Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
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Ralph Green
Abstract
Prevalence rates for folate deficiency and hyperhomocysteinemia have been markedly reduced following the introduction of folic acid fortification in the United States. We report the prevalence of hyperhomocysteinemia in a population of community-dwelling elderly Latinos in the post-folic acid fortification era. We measured homocysteine, total vitamin B12, holotranscobalamin, red blood cell folate, and serum creatinine in 1096 subjects aged ≥60years. Hyperhomocysteinemia (>13μmol/L) was observed in 16.5% of the subjects. The population attributable risk percentages for hyperhomocysteinemia were 29.7% for total B12 <148pmol/L, 36.4% for holotranscobalamin <35pmol/L, and 41.4% for creatinine >115μmol/L. In contrast, the population attributable risk percentage for hyperhomocysteinemia was only 0.3% for red blood cell folate <365nmol/L. We conclude that in the post-folic acid fortification era, low vitamin B12 status has become the dominant nutritional determinant of hyperhomocysteinemia. Steps to either reduce the prevalence of vitamin B12 deficiency or to identify and treat individuals with vitamin B12 deficiency could further reduce the prevalence of hyperhomocysteinemia.
References
1. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49:31–62.10.1146/annurev.med.49.1.31Search in Google Scholar
2. McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum homocysteine in senile dementia of the Alzheimer's type. Int J Geriatr Psychiatry 1998; 13:235–9.10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8Search in Google Scholar
3. Lehmann M, Gottfries CG, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dementia Geriatr Cogn Disord 1999; 10:12–20.10.1159/000017092Search in Google Scholar
4. Riggs KM, Spiro A, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 1996; 63:306–14.10.1093/ajcn/63.3.306Search in Google Scholar
5. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 2001; 73:927–33.10.1093/ajcn/73.5.927Search in Google Scholar
6. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002; 75:908–13.10.1093/ajcn/75.5.908Search in Google Scholar
7. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002; 346:476–83.10.1056/NEJMoa011613Search in Google Scholar
8. McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004; 350:2042–9.10.1056/NEJMoa032739Search in Google Scholar
9. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004; 350:2033–41.10.1056/NEJMoa032546Search in Google Scholar
10. Mills JL, Signore C. Neural tube defect rates before and after food fortification with folic acid. Birth Defects Res A Clin Mol Teratol 2004; 70;844–5.10.1002/bdra.20075Search in Google Scholar
11. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 340:1449–54.10.1056/NEJM199905133401901Search in Google Scholar PubMed
12. Wright JD, Bialostosky K, Gunter EW, Carroll MD, Najjar MF, Bowman BA, et al. Blood folate and vitamin B12: United States, 1988–94. Vital Health Stat 11 1998; 243:1–78.Search in Google Scholar
13. Liaugaudas G, Jacques PF, Selhub J, Rosenberg IH, Bostom AG. Renal insufficiency, vitamin B(12) status, and population attributable risk for mild hyperhomocysteinemia among coronary artery disease patients in the era of folic acid-fortified cereal grain flour. Arterioscler Thromb Vasc Biol 2001; 21;849–51.10.1161/01.ATV.21.5.849Search in Google Scholar
14. Wu CC, Mungas D, Petkov CI, Eberling JL, Zrelak PA, Buonocore MH, et al. Brain structure and cognition in a community sample of elderly Latinos. Neurology 2002; 59:383–91.10.1212/WNL.59.3.383Search in Google Scholar
15. Miller JW, Green R, Ramos MI, Allen LH, Mungas DM, Jagust WJ, et al. Homocysteine and cognitive function in the Sacramento Area Latino Study on Aging (SALSA). Am J Clin Nutr 2003; 78:441–7.10.1093/ajcn/78.3.441Search in Google Scholar PubMed
16. Miller JW, Garrod MG, Rockwood AL, Kushnir MM, Allen LH, Haan MN, et al. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem. Submitted for publication.Search in Google Scholar
17. Gilfix BM, Blank DW, Rosenblatt DS. Novel reductant for determination of total plasma homocysteine. Clin Chem 1997; 43:687–8.10.1093/clinchem/43.4.687Search in Google Scholar
18. Ulleland M, Eilertsen I, Quadros EV, Rothenberg SP, Fedosov SN, Sundrehagen E, et al. Direct assay for cobalamin bound to transcobalamin (holotranscobalamin) in serum. Clin Chem 2002; 48:526–32.10.1093/clinchem/48.3.526Search in Google Scholar
19. Herzlich B, Herbert V. Depletion of serum holotranscobalamin II: an early sign of negative vitamin B12 balance. Lab Invest 1988; 58:332–7.Search in Google Scholar
20. 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; 41:1478–88.10.1515/CCLM.2003.227Search in Google Scholar PubMed
21. Lindgren A, Kilander A, Bagge E, Nexo E. Holotranscobalamin − a sensitive marker of cobalamin malabsorption. Eur J Clin Invest 1999; 29:321–9.10.1046/j.1365-2362.1999.00446.xSearch in Google Scholar PubMed
22. Hennekens CH, Buring JE. Epidemiology in medicine. Boston, MA: Little Brown and Co, 1987.Search in Google Scholar
23. Carmel R, Vasireddy H, Aurangzeb I, George K. High serum cobalamin levels in the clinical setting: clinical associations and holo-transcobalamin changes. Clin Lab Haematol 2001; 23:365–71.10.1046/j.1365-2257.2001.00134.xSearch in Google Scholar PubMed
24. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J Am Med Assoc 1993; 270:2693–8.10.1001/jama.1993.03510220049033Search in Google Scholar PubMed
25. Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate, and homocysteine. Hematology (Am Soc Hematol Educ Program) 2003; 2003:62–81.10.1182/asheducation-2003.1.62Search in Google Scholar
26. Ray JG, Cole DE, Boss SC. An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise? Clin Biochem 2000; 33:337–43.10.1016/S0009-9120(00)00083-7Search in Google Scholar
27. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. J Am Med Assoc 1995; 274:1049–57.10.1001/jama.1995.03530130055028Search in Google Scholar PubMed
©2005 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
