Preventive factors for ALS

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Protective factors found to prevent ALS.

Nutrition

Fruits and vegetables

"A higher consumption of all fruits and vegetables and fruit alone in the highest quartiles was associated with a statistically significantly reduced risk of ALS. Although not statistically significant, a beneficial association between intake of all vegetables, green and yellow vegetables and other vegetables and ALS was found. No statistically significant dose-response relationship was observed between intake of beta-carotene, vitamin C and vitamin E and the risk of ALS. ... Our findings suggest that higher intake of food rich in antioxidants such as fruit and vegetables confer protection against the development of ALS."[1]

"Vigorous physical activity, self reported stress, a type A behavior pattern, and less frequent intakes of green-yellow vegetables were significantly associated with increased risk of ALS, whereas smoking and drinking habits were not. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and less frequent intakes of green-yellow vegetables (adjusted OR, 11.2; 95% CI, 3.8 to 33.0). ... These data suggested that imbalances between excessive productions of oxidants as patient-specific factors and a diminished or missing antioxidant defense system in motor neurons may increase the risk of ALS."[2]

Carotenoids

"A greater total major carotenoids intake was associated with a reduced risk of ALS (pooled, multivariate-adjusted RR for the highest to the lowest quintile = 0.75, 95% confidence interval [CI] = 0.61-0.91, p for trend = 0.004). Individually, higher dietary intakes of β-carotene and lutein were inversely associated with ALS risk. The pooled multivariate RRs comparing the highest to the lowest quintile for β-carotene and lutein were 0.85 (95% CI = 0.64-1.13, p for trend = 0.03) and 0.79 (95% CI = 0.64-0.96, p for trend = 0.01), respectively. Lycopene, β-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS. ... Consumption of foods high in carotenoids may help prevent or delay onset of ALS." [3]

Vitamin E

"A high intake of polyunsaturated fatty acid (PUFA) and vitamin E was significantly associated with a reduced risk of developing ALS (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p = 0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E appeared to act synergistically, because in a combined analysis the trend OR for vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03). ... A high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of developing ALS, and these nutrients appear to act synergistically."[4]

PUFAs (polyunsaturated fatty acids)

"A high intake of polyunsaturated fatty acid (PUFA) and vitamin E was significantly associated with a reduced risk of developing ALS (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p = 0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E appeared to act synergistically, because in a combined analysis the trend OR for vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03). ... A high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of developing ALS, and these nutrients appear to act synergistically."

"A high intake of carbohydrate was significantly associated with an increased risk of ALS (adjusted OR = 2.14, 95% CI 1.05-4.36; the highest versus the lowest tertile). ORs for the second and third tertile of total fat were 0.57 and 0.41 (95% CI 0.21-0.80), respectively. ORs for the highest tertile of intake versus the lowest were 0.41 (95% CI 0.21-0.80) for total fat, 0.30 (95% CI 0.16-0.5) for saturated fatty acids (SFAs), 0.35 (95% CI 0.18-0.69) for monounsaturated fatty acids (MUFAs) and 0.58 (95%CI 0.40-0.96) for polyunsaturated fatty acids (PUFAs). Our findings suggest that high intakes of carbohydrate and low intakes of fat and some kinds of fatty acids may, when combined, increased the risk of ALS."[5]

Dietary fats in general

"The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06) ... the associations with fat and fiber intake warrant further study and biologic explanation."[6]

Dietary fiber

"...dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02)."[7]

Glutamate

"Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). ... The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS..."[8]

Alcohol (ethyl alcohol)

"Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis."[9]

"... Current alcohol consumption was associated with a reduced risk of ALS (incident patient group: odds ratio = 0.52, 95% CI: 0.40, 0.75)" [10]

Pharmaceuticals

Aspirin

"The inverse association between aspirin and ALS was present predominately in patients older than 55 years. ... The results of this study suggested that aspirin use might reduce the risk of ALS, and the benefit might be more prominent for older people."[11]

Lifestyle, psychology, behavioural patterns

"Vigorous physical activity, self reported stress, a type A behavior pattern, and less frequent intakes of green-yellow vegetables were significantly associated with increased risk of ALS, whereas smoking and drinking habits were not. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and less frequent intakes of green-yellow vegetables (adjusted OR, 11.2; 95% CI, 3.8 to 33.0). ... These data suggested that imbalances between excessive productions of oxidants as patient-specific factors and a diminished or missing antioxidant defense system in motor neurons may increase the risk of ALS."


