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
American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. Washington, DC, American Psychiatric Association, 2000.
Davis C.: Eating disorders and hyperactivity: a psychobiological perspective. Can. J. Psychiatry, 42, 168–175, 1997.
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.
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.
Birmingham C.L., Gritzner S.: How does zinc supplementation benefit anorexia nervosa? Eat. Weight Disord., 11, e109–e111, 2006.
Fetissov S.O., Dechelotte P.: The putative role of neuropeptide autoantibodies in anorexia nervosa. Curr. Opin. Clin. Nutr. Metab. Care, 11, 428–434, 2008.
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.
McNally L., Bhagwagar Z., Hannestad J.: Inflammation, glutamate, and glia in depression: a literature review. C.N.S. Spectr., 13, 501–510, 2008.
Bowie D.: Ionotropic glutamate receptors & CNS disorders. C.N.S. Neurol. Disord. Drug Targets, 7, 129–143, 2008.
Kaye W.: Neurobiology of anorexia and bulimia nervosa. Physiol. Behav., 94, 121–135, 2008.
Finkelstein J.D.: Methionine metabolism in mammals. J. Nutr. Biochem., 1, 228–237, 1990.
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.
Refsum H., Ueland P.M., Nygard O., Vollset S.E.: Homocysteine and cardiovascular disease. Annu. Rev. Med., 49, 31–62, 1998.
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.
McCully K.S.: Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am. J. Pathol., 56, 111–128, 1969.
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.
Wilcken D.E., Wilcken B.: The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J. Clin. Invest., 57, 1079–1082, 1976.
Israelsson B., Brattstrom L.E., Hultberg B.L.: Homocysteine and myocardial infarction. Atherosclerosis, 71, 227–233, 1988.
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.
Olszewski A.J., Szostak W.B.: Homocysteine content of plasma proteins in ischemic heart disease. Atherosclerosis, 69, 109–113, 1988.
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.
Bleich S., Degner D., Javaheripour K., Kurth C., Kornhuber J.: Homocysteine and alcoholism. J. Neural. Transm. Suppl., 187–196, 2000.
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.
Carmel R., James S.J.: Alcohol abuse: an important cause of severe hyperhomocysteinemia. Nutr. Rev., 60, 215–221, 2002.
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.
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.
Hultberg B., Berglund M., Andersson A., Frank A.: Elevated plasma homocysteine in alcoholics. Alcohol Clin. Exp. Res., 17, 687–689, 1993.
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.
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.
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.
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.
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.
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.
Bjelland I., Ueland P.M., Vollset S.E.: Folate and depression. Psychother. Psychosom., 72, 59–60, 2003.
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.
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.
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.
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.
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.
Striegel-Moore R.H., Wonderlich S.: Diagnosis and classification of eating disorders: Finding the way forward. Int. J. Eat. Disord., 40, S1–S1, 2007.
Fairburn C.G., Cooper Z.: Thinking afresh about the classification of eating disorders. Int. J. Eat. Disord., 40, Suppl., S107–S110, 2007.
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.
Fairburn C.G., Harrison P.J.: Eating disorders. Lancet, 361, 407–416, 2003.
Hay P., Fairburn C.: The validity of the DSM-IV scheme for classifying bulimic eating disorders. Int. J. Eat. Disord., 23, 7–15, 1998.
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.
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.
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.
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.
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.
Birmingham C.L., Stigant C., Goldner E.M.: Chest pain in anorexia nervosa. Int. J. Eat. Disord., 25, 219–222, 1999.
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.
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.
Miller A.L.: The methylation, neurotrasnmitter, and antioxidant connections between folate and depression. Altern. Med. Rev., 13, 216–226, 2008.
Bottiglier T.M.: Folate, B12, and neuropsychiatric disorders. Nutr. Rev., 54, 38–90, 1996.
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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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DOI: https://doi.org/10.1007/BF03325115