Science Says!
N—154
Welcome to Issue 154 of Science Says! Our weekly newsletter where you’ll learn the latest healthy aging and C15:0 research news that our team of doctors, scientists, and experts are most excited about—without having to go search for it.
Eric and Steph
Co-Founders, Doctors, Nerds
What Dr. Stephanie Venn-Watson, our co-founder and author of The Longevity Nutrient and over 80 peer-reviewed scientific publications, is reading.
It’s back to school time, so we thought, what better time to do a Round-Up Series on what makes C15:0, well, so science-backed? In this series, we have been covering the following six key topics on C15:0:
What makes the science behind C15:0 so robust is its consistency across all six topics above – including 100+ studies across numerous independent research teams throughout the world. We have also been sharing how C15:0 study outcomes – from its mechanisms of action to clinical trials – are intricately interlinked.
Last week, we covered how C15:0 activates receptors that support our immune, cognitive, and mood health. For the last week of this series, we share how to achieve optimal C15:0 levels.
Sounds good. But how do you know what C15:0 levels are optimal?
Good question! We are able to define optimal C15:0 concentrations, thanks the following:
Dose-dependent mechanisms of action. Over the past few weeks, we have covered multiple mechanisms of action of C15:0, including how C15:0 activates AMPK, AKT, and PPARɑ/δ… all while inhibiting mTOR, JAK-STAT, FAAH, and MAO-B. Importantly, these mechanisms have been shown to be dose-dependent, which means that the higher the concentration of C15:0 within a certain range, the better the activities. In almost all cases, optimal C15:0 activities were between 10 and 50 µM. An example of a C15:0 dose-dependent curve for inhibiting FAAH and MAO-B, which we published earlier this year, is provided below.
Dose-dependent cell-based efficacy. In our study co-authored with Dr. Nicholas Schork, who is the lead scientist of the NIH-funded Longevity Consortium, we assessed the dose-response effects of C15:0 in human cell systems that mimic a variety of aging-associated conditions. In this study, we found that C15:0 has a beneficial dose-response effect on 36 biomarkers across 10 human cell systems relevant to immune, heart, liver, gut, and lung health. In this extensive study (and similar to the mechanism of action studies above), efficacy was observed between 6.7 and 50 µM, with the broadest number of C15:0 benefits at around 20 µM.
Helping-dolphin studies. Our initial studies to support the health of older Navy dolphins showed that increasing C15:0 in the diet resulted in higher C15:0 concentrations in their red blood cell membranes. Importantly, if dolphins achieved red blood cell membrane C15:0 levels greater than 5 µg/ml (aka 20 µM), they also achieved optimal red blood cell health (aka healthy hemoglobin levels).
Human population studies. As shown below by Chen et al., human C15:0 concentrations range from about 5 to 70 µM, with most people having between 10 to 30 µM (left graph). This is equivalent to between 0.15 to 0.25% of C15:0 among all fatty acids (right graph). This overlays well with optimal C15:0 concentrations above, which are between 10 to 50 µM. Isn’t it great when science in the lab aligns with real world data?
The dose-response curves of C15:0’s health benefits also translate to human population studies. As shown below, both Trieu et al. and Chen et al. showed that, as C15:0 concentrations in humans increased from 0.2% to 0.5% (approximately equal to 20 to 50 µM), this increased the likelihood of having optimal cardiovascular health and blood pressure, respectively. As we have shared previously, Manca et al. showed that people living in Sardinia’s High Longevity Zone have average C15:0 concentrations > 0.4% (approximately equal to 40 uM).
Given all the above, optimal C15:0 levels are between 20 and 50 µM. There is increasing evidence (at least for cardiovascular health and longevity) that the higher our C15:0 within this range, the better our health.
So, how do I achieve these optimal C15:0 levels?
Here’s the good news: It’s well established that the more C15:0 we eat, the higher our C15:0 levels. In fact, even before the world knew about C15:0’s health benefits, researchers had long been using circulating C15:0 levels as a reliable biomarker of how much dairy fat (our primary source of dietary C15:0) a person ate.
Further, based on their extensive clinical trials in humans, Stallings et al. and Mascarhenas et al. demonstrated that for every 100 mg of pure C15:0 ingested, our circulating C15:0 levels go up, on average, by 1 µg/ml (or 10 µM).
As shown above, the average person has a baseline of 10 to 30 µM. That means that adding 100 to 200 mg of C15:0 to a daily routine will help most people get comfortably within the optimal zone of 20 to 50 µM.
In addition to increasing daily C15:0 intake via dairy fat or supplements, there are a number of ways that C15:0 levels can be further boosted:
Combined with diet and supplements, these approaches can help a person achieve Sardinian longevity-supporting C15:0 levels.
Wrap-Up of our C15:0 Science Round-Up Series.
With that, we have officially completed our Science Round-Up Series. Congratulations, fellow Science Says readers!
Over the past couple of months, this round up included the following support of C15:0’s health benefits:
This all adds up to how and why C15:0 plays an important role in supporting our long-term health and wellness. Next week, we’ll get back to covering the latest and greatest science on C15:0. In the meantime, have a fantastic week, everyone!
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