If you are measuring urine ketones, it makes sense that the kidneys would eventually improve their ability to recapture ketones from the urine. Many people also experience a drop in serum β-hydroxybutyrate, as well, and our speculation is that after the muscles become fat-adapted, the liver does a more precise job of matching production to consumption.
After 2 or 3 years on keto, the question is “Do we have ‘low’ ketones or just low ‘measurable’ ketones”? We don’t know simply because we have no way to measure actual ketone usage only ketones ‘in transit’ (β-hydroxybutyrate primarily via blood tests) and excreted ketones (acetoacetate mostly in urine and acetone mostly in breath). And as Bob points out, we don’t know if low measurable ketones is a good or bad thing.
One of my major areas of curiosity is just how does this affect the brain. We know that a ‘brain on ketones’ is a healthy brain and a ‘brain on glucose’ not so much, especially in your elder years, which is where I’m at. So my question is: if 99% of the glucose in my body comes from gluconeogenesis is my ‘brain on ketones’, sparing the glucose for other things that can not use ketones or fatty acids?
We joke around with newbies: if you’re eating sub-20 grams of carbs per day and still conscious and breathing, you’re in ketosis. But how much? Does it matter? Is there some natural level at which we each eventually ‘settle out’ at? Is efficient fat adaptation more important than ketone concentration? I don’t know the answers to these and many other questions.
Dr Ali represents the school of thought that the brain can use up to 2/3-3/4 of its energy requirement from ketones, but needs glucose for the rest. Dr Bikman represents the alternative school of thought that there’s probably no upper limit - that the more ketones available the more ketones the brain will use rather than glucose, even when glucose is available. But we can’t measure it. Yes, I eat sub-20 grams of carbs per day and remain conscious and breathing. Yes, I eat a lot more fat than protein and will soon readjust my macros to make it moreso. Will that be beneficial?
I read something by Dom D’Agostino the other day (he is researching ketones in the context of brain health, cancer etc) where he indicated that at 0.5 mmol blood ketones, the brain was probably running on 5% ketones and 95% glucose. At 5.0 mmol the brain would likely be running on 50% ketones.
I got a new indoor trainer for my bike. After a 45 minute ride my BG went from 112 mg/dl(a normal fasting measure for me ) to 72 mg/dl. Ketones went from 0.9 to 1.0. I felt like I started to hit a wall around the 30 minute mark. If I keep this up I might think about carbs before rides but don’t want to go there quite yet.
How long have you been keto? When I exercise, my blood sugar goes up, not down, but I’ve been keto over 7 years. I calculated even at only exercising 2-3 days/week, that’s over a thousand workouts.
I’m not sure D’Agostino is correct. When I work out, I work out in the morning. My ketones are typically 0.1 mmol/l in the morning. Is my brain really using near 100% glucose? If so, how? (I do have higher blood sugar every morning.) Where does the energy for my muscles come from? (I’m thinking FFAs, free fatty acids.)
I wonder if the brain can use FFAs? This implies it can:
Though the extent is not known (particularly for someone like me), and I see other studies indicating FFAs are still not preferred by the brain.
Anyway, if you think some carbs are helpful, there’s no reason not to try that. Maybe test every few months, to see what happens.
I have been doing keto for about 16 months.
My BG goes up with strength training I think. I have gotten 140-ish numbers in morning to realize that I had taken them shortly after using my pull up bar. Same thing when I have tested shortly after going to the gym to lift weights. My theory is that the stress sends a signal to my liver to release glucose but lifting weights/pull ups don’t ultimately burn much energy.
With low enough intensity exercise my BG is stable, maybe even creeps up. So for example I can fast all day and hit 13,000 steps on my fitbit walking around, going up stairs, gardening etc and still have BG of 112-120 at the end of the day. So I think the idea that we adapt to power our muscles with FFA makes sense.
But on the bike I hit 130-150 heart rate for extended periods and my BG is much lower when I am done. I assume I’m pushing beyond “fat burning” zone when I am doing sprint intervals etc. I’m using this app called Zwift where you ride virtually through cities with other people and it pushes me to go harder than I probably would otherwise.
I’m curious about the limits of GNG. I eat well below 20 grams carbs, got my BG down to 72 today but I’m sure I will be back at 112 or so tomorrow morning. Could GNG supply all the energy I need for my brain at least? Maybe our bodies get better at GNG and downregulates ketogenesis? If I can make glucose out of amino acids or the glycerol backbone of fats why should my body care to make ketones?
I’m wondering how he came up with these estimates. I hate to challenge his expertise, but . . . .
My understanding is that the brain uses ketones because they are small enough to pass the blood-brain barrier, whereas fatty acids are too large to do so. And of course, if fatty acids are too large, triglycerides are definitely too large. So my guess would be that the brain probably could use fatty acids but has no way of getting them.
