Podcast conversation (Ben Greenfield with Latt Mansor) about recent research and mechanistic ideas on ketone supplementation (Keto/‘Ketone IQ’ plus carbohydrates). Key points from this chunk: - Small clinical exercise study (participants aged ~18–24) combined a 5k run immediately followed by an anaerobic Wingate protocol (five 10-second sprints with 30s rest; resistance 7.5% body weight). - Intervention: Ketone IQ plus carbs vs placebo/carbs (treatment details not fully specified here). Manuscript submitted to Frontiers in Physiology and under review. - Primary reported outcomes: increased average power, peak power, and velocity in the ketone group; subjects reported less fatigue. - Physiology measurements: RER lower in ketone group (approx. 0.89) vs placebo (approx. 0.94), and blood ketones decreased over the 5k, suggesting ketone oxidation; lactate rose during anaerobic exercise with no major difference between groups. - Mechanistic hypotheses discussed: glycogen-sparing during the 5k; possible analgesic/altered pain perception effects of ketones during high-acidosis anaerobic efforts; concerns about combining ketone esters with anaerobic exercise due to pH drop and GI issues. - Broader clinical relevance: Latt Mansor reviewed literature on ketones/lactate in traumatic brain injury (TBI). He describes post-TBI metabolic shifts (early hyperglycolysis, later decreased glucose metabolism and increased lactate reliance) and proposes ketones as an alternative fuel (via MCT transport) and an anti-inflammatory agent (NLRP3 inflammasome modulation). He mentions planned or ongoing pilot TBI studies with Ketone IQ (Naval Health Research Center and a group at University of Western Australia).
Questions this video answers
18–24 years old
Five 10-second sprints with 30 seconds rest, resistance set at 7.5% of body weight
Placebo ~0.94; Ketone IQ+carb ~0.89
Frontiers in Physiology (under review)
Chapters
I saw before our podcast that there was some new research out on ketones related to anaerobic performance, when traditionally they've only been associated with aerobic performance. So explain to me what's going on now with ketones and anaerobic performance. Yep.
So first and foremost, because ketones are so much more related to fats, because fats break broken, you know, gets broken down into ketones and then we metabolize it. Right. So then automatically we are thinking that, okay, it must be good, better for endurance, because for endurance we want to tap into that fat. Like you said earlier, rer. You want the RER to go towards fat metabolism instead of glucose, because glucose will always be king when it comes to anaerobic, because glycolysis gives you that fast ATP without even having to use any oxygen. Right, right. So that's why nobody has been, has done anaerobic performance on ketones.
But then we decided, you know, hvmn, as usual, we do some crazy things. We do things that no one wants to do and let's see what the science says. And we partnered with University of North Georgia, one of the best military college in the US to look at effect on ketone IQ with carbs in anaerobic performance. So what we have done is that we put participants 18 to 24 year olds on a 5k run. Immediately after the 5k run, we put them on a stationary bike ergometer and they go, they went through the anaerobic wingate test. So for those.
You guys are cruel.
I know.
Explain the Wingate test to people because, I mean, 5K is tough, but Wingate's really tough.
Yes. So Wingate. So these participants have to go through five bouts of test, 10 second sprints on that bike at 7.5% body weight, as a load, as a resistance, 7.5% body.
I'd have 150 watts.
Something like that.
Yeah. Wait, was that, was that the wattage or is that the resistance?
It's a resistance.
That was a resistance.
That was a resistance. So then during that five bouts, they have 10 seconds sprint, 30 seconds rest. 10 seconds sprints, 30 seconds rest five times. Right. And they got their ketones measured. They got. So they had ketones before the 5k run and then topped up after the 5k run.
Okay, okay, but after the run, but before the wingate.
Yes. Okay, correct. So during this wingate test, you know, they, they, they were asked to go as fast as hard as possible. Right. And we just submitted this manuscript to Frontiers in Physiology and they're under Review right now.
Okay.
And we saw increase in average power.
Peak power and velocity. So not only these people are paddling harder, they're also paddling faster. And on top of that, we also measure fatigue levels, because as you go through that five bouts of exercise, you are inevitably going to be more and more fatigued.
