Geoff

This year's Tour de France clearly ranks as one of the greatest in history. Congratulations to all the riders for an amazing performance. Special recognition goes to the winner, Egan Bernal of team Ineos, who's the youngest winner since 1909, at age 22 and representing Columbia for the country's first ever victor.

We should also recognize Julian Alaphilippe, of Deceuninck–Quick-Step for astounding the world and holding onto the yellow jersey for 14 days. One particularly dramatic point in this year's tour, especially for those with special interest in performance, nutrition, and sports physiology, was the emergence, public, confirmation, and the subsequent controversy and debate around exogenous Ketones and Ketone Esters. Team Jumbo–Visma sparked everything off when they publicly came out to discuss the incorporation of Ketone Esters into their nutritional strategy. Are Ketone Esters an unfair advantage? Are they considered doping? Should they be banned or is this simply the next generation of sporting and performance food?

Just like how Gatorade, Powerade, or other carbohydrate drinks changed fueling strategy some 50 years ago. Are we simply seeing the same level of paradigm shift today with Ketones? Enter H.V.M.N. Ketone Ester. I'm Geoffrey Woo, CEO of H.V.M.N. and we partnered exclusively with Oxford University professor Kieran Clark, the co-inventor of Ketone Esters, to commercialize the Ketone Ester technology.

Let's break this down together. As there has been somewhat of a controversy and misinformation spread around with all the recent press and I can't think of anyone better to help me do that, then the co-inventor of Ketone Ester herself, Professor Kieran Clark.

Let's go over the history of Ketone Esters. Kieran, can you introduce yourself? What is your background and what is the history behind Ketone Esters?

Kieran C.

I am professor Kieran Clark and I am a professor of physiological biochemistry at the University of Oxford. In about 1993 I started working or collaborating with a person, a scientist from the NIH, called Richard Beach and we worked on Ketone metabolism. It was really interesting. We were awarded a grant from the US Army to develop a Ketone Ester drink and that's what we did. We have now got to the point where we scaled up.

We've actually had it. It wasn't commercially available, but if people had come to see me in Oxford and said, "Can we give it a go?" And I'd say, "I don't know if it'll work, but you can try if you want" And so they did. I don't think I'm allowed to say their names, but yes, they did. People have been using it for years.

Geoff

When there were reports of Tour de France riders using Ketone Esters back since almost 2012, those rumors perhaps have some substantiation as Ketone Esters were being developed for commercialization. However, this is indeed the first year where Ketone Ester usage has really exploded to the forefront. Even Lance Armstrong's Tour de France podcast called "The Move" started covering Ketones in the middle of the tour.

So, what's the controversy? Some on the Peloton don't think Ketones actually work. A representative from team Sun Web says there is no real effect in using ketones. He says, "There's too much uncertainty about the efficacy. There are even studies that show that it has a negative effect on sports performance". To address Dr Boelens, "Not all exogenous Ketones on the market are the same. You have to understand that the H.V.M.N. Ketone Ester is a different molecule and a very different feel compared to the other stuff on the market. Just like the category of carbohydrates, a complex starch from a sweet potato is very different from a corn syrup in a soda. Both are considered carbohydrates, but they have very different impact on metabolism". Kieran, can you explain the key differences here?

Kieran C.

There are several things out there that you can buy, that you can take to raise your Ketone levels. Some don't work at all, for example, raspberry Ketones are hopeless and a total scam. Then there are Ketone salts, which again have their problems and their problems are that half the salt isn't the Ester that we find or isn't the actual Ketone that we find in our body so half of the molecule is wasted and then the other half, because there's so much salt in the drink itself, you just can't absorb it. You either can't absorb it in your stomach, or it just doesn't raise your Ketone levels high enough to help with performance. Then you have the Ketone Ester and you can have two different types of Ester.

Geoff

Professor Clark just mentioned a really interesting point that most people misunderstand. Within the context of Ketone Esters, there's actually multiple forms of Ketone Esters. The Ketone Ester within our H.V.M.N. product is the Beta Hydroxybutyrate Monoester. Very, very specific compound with a tremendous history of safety and efficacy study that Betta Hydroxybutyrate Monoester is Beta Hydroxybutyrate asterofied with Butanediol. BHB and that Butanediol completely convert into the form of Ketones that our body metabolizes for energy. However, for the Acetoacetate diesters, there is two Acetoacetate, which are more of a volatile form of Beta Hydroxybutyrate and that's bound to a Butanediol. You're getting two parts of Acetoacetate to one part Beta Hydroxybutyrate delivered into the system. Karen, do you want to add additional color to the biochemistry happening in the cell?

Kieran C.

Beta Hydroxybutyrate forms Acetoacetate in the Mitochondria and the Beta Hydroxybutyrate is the one that we use and that makes NADH, which is the reduced form of NAD and that is what you want. That's what's produced by the crib cycle as well, but the, the Beta Hydroxybutyrate dehydrogenase makes Acetoacetate and at the same time forms in ADH. If you use Acetoacetate it goes the other way and and forms Beta Hydroxybutyrate and makes NAD. You don't want that. That's just the wrong thing.

Geoff

What are some of the stories on how Ketone Esters work?

Kieran C.

When we found out that it really worked, it was in rowers and we ran a placebo controlled crossover study. They didn't know what they were drinking. The placebo drink tasted just as horrible as the Ketone drink and they rowed and just about every one of them, they were about 22 people in the study, and I think only one didn't row better when they were on the Ketone. We knew that it worked and the army knew that it worked as well. Yes. That was the first study we did and then we've done other studies on cyclists and all different sorts, but the cyclist is the easiest one to do. In that you can take blood and things like that at the same time and so you can get to the mechanism for why it's working.

Geoff

Beyond the efficacy, there are also some questions and doubts on the longterm health impacts of Ketone Esters. Boelens also says, "We think that there should be more clarity about the effects of this "medicine" on the health of the athlete in the longterm." In addition, Simon Verdonck, the team doctor at the French team Cofidis, says he first heard of Ketones five years ago, but admitted that he thinks that the effects remain mysterious over the long term and Cofidis won't use Ketones until tests have been done on the potential negative effects of Ketones.

Let me address this concern about longterm health and safety. In fact, the truth is tremendous amounts of safety studies have been done. H.V.M.N. Ketone Ester is considered FDA generally recognized as safe and is a food component. I'll let professor Clark talk about the safety studies that she has run and how the data shows that there's no evidence that this is impactful on the longterm. In fact, there actually might be longterm health benefits of use of Ketone Esters.

Kieran C.

If they looked into it, they would see that the safety studies have been done and it really is safe. In 2009 we went to the army and said, "We invented this Ester, we know this will work" And they said, "You have to prove it", And so we showed that it actually improved performance in rats and they were quite impressed. We said, "We'll now show it works in humans" And they said, "No you won't. We're going to have to grass it", which is generally recognized as safe. We went to the FDA, our first meeting with the FDA was probably 2007 and they said, "All right, you have to do all these studies to show that it's safe". We did all those studies and then we finally went in and used it with humans and that was all fine. We didn't have anything go wrong and then we just kept going and doing more studies until we got it through the FDA as a drink for the sports people.