Thread by @Sam_Apple1

Thread: Can epilepsy provide us with any clues about cancer prevention?  It sounds strange, but the science is intriguing. In my new book Ravenous (very grateful for pre-orders: amzn.to/3gt7vhT), I discuss the importance of the PI3K enzyme in cancer

Thanks to metabolism researcher Lewis Cantley of Weill Cornell, we know that mutations in the PI3K pathway play a role in the vast majority of cancers deaths. The Memorial Sloan Kettering scientist Li Ming  recently referred to PI3K as “the Commander-in-Chief of Metabolism.”

It's not especially surprising that the PI3K pathway is central to cancer. Cancer is a problem of growth and  PI3K  is activated, first and foremost, by insulin, a hormone that tells our cells to grow and swallow nutrients.

Mutations in the PI3K pathway will make our cells exquisitely sensitive to insulin's growth signals. faseb.onlinelibrary.wiley.com/doi/abs/10.109…

But, until very recently, I never knew that epilepsy had anything to do with the PI3K pathway. In this talk, Cantley explains the connection:  

In the last decade, researchers sequencing the genes of neurons in epilepsy patients have discovered that they often have mutations in this same PI3k pathway -- the pathway that is so commonly mutated in deadly cancers:  ncbi.nlm.nih.gov/pmc/articles/P…

In the case of the neurons, the mutations occurs during the development of the embryo. Because the neurons don't divide endlessly, the mutations don't  lead to cancer. But they do lead to clusters of cells that are hypersensitive to insulin.

And this is where things get especially interesting. It's been known for a century that the ketogentc diet is a powerful treatment for epilepsy. The diet is a remarkably effective treatment even when all epilepsy drugs have failed.

Now we finally have a good explanation for the phenomenon: the ketogenic diet keeps insulin levels low, meaning less activation of the neurons with mutations in the PI3K pathway that are so sensitive to insulin.

To be clear: the ketogenic diet is not a cure for cancer--though it may yet prove to be beneficial in combination with other drugs. 
sciencemag.org/news/2021/04/s…  But what about cancer prevention?

Is it possible that keeping insulin low by way of a low-carb or ketogenic diet would help prevent cells that have mutations in the PI3K pathway from taking off on the path to cancer?

We don't yet know, but it's  a question that we should be investigating urgently.  As I discuss in Ravenous, there is a remarkable body evidence linking insulin to cancer. nature.com/articles/s4156…

And while insulin almost certainly plays a role in the hundreds of thousands of obesity-related cancers diagnosed each year, this is not only an issue of concern for those who are overweight.

Almost 90 percent of American adults are thought to have some degree of the metabolic syndrome which leads to elevated insulin: sph.unc.edu/sph-news/only-…

Epilepsy can't provide any conclusive answers about cancer prevention, but maybe it can tell us where we should be looking.

Btw, if you pre-order Ravenous and use this link-- amzn.to/3gt7vhT -- all Amazon commissions will go to cancer metabolism research.

And ordering on Bookshop supports local bookstores: bookshop.org/books/ravenous…