Lifetime physical activity and the risk of amyotrophic lateral sclerosis
Open accessAbstract
BACKGROUND: It has been hypothesised that physical activity is a risk factor for developing amyotrophic lateral sclerosis (ALS), fuelled by observations that professional soccer players and Gulf War veterans are at increased risk. In a population based study, we determined the relation between physical activity and risk of sporadic ALS, using an objective approach for assessing physical activity. METHODS: 636 sporadic ALS patients and 2166 controls, both population based, completed a semistructured questionnaire on lifetime history of occupations, sports and hobbies. To objectively compare the energy cost of a lifetime history of occupational and leisure time physical activities and to reduce recall bias, metabolic equivalent scores were assigned to each activity based on the Compendium of Physical Activities. RESULTS: ALS patients had significantly higher levels of leisure time physical activity compared with controls (OR 1.08, 95% CI 1.02 to 1.14, p=0.008). No significant difference was found between patients and controls in the level of vigorous physical activities, including marathons and triathlons, or in occupational activity. Cumulative measures of physical activity in quartiles did not show a dose-response relationship. CONCLUSIONS: An increased risk of ALS with higher levels of leisure time physical activity was found in the present study. The lack of association with occupational physical activity and the absence of a dose-response relationship strengthen the hypothesis that not increased physical activity per se but rather a genetic profile or lifestyle promoting physical fitness increases ALS susceptibility.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a Dutch study, rates of vigorous physical activities were not different between patients and controls (16% vs 14%, adjusted OR=1.24, 95% CI=0.96-1.61), not supporting an association between vigorous physical activity and ALS risk.
“Likewise, rates for participants with vigorous physical activities (including marathon and triathlon) were not different for patients and controls (16% vs. 14%, adjusted OR = 1.24, 95%‐CI = 0.96–1.61) in a Dutch study, not supporting an association between vigorous physical activity and the ALS risk (Huisman et al., 2013).”
From Prevalence of potential sports‐associated risk factors in Swiss amyotrophic lateral sclerosis patients (2017) · cites this paper as Huisman et al., 2013
It was proposed that not increased physical activity per se, but rather a yet unknown genetic profile or lifestyle-promoting physical fitness increases ALS susceptibility.
“With several extensive literature reviews reporting no evidence for a link between sports‐ or work‐related physical activity and ALS (Armon, 2007; Hamidou et al., 2014; Veldink et al., 2005), it was proposed that not increased physical activity per se, but rather a—yet unknown—genetic profile or lifestyle‐promoting physical fitness increases ALS susceptibility (Huisman et al., 2013; Turner, Wotton”
From Prevalence of potential sports‐associated risk factors in Swiss amyotrophic lateral sclerosis patients (2017) · cites this paper as Huisman et al., 2013
The hypothesis that not increased physical activity per se but other factors increase ALS susceptibility was supported by the observed discrepancy between increased risk with higher leisure time physical activities and lack of association with occupational physical activity and absence of dose-response relationship.
“This hypothesis was supported by the observed discrepancy between an increased risk for ALS with higher levels of leisure time physical activities and lack of association of ALS risk and occupational physical activity and the absence of a dose–‐response relationship (Huisman et al., 2013).”
From Prevalence of potential sports‐associated risk factors in Swiss amyotrophic lateral sclerosis patients (2017) · cites this paper as Huisman et al., 2013
Our observations fit well into the hypothesis that not increased physical activity per se but other unknown environmental factors and/or an unknown genetic profile or lifestyle-promoting physical fitness increases ALS susceptibility.
“While (repetitive) head traumata may be linked to earlier symptom onset, our observations fit well into the previously stated hypothesis that not increased physical activity per se but other unknown environmental factors and/or an—as yet unknown—genetic profile or lifestyle‐promoting physical fitness increases ALS susceptibility (Huisman et al., 2013).”
From Prevalence of potential sports‐associated risk factors in Swiss amyotrophic lateral sclerosis patients (2017) · cites this paper as Huisman et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Environment and Disease: Association or Causation?
