (2002) Elevation in S–adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine–related pathology. Journal of Nutrition 132, 2361S2366S.CrossRefGoogle ScholarPubMed
Jatoi, A, Daly, BD, Kramer, G & Mason, JB (2001) Folate status among patients with non–small cell lung cancer: a case–control study. Journal of Surgery and Oncology 77, 247252.CrossRefGoogle ScholarPubMed
Jimenez-Jimenez, FJ, Molina, JA, Hernanz, A, Fernandez-Vivancos, E, de Bustos, F, Barcenilla, B, Gomez-Escalonilla, C, Zurdo, M, Berbel, A & Villanueva, C (1999) Cerebrospinal fluid levels of thiamine in patients with Parkinson's disease. Neuroscience Letters 271, 3336.CrossRefGoogle ScholarPubMed
Joshi, R, Adhikari, S, Patro, BS, Chattopadhyay, S & Mukherjee, T (2001) Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radical Biology and Medicine 30, 13901399.CrossRefGoogle ScholarPubMed
Kalmijn, S, Launer, LJ, Lindemans, J, Bots, ML, Hofman, A & Breteler, MM (1999) Total homocysteine and cognitive decline in a community–based sample of elderly subjects: the Rotterdam Study. American Journal of Epidemiology 150, 283289.CrossRefGoogle Scholar
Kauwell, GP, Lippert, BL, Wilsky, CE, Herrlinger-Garcia, K, Hutson, AD, Theriaque, DW, Rampersaud, GC, Cerda, JJ & Bailey, LB (2000) Folate status of elderly women following moderate folate depletion responds only to a higher folate intake. Journal of Nutrition 130, 15841590.CrossRefGoogle ScholarPubMed
Kesavan, V & Noronha, JM (1983) Folate malabsorption in aged rats related to low levels of pancreatic folyl conjugase. American Journal of Clinical Nutrition 37, 262267.CrossRefGoogle ScholarPubMed
Khosraviani, K, Weir, HP, Hamilton, P, Moorehead, J & Williamson, K (2002) Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut 51, 195199.CrossRefGoogle ScholarPubMed
Klerk, M, Verhoef, P, Clarke, R, Blom, HJ, Kok, FJ & Schouten, EG (2002) MTHFR 677C → T polymorphism and risk of coronary heart disease: a meta–analysis. Jama 288, 20232031.CrossRefGoogle ScholarPubMed
Konings, EJ, Goldbohm, RA, Brants, HA, Saris, WH & Van Den Brandt, PA (2002) Intake of dietary folate vitamers and risk of colorectal carcinoma. Cancer 95, 14211433.CrossRefGoogle ScholarPubMed
Lamprecht, SA & Lipkin, M (2003) Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nature Reviews. Cancer 3, 601614.CrossRefGoogle ScholarPubMed
Lang, D, Kredan, MB, Moat, SJ, Hussain, SA, Powell, CA, Bellamy, MF, Powers, HJ & Lewis, MJ (2000) Homocysteine–induced inhibition of endothelium–dependent relaxation in rabbit aorta: role for superoxide anions. Arteriosclerosis, Thrombosis and Vascular Biology 20, 422427.CrossRefGoogle ScholarPubMed
Le Marchand, L, Donlon, T, Hankin, JH, Kolonel, LN, Wilkens, LR & Seifried, A (2002) B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes and Control 13, 239248.CrossRefGoogle ScholarPubMed
Lievers, KJ, Kluijtmans, LA & Blom, HJ (2003) Genetics of hyperhomocysteinaemia in cardiovascular disease. Annals of Clinical Biochemistry 40, 4659.CrossRefGoogle ScholarPubMed
Lindeman, RD, Romero, LJ, Koehler, KM, Liang, HC, LaRue, A, Baumgartner, RN & Garry, PJ (2000) Serum vitamin B12, C and folate concentrations in the New Mexico elder health survey: correlations with cognitive and affective functions. Journal of the American College of Nutrition 19, 6876.CrossRefGoogle Scholar
Lopez-Sobaler, AM, Ortega, RM, Quintas, ME, Navarro, AR, Aparicio, A, Gomez-Rodriguez, N, Cocho, M & Requejo, AM (2002) The influence of vitamin B2 intake on the activation coefficient of erythrocyte glutation reductase in the elderly. Journal of Nutrition, Health and Aging 6, 6062.Google ScholarPubMed
Ma, J, Stampfer, MJ, Giovannucci, E, Artigas, C, Hunter, DJ, Fuchs, C, Willett, WC, Selhub, J, Hennekens, CH & Rozen, R (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Research 57, 10981102.Google ScholarPubMed
