Fern extract reverses severe actinic keratosis lesions

The combination of local and oral preparations of polypodium leucotomos extract led to clinical reversal of actinic keratosis (AK) lesions at 12 months in a retrospective Italian trial. Treatment also markedly reduced the occurrence of new lesions.

Previous studies have shown that the extract of the South American fern polypodium leucotomos (PLE) is a powerful antioxidant due to its high content of phenolic compounds [1]. It not only inhibits the generation of reactive oxygen species by ultraviolet light but also prevents ultraviolet- and reactive oxygen species-induced DNA damage. Therefore, PLE extracts are a common ingredient in sun creams. A study in healthy participants showed that the fern extract is an effective chemophotoprotector against PUVA-induced skin phototoxicity [2]. To investigate if topically and orally PLE is really able to reverse severe actinic damage, a study including 131 patients with severe signs of photoaging and at least 3 AK lesions was performed [3].

Participants were randomised into 3 treatment groups. The first received topical photoprotection with SPF ≥100 together with a topical PLE-preparation alone, the second group was treated in the same way plus the fern extract in an oral form once daily, and the third and control group only used the topical photoprotection. In case new AK lesions were noted, participants were permitted to undergo additional therapy, e.g. imiquimod or cryotherapy. At 12 months, skin changes were evaluated with reflectance confocal microscopy, and clinical changes by 2 different AK-specific scores and the appearance of new AK lesions or the need for specific AK interventions.

Data from 116 participants showed distinct improvements in the AK Field Assessment Scale Area (AK-FAS), especially in the arm also treated with the oral fern preparation: it improved by 26% compared with 4% in participants on topical PLE only, and a worsening by 13% in the control group. “It is interesting that the control group that was given only common advice had increased photodamage and an increased number of new AK lesions,” said Dr Stefania Guida (Sapienza University of Rome, Italy) who presented the study results. In contrast, there were no new lesions in both PLE groups. Participants in both intervention groups improved in the Actinic Keratosis Area Score Index (AKASI) score by 7%, whereas there was a deterioration by 6% in the placebo arm (P<0.001).

Reflectance confocal microscopy supported this clinical data: 51% of those receiving the oral and local preparation of PLE and 45% of those receiving the local PLE preparation only had normalisation of the honeycomb pattern compared with 26% in the control group (P=0.04 for both comparisons). Also measured was a difference in the percentage of participants that needed additional therapy due to the occurrence of new lesions, which was necessary for 2% of participants taking both the oral and topical PLE preparation, in 11% of those only taking the topical PLE preparation, and in 38% of controls.

1. Parrado C, et al. Int J Mol Sci 2016:17:pii:E1026.
2. Middelkamp-Hup MA, et al. J Am Acad Dermato 2004:50:41-9.
3. Pellacani G. Topical and topical plus oral immune photoprotection with Polypodium Leucotomos extract in severe actinic damage. A multicenter, randomised, prospective, assessor-blinded, 12-month controlled trial with confocal microscopy evaluation in 132 subjects. FC05.03, EADV Congress 2022, Milan, Italy, 7–10 September.

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Posted on 5 November 2022