ALS is not one disease. It is a conspiracy.
Genes load the gun. The environment points it. Time pulls the trigger.
That is the model laid out by researchers Ammar Al-Chalabi and Orla Hardiman.
"The liability threshold model of disease. In the population as a whole, the burden of disease-causing factors varies. Individuals with a burden greater than the threshold develop disease."
The epidemiology of ALS: a conspiracy of genes, environment and time
Their work shows that ALS should not be understood as a single, neat disease with one cause and one cure. It is a messy syndrome made up of many subtypes. Some people inherit mutations with heavy risk. Others live for decades without obvious family history until something in their environment tips the scale.
The conclusion is blunt. ALS only shows itself when enough risk has piled up. A person can carry high-risk genes and get sick young. Or carry moderate risk and need decades of exposure to toxins, poor diet, infections, or trauma before the threshold is reached. Once the threshold is crossed, the process becomes self-perpetuating. Neurons die. The decline accelerates.
"a | A healthy individual. At birth, only the genetic load exists. With time, the deleterious gene variation results in accumulating cell damage. Environmental exposures also accumulate with time. Unless the disease threshold is reached, the individual will not develop ALS. b | Development of ALS. Eventually, the threshold for disease is reached and ALS manifests. The neurodegenerative process is probably self-perpetuating."
The paper that laid out this model is now more than 12 years old, yet it still holds up. More recent research has only reinforced the idea that ALS emerges from a mix of genetics, environment, and time, with no single factor telling the whole story.
Why this matters
This could explain why some regimens or supplements seem to work well for certain people and not for others. The disease does not present the same way in everyone. One person’s ALS might be heavily genetic and move fast no matter what. Another person’s ALS might be driven more by environmental stressors, diet, or toxins, leaving more room for interventions to make a dent.
That means when someone swears by a supplement stack, it might genuinely help them, while doing little for someone else. The difference lies in how much of their personal tipping point came from genes versus environment.
The levers you can pull
The science is messy, but it points to a handful of levers that keep showing up:
- Food: Diets high in vegetables, healthy fats, and antioxidants are linked with lower stress on neurons. Processed meats and excess carbs add to the burden.
- Toxins: Pesticides, heavy metals, solvents, and pollution have all been tied to higher risk. Reducing exposure lowers the load.
- Gut and immune health: A balanced microbiome supports a calmer immune system. Dysbiosis pushes inflammation higher.
- Lifestyle: Moderate exercise helps, overexertion harms. Good sleep and stress reduction protect energy balance.
- Targeted support: A few safe supplements like creatine, CoQ10, vitamin D, omega-3s, and high-dose B12 may help support mitochondria and nerve health, even if none are proven cures. Some people also use red light therapy as a way to support mitochondrial function, since certain wavelengths of light can stimulate energy production inside cells and may help reduce oxidative stress.
It is important to be clear that research has struggled to pin down any single environmental cause of ALS. The exposures are too varied, the evidence is messy, and the search space is endless. That means we are unlikely to identify the cause for any one person, let alone treat it directly. Pulling these levers is not about fixing a root cause. It is about reducing the load wherever possible and giving yourself the best chance you can in the face of the diagnosis.
The bigger picture
ALS is not destiny. It is probability. The Al-Chalabi and Hardiman model shows that for most people, the disease only appears once enough factors line up.
Genetics set the foundation, and when environment and time stack up high enough, you break through the threshold and ALS begins.
That means interventions aimed at reducing environmental stressors may not cure ALS, but they have the potential to slow it down. Especially in people whose genes alone would not have pushed them over the edge.
This is not false hope. It is practical hope. Hope that comes from stacking odds in your favor. Hope that comes from refusing to hand everything over to the ticking clock.
My own path
Since my diagnosis I discovered I was living inside this model. I suspect my genetics are not enough on their own. Something in my environment and my history tipped me into ALS. That is why I track my regimen closely. I take supplements, I changed my diet, I manage stress, I look after sleep, I reduce toxins where I can.
And I built StackDat because I needed a way to organize it all. To see what I was taking, why I was taking it, and how it fit together. To share it with my care team. To be part of the bigger picture of data that is not being collected in the clinics.
If genes, environment and time conspire to create ALS, then we need to conspire back with every tool we have.
