Kjetil Bjornevik1, Éilis J O'Reilly2, James D Berry2, Clary B Clish2, Sarah Jeanfavre2, Ikuko Kato2, Laurence N Kolonel2, Loic Le Marchand2, Marjorie L McCullough2, Sabrina Paganoni2, Michael A Schwarzschild2, Evelyn O Talbott2, Robert B Wallace2, Zhongli Zhang2, JoAnn E Manson2, Alberto Ascherio2. 1. From the Departments of Nutrition (K.B., É.J.O., Z.Z., A.A.) and Epidemiology (J.E.M., A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health (É.J.O.), College of Medicine, University College Cork, Ireland; Department of Neurology (J.D.B., M.A.S.), Massachusetts General Hospital (S.P.), Boston; Metabolomics Platform (C.B.C., S.J.), Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Department of Oncology (I.K.), Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Epidemiology Research Program (M.L.M.), American Cancer Society, Atlanta, GA; Department of Physical Medicine and Rehabilitation (S.P.), Spaulding Rehabilitation Hospital, Charlestown; Harvard Medical School (S.P., M.A.S.), Boston, MA; Department of Epidemiology (E.O.T.), Graduate School of Public Health, University of Pittsburgh, PA; Department of Epidemiology (R.B.W.), College of Public Health, University of Iowa, Iowa City; and Department of Medicine (J.E.M.) and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. kbjorne@hsph.harvard.edu. 2. From the Departments of Nutrition (K.B., É.J.O., Z.Z., A.A.) and Epidemiology (J.E.M., A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health (É.J.O.), College of Medicine, University College Cork, Ireland; Department of Neurology (J.D.B., M.A.S.), Massachusetts General Hospital (S.P.), Boston; Metabolomics Platform (C.B.C., S.J.), Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Department of Oncology (I.K.), Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Epidemiology Research Program (M.L.M.), American Cancer Society, Atlanta, GA; Department of Physical Medicine and Rehabilitation (S.P.), Spaulding Rehabilitation Hospital, Charlestown; Harvard Medical School (S.P., M.A.S.), Boston, MA; Department of Epidemiology (E.O.T.), Graduate School of Public Health, University of Pittsburgh, PA; Department of Epidemiology (R.B.W.), College of Public Health, University of Iowa, Iowa City; and Department of Medicine (J.E.M.) and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.
OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.
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