Introduction to Aminolevulinic Acid
Aminolevulinic acid, often abbreviated as ALA, is a naturally occurring amino acid that plays a crucial role in modern medicine, particularly in dermatology and oncology [1.3.5, 1.5.4]. It is classified as a photosensitizing agent, which means it makes cells more sensitive to light [1.2.2]. This property is harnessed in a medical procedure called photodynamic therapy (PDT) [1.3.3]. ALA is not typically used on its own but as a precursor that, once absorbed by the body's cells, is converted into a potent photosensitizer called protoporphyrin IX (PpIX) [1.3.1]. When PpIX accumulates in targeted abnormal cells and is exposed to a specific wavelength of light, it produces a reaction that destroys those cells [1.3.5].
There are two primary applications for aminolevulinic acid that have received FDA approval:
- Topical Use: Applied directly to the skin as a solution or gel (e.g., Levulan Kerastick, Ameluz) to treat actinic keratoses (AKs) [1.2.2, 1.4.4].
- Oral Use: Taken by mouth as a liquid (e.g., Gleolan) to serve as an optical imaging agent during surgery for certain types of brain tumors (gliomas) [1.2.3, 1.5.1].
Mechanism of Action: How ALA Works
The effectiveness of aminolevulinic acid lies in its metabolic pathway. All cells use ALA to produce heme, a vital component of hemoglobin, through a series of steps. One of the intermediate compounds in this process is protoporphyrin IX (PpIX) [1.3.5]. Normally, the production of ALA is tightly regulated to prevent an overaccumulation of PpIX [1.3.5].
When external ALA is administered (either topically or orally), it bypasses this regulation, causing a significant buildup of PpIX, particularly in rapidly dividing cells like those found in actinic keratoses or malignant tumors [1.3.1, 1.3.5]. These cells selectively accumulate high concentrations of PpIX.
- Photosensitization: After an incubation period, the accumulated PpIX is a powerful photosensitizer [1.3.5].
- Light Activation: A specific type of light (blue light for some skin treatments, red light for others, or a special microscope light for surgery) is directed at the target area [1.2.1, 1.7.5].
- Cell Destruction: This light activates the PpIX, which then reacts with oxygen to create reactive oxygen species (ROS), such as singlet oxygen [1.3.1, 1.3.5]. These ROS are highly toxic to the cells, causing oxidative damage to cellular components and leading to cell death (apoptosis and necrosis) [1.3.5].
This targeted approach allows for the destruction of abnormal cells while minimizing damage to surrounding healthy tissue, which does not accumulate PpIX to the same degree [1.5.4].
Dermatological Application: Treating Actinic Keratosis
The most common use of aminolevulinic acid is in the treatment of actinic keratosis (AK), which are rough, scaly patches on the skin caused by years of sun exposure [1.2.2]. AKs are considered precancerous, as they have the potential to develop into squamous cell carcinoma [1.10.3]. ALA-based photodynamic therapy (PDT) is approved for treating mild to moderately thick AKs, particularly on the face and scalp [1.4.1, 1.4.2].
The procedure involves a healthcare provider applying the ALA solution or gel directly to the AK lesions [1.7.2]. The area is often covered with an occlusive dressing for an incubation period, typically ranging from 3 to 18 hours, depending on the product and location [1.7.1]. During this time, the patient must avoid exposure to sunlight and bright indoor lights [1.8.1]. After incubation, the patient returns to the clinic, where the area is illuminated with a special blue or red light source for several minutes [1.7.1, 1.7.3]. This light exposure can cause sensations of burning, stinging, or tingling, which subside after the treatment [1.6.3]. Following the procedure, the skin will be red and may scale or crust for up to four weeks as it heals [1.6.1]. Strict sun avoidance is crucial for at least 48 hours post-treatment, as the skin remains highly sensitive to light [1.8.1].
Comparison of Actinic Keratosis Treatments
| Treatment | Mechanism | Efficacy & Process | Common Side Effects |
|---|---|---|---|
| ALA-PDT | A photosensitizer (ALA) is applied and activated by light to destroy targeted cells [1.3.1]. | High clearance rate (around 82% in one study), short treatment duration, and few office visits [1.9.3]. Good cosmetic outcome [1.9.2]. | Light sensitivity, burning/stinging during treatment, redness, swelling, crusting [1.6.1]. |
| Cryotherapy | Liquid nitrogen is used to freeze and destroy the lesions [1.9.2]. | Good clearance rate (around 71% in one study), but may require multiple sessions [1.9.3]. | Pain, blistering, scarring, and potential for hypopigmentation (white spots) [1.9.2]. |
| Topical 5-Fluorouracil (5-FU) | A chemotherapy agent that interferes with abnormal cell growth [1.9.1]. | Effective for field treatment, but requires weeks of application [1.9.5]. High clearance rate but can cause significant inflammation [1.9.1]. | Redness, irritation, inflammation, erosion, and pain during the treatment course. |
| Imiquimod | An immune response modifier that stimulates the body's immune system to attack the abnormal cells [1.9.1]. | Lower clearance rate compared to PDT in some studies (around 68%) [1.9.3]. Requires several weeks of application. | Local skin reactions including redness, swelling, itching, and flu-like symptoms. |
Oncological Application: Brain Tumor Visualization
Beyond dermatology, aminolevulinic acid has a critical role in neurosurgery. Under the brand name Gleolan, it is administered orally to patients with high-grade gliomas (malignant brain tumors) a few hours before surgery [1.2.3, 1.5.1]. The principle is the same: the cancerous glioma cells preferentially metabolize the ALA into fluorescent PpIX [1.3.5].
During the operation, the neurosurgeon uses a surgical microscope equipped with a special blue light filter. Under this light, the cancerous tissue that has accumulated PpIX glows a distinct reddish-pink, while healthy brain tissue appears blue [1.2.3]. This fluorescence-guided surgery allows the surgeon to more clearly distinguish the boundaries between the tumor and normal brain tissue. The goal is to achieve a more complete and precise resection of the tumor, which is a key factor in improving patient outcomes, while sparing as much healthy brain tissue as possible [1.5.1]. Patients who take Gleolan must avoid sun and bright light exposure for 48 hours after administration due to the risk of severe systemic photosensitivity [1.2.3].
Conclusion
Aminolevulinic acid is a versatile medication that leverages a natural metabolic pathway for highly specific therapeutic and diagnostic purposes. In dermatology, its use in photodynamic therapy offers a highly effective, targeted treatment for precancerous actinic keratoses with excellent cosmetic results [1.2.2, 1.9.2]. In oncology, it serves as an indispensable tool for neurosurgeons, illuminating malignant brain tumors to enable more complete and safer removal [1.5.1]. By making abnormal cells vulnerable to light, ALA provides a powerful method for both treating and visualizing disease.
For more information from an authoritative source, you can visit the National Cancer Institute's page on aminolevulinic acid hydrochloride.
