Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial

J Am Acad Dermatol. 2022 Jul;87(1):80-86. doi: 10.1016/j.jaad.2022.02.067. Epub 2022 Mar 18.


Background: In mouse models of skin cancer, high-dose oral vitamin D3 (VD3; cholecalciferol) combined with photodynamic therapy (PDT) can improve the clearance of squamous precancers (actinic keratoses [AKs]).

Objective: To determine whether oral VD3 can improve the clinical efficacy of a painless PDT regimen in humans with AK.

Methods: The baseline lesion counts and serum 25-hydroxyvitamin D3 levels were determined. In group 1, 29 patients underwent gentle debridement and 15-minute aminolevulinic acid preincubation with blue light (30 minutes; 20 J/cm2). In group 2, 29 patients took oral VD3 (10,000 IU daily for 5 or 14 days) prior to debridement and PDT. Lesion clearance was assessed at 3 to 6 months.

Results: In group 1, the mean clearance rates of facial AK were lower in patients with VD3 deficiency (25-hydroxyvitamin D3 level < 31 ng/dL; clearance rate, 40.9% ± 42%) than in patients with normal 25-hydroxyvitamin D3 levels (62.6% ± 14.2%). High-dose VD3 supplementation (group 2) significantly improved the overall AK lesion response (72.5% ± 13.6%) compared with that in group 1 (54.4% ± 22.8%). No differences in side effects were noted.

Limitations: Nonrandomized trial design (interventional cohort matched to registry-based controls).

Conclusions: Oral VD3 pretreatment significantly improves AK clinical responses to PDT. The regimen appears promising and well tolerated.

Trial registration: NCT03319251 NCT04140292.

Keywords: actinic keratosis; clinical research; oncology; photodynamic therapy; phototherapy; skin cancer; therapeutics; vitamin D.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminolevulinic Acid
  • Animals
  • Humans
  • Keratosis, Actinic* / drug therapy
  • Keratosis, Actinic* / pathology
  • Mice
  • Photochemotherapy* / adverse effects
  • Photosensitizing Agents
  • Treatment Outcome
  • Vitamin D / therapeutic use
  • Vitamins / therapeutic use


  • Photosensitizing Agents
  • Vitamins
  • Vitamin D
  • Aminolevulinic Acid

Associated data