Written by Christopher Kelly
Feb. 10, 2017
[0:00:00]
Chris: Hello, and welcome to the Nourish Balance Thrive podcast. My name is Christopher Kelly, and today I’m joined by Brianna Stubbs. Hi, Brianna.
Brianna: Hello, Chris.
Chris: Thanks for coming on today. I’m slightly in awe of your CV and your athletic prowess. I really can’t believe all of the things that you excel at. Not only is Brianna a world-class, literally world-class rower, she is also a research scientist that has been working with Prof. Kieran Clarke’s deltaG group on ketone esters. I don’t even know where to start with you, Brianna, because you’re so amazing. Why don’t we start with the rowing. Tell me about your rowing.
Brianna: I’ve been rowing since I was about nine. It was all in the family because my dad did the first ever ocean rowing race in 1997 that went from Tenerife to Barbados, so it was always obvious I was going to try rowing at some stage because I grew up in a household of it. Now my first time in the boat, I think I might have been about nine. I’ve got this great picture of me, I’m a tiny, little girl in this massive boat. The blades are bigger than my arms and legs, and I looked like I was having a great time. From there, when I was 12, my dad was planning another ocean row and as one of their practice outings, we rode across the Channel together. So age 12, I was the youngest person to row the English Channel. By that stage, all quite keen on rowing, and I managed to get a scholarship to go to school where I was able to row, sort of, around my studies. Then I went to the Junior World Championships, and that was the first time that I won a medal for GB, won a silver medal in the Women’s Four. From there, came to Oxford and rowed in the Women’s Boat Race, rowed as an under-23 open-weight in the eighth, lost some weight and did lightweight rowing and became a wold champion there. Now I’m on senior team, and I won a silver medal and most recently a gold medal in the lightweight women’s squad.
Chris: It’s amazing, absolutely amazing. You’re going to have to go back a bit and explain some of these terms. GB is Great Britain. You’re representing Great Britain in the world. Talk to me about the type of boat that you’re rowing because people like me don’t really understand the difference between all these different types of boats.
Brianna: So with rowing, you can either have two sticks, one in each hand, or one stick and you hold it with both hands. If you’ve ever seen the Oxford-Cambridge boat race, when they row in boats of eight people, that’s normally just one blade each. We call that rowing. The two blades, that’s sculling. So when I was a junior, I did rowing, so one blade, up until -- well here at Oxford, I rowed as well. Then for the lightweight discipline, for that, the average crew weight has to be 57 kilograms. I’m afraid I don’t know it in stone. They only do sculling for those events, so I have to -- you do a lot of your training in the single-person boat anyway, all the way through the sport, so most people can do both. But I have to get my specialism up, as it were, to be a two-oar athlete rather than a one-oar athlete when I made the change to lightweight discipline.
Chris: Okay, and tell us about how long the events are that you compete in because this may be relevant later when we get into a discussion of ketone esters.
Brianna: Rowing is a really funny sport in that, actually, probably a good 85 to 90% of my training is endurance training. Like this morning, I went out and I rowed for an hour-and-a-half, the heart rate like 150, so it’s quite a lot of endurance training, but the events themselves are quite short. For the fastest boat cross in the Olympics is probably five-and-a-half minutes and that’s like a men’s eight. But more typically for me, if I’m racing, I have 2 kilometers in my single. That will take me eight minutes. So it’s still pretty short. We do do some competitions that last longer, so there’s quite a lot of time trial racing, but that still never really last more than 20 minutes. In the grand scheme of things, compared to, say, triathlon and that sort of thing, it’s quite short and quite intense. They define it as a strength endurance sport. It’s a combination of endurance so basically that’s why we do a lot of steady state training. We also do a quite lot of weightlifting as well to build the power.
Chris: Okay, quite intense, six minutes or eight minutes, that must be incredibly intense. It must make you -- do you ever --
Brianna: It’s really resistance.
Chris: Yeah. Does it ever make you sick in the boat afterwards?
Brianna: When I was younger I used to be sick more, but now it’s more like you’re going along. Especially if it’s like a really important race, you get so caught up in the race and then sometimes it gets to the 200 meters out in the end, so probably still a minute to go, and then I’m like, oh, crap, I’m going to run out of steam here. Then you’re so full of lactate and stuff, everything ceases up and stops working and you go from being able to put down all of this power, to just, you almost feel like you’re flopping around. But if you’re on a boat with other people, you’re going to have to keep up. There has just been a couple of times in my single where I just got my pacing really, really, really wrong and gone from taking 30, 32 strokes a minute, to not even being able to coordinate myself, going up and down the slide at 24 strokes a minute and just hanging on. Sometimes we have physiologists who take our blood lactates, and they clocked me once. I think it was about 24. I could hardly walk. I tried to stand up getting out of the boat. My legs just collapsed. Yeah, you can bury yourself pretty deep. I guess that’s like intermediate distance where we have to sprint.
[0:05:13]
Chris: Oh, my God. I have some appreciation of how much lactate that is. I did a lactate threshold test with Matt Larson recently. I’m pretty sure, I need to double check it, but I’m pretty sure that my lactate topped out at 11, and that’s where I stopped. I know what that felt like, and it was not a good feeling.
