[image from Science Life, University of Chicago Medicine]

 

One of the challenges I have when working with a patient undergoing radiation for prostate cancer is whether or not to have them take dietary supplements.

You see, radiation works by producing oxidative stress (free radicals) in an effort to kill cancerous cells. So, in theory, if you take, say, 500mg of vitamin C, an antioxidant, that would protect the cancerous cells from radiation treatment, and the patient would not be cured.

The premise that antioxidants from dietary supplements protect cancerous cells from radiation therapy is a lousy theory.

Allow me to explain…

How Radiation Treatment Works for Prostate Cancer

The goal from radiation treatment (RT) either by external beam RT or brachytherapy (seeds) for prostate cancer is to cause irreparable damage to the DNA of the cell and thereby to cause cell death.

DNA damage is caused both by the direct and indirect effects of RT. About two-thirds is an indirect effect produced from the ionizing radiation creating active oxygen radicals (free radicals) such as hydroxyl radicals that may increase oxidative stress, not only to cancer cells but the whole body of the patient.

Oxidative stress is the primary cause for most side effects that include secondary cancers, urinary and fecal problems experienced by prostate cancer patients during and after RT.

Patients are going to use dietary supplements during and after RT for cancer in hopes to improve their outcome. About 81% of RT cancer patients do so without ever telling their physician.

Can Antioxidants Help or Hurt During  Radiation Therapy for Cancer?

In this paper  Dr.Kenneth Conklin, MD, Ph.D. from the University of California, Los Angeles (UCLA) Medical Center, questions the theoretical basis for the argument against concurrent anti-oxidant usage while undergoing RT.

Dr. Conklin acknowledges that radiation does indeed kill cells by generating high levels of free radicals, but this does not necessarily preclude the use of antioxidants as adjuvant dietary supplements during treatment. Conklin points out that radiotherapy is most useful in well-oxygenated tissues.

Antioxidants, as a class, improve blood flow and therefore promote the normal oxygenation of tissues, thereby rendering tumors more—not less—susceptible to radiation.

Numerous studies have shown that vitamin E and selenium, two known anti-oxidants,  protect against radiation-induced cancers.

A precise combination of antioxidants can help decrease damage expected from radiotherapy, including the formation of other cancer, especially in high-dose radiation since RT reduces tissue antioxidants.

In laboratory animals, for example, radiation exposure has demonstrated to reduce cellular vitamin E levels.

In other studies, radiation has shown to reduce bone marrow vitamin C and E levels, and in clinical studies in breast cancer patients, vitamin A, C, and E and selenium levels were found to be reduced during cancer radiotherapy.

Dr. Charles Simone, a radiation oncologist, surveyed the peer-reviewed literature on the use of supplements and antioxidants administered with chemotherapy and radiation therapy from 1996 through 2003.

He identified 280 peer-reviewed articles on this topic, of which 50 were clinical trials involving a total of nearly 9000 patients. Dr.Simone concluded that these studies have “consistently shown that non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer.”

In fact, according to Dr. Simone, antioxidants enhanced the effectiveness of standard therapeutic modalities while diminishing adverse effects and protecting healthy tissue.

In 15 of the studies reviewed by Dr. Simone and his group, close to 4000 patients who took non-prescription supplemental antioxidants not only did not fare worse from dietary supplement intake but improved survival.

Major Study on Antioxidants during Radiation Therapy for Cancer

There is one major study that conclude against antioxidant use during RT.

Bairati and colleagues set out to determine whether supplementation with antioxidants (alpha-tocopherol (vitamin E) and/or beta-carotene) significantly mitigated the adverse effects of radiation in 540 patients undergoing treatment for head and neck cancer.

Superficially reading this paper you’d think antioxidants promote worse outcomes when taken during RT since patients receiving supplementation in addition to radiation had a higher rate of second primaries and local recurrences while receiving the vitamins.

A closer reading of the Bairati study, in fact, shows that by the completion of the study, eight years after the start of radiotherapy, there were fewer second primaries or recurrences in the supplementation group compared with those receiving a placebo (113 vs. 119 participants, respectively).

Also, there was a 62% reduction in severe adverse effects on the larynx and other anatomical sites in those who were randomized to receive both antioxidants.

These mitigating facts were generally downplayed or ignored in a storm of negative publicity that was generated around the Bairati trial, after publication on the Journal of Clinical Oncology.

A 2006 study further analyses of the group studied by Bairati showed that during the follow-up period (average 6.5 years), 179 deaths were recorded in both groups. All-cause mortality, not only cancer-related in the vitamin E group was increased by 38%.

These results, the authors said, concurred with their earlier reports suggesting that high-dose vitamin E could be harmful in head-and-neck cancer patients receiving conventional therapy.

That conclusion is no surprise.

Synthetic alpha-tocopherol vitamin E should not be consumed especially in higher quantities than 50 IU a day.

