C15:0 (Pentadecanoic Acid) As an Evidence-Based Nutrient

While there is important overlap between medicine, pharmaceuticals, and nutrition, there is a need to recognize differences between traditional drugs (used to treat diseases) and nutrition (used to protect health). In this article, we cover a position paper published in Nutrition Reviews by a consortium of experts to help answer the question: Should drugs and nutrients be judged using the same criteria?

After catching up on the appropriate evidence needed to meet the criteria of a nutrient, we’ll walk through the evidence supporting C15:0 (pentadecanoic acid) as an emerging essential nutrient…followed by a call to action that aims to meaningfully improve health for all.

Let’s Start By Defining “Nutrient”

A nutrient is a substance that provides nourishment essential for growth and the maintenance of life.

Easy enough. We can further break that definition down into three sections.

First up, substances  are classified into the following six nutrient categories (plus, a bonus category of fiber is making its way onto this list):

• Carbohydrates
• Proteins
• Fats
• Vitamins
• Minerals
• Water

Next, providing nourishment essential for growth means there is support that a nutrient is needed during our earliest, developing years…and without this nutrient, our growth and development would be compromised.

Finally, providing nourishment essential for the maintenance of life means there is support that a nutrient is needed to support health throughout our lives…and without this nutrient, our long-term health would be compromised.

With this understanding of how a nutrient is defined, let’s move on to Blumberg et al.’s thoughts on how to assess the value of a nutrient (aka, evidence that a substance is truly a nutrient).

What Are The Evidence-Based Criteria For A Nutrient?

A consortium of experts with long-standing careers in nutritional science, policy and practice met for two days in Omaha, Nebraska, to discuss evidence-based nutrition (EBN) versus evidence-based medicine (EBM). Here, they wanted to differentiate between the criteria needed to demonstrate the effectiveness of a substance in treating a specific disease (aka, EBM) versus protecting long-term health (aka, EBN). The product of this consortium was the Blumberg et al. paper.

As a primary theme of this paper, they call out the rising popularity of randomized clinical trials (RCTs), which have been the long-term gold standard to demonstrate a pharmaceutical drug’s safety and efficacy in treating a disease.

While RCTs are great for determining whether a specific compound treats a specific disease, Blumberg et al. conclude that, in isolation, RCTs can be limited and even unfeasible for determining the intended protective benefits of nutrients.

For example:

Nutrient RCT #1 for Kids: Show that 1) providing a given nutrient is essential to the growth and development of  infants and children, and 2) withholding the nutrient compromises the growth and development of  infants and children.

Nutrient RCT #2 for Adults: Show that 1) providing a given nutrient is essential to the maintenance of long-term health in adults, and 2) withholding the nutrient compromises the long-term health in adults.

It should be clear that these types of clinical trials would either be unethical to conduct with infants or unfeasible to conduct with adults due to the duration of time. Understanding that, Blumberg et al. sought to provide solutions beyond RCTs.

The Totality of Evidence

In their paper, Blumberg et al. emphasize the need to understand the totality of evidence beyond RCTs to identify and validate the core benefits of nutrients. This totality of evidence for nutrients includes the following:

• Prospective cohort studies
• Case-control studies
• Randomized controlled studies
• Biological plausibility
• Replication and multiplicity of studies
• Dose-response relationships
• Presence of low-intake groups
• Correct temporal sequence
• Low between-subject variance
• Intake estimate validation  
• Evidence of supporting early-stage growth 
• Evidence of neonatal disease caused by nutrient deficiency 
• Evidence of protecting long-term health throughout life
• Evidence of diseases in adults caused by nutrient deficiency

The bottom line? Meeting the evidence-based criteria of a nutrient that is essential to healthy development and maintaining our overall health throughout our lives is harder than meeting the criteria of a drug that is targeted to treat a disease. For nutrients, it’s the totality of data that repeatedly point to the same story that counts.

The Totality Of Evidence Behind C15:0 As An Emerging Essential Nutrient

C15:0 (pentadecanoic acid) is an odd-chain saturated fatty acid that has long been sidelined as a simple, inactive biomarker of dairy intake. We now know, however, that C15:0 is not only a beneficial fat, but one that is emerging as an essential nutrient.

This is an incredibly exciting discovery, backed by 100+ peer-reviewed studies and with the rare potential to meaningfully and relatively quickly improve global health.

