Brianna Stubbs transcript

Written by Christopher Kelly

Nov. 6, 2017

[0:00:00]    

Christopher:    Hello and welcome to The Nourish Balance Thrive podcast. My name is Christopher Kelly, and I’m joined today once again by Dr. Brianna Stubbs.   

Brianna:    Hello. It’s nice to hear you call me doctor. I think last time I hadn’t quite made it yet.

Christopher:    That’s right.

Brianna:    I’m still getting used to people calling me doctor.

Christopher:    It’s amazing. You’ve done some incredible things in your very short life already. Absolutely astonishing. We’re here in person in San Francisco, the city on the edge of the world, quite an incredible place. I had a fantastic bike ride this morning.

Brianna:    Yeah. I was at Headland trekking. We actually could see the Golden Gate Bridge for a change rather than it being covered in fog.

Christopher:    The autumn is the best time to visit San Francisco. It’s absolutely fantastic. I used to live here and I really missed it in the autumn. It’s an incredible weather, just fantastic climate, and sunny and lovely. It’s just so beautiful.

Brianna:    Yeah. It’s [0:00:43][inaudible] to the ground with the outdoor lifestyle getting out on the bike and doing a bit of running. It’s great.

Christopher:    Why don’t we start there? Last time we spoke you were a world class, possibly one of the best rowers in the world. What’s changed since then?

Brianna:    Well, I’m definitely not one of the best rowers in the world currently at the moment. I retired from the British Rowing team in March. It was a difficult decision. It was a combination of winning the World’s Championship last year. It was a combination of many many years of work. I started rowing when I was nine and so to step away from that it was a big decision. But I had an opportunity to move out there and kind of pursue my research interest, and it just wasn’t really compatible with training full time rowing anymore.

    I felt that having won the World Championship I’ve checked up a big performance goal for myself and was ready to have a lifestyle where I could fit other things I enjoy and enjoy exercising again rather than just being on a really super rigid training program where I couldn’t decide what I was doing and sort of get the love for sport back again.

Christopher:    Go out on a high note.

Brianna:    I was very pleased to win the World. It was a fantastic feeling, and it took a while to sink in the enormity of what it represented. Because you crossed the line and I remember feeling relieved and excited and a lot of things. But you hear a lot of athletes who win big championship say they kind of just simply sink in and develop over time.

    For me, I think I was always insecure about how good I was and even though I was no better at rowing the week after I won the World’s Championship than the week before having that title meant a lot to me. So, I feel like I can sit here now and say I was the best in the world at something and I know what it takes to be the best in the world at something, and I learned a ton of stuff about elite performance and sports physiology and dealing with myself and dealing with other people and working under pressure.

    You learned so much. I think when you meet other people who are elite athletes or meet people that know other elite athletes it’s kind of this unspoken thing that you just – there’s a shared understanding.  

Christopher:    Right. It’s very interesting to hear the similarities. You know I interviewed Lesley Paterson and she talked about insecurity and athlete’s identity issues. Did you ever pluck up the courage to when someone asked you what you do you in the supermarket did you say I’m a rower?

Brianna:    I definitely identified personally as an athlete quite strongly, and that’s been something that’s been difficult to transition off of. For example, I got into an argument with one of my friends on Strava because I’ve shared this workout and he was like why are you training like an athlete. You’re not an athlete anymore.

    I just have this massive visceral kind of like no I am still an athlete because I picked my training really hard and I take a sort of structured approach to it. I’m not just working out without a purpose. I’m working out with intent. I think it’s I’m not an athlete anymore. I’m not paid to row anymore and I’m not at the world level anymore. But I still feel like I identify as an athlete.  

Christopher:    I think you should. I mean I’ve never earned any money from riding my bike and I still identify as an athlete.

Brianna:    It’s a mindset, isn’t it?

Christopher:    It is a mindset and we’ve worked with all kinds of clients who are performing at the highest level in the world and they’re still not earning any money doing what they love.

Brianna:    No.

Christopher:    So, it’s not about money. I’m certain of that.

Brianna:    No. There’s very few people that can do and make a living off of it for sure.

Christopher:    Talk about the pool. So you probably would still be rowing had you not left the UK, would you not? What was the draw to San Francisco?

Brianna:    Just as I was finishing up my PhD and last time we spoke we were looking to researching the ketone ester for a years now and I’ve been part of the team and seen it as a participants in the study my first year at university and then through doing my PhD. Looking at the ketone ester and comparing it to the ketone salts and helping run all the human trials in athletes for the last four or five years now.

    Obviously, all the while people are kind of asking when is this sort of thing going to become available for people to use more widely. I mean to be perfectly honestly I spent a lot of time asking the question myself like when is this going to happen? Is it ever going to happen? Just around the time I was finishing my PhD, Professor Kieran Clarke, she is the CEO of a spinoff company called TdeltaS.

[0:05:01]

    And TdeltaS have all of the patents around the ketone ester that I was working on, the process of making it, and the different use cases for the ketone ester. So she found a partner to sublicense out those patents in order to commercialize ketone esters for the very first time. So this is all happening just as I finished my PhD.

    Actually what happened was the company that I now worked for which is called HVMN they are based here in San Francisco and they came over to Oxford to meet with Kieran and secured the rights to commercialize the ester. And they pitched to us at Oxford and they were talking about their vision their ketone drinks and the passion that they have for their company and that they have for their space and I was sitting there listening and it was the first time in a really long time that I felt like really really excited about something.    

Christopher:    Cool.

Brianna:    And I was just like this is going to happen.

Christopher:    Yeah.

Brianna:    In 12 months’ time there’s going to be a ketone product with everything that I worked on backing up and it’s going to be out there in the world and what’s that going to look like and can I be a part of it. Is there a way that I can be involved? There wasn’t actually a formal role preexisting here at HVMN for me. They didn’t have a research department or a ketene department even.

    And I went out for dinner with the two co-founders of the company and sort of sweet talk them about. I was like you know I’m an athlete. I got my PhD in this. I really think I could add a lot of value to what you’re trying to do when you launch and help speak about it and educate people about it and look at more research avenues. I think I would bring a lot to your team.

    They were like well you know. Come out. See how you get on. See how you like us. So just very shortly after my PhD defense I came and visited the company here and it was just really refreshing to be somewhere everyone was really really passionate about what they were doing. Everyone here at the company really really cares and everyone here at the company is really really very good at what they do because it still a small company and I think everyone here punches massively above their weight.

    It was similar enough to an elite sports performance environment but also there was this added bonus that everyone was on the same team pulling the same thing and there really wasn’t anyone out for themselves. There’s no point in me making things difficult for operations or sales because we’re all in the same boat and we all want the products to sell and to do their job and to deliver good experience to the user.

    So we’re all on the same page, which is really refreshing rather than where you’re on a rowing team and it’s like well if I come second and my best friend comes third then that’s great for me getting selected. It’s like a lot. It’s a much more friendly team environment but also high achieving and everyone is pushing really hard.

    So I could really get a strong sense of that one. I came and visited and it was a really enjoyable week and so I decided that I would and obviously being in California is a draw as well. So I thought that…

Christopher:    It wasn’t hard for me to make that decision.

Brianna:    No.

Christopher:    Especially as the winter sets in London.

