Finally! How Ketosis Really Works.

Keto, fasting, tahini, cancer. We're going to hit on all these disparate topics together, I promise you that. But to tie this awkward band of misfits together, let's start our story somewhere else. Sometimes you don't know what you don't know, and here's an example. You may indeed know that fasting or very low carbohydrate ketogenic diets promote the metabolic state of ketosis, a state where your body turns fats into ketone bodies, which are fuel for the brain and body and which require metabolism. But do you know how this process occurs? Like, do you really know how not eating, or not eating carbs, causes your body to metabolically rewire itself into a ketone body producing state, ketosis? I bet you don't. In fact, for a second now, imagine your go-to metabolism or keto guru, scientist, doctor, provided it's not yours truly, I bet they don't know the answer to this question either. But after watching this video, you will be able to teach them. And then, after we demystify this metabolic mystery, I promise you some practical fun facts about the fats in nuts and seeds and butters like tahini and regular butter and beef. And I'm gonna teach you how I increase my ketone levels to the equivalent of a 6-day fast in just 1 day. And I'm gonna tell you some shocking science about cancer as well. So stick around till the end. But now for these new data. A new study in the journal Nature recently characterized the role of a keystone protein, eukaryotic translation initiation factor 4E. Yeah, that's a mouthful. Or EIF4E for short. Its role in the feeding to fasting metabolic transition. EIF4E is already known to be a player in the central dogma of molecular biology, where your genetic code, your DNA, is transcribed into messenger RNA, which are then translated into proteins. So it's DNA to messenger RNA to protein. And the proteins of the body do the work of the body. Now, the efficiency of each of these steps determines the overall balance of the over 100,000 different proteins in the human body, across tissues, across organs, and over time. And EIF4E helps to control the process of translation, turning mRNA into proteins. Basically, the researchers here discovered that fasting or a ketogenic diet causes a rise in fatty acids, circulating around in the blood that then go to the liver where they activate an enzyme called AMPK. And AMPK is a cellular energy sensor that modifies other proteins, including a protein called MNK, which directly phosphorylates and modulates EIF4E. And if this went over your head a bit, don't fret. The punchline is that fatty acids, which are the primary fuel when you're fasting or on a ketogenic diet, they're not just fuel, but they're signaling molecules that can bind to pockets on enzymes including AMPK, setting in motion a cascade of events: activation of AMPK, activation of MNK, and modification of EIF4E. And then EIF4E alters the translatome— how mRNA are read into proteins— to increase proteins that are themselves involved in fat burning, fat oxidation, making ketone bodies, ketosis, and hormonal signaling, and many other functions. And I can't overstate how cool this is. In the author's own words, "Our findings reveal a new signaling property of fatty acids, which are released during fasting or on ketogenic diets." Now, I promised you facts about the fats in nuts and seeds versus those in butter and beef. As you may know, whole foods with fat each have a buffet of fatty acids within them. In other words, nuts don't just have unsaturated fat and butter and beef don't just have saturated fat. Each fatty food is a mix of many, many different fatty acids. However, certain foods skew towards having more of some fats and less of others. Now consider what we learned about fats. They are signaling molecules that bind AMPK. Well, different fats have different shapes and will bind, or probably bind, AMPK with different affinities, exerting different activating effects. Thus, it would make sense that some fatty foods with different compositions of fatty acids are going to increase ketones by changing ketone body-producing machinery more than other fatty foods. In truth and for transparency, there's a lot more at play here than just fatty acids activating the AMPK-MNK-EIF4E axis— I know, a mouthful— which controls ketogenesis. However, this may indeed be part of the puzzle, and it's a part of the puzzle I think provides an intellectual handle and heuristic to understand why some foods bump ketones more than others. With that in mind, consider this hack that I've applied on myself. I can get my ketone beta-hydroxybutyrate levels in my blood to 6 millimole in about 24 hours levels most people can't reach without fasting for the better part of a week, maybe 5 or 6 days. And I can do this by leveraging my knowledge about what fat sources are most ketogenic in me, including and especially sesame and sesame products like the sesame butter tahini, one of my favorite nut butters along there with macadamia butter. A large fraction of the fat in sesame and tahini is linoleic acid, which was studied in this study and shown to potently activate AMPK, leading to downstream increases in ketone body producing enzymes. And I've I've personally found that if I consume 3 to 4 tablespoons of sesame oil or tahini with dinner before a 24-hour fast, my ketone levels will jump to 5 to 6.5 millimoles. By comparison, if I do this protocol with butter, my beta-hydroxybutyrate will only reach about 2 millimoles in the same time frame, which is totally wild. And one reason for this discrepancy between the tahini and the butter may have to do with the different fat profiles of seeds and nuts versus butter, the unsaturated versus saturated fatty acid profile. It's unlikely the whole picture, but it might be part of the picture. Isn't that interesting? Now, setting value judgments aside on unsaturated versus saturated fatty acids, because that's not what this is about. This is just interesting physiology. I hope you think so. I certainly think so. Finally, I promised you information about cancer. Well, while many cancers love to feed off glucose and sugar, and some cancers respond very well to ketogenic diets, some other cancers are very adept at switching their metabolisms to rely on ketone bodies for fuel. One example is pancreatic cancer. Thus, where ketogenic diets might be helpful in preventing and treating some cancers, pancreatic cancer will be one that's resistant or in the resistant category. However, given what we now know about the central role of EIF4E in the metabolic switch from carbohydrate to fat metabolism with carbohydrate restriction or fasting, it would be reasonable to hypothesize that pancreatic cancer cells rely depends especially on EIF4E for survival in a ketogenic state, and that combining an EIF4E inhibitor with a ketogenic diet might provide a one-two punch against pancreatic cancer. Indeed, the researchers found this was true. While neither ketogenic diets nor an EIF4E inhibitor were alone sufficient to reduce pancreatic tumor growth in a mouse xenograft model, which is where you inject pancreatic cancer cells into mice, the combination of a ketogenic diet with an EIF4E inhibitor did together inhibit tumor growth, providing an incredible example of the clinical utility of mastering metabolism. Isn't that beautiful? I just want to emphasize that through metabolic knowledge, we find solutions, even if we weren't looking for the solutions when we started seeking the knowledge. And that's pretty cool, and in part why I always say Stay curious.