Aminolevulinic acid

Summary

5‑Aminolevulinic acid (ALA) is a prescription amino‑acid precursor of porphyrins used orally or topically. In neurosurgery it is administered before resection of malignant glioma to cause tumour cells to fluoresce, aiding more complete removal. Topically, ALA serves as a photosensitiser in photodynamic therapy (PDT) for skin disorders such as acne and psoriasis. Its dual routes allow both systemic and local applications, but clinical benefits vary across indications.

Mechanism of Action

After administration, ALA enters cells and enters the heme biosynthetic pathway, where it is converted to protoporphyrin IX (PpIX). PpIX accumulates preferentially in rapidly proliferating or metabolically active cells, such as glioma or acne‑associated follicular epithelium. When illuminated with specific wavelengths, PpIX emits red fluorescence for tumour visualization or generates reactive oxygen species that destroy targeted skin cells during PDT. The fluorescence or cytotoxic effect is therefore a downstream consequence of ALA‑driven PpIX buildup.

What the Research Shows

A multicentre phase III trial in 322 patients with malignant glioma showed that oral 20 mg/kg ALA increased complete resection of contrast‑enhancing tumour from 36% to 65% and improved 6‑month progression‑free survival (41% vs 21%). No increase in severe adverse events was observed within 7 days post‑surgery. Systematic review of acne therapies identified ALA‑PDT as one of two modalities that modulate the cutaneous microbiome, though evidence is limited. A separate review of psoriasis PDT reported inconsistent efficacy and frequent severe pain, rendering topical ALA‑PDT unsuitable for chronic plaque psoriasis. Overall, robust data support neurosurgical use, while dermatologic applications remain exploratory.

Reported Benefits

In malignant glioma, ALA‑guided fluorescence enables surgeons to visualise tumour margins, leading to more complete resections and longer progression‑free intervals. Topical ALA in PDT can alter the skin microbiome and reduce acne lesions, offering a non‑antibiotic option. The oral formulation is well tolerated in the peri‑operative setting, with no excess severe adverse events reported in the glioma trial.

Limitations of the Evidence

Evidence for dermatologic uses is mixed; psoriasis studies report variable response and intolerable pain, while acne data are limited to small numbers and indirect microbiome effects. ALA‑PDT requires specialised light sources and can cause discomfort, restricting its practicality. Benefits in glioma are confined to fluorescence‑guided surgery and do not translate to overall survival data. Long‑term safety beyond the peri‑operative period remains under‑studied.

Safety Considerations

The glioma trial found no difference in severe adverse events between ALA and standard surgery within the first week. Dermatologic PDT with topical ALA commonly produces intense pain, burning sensations, and occasionally severe discomfort that can limit treatment completion. Systemic administration may cause transient photosensitivity, requiring avoidance of bright light for several hours. Routine monitoring for hepatic or renal changes is not indicated for single‑dose use, but clinicians should counsel patients on light‑avoidance precautions.

How It Is Administered

ALA is available as an oral capsule (e.g., 20 mg/kg given 3–4 hours before neurosurgery) and as a topical cream or gel for photodynamic therapy of skin lesions. The topical formulation is applied to the target area, followed by a drug‑light interval (typically 3–4 hours) before illumination with a specific wavelength light source. Both routes require prescription and are supplied in regulated concentrations.

Routes of Administration

Goals & Uses

• Bladder cancer detection (blue-light cystoscopy)Urology / OncologyHigh
• Photodynamic therapy of basal cell carcinomaDermatology / OncologyModerate
• Photodynamic therapy of actinic keratosisDermatology / OncologyHigh
• Fluorescence-guided resection of high-grade gliomaNeurosurgery / OncologyHigh
• PDT of field cancerization / photodamaged skinDermatologyModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• PorphyriaMetabolic DisorderHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Photodermatoses or photosensitizing drug useDermatology / PharmacologyModerate
• Hypersensitivity to ALA or porphyrinsAllergy / ImmunologyHigh

Adverse Effects

• Nausea and vomitingGastrointestinalCommon
• Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
• Phototoxic skin reactions (erythema, burning, stinging, edema)DermatologicCommon
• Transient hypotensionCardiovascularUncommon
• Crusting, vesiculation, pustulation at treatment siteDermatologicUncommon
• Photosensitivity / sunburn-like reactionDermatologicCommon

Drug Interactions

• Iron chelators (e.g., deferoxamine)Low
• Antioxidants (e.g., vitamin C, vitamin E, beta-carotene)Low
• Other photosensitizing agents (e.g., tetracyclines, fluoroquinolones, St. John's Wort, thiazides)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Pregnant womenReproductiveAbsolute
• Patients with known porphyriaMetabolicAbsolute

Regulatory Status

• European UnionApprovedApproved: Actinic keratosis (Ameluz, topical PDT), Superficial and nodular basal cell carcinoma (Ameluz, topical PDT), Fluorescence-guided resection of high-grade glioma (Gliolan, oral)EMA-approved; Ameluz has broader dermatology indications than in the US including BCC.
• United StatesApprovedApproved: Actinic keratosis of the face and scalp (Levulan Kerastick, topical PDT, 1999), Actinic keratosis (Ameluz 10% gel, topical PDT, 2016), Fluorescence-guided surgery of high-grade glioma (Gleolan oral solution, 2017)FDA-approved for multiple indications; Levulan and Ameluz are topical; Gleolan is oral.
• United KingdomApprovedApproved: Actinic keratosis (topical PDT), Superficial and nodular basal cell carcinoma (topical PDT), Fluorescence-guided surgery of high-grade glioma (oral)MHRA approved; largely aligned with EMA approvals post-Brexit via retained EU marketing authorizations.

FDA-approved: Levulan Kerastick (20% topical solution) for AK of the face/scalp (1999); Ameluz (10% gel) for AK (2016); Gleolan (oral solution, 1.5 g/vial) for fluorescence-guided surgery of high-grade gliomas (2017). EMA-approved: Gliolan (oral) for gliomas; Ameluz (topical) for AK and basal cell carcinoma.

Evidence & Sources

• Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial
  Journal ArticleModerateStummer W, et al.2006-01-01T00:00:00.000000Z
• Acne and the cutaneous microbiome: A systematic review of mechanisms and implications for treatments
  Journal ArticleHighPodwojniak A, et al.2025-01-01T00:00:00.000000Z
• Photodynamic therapy for psoriasis
  Journal ArticleModerateChoi YM, Adelzadeh L, Wu JJ2015-01-01T00:00:00.000000Z
• Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria
  Journal ArticleModerateBalwani M, et al.2020-01-01T00:00:00.000000Z

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