Abstract
Previous studies have suggested a close but inconsistent relationship between essential nutrients and the risk of amyotrophic lateral sclerosis (ALS), and whether this association is causal remains unknown. We aimed to investigate the potential causal relation between essential nutrients (essential amino acids, essential fatty acids, essential minerals, and essential vitamins) and the risk of ALS using Mendelian randomization (MR) analysis. Large-scale European-based genome-wide association studies’ (GWASs) summary data related to ALS (assembling 27,205 ALS patients and 110,881 controls) and essential nutrient concentrations were separately obtained. MR analysis was performed using the inverse variance–weighted (IVW) method, and sensitivity analysis was conducted by the weighted median method, simple median method, MR–Egger method and MR–PRESSO method. We found a causal association between genetically predicted linoleic acid (LA) and the risk of ALS (OR: 1.066; 95% CI: 1.011–1.125; p = 0.019). An inverse association with ALS risk was noted for vitamin D (OR: 0.899; 95% CI: 0.819–0.987; p = 0.025) and for vitamin E (OR: 0.461; 95% CI: 0.340–0.626; p = 6.25 × 10−7). The sensitivity analyses illustrated similar trends. No causal effect was observed between essential amino acids and minerals on ALS. Our study profiled the effects of diet-derived circulating nutrients on the risk of ALS and demonstrated that vitamin D and vitamin E are protective against the risk of ALS, and LA is a suggested risk factor for ALS.
Highlights
Introduction published maps and institutional affilAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with muscle weakness and atrophy, and patients usually die as a result of respiratory failure within 3–5 years of symptom onset [1,2]
The 29 dietary-derived potential risk factors for amyotrophic lateral sclerosis (ALS) that we evaluated involved five traits related to amino acids, seven to fatty acids, eight to minerals, and nine to vitamins, including 2–168 SNPs as genetic proxies for each of them
We found a suggestive significant association between linoleic acid (LA) and the risk of ALS, which was elevated by 6.6% for a one standard deviation unit increase in the LA concentration (IVWOR: 1.066, 95% CI: 1.011–1.125, p value = 0.019)
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with muscle weakness and atrophy, and patients usually die as a result of respiratory failure within 3–5 years of symptom onset [1,2]. No treatment is currently effective in reversing the progression of ALS, with the exception of riluzole, which probably prolongs median survival by 2–3 months [3]. The etiology of ALS is complex, largely unknown, and involves genetic and environmental factors [4]. Given the accumulated studies investigating risk factors for ALS, the implication of such findings has been a focus. Targeted lifestyle and dietary changes have been shown to be beneficial in the early stages of ALS [5,6]. Supplementing essential nutrients is considered a promising preventive intervention for many diseases due to its ability to maintain metabolic homeostasis and to mitigate oxidative stress [7–9].
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