Unlike a lot of my more conventionally-minded MD peers, I’m bullish about the potential of supplements to meaningfully improve health and, quite possibly, longevity. That is, certain supplements, like the telomerase-enhancer TA-65, or NR or NMN, which upregulate the energy production co-enzyme NAD+. They’re all backed up by a respectable amount of research evidence, if not with the rigor that the FDA requires when it comes to pharmaceutical drugs. But like anyone who follows the field, I’m well aware of how early-days research in vitro or in animals can be inflated into the latest must-have supplement, good for what ails you. I would place In that category a supplement that’s now generating a fair amount of buzz, with a memorable name, Fatty 15, and a hell of a catchy origin story – all about dolphins. As Stephanie Venn-Watson, the veterinary scientist who’s published almost all the recent Fatty 15 research, said in her 2022 TEDx talk, “Save the dolphins, save the world.” But just like Fatty 15, we’re getting ahead of ourselves.
The ”15” in Fatty 15 refers to a particular saturated fat, C15:0. While this molecule itself isn’t a new discovery, nutritional researchers used to regard it as biochemically almost inert, hardly in the same league as the polyunsaturated omega 3 fatty acids which, for decades, have been touted as inflammation-fighters.
That changed with a series of papers produced by Venn-Watson, whose husband runs the San Diego-based Seraphina Therapeutics company that makes Fatty 15. She had the rare opportunity to study tame bottlenose dolphins managed by the U.S. Navy, to try to figure out why some dolphins, just like some people, aged better than others. (Animals in nature don’t have the luxury of growing old.) After testing a number of molecules circulating in the dolphins’ systems, she settled on this saturated fat, C15:0, as the one that correlated most usefully with good metabolic health. In a small intervention trial, dolphins who were fed Fatty 15 fared better than those who were not. In an assay study, bathing human cells in vitro with different compounds to measure positive biochemical changes, C15:0 emerged as co-champion, along with the drug rapamycin.
On its face, this is remarkable -- an everyday saturated fat molecule with no known side-effects going head to head with a powerful pharma drug, toxic at higher doses, derived from a rare strain of bacteria known to interact with the mTOR longevity pathway. Venn-Watson’s explanation? She draws on earlier research speculating that the degree to which oxidative stress breaks down cells’ protective lipid membranes helps determine longevity. When red blood cells fall apart in this way, iron leaks out into the system and oxidizes, a pathological process known as ferroptosis. Ferroptosis was a known, if not well-known, phenomenon. But Venn-Watson theorizes that it may be helping to drive metabolic disease on a mass global scale, particularly type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Big picture, what’s driving the ferroptosis is, she thinks, a nutritional C15:0 deficiency, she has coined the Cellular Fragility Syndrome.
But is this syndrome, if indeed it exists in a meaningful way, really so hard to combat? The saturated fatty acid C15:0 is readily found in our diet, most abundantly in whole fat dairy to such a degree that if you have an idea how much you regularly consume, you can make an educated guess as to whether your levels are high, low or average. (If that’s not good enough, there is a home test kit to measure those levels, offered by Genova Diagnostics. The top tertile, greater than 0.4% of total fatty acids, seems mostly based on epidemiological research that suggests that long-lived residents of the Sardinian “Blue Zone” benefit from these kinds of high levels.)
While the Fatty 15 website bemoans the decline in our whole-fat dairy consumption, driven by exaggerated fears that saturated fat promotes heart disease, it does not put forward a glass of milk as an acceptable answer to Cellular Fragility Syndrome. Too many bad types of saturated fats in the dairy matrix, it says. (The Sardinians are a special case, Venn-Watson writes in one of her academic papers, their sheep and goats fed on super-nutritious wild grasses.) Which conveniently leaves us with Fatty 15 as the only viable solution to the problem. That, to my mind, overlooks the most recent epidemiological research which has consistently made the correlation between dairy consumption and better health outcomes.
My message to the makers of Fatty 15: if you are going to make claims that your product may enhance human longevity by pushing back against many of the “Hallmarks of Aging” (mitochondrial dysfunction, chronic inflammation, cellular senescence, etc.), do some more research. I’m talking about cell studies with measurable end-points and basic clinical studies – cohort studies – that produce a strong correlation between taking Fatty 15 and suffering less chronic disease.
For sure, there is some intriguing science behind Fatty 15. But right now, I see it more as a teachable moment about how to evaluate supplement claims, an invitation, as it were, to find a workable balance between enthusiasm (hey, suppose this really works?!) and appropriate skepticism (show me the data!). If, in the end, Fatty 15 turns out to be the super-supplement its boosters say it is, I’ll be standing in line to buy a bottle.
Stephanie Venn-Watson. The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome. Metabolites 2024. 14(7), 355. doi.org/10.3390/metabo14070355
Stephanie Venn-Watson, Nicholas J Schork. Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds. Nutrients. 2023 Oct 30; 15 (21): 4607. doi: 10.3390/nu15214607
A.J. Hulbert. On the importance of fatty acid composition of membranes for aging. Journal of Theoretical Biology. Volume 234, Issue 2, 21 May 2005, Pages 277-288. doi.org/10.1016/j.jtbi.2004.11.024
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