Brianna: No, no. It’s very interesting. We get a lot of physiology testing and monitoring done when we’re on the team, so sometimes when we do our pieces, they put out the people’s lactate scores next to the pieces. I’ve got quite a high ability to produce it, let’s just say, but that doesn’t always correlate. Everyone is pushing as hard as they can. Some people produce a lot and some people don’t produce very much. But I can quite regularly hit 15, 16. Sometimes I ask the physiologist, “Can you feel it coming off me?” The other thing that really annoys me is that -- it’s fine, it’s probably good practice --- is that they encourage us to do lots and lots of warm-down to bring down your blood lactate after a race. So they get us to come back after you’ve been on a bike for, say, 20 minutes or been walking for a bit, to see if your lactate has come down from what it was, immediately, post-race, to a level they set. The standard is 2 millimoles. I tell you what, I could walk and run for an hour, and I’d still be at 5 or 6. I just don’t clear it.
Chris: How interesting.
Brianna: The upsetting thing is they always give people -- they have little prizes for people that manage to get their lactate on the 2. They have a little box of sweets. I never get the sweets because my lactate always is still over 5.
Chris: Maybe that’s a good thing.
Brianna: Yeah, it will be for being a lightweight rower.
Chris: This is one way in which you are quite extraordinary and I really can’t get my head around. The second is your academic and professional life where you have tremendous insight into your own physiology because you’re in the process of finishing up your PhD in Biochemical Physiology at Oxford University. So why don’t you tell us about how you got into that and are you on [0:07:09] [Indiscernible] to medical school.
Brianna: I actually started off studying medicine in Oxford. When I was 18 I wanted to be a medical doctor. I applied and got a place here. It’s very competitive and so I was really pleased to do that. While I was here studying, I got invited to take part in a study that was looking at effect of the ketone ester on performance. To be honest, I didn’t really know what I was signing up for. I just saw an advert. It was like, £50 if you come and do a rowing machine test for us. I was like, great, I’d be doing that as part of my training anyway. I’ll definitely go and do that. I got talking to the study team, and what they were doing was so interesting that when it came to my third year of undergraduate medicine, I have to do a research project and I got back in touch with them and asked if they would have me. So I did some research with them then. In Oxford, you study all of their science like human physiology basically for the first three years with a bit of an applied bent to it. So you’re always thinking about it in the context of medicine, but you don’t actually touch any people or stick any needles in anyone or do anything to people. Then you do all of the clinical skills in the second three years. It’s a six-year course.
So I finished the first three. I knew all about how people worked but I haven’t done anything with people. It came to a point with my rowing where I was like, if I start clinical school then I’m going to be potentially doing a few night shifts and then you go out on placements and you go to different parts of the Oxfordshire region. I was like, this isn’t going to fit that well with my training. Maybe I can take a year to really concentrate on the training and come back to medical school the next year. So when I was doing that, I spoke to Kieran Clarke and said, “I’ve done my dissertation with you. Can I be employed perhaps as a research assistant and maybe I’ll help you with analyzing the bloods or analyzing all the data that was being collected. Can I help?” She took me on as a research assistant which was a really, really great learning experience. At the back of that, she suggested that I apply for my PhD for which I then got. Because I have an academic reason not to be going back to medical school, the medical school were already happy for me to take that time. It’s only being this last year where I have to let them know whether or not I’m planning on going back to medicine or not. Right now I’ve kind of decided that if I wanted to go back and do medicine, I would re-apply and do graduate and pre-medicine. So I’m not definitely going back to finish medical school now, but that’s what I started doing.
Chris: How did you juggle your elite rowing with your academic work? I’ve been to university and not taking it quite as far as you, and it’s pretty intense at times. I don’t know whether I could have done what you’re doing now, like that amount of exercise, that amount of training. How did you juggle and make it all work?
Brianna: Looking back at it, I think I’m a little bit in awe of myself. It’s a lot easier to just get your head down and get on with it when you’re doing it. When I started doing my PhD, I had this really keen sense that I wanted to show to everyone in the lab I was always really serious about it and I wasn’t just doing it so that I could do rowing. So I was in all the time, and I do things like I’d stay in the office until 7 because Kieran was still there. I’d wait for her to walk out the door and then I’d go out the door, just doing silly little tricks to be like, no, look, I’m still here, I’m still here, and I’m still working because I would be training in the morning and then coming into the lab at lunchtime. But I was really good at being productive with the time that I had. I’m actually probably less good at that now, I mean, in office culture and in research culture. There’s certainly a lot to be said for being able to have conversations with the people that you’re working with because they’ve often got insights to what you’re doing or different techniques that you can exploit a little bit. But when I was doing my first couple of years, I would just come in and get my head down and get on with it and then just leave, so I was a bit less collaborative than I am now.
[0:11:04]
Chris: Why do you think that medicine may not be the right path for you? Why did you choose to stop studying it?
Brianna: It’s quite difficult in this country at the moment because -- so they’re changing the contracts that employs the doctors in the UK. It has to do with working hours and where in the country you can work. There’s just a little bit of a bad taste in a lot of doctors’ mouths at the moment in the UK, so I’m just going to wait and see what happens in the end with that before I commit myself to that kind of way.
Chris: Tell me about your PhD. What did it entail?
Brianna: I actually started off doing some fairly basic kinetic studies with the ester, so giving it to people when they had had a meal compared with when they hadn’t had a meal, also giving it to them on separate occasions, look at how repeatable the profiles of ketones were in the blood. Then I moved onto looking at ketone salts as well, and as part of that, I was looking at their side effects and that sort of thing.
