Dietary Supplements and Head and Neck Cancer Treatment

Dietary Supplements and Head and Neck Cancer Treatment

Review of J Natl Cancer Inst. 2005;97(7):481-88.

A study published in the Journal of the National Cancer Institute looked at use of beta-carotene and vitamin E dietary supplements during and after treatment for head and neck cancer. This study found that head and neck cancer patients who received a vitamin E dietary supplement during treatment and for approximately 3 years after treatment ended, had significantly greater risk of recurrence of their original head and neck cancer, as compared to people not receiving the vitamin E supplement. As well, the people receiving the vitamin E supplement during and after treatment had a significantly greater risk of having a new cancer (different from their original cancer) as compared to people not receiving vitamin E supplements. We provide PRACTICAL information on what these results mean. We discuss how the finding that vitamin E may increase risk of future head and neck cancers in people being treated for these cancers fits in with other research on vitamin E. This information will help people make informed decisions about the best nutrition plan to promote healing and long-term wellness after a diagnosis of head and neck cancer.

Note: Numbers appearing at the end of sentences indicate research references. References are listed at the end of each article.

Background

The two biggest risk factors for head and neck cancer (also called the upper aero-digestive tract cancers) are tobacco (smoking and chewing) and alcohol (drinking) (1-4). But even for individuals who have a history of using tobacco and alcohol, certain types of diet may increase or decrease risk of these cancers (5). And even though tobacco and alcohol are the major causes of head and neck cancer, dozens of studies tell us that diet and nutrition are important in the prevention of these cancers (6-31). The fact that diet can affect the risk of head and neck cancer has led to interest in how diet and nutrition may be used to help people even after a diagnosis of head and neck cancer.

A study published in the Journal of the National Cancer Institute looked at use of beta-carotene and vitamin E dietary supplements during and after treatment for head and neck cancer (32). In this study, head and neck cancer was defined as cancers of the tongue, gum, mouth, oropharynx, hypopharynx, pharynx, and larynx. The oropharynx, hypopharynx, and pharynx include the back portion of the tongue and the throat behind the oral cavity (the visible portion of the mouth) down to where the throat meets up with the esophagus. The larynx is commonly called the "voicebox". For a picture of some of these different areas of the throat, please see the on-line Merriam-Webster Medical Dictionary. It is hoped that this type of research will yield important information that will help people make informed decisions about the best nutrition plan to promote healing and long-term wellness after a diagnosis of head and neck cancer.   

What The Researchers Studied

For this study, researchers randomly assigned 540 people who were 18 years or older and who had been diagnosed with stage I or II head and neck cancer to receive either 400 IU (268 mg) of vitamin E and 30 mg of beta-carotene per day or a placebo. A placebo looks like a medication, in this case a dietary supplement, but it does not contain any active ingredients. This study was double-blind, which means that neither the people in the study nor the researchers who worked with these people knew who was receiving the vitamin E and beta-carotene supplement and who was receiving the placebo.

Two years after the researchers began inviting people to participate in this study, other research was published that suggested that beta-carotene supplements may increase the risk of cancer and other serious diseases, especially among smokers and former smokers (33). For this reason, the researchers discontinued using beta-carotene supplements in this study at that time. They continued the study by giving only the vitamin E and the placebo from that point forward.

The study participants were given the dietary supplements or placebo beginning on the first day of radiation treatment and continued to take them for an average of 3 years after radiation treatment ended. Information on other important factors, including gender, age, type and stage of head and neck cancer, past and current smoking habits, and blood levels of vitamin E and beta-carotene was collected and accounted for by the researchers. The average age of the people in the study was approximately 62 years.

What The Study Found

First, after following the people in the study for 3.5 years, the researchers found that the people who had received the vitamin E supplements had 2.88 TIMES the risk of getting another, new cancer as compared to those who received the placebo (no vitamin E). In other words, taking 400 IU of vitamin E during radiation and for up to 3.5 years after treatment very significantly increased the risk of getting another, new cancer. Those who took vitamin E had nearly 3 times the risk of getting another cancer compared to those not using a vitamin E supplement.

