The extension of life span by caloric restriction has been studied across species from yeast and C aenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP3) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d-β-hydroxybutyrate (d-βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d-βHB to cultures of C. elegans extends life span. We hypothesize that increasing the levels of ketone bodies will also extend the life span of humans and that calorie restriction extends life span at least in part through increasing the levels of ketone bodies. An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.
Thank you. This is a good one. I downloaded this paper a few months ago.
My brain does much better when it runs on fat but my gallbladder objects. A couple months ago, I realized I might be able to have the same cognitive and also metabolically stable effect by taking ketones. I’ve since gone through a couple kilos of them at 30 mg three times a day with meals since.
It has helped a lot. I ran on ketones for several years. Before that I woke up grumpy until I ate some carbs and felt better for a couple hours and then I crashed and I repeated this several times a day. I’ve been like this since I was a child. When eating cooked vegetables with tons of olive oil and meat and salad, all that instability went away. I didn’t wake up grumpy I didn’t become confused during the day between meals. The other thing about the no-carb diet was that my PCP said I had the best lipid profile of anybody she had ever seen over the age of 12.
Then my gallbladder went bad and I had to eat carbs and I returned to the cycle of cognitively incompetent to smart to incompetent to smart throughout the day.
It’s feeling like I’ll be able to keep my brain working for a few more decades now that I can run on ketones again.
I don’t think “taking ketones” does anything more… but you don’t have to consume all the fat, so its more a case of the benefits without the negatives I think.
Unfortunately, because of my gallbladder pain after eating fat, I can’t eat enough fat to be in ketosis.
After reading this paper, I looked at the doses and did some research on where I could buy my own exogenous ketones.
These two products are each linked to a different mineral. I have SNPs that make me pee out sodium. I have to take an unbelievable amount of sodium to keep my nervous system working so I chose to use a mixture of sodium and potassium BHB.
Different kinds of fat affect my gallbladder differently. Crap seed oils make it hurt right away. Good olive oil is the least bothersome to it. I used to take MCT oil and that works great and fast. But my gallbladder doesn’t like to saturated fat.
So all you people with normal gallbladders and livers can eat enough fat to be in ketosis. That is assuming you’re eating low enough carbs.
My gallbladder hurts too much if I try to eat fat so I need an alternative.
This paper shows how to get the beneficial effects of ketones even when burning a lot of glucose. That’s the magic of this paper. We can use exogenous ketones while on a low-fat diet and get the benefits of a ketogenic diet.
They are very bitter. At first I would make a cup of strong coffee and put two tablespoons of ketone powder in and froth it up with a bunch of stevia. It was close to palatable.
Over the weeks, I found myself less and less disgusted by the bitter taste and began putting a couple tablespoons in water and chugging it down.
I’m theorizing that the well-being soon after consuming the ketones is programming my nervous system to link that well-being with the bitter taste. And the well-being from chugging two tablespoons of ketones happens pretty quickly.