Chris: Well we better explain to people what a ketone ester versus a ketone salt is because I’m sure there will be some people listening that are not quite clear. So what exactly is a ketone ester?
Brianna: So the ketone ester that I’m working on is an ester for 3-hydroxybutyrate diol, and those two molecules are joined by an ester bond. When you drink this, it gets cleared in the body and it produces hydroxybutyrate straightaway and then butane-diol. The butane-diol gets converted by the liver in 3-hydroxybutyrate. So it’s basically a way of giving yourself a big, as you saw with your little experiment that you published recently on your blog, quite a big level of ketosis quite quickly without having to do any dietary manipulation.
Chris: What’s the difference with the salt?
Brianna: The salt, rather than be two ketone bits joined together, it’s just sodium hydroxybutyrate, so it’s ionic. The chemical structure of it isn’t the same when, from what it looks like, it doesn’t quite elevate levels of ketones in the blood as rapidly as the ester perhaps, or as much.
Chris: Why would you be interested in developing a supplement of this form in the first place? Can you explain exactly how it might improve athletic performance?
Brianna: The ways the ketones could improve athletic performance, there are several stages to it. The first is by offering an alternative substrate to carbohydrate for mainly high intensity of exercise. One way that I explain it to people is that if you’ve got ketones in the body, your body will burn those and then it will still have all of the carbohydrate that you had in your body anyway. This is if you were consuming a normal mixed diet. Although most recent literature suggest that even people following a low carb diet have circulating glucose and muscle glycogen, and that’s enough to be sustaining high-intensity exercise for at least some amount of time. So the ketones are offering an alternative fuel. The other way that they could be benefiting endurance performance is because they’re quite oxygen-efficient so when you burn ketones, each molecule of ATP that you produce has got a higher pre-energy of hydrolysis. I like saying that it’s like putting better petrol in your car basically.
Chris: Okay, like a higher octane rather.
Brianna: Yeah, like a higher octane but that’s pretty much it. For acutely improving performance, I think that’s probably where it comes in. Then you can get into thinking about whether taking it long-term would up-regulate your ability to use ketones and to use maybe fat and to sort of bias you in that way a bit more. Another thing that could be of use to athletes is ketones seem to spare protein breakdowns, so they could be useful for recovery as well perhaps.
Chris: Tell me about what sort of activity is likely to benefit from ketone supplementation. You said earlier that your events are between five and eight minutes, say. Would the availability of carbohydrate be an issue in events so short? Surely you would have enough glycogen to see you through such an event.
[0:15:00]
Brianna: Yes, and we’ve seen with our own studies that really these ketones are only improving performance when the effort is between 30 minutes and an hour, let’s just say. So I think the longer that you’re exercising, the more potential these have to be of benefit. In the short, more intense exercise bouts, you are really heavily relying on glycolysis naturally. As you said before in some of the interviews that you’ve done, if you have high levels of ketones, whether they’re endogenous or exogenous, you’ve got a degree of inhibition of glycolysis and that’s not going to be helpful to your performance.
Chris: Right. I’m just trying to figure out which sort of athletes would benefit from this then. I’ve done cyclo-cross a lot recently. That’s a 60-minute event, and it’s highly glycolytic. I’m just wondering whether I would really benefit. After talking to Kieran, I’m like, uhh. On the one hand you’re talking about more efficient production of ATP, but on the other hand you’re talking about inhibition of glycolysis. I’m thinking, do I really want to do this?
Brianna: Well your ketone levels were about 6, which I’d say was probably a little on the high side. You’d certainly be quite strongly inhibiting glycolysis. But we’ve got to look and see whether there’s an upper limit for this sort of thing. So that’s a study that we’re looking at running soon, whether the more you put in, the more you oxidize and the more strongly glycolysis is inhibited, for example. We don’t know that yet. The feeling that we get from the work that we’re doing is that actually there might be a sweet spot between, say, 2 and 4 where you’re actually not really inhibiting your glycolytic property too much but also providing this extra energy source. So that could be beneficial for athletes that do like cyclo-cross, longer, but perhaps also reliant on glycolytic events. I do think that, say for rowing, it’s just too short. It’s limited by other factors. Then definitely marathon runners or stage racing cyclists, that sort of thing where you are just so strapped for energy and you go moderate to high intensity but not really, really intense. Most of the competition is just -- it’s difficult because like the Trent Stellingwerff paper where they had a time trial and then they did 1K performances, sprints, and 4K performances and that was looking at the effects of a low carb diet. I think they saw that there was no difference in 4K sprint performance compared to 1K performance and that they actually attributed that to a decrease in glycolysis or glycolytic capacity because of the low carb-high fat diet. You wonder whether that sort of thing would also apply to exogenous ketones as well.
Chris: I have not actually read that paper, I don’t think, but I’ll find it and I’ll link it on the show notes.
Brianna: Oh, I’ll give you the link to it, yeah.
Chris: So tell me about the palatability of these supplements because I know that it is a concern, and I know that most endurance athletes at some point or another, experience some GI distress from whatever type of food they’re trying to eat during an event. So how does the palatability look of these things?
