Geoff

Brianna, good to have you on the program.

Brianna

Thanks for having me, as ever, Geoff. It's good to see you back from your trip.

Geoff

Yeah. Context there is I just came back from a trip to China, sight seeing and visiting my grandfather, who's 94.

Brianna

Good longevity genes.

Geoff

Yes, I've got some good genes there. But this will be a special episode talking about the story of Dr. Brianna Stubbs and her work here at HVMN. So, one of the bittersweet news that we're announcing on this podcast today is that Brianna is transitioning from her head of research role at HVMN to a part-time subject matter expert research advisor role with us, and has a new beginning back in the world of academia at the Buck Institute. So, we'll talk a lot about that; but before talking about the future, let's talk about the last couple years of working closely together.

It's a bittersweet announcement, and maybe to add some words before talking about the history one of the most proud things that I personally really care about, and what talk a lot about at HVMN, is that our team was world class and we're excited about working with the best people in their role. One thing that I've found that you represent, or you really epitomize, is that you're truly world class at what you do. I've told you privately that you're probably one of the top handful of people that understands exogenous ketones and human physiology. There's just literally people that we could count on our hands, within less than 10 people, that have done the studies, personally looked at the data on humans with all the different types of ketone count balance.

So, from that aspect, top-tier, world-class in terms of academic knowledge of understanding of the physiology, but also just your previous career as a world champion rower. You get that double stack of being world-class from an academic perspective and world-class from an athletic perspective. I think that's a very rare combo.

Brianna

Yeah.

Geoff

So it's really been an honor and a privilege to work with you over the last four years.

Brianna

Likewise, I think for me to be able to reflect back on the two years taking Delta G ketone ester, from being this liquid that we just kept in plastic bottles, and sort of syringed out, and did all of those experiments to seeing now, all of these beautiful bottles of HVMN Ketone that are being shipped all over the world, and being used by people to break records, and compete in elite sporting events. Hearing all the customer feedback and having been part of making that a reality has been, and I'm sure it will always be, one of the absolute biggest achievements of my life. I mean, it's something that I'll always be really proud of.

Sort of for me, I just want to be able to get more into the detail of how this is working. I'm so passionate about making discoveries, and advancing the field, and then communicating those discoveries that, for me, I just want to be able to get super hands on, and dirty, and grow the world of exogenous ketones because I think there's so much potential to help people there. I've got this fantastic opportunity to go and work with two of the scientists that I think they were first people to ever publish on BHB being an HDAC inhibitor. So, ketone body BHB actually effecting gene expression. The two scientists I'll be working with, John Newman and Eric Verdin, they really understand not just how ketones are used as a fuel, but as a signal as well. For me, I think that's the next frontier in our understanding

And then we recently did a research roundup about BHB and inflammation, and there's all of these things that we're speculating about what might ketone ester be good for, and now I'm going to be back at the lab just really trying to understand that. So, I'm really excited about that, but as you say it's like, really, really bittersweet because before I joined here I'd never really been... Other than obviously being an athlete, but I'd been in the lab and never really exposed to what it takes to make something that's just a concept and a research a chemical, and what would it take to ship that out to thousands and thousands of people. And everyone here at HVMN has an absolute world-class attitude to productization and actually making a business around helping people live better lives.

I've learned so much from you and from Michael about strategy, and fundraising, and all of the things that go into keeping the lights on. And then Chrissy, what does it take to ship something and put it in a bottle, and Zill, and Paul, and everyone who works on content and writing our blog posts, making the podcast. So, I mean, there's just so much that goes on behind the scenes here. I think one of the things that's most inspiring is how much everyone here cares about the customers and making better humans. That's the mission above the door, but everyone here really lives that.

It's certainly was not an easy decision for me personally, because of how I feel about the team here, but I think that long-term I would love to continue to build myself as a world expert in this field, and this is a fantastic opportunity to do that. So, yeah, as you said, going to be staying on as an advisor and still part of the family.

Geoff

So I think it is a transition, but it's not going to be a farewell or the end of you being part of our family.

Brianna

It was a farewell rather than a goodbye, it's kind of like, "Until next time."

Geoff

Exactly, and hopefully next time, in very shortly, you'll be Professor Brianna Stubbs, as well.

Brianna

Fingers crossed, yeah.

Geoff

We're super supportive and really excited for you to be able to double down into the basic science research; and I think that's where, as a products company, we're just not going to be fully fitted out to enable that kind of level of basic science, research, and understanding. Which is just going to be much more of a natural fit at a research institution. So, very excited and support you there.

Brianna

Thank you.

Geoff

So I think it'd be fun to just reminisce on some of the highlights. I remember the first time I met you was probably close to two and half, almost three years ago, at Oxford. This was me meeting your thesis advisor, Professor Kieran Clark over at Oxford, and getting the first initial introduction and tutoring session, essentially, about ketone esters. And she invited you, who, one of her star PhD students at the time, to run through your thesis work at the time, and then also do a bit of a tour around Oxford campus.

It was very much like visiting Harry Potter for me. I had just gone to Europe, I was over at Oktoberfest before coming back home to the United States and made a layover, essentially, over at Oxford. And then getting dropped in the Oxford campus for the first time, which is very idyllic, beautiful, Harry Potter-esque sort of campus. And then meeting and talking science with a bunch of British, smart sounding ladies. And then getting a tour of the different castles, essentially.

