Many oncologists and other conventionally trained specialists become very nervous when their cancer patients take nutritional supplements, especially those containing antioxidants, before or during cancer chemotherapy. The concern is understandable, but it may not be scientifically valid. In fact, there is growing evidence that antioxidants can actually benefit patients undergoing certain types of chemotherapy.
A case in point is a recent study of 62 women with ovarian cancer who underwent conventional chemotherapy with cisplatin, 100 mg/m2 and cyclophosphamide 600 mg/m2. Half were also assigned to a multi-nutrient supplement taken four times daily, and providing a daily total of 200 g/day selenium, 100,000 IU β-carotene (the form of β-carotene was not specified), 800 mg vitamin C, 144 IU vitamin E (the form was not specified), 18 mg vitamin B2, and 180 mg niacin, for three months. The other half of the cohort acted as a control, receiving the chemotherapy alone. The investigators measured CBC and assessed patients for treatment-related side effects on a monthly basis.
The group of women receiving the antioxidant supplementation and chemotherapy had a reduction in chemotherapy-associated WBC decline when compared with the control group. Nausea/vomiting increased 5% between the first and the third months in the control group, but decreased 56% in the supplement group. Diarrhea in the control group increased 69% between months one and three but decreased 40% in the supplement group.
Women in the antioxidant group also faired better in terms of hair loss. Hair loss increased 65% between months one and three in the control group, but increased by only 16% in the supplement group. Results were similar for anorexia with scores increasing in the control group, and falling in the supplement group by 65%. There were disparities in the incidence of other side-effects included malaise, weakness, stomatitis, and abdominal pain, all favoring the antioxidant group (Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004; 93: 320–327).
These findings suggest that a simple antioxidant formula including vitamin E, selenium and beta carotene plus small amounts of Vitamin B2 and niacin can significantly reduce signs and symptoms induced by cisplatin chemotherapy in those who are being treated for ovarian cancer. Although some practitioners are still concerned about using antioxidants with chemotherapy, little evidence supports their fears. In fact, the opposite seems to be the path supported by significant scientific evidence. Chemotherapy without antioxidants may actually create a significantly greater risk in terms of treatment associated side effects (J Am Coll Nutr 2001; 20:450S–463S; Nutr Cancer 2000; 37: 1–18; Altern Med Rev 1999; 4: 304–329).
Black Cohosh, Breast Cancer, and Interactions with Conventional Cancer Treatment
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| Black Cohosh (Cimicifuga racemosa) grown on Herb Pharm’s certified organic farm. Photo Courtesy of Herb Pharm. |
Many conventional oncologists will strongly discourage patients with cancer from using botanical medicines of any kind. This is driven by the belief that botanicals will interfere with chemotherapy and radiation. Such admonitions can create a real challenge for postmenopausal breast cancer patients who want to manage their menopause symptoms, especially hot flashes and night sweats, without hormone replacement therapy. Soy isoflavones, black cohosh and isoflavones derived from red clover are the most popular botanicals used for menopausal relief.
Previous reports/studies have concluded that black cohosh does not increase breast cancer cell division and actually markedly inhibits the proliferation rate of estrogen receptor positive breast cancer cells (Nesselhut T, Schellhase C, Dietrich R, Kuhn W. Examination of the proliferative potential of phytopharmaceuticals with estrogen-mimicking acting in breast carcinoma. Arch Gynecol Obstet 1993; 254: 817–818).
Lupu and colleagues also showed in 2003 that black cohosh does not have estrogenic activity and does not promote breast cancer cell growth (Lupu R, Mehmi I, Atlas E, et al. Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth. Int J Oncol 2003; 23(5): 1407–1412). To my knowledge, there has not been one published in vitro, animal or human study that shows black cohosh as an inducer or proliferative factor in breast cancer.
A recent cell culture study attempted to address the issue of whether black cohosh could interfere with the efficacy of conventional chemotherapy or radiation. While it is difficult to draw firm conclusions from in vitro work, the findings are interesting.
The investigators used mouse breast cancer cell lines, commonly used in breast cancer research, to see if black cohosh extracts altered the response of cancer cells to radiation and to four drugs commonly used in cancer therapy. Contrary to many oncologists fears, the herbal extracts actually increased the cytotoxicity of doxorubicin and docetaxel. However, it decreased the cytotoxicity of cisplatin. It did not alter the effects of radiation or an analog of cyclophosphamide (Rockwell S, Liu Y, Higgins S. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005; 90(3): 233–239).
This latest study is yet one more encouraging step in the assessment of the safety of black cohosh for menopausal breast cancer patients. This herb is one of our most important tools in alleviating their menopausal symptoms. According to this study, black cohosh should be avoided if patients are on a cisplatin regimen, most likely utilized in ovarian cancer patients.
Isoflavones Show Little Estrogenic Effect on Endometrium
In the last installment of Women’s Health Update (see Holistic Primary Care Summer 2005), I explored the complex issue of how soy isoflavones and their potential to induce endometrial hyperplasia. Existing data, taken as a whole, are somewhat conflicting. Some studies indicate that soy can induce hyperplasia, while other studies show no effect, or in fact, anti-estrogenic effects.
A recently published randomized, double-blind, placebo-controlled, crossover trial provides further suggestive evidence that isoflavone use in postmenopausal women does not affect the endometrium. However, it also shows that soy isoflavones do not improve vaginal dryness. A total of 64 postmenopausal women aged 35 to 69 years were given either 114 mg/day of soy isoflavones or placebo for 3 months. They were then crossed over to the other arm after a washout period of 2 months. All women were breast cancer survivors and had menopause symptoms including moderate to severe hot flashes, when the study began.
The isoflavone therapy produced no effect on any of the endpoints measured, including vaginal maturation index, endometrial thickness, endometrial histology, estrogen and progesterone receptor expression, and the endometrial proliferation marker Ki-67. Placebo had no effect on any end point as well except for a decreased maturation index, although the difference was not statistically significant. Vaginal dryness did not improve in either group (Nikander E, Rutanen E, Nieminen P, et al. Lack of effect of isoflavonids on the vagina and endometrium in postmenopausal women. Fertil Steril 2005; 83: 137–142).
The isoflavone intake of 114 mg/day in this study is higher than the typical Chinese diet intake of up to 80 mg/day, so if there is indeed a proliferative effect, one would expect to see it. One could argue that the three-month study period was too short to see a thickening of the endometrium or change in histology. However, the Ki-67 marker used to indicate endometrial proliferation can detect effects within this time period, and all of the treated women expressed this antigen while on the isoflavone treatment. Endometrial biopsies were obtained in only 29 of 46 women who had not undergone hysterectomy which leaves 17 women where no sample was obtained. This leaves us short of a good understanding of whether or not soy isoflavones have a stimulatory effect on the endometrium.
Also of interest, is that here is another study showing no effect of soy isoflavones on vasomotor symptoms that we can add to the pool of previous studies with mixed results. It seems that the jury is still out with regard to the risks and benefits of soy isoflavones for the management of menopausal symptoms. It may very well be that long term (5 years of more) exposure to quite high intakes (150 mg/day) is associated with a proliferative effect on the endometrium, but the lower doses in the dietary intake range, do not.
