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Dietary predictors of plasma total homocysteine in the Hordaland Homocysteine Study

  • Svetlana V. Konstantinova (a1), Stein Emil Vollset (a1), Paula Berstad (a2), Per Magne Ueland (a3), Christian A. Drevon (a2), Helga Refsum (a2) (a4) and Grethe S. Tell (a1)...


Established dietary predictors of plasma total homocysteine (tHcy) include folate, riboflavin, and vitamins B6 and B12, while information is scarce regarding other dietary components. The aim of this study was to examine the relation between a variety of food groups, food items and nutrients, and plasma tHcy in a large population-based study. The study population included 5812 men and women aged 47–49 and 71–74 years who completed a 169-item FFQ. tHcy was examined across quartiles of dietary components by multiple linear regression analyses adjusting for age, sex, energy intake, various risk factors for elevated tHcy, as well as for dietary and plasma B-vitamins. Among 4578 non-users of vitamin supplements, intake of vegetables, fruits, cereals, eggs, fish and milk, as well as chicken and non-processed meats were inversely associated with tHcy level. The estimated mean difference in tHcy per increasing quartile of intake ranged from − 0·11 (95 % CI − 0·21, − 0·01) μmol/l for milk to − 0·32 (95 % CI − 0·42, − 0·22) μmol/l for vegetables. Positive associations were found for sweets and cakes. Whole-grain bread was significantly inversely related to tHcy only after additional adjustment for dietary and plasma B-vitamins. The nutrients folate, vitamin B6, B12, and riboflavin were inversely related to tHcy. Complex carbohydrates were inversely, and fat positively associated with tHcy, also after adjustment for dietary and plasma B-vitamins. In conclusion, food items rich in B-vitamins and with a low content of fat and sugar were related to lower tHcy levels. Eggs, chicken, non-processed meat, fish and milk were inversely associated with tHcy.

