Editing Preventive factors for ALS


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."{{#pmid: 19209004 | Okamoto2009}}

"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."{{#pmid: 19342254 | Okamoto2009}}

===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'''." {{#pmid: 23362045 | Fitzgerald2013}}

===Vitamin E===

"Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend=0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ≤1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2-4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ≥5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend=0.002) but not in men (P-trend=0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration."{{#pmid: 21335424 | Wang2011}}

"'''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'''."{{#pmid: 16648143 | Veldink2007}}

===PUFAs (polyunsaturated fatty acids) ===

"A total of 995 ALS cases were documented during the follow-up. A greater ω-3 PUFA intake was associated with a reduced risk for ALS. The pooled, multivariable-adjusted RR for the highest to the lowest quintile was 0.66 (95% CI, 0.53-0.81; P < .001 for trend). Consumption of both α-linolenic acid (RR, 0.73; 95% CI, 0.59-0.89; P = .003 for trend) and marine ω-3 PUFAs (RR, 0.84; 95% CI, 0.65-1.08; P = .03 for trend) contributed to this inverse association. Intakes of ω-6 PUFA were not associated with ALS risk. ... Consumption of foods high in ω-3 PUFAs may help prevent or delay the onset of ALS."{{#pmid: 25023276 | Fitzgerald2014}}

"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."{{#pmid: 16648143 | Veldink2007-2}}

===Higher HDL and apolipoprotein A1 levels===
"Controlling for age and sex, '''higher HDL (HR 0.84, 95% CI 0.73 to 0.96, p=0.010) and apoA1 (HR 0.83, 95% CI 0.72 to 0.94, p=0.005) were associated with a reduced risk of ALS.''' Higher total cholesterol:HDL was associated with an increased risk of ALS (HR 1.17, 95% CI 1.05 to 1.31, p=0.006). In models incorporating multiple metabolic markers, higher LDL or apoB was associated with an increased risk of ALS, in addition to a lower risk with higher HDL or apoA. Coronary artery disease, cerebrovascular disease and increasing age were also associated with an increased risk of ALS."[https://jnnp.bmj.com/content/93/1/75 Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis]

===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)."{{#pmid: 10645819 | Nelson2000-2}}

===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."{{#pmid:27103621|Yu2016}}

"... Current alcohol consumption was associated with a reduced risk of ALS (incident patient group: odds ratio = 0.52, 95% CI: 0.40, 0.75)" {{#pmid:22791740|deJong2012}}

==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."{{#pmid: 25721071 |Tsai2015}}

===Angiotensin-converting enzyme inhibitors===
"There was a dose-dependent inverse association between ACEI use and the risk for developing ALS. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 (95% CI, 0.65-1.07; P = .15) for the group prescribed ACEIs lower than 449.5 of the cDDD and 0.43 cDDD (95% CI, 0.26-0.72; P = .001) for the group with a cumulative ACEI use of greater than 449.5 cDDD. The association was most predominant in men older than 55 years. ... Use of ACEIs exhibited a dose-dependent inverse association with ALS. This study demonstrated a 57% risk reduction in the chance for developing ALS in people who used ACEIs greater than 449.5 cDDD in 4 years."{{#pmid: 25383557 |Lin2015}}


==Risk factors==

===Lifestyle, psychology, behavioural patterns===
====Vigorous physical activity, stress, type A behavior====
"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."

"...suggests a positive causal relationship between ALS and physical exercise. Exercise is likely to cause motor neuron injury only in patients with a risk-genotype. Consistent with this we have shown that ALS risk genes are activated in response to exercise. In particular, we propose that G4C2-repeat expansion of C9ORF72 predisposes to exercise-induced ALS. "{{#pmid:  34051439 | Julian2021}}

===Dietary factors===
====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..."{{#pmid: 10645819 | Nelson2000-3}}

====Dietary fats in general====
"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."{{#pmid: 10645819 | Nelson2000}}

"...'''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"{{#pmid:  26280944 | Huisman2015}}

====High LDL and apolipoprotein B levels, high total cholesterol:HDL ratio, coronary artery disease, cerebrovascular disease====
"Controlling for age and sex, higher HDL (HR 0.84, 95% CI 0.73 to 0.96, p=0.010) and apoA1 (HR 0.83, 95% CI 0.72 to 0.94, p=0.005) were associated with a reduced risk of ALS. '''Higher total cholesterol:HDL was associated with an increased risk of ALS (HR 1.17, 95% CI 1.05 to 1.31, p=0.006)'''. In models incorporating multiple metabolic markers, '''higher LDL or apoB was associated with an increased risk of ALS, in addition''' to a lower risk with higher HDL or apoA. '''Coronary artery disease, cerebrovascular disease and increasing age were also associated with an increased risk of ALS'''."[https://jnnp.bmj.com/content/93/1/75 Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis]

====High intake of carbohydrate and low intakes of fat====
"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'''."{{#pmid: 17852010 | Okamoto2007}}

====Less frequent intakes of green-yellow vegetables====
"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==