Palmitoleic Acid is a monounsaturated fatty acid belonging to the omega-7 family. It is naturally present in human sebum, making it highly compatible with the skin. Palmitoleic acid is found in significant amounts in plant oils such as macadamia oil and sea buckthorn oil, as well as in certain fish oils. It is particularly known for its regenerative, anti-inflammatory, and moisturizing properties. It is frequently used in skincare products to repair the skin barrier, promote healing, and improve skin elasticity.

Chemical Composition and Structure

Itis a monounsaturated fatty acid with a double bond located between the seventh and eighth carbon atoms from the end of the chain, classifying it as an omega-7. This chemical structure gives it a remarkable ability to penetrate the skin, making it an excellent emollient and skin regenerator. Its structure, similar to fatty acids naturally found in the skin, makes it effective in strengthening and protecting the skin barrier.

Physical Properties

Palmitoleic acid is a clear or slightly yellow liquid, with a light texture and a low melting point. It is oil-soluble and more stable compared to other fatty acids, making it ideal for use in long-lasting cosmetic products. Due to its lightweight texture, it is easily absorbed into the skin without leaving a greasy residue, contributing to smooth, hydrated skin.

Production Process

Palmitoleic acid is extracted from natural sources such as macadamia oil and sea buckthorn oil through cold pressing or supercritical CO2 extraction processes. These methods preserve the chemical integrity of the fatty acids, ensuring that the beneficial properties of palmitoleic acid remain intact. 

• Selection of Raw Materials: Palmitoleic acid is primarily extracted from plant and animal sources, such as macadamia oil, sea buckthorn oil, and animal fat. These sources are selected for their high content of palmitoleic acid.

• Extraction: The extraction of palmitoleic acid occurs through appropriate methods, such as cold pressing or solvent extraction. In cold pressing, the fruits or seeds are mechanically pressed to obtain the oil, while in solvent extraction, the plant materials are immersed in a solvent to dissolve the oils.

• Filtration: After extraction, the obtained oils are filtered to remove undissolved solids and impurities, resulting in pure, high-quality oils.

• Refining: The extracted oil may be refined to remove further impurities and improve the flavor and appearance of the final product. This process may include deodorization and bleaching.

• Hydrolysis (If Necessary): In some cases, palmitoleic acid can be isolated through hydrolysis of the extracted oils, using specific acids or enzymes to break down triglycerides and release the fatty acid.

• Quality Control and Packaging: Finally, palmitoleic acid undergoes quality control checks to verify its purity, efficacy, and compliance with standards. After analysis, it is packaged in appropriate containers for distribution and use in cosmetic products and dietary supplements.

Applications

• Skincare: Palmitoleic acid is used in serums, creams, and facial oils for its moisturizing and regenerative properties. It is ideal for mature, dry, or damaged skin, as it helps restore skin elasticity and softness.

• Anti-aging Products: With its ability to stimulate cell regeneration and improve skin elasticity, palmitoleic acid is often included in anti-aging products to reduce wrinkles and fine lines.

• Healing Products: Palmitoleic acid is known for its healing properties, promoting wound healing and skin recovery, making it ideal for after-sun treatments and soothing irritated skin.

Health and Safety Considerations

Safety in Use
Palmitoleic acid is considered safe for use in cosmetic products. It is well tolerated by the skin and poses no significant risks of irritation or sensitization. Major regulatory authorities, including the European Union and the FDA, approve its use in skincare products.

Allergic Reactions
Allergic reactions to palmitoleic acid are rare, but it is advisable to perform a patch test before use on sensitive or reactive skin, especially if the acid is derived from plant sources like macadamia oil.

Toxicity and Carcinogenicity
It is considered beneficial for skin health due to its anti-inflammatory and regenerative properties.

Environmental Considerations
Palmitoleic acid is extracted from renewable sources such as plants and trees, including sea buckthorn and macadamia. Sustainable extraction techniques, such as cold pressing and CO2 extraction, make the production of palmitoleic acid environmentally friendly and biodegradable.

Regulatory Status
Palmitoleic acid is approved for use in cosmetics by major regulatory authorities, such as the European Union and the FDA in the United States. It is widely used in skincare formulations, particularly in anti-aging and regenerative products.

