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Regimen Lab Skincare Encyclopedia

Essential Fatty Acids


Regimen's Take

What are essential fatty acids?


Essential fatty acids (EFAs) are polyunsaturated fatty acids (PUFAs) which humans are unable to synthesize themselves, and thus can only be obtained through dietary intake. Plants are the primary source of EFAs as they contain the enzymes required to synthesize these compounds which humans lack. Plant oils, such as safflower, grape seed, sunflower, palm, and cottonseed, are significant sources of LA with low proportions of ALA [1]. Significant sources of ALA are more limited, as this EFA is mainly obtained through green leafy vegetables, flaxseed, walnuts, soybean, and canola oils [1].

Brief History

The concept of EFAs was first introduced 95 years ago by Burr and Burr [2]. A condition caused by the exclusion of fatty acids from the diet which manifested cutaneous symptoms in rats was reported. Cutaneous symptoms include redness, scaling, itch, poor wound healing, increased trans-epidermal water loss, and are characteristic of what is now deemed as essential fatty acid deficiency (EFAD) [3]. Once the diet was supplemented with PUFAs, these symptoms reversed indicating that EFAs are a key component in maintaining skin barrier function. 

However, the use of topical EFAs to treat cutaneous symptoms arising from EFAD was not investigated until the 1970s. It was observed that in EFA-deficient rats and EFA-deficient humans impaired barrier function could be restored following topical application of EFAs and two mechanisms were later proposed to explain these findings. It was hypothesized that linoleic acid either had (i) a direct structural involvement in skin barrier membranes, or (ii) it was first converted to prostaglandins for the regulation of keratinization and epidermal replication processes [4]. Since then, research efforts have disproved these early hypotheses and provided new evidence on EFAs biochemical and physical roles in maintaining skin barrier function.


PUFAs can be divided into two families, n-3 and n-6, according to their chemical structure. Omega-3 FAs have an acyl chain composed of 18 carbon atoms and contain an unsaturated (double) bond three carbon atoms away from the methyl terminal (n-3 position) of the molecule. Omega-6 FAs also contain 18 carbon atoms in their acyl chain, but the double bond is found six carbons away from the methyl terminal (n-6 position). At the other end of both EFA chains is a carboxyl group composed of a carbon atom double bonded to an oxygen atom (C=O) and single bonded to a hydroxyl group (-OH).

Although all EFAs are PUFAs, not all PUFAs are EFAs. The term EFAs is specifically used to refer to linoleic acid (LA) and alpha-linolenic acid (ALA). LA and ALA are the parent fatty acids (FAs) of the omega-6 and omega-3, respectively, families from which other PUFAs are derived. LA is the precursor for the biosynthesis of the omega-6 derivatives gamma-linolenic acid (GLA), dihomo-gamma linolenic acid (DGLA), arachidonic acid (AA), docosatetraenoic acid, and docosapentaenoic acid [5]. ALA is the precursor for the biosynthesis of the omega-3 derivatives octadecatetraenoic acid, eicosatetraenoic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA) [5].

What are their benefits on the skin?

Barrier Repair

The skin is the first organ to be affected by EFA-deficiency as EFAs play a significant role in maintaining the permeability barrier. As levels of EFAs in the skin decrease, especially LA, trans-epidermal water loss (TEWL) increases. Impaired barrier function is often associated with skin diseases such as atopic dermatitis (AD) or psoriasis. EFAs make up one component of the 3:1:1:1 ratio which is known to improve and accelerate barrier recovery. Structurally, when EFAs are applied in this lipid mixture, they form lamellar layers with ceramides and cholesterol to reduce TEWL. LA is the EFA most often used in physiologic lipid barrier repair studies. Topical applications of various plant oils enriched in EFAs are also known to improve cutaneous symptoms, such as erythema and inflammation, that are associated with poor barrier function.


Omega-3 fatty acids are thought to play a role in skin inflammation due to their ability to reduce the production of proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha, for immune modulation. PUFAs, specifically dihomo-gamma linolenic acid (DGLA), are converted by the epidermal enzyme 15-lipoxygenase into anti-inflammatory mediators which compete with the metabolism of the LA derivative arachidonic acid (AA). Through this direct competition, the production of the inflammatory mediator leukotriene B4, which is derived from the proinflammatory enzyme 5-lipoxygenase on AA, is reduced [6].