Brianna:    Everyone I spoke to is like oh California. You’ll love it, the great weather and great outdoor lifestyle as I said at the start. So it’s been a nice way to transition away from being an elite athlete. I think it would have been really difficult to stay in Oxford and all my friends still be rowing and to be that close to it.

    Here I’m so far away and I can just really focus on the new chapter. Although in the last few weeks, it’s been interesting. The World Rowing Championship is about to happen so it’s been a bit of nostalgia in remembering back to where I was this time last year. I can’t be an elite athlete forever. No one can be an elite athlete forever or at the very highest level.

Christopher:    Of course.

Brianna:    Just physically and emotionally it’s difficult to sustain the energy. Those very few people that make careers and their living from being an athlete very few people from being a rower. I think I was very lucky that I was studying alongside and had this as an option and that the timing just married up very well. Because if the agreement had been reached six months earlier I would still be finishing my PhD.

Christopher:    I see the timing was.

Brianna:    It was pretty perfect and then equally if it had been six months later I probably would have taken some of the role doing post doc research or I was looking at biotech consultancy. I could have done any number of things. I could have gone back to medical school. So I think the timing was really spot on and I see what I’m doing here as a really fantastic opportunities to be part of the next chapter of the story of the ketone ester.

    

    Before I was involved, it was this big military grant and people mixing up ketone ester in the basement and feeding it to rats and the rat is running all night. And that was the very first stuff. And then the second chapter was the human studies in athletes. That was where I came in as an athlete, and then as an investigator and my own personal story going from just drawing the blood off he cannulas and sitting there. Doing all the analysis until 10 p.m. type thing through to doing my PhD and having some intellectual control over the experiment and where the results were going which was really cool.

[0:10:03]

    Now it’s an interesting time because when it’s available I’m sure they’ll be a lot more research done and I hope that there is. I hope that people have the opportunity to use it for all of the different potential use cases that have been suggested for ketones up until this point. And I hope that the exposure of research is a positive thing for the field.

Christopher:    Before we go into the details of the ketones. I really wanted to talk to you more about the transition. It sounds to be like you re-found your purpose. This is really really interesting. Had I woken you up at 2 o’clock in the morning on Monday you just said I’m rower. This is what I do. This is my identity. I’m an athlete.

    And then almost the next day have I woken you up at 2 o’clock in the morning you just said my purpose has changed. I’m no longer an elite rower. I’m doing something else. I’m going to commercialize this thing and it’s something different.

    Did you have a way that resolve? Did you have anything that you use to make that decision? How did you resolve the ambivalence? You must have had thoughts in both directions? Was there a way, any techniques that you use? Did you do a cost benefit analysis?

Brianna:    No, I really did. I sat and when I was rowing full time I used to journal quite a bit because there was a lot of things that you’re always processing. Everything you do is quite an intense experience as an athlete. Even just something like a weekly training piece that had gone really really badly but its 10 days out from a trial that’s important. I remember waiting for the result sheets to come out from just a normal training piece rowing session and getting nervous about the result sheet and then having just completely out of proportion emotional response either way good.

    Well the thing was actually even if I’ve done better than I thought, I wouldn’t really give myself a pat on the back. It was more like relief. That’s reasonable. That’s okay. If the result was bad and I was six seconds behind someone who I’d be the same speed us the previous week, I’d spend all afternoon beating myself up and getting worried about the trial. So through the rowing process and my time on the team, I would journal as kind of a way to talk things out in my head.

    Around about that time where I was finishing my PhD and making these decisions, there was just so much that I was trying to resolve. Just even having been writing the thesis for six or seven months and all of a sudden finishing that is a big big change. Trying to work out what you want to do with the rest of your life. And it’s quite easy to get a little bit over dramatic like I make this decision that’s it.  

Christopher:    It’s the only decision I could ever make of course. You just make another decision, right.

Brianna:    Yeah. So I spend a lot of time writing everything out and also I have a few people who are just really great mentors to me. One of my medical professors at Oxford, he helped me decide to actually do my PhD and not to carry on with medical school two or four years ago. And I went back and had a conversation with him and I was like, you know, if I do this will I be able to come back in the academia if I want to. What’s that progression like? What about medical school? What should I do with all of these different options that I have?

    And he said you can do graduate and premed at any point. If you got a PhD. You’re a good candidate. If you go into and do commercial stuff for a little bit, there may actually be more opportunities for you to push forward research in areas you’re interested in and be involved in research anyway which is fine. Or if you don’t like it then the exposure to business and industry will probably help you to get an academic position in the long run anyway. I’m hoping that this period of time I’m going to gain a load of skills and also Oxford is this tiny little bubble. It’s very sheltered. So I think getting outside the bubble is really important.

Christopher:    Congratulations. I’m proud of you.

Brianna:    Yeah. I’m sort of going from treading water to swimming. It was a difficult time and there were lots of things going on. I think as you said you just make a decision and accept there’s always a way to not necessarily reverse the decision but you can always make another decision.

Christopher:    Right. You know you’re incredibly smart and there will always be opportunities for you and you don’t need to worry about one window closing.

Brianna:    That’s very kind of you. I hope I’m meeting a lot of people so there’s always going to be options.

Christopher:    That’s how I convinced myself when I left my job as a computer programmer to start a business. I thought what’s the worst that can happen here? I mean we fail and I get another job as a computer programmer.  Would that really be so terrible? And when you think about it like that, it makes the decision to do something that sounds a bit crazy a lot easier at least in my mind.

Brianna:    Yeah. I think the most difficult thing is when you feel kind of paralyzed by indecision.

Christopher:    Exactly.

Brianna:    When you got all the options.

Christopher:    You start to procrastinate, right. If you don’t resolve this ambivalent, you start to procrastinate as Simon Marshall talks about in the podcast recently.

Brianna:    And you waste a lot of time doing something that you’re not passionate about.

Christopher:    Right. A year passes. I’m still sitting in the window this room thinking what would have happened if I’ve gone to San Francisco and work for that company that wanted to…

Brianna:    I’m pleased and I’m excited and I hope that me being part of the team here will smooth and improve the overall kind of like rolling out the ketone ester to the world.

[0:15:02]

Christopher:    I’m super excited about the people that you’ve been working with. That’s today podcast with Geoff this morning. I’ll link to that new podcast it’s called the…

Brianna:    The human enhancement podcast.

Christopher:    Human Enhancement podcast and I’ll be listening to few episodes as I drove up. It’s not brand new but it’s new new and I listen to a few episodes as drove up from Boonie Doon to San Francisco this morning. It’s fantastic. I think you’re doing a really fantastic job and the guys I have a lot of common with computer scientist from Stanford. We talked about Tony Shay from Zappos. We talked about Y Combinator. They’re really cool guys and I think you make a really smart decision.

Brianna:    I think you guys taking a computer scientist approach to the human body is just really refreshing and also very useful way to approach physiology, right, because it’s not just like an isolated effect. That’s network effect. So I think that that background is really valuable for people coming in to try to understand physiology a little bit better.

Christopher:    Yeah. As Ken Ford pointed it out to me as long as you understand the limits of your knowledge, we talked about this as we rode about the Golden Gate Bridge earlier, understanding the limits of my knowledge. I know that my education only go so far and I need to understand that I don’t know everything. So that can be the danger. A really smart computer scientist come to a different discipline they think they know all about they do in computer science and that could be quite dangerous.