Brianna

I think it's funny, because at that time Professor Clark had been sort of thinking about commercializing the Delta G ketone ester for a long time. So it wasn't my first rodeo, it wasn't my first tour that I'd given for entrepreneurs and people who were interested in being business partners coming through. I think it says a lot for what Professor Clark saw in you at that meeting, that she saw you were the right people to take all of those years of research and make it a product.

I remember that meeting, and I remember at that time I was coming towards the end of my PhD and had like half a mind on what would I be doing afterwords. Not really all of that much, but I remember when we said goodbye, I was like, "You know, if this ever goes anywhere you know where to find me. I would be really, really interested in helping with the launch here. I'm not sure how we could work together, but let's see what happens."

And then, you know, a few months later you were back in touch with her, and coming over to visit, and it was all kind of really taking off. So, it was just a really cool example of being in the right place at the right time, for me anyways. Also for you, reaching out to her and making the agreement there.

Geoff

Yeah, a lot of things stacked and lined up really nicely for the group from the research and the regulatory coming online, us, as a startup and as a business really coming to maturity, and then you from timing productive in terms of becoming a freshly minted PhD and looking for your next opportunity. It was luck, but I think it goes back to something that I've come to realize a lot over the last four or five years of running HVMN, but also just my full career just being in startups, and building business for my entire career. It's just a lot of things require a lot of luck, there's a lot of smart people, a lot of energy, but also decries a lot of luck in terms of all these things coming together at the right place, at the right time.

Brianna

Yeah, I think what we have here at HVMN is a lot of vision. I think when you came with Michael to speak at the lab meeting... So, sort of fast forward a couple of months on from us meeting initially, Geoff and Michael came to visit Oxford again and I don't know whether that was when you were kind of finalizing things with Professor Clark, but you spoke at a meeting with all of the people who were researching ketones, and researching cardiac metabolism. So you came and sort of spoke in front of a big group of us, and I remember sitting in the audience, and you had some mock-ups of what it might look like, and you had your go-to market plan, and all of this stuff that I didn't really know that much about at the time, but I was like, "Wow, this looks so exciting." And for me, at that time in my life, I was working really hard on writing my PhD thesis, and I'd just come off the back of like four years of training on the British rowing team, and I was just kind of jaded by both of those things. It was kind of tiring doing both of those at that level. And it was like, hearing you guys speak sort of switched something on inside of me, and I was like, "Wow, yeah. I've got some energy back to go out and do this."

By that point, I was like, "PhD... Oh, rowing..." I wasn't feeling super energetic for those things, and then you came, and you spoke, and I saw what a bottle of HVMN Ketone might look like. It wasn't actually anything like it ended up looking like, but seeing it be a thing, it was just so energizing. And for me, joining the team, and after that presentation we connected over dinner, and you invited me out to San Francisco, and then eventually ended up moving here.

But there was just so much work to be done, and so much opportunity, and so many unknowns that it was really cool to come out here and sort of set about addressing all of the things that needed to happen that I could help with that were needed to sort of make it a reality. Whether that was... I mean, one of the first things I worked on was... I remember at that time we were working really closely with Dr. Manuel Lam, who is writing a lot of that kind of, "Oh, this is what we're going to say about ketones. This is how ketones work." Or, we've been through so many iterations of what's the elevator pitch of how you explain how ketones work. So one of the first projects that I worked on was just like, what were the words that we were going to use to explain the backgrounds of the basic biology?

Geoff

Yeah.

Brianna

A big project I worked on was putting a lot of the knowledge that I'd written up in my thesis into some big kind of like educational guides that were the forerunner to our blog content now. So it was like the very, very first iteration of now what is something where thousands and thousands of people click on a month to learn about ketosis. We were then alongside that kind of project, you and I went to a load of meetings with sports teams, and journalists, and we had so much education to do. This was even before we had the product. We were sort of talking to people, and we would go, and Geoff would talk business, and then every now and again I would chip in with something smart about the science, and we'd have our little bottles of ketone, and at that time they were not as they look now. They were kind of like a little bit OG, and they were home-bottled.

Geoff

Yeah, they were like basically hand-artisan-crafted bottles of ketone ester.

Brianna

Yeah, and we only like 20 of them in the world. At any one time we had very few, and we'd go to the meeting, and we'd do our little spiel, give it to people, and then do the finger stick reading. And that's always been one of the things that's most compelling about this technology, is that people can actually measure it working. It doesn't have to be, "Oh, do you feel like it's working?" There and then in a meeting we could demonstrate to people that it was actually really profoundly shifting metabolism. We only had issues with our ketone meter reading like one time. One time we gave someone ketone ester, and their ketones didn't go up as much as we thought. It still went up, but it wasn't as impressive as it normally was.

Geoff

No, I think I would say the same. The ketone meter totally fucked up, that was totally just like... It didn't move, and it was so embarrassing.

Brianna

Yeah, that was really embarrassing. That was one of our worst meetings, because I think also at that meeting I feel like I'd bought the ketone meter, but we didn't have enough ketone strips, and we were like five blocks away, and you were like, "Yeah, you have to go back and get ketone strips." And then you're entertaining these two people we were meeting, and I jumped back... And then I got back, and I was sweating, and dripping on the people as I was trying to finger prick them. That was a bit embarrassing, and then the ketone levels didn't go up. When we got out of that meeting we were like, "Well..."

Geoff

"That didn't work."

Brianna

"Let's tee that one up to experience."