References

  1. ↑ Okamoto et al.: Fruit and vegetable intake and risk of amyotrophic lateral sclerosis in Japan. Neuroepidemiology 2009;32:251-6. PMID: 19209004. DOI. BACKGROUND: There has been little interest in the role of nutrition in the prevention of amyotrophic lateral sclerosis (ALS). We investigated the relationship between dietary intake of vegetables, fruit, and antioxidants and the risk of ALS in Japan. METHODS: Between 2000 and 2004, we recruited 153 ALS patients aged 18-81 years with disease duration of 3 years within the study period in accordance with El Escorial World Federation of Neurology criteria. Three hundred and six gender- and age-matched controls were randomly selected from the general population. Information on dietary factors was collected using a validated self-administered diet history questionnaire. RESULTS: A higher consumption of all fruits and vegetables and fruit alone in the highest quartiles was associated with a statistically significantly reduced risk of ALS. Although not statistically significant, a beneficial association between intake of all vegetables, green and yellow vegetables and other vegetables and ALS was found. No statistically significant dose-response relationship was observed between intake of beta-carotene, vitamin C and vitamin E and the risk of ALS. CONCLUSION: Our findings suggest that higher intake of food rich in antioxidants such as fruit and vegetables confer protection against the development of ALS.
  2. ↑ Okamoto et al.: Lifestyle factors and risk of amyotrophic lateral sclerosis: a case-control study in Japan. Ann Epidemiol 2009;19:359-64. PMID: 19342254. DOI. PURPOSE: We examined the associations between lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) using a case-control study in Aichi Prefecture, Japan. METHODS: The study comprised 183 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria as well as 366 gender- and age-matched controls randomly selected from the general population with the use of the basic register of residents. Detailed information on lifestyle factors was obtained through a mailed self-administered questionnaire. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Vigorous physical activity, self reported stress, a type A behavior pattern, and less frequent intakes of green-yellow vegetables were significantly associated with increased risk of ALS, whereas smoking and drinking habits were not. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and less frequent intakes of green-yellow vegetables (adjusted OR, 11.2; 95% CI, 3.8 to 33.0). CONCLUSION: These data suggested that imbalances between excessive productions of oxidants as patient-specific factors and a diminished or missing antioxidant defense system in motor neurons may increase the risk of ALS.
  3. ↑ Fitzgerald et al.: Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: pooled results from 5 cohort studies. Ann. Neurol. 2013;73:236-45. PMID: 23362045. DOI. OBJECTIVE: Prior research has suggested the possible role of oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS). Prospective data examining dietary antioxidants such carotenoids and vitamin C are limited. METHODS: Risk of ALS associated with carotenoid and vitamin C intake was investigated in 5 prospective cohorts: the National Institutes of Health-Association of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study (HPFS), and the Nurses Health Study (NHS). ALS deaths were documented using the National Death Index, and confirmed nonfatal ALS cases were included from HPFS and NHS. A total of 1,153 ALS deaths occurred among 1,100,910 participants (562,942 men; 537,968 women). Participants were categorized into cohort-specific quintiles of intake for dietary variables. We applied Cox proportional hazards regression to calculate cohort-specific risk ratios (RRs), and pooled results using random-effects methods. RESULTS: A greater total major carotenoids intake was associated with a reduced risk of ALS (pooled, multivariate-adjusted RR for the highest to the lowest quintile = 0.75, 95% confidence interval [CI] = 0.61-0.91, p for trend = 0.004). Individually, higher dietary intakes of β-carotene and lutein were inversely associated with ALS risk. The pooled multivariate RRs comparing the highest to the lowest quintile for β-carotene and lutein were 0.85 (95% CI = 0.64-1.13, p for trend = 0.03) and 0.79 (95% CI = 0.64-0.96, p for trend = 0.01), respectively. Lycopene, β-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS. INTERPRETATION: Consumption of foods high in carotenoids may help prevent or delay onset of ALS.
  4. ↑ Veldink et al.: Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatr. 2007;78:367-71. PMID: 16648143. DOI. BACKGROUND: To assess whether the premorbid dietary intake of fatty acids, cholesterol, glutamate or antioxidants was associated with the risk of developing amyotrophic lateral sclerosis (ALS). METHODS: Patients referred to our clinic during 2001-2002, who had definite, probable or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in a case-control study (132 patients and 220 healthy controls). A food-frequency questionnaire was used to assess dietary intake for the nutrients of interest. Multivariate logistic regression analysis was performed with adjustment for confounding factors (sex, age, level of education, energy intake, body mass index and smoking). RESULTS: A high intake of polyunsaturated fatty acid (PUFA) and vitamin E was significantly associated with a reduced risk of developing ALS (PUFA: odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2 to 0.7, p = 0.001; vitamin E: OR = 0.4, 95% CI = 0.2 to 0.7, p = 0.001). PUFA and vitamin E appeared to act synergistically, because in a combined analysis the trend OR for vitamin E was further reduced from 0.67 to 0.37 (p = 0.02), and that for PUFA from 0.60 to 0.26 (p = 0.005), with a significant interaction term (p = 0.03). The intake of flavonols, lycopene, vitamin C, vitamin B2, glutamate, calcium or phytoestrogens was not associated with the risk of developing ALS. CONCLUSION: A high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of developing ALS, and these nutrients appear to act synergistically.
