Clinical research study| Volume 124, ISSUE 11, P1058-1063, November 2011

Download started.


Individuals Reporting Idiopathic Malodor Production: Demographics and Incidence of Trimethylaminuria



      Individuals with the metabolic disorder trimethylaminuria may sporadically produce malodors despite good hygiene. The psychosocial impact of trimethylaminuria can be considerable. However, trimethylaminuria is difficult to diagnose without specialized tests, in part because odor production is diet-dependent, and malodors may not be present during medical examinations. Thus, the prevalence and demographics of trimethylaminuria remain unclear.


      We tested 353 patients who had unexplained (idiopathic) malodor production for trimethylaminuria using a standard choline challenge. We also collected basic demographic information.


      Approximately one third of patients (118) tested positive for trimethylaminuria. Consistent with previous reports, women, particularly African American women, were significantly overrepresented among trimethylaminuria-positive patients. Of note, the same pattern was seen among trimethylaminuria-negative patients. Also consistent with previous reports, trimethylaminuria-positive women who were still menstruating tended to produce higher levels of trimethylamine within ±7 days of menses, although this trend was statistically marginal (P = .07).


      If our patient sample is representative of patients with idiopathic malodor, demographic information (race and gender) may not be useful in a differential diagnosis of trimethylaminuria. However, undiagnosed cases of trimethylaminuria may be fairly common among patients with idiopathic malodor. If so, choline challenge testing should be indicated for all such patients because trimethylaminuria is responsive to dietary and other treatments. We speculate that testing also might reveal cases of trimethylaminuria among those diagnosed with certain psychologic disorders, including olfactory reference syndrome.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • van den Velde S.
        • Quirynen M.
        • van Hee P.
        • van Steenberg D.
        Differences between alveolar air and mouth air.
        Anal Chem. 2007; 79: 3425-3429
        • Gallagher M.
        • Wysocki C.J.
        • Leyden J.J.
        • Spielman A.I.
        • Sun X.
        • Preti G.
        Analyses of volatile organic compounds from human skin.
        Br J Dermatol. 2008; 159: 780-791
        • Walker V.
        The fish odour syndrome: the problems are psychosocial.
        BMJ. 1993; 307: 539
        • Cashman J.R.
        • Camp K.
        • Fakharzadeh S.S.
        • et al.
        Biochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria.
        Curr Drug Metab. 2003; 4: 151-170
        • Phillips I.R.
        • Shepard E.R.
        Flavin-containing monooxygenase: mutations, disease and drug response.
        Trends Pharmacol Sci. 2008; 29: 294-301
        • Yeung C.K.
        • Adman E.T.
        • Rettie A.E.
        Functional characterization of genetic variants of human FMO3 associated with trimethylaminuria.
        Arch Biochem Biophys. 2007; 464: 251-259
        • Tjoa S.
        • Fennessey P.V.
        The identification of trimethylamine excess in man: quantitative analysis and biochemical origins.
        Anal Biochem. 1991; 16: 587-597
        • Whittle C.L.
        • Fakharzadeh S.S.
        • Eades J.
        • Preti G.
        Human breath odors and their use in diagnosis.
        Ann N Y Acad Sci. 2007; 1098: 252-266
        • Shelley E.D.
        • Shelley W.B.
        The fish odour syndrome, trimethylaminuria.
        JAMA. 1984; 251: 253-255
        • Spellacy E.
        • Watts R.W.
        • Goolamali S.K.
        J Inherit Metab Dis. 1980; 2: 86-88
        • Marks R.
        • Greaves M.W.
        • Prottey C.
        • Hartop P.J.
        Trimethylaminuria: the use of choline as an aid to diagnosis.
        Br J Dermatol. 1977; 96: 399-402
        • Mitchell S.C.
        • Zhang A.Q.
        • Barrett T.
        • Ayesh R.
        • Smith R.L.
        Studies on the discontinuous N-oxidation of trimethylamine among Jordanian, Ecuadorian and New Guinean populations.
        Pharmacogenetics. 1997; 7: 45-50
        • Danks D.M.
        • Hammond J.
        • Schlesinger P.
        • Faull K.
        • Burke D.
        • Halpern B.
        Trimethylaminuria: diet does not always control the fishy odor.
        N Engl J Med. 1976; 25: 962
        • Treacy E.
        • Johnson D.
        • Pitt J.J.
        • Danks D.M.
        Trimethylaminuria, fish odour syndrome: a new method of detection and response to treatment with metronidazole.
        J Inherit Metab Dis. 1995; 18: 306-312
        • Yamazaki H.
        • Fujieda M.
        • Togashi M.
        • et al.
        Effects of the dietary supplements, activated charcoal and copper chlorophyllin, on urinary excretion of trimethylamine in Japanese trimethylaminuria patients.
        Life Sci. 2004; 74: 2739-2747
        • Preti G.
        • Lawley H.L.
        • Hormann C.A.
        • et al.
        Non-oral and oral aspects of oral malodor.
        in: Rosenberg M. Bad Breath: Research Perspectives. Ramot Publishing-Tel Aviv Univ, Ramat Aviv, Israel1995: 149-173
        • Leopold D.A.
        • Preti G.
        • Mozell M.M.
        • Youngentob S.L.
        • Wright H.N.
        Fish-odor syndrome presenting as dysosmia.
        Arch Otolaryngol. 1990; 116: 354-355
        • Zhou J.
        • Shepard E.A.
        Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3.
        Mutat Res. 2006; 612: 165-171
        • Zhang A.Q.
        • Mitchell S.C.
        • Smith R.L.
        Exacerbation of symptoms of fish-odour syndrome during menstruation.
        Lancet. 1996; 348: 1740-1741
        • Shimizu M.
        • Cashman J.R.
        • Yamazaki H.
        Transient trimethylaminuria related to menstruation.
        BMC Med Genet. 2007; 8: 2
        • Metz C.E.
        Basic principles of ROC analysis.
        Semin Nucl Med. 1978; 8: 283-298
        • Cashman J.R.
        • Xiong Y.
        • Lin J.
        • et al.
        In-vitro and in-vivo studies inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles.
        Biochem Pharmacol. 1999; 58: 1047-1055
        • Begum M.
        • McKeena M.J.
        Olfactory reference syndrome: a systematic review of the world literature.
        Psychol Med. 2011; 41 (Epub 2010 Jun 9): 453-461
        • Human BioMolecular Research Institute
        TMAuria [Web page].
        HBRI, San Diego, CA2009 (Accessed March 16, 2011)
        • Denver Genetics Laboratories, University of Colorado School of Medicine
        Trimethylamine (TMA) and TMA N-oxide (TMAO), quantitative, urine clinical test information [Web page].
        The Regents of the University of Colorado, Denver, CO2008 (Accessed March 16, 2011)
        • The Monell Chemical Senses Center
        TMAU & body malodors [Web page].
        The Monell Chemical Senses Center, Philadelphia, PA2008 (Accessed March 16, 2011)