Publication of a Paper on the Improvement of Glucose Tolerance in Mitochondrial Diabetes by 5-Aminolevulinic Acid (5-ALA)

Confirmed Effects of 5-Aminolevulinic Acid (5-ALA) on Improving Glucose Tolerance in Mitochondrial Diabetes – Potential as a Future Therapeutic Candidate

We are pleased to announce that Nagasaki University*1 (1-14 Bunkyo-cho, Nagasaki City, Nagasaki Prefecture, President: Shigeru Kawano; hereafter referred to as Nagasaki University) and NeoPharma Japan Co., Ltd.*2 (6-2-6 Kojimachi, Chiyoda-ku, Tokyo, CEO: Satoshi Kawada; hereafter referred to as NPJ), have confirmed the effectiveness of 5-aminolevulinic acid*4 (hereinafter, “5-ALA”) and sodium ferrous citrate (hereinafter, “SFC”) in improving glucose tolerance in patients with mitochondrial diabetes*3 (MIDD), characterized by ATP production disorder and insulin secretion impairment. This discovery points to a novel and effective adjunctive therapy for MIDD. The study was officially published in the international journal ‘Diabetes Therapy’ on November 22, 2022 (Japan Time).

【URL】

https://link.springer.com/article/10.1007/s13300-022-01335-8

 

【Research Highlights】

• Mitochondrial Diabetes (MIDD) is estimated to affect approximately 1% of diabetic patients in Japan.
• We examined the efficacy of 5-ALA/SFC as an adjunct therapy to insulin injections for MIDD patients.
• After 24 weeks of administering 5-ALA/SFC, the following results were observed during a glucose tolerance test:
• Significant reduction in blood glucose levels.
• An increasing trend in insulin secretion.
• HbA1c levels decreased from a baseline of 8.3±1.2% to 7.9±0.3%, although not significantly different.
• 5-ALA/SFC is anticipated as a promising new adjunct therapy for MIDD.

【Overview】

Mitochondrial Diabetes (MIDD) is a form of diabetes caused by mutations in mitochondrial DNA, characterized by hearing loss and ultimately requiring frequent insulin treatment. 5-ALA is a naturally occurring amino acid that has been utilized in various healthcare products for over a decade. At Nagasaki University, the functionality of 5-ALA has been focused upon for developing treatments for malaria and COVID-19*5. Additionally, combining 5-ALA with sodium ferrous citrate (SFC) is known to improve mitochondrial function. We conducted a preliminary study to assess its efficacy as an adjunct therapy for insulin injections in MIDD patients. The results after 24 weeks of 5-ALA/SFC administration showed a significant decrease in blood glucose levels in the late phase (AUC60-120min) and an increasing trend in insulin secretion (AUC0-120min) and a downward trend in HbA1c levels. Further research is deemed valuable to continue exploring this new and effective adjunct therapy for MIDD.

 

【Paper Title and Authors】

Title
Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness

Authors
Yuta Nakamura
(Department of Endocrinology and Metabolism, Graduate School of Biomedical Sciences, Nagasaki University)
Ai Haraguchi
(Department of Endocrinology and Metabolism, Graduate School of Biomedical Sciences, Nagasaki University)
Ichiro Horie
(Lecturer, Department of Endocrinology and Metabolism, Graduate School of Biomedical Sciences, Nagasaki University)
Jun Kawakami
(Professor, Department of Endocrinology and Metabolism, Graduate School of Biomedical Sciences, Nagasaki University)
Kyosei Abiru
(Department of Endocrinology and Metabolism, Graduate School of Biomedical Sciences, Nagasaki University)

Published in
Diabetes Therapy 2022 Nov 22.
DOI: 10.1007/s13300-022-01335-8. Online ahead of print

【Glossary】

*1 Nagasaki University
Nagasaki University is a national comprehensive university established in 1949. The campus, relocated and integrated in the 1950s and 1960s, hosts the medical faculties and institutes (Medical School, Dental School, Nagasaki University Hospital, Tropical Medicine Research Institute, etc.) at the Sakamoto Campus. Due to its geographical and historical background, Nagasaki University boasts outstanding achievements in tropical medicine, infectious diseases, and radiation medical science, holding a rich accumulation of research and a strong lineup of researchers in the field of infectious diseases, making it a leading educational and research base for infectious diseases both domestically and internationally.
http://www.nagasaki-u.ac.jp/

*2 NeoPharma Japan Co., Ltd.
NeoPharma Japan Co., Ltd. is a pharmaceutical company specializing in the research and development, and commercialization of 5-aminolevulinic acid (5-ALA), a natural amino acid. With years of research on plants, animals, and humans confirming the utility of 5-ALA, the company aims to commercialize its applications across various domains. It is also the only company in the world that has the facilities to mass-produce 5-ALA, manufacturing it under the same quality control as pharmaceuticals for use as food ingredients. We are committed to contributing to global healthcare through 5-ALA.
https://www.neopharmajp.co.jp/

*3 Mitochondrial Diabetes
Mitochondria play a crucial role in energy production within cells. Known to contain their own DNA (mitochondrial DNA), mutations in this DNA cause a form of diabetes known as mitochondrial diabetes. Often overlooked, mitochondrial diabetes is believed to affect about 1% of diabetes patients in Japan, making it the most common form of monogenic diabetes. Additionally, mitochondrial DNA is prone to acquire mutations over time, which could accumulate with aging and potentially impair mitochondrial function. Clinically, this form of diabetes can present as Type 1 diabetes, SPIDDM, or Type 2 diabetes, often accompanied by sensorineural hearing loss (approximately 90% of cases), as well as more frequently observed symptoms of cardiomyopathy, cardiac conduction defects, and myopathy.

*4 5-Aminolevulinic Acid (5-ALA)
Humans, animals, and plants maintain their vital functions by producing energy in mitochondria, small organelles within their cells. 5-aminolevulinic acid (5-ALA) plays a critical role in the function of mitochondria. It is an amino acid that has been safely used in health foods, cosmetics, pet supplements, feed, and fertilizer for over a decade. Moreover, 5-ALA is known to enhance mitochondrial function, and a phase III clinical trial led by Saitama Medical University is currently underway to investigate its effects on mitochondrial diseases. http://5ala-journal.com/

*5 April 13, 2022, Press Release by Nagasaki University
This release reports on the confirmation of the inhibitory effect of 5-aminolevulinic acid (5-ALA) on the Omicron variant of the coronavirus disease (COVID-19). Previous studies at Nagasaki University had shown that 5-ALA could completely inhibit the infection of SARS-CoV-2, the virus causing COVID-19, including four variant strains, in cultured cells at certain concentrations. Similar results were obtained in this study, where cell-based tests showed inhibition of the Omicron variant.
https://www.nagasaki-u.ac.jp/ja/science/science266.html