That’s an interesting possibility (?). Maybe it can get them somehow… I would also question where D’Agostino got his numbers. I currently have quite low ketones (via Ketonix), but my brain function does not feel any different from when I had high ketones (via Ketonix) a couple years ago.
I am soon going to purchase another FreeStyle Libre sensor and track my glucose for a couple weeks to see where that is. I expect it will be the same as last time, but I’ll see.
@fitbod I believe what’s happening is that the body takes whatever steps it has to take to allow you to exercise.
Consider this study of long-term fat-adapted cyclists (LC, low carb) versus carb-using cyclists (HC, high carb):
The muscle glycogen levels were similar after a while.
Now, how that actually happens, I’m not sure. I don’t know the extent to which GNG can power this, and I assume (just based on my own experience) that this changes over time. For instance, I started keto/LC on 1/1/14. As of 2.5 years later, I still had some high ketones (blood and breath). As of a year-two years later, they were lower. As of another 1-2 years later, even lower:
I think of it as a balance equation: energy we can use = glycogen + GNG-derived blood sugar + ketones + FFAs (+ am I missing something? probably).
Based on this, I used to think “athletes” who are low carb/keto would have higher blood sugar than people who are low carb and not athletes. From what I’ve seen, that does seem to be true.
But then Shawn Baker came along and somehow dropped his blood sugar (from an HbA1c over 6 while being carnivore) to very low blood sugar (not sure what his HbA1c is now, though). The 6 made sense to me, as he’s an incredible athlete, so I figured he needed GNG to power his workouts.
Is the same thing that happened to me (lower ketones over time, better use of FFAs as fuel) happening to him? Or is there something else? I don’t know.
But if you see people who start low carb, for the first while, they get really high ketones. I assume that’s because they need them, as the muscles/other cells aren’t used to using FFAs. Meanwhile, over time, fewer ketones are necessary.
But this brings up an issue outlined above, which is what happens to those of us on low carb for a long time and making very small amounts of ketones? There have to be some cells/muscles that use glucose, otherwise we wouldn’t have higher glucose in the morning or higher glucose when we exercise. Is this to counteract the ketones lowering? Should we get higher blood glucose over time?
I really don’t know, and haven’t had a CGM in a while. They got too expensive ($150/month without insurance, at least where I live, and I have to get a doctor’s prescription).
Anyway, if anyone finds more research about this, I’d be interested in it. But people like me (LC/keto 7+ years) usually aren’t the subjects of studies, and therefore, little is known about us.
By the way, this is a good article about blood sugar in general on low carb:
From the study linked by @ctviggen above:
… Nevertheless, fatty acids are taken up during brain development, and it has been reported that fatty acid oxidation could contribute up to 20% of the total brain energy requirement.15, 16 In addition, fatty acid-binding proteins and carnitine have been found in the brain tissue,17 suggesting that fatty acid metabolism has a role in neurodevelopment, neurotransmission, and repair processes.18 Moreover, carnitine, widely known for its major role in transport of fatty acids across the inner mitochondrial membrane, is indeed essential for brain functioning.19…
Figure1 shows the two major steps in the route of fatty acid metabolism in neural cells. Long-chain fatty acids circulate in the nonesterified, albumin-bound form in the blood. After dissociation from albumin, in the first step, NEFA have to migrate across the BBB and, thereafter have to enter neural cells. NEFA become activated to acyl-CoA-derivatives in the cytosol of neural cells. In the activated form, fatty acids are either used for the esterification to membrane lipids or in the β -oxidation. The latter represents a plentiful source of reducing equivalents NADH and FADH2 inside the mitochondria. Oxidation of both types of reducing equivalents by the electron transport chain (ETC) generates the electrochemical proton gradient, the driving force for ATP synthesis.
As outlined in Figure 1, the reluctant oxidative utilization of fatty acids in the brain tissue raises three important questions: First, does the BBB limit the uptake of NEFA by the brain parenchyma and neural cells and therefore reduce the availability of fatty acids for metabolic consumption in the brain? This question will be discussed in the next chapter. The second question is whether fatty acid uptake would override oxidation. This imbalance results in the accumulation of fatty acids in the free and/or in their esterified forms in the cytosol. Thus, it could be that brain mitochondria are particularly vulnerable against high concentrations of NEFA and those of acylcarnitines and/or acyl-CoA-thioesters. This might explain that mitochondria from individual types of tissue differ considerably in their enzymatic equipment for the oxPhos machinery.26 The third question is, whether possibly further drawbacks exist. This is indicated by the fact that substantial fatty acid oxidation increases the risk of neural tissue to become hypoxic, which would not be compatible with rapid and sustained neuronal signaling. These latter issues are discussed in the last chapter and lead to a further clue to understand the low usage of fatty acids for brain energy, which has not been considered so far.