Brianna: From working with the esters and the salts, neither of them is great, if I’m honest, and they’re both pretty similarly poor just in terms of taste. I’ve given the same study, cohort of people both the ester and the salt, and it’s pretty even split between the people that think the ester or the salt is more disgusting. So I wouldn’t that say one of them is reliably worse-tasting. In terms of tolerability issues, in the main, they’re tolerated really quite well. Actually, one of the really surprising findings of my thesis was that it looks like during exercise that the ketone esters are even better tolerated than when the same amount is given at rest. I don’t know whether that’s because people are distracted because they’re exercising and thinking, “Oh, how do I feel,” a bit less; or whether because you’re exercising and compensating for an acidosis and also producing lactic acid yourself. You’ve got other things that are making you feel a bit uncomfortable. But it’s never common that people are finding them badly tolerable. I didn’t really say that very clearly. Most of the time people find them tolerable.
Chris: That has been my experience as well is both the salts and the esters taste catastrophically awful, but they don’t cause any GI distress in the way that some other things I could consume, would. Something with dairy, for example, would definitely not go down well with me, but I haven’t had trouble with either the esters or the salts. Can I ask you, where did your salts come from? Do you manufacture both the esters and the salts in the lab yourself?
Brianna: No, no, we buy the salt end from a supplier in the States.
Chris: Okay, that’s interesting. Do you mind saying who that is?
Brianna: I can tell you, but you’re going to have to cut it out.
Chris: Okay, don’t tell me then. That’s fine. Tell me how you think this is relevant to the average athlete. Is this just going to be people who are world-class performers that are going to be concerned with ketone supplementation, or do you think that anybody can benefit?
[0:20:08]
Brianna: I think there are a few questions you’d have to ask. The first thing is, are there other things that contribute to your performance that are going to make a bigger difference? For example, caffeine, that’s a reliable way to improve performance especially overshort events like rowing. Then if you take another step back, is your sleep and your general nutrition and your training, are those all optimal? Because in the long run, all of those things are going to have a much bigger impact on your performance than taking any supplement on the day of racing. I think if we do more research into exogenous ketones and also like low carb-high fat diets, generally, it might become appreciated that they have an important role in training that will have an additive effect on the eventual performance, say. So if you can really, really optimize a block of training where you’re either using exogenous ketones or, say, following a low carb diet to train your body to metabolize fat better then that might benefit your performance especially if you’re an ultra-endurance athlete.
The performance benefits of taking the ketone along with carbohydrates, as we published recently, were pretty reliable, so maybe it is something that you consider as well but depends on whether that -- we saw a 2% improvement in cycling performance over a one-hour time trial, so you’d have to make your own judgment whether or not that was relevant or whether that was outside your own variability. That’s a little thing that I looked up on the side with my PhD. I asked athletes what they would consider an average performance for them and what they consider to be a best performance for them. The elite athletes, the difference between an average and a best performance was about 2%. For athletes that categorize themselves as serious amateurs, that went up, and that was nearer like 5 to 6%. That’s just them specifying that themselves, so all of a sudden it starts to look like 2%, maybe from a ketone ester, may or may not be relevant to those people. Whereas, 2% for an elite athlete, that is more likely to be relevant.
Chris: Yeah, absolutely, it’s not difficult calculation to do. Just look at the results from your last race and say, okay, if I was 2% faster, where would I have placed?
Brianna: Yeah, exactly. So before people go and shell out loads of money on this supplement, you need to think about -- but then there’s also a massive potential for placebo effects of these things as well. In our study we blinded for that. But it might be that you just need to mix yourself up something or get someone to mix something up for you and tell you that [0:22:45] [Indiscernible], and that will make you 2% faster. You never know.
Chris: Do you think that some of the benefits could come from just eating a low carb-high fat-moderate protein diet? It has never been quite clear to me, like, why would I want to take the supplement? If I can raise my blood ketones to 2 millimoles through a dietary intervention, why wouldn’t I just do that?
Brianna: My response to that would be, why would you do that when you can have ketones and carbohydrate and when you could do more intense training, real high-intensity intervals and really get your glycolytic system up and running and then also provide ketones and have this alternative energy source? If we’re looking at it just as an acute energy source, not optimizing your body to metabolize fat rather than carbohydrates and really upping your FatMax type thing. From my perspective, exogenous ketones, they allow you to harness that evolutionary ability to metabolize ketones without having to go through the restrictiveness and the potentially compromising and glycolytic ability that happens when you’re on a low carb diet.
Chris: Yeah, I know. I’m absolutely open to that. I think that’s a really great answer. When you first started looking at these in the lab, were you surprised at how well people used the ketones? So here’s some metabolic fuel perhaps the person has never seen before in their whole life because they’ve never done any fasting, they’ve never eaten a low carb diet, and suddenly they’re just oxidizing it and getting great results. Were you surprised by that?
Brianna: No, not at all because -- and this is one of the things that I’m talking about. When I listened to your last interview, he was saying that he was surprised that people used ketones so well. Actually, athletes are perfectly, perfectly placed to metabolize ketones because ketones are taken up into the cells via this transporter called the monocarboxylate transporter, and also into the mitochondria as well by the monocarboxylate transporter. Those transporters also transport lactate. So if you are athletically trained and frequently exposing your body to lactate then your cells are wide open, ready for ketones to come up into them. Really, metabolically, one of the things that’s really great about ketones is that you don’t need insulin, rather they’re hormone-independent for their uptake and also for their utilization as well. They’re quite a simple molecule. All of a sudden they’re in the cell and then [0:25:07] [Indiscernible] and they’re there, ready to go in the TCA cycle, and also changing the redux potential of your mitochondria membrane and producing this ATP which is superior. They’re this instant, quite good energy source, no complex glycolysis that has to go through with all these regulatory steps like with your PDH and your PFK and all that that has got to go on before your blood sugar is in your mitochondria and ready to use. The same with fat, there’s all this regulation and the Randle cycle where carbs inhibit fat use. Whereas ketones, there’s not as much of that complexity going on. They’re very, very ready, very rapid energy source.
