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Are plasma homocysteine and methionine elevated when binging and purging behavior complicates anorexia nervosa? Evidence against the transdiagnostic theory of eating disorders

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Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Objective: To determine whether plasma total homocysteine (tHcy) and plasma methionine levels are different in anorexia nervosa restricting type (AN-R) compared to anorexia nervosa binge eating/purging type (AN-BP). Methods: Cross-sectional design. Subjects: Subjects were recruited from the outpatient program of the Eating Disorders Program at St. Paul’s Hospital, Vancouver, Canada. All subjects had a current Diagnostic and Statistical Manual of mental Disorders — Fourth Edition (DSM-IV) AN-R, or AN-BP diagnosis. Controls were recruited from staff and trainees of Child and Family Research Institute, and Children’s and Women’s Hospital, University of British Columbia. Results: Samples were obtained from AN-R (N=30), AN-BP (N=32) and control women (N=73) and men (N=33). The 5–95th% confidence intervals from the control women were taken as the normal range. The plasma tHcy and methionine for the control group had a 5-95th percentile range of 5.66–10.57 and 15.3–40.2 μM, respectively. Plasma tHcy was elevated in women with AN-BP (9.24±0.85 μM, N=32) but not with AN-R (7.90±0.38 μM, N=30). Plasma methionine was decreased in women with AN-BP (22.2±1.43 μM, N=32) compared to the control group of women (25.1±0.89 μM). The plasma methionine/tHcy ratio was elevated in the women with AN-BP (0.50±0.09) but not in those with AN-R (0.34±0.03). Conclusion: Elevated plasma tHcy and decreased plasma methionine are consistent with impaired homocysteine remethylation. Altered methyl transfer capacity or methyl deficiency could impair monoamine neurotransmitter metabolism potentially impacting cognitive and psychological function.We hypothesize that the treatment of AN-BP should consider the need for nutritional support of methyl metabolism.

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References

  1. American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. Washington, DC, American Psychiatric Association, 2000.

    Google Scholar 

  2. Davis C.: Eating disorders and hyperactivity: a psychobiological perspective. Can. J. Psychiatry, 42, 168–175, 1997.

    CAS  PubMed  Google Scholar 

  3. Birmingham C.L., Gutierrez E., Jonat L., Beumont P.: Randomized controlled trial of warming in anorexia nervosa. Int. J. Eat. Disord., 35, 234–238, 2004.

    Article  PubMed  Google Scholar 

  4. Kas M.J., Kaye W.H., Foulds Mathes W., Bulik C.M.: Interspecies genetics of eating disorder traits. Am. J. Med. Genet. B Neuropsychiatr. Genet., 150, 318–327, 2009.

    Article  Google Scholar 

  5. Birmingham C.L., Gritzner S.: How does zinc supplementation benefit anorexia nervosa? Eat. Weight Disord., 11, e109–e111, 2006.

    Article  CAS  PubMed  Google Scholar 

  6. Fetissov S.O., Dechelotte P.: The putative role of neuropeptide autoantibodies in anorexia nervosa. Curr. Opin. Clin. Nutr. Metab. Care, 11, 428–434, 2008.

    Article  CAS  PubMed  Google Scholar 

  7. Cleveland M.J., Feinberg M.E., Bontempo D.E., Greenberg M.T.: The role of risk and protective factors in substance use across adolescence. J. Adolesc. Health, 43, 157–164, 2008.

    Article  PubMed Central  PubMed  Google Scholar 

  8. McNally L., Bhagwagar Z., Hannestad J.: Inflammation, glutamate, and glia in depression: a literature review. C.N.S. Spectr., 13, 501–510, 2008.