Molecular Formula  C₁₆H₃₀O₂

Molecular Weight  254.41 g/mol

CAS     373-49-9

UNII    209B6YPZ4I

EC Number  206-765-9

CHEMBL453509

DTXSID0041197

Synonyms:

cis-9-Hexadecenoic acid

palmitoleate

palmitelaidic acid

References__________________________________________________________________________

Chen Y, Mai Q, Chen Z, Lin T, Cai Y, Han J, Wang Y, Zhang M, Tan S, Wu Z, Chen L, Zhang Z, Yang Y, Cui T, Ouyang B, Sun Y, Yang L, Xu L, Zhang S, Li J, Shen H, Liu L, Zeng L, Zhang S, Zeng G. Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis. Gut Microbes. 2023 Jan-Dec;15(1):2211501. doi: 10.1080/19490976.2023.2211501.

Abstract. Magnitude and diversity of gut microbiota and metabolic systems are critical in shaping human health and diseases, but it remains largely unclear how complex metabolites may selectively regulate gut microbiota and determine health and diseases. Here, we show that failures or compromised effects of anti-TNF-α therapy in inflammatory bowel diseases (IBD) patients were correlated with intestinal dysbacteriosis with more pro-inflammatory bacteria, extensive unresolved inflammation, failed mucosal repairment, and aberrant lipid metabolism, particularly lower levels of palmitoleic acid (POA). Dietary POA repaired gut mucosal barriers, reduced inflammatory cell infiltrations and expressions of TNF-α and IL-6, and improved efficacy of anti-TNF-α therapy in both acute and chronic IBD mouse models. Ex vivo treatment with POA in cultured inflamed colon tissues derived from Crohn's disease (CD) patients reduced pro-inflammatory signaling/cytokines and conferred appreciable tissue repairment. Mechanistically, POA significantly upregulated the transcriptional signatures of cell division and biosynthetic process of Akkermansia muciniphila, selectively increased the growth and abundance of Akkermansia muciniphila in gut microbiota, and further reprogrammed the composition and structures of gut microbiota. Oral transfer of such POA-reprogrammed, but not control, gut microbiota induced better protection against colitis in anti-TNF-α mAb-treated recipient mice, and co-administration of POA with Akkermansia muciniphila showed significant synergistic protections against colitis in mice. Collectively, this work not only reveals the critical importance of POA as a polyfunctional molecular force to shape the magnitude and diversity of gut microbiota and therefore promote the intestinal homeostasis, but also implicates a new potential therapeutic strategy against intestinal or abenteric inflammatory diseases.

Bermúdez MA, Pereira L, Fraile C, Valerio L, Balboa MA, Balsinde J. Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer. Cells. 2022 Jul 8;11(14):2146. doi: 10.3390/cells11142146.

Abstract. In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, β cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations.

Guo X, Jiang X, Chen K, Liang Q, Zhang S, Zheng J, Ma X, Jiang H, Wu H, Tong Q. The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice. Nutrients. 2022 Apr 1;14(7):1482. doi: 10.3390/nu14071482. 

Abstract. Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver's response to nutrient deprivation, such as fatty acid oxidation and ketone body formation. However, it is unknown whether SIRT3 also regulates gluconeogenesis. Our study revealed that palmitoleic acid reduced hepatic gluconeogenesis and the expression of SIRT3 under high-fat diet conditions. Overexpression of SIRT3 in the liver and hepatocytes enhanced gluconeogenesis. Further study revealed that SIRT3 played a role in enhancing the activities of gluconeogenic enzymes, such as PEPCK, PC, and MDH2. Therefore, our study indicated that under a high-fat diet, palmitoleic acid decreased gluconeogenesis by reducing enzymatic activities of PEPCK, PC, and MDH2 by down-regulating the expression of SIRT3.

Bolsoni-Lopes A, Festuccia WT, Chimin P, Farias TS, Torres-Leal FL, Cruz MM, Andrade PB, Hirabara SM, Lima FB, Alonso-Vale MI. Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation. Lipids Health Dis. 2014 Dec 20;13:199. doi: 10.1186/1476-511X-13-199. 

Abstract. Background: Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes. Methods: For this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from mice treated with 16:1n7 (300 mg/kg/day) or oleic acid (18:1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes. Results: Treatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p)Thr172AMPKα, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16:1n7, was prevented by pharmacological inhibition of AMPK with compound C. Conclusions: In conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation.