Antioxidant Effects
The question of whether it is safe to take antioxidants during chemotherapy or radiation therapy is not a simple one to answer. Experts have been trying to definitively answer this question for many years, but it remains very controversial (REF). To play it safe, most oncologists recommend to their patients that they avoid taking antioxidant supplements during these treatments due to the concern that they might reduce their efficacy.
Radiation therapy and many chemotherapy drugs kill cancer by producing molecules called free radicals, which damage DNA through a process called oxidation. (This is why free radical damage is also called “oxidative damage.”) Normal, non-cancer cells are able to repair most, if not all, of this DNA damage within hours. Cancer cells, on the other hand, typically have defective DNA damage repair mechanisms, so they accumulate excessive amounts of DNA damage that cause cell death through a process called apoptosis – a type of cell suicide.
Antioxidants are compounds that protect against oxidation and can inactivate free radicals (such as those purposely created by radiation therapy and chemotherapy to kill cancer cells). Thus, they can reduce or eliminate the DNA-damaging effects of the free radicals. In theory, they could therefore protect malignant cells from cancer treatments that rely on oxidative DNA damage.
When searching the medical literature for evidence of an antioxidant protective effect on cancer cells, there are unfortunately no clear answers (REF). The complexity of this issue is beyond the scope of this article, but suffice it to say there is no global rule of thumb that can be applied to all antioxidants.
We know that various compounds that possess antioxidant properties may exert either anticancer or cancer-protective properties, as well as normal tissue protective properties, depending on their dose, timing and route of administration, the use of other concurrent therapies and lifestyle factors. Furthermore, a compound may act as an antioxidant within one dose range (such as oral/low-dose vitamin C), but as a pro-oxidant (such as intravenous/high-dose vitamin C) at another (such as vitamin C).
The vast majority of data does not seem to indicate a decrease in anticancer effectiveness of chemotherapy nor radiation therapy. However, not all data support the safety of antioxidant supplementation during cancer treatment that relies upon the production of free radicals. For example, one study found that smokers who supplemented with alpha-tocopherol (vitamin E) and beta-carotene during their head and neck radiation therapy had increased recurrence and mortality compared to those who didn’t supplement. These authors found no differences in the non-smokers (REF). Furthermore, there may even be a reduction in the capability of built-in, protective, anticancer mechanisms (i.e. apoptosis) in cancer cells, to die when supplemental antioxidants are taken (REF).
In reviewing the evidence of supplemental antioxidant protection of normal tissues from the damaging effects of chemotherapy and radiation therapy, the preponderance of data supports the potential use of these antioxidant compounds for this indication (REF). In fact, the U.S. FDA approved a potent antioxidant drug (Amifostine, WR-2721 or Ethyol), for use during radiation therapy and chemotherapy to protect sensitive tissues from the damaging effects of treatment. The approval was based on an extensive review of the data, which found no reduction in the efficacy of radiation therapy or chemotherapy when Amifostine is administered during treatment.
Dr. Lawenda’s Experiment (EGCG, Vitamin E, Breast Cancer, Mice, Radiation Therapy)
During Dr. Lawenda’s residency, he conducted a study at the USDA’s Antioxidant Research Laboratory, to explore whether vitamin E or green tea would interfere with the effect of radiation therapy on tumors (REF). He specifically chose these two dietary antioxidant sources as they are among the most commonly used antioxidants reported by people undergoing cancer treatments.
He fed mice one of three diets:
- Regular mouse food (with all the recommended nutrients mice need to be healthy)
- Regular mouse food with extra vitamin E (alpha-tocopherol; the amount of vitamin E was equivalent to the human consumption of 400 I.U. per day, the amount most patients take in their vitamin E supplements)
- Regular mouse food with green tea extract (the extract is called EGCG, a well-known antioxidant; the amount of EGCG was equivalent to what would be found in the human consumption of 3-4 cups of green tea per day – an amount of green tea that is not unreasonable for most green tea drinkers to consume each day.)
The mice stayed on these three diets and then were implanted with a breast cancer into their hind legs. He then waited for the tumors to grow while the mice continued on their diets.
