Omega-3 Fatty Acids and Their Possible Benefits for People with Acne

In the pursuit of skin health, and particularly in a juvenile patient cohort, such as acne vulgaris, clinicians and patients are more than ever seeking treatment approaches that go beyond the conventional options of topical and systemic prescription medications.1, 2, 3 As the understanding of the interplay between so‐called exposome factors and skin health deepens, there is increasing evidence pointing to the pivotal role of nutrition in shaping dermatoses.4 Exposome factors for acne are defined as the sum of skin care, diet, pollutants, occupational factors, climatic influences, and psychosocial mediators that influence the onset, duration, and clinical severity of the disease.5 Although their impact cannot be neglected, clinicians rarely educate their patients accordingly, and the potential to positively influence these factors is not being exploited.6, 7

Diet, in particular, is a variable that can be positively influenced by individuals with the appropriate knowledge. With regard to acne, ultra‐processed foods with added refined sugars/saturated fats, cow's milk, and dairy product have been implicated in the pathogenesis of acne, including sebum overproduction, altered follicular keratinization, inflammation, and follicular colonization with Cutibacterium acnes (C. acnes).8, 9, 10, 11 The implementation of dietary interventions with nutrients that may alleviate acne severity as an adjunctive, feasible treatment option is promising, but scientific evidence remains scarce. In this context, Omega‐3 (ω‐3) fatty acids (FA), including alpha‐linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been proposed as promising agents due to their diverse biological functions.12, 13 While ALA is an essential FA, meaning that it must be obtained from the diet, EPA and DHA can be biosynthesized from ALA, albeit in very small amounts. Food and supplements are therefore necessary sources for all ω‐3 FA. Recent studies suggest that daily ω‐3 FA requirements may vary between age, gender, and life circumstances such as pregnancy and breastfeeding; however, target values are rarely assessed.14 According to the European Food Safety Authority (EFSA), the daily intake through oral supplementation should not exceed 5 g, while the Food and Drug Administration (FDA) advises a daily maximum of 3 g daily.15 Balancing the intake of these fatty acids has significant clinical implications. Particularly in Western countries, where the common diet is characterized by an excess of ω‐6 FA, compared to ω‐3 FA. Whereas humans used to consume ω‐3 FA and ω‐6 FA in a ratio of approximately 1:5, modern diets have a ratio as high as of 1:20 or more.16 While both are essential for our overall health, ω‐6 FA promote inflammatory pathways when consumed in excess. The main type of ω‐6 FA is linoleic acid (LA), which is commonly found in vegetable oils and therefore in fried foods, can be converted to arachidonic acid (AA), a precursor of inflammatory eicosanoids.17 A balanced ratio may not only reduce inflammation in general, but specifically inflammatory dermatoses, including acne.18, 19

Several mechanisms have been proposed to elucidate the potential impacts of ω‐3 FA on acne. These include modulation of sebum production, reduction of inflammatory cytokines, inhibition of C. acnes growth, improvement of skin barrier function, and antioxidant properties.12, 13, 20, 21 Insulin‐like growth factor (IGF)‐1 signaling stands out as a pivotal acne pathway, inducing an array of pro‐inflammatory cytokines and matrix metalloproteinase (MMP) in human sebocytes. This pathway also activates the nutrient‐sensitive kinase mammalian target of rapamycin complex (mTORC1), which is intertwined with anabolic pathways, including sebaceous lipogenesis and follicular hyperkeratosis, all of which play key roles in the pathogenesis of acne vulgaris.10, 22 ω‐3 FA have shown to decrease serum levels of IGF‐1 while increasing IGF binding protein‐3 (IGFBP‐3). This prevents IGF‐1 from binding to its receptors on sebocytes and acroinfundibular keratinocytes.10, 23 Moreover, ω‐3 FA have exhibited the capacity to inhibit toll‐like receptor (TLR)‐signaling pathways, with both DHA and EPA leading to a decreased inflammatory response in keratinocytes and macrophages.24 Consequently, this results in a reduced activation of nuclear factor‐kappaB (NF‐ κB) and mitogen‐activated protein kinase (MAPK) pathways, subsequently curbing the production of interleukins (IL)‐1, IL‐6, IL‐8, tumor‐necrosis factor (TNF)‐alpha, and MMP production by ω‐3 FA.25, 26 Furthermore, ω‐3 FA have inhibitory effects on the NLRP3 inflammasome, a cytoplasmic multiprotein complex that can be initiated in response to various signals, including those of C. acnes.27, 28 This inhibition ultimately leads to a decreased caspase‐1 activation with reduced IL‐1beta‐driven Th17 activation, which contributes to acne's inflammation and dyskeratinization.29

