title: Blood levels of trace metals and amyotrophic lateral sclerosis.
abstract: Some trace metals may increase risk of amyotrophic lateral sclerosis (ALS), whereas others may be beneficial. Our goal was to examine associations of ALS with blood levels of selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn). We conducted a case-control study of 163 neurologist confirmed patients from the National Registry of Veterans with ALS and 229 frequency-matched veteran controls. We measured metal levels in blood using inductively coupled plasma mass spectrometry and estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between ALS and a doubling of metal levels using unconditional logistic regression, adjusting for age, gender, and race/ethnicity. ALS was inversely associated with both Se (OR=0.4, 95% CI: 0.2-0.8) and Zn (OR=0.4, 95% CI: 0.2-0.8). Inverse associations with Se were stronger in patients with bulbar compared to spinal onset, worse function, longer diagnostic delay, and longer collection delay; inverse associations with Zn were stronger for those with worse function and longer collection delay. In contrast, ALS was positively associated with Cu (OR=3.4, 95% CI: 1.5-7.9). For Mn, no linear trend was evident (OR=0.9, 95% CI: 0.6-1.3, Ptrend=0.51). Associations of Se, Zn, Cu, and Mn with ALS were independent of one another. Adjustment for lead levels attenuated the positive association of ALS with Cu but did not change associations with Se, Zn, or Mn. In conclusion, Se and Zn were inversely associated with ALS, particularly among those with worse function, suggesting that supplementation with these metals may benefit such patients, while Cu was positively associated with ALS. Deficiencies of Se and Zn and excess Cu may have a role in ALS etiology.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Peters
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Beard
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.affiliation: Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, NC, USA; Department of Medicine and Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Allen
authors.affiliation: Westat Inc., Durham, NC, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Keller
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mariosa
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA.
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA. Electronic address: kamel@niehs.nih.gov.
authors.forename: Freya
authors.initials: F
authors.lastname: Kamel
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D016022:Case-Control Studies; D003300:Copper; D005260:Female; D006801:Humans; D007854:Lead; D008297:Male; D008345:Manganese; D008875:Middle Aged; D012643:Selenium; D014131:Trace Elements / Q000097:blood*; D015032:Zinc
chemical_list: D014131:Trace Elements; D007854:Lead; D008345:Manganese; D003300:Copper; D012643:Selenium; D015032:Zinc
keywords: Amyotrophic lateral sclerosis; Case-Control study; Motor neuron disease; Risk factors; Trace metals