Hill, A. B. (1965) · Proceedings of the Royal Society of Medicine · doi:10.1177/003591576505800503 · Cited by 6,974 · see citing works
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409 · see citing works
Kiernan, M. C., Vucic, S., Cheah, B. C., Turner, M. R., Eisen, A., Hardiman, O., Burrell, J. R., & Zoing, M. C. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61156-7 · Cited by 2,603 · see citing works
Participation Rates in Epidemiologic Studies
Galea, S., & Tracy, M. (2007) · Annals of Epidemiology · doi:10.1016/j.annepidem.2007.03.013 · Cited by 1,877 · see citing works
Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players
Chio, A. (2005) · Brain · doi:10.1093/brain/awh373 · Cited by 484 · see citing works
Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis
Ilieva, E. V., Ayala, V., Jove, M., Dalfo, E., Cacabelos, D., Povedano, M., Bellmunt, M. J., Ferrer, I., Pamplona, R., & Portero-Otin, M. (2007) · Brain · doi:10.1093/brain/awm190 · Cited by 358 · see citing works
ALS in Italian professional soccer players: The risk is still present and could be soccer-specific
Chiò, A., Calvo, A., Dossena, M., Ghiglione, P., Mutani, R., & Mora, G. (2009) · Amyotrophic Lateral Sclerosis · doi:10.1080/17482960902721634 · Cited by 180 · see citing works
Longstreth, W. T., Nelson, L. M., Koepsell, T. D., & Van Belle, G. (1991) · Medical Hypotheses · doi:10.1016/0306-9877(91)90183-y · Cited by 51 · see citing works
Flagged first, then by citations
Research works printed but not linked: 30
- Lehman EJ, Hein MJ, Baron SL, et al. Neurodegenerative causes of death among retired National Football League players. Neurology 2012;79:1970-4.
- Weisskopf MG, O'Reilly EJ, McCullough ML, et al. Prospective study of military service and mortality from ALS. Neurology 2005;64:32-7.
- Huisman MH, de Jong SW, Verwijs MC, et al. Family history of neurodegenerative and vascular diseases in ALS: a population-based study. Neurology 2011;77:1363-9.
- Harwood CA, McDermott CJ, Shaw PJ. Physical activity as an exogenous risk factor in motor neuron disease (MND): A review of the evidence. Amyotroph Lateral Scler 2009;10:191-204.
- Vanacore N, Cocco P, Fadda D, et al. Job strain, hypoxia and risk of amyotrophic lateral sclerosis: Results from a death certificate study. Amyotroph Lateral Scler 2010;11:430-4.
- Armon C. An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis. Neuroepidemiology 2003;22:217-28.
- Veldink JH, Kalmijn S, Groeneveld GJ, et al. Physical activity and the association with sporadic ALS. Neurology 2005;64:241-5.
- Armon C. Sports and trauma in amyotrophic lateral sclerosis revisited. J Neurol Sci 2007;262:45-53.
- Beghi E, Logroscino G, Chio A, et al. Amyotrophic lateral sclerosis, physical exercise, trauma and sports: results of a population-based pilot case-control study. Amyotroph Lateral Scler 2010;11:289-92.
- Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32: S498-504.
- Brooks BR, Miller RG, Swash M, et al. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2000;1:293-9.
- Ishiura H, Takahashi Y, Mitsui J, et al. C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii Peninsula of Japan. Arch Neurol 2012;69:1154-8.
- Logroscino G, Traynor BJ, Hardiman O, et al. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 2010;81:385-90.
- Scarmeas N, Shih T, Stern Y, et al. Premorbid weight, body mass, and varsity athletics in ALS. Neurology 2002;59:773-5.
- Mattsson P, Lonnstedt I, Nygren I, et al. Physical fitness, but not muscle strength, is a risk factor for death in amyotrophic lateral sclerosis at an early age. J Neurol Neurosurg Psychiatry 2012;83:390-4.
- Turner MR, Wotton C, Talbot K, et al. Cardiovascular fitness as a risk factor for amyotrophic lateral sclerosis: indirect evidence from record linkage study. J Neurol Neurosurg Psychiatry 2012;83:395-8.
- Chio A, Mora G. Physical fitness and amyotrophic lateral sclerosis: dangerous liaisons or common genetic pathways? J Neurol Neurosurg Psychiatry 2012;83:389.
- Longstreth WT, McGuire V, Koepsell TD, et al. Risk of amyotrophic lateral sclerosis and history of physical activity: a population-based case-control study. Arch Neurol 1998;55:201-6.
- Lee JR, Annegers JF, Appel SH. Prognosis of amyotrophic lateral sclerosis and the effect of referral selection. J Neurol Sci 1995;132:207-15.
- Sorenson EJ, Mandrekar J, Crum B, et al. Effect of referral bias on assessing survival in ALS. Neurology 2007;68:600-2.