Brianna:    Yeah. Nobody knows everything.

Christopher:    Yeah.

Brianna:    And also there are no knowns and unknown knowns and all those things. There’s a ton of things that research is still going to be done to kind of illuminate the question. And so I think if anyone tells you that they definitely know anything with a 100% certainty they’re probably lying.

Christopher:    Can I talk about some personal stuff about your body composition?

Brianna:    Yes.

Christopher:    You deliberately change your body composition. Perhaps before it was somewhat artificially something in order to be the best rower in the world and you’ve made a decision there too and change your body composition. Can you talk about what you’ve done and why you did it?

Brianna:    Yes. While I was on the British Rowing Team as a light weight my racing weight had to be 57 kilos which I think is one 125 pounds and I’m 5’7-5’8 so in order to be…

Christopher:    Which is quite tall for a woman.

Brianna:    I’m not a giant. I was never going to be elite level open weight rower because I’m not tall enough. So I had to over the time we did a lot of weight lifting but also had to be very careful about what I was eating at the time that I was training. It was very difficult to make sure that you have enough to fuel the training and perform but also be lean enough.

    That was probably part of the reason why I ended up on hormone replacement therapy. I think we discussed in January. I was on estrogen replacement therapy for a number of years because I think being so lean ultimately led to downstream negative effects on my hormone balance.

Christopher:    It’s just normal physiology.

Brianna:    For four to five years like putting these extreme limits on my body pushing my muscle bulk up and fat mass down and so looking back at data report I have from last year I was sort of around 10% body fat, which is pretty lean for a woman. Now it’s not being so much like an active choice but I restrict what I’m eating less.

    I practice intermittent fasting which I’m able to do now because I can control my training. Whereas before I think the training program was set for me and trying to build fasting and around that you have to change what you’re doing on days when you’re going to restrict what you’re eating.

Christopher:    Can you define that specifically the intermittent fasting? What exactly do you mean? Do you mean skipping breakfast?

Brianna:    For me at the moment I do one 24 or 36 hours fast a week. Sometimes when it fits around my training I try and limit my feeding window to 8 hours so it’s sort of 16-8. But I wouldn’t say I do that seven days a week. I think especially having come off as super restrictive eating program that anything that gives me like too many rules is not really constructive.

    It’s really easy to just like have one day where I don’t eat and actually it’s today. Today is Tuesday. I haven’t had anything to eat. I know I probably shouldn’t have gone out and done such a big bike ride. But now I actually if I just do 24 hours I can just refill in the evening and if I don’t feel so great tomorrow then I’ll just train a bit less. It just matters a lot less when you’re not an elite elite athlete on a training program.

    Obviously, there are tons of different definitions of intermittent fasting. We have fasting community called We Fast. It’s a Facebook group where people can support one another and share stories and advice around fasting. It becomes very apparent that people have different ideas about what fasting actually is.

    In a way that’s fine. For some people 16-8 works and they do that every day. For some people like we do here there’s sort of one day a week where there’s a longer fast, fine. Some people wonder if they can drink – one guy in the group asked how many eggs can I eat while I’m fasting. I’m like calories, mate. That’s the most common question. Can I have milk in my tea while I’m fasting? You know things like that. I mean it depends.

[0:20:00]

    But I think for me it’s actually been a really really useful talk in even just readdressing my own relationship with food because it’s just so much easier to be like today I’m not eating. And when I do eat again I’m more aware of when I’m snacking and when I’m full. I’m just a bit more in touch with it. For me, it’s been a useful thing to happen.

Christopher:    You’re not still doing DEXA scan now?

Brianna:    Here in San Francisco obviously being tech central, there’s all sort so mobile, funky ways to get this test done so I actually went and had a DEXA scan about three months ago I would have been off my diet for six months or so. And so I put on about 20 pounds. So I’m more like mid 60 kg now than mid 50s. But most of that gain is muscle. I held on to all of my muscles and gained muscle.

    Now I’m more like 15% to 16% body fat. Actually when you and I were talking earlier, it’s important when you take off the restrictions on the body, the body is not just going to put on fat especially if you keep exercise training like I have. I think it’s been a beneficial change to my body composition. I’m hoping that overall my reproductive health and my hormonal health is going to improve.

    I definitely feel a lot less fatigue and a lot less stress. I mean so many things in my life have changed. It’s hard to pin it down to just eating. I mean I’m getting more sunshine, more vitamin D, better quality sleep. I’m less stress about work.

Christopher:    Really. You’re less stress now in a start of environment than you are in academia.

Brianna:    This is so much more. So much more fan than doing a PhD.

Christopher:    Interesting.

Brianna:    PhD all of the onuses is on you and you everyone in the lab is working on their own subprojects. So if you need help with something, you’re taking someone away from their allotted task. As whereas here like I said earlier everyone is pulling for the same goal so there’s just this much more sensitive support and camaraderie and shared responsibility around the – if the launch goes well it won’t because of me. It will be because we’ve all worked together to make it really really good. As where if my PhD was bad, it was all on me. All on me.

Christopher:    I think that’s an important point to note when you gain weight you don’t just gain fat. Nobody gains 30 pounds of pure fat. It’s not possible. You almost gain muscle with it and then the same is true when you lose weight. You almost lose a certain amount of muscle with it.

Brianna:    Yeah. Definitely. I feel stronger now. I can’t lift as much. My rowing machine aren’t quite as good but I’m not training those specific kind of systems.

Christopher:    Right. But you feel better. When I was a super duper skinny on the ketone diet, I feel like a frail old person. I just didn’t feel good in my body. I don’t know whether you recognize any of that. You just feel better overall. Just even when you just stood around just talking to someone you feel better.

Brianna:    I’m glad that I put my body through what I did and got the outcome that I did. It was certainly worth it. But it wasn’t sustainable long term. I think that’s the real key kind of concept through with all diets and training program is sustainability and appreciating that there’s a season in your life for everything.

    There was a season for me where I could be 125 pounds super lean, training three times a day, and also doing my PhD. Running everything at 110%. But that’s just not necessarily sustainable for the whole time. So you need to shift your environment, shift things around so you can thrive rather than just getting rundown.

Christopher:    Very interesting to unpick the decision making skill of a very smart person.

Brianna:    I think talk to other smart people and give yourself plenty of time to percolate over a decision. Definitely it became apparent to me through conversation that I was having with my parents and my with partner and my family what was actually going on in my heart. You just know after a bit of time.

Christopher:    Awesome. Good for you. Good for you. I have no doubt that you’ll be out crushing it in local competitions here in California and then you’re going to be addicted and then you’re going to be like world champion in some other sports. Before you know it you’ll be back to…

Brianna:    Don’t speak too soon. I think you might be right but we’ll see. You know a new challenge would be great. I just thought the rowing was no longer challenging in a constructive way. It was just…

Christopher:    I think there is like an 80-20 principle there with a sport, right. You couldn’t have a ton of fun with your racing and get a lot out of it without compromising your hormone health and your mental health.

Brianna:    It’s like what price do you want to pay.

Christopher:    Exactly.

Brianna:    What price do you want to pay? To get to that level I did have to make all of those sacrifices and I just don’t want to carry on doing that for another four years. There’s nothing saying like you said I want to do some competing cause that’s also in my blood and I’m hardwired to compete and push myself. So we’ll just see what happens.

