Paganoni S, Deng J, Jaffa M, Cudkowicz ME, Wills AM.
Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis.
Muscle Nerve. 2011 Jul;44(1):20-4.
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In my opinion, this is a key paper in the field. The authors definitely confirm our previous results, and those of Albert Ludolph's group, that showed dyslipidemia was associated with increased survival. Here, they provide much deeper statistical analysis than we initially did, and show that body mass index (BMI), rather than cholesterol levels, is an independent prognostic factor in ALS. This study is very much in line with previous studies from Couratier and colleagues (see, e.g., Marin et al., 2011) showing that BMI is an important predictor of ALS patients’ survival. In my eyes, it is no surprise that adjusting for BMI in statistical analysis decreases the association level of cholesterol with survival: It is common sense that lipid levels are strongly associated with BMI.
An important point of this study is that they first performed longitudinal analyses of blood lipids in ALS. The authors show that blood lipids manifest little change with time, suggesting that they do not represent a distal consequence of disease progression as suggested by other authors. The most original finding of this study is the U-shaped dose response curve between BMI and survival. They showed not only that lean patients have shortened survival, but also that morbidly obese patients also have such decreased survival. This suggests that risk factors associated with morbid obesity are also risk factors for shortened ALS survival. The authors suggest that cardiovascular risks might be such risk factors. I would rather suggest insulin resistance, which, from an energetic point of view, has the same consequences for the cell as does starvation (i.e., decreased nutrient entry).
In all, this study strongly confirms that increasing BMI seems to represent a valid therapeutic strategy for ALS, to be tested in future clinical trials.
This may be congruent with a preliminary hypothesis based on my current research that a component of animal fat is neuroprotective, and that the myelin sheath is vulnerable in some individuals as consumption of animal fat decreases. As more individuals adopt a vegan lifestyle, we need to analyze whether the rate of certain psychiatric and neurological disorders, such as ALS, increases in this population.