Although preliminary studies suggest a potential benefit of ω‐3 FA in acne, the data remain inconclusive due to limited study designs and, most importantly, a failure to address existing deficits.12, 13, 30, 31, 32, 33

The aims of this prospective 16‐week study were to assess EPA/DHA levels in acne patients using the HS‐omega‐3 Index® in erythrocytes (%), to raise levels to the target range (HS‐omega‐3 Index® 8%–11%) using dietary recommendations based on current evidence (plant‐focused Mediterranean diet with limited intake of milk/dairy/ultra‐processed ingredients) and oral supplementation with algae‐derived EPA/DHA, and to assess the effect on clinical severity. The findings may reshape future treatment protocols and enable both healthcare providers and patients alike to contribute to clinical outcomes.

While prescription medications are mandatory for the treatment of acne vulgaris, especially in severe clinical presentations, to avoid unnecessary prolongation of suffering and long‐term sequelae of scarring,44 the potential of lifestyle interventions should not be neglected. In particular, dietary recommendations, as they are not contradictory to conventional medicine, but rather a valuable adjunct to any modern treatment plan.7, 8, 20, 45, 46 This prospective study investigated the benefits of targeting ω‐3 FA levels in patients with mild to moderate acne vulgaris without prescription medication. Many of the acne patients studied had a severe EPA/DHA deficit at baseline, with an average HS‐omega 3 index® of 4.9%, which was increased to a target range of 8.3% over the course of 16 weeks. Throughout the study, patients were encouraged to follow a varied, plant‐focused Mediterranean diet and to take oral supplements of algae‐derived DHA/EPA.

A significant improvement in the number of noninflammatory and inflammatory acne lesions was seen between V1 and V4 (p < 0.001). At the end of the intervention, a significantly higher HS‐omega 3 index® was observed in patients with AC compared to AP. This finding may be explained by the proposed anti‐inflammatory properties of ω‐3 FA,47, 48, 49 corresponding to clinically reduced inflammation in patients with higher levels. There was no correlation between facial sebum levels and the HS‐omega‐3 Index®, but there was a correlation with the number of comedones, highlighting the known pathophysiological link between seborrhea as the driving force for these initial acne lesions.

While the mean HS‐omega‐3 Index® of the entire cohort reached the target value when comparing V1 and V4, some participants did not respond adequately within 16 weeks. Noncompliance, as reflected in patients' FFS, is a possible explanation. In addition, there may be differences in the individual response of patients to ω‐3 FA supplementation.32 Although patients' were advised to take EPA/DHA supplements in addition to an adequate fat intake, the bioavailability of ω‐3 FA supplements may vary between individuals.32 Future studies may need to adjust the dosage according to the individual HS‐omega‐3 Index® in order to reach the target range in all patients. It will also be of interest to determine whether blood levels at the upper end of the target range, around 11%, confer any clinical benefit. This could be achieved either by prolonged supplementation or by higher doses of DHA/EPA, especially as there have been no adverse events associated with the current supplementation.

Interestingly, patients reported the most significant clinical change after an average of 40 days. By this time (between V2 and V3), the dosage of EPA/DHA supplementation had been increased and the HS‐omega‐3 Index® had increased overall, with only one patient still having with a severe deficit. This again supports the hypothesis of clinical benefit from supplementation of deficits. Although most patients benefited, three patients reported a subjective worsening of their acne during the study, and two withdrew from the study due to worsening. It is therefore important to tailor treatment plans individually, especially when there is an inadequate response to treatment, and to always offer patients prescription medication when needed.

The assessment of EPA/DHA blood levels in this study provides unprecedented data from a German acne cohort. While previous data show a general tendency toward a ω‐3‐FA deficit in the European population, exemplarily with a HS‐omega 3 index® below 8% in 76.15% of a cohort of 23.615 European volunteers,32 and a mean value of 5.49% observed in a German nationwide cohort of middle‐aged women,50 our study suggests an exacerbation in acne patients. To date, only a few prospective, intervention human studies have been conducted to investigate the clinical effects of ω‐3 FA on acne, and remarkably, none of these have investigated patient blood levels.13 Rubin et al.30 conducted a study in 2008 with five acne patients. After 8 weeks of EPA supplementation, combined with a green tea antioxidant, the number of inflammatory facial lesions decreased, and the patients' self‐rated mental status improved. In 2012, Khayef et al.31 investigated the effects of DHA and docosapentaenoic acid (DPA) in 13 men. In addition to the number of facial lesions, the authors assessed patients' skin redness and evaluated a 3‐day dietary diary. No significant differences were found when comparing the number of lesions at baseline and 12 weeks after the intervention. Jung et al. conducted the highest quality intervention study to date, including histopathologic analysis of facial lesions after 12 weeks of oral ω‐3‐FA/ω‐6‐FA supplementation, which impressively demonstrated a reduction in inflammatory markers.12 With these limited and sometimes conflicting data in mind, this study adds new data on EPA/DHA deficits in acne patients and shows what can be achieved by dietary intervention with oral supplementation.

