Researcher Elaborates on Vitamin D Pretreatment to Enhance PDT for AK
Vitamin D pretreatment can enhance photodynamic therapy (PDT) treatment of actinic keratoses (AK), and vitamin D receptor alleles correlate with serum vitamin D levels and squamous neoplasia, dermatology resident Taylor Bullock, MD, showed in a presentation at the Noah Worcester Dermatological Society meeting in Quebec City, Quebec.
Dr. Bullock highlighted results from research he published in a paper titled, “Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial.”1
“We know that PDT really hinges on our ability to accumulate the photosensitizer within our target cells,” Dr. Bullock said. “And we have learned that there are a few agents—namely, methotrexate, 5-fluorouracil, and Vitamin D—that help us increase the accumulation of the photosensitizer within these target cells. Vitamin D, obviously, stands out because it’s very safe and has very few side effects. In medical school, we all remember learning, what does vitamin D do? It really just helps us absorb calcium. What we’ve learned over the past few years: It does way more than that. It’s a transcription factor, and it targets many genes—sure, genes involving calcium metabolism but also cellular growth, differentiation, and even proteins having to do with cancer involvement. We believe it also involves mini enzymes in the mitochondria that are involved in PDT.”
Seeking to determine whether oral vitamin D3 could improve clinical efficacy of a painless PDT regimen in humans with AK, Dr. Bullock and colleagues obtained baseline lesion counts and serum 25OH-D3 levels. Half of the patients received gentle debridement and 15-min ALA preincubation followed by blue light (30 min; 20 J/cm2) and the other half took oral vitamin D3 (10,000 IU daily, 5 or 14 days) prior to the debridement/PDT.
When lesion clearance was assessed at 3 to 6 months, mean clearance rates of facial AK were lower in patients with vitamin D3 deficiency (25OH-D3 <31 ng/dL; clearance rate 40.9 ± 42%) than in patients with normal 25OH-D3 levels (62.6 ± 14.2%). High-dose vitamin D3 supplementation significantly improved overall AK lesion response (72.5 ± 13.6%) compared to those without it (54.4 ± 22.8%). They noted no differences in side effects.
They attributed much of the impact to two alleles: Fok1 and Poly-A.
“[Fok1] is associated with non-melanoma skin cancer and many other skin cancers, like breast cancer and prostate cancer, and it's the only allele that's been shown to physically change the structure of the vitamin D receptor,” Dr. Bullock said. “The other allele … there isn’t a whole lot of literature about it, but it has been associated with carcinogenesis and we just still don't know a whole lot about it. … Poly-A allele, really all it is is just stretches of adenosine repeats in this gene, and people either have short stretches or really long stretches. So, this allele is basically long or short.”
In their research, Dr. Bullock and colleagues found Fok1 to be associated with increased serum vitamin D and increased history of squamous cell carcinoma incidents. They found the Poly-A allele to be associated with increased serum vitamin D but also fewer AK lesions and decreased history of squamous cell carcinoma.
- Bullock TA, Negrey J, Hu B, Warren CB, Hasan T, Maytin EV. 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;87(1):80-86. doi: 10.1016/j.jaad.2022.02.067. Epub 2022 Mar 18.