Antioxidant Supplements and Gastrointestinal Cancer Risk

Antioxidant Supplements and Gastrointestinal Cancer Risk

Review of Lancet. 2004;364(9441):1219-28.

A study in the journal Lancet looked at how using antioxidant dietary supplements affects the risk of gastrointestinal cancers. Gastrointestinal refers to cancers of the esophagus, stomach, colon, rectum, pancreas and liver. The researchers looked at several antioxidant dietary supplements including beta-carotene, vitamins A, C, and E, and selenium. This study suggests that antioxidant dietary supplements do not protect against gastrointestinal cancers and may actually increase the risk of these cancers. We provide practical information on what these results mean. We provide ideas for how this information can be incorporated into a healthy dietary plan with the goal of minimizing cancer risk. This will provide useful information to people who are trying to use nutrition to reduce their risk of cancer.

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

Background

Dozens of research studies have shown that eating plenty of foods that contain antioxidants may reduce the risk of gastrointestinal cancers (1-29). However, studies of people who take antioxidant dietary supplements do not show a consistent protective effect against gastrointestinal cancers (30-47). In other words, eating foods that contain antioxidants appears to lower the risk of gastrointestinal cancers, but we do not know if taking antioxidant dietary supplements (pills) gives the same benefit.

A recent study published in the journal Lancet looked at this question again (48). Researchers used a special type of research study to look at how antioxidant dietary supplements might affect the risk of gastrointestinal cancers. It is hoped this research will help us gain more information about the possible benefits or risks of taking antioxidant dietary supplements.

What The Researchers Studied

For this study (48), researchers combined people from many smaller studies to allow them to better examine the possible connection between antioxidant dietary supplements and risk of gastrointestinal cancers. This type of research is called a meta-analysis. A meta-analysis allows researchers to have larger numbers of people to study. It is hoped that by increasing the numbers of people being studied, the researchers will get clearer answers about the possible risks and benefits of using antioxidant dietary supplements.

The researchers identified 14 studies in which people took antioxidant dietary supplements in an effort to decrease risk of cancer. They looked at dietary supplements containing beta-carotene, vitamins A, C, and E, and selenium, either alone or in various combinations. They analyzed the results of all of these studies together to get a total of 170,525 people who either took an antioxidant dietary supplement or took a placebo pill. A placebo is a 'dummy pill' or a 'fake' version of an active medication and helps researchers separate the 'power of suggestion' from the real effects of a medication, therapy or dietary supplement. Using this information, they determined how antioxidant dietary supplements may affect risk of gastrointestinal cancers.

What The Study Found

First, when the researchers considered all of the studies together, they did not find any benefit to using antioxidant dietary supplements, either individually, or in various combinations. In other words, people who were taking antioxidant dietary supplements had the same risk of gastrointestinal cancers as people who were not using these supplements.

Second, when the researchers included only what they determined to be "good-quality" research studies (7 total studies), they found that people taking any type of antioxidant dietary supplements had approximately 6% greater risk (1.06 times the risk) of dying of all causes (cancer and other causes) when compared to people not taking these supplements. In other words, taking antioxidant dietary supplements seemed to slightly increase risk of death from all causes combined in this study.

Third, when the researchers looked at specific dietary supplements separately, they found that certain supplements or combinations of supplements increased risk of death more than others. Specifically, the researchers found that:

• People taking beta-carotene plus vitamin A had approximately 29% higher risk (1.29 times the risk) of dying of all causes (cancer and other causes) when compared to people not taking these supplements. In other words, taking beta-carotene plus vitamin A seemed to increase risk of death from all causes by about 29%.
• People taking beta-carotene plus vitamin E had approximately 10% higher risk (1.10 times the risk) of dying of all causes (cancer and other causes) when compared to people not taking these supplements. In other words, taking beta-carotene plus vitamin E seemed to increase risk of death from all causes by about 10%.

Fourth, the researchers found that people who were taking a selenium supplement had approximately 50% less risk (0.50 times the risk) of liver cancer when compared to people not taking a selenium supplement. This was true for people who were at high risk of liver cancer, such as people who had a strong family history of liver cancer or who had a history of infection with hepatitis B virus. In other words, in people who have a higher than normal risk of liver cancer (not the general population), taking selenium appeared to decrease risk of liver cancer by approximately 50% (decrease by half).

Finally, the researchers found that people who were taking a selenium supplement had approximately 51% less risk (0.49 times the risk) of all gastrointestinal cancers combined when compared to people not taking a selenium supplement. In other words, taking selenium appeared to decrease the risk of gastrointestinal cancers, which includes cancers of the esophagus, stomach, colon, rectum, pancreas and liver, by about 51%. 

What do these results mean?

If the people in this study are similar to most people, then this study suggests that taking antioxidant dietary supplements does not provide any benefit for preventing gastrointestinal cancers. On the contrary, this study tells us that these supplements actually may increase the risk of gastrointestinal cancers and death from all causes combined.

The one exception to this pattern is selenium. Only selenium appears to offer protection against gastrointestinal cancers in people in general. Only selenium appeared to protect against liver cancer in people at high risk for this disease.

If you've been using antioxidant dietary supplements, don't panic!