[0:25:47]
Chris: You can probably hear me flip-flopping over here. I thought we had this thing nailed where really the goal was metabolic flexibility. The interview that you’re referring to is Mike T. Nelson’s, and Mike T. Nelson is also a PhD, exercise physiologist. I’ll link to the episode to which we’re referring, in the show notes for this one. Coming out of that interview, I was like, yes, I think I finally understand it. The goal is to maximize your ability to oxidize fat and maybe some faster state training will be really good for that, and maybe some periods of carbohydrate restriction might be good for pushing that process. But the same time, you don’t want to lose your ability to do glycolysis when it matters. Certainly in cyclo-cross it matters. Certainly in mountain bike racing it matters. In rowing, obviously it matters. Do you think that’s wrong then? What did you think when you heard that conclusion? Did you think it --
Brianna: No, I agree with everything that you’ve just said. What surprised me was that he had said that he was surprised that the boy could use ketones, and what it’s saying to you is there’s no reason why the body shouldn’t be able to use ketones even if they haven’t seen them before.
Chris: Okay, right, that makes perfect sense.
Brianna: Actually perhaps the subtle point to make is that with carb or fat, you can be more biased towards using one or the other, and, like you were saying, you can be less metabolically flexible, more rigidly fixed on carbs, say, and less able to use fat, or more rigidly fixed on fat and less able to use carbs. With ketones, it’s independent of that. So this is the difference between exogenous and endogenous ketones because if you’ve got endogenous ketones, you’re going to be biased towards metabolizing fat and less flexible towards the carbohydrate because you’re going to have been following some dietary restrictions that are going to push your body in that direction. Whereas with exogenous ketones, you don’t need to be too much one way or the other, so you can still use ketones.
Chris: And you don’t think there might be a problem with creating this physiologically implausible state where you’ve got both glucose and ketones high. I don’t know enough of their physiology to really put anything that’s, oh, this is a real problem, and be very precise about it, but you can see how Mike T. Nelson is raising an eyebrow, saying, wow, you’ve got high ketones and high glucose. I guess that never would have happened in nature. You don’t think that’s a cause for concern?
Brianna: The first thing that I thought when I heard him say that was actually when we give exogenous ketones that does lower blood glucose. You’re not going to have, let’s say, a post -- so even when I gave ketones to people after having had a meal and also measure their blood glucose, I gave them a meal and had this massive insulin spike, but their blood glucose still went down. So exogenous ketones have a profound hypoglycemic effect even in the presence of dietary carbohydrates. You’re not washing around with 5 millimole ketones and 10 millimoles of blood glucose, say, ever.
Chris: Well isn’t that exactly what I saw though when I wore a continuous blood glucose monitor in a cyclo-cross race? The ketones actually didn’t seem to make much of a difference because I’ve done that experiment without the ketones at all and then also with salt, and I just saw exactly the same thing. It seems like it’s really easy for me to put myself under enough stress to get my blood glucose up to, like, 8, 9, 10 millimole.
Brianna: That’s during exercise.
Chris: And that’s during exercise. I’m not sure I could repeat it quite that high just by doing some kettlebell swings, but I could certainly raise it considerably obviously without eating anything. So you don’t know how each person is different.
Brianna: No. This is the thing, at this stage, all these exogenous ketone supplements are so new that people really need to do quite a lot more work looking at their effects on physiology before we really know. So when I'm talking and saying it earlier about we don’t know what effects these supplements would have if people were taking them long-term. We really don’t know. Would it beneficial or would it be detrimental to actually take exogenous ketones? We really don’t know.
Chris: What applications do you see for the ketone ester outside of athletic performance? Because we did the Keto Summit and there was lots of talk of how the ketogenic diet might help with neurological diseases and maybe even with cancer. Do you think that the ester might play any role in the treatment of those conditions?
[0:30:13]
Brianna: Yeah. That’s probably where I’m more excited to see where it goes because there is just such a bigger number of people that it will help. I love being an elite athlete, and I love talking to other elite athletes, but there’s a very small number of us at the top of the pyramid that really are going to benefit from this, I think, and in the world when you compare to the number of people that have cancer and the number of people that are going to be suffering from Alzheimer’s over the next few decades, whatever, where this is being developed and where this might help. So, yeah, I think this could be really interesting therapy for those people.
Chris: How do you think it would work? Do you think it would be for the, maybe people who are unwilling -- I’ll give you an example. Maybe someone with dementia is not willing to change their diet and so there may be some therapeutic advantage of ketone so maybe adding in the ester would be an advantage. Is that the sort of thing that you’re thinking about or maybe something else?
Brianna: Yeah, definitely helping people that struggle with complying with a ketogenic diet or perhaps -- I’ve never gone really properly low carb myself, but some people have said it can be a bit of a road bump, say, two or three days in where you’re not really producing very many ketones but also -- yeah, you’re not properly ketotic. Your blood glucose is quite low. So it might help people in that transition from a normal mixed diet into a ketogenic diet as well, and you’re maybe using them to top up levels of ketones if people aren’t able to produce very many of their own. I don’t know why that would be but.