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Corresponding author

*Corresponding author: Dr Svetlana V. Konstantinova, fax +47 555 86 130, email


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Andersen, LF, Nes, M, Lillegaard, IT, Sandstad, B, Bjorneboe, GE & Drevon, CA (1995) Evaluation of a quantitative food frequency questionnaire used in a group of Norwegian adolescents. Eur J Clin Nutr 49, 543554.
Andersen, LF, Solvoll, K, Johansson, LR, Salminen, I, Aro, A & Drevon, CA (1999) Evaluation of a food frequency questionnaire with weighed records, fatty acids, and alpha-tocopherol in adipose tissue and serum. Am J Epidemiol 150, 7587.
Appel, LJ, Miller, ER 3rd, Jee, SH, Stolzenberg-Solomon, R, Lin, PH, Erlinger, T, Nadeau, MR & Selhub, J (2000) Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study. Circulation 102, 852857.
Bonaa, KH, Njolstad, I, Ueland, PM, Schirmer, H, Tverdal, A, Steigen, T, Wang, H, Nordrehaug, JE, Arnesen, E & Rasmussen, K (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354, 15781588.
Bostom, AG, Jacques, PF, Liaugaudas, G, Rogers, G, Rosenberg, IH & Selhub, J (2002) Total homocysteine lowering treatment among coronary artery disease patients in the era of folic acid-fortified cereal grain flour. Arterioscler Thromb Vasc Biol 22, 488491.
Brude, IR, Finstad, HS, Seljeflot, I, Drevon, CA, Solvoll, K, Sandstad, B, Hjermann, I, Arnesen, H & Nenseter, MS (1999) Plasma homocysteine concentration related to diet, endothelial function and mononuclear cell gene expression among male hyperlipidaemic smokers. Eur J Clin Invest 29, 100108.
Castro, R, Rivera, I, Blom, HJ, Jakobs, C & de Almeida, IT (2006) Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview. J Inherit Metab Dis 29, 320.
Cho, E, Zeisel, SH, Jacques, P, Selhub, J, Dougherty, L, Colditz, GA & Willett, WC (2006) Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr 83, 905911.
Clarke, R (2005) Homocysteine-lowering trials for prevention of heart disease and stroke. Semin Vasc Med 5, 215222.
Daly, S, Cotter, A, Molloy, AE & Scott, J (2005) Homocysteine and folic acid: implications for pregnancy. Semin Vasc Med 5, 190200.
de Bree, A, Verschuren, WM, Blom, HJ & Kromhout, D (2001) Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20–65 y. Am J Clin Nutr 73, 10271033.
de Bree, A, Verschuren, WM, Kromhout, D, Kluijtmans, LA & Blom, HJ (2002) Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease. Pharmacol Rev 54, 599618.
Finkelstein, JD (1990) Methionine metabolism in mammals. J Nutr Biochem 1, 228237.
Fiskerstrand, T, Refsum, H, Kvalheim, G & Ueland, PM (1993) Homocysteine and other thiols in plasma and urine: automated determination and sample stability. Clin Chem 39, 263271.
Flood, VM, Smith, WT, Webb, KL & Mitchell, P (2004) Issues in assessing the validity of nutrient data obtained from a food-frequency questionnaire: folate and vitamin B12 examples. Public Health Nutr 7, 751756.
Fung, TT, Rimm, EB, Spiegelman, D, Rifai, N, Tofler, GH, Willett, WC & Hu, FB (2001) Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am J Clin Nutr 73, 6167.
Ganji, V & Kafai, MR (2004) Frequent consumption of milk, yogurt, cold breakfast cereals, peppers, and cruciferous vegetables and intakes of dietary folate and riboflavin but not vitamins B-12 and B-6 are inversely associated with serum total homocysteine concentrations in the US population. Am J Clin Nutr 80, 15001507.
Ganji, V & Kafai, MR (2006) Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988–1994, 1999–2000, and 2001–2002. J Nutr 136, 153158.
Gao, X, Yao, M, McCrory, AM, Ma, G, Li, Y, Roberts, SB & Tucker, KL (2003) Dietary pattern is associated with homocysteine and B vitamin status in an urban Chinese population. J Nutr 133, 36363642.
Gjesdal, CG, Vollset, SE, Ueland, PM, Refsum, H, Drevon, CA, Gjessing, HK & Tell, GS (2006) Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med 166, 8894.
Holm, PI, Ueland, PM, Vollset, SE, Midttun, O, Blom, HJ, Keijzer, MB & den Heijer, M (2005) Betaine and folate status as cooperative determinants of plasma homocysteine in humans. Arterioscler Thromb Vasc Biol 25, 379385.
Huerta, JM, Gonzalez, S, Vigil, E, Prada, M, San Martin, J, Fernandez, S, Patterson, AM & Lasheras, C (2004) Folate and cobalamin synergistically decrease the risk of high plasma homocysteine in a nonsupplemented elderly institutionalized population. Clin Biochem 37, 904910.
Jacques, PF, Bostom, AG, Wilson, PW, Rich, S, Rosenberg, IH & Selhub, J (2001) Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 73, 613621.
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PW & Rosenberg, IH (1999) The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 340, 14491454.
Kelleher, BP & Broin, SD (1991) Microbiological assay for vitamin B12 performed in 96-well microtitre plates. J Clin Pathol 44, 592595.
Koehler, KM, Baumgartner, RN, Garry, PJ, Allen, RH, Stabler, SP & Rimm, EB (2001) Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use. Am J Clin Nutr 73, 628637.
Lasheras, C, Huerta, JM, Gonzales, S, Prada, M, Braga, S, Fernandez, S & Patterson, AM (2003) Diet score is associated with plasma homocysteine in a healthy institutionalised elderly population. Nutr Metab Cardiovasc Dis 13, 384390.
Loscalzo, J (2006) Homocysteine trials – clear outcomes for complex reasons. N Engl J Med 354, 16291632.
Malinow, MR, Bostom, AG & Krauss, RM (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99, 178182.
Molloy, AM & Scott, JM (1997) Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method. Methods Enzymol 281, 4353.
Morris, MS (2003) Homocysteine and Alzheimer's disease. Lancet Neurol 2, 425428.
Nygard, 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, 263270.
Olthof, MR, Brink, EJ, Katan, MB & Verhoef, P (2005) Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 82, 111117.
Ortega, RM, Requejo, AM, Lopez-Sobaler, AM, Navia, B, Mena, MC, Basabe, B & Andres, P (2004) Smoking and passive smoking as conditioners of folate status in young women. J Am Coll Nutr 23, 365371.
Perna, AF, Ingrosso, D, Satta, E, Lombardi, C, Acanfora, F & De Santo, NG (2004) Homocysteine metabolism in renal failure. Curr Opin Clin Nutr Metab Care 7, 5357.
Pfeiffer, CM, Caudill, SP, Gunter, EW, Osterloh, J & Sampson, EJ (2005) Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000. Am J Clin Nutr 82, 442450.
Ranheim, T & Halvorsen, B (2005) Coffee consumption and human health – beneficial or detrimental? Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus. Mol Nutr Food Res 49, 274284.
Rimestad, A, Borgejordet, Å, Vesterhus, K, Sygnestveit, K, Løken, E, Trygg, K, Pollestad, M, Lund-Larsen, K, Omholt-Jensen, G & Nordbotten, A (2001) Den store matvaretabellen. (The Norwegian Food Composition Table.). Oslo: National Nutritional Council, Gyldendal undervisning.
Sakamoto, A, Nishimura, Y, Ono, H & Sakura, N (2002) Betaine and homocysteine concentrations in foods. Pediatr Int 44, 409413.
Scholl, TO & Johnson, WG (2000) Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 71, 1295S1303S.
Shimakawa, T, Nieto, FJ, Malinow, MR, Chambless, LE, Schreiner, PJ & Szklo, M (1997) Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults. Ann Epidemiol 7, 285293.
Stolzenberg-Solomon, RZ, Miller, ER 3rd, 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, 467475.
Tucker, KL, Selhub, J, Wilson, PW & Rosenberg, IH (1996) Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J Nutr 126, 30253031.
Ueland, PM, Holm, PI & Hustad, S (2005) Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clin Chem Lab Med 43, 10691075.
US Department of Agriculture (2005) USDA National Nutrient Database for Standard Reference: Nutrient Data Laboratory, release 18, Beltsville, MD: US Department of Agriculture.
Verhoef, P & de Groot, LC (2005) Dietary determinants of plasma homocysteine concentrations. Semin Vasc Med 5, 110123.
Vollset, SE, Refsum, H, Nygård, O & Ueland, PM (2001) Lifestyle factors associated with hyperhomocysteinemia. In Homocysteine in Health and Disease, pp. 341355 [Carmel, R and Jacobsen, DW, editors]. Cambridge: Cambrige University Press.
Wald, DS, Law, M & Morris, JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J 325, 1202.
Weikert, C, Hoffmann, K, Dierkes, J, Zyriax, BC, Klipstein-Grobusch, K, Schulze, MB, Jung, R, Windler, E & Boeing, H (2005) A homocysteine metabolism-related dietary pattern and the risk of coronary heart disease in two independent German study populations. J Nutr 135, 19811988.
Willett, W & Lenart, E (1998) Reproducibility and validity of food-frequency questionnaires. In Nutritional Epidemiology, 2nd ed. pp. 101–147 [Willett, W, editor]. Oxford: Oxford University Press.
Zeisel, SH, Mar, MH, Howe, JC & Holden, JM (2003) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133, 13021307.



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