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Myristoleic acid

Linear Formula

C14H26O2

Synonyms

(Z)-Tetradec-9-enoic acid, 9Z-tetradecenoic acid, cis-9-tetradecenoic acid

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Myristoleic acid is a tetradecenoic, long chain fatty acid found in natural compounds such as Serenoa repens (Saw palmetto) extract, nutmeg, butter, and milk1. Long-chain fatty acids support heart health and healthy blood pressure, cholesterol levels, and joints. Myristoleic acid can be synthesized from myristic acid–found in palm seed oil, coconut oil, and butter–by the enzyme stearoyl-CoA desaturase (SCD)-1 in various organisms, including humans. Additionally, myristoleic acid is a substrate for the cytochrome P450 enzyme CYP102D1, which mediates cell metabolism. Because it is an amphipathic acid, it may be able to integrate into cell membranes, creating structural defects and causing cell death at high concentrations2. Myristoleic acid levels in humans can also be modulated by the gut microbiome, and several studies have shown that microbes can produce or consume myristoleic acid.

Myristoleic acid and cancer

S. repens extracts have been historically used to treat prostatic hyperplasia and nonbacterial prostatitis, and myristoleic acid is the main cytotoxic component of this extract. In an in vitro model of prostate cancer, myristoleic acid causes cell death via both apoptosis and necrosis of LNCaP cells, a human prostatic carcinoma cell line3. These data suggest that myristoleic acid may be an attractive antitumor agent for prostate cancer. However, further studies are needed to examine the effects of myristoleic acid on primary tumors.

Myristoleic acid and endocrine disorders

Long-term consumption of the ginseng root has been shown to have anti-obesity effects. Notably, ginseng promotes the growth of Enterococcus faecalis, a gut bacterial species that produces high levels of myristoleic acid and other long chain fatty acids. Among several fatty acids, myristoleic was shown to be the most effective at upregulating brown adipocyte oxygen consumption and beige fat formation in vitro and reducing mouse weight gain in vivo4. Downregulation of the enzyme Acyl- CoA thioesterase, which contributes to myristoleic acid biosynthesis by E. faecalis, reverses the protective effects of myristoleic acid against weight gain in mice, suggesting that it may be a promising therapeutic for the prevention of obesity.

Myristoleic acid may also play an important protective role against nonalcoholic fatty liver disease (NAFLD). High-fat/high-sucrose diet-fed mice supplemented with nobiletin, a naturally occurring polymethoxyflavone, had reduced signs of NAFLD along with increased Allobaculum and Lactobacillus in the gut and increased systemic levels of myristoleic acid5. When fed myristoleic acid, these mice displayed reduced body weight, total triglycerides, total cholesterol, and free cholesterol, and reversed hepatocyte ballooning or degeneration. These results suggest that myristoleic acid oral supplementation may be a viable treatment for NAFLD and other chronic liver diseases, such as nonalcoholic steatohepatitis.

Myristoleic acid and bone health

Administration of myristoleic acid to mice significantly prevents bone loss, osteoclast formation, and differentiation. Furthermore, osteoclasts treated with myristoleic acid show abnormal actin ring formation and abnormal shape. In osteoclasts, myristoleic acid suppresses the kinase activity of Src by inhibiting myristolyation and blocks Pyk2 phosphorylation indirectly. This relationship may be due to myristoleic acid’s ability to inhibit N-myristoyl-transferase, an essential enzyme that aids osteoclast cytoskeleton rearrangement. These results suggest that myristoleic acid may be a new therapeutic candidate for osteoporosis and other bone disorders6.

Myristoleic acid and skin and hair disorders

Cutibacterium acnes colonizes the human skin and contributes to the pathogenesis of acne vulgaris. Although often resistant to antibiotics, biofilm formation by this bacterium has been effectively inhibited by myristoleic acid, which inhibits cell growth and bacterial excretion of extracellular polymeric substances and reduces cell hydrophobicity. Treatment of C. acnes bacteria with myristoleic acid upregulates several lipase genes, which are hypothesized to play a role in the conversion of myristoleic acid to a less toxic metabolite. Therefore, myristoleic acid may be useful for treating or preventing acne and C. acnes-associated diseases. However,  further studies are needed to confirm its ability to inhibit C. acnes infection and acne development in vivo7.

