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Fatty15 Is Your Longevity Supplement: Science Deep Dive

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fatty15

Fatty15 as Your Longevity Supplement: A Science Deep Dive

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights

Here at fatty15, we’re a crew of nerdy do-gooders who made the groundbreaking discovery of C15:0 as The Longevity Nutrient. Our doctors and scientists have spent a decade to research, optimize and deliver fatty15: your pure, award-winning, bioavailable and vegan-friendly C15:0 supplement. 

We’re on a global mission to replenish, restore, empower, and optimize longer life with longer health. The result? More time to celebrate that amazing sunshine within you.

So, let’s dive deep into the science behind fatty15, C15:0, and longevity, including 1) how C15:0 was discovered as an essential fatty acid, 2) how fatty15 meets the seven criteria of being a geroprotector that slows aging and extends longevity, and 3) how fatty15 performed when tested head-to-head against three leading longevity-extending candidates (including you, rapamycin).

As a special note to our fellow nerds, most of our fatty15 studies were funded by the Office of Naval Research, and all of our studies have been extensively peer-reviewed and published in reputable scientific journals with rigorous standards. Further, scientific statements below are linked to a peer-reviewed paper source (or two), allowing you to dive even deeper into the science. Just roll over the statement to find the link.

With that, let’s get started.

What are C15:0 and fatty15?

C15:0 (also called pentadecanoic acid) is the first essential fatty acid to be discovered in over 90 years. C15:0 is an odd-chain saturated fatty acid, and our primary dietary source of this essential nutrient is dairy fat. 

Why is C15:0 considered an essential fatty acid? Well, studies support that our bodies must sustain certain levels of C15:0 (> 0.2% total fatty acids) to maintain our physiological health - especially the health of our liver, red blood cells, metabolism and heart. Since our bodies can’t make enough of this nutrient on its own, we have to routinely get adequate added amounts from our diet (between 100 and 300 mg per day). While the essentiality of C15:0 was initially discovered by our co-founder, Dr. Stephanie Venn-Watson, other scientists have since agreed that C15:0 meets the criteria of an essential fatty acid.

Fatty15 was developed by our team of doctors and scientists to provide a pure, optimized, and science-backed C15:0 supplement that tangibly supports your long-term health and wellness. Our award-winning supplement is proven in randomized and controlled clinical trials to achieve and maintain healthy C15:0 levels, resulting in significant liver, red blood cell, heart, and gut health benefits. This is particularly important because fatty15 has emerged as a top longevity-extending geroprotector.

Sounds great! But wait, what is a geroprotector?

Good question. A geroprotector is a molecule that slows biological aging. By doing so, geroprotectors stem aging-related breakdown, which allows us to live healthier longer. In turn, this helps to extend our longevity. 

Geroprotectors are the holy grail of healthy aging, and meeting the criteria of a geroprotector is no small feat. In fact, only a handful of molecules are top geroprotector contenders (we’ll get to those later). So, what does it take to be a molecule that extends both our health and lifespan? 

Well, to be a bonafide geroprotector, a molecule should meet all seven of the following criteria:

  • Target core mechanisms that enable longevity
  • Protect against and reverse key hallmarks of aging (how we age at the cellular level)
  • Improve clinically relevant indices within months
  • Show evidence of slowing biological aging rates
  • Tangibly protect long-term health
  • Be safe to use over long periods of time
  • Be relevant to a majority of the population (aka not have efficacy driven by genetics)

We’ll cover how fatty15 not only meets the criteria of a geroprotector, but how this groundbreaking supplement has emerged as a leading geroprotector. But before doing so, let’s talk about how C15:0 was initially discovered as a beneficial nutrient, thanks to caring for older dolphins. Yeah, perhaps the best origin story ever.

A surprising discovery in healthy, older dolphins.

Over a 10-year period (between 2004 and 2014), our co-founder Dr. Stephanie Venn-Watson uncovered a series of parallels in aging dolphins and humans that would result in the discovery of C15:0’s importance to large-brained, long-lived mammals. 

As a veterinary epidemiologist working for the World Health Organization and Centers for Disease Control and Prevention, Steph was recruited by the U.S. Navy to better understand and continually improve the health of aging Navy dolphins. While dolphins in the wild live, on average, about 20 years, Navy dolphins have been increasingly living well into their 30s and 40s.

During this first decade of work, Steph and others found that some older dolphins, like older humans, can develop high cholesterol, high triglycerides, chronic inflammation, metabolic syndrome, insulin resistance, anemia, iron overload, fatty liver disease, and even changes in the brain consistent with Alzheimer’s disease. Importantly, only about 1 in 3 older dolphins appeared to develop these aging-associated changes.

