Skip to main content
NCBI home page
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2025 Apr 24;47(5):820–826. doi: 10.1111/ics.13068

n‐3 PUFAs docosahexaenoic acid and eicosapentaenoic acid are effective natural pro‐resolution ingredients for topical skin applications

John Nip 1,✉, Kevin Hermanson 1, Jian‐ming Lee 1
PMCID: PMC12489883  PMID: 40274542

Abstract

Skin encounters many challenges that lead to an inflammatory response. Resolution of this inflammation is needed to return the skin to a healthy state. A review of the role of topical n‐3 PUFAs, particularly DHA and EPA, in resolving skin inflammation and promoting skin health is presented. A review of the literature and Unilever data on DHA/EPA pro‐resolution skin benefits. PubMed/MEDLINE, Google search of external literature as well as Unilever data relating to skin inflammation, pro‐resolution, and the role of DHA and EPA. Evidence of DHA and EPA in providing pro‐resolution of skin inflammation are summarized. DHA and EPA, and their derived specialized pro‐resolving mediators (SPMs), can attenuate the skin inflammatory response induced by various stressors and maintain skin health.

Skin encounters many challenges that lead to an inflammatory response. Resolution of this inflammation is needed to return the skin to a healthy state. A review of the role of topical n‐3 PUFAs, particularly DHA and EPA, in resolving skin inflammation and promoting skin health is presented.

graphic file with name ICS-47-820-g003.jpg

INTRODUCTION

Injury to tissues like the skin by severe trauma or pathogens, as well as everyday challenges such as UV and shaving, can lead to the release of proinflammatory chemical mediators resulting in acute inflammation. The initial signs of inflammation include redness, heat, swelling and pain, and loss of function—the five cardinal signs of inflammation [1, 2]. This initial response is needed to contain the inflammation and protect the host and is characterized by activation and recruitment of leucocytes that need to remove cellular debris from the site of inflammation. However, this inflammation needs to be resolved to prevent the inflammation from spreading or becoming chronic [3, 4]. Chronic inflammation can lead to disease. This active pro‐resolution process involves chemical mediators released by the cells which help the skin return to homeostasis [5].

Polyunsaturated fatty acids (PUFAs), especially the n‐3 PUFAs, like DHA and EPA, naturally found in the cell membrane in the form of phospholipids, ensure the skin is able to properly resolve inflammation and repair damage that has occurred in the process.

In this review, we discuss inflammation and its resolution, with emphasis on skin and the importance of pro‐resolution mediated by n‐3 polyunsaturated fatty acids, namely DHA and EPA. We used PubMed/Medline searches as well as online Google searches with relevant keywords and phrases to identify relevant articles. Searches of PubMed included key words (and combinations) such as pro‐resolution, n‐3 PUFA, inflammation, skin, lipid mediators, DHA and EPA. For example, a search using terms ‘inflammation and skin’ yielded over 55 242 articles. The articles were dated from ~1857 to 2025. All the articles were in the English language. Further, using the word ‘pro‐resolution’ in the search narrowed the number of articles to 16, ranging from 2011 to 2025. Along with combinations of the other keywords yielded lists of relevant articles that we reviewed, which are listed in the references. We also provided supporting Unilever studies to highlight the importance of DHA/EPA in pro‐resolution from topical skin applications.

Inflammation and pro‐resolution

Inflammation is a natural reaction of the body when tissues are damaged by infections, injuries or other factors. Its main goal is to repair tissue balance and defend the host. When inflammation is regulated and resolved properly, it helps the body recover and return to normal function. However, when inflammation is unregulated or unresolved, it can damage tissues and cause chronic inflammatory diseases. These conditions can involve metabolic disorders, autoimmunity, cardiovascular diseases and even cancer. Chronic inflammation can cause ongoing harm, affecting organs and overall health. We now understand that resolution is not a passive and linear stage of inflammation (from initiation to resolution), but an active and dynamic one. Pro‐resolution processes start soon after the inflammatory response begins [6] to stop the progress from non‐resolving acute inflammation to persistent chronic inflammation; these include the lowering of the local chemokine levels that prevent more immune cells (such as neutrophils) from entering the tissue. Neutrophils also have a dual role in both the acute inflammation phase and the switch from the inflammation to the resolution phase. Pro‐resolution chemical mediators consist of the SPMs such as lipoxins, resolvins, protectins and maresins that deactivate the proinflammatory signals and support resolution. Omega‐3 polyunsaturated fatty acids (n‐3 PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), play a significant role as precursors of resolvins in the resolution of inflammation. DHA and EPA are essential omega‐3 fatty acids that are obtained from dietary sources, such as fish, algae or supplements. They are incorporated into the cell membranes, where they can influence the membrane fluidity, permeability and signalling. As they are converted into SPMs by various enzymes, such as cyclooxygenases (COX), lipoxygenases (LOX) or cytochrome P450 (CYP), these molecules can bind to specific receptors on the cell surface and modulate the cellular responses to inflammation [7].

Resolvins are derived from both DHA and EPA [8] and are named based on their precursors—D series from DHA and E series from EPA. They help to reduce neutrophil infiltration, promote macrophage phagocytosis of debris and enhance tissue regeneration.

Protectins, including neuroprotectin D1 (when synthesized in neural tissues), are derived from DHA [9]. They have potent anti‐inflammatory effects and play a role in protecting neural tissues and promoting brain health [10].

Maresins are synthesized from DHA by macrophages [11]. These mediators help the resolution of inflammation and tissue regeneration and have shown potential as therapeutic agents for chronic inflammatory diseases [12].

In summary, n‐3 PUFAs like DHA and EPA are essential for the resolution of inflammation due to their conversion into SPMs, which actively facilitate the return to tissue homeostasis and health. Efforts to develop strategies based on inflammation resolution are characteristics of the field of resolution pharmacology [13].

Inflammation and pro‐resolution in the skin

Skin inflammation is a common condition that affects millions of people worldwide. It can be caused by various factors, such as infections, allergies, injuries, autoimmune disorders or environmental stressors. Skin inflammation can manifest as redness, swelling, itching, pain or heat in the affected area [1, 2]. It can also impair the skin barrier function, increase the risk of infection and affect the quality of life.

Similar to other body sites, inflammation of the skin is usually resolved by the innate immune system, which initiates a cascade of events to eliminate the inflammatory stimuli and restore tissue homeostasis [3]. However, in some cases, the resolution process can be impaired or delayed, leading to chronic or excessive inflammation. This can result in tissue damage, scarring or dysregulation of the immune system. For example, post‐inflammatory hyperpigmentation [14] is one of the typical symptoms of skin inflammation that is not completely resolved. Therefore, it is important to find ways to enhance the resolution of skin inflammation and prevent its adverse consequence of unresolved inflammation.

Importance of DHA/EPA in skin inflammation resolution

One of the potential strategies to promote the resolution of skin inflammation is to modulate the production and action of the SPMs that are generated from the metabolism of omega‐3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) [4, 5, 15]. Studies have shown that using oral or topical applications of DHA/EPA can lead to skin benefits including anti‐Inflammatory effects, to help reduce skin inflammation associated with conditions [16] like eczema, psoriasis [17] and acne. Additionally, these n‐3 PUFAs support the skin's lipid barrier, enhancing moisture retention and preventing dryness [18]. Wound healing is another area where DHA/EPA demonstrate benefit. n‐3 PUFA can also accelerate wound healing. In a Wistar rat model of age‐impaired wound healing, daily topical application of DHA (30 μM) showed faster wound healing, showing a 50% wound resolution by Day 5.75 versus Day 6.75 for untreated control [19].