Christopher:    Awesome. Let’s talk about the ketone ester.

Brianna:    Let’s do it.

Christopher:    For the people who haven’t listened to the first episode, I will of course link to that in the show notes. You can listen to the first episode. Could you briefly define what the d-beta hydroxybutyrate ketone monoester is?

[0:25:03]

Brianna:    You summarized it kind of yourself there. Back in 2003, the US Military put out a grant of $10 million to develop a new super fuel for war fighters and that grant was won by collaborative effort by Dr. Richard Veech at the NIH and Professor Kieran Clarke at the University of Oxford. Richard Veech, he was a student of Hans Krebs, the guy who discovered the Krebs Cycle so very very well grounded in basic biochemistry and metabolism.

    And working with Kieran at Oxford they proposed that ketone based fuel may be a really good way to fuel war fighter performance physical and cognitive. One of the things that’s very special about ketone is that they can fuel the brain as well as the body because they can cross the blood brain barrier.

    So over a number of years they were developing the compound itself. The compound is made up of DBHB like you said beta hydroxybutyrate which is one of the main ketone bodies that circulate in the blood when you produce them yourself and it’s joined by alcohol as you said called butanediol by an ester bond.  

    When you drink the ketone ester drink, we have esterase enzyme all throughout our gut and they break apart of the ester bond. The DBHB part of the ketone ester is available in the blood straight away. It goes through the liver. The liver can’t use ketone so it’s often systemic circulate and the butanediol that is taken up by the liver. The liver has alcohol and aldehyde, the hydrogenase enzyme that again universally express obviously like some slight differences between ethnicities Asian type thing.

Christopher:    Really interesting.

Brianna:    I mean we’ve never really looked at this with the ketone ester but it’s well characterized with ethanol that those ethnicities specific differences. Anyway so your butanediol is converted by these enzymes into beta hydroxybutyrate. So for each one molecule of ketone ester DBHD butanediol ketone ester, you get two molecules of BHD circulating in the blood.

    So there we did a ton of clinical safety studies on humans and in animals and also some initial early studies on rats looking at physical and cognitive performance. Those studies were kind of showing some really exciting results so the rats being fed ketone everyday and being run on a treadmill to exhaustion every day, they were running like I think it’s like 20%-30% further on the ketone ester supplemented diet compared with the western diet and also they fed them a high fat diet.

    This isn’t really like a keto adaptation study cause they were only on these diet acutely for five days. So I mean kind of set that aside as a potential issue with [0:27:34][inaudible]. But they also put the rats in a radial maze. So there’s a little central chamber and then arms coming off the side and the rats have to pick their correct arm to get out of the maze and their time to solve the maze was quicker with the ketone esters as well.

    So these early animal studies are suggesting some really interesting and quite profound effects on physical and cognitive performance. Then they took these results and starting looking at humans. And so the end results of the human study with cell metabolism paper which was published last year and it was five studies long looking at ketone ester metabolism in elite athletes.

    I first became involved with this study team as an athlete participant and then graduated through as a research assistant and then a PhD student working on this project. The ketone ester has been worked on now for over ten years. It’s had very extensive animal studies and also now human athletes study as well sort of basic pharmacokinetic studies and healthy people at rest.

    And then also more recent some other studies coming out looking at effects of recovery as well. And also some case study report of people using it in clinical cases. So Mary Newport who is very well-known in the Alzheimer’s and ketone community, she gave her husband our ketone ester for six months and wrote up a case report about that which is published as well.

    And she saw an improvement in his cognitive symptoms taking this ketone ester every day. I mean certainly it needs to be investigated further with more like properly control trials. There’s a ton of potential interesting applications and a lot of preliminary works that’s been done over at this process that the research is going on.

    Kieran is also protecting all of the technology with patents and going through the FDA to get approval for the ketone ester to be generally recognized as safe. So that means that it is considered as a food source by FDA not a supplement and not a research chemical. I mean it’s regulated as such.

    Also Kieran wrote to WADA, the world anti-doping agency to confirm that the ketone ester is not on ban substances. So, all of these things have been going on behind the scenes. It just takes a really long time. So for example in Europe, we failed to have this recognized as a noble food many years ago and that’s still kind of going through. So some of these processes just take a while.

    Ketones are considered by some as a fourth macronutrient. Until now there’s been no ways to include this macronutrient in the diet. You have to follow the ketogenic diet to really be able to play with ketones.

[0:30:00]

    And then if you’re doing that then you’re restricting carbohydrates and fats and there’s a lot of changes going on. Whereas now here at HVMN we’re kind of looking at ketones as new lever. A new import to sort of play with human physiology and potentially optimize for a lot of different outcomes whether that’s performance or whether that’s health.  

Christopher:    I think this would be a good point to segue into Uncle Tommy’s question. Tommy has given me some rather excellent questions. Here we go. Given the human study of the ester were performed mainly in highly trained endurance athlete in a specific sport which was cycling, who will the ester be marketed at and what are the likely benefits?

Brianna:    That’s a great question. Initially for the first launch, we’re definitely focusing in on high performing athletes. Obviously like elite athletes, a small number of those. But we do feel that this could be of benefit to anyone who is training and competing regularly.

    In terms of performance the main benefits are going to be hard for people who are competing in endurance sports in terms of actually physically making you feel better. It would be interesting to do more research and see if there’s a greater performance effect on people who are following ketogenic diets because they’re already adapted to born ketones versus athletes who are on a normal western diet.

    But at this stage, it’s sort of the formulation will not have any carbohydrate in it. So the keto-adaptive athlete can take it and not spike their blood glucose or insulin.  

Christopher:    What were the instructions be then? You need to take a glucose source with it.

Brianna:    Yeah. The instructions will be to take it with your normal pre-workout fuel.

Christopher:    Okay. So [0:31:31][inaudible] doing a stack?

Brianna:    In the future hopefully we’ll have different [0:31:34][inaudible] towards performance and then also perhaps recovery as well where we stack in with protein. I mean another interesting thing that you can stack in with performance is caffeine. And so actually some of the ketone salts manufacturers stack their salts in with caffeine.

Christopher:    So you know that it’s doing something.

Brianna:    Yeah. Exactly. A paper came out about two to three weeks ago. So in the last sort of three or four months, there have been three papers looking at ketone salts in athletes, which is surprising that these are the only three that’s out to date of ketone salts and human just full stop.

Christopher:    Right. People have been taking these for years.

Brianna:    Yeah. People have taken these for years. People have no idea if and how they work. But the first two papers one of them showed null effect on performance so no increase. One of them showed a decreased in performance. It was either 2% or 4%. It was sort of you know a small…

Christopher:    I’ll find these studies and cite them.

Brianna:    Yeah. We should link them. It’s interesting but the thing is as well they didn’t give the ketones with carbohydrate. The problem I see of this no carbohydrates in with the ketones. Ketone level is very low like 9.8 to 9.5mmols.

Christopher:    Which is typical with the salt.

Brianna:    Which is typical with the salt. It’s quite low. In comparison with the ester where levels are say 3 to 5 you know. It’s very dose dependent so you can titrate up and down with a lot more finesses than with the salt. The salt is either kind of like 9.8 or like 1. You could double. In my own work, I tried doubling the does and didn’t really get very much of an actual increased in BHB.