Wound Healing

Cutaneous wound healing can broadly be divided into three stages: inflammation, proliferation, and maturation. The inflammatory phase is initiated and amplified by pro-inflammatory cytokines. Cell migration and the release of arachidonic acid (AA) during this stage play a key role in the wound healing process and have a large influence on final tissue repair [7]. As linoleic acid is a precursor to the formation of AA, it is thought that it may have a role in modifying the inflammatory stage during wound healing. The topical application of LA on wounds has been shown to have a minor improvement in healing during the first 48 hours, while the topical application of ALA significantly delays wound closure [7]. Although the effects of LA and ALA on wound healing are opposing, it suggests that n-6 and n-3 PUFAs have a relevant role in modulating inflammatory responses at wound sites.


Patients affected by acne are reported to have a linoleic acid deficiency in their skin surface lipids when compared to normal subjects [8]. It is also reported that there is an inverse relationship between sebum secretion rate and linoleate present in the wax esters of the skin, with high secretion rates being characteristic of acne [9]. It is hypothesized that lower levels of linoleate in sebum induce a localized EFA-deficiency in comedo-cells of the follicular epithelium, thus inducing hyperkeratosis and promoting bacterial growth and inflammation [10]. These symptoms can be reversed indirectly by decreasing the amount of sebum secreted, or directly by increasing the concentration of LA in the skin. Topical application of LA has been found to reduce the size of microcomedones on the faces of acne-prone patients [11].


Both LA and ALA are capable of decreasing melanin production and inhibiting tyrosinase for the suppression of hyperpigmentation in the skin [12]. It is suggested that LA is able to regulate the proteolysis of tyrosinase, which results in the alteration of tyrosinase protein [12].

How do Essential Fatty acids work?

Free fatty acids (FFAs) compose approximately 15% of the stratum corneum (SC) multilamellar lipid matrix; of those FFAs, 2% are in the form of linoleic acid [13]. Linoleic acid is one of the two unsaturated FFAs present in the SC and plays key structural roles in the epidermis. In contrast, omega-3 PUFAs, like alpha-linolenic acid, are not considered to have fundamental roles in maintaining the structure of the skin barrier as the SC is largely devoid of them.

In the body, EFAs obtained through dietary intake can be metabolized following three different pathways [1]:

  • Beta-oxidation to provide energy for ATP formation
  • Esterification into cellular lipids as phospholipids, triacylglycerols, and cholesterol esters
  • Being an initiating structure for the process of elongation and desaturation through enzymatic reactions to create long-chain PUFAs

The small portion of EFAs that is elongated and desaturated gives rise to their longer-chain PUFA derivatives through an alternating metabolism sequence. The desaturation and elongation processes occur near the carboxyl group end of the chain, thus preserving the location of the double bond relative to the methyl terminal [14]. As the n-3 and n-6 positions of the double bond in each respective EFA is retained during metabolism, no interconversion between PUFA families occurs. Both LA and ALA are competitive inhibitors of one another in this process as they utilize the same enzymes, however preference is given to ALA by Δ-6 desaturase in the first rate-limiting desaturation step [14]. Although LA and ALA, as well as their long-chain derivatives can be found in the skin, the required Δ-6 and Δ-5 desaturase enzymes for the metabolism sequence are not. Therefore, the epidermis uptakes dietary EFAs and PUFAs from the liver via the bloodstream.