The term vitamin E describes a family of eight antioxidants (called isoforms)

4 – tocopherols (alpha-, beta-, gamma-, and delta-) and 4 tocotrienols (alpha-, beta-, gamma-, and delta-)

Alpha-tocopherol is the only form of vitamin E that was studied in the SELECT trial and the Bairati study.

In a study of over 10,000 men at the prestigious Johns Hopkins School of Public Health, men who had the highest blood levels of gamma-tocopherol were five times less likely to get prostate cancer (Helzlsouer et al. 2000).

In the SELECT trial, 400IU of synthetic vitamin E was given a group of patients, eventually causing worse prostate cancer.

I have written extensively about the SELECT study, here, here and at the Natural Medicine Journal.

Another Study conceded numerous pathways of most plant chemical antioxidants, far from being pure scavengers of free radicals also induce cancer cell death. A few of these pathways, however, may also lead to tumor cell survival. These authors concluded that although patients should avoid what they call “unnecessary supplementation” during and after radiotherapy, using antioxidants to improve the therapeutic index of radiation is a reasonable and commendable goal.

Studies on Dietary Supplements for Prostate Cancer during Radiation Therapy

Until date, there is one randomized trial looking at the effects of antioxidants supplementation during RT specifically for prostate cancer.

In a group of nearly 140 patients, using green tea extract (500– 750mg BID, standardized to 80% catechins), melatonin (20 mg daily at bedtime), vitamin C (500–1000 mg TID), and vitamin E (200–400IU BID) no adverse events were observed after two years from the supplement group vs. the non-supplement group.

Curcumin during radiation for prostate cancer

There are protective effects of curcumin during radiation therapy. In one study,   men on curcumin supplementation during RT experienced milder urinary symptoms compared with the placebo group . No bowel symptoms or sexual function difference was noticed.

In addition to likely protecting against unwanted urinary symptoms, curcumin use can probably have a radiosensitive effect on cancer cells making them more vulnerable to RT.

For the scientifically minded reader;  curcumin increases radiation sensitivity and promotes inhibition of radiation-induced elevation of growth factors, cytokines, cyclins, NF-κB, PKC, TNF-α, and inhibition of cell cycle at the G2 + M phase, increased apoptosis, and some other unknown mechanisms

There is a possibility that curcumin can protect normal tissues against the deleterious effects of ionizing radiation as an antioxidant while enhancing the sensitivity of cancer cells to the radiation by mechanisms mentioned above.

A randomized study showed that curcumin improves the antioxidant status of patients with prostate cancer without compromising the therapeutic efficacy of radiotherapy.

The researchers also observed a  significant inverse relationship (protective) between the antioxidant levels and urinary symptoms in patients after RT. In other words, curcumin seems to have protected the healthy cells of the urinary system where less urinary problems were noticed after RT.

Dr. Geo’s Take on the Use of Dietary Supplements During and After Radiation Therapy for Prostate Cancer

Almost every day of my life I am asked questions regarding supplements during RT.

Radiation oncologist vehemently discourage patients from taking antioxidants during radiation treatment in an effort to provide maximal therapeutic benefit with little interference with the treatment. Still, a majority of patients will take dietary supplements undergoing RT without ever telling their physician.

The problem is, I’m not sure the patient benefits much from eliminating the careful use of antioxidants during radiation therapy. In fact, the proper combination of antioxidants may likely protect healthy cells from becoming damaged or malignant and likely enhance, not interfere, with more cancer cell death in conjunction with RT, rather than RT alone.

When counseling prostate cancer patients undergoing RT on supplements my primary goal is to cause less confusion  while providing a sustainable health plan that will keep him well during and after treatment. Such confusion only causes more frustration to the patient and his family.

However, a one hundred million dollar randomized, twenty year study proving or disproving the effects of antioxidants during RT for prostate cancer will never happen, so I think is prudent to take numerous dietary supplement during RT for prostate cancer.

Detailed Recommendations on AntiOxidant During and After Radiation Therapy for Prostate Cancer.

• Report supplements you are taking to all physician’s in your healthcare team.
• Seek the help of a nutritionally oriented healthcare expert who works with an oncologist.
• Naturopathic and functional medicine doctors are well-trained in nutrition and non-conventional approaches, but not all are versed in oncology. An organization of doctors who are experts in oncological nutrition is OncANP.
• Synthetic alpha-tocopherol vitamin E should NEVER be used for cancer regardless of treatment for cancer.  There is no reason to use anything other than mixed tocopherol.
• Vitamins with antioxidant capacity should be used in combination with others. For example, vitamin C, vitamin E, zinc, and alpha-lipoic acid work synergistically and prevents too much pro-oxidation.
• If your radiation oncologist digs her heels into the ground and does not allow you to take dietary supplements during RT, and you are not working with a nutritionally oriented doctor, take curcumin and melatonin on the days you undergo RT.
• Print this blog post or forward it to your physician. Maybe they will be open in allowing you to consume the right combination of dietary supplements after reading

 

Good Luck!