Body weight link with Lou Gehrig’s disease

Carrying excess weight is linked to a plethora of chronic health conditions, but amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is not one of them, according to a Norwegian population study.

The research, published in the journal Neurology, found that people who are overweight or obese are up to 37% less likely to develop the rare neurodegenerative disease.

Physicist Stephen Hawking’s personal experience with ALS propelled it into global awareness. The disease progressively kills motor neurons (cells that control voluntary muscle movement), ultimately leading to paralysis and death. 

Although some cases have genetic variants, the cause is largely unknown and there is no available cure.

However, it has become increasingly evident that motor neurons are remarkably vulnerable to energy depletion, says the lead author of the new study, Ola Nakken from the University of Oslo.

In line with this, a body of research has found that ALS patients burn energy more quickly – and this elevated metabolic rate appears before clinical signs of the disease.

“It is hypothesised that such hypermetabolism and weight loss starts early in ALS patients, possibly many years before diagnosis,” Nakken says, adding that extra weight and energy reserves might be protective in these individuals.

Several other studies have linked high body mass index (BMI) and weight gain to lower ALS risk, but causality and timing of events have been unclear.

To investigate the temporal relationship in a large, prospective study, Nakken and co-authors mined a population database for health details of nearly 1.5 million people aged 20 to 70 years between 1963 and 1975. 

Over an average 33 years’ follow-up – during which time 190,500 people completed additional health surveys – they identified 2968 new cases of ALS through death certificates and a national patient registry. 

Overall, every five-point increase in BMI from the low to normal range was associated with 17% lower risk of developing ALS. After 50 years, this increased to 31% lower risk.

People whose BMI increased the most had 37% lower risk than those who didn’t gain weight or lost weight.

Perhaps more surprising, participants who were obese and overweight at the study’s inception had, respectively, a 34% and 18% lower chance of developing ALS than those in the low to normal BMI range.

These results remained unchanged when other potential risk factors such as smoking, cholesterol levels and physical activity were factored into analyses.

The findings could reflect disease-induced weight loss prior to diagnosis, Nakken says.

But the nature of the relationship – which started slowly during the first few years of follow-up before increasing linearly for 50 years – is not consistent with the hypothesis that hypermetabolism causes ALS.

“These results rather point to shared genetic or environmental risk factors between BMI and ALS,” the researchers write.

It’s important to note that, although the study is prospective, it is still observational.

Nakken says it is possible that genetics could make a person more likely to have both a low BMI and a higher risk of ALS without one causing the other.

“People must not interpret the results of our study as a suggestion that gaining weight may prevent ALS,” she says. “Plus, the health risks of having a high BMI would be greater than any protective effect.”

Carmel Armon and Bryan Traynor, from Tel Aviv University in Israel, concur with this statement in a related editorial.

“The possibility that elevated BMI per se increases the resistance of the motor neuron super-network to the processes that lead to ALS and its role in shaping the clinical course of patients’ needs to be explored further,” they write.