The journal of nutrition, health & aging

, Volume 14, Issue 4, pp 283–287

Short-term influence of elevation of plasma homocysteine levels on cognitive function in young healthy adults

  • P. Alexopoulos
  • S. Lehrl
  • T. Richter-Schmidinger
  • A. Kreusslein
  • T. Hauenstein
  • F. Bayerl
  • P. Jung
  • T. Kneib
  • A. Kurz
  • J. Kornhuber
  • S. Bleich
Article

Abstract

Background

Acute homocysteine elevation has been shown to have a significant impact on cognitive function in animal models.

Objectives

Investigation of the short-term impact of elevation of plasma homocysteine levels through a dietary intervention on cognitive abilities of young healthy adults.

Participants

100 healthy medical students of both genders were enrolled in the study.

Design and Measurements

Homocysteine levels and cognitive abilities were measured at 08:30 (before breakfast) and at 15:00 (two hours after lunch and six hours after breakfast). Food intake was restricted to specified comestibles. The cognitive assessment comprised a version of the Short Test for General Intelligence, three subtests of the Syndrome Short Test and the Stroop test.

Results

At 15:00 plasma homocysteine was significantly elevated in 56 participants (P<0.00001), whilst in 44 it was decreased (P<0.00001) in comparison to baseline (08:30). The decrease was however of limited clinical significance. The differences in the changes in cognitive performance between the two groups did not attain statistical significance (P>0.05) and the direction of the changes did not differ between them. Accordingly, the multiple linear regression analysis did not reveal an important influence of homocysteine elevation on cognitive performance variations.

Conclusions

Significant increase of plasma homocysteine is not associated with a straightforward inhibitory or facilitatory short-term effect on physiological cognitive parameters in young healthy adults.

