Table 2.
Clinical studies of sunscreens incorporating photoprotective ingredients (PINGs)
| Sunscreen | Principal PING(s) | Study design | Key findings | Reference |
|---|---|---|---|---|
| SPF50 | Diethylhexyl syringylidene malonate, vitamin E, ascorbyl palmitate, licochalcone A, glycyrrhetinic acid (antioxidant PINGs) | Prospective, controlled clinical study; n = 10 (9 completed; all female, Fitzpatrick IV–VI); five test sites on back treated with SPF 50 ± antioxidants or tinted SPF 20 control; single VL + UVA1 (370–700 nm, 380 J/cm2) exposure; clinical photography, IGA scoring, and DRS at 0, 24 h, 7 days | 5-AO blend SPF 50 significantly reduced visible-light and UVA1-induced pigmentation and erythema versus SPF without AO (p < 0.05), achieving protection comparable to tinted sunscreen while avoiding cosmetic coloration | Ruvolo et al. [42] |
| SPF25 | Caffeine, vitamin E, vitamin C (aminopropyl ascorbyl phosphate), echinacea pallida extract, gorgonian extract, and chamomile essential oil (Antioxidant PINGs) | Prospective, controlled in vivo human study; n = 5 (18–40 y; mean 25; Fitzpatrick I–III, mainly II). Two SPF-25 formulations (with and without antioxidants) applied 2 mg/cm2 to buttock skin 15 min before solar-simulated UVR (2 × MED, 290–400 nm); biopsies 48 h later for CD1a and MMP-1 immunohistochemistry | SPF 25 + AOX reduced UV-induced MMP-1 expression by 60% versus 43% with SPF alone (p < 0.05) and prevented Langerhans-cell loss (4% versus 35% reduction in untreated skin) | Matsui [43] |
| SPF 25 | Caffeine, vitamin E, vitamin C (aminopropyl ascorbyl phosphate), echinacea pallida extract, gorgonian extract, and chamomile essential oil (antioxidant PINGs) | Randomized controlled in vivo clinical study; n = 40 healthy women (20–45 y; Fitzpatrick III–IV). Seven test sites on lower back exposed to solar-simulated UVR (1.5 × MED) for 4 days. Treatments: vehicle, SPF 25 alone, AOX alone, or SPF 25 + AOX. Biopsies 72 h post-exposure for histology and immunohistochemistry | Compared with SPF 25 alone, SPF 25 + AOX reduced melanin formation by 70% (versus 60%, p = 0.05), completely prevented MMP-9 induction, and better-preserved Langerhans cells. AOX alone reduced pigmentation 30% and prevented epidermal thickening (−40% versus control) | Wu [44] |
| SPF 30 | Vitamin E, vitamin C, ubiquinone, grape-seed extract (antioxidant PINGs) | Randomized, double-blind, vehicle-controlled clinical study; n = 30 healthy adults (11 M, 19 F; mean age ≈ 48 y). Two 3 × 3 cm buttock sites treated for 10 days with SPF 30 ± AO cocktail (2 mg/cm2); single IR-A exposure (360 J/cm2; 760–1440 nm); 24 h biopsies analyzed for MMP-1 mRNA expression | SPF 30 + AO significantly reduced IR-A-induced MMP-1 mRNA upregulation (p < 0.05) versus untreated and SPF-only sites; SPF alone showed no significant protection. Antioxidants were required for effective IR-A photoprotection | Grether-Beck et al. [45] |
| SPF 30 | Ectoine + mannitol (Osmolyte PINGs) | Open, intra-individual, investigator-approved clinical study; n = 10 men aged 20–44 years (Fitzpatrick II–III) with oily skin on the back. Four test areas received vehicle or active formulation (0.1% ectoine + 0.1% mannitol) ± UV filters for 3 days; 2 MED UVA + UVB irradiation at D3; biomarker sampling at D4 | Active formulation significantly protected skin lipids and enzymes after UV exposure: squalene oxidation ↓ 58%, catalase activity ↑ 60%, and trans-urocanic acid isomerization ↓ 14% versus irradiated control (all p < 0.01). Combined with UV filters, protection rose to 77–84% for squalene and catalase (synergistic CDI = 0.9) | Fontbonne et al. [46] |