Geoff

Yeah, we tested with a meter. But that experience really turned me off on that specific brand of the ketone meter.

Brianna

Yeah, it seemed like it would sort of, somewhat, tether the reading based on what the previous reading had been. And I've seen this with a breath acetone meter that I'd used one time; if you used it, and then used it again, and then took another reading directly after the second use, the second reading would be kind of like more. So it was almost like it needed to like...

Geoff

Fully clear.

Brianna

Yeah, I don't know. There was something. But I'm not sure that could happen with a blood reader.

Geoff

I mean, the strip should just completely change. But yeah, regardless I think I've seen... There's some unreliability there, let's just put it that way.

Brianna

Yeah. But most of the time we would go to these meetings, and the ketone ester would perform beautifully, and the ketone meters would perform beautifully, and it was this great... We were able to really give people the background, and then show them how it worked. And it was always funny the different reactions we'd get when people would taste it, because at that time, again, I feel like it probably wasn't quite the finished product. Wasn't tasting as good slash not bad as it is now. So those were all very interesting meetings. I remember the weekend before we went live and launched I spent a lot of time in the office with the design team, and then the engineering team, Paul and Mike Lee, working on the website copy, and we were working on what graphs we were going to use.

I remember there was quite a lot of complexity on the homepage at that time because we really wanted to be able to explain it. And now it's interesting to see how we've kind of had to par things right back and try to make the message super simple so that people aren't overwhelmed by information. So, it's been interesting to see that.

Geoff

Yeah, definitely a learning experience for me because I think I'm cut from more of a similar cloth to you, I like the science, I like the data. It's like, okay, let's explain this stuff. And then you sort of see that, okay, from a product perspective and an education perspective, sometimes it's too much information. It's like, how do you explain something that is very, very deep biochemistry, a novel physiological state we're inducing in people? But even that, what I just said sounds pretty complicated. I think our listeners understand, but general population might think, "Okay, what is this guy talking about?"

Brianna

Yeah.

Geoff

And I think that's been, and will continue to be a challenge of this ketone space, probably. Because, one, there is interesting effects of why ketogenic diets, ketones, ketosis, is interesting; but you don't want to fall into one side of the equation, which is like, "It's magic Jesus juice that's going to solve all your problems, melt fat off your body." But it's also not like it doesn't work.

Brianna

Yeah.

Geoff

Just like, okay, how do we get the right level of the coolness and the amazingness of the technology without going too far on either side of the spectrum?

Brianna

Yeah, I think you also touch on an interesting problem there, and this is what I'm hopefully going to be able to unblock more in the future by being involved in the research. There's all of these different use cases that have still got to be fully proven out. I think the inflammation is a really interesting case study, because we had all of this animal data suggesting one thing and now the very first human studies are starting and the results aren't marrying up.

But it's like we actually have to take that theoretical stuff, or early animal evidence, and start to translate it through to humans. One thing that I'm really proud of is that we've always only told people what we know ketone ester does, specific things where we already have the evidence. We talk about performance, we talk about some of the recovery aspects, and some of the cognitive aspects. As soon as there's data, I feel like we're happy to say, "Yeah, you can use ketone ester for athletic performance with carbohydrate, under these specific use cases."

Geoff

Yup.

Brianna

But all of the other stuff, I think we're pretty open about it being a bit more speculative at this stage. So, I think that's something that excites me to be able to unpack and further open up avenues for people who work on exogenous ketones to be like, "Actually, hey look, we really know that it works for metabolic syndrome, or we really know that it works for Alzheimer, or TBI." But we're still early stage there, and want to be able to be part of unblocking all of the people who are actually waiting for the evidence before they just start making these promises.

Geoff

Yeah, I think a lot of credit to you as our researcher lead helping really define the evidence grading, and the standards in which operate. I think that's been one of our strongest assets as a brand, and I think that's why a lot of people do trust us, because we are direct with the science and the evidence.

Brianna

Yeah.

Geoff

But I do want to come back to some of the funny anecdotes in terms of our favorite trips or experiments that we've done with VIP's, or with different teams, or investors. I remember some of our trips where we visited this woman, relatively high profile in the media world, and it was interesting when we gave her the ketone ester test that her initial blood sugar was kind of high. She was basically pre-diabetic, diabetic looking blood sugar. I think that was kind of some of the interesting experiences where we hear the top level number of a lot of people have pre-diabetes or metabolic syndrome in the world, especially in the United States, and you actually go out and test peoples' blood levels.

Brianna

There are definitely those people that have...

Geoff

And people that have highly elevated blood sugar and they don't really realize it.

Brianna

Yeah.

Geoff

That's kind of on a low light, but I think some of the sports stuff was really fun in the beginning where we'd have people that are celebrity athletes that we're just stabbing in the finger.

Brianna

Yeah.

Geoff

Do you have any favorite anecdotes there, in terms of from a medical... You know, we're not trying to make a medical diagnosis ad-hoc on the ketone ester demo, but it was interesting from a general awareness of the prevalence of metabolic syndrome or high blood sugar, to like just being able to interact and work with celebrity athletes. Any highlights for you?

Brianna

I think definitely working with Victoria Bussi on the world record attempt, especially having been an elite athlete, I really felt the sense that we had a responsibility to her to get it right, and at the very minimum not do anything that could possibly compromise all of the training that she'd put on and at the very best case let's work out how to support her so that she can get that extra tiny percent that she needs to break the world record. So I felt empathy with her and responsibility to make sure that we kind of tested it thoroughly, and she and I were in touch quite a bit, and by what's happened she would tell me some of the numbers from the training sessions that she'd been doing.

