Nutritional Outlook’s 2021 Best of the Industry Awards, Ingredient Supplier: Seraphina Therapeutics

Nutritional Outlook, Volume 24, Issue 10

With the discovery and commercialization of what may be a new essential fatty acid, Seraphina Therapeutics is poised to become a leader in developing scientifically substantiated nutritional solutions.

Founded by the husband-and-wife team of Eric and Stephanie Venn-Watson, San Diego, CA–based Seraphina Therapeutics has played a central role in the scientific investigation and now commercialization of pentadecanoic acid, an odd-chain fatty acid that the scientific literature shows meets the criteria for being an essential fatty acid. Pentadecanoic acid is an odd-chain saturated fatty acid with 15 carbons (C15:0) that is naturally present in foods such as whole-fat dairy, but has found itself removed from our diets for the last four decades over fears of saturated fats in general. This decision may have resulted in higher risk of type 2 diabetes, coronary heart disease, chronic inflammation, and obesity globally. C15:0 is a key nutrient with the potential to support global health. Seraphina Therapeutics has commercialized it as the ingredient FA15, and as a finished product called Fatty15. The company has not only taken on the mantle of bringing a completely novel nutrient to market, but a larger ambition of correcting a major nutrient deficiency.

“We have methodically removed and lowered C15:0 levels in our diets population-wide across the globe, and so the big hypothesis that we’re chasing here is that we have created population-wide C15:0 deficiencies that are the cause of the rise of heart disease and diabetes and liver disease, and what keeps Eric and me and the Seraphina team going every day is that we have the opportunity to fix, to restore, C15:0 in a vegan-friendly, sustainable way, and hopefully reverse this increase in diseases that impact all of us every day,” says Stephanie Venn-Watson, DVM, MPH, Seraphina’s CEO.

Stephanie is a veterinary epidemiologist by training who has worked for the Centers for Disease Control and Prevention to help investigate outbreaks, as well as for the World Health Organization to help install disease surveillance systems all over the world. Eric Venn-Watson, MD, MBA, Seraphina Therapeutics’ COO, is a physician and U.S. Navy veteran who was deployed multiple times to places like Afghanistan, Iraq, and East Africa, where he was tasked with “creating medical systems where none existed and taking care of people in very austere environments.” Eric went on to use the skills he developed in the military to get his MBA and become an entrepreneur, starting successful companies such as a medical device company called XpandOrtho, which created a device to improve total knee replacements.

Both Stephanie and Eric have a great deal of experience in creating solutions, so it’s no surprise that when they discovered the therapeutic potential for C15:0, they took action. “With both Eric and I coming from long careers in civil and military service, it instilled in us that if you are going to make a discovery, you need to translate it, and it needs to be meaningful, or you leave it and move on to something else,” says Stephanie.

The Discovery

Stephanie first learned about the potential health implications of C15:0 when she was recruited by the U.S. Navy Marine Mammal Program 20 years ago to help start and lead a clinical research program to improve the health and welfare of Navy dolphins. There, she explains, she “was able to bring the passion and excitement for pattern recognition to look at improving dolphin health, the same way we look at improving global public health. I came to understand that the Navy dolphins live 50% longer than dolphins in the wild because the Navy takes really good care of them. As the dolphins get older, like people, some but not all develop chronic aging–associated conditions like high cholesterol, and chronic inflammation, and even the full suite of changes in the brain consistent with Alzheimer’s disease.”

In short, mammals with the same healthcare and diets were seeing different health outcomes. But why? To determine this, Stephanie applied advanced metabolomics on the serum of what she called an “unprecedented longitudinal cohort of long-lived, large-brained mammals” to discover which small molecules in their serum were predictive of healthy aging dolphins. As it happened, higher serum C15:0 levels were associated with better health outcomes in the dolphins.

The quality of the population cannot be overstated, as it lends immense credence to the results Stephanie found. “It’s a really healthy population of animals,” states Eric. “They see their doctor every day, get routine labs, they don’t smoke and don’t eat fatty foods. It would be very hard to recreate something on the human side that would be as healthy as this population. So that really allows us to get through all the white noise of drinking coffee and other things, and use these advanced technologies like metabolomics, lipidomics, and genomics to understand what molecules are beneficial and which are essential.”

“The sole intent was to improve the dolphins’ health, and it was through understanding and improving this incredible population that we came to understand the parallels between aging dolphins and aging people,” says Stephanie. “And that opened up this incredible world where not only can we help dolphins, but we can help people, too, and that’s where C15:0 came from.”

The Science

“When we really came to understand that C15:0 is not only an active and beneficial fatty acid, but met the criteria of being essential, it changed from exciting research to a moral obligation to get the science out and move quickly to be able to help improve global health,” says Stephanie. Being scientists and medical professionals, credibility, and therefore scientific substantiation, were paramount to the Venn-Watsons. Eight studies were conducted over three years, and the results were published in Scientific Reports. It was in this study that Seraphina Therapeutics made the case for C15:0 to be an essential fatty acid.

The results showed that C15:0 attenuated inflammation, anemia, dyslipidemia, and fibrosis in vivo, potentially by binding to key metabolic regulators such as peroxisome proliferator-activated receptors (PPARs), as well as repairing mitochondrial function. The study argues that the odd-chain saturated fatty acid is essential because C15:0 is not made endogenously in the body, and lower intakes and blood concentration are associated with higher mortality and poorer physiological states, while supplementation has demonstrated activities and efficacy that parallel associated health benefits in humans.

