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-Ī²-hydroxybutyrate (d-Ī²HB), 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-Ī²HB 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.
Open Access Paper:
https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1627
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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. Iāve 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. Iāve 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 didnāt wake up grumpy I didnāt 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.
Itās feeling like Iāll be able to keep my brain working for a few more decades now that I can run on ketones again.
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Alpha
#3
How do you take ketones?
Does taking ketones do anything more than a ketogenic diet?
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I donāt think ātaking ketonesā does anything moreā¦ but you donāt have to consume all the fat, so its more a case of the benefits without the negatives I think.
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Would you please let me know what you mean buy consuming ketones. Which product etc.?
Do you mean something like MCT oil?
Unfortunately, because of my gallbladder pain after eating fat, I canāt 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.
https://www.amazon.com/gp/aw/d/B07NGKW2RZ?psc=1&ref=ppx_pop_mob_b_asin_title
https://www.amazon.com/gp/aw/d/B0CK3ZLWMC?psc=1&ref=ppx_pop_mob_b_asin_title
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 doesnāt like to saturated fat.
So all you people with normal gallbladders and livers can eat enough fat to be in ketosis. That is assuming youāre 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. Thatās the magic of this paper. We can use exogenous ketones while on a low-fat diet and get the benefits of a ketogenic diet.
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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.
Iām 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.
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jakexb
#11
Iāve been putting a small amount of magnesium ketone salts in my coffee and itās a really remarkable boost for my brain. Makes me feel like my brain works as well as it did when I was much much younger. Also dampens the need to snack.
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BulkSupplements.com has a magnesium BHB. Is that the type of thing you use?
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jakexb
#13
Thatās who I got mine from actually
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Okay, thanks for sharing. And when you say āa small amountā in your coffee, can you be a little more specific about how you measure the quantity and any reasoning behind the quantity you use? I donāt think any drug or supplement I have used other than coffee itself has ever made me feel anything (besides satisfaction looking at a lab report).
jakexb
#15
I know some people are using teaspoon to tablespoon doses, I do great with 1/4 teaspoon. I feel like a tablespoon would have me blasting into space.
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Wouldnāt be the first time I ever ingested a compound expecting to blast into space, but Iāve mostly left that sort of thing behind. Thanks for the heads up!
A blasting to the toilet not space. I A tablespoon of the Ketone salts three times a day had me a blasting to the toilet. I cut my dose down to a half a tablespoon and I seem to be okay.
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does 1,3-butanediol count as a ketone ester that works?
[as much as juvenescenceās ketoneās?]
A small study found that drinking ketones improved heart efficiency in type 2 diabetes patients, supporting the hypothesis that ketosis benefits cardiovascular health, though further research is needed.
Drinking ketones improves heart health, according to a new small-scale study from the University of Portsmouth.
This is the first time people with type 2 diabetes (T2D) have been given a drink containing ketone estersāa supplement designed to induce ketosisāto monitor its effects on the heart.
The trial involved 13 participants who were given a drink with ketones, and then a placebo drink over a week later. Their cardiovascular function was measured 30 minutes later using non-invasive monitoring, similar to an ECG; ultrasound to assess microvascular function, which looks at the health of the vessels; and infrared spectroscopy, which assesses the blood flow into small vessels.
Dr. Perissiou said: āIn all 13 of the participants, their hearts were working more efficiently after the ketone drink at rest and during moderate-intensity exercise, compared to the placebo drink. Iām feeling very positive about the results, but more research is needed because we only assessed participants on the day, which means we have no idea what the chronic impact of drinking ketones would be.ā
https://scitechdaily.com/scientists-discover-that-drinking-this-supplement-could-improve-your-heart-health/
Reference: āKetone monoester ingestion improves cardiac function in adults with type 2 diabetes: a double-blind, placebo controlled, randomised, crossover trialā by M. Perissiou, Z.L. Saynor, K. Feka, C. Edwards, T.J. James, J. Corbett, H. Mayes, J. Shute, M. Cummings, M.I. Black, W.D. Strain, J.P Little and A.I. Shepherd, 17 January 2025, Journal of Applied Physiology .
DOI: 10.1152/japplphysiol.00800.2024
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Bicep
#20
Esters are expensive and taste bad. I drink ketone salts most days, when Iām worn out and before eating.
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