C15:0 Science Round-Up Series: Clinical Trials

Healthy Aging

A Growing Body of C15:0 Clinical Trials

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 will cover the following six key topics on C15:0:

• Mechanisms of Action: How C15:0 works
• Optimal Effective Levels & Daily Intake: C15:0 bioavailability and amounts needed to achieve active levels
• Cell-Based Efficacy: What C15:0 does at the cellular level
• In Vivo Efficacy: What C15:0 does at the whole-body level
• Epidemiological Studies: People who have higher levels of C15:0 have healthier _____ (we’ll fill in the blanks)
• Clinical Trials: Randomized controlled clinical trials with 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’ll also share how C15:0 study outcomes – from its mechanisms of action to clinical trials – are intricately interlinked. Let’s start with the last topic and work our way up, shall we? Hello, Clinical Trials.

The number of C15:0 clinical trials is building.

Today, there are seven peer-reviewed publications covering six clinical trials on C15:0. These clinical trials were conducted by different research teams, who focused on different health areas, including:

• C15:0 bioavailability & pharmacokinetics
• Liver & red blood cell health
• Cholesterol & gut health
• Mood health
• Vascular health
• Skin health

Below are highlighted findings from each of these clinical trials.

Clinical Trials 1 & 2: C15:0 is bioavailable. Like, really bioavailable.

Stallings et al. led a clinical trial with healthy humans to determine the oral bioavailability and pharmacokinetics of pure C15:0 [1]. Participants were provided a single oral dose of C15:0, and this study showed that C15:0 circulating levels (referred to as PA, for pentadecanoic acid, in the figure below) reliably increased over a period of 8 hours. For every 100 mg of ingested pure free fatty acid C15:0, C15:0 circulating levels increased by an average of 1 ug/ml.

Mascarhenas et al. then led a clinical trial with an increased number of healthy humans, including adults and children, to extensively model the oral bioavailability and pharmacokinetics of pure C15:0. Participants were provided a single oral dose of C15:0, and this study repeated the findings from Stallings et al. study. The authors concluded that pure free fatty acid C15:0 is, on average, 100% bioavailable.

Clinical Trial 3: Young adults who avoided dairy fat products had low C15:0 levels, and increasing their C15:0 levels above a critical threshold supported liver & red blood cell function.

Robinson et al. led a randomized, double-blinded and placebo-controlled clinical trial with young adults (ages 18 to 24 years old) at risk of metabolic syndrome and who were purposely avoiding whole fat dairy products. The purpose of this clinical trial was to evaluate the ability for daily C15:0 supplementation to be safe, raise C15:0 levels, and change physiological markers. Participants were asked to take 200 mg of C15:0 per day for 12 weeks. At the beginning of this study, this population also had elevated liver enzymes, indicative of suboptimal liver function. This study showed the following:

• C15:0 supplementation was safe and raised C15:0 levels.
• C15:0 levels increased among participants who strictly adhered to the protocol.
• Among participants who adhered to the protocol, their C15:0 levels increased at the same amounts demonstrated by Mascarhenas et al. and Stallings et al. Namely, 200 mg of C15:0 resulted in raised circulating C15:0 levels by 2.3 µg/ml.
• This group with raised C15:0 levels > 5 µg/ml (called the “Threshold” group in the table below) also had significantly lower ALT and AST, which are markers of improved liver function, as well as raised hemoglobin, demonstrating improved red blood cell function.

The authors conclude that C15:0 supplementation was safe, raised C15:0 levels, and had early evidence of providing clinically relevant benefits related to improved liver health and red blood cell function among people who achieved C15:0 levels > 5 µg/ml (which is emerging as the threshold for C15:0 nutritional sufficiency).

Clinical Trial 4: Women who eat a hypocaloric, Mediterranean diet get added healthy cholesterol and gut microbiome benefits by supplementing with C15:0.

Chooi et al. led a randomized, controlled clinical trial that included women to evaluate the ability for C15:0 supplementation to be safe, raise C15:0 levels, and change physiological markers above and beyond the benefits of concurrent caloric restriction and the Mediterranean diet. Participants took 300 mg of C15:0 per day for 12 weeks. This study showed the following:

• C15:0 supplementation was safe and raised C15:0 levels.
• While all three groups had lowered liver fat and body weight loss, the C15:0 supplemented group trended to having the greatest loss of body fat. It is important to note, however, that these shared improvements among all three groups were not statistically significantly between the groups.
• Compared to the other groups, however, the C15:0 supplemented group had healthier LDL cholesterol and improved abundance of a healthy gut microbe called Bifidobacterium adolescentis.

The authors conclude that C15:0 supplementation was safe, raised C15:0 levels, and had early evidence of providing clinically relevant benefits related to supporting healthy cholesterol levels and a healthy gut microbiome.

Clinical Trial 4 (Part 2): There is early evidence that C15:0 may improve mood within 12 weeks.

Salamanca-Sanabria et al. did a post-hoc analysis of the Chooi et al. randomized and controlled clinical trial above to evaluate the ability for C15:0 supplementation to support healthy mood among women. This post-hoc analysis showed that, while all three groups had lower body weight and improved mood, the C15:0 supplemented group had the most significant improvement in mood. The authors conclude that C15:0 supplementation + the Mediterranean diet may have a positive effect on improving mood.

Clinical Trial 5: Raised C15:0 levels were correlated with improved vascular function.

Arghavani et al. led a cross-over clinical trial that included healthy adults to evaluate the potential effects of dairy fat diets, as well as individual fatty acid components within dairy fat, on blood pressure and vascular stiffness. In this trial, participants followed: 1) a moderate dairy fat diet (< 4 servings of dairy products per day) and 2) a high dairy fat diet (≥ 4 servings of dairy products a day) for 12 weeks each, with a washout period between the two diets. This clinical trial showed the following:

• Increased C15:0 intake from the diet directly correlated with increased circulating C15:0 concentrations.
• Increased C15:0 circulating levels from the high dairy fat diet independently predicted lowered arterial stiffness (measured as cfPWV).

The authors show that increased intake of dietary C15:0 raised C15:0 levels, and these raised C15:0 levels were associated with improved vascular function. They also concluded that different fatty acids in dairy fat had different effects (e.g. raised C16:0 from the high dairy fat diet independently predicted raised blood pressure), and that individual fatty acids within the whole dairy fat matrix can have conflicting effects.

Clinical Trial 6: High C15:0-containing supplementation improved skin health.

Kaneko et al. led a randomized, placebo-controlled clinical trial that included older women to evaluate the potential effects of an oral high-C15:0 supplement on skin elasticity, collagen density, and skin moisture. This clinical trial showed that daily oral intake of high-C15:0 supplements for 12 weeks improved skin elasticity, collagen density, and skin moisture. The authors conclude that oral intake of high C15:0-containing supplementation provides skin health benefits.