The body of research on C15:0 continues to grow. Seraphina recently announced an upcoming randomized, double-blind, single-center, controlled study that will investigate whether supplementation with C15:0 will reduce the risk of metabolic syndrome in young adults. This study is being led by Jeffrey Schwimmer, MD, from the University of California, San Diego, who is a pediatric gastroenterologist at the Rady Children’s Hospital. The interest in C15:0 also extends well beyond Seraphina Therapeutics.

“When you look at the peer-reviewed scientific literature, an average of 2.4 peer-review papers are on C15:0 over the last seven years. This year alone, and we’re not done yet, there have been at least 18 independent peer-reviewed published papers on the benefits of C15:0,” says Stephanie. “And this is coming from folks like Harvard, Johns Hopkins, and Cambridge, and many of them are these large, longitudinal studies showing that people who have higher C15:0 blood levels, or in their diet, are less likely to develop type 2 diabetes, heart disease, and heart failure, and are even less likely to die during the study period.”

All this will only contribute to the credibility of C15:0 as an essential fatty acid and as FA15 as an ingredient for supplementation and food fortification.

The Product

Seraphina Therapeutics launched its finished-product brand Fatty15 in January 2021 to serve as an ambassador for its FA15 ingredient and spread the word of C15:0. Fatty15 is sold directly to consumers with a subscription program that helps determine customer retention. Despite being a product that is novel and largely unknown, Fatty15 has been immensely successful.

“We sold out within six weeks,” says Eric. “Then we scaled up production to one ton and now have the supplies to continue to sell. Right now, we have almost 4,000 subscribers, and they’re staying. We have retention rates of over 90% per month, which is incredible, and part of the reason for this is people are seeing both near-term and long-term effects. People are feeling better, they’re sleeping better, they have more energy, they’re snacking less, and it’s amazing to hear from our customers because they’re becoming incredible advocates.”

The direct-to-consumer model is a great resource for Seraphina as it grows, serving not only as a proof of concept but also building a consumer base that will buy other products featuring FA15 down the road. These consumers also serve as an anecdotal research population, offering insights about C15:0’s benefits. With a recent self-GRAS (Generally Recognized as Safe) affirmation, FA15 can now be used in food and beverage products. Seraphina Therapeutics touts FA15 as highly pure, tasteless, scentless, and vegan-friendly, making it a versatile ingredient for food and beverage formulators.

“We advertise our ingredient as being over 98% pure. But if you look at our recent batches, the last two were 99.8% and 99.7%, so it is an extremely pure ingredient. That’s our promise to customers on the supplement and the food ingredient side, that we will provide the purest, most bioavailable ingredient that we can,” says Eric. “So, the GRAS status was important to further our research and our safety studies, and everything we’ve done is accessible to everybody. The plan now is to start getting that [knowledge] out to the world of food and beverage.”

Compared to other essential fatty acids such as omega-3 fatty acids, for example, FA15 is not susceptible to the same challenges as fish oil, such as lipid peroxidation, poor organoleptic properties, or large dosage sizes, says Stephanie.

“From a dosing side, FA15 offers similar benefits but at much lower doses,” says Eric. “We’re looking at a hundred milligrams per our very small size-two capsule, and then using that same dose or less, potentially, in a food ingredient.”

Stephanie and Eric see a great deal of potential in food and beverage fortification, particularly where C15:0 is lacking. “Of particular near-term interest includes foods that have typically had C15:0 in them, like whole-fat dairy, and to look at the rise in the market of non-dairy alternatives,” says Stephanie. “Milk alternatives, for example—oat milks, soy milks, and others—are completely devoid of C15:0. People choosing plant-based milks, or meats, could benefit from having those products fortified with FA15.”

The Future

Seraphina Therapeutics is not interested in being a one-trick pony, and while the company is a thought leader and innovator, it will only be a matter of time before other companies follow its lead. With more and more companies applying the same advanced technologies like metabolomics, which have become rather accessible and affordable, Stephanie says that it’s a wonderful moment for new discoveries in nutrition, and that Seraphina Therapeutics will not be alone in forging new ground. Seraphina’s advantage is having access to the advanced technologies as well as the Navy dolphin population and 50 years’ worth of longitudinal serum samples collected throughout their lifetime. As a result, Seraphina Therapeutics has 200 molecules, of which C15:0 was one, to study and potentially commercialize.

“The data from these populations are so clean that it’s like finding a needle in a needle stack when you’re looking for important molecules. We’ve taken those molecules, and we’ve run most of them now through cell-based studies to look for not just associations with better health but with direct activities that support them,” explains Stephanie. “We’ve had an amazingly high positive hit rate on that batch of molecules. [Seraphina Therapeutics] and also Seraphina’s parent company, Epitracker, have been funded by the Department of Defense to basically rinse, wash, repeat what we did for C15:0 for the next molecules.”

The goal with the new batch of molecules is to look for broad benefits that can support the health of a large population, says Stephanie. “The biggest win for nutrition and for public health is to find something generic that’s essential, that has these widespread benefits,” she explains. “However, we’re also working on finding molecules that may be more targeted towards liver health or brain health. In the nearest term, we have three molecules that we are actively working on and pursuing, and we hope to be able to share new information on the next exciting discovery in the coming six months.”

Despite making a big splash, the story has only just begun for Seraphina Therapeutics. We won’t know the true impact of C15:0 until there is widespread adoption of the odd-chain fatty acid through supplements and food, which will take time in our saturated and competitive nutrition space. In the meantime, the scientific literature continues to grow, and Seraphina Therapeutics will continue to innovate by analyzing the therapeutic potential of hundreds of molecules. Put quite simply by Eric, “There’s a lot to do.”