Nutritional Interventions for Cancer-induced Cachexia Norleena P. Gullett,a Vera Mazurak,b Gautam Hebbar,c and Thomas R. Zieglerc
Abstract Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate.
Source : Curr Probl Cancer. 2011 Mar-Apr; 35(2): 58–90. doi: 10.1016/j.currproblcancer.2011.01.001 Link to full Article
Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma
We previously showed that the natural herb Coptidis rhizoma has an anticachectic effect in nude mice bearing human esophageal cancer cells. We further investigated this phenomenon by examining the anticachectic effect of C. rhizoma in syngeneic mice bearing colon 26/clone 20 carcinoma cells, which cause IL-6–related cachexia after cell injection. We evaluated nutritional parameters such as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal diet. IL-6 levels in those mice were quantified by ELISA and real-time RT-PCR. CR supplementation significantly attenuated weight loss in tumor-bearing mice without changing food intake or tumor growth. Furthermore, these mice maintained good nutritional status. IL-6 mRNA levels in tumors and spleens and IL-6 protein levels in tumors and sera were significantly lower in tumor-bearing mice treated with CR supplement than in those treated with a normal diet. CR supplementation did not affect food intake, body weight, nutritional parameters and IL-6 levels in non-tumor-bearing mice. An in vitro study showed that C. rhizoma and its major component, berberine, inhibited IL-1–induced IL-6 mRNA expression in a dose-dependent manner in colon 26/clone 20 cells. Our results showed that C. rhizoma exerts an anticachectic effect on colon 26/clone 20–transplanted mice and that its effect is associated with tumor IL-6 production. We also suggest that its effect might be due to berberine.
Cancer cachexia is a paraneoplastic syndrome characterized by profound weight loss, anorexia and weakness that occurs in most malignancies.1, 2 IL-6, a mediator produced by tumors or the host as a result of tumor–host interaction, is considered to play an important role in cancer-induced cachexia, suggesting that downregulation of IL-6 levels may improve cachexia or malnutrition in cancer patients.3–6 Indeed, an anti-IL-6 receptor antibody has been shown to prevent cancer-induced cachexia in a rodent model.4 Also, medroxyprogesterone acetate (MPA), a synthetic progesterone derivative, has anticachectic activity, likely due in part to the suppression of IL-6 secretion from tumor cells.7 Thus, blockade of IL-6 function might be a useful intervention for the treatment of cachectic patients. Since these patients usually have a poor quality of life, it is essential to treat them with minimal adverse effects. These findings and considerations prompted us to look for a novel agent capable of inhibiting IL-6 with little toxicity.
From the standpoint of providing mild therapy, we focused on the use of herbs in cancer treatment. In a previous study, we identified Coptidis rhizoma as an agent possessing potent antitumor activity.8, 9 We also showed that C. rhizoma significantly attenuated weight loss in nude mice bearing IL-6–producing esophageal cancer cells at a dose that does not alter tumor growth.10 However, we were unable to clarify the relation between IL-6 and the anticachectic effect of C. rhizoma in this model. Another study showed that s.c. inoculation of colon 26/clone 20 murine colon carcinoma cells into syngeneic mice causes progressive weight loss, adipose tissue and muscle wasting and other homeostasis disorders associated with cachexia.11 Since it is likely that IL-6 is one of the critical mediators in these mice bearing colon 26/clone 20 carcinoma, we used this model to examine the link between the anticachectic effect of C. rhizoma and IL-6. Samples were analyzed by real-time RT-PCR and ELISA. We measured IL-6 mRNA and protein levels in tissues of mice treated with C. rhizoma (CR) supplement or provided the normal diet.
..................In conclusion, our study showed that C. rhizoma exerts an anticachectic effect on colon 26/clone 20–transplanted mice and that the effect is associated with tumor IL-6 production. We also suggest that berberine, its major component, might play a role in the prevention of cachexia. Now, evidence from large-scale clinical trials will be necessary to incorporate this herb into mainstream cancer therapies.
Isabelle M. Berquin1,2, Iris J. Edwards2, and Yong Q. Chen1* 1Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina. 2Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are essential fatty acids necessary for human health. Currently, the Western diet contains a disproportionally high amount of n-6 PUFAs and low amount of n-3 PUFAs, and the resulting high n-6/n-3 ratio is thought to contribute to cardiovascular disease, inflammation, and cancer. Studies in human populations have linked high consumption of fish or fish oil to reduced risk of colon, prostate and breast cancer, although other studies failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of n-3 PUFAs on cancer in animal and cell culture models, has motivated the development of clinical interventions using n-3 PUFAs in the prevention and treatment of cancer, as well as for nutritional support of cancer patients to reduce weight loss and modulate the immune system. In this review, we discuss the rationale for using long-chain n-3 PUFAs in cancer prevention and treatment and the challenges that such approaches pose in the design of clinical trials.
Source Cancer Lett. 2008 October 8; 269(2): 363–377. doi:10.1016/j.canlet.2008.03.044 LINK TO FULL ARTICLE