View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Hindawi Publishing Corporation Journal of Toxicology Volume 2011, Article ID 628151, 6 pages doi:10.1155/2011/628151 Research Article Blood Harmane Concentrations in 497 Individuals Relative to Coffee, Cigarettes, and Food Consumption on the Morning of Testing Elan D. Louis,1, 2, 3, 4 Pam Factor-Litvak,3 Marina Gerbin,1 Wendy Jiang,5 and Wei Zheng5 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, Unit 198, Neurological Institute, 710 West 168th Street, New York, NY 10032-2699, USA 2 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10027-6900, USA 3 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032-3727, USA 4 Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 5 School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, USA Correspondence should be addressed to Elan D. Louis, [email protected] Received 23 November 2010; Revised 11 February 2011; Accepted 16 February 2011 Academic Editor: Margaret James Copyright © 2011 Elan D. Louis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Harmane, a potent neurotoxin linked with several neurological disorders, is present in many foods, coffee,andcigarettes.We assessed whether morning food/coffee consumption and smoking were reflected in blood harmane concentrations (BHCs) we obtained in an epidemiologic sample (n = 497). Participants who smoked on the morning of phlebotomy had similar logBHCs to those who had not smoked (P = .57);therewasnocorrelationbetweenlogBHCsandnumberofcigarettes(P = .59). Among the coffee drinkers, there was no correlation between number of cups and logBHCs (P = .98). Participants who had eaten on the morning of phlebotomy had similar logBHCs to those who had not (P = .49); logBHCs did not correlate with the time latency between last food consumption and phlebotomy (P = .74). BHCs in this sample of ∼500 individuals did not covary with recent smoking, coffee, or food consumption, suggesting that our inability to withhold these exposures on the morning of phlebotomy was not reflected in the BHCs we measured. 1. Introduction (harmane dissolved in corn oil), blood harmane levels in rats peaked rapidly (in approximately 30 minutes) and then Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent gradually returned to baseline within 3–5 hours [9]. neurotoxin that has been linked with several neurological Studies of harmane and its relation to neurological outcomes [1, 2]. Although it is produced endogenously outcomes (essential tremor [ET] and Parkinson’s disease) by the body, harmane is also present in many foods (esp. often involve work with frail and elderly study subjects meats but also plant-derived foods) [3]. Studies have shown for whom fasting on the morning of testing is not fea- that harmane concentrations are particularly high in certain sible, especially as many of these patients must also take commonly consumed beverages (esp. coffee) [3–6]aswell prescription medications (often accompanied with food). as cigarettes [3, 5, 7]. Coffee consumption and smoking are It is also difficult to ask smokers to refrain, and their widespread and common human behaviors. attempts to do so can transiently exacerbate their tremor, Smoking [8] and food ingestion [9] have been shown to confounding the accurate assessment of tremor severity. result in transient elevations in BHCs. After smoking, blood Given these limitations, it is important to know whether harmane levels rise rapidly and seem to return to baseline food consumption, coffee consumption, and/or smoking on within one hour, although the number of tested human the morning of phlebotomy are reflected in blood harmane volunteers has been small (n = 3) [8]. After oral dosing concentrations (BHCs). 2 Journal of Toxicology Our overarching question was whether morning [53.9%] female, chi-square = 0.00, and P = .96), years of food/coffee consumption and smoking were reflected in education (15.4 ± 3.5versus15.3 ± 3.5years,t = 0.49, and the BHCs we obtained. The specific questions we asked P = .63), and proportion who were current smokers (43 were the following. (1) Did participants who smoked on [8.7%] versus 57 [8.2%]) chi-square = 0.09, and P = .77). the morning of phlebotomy have higher BHCs than those who did not smoke? (2) Was the the number of cigarettes 2.2. Clinical Evaluation. All participants were evaluated in smoked on the morning of phlebotomy correlated with person by a trained tester. The tester administered clinical ff BHCs? (3) Did participants who consumed co ee on the questionnaires and performed a videotaped tremor exami- morning of phlebotomy have higher BHCs than those nation and phlebotomy. ff who did not? (4) Was the number of cups of co ee on the As noted above, most evaluations were home visits and, morning of phlebotomy correlated with BHCs? (5) Was