Using an advanced technology called metabolomics, Steph and her team studied hundreds of small molecules to find which molecules in the dolphin’s archived serum and their all-fish diet predicted the healthiest aging dolphins. The surprising result? By 2015, Steph had discovered that C15:0 was a top predictor of the healthiest aging dolphins. With this discovery, Steph and team moved C15:0 into the lab to see if this odd-chain saturated fat was not only associated with better health, but if it was indeed the cause of healthy aging.

You can check out Steph’s TEDx talk summarizing these initial discoveries.

The science behind fatty15 as a geroprotector to extend human longevity.

Steph, along with fellow doctors and scientists around the world, have spent the past decade studying pure C15:0 (aka fatty15) in the lab, along with large scale prospective human cohort studies on circulating C15:0 and clinical trials with C15:0 supplementation. As a result, there have been over a hundred peer-reviewed studies supporting C15:0 and fatty15’s health benefits.

Here’s a summary of evidence demonstrating how fatty15 meets the seven criteria of being a geroprotector that slows aging.

#1 Geroprotector Criterion: Fatty15 targets core mechanisms that extend longevity. 

Fatty15 targets the following three core longevity-extending mechanisms: 

So, fatty15 targets not just one, but three core mechanisms that can extend longevity. Let’s move onto evidence on how fatty15 reverses six hallmarks of aging.

#2 Geroprotector Criterion: Fatty15 reverses at least five hallmarks of aging.

A major breakthrough in anti-aging science was made upon the description of specific changes within cells that define how we age. These hallmarks of aging empowered longevity scientists with clear instructions: fix hallmarks of aging, and you can slow aging itself. 

Here’s how the pure C15:0 ingredient in fatty15 directly reverses five hallmarks of aging:

In addition to fatty15’s direct effects on the five hallmarks of aging above, there is evidence that C15:0 slows epigenetic alterations (another hallmark of aging). A recent study using epigenetic clocks showed that people who had more C15 in complex lipids had slower biological aging - in fact, these people had younger biological ages than their chronological age. Yes, please.

While a good number of molecules have been shown to target a variety of different hallmarks of aging, they don’t qualify as longevity-extending geroprotectors if they don’t meaningfully improve clinically relevant indices within months. So, let’s see how fatty15 does in this more challenging realm.

#3 Geroprotector Criterion: Fatty15 improves clinically relevant indices within months.

Given fatty15’s demonstrated longevity-extending mechanisms of action described above, it is expected that fatty15 will result in improved metabolic, liver, red blood cell, heart, and immune health. 

So, it is not surprising that 12-week supplementation studies with the pure C15:0 ingredient in fatty15 have shown health benefits in whole body models of metabolic, liver, red blood cell, heart, and immune conditions, as well as in human clinical trials relevant to liver, heart and gut health.

Specifically, in relevant whole body models, daily supplementation with the pure C15:0 ingredient in fatty15 resulted in:

These clinically relevant outcomes are not only aligned with fatty15’s demonstrated geroprotector mechanisms of action, they are aligned with two recent human clinical trials. In these 12-week, single-dose clinical trials involving people with less-than-optimal liver health, people who took a pure C15:0 supplement and achieved healthy C15:0 levels also demonstrated:

These health benefits were not seen among controls who did not receive C15:0 supplementation. While the culmination of science we’ve provided so far is checking off important criteria for a longevity-extending geroprotector, is there evidence that fatty15 slows biological aging rates?

#4 Geroprotector Criterion: Fatty15 has evidence of slowing biological aging rates.

The answer is, “Yes”. To explain how fatty15 slows aging, let’s start with biomarkers of aging rate. 

Two of fatty15’s co-founders, Dr. Stephanie Venn-Watson and Dr. Nicholas Schork, went back to Navy dolphin health data to see if this population could help show what has long been assumed, but not proven in humans. Specifically, that long-lived individuals within the same population exhibit different aging rates. 

Indeed, Steph and Nik showed that some dolphins had faster biological aging compared to others within the same population. Just as importantly, they identified clinically relevant biomarkers that determined how fast (or slow) an individual was aging. One of these biomarkers was hemoglobin: the faster an individual’s hemoglobin declined with age, the faster their aging rate. It ends up, the same has been shown for humans.

So, what is hemoglobin? Hemoglobin is a molecule within our red blood cells that carries oxygen to our tissues. Oxygen to our hearts, our brains, our toes, etc. So, that’s important. As we get older, our red blood cells get more fragile, our hemoglobin goes down, and our overall frailty goes up. Another important biomarker of fragile red blood cells and aging rates is higher “red blood distribution width” (also called RDW). In fact, maintaining healthy hemoglobin and RDW with age are markers not only of slower aging rates, but of overall resilience, and even longevity.