Chris: Talk to me about the role of these ketone esters in weight loss. I know that this is something that you have studied. Do you think there is -- Mark T. Nelson mentioned this as well in his interview that there might be an anorexic effect to ketone supplementation. Do you think that’s true?
Brianna: Yes. There’s quite a lot of interesting literature on the effect of ketogenic diets on appetite, and I can send you a link to this really good review that was a meta-analysis of all of the published studies that had done calorie restriction and ketogenic diets and looking at all the different matrix that you can use to measure satiety. It’s like desire to eat/hunger/satiating, all the different semantics of it, but often they measure these things with visual analogue scales. They basically put all of these studies together, thousands of people’s work, in the end, and they saw that actually being in ketosis was quite strongly related to an appetite-suppressing effect. So people are trying to work out why that is; whether it’s an effect of low carb diet, the fact that it’s higher in fat and protein and those things might be seen to being more satiating, or is it the BHB and the ketones itself? Because obviously, ketones can cross into the brain and cause a blood-brain barrier and be oxidized in the brain, so they might be acting centrally, but also it might be acting peripherally as well. I did a poster, a conference where I showed that we measured the level of ghrelin which is a hunger hormone, in the blood after people had had our ketone ester. It seemed that ketone were depressing ghrelin secretion so keeping people -- once ghrelin is high, you’re more hungry, so ghrelin levels are low, people will feel fuller for longer.
Chris: So you think you might be able to give someone a small dose of the ketone ester and get that ghrelin suppressing effect without actually changing or changing much of a calorie intake?
Brianna: Exactly, but I think one of the benefits of being in ketosis and following a low carb diet is, because you’re less hungry, you do take in fewer calories. You’d hope that if people were less hungry because they’d had a ketone ester, they might also take in fewer calories.
Chris: Right. We’ve speculated on the podcast before that maybe you feel less hungry and feel really good in a ketogenic state because your brain wants you to go get food. Like if you were to sit down underneath a tree and just go to sleep then obviously that will be fatal. Really what you want to do is feel awesome. I wonder, do you have any thoughts about why people feel less hungry on a ketogenic diet?
Brianna: I agree with you. I think whenever anyone has asked me about it, I’ve always said that the last thing you want when you’re starving is being driven mad with hunger. You probably already registered that you’re hungry and you need to look for food, but it can’t be a distraction from the immediate job of finding food, evolutionarily.
Chris: We know this from other things like your experience of discomfort. It’s really the difference that you notice when you go from comfort to discomfort. You notice that change a lot. But if the discomfort continues, eventually you stop noticing it, and it’s almost like your brain said, “Okay, this guy is not really going to do anything about this discomfort, so I’m going to stop telling him about it.”
Brianna: Exactly, yeah, I think that’s probably the function of it, evolutionarily.
Chris: Well tell me about your plans for the future. There are so many different, exciting ways in which you could go. Do you know which way you’re going to go?
Brianna: No, I’m just taking stock at the moment. I’d love to stay involved with ketone research because I feel I’ve evolved now for seven years as a study participant myself and now as a researcher. As I was saying, I see so many different applications for this, and it touches on so many areas that I’m interested in, with the sport and also the health as well, that would be fantastic to find someone that I could carry on doing this with in the future. I would like to move out from Oxford perhaps. I’ve been here for, gosh, is it seven or eight years now? I think being somewhere else in the world would be really interesting. Now that ketones are a bit more of a hot topic, there are perhaps a few other places in the world where I could go and carry this on, or people like you guys where you’re aware of the benefits of ketogenic diets and ketone supplements, that sort of thing. It will be great to be able to stay involved with their research. If not then I’ll probably end up doing a standard Oxford graduate job like consultancy or something like that.
[0:35:52]
Chris: You’re going to get snapped up, yeah, snapped up by one of these management consultancy companies that just know that you’re dead smart and could do anything.
Brianna: I hope not.
Chris: Where are the other centers of excellence? Obviously you’ve got Kieran Clarke there in Oxford. I’m thinking about Dominic D’Agostino’s lab in the University of South --
Brianna: I’d be happy to work for Dom, but I don’t know what Kieran would say if I went and worked for Dom.
Chris: Oh, really? Is it like a bitter rivalry? I don’t know anything about this. Tell us about it.
Brianna: I don’t know what to say [0:36:14] [Indiscernible] anything much, but obviously Kieran has got an interest in our specific ketone ester and Dom has got his own specific ketone ester as well. I don’t know how they know one another, professionally or personally, but there’s that sort of conflict there, I guess. Then there’s [0:36:34] [Indiscernible] doing the low carb research and that sort of thing, so perhaps somewhere like that.
Chris: I should mention that we did our own tiny little bit of research. That was how I first became aware of Brianna was through Tommy who asked us to take part in this study that we did of the MCT oil powder that we produced. So we made this MCT oil powder. With the profits that we made from the first run, we used it to fund this study where we made sure that it was really doing what we thought it was. Did you have any thoughts on how we could have made that study better? It has actually been accepted for publication in a peer-reviewed journal, and we’re quite excited about that. I’ll send people the link once that’s out. But did you have any thoughts on the study?
Brianna: Well I read your paper and I was very impressed. Personally I thought it was good. I liked the way that you could run the study remotely by using blood spots. I know that you had some problems with that, but I thought that it was a really good way to get engagement of people from a more diverse range of backgrounds. Because I know that, working in the university, a lot of my research participants are undergraduate students, so I’ve not always got a very representative population, let’s just say, because I’ve got people who have got free time in the day who are going to come. So I think that that was a real strength of your study.
