Abstract
Objective: To assess the folate status of Finnish adults using plasma folate and homocysteine as biomarkers and to evaluate dietary and supplementary folate intakes.
Materials and methods: Plasma folate, vitamin B12 and total homocysteine (tHcy) were determined in a random sample of 643 subjects aged 25–74 y living in the Helsinki area. The methylenetetrahydrofolate reductase (MTHFR)-genotypes were analyzed from a subsample (n=394). Dietary intake data by 24 h recall and use of vitamin supplements were collected.
Results: Plasma folate was normal (≥5 nmol/l) in 99% of subjects and optimal (≥8 nmol/l) in terms of a minimum tHcy in 90%. Mean plasma folate of non-supplement users was 13.7 and 12.9 nmol/l and tHcy 11.3 and 9.2 µmol/l for men and women, respectively. Elevated tHcy (>14 µmol/l) was found in 11% of subjects. Homozygote frequency for MTHFR genotype TT was 5.0% and their plasma tHcy was 14.8 µmol/l compared to the mean of the other subjects, 10.5 µmol/l, P<0.05. The mean dietary folate intake was 241 µg/day (29 µg/MJ of energy) for men and 205 µg/day (33 µg/MJ) for women, respectively. The main dietary sources of folate were vegetables 12%, wholemeal ryebread 11%, fruits 10%, and potato 10%. Regular supplement users (n=97) received on average 207 µg folic acid per day from supplements.
Conclusion: The folate status of Finnish adults seems to be adequate according to energy adjusted folate intake, plasma folate and homocysteine. The MTHFR homozygote frequency was low compared to other countries. Regular use of supplementary folic acid less than 300 µg increased plasma folate, but supplemental folic acid over 300 µg was required to lower tHcy values significantly.
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References
Alfthan, G, Pekkanen, J, Jauhiainen, M, Pitkäniemi, J, Karvonen, M, Tuomilehto, J, Salonen, JT & Ehnholm, C (1994). The relation of serum homocysteine and lipoprotein (a) concentrations to atherosclerotic disease in a Finnish population-based cohort. Atherosclerosis, 106, 9–19.
Appel, LJ, Miller, ER III, 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, 852–857.
Bell, GI, Karam, JH & Rutter, WJ (1981). Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc. Natl Acad. Sci., 78, 5759–5763.
Bergström, L (1994). Nutrient losses and gains in the preparation of foods, National Food Administration (Report 32. Uppsala:)
Boushey, CJ, Beresford, SAA, Omenn, GS & Motulsky, AG (1995). A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA, 274, 1049–1057.
Brattström, L, Wilcken, DEL, Ohrvik, J & Brudin, L (1998). Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease. Circulation, 98, 2520–2526.
Brouwer, DAJ, Welten, HTME, Reijngoud, D-J, van Doormaal, JJ & Muskiet, FAJ (1998). Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine. Clin. Chem., 44, 1545–1550.
Brouwer, IA, van Dusseldorp, M, Thomas, CMG, Duran, M, Hautvast, JGAJ, Eskes, TKAB & Steegers-Theunissen, RPM (1999a). Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am. J. Clin. Nutr., 69, 99–104.
Brouwer, IA, van Dusseldorp, M, West, CE, Meyboom, S, Thomas, CMG, Duran, M, van het Hof, KH, Eskes, TKAB, Hautvast, JGAJ & Steerers-Theunissen, RPM (1999b). Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J. Nutr., 129, 1135–1139.
Brussaard, JH, Löwik, MRH, van den Berg, H, Brants, HAM & Goldbohm, RA (1997). Folate intake and status among adults in the Netherlands. Eur. J. Clin. Nutr., 51, S46–S50.
Christen, WG, Ajani, UA, Glynn, RJ & Hennekens, CH (2000). Blood levels of homocysteine and increased risks of cardiovascular disease. Causal or casual?. Arch. Intern. Med., 160, 422–434.
Czeizel, AE & Dudas, I (1992). Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. New Engl. J. Med., 327, 1832–1835.
