As we discussed in our previous blog, the headlines last week were warning cancer patients about the potential problems with taking antioxidants while undergoing chemotherapy treatment. These headlines were generated from a recent study by a group of Swedish researchers, who used two antioxidants in studying mouse tumors. The antioxidants were n-acetyl cysteine (often called NAC) and a water-soluble form of vitamin E called Trolox. Both NAC and Trolox gave mouse melanoma cells properties that made them more invasive, and both of them increased levels of reduced glutathione in the melanoma cells.
Glutathione produced internally by cancer cells, as we mentioned previously, has some potential problems. So you would think that giving glutathione to cancer patients would cause no end of problems. But this is not what we found when we reviewed literature on the interaction of antioxidants and chemotherapy. In that review, we found 7 randomized trials in which glutathione was given intravenously to cancer patients receiving chemotherapy to reduce chemo side effects. In most of the trials there was some improvement in side effects. In none of the trials did the patients who received glutathione have worse survival or tumor regression in response to chemotherapy than the control patients. Of course, this was in the context of patients receiving intensely oxidative chemotherapies – and I wouldn’t suggest that glutathione be given to patients not receiving chemotherapy. It’s possible, also, that the rather high doses of glutathione used in these studies actually had a pro-oxidative effect, as some antioxidants do when given at high doses. The pro-oxidative effect of high-dose antioxidants is the reason that intravenous vitamin C may be helpful for cancer patients.
If one or two antioxidant supplements by themselves are not optimal for cancer patients, what about antioxidant multivitamins, which are a little closer to the way we get nutrients in our food? I don’t believe that multivitamins by themselves are a good way to supplement cancer treatment, but they do fare a little better than studies of NAC by itself. For instance, a 2013 study of over 7000 postmenopausal women with invasive breast cancer found that those who took multivitamins had a 30% lower mortality rate from breast cancer than non-users. Of course, this could be explained if the multivitamin users had healthier lifestyles, ate better or exercised more, which has often been observed for multivitamin users. This improved survival, however, stood up after multiple statistical manipulations of the data to account for all these possibilities.
But human trials are full of complications. What if we go back to the level of the mouse? What do other studies say about the effects of antioxidants on melanoma metastasis or tumor growth in mice? We searched the literature back as far as 2010 to see what we could find about other antioxidant compounds that were given to mice. In the studies we found, the antioxidant flavonoid quercetin reduced lung metastases in animals injected with mouse melanoma cells. It also inhibited enzymes in the cell called “matrix metalloproteinases” that facilitate metastasis. An antioxidant soy isoflavone, genistein, was given to mice with injected melanoma cells. It reduced tumor growth and weight by 30%, and none of the genistein-treated group developed liver metastases, which did appear in the control group. An antioxidant in black tea, theaflavin, also reduced the matrix metalloproteinases in human melanoma cells. And mice treated with theaflavin had smaller tumors than controls. There were more lab studies indicating that natural antioxidants inhibited metastases in mice, or metastasis-promoting factors in melanoma cells, through a variety of mechanisms, although we did not find other papers dealing with the glutathione system in our brief search.
So what can we make of this study of NAC and mouse metastases? Did the Swedish researchers simply ignore the fact that clinical study has already indicated that NAC doesn’t have much effect on cancer patients, that melanoma patients treated with Co-Q10 had fewer disease recurrences and that multiple studies of antioxidant phytochemicals did not find signs of promoting metastases? Actually, I suspect not. It’s perfectly reasonable to want to study the effects of intracellular glutathione on metastases, and NAC and Trolox are two of the common chemicals that researchers turn to for studies like these. But the conclusion that cancer patients shouldn’t take any antioxidant supplements is going considerably beyond what their data say.
I certainly don’t think that a reasonable supplementation or integrative program for a patient consists of one or two antioxidants. Cancer is a multi-faceted disease. A multifaceted disease begs for a multifaceted treatment. And we know that individual patients differ in their internal biochemistry as well as in the genetics of their tumors. Integrative, multifaceted treatment thus demands not only multiple evidence-based therapies, but also testing of patients’ metabolic and biochemical terrain and, where possible, tumor genetics to develop individualized programs. If you’re a cancer patient who wants more than what your conventional doctor is giving you, you should not just run out to the health food store and grab one, two or twenty-two supplements off the shelf. Go to a comprehensive integrative center, like the Block Center, where a truly individualized program can be developed for you, based on clinical and historic evaluation as well as thorough testing and assessment.
And when you see scarecrows around town this Halloween season, let them remind you of the problems of setting up straw men (or straw mice) in cancer research!