I was quite impressed by the level of ketones I got. I think it was above 1 or near 1, which for not having had a ketone salt or ketone ester, was pretty good. Because my experience of working with people with the ketone salts was that people weren’t getting that much higher than 1 to 1.5. My mean for the highest dose of the salt I gave, was 1.1 millimole. I think when you work with a ketone ester and you can get people up to 6 millimoles within the hour, you get a very skewed perspective of what’s a high level of ketone. So I was quite impressed by the fat fiber. I thought that it was tolerable as well.
I was a bit worried about taking something that was MCT-based, that I was going to be glued to the toilet for an hour or so, but as all things go, I thought, yeah, overall, positive experience. I’m really interested to learn about more ketogenic supplements a little bit like that, so I’m actually planning a study at the moment where I look at giving the ketone ester along with some MCT. I’ve been piloting that on myself over the weekend, and so far, that has gone without incident as well, no toilet incidents which is good.
Chris: Well that was the whole reason for the fat fiber was I experienced that same kinds of issues with all the different types of MCT oil, and I thought, well, how could I slow this thing down a bit? The answer is, you use it to plate a fiber and that fiber is going to presumably slow it down a bit. It does seem to be what we’re finding, that there’s zero gastic distress when it’s plated on a fiber.
Brianna: How high have you got yourself with just MCTs?
Chris: About the same as you, just over 1 millimole, maybe 1.2 millimole, but I’ve never seen anything like the ester before.
Brianna: No, no, the ester is just in a whole other league really, even as I compared it to the ketone salts. The interesting thing about the ketone salt is that I wonder how much of it is like -- because it’s a really hypotonic solution, whether it’s quite slow in being absorbed, say, compared with the ester. The other thing which we’re doing or open but much of a big can of worms, is the whole issue of racemic mixtures of D and L-hydroxybutyrate. When you use the Abbott hand-held meter, you’re only measuring D, so if the salt is a racemic mixture then you’d expect that that would be L-hydroxybutyrate in there as well.
[0:40:05]
Chris: I forgot to ask you about this. I know you’ve looked at it. So you’re not seeing the same sort of dose response with salts versus the ester. It’s almost like you can only get yourself up to a certain point and no more with the salts.
Brianna: Of D-hydroxybutyrate, yeah. It was like we would double the dose of the salt and we’re only getting a 0.2 or 0.3 increase in hydroxybutyrate. I think with one dose, people were getting up to 0.8 and the other dose, like I said, 1.1 with the salt. Whereas with the ester, when you double the dose, you get double the peak hydroxybutyrates. So with the D form and with salt, it wasn’t as responsive.
Chris: Do you measure both isomers in the lab or are you just using the same hand-held meters that we have access to?
Brianna: We are using the same hand-held meters, day to day. We can do that with the ester because it’s pure, only is the D, only forms -- provides the D isoform, so that’s accurate for us. Whereas when we started studying the salts, we had to start thinking about whether we would use mass spectometry, chiral analysis and look for the L as well, so that was a problem that we had to solve when we were doing that study.
Chris: So you have done that then and you were able to measure both forms.
Brianna: Yeah, we were, we were. I don’t know exactly how much I can say about this because I’ve got to make sure that I get this published in my big [0:41:26] [Indiscernible] my thesis paper, but, yeah, certainly some interesting things going on. I don’t think that there’s anything to be worried about when you have a racemic mixture. I just think it’s a really big unknown, so if you are providing the D, and we know that it’s not -- you’ve linked on your past shows to the literature by Brunnengraber and the [0:41:46] [Indiscernible] colleague who did a lot of the work looking at hydroxybutyrate. It is metabolized but it’s not metabolized by the same root as the D. So you wonder, if you’re giving them actually the two, is there any way that D and L could be competing with one another for, say, uptake? There was this really interesting paper which you didn’t link to, which I found and I found truly fascinating, which is done by this group in China. They found our hydroxybutyrate inside cells and they suggested that they thought that perhaps D-hydroxybutyrate was the form which released and were circulating in the blood. The L was also physiologically present but was intracellular.
This is the thing with the D and the L, everyone is usually focused on the D but nobody has completely excluded the possibility that the L form could be present and doing lots of stuff physiologically. So this group, they then looked at the ratio of D to L inside the cells of heart tissue from normal rat hearts and from diabetic rat hearts, and they saw a really big change in the ratio of this D to L hydroxybutyrate between the normal and the diabetic rat hearts. So they hypothesized that perhaps some abnormal production or metabolism of the two isoforms of hydroxybutyrate was occurring naturally, was something that could be contributing to pathological glucose metabolism in diabetes, which I find really interesting. So I think with D and L hydroxybutyrate, the jury is definitely out. It isn’t perhaps as ready in oxidative fuel, but maybe it’s doing something else. We just don’t know. Why not?
Chris: You should definitely send me that paper and I’ll link to it in the show notes and then read it carefully. I wonder, you don’t know if there were any follow-up studies done. Do you know how old it is?
Brianna: No, I haven’t seen anything. They’re very obscure, and it’s not yet a very fashionable area of research. And because what we found is, doing this analysis, looking for LDHB, it’s very expensive to do the mass spectrometry. I remember when I wanted to do that experiment. I said to Kieran, “I’d quite like to measure the L.” She wasn’t keen because it was so expensive. Now I’ve got the results. She’s happy that we did. But it was one of those things where it was like, hmm, I wonder whether we’re going to do that or not because, financially, we haven’t got all the money in the world to spend on doing these investigations.