McKay, DL, Perrone, G, Rasmussen, H, Dallal, G & Blumberg, JB (2000) Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate–fortified diet. Journal of Nutrition 130, 30903096.CrossRefGoogle ScholarPubMed
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. American Journal of Clinical Nutrition 73, 759764.CrossRefGoogle ScholarPubMed
McKinley, MC, McNulty, H, McPartlin, J, Strain, JJ & Scott, JM (2002) Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status. European Journal of Clinical Nutrition 56, 850856.CrossRefGoogle ScholarPubMed
McNulty, H, McKinley, MC, Wilson, B, McPartlin, J, Strain, JJ, Weir, DG & Scott, JM (2002) Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements. American Journal of Clinical Nutrition 76, 436441.CrossRefGoogle ScholarPubMed
Madigan, SM, Tracey, F, McNulty, H, Eaton-Evans, J, Coulter, J, McCartney, H & Strain, JJ (1998) Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free–living elderly people. American Journal of Clinical Nutrition 68, 389395.CrossRefGoogle ScholarPubMed
Malinow, MR, Duell, PB, Hess, DL, Anderson, PH, Kruger, WD, Phillipson, BE, Gluckman, RA, Block, PC & Upson, BM (1998) Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. New England Journal of Medicine 338, 10091015.CrossRefGoogle ScholarPubMed
Marshall, TA, Stumbo, PJ, Warren, JJ & Xie, XJ (2001) Inadequate nutrient intakes are common and are associated with low diet variety in rural, community–dwelling elderly. Journal of Nutrition 131, 21922196.CrossRefGoogle ScholarPubMed
Mason, JB (2003) Biomarkers of nutrient exposure and status in one–carbon (methyl) metabolism. Journal of Nutrition 133, Suppl. 3, 941S947S.CrossRefGoogle ScholarPubMed
Mattson, MP, Kruman, II & Duan, W (2002) Folic acid and homocysteine in age–related disease. Ageing Research Reviews 1, 95111.CrossRefGoogle ScholarPubMed
Maxwell, CJ, Hogan, DB & Ebly, EM (2002) Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly persons. Dementia and Geriatric Cognitive Disorders 13, 225234.CrossRefGoogle ScholarPubMed
Medrano, MJ, Sierra, MJ, Almazan, J, Olalla, MT & Lopez-Abente, G (2000) The association of dietary folate, B6, and B12 with cardiovascular mortality in Spain: an ecological analysis. American Journal of Public Health 90, 16361638.Google ScholarPubMed
Meleady, R, Ueland, PM, Blom, H, Whitehead, AS, Refsum, H, Daly, LE, Vollset, SE, Donohue, C, Giesendorf, B, Graham, IM, Ulvik, A, Zhang, Y & Bjorke Monsen, AL (2003) Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. American Journal of Clinical Nutrition 77, 6370.CrossRefGoogle ScholarPubMed
Meltzer, HM, Aro, A, Andersen, NL, Koch, B & Alexander, J (2003) Risk analysis applied to food fortification. Public Health Nutrition 6, 281291.CrossRefGoogle ScholarPubMed
Miller, JW, Green, R, Mungas, DM, Reed, BR & Jagust, WJ (2002) Homocysteine, vitamin B6, and vascular disease in AD patients. Neurology 58, 14711475.CrossRefGoogle ScholarPubMed
Miller, JW, Green, R, Ramos, MI, Allen, LH, Mungas, DM, Jagust, WJ & Haan, MN (2003) Homocysteine and cognitive function in the Sacramento Area Latino Study on Aging. American Journal of Clinical Nutrition 78, 441447.CrossRefGoogle Scholar
Moat, SJ, Bonham, JR, Cragg, RA & Powers, HJ (2000) Elevated plasma homocysteine elicits an increase in antioxidant enzyme activity. Free Radical Research 32, 171179.CrossRefGoogle ScholarPubMed
Moat, SJ, Hill, MH, McDowell, IF, Pullin, CH, Ashfield-Watt, PA, Clark, ZE, Whiting, JM, Newcombe, RG, Lewis, MJ & Powers, HJ (2003) Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage. European Journal of Clinical Nutrition 57, 483489.CrossRefGoogle ScholarPubMed