    So low carbs with it. Low BHB levels. Big old electrolyte load which could impact on the performance anyway. But also the performance tests they were using were pretty short so like a 10k cycling time trial. I think that all of these things are probably too heavily glycolytic to be really getting a benefit from also having ketones.

    So if you look back at the metabolism paper, the main effects of ketones were to spare glycogen lower blood lactate and all of these are kind of indicating that body is burning the ketones and sparing glucose which is only going to really really be of benefit if you are going out to point where glucose supply becomes the limiting factor.

Christopher:    Is it sparing or impairing glycogen use?

Brianna:    I mean it doesn’t have to be mutually exclusive, right.

Christopher:    Okay.

Brianna:    So if you are impairing glycogen use, you’re also kind of sparing it for later on. For me the word “impairing” has negative connotation.

Christopher:    It does. I don’t want to finish the race with a whole bunch of glycogen because something I was taking stopped me from using it, right?

Brianna:    Yeah. But it depends on whether the fact that you are running out of glycogen would have been a limiting factor to your performance in the first place.

Christopher:    I would agree. Yes.

Brianna:    So I mean it’s interesting for events that are kind of over an hour long I would say. You know people doing…

Christopher:    Let’s name some specific sports then. So road cycling, triathlon.

Brianna:    Road cycling, triathlon, long distance running. So, most people aren’t running a marathon in two hours so people who are running marathon. I think these people could expect to see a performance benefit.

Christopher:    Right. Cross country skiing maybe.

Brianna:    Yeah. For sure. I mean that’s highly oxygen. I can see that being useful. I can see useful for being used in training for any sports that does a lot of aerobic training. So I think for rowing I could see people using it periodically for a period of intensive training where you want to support the body where there’s a lot of other stresses going on. But then also there are definitely benefits for more mixed intensity sports in terms of recover.

[0:35:00]    

    If you got a sport like soccer or basketball or NFL, anything where the nature of the sport is kind of intermittent, it’s an interesting idea whilst ketones aren’t going to be contributing to contributing to the more anaerobic energy system and may actually be scrubbing off like a bit of performance there, maybe. And not affect the whole game because you’re actually not sprinting the whole time. You got to also be making cognitive decisions and you also going to be moving around the pitch and all of this things. Like what were the net effect be over a whole game. Cause I think your original question okay this is in the lab. This is highly controlled. This isn’t anything necessarily like a race.

Christopher:    It’s not like any race I’ve ever been in or known of.

Brianna:    But then equally doing a 10-second Windgate type test is also not really like it. So I think for people doing those intermittent sports if you’re producing less lactate and able to hold on to your glycogen a bit better, and another really interesting effect of the ketone ester is that it attenuated the exercise induced rise in muscle branched-chain amino acid.

    So in kind of like layman speak it looks like if you got ketone you don’t break down as much muscle protein and that fits evolutionarily really nicely with the role of ketone as sort of signal to get the body to hold onto its stores whether that’s protein or carbohydrate. Potentially for these mixed intensity athlete and for endurance athletes trying to hold on to muscle mass.

    But also recent paper came published by Peter [0:36:31][inaudible] and they saw that with the ketone ester drink, there was higher activation of downstream targets of muscles mTOR. It may be that for mixed intensity sport, this won’t necessarily a net gained on performance due to the sport the performance time because it’s more dependent on anaerobic energy system. But then if you’re trying to recover, especially the pro level basketball players playing like very often and traveling a lot as well.

Christopher:    Yeah. Most of the event.

Brianna:    So we worked with some pro cyclist and some of the feedback is that they would use it at the start of the stage that was going to be hilly at the end because the ketone will have worked its way out of the system. You know they’ll burn the ketone, spear their glycogen.

Christopher:    And then when it’s game time.

Brianna:    Yeah. Exactly. So like you were saying earlier like a race is sort of all this four hours of jockeying and just looking after yourself, looking at yourself and then you climb at the end.

Christopher:    Right. So not everything is a time trial.

Brianna:    Yeah. So I mean it’s quite possible that pro level cyclist like that could benefit from taking ketones at the start of the stage, be in better condition for the end of the stage. But then also taking it afterwards if they’re going to have to go out and do it again the next day.

Christopher:    For three weeks.

Brianna:    Yeah. Exactly. It’s so intense. So that period of time you definitely want to support the body in way you can to get the overall net biggest sort of performance improvement. So to summarize, definitely a performance benefit for people doing endurance sports, potentially a performance effect for people doing a mixed sports but sort of to be validated in further studies, and then interesting implications for athletes who are looking to recover better if they got a multiday event or multiple bouts in the same day or supporting intensive periods of training, which we all do kind of like a training camp where you’re kind of trying to really screw yourself basically.

    So I spoke to the British Rowing Team. I was like if I had this available to me when I was training especially as a light weight where everything comes so much for premium, I would have been really interested to use this because it would have not only would it have given me a fuel. It would have protected my lean mass which was a premium. You know you’re trying to optimize your body composition and the ketogenic diet certainly had some interesting research done around like optimizing body composition.

    So it’s kind of interesting kind of similarities there. But then also recently coming out there’s lots of research around ketones having beneficial anti-inflammatory effects through acting on NLRP3 inflammasome which I know James McArthur talked about last week.

Christopher:    Mentioned. Yeah.

Brianna:    So this means that all of a sudden these things have got like kind of quite broad global applications especially for someone who is immune compromised and you’re trying to support them through a difficult period of training or racing. I mean I think at this stage there are studies that exist today are kind of limited. If you extrapolate off the real results that we saw, there are definitely many potential use cases but they need to be not only investigated in the lab but also part of my role here at the company is to get a feedback from people using it in the field.

    We don’t want to tell people to use it for something it’s not working for but also different people are going to respond differently. So it’s kind of taking a balance view and collating feedback as it comes and trying to decide which are the worthwhile research avenues to kind of pursue.

Christopher:    Can you explain briefly why the source of glucose is required for the increase in exercise performance?

[0:40:00]

Brianna:    Sure. I mean we choose to study it like that for the initial human studies because we wanted to – in one of the earlier study we look at ketones by themselves versus glucose by itself and we saw that by their performance and their physical output could be generated with those two substrates was equivalent.

    There was a fixed steady state cycling exercise. No improvement with just ketones by themselves compared with glucose and it was synergistically giving the two that was able to really unlock the next kind of next gear. You know unlock the extra 2%-2.3% improvement and performance that we saw.

    I think it’s really about providing the body with all of the fuels that it needs to exercise. Cause when you’re exercising, you’re never just glucose burning or never just fat burning. Equally when you have a ketone ester, it’s accounting for like 16% to 18% of the oxygen that you’re consuming we believe. So it’s not even just all ketones.

    Part of the reason is to do with arming the cell to be able to metabolize ketones through this process called anaplerosis, which I know you discussed a little bit before. So some of my work in my PhD looked at experimentally increasing or decreasing the amount of glycogen in a muscle and then seeing how much ketone it could burn.

    

    And so if you deplete a muscle of glycogen it then can’t burn ketones. That’s a bit counterintuitive cause you’re like well this muscle hasn’t got any glycogen. How is it carrying functioning? But the Kreb Cycle requires sort of intermediate to come in to top it up and I know I’m in the very simplest terms and ketones can’t do that.