Now that you know all that, it is more meaningful to share that fatty15 supplementation restores red blood cell health within 12 weeks in relevant models, including raised red blood cell counts, raised hemoglobin, and lowered RDW. Fatty15 supplementation also raised hemoglobin in a randomized and placebo controlled human clinical trial among people who achieved optimal C15:0 levels, effectively slowing key biomarkers of biological aging and boosting biomarkers of longevity.

Additionally, as shared above, in an epigenetic clock study, people with more 15-carbon chains in their lipids (specifically lysophosphatidylethanolamides, or LPEs) have slower biological aging - their biological ages are younger than their chronological age. Fatty15 supplementation increases not only total C15:0 levels, but C15-containing LPEs, too. 

So, evidence that fatty15 slows a core aging rate biomarker? Check. 

On to the science showing that fatty15, by helping to achieve and sustain healthy C15:0 levels, tangibly protects our long-term health.

#5a Geroprotector Criterion: Fatty15, by supporting healthy C15:0 levels, tangibly protects long-term health. 

To demonstrate that a molecule protects our long-term health requires tracking thousands of people over decades. This also requires people to start as healthy, then stay healthy. Because most long-term human clinical trials start with people who have a disease, most molecules don’t have extensive data to show that they protect health (versus treat disease).

As an essential fatty acid, however, there are many studies-of-studies (called meta-analyses) effectively demonstrating that healthy people who have higher C15:0 levels are more likely to stay healthy. This includes better long-term health related to:

As an even rarer situation, because C15:0 is a saturated fatty acid in whole fat dairy products (especially whole fat cow’s milk and butter), we have undergone a 50-year experiment of dramatically lowering C15:0 from our diets, resulting in lower population-wide C15:0 levels. And with lower C15:0 levels have come population wide declines in metabolic, heart, and liver health, especially among younger people.

So, let’s talk about evidence of how nutritional C15:0 deficiencies lead to a new form of cell death, called ferroptosis. And how ferroptosis accelerates aging.

#5b Geroprotector Criterion: Nutritional C15:0 deficiencies cause Cellular Fragility Syndrome and accelerate aging. 

In our recent peer-reviewed paper published in Metabolites, we describe the first nutritional deficiency to be discovered in 75 years. This C15:0 deficiency syndrome is called Cellular Fragility Syndrome. You can learn more about Cellular Fragility Syndrome in a separate blog, but the key points described in the Metabolites paper are as follows:

It is estimated that as many as 1 in 3 people have Cellular Fragility Syndrome. While that may seem daunting, here’s the good news: fatty15 treats nutritional C15:0 deficiencies and reverses Cellular Fragility Syndrome.

#5c Geroprotector Criterion: Fatty15 treats nutritional C15:0 deficiencies and Cellular Fragility Syndrome to stop ferroptosis and slow aging.

Peer-reviewed studies have shown that C15:0 supplementation effectively raises C15:0 levels, stops ferroptosis, and treats nutritional C15:0 deficiencies. In relevant models, this includes fatty15’s ability to:

Unlike any other geroprotector candidate, C15:0 is so essential to our health that without it, evidence supports that our health can decline, which can result in decreasing longevity. 

#6 Geroprotector Criterion: Fatty15 is safe to use over long periods of time.

So, five criteria down. Two to go. Starting with safety. To effectively protect and extend our longevity, a geroprotector will need to be taken routinely throughout one’s life. That means safety is a really important criterion for a geroprotector.

Today, the other top geroprotector candidates are not only not nutrients, they are pharmaceutical drugs. Rapamycin. Metformin. Acarbose. As drugs, these molecules come with safety issues and side effects. Rapamycin, what has long stood as the leading longevity-enhancing compound, has more than 30 side effects listed by the Mayo Clinic, which is not ideal for long-term use in healthy people.

In contrast, C15:0 is in the food source that every baby gets from birth: milk fat. Fatty15 daily doses match that which we used to get from whole milk fat, but are not likely getting today. Either because of cow’s milk fat avoidance or changes in industry practices that lower how much C15:0 is present in milkfat. Additionally, our C15:0 levels decline as we age.

Extensive safety studies have been done with the pure C15:0 ingredient in fatty15. From robust human cell studies to being part of NIH’s Tox21 safety assessment panel. From animal studies to human clinical trials, the pure C15:0 ingredient in fatty15 has been demonstrated as safe. This is why an independent panel of experts determined that fatty15 is Generally Recognized as Safe. Which, as an essential nutrient we need in our diet to maintain a healthy physiological state, makes sense.

#7 Geroprotector Criterion: Fatty15 efficacy is not overtly genetically driven (aka fatty15’s efficacy is evolutionarily expected across diverse populations)

Okay, last but not least, a geroprotector needs to be effective across diverse global populations. In many cases, the efficacy of even pharmaceutical drugs (including rapamycin) is significantly influenced by genetics. This means there are large subsets of people who do not benefit from drugs, simply because of a gene-driven physiological mechanism that doesn’t allow a person to properly metabolize a given therapeutic. A recent study even showed that severe dietary restriction, which used to be a “given” longevity extender in mice, had longevity outcomes greatly influenced by an individual's genetics.