Nichols, HK & Basu, TK (1994) Thiamin status of the elderly: dietary intake and thiamin pyrophosphate response. Journal of the American College of Nutrition 13, 5761.CrossRefGoogle ScholarPubMed
Niculescu, MD & Zeisel, SH (2002) Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. Journal of Nutrition 132, 2333S2335S.CrossRefGoogle ScholarPubMed
Nightingale, AK, James, PP, Morris-Thurgood, J, Harrold, F, Tong, R, Jackson, SK, Cockcroft, JR & Frenneaux, MP (2001) Evidence against oxidative stress as mechanism of endothelial dysfunction in methionine loading model. American Journal of Physiology 280, H1334H1339.Google ScholarPubMed
Nygard, O, Vollset, SE, Refsum, H, Stensvold, I, Tverdal, A, Nordrehaug, JE, Ueland, M & Kvale, G (1995) Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. Journal of the American Medical Association 274, 15261533.CrossRefGoogle ScholarPubMed
Olivares, M, Hertrampf, E, Capurro, MT & Wegner, D (2000) Prevalence of anemia in elderly subjects living at home: role of micronutrient deficiency and inflammation. European Journal of Clinical Nutrition 54, 834839.CrossRefGoogle ScholarPubMed
Olszewski, AJ & McCully, KS (1993) Homocysteine metabolism and the oxidative modification of proteins and lipids. Free Radical Biololgy and Medicine 14, 683693.CrossRefGoogle Scholar
Platz, EA, Giovannucci, E, Rimm, EB, Rockett, HR, Stampfer, MJ, Colditz, GA & Willett, WC (1997) Dietary fiber and distal colorectal adenoma in men. Cancer Epidemiology, Biomarkers and Prevention 6, 661670.Google ScholarPubMed
Potter, JD (2002) Methyl supply, methyl metabolizing enzymes and colorectal neoplasia. Journal of Nutrition 132, 2410S2412S.CrossRefGoogle ScholarPubMed
Quinlivan, EP, McPartlin, J, McNulty, H, Ward, M, Strain, JJ, Weir, DG & Scott, JM (2002) Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 359, 227228.CrossRefGoogle ScholarPubMed
Quinn, K & Basu, TK (1996) Folate and vitamin B12 status of the elderly. European Journal of Clinical Nutrition 50, 340342.Google ScholarPubMed
Raghuveer, G, Sinkey, CA, Chenard, C, Stumbo, P & Haynes, WG (2001) Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. American Journal of Cardiology 88, 285290.CrossRefGoogle ScholarPubMed
Rampersaud, GC, Kauwell, GP, Hutson, AD, Cerda, JJ & Bailey, LB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. American Journal of Clinical Nutrition 72, 9981003.CrossRefGoogle ScholarPubMed
Ravaglia, G, Forti, P, Maioli, F, Bastagli, L, Facchini, A, Mariani, E, Savarino, L, Sassi, S, Cucinotta, D & Lenaz, G (2000) Effect of micronutrient status on natural killer cell immune function in healthy free–living subjects aged >/=90 y. American Journal of Clinical Nutrition 71, 590598.CrossRefGoogle ScholarPubMed
Ravaglia, G, Forti, P, Maioli, F, Muscari, A, Sacchetti, L, Arnone, G, Nativio, V, Talerico, T & Mariani, E (2003) Homocysteine and cognitive function in healthy elderly community dwellers in Italy. American Journal of Clinical Nutrition 77, 668673.CrossRefGoogle ScholarPubMed
Ray, JG, Vermeulen, MJ, Boss, SC & Cole, DE (2002) Declining rate of folate insufficiency among adults following increased folic acid food fortification in Canada. Canadian Journal of Public Health 93, 249253.CrossRefGoogle ScholarPubMed
Robinson, K, Arheart, K, Refsum, H, Brattstrom, L, Boers, G, Ueland, P, Rubba, P, Palma-Reis, R, Meleady, R, Daly, L, Witteman, J & Graham, I (1998) Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC group. Circulation 97, 437443.CrossRefGoogle ScholarPubMed
Rooprai, HK, Pratt, OE, Shaw, GK & Thomson, AD (1990) The age dependence of the activity and activation of human red blood cell transketolase. Alcohol and Alcoholism 25, 453456.Google ScholarPubMed
Rucker, RB (editor) (2001) Handbook of Vitamins, 3rd ed. New York and Basel: Marcel Dekker Inc.Google Scholar
