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


METHODS
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.


METHODS
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
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.
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Mark H B
MH
Huisman
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Meinie
M
Seelen
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Perry T C
PT
van Doormaal
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Sonja W
SW
de Jong
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.
Jeanne H M
JH
de Vries
Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Anneke J
AJ
van der Kooi
Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Marianne
M
de Visser
Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
H Jurgen
HJ
Schelhaas
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Leonard H
LH
van den Berg
Department of Neurology, Rudolf Magnus Brain Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
Jan H
JH
Veldink
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000438:Alcohols; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D015992:Body Mass Index; D002149:Energy Intake / Q000502:physiology*; D005216:Fat Body / Q000378:metabolism*; D005223:Fats / Q000008:administration & dosage* / Q000378:metabolism; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors
D000438:Alcohols; D005223:Fats