With the absence of Δ-6 and Δ-5 desaturase enzymes in the epidermis, the earlier hypothesis that topical EFAs, specifically LA, are converted to prostaglandins for barrier repair is rejected [15]. The current widely accepted theory as to why EFA supplementation improves cutaneous symptoms in EFA deficiency is that linoleic acid is a structural precursor for ceramides. Ceramide structures consist of a sphingosine or sphingoid base amide linked to a fatty acid. O-acylated ceramides are long-chain ceramides with an O-acylated linoleic acid for the fatty acid-linked portion. In order for these ceramides to form in the SC, several metabolic steps must take place, including the synthesis of very long-chain fatty acids, omega-hydroxylation of the fatty acids, and esterification of the omega-hydroxy group with linoleic acid [16]. Evidence also suggests that LA-linked O-acylglucosylceramides also play a key role in maintaining skin barrier function [14]. O-acylglucosylceramides are rich in linoleate, with the linoleate portion linked to the omega hydroxyl group. They are largely found in the stratum granulosum and are believed to be associated with lamellar granules for the maintenance of skin barrier function [5]. Due to the linoleate moiety, these molecules take on a unique geometrical conformation that is a precursor for the formation of sheets of stacked lipid lamellae which surround corneocytes in the SC [5, 14]. In EFA-deficiency it has been noted that oleic acid replaces the linoleate portion in O-acylglucosylceramides, causing changes in geometry and, as a result, barrier function is impaired due to the inability to form normal lipid lamellae [17].

LA can also be metabolized by the epidermal enzyme 15-lipoxygenase into its metabolite 13-hydroxyoctadecadienoic acid (13-HODE); a minor by-product of this metabolic pathway is 9-HODE [18]. As the epidermis is not capable of desaturating LA into gamma-linolenic acid (GLA), the 15-lipoxygenase metabolic pathway is preferred which suggests that 13-HODE may play a key role in the reversal of skin scaliness observed in EFA-deficiency. 13-HODE is incorporated into epidermal phosphatidylinositol 4,5-bisphophate and then released into a novel 13-HODE-containing diacylglycerol which is believed to modulate epidermal hyperproliferation and differentiation [18].

The LA derivative dihomo-gamma linolenic acid (DGLA) is formed readily by the elongation of dietary GLA via an elongase enzyme present in the epidermis [19]. Although DGLA is present in small amounts, when its concentration is elevated, the epidermal enzyme cyclooxygenase metabolizes it to the 1-series prostaglandin (PGE1) [18]. The 15-lipoxygenase enzyme can also metabolize DGLA into 15-hydroxyeicosatrienoic acid (15-HETrE) [18]. PGE1 and 15-HETrE are believed to play roles in epidermal inflammatory hyperproliferation.

Conjugated linoleic acid (CLA) is an isomeric derivative of LA and differs from it in respect to the position and configuration of the double bonds. It is believed that the two isomers cis-9, trans-11 and trans-10, cis-12 are the most biologically active [14]. Of the two, the cis-9, trans-11 CLA isomer is a natural PPAR mediator [6]. LA is also known to be a potent PPAR-alpha activator for the regulation of keratinocyte proliferation, inflammation, and barrier homeostasis [20].

Do Essential Fatty Acids penetrate the skin?

EFAs are able to perturb the skin and behave as penetration enhancers for delivery of compounds. They are able to penetrate the skin due to their alkyl chain length, chemical structure, and degree of unsaturation. Both LA and ALA contain an 18-carbon (C18) unsaturated alkyl chain, which is near optimum length for potent penetration [21]. These two EFAs also adopt the cis-configuration instead of the trans-configuration which allows them to better disturb the intercellular lipid packing of the epidermis. The higher degree of unsaturation (> 1) present in LA and ALA also contributes to their enhanced activity. However, the increase from two cis-double bonds in LA (degree of unsaturation = 2) to three in ALA (degree of unsaturation = 3), results in lower penetration due to structural changes that occur due to the additional double bond [22]. Linolenic acid contains kinks and bends due to the three cis-double bonds which is believed to cause steric hindrance during partition into the SC [23]. Therefore, LA better penetrates the skin than ALA.

When formulated with hydrophilic co-solvents (i.e. propylene glycol), the efficacy of SC penetration by these long-chain fatty acids increases. The dermal irritancy associated with trans-dermal penetration can also be mitigated by use of the mono-ester of LA, linoleate, conjugated with propylene glycol [22].

