– Success in ameliorating muscle weakness with a ketogenic diet containing medium-chain triglycerides –
Researchers) FUJIKURA Yuri, Researcher, OOISHI Katsutaka, Group Leader, Healthy Food Science Research Group, Cellular and Molecular Biotechnology Research Institute
- A ketogenic diet containing medium-chain triglycerides attenuated muscle weakness in model rats with Duchenne muscular dystrophy
- The ketogenic diet not only inhibited muscle necrosis but also promoted proliferation of muscle satellite cells responsible for muscle regeneration
- This study contributes to the development of new treatment methods for muscular dystrophy
Reduction of fibrosis and increase muscle strength in DMD model rats (9 months old) on a ketogenic diet.
In the two photographs on the left, the red areas show normal muscle fibers; the blue shows fibrotic areas. The graph on the right shows muscle strength by body weight. “*” indicates there was a significant difference (P < 0.01) when compared to normal diet. (Quoted from Fig. 5 of Citation 1 with some modifications) A ketogenic diet reduced fibrosis in DMD model rats and improved muscle weakness.
Duchenne muscular dystrophy (DMD) is a hereditary muscular disease caused by mutations in the dystrophin gene; it is a progressive intractable disease in which muscle strength gradually weakens throughout the whole body. Loss of the ability to walk and impaired respiratory and cardiac function greatly affect quality of life (QOL) and longevity. The number of DMD patients in Japan is estimated to be 3,000 to 4,000, with an average life expectancy of 30 to 40 years. Although drug and gene therapy have been tried as treatment methods for DMD, a sufficiently effective treatment to prevent premature death has not yet been established.
Recently, it has been reported that ketone bodies may promote the proliferation of muscle satellite cells (stem cells). Since ketogenic diet increases the concentration of ketone bodies in the body, it could promote muscle regeneration in muscular dystrophy. However, the classical ketogenic diet contains limited amount of carbohydrates and protein, so it has also been indicated this could induce muscular weakness due to muscular atrophy from lack of carbohydrates and protein, and therefore classical ketogenic diet is not considered to be a suitable diet therapy for DMD patients.
For this reason, AIST conducted the research to develop a diet that does not induce muscular atrophy from undernutrition while efficiently increasing the concentration of ketone bodies in the body.
In collaboration with the University of Tokyo and Miyagi Health Innovation Co., Ltd., researchers in AIST found that the pathology of Duchenne muscular dystrophy model rats was improved with intake of a ketogenic diet containing medium-chain triglycerides.
The research group have shown that having DMD model rats that have a similar phenotype to human DMD take a ketogenic diet improves skeletal muscle atrophy and muscle weakness. The ketogenic diet not only suppressed muscle necrosis and fibrosis in DMD model rats, but also promoted muscle satellite cells proliferation. Our observations may have broad implications for developing new therapeutic methods for DMD, clarifying the new mechanism of its pathological progression.
Citation 1: Fujikura, Y; Sugihara, H; Hatakeyama, M; Oishi, K; Yamanouchi, K.
Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy.
FASEB J. 2021 Sep;35(9):e21861. https://doi.org/10.1096/fj.202100629R