Chris: Of course, of course. Wow, amazing stuff.
Brianna: Yeah, it’s interesting. It’s really interesting. I think there’s a whole chapter of that book still to be written really. [0:44:20] [Indiscernible] how much we still don’t understand.
Chris: Yeah, absolutely. So I’m thinking what I want to do now is maybe wrap up here and then get you back on the show in a few months time and you can tell me about what has changed since the last time we spoke.
Brianna: Science moves very slowly. I doubt very much will change in a few months.
Chris: Okay, I’ll get you back on in 20 years time. We can talk about what you’ve achieved in your --
Brianna: Yeah, yeah, I will be a professor of ketones, and I can tell you all about it.
Chris: Excellent.
Brianna: And we’ll laugh at all the things we thought we knew now.
Chris: Exactly. That’s probably the most important point, isn’t it, is to appreciate how little you know and how everything is going to change at some point in the future.
Brianna: Yeah, I wouldn’t say [0:44:58] [Indiscernible] swayed by popular opinion. I’m a very young researcher. I wouldn’t say that I absorb opinions like a sponge. I try to be as critical as I can, but you don’t have as much confidence and your inability to form hard and fast opinion, so it’s part of the growing and maturing process to find your own opinions and defend them a bit and see who comes back at you and you need to change them or not, so we’ll see what happens.
[0:45:23]
Chris: The other thing that makes you so interesting is you don’t really have much at stake. I look at some of these researchers that have, literally, decades, their entire career’s worth of work resting on this one idea, and if it turns out to be a bad idea then basically you could have sat on the beach somewhere for 40 years and achieve the same thing. Whereas, you’re so young and you don’t really have that at stake, so you can afford to change your mind and go on a different direction, and it’s not really going to make that much difference to you.
Brianna: Yeah. I certainly would like to carry on with researching ketone supplementation because I do think that there’s a lot to [0:45:57] [Indiscernible], but I’m not sure the we happened upon the optimal candidate for it or the optimal dosing strategy for it or even necessarily the optimal compound, say. It might be that there are better compounds out there than Kieran’s ketone ester. I think the ketone ester that Kieran is working on is really good. It’s probably better than the salts, but who knows what we’ll come up with in the next 10, 15 years time. It’s really, really exciting to be part of, especially now. I’ve got real interest in watching the whole political landscape change where people are asked to choose, to sugar and fat, and doing a lot of the reading of Gary Taubes’ book. He has just brought one over Christmas which I’ve gotten and working my way through now, talking about how sugar is all of a sudden this toxin. You see on the front page of the papers, oh, sugar is a villain. Ten years ago, I remember growing up, and it was like low fat, low fat. So public opinion is just shifting so much as we speak that where are we going to be in ten years time? We’re going to be back low fat, or are we just going to be eating liquid meals? Who knows what we’re going to be doing.
Chris: Right. The real danger here, and I think Chris Masterjohn has talked about this, is it’s changing one nutritional bogeyman for another. That’s probably going to be a mistake, I think.
Brianna: Yeah, definitely. My stand at the moment is most things, most things in moderation, and maybe that’s going to include exogenous ketones as well because I wouldn’t put anyone on long-term because we just don’t know enough about it yet. But certainly if you’ve got cancer and it’s your only -- not your only hope, but if it’s going to make a really big difference then the cost-benefit analysis is just really different for different people. But as an athlete, I would probably use it one-of if I thought it was going to help me for my event, my specific event. It’s the sort of thing where if you were just a healthy, normal person then you probably go for a dietary and maybe do like what Dom says and top this off with a ketone salt if you’re going to do a big workout or if you’re feeling like you’re not -- if you’re going to have a meal with more carbs or something like that, play around with them rather than make it a ritual that you’re --
Chris: A staple.
Brianna: -- getting your ketosis through exogenous ketones everyday. We don’t know enough about either of them yet to know, ketone esters or ketone salts, for that to be a great idea.
Chris: Just one final question, I promise. Do you know when the ketone ester will be available as a commercial product?
Brianna: Oh, gosh, if I knew the answer to that question then I would be able to tell you probably what I was doing in my future. There are so many people that have been interested in that, that I think Kieran is very keen to make sure that she picks the right person to work with her and [0:48:34] [Indiscernible] taking it forward. There are always discussions going on and for the last two years, it has always been next year, next year. At the end of last year it looked like it might be this year, so maybe it will be this year. I can’t tell you. That’s because I don’t know, not because I’m hiding it. It’s an exciting time to be working on it. I’m looking forward to seeing it out there actually for people to use. Equally as well, as a researcher, it’s quite nice having exclusive access to at the moment because there’s still a lot of research to be done. Because the minute we put it out there and it’s commercially available and everyone can go out and do their own studies on it, which is competition as it were.
Chris: Do you have an athlete page somewhere that people can come and find you if they want to make contact?
Brianna: I have my own Twitter. I can give you that, and you can link to it on the show notes. That’s probably the best way of getting in touch with me.
Chris: Okay, sounds good. Well this has been fantastic. Thank you so much for your time. I really appreciate you, Brianna.
Brianna: Thank you very much.
Chris: Okay, cheers then.
Brianna: Bye.
[0:49:38] End of Audio
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