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Original Investigation |

Effect of Presymptomatic Body Mass Index and Consumption of Fat and Alcohol on Amyotrophic Lateral Sclerosis

Mark H. B. Huisman, MD1; Meinie Seelen, MD, PhD1; Perry T. C. van Doormaal, MD1; Sonja W. de Jong, MD, PhD1; Jeanne H. M. de Vries, PhD2; Anneke J. van der Kooi, MD, PhD3; Marianne de Visser, MD, PhD3; H. Jurgen Schelhaas, MD, PhD4; Leonard H. van den Berg, MD, PhD1; Jan H. Veldink, MD, PhD1
[+] Author Affiliations
1Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands
2Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands
3Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
4Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
JAMA Neurol. 2015;72(10):1155-1162. doi:10.1001/jamaneurol.2015.1584.
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Importance  Because dietary intake may influence pathophysiologic mechanisms in sporadic amyotrophic lateral sclerosis (ALS), the association between premorbid dietary intake and the risk of sporadic ALS will provide insight into which mechanisms are possibly involved in ALS pathophogenesis.

Objective  To systematically determine the association between premorbid dietary intake and the risk of sporadic ALS.

Design, Setting, and Participants  A population-based case-control study was conducted in a general community setting in the Netherlands from January 1, 2006, to September 30, 2011. Analysis was conducted April 1, 2013, to November 15, 2014. All patients with a new diagnosis of possible, probable (laboratory supported), or definite ALS according to the revised El Escorial criteria were included and multiple sources were used to ensure complete case ascertainment. Of 986 eligible patients, 674 gave informed consent and returned a complete questionnaire; 2093 controls randomly selected from the general practitioners’ registers and frequency matched to the patients for sex and age were included.

Main Outcomes and Measures  We studied the premorbid intake of nutrients in association with the risk of ALS by using a 199-item food frequency questionnaire adjusted for confounding factors and corrected for multiple comparisons while minimizing recall bias.

Results  Presymptomatic total daily energy intake in patients, reported as mean (SD), was significantly higher compared with controls (2258 [730] vs 2119 [619] kcal/day; P < .01), and presymptomatic body mass index (calculated as weight in kilograms divided by height in meters squared) was significantly lower in patients (25.7 [4.0] vs 26.0 [3.7]; P = .02). With values reported as odds ratio (95% CI), higher premorbid intake of total fat (1.14; 1.07-1.23; P < .001), saturated fat (1.43; 1.25-1.64; P < .001), trans-fatty acids (1.03; 1.01-1.05; P < .001), and cholesterol (1.08; 1.05-1.12; P < .001) was associated with an increased risk of ALS; higher intake of alcohol (0.91; 0.84-0.99; P = .03) was associated with a decreased risk of ALS. These associations were independent of total energy intake, age, sex, body mass index, educational level, smoking, and lifetime physical activity. No significant associations between dietary intake and survival were found.

Conclusions and Relevance  The combination of independent positive associations of a low premorbid body mass index and a high fat intake together with prior evidence from ALS mouse models transgenic for SOD1 and earlier reports on premorbid body mass index support a role for increased resting energy expenditure before clinical onset of ALS.

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Association Between Risk of Amyotrophic Lateral Sclerosis (ALS) and Quintiles of Nutrient Intake

Adjusted odds ratios (ORs) for the association between ALS and quintiles of nutrient intake. Adjusted for energy intake, age (at ALS onset in patients; at the time of the questionnaire in controls), sex, body mass index, educational level, current smoking, and lifetime physical activity. The lowest quintile served as the reference group (thick horizontal line; OR, 1.0). P values are for the trend across quintiles.

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