What happened?
Dr. Lawenda examined tissue samples, and found that the EGCG and vitamin E concentrations in the tumors were 150-220% greater than in the surrounding muscle tissue. This means the tumors had gobbled up the antioxidants much more enthusiastically than the surrounding tissues. With these findings, he expected to see some dramatic differences in the effects of the diets on tumor growth and responsiveness to radiation.
Once the tumors had grown to the size of a small pea (they all grew, but the EGCG diet group tumors grew 10% more slowly), Dr. Lawenda irradiated the hind leg with the implanted tumor of all the mice to see whether the radiation was made less effective by their diets. He made several interesting discoveries:
- Neither the EGCG nor the vitamin-E supplemented diets decreased the effectiveness of radiation therapy.
- The tumors that recurred after radiation therapy re-grew more slowly in the mice consuming the EGCG (24% slower) and vitamin E (25% slower) supplemented diets than in those mice eating a standard diet.
- The normal tissues of the hind legs of the mice on the EGCG and vitamin E diets were significantly protected from the damaging effects of radiation (much less tissue scarring, fibrosis and necrosis).
In summary, Dr. Lawenda found no tumor protection and significant healthy tissue protection with the antioxidant-rich diets.
Dr. Lawenda and Colleagues Published a Review in The Journal of the National Cancer Institute
Dr. Lawenda and his colleagues published a review article for the Journal of the National Cancer Institute on this topic in 2008 (REF). The findings and conclusions conclusions remain unchanged over 10 years later:
- Although most studies do not show that antioxidants protect tumors from the effects of chemotherapy or radiation, a small number of animal and cell studies have shown a reduced efficacy of radiation therapy and chemotherapy.
- No human studies have reported reduced efficacy of either chemotherapy or radiation therapy when administered at the same time as antioxidants (exception: smokers who took vitamin E and beta-carotene during head and neck cancer radiation therapy).
- Numerous studies have reported reduced side effects and improved treatment tolerance when chemotherapy or radiation therapy is administered along with antioxidants in humans.
Dr. Lawenda’s Year 2020 Recommendations Regarding Antioxidants
Depending on various factors (i.e. the patient’s condition, cancer, stage, type of treatments they received or are receiving, their interest level in using antioxidants, etc.), Dr. Lawenda usually counsels his patients on taking either a more-cautious or a less-cautious approach.
Cautious Approach
- Avoid high-dose antioxidants during chemotherapy and radiation therapy.
- Consume your antioxidants through food and beverages (i.e. fruits, vegetables, teas, etc.) or low dose supplements (not to exceed the recommended daily allowance, RDA) is not likely to offer any significant protection to tumors.
- Antioxidants supplements for which there are no established RDA’s (i.e. EGCG, curcumin), should either be consumed in moderation only in their whole plant forms (i.e. green tea instead of EGCG, turmeric instead of curcumin) or avoided.
- While it may be safe to resume higher-dose antioxidants after the completion of chemotherapy or radiation therapy, these may reduce the effectiveness of natural, mechanisms your cancer cells employ to activate cell death pathways (i.e. apoptosis) leading to enhanced cancer cell survival. Furthermore, there are established concerns from some studies that suggest high-dose antioxidant supplements may increase the risk of certain cancers (i.e. beta-carotene supplements increased the risk of lung cancer in smokers) and other untoward effects (i.e. vitamin E supplements increased risks of hemorrhagic/bleeding stroke and prostate cancer) REF.
- Always talk with your oncology team before taking any supplement.
Less Cautious Approach
- Consider taking various antioxidant supplements (along with fruits and vegetables) to improve treatment tolerance and quality of life. Your selection of these antioxidants should be informed by the scientific evidence in the published literature.
- Work with a provider who is highly knowledgeable in the safety of these supplements and their potential interactions with conventional treatments (i.e. prescribed and over-the-counter drugs, botanicals, chemotherapy agents, surgery, radiation therapy, etc.)
- Consider targeted intake (preferably through foods) of antioxidant micronutrient deficiencies, as identified on micronutrient lab testing.
- Before starting any new supplement, always discuss this with your oncology team.