@ctviggen, thanks for posting that article. I think I may have heard Zach Bitter mention being a participant in that study.
From the discussion section of the paper:
“The most notable findings were that compared to HC athletes, the LC keto-adapted runners showed: (1) two-fold higher rates of peak fat oxidation during graded exercise, (2) greater capacity to oxidize fat at higher exercise intensities, (3) two-fold higher rates of fat oxidation during sustained submaximal running, and (4) no differences in pre-exercise muscle glycogen concentrations, the rate of glycogen utilization during exercise, and the rate of glycogen synthesis during recovery.”
I found this very interesting. I had read elsewhere that it takes longer for muscle glycogen to get replenished when following low carb, but their results showed otherwise. It also mentions that the low carb athletes used less muscle glycogen, but that makes sense. If they are burning more fat, they need less glycogen.
I have seen advice that states if one wants to exercise twice a day, it is good to eat carbs to get the muscle glycogen restored before the next workout. Maybe we just need to eat enough low carb food to replenish, it doesn’t necessarily need to be carbs.
All the test subjects had been low carb for some time and were fat adapted. I’m curious, @cooked, how long have you been eating keto?
I have no idea how we would go about verifying that the brain can use fatty acids as well as ketones, given that the blood-brain barrier won’t let fatty acids pass through. I’m having a hard enough time as it is, without giving up some of my precious brain tissue to be studied under a microscope!
Two pieces of the puzzle to ponder: first, muscle glycogen cannot be shared, but liver glycogen can be. I have read somewhere that the product of gluconeogenesis is stored as liver glycogen, and then, when explosive power is needed, the liver glycogen gets turned back into glucose and released into the bloodstream for the muscles.
The second piece is that muscles much prefer fatty acids to ketone bodies, which are partially metabolised fatty acids.
So from this, I conclude that in a fat/keto-adapted athlete, the equation is Energy = muscle glycogen + liver glycogen + fatty acids. Phinney says that as far as endurance is concerned, running on mostly fatty acids makes an athlete bonk-proof. As far as explosive power is concerned, however, the anecdotal experience of forum members is that their endurance performance returned a lot sooner than their explosive power. And yet we know from the Volek study that by two years of keto-adaptation explosive power had returned in the athletes they studied.
I can’t seem to shake my idea about the difference between circulating ketones versus production and consumption. I guess you don’t find it at all satisfactory as an explanation. My understanding of the dawn phenomenon is that the body is preparing to make explosive effort possible in case of need (such as waking up to find a sabre-toothed tiger invading your cave). It also makes sense that serum glucose would rise during exercise, so as to be available for explosive performance as needed.
As far as cells that require glucose and that cannot use fatty acids or ketones are concerned, that would be primarily the erythrocytes (red blood corpuscles) and certain parts of brain neurons that are too narrow to contain mitochondria (this latter, according to Dr. Georgia Ede). I believe I have read that there are certain other cells that also cannot handle fatty acids or ketones, but no longer remember what cells those might be. And of course Prof. Bikman contests the notion that the brain needs any glucose at all, maintaining that it can get 100% of its energy from ketone bodies.
The brain may very well make it’s own ketone supply and not rely on liver synthesized ketones at all or only slightly. Thus, it’s possible that low circulating ketones do not reflect the degree of ketone usage in the brain. This could explain why those of us on keto for several years and fat adapted can measure very low/no ketones, but still have a healthy, functioning brain. See my links in comment 33 above
I’ve decided to follow up on this possibility and post my findings here:
I just finished listening to this podcast where Zach Bitter talks a fair bit about what he eats. It seems workout intensity definitely comes into play where his use of carbs is concerned.
Today I did 45 minutes on the bike again but with no sprints and I kept my heart rate around 120-125. This time my BG did not come down and was 100 mg/dl when I tested after my ride. So it may well be the case that the BG is only used in the “explosive” moments.
I wore a CGM for a couple of weeks a while back and long endurance runs seemed to bring my BG down. I came back from 6 or 7 miles (which was long for me at the time) with BG in the high 60s, down from the 90s when I started the run.
For me, shorter, higher intensity workouts would leave me with higher BG. I think my body sensed it needed it, so released sugar from my liver and kept it up, where with the long, slower effort it drew my BG down without releasing a bunch.
I really don’t know exactly what was going on, but that makes some sense to me.
Stop the presses!
The paper (unfortunately behind a paywall):
In my unhappy experience drinking a cold beer immediately after a hard run results in me feeling very ill. I have seen the same thing happen to others.
However I’m happy to know that a beer or two the night before a run is more or less OK.