Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study

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Radioprotective Herbs
Radioprotection is an important function in complementary oncology. Ionizing radiation (IR) therapy has been used in cancer treatment for many decades; it is used to eradicate cancer and as a palliative to relieve pain associated with metastases. In the course of treatment, radiation produces numerous biological perturbations in cells; because normal cell toxicity limits the doses used in effective treatment, approaches are designed to strike a balance between eliminating cancer cells and protecting normal tissues. The primary focus in radiotherapy is to increase DNA damage in tumor cells, as double strand breaks are important in cell death.

Radioprotective compounds ameliorate the destructive aspects of radiation therapy without interfering with the function of radiation therapy. Side effects of radiotherapy may be acute, occurring during or within a few weeks after therapy, or intermediate to late, occurring months to years after therapy. Acute radiation toxicity is primarily due to cell killing, but inflammation or infection may also be contributing factors. Intermediate and late effects result from complex responses as tissues attempt to heal or fail to heal, and may be exacerbated by trauma or infection. There is a need to reduce radiation toxicity and thus provide a therapeutic benefit and improve overall quality of life. Curcumin has long been understood to be a radioprotective substance but some recent research suggests it is not as effective as thought (see article below) but remains a central radioprotective compound.

In TCM, there are a number of herbs and formulas that are radioprotctive. Gui Pi Tang (GPT) formula has been suggested to have therapeutic effects on hemato-deficient diseases and radiation-related injuries. GPT has been demonstrated to increase the recovery of cellular immunocompetence, particularly when administered at a concentration of 20 mg/20 g body weight following γ-ray irradiation (Hsu et al., 1993). Additionally, Ren Shen Yang Rong Tang, Zaizhang-I (composed of herbs including Radix astragali, Herba cistanchis, Radix saliae miltiorrhizae, Flos lonicerae) and Juzen-Taiho-Toh (Shi Quan Da Bu Tang) have demonstrated effects on the hematopoietic recovery from radiation-related injury in mice, by stimulating hematopoietic stem cells and by improving the hematopoietic inductive microenvironment (HIM).  The results demonstrated that these TCM herbs significantly promoted the recovery of the colony-forming unit-spleen (CFU-S) and the colony-forming unit-granulocyte/macrophage (CFU-GM) (Ohnishi et al., 1990; Yang et al., 1994; Fujii et al., 1994).

In 2010, Qi and colleagues provided a systematic review of Chinese herbal medicines in clinical trials, mainly as adjuvant treatments to reduce complications and side effects of chemo- or radiotherapy. Several traditionally used Chinese herbal medicines, including astragalus (Wang et al., 1992; Yoshida et al., 1997), Turmeric (curcumin) (Li et al., 2007; Jurenka  et al. 2009), Ginseng (Lee et al., 2005; Hofseth & Wargovich, 2007), Bu-Zhong-Yi-Qi-Tang (Kim  et al., 2002; Jeong et al., 2010), PHY906 (Saif  et al., 2010), and Huachansu (Qin et al., 2008) are commonly used by cancer patients to either “treat” cancer and/or “reduce the toxicity” induced by chemotherapy or radiotherapy.

Curcumin Study
Curcumin has long been seen as a radioprotective but this recent research casts doubt on that assumption (see below). Chinese herbs and formulations do have evidence of efficacy both as radioprotective as well as a radiosensitizer. A series of studies concerning the radioprotective and radiosensitizing functions of TCM have been conducted over a long time period and a series of bioactive components isolated from TCMs and the mechanisms of radioprotection were studied.

Curcumin is an antioxidant agent with both radiosensitizing and radioprotective properties. The aim of this study by Hejazi et al., (2016) was to evaluate the effect of curcumin supplementation on oxidative status of patients with prostate cancer who undergo radiotherapy. Forty patients treated with radiotherapy for prostate cancer were randomized to the curcumin (CG, n = 20) or placebo group (PG, n = 20). They received curcumin (total 3 g/day) or placebo during external-beam radiation therapy of up to 74 Gy. Plasma total antioxidant capacity (TAC) and activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) were measured at baseline and 3 mo after radiotherapy completion.

Analysis of covariance was used to compare the variables between groups following the intervention. Serum PSA levels and MRI/MRS images were investigated. In CG, TAC significantly increased (P < 0.001) and the activity of SOD decreased (P = 0.018) after radiotherapy compared with those at baseline. In CG, however, the activity of SOD had a significant reduction (P = 0.026) and TAC had a significant increase (P = 0.014) compared with those in PG. PSA levels were reduced to below 0.2 ng/ml in both groups, 3 mo after treatment, however, no significant differences were observed between the 2 groups regarding treatment outcomes.

Application of ionizing radiation, along with its direct effect such as DNA damage of the cells in its field, has some indirect impacts such as radiolysis of water and production of free radicals represented by hydroxyl ions as well (Erhola, et al., 1998). These ROS can cause the adverse reactions immediately after radiation, by breaking chemical bonds and promoting lipid peroxidation which explains, at least to some extent, the side effects that are induced by radiotherapy (Huang et al., 2012).

In a previous study on the authors’ radioprotective effects of curcumin, supplementation in patients with prostate cancer has been investigated and it was shown that patients in the curcumin group experienced much milder urinary symptoms compared with the placebo group although the differences between the 2 groups in terms of other radiation induced side effects (bowel symptoms, sexual function, etc.) was not significant (Hejazi et al., 2013). In the present study curcumin as a potent antioxidant agent has increased the antioxidant capacity of plasma and it is plausible that the observed reduction in the severity of radiotherapy related urinary symptoms in CG is because of this increment in TAC. A significant inverse relationship is observed between the increment of TAC levels and urinary symptoms, 3 mo after radiation therapy completion (r = −0.354, P = 0.047); however the relationship between activity of antioxidant enzymes and urinary symptoms did not reach statistical significance.

In the present study, patients in PG also showed an insignificant increase in their TAC, 3 mo after radiotherapy completion, which may be of note considering the production of large amount of free radicals during radiotherapy. In a study by Chevion on 14 patients who underwent total body irradiation prior to bone marrow transplantation, TAC was reduced by 36% short after radiotherapy, but after 4 mo recovered to a level 22% higher compared with that before the treatment (Chevion et al., 1999). The authors concluded that the antioxidant system of body can compensate the increment of oxidative stress after this period. This mechanism possibly accounts for the mentioned observation in PG.

Hejazi J, Rastmanesh R, Taleban F-Z, et al. Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. Nutrition and Cancer. Volume 68, Issue 1, 2016  DOI:10.1080/01635581.2016.1115527


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