| SPF 50 | Photolyase (Anacystis nidulans) (DNA repair PING) | Randomized, controlled in vivo study; n = 10 healthy volunteers (5 M, 5 F; 25–36 y; Fitzpatrick II). Each subject received four daily solar-simulated UVR exposures (3 × MED) on marked skin sites treated with vehicle, SPF 50 alone, or SPF 50 + 1% liposomal photolyase* | Compared with SPF 50 alone, SPF 50 + photolyase reduced UV-induced CPDs by 93% (versus 62%) and apoptosis by 82% (versus 40%) (p < 0.001), demonstrating superior DNA-damage repair and anti-apoptotic protection | Berardesca et al. [47] |
| SPF 50 | Photolyase (Anacystis nidulans) + endonuclease (Micrococcus luteus) (DNA repair PINGs) | Prospective, intra-individual pilot clinical study; n = 12 healthy white adults (6F/6 M; Fitz I–II). Six 10-mm back sites per subject: untreated; UVR only; vehicle + UVR; SPF50 + UVR; SPF50 + endonuclease + UVR; SPF50 + photolyase + endonuclease + UVR. 3 × MED solar-simulated UVR on 4 consecutive days; biopsies 24 h after final exposure | SPF50 alone: modest attenuation of telomere loss and c-FOS upregulation. SPF50 + endonuclease: greater protection versus SPF alone. SPF50 + photolyase (pre-irradiation) + endonuclease (post-irradiation): complete abrogation of UV-induced telomere shortening and c-FOS hyperexpression (restored to nonirradiated levels) | Emanuele et al. [48] |
| SPF 50 + | Sclareolide + niacinamide (anti-inflammatory and depigmenting PINGs) | Investigator-blinded, randomized, intra-individual controlled study; n = 20 (24–49 y; Fitzpatrick IV–V) with history of PIH. Six back sites (tape-stripped or intact) received UV (1.5 × MED) + VL (14 J/cm2) exposures ± sunscreen for 20 days; colorimetry (ΔITA°, ΔL*, Δa*, Δb*, ΔE) and clinical scoring through Day 36 | Sunscreen significantly prevented UV/VL-induced pigmentation and erythema. ΔITA° protection: + 5.96 (stripped, p < 0.001) and + 11.76 (nonstripped, p < 0.001) versus unprotected; pigmentation ↓ 26–53%, erythema ↓ 43–94%. Colorimetric indices improved 48–87%. No adverse events. Demonstrated dual anti-inflammatory and depigmenting benefit for PIH prevention in skin of color | Passeron et al. [49] |
AO antioxidant, AOX antioxidants, 5-AO five-antioxidant blend (diethylhexyl syringylidene malonate + vitamin E + ascorbyl palmitate + licochalcone A + glycyrrhetinic acid), CDI combination drug index, CD1a cluster of differentiation 1a, CPD cyclobutane pyrimidine dimer; ΔE, ΔL*, Δa*, Δb*, ΔITA°, CIELAB colorimetric parameters (total color, lightness, red–green, yellow–blue, individual typology angle), DRS diffuse reflectance spectroscopy, F female, M male, FPT Fitzpatrick phototype, IGA investigator global assessment, IL-1α interleukin-1 alpha, IR-A infrared-A radiation, MED minimal erythema dose, MMP-1/-9 matrix metalloproteinase-1/-9, NIAC niacinamide, PIH postinflammatory hyperpigmentation, PING photoprotective ingredient with nonfiltering gain, ROS reactive oxygen species, SPF sun-protection factor, ssUV/ssUVR solar-simulated ultraviolet (radiation), UVA/UVB/UVR ultraviolet A/B/radiation, VL visible light (≈ 400–700 nm)