One of the highlights there was when she'd been training with the ketone ester, and then she was like, "You know, I've got to train without it a couple of times because I want to reset and just see what that feels like." And she did a session, and she came back to me, and she was like, "Yeah, I totally want to use it because I did this session and it just wasn't the same and I felt like I get so much better focus, and energy, and performance with the ketone ester." So for me, especially as a sort of skeptical scientists, I feel like I want to stay in that state of being kind of skeptical, I still feel this huge buzz...

Geoff

Hey, don't sip the Kool-Aid too much, right?

Brianna

Yeah. I still feel this huge buzz when someone tells me they think it works for them, just because I feel kind of personally proud of that. So when she came back with that kind of feedback, and then ultimately went on to break the record, I was very pleased and proud to see something that we worked on translate, and really pleased to have been involved in that attempt.

Geoff

Yeah. I think when we see these world record, or these amazing achievements, it's like, that took months, years of training to get there. I mean, she was busting her butt for months ahead of that attempt. And I think we all just think, "Okay, you just spent 60 minutes on a bike and you're done." No, that's a culmination of hours, and hours over weeks and months of sacrifice to get to that stage.

Brianna

Yeah. I think that's kind of like life, though. I feel like especially with today's attitude to social media you kind of see edited highlights of everyone's lives. Then, firstly, that may or may not be a true representation of what it's like, but also you don't necessarily understand the grind that goes in day to day to making HVMN Ketone, or to being an elite cyclist, or an elite rower, or even an elite scientist. All of the hours of frustration of trying to get something to work in the lab, or all of the hours reading papers, it's like a lot of non-glamor in every single job that you don't see when you kind of see the end result.

Geoff

Yeah.

Brianna

So I think that personally I've never been afraid of the grind and I think there's something that we can kind of share here. It was a grind, and we spent a lot of time in the trenches together working on making HVMN Ketone a thing. But everyone who we've worked with is in their own grind. Victoria was in her own grind, all of the cycling teams that we're working with, the training and stuff is a grind. And then all of the military, all of those kind of things. Everyone's working really hard, day after day, to build the best version of themselves that they can and it's not an insignificant amount.

Geoff

Yeah, 100%. I remember that the first time they were importing the ketone ester it was like no one knew. It was never imported before.

Brianna

No one knew what it was. And even things like how are we going to do the food label? All of these things had never been done before, and I remember there was a point where Chrissy was talking to the FDA, and it looked like it could even be classified as a carbohydrate because it wasn't fat, and it wasn't protein. But we're like, "But it's not a carbohydrate. It's just not. How are we going to reconcile this?" It was so many things that had never been done before that we really had to do for the very first time that weren't easy.

I remember when, in that weird transitional period, so we'd launched for... I joined the company in May, and I remember when I met you and Michael in Oxford, you'd been like, "We need you as soon as we can. We're going to be launching in June, July. Go, go, go." So I quickly uprooted my life and moved over here. And then it was like, "Oh, are we doing to make it?" There was so many things we had to work through, it was a lot of slower, and there's so many more obstacles to overcome than perhaps we could have ever imagined before we started.

Geoff

We had some delays in the manufacturing, this and that.

Brianna

Yeah, so then we get to like... I remember we went on summer retreat and we were like, "Okay, we're drawing a line in the sand where no matter what, we're launching for pre-sales on the first of November."

Geoff

Yeah.

Brianna

And so we were all building up towards that point and when we launched for pre-sales we still weren't at the point where we were able to fulfill, by that point we were kind of out in the public and talking to people about it. And then there was this horrible, really, really difficult few months where people were like, "Let's try it." And we still didn't have it to give to them. That was the worst. That was one of the most difficult times, just every week, or every other week being like, "When are we going to have it? When are we going to have it? When are we going to have it?" All of these people knew about it, and wanted to try it, and we had to slow roll people.

Geoff

I remember a lot... I think this is public now, but a lot of cycling teams were ramping up for the Tour De France at that time.

Brianna

And we had very limited amounts, and we were just sort of sending whatever we had over to them; but we didn't have very much of it at that time because we were still doing very small pilot batches. We weren't at full scale production. And then I remember when the very first batch arrived at headquarters, and there's this picture of me, I'd made a chair out of... We had, I don't know, like 20 boxes, and I'm in the little storeroom, like sitting on it. And we finally have HVMN Ketone, and then that day Chrissy and I went and hand-delivered for the cycling teams boxes that were going out to Europe for their grand tour racing season.

So there was this period of time where wee were doing everything, everything was coming to headquarters, and we were doing it by hand, and we didn't have very much of it, and now it's so much more mature, and everything kind of goes out through the warehouse, and we don't have to send out anything ourselves anymore.

Geoff

Yeah.

Brianna

But you know, we have it, and there's no angst about, "Oh, we only have 10 bottles of ketone in the world. Can we really give 5 to this celebrity that we're trying to schmooze?" Or something like that.

Geoff

Yeah. Definitely some crazy highlights, and some crazy grind stories. Yeah, the initial batches are hand-sent by your hands and Chrissy's hands.

Brianna

Yeah.

Geoff

I mean, that's like some VIP service there.

