Table 1.

Description of study characteristics.

Type of Case	Type of Application	Form of Vitamin D	Stage of Administration	Type of Photosensitizer	The Source of Light	Effect on PDT Efficacy (Comments)	Reference
in vitro studies: germ-free fetal rat keratinocytes	application of calcitriol to the cell solution	medium containing calcitriol, final concentration $[{10}^{-6}\mathrm{M}]$	before and after phototherapy	tetrasulfonate (AlPcTs)	500 W halogen lamp (SX-UI 500 JH; Ushio, Tokyo, Japan)	The addition of calcitriol enhanced DNA fragmentation of cells, thus improving the effectiveness of PDT.	[40]
in vitro studies: human breast cancer cell lines MCF7 and MDA-MB-231	application of calcitriol to the cell solution	calcitriol $[{10}^{-8}\mathrm{M}, {10}^{-10}\mathrm{M},$${10}^{-12}\mathrm{M}, {10}^{-14}\mathrm{M},$ ${10}^{-16}\mathrm{M}]$	before therapy	hematoporphyrin derivatives (HPD)	diode laser with a power density of 7.5 J/cm2 (XD635AB; Xingda, Guilin, China)	Calcitriol improved the efficacy of PDT by increasing the PpIX levels in cells.	[43]
in vitro studies: human glioma cell lines U87 and T98	application of calcitriol to the cell solution	calcitriol $[{10}^{-8}\mathrm{M}, {10}^{-10}\mathrm{M},$${10}^{-12}\mathrm{M}, {10}^{-14}\mathrm{M}]$	before therapy	5-aminolevulinic acid (ALA)	laser with a power density of 30 mW/cm2 (XD-635AB; Xingda, Guilin, China)	Calcitriol treatment of glioblastoma cells selectively increased PpIX levels and increased ALA-induced phototoxicity. Additionally, the administered calcitriol significantly increased the number of tumor cells killed after ALA-PDT treatment.	[44,45]
in vitro studies: human squamous cell carcinoma A431 cells	application of calcitriol to the cell solution	calcitriol $[{10}^{-9}-{10}^{-6}\frac{\mathrm{mol}}{\mathrm{L}}]$	96 h before therapy	methyl aminolevulinate (MAL)	fluorescent lamps (Model 3026; Applied Photophysics, London, UK) in the wavelength range 370–450 nm	Calcitriol enhanced PDT.	[46]
in vitro studies: LNCaP prostate cancer cells	application of calcitriol to the cell solution	calcitriol and its analogues (R0-25-9022 and R0-26-2198) $[10 \mathrm{mM}, 1 \mathrm{nM},$ $10 \mathrm{nM},1 \mathrm{nM}]$	96 h before therapy	5-aminolevulinic acid (ALA)	argon laser with a wavelength of 514 nm (Coherent, Inc., Santa Clara, CA, USA)	Calcitriol and its analogues significantly increased ALA–PpIX accumulation in cells	[47]
animal studies: human squamous cell carcinoma cell line	diet or systemic administration	one of three forms: • D3: cholecalciferol $\left[40\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{kg}}\right]$ • monohydroxy D3: calcidiol(25(OH) D3) $\left[250\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{kg}}\right]$ • dihydroxy D3: calcitriol, (1,25(OH)2 D3) $\left[1\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{kg}}\right]$	diet: 10 days before phototherapy systemic administration: 3 days before	5-aminolevulinic acid (ALA)	633 nm noncoherent light source (LumaCare Products, Newport Beach, CA, USA)	Tumor cells treated with D3 and monohydroxy D3 showed an approximately 2.5- and 3-fold increase in PpIX (protoporphyrin IX) levels compared to vehicle control. Tumors treated with dihydroxy D3 showed an approximately 3.5-fold increase in PpIX (protoporphyrin IX) levels compared to vehicle control. Research showed a clear pattern of increase in cell death induced by ALA-PDT (5-aminolevulinic acid-photodynamic therapy) with vitamin D3 pretreatment.	[48]
animal studies: murine model of breast cancer	intraperitoneally	calcitriol $\left[1\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{kg}}\right]$	3 days before	5-aminolevulinic acid (ALA)	633 nm noncoherent light source (LumaCare USA, Newport Beach, CA, USA)	Increased cell death was observed in tumors injected with calcitriol prior to ALA-PDT compared to ALA-PDT alone. ALA with calcitriol treatment induced 3.3 ± 0.5-fold increase in intracellular PpIX levels.	[49]