This study also included a subjective assessment of dietary acne triggers and beneficial foods. Defined dietary acne triggers were consistent with the current literature.51, 52, 53 Vegetables, fruit, whole grains, and nuts were perceived as the most beneficial. A possible explanation for the attributed positive effect of nuts on acne severity may be due to their high levels of ω‐3 FA.21 All these foods also comprised the recommended plant‐focused Mediterranean diet. Overall, the fact that triggers were more clearly defined than beneficial foods underlines the importance of this study, which aimed to identify nutrients that might alleviate acne severity.

As this study did not include any prescription drugs, clinical changes need to be assessed realistically. (Figure 1) However, even a small clinical improvement led to a significant improvement in the quality of life of affected patients as seen by the DLQI results and underlines the importance of incorporating lifestyle interventions. In our experience, investing time in individualized (nutritional) counseling and patient education, especially at the first visit, whether as a stand‐alone treatment or as a basis for prescription medication, not only increases patients' ability to contribute to their health, but also improves overall treatment satisfaction and outcome.

As with previous studies investigating the effects of diet on clinical parameters in acne patients, the challenge of this study remains to establish direct causal relationships as to whether increased EPA/DHA levels, changed dietary habits, or other cofactors led to the improved clinical severity of acne and improved quality of life in patients. This study therefore has its strengths and limitations. Unfortunately, a randomized, placebo‐controlled design, although initially intended, was not approved by the ethics committee at the time of the study. In addition, relying on FFS to assess patients' adherence to dietary recommendations imposes potential recall bias. Ideally, meals and supplements should be provided to each participant throughout the study period in a controlled environment throughout the study, but this is not feasible over 16 weeks. Study dropouts due to worsening clinical appearance should be addressed in future studies by reanalyzing patients' EPA/DHA levels to rule out insufficient increases and to allow individual adjustment of EPA/DHA supplement dosage. Another limitation is the predominance of female participants. As the recruiting clinic primarily serves patients with severe clinical presentations requiring prescription medication, it is worth noting that male patients, especially at a younger age, often have a more severe clinical presentation, which may explain why most male patients were not eligible to participate without prescription medication. In addition, in our experience, women tend to be more willing to participate in clinical trials and are generally more motivated to engage in lifestyle interventions, including dietary changes. While we recognize this gender imbalance, we hypothesize that it may not have significantly impacted the current results. This is supported by the observation that both male patients had an ω‐3 FA deficit at baseline, and existing data suggest that EPA/DHA deficits may occur in humans regardless of gender.32 Future studies should build on the foundation laid by our current findings in a randomized, placebo‐controlled design to improve dietary recommendations for acne patients.

Many patients with acne have an EPA/DHA deficit. Lifestyle interventions, including a plant‐focused Mediterranean diet and EPA/DHA supplementation for 16 weeks, led to a significant increase in ω‐3 FA levels, as assessed by the HS‐omega‐3 Index®, in patients with mild to moderate acne. Improvements in clinical appearance and quality of life were observed. While this study evaluated the approach as a stand‐alone treatment, future studies should investigate ω‐3 FA as an adjunct to any acne treatment plan.

Conceptualization: AG, DL, and MR. Methodology: AG and KN. Validation: MR and LEF. Formal analysis: AG, MR, and KN. Investigation: KN and AG. Data curation: KN, AG, and MR. Writing—original draft preparation: AG. Writing—review & editing: AG, KN, DL, BCE, LEF, and MR. Visualization: AG, KN, DL, and BCE. Supervision: MR and LEF.

No funding was received. Omegametrix® GmbH performed the analysis of the HS‐omega‐3 Index® free of charge. Queisser Pharma GmbH & Co. KG offered omega‐3 supplements free of charge. Neither Omegametrix® GmbH, nor Queisser Pharma GmbH & Co. KG had any role in the study design, evaluation, or interpretation of data.

All authors declare that they have no competing interests.

For all personal information used in this article, for example, personal images, a consent for publication has been obtained.

Open Access funding enabled and organized by Projekt DEAL.

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.