Whole Health Library

Adopted from Alschuler [3]

Although antioxidant-rich foods are commonly associated with reduced risks of a variety of cancers, use of antioxidant supplements during chemoradiotherapy can be associated with harm, and this has remained a controversial area. Conventional oncologists recommend against concurrent use of oral or intravenous antioxidants and chemoradiotherapy, as there is some potential for decreasing the effectiveness of conventional therapy. Most concerns are theoretical, although limited evidence for harm exists, mainly for vitamin E with head and neck patients. Experts cite large amounts of preclinical data and some human data to support use of antioxidants, such as vitamin C, coenzyme Q10, and vitamin E, for reduction of chemoradiotherapy-related toxicity.[5]

In a review of antioxidants which included glutathione, melatonin, vitamin A, an antioxidant mixture, N-acetylcysteine, vitamin E, selenium, L-carnitine, Co-Q10, and ellagic acid, 24 out of 33 studies reported decreased toxicities from the concurrent use of antioxidants with chemoradiotherapy. Only one trial with vitamin A reported a significant increase in toxicity in the antioxidant group. Five studies reported that the antioxidant group was able to complete more full doses of chemotherapy or had less-dose reduction than control groups.[6]

In an earlier review of vitamin A, beta-carotene, vitamin E, and glutathione used concurrently during chemoradiotherapy, studies repeatedly reported beneficial effects. Doses of vitamin A ranging from 30,000 IU to 500,000 IU daily to twice a week increased the treatment response rate, duration of response, and projected survival, lowered toxic side effects, and enhanced the cellular sensitivity to radiation. Two studies of beta-carotene given concurrently decreased side effects and allowed for a longer-than-expected disease-free interval. Those who received high-dose vitamin E in several studies had fewer toxicities, increased response rate, and reduced alopecia, and they were able to prevent oral mucositis. Patients given antioxidant mixtures via total parenteral nutrition (TPN) also had fewer side effects and a higher response rate. Oral combined antioxidant regimens decreased rates of recurrence, and increased quality of life, survival rates, and partial remission rates. Concurrent intravenous glutathione therapy increased response rates, reduced side effects, prevented nephro- and neurotoxicity, and improved survival.[7][8]

There are several potential mechanisms of action thought to be responsible for the beneficial effects of concurrent antioxidant treatment and chemotherapy/radiation. Cancer cells lose their homeostasis control mechanism for the uptake of antioxidants, leading them to accumulate them excessively. This causes cancer cells to shut down the oxidative reactions necessary for generating energy. In addition, studies have found that antioxidants increase apoptosis, inhibit cancer cell growth, inhibit oncogene expression, and selectively inhibit the repair of cancer cells damaged by radiation. These changes can lead to higher rates of cancer cell death and reduced rates of cell proliferation and induction of differentiation. The changes seem to override any protective action that antioxidants have against free radical damage on cancer cells.[7][8]

The following section reviews the effects of antioxidant supplementation on cancer risk:

General Evidence

A meta-analysis of 22 randomized controlled trials indicated that there is no clinical evidence to support primary or secondary prevention of cancer with antioxidant supplements.[9] Other studies confirm that there is no evidence that antioxidants prevent colorectal,[10] skin,[11] or prostate[12] cancer. A Cochrane review demonstrated increased mortality of patients with gastric cancer when supplemented with antioxidants.[13] There may be some preventive effects for cervical cancer.[14]

Vitamins A, C, and E

A systematic review did not find that vitamin C or vitamin E prevents or treats cancer.[15] Total intake of vitamin A and retinol could reduce breast cancer risk, but associations between vitamins C and E and breast cancer were limited.[16] Systematic reviews have shown no benefit of intravenous vitamin C therapy on patients with cancer.[17][18]

Carotenoids

A systematic review found no effect of beta-carotene supplementation on the incidence of all cancers, or specifically, pancreatic, colorectal, prostate, breast, or skin cancer. The incidence of lung and stomach cancers was significantly increased in individuals supplemented with beta-carotene, in smokers and asbestos workers.[19] In a smaller meta-analysis, beta-carotene had no preventive effect on cancer incidence or mortality, while it increased the risk of bladder cancer.[20] Two reviews found that increased blood concentrations of carotenoids were associated with reduced breast cancer risk.[21][22] A Cochrane review concluded that there is insufficient evidence to either support, or refute, the use of lycopene for the prevention of prostate cancer.[23]

Selenium

A Cochrane review found no beneficial effect of selenium supplements in reducing cancer risk, noting that evidence offered a high certainty to make this conclusion.[24] There is no association between selenium and thyroid cancer.[25] Selenium may have a protective role against the development of prostate cancer and its progression.[26] There is an inverse relationship between selenium levels and bladder cancer risk, particularly in women.[27]

There are numerous contraindications for using certain supplements and botanicals in patients undergoing cancer treatment. The most concerning interactions include those that upregulate the metabolism of a chemotherapy agent, thereby reducing its availability and effectiveness. Additionally, as patients receiving chemotherapy often have low blood counts, it is imperative to be wary of supplements that may increase bleeding or infection risk. Finally, antioxidant supplementation during chemoradiotherapy is still controversial. Until more rigorous trials are conducted, advise patients to obtain antioxidants naturally through food sources while receiving active treatment.

Supplement/Botanical Interactions with Chemotherapy and Radiation was written by Srivani Sridhar, MD (2014, updated 2020).