animal studies: squamous cell skin cancers	topically/Intraperitoneally	calcipotriene 0.005% $\mathrm{calcitriol} \left[3\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$ deep tumors: $\mathrm{systemic} \mathrm{vitamin} \mathrm{D} \mathrm{in} \mathrm{PBS} \left[1\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{kg}}\right]$	3 days before	5-aminolevulinic acid (ALA)	633 nm non-coherent light source (LumaCare Products, Newport Beach, CA, USA)	There was a 10-fold increase in the accumulation of ALA protoporphyrin-IX (PpIX) in neoplastic cells due to changes in the expression of porphyrin synthesis enzymes.	[39]
animal studies: precancerous lesions in the buccal	ointment	calcipotriol 0.005% [100 µL]	every 24 h 3 times	5-aminolevulinic acid (ALA)	LED with 640 nm wavelength	Pre-conditioning of precancerous lesions with calcipotriol affects the amount of PpIX, which may improve the efficacy of PDT.	[50]
animal studies: non-melanoma skin cancer mouse models	topical for the skin	calcitriol $\left[3\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	3 days before	5-aminolevulinic acid (ALA)	633 nm noncoherent light source (LumaCare USA, Newport Beach, CA, USA)	Histological examination of tumor tissues from combination therapy (calcitriol + ALA-PDT) showed pyknotic/shrunken testes, reduction of collagen, and growth of dead areas.	[51]
human studies: human psoriasis	cream or ointment	calcipotriol $[0.005\%]$	6 days before	5-aminolevulinic acid (ALA)	635 nm diode laser (HPD 7401, High Power Devices, Inc., North Brunswick, NJ, USA)	In a combination of ALA-PDT therapy with calcipotriol, there was an improvement in the clinical response in psoriatic plaques.	[36]
human studies: actinic keratoses	ointment	calcipotriol $\left[50\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	15 days before	methyl aminolevulinate (MAL)	daylight-mediated photodynamic therapy (DL-PDT)	There was a 15% increase in overall response to treatment with DL-PDT in combination with calcipotriol compared to DL-PDT alone.	[52]
human studies: actinic keratoses	ointment	tacalcitol $20 \mathrm{g} \left[4\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	15 days before	5-aminolevulinic acid (ALA)	630 nm diode (S630, AlphaStrumenti, Milan, Italy)	The combination of PDT with tacalcitol was more effective than the practiced PDT alone. The percentage reduction in the total number of lesions was 44.4%.	[53]
human studies: follicular mucinosis of the scalp	ointment	tacalcitol $\left[4\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	1 month before and continued throughout the treatment period	5-aminolevulinic acid (ALA)	ded diode with a wavelength of 630 nm	Applied PDT with tacalcitol effectively reduced inflammation and increased the penetration of 5-ALA into the skin.	[54]
human studies: actinic keratoses	oral	cholecalciferol 10,000 IU	before therapy	5-aminolevulinic acid (ALA)	blue light (10 mW/cm2, Blu-U, Sun/DUSA Pharmaceuticals)	Oral vitamin D3 therapy before PDT led to an 18% increase in response to treatment. An increase in the effectiveness of the therapy (by 11%) in removing lesions was also observed.	[37]
human studies: actinic keratosis	cream	calcipotriol 0.005%	2 times a day for 2 weeks before therapy	methyl aminolevulinate (MAL)	red diode lamp (dose 37 J/cm2)	Topical therapy with calcipotriol before PDT enhances cell differentiation and apoptosis, thereby increasing the effectiveness of treatment.	[55]
human studies: actinic keratoses	ointment	calcitriol $\left[3\frac{\mathrm{mg}}{\mathrm{g}}\right]$	14 days before	methyl aminolevulinate (MAL)	daylight-mediated photodynamic therapy (DL-PDT)	The effectiveness of the therapy with calcitriol was higher by 6.11% compared to the therapy without calcitriol.	[56]
human studies: actinic keratoses	ointment	calcipotriol $\left[50\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	15 days before	methyl aminolevulinate (MAL)	-	After 12 months, PDT in combination with calcipotriol was safer and more effective (by approximately 27%) compared to conventional PDT.	[57]
human studies: actinic keratosis	ointment	calcipotriol $\left[50\frac{\mathsf{\mu }\mathrm{g}}{\mathrm{g}}\right]$	15 days before	methyl aminolevulinate (MAL)	red light-emitting diode (LED) (Aktilite; PhotoCure, Oslo, Norway)	The use of PDT with calcipotriol doubled the number of actinic keratoses compared to untreated PDT.	[58]

Note: tacalcitol—synthetic vitamin D3; calcipotriol—synthetic derivative of calcitriol, the active form of vitamin D.