Several studies have demonstrated the beneficial effects of DHA and EPA, and their derived SPMs, on the resolution of skin inflammation. For example, DHA and EPA have been shown to reduce the severity and duration of ultraviolet (UV)‐induced skin inflammation in humans [18]. UV radiation is a major environmental factor that can trigger skin inflammation and damage. It can induce the production of reactive oxygen species (ROS), pro‐inflammatory cytokines and chemokines, and activate the inflammasome pathway. DHA and EPA can attenuate the UV‐induced inflammatory response by reducing the expression of COX‐2, interleukin (IL)‐1beta, IL‐6 and tumour necrosis factor (TNF)‐alpha, and increase the expression of SPMs, such as resolvin D1 (RvD1), resolvin E1 (RvE1) and protectin D1 (PD1). These SPMs can inhibit the activation of nuclear factor (NF)‐kappaB, a key transcription factor that regulates the expression of pro‐inflammatory genes, and enhance the clearance of apoptotic neutrophils, which are the main inflammatory cells in the UV‐induced skin inflammation [4].

UV induces skin inflammation, damage and photoaging by modulating the production of eicosanoids and cytokines such as proinflammatory COX‐2. Topical application of DHA in a hairless mouse model resulted in the attenuation of COX‐2 expression [20]. In another hairless mouse model, Jin et al. [21] showed that UV‐induced epidermal hyperplasia and inflammatory cell infiltration were mitigated by topical EPA application. Furthermore, the researchers also showed that topical EPA induced stratum corneum hydration and decreased transepidermal water loss (TEWL), resulting from UV B irradiation.

DHA and EPA have also been shown to improve the resolution of atopic dermatitis (AD) in mice and humans [16]. AD is a chronic inflammatory skin disease that is characterized by pruritus and erythema. It is caused by an abnormal immune response to environmental allergens, such as dust mites, pollen or food. DHA and EPA can modulate the AD by reducing the levels of immunoglobulin (Ig)E, histamine and eosinophils, and increasing the levels of SPMs, such as RvD2, RvE2 and PD1 [16]. These SPMs can suppress the activation of mast cells, which are the main effector cells in the disease.

Evidence of skin benefits of topical or oral DHA/EPA from human studies

UV induces skin inflammation, damage and photoaging. In a human study where subjects were irradiated with UV (285–350 nM), topical application of EPA decreased UV‐induced epidermal thickening and inhibited procollagen decrease. UV‐induced increase in MMP‐1 and MMP‐9 expression was also inhibited by topical EPA application [22]. The topical application of EPA has a beneficial effect on photoaging end points.

A psoriasis study demonstrated the benefits of oral DHA/EPA supplements [23]. Ten patients with psoriasis that was resistant to conventional topical treatments were given dietary fish oil supplements, providing approximately 12 g of eicosapentaenoic acid daily for at least 6 weeks. Eight of the patients showed modest improvement in their psoriasis, with the primary effects being a reduction in erythema and scaling [23].

In a Unilever collaborative study, Lin et al. [24] showed that dietary supplementation with fish oil protected skin from pollution‐induced inflammation. In this randomized, double‐blind, placebo‐controlled trial among 65 healthy young adults in Shanghai, China, they assigned them to take either fish oil or placebo 2.5 g daily for 4 months. They collected skin samples and measured five biomarkers of skin inflammation and oxidative stress. The authors showed exposure to fine particulate matter (PM2.5) was associated with increased levels of interleukin‐1α and carbonyl protein, two biomarkers of skin inflammation and oxidative stress, in the placebo group. However, these associations were weaker or reversed in the fish‐oil group, suggesting that fish oil may have protective effects on the skin.

Evidence of skin benefits of DHA/EPA from Unilever in vitro and human studies

Further work at Unilever has focused on in vitro models of inflammation as well as clinical models. For the in vitro work, a THP‐1 cell model for inflammation was used. In this model, THP‐1 macrophages are treated with LPS to induce inflammation, which is shown as an increase in the pro‐inflammatory cytokine, IL‐6. DHA/EPA treatment of the cells resulted in a significant decrease in IL‐6 production. Similarly, the anti‐inflammatory corticosteroid, dexamethasone, also caused a large inhibition of LPS‐induced IL‐6 (Figure 1).

