Blood Harmane (1-Methyl-9H-Pyrido[3,4-b]indole) and Mercury in Essential Tremor: A Population-Based, Environmental Epidemiology Study in the Faroe Islands

Abstract

Background: Essential tremor (ET) is among the most prevalent neurological diseases. Its environmental determinants are poorly understood. Harmane (1-methyl-9H-pyrido[3, 4-b]indole), a dietary tremor-producing neurotoxin, has been linked to ET in a few studies in New York and Madrid. Mercury, also a tremor-producing neurotoxin, has not been studied in ET. The Faroe Islands have been the focus of epidemiological investigations of numerous neurological disorders. Objective: In this population-based, case-control study, we directly measured blood harmane concentrations (HA) and blood mercury concentrations (Hg) in ET cases and controls. Methods: In total, 1,328 Faroese adults were screened; 26 ET cases were identified whose (HA) and (Hg) were compared to 197 controls. Results: Although there were no statistically significant differences between diagnostic groups, median (HA) was 2.7× higher in definite ET (4.13 g -10 /mL) and 1.5× higher in probable ET (2.28 g -10 /mL) than controls (1.53 g -10 /mL). Small sample size was a limitation. For definite ET versus controls, p = 0.126. (Hg) were similar between groups. Conclusions: We demonstrated marginally elevated (HA) in definite and probable ET. These data are similar to those previously published and possibly extend etiological links between this neurotoxin and ET to a third locale. The study did not support a link between mercury and ET.

Meat Consumption and Meat Cooking Practices in Essential Tremor: A Population-Based Study in the Faroe Islands

“…These data lend further credence to the notion that non-dietary factors (e.g., metabolic and genetic differences) underlie the case-control difference in blood harmane concentrations observed in this or previous studies [11,24]. The link between harmane and ET has been established now in three different populations -the USA [2], Spain [4], and the Faroe Islands [3]. Future research must now focus on examining the mechanism of this elevation.…”

“…As discussed previously [3], median blood harmane concentration was observed to be 2.7 times higher in definite ET (4.13 ng/ml) and 1.5 times higher in probable ET (2.28 ng/ml) than controls within this population. When stratified by diagnostic groups to compare definite and probable ET cases (n = 16) to controls we did not observe any significant difference between total quantity of meat consumption: 123.9 ± 142.8 g/day vs. 113.6 ± 71.2 g/day (median values 85.3 vs. 95.8; p = 0.53).…”

“…Additionally, its genetically homogenous, highly delimited and well-defined population, make the Faroe Islands a well-suited site to conduct epidemiological studies. Recently, a study in the Faroe Islands noted a mild elevation in blood harmane concentrations in probable and definite ET cases [3], further facilitating and prompting the current analyses. The underlying mechanism for this elevation is not understood, and in these analyses, we explored dietary ones.…”

“…Participants were identified using a two-phase, population-based study design described previously [3,[16][17][18]. All study procedures were approved by the local Ethical Review Committee of the Faroe Islands and the Institutional Review Board at Yale University, with participation on a voluntary basis and signed informed consent obtained from each enrollee.…”

“…Essential tremor (ET) is among the most prevalent neurological diseases, yet potential modifiable environmental factors contributing to its etiology are poorly understood. Past studies have identified exposure to β-carboline alkaloids (BCAs), especially harmane, as a possible link to ET [1][2][3].…”