Whole Body Health & Wellness
A strong body of science shows that C15:0 promotes cardiometabolic, immune and liver health, while a key C15:0 metabolite can support mental and cognitive health.

Promising broad benefits from C15:0
Why C15:0 is becoming the essential, essential fatty acid.

Metabolic Health
Numerous studies have shown that people with higher circulating C15:0 concentrations have a lower risk having or developing type 2 diabetes. These studies were performed by prestigious research teams around the world, including Sweden, England, Canada, and Asia. One study showed that pregnant women with higher circulating C15:0 concentrations had a lower risk of developing gestational diabetes.
These benefits are likely due to C15:0’s demonstrated ability in animal models to and positive associations in human studies with:
- Lower glucose and promote insulin-stimulated glucose uptake
- Healthier fasting glucose and glucose tolerance
- Lower total and LDL cholesterol
- Lower triglycerides
- Lower adipokines
- Support healthier body weight
- Activate PPAR-ɑ/δ receptors, which regulate metabolism
- Activate AMPK, which regulates cellular homeostasis
Selected References
- Aglago, E. K. et al. Association between serum phospholipid fatty acid levels and adiposity in Mexican women. J Lipid Res 58, 1462–1470 (2017).
- Forouhi, N.G., Koulman, A., Sharp, S.J., Imamura, F., Kroger, J., Schulze, M.B., et al. Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study. Lancet Diab Endocrinol 14, 70146–9 (2014).
- 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).
- 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).
- Krachler, B. et al. Fatty acid profile of the erythrocyte membrane preceding development of type 2 diabetes. Nutr Metab Cardiovasc Dis 18:503-510 (2008).
- Kurotani, K. et al. Even- and odd-chain saturated fatty acids in serum phospholipids are differentially associated with adipokines. PLOS ONE 12, e0178192 (2017).
- Santaren, I.D. et al. Serum pentadecanoic acid (15:0), a short-term marker of dairy food intake, is inversely associated with incident type 2 diabetes and its underlying disorders. Am J Clin Nutr 100, 1532-1540 (2014).
- Smedman, A.E.M., Gustafsson, I.B., Berglund, L.G.T., Vessby, B.O.H. Pentadecanoic acid in serum as a marker of intake of milk fat: relations between intake of milk fat and metabolic risk factors. Am J Clin Nutr 69, 22-29 (1999).
- 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 (2020).
- Zheng, J.S. et al. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-Interact study. BMC Med 15, 203 (2017).
- Zheu, Y. et al. A prospective study and longitudinal study of plasma phospholipid saturated fatty acid profile in relation to cardiometabolic markers and the risk of gestational diabetes. Am J Clin Nutr 107, 1017-1026 (2018).
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Liver Health
Multiple studies have shown that people with higher circulating C15:0 concentrations have a lower risk of having nonalcoholic fatty liver disease (NAFLD) and severe nonalcoholic steatohepatitis, including children. NAFLD now affects 1 in 3 people, including 1 in 10 children, globally. It has been hypothesized that nutritional C15:0 deficiencies may be driving the global pandemic of fatty liver disease.
C15:0’s liver health benefits may be due to its demonstrated ability in relevant models to and positive associations in human epidemiological studies with:
- Lower severity of liver fibrosis
- Stop fibrotic cells from proliferating
- Prevent damaging iron deposition in the liver
- Lower inflammation
- Lower AST. ALT and GGT
- Activate PPAR-ɑ/δ receptors, which can help protect the liver
Selected References
- Jiao, J.etal. Circulating fatty acids associated with advanced fibrosis and hepatocellular carcinoma in south Texas hispanics. Cancer Epidemiol Biomarkers Prev 30, 1643-1651 (2021).
- Kratz, M. et al. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans. Am. J. Clin. Nutr. 99:1385-1396 (2014).
- Sawh, M.C., Wallace, M., Shapiro, E, Goyal, N. et al. Dairy fat intake, plasma pentadecanoic acid, and plasma iso-heptadecanoic acid are inversely associated with liver fat in children. J Pediatr Gastroenterol Nutr 72:e90-e96 (2021).
- Venn-Watson, S.K., Butterworth, C.N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE https://doi.org/10.1371/journal.pone.0268778 (2022).