  5. ↑ Okamoto et al.: Nutritional status and risk of amyotrophic lateral sclerosis in Japan. Amyotroph Lateral Scler 2007;8:300-4. PMID: 17852010. DOI. Only a few human studies have reported the relationship between dietary factors and the risk of amyotrophic lateral sclerosis (ALS). We therefore analyzed the relationship between macronutrients (carbohydrate, protein and fat) and the risk of ALS using a case-control study in Japan. The study comprised 153 ALS patients diagnosed by the El Escorial World Federation of Neurology criteria, and 306 gender- and age- matched controls randomly selected from the general population. A self-administered food frequency questionnaire was used to estimate pre-illness intakes of food groups and nutrients. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). A high intake of carbohydrate was significantly associated with an increased risk of ALS (adjusted OR = 2.14, 95% CI 1.05-4.36; the highest versus the lowest tertile). ORs for the second and third tertile of total fat were 0.57 and 0.41 (95% CI 0.21-0.80), respectively. ORs for the highest tertile of intake versus the lowest were 0.41 (95% CI 0.21-0.80) for total fat, 0.30 (95% CI 0.16-0.5) for saturated fatty acids (SFAs), 0.35 (95% CI 0.18-0.69) for monounsaturated fatty acids (MUFAs) and 0.58 (95%CI 0.40-0.96) for polyunsaturated fatty acids (PUFAs). Our findings suggest that high intakes of carbohydrate and low intakes of fat and some kinds of fatty acids may, when combined, increased the risk of ALS.
  6. ↑ Nelson et al.: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am. J. Epidemiol. 2000;151:164-73. PMID: 10645819. The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.
  7. ↑ Nelson et al.: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am. J. Epidemiol. 2000;151:164-73. PMID: 10645819. The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.
  8. ↑ Nelson et al.: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am. J. Epidemiol. 2000;151:164-73. PMID: 10645819. The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.
  9. ↑ E et al.: Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies. Neurol. Sci. 2016;37:1203-8. PMID: 27103621. DOI. The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.
  10. ↑ de Jong et al.: Smoking, alcohol consumption, and the risk of amyotrophic lateral sclerosis: a population-based study. Am. J. Epidemiol. 2012;176:233-9. PMID: 22791740. DOI. Smoking has been posited as a possible risk factor for amyotrophic lateral sclerosis (ALS), but large population-based studies of patients with incident disease are still needed. The authors performed a population-based case-control study in the Netherlands between 2006 and 2009, including 494 patients with incident ALS and 1,599 controls. To prove the relevance of population-based incidence cohorts in case-control studies, the authors compared results with those from cohorts including patients with prevalent ALS and referral patients. Subjects were sent a questionnaire. Multivariate analyses showed an increased risk of ALS among current smokers (odds ratio = 1.38, 95% confidence interval (CI): 1.02, 1.88) in the incident patient group only. Cox regression models showed that current smoking was also independently associated with shorter survival (hazard ratio = 1.51, 95% CI: 1.07, 2.15), explaining the lack of association in the prevalent and referral patient groups. Current alcohol consumption was associated with a reduced risk of ALS (incident patient group: odds ratio = 0.52, 95% CI: 0.40, 0.75). These findings indicate that current smoking is associated with an increased risk of ALS, as well as a worse prognosis, and alcohol consumption is associated with a reduced risk of ALS, further corroborating the role of lifestyle factors in the pathogenesis of ALS. The importance of population-based incident patient cohorts in identifying risk factors is highlighted by this study.
  11. ↑ Tsai et al.: Aspirin use associated with amyotrophic lateral sclerosis: a total population-based case-control study. J Epidemiol 2015;25:172-7. PMID: 25721071. DOI. BACKGROUND: The association of aspirin use and nonsteroid anti-inflammatory drug (NSAID) use with amyotrophic lateral sclerosis (ALS) risk is unclear. This study determined whether use of any individual compound is associated with ALS risk by conducting a total population-based case-control study in Taiwan. METHODS: A total of 729 patients with newly diagnosed ALS who had a severely disabling disease certificate between January 1, 2002, and December 1, 2008, comprised the case group. These cases were compared with 7290 sex-, age-, residence-, and insurance premium-matched controls. Drug use by each Anatomical Therapeutic Chemical code was analyzed using conditional logistic regression models. False discovery rate (FDR)-adjusted P values were reported in order to avoid inflating false positives. RESULTS: Of the 1336 compounds, only the 266 with use cases exceeding 30 in our database were included in the screening analysis. Without controlling for steroid use, the analysis failed to reveal any compound that was inversely associated with ALS risk according to FDR criteria. After controlling for steroid use, we found use of the following compounds to be associated with ALS risk: aspirin, diphenhydramine (one of the antihistamines), and mefenamic acid (one of the NSAIDs). A multivariate analysis revealed that aspirin was independently inversely associated with ALS risk after controlling for diphenhydramine, mefenamic acid, and steroid use. The inverse association between aspirin and ALS was present predominately in patients older than 55 years. CONCLUSIONS: The results of this study suggested that aspirin use might reduce the risk of ALS, and the benefit might be more prominent for older people.
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