While this study shows that these supplements do not protect against gastrointestinal cancers and other causes of death, it helps to put the results into perspective. Keep the following points in mind:

• The overall finding that taking antioxidant dietary supplements increases risk of death shows a very small increase in risk. This study showed a 6% increase in risk of death. While this is important, it is a very small number. This number is important on a large scale, for example when we look at public health measures that involve millions of people. However, on an individual level, this number is so small that it is almost meaningless.
• Several of the studies that were part of this larger study included people who were at very high risk for gastrointestinal cancers. For example, researchers included people with a strong family history of these diseases, or people who had other reasons for being at high risk, such as those who had been infected with the hepatitis B virus. Hepatitis B virus infection is known to greatly increase risk of liver cancer. This means that people with this infection are different from people in the general population. For this reason, they may respond differently to dietary supplements and nutrition factors than an average person.
• Much of the increase in risk of gastrointestinal cancers and death appears to be linked with taking beta-carotene supplements in particular. This is not a new finding. Previous research studies have told us that beta-carotene supplements may not be a good thing for some people (39,43). For example, in people with other risky behaviors, such as smoking and heavy use of alcohol, beta-carotene appears to increase risk of cancer rather than decrease risk. Some health experts believe that there is an interaction between risk factors like smoking and beta-carotene supplements. In other words, in smokers, beta-carotene may cause more harm than good, but in non-smokers, this is not true. This is one explanation for why there may be harmful effects from beta-carotene or other dietary supplements in some people, but not in others (49-53). But for people who do not have these other risks, beta-carotene probably doesn't help, but it probably doesn't hurt either.
• This study included research in which the antioxidant dietary supplements were given at high doses that are well beyond what would be found in a healthy diet. And some of the antioxidant doses were above what health experts consider to be safe 'upper limits' for these nutrients. The excess amounts of nutrients given in the reviewed research may explain the lack of benefit shown. 

Antioxidants & Cancer Prevention

Making Sense Of The Research

• There is no controversy about eating foods that contain antioxidants, including beta-carotene. Eating these foods is a healthy, safe option for improving health in all people.
• EATING foods that are rich in antioxidants, such as vegetables and fruit, still appears to be one of the most effective ways to use nutrition to reduce the risk of many types of cancer, including gastrointestinal cancers! Study after study tells us that this is true (3,10,18,20,28,54-60).
• The conflicting findings on benefits of taking antioxidant dietary supplements tell us that simply taking a dietary supplement that contains some of the antioxidants that are found in food may not give the same benefit as eating the foods that contain these nutrients.
• There are thousands of potential cancer-fighting nutrients in the foods we eat, including antioxidants and other phytochemicals. Plant foods such as vegetables, fruit, whole grains and legumes (beans) contain the most antioxidants and cancer-fighting phytochemicals. It is impossible to get this same array of nutrients from a pill.
• Many health experts now believe that antioxidants alone do not explain why diets rich in fruits and vegetables protect against cancer and other diseases (61,62). It is more likely that the combination of phytochemicals in these foods is the reason they protect against cancer. This explains why no single antioxidant or few antioxidants can replace the combination of natural phytochemicals in fruits and vegetables to effectively prevent cancer.

Keep It In Perspective

• Remember, keep these research findings in perspective! If you have been taking antioxidant dietary supplements, it does not mean that you have increased your risk of cancer and death! But what it does mean is that we need to step back and evaluate why we might get benefit (or harm) from the various dietary supplements that we use.
• Dietary supplements are not all good or all bad. There are many dietary supplements that may be very beneficial for addressing a number of health problems.
• Keep in mind that the reason for using dietary supplements is right in the word "supplement"! If you are taking a dietary supplement, you should be SUPPLEMENTING something. For the best cancer prevention, you should supplement a good, healthy diet that contains plenty of antioxidant-rich foods.

Make Practical Diet Changes That Count

Before you give up on antioxidants, remember that antioxidants that you get in your diet FROM FOOD are good for health and can reduce the risk of many diseases, including cancer! Use the following steps to increase antioxidant-rich foods in your diet.

• Go for color! Generally, the more brightly colored the food, the higher it's content of antioxidants and other disease fighting nutrients. Try to eat orange, red, green, yellow, blue, purple, and dark green foods. For example, try carrots, sweet potatoes, peppers, mangoes, papaya, blueberries, eggplant, kale, collard greens, spinach, etc. The choices are endless.
• Start with one change at a time. You can't expect to change your whole diet overnight! Instead, think of one place where you can add in a healthy antioxidant-rich fruit or vegetable, such as for breakfast or as a mid-day snack, and do this first. Once you have successfully made this change for a number of weeks, pick another place in your diet to eat these foods.
• Fresh vs. Frozen: Many people mistakenly believe that fruits & vegetables have to be fresh to give health benefits. This is not true. Frozen fruits & vegetables are an excellent option during the off-season and the freezing process often helps to preserve the antioxidants and other nutrients!
• As you use more frozen foods, try a handful of frozen blueberries, strawberries, or blackberries in your cereal. Frozen fruit can be 'mushy', which means it is not as nice to eat plain. However, mixed with oatmeal, cold cereal or yogurt, these foods can be delicious and give a much-needed antioxidant boost to your meal.
• Stuff your favorite potato with antioxidant-rich toppings such as tomatoes (stewed or fresh), green and red peppers, onions, broccoli, and low-fat or soy cheese. Use a sweet potato instead of a white potato and you get even more nutrition value.
• Make it your long-term goal to have three-quarters of your plate covered by plant foods such as fruit, vegetables, whole grains and legumes. Meat or other 'main dish' foods should take up no more than one-quarter of the plate.
• Enjoy fruit smoothies as a substantial snack or for dessert. Try our Apricot Smoothie. 
• Try our Fruit and Grainsdessert to get a sweet treat that also contains plenty of fruit & whole grains.
• Try our Super Carotene Smoothieas a way to increase the antioxidant carotenes, from food, in your diet. Beta-carotene is one example of a carotene, but there are hundreds of carotenes in the foods we eat!

NOTE: If you are in cancer treatment, these diet changes may not be right for you.

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Publish Date: 12/2004