FIGURE 1.

FIGURE 1

Open in a new tab

Inhibition of LPS‐induced pro‐inflammatory IL‐6 production in THP‐1 macrophages. Cells were dosed with the indicated individual treatments or combinations of LPS (1 μg/mL), DHA (26 μM)/EPA (39 μM) and dexamethasone (50 nM). Data shown as percentage of LPS‐stimulated control (mean ± SEM, N = 3). Internal data contributed by Frank Huang and Sheila Rocha.* and Δ indicate significant differences from LPS control (ANOVA with Tukey's post hoc comparison).

To further investigate the role of DHA/EPA in this THP‐1 cell model on pro‐resolution mediators, resolvin E1 was measured following LPS challenge. Figure 2 shows that in the presence or absence of LPS, resolvin E1 is produced at low levels. The addition of DHA/EPA to the LPS challenged cells resulted in a significantly large increase in resolvin E1. Interestingly, the anti‐inflammatory active dexamethasone did not increase resolvin E1. These data suggest that DHA and EPA reduce LPS induced inflammation via a different mechanism versus dexamethasone and is involved in the pro‐resolution process.

FIGURE 2.

FIGURE 2

Open in a new tab

Production of Resolvin E1 by LPS‐stimulated THP‐1 macrophages at 24 h and 48 h. Data shown as mean ± SEM, N = 10. Cells were dosed with the indicated individual treatments or combinations of LPS (1 μg/mL), DHA (26 μM)/EPA (39 μM) and dexamethasone (50 nM). Unilever data contributed by Frank Huang and Sheila Rocha.* and Δ indicate significant differences from LPS control for the respective timepoints (ANOVA with Dunnett's post‐ comparison).

In addition to in vitro models of inflammation, Unilever has developed a proprietary clinical methodology for assessing technologies for skin irritation/redness and skin tone. Post‐inflammatory hyperpigmentation (PIH) is a common concern in consumers with darker skin types. PIH is induced by shaving over the course of several weeks (Figure 3) in subjects recruited from multicultural and darker skin types. Treatment with 2% DHA/EPA continued for a total of 4 weeks and improved the hyperpigmentation induced by the shaving. There was a significant difference from vehicle control of the DHA/EPA treatment (p = 0.031) at week 4. Additionally, there was a trending significant difference between DHA/EPA treatment and the vehicle control (p = 0.06) at week 3.

FIGURE 3.

FIGURE 3

Open in a new tab

DHA/EPA improves uneven skin tone. A proprietary clinical methodology developed for assessing technologies for skin irritation/redness and skin tone. Internal data contributed by Brian Potterf. * indicate significant difference from vehicle control of the DHA/EPA treatment (p = 0.031). Statistical analysis done by Jeremy Shen.

A recent study [25] sponsored by Dermalogica demonstrated the importance of n‐3 PUFAs in improving skin outcomes following microneedling. The researchers provide evidence for the role of a novel multiple‐active‐ingredient formulation containing algae‐derived n‐3 PUFAs for improving skin outcomes up to 28 days following microneedling in adults with healthy skin when compared with a hyaluronic acid serum. The n‐3 PUFA content of this formulation may drive accelerated inflammation resolution and wound healing alongside the complementary action of the other active ingredients, leading to the observed improvements in erythema, luminosity and skin texture. A novel formulation with multiple active ingredients or a standard microneedling protocol with a hyaluronic acid control serum was used to treat 32 healthy female participants (30–70 years old) for 4 weeks after microneedling treatment. Blinded clinical photography [25] and expert evaluation measured changes in skin condition. The results showed that the novel formulation with n‐3 PUFA had significantly better improvements in expert‐graded luminosity than the hyaluronic acid control serum (Figure 4). Redness, brightness and skin texture also improved [25].

FIGURE 4.