Brianna

We actually used it with one of the football teams when it was just raw Delta G. They were so desperate to get their hands on it, they were like, "Can you get some of those?" And we were like, "Well, to supply this team I could deliver some of this to them."

Geoff

Yeah, I mean you basically hand delivered it, which probably limits the geographic location of what these teams could be. But yes, I remember that day. It was like your first check from an NFL team, which was kind of cool.

Brianna

Yeah.

Geoff

Which I have a picture of. One of the questions that producer Zill wanted me to ask, and I think it's a good question; coming from the academic world, what impressed you about HVMN that you wanted to join in and be part of a startup? What was the initial... And this is me expanding on that, what were your thoughts coming in to Silicon Valley, San Francisco, the world of startups?

Brianna

Yeah.

Geoff

Was it what you expected over in Oxford? Obviously reality's different than fiction, what were the biggest differences? What have you learned?

Brianna

I don't know. I feel like it was much more glamorized in my head as to what it would be. It was literally like half the world away, and it seemed like a place that was really, really flush with money. And it just seemed like very... Glamorous I think is the right word. Glamorous and fast paced. And certainly there is elements that are glamorous, but there's like as many elements that are not as glamorous. And I think the idea that a startup is awash with money is completely false. I think startups have to be super, super scrappy and that's one of the things that was most impressive about here, how much you can do with the resources that you have. Really maximizing everything that comes in and out in the company. So I think, especially given you flew me out here, and I was like, "Oh, am I traveling on business for the first time?"

It seems like it's going to be much more glamorous than academia, when in reality there's that same kind of grind and scrappiness. There is access to capital and all of that you don't have when you're in academia or when you're in academic. So, I think that was something where the reality and my expectation were maybe a little bit misaligned. But I think that I expected that things would happen quicker than academia, and that has definitely been the case because you're not beholden to a funding body or anything the same way. You can actually execute pretty quickly, and I think a startup, especially, when you can talk directly to every single member of the team...

Brianna

Everyone's like over stretched or stretched at the very least, in the terms of like what they're working on. But you can work very closely, and cohesively, and make decisions, and progress a lot quicker than academia or in a big business. I think that was something that was really, really refreshing and that I kind of had hoped would be the case, and was the case. I think one thing that I expected that was there, but also not there, we had a high amount of biohacking ethos within the company. And so I think that seeing that from the outside, you came and the first time you were wearing a CGM, and you just finished a seven day fast, and it's just a funny story.

So Geoff and Michael had just finished a seven day fast, and I went for dinner with them and we had one dinner, and I was like, "This is great." And then they were like, "We need more food." And we went to two more restaurants. We started off with like tapas, but I guess in retrospect tapas would not really fill the hole after a seven day fast. And then maybe we got some curry, and then we finished off with the pizza. So it got progressively more junkfood-y. But we went to three restaurants that night.

Geoff

Yeah.

Brianna

But anyway, you guys were like embodied a lot of biohacking, but I think it's like also that coming and working with everyone is like, yeah, everyone's already interested in optimizing their health, but nobody's a drone, or a droid, or a robot. Everyone's also got that human side where, yeah, you need to have an ice cream sometimes. Or if there's definitely a human element to that rigorous biohacking as well. So that was something that I didn't know whether if I worked here that I'd be forced to fast 36 hours like twice a week, or whether I'd be... I don't know, doing some kind of weird self-experiments, or whether two years later I'd have some kind of weird implant. But, no, I'm still firmly 100% an HVMN human and all of that jazz.

Geoff

You were pretty extreme on the Ironman and endurance triathlons.

Brianna

It's a different kind of biohacking.

Geoff

So it's pretty aggressive in terms of what you're doing on the side as well, right?

Brianna

Yeah.

Geoff

I would say that doing an Ironman, 7.3, that's like as hardcore as a long intermittent fast if not more hardcore.

Brianna

Yeah, I think it's going to be... I'm training for my first full Ironman, which will be in July so I'll keep you guys posted with how that goes. I'll be definitely using HVMN and ketone for that race, probably more than one serving to get me through that one.

Geoff

Yeah, yeah we'll give you a special stack.

Brianna

I have some, yeah.

Geoff

Hey listeners, if you're enjoying this episode thus far please consider writing a review on our iTunes page. It really does help increase the visibility of our podcast. That's really the best way to support our work. In appreciation for your review, we'll hook you up with $15 of HVMN store credit. We also love it when we see you guys share our episodes that you've enjoyed on your Twitter, Instagram, or Facebook and we often re-share those posts. Just tag us at our handle @HVMN. Now, back to the show.

I'm just like thinking about some of the cool trips that we had. I remember when we were initially launching HVMN Ketone and we did a trip out to New York, and D.C. and I think this was your first time in New York and D.C. because they had a lot of reporters out there that we were supposed to brief.

Brianna

Yeah. I'd only been to America one time before I came to visit here in San Francisco. So, my time here at the company, pretty much everywhere that I visited it's been the first time I've been in that place in America. I'm like first trip to L.A., first trip to New York, first trip to D.C. and then we've also been off on some of the military bases and slightly more obscure places as well. But as a British person as well who grew up watching Friends on TV, to go to New York and see it in the flesh was really awesome.

