Resveratrol-Containing Gel for the Treatment of Acne Vulgaris

A Single-Blind, Vehicle-Controlled, Pilot Study


Background: Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation.

Aim: The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin.

Methods: Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment.

Results: HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel.

Conclusion: This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.

This is a preview of subscription content, log in to check access.

Table I
Fig. 1
Table II
Fig. 2
Fig. 3
Table III
Fig. 4
Fig. 5


  1. 1.

    Goodman G. Acne and acne scarring: the case for active and early intervention. Aust Fam Physician 2006; 35: 503–4

    PubMed  Google Scholar 

  2. 2.

    Morohashi M, Toyoda M. Pathogenesis of acne: medical electron microscopy. Med Electron Microsc 2001; 34 (1): 29–40

    PubMed  Article  Google Scholar 

  3. 3.

    Peck G, Olsen T, Yoder F, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med 1979; 300: 329–33

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Strauss J, Rapini R, Shalita A, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 1984; 10: 490–6

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Newman MD, Bowe WP, Heughebaert C, et al. Therapeutic considerations for severe nodular acne. Am J Clin Dermatol 2011; 12: 7–14

    PubMed  Article  Google Scholar 

  6. 6.

    Ganceviciene R, Zouboulis CC. Isotretinoin: state of the art treatment for acne vulgaris. J Dtsch Dermatol Ges 2010; 8: 47–59

    Article  Google Scholar 

  7. 7.

    Wysowski D, Pitts M, Beitz J. Depression and suicide in patients treated with isotretinoin [letter]. N Engl J Med 2001; 344: 460

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Jick S, Kremers H, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 2000; 136: 1231–6

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Zouboulis CC, Eady A, Philpott M, et al. What is the pathogenesis of acne? Exp Dermatol 2005; 14: 143–52

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Norris JF, Cunliffe WJ. A histological and immunocytochemical study of early acne lesions. Br J Dermatol 1988; 118: 651–9

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Jeremy AHT, Holland DB, Roberts SG, et al. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol 2003; 121: 20–7

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Auffret N. Pathophysiological advances in acne. Ann Dermatol Venereol 2010; 137 Suppl. 2: S52–6

    Article  Google Scholar 

  13. 13.

    Webster JF. Acne vulgaris. BMJ 2002 Aug 31; 325 (7362): 475–9

  14. 14.

    Kim J, Ochoa MT, Krutzik SR, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 2002; 169: 1535–41

    PubMed  CAS  Google Scholar 

  15. 15.

    Nagy I, Pivarcsi A, Koreck A, et al. Distinct strains of Propionibacterium acnes induce selective human b-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol 2005; 124: 931–8

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Fan E, Zhang L, Jiang S, et al. Beneficial effects of resveratrol on atherosclerosis. J Med Food 2008 Dec; 11 (4): 610–4

  17. 17.

    Dawber R. Skin surface biopsy and follicular cast. In: Serup J, Jemec GBE, editors. Handbook of non-invasive methods and the skin. Boca Raton (FL): Informa Healthcare, 1995: 121–3

    Google Scholar 

  18. 18.

    Pagnoni A, Kligman AM, Stoudemayer T. Image analysis of cianoacrylate follicular biopsies. In: Wilhelm K-P, Elsner P, Berardesca E, et al., editors. Bioengineering of the skin: skin surface imaging and analysis. Boca Raton (FL): Informa Healthcare, 1997: 113–9

    Google Scholar 

  19. 19.

    Witkowski J, Parish L. The assessment of acne: an evaluation of grading and lesion counting in the measurement of acne. Clin Dermatol 2004; 22: 394–7

    PubMed  Article  Google Scholar 

  20. 20.

    Chen X, He H, Wang G, et al. Stereospecific determination of cis- and transresveratrol in rat plasma by HPLC: application to pharmacokinetic studies. Biomed Chromatogr 2007 Mar; 21 (3): 257–65

  21. 21.

    Wyckoff TJ, Raetz CR, Jackman JE. Antibacterial and anti-inflammatory agents that target endotoxin. Trends Microbiol 1998; 6: 154–9

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Subbaramaiah K, Chung WJ, Michaluart P, et al. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem 1998; 273: 21875–82

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Donnelly LE, Newton R, Kennedy GE, et al. Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physio Lung Cell Mol Physiol 2004; 287: L774–83

    Article  Google Scholar 

  24. 24.

    Lawrence M, Szewczuk, Luca Forti, et al. Stivala resveratrol is a peroxidasemediated inactivator of COX-1 but not COX-2 a mechanistic approach to the design of COX-1 selective agents. J Biol Chem 2004; 279 (21): 22727–37

    Article  Google Scholar 

  25. 25.

    Holian O, Walter RJ. Resveratrol inhibits the proliferation of normal human keratinocytes in vitro. Cell Biochem 2001; Suppl. 36: 55–62

    Google Scholar 

  26. 26.

    Fabbrocini G, Kisslinger A, Iannelli P, et al. Resveratrol regulates p66shc activation in HaCaT cells. Exp Dermatol 2010 Oct; 19 (10): 895–903

  27. 27.

    Kundu JK, Surh YJ. Molecular basis of chemoprevention by resveratrol: NFkappaB and AP-1 as potential targets. Mutat Res 2004; 555 (1-2): 65–80

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Gao X, Deeb D, Media J, et al. Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects. Biochem Pharmacol 2003; 66 (12): 2427–35

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Docherty JJ, Fu MM, Tsai M. Resveratrol selectively inhibits Neisseria gonorrhoeae andNeisseria meningitidis. J Antimicrob Chemother 2001; 47: 243–4

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Mahady GB, Pendland SL. Resveratrol inhibits growth of Helicobacter pylori in vitro [letter]. Am J Gastroenterol 2000; 95: 1849

    PubMed  CAS  Google Scholar 

  31. 31.

    Chan MM. Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin. Biochem Pharmacol 2002; 63: 99–104

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Wang WB, Lai HC, Hsueh PR, et al. Inhibition of swarming and virulence factor expression in Proteus mirabilis by resveratrol. J Med Microbiol 2006; 55: 1313–21

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Docherty JJ, Heather A, McEwen Thomas J, et al. Resveratrol inhibition of Propionibacterium acnes. J Antimicrob Chem 2007; 59: 1182–4

    Article  CAS  Google Scholar 

Download references


This study was achieved thanks to the contribution of the “Assessorato all’Agricoltura e alle Attivita Produttive della Regione Campania.” The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information



Corresponding author

Correspondence to Dr Gabriella Fabbrocini.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fabbrocini, G., Staibano, S., De Rosa, G. et al. Resveratrol-Containing Gel for the Treatment of Acne Vulgaris. Am J Clin Dermatol 12, 133–141 (2011).

Download citation


  • Resveratrol
  • Acne
  • Isotretinoin
  • Acne Lesion
  • Oral Isotretinoin