    Google Scholar 

  9. Bowie D.: Ionotropic glutamate receptors & CNS disorders. C.N.S. Neurol. Disord. Drug Targets, 7, 129–143, 2008.

    Article  CAS  Google Scholar 

  10. Kaye W.: Neurobiology of anorexia and bulimia nervosa. Physiol. Behav., 94, 121–135, 2008.

    Article  CAS  PubMed Central  Google Scholar 

  11. Finkelstein J.D.: Methionine metabolism in mammals. J. Nutr. Biochem., 1, 228–237, 1990.

    Article  CAS  PubMed  Google Scholar 

  12. Refsum H., Smith A.D., Ueland P.M., Nexo E., Clarke R., McPartlin J., Johnston C., Engbaek F., Schneede J., McPartlin C., Scott J.M.: Facts and recommendations about total homocysteine determinations: an expert opinion. Clin. Chem., 50, 3–32, 2004.

    Article  CAS  PubMed  Google Scholar 

  13. Refsum H., Ueland P.M., Nygard O., Vollset S.E.: Homocysteine and cardiovascular disease. Annu. Rev. Med., 49, 31–62, 1998.

    Article  CAS  PubMed  Google Scholar 

  14. Boushey C.J., Beresford S.A., Omenn G.S., Motulsky A.G.: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. J.A.M.A., 274, 1049–1057, 1995.

    Article  CAS  PubMed  Google Scholar 

  15. McCully K.S.: Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am. J. Pathol., 56, 111–128, 1969.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Stampfer M.J., Malinow M.R., Willett W.C., Newcomer L.M., Upson B., Ullmann D., Tishler P.V., Hennekens C.H.: A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. J.A.M.A., 268, 877–881, 1992.

    Article  CAS  PubMed  Google Scholar 

  17. Wilcken D.E., Wilcken B.: The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J. Clin. Invest., 57, 1079–1082, 1976.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Israelsson B., Brattstrom L.E., Hultberg B.L.: Homocysteine and myocardial infarction. Atherosclerosis, 71, 227–233, 1988.

    Article  CAS  PubMed  Google Scholar 

  19. Ubbink J.B., Vermaak W.J., Bennett J.M., Becker P.J., van Staden D.A., Bissbort S.: The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. Klin. Wochenschr., 69, 527–534, 1991.

    Article  CAS  PubMed  Google Scholar 

  20. Olszewski A.J., Szostak W.B.: Homocysteine content of plasma proteins in ischemic heart disease. Atherosclerosis, 69, 109–113, 1988.

    Article  CAS  PubMed  Google Scholar 

  21. Blasco C., Caballeria J., Deulofeu R., Lligona A., Pares A., Lluis J.M., Gual A., Rodes J.: Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics. Alcohol Clin. Exp. Res., 29, 1044–1048, 2005.

    Article  CAS  Google Scholar 

  22. Bleich S., Degner D., Javaheripour K., Kurth C., Kornhuber J.: Homocysteine and alcoholism. J. Neural. Transm. Suppl., 187–196, 2000.

    Google Scholar 

  23. Bleich S., Degner D., Wiltfang J., Maler J.M., Niedmann P., Cohrs S., Mangholz A., Porzig J., Sprung R., Ruther E., Kornhuber J.: Elevated homocysteine levels in alcohol withdrawal. Alcohol Alcohol, 35, 351–354, 2000.

    Article  CAS  PubMed  Google Scholar 

  24. Carmel R., James S.J.: Alcohol abuse: an important cause of severe hyperhomocysteinemia. Nutr. Rev., 60, 215–221, 2002.

    Article  PubMed  Google Scholar 

  25. Cravo M.L., Gloria L.M., Selhub J., Nadeau M.R., Camilo M.E., Resende M.P., Cardoso J.N., Leitao C.N., Mira F.C.: Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am J Clin Nutr, 63, 220–224, 1996.

    CAS  PubMed  Google Scholar 

  26. Halsted C.H., Villanueva J., Chandler C.J., Stabler S.P., Allen R.H., Muskhelishvili L., James S.J., Poirier L.: Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation. Hepatology, 23, 497–505, 1996.

    Article  CAS  PubMed  Google Scholar 

  27. Hultberg B., Berglund M., Andersson A., Frank A.: Elevated plasma homocysteine in alcoholics. Alcohol Clin. Exp. Res., 17, 687–689, 1993.