I feel like perhaps Americans kind of take that for granted. It's very iconic and even things like here in San Francisco, like the Golden Gate Bridge which is super iconic landmark, now I bike ride over that like two or three times a week but it still has a big impact on me when I do that. I still feel like I'm super lucky to be able to live in a beautiful place like this but it was like that to go to New York and be like, "Wow I'm actually here at Ground Zero at the World Trade Center. Or you know, here it is the real Yellow taxi cabs. And, "oh, I'm in a real New York traffic jam." You know. That can even be exiting the first time you do it. "Yeah, we were late somewhere weren't we because we decided to take a cab and then the journalist got upset with us because he told us to take...

Geoff

The subway.

Brianna

Yeah, he got upset with us because we were late because we took a cab and got stuck in one of the tunnels.

Geoff

Yeah. I remember that. He didn't end up writing about us anyways.

Brianna

No.

Geoff

It is what it was.

Brianna

It was an interesting chat because I think we sat down to talk with him, and then he turned a video camera on, and we were like, "Oh you're videoing this now. Okay."

Geoff

Yeah, we had to do like a little live demo.

Brianna

Yeah, I wonder whether that tape will ever see the light of day?

Geoff

We'll see!

Brianna

Yeah, as a British person who hadn't really been much in America, I didn't have a good appreciation of how diverse it is and how different the east coast and west coast are. And then you know like more of provincial America how culture and even architecture vary place to place. Got an awesome country, I like it.

Geoff

Yeah, no, and I would say that even for... I'm American, born, and raised, grew up in California. But I think even most Americans don't see as much of America as they should. I think it is like you go to your New Yorks, you go to your L.A.'s.

Brianna

But it's always challenging as well, too, if you end up somewhere and work, actually getting out and seeing the place and I think one of the things that I've enjoyed is that in all of these places that we've been, you and I together, and whenever I've been somewhere on work is that I often go for a run. So I get to see one of my personal highlights was the first time when we were in D.C. I went for a run and went around Capital Hill and saw the Lincoln statue, and the pool that was in Forest Gump, and the white house. I'd never been there and seen it, so actually being able to go and run around there ,and see all to of the sights kind of quickly, that was kind of a cool thing. And New York as well, I ran around the outside.

Geoff

Central park.

Brianna

Well, I ran around Central Park but then I ran also ran around the sea front. I don't know what the correct term for it would be, but around the outside of the Manhattan Island so I sort of did that as well.

Geoff

So either probably saw New Jersey or Brooklyn.

Brianna

Yeah. Actually on the land mass that Central Park is on, I kind of like ran to the edge and ran around the outside so those are like cool places to run. But then you know I've also been to like a trade fair in Indianapolis and that's like not a very exciting place to run. Not much to see and not directly outside...

Geoff

We're not trying to offend Indiana.

Brianna

No, no.

Geoff

I didn't say that, Bri said that. Blame the British person.

Brianna

It was quieter. I didn't spend much time in the center of town, we were at the convention center.

Geoff

Yeah.

Brianna

That was funny because we were there, and it was my birthday, and we were presenting at this trade fair, and I was with Michael and Adam and they forgot that it was my birthday and we sort of like went through the day and got to the airport in the evening and I was like guys you know it's my birthday today, and they were like oh what. So they bought me Chic-Fil-A. So that was my birthday celebration. Like, "Oh, okay. We'll buy you something nice at the airport." And it was the best that Indianapolis airport had, was Chic-Fil-A.

Geoff

It's not gourmet, but it's a yummy sandwich.

Brianna

I'm going to say that the chicken strips are better than the little bites. More crispiness.

Geoff

I don't know, I have never really tried... I like the sandwiches.

Brianna

Yeah.

Geoff

Sandwiches are great, and the waffle fries.

Brianna

No, you got to get rid of that bread. That carb. Extra carb.

Geoff

What was the most surprising thing about our community, or launching ketone esters that you didn't expect? Because I know that obviously you've worked at it on the ketone ester as a research compound. I saw it from a research perspective and a science perspective before looking at it as a product perspective. What are your thoughts in response?

Brianna

To be honest I think one of the things that was surprising, and I don't know why it surprised me because I think I should have expected it. Surprised me and has frustrated me the most is the amount of conflation between ketone drinks will do and what the diet will do and the amount of confusion that there is around ketosis and drinks and fat for fuel and I think that a lot of other companies out there in the space deliberately conflate it because it sells product really nicely to be like, "Yeah, magic weight loss. Ketosis equals weight loss. Ketone drinks equals ketosis, therefore ketone drinks equals weight loss." And I think that perhaps there's an interaction there, but we're definitely not at that stage and in fact I think we've talked about this loads of times. When you drink exogenous ketones in the short term you inhibit your own fat release. So I kind of get interested. If you drink a ketone drink you slow down the release of let's say belly fat, but actually what we found when we looked at the muscles of athletes when they were exercising having had exogenous ketones is that they burn more of that intramuscular lipid.

So you have to be super nuanced, and fat burning isn't a nuanced-enough term. You shut down fat release, but you may enhance fat oxidation.

Geoff

Within the muscle.

Brianna

There's a lot of nuance there, and I guess it shouldn't be surprising that 99.9% of people miss all of the nuance, but I think that the amount that we had to we have to really spell things out really clearly, it's sort of been sort of surprising how entrenched some of the views are within the community. And also maybe surprised at how negative that some people in the ketone community are like, "Exogenous ketones? Why would you even do that?" People get kind of like defensive of the fact that you want to be in endogenous ketosis, and I think it's actually like let's look at the time, and the place, and the context, and I don't think anyone's saying at this stage that ketone drinks will completely ever replace the ketogenic diet for certain use cases. But I think that the surprise was that 95% of people who are interested in ketosis are interested in it for weight loss or metabolic health, and specifically for weight loss you can't just have calories from ketone ester and not change anything else about your diet and assume that's going to be a magic pill.