Here are some of the studies that are helping to check off Blumberg et al.’s totality of evidence list supporting C15:0 as a bona fide nutrient:

• Prospective cohort studies. Meta-analyses (studies of multiple prospective studies) tracking tens of thousands of people over many years repeatedly show that people with higher C15:0 are associated with better protected long-term cardiovascular and metabolic health.
• Case-control studies. Similarly, case-control studies in numerous animal models repeatedly show that oral C15:0 actively protects cholesterol, immune, red blood cell, liver, glucose handling, and gut health compared to non-C15:0 controls. That means, beyond association, C15:0 can actively protect health.
• Biological plausibility. Further, we know that C15:0 directly activates AMPK, AKT and PPARs, which are mechanisms of action well established to protect cardiometabolic health. Thus, we have a direct link between how C15:0 works and observed long-term benefits in humans.
• Replication and multiplicity of studies. Across prospective cohort studies, cell-based studies, mechanistic studies, and RCTs, C15:0’s beneficial role as a nutrient has been successfully repeated using a multiplicity of studies from different research teams.
• Dose-response relationships. Mechanism of action studies, human cell system studies, prospective cohort studies, and RCTs have all shown that the higher the C15:0 level, the greater the associated benefit (aka dose-response relationship).
• Presence of low-intake groups. Thanks to global dietary recommendations to decrease our intake of whole dairy fat, there are large swaths of populations that have had low C15:0 intake since the late 1970s, resulting in lower population wide C15:0 levels. 
• Correct temporal sequence. The benefits of prospective control studies are that they can show that people who start with higher C15:0 levels at Day 1 are more likely to have protected cardiometabolic health at Year 10. Controlled animal studies and RCTs also prove that providing C15:0 resulted in health benefits that weren’t seen in non-exposed controls.
• Low between-subject variance. A large genetic study by Otto et al. showed that there are no detectable genetic drivers for C15:0 levels, meaning that C15:0 levels are likely ubiquitously raised among individuals. This ubiquitous benefit of C15:0 as an essential nutrient has been emerging across species too, including C. elegans,  rats,  piglets, dolphins, and humans.
• Intake estimate validation. Numerous large scale studies support that we need 100 to 200 mg of C15:0 a day to maintain healthy C15:0 levels of > 0.2% (> 20 uM, > 5 ug/ml). Based on reports from the USDA and declining whole fat milk intake over the past 50 years, the average person in the U.S. today may be getting as little as 25 mg of C15:0 per day.
• Randomized clinical trials. Across seven randomized clinical trials, higher C15:0 intake has been shown to increase C15:0 levels, and these higher C15:0 levels have been associated with protected red blood cell, liver, cholesterol, gut microbiome, and vascular health.
• Evidence of supporting early-stage growth & the presence of poor growth caused by nutrient deficiency. Both prospective cohort studies of mother-infant pairs and controlled studies with multiple hallmark deficiency animal models support that lower or no dietary C15:0 among infants results in poorer growth, and supporting normal C15:0 levels results in healthier body growth and better cognitive development. This is one of the rarest and toughest criteria for a candidate nutrient to meet.
• Evidence of protecting long-term health & the presence of diseases in adults caused by nutrient deficiency. All the above supports how C15:0 protects long-term health. Additionally, the detailed pathophysiology of a C15:0 nutritional deficiency syndrome, called Cellular Fragility Syndrome, was published in 2024. This described syndrome  involves a new form of cell death called ferroptosis and may be impacting as many as 1 in 3 people globally. Importantly, the ability for C15:0 to reverse this syndrome was recently revalidated, in detail, by a second independent team in India.

Alas, due to the 1977 Congressional recommendations to dramatically lower whole dairy fat intake for all Americans, we have undergone a 50-year experiment of decreasing our C15:0 intake - including infants, children, and adults. Thus, one can argue that the ultimate RCTs (#1 and #2 defined above) for C15:0 a nutrient have already been done.

This half-century experiment helps to explain why prospective cohort studies have been so reliable - and why studies have repeatedly shown that 1) infants and children with lower C15:0 intake have been associated with poorer body growth and cognitive development, and 2) adults with lower C15:0 have been associated with poorer long-term cardiometabolic health.