In comparison, as an essential fatty acid, we have evolved as a species to rely upon C15:0 to maintain our long-term health. It also means that we don’t heavily rely on C15:0 metabolites to reap its direct benefits. A large genome-wide association study found no genetic drivers for C15:0 levels in humans, which is expected of a true essential fatty acid.

All in, fatty15 has peer-reviewed evidence of meeting seven criteria of an effective geroprotector. Given that, our co-founders wanted to test how fatty15 would perform when tested head-to-head against three leading geroprotectors? 

Fatty15 has more clinically relevant cellular benefits than other leading longevity-extending geroprotector candidates (that’s you, rapamycin)

So, how did fatty15 do compared to three leading geroprotector candidates: rapamycin, metformin, and acarbose? Pretty well. In fact, fatty15 had the most clinically relevant cell-based benefits.

Before sharing the detailed results, however, let’s talk about the testing platform called BioMAP Diversity PLUS used in this study. BioMAP Diversity PLUS is a pharmaceutical industry standard screening platform, led by an independent third party, that was specifically developed to successfully predict clinical outcomes of active molecules. This impressive platform assesses four ascending doses of molecules across 12 systems and 147 mechanistic-relevant biomarkers.

As stated by the company that runs this system: “BioMAP Diversity PLUS systems are comprised of human primary cell-based assays stimulated to recapitulate disease states and to model complex tissue and disease biology of organs (vasculature, immune system, skin, lung) and general tissue biology. Phenotypic profiling with BioMAP Diversity PLUS evaluates the biological impact of test agents in conditions that preserve crosstalk and feedback mechanisms relevant to in vivo (aka whole body) outcomes.”

Importantly, we held fatty15 to BioMAP’s highest standards used by the therapeutics industry. Specifically, in order to count as a clinically relevant cell-based activity, fatty15 had to be annotated. Annotated means that fatty15 activities identified by the BioMAP team had to demonstrate:

  • Dose dependence. Fatty15 had to have two or more consecutive concentrations that significantly changed biomarkers in the same direction relative to vehicle controls.
  • Significant difference from vehicle controls. Fatty15 had to cause statistically significant differences outside the control envelope. This aspect is an added accumulation of robust controls that make up a “control envelope” in the BioMAP system.
  • Meaningful effect. Fatty15 not only had to be statistically significantly better than controls, it also had to have at least one concentration with a biomarker effect size > 20% (|log10 ratio| > 0.1) compared to controls. This magnitude of effect has been demonstrated to translate to clinically meaningful effects in humans.

With that knowledge in your back pocket, let’s get to the results. Here, we found that fatty15 had the most cellular benefits, with 36 dose-dependent, statistically significant and clinically relevant annotated activities across 10 of the 12 systems. Rapamycin had 32 activities across 12 of 12 systems, metformin had 17 activities across 7 systems, acarbose had 5 activities across 3 systems. We also included pure omega-3 (EPA), which had 7 annotated activities across 4 systems.

Importantly, these results are consistent with studies showing that both fatty15 and rapamycin are 1) mTOR inhibitors, and 2) have demonstrated not just cellular but whole-body effects on lowering inflammaging-associated cytokines, lowering oxidative stress, protecting tissue function, stopping proliferation of bad-acting cells, and stopping proliferation of bad-acting microbes.

The take home from this study? Instead of having to resort to a complex drug discovered from bacteria on Easter Island (aka rapamycin), fatty15 has emerged as a leading longevity-extending geroprotector that contains optimized and pure C15:0, an essential nutrient that every mammal gets and needs, safely, from birth.

Fatty15 as Your Longevity Supplement

The take home point? Well, we’ll let our co-founder, world’s leading longevity expert, and Head of the prestigious Longevity Consortium, Dr. Nicholas Schork, sum it all up for us:

"The breadth of evidence for C15:0’s health benefits is what makes it so compelling. Very few, if any, candidate geroprotectors have been subjected to the same level of rigor in a wide variety of settings—cell-based studies, studies involving non-human species, human population studies, clinical trials, pharmacology studies, and more—and all have resulted in very positive findings." 

But really, this is not about us. It’s about you. This past decade of science has led to fatty15, which is here to help give you more time to do the things you love. And isn’t that why we all want to enjoy the healthiest, longest lives possible?

Read the Science

In addition to providing rollover links to the supportive peer-reviewed science thought the article above, you can also nerd out on all 100+ published C15:0 studies at DiscoverC15.com. Enjoy!

Profile photo for Eric Venn-Watson

Eric Venn-Watson M.D.

Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.

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