- 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 (2020).
- Yoo, W. et al. Fatty acids in non-alcoholic steatohepatitis: focus on pentadecanoic acid. PLOS ONE 12:e0189965 (2017).
- Zheng, J.S. et al. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-Interact study. BMC Med 15, 203 (2017).
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Immune & Joint Health
People with higher circulating C15:0 concentrations have lower inflammation. Additionally, a study evaluating a model of arthritis demonstrated that higher C15:0 concentrations in the serum and joint fluid was associated with a lower risk of joint degradation and osteoarthritis.
These benefits may be due to C15:0’s demonstrated ability to:
- Activate PPAR alpha/delta receptors and inhibit JAK-STAT signaling, both of which lower inflammation.
- Lower many pro-inflammatory cytokines, including IL-6, MCP-1, PAI-1, and VCAM-1.
- Decrease inflammation in human cell systems mimicking chronic inflammation.
- Decrease pain by raising circulating concentrations of pentadecanoylcarnitine (PDC), a C15:0 metabolite that naturally activates CB1 and CB2 receptors.
Selected References
- Kurotani, K. et al. Even- and odd-chain saturated fatty acids in serum phospholipids are differentially associated with adipokines. PLOS ONE 12, e0178192 (2017).
- Matthan, N.R. et al. Spillover effects of a family-based childhood weight-management intervention on parental nutrient biomarkers and cardiometabolic risk factors. Curr Dev Nutrition 6:nzab152 (2022).
- 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).
- Venn-Watson, S.K., Butterworth, C.N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE https://doi.org/10.1371/journal.pone.0268778 (2022).
- 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 (2020).
- Venn-Watson, S., Reiner, J., Jensen, E.D. Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health.Scientific Reports 12:13717 (2022).
- Wu, C.L. et al. Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair. Scientific Rep 7:44315 (2017).
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Heart Health
Dozens of large, prospective cohort studies have consistently shown that people with higher circulating C15:0 concentrations are less likely to develop heart disease, including coronary heart disease, first myocardial infarction, and heart failure.
These benefits may be due to C15:0’s demonstrated ability in relevant models to and positive associations in human epidemiological studies with:
- Lower total and LDL cholesterol, triglycerides, ApoA1 and ApoB
- Lower, healthier blood pressure
- Activate PPAR-alpha receptors, which can lower triglycerides
- Activate PPAR-delta receptors, which can be heart protective
- Direct, broad, dose-dependent and clinically relevant beneficial activities across multiple primary human cell systems mimicking cardiovascular disease.
Selected References
- Biong, A.S., Veierod, M.B., Ringstad, J., Thelle, D.S., Pedersen, J.I. Intake of milk fat, reflected in adipose tissue fatty acids and risk of myocardial infarction: a case-control study. Eur J Clin Nutr 60, 236-244 (2006).
- Djousse, L. et al. Serum individual nonesterified fatty acids and risk of heart failure in older adults. Cardiology 146:351-358 (2021).
- Kaikkonen, J.E. et al. Associations of serum fatty acid proportions with obesity, insulin resistance, blood pressure and fatty liver: the cardiovascular risk in young Finns study. J Nutr 151, 970-978 (2021).
- Khaw, K.T., Friesen, M.D., Riboli, E., Luben, R. & Wareham, N. Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study. PLOS Med 9, e1001255 (2012).
- Liang, J., Zhou, Q., Amakye, W.K., Su, Y., Zhang, Z. Biomarkers of dairy fat intake and risk of cardiovascular disease: a systematic review and meta analysis of prospective studies. Crit Rev Food Sci Nutr 58, 1122-1130 (2018).
- 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).
- 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 (2020).
- Venn-Watson, S.K., Butterworth, C.N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE https://doi.org/10.1371/journal.pone.0268778 (2022).
- Warensjo, E. et al. Estimated intake of milk fat is negatively associated with cardiovascular risk factors and does not increase the risk of a first myocardial infarction. A prospective case-control study. Br J Nutr 91, 635-642 (2004).
- Zheng, J.S. et al. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-Interact study. BMC Med 15, 203 (2017).
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Anti-Cancer Activities
People with higher circulating C15:0 levels have a lower risk of having a variety of cancer types, including breast, small lung cell, squamous cell, colorectal, pharyngolaryngeal, and hematological cancers. C15:0 has direct anticancer activities and phenotypes.
