Ketone levels - optimum for brain ?

yarwell

In the thread on Cortisol @wabmester opined that it was nonsensical of Volek & Phinney to suggest there was an optimum and that "The uptake (of ketones) rises linearly with blood levels. But the utilization does not.".

Thought this point was worth separating out here.

A 1968 paper referenced by wabmester looked at 3 obese people in extended starvation for 6 weeks who achieved arterial whole blood B-OHB levels of 5, 7 and 8 mmol/l with AcetoAcetate at 0.9, 1 and 1.7 mmol/l (rounded). These are way above V&P's "optimum" and the returning venous blood levels are 0.34 (B-OHB) and 0.06 (AcAc) mmol/l lower on average. In this case the energy supplied to the brain by B-OHB was about double that supplied by glucose.

Volek & Phinney's chart is reproduced below -


Other published work explains how the quantity of ketones used by the brain is influenced by the concentration. More on this after lunch.

Meanwhile, here's a picture from "Scientific American" -

wabmester

The people most interested in the "optimal" level are epileptics who use ketosis to manage their symptoms. They haven't yet found a correlation with ketone levels and symptoms, AFAIK. They used to try to maximize the "ketogenic ratio" of their diets, but now they're finding that Atkins and low-glycemic diets are just as effective.

I have seen studies that show the brain uptake is up-regulated as blood levels increase, but the brain metabolic rate is pretty constant -- always around 500 kcal/day I think. At saturation, about 60-70% of that can be fueled by ketones.

Sunny_Bunny_

I definitely believe the brain functions more efficiently in ketosis. As someone with ADHD that takes medication in order to be able to focus and complete tasks, I have noticed that I feel more "with it" in general. Though I still take my medicine, some days I take a break from it and on those days I feel much more "normal" than I ever had in the past on my off meds days. I would describe those days before as feeling kind of in a fog and very daydreamy. Now It's not so much a fog, but I feel slow and a bit daydreamy still. It's still a noticeable improvement though.
Yesterday, after a cheat night while celebrating, my ketones were 1.4 mmol/l. I'm sure without the cheat I am typically in the optimal range.

greenautumn17

Well, I figure the body must know how to function on either glucose or ketones or we would not have survived this long.

Dragonwolf

Sunny_Bunny_ wrote: »

I definitely believe the brain functions more efficiently in ketosis. As someone with ADHD that takes medication in order to be able to focus and complete tasks, I have noticed that I feel more "with it" in general. Though I still take my medicine, some days I take a break from it and on those days I feel much more "normal" than I ever had in the past on my off meds days. I would describe those days before as feeling kind of in a fog and very daydreamy. Now It's not so much a fog, but I feel slow and a bit daydreamy still. It's still a noticeable improvement though.
Yesterday, after a cheat night while celebrating, my ketones were 1.4 mmol/l. I'm sure without the cheat I am typically in the optimal range.

Have you talked to your doctor about reducing you medication? It sounds like you might be able to (which is awesome).

yarwell

More snippets :-

http://www.ncbi.nlm.nih.gov/pubmed/3918903 reports ketone body utilization highest at high concentrations "A maximal metabolic disposal rate of about 2.3 mmol/min/1.73 m2 is attained in both groups at concentrations of 10-12 mM" - this refers to all tissues, not just the brain.

60% of 500 kcal is equivalent to 75 grams a day of glucose so it makes sense to me that we need a good rate of supply to allow use of ketones as an alternative fuel rather than glucose from GNG, unless one happens to be a sheep. 75 g/day is 0.3 mmol/min.

http://www.ncbi.nlm.nih.gov/pubmed/4275704 (in rats) "12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood-brain barrier may be the rate-limiting step in their metabolism."

More rats at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874681/ showed that ketones impaired utilization of glucose by the brain and that increasing B-OHB from 0.04 to 1.0 would increase both availability and extraction (from 8% to 12%) giving a 40 fold increase in energy supply to the brain from ketones.

So I conclude that higher ketone levels are probably beneficial if one is to rely on ketones as fuel and avoid the risk of "running dry" in the absence of sufficient dietary carbohydrate or using an excess amount of protein to fuel GNG.

wabmester

I've read that burning BHB yields about 487 kcal/mole. So 2.3 mmol/min ~= 1 kcal/min or about 1440 kcal/day. That's the entire metabolic burn of some people, so 2.3 mmol sounds high to me.

In any case, there's probably no downside to supersaturation as long as you avoid acidosis. There's probably no upside either.

totaloblivia

I've never been higher than 1.3mmol, I don't know why as I generally am 20g total carbs or thereabouts. Why do some people run lower on ketones than others?

wabmester

totaloblivia wrote: »

I've never been higher than 1.3mmol, I don't know why as I generally am 20g total carbs or thereabouts. Why do some people run lower on ketones than others?

Great question, and like anything else associated with metabolism, the answer is too complex.

First, remember the difference between arterial blood and venous blood. Arteries supply nutrients. Veins return depleted blood for resupply. You're measuring venous blood, so you're just measuring leftovers. It tells you nothing about how much you're metabolizing.

The ketones themselves are produced in the liver mitochondria and regulated by enzymes. There's feedback involving both sugar levels (higher down-regulates ketone production) and ketones themselves, which down-regulate lipolysis to keep FA levels from going too high.

So if you're consuming 20g of carbs, your body is making as many ketones as it needs to meet your metabolic needs, and you're just measuring whatever is left over. It's not one of the tighter regulated systems (like blood sugar), so there's a lot of slop. So much so that you lose some in your urine, which isn't normally true for any other useful macronutrient.

It's almost like ketosis is still in beta-testing, from an evolutionary standpoint.

GaleHawkins

This is interesting since I have been reading on the subject this weekend. I tested this AM for the first time in a while. 18 hour fasting BG was 93 and ketone read 1.2 so that is in the mild range.