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February 6, 2023
It started around 2018. I was approached by a client, a successful food entrepreneur with a closet full of black t-shirts. He had started a great new company in the functional drink space. And he was energized about a top-secret skunkworks project that would rule the world with a drink experience like no other.
But we had to check all the boxes. All natural. Refreshing and tastes great. No sugar or calories. Makes you feel like you could dominate the world for 16 hours, then get a great night of sleep, and do it all over again the next day. And the kicker: zero caffeine.
I remember sitting at my desk in a dark cloud of impossibility and despair. How would we ever compete with caffeine, the stimulant that makes the world go round? Yet something about it was exciting in the way that seemingly impossible but potentially world-changing ideas are.
I stared out my office window at Abby, the neighborhood red squirrel, while she tilted her head quizzically at me, nibbling on a nut. I wondered about what was in the nut that made Abby live, evolve and dodge traffic? What kind of nutrients were essential to her cellular function? Surely, it wasn’t caffeine. With a thought, I tilted my head back at Abby with a smile.
Maybe the answer was in the nutrients used by the cellular powerhouses that are shared by all animals, embedded and ingrained by evolution in plants and animals, and our food. What if we could simply select the ingredients clinically shown to efficiently fuel our cells, power our brains and give us real, tangible energy? What if we could make caffeine and other stimulants unnecessary to the algorithm of human life?
The idea to eliminate caffeine for improved cellular and general health is intriguing. Experientially, caffeine doesn’t really give us energy. In a way, caffeine borrows it from later. This is because the body’s release of adrenaline from caffeine is tightly regulated: more adrenaline now means you crash later. Caffeine also amplifies blood pressure and heart rate after stress, which we often experience as increased cortisol levels, fluttering heart rates, roller-coaster adrenaline levels and restless nights. But what can replace caffeine without the downside of adrenaline roller coasters? The idea of caffeine-free energy seemed crazy and different enough to be potentially world-changing, and this wasn’t the same-old-same-old idea. So I poured my energy into caffeine-free energy, and dug into the literature.
First, I made a list of candidate mito-nutrients. The list grew to nearly a hundred long—including all the likely suspects across the range of food nutrients. Vitamins and minerals, amino acids, botanical polyphenols, carotenoids, triterpene saponins, fatty acids, alkaloids, probiotics, peptides and cellular cofactors. I was surprised at how many on the list had beneficial activity within mitochondria, demonstrated by well-designed scientific studies.
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In a moment of clarity, I realized that the evolution of life on Earth requires nutrients consumed by animals for millions of years to be useful—if not essential—for something so important as the powerhouses of our cells. These nutrients sustain us, and fuel our inner life forces. Traditionally, they heal sickness and maybe they extend life span, as we now see substantial evidence of in the scientific literature.
I whittled down the ingredient options to a “benchtop sandbox” list—cutting any that were not GRAS, or generally recognized as safe for foods. I also removed ingredients that did not have strong clinical backing, were cost-prohibitive, or wouldn’t work in a shelf-stable drink for whatever reason. Sadly, the ones that didn’t make the first cut included L-carnitine, NAD (nicotinamide adenine dinucleotide)-producing vitamin B3 metabolites like nicotinamide mononucleotide (NMN), polyphenols like resveratrol, and a few other key botanicals and amino acids. (We would save many of these for the pill or powder line extensions, later down the road.)
After more whittling and cutting, followed by many months of mixing, flavoring and prototyping, and many formula tweaks and revisions, we were getting close. Then, finally, the home stretch—commercial production, shelf stability, regulatory review, marketing, copywriting, 10x ad nauseam, we had the final formula, packaging and FDA-compliant messaging locked in. The ultimate mito-drink was led by three hero ingredients:
CoQ10: Coenzyme Q10 is a mitochondrial antioxidant and co-vitamin that protects cells from everyday oxidative damage. It is most important as an electron carrier in the mitochondrial electron transport chain. But controversy exists around CoQ10 form and bioavailability (as with many other ingredients). Ubiquinol, the reduced form of CoQ10, is more bioavailable than ubiquinone, the oxidized form. We don’t really know whether improved bioavailability for CoQ10 results in a difference in health—maybe there is saturation at a certain point, like with other nutrients. And it depends on what health outcome we are looking to achieve. In any case, we would need a human study comparing efficacy side by side, which did not exist (to my knowledge). So I picked ubiquinone, because it’s been more frequently studied in clinical studies, and shown to improve multiple mito-related endpoints.
PQQ: Pyrroquinoline quinone is cosmically interesting for many reasons, including the fact that it’s been found in space dust. Coincidentally, it’s also in the foods that both humans and squirrels like to eat—such as nuts and legumes. A biocatalyzing antioxidant in almost every cell, PQQ supports the genetic programming that underlies mitochondrial function. Combining CoQ10 and PQQ results in mitochondrial biogenesis, the creation of new mitochondria. Unsurprisingly then, PQQ has also been shown to improve stress, fatigue and sleep quality in humans. And like other mito-nutrients, clinical studies tend to show PQQ has a positive impact on cognitive function.
Astaxanthin: Kind of like an ant, each molecule of astaxanthin lifts several times its weight, and works in duplicitous ways to prime our cellular engines. That’s why clinical studies show efficacy starting at a miniscule 2 to 4 mg per day. With astaxanthin, a few recent meta-analyses review many of the 50 or so human clinicals that support claims from exercise performance to brain health, to various aging-related conditions. Similar to PQQ, brain health is also one of the most interesting and promising areas of research on astaxanthin. As for the source, I picked the natural, sustainable source grown in the United States from microalgae, because of its clinical pedigree, quality and traceability.
Beyond these three ingredients, we also qualified some powerful plant roots with true roots to the Earth—literally connected to the soil. These roots were traditionally used for millennia to strengthen life force and resilience, and showed reliability as food and medicine. To nobody’s surprise, these roots have been recently studied for their impact on mitochondrial function and longevity. They include:
For sure, when you combine clinically effective amounts of these six ingredients, you get an effect that’s far better than any energy drink out there. Dozens of focus groups, management and investor agreements, and repeated trials confirmed it. The formula freed me from a longtime triple espresso habit. We were primed and ready to go.
Then, it stopped.
Like with many startup side projects ahead of their time, years of development met bad timing. Ultimately, after surviving and navigating Covid, we lacked support of investors (who demanded short-term gains from their core business). As it turns out, there’s a reason why skunkworks projects end up stinking most of the time. For all the work in exchange for a small slice of equity, I got the product developer’s equivalent of a t-shirt: a bit of mito-knowledge, and the client’s permission to share some of the story. The shirt may be a fun reminder, but I won’t be filling my closet with them.
Today, when I look out my office window, I still see Abby the squirrel, chewing on a nut that contains several mitochondrial nutrients. She winks at me, and I wink back. Because we both know that in time, smartly developed mitochondria-focused food and supplement products will eventually have a real impact on human health, performance and longevity.
Blake Ebersole has led several botanical quality initiatives and formed collaborations with dozens of universities and research centers. As president of NaturPro Scientific, Ebersole established quality compliance and product development services for supplements and ingredients such as ID Verified. Follow him on Twitter at @NaturalBlake.
President, NaturPro Scientific
Blake Ebersole has led several botanical quality initiatives and formed collaborations with dozens of universities and research centers. As president of NaturPro Scientific, Ebersole established quality compliance and product development services for supplements and ingredients such as ID Verified™. Follow him on Twitter at @NaturalBlake.
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