Physical activity and risk of multiple sclerosis: A Mendelian randomization study, 2022, Chunyu Li et al

Seems weak, frankly. Have to put lots of trust that the statistical analysis is reliable, which all depend on the quality and accuracy of the data. And lots of faith that confirming past/expected results means something, rather than something aspirational. There's not a lot of depth to the data, it seems as muddy as nutrition data, too many confounding factors.

It did not find such an association with vigorous activity:
In contrast, no association was identified between SSOE, VPA and MS, suggesting too strenuous physical activity might not be protective against the risk of MS
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If true, how would it differ from the generic benefits of regular activity, which most people meet easily by simply living a normal life? It's supposed to always be good, that's the mantra, so if it's good for all conditions then there should be a tiny statistical benefit found in any patient population. At least that's what claiming that exercise is good for everyone with any condition demands.

And given the now known risk factor of infectious mononucleosis as a causative factor in MS, it could be that the prodrome period is far longer than is known and reduction of activity is simply an early phase outcome of the disease process.

The study seems to suffer from the same aspirational bias found all over medicine, that a simple solution can't be wrong and that exercise is always good.
 
There's also the issue of what is meant by "physical activity is protecting". Does it mean before contracting the disease, or since? Because there is discussion of how vigorous activity can be a problem with MS, but then that would be only after the disease process has started:
Consistent with this finding, a majority of MS patients feel high-temperature intolerance which might be related to temporary exacerbation of clinical manifestations. Vigorous physical activity might increase the core body temperature, and thus bringing harm to patients with MS. Therefore, too light or too aggressive physical activity both were not beneficial for MS. Further studies investigating physical activity in MS could pay attention to the effect of excessive levels of physical activity.
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Because if physical activity before the disease started were protective, lowered risk, it would be expected to continue to correlate, at least to some point, in the vigorous range. But it doesn't, and speculation is over what this means after the disease has started, rather than before.

So then it wouldn't really be risk factor so much as disease-modifying, or more likely disease-reflecting, and we're right back to being unable to tell whether it's simply a consequence of the disease process, with variations between individuals.

Meanwhile this seems like a waste of time and resources:
Considering that different types of physical activity might have different benefits and involve different parts of the body, further investigation into subtypes of physical activities might provide additional insights.
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