ResearchandDevelopment

About Research and Development

Our research on γ-linolenic acid started with one type of oil.
We aimed to alleviate the severe itchiness of dialysis patients,
which greatly affects their Quality of Life (QOL).

Trial for dialysis pruritus

γ-linolenic acid had been used in Europe as a treatment for atopic dermatitis, so we considered whether it might also be effective against the difficult-to-treat itching of dialysis patients.

The pain of itching in dialysis patients is known only to the patients themselves, and at the time, the cause was often unclear, making treatment difficult. We used capsules containing oil with γ-linolenic acid, the main component, and vitamin E and administered them to dialysis patients who complained of itching. We recorded observations of six symptoms on the day of dialysis, including itching, redness, infiltration, scratch marks, and psoriasis-like changes. As a result, improvement was observed when capsules containing γ-linolenic acid were used for dialysis patients who complained of itching.

We presented our findings at various academic conferences, such as the 4th Itching Symposium in 1994 and the 42nd Japanese Society for Dialysis Therapy in 1997,

and also obtained a patent for a therapeutic composition for pruritus in artificial dialysis patients and secondary hyperparathyroidism treatment composition (Patent No. 3816545).

We also attempted to improve blood cell fluidity. It was known that the flow of blood cells (red blood cells and white blood cells) in the blood of dialysis patients was poor.

We considered that when white and red blood cells passed through the dialysis membrane (dialyzer), which is used during dialysis, they received physical stimulation, and each blood cell was activated, which could be one of the causes of itching.

If the membrane of red and white blood cells is not soft enough, they cannot pass through capillaries smoothly.

The kidney is a collection of thin blood vessels, and if blood cells are not soft enough, they can clog the vessels, leading to a decrease in kidney function. Currently, chronic kidney disease (CKD), which we often hear about on television, is also caused by a decrease in kidney function.

In our research, we have focused on the smooth flow of blood as a key factor in addressing the three major complications of diabetes: diabetic nephropathy, retinopathy, and diabetic neuropathy.

We believe that the hardness of blood cells contributes to these complications. We have conducted studies that demonstrate the effectiveness of oral intake of γ-linolenic acid in cases of diabetic gangrene in blood dialysis patients.

Reference: Nishinippon Hifuka (West Japan Dermatology), Vol. 64, No. 5 (2002)

[Summary of the Research Paper]

We observed the progress of gangrene occurring in the plantar region of patients undergoing maintenance blood dialysis for diabetic nephropathy. We administered a capsule containing a mixture of γ-linolenic acid and vitamin E and monitored the patient’s condition. Despite being a difficult-to-treat ulcer, with the continued use of the capsule and antibiotic therapy, epithelialization and granulation tissue formation were observed.

[Presentation at Academic Conferences]

1997: 7th Pruritus Symposium – Itch and Blood Flow in Blood Dialysis Patients

1997: 22nd Annual Meeting of the Japanese Society for Microcirculation – Effectiveness of γ-Linolenic Acid on Red Blood Cell Deformability in Blood Dialysis Patients

1998: 23rd Annual Meeting of the Japanese Society for Microcirculation – Changes in White Blood Cell Membrane Fluidity and Membrane Fatty Acid Composition before Administration of γ-Linolenic Acid in Blood Dialysis Patients

[Patent]

Title: Blood Cell Flow Improvement Agent

Patent No. 4473968

Diabetes-related Attempt:

In recent years, it has been reported that many patients with type 2 diabetes develop non-alcoholic fatty liver disease.

The increasing prevalence of NAFLD can be attributed to factors such as changes in dietary habits, sedentary lifestyles leading to obesity, and the rising number of individuals with diabetes. Given the close relationship between lipid metabolism and glucose metabolism in the progression from diabetes to fatty liver, we are conducting research to investigate which fatty acids contribute to the exacerbation of NAFLD.

[Summary of the Research]

In this study, we allowed KK-Ay mice to freely consume diets containing different levels of unsaturated fatty acids to induce obesity and diabetes. We examined how these variations in fatty acids affected the expression of lipid metabolism-related genes in the liver. The results showed the following:

The increase in hepatic lipid accumulation in diabetic mice was suggested to involve enhanced lipogenesis (fat synthesis) and lipid uptake.

A strong positive correlation was observed between the expression of the ACD-1 gene and liver triglyceride levels, suggesting that this correlation is mediated through two pathways: SrebA1c and CD36.

Among them, a diet deficient in essential fatty acids significantly worsened fatty liver in diabetic mice.

[Conference Presentations]

2018: 91st Annual Meeting of the Japanese Biochemical Society – Effects of Dietary Fatty Acids on Lipid Metabolism in a Type 2 Diabetes Mouse Model.

2019: 71st Annual Meeting of the Japanese Society of Vitamins – Effects of Dietary Fatty Acids on the Development of Fatty Liver in a Type 2 Diabetes Mouse Model.

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