therefore, were performed in the late morning, making there a correlation between the time of last food ingestion fasting BHCs impractical. ffi and BHCs? If these questions were answered a rmatively, The tester used a structured questionnaire to collect this would suggest that these exposures are important to demographic information including age in years, gender, ff consider when assessing case-control di erences in BHCs. race, years of education, current smoker (yes versus no), the If not, it would suggest that these exposures are relatively number of cigarettes smoked per day, cigarette pack years, the unimportant in this context. Using data from a large number of cigarettes smoked on the morning of phlebotomy, epidemiological study of ET, we evaluated these exposures and the number of cups of coffee consumed on the morning in approximately 500 individuals. In addition to BHCs, of phlebotomy. Several years into the study, questions were ff information on smoking, co ee consumption, and food added as to whether food was consumed on the morning intake on the morning of phlebotomy were available. of phlebotomy and the number of hours between last food consumption and the phlebotomy. Similar data on number of hours between smoking or coffee consumption and 2. Methods phlebotomy were not available. Medical comorbidity was assessed with the cumulative illness rating scale (range = 0– 2.1. Participants. All participants were enrolled between 42 (high comorbidity)) [13]. June 2000 and May 2008 in a study of the environmental The tester videotaped a tremor examination in all epidemiology of tremor at Columbia-University Medical participants [10, 12]. Each of 12 videotaped action tremor Center (CUMC). Participants consisted of ET cases and items was rated by a senior movement disorder neurologist controls. By design, ET cases were identified from several (E.D.L.) on a scale from 0 (none) to 3 (severe tremor) sources; the major ones were a computerized billing database [10–12]. of patients at the Neurological Institute of New York, CUMC, and the International Essential Tremor Foundation, whose members were mailed advertisements [2, 10]. All cases had 2.3. BHCs. At the time of the evaluation, phlebotomy was received a diagnosis of ET from their treating neurologist performed. When the evaluation was performed in the par- and lived within two-hour driving distance of CUMC in ticipant’s home, blood samples were temporarily stored on − ◦ the New York Metropolitan area. Based on a videotaped ice packs and then several hours later transferred to a 20 C tremor examination, described below, their diagnoses were freezer; if performed at CUMC, they were placed immedi- − ◦ confirmed by a senior movement disorder neurologist ately into a 20 C freezer. Blood harmane concentrations (E.D.L.) using published diagnostic criteria (moderate or were measured blinded to all clinical information with a greater amplitude action tremor during ≥3 activities or a well-established high-performance liquid chromatography head tremor in the absence of Parkinson’s disease, dystonia, method described in detail in our previous studies [2, 10, 14]. ffi or another neurological disorder) [10–12]. The intraday precision, measured as a coe cient of variation Normal control subjects were also recruited during the at 25 ng/mL, was 6.7%. The interday precision was 7.3% [14]. same time period [2, 10].Thesecontrolswereidentified Our method uses whole blood rather than plasma. Harmane using random digit telephone dialing within a defined set of is highly lipophilic, accumulating inside of blood cells, with telephone area codes in the New York Metropolitan area that published studies demonstrating low relative recovery of were represented by the ET cases. Controls were frequency harmane from plasma [9, 14]. matched to cases based on gender, race, and current age. The CUMC Internal Review Board approved of all 2.4. Statistical Analyses. Statistical analyses were performed study procedures, and signed written informed consent was in SPSS (Version 18.0). The empirical distribution of BHCs obtained from all participants upon enrollment [2, 10]. was positively skewed (one-sample Kolmogorov-Smirnov Of 698 ET cases and controls enrolled, complete data test, z = 9.37, P<.001), even after log transformation were available in 497 (71.2%). The majority of the remaining (one-sample Kolmogorov-Smirnov test, z = 2.37, P<.001). participants had refused phlebotomy or had had an unsuc- Hence, nonparametric tests (Mann Whitney U, Kruskal- cessful phlebotomy attempt. The final sample of 497 was Wallis, Spearman’s rho) were used when assessing this similar to the base sample of 698 in terms of age (mean ± variable. For smoking, pack years was assigned the value “0” standard deviation = 66.0 ± 14.4versus67.2 ± 14.2years, for nonsmokers.