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There was absolutely no theoretical reason that some moldy cheese would kill bacteria but thankfully Fleming noticed what happened and we got antibiotics. Ther

There was absolutely no theoretical reason that some moldy cheese would kill bacteria but thankfully Fleming noticed what happened and we got antibiotics. There was no theoretical reason that washing your hands would do anything to combat the spread of disease and all the smart doctors knew otherwise. Some kooky doctor named Semmelweisz proposed that doctors should wash their hands between childbirths in 1847, 14 years before Pasteur published his findings on germ theory in 1861. When some doctors listened to him maternal mortality dropped from 18% to 2%. I'm all for basic science when the statistical significance becomes so great it really starts to look like causality and then you start figuring stuff out. It doesn't seem like the statistical significance of the amyloid theory is strong enough that the direction of the arrow of causality can be determined. That's too bad. The strength of the effect of keto diet interventions in Alzheimer's is pretty strong to my understanding. Which should be aggressively hinting that there's likely some as-yet unknown causality that's worth investigating. We don't have to spend billions to do that. But we do need more funding for it which is hard to get while all the amyloid hypothesis folks are really invested and clamoring.

DavidSJ 2y ago
There was absolutely no theoretical reason that some moldy cheese would kill bacteria but thankfully Fleming noticed what happened and we got antibiotics. Again, I'm in favor of people investigating all sorts of random shit. I agree that sometimes unexpected things pan out. If you want to run a carefully conducted, large long-term trial on ketogenic diets in Alzheimer's, I support you. I'm just skeptical it'll pan out, and on priors I'll put greater expectation on the approach with a scientifically demonstrated mechanistic theory behind it. I'm all for basic science when the statistical significance becomes so great it really starts to look like causality and then you start figuring stuff out. It doesn't seem like the statistical significance of the amyloid theory is strong enough that the direction of the arrow of causality can be determined. What are you basing this one? The p-value on lecanemab's single phase 3 trial was below 0.0001. And the causal role (not mere association) of amyloid in the disease has been demonstrated for years before significant efforts were invested developing therapies to target amyloid in the first place; most convincingly in the genetic mutations in APP, PSEN1, and PSEN2.
- absolutelastone 2y ago
  I agree more science is certainly better than less. But patentable therapies will always get a disproportionate amount of funding for big science (versus a basically-free dietary change). For ketones and cognition, also look for studies on MCT oil. Such as https://pmc.ncbi.nlm.nih.gov/articles/PMC10357178/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10357178/

DavidSJ 2y ago

There was absolutely no theoretical reason that some moldy cheese would kill bacteria but thankfully Fleming noticed what happened and we got antibiotics. Again, I'm in favor of people investigating all sorts of random shit. I agree that sometimes unexpected things pan out. If you want to run a carefully conducted, large long-term trial on ketogenic diets in Alzheimer's, I support you. I'm just skeptical it'll pan out, and on priors I'll put greater expectation on the approach with a scientifically demonstrated mechanistic theory behind it. I'm all for basic science when the statistical significance becomes so great it really starts to look like causality and then you start figuring stuff out. It doesn't seem like the statistical significance of the amyloid theory is strong enough that the direction of the arrow of causality can be determined. What are you basing this one? The p-value on lecanemab's single phase 3 trial was below 0.0001. And the causal role (not mere association) of amyloid in the disease has been demonstrated for years before significant efforts were invested developing therapies to target amyloid in the first place; most convincingly in the genetic mutations in APP, PSEN1, and PSEN2.

absolutelastone 2y ago
I agree more science is certainly better than less. But patentable therapies will always get a disproportionate amount of funding for big science (versus a basically-free dietary change). For ketones and cognition, also look for studies on MCT oil. Such as https://pmc.ncbi.nlm.nih.gov/articles/PMC10357178/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10357178/