    By the time ketones get to the Kreb Cycle, they can only offer two carbon intermediate and you need things that can give three and four carbon intermediates into the Kreb Cycle. Carbohydrates can do that and ketones can’t. So it’s having full glycogen reserve does put you in a better position to actually be able to burn ketones and we’ve seen that experimentally as well.

Christopher:    Okay. Excellent. Next question from Tommy. All the studies today on ketone salts in athletes have failed to show any real performance benefit probably because they don’t raise BHB levels enough. Should we just stop messing around with the salts until the ester comes out?

Brianna:    I mean I think we discussed this. We answered that stuff a minute ago.

Christopher:    Yeah. I got a bottle of the salt in my refrigerator. It’s been there for about a year now. Is it time for me to pop that in the bin?

Brianna:    Well it depends. Different levels of ketosis have uses for different things. So there’s some really interesting matter [0:42:33][inaudible] looking at the effects of ketones on appetite and they collated the results of a lot of different studies. And they saw that the appetite suppressing effect of ketones they said kicks in at 0.5 to 0.6 mmol.

    So depending on what you are using it for, ketones salts may be adequate. Also there’s a lot of interesting questions still to answer around ketone salts to do with how the body handles D- and L-hydroxybutyrate. So I think it certainly is still valuable to the overall kind of field to continue research in ketone salts and understanding how they work.

    But I supposed for my personal perspective I feel like it kind of confuses the issue cause people don’t really understand that there is a difference between the ketone salts and the ketone esters. It’s like one person says ketone improve performance. One person says ketones don’t improve performance. Not only is it well the BHB is the same. It’s really just the efficacy of delivery.

Christopher:    The delivery. The vehicle. Yeah.

Brianna:    I mean with the salts as well you do get the big electrolyte loads which I’ve seen cause GI distress and also it’s just probably not I think to be pouring into your body right before you and do intense exercise. It’s perturbing your homeostasis in any case. The salts are still valuable research tools. At the moment, they are much more accessible than the ester and the price of the salt still will be lower than the price of the ester when it comes out initially.

    And also interesting to see what happens when people more widely purify pure BHB salts whether they can get the levels any higher than that. But I know that Dom D’Agostino’s group is talking about giving ketones along with amino acids whether that will be beneficial as well. So I certainly wouldn’t rule out any of these things could potentially be interesting and useful.

    But I think that the ester is interesting because it delivers only the physiologically most relevant [0:44:24][inaudible] form without giving you a big [0:44:28][inaudible] unload. So I think if you’re researcher and you want to manipulate up and down level of ketosis and really tease out threshold for where things are useful and where things aren’t useful and isolate the effects of ketones on any number of pathways whether that’s as I was sort of saying then appetite which is kind of a personal interest of mine versus whether it’s the threshold for [0:44:47][inaudible] control versus any other number of applications then I think the ester gives you a bit more fine control and fewer potential compounding variables.

[0:44:57 ]

Christopher:    Tommy has got another really good question here which I think for most people listening the answer will be obvious but I’ll ask anyway. You previously said that for most people the performance benefit of the ester is going to be much less in terms of percentage compare to optimizing diet and lifestyle. Do you still think that’s the case?

Brianna:    Yeah. I mean…

Christopher:    Probably true for every single application, right.

Brianna:    Yeah.

Christopher:    Whether you’re interested in epilepsy, Alzheimer’s, cancer, sports performance, whether you’re a Navy Seal diver. Probably the diet and lifestyle is still going to be the biggest lever you can pull.

Brianna:    For sure. I mean I think maybe some of the clinical use cases is a little bit different because there are clear effects of being above a certain level of ketones. I think especially for the sport application. It’s going to give you the biggest benefit if it’s part of an optimal protocol training protocol, sleep and other dietary things. There’s no magic bullet.

    I know ketone is sometimes being built as a magic bullet. It’s very very exciting and if you use this correctly, it will potentially unlock more performance because you’re giving your body a fuel that it wouldn’t otherwise have access to. You know fuel limitations are aerobic limiting factors for endurance performance. I think there’s massive, massive potential.

    But if you go out mashed your prerace training run a bit hard then you’re not going to perform better or if you don’t recover better and you get sick the week before your competition then it’s not going to rescue. I always look at it as a way to make you a better version of yourself that you can be on that day.

    But there are lots of different things that you can do that be building towards that whether that’s caffeine or nitrates or beta-alanine or bicarbonate. Every athlete is going to have a slightly different supplementation protocol. Some athletes used a ton of supplements and some athletes used none at all. I think take it if it makes you feel better and don’t take it if it doesn’t make you feel better.

Christopher:    Exactly. You raised a valid point which is it’s really up to you to decide whether this thing is really making a difference that’s worth it to you. Sure it requires a cost benefit analysis not unlike the one that you described where you made the decision to leave academia and rowing.  

Brianna:    I think if you’re thinking about using ketone supplements then I think it’s like try and be as methodical as you can about it.

Christopher:    Keep all things equal.

Brianna:    Yeah. Keep all things equal. Try it for workout and then next day do the same workout without or work out you perform regularly. So for the study that I was a participant in, we looked at ketone ester in 30 minute rowing performance and I would do those rowing machine tests week after week after week after week.

    

    I just knew how I would perform and I knew how I would feel. And therefore, the difference when there’s something that actually moves needle you can really tell. So when we launched the ketone ester we’re going to be encouraging people to actually measure their blood ketones because once you measure your blood ketones you can’t argue with the fact that it’s raising your blood ketones.

    So it’s about tracking as many outputs as you can and being as systematic as you can about whether or not this is improving your performance. Most people won’t do that. Most people will just say I feel better. I think it works.

Christopher:    Well see you may have some power users in the beginning that do track all this stuff and give you a ton of really great data.

Brianna:    I hope so and I know we worked with some teams in the past and I knew that they would have power data that we didn’t get it. It would have been an interest to see that.

Christopher:    Really. I was going to say so yeah when you’re working with the cycling team surely they have tons of historical data and they’re able to tell you exactly what it’s doing.

Brianna:    I’m sure it will become more obvious in the future. I think the difficult thing has been for the last few months talking to people about perspective ketone ester product is that people feel like it’s not launch yet. I don’t want to say we’ve used because not doping concerns about the ketone ester but the climate at the moment around sports nutrition is very suspicious.

    And so people don’t want to be in anyway link with anything that’s a bit different. People are kind of afraid. So I think that hopefully when this is mainstream and not being obtained from directly as research chemical from the University of Oxford and its sort of all public and something that every athlete can buy and use then hopefully they’ll be more discussion around oh yeah I used it and I saw this improvement or let’s hope that people will be a bit more transparent.

Christopher:    That’s very interesting. Another interesting question here. Brandon Egan he did an excellent with Danny Lennon on his segment nutrition podcast that we very much enjoy at The Nourish Balance Thrive is episode no. 195. Brandon Egan recently made an interesting suggestion that anti-inflammatory and antioxidant properties of ketones.

