By Geoffrey Woo & Michael Brandt, Co-founders and Dr. Latt Mansor, Research Lead

Dec 19, 2023

Ancestral Metabolism

Ketones — specifically D-β-hydroxybutyrate (D-BHB) — are a metabolic superfuel. Scientists have known for decades that the human body naturally creates ketones during both fasting and intense exercise. Essentially in ancestral humans, when the body was metabolically challenged during periods of starvation, ketones came and saved the day. However, in the hyper-industrialized and hyper-consumption food environment of today, humans rarely, if ever, use ketones. 

Thus, the key question is this: is it possible to invent something that delivers the benefits of ketones in a quick and easy way? This was what the United States Defense Advanced Research Projects Agency (DARPA) began pondering in the early 2000s.

DARPA

DARPA is often at the forefront of what is possible. Enhancing human performance and endurance is usually sci-fi fodder, but it’s science reality for DARPA and collaborators.

For decades, the standard fueling for endurance performance has been simply to slam more carbs — sports drinks, glucose pouches, etc. While that works to an extent, it’s an incomplete strategy with biochemical limits. Plus, consuming too much sugar over time can lead to insulin insensitivity. Joe Belitski, a DARPA Program Manager, was interested in novel ways of improving mitochondrial (the “power plant” of the cell) functioning. In his words, he only looks at projects that are “revolutionary,” not “evolutionary.” 

Take a rare look behind the scenes at DARPA with H.V.M.N. co-founder, Geoffrey Woo, sitting down with Joe on the H.V.M.N. Podcast.

Gen Peter Pace, Vice Chair of the Joint Chiefs of Staff of the US Department of Defense, signed off on the initial DARPA research. We'll come back to him later.

The initial reserach program was called “Metabolic Dominance” (later renamed to “Peak Soldier Performance”). A number of research projects spun off from this initial seed. As expected with moonshot type endeavors, many of these efforts never left the academic lab bench.

In 2017, H.V.M.N. entered the picture. Co-founders Geoff and Michael were early pioneers of intermittent fasting and biohacking in Silicon Valley. They intuitively understood the power of ketones and the discipline required to actually re-shape one’s metabolism to generate them. 

Geoff and Michael became obsessed with finding better methods and techniques to more easily metabolize ketones and stumbled upon the nigh forgotten research initiated by DARPA. After deep literature review, conversations with top researchers, and recruiting world-class metabolic biochemists like Dr. Latt Mansor from University of Oxford, H.V.M.N. quickly realized that ketones were a nutritional primitive, something different from anything else out there. H.V.M.N. led the effort to re-invigorate the languishing research and funded the supply chain to productize and launch H.V.M.N. Ketone 1.0, the first-ever drinkable ketone. 

Soon after, H.V.M.N. made headlines around the world and became trusted partners with some of the best performers in the world. We supplied drinkable ketones to many of the top teams on the Tour de France; helped cyclist, Vittoria Bussi, break a world record; and supplied athletes in every three-letter sports league in the United States.

After launching H.V.M.N. Ketone v1, the team recruited General Peter Pace (retired), former Chair of the Joint Chiefs of Staff, the highest ranking military officer in the nation, to be a Senior Advisor to H.V.M.N. He was the senior official who signed off on the initial DARPA work in the early 2000s. We also recruited Rear Admiral (ret.) Alex Krongard, a Naval Special Warfare Officer with deep knowledge in operator field performance, to our Advisory Board.

With their help and guidance, H.V.M.N. is continuing the next chapter of research and deployment of ketones in the US Department of Defense.

H.V.M.N. x USSOCOM Phase 1

In 2018, H.V.M.N., in partnership with the Institute for Human & Machine Cognition (IHMC), was awarded a Phase I STTR by the US Special Operations Command (USSOCOM) to look at the application of ketones for operator performance in extreme environments, specifically hypoxic or low-oxygen environments. This research has applications for soldier performance at altitude, in mountains, on fighter jets, and, potentially one day, in space. 

Low oxygen degrades and can compromise both individual and team performance. In the brain, this is linked to falling energy levels, an increased reliance on anaerobic energy production from glucose, and the accumulation of lactate. Could ketones be the reserve superfuel that mitigates performance decrements? Our study was designed to answer this question. 

Long story short, the data was so impressive that USSOCOM chose to fund H.V.M.N. with a $6 million award to pursue a broader and more expansive R&D effort in 2019.