The emerging hypothesis, now from multiple research teams backed by 100+ peer-reviewed studies, is that nutritional C15:0 deficiencies may be contributing to the rise in poorer cardiometabolic health, including among younger and younger people. More importantly, studies are supporting that getting C15:0 back into our lives can help protect healthy development during our earliest years, as well as long-term health throughout our adult years.

Here’s another way to gain a healthy perspective on the excitement behind C15:0: How many other substances, be they in supplements or pharmaceuticals, are able to check off the evidence-based criteria boxes above similar to or better than C15:0? Answer: Very few.

As shared by Blumberg et al., a failure to ignore the totality of evidence specific to a nutrient, paired with nutrients’ general safety and accessibility, could result in a greater risk of not implementing recommendations that could meaningfully improve public health. Our movement has gained tremendous momentum in 2025 and will continue into 2026, along with science.  Here’s to evidence-based nutrients.

Relevant Studies

Nerd out on all the C15:0 studies at DiscoverC15.com/resources.

Blumberg et al. Evidence-based criteria in the nutritional context. Nutr Rev 68, 478-484 (2010).

Otto et al. Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium. PLOS ONE 13, e0196951 (2018)

Stewart, H. Fluid milk consumption continues downward trend, proving difficult to reverse. USDA Economic Research Service June 2022.

Selected Venn-Watson et. al studies

●     Venn-Watson & Schork. Pentadecanoic acid (C15:0), an essential fatty acid, shares clinically relevant cell-based activities with leading longevity-enhancing compounds. Nutrients 15, 4607 (2023).

●      Venn-Watson et al. Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids. PLOS One 15:e0230769 (2020a).

●      Venn-Watson, S., Lumpkin, R., Dennis, E.A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? Sci Rep 10:8161 (2020b).

●     Venn-Watson, S.K., Jensen, E.D. Aging-associated amyloid-beta plaques and neuroinflammation in bottlenose dolphins (Tursiops truncatus) and novel cognitive health-supporting roles of pentadecanoic acid (C15:0). Int J Mol Sci 26:3746 (2025).

●      Venn-Watson et al. The Cellular Stability Hypothesis: evidence of ferroptosis and accelerated aging-associated diseases as newly identified nutritional pentadecanoic acid (C15:0) deficiency syndrome. Metabolites 14, 355 (2024).

C15:0 Mechanisms of Action & Efficacy

●     Aabis, M. et al. Pentadecanoic acid attenuates thioacetamide-induced liver fibrosis by modulating oxidative stress, inflammation, and ferroptosis pathways in rat. Nauyn Schmied Arch Pharmacol doi: 10.1007/s00210-025-04143-6 (2025)

●     Bishop et al. Hepatadecanoic Acid is Not a Key Mediator in the Prevention of Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice. Nutrients 15, 2052 (2023).

●     Duan et al. Odd-chain fatty acid-enriched fats improve growth and intestinal morphology and function in milk replacer-fed piglets. J Nutr 155: 1298-1310 (2025)

●     Fu, W.C. et al. Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes. Food Nutr Res 65:10.29219/fnr.v65.4527 (2021).

●     Li, Y. et al. Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor. Bioorg Med Chem Letters 72:128881 (2022).

●     To, N.B., Nguyen, Y.T., Moon, J.Y., Ediriweera, M.K., Cho, S.K. To, N.B., Nguyen, Y.T., Moon, J.Y., Ediriweera, M.K., Cho, S.K. Pentadecanoic acid, an odd-chain fatty acid, suppresses the stemness of MCF-7/SC human breast cancer stem-like cells through JAK2/STAT3 signaling. Nutrients 12, 1663 (2020).

●     To, N.B., Truong, V.N.P., Ediriweera, M.K., Cho, S.K. Effects of combined pentadecanoic acid and tamoxifen treatment on tamoxifen resistance in MCF-7/SC breast cancer cells. Int J Mol Sci 23, 11340 (2022).

●     Wu et al. Galactooligosaccharides and Limosilactobacillus reuteri synergistically alleviate gut inflammation and barrier dysfunction by enriching Bacteroides acidifaciens for pentadecanoic acid biosynthesis. Nature Communications 15:9291 (2024).

●     Wei et al. Parabacteroides distasonis Uses Dietary Inulin to Suppress NASH via Its Metabolite Pentadecanoic Acid. Nature Microbiology 8, 1534–1548 (2023)

●     Singh et al. Anti-Inflammatory Effect of Dietary Pentadecanoic Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice. Nutrients 16, no. 17 (2024): 3031.

