# Infrared Photobiomodulation Modulates PpIX Production After Topical Methyl Aminolevulinate in Normal Human Skin: An Exploratory Study

**Authors:** Letícia Palombo Martinelli, Natasha Ferreira Mezzacappo, Ana Paula Silva, Priscila Menezes, Vanderlei Salvador Bagnato

PMC · DOI: 10.1002/jbio.70262 · Journal of Biophotonics · 2026-03-27

## TL;DR

This study explores how infrared light can influence the production of a key compound used in skin treatments, though results show large differences between individuals.

## Contribution

The study demonstrates that near-infrared photobiomodulation may influence protoporphyrin IX accumulation in human skin.

## Key findings

- PBM showed a trend toward modulating PpIX accumulation, but results were not statistically significant.
- High interindividual variability (up to 35% coefficient of variation) limited conclusive results.
- The findings suggest PBM could be a noninvasive adjuvant for photodynamic therapy.

## Abstract

Photodynamic therapy (PDT) for skin lesions requires optimized photosensitizer accumulation. Since protoporphyrin IX (PpIX) synthesis is linked to mitochondrial activity, photobiomodulation (PBM) may modulate this process. This exploratory study examined the effects of PBM at 780 or 808 nm on MAL‐induced PpIX in normal human skin. Eleven volunteers received paired‐arm treatments (5, 10, or 15 J/cm2). Following 30 min of MAL, PBM was applied, with total incubation lasting 210 min. PpIX was assessed via spectroscopy and widefield imaging. Although mean PBM/no‐PBM ratios were nominally above 1, no statistically significant differences were found among fluences or against unity, primarily due to high interindividual variability (CV up to 35%). These findings suggest that while PBM shows a trend toward modulating photosensitizer accumulation, the response is highly heterogeneous. This study provides a rationale for further investigation into personalized PBM‐assisted PDT protocols to manage biological variability and refine clinical outcomes.

We demonstrate that NIR photobiomodulation can influence PpIX accumulation in normal human skin. Although subject to interindividual variability, the observed trends support PBM as a promising, noninvasive adjuvant to refine PDT protocols and manage photosensitizer production through mitochondrial stimulation.

## Linked entities

- **Chemicals:** methyl aminolevulinate (PubChem CID 157922), protoporphyrin IX (PubChem CID 4971), PpIX (PubChem CID 9548816)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** MAL (mal, T cell differentiation protein (MAL blood group)) [NCBI Gene 4118] {aka HLD28, MVP17, VIP17}, FECH (ferrochelatase) [NCBI Gene 2235] {aka EPP, EPP1, FCE}
- **Diseases:** AK (MESH:D055623), cancer (MESH:D009369), skin cancers (MESH:D012878), glioma (MESH:D005910), precancerous (MESH:D011230), inflammation (MESH:D007249), skin lesions (MESH:D012871), pain (MESH:D010146), burns (MESH:D002056), pigmentation (MESH:D010859)
- **Chemicals:** oxygen (MESH:D010100), dimethyl sulfoxide (MESH:D004121), PpIX (MESH:C028025), NO (MESH:D009569), DMSO (-), ROS (MESH:D017382), EDTA (MESH:D004492), ALA (MESH:D000622), heme (MESH:D006418), melanin (MESH:D008543), ATP (MESH:D000255)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13022744/full.md

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13022744/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC13022744/full.md

---
Source: https://tomesphere.com/paper/PMC13022744