Second, after 3.5 years, the researchers found that the people who had received the vitamin E supplements had 1.86 TIMES the risk of having a recurrence of their original head and neck cancer and/or getting another, new cancer as compared to those who received the placebo (no vitamin E). In other words, taking 400 IU of vitamin E during radiation and for up to 3.5 years after treatment very significantly increased the risk of having a recurrence of the original cancer and/or getting another, new cancer. Those who took vitamin E had nearly 2 times the risk of cancer recurrence or of getting a new cancer compared to those not using a vitamin E supplement.

Third, the researchers did not find any difference in either the risk of having a recurrence of the original head and neck cancer or of getting a new cancer between those who took  beta-carotene supplements and those who took the placebo. In other words, the beta-carotene supplements did not appear to help or hurt those who took them. Keep in mind that the beta-carotene supplement was discontinued partway through the study. The researchers only had a small portion of the total number of people in the study to look at the effects of beta-carotene supplements in head and neck cancer survivors.

Finally, the researchers followed those in the study for another 2 years beyond the original 3.5 years (for a total of about 5.5 years). Keep in mind that the supplements and placebos had been given for the first three years of the study only. So, when the researchers continued to follow the people for 2 more years, the supplements were NOT being given at this time. They found that the increased risks of having a recurrence of the original head and neck cancer or of getting a second, new cancer disappeared. In other words, after people stopped taking the vitamin E dietary supplements, it appeared that the increased risks of having previously used those supplements disappeared over time.

What do these results mean?

If the people in this study are like most people who have been diagnosed with head and neck cancer, then this study suggests that taking a 400 IU (268 mg) vitamin E supplement during radiation treatment and for several years after treatment causes more harm than benefit. In particular, a vitamin E supplement appears to greatly increase the risk of both a recurrence of the original head and neck cancer and the risk of getting another, new cancer.

However, before we decide what these results mean, it is important to consider some of the limitations of this study.

First, the researchers tested only one specific type of vitamin E, known as dl-alpha-tocopherol. This is a synthetic (man-made) form of vitamin E. Some health experts feel that synthetic versions of some vitamins will not provide the same benefits as the natural forms of the vitamin that can be found in food. There are dietary supplements available that contain natural vitamin E, but these were not used in this study. For this reason, we cannot know if the results would have been the same if the researchers had studied natural vitamin E instead of synthetic vitamin E.

Second, part of the study was discontinued because of other research that became available. The beta-carotene supplements were only given to a small subset of the total number of people in the study and they were only given for a short period of time. For this reason, we can't know how beta-carotene supplements would have affected the results. It's possible that the results would be different if beta-carotene were given for the full duration of 3 years. For example, maybe vitamin E and beta-carotene would work differently in the body if taken as supplements together.

Third, the researchers studied all head and neck cancers together as one big group. It is possible that vitamin E would be helpful for some types of cancer, but not others. The study was not large enough to sort out how the vitamin E supplements might affect people with different types of head and neck cancer.

Finally, the dietary supplements were given starting on the very first day of cancer (radiation) treatment. Some health experts feel that antioxidant dietary supplements can interfere with some cancer treatments. Two previous studies that looked at beta-carotene supplements that were given to head and neck cancer patients AFTER they completed their treatment did NOT show harm from these supplements (34,35). This suggests that part of why the study we reviewed showed harm from vitamin E supplements may be due to the fact that they were given DURING cancer treatment. Perhaps if the same supplement had been started AFTER treatment ended, the results would have been different. 

On a positive note, this type of study (32), which is referred to as a randomized, placebo-control, double-blind trial, is the best type of research for helping to establish cause and effect. Unlike observational studies in which researchers simply observe possible connections between factors such as diet and cancer risk, this study actually gave an active dietary supplement and followed the people to see how this might affect their health.

A randomized controlled trial is less likely to be affected by some of the problems that can occur in an observational study. For example, in a controlled trial, the researchers are not relying on the participants' memories to determine who had what amounts of vitamin E in the diet. Instead, the researchers can determine exactly who did and who did not receive the dietary supplement when they analyze the study findings.

