C15:0: An Emerging Essential Fatty Acid You Need to Know About

James Odell, OMD, ND, LAc

Emerging studies indicate that pentadecanoic acid (C15:0), a saturated fat naturally present in dairy products and certain fish, may qualify as an essential fatty acid because of its important role in promoting heart, metabolic, and immune health. Research has linked C15:0 to a variety of health benefits, such as reducing inflammation, supporting liver function, improving insulin sensitivity, and potentially contributing to healthy aging. This article will discuss the renewed research within the scientific community on the importance of the “essential” odd-chain saturated fatty acid pentadecanoic acid (C15:0).

The Importance of Fatty Acids

Fatty acids are key energy sources and membrane constituents that have wide biological activities influencing cell and tissue metabolism, function, and responsiveness to hormonal and other signals. A growing body of evidence demonstrates that pentadecanoic acid (C15:0), an odd-chain saturated fatty acid found in raw milk and butter, is essential in the diet to support long-term metabolic, cardiovascular, and immune health. 

The Chemical Structure of Fatty Acids

Fatty acids are chains of carbon and hydrogen atoms with a carboxyl group (―COOH) at one end. They are building blocks of lipids and can be saturated (with no double bonds between carbon atoms) or unsaturated (with one or more double bonds). 

Classifying Fatty Acids

Fatty acids are classified in many ways: by length, by saturation vs unsaturation, by even vs odd carbon content, and by linear vs branched. Most nutritionists classify fatty acids into four general categories: saturated, monounsaturated, polyunsaturated, and trans fats. 

Fatty Acids and Disease

Proponents of the inflammation theory of heart disease cite the massive replacement of saturated fats (such as butter, lard, and fat in red meat) by unsaturated fats (certain seed oils) as a cause of increased heart disease. Certain unsaturated fats can increase inflammation, particularly certain seed oils that are heavily processed. Ironically, this huge dietary shift was caused by the recommendations of the so-called heart experts at the time (the 1950s, gaining momentum in subsequent decades). Worse yet, they recommended margarine to replace butter. Margarine is composed mostly of “hydrogenated vegetable oils”. These artificially created fats, known as trans fats, are now known to be among the unhealthiest fats.1 

Trans Fats

Trans-fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for heart health and may pose a risk for certain cancers and are associated with an increased risk of coronary heart disease, atherosclerosis, fatty liver disease, inflammatory diseases, and Alzheimer’s disease.

Essential Fatty Acids

It is commonly viewed that the healthiest fats to eat are polyunsaturated and monounsaturated fats, which are considered beneficial for cardiovascular health. Foods rich in polyunsaturated fats include fatty fish, such as salmon, mackerel, herring, and tuna, as well as nuts like walnuts, and seeds like flaxseeds and chia seeds. Monounsaturated fats are found in olive oil, avocados, and nuts like almonds and pecans. 

Essential fatty acids (EFAs) are a type of polyunsaturated fat that the body cannot synthesize on its own and must be obtained from food. The two main types are omega-3 fatty acids (found in fish and certain algae oils) and omega-6 fatty acids (found in plant oils). These fatty acids are crucial for various bodily functions, including brain and nervous system development, cell membrane formation, and immune system support. Associations between essential fatty acids and lower risks of heart disease, type 2 diabetes, cancer, mood disorders, arthritis, and neurological diseases have suggested their potential to prevent, manage, and treat a wide variety of diseases.2, 3 Anti-inflammatory properties of omega-3s may help people manage rheumatoid arthritis and other inflammatory conditions, such as asthma.4 The pathway by which omega-3s are delivered to the brain supports their development as therapeutics for neurodegenerative disorders. 

Odd Chain Fatty Acids

As previously described, fatty acids can also be classified by their even or odd carbon content. Most fatty acids are even-chained, e.g. stearic (C18) and oleic (C18), meaning they are composed of an even number of carbon atoms. Some fatty acids have odd numbers of carbon atoms and are referred to as odd-chain fatty acids (OCFA).  The most common OCFA are the saturated C15 pentadecanoic acid and C17 heptadecanoic acid. On a molecular level, OCFAs are biosynthesized and metabolized slightly differently from their even-chained relatives.