FIGURE 4

Open in a new tab

Expert‐graded luminosity mean change from baseline at immediate and long‐term time points following microneedling treatment with a novel multiple‐active ingredient formulation and a hyaluronic acid control serum. *p < 0.05; ***p < 0.001.

DISCUSSION AND CONCLUSION

In this review, we have discussed the role of n‐3 PUFA, particularly DHA and EPA, in resolving skin inflammation and promoting skin health. Evidence from the literature and Unilever studies demonstrate that DHA and EPA, and their derived specialized pro‐resolving mediators (SPMs), can attenuate the skin inflammatory response induced by various factors, such as UV, shaving or pollution, and enhance the skin barrier function, skin tone and wound healing when applied topically. DHA/EPA can be effective natural pro‐resolution ingredients for various skin conditions, such as eczema, psoriasis, acne and photoageing. This may also help or promote benefits for post‐treatment skin recovery.

Skin inflammation and its resolution are complex, involving many biological processes that are essential for the skin's ability to return to homeostasis and health after inflammation. Strategies that target different aspects of inflammation, including pro‐resolution, can be beneficial for cosmetic dermatology.

FUNDING INFORMATION

This work was funded by Unilever Research and Development. Unilever provided support in the form of salaries for authors (JN, KH and JML).

CONFLICT OF INTEREST STATEMENT

The authors declare that no competing interest exists.

ACKNOWLEDGEMENTS

This work was funded by Unilever Research and Development. Unilever provided support in the form of salaries for authors (JN, KH and JML), but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors gratefully acknowledge Frank Huang, Sheila Rocha and Brian Potterf for their contributions to the data, while Unilever employees and Jeremy Shen for data analysis.

Nip J, Hermanson K, Lee J‐m. n‐3 PUFAs docosahexaenoic acid and eicosapentaenoic acid are effective natural pro‐resolution ingredients for topical skin applications. Int J Cosmet Sci. 2025;47:820–826. 10.1111/ics.13068