Prospective Cohort Meta-Analyses

●     Chen et al. Biomarkers of fatty acids and risks of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies. Critical Reviews in Food Science and Nutrition 61, 2705–2718 (2021).

●     Huang, L. et al. Circulating saturated fatty acids and incident type 2 diabetes: A systematic review and meta-analysis. Nutrients 11:998 (2019).

●     Imamura, F. et al. Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLOS Med 15, e1002670 (2018).

●     Li et al. Saturated fatty acid biomarkers and risk of cardiometabolic diseases: a meta-analysis of prospective studies. Frontiers in Nutrition 9, 963471 (2022).

●     Trieu, K. et al. Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis. PLoS Med 18:e1003763 (2021).

Clinical Trials

●     Arghavani et al. Impact of dairy intake on circulating fatty acids and associations with blood pressure: A randomized crossover trial. Nutr Metab, Cardiovasc Dis In Press (2025).

●     Chooi et al. Effect of An Asian-Adapted Mediterranean Diet and Pentadecanoic Acid on Fatty Liver Disease: The TANGO Randomized Controlled Trial. American Journal of Clinical Nutrition 119, 788-799 (2024).

●     Kaneko et al. Effect of continuous ingestion of pentadecyl-containing aurantiiochytrium oil on skin condition: A randomized, double blind, placebo-controlled study. Med Cons New-Remed 60, 459-470 (2023).

●     Mascarenhas et al. Malabsorption blood test: Assessing fat absorption in patients with cystic fibrosis and pancreatic insufficiency. J Clin Pharmacol 55, 854-865 (2015)

●     Mitri et al. Plasma free fatty acids and metabolic effect in type 2 diabetes, an ancillary study from a randomized clinical trial. Nutrients 13, 1145 (2021).

●     Robinson et al. C15:0 Supplementation in Young Adults at Risk for Metabolic Syndrome: A Randomized Controlled Trial. Journal of Clinical Nutrition 154, 2763-2771 (2024).

●     Salamanca-Sanabria et al. Potential effects of Asian-adapted Mediterranean diet in depression and anxiety among women with metabolic dysfunction-associated steatotic liver disease: a secondary analysis. Frontiers Nutrition 12 (2025).

●     Stallings et al.  Diagnosing malabsorption with systemic lipid profiling: pharmacokinetics of pentadecanoic acid and triheptadecanoic acid following oral administration in healthy subjects and subjects with cystic fibrosis. Int J Clin Pharmacol Ther 51, 263-273 (2013).

Essential Fatty Acid & Nutritional C15:0 Deficiency

●     Aabis, M. et al. Pentadecanoic acid attenuates thioacetamide-induced liver fibrosis by modulating oxidative stress, inflammation, and ferroptosis pathways in rat. Nauyn Schmied Arch Pharmacol doi: 10.1007/s00210-025-04143-6 (2025)

●     Ciesielski, V. et al. Dietary pentadecanoic acid supplementation at weaning in essential fatty acid-deficient rats shed light on the new family of odd-chain n-8 PUFAs. J Nutritional Biochemistry 137:109814 (2025)

●     Ciesielski, V. et al. New insights on pentadecanoic acid with special focus on its controversial essentiality: a mini-review. Biochimie 227:123-129 (2024)

●     Dornan, K. et al. Odd chain fatty acids and odd chain phenolic lipids (alkylresorcinols) are essential for diet. J Am Chem Soc 98:813-824 (2021)

●     Duan et al. Odd-chain fatty acid-enriched fats improve growth and intestinal morphology and function in milk replacer-fed piglets. J Nutr 155: 1298-1310 (2025)

●     George, A.D. et al. The fatty acid species and quantity consumed by the breastfed infant are important for growth and development. Nutrients 13:4183 (2021).

●     Ruan, M. et al. Free long-chain fatty acids trigger early postembryonic development in starved Caenorhabditis elegans by suppressing mTORC1. PLOS Biol 22:e3002841 (2024)

●     Yuan, W.L. Associations between perinatal biomarkers of maternal dairy fat intake and child cognitive development: results from the EDEN mother-child cohort. Eur J Clin Nutrition 79:320-328 (2025).