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.
Neurology. 2019 Apr 30;92(18):e2081-e2088. doi: 10.1212/WNL.0000000000006669. Epub 2018 Nov 14.
To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk.
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.
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.
The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.
评估诊断前血浆支链氨基酸（BCAAs）水平是否与肌萎缩侧索硬化症（ALS）风险相关。
我们纳入了来自 5 项大型队列研究的参与者，即护士健康研究、健康专业人员随访研究、癌症预防研究 II 营养、多民族队列研究和妇女健康倡议，并在随访期间确定了 275 名患有 ALS 的个体。每例病例随机选择 2 名对照，按队列、年龄、性别、禁食状态和采血时间进行匹配。我们使用液相色谱-质谱法测量代谢物，并使用条件逻辑回归估计个体 BCAAs 与 ALS 风险的关联的率比（RR）和 95%置信区间（CI）。
没有一种 BCAAs 与更高的 ALS 风险相关。在多变量分析中，亮氨酸（RR 最高四分位与最低四分位比：0.87，95%CI 0.57-1.33）、异亮氨酸（RR 最高四分位与最低四分位比：0.81，95%CI 0.52-1.24）和缬氨酸（RR 最高四分位与最低四分位比：0.80，95%CI 0.52-1.23）的风险估计值相似，调整了体重指数、吸烟、教育水平和体力活动。这些估计值在按性别、禁食状态或采血时间与发病时间间隔分层后没有显著差异。
这项研究的结果不支持 BCAAs 是 ALS 风险因素的假设。