Geoff

A magic, yeah.

Brianna

Yeah, you could use ketone ester as part of a ramping onto keto, or as to support workouts when you're on keto, or support fasting, and all of that. But yeah, you're not magically melting off fat by drinking ketone ester. You have to make other changes. So I think trying to articulate nuance it surprised me how much confusion that there was and how careful we had to be and it's still something where I think that people like us and people who are doing the research need to really hold ourselves to a high bar of language. And unfortunately a lot of the other product companies don't do that because it helps them to deliberately conflate things a little bit.

Geoff

Yeah and I mean there's much education and good work to be done on the science side. So as you ramp down into an advisory consolatative role with HVNM and ramping up with the full-time role at the Buck Institute, what are some the interesting scientific questions that you're looking for to answering? Or, help answer?

Brianna

So I think one of the things that's like a little bit of a hangover from my PhD is the different ways that the body could use the different isoforms of BHB. So in Delta-G, the ketone ester in HVMN Ketone, we have pure BHB and the reason is we know that is a really great fuel for the cells of the body.

Geoff

It's the natural form that the body endogenously produces.

Brianna

It's the natural form. So we always focused our research in on this form because we were really focused in on providing a substrate for the body. Now, in my PhD I was looking at racemic, so that means a mixture of the physiologic and the non-physiologic forms of BHB, I was looking at racemic ketone salts. They were a mixture of D, which is the natural form, and L, which is the form that the body doesn't make. The unnatural form.

Geoff

And just to add some context, a lot of organic compounds, things with carbon have these isoforms. These chiral forms. They're like the left-handed, right-handed versions of molecules. Same exact chemical compound but they don't look the same.

Brianna

They don't overlay. And that means that they interact with the body a little bit differently. So with ketones this means specifically that the form is really great for being used for energy as an oxidative fuel, so my PhD... There had been some early work done on animals but this is the first time that in humans we'd looked at the rate of removal of the non-natural form from the body. So in my PhD I found that if you had a drink that contained both of the forms both went up but then this non-natural form would persist in the blood for a really, really long time.

So it's clearly not being used for an energy source as rapidly, if at all, compared with the natural form. But is it doing anything in the body? Some of the other interactions of ketones with the body may not be isoform specific, we know that ketones bind to certain receptors and affect gene expression. And you and I have been tracking the literature and we're seeing work come out. There was a paper about vascular senescence and they were starting to look at the difference between the D and L form.

So there's people who are starting to do this work and seeing that the signaling properties of this non-natural form maybe important. And so for me, especially going to the book where they were the first people to publish on BHB as a signal and they actually write every year kind of like the ketone-signaling bible, it's called "The Ketogenic Bible". It's like 300 pages long and it really summarizes all of the evidence around the non fuel uses of ketones. So I'm really interested.

Geoff

It's a pretty deep read, it's a good read though.

Brianna

Yeah. It is cool because it covers all of the receptor interactions, all of the gene expression interactions, and all of the data that there is today. And so now we're getting a point where there is some signal that this L, non natural form maybe signaling in a way that's comparable. So I want to start unpacking how that works, what that might be useful for, and if therefore that there is ultimately in the world for mixture drinks or products that contain mixtures of the two. So would it be really helpful for an athlete to be drinking HVMN Ketone but if you want longevity, do you actually want a blend of the two? And what's the ideal blend of the two? And all of those things, so for me that's an area that I'm really interested to understand specifically stemming from my own PhD research having been one of the first people to look at this. I'm really excited to use the tools and the expertise that they have there to start unpacking that.

I think that I'm just super excited to see the field of exogenous ketones and that research grow. Because there's so much interest and we really need to start backing it up with good science and expanding all of that. More and more good science to expand out more and more use cases, more and more nuanced understanding of like, "Oh, when do you want your ketones at 5mM? Or when do you want your ketones at 1? At when will that do?" And all of these different questions, like threshold effects. That's another thing that I really want to start looking at that people just have never done. What's the level of blood ketones where you're burning as much ketone as you can? Or what other factors effect that?

So again in my PhD I was looking at manipulating the level of stored carbohydrate or glycogen in a rat heart and I found that when the glycogen was low the heart wasn't able to burn as much ketone. Which is kind of counter intuitive, because you'd think that if it was out of carbohydrate that it would want to burn more ketone. Actually we're seeing that carbohydrate was sort of like permissive at ketone use, and so really trying to unpack what's the optimum level, and what are the optimum conditions for burning ketones, or for ketones being used as a fuel but then also as a signal. At what level do you kind of reach maximum receptor activity let's just say.

So we know that when you have a drink of HVMN Ketone your blood levels of free fatty acids fall because the ketones are slowing down fat release as we kind of just discussed. But when does that effect become maximal? Because you actually, like with blood glucose, your ketones drop blood glucose but glucose never goes to zero. So there's some kind of dose response, but when is that physiological maximum? So it's important to start understanding so we know how to apply ketones best. And what's the best dosing strategies? It's important to start understanding some thresholds as well.

Geoff

Yeah.

Brianna

And that's going to be completely context dependent, so for an athlete everything that we've seen to date really suggests that you want to be like two to four mM during exercise. Which means that if you were at rest your ketone levels are actually going to be like five or six, yeah.

