. 2019 Apr 30;92(18):e2081-e2088.

doi: 10.1212/WNL.0000000000006669. Epub 2018 Nov 14.

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis

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

Affiliations

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.

PMID: 30429276
PMCID: PMC6512885
DOI: 10.1212/WNL.0000000000006669

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis

Kjetil Bjornevik et al. Neurology. 2019.

. 2019 Apr 30;92(18):e2081-e2088.

doi: 10.1212/WNL.0000000000006669. Epub 2018 Nov 14.

Authors

Affiliations

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.

PMID: 30429276
PMCID: PMC6512885
DOI: 10.1212/WNL.0000000000006669

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.

PubMed Disclaimer

Cited by

Branched-Chain Amino Acids in Parkinson's Disease: Molecular Mechanisms and Therapeutic Potential.
Huang HY, Tsao SP, Yeh TH. Huang HY, et al. Int J Mol Sci. 2025 Jul 21;26(14):6992. doi: 10.3390/ijms26146992. Int J Mol Sci. 2025. PMID: 40725241 Free PMC article. Review.
Unbiased metabolome screen leads to personalized medicine strategy for amyotrophic lateral sclerosis.
Boddy S, Islam M, Moll T, Kurz J, Burrows D, McGown A, Bhargava A, Julian TH, Harvey C, Marshall JN, Hall BP, Allen SP, Kenna KP, Sanderson E, Zhang S, Ramesh T, Snyder MP, Shaw PJ, McDermott C, Cooper-Knock J. Boddy S, et al. Brain Commun. 2022 Mar 17;4(2):fcac069. doi: 10.1093/braincomms/fcac069. eCollection 2022. Brain Commun. 2022. PMID: 35441136 Free PMC article.
The Big Picture of Neurodegeneration: A Meta Study to Extract the Essential Evidence on Neurodegenerative Diseases in a Network-Based Approach.
Ruffini N, Klingenberg S, Heese R, Schweiger S, Gerber S. Ruffini N, et al. Front Aging Neurosci. 2022 Jun 27;14:866886. doi: 10.3389/fnagi.2022.866886. eCollection 2022. Front Aging Neurosci. 2022. PMID: 35832065 Free PMC article.
Soccer (football) and brain health.
Pensato U, Cortelli P. Pensato U, et al. J Neurol. 2024 Jun;271(6):3019-3029. doi: 10.1007/s00415-024-12320-5. Epub 2024 Apr 1. J Neurol. 2024. PMID: 38558150 Free PMC article. Review.
Unveiling amyotrophic lateral sclerosis complexity: insights from proteomics, metabolomics and microbiomics.
Scarcella S, Brambilla L, Quetti L, Rizzuti M, Melzi V, Galli N, Sali L, Costamagna G, Comi GP, Corti S, Gagliardi D. Scarcella S, et al. Brain Commun. 2025 Mar 19;7(2):fcaf114. doi: 10.1093/braincomms/fcaf114. eCollection 2025. Brain Commun. 2025. PMID: 40161216 Free PMC article. Review.

See all "Cited by" articles

References

1. Yudkoff M, Daikhin Y, Nissim I, et al. . Brain amino acid requirements and toxicity: the example of leucine. J Nutr 2005;135:1531S–1538S. - PubMed
1. Plaitakis A. Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis: a hypothesis. Ann Neurol 1990;28:3–8. - PubMed
1. Plaitakis A, Smith J, Mandeli J, Yahr MD. Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. Lancet 1988;1:1015–1018. - PubMed
1. The Italian ALS Study Group. Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? Neurology 1993;43:2466–2470. - PubMed
1. Tandan R, Bromberg MB, Forshew D, et al. . A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I: clinical, functional, and maximum isometric torque data. Neurology 1996;47:1220–1226. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis

Affiliations

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous