C15:0 & Bliss: Lessons from a Tour de France Study

Healthy Aging

What Happens to C15:0 & A Key Metabolite During Extreme Exertion

A research team from Belgium wanted to know what extreme exercise does to our bodies. What better way to do that than to measure changes in elite cyclists as they were powering their way through 3,404 km (that’s 2,115 miles) and 56,482 meters of elevation gain during 23 days of the Tour de France? This week, we cover a recently published study from Robberechts et al. that surprisingly resurfaced a discovery we made while caring for older Navy dolphins. Bottom line: Whether a top-of-the-world athlete or aging mammal, C15:0 is needed to deliver a bit of bliss.

I’m in. What did this study evaluate in Tour de France athletes?

Robberechts et al. followed seven elite cyclists throughout the 2023 Tour de France. This research team measured and compared 274 metabolites in the athletes’ serum at four time periods:

• The start of the race at Day 1 (START)
• Rest day 1 at Day 10 (RD1)
• Rest day 2 at Day 17 (RD2)
• The end of the race at Day 23 (FINISH)

When we’re talking about metabolites, we’re referring to small molecules that are present and detected in serum. In this study, molecules were measured using well-established methods that are routinely used in metabolomic studies. Most of the quantified metabolites were lipids, lipid-like molecules and organic acids.

Got it. So, what did they find?

Well, extreme exercise resulted in extreme changes in the cyclists’ metabolomes. Of the 274 molecules measured, 118 (43%) were significantly altered when comparing serum at the START vs. FINISH. Among these, 15 metabolites were characterized as the most significant movers and shakers (literally called “VIP”s).

Here are a few of the most important findings around the VIP metabolites in this study:

• At first, a good number of metabolite levels increased. Compared to the START, about half of the VIP metabolites increased at RD1 (Day 10). As the authors shared, this finding was consistent with other exercise studies, where metabolites get released from tissue stores and increase in circulation.
• That trend, however, changed dramatically as the race went on. By the time the cyclists reached RD2 (Day 17) and the FINISH, most VIP metabolites decreased. This meant that, overall, extreme exercise resulted in drastic depletion of key metabolites.
• The top (VIP) depleted metabolite was pentadecanoylcarnitine (PDC). This finding held when comparing START vs. FINISH, START v. RD1, and RD1 vs. RD2.

Which begs the question…

What is pentadecanoylcarnitine?

Glad you asked! Pentadecanoylcarnitine (PDC) is a metabolite made by our bodies by combining:

Pentadecanoic acid (C15:0) + Carnitine

PDC is categorized as an acylcarnitine, which simply means that it is a carnitine molecule attached to a fatty acid. In general, acylcarnitines are molecules that deliver fatty acids to mitochondria to make energy. So, that’s pretty important.

Now that you know what acylcarnitines do, it’s perhaps not so surprising that acylcarnitines would be depleted in the face of extreme exercise. You need more energy, you burn more acylcarnitines.

What was surprising in this study: only C15:0 and C17:0 acylcarnitines made the VIP list, with the C15:0 acylcarnitine (aka PDC) being the most depleted molecule among ALL metabolites. The authors conclude that understanding which key metabolites are depleted during extreme exercise could help prioritize what fuel our bodies need to thrive. That could include PDC.

A compelling PDC parallel between elite Tour de France cyclists & bottlenose dolphins.

Back in 2022, we published two big discoveries in Scientific Reports while aiming to continually improve the health of aging Navy dolphins.

First, bottlenose dolphins provided a modified diet higher in C15:0 had higher levels of both C15:0 and PDC in their serum. In fact, among 400+ metabolites measured in this modified diet study, PDC was the VIP-est of all VIP metabolites by Month 3 and Month 6 (see figure below).

Second, when we tested pure PDC in the lab for relevant biological activities, we found that PDC fully activated two core receptors responsible for whole-body balance and bliss (aka, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). This made PDC the second-ever discovered full-acting endocannabinoid.

Here’s the important parallel between our study and the most recent one with Tour de France athletes: While our dolphin study showed that increasing C15:0 intake increased PDC levels, the Robberechts et al. study showed that extreme exercise decreased C15:0 levels, which were directly and strongly correlated with decreasing PDC levels (r=0.58, p=0.001).

What does this all mean? 1) PDC is an important (VIP) molecule in our bodies, 2) these levels can become depleted, and 3) increasing our C15:0 levels has a direct and positive effect on our PDC levels, which can support our endocannabinoid system.