Table 1. Proposed Risk factors for ALS.
| Proposed Risk Factor | Level of Increased Risk | Strength62 and Type of Evidence | Proposed Mechanisms | References |
|---|---|---|---|---|
| Male gender | OR, 1.5 | Level A | Early testosterone exposure | 4 |
| Smoking | OR, 1.1 | Level A | Oxidative stress Lead Other toxins |
63 |
| US military service | OR, 0.22 to SMR, 1.92 | Level B | Multiple | 29 |
| Lead | OR, 1.81 | Level B | Neurotoxicity | 42 |
| Pesticides | OR Men, 1.88 Women, 1.31 |
Level B | Neurotoxic | 51 |
| Physical activity (or predilection thereof) | Unknown | Level U | Physical fitness, early testosterone exposure | 43,44 |
| Head trauma | Unknown | Level U | Direct neuronal injury | 64 |
| Electromagnetic radiation | Unknown | Level U | Electromagnetic field | 37 |
| Low body mass index | Unknown | Level U | Higher metabolism | 45 |
| Statin treatment | Unknown | Level U | Altered lipid metabolism | 47 |
| BMAA | Unknown | Level U | Neurotoxicity | 17,18 |
Abbreviations: BMAA, β-N-methylamino-l-alanine; OR, odds ratio; SMR, standardized morbidity/mortality ratio.
Level A rating: This is an established risk factor, Level B rating: This is a probable risk factor (‘more likely than not’), Level C rating: This is a possible risk factor (does not attain a ‘more likely than not’ status). Better-designed studies may be warranted with regard to this risk factor, Level U rating: It is unknown whether this is a risk factor.