Usage Rate and Effective Concentration

Essential fatty acids are best formulated in the 3:1:1:1 molar ratio for barrier repair. It is also best to use pure EFAs as this allows for control over the final concentration present in the formula. Caution should be taken when using EFA-enriched plant oils, as it should be ensured that they are low oleic acid as it is not great for barrier repair.

Formulation Considerations

Essential fatty acids are oil soluble and are most often incorporated into the oil phase of product formulations. Both linoleic acid and alpha-linolenic acid are heat sensitive, so they must be processed at lower temperatures to avoid degradation. They are also easily oxidized, so it is best to include an antioxidant such as tocopherol in the formulation.

Clinical Studies


[1] Balić, A., Vlašić, D., Žužul, K., Marinović, B., & Mokos, Z. B. (2020). Omega-3 Versus Omega-6 Polyunsaturated Fatty Acids in the Prevention and Treatment of Inflammatory Skin Diseases. International Journal of Molecular Sciences, 21, 741. DOI: 10.3390/ijms21030741

[2] Burr, G. O., & Burr, M. M. (1929). A New Deficiency Disease Produced by the Rigid Exclusion of Fat From the Diet. The Journal of Biological Chemistry, 82 (2), 345-367. DOI: 10.1016/S0021-9258(20)78281-5

[3] Wright, S. (1991). Essential Fatty Fatty Acids and Atopic Dermatitis. Pediatric Allergy and Immunology, 2 (S1), 23-30. DOI: 10.1111/j.1399-3038.1991.tb00317.x  

[4] Prottey, C. (1978). Essential Fatty Acids and Skin Scaliness. In R. Marks & P. J. Dykes (Eds.), The Ichthyoses (pp. 11-17). Springer. DOI: 10.1007/978-94-010-9851-9

[5] Wright, S. (1989). Essential Fatty Acids and the Skin. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 38 (4), 229-236. DOI: 10.1016/0952-3278(89)90126-9  

[6] McCusker, M. M., & Grant-Kels, J. M. (2010). Healing Fats of the Skin: The Structural and Immunologic Roles of the Omega-6 and Omega-3 Fatty Acids. Clinics in Dermatology, 28, 440-451. DOI: 10.1016/j.clindermatol.2010.03.020 

[7] Cardos, C. R. B., Souza, M. A., Ferro, E. A. V., & Favoreto, S., Pena, J. D. O. (2004). Influence of Topical Administration of n-3 and n-6 Essential and n-9 Nonessential Fatty Acids on the Healing of Cutaneous Wounds. Wound Repair and Regeneration, 12 (2), 235-243. DOI: 10.1111/j.1067-1927.2004.012216.x

[8] Morello, A. M., Downing, D. T., & Strauss, J. S. (1976). Octadecadienoic Acids in the Skin Surface Lipids of Acne Patients and Normal Subjects. Journal of Investigative Dermatology, 66 (5), 319-323. DOI: 10.1111/1523-1747.ep12482300 

[9] Stewart, M. E., Wertz, P. W., Grahek, M. O., & Downing, D. T. (1985). Relationship Between Sebum Secretion Rates and the Concentration of Linoleate in Sebum and Epidermal Lipids. Clinical Research, 33, 684 (Abst.). 

[10] Downing, D. T., Stewart, M. E., Wertz, P. W., & Strauss, J. S. (1986). Essential Fatty Acids and Acne. Journal of the American Academy of Dermatology, 14 (2), 221-225. DOI: 10.1016/s0190-9622(86)70025-x

[11] Letawe, C., Boone, M., & Piérared, G. E. (1998). Digital Image Analysis of the Effect of Topically Applied Linoleic Acid on Acne Microcomedones. Clinical and Experimental Dermatology, 23, 56-58. DOI: 10.1046/j.1365-2230.1998.00315.x

[12] Ando, H., Funasaka, Y., Oka, M., Ohashi, A., Furumura, M., Matsunaga, J., Matsunaga, N., Hearing, V. J., & Ichihashi, M. (1999). Possible Involvement of Proteolytic Degradation of Tyrosinase in the Regulatory Effect of Fatty Acids on Melanogenesis.

