Skip to main content
Log in

Changes in predictors and status of homocysteine in young male adults after a dietary intervention with vegetables, fruits and bread

  • ORIGINAL CONTRIBUTION
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Background

Elevated plasma total homocysteine (p-tHcy) is associated with increased risk of cardiovascular disease, and an inverse association has been shown between the dietary intake of B-vitamins, B-vitamin profile and the concentration of p-tHcy.

Aim of the study

The main objective of this investigation was to study the effect of a dietary intervention focusing on an increased intake of vegetables, fruits and bread. The effect of the dietary intervention was determined by the changes in plasma concentrations of tHcy, cysteine (cys), riboflavin, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and serum concentrations of folate and vitamin B12.

Method

An intervention study with duration of 5 months, including 541 male recruits from the Norwegian National Guard, Vaernes and a control group, including 209 male recruits from the Norwegian Army, Heggelia.

Results

The dietary intervention resulted in decreased concentration of p-tHcy (−10%, P = 0.002), p-cys (−6%, P < 0.001) and FMN (−11%, P = 0.310) and increased concentration of riboflavin (+23%, P < 0.001) and FAD (+10%, P = 0.008) in the intervention group compared with the control group. The change in p-tHcy concentration was positively related to the change in the concentration of p-cys (P < 0.001) and FMN (P = 0.035) and inversely related to the change in concentration of folate (P = 0.021).

Conclusions

A dietary intervention program focusing on an increased intake of vegetables, fruits and bread showed a favourable effect on the concentration of p-tHcy and its metabolites. Our findings suggest that the changes in the concentration of p-cys, folate and FMN seem to be predictors of changes in the p-tHcy concentration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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(8):852–857

    CAS  Google Scholar 

  2. Bates CJ, Mansoor MA (1997) Plasma total homocysteine in a representative sample of 972 British men and women aged 65 and over. Eur J Clin Nutr 51(10):691–697

    Article  CAS  Google Scholar 

  3. Bates CJ, Mansoor MA, Gregory J, Pentieva K, Prentice A (2002) Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British national diet and nutrition survey of young people aged 4–18 years, and a comparison with the survey of people Aged 65 years and over. Br J Nutr 87(1):71–79

    Article  CAS  Google Scholar 

  4. Becker W (1999) Vilka är källorna till våra näringsämnen? Vår Föda 3:16–20

    Google Scholar 

  5. Bogers RP, Dagnelie PC, Bast A, van Leeuwen M, van Klaveren JD, van den Brandt PA (2007) Effect of increased vegetable and fruit consumption on plasma folate and homocysteine concentrations. Nutrition 23(2):97–102

    Article  CAS  Google Scholar 

  6. Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Rasmussen K, NORVIT Trial Investigators (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354(15):1578–1588

    Article  Google Scholar 

  7. 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. JAMA 274(13):1049–1057

    Article  CAS  Google Scholar 

  8. Brattstrom L, Lindgren A, Israelsson B, Andersson A, Hultberg B (1994) Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. J Intern Med 236(6):633–641

    Article  CAS  Google Scholar 

  9. Brody T (1994) Nutritional biochemistry. Academic Press, San Diego

    Google Scholar 

  10. Broekmans WMR, Klopping-Ketelaars IAA, Schuurman CRWC, 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. J Nutr 130(6):1578–1583

    CAS  Google Scholar 

  11. Brouwer IA, van Dusseldorp V, 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. J Nutr 129(6):1135–1139

    CAS  Google Scholar 

  12. Chambers JC, Obeid OA, Refsum H, Ueland P, Hackett D, Hooper J, Turner RM, Thompson SG, Kooner JS (2000) Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men. Lancet 355(9203):523–527

    Article  CAS  Google Scholar 

  13. De Bree A, van Dusseldorp M (1997) Folate intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 51(10):643–660

    Article  CAS  Google Scholar 

  14. El-Khairy L, Vollset SE, Refsum H, Ueland PM (2003) Plasma total cysteine, mortality, and cardiovascular disease hospitalizations: the hordaland homocysteine study. Clin Chem 49(6):895–900

    Article  CAS  Google Scholar 

  15. Ganji V, Kafai MR (2003) Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third national health and nutrition examination survey, 1988–1994. Am J Clin Nutr 77(4):826–833

    CAS  Google Scholar 

  16. 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(6):1500–1507

    CAS  Google Scholar 

  17. Gaume V, Mougin F, Figard H, Simon-Rigaud ML, N’Guyen UN, Callier J Kantelip JP, Berthelot A (2005) Physical training decreases total plasma homocysteine and cysteine in middle-aged subjects. Ann Nutr Metab 49(2):125–131

    Article  CAS  Google Scholar 

  18. Henriquez P, Doreste J, Deulofeu R, Fiuza MD, Serra-Majem L (2007) Nutritional determinants of plasma total homocysteine distribution in the Canary Islands. Eur J Clin Nutr 61(1):111–118

    Article  CAS  Google Scholar 

  19. Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288(16):2015–2022

    Article  Google Scholar 

  20. 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(10):904–910

    Article  CAS  Google Scholar 

  21. Hustad S, Ueland PM, Vollset SE, Zhang Y, Bjorke-Monsen AL, Schneede J (2000) Riboflavin as a determinant of plasma total homocysteine; effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem 46(8):1065–1067