    Article  CAS  PubMed  Google Scholar 

  28. Zoccolella S., Simone I.L., Lamberti P., Samarelli V., Tortelli R., Serlenga L., Logroscino G.: Elevated plasma homocysteine levels in patients with amyotrophic lateral sclerosis. Neurology, 70, 222–225, 2008.

    Article  CAS  PubMed  Google Scholar 

  29. Clarke R., Smith A.D., Jobst K.A., Refsum H., Sutton L., Ueland P.M.: Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch. Neurol., 55, 1449–1455, 1998.

    Article  CAS  PubMed  Google Scholar 

  30. Seshadri S., Beiser A., Selhub J., Jacques P.F., Rosenberg I.H., D’Agostino R.B., Wilson P.W., Wolf P.A.: Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N. Engl. J. Med., 346, 476–483, 2002.

    Article  CAS  PubMed  Google Scholar 

  31. van Meurs J.B., Dhonukshe-Rutten R.A., Pluijm S.M., van der Klift M., de Jonge R., Lindemans J., de Groot L.C., Hofman A., Witteman J.C., van Leeuwen J.P., Breteler M.M., Lips P., Pols H.A., Uitterlinden A.G.: Homocysteine levels and the risk of osteoporotic fracture. N. Engl. J. Med., 350, 2033–2041, 2004.

    Article  PubMed  Google Scholar 

  32. McLean R.R., Jacques P.F., Selhub J., Tucker K.L., Samelson E.J., Broe K.E., Hannan M.T., Cupples L.A., Kiel D.P.: Homocysteine as a predictive factor for hip fracture in older persons. N. Engl. J. Med., 350, 2042–2049, 2004.

    Article  CAS  PubMed  Google Scholar 

  33. Gjesdal C.G., Vollset S.E., Ueland P.M., Refsum H., Meyer H.E., Tell G.S.: Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture: the hordaland homocysteine study. J. Bone Miner. Res., 22, 747–756, 2007.

    Article  CAS  PubMed  Google Scholar 

  34. Bjelland I., Ueland P.M., Vollset S.E.: Folate and depression. Psychother. Psychosom., 72, 59–60, 2003.

    Article  PubMed  Google Scholar 

  35. Kim J.M., Stewart R., Kim S.W., Yang S.J., Shin I.S., Yoon J.S.: Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression. Br. J. Psychiatry, 192, 268–274, 2008.

    Article  PubMed  Google Scholar 

  36. Frieling H., Romer K., Roschke B., Bonsch D., Wilhelm J., Fiszer R., de Zwaan M., Jacoby G.E., Kornhuber J., Bleich S.: Homocysteine plasma levels are elevated in females with anorexia nervosa. J. Neural Transm., 112, 979–985, 2005.

    Article  CAS  PubMed  Google Scholar 

  37. Moyano D., Vilaseca M.A., Artuch R., Valls C., Lambruschini N.: Plasma total-homocysteine in anorexia nervosa. Eur. J. Clin. Nutr., 52, 172–175, 1998.

    Article  CAS  PubMed  Google Scholar 

  38. Vilaseca M.A., Moyano D., Artuch R., Ferrer I., Pineda M., Cardo E., Campistol J., Pavia C., Camacho J.A.: Selective screening for hyperhomocysteinemia in pediatric patients. Clin. Chem., 44, 662–664, 1998.

    CAS  PubMed  Google Scholar 

  39. Frieling H., Romer K.D., Beyer S., Hillemacher T., Wilhelm J., Jacoby G.E., de Zwaan M., Kornhuber J., Bleich S.: Depressive symptoms may explain elevated plasma levels of homocysteine in females with eating disorders. J. Psychiatr. Res., 42, 83–86, 2008.

    Article  Google Scholar 

  40. Striegel-Moore R.H., Wonderlich S.: Diagnosis and classification of eating disorders: Finding the way forward. Int. J. Eat. Disord., 40, S1–S1, 2007.

