Using Exogenous Ketones to Get a Low GKI

[KetoCancerMom]

A post of mine spiraled of a bit from another topic. I’d rather start a new topic than totally hijack the other topic.

I’m looking for information about using exogenous ketones to boost my BHB levels, to drive my GKI closer to 1.

Mouse models of metastatic cancer show that exogenous ketones themselves have direct cytotoxic effects on tumor viability.
β-hydroxybutyrate can modify chromatin by binding to and thereby inhibiting histone deacetylase, ultimately repressing transcription and curbing cancer cell proliferation

Ketogenic Diets and Cancer: Emerging Evidence

Previously, the anticancer effects of these dietary manipulations have largely been attributed to decreased circulating blood glucose, which limits energy substrates for cancer cells. New evidence suggests, however, that the physiological state of ketosis and elevated circulating ketones also have anticancer effects

Ketone supplementation decreases tumor cell viability and prolongs survival...

[Ilana_Rose]

Thank you @KetoCancerMom. I’m looking forward to reading these.

[FrankoBear]

Look for the latest podcast episodes with Dom D’Agostino.

From my research he is the preeminent researcher in this area.

Even listen to the podcast episode on Peter Attia’s Drive podcast. The better episodes may be on STEM talk.

I understand that Dom has done some work with Prof Thomas Seyfried in Harvard/Boston?

He talks about the ketone salts and esters, and the glucose:ketone ratio in therapeutic ketosis.

You probably already have all this information. I’ll just post it just in case.

STEM-Talk Episode 87 with Dom D’Agostino

Older stuff (2016):

[Ilana_Rose]

I read the Dom D’Agostino paper carefully yesterday and initially I was impressed that it had an interesting and novel finding with respect to ketogenesis and cancer. There was, however, a serious caveat, which I’ll explain below, with respect to the interpretation that taking exogenous ketones would mimic the results.

As I approached the end of the results section, however, I found a very serious flaw which basically renders the study without any significant finding at all. More on this shortly.

First the caveat. He didn’t use exogenous ketones at all. He used precursors to ketone production. In other words, the body is still making 100% of the ketones. No βHB was given to those mice.

This is very important for two reasons. First, any suppression of cancer growth found might be some function of the metabolism of ketones production rather than the ketones themselves. Second, and perhaps more importantly, exogenous ketones are not the same as naturally produced ones. They have a different chirality (the molecular shape is literally backwards) and may not act in a similar fashion within the body. This is the main reason Richard Morris is suspect of any use of exogenous ketones. We don’t know how they would effect our metabolic state. They aren’t the same.

Here is a link to a podcast where Richard Morris discusses these concerns.

https://breaknutrition.com/episode-31-richard-morris-joins-gabor-raphael-for-a-nutrition-nerd-safari/

I have no idea why D’Agostino made this choice given that he wants to interpret the results as indicating that exogenous ketones might be valuable for cancer growth suppression. All I can think is that he was actually concerned that one of the above might actually be an issue but that he wanted to establish first that ketones were important independent of the metabolic state that produces them under natural feeding conditions and that he intends future experiments to actually try to determine the efficacy of exogenous ketones.

But all of the above is actually less important than the real flaw in the study as the result would still be interesting; albeit preliminary and not really pointing to any value to exogenous ketones.

So here is the bigger problem. Dom D’Agostino understood that weight loss could be a confounding variable for this experiment. The reason for this is that we know from many other studies that weight loss is correlated with slowed cancer growth. We also know that ketogenic diets result is strong appetite suppression and concomitant weight loss.

So he knew that he needed to have a control that would enable him to distinguish between an effect of weight loss and a direct effect of ketones. So far so good. He created a calorie restricted control group that were not given additional ketone precursors.

The problem was, that it wasn’t an adequate control. The group getting the ketone esters still lost more weight. Further,

“Interestingly, linear regression analysis of tumor bioluminescence versus blood βHB did not reveal a significant correlation.”

In other words there was no correlation between blood βHB levels and tumor growth suppression. What he did find, but which he barely discusses, is that over all four groups the best correlation was with weight loss. So all he’s really shown is a correlation we’ve known about for ages which is that you can starve cancer into slowing. This is the very thing that he was trying to control for, but as often happens in science, his control failed to do the work he’d hoped for.

That’s my analysis. If it were me I’d not go the route of exogenous ketones based on this. I’d first try something like an 80-90% fat diet while staying away from dairy if possible. I’m actually planning on testing this myself to see where it will take my own GKI.

[KetoCancerMom]

That would take some careful meal planning for me. I’d have to measure again to see where I stand with macros. I’ve been using a cup of heavy cream to boost my fat intake.