    Do you think the use of exogenous ketones to enhance recovery might diminish the adaptive response to training like we see with N-acetyl cysteine and cold therapy? So basically when you exercise you see an inflammatory response and the response is part of signaling cascade that then leads to training adaption and should you try and stop that signaling cascade you may blunt the effects of the training, which would be probably not what you want unless you were doing like we said earlier like the stage race. It could be helpful. Do you think that could happen with ester? Do you think that might blunt the effect of training?

[0:50:12]

Brianna:    I think at the moment with this whole field it’s really interesting. It does seem like there’s two camps so like people who are all about supporting immune function and being anti-inflammatory and looking after the body. And then people who take the line a little more like you were saying is that stresses the helpful adaptive thing that is driving training.

    

    I think personally I feel like it’s the middle ground where it’s the most constructive kind of path growing forwards. You can see this with exercise training. You can periodize time with hard training. For example like lactate threshold training at hard intervals and then you have like a downswing where you do more of the aerobic base and you let the body recovery.

    I think actually nutritional things that maybe blunt information but have more recovery kind of – so if you’re in a training camp and you need to recover and train the next day and you’re doing much increase volume and it’s tough and you need to replete and get ready to go again and your immune system is compromise then I think it would be of more benefit to refuel that.

Christopher:    So you have to look at the big picture.

Brianna:    I think if you just took exogenous ketones, 365 days in the year then maybe you would get some blunting of the training adaptation. But if you use it strategically around periods of intense training then that will allow you to complete the training, which would be more beneficial than any decrement in the molecular adaptation to that training.

    Cause doing the training, being able to complete more high quality especially with rowing where the movement has to be at a very high quality otherwise you’re rowing in bad habits. So you want to be out doing long or high intensity but quality, quality training to improve. I think anything that helps you sustain those kind of more intense periods that will be useful.

    There’s a lots of question still to ask about the long term implications of taking exogenous ketones long term. So I mean at this stage it’s all just speculation. Then there may be positive effects. So being in ketosis through exogenous ketones may increase fat oxidation long term in the same way that [0:52:21][inaudible] with the fat study. So in his study he saw athletes had twice the capacity to oxidize fat during exercise compared with athletes on a normal diet.

    And we saw in our cell metabolism paper we showed that the ketone was increasing intramuscular fat oxidation. So it looks like there’s an effect of ketones on fat burning. And so maybe if you took ketones everyday for six months or maybe not that long two or three months, that you would by nature sort of forcing ketones through that pathway and increasing fat oxidation that you may even without needing to do tons and tons of aerobics based increase your fat oxidation more than you would have done otherwise. I mean that’s interesting and then you can get into the whole ketone as a signaling metabolite kind of field.

 

Christopher:    That’s what I was going to ask you. So this antioxidant property we’re probably not talking about a direct effect. Am I right thinking that? That the beta-hydroxybutyrate is a signaling molecule that then leads to the up regulation of endogenous oxidation. Am I right in thinking that?

Brianna:    It’s very complicated.

Christopher:    God, biology. It’s so blood complicated.

Brianna:    Yeah. So I mean sometimes people focus on the effects of ketones in the mitochondria. It’s like producing less superoxide or affecting the glutathione couples and [0:53:36][inaudible] couples and scavenging [0:53:37][inaudible] and then other you can look at beta-hydroxybutyrate as a histone deacetylase inhibitor. It’s an endogenous HDAC inhibitor so affecting gene expression and that has all to do with anti-inflammatory properties, longevity link pathway.

.

Christopher:    So it’s super complex. You’re not talking about something that’s just going to donate its electrons.

Brianna:    No. Unfortunately ketones do a lot more. Fortunately/unfortunately ketones do a lot more than just get burn up by a fuel. I mean even beta-hydroxybutyrate relation so sticking BHB onto proteins in the body and the DNA so I mean there’s a ton of things that we don’t understand.

Christopher:    [0:54:15][inaudible] affection gene transcription or something.

Brianna:    Yeah.

Christopher:    And then you’re kind of lost at that point so you don’t know what’s going on.

Brianna:    Being metabolized, acting on d-protein coupled receptors like the nicotinic acid receptor and affecting lipolysis. So they have receptors the BHB acts on as well so [0:54:30][inaudible] and then gene expression, histone deacetylation, acetylation and then on a substrate level like the mitochondrial. I mean there’s so many many layers. It’s very very complicated.

    So I think to give you a definitive answer about what would the net effect of taking exogenous ketones for six months be. There are many many potential answers and I don’t think one study is going to even answer all of them because you just need to focus it on. It’s going to be really difficult to really tease out. But I think increasing availability of ketone supplements so hopefully it mean that this study are kind of more done, more carried out in the future.

[0:55:04]

Christopher:    This is like a lot of things when I interviewed people recently it’s reminding me of Robert Sapolsky’s new book where essential thesis is the way that biology works is not through single causes and single effects. It’s about modulation. It’s about propensities. It’s about predisposition. It’s about feet forward and feedback loops, if then else clauses. It’s incredibly complicated and you almost need a computer and some sort of directed graph to try to understand all things that are happening in the system.

Brianna:    I agree and I think whilst we are increasing our understanding and whilst the research is being done it’s certainly important for individual to share experiences and share any data that they collect whether that’s positive or whether that’s negative and looking at the body of evidence with a balance view.

    Because on one level there is no point in sitting on something for a really long time until we have a definitive answer about exactly how it’s doing what it’s doing. I mean we use general anesthetics million of times a day and we don’t know how they work. Really. We’re still very unclear about how.

Christopher:    So it’s a top down approach. Let’s figure out that it works and then we’ll figure how it works. Once we know it does work.

Brianna:    I mean I’m not entirely implicating that but I do think that once ketone drinks are available people are going to use them for different things and so hopefully the different use cases will become more at least anecdotally evidence base and that we’ll target the research going forward. I hope.

Christopher:    His last question is very special. Only Tommy could have written this question here. Sometimes people say to me you have such great question on the podcast. Well I have to give Dr. Tommy works much great for the question asked.

Brianna:    He’s a brilliant mind.

Christopher:    He is. He is a fantastic guy and I very much appreciate it. Here we go. You’re probably not going to like him once I asked this question. Are you ready?

Brianna:    Yeah.

Christopher:    So Kieran, he’s talking about Professor Kieran Clarke. Your…

Brianna:    My PhD supervisor.

Christopher:    Your PhD supervisor. Kieran’s working ethics have shown that the ester can depending on the scenario increase muscle protein and glycogen synthesis and may also increase instant responses to hypoglycemia. That’s high level of blood glucose. However, Richard Veech who is…

Brianna:    Kieran’s collaborator over here in the NIH in the US.

Christopher:    Prestigious biochemist recently published a paper stating that the same ester can be used to mimic calorie restriction and therefore treat metabolic disease and enhance longevity. How can the same supplement have two diametrically oppose mechanism of action and in what context do we need to get the opposite effect from the supplement?

Brianna:    Yes. Very complicated question. So I think what I’ll do first is just explain the two different results that Richard Veech and Kieran Clarke are talking about. So the human work that was carried by Professor Clarke’s group in the University of Oxford showed that if you as you said induced hyperglycemia. So if you raised people’s blood sugar by infusing glucose. So they were having glucose infused so that their levels were about 10mmol and then also having a ketone drink that that increase the muscle glycogen [0:58:05][inaudible]. The propose mechanism for that was an increase in insulin secretion. So they were proposing that if you have high blood sugar and have ketone you secret more insulin and store more glycogen and that was the observation of this one study published recently this year.

