Lots of good research on how β-Hydroxybutyrate can be helpful in mitigating aging:
Here: β-Hydroxybutyrate suppresses colorectal cancer
Here: β-Hydroxybutyrate Alleviates Cartilage Senescence / Osteoarthritis
Here: Your experiences using Supplemental BHB esters to reduce blood glucose, appetite, triglycerides, free fatty acids, Slow Aging, etc? - #2 by AlexKChen
β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxybutyric acid is a chiral compound with two enantiomers: D-β-hydroxybutyric acid and L-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, D-β-hydroxybutyric acid is one of two primary endogenous agonists of hydroxyc...
Ketone bodies are water-soluble molecules or compounds that contain the ketone groups produced from fatty acids by the liver (ketogenesis). Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA (acetyl-Coenzyme A)—which then enters the citric acid cycle (Krebs cycle) and is oxidized for energy. These liver-derived ketone groups include acetoacetic acid (acetoacetate), beta-hydroxybutyrate, and acetone, a spontaneous breakdown p Ketone bodi...
2 Likes
Bicep
January 8, 2024, 6:28pm
#3
It looks like $5/day. Might be nice to try for awhile just to see what works. Thanks
2 Likes
Neo
January 8, 2024, 8:41pm
#4
Amazing. Have been waiting for Abbots promised version, and this is already out?
Could also get me over the line to try Cana / SGLTi given that it seems like a good way decrease risks/monitor in that context:
Seems like SGLT2 inhibitors don’t mix well with anesthesia due to increased risk of ketoacidosis , note it seems it may also be an issue with concomitant use of SGLT2 inhibitors during prolonged fasting (so, it sounds best to avoid SGLT2 inhibitors during fasting, or if you are on a Keto Diet) …
Perhaps he’s referring to this phenomenon (euglycemic diabetic ketoacidosis) which occurs with extreme rarity in diabetic patients taking SGLT2 inhibitors:
[SGLT2 Inhibitor–Induced Euglycemic Diabetic Ketoacidosis: A Case Report - Kidney Medicine]
https://www.kidneymedicinejournal.org/article/S2590-0595(20)30031-5/fulltext
I saw this paper a couple of months ago and was initially concerned until I read the full text. The rare cases of euglycemic ketoacidosis have turned up mostly in patients using SGLT2i off-label for type 1 diabetes (dangerous since they can’t shut down ketosis without insulin) or in type 2 diabetics who have either progressed to the point of extremely low insulin secretion or who are undergoing major trauma/surgery, infection and/or decreased food/fluid intake.
Euglycemic ketoacidosis is rapidly reversible with fluids, carbs and insulin. Since non-diabetics can secrete our own insulin, my take-home message was to make sure I stay hydrated and to stop the SGLT2i if I get sick or with any major metabolic challenges (and to make extra sure to stay hyrated/fed during those states, since the effects of the SGLT2i appear to last up to 10 days after stopping!). I could also see a potential problem if taking SGLT2i while doing an extended fast or fasting-mimicking protocol, with or without rapamycin on board.
Now if rapamycin were a potent and rapid inhibitor of insulin secretion at the doses typically used for anti-aging purposes (thus mimicking a type 1 diabetic taking SGLT2i), then I could see a real potential problem here.
But is it? It seems hard to quantify in the papers I’ve read so far in human subjects. It definitely can suppress insulin production, but is this only in high doses and/or chronic rather than intermittent use in humans? That’s what Blagosklonny seems to suggest (requires chronic high doses):
[Fasting and rapamycin: diabetes versus benevolent glucose intolerance | Cell Death & Disease nature.com )](Fasting and rapamycin: diabetes versus benevolent glucose intolerance | Cell Death & Disease
Seems like the latter could be addressed / monitored via continuous ketone monitoring (CKM)?
“continuous glucose-ketone monitor is especially important for people with diabetes who may be at higher risk of developing diabetic ketoacidosis (DKA)”
”Recent studies show continuous ketone monitoring (CKM) could help prevent DKA.3 With continuous monitoring, rising ketone levels can be detected early, as a warning of impending ketoacidosis, and inform care so that DKA does not develop. Leading diabetes experts have called for expansion of ketone monitoring, including its integration with CGM technology in a single sensor.7,8”
Also adding @John_Hemming @adssx
3 Likes
Bicep
January 8, 2024, 10:33pm
#5
I’m keto and tried both dapa and empag for a few weeks each. Never noticed extra low blood sugar. I thought it was lowering it maybe 10 points overnight. Not really consistent. I don’t think they are the best at reducing fasting blood sugar for somebody that’s in pretty good control already. I’ve switched to metformin. My hba1c was 5.2 this time around and I’m pretty happy with that but lower would be better.
2 Likes
Neo
January 8, 2024, 10:48pm
#6
For me SGLT2 (and 1) inhibition would be about so much more than the glucose control aspects.
1 Like
EnrQay
January 8, 2024, 11:32pm
#7
Euglycemic ketoacidosis is very rare, even in type 1 diabetics. I have type 1 under good control and I’m on a keto diet with biweekly rapamycin. Even when I do fasts, my ketones are never above 3.5mM (usually 2.5mM), still in a healthy range and a far cry from ketoacidosis range.
2 Likes
Neo
January 9, 2024, 4:05pm
#8
Thx. At the same time, very rare is something one has to take into account if one is very healthy and thinking about taking a medicine for conjectured effects.
And if monitoring can make the very rare even more rare I think I’d take it.
