Effects of Combined Treatment with Branched-Chain Amino Acids, Citric Acid, L-Carnitine, Coenzyme Q10, Zinc, and Various Vitamins in Tumor-Bearing Mice

Abstract

A functional dietary supplement (FDS) containing Coenzyme Q10, branched-chain amino acids and L-carnitine was administered to tumor-bearing mice, investigating its effects on tumor and muscle tissues. Experiment (A): B16 melanoma cells were implanted subcutaneously into the right side of the abdomen of 8-to 9-week-old C57BL/6J mice. The mice were divided into two groups: a FDS group that received oral administration of FDS (n=10), and a control group that received oral administration of glucose (n=10). The moribund condition was used as the endpoint, and median survival time was determined. Experiment (B): On day 21 after tumor implantation, tumors, soleus muscle, gastrocnemius muscle, and suprahyoid muscles were collected. Tumor and muscle weight and other aspects were evaluated in each group: FDS group (n=15) and control group (n=15). The median survival time was comparable (21 d in the FDS group vs. 18 d in the control group, p=0.30). However, cumulative food intake was significantly higher in the FDS group than the control group (p=0.011). Metastasis of melanoma to the lung was observed in the control group but not in the FDS group (p=0.043). The weight of the suprahyoid muscles was significantly higher in the FDS group than in the control group (p=0.0045). The weight of the tumor was significantly lower in the FDS group than in the control group (p=0.013). The results possibly suggest oral administration of FDS in tumor-bearing mice enhances the maintenance of suprahyoid muscles, resulting in an extended feeding period and suppression of tumor growth and metastasis.Key words cancer therapy; cachexia; metabolism; branched-chain amino acid; functional maintenance Cancer cachexia is a syndrome that affects many patients with advanced cancer. It is characterized by refractory malnutrition and has significant impact on prognosis and QOL. Managing cachexia is therefore a high priority when providing palliative care. Cachexia is a complex metabolic syndrome, with loss of muscle mass being a primary symptom. Development of cachexia involves many factors and accompanies progressive functional impairment, but the pathogenesis remains unknown. 1,2) Recent studies suggest that metabolic and neuroendocrinological abnormalities in cancer cachexia are caused by inflammatory cytokines secreted by the tumor and host cells and other tumor-derived substances. It is essential for cancer patients to maintain good nutritional status for better prognosis and QOL. As such, managing cancer cachexia is a major goal for the future of cancer therapy and palliative care. Since its foundation in 2003, our laboratory has implemented a unique nutritional support system to manage cancer cachexia.3-5) With the nutritional support, patients with cachexia have shown reduced symptoms and improved bodily function through control of metabolic dynamics. We have developed a functional dietary supplement (FDS) for improving symptoms and function, containing Coenzyme Q10 (CoQ10), branchedchain amino acids (BCAA), L-carnitine and citric acid and repo...

Nutritional Interventions in Cancer Cachexia: Evidence and Perspectives From Experimental Models

“…Furthermore, this combination attenuated weight loss and inflammatory markers, and reduced pathogen levels and bacterial translocation in a chemotherapy model (140). In mice bearing the B16 melanoma, the effect of a multi-nutrient intervention with BCAAs, citric acid, Lcarnitine, coenzyme Q10 and various vitamins and minerals was investigated on the development of cancer cachexia (141). The mice receiving the intervention diet showed a higher cumulative food intake compared to tumor-bearing control.…”

“…In addition, tumor weight was significantly lower and lung metastasis of the B16 melanoma cells were absent in the intervention group. However, attenuation of muscle tissue loss was only observed for the suprahyoid muscles in the neck but not for gastrocnemius or soleus muscles in the lower leg (141). More recently, the effect of total nutrition formula on LLCbearing mice was investigated (142).…”

Effect of antioxidants coenzyme Q10 and β‑carotene on the cytotoxicity of vemurafenib against human malignant melanoma

“…To the best of our knowledge, the present study is the first to have reported the inhibitory effect of CoQ10 on the migration of cancer cells. It has been previously reported that a functional dietary supplement containing CoQ10 branched-chain amino acids and L-carnitine completely inhibited the metastasis of melanoma to the lung (84). In addition, exogenous CoQ10 reduced matrix metalloproteinases 2 (MMP-2) activity in a breast cancer cell line (MCF-7), suggesting the importance of coenzyme Q10 on cell invasion effector molecules (85).…”

Lung cancer cachexia

“…Furthermore, this combination attenuated weight loss and inflammatory markers, and reduced pathogen levels and bacterial translocation in a chemotherapy model (142). In mice bearing the B16 melanoma, the effect of a multi-nutrient intervention with BCAAs, citric acid, L-carnitine, coenzyme Q10 and various vitamins and minerals was investigated on the development of cancer cachexia (143). The mice receiving the intervention diet showed a higher cumulative food intake compared to tumor-bearing control.…”

“…In addition, tumor weight was significantly lower and lung metastasis of the B16 melanoma cells were absent in the intervention group. However, attenuation of muscle tissue loss was only observed for the suprahyoid muscles in the neck but not for gastrocnemius or soleus muscles in the lower leg (143). More recently, the effect of total nutrition formula on LLC-bearing mice was investigated (144).…”