Skip to main content
SpringerLink
Log in

Hyperhomocysteinemia and the response to vitamin supplementation

  • Original Article
  • Published:
The clinical investigator Aims and scope Submit manuscript

Summary

The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 μmol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 μmol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

HPLC:

high-performance liquid chromatography

Lp(a):

lipoprotein(a)

PLP:

pyridoxal 5′-phosphate

References

  1. Allen RH, Stabler SP, Savage DG, Lindenbaum J (1990) Diagnosis of cobalamin deficiency 1: usefulness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol 34:90–98

    Google Scholar 

  2. Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by HPLC with fluorescence detection. J Chromatogr 422:43–52

    Google Scholar 

  3. Brattström LE, Hardebo JE, Hultberg BL (1984) Moderate homocysteinemia — a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke 15:1012–1016

    Google Scholar 

  4. Brattström LE, Israelsson B, Jeppson JO, Hultberg BL (1988) Folic acid — an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 48:215–221

    Google Scholar 

  5. Brattström L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A (1990) Impaired homocysteine metabolism in early — onset cerebral and peripheral occlusive arterial disease. Atherosclerosis 8:51–60

    Google Scholar 

  6. Christensen B, Refsum H, Vintermyr O, Ueland PM (1991) Homocysteine export from cells cultured in the presence of physiological or superfluous levels of methionine: methionine loading of non-transformed, transformed, proliferating, and quiescent cells in culture. J Cell Physiol 146:52–62

    Google Scholar 

  7. Coull BM, Malinow MR, Beamer N, Sexton G, Nordt F, De Garmo P (1990) Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke 21:572–576

    Google Scholar 

  8. Food and Nutrition Board, National Academy of Sciences (USA) Recommended Dietary Allowances, 1989. National Academy Press, Washington DC

    Google Scholar 

  9. Genest JJ, McNamara DN, Salem JR, Wilson PWF, Scaefer EJ, Malinow MR (1990) Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol 16:1114–1119

    Google Scholar 

  10. Gouws E, Langehoven ML (1986) NRIND food composition tables, 2nd edn. National Research Institute for Nutritional Diseases, South African Medical Research Council, Parow, South Africa

    Google Scholar 

  11. Harker LA, Ross R, Slichter SJ, Scott CR (1976) Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. J Clin Invest 58:731–741

    Google Scholar 

  12. Harpel PC, Chang VT, Borth W (1992) Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism. Proc Natl Acad Sci USA 89:10193–10197

    Google Scholar 

  13. Israelsson B, Brattstrom LE, Hultberg BL (1988) Homocysteine and myocardial infarction. Atherosclerosis 71:227–233

    Google Scholar 

  14. Kang SS, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N (1991) Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 48:536–545

    Google Scholar 

  15. Malinow MR, Kang SS, Taylor LM, Wong PWK, Coull B, Inahara T, Mukerjee D, Sexton G, Upson B (1989) Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 79:1180–1188

    Google Scholar 

  16. Mudd SH, Levy HL, Skovby F (1989) Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGrawHill, New York, pp 693–734

    Google Scholar 

  17. Parthasarathy S (1987) Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. Biochim Biophys Acta 917:337–340

    Google Scholar 

  18. Stampfer MJ, Malinow R, Willet WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881

    Google Scholar 

  19. Starkebaum G, Harlan JM (1986) Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 77:1370–1376

    Google Scholar 

  20. Stipanuk MH (1986) Metabolism of sulfur-containing amino acids. Anna Rev Nutr 6:179–209

    Google Scholar 

  21. Svardal AM, Djurhuus R, Refsum H, Ueland PM (1986) Disposition of homocysteine in rat hepatocytes and in non-transformed and malignant mouse embryo fibroblasts following exposure to inhibitors of s-adenosylhomocysteine catabolism. Cancer Res 46:5095–5100

    Google Scholar 

  22. Taylor LM, DeFrang RD, Harris EJ, Porter JM (1991) The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg 13:128–136

    Google Scholar 

  23. Ubbink JB, Serfontein WJ, De Villiers LS (1985) Stability of pyridoxal-5-phosphate semicarbazone: application in plasma vitamin B6 analysis and population surveys of vitamin B6 nutritional status. J Chromatogr 342:277–284

    Google Scholar 

  24. Ubbink JB, Vermaak WJH, Bennett JM, Becker PJ, Van Staden DA, Bissbort S (1991) The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. Klin Wochenschr 69:527–534

    Google Scholar 

  25. Ubbink JB, Vermaak WJH, Bissbort S (1991) Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr 565:441–446

    Google Scholar 

  26. Ubbink JB, Vermaak WJH, Van der Merwe A, Becker BPJ (1993) Vitamin B12, vitamin B6 and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 57:47–53

    Google Scholar 

  27. Ueland PM, Refsum H, Brattström L (1992) Plasma homocysteine and cardiovascular disease. In: Francis BR (ed) Atherosclerotic cardiovascular disease, hemostatis, and endothelial function. Dekker, New York, pp 183–235

    Google Scholar 

  28. Wilcken DEL, Gupta VJ, Betts AK (1981) Homocysteine in the plasma of renal transplant recipients: effects of cofactors for methionine metabolism. Clin Sci 61:743–749

    Google Scholar 

Download references

Author information

Author notes

  1. J. B. Ubbink

    Present address: Department of Chemical Pathology Faculty of Medicine, University of Pretoria, P.O. Box 2034, 0001, Pretoria, South Africa

Authors and Affiliations

  1. Department of Chemical Pathology, Faculty of Medicine, University of Pretoria, South Africa

    J. B. Ubbink, A. van der Merwe, W. J. H. Vermaak & R. Delport

Authors
  1. J. B. Ubbink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. van der Merwe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. H. Vermaak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Delport
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ubbink, J.B., van der Merwe, A., Vermaak, W.J.H. et al. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig 71, 993–998 (1993). https://doi.org/10.1007/BF00180030

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00180030

Key words

Search

Navigation