REFERENCES

  • 1. Rather LJ. Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Galen to the four cardinal signs of Celsus. Bull NY Acad Med. 1971;47(3):303–322. [PMC free article] [PubMed] [Google Scholar]
  • 2. Tracy RP. The five cardinal signs of inflammation: Calor, dolor, Rubor, tumor … And Penuria (Apologies to Aulus Cornelius Celsus, De medicina, c. a.D. 25). J Gerontol A Biol Sci Med Sci. 2006;61(10):1051–1052. 10.1093/gerona/61.10.1051 [DOI] [PubMed] [Google Scholar]
  • 3. Headland SE, Norling LV. The resolution of inflammation: principles and challenges. Semin Immunol. 2015;27(3):149–160. [DOI] [PubMed] [Google Scholar]
  • 4. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti‐inflammatory and pro‐resolution lipid mediators. Nat Rev Immunol. 2008;8(5):349–361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Serhan CN, Chiang N, Dalli J, Levy BD. Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol. 2014;7(2):a016311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Basil MC, Levy BD. Specialized pro‐resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol. 2016;16(1):51–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Calder PC. n‐3 PUFA and inflammation: from membrane to nucleus and from bench to bedside. Proc Nutr Soc. 2020;79:1–13. [DOI] [PubMed] [Google Scholar]
  • 8. Liu WC, Yang YH, Wang YC, Chang WM, Wang CW. Maresin: macrophage mediator for resolving inflammation and bridging tissue regeneration‐a system‐based preclinical systematic review. Int J Mol Sci. 2023;24(13):11012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Ishihara T, Yoshida M, Arita M. Omega‐3 fatty acid‐derived mediators that control inflammation and tissue homeostasis. Int Immunol. 2019;31(9):559–567. [DOI] [PubMed] [Google Scholar]
  • 10. Beyer MP, Videla LA, Farias C, Valenzuela R. Potential clinical applications of pro‐resolving lipids mediators from docosahexaenoic acid. Nutrients. 2023;15(15):3317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Blaauw R, Calder PC, Martindale RG, Berger MM. Combining proteins with n‐3 PUFAs (EPA + DHA) and their inflammation pro‐resolution mediators for preservation of skeletal muscle mass. Crit Care. 2024;28(1):38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Joffre C, Rey C, Laye S. N‐3 polyunsaturated fatty acids and the resolution of neuroinflammation. Front Pharmacol. 2019;10:1022. 10.3389/fphar.2019.01022 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Costa VV, Resende F, Melo EM, Teixeira MM. Resolution pharmacology and the treatment of infectious diseases. Br J Pharmacol. 2024;181(7):917–937. [DOI] [PubMed] [Google Scholar]
  • 14. Chaowattanapanit S, Silpa‐Archa N, Kohli I, Lim HW, Hamzavi I. Postinflammatory hyperpigmentation: a comprehensive overview: treatment options and prevention. J Am Acad Dermatol. 2017;77(4):607–621. [DOI] [PubMed] [Google Scholar]
  • 15. Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro‐resolving superfamily of mediators. J Clin Invest. 2018;128(7):2657–2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Sawada Y, Saito‐Sasaki N, Nakamura M. Omega 3 fatty acid and skin diseases. Front Immunol. 2020;11:623052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Sorokin AV, Arnardottir H, Svirydava M, Ng Q, Baumer Y, Berg A, et al. Comparison of the dietary omega‐3 fatty acids impact on murine psoriasis‐like skin inflammation and associated lipid dysfunction. J Nutr Biochem. 2023;117:109348. [DOI] [PubMed] [Google Scholar]
  • 18. Huang TH, Wang PW, Yang SC, Chou WL, Fang JY. Cosmetic and therapeutic applications of fish Oil's fatty acids on the skin. Mar Drugs. 2018;16(8):256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Arantes EL, Dragano N, Ramalho A, Vitorino D, de‐Souza GF, Lima MH, et al. Topical docosahexaenoic acid (DHA) accelerates skin wound healing in rats and activates GPR120. Biol Res Nurs. 2016;18(4):411–419. 10.1177/1099800415621617 [DOI] [PubMed] [Google Scholar]
  • 20. Rahman M, Kundu JK, Shin JW, Na HK, Surh YJ. Docosahexaenoic acid inhibits UVB‐induced activation of NF‐kappaB and expression of COX‐2 and NOX‐4 in HR‐1 hairless mouse skin by blocking MSK1 signaling. PLoS One. 2011;6(11):e28065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Jin XJ, Kim EJ, Oh IK, Kim YK, Park CH, Chung JH. Prevention of UV‐induced skin damages by 11,14,17‐eicosatrienoic acid in hairless mice in vivo. J Korean Med Sci. 2010;25(6):930–937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Kim HH, Shin CM, Park CH, Kim KH, Cho KH, Eun HC, et al. Eicosapentaenoic acid inhibits UV‐induced MMP‐1 expression in human dermal fibroblasts. J Lipid Res. 2005;46(8):1712–1720. [DOI] [PubMed] [Google Scholar]
  • 23. Maurice PD, Allen BR, Barkley AS, Cockbill SR, Stammers J, Bather PC. The effects of dietary supplementation with fish oil in patients with psoriasis. Br J Dermatol. 1987;117(5):599–606. [DOI] [PubMed] [Google Scholar]
  • 24. Lin Z, Niu Y, Jiang Y, Chen B, Peng L, Mi T, et al. Protective effects of dietary fish‐oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double‐blind, placebo‐controlled trial. Br J Dermatol. 2021;184(2):261–269. [DOI] [PubMed] [Google Scholar]
  • 25. Wong R, Murphy A, Lira M, Sichmann MGO, Kim AR, Saechee VD, et al. Microneedling with a novel, n‐3‐PUFA‐rich formulation accelerates inflammation resolution to improve skin recovery outcomes in adults with healthy skin. Dermatol Ther (Heidelb). 2023;13(12):3057–3069. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from International Journal of Cosmetic Science are provided here courtesy of Wiley

RESOURCES