H.V.M.N. x USSOCOM Phase 2

Phase 2 broadened out the R&D parameters. We were no longer just investigating efficacy for cognition, but potential efficacy of ketones for a number of physical performance and recovery variables.

Our research team led by Dr. Latt Mansor has been working on this project since August 2019, and we finally crossed the finishing line in September 2023. The objectives of this $6 million contract and research were to investigate:

• How ketones impact cognition under stressors like hypoxia
• Ketones and physical endurance under stressors like hypoxia
• Ketones’ impact on physiological reserve and oxygen availability during hypoxic exposure
• Strategies to improve the taste, affordability, stability, and scalability of ketones

This research has come full circle after more than twenty years, from DARPA to H.V.M.N. We’re proud to continue the important work of basic science, standing on the shoulders of brilliant researchers, advisors, and mentors.

Below, check out co-founder Geoff participating in a trial simulation of a high-altitude cognitive and physical performance assessment.

H.V.M.N. Innovation x Ketone-IQ

This Phase II STTR research contract is by far the most comprehensive and extensive study to date on exogenous ketones, putting H.V.M.N. on the forefront of the cutting edge research as the subject matter experts of exogenous ketone science.

We observed that exogenous ketones drive:

• Increase in cognitive efficiency.
• Decrease in reaction time.
• Increase in vigilance.
• Increase in blood Oxygen.
• Among other positive physiological markers for physically and cognitively demanding work.

While we observed benefits from raising ketone levels, we also observed important difference between types of ketone delivery in our work with the DoD and outside research.

Comparing our v1 formula ("H.V.M.N. Ketone v1" aka ketone monoester) and our v2 formula ("Ketone-IQ" aka ketone diol), we saw:

• The main conclusion of the final technical report submitted to USSOCOM, based on the data run by the independent subcontractor, IHMC, the ketonemonoester drink is not suitable to be deployed for USSOCOM operators.
• Ketone monoester has a very bitter taste that causes nausea and is very difficult to flavor. Ketone monoester has been shown to produce significant GI discomfort not only in this STTR project but also in other independent published studies due to the pharmacokinetic properties as well as the bitter taste.
• Ketone diol is significantly more palatable and easier to flavor.
• Ketone monoester has inferior pharmacokinetics that have potential adverse effects for USSOCOM operators by decreasing blood pH levels and thus increases cardiorespiratory stress biomarkers as illustrated in McCarty et al. (1).
• Ketone diol increases blood ketones to the optimal range (1-2.5 mmol/L) without the pH drawbacks of the ketone monoester
• Ketone diol technology brings the cost per gram of ketones down to 33% of the cost of the ketone monoester.
• The cognitive benefits of ketone monoester in hypoxia at rest were not reproduced when moderate to high intensity physical exercise was introduced.
• Ketone diol, in an adjunct study with a senior US military college, showed significant ability to preserve operators' ability to perform anaerobic sprints after a sustained run. 

Ketone-IQ is signfificantly more suitable to be deployed to the USSOCOM operators due to better pricing, pharmacokinetics and performance, and the lack of GI discomfort. 

Read more about the specific changes between H.V.M.N. Ketone v1 and H.V.M.N. Ketone-IQ in our product change log here. 

While we might not all be elite operators, we all want better health and a healthier metabolism. We hope to extend our understanding of extreme performance in demanding environments to support better metabolic health and wellness for every human.

One of the most exciting and important aspects of our mission at H.V.M.N. is the work we do with the US Department of Defense to research and develop best-in-class nutrition for our troops. On a patriotic note, there’s nowhere else in the world we’d rather be as inventors and citizens, and we’re glad to do our part to contribute.

Future of Possibilities

As we continue to innovate and evolve using the insights from research studies such as the STTR contract, we are creating another wave of expansive research studies using an improved technology that is Ketone-IQ, the same way we put ketone monoester on the world map in 2017.

We have studies in various stages ranging from study design finalization to study completion and pending publication with well established institutions including: Naval Health Research Center, University of North Georgia, Johns Hopkins Medicine, University of British Columbia and KU Leuven. In due time, we are expecting more data on the different use cases of Ketone-IQ to be published and be available to the public.

Reference

1. McCarthy DG, Bostad W, Powley FJ, Little JP, Richards DL, Gibala MJ. Increased cardiorespiratory stress during submaximal cycling after ketone monoester ingestion in endurance-trained adults. Appl Physiol Nutr Metab. 2021 Aug;46(8):986-993. doi: 10.1139/apnm-2020-0999. Epub 2021 Mar 1. PMID: 33646860.