    CAS  Google Scholar 

  22. 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(1):7–9

    CAS  Google Scholar 

  23. Jacques PF, Bostom AG, Wilson PWF, Rich S, Rosenberg IH, Selhub J (2001) Determinants of plasma total homocysteine concentration in the Framingham offspring cohort. Am J Clin Nutr 73(3):613–621

    CAS  Google Scholar 

  24. Jacques PF, Kalmbach R, Bagley PJ, Russo GT, Rogers G, Wilson PW, Rosenberg IH, Selhub J (2002) The relationship between riboflavin and plasma total homocysteine in the Framingham offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr 132(2):283–288

    CAS  Google Scholar 

  25. Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH, Huang YC (2004) Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr 58(3):481–487

    Article  CAS  Google Scholar 

  26. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fedor G, Held C, Genest J Jr, Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators (2006) Homocysteine lowering with folic acid and b vitamins in vascular disease. N Engl J Med 354(15):1567–1577

    Article  CAS  Google Scholar 

  27. Mansoor MA, Bergmark C, Svardal AM, Lønning PE, Ueland PM (1995) Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and peripheral vascular disease. Arteriscler Thromb Vasc Biol 15(2):232–240

    CAS  Google Scholar 

  28. Mansoor MA, Svardal AM, Ueland PM (1992) Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. Anal Biochem 200(2):218–229

    Article  CAS  Google Scholar 

  29. 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(4):759–764

    CAS  Google Scholar 

  30. 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. Eur J Clin Nutr 56(9):850–856

    Article  CAS  Google Scholar 

  31. McNulty H, Dowey LC, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM (2006) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation 113(1):74–80

    Article  CAS  Google Scholar 

  32. Mills JL (2000) Fortification of foods with folic acid—how much is enough? N Engl J Med 342(19):1442–1445

    Article  CAS  Google Scholar 

  33. Moat SJ, Ashfield-Watt PAL, Powers HJ, Newcombe RG, McDowell IFW (2003) Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. Clin Chem 49(2):295–302

    Article  CAS  Google Scholar 

  34. Moore SE, Mansoor MA, Bates CJ, Prentice AM (2006) Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults. Br J Nutr 96(3):508–515

    CAS  Google Scholar 

  35. 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. JAMA 274(19):1526–1533

    Article  CAS  Google Scholar 

  36. Ozkan Y, Ozkan E, Simsek B (2002) Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease. Int J Cardiol 82(3):269–277

    Article  Google Scholar 

  37. Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygard O, Vollset SE (2006) The hordaland homocysteine study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 136(6):1731–1740

    Google Scholar 

  38. Rowley KG, Su Q, Cincotta M, Skinner M, Skinner K, Pindan B, White GA, O’Dea K (2001) Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian aboriginal community. Am J Clin Nutr 74(4):442–448

    CAS  Google Scholar 

  39. Ruiz JR, Sola R, Gonzalez-Gross M, Ortega FB, Vicente-Rodriguez G, Garcia-Fuentes M, Gutierrez A, Sjostrom M, Pietrzik K, Castillo MJ (2007) Cardiovascular fitness is negatively associated with homocysteine levels in female adolescents. Arch Pediatr Adolesc Med 161(2):166–171

    Article  Google Scholar 

  40. Selhub J, Jacques PF, Bostom AG, Wilson PW, Rosenberg IH (2000) Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Public Health Rev 28(1–4):117–145

    CAS  Google Scholar 

  41. Stea TH, Johansson M, Jagerstad M, Frolich W (2007) Retention of folates in cooked, stored and reheated peas, broccoli and potatoes for use in modern large-scale service systems. Food Chem 101(3):1095–1107

    Article  CAS  Google Scholar 

  42. The Norwegian directorate for health and social affairs (2006) Utviklingen i norsk kosthold. Matforsyningsstatistikk og forbrukerundersøkelser. Oslo, pp 1–103

  43. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH (1993) Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39(9):1764–1779

    CAS  Google Scholar 

  44. Uglem S, Frølich W, Stea TH, Wandel M (2007) Correlates of vegetable consumption among young men in the Norwegian national guard. Appetite 48:46–53

    Article  Google Scholar 

  45. Venn BJ, Mann JI, Williams SM, Riddell LJ, Chisholm A, Harper MJ, Aitken W (2002) Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine. Am J Clin Nutr 76(4):758–765

    CAS  Google Scholar 

  46. Vickers AJ, Altman DG (2001) Statistics notes: analysing controlled trials with baseline and follow up measurements. BMJ 323(7321):1123–1124

    Article  CAS  Google Scholar 

  47. Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, Friedman JM (2006) Improvement in stroke mortality in Canada and the United States, 1990–2002. Circulation 113(10):1335–1343

    Article  Google Scholar 

  48. Zimmermann MB, Shane B (1993) Supplemental folic acid. Am J Clin Nutr 58(2):127–128

    CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by the Norwegian Research Council. The authors want to thank the personnel at The Norwegian National Guard, Værnes and the Norwegian Army, Heggelia for support and positive attitude regarding data collections. We also want to thank Madelene Johansson for participating in the data collection of the control group and Betzy Kvarme and Elin Skarland Frøyland for their help with analyses of p-tHcy and riboflavin, FAD and FMN in plasma.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tonje Holte Stea.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stea, T.H., Mansoor, M.A., Wandel, M. et al. Changes in predictors and status of homocysteine in young male adults after a dietary intervention with vegetables, fruits and bread. Eur J Nutr 47, 201–209 (2008). https://doi.org/10.1007/s00394-008-0714-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-008-0714-y

Keywords

Navigation