    Article  Google Scholar 

  41. Fairburn C.G., Cooper Z.: Thinking afresh about the classification of eating disorders. Int. J. Eat. Disord., 40, Suppl., S107–S110, 2007.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Fairburn C.G., Cooper Z., Shafran R.: Cognitive behaviour therapy for eating disorders: a “transdiagnostic” theory and treatment. Behav. Res. Ther., 41, 509–528, 2003.

    Article  PubMed  Google Scholar 

  43. Fairburn C.G., Harrison P.J.: Eating disorders. Lancet, 361, 407–416, 2003.

    Article  PubMed  Google Scholar 

  44. Hay P., Fairburn C.: The validity of the DSM-IV scheme for classifying bulimic eating disorders. Int. J. Eat. Disord., 23, 7–15, 1998.

    Article  CAS  PubMed  Google Scholar 

  45. Wade T.D., Bergin J.L., Martin N.G., Gillespie N.A., Fairburn C.G.: A transdiagnostic approach to understanding eating disorders. J. Nerv. Ment. Dis., 194, 510–517, 2006.

    Article  PubMed  Google Scholar 

  46. Innis S.M., Davidson A.G., Melynk S., James S.J.: Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis. Am. J. Clin. Nutr., 85, 702–708, 2007.

    CAS  PubMed  Google Scholar 

  47. Friesen R.W., Novak E.M., Hasman D., Innis S.M.: Relationship of dimethylglycine, choline, and betaine with oxoproline in plasma of pregnant women and their newborn infants. J. Nutr., 137, 2641–2646, 2007.

    CAS  PubMed  Google Scholar 

  48. Eikelboom J.W., Lonn E., Genest J., Jr., Hankey G., Yusuf S.: Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann. Intern. Med., 131, 363–375, 1999.

    Article  CAS  PubMed  Google Scholar 

  49. Hall R.C., Hoffman R.S., Beresford T.P., Wooley B., Hall A.K., Kubasak L.: Physical illness encountered in patients with eating disorders. Psychosomatics, 30, 174–191, 1989.

    Article  CAS  PubMed  Google Scholar 

  50. Birmingham C.L., Stigant C., Goldner E.M.: Chest pain in anorexia nervosa. Int. J. Eat. Disord., 25, 219–222, 1999.

    Article  CAS  PubMed  Google Scholar 

  51. O’Brien K.M., Vincent N.K.: Psychiatric comorbidity in anorexia and bulimia nervosa: nature, prevalence, and causal relationships. Clin. Psychol. Rev., 23, 57–74, 2003.

    Article  PubMed  Google Scholar 

  52. Birmingham C.L., Lear S.A., Kenyon J., Chan S.Y., Mancini G.B., Frohlich J.: Coronary atherosclerosis in anorexia nervosa. Int. J. Eat. Disord., 34, 375–377, 2003.

    Article  PubMed  Google Scholar 

  53. Miller A.L.: The methylation, neurotrasnmitter, and antioxidant connections between folate and depression. Altern. Med. Rev., 13, 216–226, 2008.

    PubMed  Google Scholar 

  54. Bottiglier T.M.: Folate, B12, and neuropsychiatric disorders. Nutr. Rev., 54, 38–90, 1996.

    Google Scholar 

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Authors and Affiliations

  1. Deaprtment of Paediatrics, The Nutrition Research Program, Child and Family Research Institute, Canada

    S. M. Innis &  C. L. Birmingham

  2. Department of Psychiatry, University of British Columbia, 2255, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 2A1

    C. L. Birmingham & E. J. Harbottle

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  1. S. M. Innis
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  2. C. L. Birmingham
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Correspondence to C. L. Birmingham.

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Innis, S.M., Birmingham, C.L. & Harbottle, E.J. Are plasma homocysteine and methionine elevated when binging and purging behavior complicates anorexia nervosa? Evidence against the transdiagnostic theory of eating disorders. Eat Weight Disord 14, e184–e189 (2009). https://doi.org/10.1007/BF03325115

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