Yeah.
People who are on ketone IQ and carbs, they experience less fatigue than those on placebo.
Now, I would hypothesize that part of this would be due to the glycogen sparing effect that occurred during the 5k run. Meaning you're burning less glucose during the 5k run. Is there anything else going on there? Like, had you ever thought about doing just the wingate without the 5k run, for example?
Great question, great question. And I did ask that. So the reason why we did the 5k run is because a lot of the studies, a lot of other studies also did that 5k run, and they saw no, no difference. And we want to sort of replicate that to build on top of that, because otherwise other scientists would just scrutinize the paper and say, you know, no one has done this. No, you can't. You can't compare to anyone. So that's the reason we did the 5k. So the next step is definitely better to do just the anaerobic and see what's the difference. And during the 5k run, you were right. We did measure the RER, and people on ketone IQ and cobs have. Have significantly lower RER, meaning they are burning more fat than glucose. So in the placebo group, or glucose only group, we are looking at about 0.94 RER, whereas the Keton IQ and carb group, we are looking at 0.89. Okay.
RER, by the way, for those of you listening, is a respiratory exchange ratio. It's indicative of the amount of carbohydrates compared to fat that you're burning. Higher RER means more carbs, less fat. Lower RER means more fat, less carbs that you're burning.
Yes. So they're burning more carbs, and that is expected. And as you said, it could be the glycogen sparing effect. And also because we measure the level of blood ketones before the 5k and after the 5k, and we saw a decrease in the ketones. So together with the RER plus the decrease in ketone levels, we can assume, or we can, you know, insinuate that these people are burning the ketones, oxidizing the ketones as well. However, we are not sure if the ketones are being burned in skeletal muscles in your heart, or just simply lost via acetone in the breath. Okay, so that's, you know, whoever who's listening in terms of researchers, that's the next step. We got to. Got to measure, right? Like, what are we measuring? What are we looking at at muscle biopsy? You know, then we can look at really the glycogen sparing effect.
What about, what about the brain? Like, is there anything going on in the brain?
I was just about to say that. So. So the next reason that we think that could be why these people are performing much better at anaerobic exercise is not simply the glycogen sparing effect, because this could have a potential analgesic effect on the brain. So basically it's a pain tolerance increase after taking ketone IQ and carbs during this. Because the whole Wingate test is meant to elicit a huge shift in ph, I. E. Lowering the ph, increasing lactic acid buildup, and having excruciating pain and possibly vomiting.
You know, and pain in these sort of like target muscle groups. So having said that, if people are able to push through that, push harder and faster and, and feeling fatigue less than it could possibly having a direct effect on the perception of pain itself. Now, if you compare this to ketone ester, it may not be a good combination because anaerobic itself, like I said, it's meant to elicit a huge shift of ph. And ketone ester on its own is able to already drop ph so much.
Accelerate that PH shift.
Yeah. That people might just feel really awful. And coupled with the bad taste, they might actually have GI issue, which could also lead to an overall decrease in performance in the study, which a lot of studies have showed they did. The drop in performance is because people started vomiting, started, you know, not doing, not feeling well in general.
Now, one of the reasons that you see kind of like a shift in focus sometimes after you work out is I think in some scenarios, probably due to an increase in blood ketones due to potentially glycogen exhaustion or increased fat utilization. But then there's also this idea that in addition to ketones being one of the preferential sources of fuel for the brain, lactate is another. And you see lactate crossing the blood brain barrier and being used as an alternative fuel to glucose for the brain. Now, based on that, is there something to be said for what might be occurring from a lactate standpoint here for the brain? Or is there any studies you guys have done on lactate as related to neural performance or anything of the like?
No, we haven't actually looked. I mean, we did measure their lactate. I don't think their lactate is that much different between the two groups, but we definitely see an increase in lactate during the anaerobic exercise, which we already expect. As to directly into the brain, we didn't measure that. But it is an interesting point because I published a paper last year, a review paper on traumatic brain injury and exploring the roles of both ketones and lactate in helping both the recovery and the mitigation of damage of traumatic brain injury.