Russell, RM (2000) The aging process as a modifier of metabolism. American Journal of Clinical Nutrition 72, 529S532S.CrossRefGoogle ScholarPubMed
Russell, RM, Baik, H & Kehayias, JJ (2001) Older men and women efficiently absorb vitamin B-12 from milk and fortified bread. Journal of Nutrition 131, 291293.CrossRefGoogle ScholarPubMed
Savage, DG, Lindenbaum, J, Stabler, SP & Allen, RH (1994) Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. American Journal of Medicine 96, 239246.CrossRefGoogle ScholarPubMed
Saw, SM, Yuan, JM, Ong, CN, Arakawa, K, Lee, HP, Coetzee, GA & Yu, MC (2001) Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle–aged and older Chinese men and women in Singapore. American Journal of Clinical Nutrition 73, 232239.CrossRefGoogle ScholarPubMed
Seekamp, A, Hultquist, DE & Till, GO (1999) Protection by vitamin B2 against oxidant–mediated acute lung injury. Inflammation 23, 449460.CrossRefGoogle ScholarPubMed
Selhub, J, Jacques, PF, Wilson, PW, Rush, D & Rosenberg, IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Journal of the American Medical Association 270, 26932698.CrossRefGoogle Scholar
Selley, ML, Close, DR & Stern, SE (2002) The effect of increased concentrations of homocysteine on the concentration of (E)–4–hydroxy–2–nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiology of Aging 23, 383388.CrossRefGoogle ScholarPubMed
Seshadri, S, Beiser, A, Selhub, J, Jacques, PF, Rosenberg, IH, D'Agostino, RB, Wilson, PW & Wolf, PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer·s disease. New England Journal of Medicine 346, 476483.CrossRefGoogle ScholarPubMed
Shannon, B, Gnanasampanthan, S, Beilby, J & Iacopetta, B (2002) A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability. Gut 50, 520524.CrossRefGoogle ScholarPubMed
Shimizu, H, Kiyohara, Y, Kato, I, Tanizaki, Y, Ueno, H, Kimura, Y, Iwamoto, H, Kubo, M, Arima, H, Ibayashi, S & Fujishima, M (2002) Plasma homocyst(e)ine concentrations and the risk of subtypes of cerebral infarction. The Hisayama study. Cerebrovascular Diseases 13, 915.CrossRefGoogle ScholarPubMed
Smidt, LJ, Cremin, FM, Grivetti, LE & Clifford, AJ (1991) Influence of thiamin supplementation on the health and general well–being of an elderly Irish population with marginal thiamin deficiency. Journal of Gerontology 46, M16M22.CrossRefGoogle ScholarPubMed
Stern, LL, Mason, JB, Selhub, J & Choi, SW (2000) Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiology, Biomarkers and Prevention 9, 849853.Google ScholarPubMed
Stolzenberg-Solomon, RZ, Albanes, D, Nieto, FJ, Hartman, TJ, Tangrea, JA, Rautalahti, M, Sehlub, J, Virtamo, J & Taylor, PR (1999) Pancreatic cancer risk and nutrition–related methyl–group availability indicators in male smokers. Journal of the National Cancer Institute 91, 535541.CrossRefGoogle ScholarPubMed
Su, LJ & Arab, L (2001) Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow–up study. Annals of Epidemiology 11, 6572.CrossRefGoogle ScholarPubMed
Sydow, K, Schwedhelm, E, Arakawa, N, Bode-Boger, SM, Tsikas, D, Hornig, B, Frolich, JC & Boger, RH (2003) ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovascular Research 57, 244252.CrossRefGoogle ScholarPubMed
Symons, JD, Mullick, AE, Ensunsa, JL, Ma, AA & Rutledge, JC (2002) Hyperhomocysteinemia evoked by folate depletion: effects on coronary and carotid arterial function. Arteriosclerosis, Thrombosis and Vascular Biology 22, 772780.CrossRefGoogle ScholarPubMed
Teunissen, CE, Blom, AH, Van Boxtel, MP, Bosma, H, de Bruijn, C, Jolles, J, Wauters, BA, Steinbusch, HW & de Vente, J (2003) Homocysteine: a marker for cognitive performance? A longitudinal follow–up study. Journal of Nutrition, Health and Aging 7, 153159.Google ScholarPubMed
