Active Low-Carber Forums - View Single Post - I'n going to quit worrying about ketone levels

Exogenous ketones--assuming they're bad makes as much sense as assuming they're good. When people talk about exogenous ketones increasing insulin, so preventing weight loss, one big thing missing is any data showing that this is so. Sprinkling ketone salts on your french fries, I'd probably bet against. Supplemental ketones added to a low carb diet? I wouldn't waste money on that as an individual, but I think it's worth studying and I can't pretend to know what the outcome will be without the actual studies being done.

As fat as ketones-->insulin goes, it depends on context. Replace sugar with ketones? Probably the insulin response will be reduced. The same is true of fat. Add fat to a given sugar load, the insulin response will be higher. Replace sugar with fat, it will be lower. Without context, ketones can secretes the insulin doesn't mean much.

Now never mind dietary load of glucose, just look at exogenous glucose. If exogenous ketones reduce blood glucose--the "basal" glucose that the beta cells are exposed to is reduced, some of the ketones are replacing glucose in the blood, rather than just being plopped on top.

Quote:

Effects of ketone bodies on insulin release and islet-cell metabolism in the rat.
Biden TJ, Taylor KW.
Abstract
Ketone bodies promote insulin secretion from isolated rat pancreatic islets in the presence of 5 mM-glucose, but are ineffective in its absence. At concentrations of 10 mM or less, the relative abilities of the ketone bodies to potentiate release are in the order D-3-hydroxybutyrate greater than DL-3-hydroxybutyrate greater than acetoacetate. The response curve relating insulin release to D-3-hydroxybutyrate concentration displays a threshold at 1 mM and a maximum at 10 mM. D-3-Hydroxybutyrate (5 mM, but not 10 mM) promotes insulin secretion in the presence of 5 mM concentrations of both L-arginine and DL-glyceraldehyde, but not with L-leucine, L-alanine, L-glutamate or 4-methyl-2-oxopentanoate. The oxidation rates of the exogenous ketone bodies do not correlate well with their capacities to promote insulin release. Moreover, the oxidation of 5 mM-D-3-hydroxybutyrate can be inhibited by 25% with methylmalonate (10 mM) without any diminution of release. The potentiation with D-3-hydroxybutyrate occurs without an observable increase in total islet cyclic AMP. However, a small net efflux matches the relative abilities of the ketone bodies to promote insulin release. With islets from 48 h-starved animals the insulin response is both diminished and less sensitive than in fed animals, since insulin secretion is not significantly raised until a threshold of 5 mM-D-3-hydroxybutyrate is reached. These results suggest that, in the rat at least, there should be a reappraisal of the physiological role of ketone bodies in the promotion of insulin release.

At least one context where ketones aren't that insulinogenic--those 24 hour starved animals. It's a context where glucose is fairly scarce. But it's in islets, not the whole animal.

Quote:

Suppression of glucose production and stimulation of insulin secretion by physiological concentrations of ketone bodies in man.
Miles JM, Haymond MW, Gerich JE.
Abstract
To determine the mechanism by which ketone bodies decrease plasma glucose in man, seven normal postabsorptive volunteers were infused for 3 h with beta-hydroxybutyrate. Total plasma ketone bodies (beta-hydroxybutyrate plus acetoacetate) increased to levels (approximately 2.5 mM) observed after a 2- to 3-day fast in normal subjects. Plasma glucose decreased 10% concomitant with decreases of 25% and 10%, respectively, in the rates of glucose production and glucose utilization determined isotopically with [3-3H]glucose. Plasma insulin and glucagon concentrations were unaltered, but plasma C-peptide levels increased from 2.6 +/- 0.1 ng/ml to a maximum of 3.9 +/- 0.2 ng/ml at 30 min (P < 0.01) and remained significantly increased for more than 2 h. Plasma alanine decreased approximately 14% (P < 0.05), while plasma lactate increased 25% (P < 0.01) so that there was no net decrease in the combined levels of these gluconeogenic substrates. These results demonstrate that physiological increments in circulating ketone body concentrations decrease plasma glucose in normal man by suppressing glucose production, an effect which can be explained by the stimulation of insulin secretion being reflected only in changes in plasma C-peptide. Thus, changes in pancreatic B cell function not sufficient to alter peripheral plasma insulin levels may cause significant changes in hepatic glucose production.

And that's why the whole animal matters, not to mention the species. An increased rate of insulin secretion that the increase in c-peptide implies might be offset by increased insulin clearance by the liver. The decrease in glucose production by the liver makes for less of a signal for further insulin secretion. Systemic regulation is what matters, not what happens in a petri-dish. An islet that secretes insulin in the body results in reduced glucose, an islet sitting in a puddle of glucose and ketones does not. An increase in insulin that can be handled by the liver, is that so bad?