FINDIET Study Group (1998). The 1997 dietary survey of Finnish adults, Publication B8. Helsinki: National Public Health Institute
Frosst, P, Blom, HJ, Milos, R, Goyette, P, Sheppard, CA, Matthews, RG, Boers, GJH, den Heijer, M, Kluijtmans, LAJ, van den Heuvel, LP & Rozen, R (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet., 10, 111–113.
Gregory, JF III (1997). Bioavailability of folate. Eur. J. Clin. Nutr., 51, (Suppl 1) 554–559.
den Heijer, M, Brouwer, IA, Bos, GMJ, Blom, HJ, van der Put, NMJ, Spaans, AP, Rosendaal, FR, Thomas, CMG, Haak, HL, Wijermans, PW & Gerrits, WBJ (1998). Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscl. Thromb. Vasc. Biol., 18, 356–361.
Homocysteine Lowering Trialists' Collaboration (1998). Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Br. Med. J., 316, 894–898.
Jacob, RA, Wu, MM, Henning, SM & Swendseid, ME (1994). Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction. J. Nutr., 124, 1072–1080.
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PWF & Rosenberg, IH (1999). The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New Engl. J. Med., 340, 1449–1454.
Knekt, P, Reunanen, A, Alfthan, G, Heliövaara, M, Rissanen, H, Marniemi, J & Aromaa, A (2001a). Hyperhomocysteinemia–a risk factor or a consequence of coronary heart disease?. Arch. Intern. Med., 161, 1589–1594.
Knekt, P, Alfthan, G, Aromaa, A, Heliövaara, M, Marniemi, J, Rissanen, H & Reunanen, A (2001b). Homocysteine and major coronary events: a prospective population study among women. J. Intern. Med., 249, 461–465.
Konings, EJM, Roomans, HHS, Dorant, E, Goldbohm, RA, Saris, WHM & van den Brandt, PA (2001). Folate intake of the Dutch population according to newly established liquid chromatographic data for foods. Am. J. Clin. Nutr., 73, 765–776.
Lewis, CA, Pancharuniti, N & Sauberlich, HE (1992). Plasma folate adequacy as determined by homocysteine level. Ann. NY Acad. Sci., 669, 360–362.
Mills, JL, Tuomilehto, J, Yu, KF, Colman, N, Blaner, WS, Koskela, P, Rundle, WE, Forman, M, Toivanen, L & Rhoads, GG (1992). Maternal vitamin levels during pregnancies producing infants with neural tube defects. J. Pediatr., 120, 863–871.
Möller, J, Rasmussen, K & Christensen, L (1999). External quality assessment of methylmalonic and total homocysteine. Clin. Chem., 45, 1536–1542.
Motti, C, Gnasso, A, Bernardini, S, Massoud, R, Pastore, A, Rampa, P, Federici, G & Cortese, C (1998). Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease. Atherosclerosis, 139, 377–383.
MRC Vitamin Study Research Group (1991). Prevention of neural tube defects: results of the Medical Research Council Vitamin study. Lancet, 338, 131–137.
Ovaskainen, ML (2001). Fineli® Elintarvikkeiden koostumustietopankki. www.ktl.fi/fineli>.2001 (in Finnish)
Pastinen, T, Perola, M, Niini, P, Terwilliger, J, Salomaa, V, Vartiainen, E, Peltonen, L & Syvänen, A-C (1998). Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum. Mol. Genet., 7, 1453–1462.
Quinn, K & Basu, TK (1996). Folate and vitamin B12 status of the elderly. Eur. J. Clin. Nutr., 50, 340–342.
Rady, PL, Tyring, SK, Hudnall, D, Vargas, T, Kellner, LH, Nitowsky, H & Matalon, RK (1999). Methylenetetrahydrofolate reductase (MTHFR): the incidence of mutations C677T and A1298C in the Ashkenazi Jewish population. Am. J. Med. Genet., 86, 380–384.