Tiemeier, H, van Tuijl, HR, Hofman, A, Meijer, J, Kiliaan, AJ & Breteler, MM (2002) Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. American Journal of Psychiatry 159, 20992101.CrossRefGoogle ScholarPubMed
Tucker, KL, Rich, S, Rosenberg, I, Jacques, P, Dallal, G, Wilson, PW & Selhub, J (2000) Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. American Journal of Clinical Nutrition 71, 514522.CrossRefGoogle ScholarPubMed
van Asselt, DZ, de Groot, LC, van Staveren, WA, Blom, HJ, Wevers, RA, Biemond, I & Hoefnagels, WH (1998) Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. American Journal of Clinical Nutrition 68, 328334.CrossRefGoogle ScholarPubMed
van Asselt, DZ, Pasman, JW, van Lier, HJ, Vingerhoets, DM, Poels, PJ, Kuin, Y, Blom, HJ & Hoefnagels, WH (2001) Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin–deficient persons. Journal of Gerontology 56A, M775M779.Google Scholar
van den Berg, H (1999) Vitamin B6 status and requirements in older adults. British Journal of Nutrition 81, 175176.CrossRefGoogle ScholarPubMed
van den Berg, H, van der Gaag, M & Hendriks, H (2002) Influence of lifestyle on vitamin bioavailability. International Journal for Vitamin and Nutrition Research 72, 5359.CrossRefGoogle ScholarPubMed
van der Wielen, RP, Lowik, MR, Haller, J, van den Berg, H, Ferry, M & van Staveren, WA (1996) Vitamin B-6 malnutrition among elderly Europeans: the SENECA study. Journal of Gerontology 51A, B417B424.Google Scholar
Ventura, P, Panini, R, Verlato, C, Scarpetta, G & Salvioli, G (2001) Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. Metabolism 50, 14661471.CrossRefGoogle ScholarPubMed
Verhaar, MC, Wever, RM, Kastelein, JJ, van Dam, T, Koomans, HA & Rabelink, TJ (1998) 5–methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 97, 237241.CrossRefGoogle ScholarPubMed
Voorrips, LE, Goldbohn, RA, Brants, HA, van Poppel, GA, Sturmans, F, Hermus, RV & van den Brandt, PA (2000) A prospective cohort study on antioxidant and folate intake and male lung cancer risk. Cancer Epidemiology Biomarkers & Prevention 9, 357365.Google ScholarPubMed
Wald, DS, Law, M & Morris, JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta–analysis. British Medical Journal 325, 1202.CrossRefGoogle ScholarPubMed
Wilkinson, TJ, Hanger, HC, George, PM & Sainsbury, R (2000) Is thiamine deficiency in elderly people related to age or co–morbidity? Age and Ageing 29, 111116.CrossRefGoogle ScholarPubMed
Woo, KS, Chook, P, Chan, LL, Cheung, AS, Fung, WH, Qiao, M, Lolin, YI, Thomas, GN, Sanderson, JE, Metreweli, C & Celermajer, DS (2002) Long–term improvement in homocysteine levels and arterial endothelial function after 1–year folic acid supplementation. American Journal of Medicine 112, 535539.CrossRefGoogle ScholarPubMed
Wright, AJ, Finglas, PM, Dainby, JR, Hart, DJ, Wolfe, CA, Southon, S & Gregory, JF (2003) Single oral doses of 13C forms of pteroylmonoglutamic acid and 5–formyltetrahydrofolic acid elicit differences in short–term kinetics of labelled and unlabelled folates in plasma: potential problems in interpretation of folate bioavailability studies. British Journal of Nutrition 90, 363371.CrossRefGoogle Scholar
Zhang, SM, Willett, WC, Selhub, J, Hunter, DJ, Giovannucci, EL, Holmes, MD, Colditz, GA & Hankinson, SE (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. Journal of the National Cancer Institute 95, 373380.CrossRefGoogle ScholarPubMed
Zhang, X, Li, H, Jin, H, Ebin, Z, Brodsky, S & Goligorsky, MS (2000) Effects of homocysteine on endothelial nitric oxide production. American Journal of Physiology 279, F671F678.Google ScholarPubMed
Ziegler, RG, Weinstein, SJ & Fears, TR (2002) Nutritional and genetic inefficiencies in one–carbon metabolism and cervical cancer risk. Journal of Nutrition 132, 2345S2349S.CrossRefGoogle ScholarPubMed