Brian Lin, PhD, discussed the current evidence linking football participation with ALS, the questions that remain unanswered, and how emerging research may help clarify the association.
With the NFL season underway, the conversation surrounding football participation and amyotrophic lateral sclerosis (ALS) continues beyond the field, as epidemiological studies have identified higher rates of the disease among former football players. In a 2021 cohort study of 19,423 National Football League (NFL) athletes, investigators found that players had nearly 4 times the incidence and mortality from ALS compared with the US population of men.1
The study also found that athletes who developed ALS had longer NFL careers than those without the disease, although the findings did not establish a direct causal relationship between football participation and ALS. Despite the growing evidence of an association, important questions remain about the factors that may contribute to ALS risk among football players and other populations with potentially elevated risk.
A newer collaborative research initiative led by Answer ALS and Augie’s Quest to Cure ALS, Champion Insights, is investigating why certain populations, including elite athletes, military personnel, and first responders, may face an elevated risk of ALS.2 The initiative integrates clinical, genetic, molecular, lifestyle, and exposure data to better understand the factors that may contribute to disease development.
In a recent conversation with NeurologyLive®,
Brian Lin, MD: Champion Insights is a collaborative research initiative that MDA is supporting and that is led by the ALS Therapy Development Institute, along with other organizations like Answer ALS. The purpose of Champion Insights is to delve into understanding what factors are driving ALS risk and disease development. We're doing so by studying individuals who we know are at a higher risk of developing ALS, including military veterans, high-performance athletes like football players, and first responders.
I think this is a very unique study because we're doing it in a very comprehensive way. We're collecting a ton of different forms of data through research questionnaires that look at lifestyle factors and ask questions like, what is the stress that they've accumulated over their lifetime?
We're also collecting blood to look at blood biomarkers, metabolomics, and genetics, as well as using wearable devices that give us continuous data so we can track patients during their regular day. And, of course, we're collecting their clinical history. By collecting all of this data together, we can finally start to connect some of those dots between their lifestyle experiences and the occupational exposures that they experience with some of the biological mechanisms that underpin their disease.
At MDA, we're really excited to be part of this project because we have had this long partnership and history with the International Association of Fire Fighters for over 70 years now. Firefighters are one of those populations included in this study that are also at a 2-times increased risk for ALS. We're excited to get some of the firefighters that we've worked with for so long some answers as to why there's a greater association.
Rory Siegel, DO, brain injury medicine attending physician at Burke Rehabilitation Hospital, discusses the emerging evidence linking football participation with ALS, the potential role of repetitive head impacts, and key questions that remain about long-term neurological risk.
In terms of takeaways for clinicians, I think right now, based on the research that we have today, it's really simply to be aware that this association exists between football participation and ALS.
I think it's important not to overreact or over-interpret the research and data that we have, because we don't necessarily know a lot of things about how this association actually manifests. Not everyone with a history of ALS has played a high-contact, high-impact sport like football in their lifetime, and not every athlete or football player develops ALS.
And so, we can't really pinpoint exactly what this association is produced through. I think Champion Insights is one way that we'll understand a lot more about the biology, the occupational exposures, and the risks of the disease. This is a really complex disease, and we hope to get a lot more answers from this initiative.
At this point, we can't really establish a direct causal relationship between football participation and ALS. We just have multiple studies now that have shown this association, with a 3- to 4-times increased mortality risk or incidence of ALS in former football players.
We have a ton of different hypotheses, but we can't necessarily say that football participation itself causes ALS or that any specific part of the game actually does. We can't pinpoint any specific part of the game that really contributes to that risk.
In regard to how the sport has changed, I think it's an important caveat that's considered for some of the retrospective studies, but it also highlights the importance of having prospective studies that look at players in the game today.
Some of the limitations of the past findings, or even current research that's been done in former football players, are that the game and safety around the game have changed so much. Players are using Guardian Caps and other protective equipment now. There are different rules about how you can hit someone in the game. There is different coaching, and probably different strength and conditioning approaches, combined with surveillance for concussions.
Also, today's players are probably faster and stronger. They're very different from football players in the past. As a result, all those factors must be taken into account when considering retrospective studies and how they apply to the current generation of football players. Any clues or research into those areas will provide a lot of insights.
I think it's exciting that we now have established this association epidemiologically. Now, a lot of the research needs to delve even more into understanding how and why that association actually exists.
That means getting research studies that are looking even more granularly into some of these aspects. There are a lot of hypotheses associated with football, such as repetitive head trauma and some of the lifestyle factors as well. But we have to really look at those in greater detail, like tracking the exact number of repetitive head impacts or measuring the force of those impacts, assessing certain factors like career length and the age of first exposure, and linking that all to some of the underlying biology.
If we're able to have all that information and study all that information, we'll be able to start piecing it together and create this line of evidence between having an epidemiological association, understanding what exposures are present in the game today, and then linking biological mechanisms through understanding some of the genetics and metabolomics from blood.
Ultimately, I think putting all this evidence together through these research studies will allow us to take the next step toward identifying people who are at risk and also finding out and developing ways to further protect those individuals.
Transcript edited for clarity.