Geoff

Will be at six, yeah.

Brianna

We know that high level is going to be important for athletic performance because the substrate role of ketones is important there. But for the signaling stuff, maybe you could...

Geoff

For recovery, for blood sugar suppression.

Brianna

Or for recovery. All of these things are going to be a little different, and maybe lower. So actually like being able to develop like really good, sound goodliness. I don't know, there aren't just speculative, there's backed by some human research. And be like, yeah, this is what you need to be targeting for this effect, and for this use case you want to take 100% D only, or 100% L only. So mixing up these two isoforms, and there's just a lot of levers to play with.

Geoff

Yeah.

Brianna

So I just sort of hope that I'll be able to sort of start scratching the surface there. I don't know how much of it one person can do.

Geoff

Yeah, I mean it sounds super exciting. I know we've talked about some of the ideas over the last couple of years just in our own discussions over at HVNM. So very excited for you to have that platform to actually start answering these very fundamental questions on how ketones work.

Brianna

Yeah, you know I guess...

Geoff

And hopefully we can work together and support each other in a new context there.

Brianna

Yeah, and I think that one thing that I've enjoyed hugely as part of the job is the opportunity to have this kind of conversation and actually speak and hopefully educate people in the space more and I hope I'll either come back and be a guest again on the podcast, or be involved more throughout my career in more of this like education because I think it's important. All of the work that's being done here, and all of the work that I've been part of, that education piece is just super, super important. So I hope that I can carry on with that.

Geoff

Absolutely, absolutely. I know that Zhill already... We've been talking about it, that while you might not be a co-host moving forward but you'll definitely be a recurring that we'll have you back on anytime that you'd want to update us on your work or things that are interesting for our community.

Brianna

Yeah, can't get rid of me that easily.

Geoff

And then I always like to ask this question towards our more science-oriented folks, but, if you had infinite money... And you might have touched upon this in some of the research ideas that you're excited about. But if you had one study to run, you had infinite resources, infinite power over putting people in cages if you really wanted to. What would that experiment look like and what would the protocol be?

Brianna

I think one thing that would just be useful broadly for the world would be a metabolic ward study, but actually comparing ketone supplementation of some kind with the ketogenic diet. So like actually trying to work out if I had infinite money, and resources, and research participants that were kind of like down, I'd probably do some muscle biopsies and probably adipose tissue biopsy and...so it'd be interesting to do I don't know minimum like a month say and maybe they wouldn't be on the ward the whole time but like diet would be controlled with both groups. Or match for calories. You know, I guess, probably the people on ketone ester probably have them not on a ketogenic diet, but have them on our best approximation of a healthy diet.

I don't necessarily think that... I think there necessarily wouldn't be an exercise component. And I just really want to understand the basic biology of maybe say gene expression and or resting metabolic rate, and or markers of cholesterol metabolism and glucose metabolite. All of those things, would getting ketone levels to one or two by diet be equivalent to getting it to one or two and keeping it one or two with the drink.

Geoff

Right.

Brianna

Like, that's just like a really interesting and not too totally technical, but like actually technical enough and difficult enough that it's not easy to do. I think that would be something that I'd be interested to do.

Geoff

Yeah, the carbohydrate restriction question. Right? How much of the benefits of ketosis is from the ketones themselves versus the carbohydrate restriction?

Brianna

Yeah.

Geoff

I think it'll be some combination of of both.

Brianna

Yeah. And I think if I had infinite resources to influence the broader research world out there, anyone that would do a study using exogenous ketones I would have a ketogenic diet included as well. Just like broadly across the board, like any study that's looking at ketone esters for a degenerative disease, I think you should also be... If money and participants were no obstacles then I think that it would be great to have the gold standard comparison be ketone drink ketogenic diet and then the control condition as well so that we could see how much of the benefit was due to the delivery of the exogenous ketones versus carbohydrate restriction.

So I think those are all pretty interesting. And I'd still like to figure out I think it's technically kind of difficult but like some of the stuff do with like brain health and metabolism. I think there's a lot of work to be done there and a lot of people that could be positively effected by a better understanding of how exogenous ketones are effecting the brain. And not only neurodegenerative conditions but also concussion and all of that kind of thing. That's an area where I'm personally excited to see the research sort of develop.

Geoff

100%. That's all the time that we have for now so very much bittersweet to bid farewell at this context, but very much look forward to working with you in a new context, in the near future. So, really an honor to have gotten to know you and work very closely with you over the years.

Brianna

Yeah, I think to all the listeners out there it's like, I think what we've been trying to work on here is making the best products and putting out the best sort of education, and really helping everyone not only in the company, but everyone who's like part of the broader HVMN community, like helping people to like self actualize. And for me, just the way that you and everyone in the company has supported me on this next step it's like as I'm trying to sort of self actualize, kind of, of myself. So, I appreciate all of the support that I've had over the last couple of years and, you know, it's definitely sort of, "So long." And not, like, "Goodbye forever." And yeah, I'm excited to carry on like growing this space from a different context. But, still very much like part of the family.

Geoff

Yeah, absolutely. So we'll miss you, but we'll not miss you too far... Too much, because you'll be close.

Brianna

Yes. People can keep up on all of my antics and Iron Man training and ketone experiments, and all of that.

Geoff

Yeah. All right, talk to you soon. We'll have you back on very shortly.