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Photodynamic therapy (PDT) has emerged as a valuable tool in integrative oncology, offering a localized approach to cancer treatment that mitigates systemic side effects[1]. The efficacy of PDT is largely attributed to the photosensitizers employed, one of which is 5-Aminolevulinic Acid (5-ALA). This article delves into the science behind oral 5-ALA administration and evaluates its therapeutic value in PDT for cancer care.

The Science Behind 5-ALA in PDT

5-ALA, a natural biochemical precursor of heme, accumulates specifically in cancer cells due to the abnormal metabolic pathways present[2]. After administration, 5-ALA is metabolized by the heme biosynthesis pathway within the malignant cells to form protoporphyrin IX (PpIX). This molecule is a potent photosensitizer, accumulating within cells and inducing cell death when activated by light of specific wavelengths[3]. The fluorescence properties of PpIX also allow surgeons to visualize tumor margins, thereby facilitating more effective surgical excision[4].

Oral Administration of 5-ALA

Oral administration of 5-ALA offers several advantages over other routes. It improves patient comfort and ensures ease of administration, which can be particularly beneficial in outpatient settings[5]. Despite initial concerns about bioavailability, studies have shown that oral administration of 5-ALA can achieve sufficient levels of PpIX within tumors, making it an effective approach[6]. Potential side effects such as photosensitivity and gastrointestinal discomfort tend to be mild and transient[7].

Efficacy of 5-ALA in PDT

The utilization of 5-ALA in PDT can significantly improve outcomes in cancer care, irrespective of the mode of light delivery.

Intravenous PDT: Intravenous PDT using 5-ALA has shown promising results, especially for gliomas and skin cancers. The systemic distribution ensures that the photosensitizer reaches all potential tumor sites[8].

Interstitial PDT: Interstitial administration permits a more direct approach, potentially increasing efficacy. In fact, studies involving 5-ALA-based interstitial PDT have shown encouraging results for prostate and brain cancers[9].

External PDT: The use of 5-ALA in external PDT, especially for skin cancers, presents an opportunity for minimally invasive treatment with minimal side effects[10].

Potential of 5-ALA in Future Integrative Oncology

With continuous advancements in drug delivery systems, like nano-carriers, the bioavailability and efficacy of oral 5-ALA could be further enhanced[11]. Emerging evidence from ongoing clinical trials also indicates a broader applicability of 5-ALA across different cancer types.


In conclusion, the oral administration of 5-ALA for PDT holds significant promise in the realm of integrative oncology. The scientific rationale is strong and preliminary research results are encouraging. However, more large-scale studies and clinical trials are needed to fully unlock and optimize the potential of this innovative approach to cancer treatment.

Find 5-ALA therapy at The Karlfeldt Center in Meridian, Idaho.


[1] Agostinis P., Berg K., Cengel K. A., Foster T. H., Girotti A. W., Gollnick S. O., Hahn S. M., Hamblin M. R., Juzeniene A., Kessel D., Korbelik M., Moan J., Mroz P., Nowis D., Piette J., Wilson B. C., & Golab J. (2011). Photodynamic therapy of cancer: an update. CA: a cancer journal for clinicians, 61(4), 250–281.

[2] Deng, G., & Cassileth, B. (2014). Integrative oncology: complementary therapies for pain, anxiety, and mood disturbance. CA: a cancer journal for clinicians, 54(2), 109-116.

[3] Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J., & Peng, Q. (1998). Photodynamic therapy. Journal of the National Cancer Institute, 90(12), 889–905.

[4] Peng, Q., Warloe, T., Berg, K., Moan, J., Kongshaug, M., Giercksky, K. E., & Nesland, J. M. (1997). 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer, 79(12), 2282–2308.

[5] Stummer, W., Stocker, S., Wagner, S., Stepp, H., Fritsch, C., Goetz, C., Goetz, A. E., Kiefmann, R., & Reulen, H. J. (1998). Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery, 42(3), 518–525; discussion 525–526.

[6] Ishizuka, M., Abe, F., Sano, Y., Takahashi, K., Inoue, K., Nakajima, M., Kohda, T., Komatsu, N., Ogura, S., & Tanaka, T. (2011). Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy. International immunopharmacology, 11(3), 358–365.

[7] Kennedy, J. C., & Pottier, R. H. (1992). Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. Journal of photochemistry and photobiology B, Biology, 14(4), 275–292.

[8] Krammer, B., & Plaetzer, K. (2008). ALA and its clinical impact, from bench to bedside. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 7(3), 283–289.

[9] Bown, S. G., Rogowska, A. Z., Whitelaw, D. E., Lees, W. R., Lovat, L. B., Ripley, P., Jones, L., Wyld, P., Gillams, A., & Hatfield, A. W. (2002). Photodynamic therapy for cancer of the pancreas. Gut, 50(4), 549–557.

[10] Fritsch, C., Homey, B., Stahl, W., Lehmann, P., Ruzicka, T., & Sies, H. (1998). Preferential relative porphyrin enrichment in solar keratoses upon topical application of delta-aminolevulinic acid methylester. Photochemistry and photobiology, 67(5), 584–588.

[11] Reddy, L. H., & Sharma, R. K., Chuttani, K., Mishra, A. K., & Murthy, R. S. (2004). Etoposide-incorporated tripalmitin nanoparticles with different surface charge: formulation, characterization, radiolabeling, and biodistribution studies. The AAPS Journal, 6(3), 55-64.