In summary, despite the weaknesses of this study, it clearly tells us that people who are being treated for head and neck cancer should NOT use vitamin E supplements that contain dl-alpha-tocopherol (synthetic vitamin E). There appears to be no benefit for people being treated for head and neck cancer from taking a vitamin E supplement. Furthermore, the dl-alpha-tocopherol form of vitamin E actually may increase risk of recurrence of the original head and neck cancer as well as the risk of getting a second, new cancer.

Healthy & Safe Food Sources of Vitamin E

From the results of the study reviewed (32), it is clear that people who are receiving radiation treatment for head and neck cancer should not use a vitamin E dietary supplement, especially one that contains synthetic vitamin E (dl-alpha-tocopherol).

However, vitamin E is an important nutrient and studies do tell us that people who get more vitamin E from vitamin E-containing FOODS in the diet have lower risk of many types of cancer, including some head and neck cancers (36-38).

Fitting Vitamin E Into The Diet

Even though this study no benefit and even possible harm from vitamin E supplements for people with head and neck cancer, keep in mind that getting nutrients from foods is still a very safe way to improve health and possibly lower risk of cancer, cancer recurrence, and heart disease.

Vitamin E needs vary by age and gender, but for most healthy adults, 15 mg of vitamin E per day from food sources is the Recommended Dietary Allowance (RDA) (39). For exact amounts of vitamin E that you should be eating for your age and gender, please see the information provided by the Food and Nutrition Information Center.

Use the following table to help you focus on food sources of vitamins E in your diet.

Some Food Sources of Vitamin E (40)

Food	Serving Size	Vitamin E in milligrams (mg)
General Mills® Whole Grain TOTAL®	1 cup	18 mg
Kellogg's® Product 19® Cereal	1 cup	13.5 mg
General Mills® TOTAL Raisin Bran®	1 cup	13.5 mg
Tomato Paste	1 cup	11.3 mg
General Mills® TOTAL Corn Flakes®	1 cup	10.1 mg
Sunflower Seeds, Dry Roasted	1/4 cup	8.4 mg
Sunflower Seeds, Dry Roasted	1 oz (small handful)	7.4 mg
Almonds	1 oz (~24 nuts)	7.3 mg
Spinach, Boiled*	1 cup	6.7 mg
Sunflower Oil	1 Tbsp	5.6 mg
Marinara (red) Pasta Sauce	1 cup	5.1 mg
Canned Tomato Sauce	1 cup	5.1 mg
Kellogg's® Special K® Cereal	1 cup	4.7 mg
Safflower Oil	1 Tbsp	4.6 mg
Kellogg's® Complete Wheat Bran Flakes®	1 cup	4.6 mg
Turnip Greens, Boiled*	1 cup	4.4 mg
Hazelnuts	1 oz (small handful)	4.3 mg
Dandelion Greens, Boiled*	1 cup	3.6 mg
Soymilk	1 cup (8 fluid oz)	3.3 mg
Mixed nuts	1 oz (small handful)	3.1 mg
Carrot juice	1 cup (8 fluid oz)	2.7 mg
Pine nuts	1 oz (small handful)	2.7 mg
Beet greens, boiled*	1 cup	2.6 mg
Pumpkin, canned	1 cup	2.6 mg
Sweet potato, cooked	1 cup	2.6 mg
Broccoli, boiled*	1 cup	2.4 mg
Canola oil	1 Tbsp	2.4 mg
Red peppers, raw	1 cup	2.4 mg
Mango, raw	1 medium	2.3 mg
Tomato soup, canned, prepared with water	1 cup (8 fluid oz)	2.3 mg
Papaya, raw	1 medium	2.2 mg
Peanuts, dry roasted	1 oz (small handful)	2.2 mg
Asparagus, boiled*	1 cup	2.2 mg
Collard greens, boiled*	1 cup	2.1 mg

*Values are for boiled vegetables. However, steaming, lightly sautéing or stir frying are preferred ways to cook these foods in order to best preserve nutrients.

NOTE: If you are in cancer treatment, these diet changes may not be right for you. Please keep in mind that dietary supplements can interfere with your cancer treatments. Please discuss your nutrition needs with your health care team.

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Publish Date: 06/2005