Were you giving people lactate and ketones?
It was a review paper. So basically looking at all the literature so far as to what we know, what happens in metabolism when you have a traumatic brain injury and why, we came to a conclusion that ketones and lactate may be able to help with that.
Ketones are something that come to mind for TBI and concussion because if you look at, for example, Dale Bredesen's book the End of Alzheimer's, there's a whole multimodal approach to Alzheimer's or other dementia like conditions that include high amounts of dha, hyperbaric oxygen, adequate hydration, the use of intranasal light or intracranial red light therapy for the brain. And I believe either coconut oil or MCT oil, or possibly ketones, I don't recall, were one of the strategies used for TBIs for concussions. And I've also seen some indications for other neurodegenerative conditions. What's going on with ketones in the brain?
So we are actually going to launch a pilot study on TBI together with the Naval Health Research center to look at specifically ketone iq, the effect of ketone IQ in recovery of TBI patients. And there's a university, University of Western Australia in Perth. I spoke to the clinician as well a few days ago and they are going to start a study on TBI using ketone IQ as well. So stay tuned on that. But as far as what we know so far on tbi, what happens when, when tbi, when you have a concussion, when you have a traumatic brain injury, within the first 48 hours, what they have seen is the hyper metabolism of glucose. Your brain start taking in all the glucose, right? And some people say because you need an increased energy, because you know that is the damage going on. But there are some scientists who shown, who has shown that the glucose is being pushed towards the pentose phosphate pathway to create more nadph, which could be helpful with the mitigation of the damage.
Yeah. And then NADPH being able to have a protective effect.
Correct. Mitochondria, neuroprotective effect as well. So and then weeks to months after, in fact seven days after, they saw a decrease in glucose metabolism because you can only ram something up so far up before it goes back down. Because that's what the body does. You know, we always stay in homeostasis and really, you know, modulate the metabolism. So when glucose goes back down in seven days they saw a huge increase in lactate, up to like 60 plus percent. Metabolism being, relying on lactate, showing that there is still an increase in energy, but somehow the brain capacity to up regulate glucose metabolism is, is, is now not able to be maintained. And then right after that, like you know, if you look at TBI patients, you know, years after, they also experience somehow a hypo metabolism of glucose, meaning that they're not as efficient in metabolizing glucose. And this is very similar to neurodegenerative diseases like Alzheimer's. Why they call it type 3 diabetes is because there's some form of insulin resistance which is where the brain is not being able to uptake and utilize glucose as efficiently as a normal human being. So that's where ketone ketones come in. Right. First and foremost, ketones are brain's super fuel. Like it's a brain's preferred fuel. So when it's present, the brain will take it up. So because ketones are being shuttled in via mct, which is monocarboxylase transporter, it's different to glucose transporters which are glutes. Right. So it's coming in from different shuttles, different channels so it can bypass that whatever insulin resistance you have. Secondly, we're looking at the anti inflammatory properties of ketones as well. The direct effect on of ketones on LRP3 inflammasome could also potentially help with both mitigation of the damage and as well as recovery down the road. So first of all is the energy deficiency gap that may be compensated with ketones and lactate and then to the anti inflammatory properties of ketones.
Why does some people still say that glucose is the preferential fuel for the brain?
I mean under normal circumstances the glucose does use a lot, I mean, sorry, the brain does use a lot of glucose. Right. But then how many people, like how many studies are there that shows that you have high glucose and high ketones and then the brain preferred ketones? Like what we know is that ketones and brains and whatnot, when ketones, when ketones are present, the brain and the heart will always take up ketones. And what's more interesting is that I know for a hot for for sure in the heart is that when the heart takes up, ketones is proportional to the availability of ketones in the blood. However, this is independent of the uptake of other substrates, meaning that when they measure the vena, the arterial blood and the venous blood, so blood going in, blood going out, the uptick of glucose and fats remain the same and ketones go up. And this is especially important for a failing heart because you are essentially providing more energy because it's uptaking more substrates and providing more energy to the failing heart. And we know in heart failure, the heart actually upregulates ketometabolism.
I didn't realize how applicable this was to heart disease. This is fascinating.