    Dr. Richard Veech, he’s done a bunch of studies where he supplements the ketone ester with mice and rats and he seen lower fasting levels of insulin in these animals and then they’ve also done glucose tolerance in those animals and seen them improved sort of insulin sensitivity there. So I mean straight up those are two very different settings, very different experiments and it may well be that what Richard Veech saw is when you take ketone ester your blood sugar goes down and this is actually a concern with ketone salts as well.

    So, exogenous ketone consumption seem to consistently lower blood glucose. And so it may be in the animal feeding studies where the animals had ketone ester for a prolong period of time their blood glucoses may have been lower at the time and therefore for their basal insulin secretion are also lower. That may explain that observation.

    And then that contrast to the kind of acute setting that was done in athletes by Professor Clarke’s group where you whack people’s glucose, whack people’s ketones and then you see an increase in insulin secretion. That result actually kind of tallies with some work that was done back in the sort of mid 1900 where an investigator called [0:59:44][inaudible].

    They had isolated pancreatic eyelets and they varied the glucose concentration and added ketones as well. And they saw that when glucose level added to the cell was above 5mmol ketone, the extra addition of ketones potentiated and increased the amount of insulin secreted.

[1:00:02]

    So it may be that there’s a physiological threshold of blood glucose whereby adding ketones on top of that potentiate insulin secretion. Interestingly enough that could have an evolutionary role because insulin is antiproteolytic so even if you were starving you would still want some insulin to protect your muscle protein. Although that said when you’re fasting and your ketones are that high, your blood glucose wouldn’t be five.

    

    In one of George Cahill’s papers, he talked really nicely about the need to still have some insulin during fasting and starvation as a protective mechanism. So you could kind of speculate that ketone affecting insulin secretion in a positive way may be evolutionary for that kind of purpose. So I think evolutionarily ketones potentiating insulin secretion could have an interesting role to prolong survival.

    They don’t have to be in conflict the two observations because the situations are very different. I was going to add that actually with my own experiments giving ketone ester by itself when you have a drink of ketone ester and this is with sweetness or anything else added, there’s a very very very tiny little rise of insulin from the basal facet level up maybe 5 to 7 mU/L and that’s in contrast to a meal which gets you an increase of over 40 to 50 mU/L.

    So it’s sort of fraction of what you’d see in a responsive meal; a small response to the ketone ester drink. I think that physiologically that tiny little increase is not super super relevant and it certainly not comparable to what you see after a meal.

Christopher:    It can be difficult to measure that kind of a change, right.  Cause insulin is continuously metabolize and so you might have to look at C-peptide or something like that to even know whether there’s a…

Brianna:    Yeah. It’s sort of all within the accuracy of the test that you’re using. So I think sort of  for me where I stand on the ketones and insulin question at the moment is that if you’re going to chug a Gatorade or chug a load of carbohydrate and take ketone ester so you got high ketones and high glucose. Ketone may boost your insulin response to that amount of carbohydrate, which if you’re an athlete actually could become beneficial for insulin signaling potentiating muscle growth and recovery and things like that.

    But then if you’re looking to use ketone esters more for a longevity kind of perspective if you were to be taking them regularly or in ketosis for a prolong period of time then the net effect may be lower blood glucose and decreased insulin. It’s subtle difference and it’s not tease out yet. The results do appear on the very high level contradictory but when you think a little bit more on the differences in the experiments it’s not that contrast.

Christopher:    We better rap up and summarize then. By the time you hear this podcast the ketone monoester will be available which is very exciting

Brianna:    Very exciting.

Christopher:    So summary who is it for?

Brianna:    Ketone ester is going to be for athletes who are looking to improve their endurance performance and athletes looking to recover faster from exercise.

Christopher:    How much will it cost?

Brianna:    It’s going to be $30 per bottle.

Christopher:    How many serving in a bottle?

Brianna:    One serving.

Christopher:    So for people like me…

Brianna:    It’s going to be a special treat.

Christopher:    It’s going to be difficult to persuade myself to invest in training.

Brianna:    But that said once we get to scale the cost is going to come down. We’re seeing it like a Tesla right. Everyone is going to have an electric car in the future. We just can’t afford it right now.

Christopher:    Right.

Brianna:    Everyone will have a chance to try ketone ester and decide if it works for them. But not everyone is going to afford it on this first run. So be patient with us. We are working really hard with all the chemists back in Oxford and all the people at manufacturing plant to bring down the cost. You know to put it in perspective. This used to be thousands and thousands and thousands of dollars. It’s an improvement and we’re doing what we can to bring it down and to bring it out to the world.

Christopher:    Good for you. It’s funny you say that about supplements. We’ve been looking at intestinal alkaline phosphatase which has some really promising properties to reduce gut inflammation and potentially prevent endotoxemia that we talk a lot about the podcast. And then Tommy looked it up and found out how much it cost, the research chemical. We’re like okay. That’s why no one has done it yet.

Brianna:    But you need to push it forward and then see because unless we had ordered a massive batch of it, it would still be too prohibitively expensive. So you have to get that initial investment to take it to scale, to take it out and then you got revenue from selling it and then you can drive the cost down further.

    Actually coming with this academic background where I would kind of like automatically shy away from anything like this, it’s a really important part of the continuing story of science to be able to bring down cost of things like this so to facilitate more science and more wider access. I think watch the space for it becoming cheaper.

    Initially the price point is steep but it’s very very well evidence based on people performing at that level who were interested I think would be great for them to try and be a part of the kind of cutting edge development of this type of technology.

[1:05:08]

Christopher:    This could be popular in Europe. I think that things are so expensive in Europe already. I pay €7 for a bottle of water the other day.

Brianna:    And here in San Francisco as well. It’s a perfect place to be launching it. But then also we’re keen to say to all people if you want some boost of energy there is like a carb free fuel for your brain to maintain focus and maintain energy levels and ketones are a much better strategy and non-stimulant way of keeping yourself kind of fuel than if you’re trying to do fasting. It’s not going to take you out of your fast.

    There’s sort of like there’s non-athlete use cases. That’s interesting going forward and that’s maybe a bit relevant here to their business exec, some people trying to optimize their performance in Silicon Valley.

Christopher:    And so the initial run is 2 metric tons made in the UK. There’s not going to be a problem with availability.

Brianna:    Well I mean it depends how high the demand is.

Christopher:    How quickly it sells out.

Brianna:    Yeah. Exactly. Excited to see.

Christopher:    Well, I will of course link to the HVMN website and I’m hoping there’s going to be, yes there will because we know there’s going to be a product page that can link to…

Brianna:     Yes, of course. There’ll be a product page where we got our design team making it all beautiful. We’re working on it right now.

Christopher:    Awesome. Awesome. Bri, thank you so much. I’m really excited to have you on and I hope to have you again on the future.

Brianna:    I hope so too. I hope that as this field grows that we can all be part of the kind of continuing discussion around how these things are best use and getting feedback from athletes in the field using them and practitioners in the field like working with the sort of thing is like immensely valuable. And so I think your expertise in this area is really really great and I hope that we can carry on talking and working together maybe in the next few years.

Christopher:    Thank you. Thank you very much.

[1:06:45]    End of Audio

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