- McGuire V, Longstreth WT Jr, Koepsell TD, et al. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology 1996;47:571-3.
- Forbes RB, Colville S, Parratt J, et al. The incidence of motor nueron disease in Scotland. J Neurol 2007;254:866-9.
- Turner MR, Wicks P, Brownstein CA, et al. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2011;82:853-4.
- Ferraiuolo L, De Bono JP, Heath PR, et al. Transcriptional response of the neuromuscular system to exercise training and potential implications for ALS. J Neurochem 2009;109:1714-24.
- Lambrechts D, Storkebaum E, Morimoto M, et al. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet 2003;34:383-94.
- Zheng C, Nennesmo I, Fadeel B, et al. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol 2004;56:564-7.
- Al-Chalabi A, Scheffler MD, Smith BN, et al. Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis. Ann Neurol 2003;54:130-4.
- Gallo V, Bueno-de-Mesquita HB, Vermeulen R, et al. Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort. Ann Neurol 2009;65:378-85.
- Sutedja NA, van der Schouw YT, Fischer K, et al. Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2011;82:638-42.
- Wicks P. Hypothesis: Higher prenatal testosterone predisposes ALS patients to improved athletic performance and manual professions. Amyotroph Lateral Scler 2012;13:251-3.
Cited by
Sorted by citations
Autoimmune disease preceding amyotrophic lateral sclerosis: An epidemiologic study
Turner, M. R., Goldacre, R., Ramagopalan, S., Talbot, K., & Goldacre, M. J. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a6cc13 · Cited by 185 · see citing works
The changing picture of amyotrophic lateral sclerosis: lessons from European registers
Hardiman, O., Al-Chalabi, A., Brayne, C., Beghi, E., van den Berg, L. H., Chio, A., Martin, S., Logroscino, G., & Rooney, J. (2017) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-314495 · Cited by 126 · see citing works
Self-citationHead injury does not alter disease progression or neuropathologic outcomes in ALS
Fournier, C. N., Gearing, M., Upadhyayula, S. R., Klein, M., & Glass, J. D. (2015) · Neurology · doi:10.1212/wnl.0000000000001522 · Cited by 44 · see citing works
Feddermann‐Demont, N., Junge, A., Weber, K. P., Weller, M., Dvořák, J., & Tarnutzer, A. A. (2017) · Brain and Behavior · doi:10.1002/brb3.630 · Cited by 29 · see citing works
“…(Armon, 2007; Hamidou et al., 2014; Veldink et al., 2005), it was proposed that not increased physical activity per se, but rather a—yet unknown—genetic profile or lifestyle- promoting physical fitness increases ALS susceptibility (Huisman et al., 2013; Turner, Wotton, Talbot, & Goldacre, 2012).”
BackgroundMethodResultInfluential
- Authors
- Huisman, M. H. B., Seelen, M., de Jong, S. W., Dorresteijn, K. R. I. S., van Doormaal, P. T. C., van der Kooi, A. J., de Visser, M., Schelhaas, H. J., van den Berg, L. H., & Veldink, J. H.
- Affiliations
- University Medical Center Utrecht (NL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Veldink, J. H.
- ORCID
- Veldink, J. H.
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2013-02-16
- Volume
- 84
- Issue
- 9
- Pages
- 976-981
- ISSN
- 0022-3050 (ISSN-L)
- OpenAlex
- W2107339266
- Cited by
- 156
- References
- 9
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 20 · 2020: 11 · 2019: 8 · 2018: 13 · 2017: 16 · 2016: 24 · 2015: 15 · 2014: 9 · 2013: 8
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- European Commission (2007–2013, FP7 2007-2013, Health Seventh Framework Programme (FP7/2007-2013, FP7/2007, 259867)
- VSB Fonds
- Adessium Foundation
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- amyotrophic lateral sclerosis, physical activity, leisure-time physical activity, occupational physical activity, sporadic ALS, metabolic equivalents, energy expenditure, sports participation, risk factors, dose-response relationship
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alcohol Drinking, Algorithms, Amyotrophic Lateral Sclerosis, Data Interpretation, Statistical, Educational Status, Energy Metabolism, Female, Humans, Leisure Activities, Life Style, Male, Middle Aged, Motor Activity, Netherlands, Population, Risk, Risk Factors, Smoking, Logistic Models, Survival Analysis, Case-Control Studies, Occupational Health, Kaplan-Meier Estimate, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
