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Background5-Aminolevulinic acid (ALA) is a precursor of heme that is fundamentally important in aerobic energy metabolism. Among the enzymes involved in aerobic energy metabolism, cytochrome c oxidase (COX) is crucial. In this study, the effect of ALA on cytochrome c oxidase activity was measured.Findingsc57BL/6N species of mice were administered ALA orally for 15 weeks. After ALA administration, mice were sacrificed and livers were obtained. COX activity in mitochondria from ALA-administered mouse livers was 1.5-fold higher than that in mitochondria from PBS-administered mouse livers (P < 0.05). Furthermore, ATP levels in ALA-administered mouse livers were much higher than those in PBS-administered mouse livers. These data suggest that oral administration of ALA promotes aerobic energy metabolism, especially COX activity.ConclusionsThis is the first report of a drug that functions in aerobic energy metabolism directly. Since COX activity is decreased in various diseases and aging, the pharmacological effects of ALA will be expanding.

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A precise diagnosis of peritoneal dissemination is necessary to determine the appropriate treatment strategy for colorectal cancer. However, small peritoneal dissemination is difficult to diagnose. 5-aminolevulinic acid (5-ALA) is an intermediate substrate of heme metabolism. The administration of 5-ALA to cancer patients results in tumor-specific accumulation of protoporphyrin IX (PpIX), which emits red fluorescence with blue light irradiation. We evaluated the usefulness of photodynamic diagnosis (PDD) using 5-ALA to detect the peritoneal dissemination of colorectal cancer. EGFP-tagged HT-29 cells were injected into the peritoneal cavity of BALB/c nude mice. After 2 weeks, the mice were given 5-ALA hydrochloride, and metastatic nodules in the omentum were observed with white light and fluorescence images. Twelve colorectal cancer patients suspected to have serosal invasion according to preoperative computed tomography (CT) were enrolled in this study. 5-ALA (15-20 mg per kg body weight) was administered orally to the patients 3 h before surgery. The abdominal cavity was observed under white light and fluorescence. Fluorescence images were analyzed with image analysis software (ImageJ 1.45s, National Institutes of Health, Bethesda, MD, USA). The mice developed peritoneal disseminations. The observed 5-ALA-induced red fluorescence was consistent with the EGFP fluorescent-positive nodules. Peritoneal dissemination was observed with conventional white light imaging in 8 patients. All nodules suspected as being peritoneal dissemination lesions by white light observation were similarly detected by ALA-induced fluorescence. In 1 patient, a small, flat lesion that was missed under white light observation was detected by ALA-induced fluorescence; the lesion was pathologically diagnosed as peritoneal metastasis. In the quantitative fluorescence image analysis, the red/(red + green + blue) ratio was higher in the metastatic nodules compared to the non-metastatic sites of the abdominal wall, fat and liver. We demonstrated better diagnostic accuracy using 5-ALA-PDD compared to conventional laparoscopy in patients with colorectal cancer. 5-ALA-PDD is a promising candidate method for diagnosing peritoneal dissemination of colorectal cancer.