[13] Menon, G. K., Cleary, G. W., & Lane, M. E. (2012). The Structure and Function of the Stratum Corneum. International Journal of Pharmaceutics, 435 (1), 3-9. DOI: 10.1016/j.ijpharm.2012.06.005 

[14] Rhodes, E. L., & Storey, A. (2006). Essential Fatty Acids: Biological Functions and Potential Applications in the Skin. In M. Loden & H. I. Maibach (Eds.), Dry Skin and Moisturizers (pp. 319-340). Taylor & Francis Group. DOI: 10.1201/b14251

[15] Chapkin, R.S., Ziboh, V. A., Marcelo, C. L., & Voorhees, J. J. (1986). Metabolism of Essential Fatty Acids by Human Epidermal Enzyme Preparations: Evidence of Chain Elongation. Journal of Lipid Research, 27, 945-954. DOI: 10.1016/S002-2275(20)38771-X 

[16] Hansen, H. S. (2012). The Fatty Acids and the Skin: A Focus on the n-6 Family of Unsaturated Fatty Acids. In V.R. Preedy (Eds.), Handbook of Diet, Nutrition, and the Skin (pp. 45-56). Wageningen Academic Publishers. DOI: 10.3920/978-90-8686-729-5

[17] Elias, P. M., Brown, B. E., & Ziboh, V. A. (1980). The Permeability Barrier in Essential Fatty Acid Deficiency: Evidence for a Direct Role for Linoleic Acid in Barrier Function. The Journal of Investigative Dermatology, 74 (4), 230-233. DOI: 10.1111/1523-1747.ep12541775 

[18] Ziboh, V. A., Miller, C. C., & Cho, Y. (2000). Metabolism of Polyunsaturated Fatty Acids by Skin Epidermal Enzymes: Generation of Antiinflammatory and Antiproliferative Metabolites. American Journal of Clinical Nutrition, 71 (1 Suppl), 361S-366S. DOI: 10.1093/ajcn/71.1.361s    

[19] Ziboh, V. A., & Chapkin, R. S. (1988). Metabolism and Function of Skin Lipids. Progress in Lipid Research, 27, 81-105. 

[20] Yu, K., Bayona, W., Kallen, C. B., Harding, H. P., Ravera, C. P., McMahon, G., Brown, M., & Lazar, M. A. (1995). Differential Activation of Peroxisome Proliferator-activated Receptors by Eicosanoids. Journal of Biological Chemistry, 270 (41), 23975-23983. DOI: 10.1074/jbc.270.41.23975

[21] Mittal, A., Sara, U. V. S., Ali, A., & Aqil, M. (2009). Saturated Fatty Acids as Skin Penetration Enhancers-A Review. Current Drug Delivery, 6, 274-279.

[22] Ben-Shabat, S., Baruch, N., & Sintov, A. C. (2007). Conjugates of Unsaturated Fatty Acids with Propylene Glycol as Potentially Less-Irritant Skin Penetration Enhancers. Drug Development and Industrial Pharmacy, 33, 1169-1175. DOI: 10.1080/03639040701199258  

[23] Choi, J., Choi, M-K., Chong, S., Chung, S-J., Shim, C-K., & Kin, D-D. (2012). Effect of Fatty Acids on the Transdermal Delivery of Donepezil: In Vitro and In Vivo Evaluation. International Journal of Pharmaceutics, 422, 83-90. DOI: 10.1016/j.ijpharm.2011.10.031 

[24] Elias, P. M., Brown, B. E., & Ziboh, V. A. (1980). The Permeability Barrier in Essential Fatty Acid Deficiency: Evidence for a Direct Role for Linoleic Acid in Barrier Function. Journal of Investigative Dermatology, 74, 230-233. DOI: 10.1111/1523-1747.ep12541775   

[25] Prottey, C., Hartop, P. J., Black, J. G., & McCormack, J. I. (1976). The Repair of Impaired Epidermal Barrier Function in Rates by the Cutaneous Application of Linoleic Acid. British Journal of Dermatology, 94, 13-21. DOI: 10.1111/j.1365-2133.1976.tb04336.x   