Rasmussen, LB, Ovesen, L, Bulow, I, Knudsen, N, Laurberg, P & Perrild, H (2000). Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women. Am. J. Clin. Nutr., 72, 1156–1163.
Riddell, LJ, Chisholm, A, Williams, S & Mann, JI (2000). Dietary strategies for lowering homocysteine concentrations. Am. J. Clin. Nutr., 71, 1448–1454.
Ridker, PM, Hennekens, CH, Selhub, J, Miletich, JP, Malinow, MR & Stampfer, MJ (1997). Interrelation of hyperhomocyst(e)inemia, factor V Leiden and risk of future venous thromboembolism. Circulation, 95, 1777–1782.
Rimm, EB, Willett, WC, Hu, FB, Sampson, L, Colditz, GA, Manson, JE, Hennekens, C & Stampfer, MJ (1998). Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA, 279, 359–364.
Ritvanen, A (1996). Neural tube defects and folic acid. Duodecim, 112, 975–982, (in Finnish)
Sandström, B & Gibney, M (2001). A framework for food-based dietary guidelines in the European Union. Public Health Nutr., 4, (2A) 293–305.
Scholl, TO & Johnson, WG (2000). Folic acid: influence on the outcome of pregnancy. Am. J. Clin. Nutr., 71, (Suppl) 1295S–1303S.
Selhub, J, Jacques, PS, Rosenburg, 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.
Syvänen, AC, Sajantila, A & Lukka, M (1993). Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing. Am. J. Hum. Genet., 52, 46–59.
Tucker, KL, Selhub, J, Wilson, PWF & Rosenburg, IH (1996). Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J. Nutr., 126, 3025–3031.
Ubbink, JB, Haywaard Vermaak, WJ & Bissbort, S (1991). Rapid high-performance liquid chromatography assay for total homocysteine levels in human serum. J. Chromatogr., 565, 441–446.
Vahteristo, LT, Lehikoinen, KE, Ollilainen, V, Koivistoinen, PE & Varo, P (1998). Oven-baking and frozen storage affect folate vitamer retention. Lebensm. Wiss. Technol., 31, 329–333.
Vartiainen, E, Jousilahti, P, Alfthan, G, Sundvall, J, Pietinen, P & Puska, P (2000). Cardiovascular risk factor changes in Finland, 1972–1997. Int. J. Epidemiol., 29, 49–56.
Voutilainen, S, Lakka, TA, Hämelahti, P, Lehtimäki, T, Poulsen, HE & Salonen, JT (2000). Plasma total homocysteine and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. J. Intern. Med., 248, 217–222.
Voutilainen, S, Rissanen, T, Virtanen, J, Lakka, TA & Salonen, JT (2001). Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Circulation, 103, 2674–2680.
Wirta, V, Huang, XH, Wirta, O, Rantalaiho, V, Pasternack, A, Jokela, H, Koivula, T & Lehtimäki, T (1998). Mutation C677T of methylenetetrahydrofolate reductase gene is not associated with coronary artery disease, but possibly with albuminuria, in type 2 diabetic patients. Clin. Chem. Lab. Med., 36, 625–628.
Woo, KS, Chook, P, Lolin, YI, Cheung, ASP, Chan, LT, Sun, YY, Sanderson, JE, Metreweli, C & Celermajer, DS (1997). Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfynction in humans. Circulation, 96, 2542–2544.
Acknowledgements
The study was supported in part by the Ministry of Social Welfare and Health. TP is supported by grants from The Finnish Heart Foundation, The Academy of Finland and the Maud Kuistilan Muistosaatio. We thank Päivi Mustonen, Pirjo Laaksonen and Minna Levander for excellent technical assistance and Meri Anttolainen and Heli Tapanainen for dietary and statistical calculations, respectively.
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Alfthan, G., Laurinen, M., Valsta, L. et al. Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur J Clin Nutr 57, 81–88 (2003). https://doi.org/10.1038/sj.ejcn.1601507
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DOI: https://doi.org/10.1038/sj.ejcn.1601507
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