The majority of research into fatty acid metabolism has been conducted primarily on even-chain fatty acids (carbon chain length of 2–26), as these represent >99% of the total fatty acid plasma concentration in humans.  However, there is also a detectable amount of odd-chain fatty acids in human tissue, and some of these are now viewed as “essential”.5, 6 Since the early 1960s, it has been erroneously concluded that odd-chain saturated fatty acids are of little physiological significance. 7, 8 

Similar Health Benefits Between Pentadecanoic Acid (C15:0) and Polyunsaturated EPAs

We have often heard that saturated fats are unhealthy. However, this is certainly not the case as several odd-chain saturated fats, such as pentadecanoic acid (C15:0), now considered essential and share similar health properties with polyunsaturated EPAs.

Among these shared activities of C15:0 and EPA – DHA, are lowered monocyte chemoattractant protein-1 (MCP-1). This protein participates in chronic inflammation, cardiovascular disease, and autoimmune disease. MCP-1 is a core chemokine that recruits monocytes and T cells into sites of inflammation, and it plays a central role in the development and severity of numerous diseases, including Alzheimer’s and Parkinson’s disease, epilepsy, multiple sclerosis, cardiovascular disease, stroke, type 2 diabetes, tuberculosis, COVID-19, osteoarthritis, rheumatoid arthritis, and osteoporosis.9 

It has been shown that C15:0 lowers MCP-1 activity. In one study daily oral C15:0 supplementation for 12 weeks successfully lowered circulating MCP-1 in a high-fat diet induced obese mouse model of type 2 diabetes.10

Additionally, higher circulating C15:0 concentrations have been repeatedly linked to a lower risk of metabolic diseases, including type 2 diabetes and nonalcoholic fatty liver disease, and daily C15:0 supplementation can attenuate these conditions in vivo.11, 12, 13, 14 

Pentadecanoic acid has broad biochemical activities relevant to protecting the heart, immune system and liver health. Furthermore, it has been extensively shown that individuals who test low with circulating C15:0 concentrations have a higher risk of having or developing type 2 diabetes, heart disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis, as well as specific types of cancer.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28  

Pentadecanoic acid (C15:0) and Longevity

There is tremendous interest in developing antiaging biochemical interventions that can simultaneously prevent or mitigate age-related diseases and thereby enhance longevity.29, 30, 31, 32 

The belief that such interventions can be developed is founded in what is often referred to as the “geroscience hypothesis”.33, 34 This hypothesis proposes that there are mechanisms that control the rate at which individuals age, and if one could identify these mechanisms and somehow slow them through an intervention, then many disease processes known to be exacerbated by aging could be mitigated simultaneously.35, 36, 37, 38

Research has shown that C15:0 is an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds. Specifically, C15:0 activates AMPK, or activated protein kinase, which is a crucial enzyme that acts as a cellular energy sensor, regulating metabolic processes and cellular energy balance. It is activated when cells experience energy stress, such as low ATP or high AMP levels, triggering a cascade of reactions to restore energy homeostasis.39  C15:0 also inhibits mTOR, a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular balance or homeostasis.

Both AMPK and mTOR are principal components of the human longevity pathway. C15:0 has a balancing effect on these pathways and the potential to enhance biochemical processes associated with longevity. 

Natural Sources of Pentadecanoic Acid (C15:0)

C15 can be found in various foods, particularly dairy products being a rich source - sour cream, butter, and cream cheese. Pasteurization of milk destroys much of the C15, thus, unpasteurized milk is a richer source. While primarily found in dairy, it is also present in certain meats - beef, lamb, fish, and some plants (vegetables, seaweeds). C15:0 is also available as a dietary supplement. 

Ted Talk

https://www.discoverc15.com/

References

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21. Djousse, Luc, Mary L. Biggs, Nirupa R. Matthan, Joachim H. Ix, Annette L. Fitzpatrick, Irena King, Rozenn N. Lemaitre et al. "Serum individual nonesterified fatty acids and risk of heart failure in older adults." Cardiology 146, no. 3 (2021): 351-358.

22. Trieu, Kathy, Saiuj Bhat, Zhaoli Dai, Karin Leander, Bruna Gigante, Frank Qian, Andres V. Ardisson Korat et al. "Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis." PLoS medicine 18, no. 9 (2021): e1003763.

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25. Wei, Wenchao, Chi Chun Wong, Zhongjun Jia, Weixin Liu, Changan Liu, Fenfen Ji, Yasi Pan et al. "Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid." Nature microbiology 8, no. 8 (2023): 1534-1548.

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27. Kruchinina, M., A. Gromov, Y. Prudnikova, M. Shashkov, A. Sokolova, and V. Kruchinin. "Erythrocyte membrane fatty acids as the potential biomarkers for detection of early-stage and progression of colorectal cancer." Annals of Oncology 29 (2018): v52.

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