[26] Prottey, C. (1977). Investigation of Functions of Essential Fatty Acids in the Skin. British Journal of Dermatology, 97, 29-38. DOI: 10.1111/j.1365-2133.1977.tb15424.x  

[27] Houtsmuller, U. M. T., & Van Der Beek, A. (1981). Effects of Topical Application of Fatty Acids. Progress in Lipid Research, 20, 219-224. DOI: 10.1016/0163-7827(81)90041-2 

[28] Prottey, C., Hartop, P. J., & Press, M. (1975). Correction of the Cutaneous Manifestations of Essential Fatty Acid Deficiency in Man by Application of Sunflower-Seed Oil to the Skin. Journal of Investigative Dermatology, 64 (4), 228-234. DOI: 10.1111/1523-1747.ep12510667   

[29] Brod, J., Traitler, H., Studer, A., & De Lacharriere, O. (1988). Evolution of Lipid Composition in Skin Treated with Blackcurrant Seed Oil. International Journal of Cosmetic Science, 10 (4), 149-159. DOI: 10.1111/j.1467-2494.1988.tb00014.x

[30] Danby, S. G., AlEnezi, T., Sultan, A., Lavender, T., Chittock, J., Brown, K., & Cork, M. J. (2013). Effect of Olive and Sunflower Seed Oil on the Adult Skin Barrier: Implications for Neonatal Skin Care. Pediatric Dermatology, 30, 42-50. DOI: 10.1111/j.1525-1470.2012.01865.x

[31] Conti, A., Rogers, J., Verdejo, P., Harding, C. R., & Rawlings, A. V. (1996). Seasonal Influences on Stratum Corneum Ceramide 1 Fatty Acids and the Influence of Topical Essential Fatty Acids. International Journal of Cosmetic Science, 18, 1-12. DOI: 10.1111/j.1467-2494.1996.tb00131.x  

[32] Wu, D. C., & Goldman, M. P. (2017). A Topical Anti-Inflammatory Healing Regimen Utilizing Conjugated Linoleic Acid for Use Post-Ablative Laser Resurfacing of the Face: A Randomized, Controlled Trial. Journal of Clinical and Aesthetic Dermatology, 10 (10), 12-17. 

[33] Takemura, N., Takahashi, K., Tanaka, H., Ihara, Y., Ikemoto, A., Fujii, Y., & Okuyama, H. (2002). Dietary, but not Topical, Alpha-Linolenic Acid Suppresses UVB-Induced Skin Injury in Hairless Mice when Compared with Linoleic Acid. Photochemistry and Photobiology, 76 (6), 657-663. DOI: 10.1562/0031-8655(2002)076<0657:dbntal>;2    

[34] Jelenko, C., Wheeler, M. L., & Scott, T. H. (1972). Studies in Burns XI. Ethyl Linoleate: The Water-Holding Lipid of the Skin. B. Effects on In Vivo Burn Eschar. The Journal of Trauma: Injury, Infection, and Critical Care, 12 (11), 974-978.  

[35] Lania, B. G., Morari, J., de Almeida, A. R., da Silva, M. N., Vieira-Damiani, G., de Almeida Lins, K., César, C. L., Velloso, L. A., Maia, N. B., Cintra, M. L., & Velho, P. E. N. F. (2019). Topical Essential Fatty Acid Oil on Wounds: Local and Systemic Effects. PLoS One, 14 (1), 1-15. DOI: 10.1371/journal.pone.0210059  

[36] Charakida, A., Charakida, M., & Chu, A. C. (2007). Double-Blind, Randomized, Placebo-Controlled Study of a Lotion Containing Triethyl Citrate and Ethyl Linoleate in the Treatment of Acne Vulgaris. British Journal of Dermatology, 157, 569-574. DOI: 10.1111/j.1365-2133.2007.08083.x

[37] Perisho, K., Wertz, P. W., Madison, K. C., Stewart, M. E., & Downing, D. T. (1988). Fatty Acids of Acylceramides from Comedones and From the Skin Surface of Acne Patients and Control Subjects. Journal of Investigative Dermatology, 90 (3), 350-353. DOI: 10.1111/1523-1747.ep12456327