Myristoleic acid is also important for the biosynthesis of the bacterial pyoverdine siderophore. Siderophores are virulence factors that drive iron sequestration by several bacteria species, including Pseudomonas aeruginosa, which can also play a role in acne development. Because the myristoleic acid residue is removed from the pyoverdine siderophore in P. aeruginosa prior to excretion, the toxic effects of myristoleic acid may be evident in extracellular bacterial space8.

Treating hamster flank organ models, comprised of dermal melanocytes, sebaceous glands, and hair follicles, with myristoleic acid and other related fatty acids inhibits the growth at the site of topical application9. This suggests that myristoleic acid may be useful as a topical treatment for skin disorders, such as acne and androgenic alopecia.

Hair loss is caused by disruption of the hair growth cycle in dermal papilla cells, found at the base of the hair follicle. Myristoleic acid may protect against hair loss in disorders such as alopecia through its ability to activate the Wnt pathway, which promotes dermal papilla cell proliferation and autophagosome formation10.

Myristoleic acid and research

As of March 2024, there are 157 citations for myristoleic acid in research publications (excluding books and documents) on Pubmed. As researchers continue to unravel the pharmacological and physiological mechanisms of myristoleic acid, more research, both in vitro and in vivo, is required to assess its potential use for the treatment of various cancers as well as endocrine, skin, and bone disorders.

References

  1. National Library of Medicine, National Center for Biotechnology Information. PubChem Compound Summary, Myristoleic acid (CID 5281119). https://pubchem.ncbi.nlm.nih.gov/compound/Myristoleic-acid
  2. Desbois AP and Smith VJ. Antibacterial free fatty acids: Activities, mechanisms of action and biotechnological potential. Appl Microbiol Biotechnol. 2010;85(6):1629-1642. doi:10.1007/S00253-009-2355-3/FIGURES/3
  3. Iguchi K, Okumura N, Usui S, et al. Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells. Prostate. 2001;47(1):59-65. doi:10.1002/PROS.1047
  4. Quan LH, Zhang C, Dong M, et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation. Gut. 2020;69(7):1239-1247. doi:10.1136/GUTJNL-2019-319114
  5. Li SZ, Zhang NN, Yang X, et al. Nobiletin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Myristoleic Acid Metabolism. J Agric Food Chem. 2023;71(19):7312-7323. doi:10.1021/ACS.JAFC.2C08637
  6. Kwon JO, Jin WJ, Kim B, Kim HH, Lee ZH. Myristoleic acid inhibits osteoclast formation and bone resorption by suppressing the RANKL activation of Src and Pyk2. Eur J Pharmacol. 2015;768:189-198. doi:10.1016/J.EJPHAR.2015.10.053
  7. Kim YG, Lee JH, Lee J. Antibiofilm activities of fatty acids including myristoleic acid against Cutibacterium acnes via reduced cell hydrophobicity. Phytomedicine. 2021;91. doi:10.1016/J.PHYMED.2021.153710
  8. Hannauer M, Schäfer M, Hoegy F, et al. Biosynthesis of the pyoverdine siderophore of Pseudomonas aeruginosa involves precursors with a myristic or a myristoleic acid chain. FEBS Lett. 2012;586(1):96-101. doi:10.1016/J.FEBSLET.2011.12.004
  9. Liao S, Lin J, Dang MT, et al. Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid. Arch Dermatol Res. 2001;293(4):200-205. doi:10.1007/S004030000203/METRICS
  10. Choi YK, Kang J il, Hyun JW, et al. Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells. Biomol Ther (Seoul). 2021;29(2):211-219. doi:10.4062/BIOMOLTHER.2020.169