Specifically, C15:0:
- Is an HDAC6 and JAK2/STAT3-inhibitor, which can slow or stop cancer cell proliferation.
- At higher doses, has clinically relevant cell-based activities that closely match that of gemcitabine and paclitaxel, two common anti-cancer therapeutics.
- Has strong dose-dependent antiproliferative effects on multiple cancer cell types, including human breast cancer (MCF-7, MDA-MB-231), lung cancer (A549), pancreatic cancer (PANC-1), and liver cancer (HepG2) cells.
- Reverses tamoxifen resistance in breast cancer cells.
- Improves upon gemcitabine anticancer activities, including in vivo
Selected References
- Budczies, J. et al. Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study. BMC Genomics 13, 334 (2012).
- Ediriweera, M.K. et al. Odd-chain fatty acids as novel histone deacetylase 6 (HDAC6) inhibitors. Biochimie 186:147-156 (2021).
- Jee, S.H. et al. Clinical relevance of glycerophospholipid, sphingomyelin and glutathione metabolism in the pathogenesis of pharyngolaryngeal cancer in smokers: the Korean Cancer Prevention Study – II. Metabolomics 12, 164 (2016).
- Hori, A. et al. Serum sphingomyelin species profile is altered in hematologic malignancies. Clin Chim Acta 514, 29-33 (2021).
- Kruchinina, M., Gromov, A., Prudnikova, Y., Shashkov, M., Sokolova, A., Kruchinin, V. Erythrocyte membrane fatty acids as the potential biomarkers for detection of early-stage and progression of colorectal cancer. Ann Oncol 29, Suppl 5 (2018).
- Li, F., Boateng, I.D., Yang, X., Li, Y. Extraction, purification, and elucidation of six ginkgo homologs from Ginkgo biloba sarcotesta and evaluation of their anticancer activities. Molecules 27, 7777 (2022).
- 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).
- Qi, S. et al. High-resolution metabolomic biomarkers for lung cancer diagnosis and prognosis. Sci Rep 11, 11805 (2021).
- 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).
- Venn-Watson, S.K., Butterworth, C.N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE https://doi.org/10.1371/journal.pone.0268778 (2022).
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Brain, Mood & Sleep Health
C15:0 and its metabolite, pentadecanoylcarnitine (PDC), can cross the blood-brain barrier and have targeted cell-based activities that support brain, cognitive, mood and sleep health. People with higher circulating C15:0 concentrations are less likely to have anxiety and distress.
Demonstrated C15:0 and PDC activities include:
- Anti-inflammatory activities, including IL-6 and MCP-1, which can support brain health.
- Activation of PPARɑ, which can support cognition, mood, brain and sleep health.
- Cell-based activities that closely matched bupropion.
- Raised circulating concentrations of pentadecanoylcarnitine (PDC), a C15:0 metabolite, that naturally activates CB1, CB2, 5-HT1A and 5-HT1B receptors, which support brain health, cognition, mood, and sleep health.
One study by Fonteh et al. showed that people with higher C15:0 in their cerebral spinal fluid were less likely to have Alzhiemer’s disease.
Selected References
- Brydges, C.R. et al. Metabolomic and inflammatory signatures of symptoms dimensions in major depression. Brain Behav Immun 102, 42-52 (2022).
- Fonteh, A.N., Cipolio, M., Chiang, J., Arakaki, X., Harrington, M.G. Human cerebrospinal fluid fatty acid levels differ between supernatant fluid brain-derived nanoparticle fractions, and are altered in Alzheimer’s disease. PLOS ONE 9, e100519 (2014).
- Nisbett KE, Pinna G. Emerging therapeutic role of PPAR-α in cognition and emotions. Frontiers Pharmacol 9:998 (2018).
- Shirai, H. et al. PPAR alpha is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders. Biochem Biophys Res Communications. 357:679-682 (2007).
- Venn-Watson, S.K., Butterworth, C.N. Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems. PLOS ONE https://doi.org/10.1371/journal.pone.0268778 (2022).
- 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 (2020).
- Venn-Watson, S., Reiner, J., Jensen, E.D. Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health.Scientific Reports 12:13717 (2022).
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