Key words

Homocysteine healthy adults cognitive function 

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References

  1. 1.
    Weir DG, Schott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull 1999; 55: 669–682.CrossRefPubMedGoogle Scholar
  2. 2.
    Clarke R, Woodhouse P, Ulvik A, Frost C, Sherliker P, Refsum H, Ueland PM, Khaw KT. Variability and determinants of total homocysteine concentrations in plasma in an elderly population. Clin Chem. 1998;44:102–107.PubMedGoogle Scholar
  3. 3.
    Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000;71:614–620.Google Scholar
  4. 4.
    Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA. 1983;249:2917–2921.CrossRefPubMedGoogle Scholar
  5. 5.
    Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ. 2004 Oct 12;171:897–904.PubMedGoogle Scholar
  6. 6.
    Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996;143:845–859.PubMedGoogle Scholar
  7. 7.
    Mann NJ, Li D, Sinclair AJ, Dudman NP, Guo XW, Elsworth GR, Wilson AK, Kelly FD. The effect of diet on plasma homocysteine concentrations in healthy male subjects. Eur J Clin Nutr. 1999; 53:895–899.CrossRefPubMedGoogle Scholar
  8. 8.
    Stolzenberg-Solomon RZ, Miller ER 3rd, Maguire MG, Selhub J, Appel LJ. Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am J Clin Nutr. 1999;69:467–475.PubMedGoogle Scholar
  9. 9.
    Regland B, Abrahamsson L, Gottfries CG, Magnus E. Vitamin B12 analogues, homocysteine, methylmalonic acid, and transcobalamins in the study of vitamin B12 deficiency in primary degenerative dementia. Dementia 1990; 1: 272–277.Google Scholar
  10. 10.
    Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55:1449–1455CrossRefPubMedGoogle Scholar
  11. 11.
    Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002; 346:476–483.CrossRefPubMedGoogle Scholar
  12. 12.
    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;75:908–913.PubMedGoogle Scholar
  13. 13.
    Wilhelm J, Bayerlein K, Hillemacher T, Reulbach U, Frieling H, Kromolan B, Degner D, Kornhuber J, Bleich S. Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism. J Neural Transm. 2006;113:357–363.CrossRefPubMedGoogle Scholar
  14. 14.
    Welch GN, Upchurch GR Jr, Loscalzo J. Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem. 1997;272:17012–17017.CrossRefPubMedGoogle Scholar
  15. 15.
    Hogg N. The effect of cyst(e)ine on the auto-oxidation of homocysteine. Free Radic Biol Med. 1999; 27:28–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Wyse AT, Zugno AI, Streck EL, Matté C, Calcagnotto T, Wannmacher CM, Wajner M. Inhibition of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to acute administration of homocysteine is prevented by vitamins E and C treatment. Neurochem Res. 2002;27:1685–1689.CrossRefPubMedGoogle Scholar
  17. 17.
    Streck EL, Zugno AI, Tagliari B, Wannmacher C, Wajner M, Wyse AT. Reduction of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochem Res. 2002;27:1593–1598.CrossRefPubMedGoogle Scholar
  18. 18.
    White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, Bush AI, Cappai R. Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer’s-type neurodegenerative pathways. J Neurochem. 2001; 76:1509–1520.CrossRefPubMedGoogle Scholar
  19. 19.
    Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the Nmethyl-D-aspartate receptor. Proc Natl Acad Sci U S A. 1997; 94:5923–5928.CrossRefPubMedGoogle Scholar
  20. 20.
    Bleich S, Wiltfang J, Kornhuber J. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003; 349:609–610.CrossRefPubMedGoogle Scholar
  21. 21.
    Christie LA, Riedel G, Algaidi SA, Whalley LJ, Platt B. Enhanced hippocampal long-term potentiation in rats after chronic exposure to homocysteine. Neurosci Lett. 2005; 373:119–124.CrossRefPubMedGoogle Scholar
  22. 22.
    Reis AE, Zugno Ai, Franzon R, Tagliari B, Matte C, Lammers ML, Netto CA, Wyse ATS. Pretreatment with vitamins E and C prevents the impairment of memory caused by homocysteine administration in rats. Metab Brain Dis. 2002;17:211–217CrossRefPubMedGoogle Scholar
  23. 23.
    Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915–7922. Review.CrossRefPubMedGoogle Scholar
  24. 24.
    Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T, Hillemacher T, Bönsch D, Kornhuber J. Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcohol Clin Exp Res. 2005;29:334–336.CrossRefPubMedGoogle Scholar
  25. 25.
    Lehrl S, Gallwitz A, Blaha L, Fischer B: Geistige Leistungsfähigkeit. Theorie und Messung der biologischen Intelligenz mit dem Kurztest KAI, ed 3 Ebersberg, Vless, 1992.Google Scholar
  26. 26.
    Lehrl S, Fischer B. The basic parameters of human information processing: Their role in the determination of intelligence. Person Individ Diff 1988; 9: 883–896.CrossRefGoogle Scholar
  27. 27.
    Lehrl S, Gerstmeyer K, Jacob JH, Frieling H, Henkel AW, Meyrer R, Wiltfang J, Kornhuber J, Bleich S. Blue light improves cognitive performance. J Neural Transm. 2007;114:457–460.CrossRefPubMedGoogle Scholar
  28. 28.
    Stroop OR. Studies of interference in serial verbal reaction. J Exper Psych 1935; 18:643–662.CrossRefGoogle Scholar
  29. 29.
    Erzigkeit H: The SKT-A short cognitive performance test as an instrument for the assessment of clinical efficacy of cognitive enhancers; in Bergner W, Reisberg B (eds): Diagnosis and Treatment of Senile Dementia. Heidelberg, Springer Verlag, 1989.Google Scholar
  30. 30.
    Haider M: Elektrophysiologische Indikatoren der Aktivierung; in Schönpflug W (eds): Methoden der Aktivierungsforschung. Stuttgart, Huber, 1969.Google Scholar
  31. 31.
    Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693–2698.CrossRefPubMedGoogle Scholar
  32. 32.
    Guttormsen AB, Schneede J, Fiskerstrand T, Ueland PM, Refsum HM. Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects. J Nutr. 1994;124:1934–1941.PubMedGoogle Scholar
  33. 33.
    Bolli GB, Dimitriadis GD, Pehling GB, Baker BA, Haymond MW, Cryer PE, Gerich JE. Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus. N Engl J Med. 1984;310:1706–1711.PubMedCrossRefGoogle Scholar
  34. 34.
    Bönsch D, Hothorn T, Krieglstein C, Koch M, Nehmer C, Lenz B, Reulbach U, Kornhuber J, Bleich S. Daily variations of homocysteine concentration may influence methylation of DNA in normal healthy individuals. Chronobiol Int. 2007;24:315–326CrossRefPubMedGoogle Scholar
  35. 35.
    Algaidi SA, Christie LA, Jenkinson AM, Whalley L, Riedel G, Platt B. Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity. Exp Neurol. 2006;197:8–21.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2010

Authors and Affiliations

  • P. Alexopoulos
    • 1
    • 2
    • 3
  • S. Lehrl
    • 1
  • T. Richter-Schmidinger
    • 1
  • A. Kreusslein
    • 1
  • T. Hauenstein
    • 1
  • F. Bayerl
    • 1
  • P. Jung
    • 1
  • T. Kneib
    • 3
  • A. Kurz
    • 2
  • J. Kornhuber
    • 1
  • S. Bleich
    • 1
    • 4
  1. 1.Department of Psychiatry and PsychotherapyFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  2. 2.Department of Psychiatry and PsychotherapyTechnische Universität MünchenMunichGermany
  3. 3.Institute of MathematicsCarl von Ossietzky Universität OldenburgOldenburgGermany
  4. 4.Department of Psychiatry, Socialpsychiatry and PsychotherapyMedizinische Hochschule HannoverHannoverGermany
  5. 5.Klinik für Psychiatrie und PsychotherapieKlinikum rechts der Isar der Technischen Universität MünchenMunichGermany

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