Study: Do antioxidants encourage the spread of cancer cells?
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This study is about:
The effect of antioxidants on the spread of cancer cells in mice.
Why is this study important?
Learning what causes cancer cells to spread can help scientists design better ways to stop this process. Antioxidants include some vitamins and nutrients that can be found in foods or taken as supplements. They protect our cells from some of the damage that occurs from day-to-day life; for example, exposure to the environment, sun, hormones, etc. Research has looked at whether taking antioxidant supplements can prevent cancer in people, and results have been mixed. In some studies, taking large amounts of certain antioxidant supplements has led to poorer outcomes among patients.
The study found that very large doses of antioxidants promoted spread of melanoma cells in mice.
What does this mean for me?
People often wonder if eating certain foods or taking supplements can help them prevent or treat their cancer. Research on the relationship between antioxidant supplements and cancer is complicated and has produced mixed results. Results vary by the population studied, the type of cancer, the antioxidant used, and even the dose. Studies in people have shown that increasing dietary antioxidants does not reduce cancer risk. In some research studies vitamin E supplements have been linked to an increase in the chance of being diagnosed with or dying from and lung cancers.
The doses of antioxidants used in this study are much higher than what people would normally get from their diet. According to experts, eating a healthy diet should provide most people with enough of the antioxidants needed for good health. You should speak with your doctor before taking any antioxidant dietary supplements.
Piskounova E, Agathocleous M, Murphy MM, et al. “Oxidative stress inhibits distant by human melanoma cells.” Nature (2015) 527: 186-91.
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This article is relevant for:
The clinical relevance of this study for people is not clear
This article is also relevant for:
Men with breast cancer
Triple negative breast cancer
Her2+ breast cancer
People with a genetic mutation linked to cancer risk
Breast cancer survivors
Women under 45
Women over 45
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Cells undergo a process called to spread from a primary tumor to other sites in the body. Few cancer cells can survive the process to spread and grow at another site in the body. It is not fully understood how cells that manage to metastasize are able to do so. Dr. Sean Morrison and colleagues at the University of Texas Southwestern Medical Center looked at the capability of metastasized melanoma cells to withstand oxidative stress. (Oxidative stress, which can damage cells, occurs when an imbalance develops between reactive oxygen species (ROS) and the body’s ability to remove them.) ROS occurs naturally in the body as oxygen is processed; they are damaging, but our bodies usually have a sufficiently strong system response to handle it. ROS increase during times of environmental stress, such as exposure to ultraviolet (UV) light or ionizing radiation. Molecules called antioxidants play a role in controlling ROS. Antioxidants are produced by the body and are also found in many different foods. Some antioxidants are sold as over-the-counter dietary supplements.
Researchers of this study wanted to know:
How oxidative stress and antioxidants affect the ability of melanoma cells to metastasize.
Population(s) looked at in the study:
Cancer cells from four patients with non-metastatic melanoma and four patients with metastasized melanoma were injected into mice that lacked functioning immune systems.
- Changes in melanoma cells in the blood and at distant points from the primary tumor indicated oxidative stress that was not found in the rodent’s primary tumors.
- Melanoma cells that successfully metastasized withstood oxidative stress.
- Large doses of the antioxidant N-acetyl cysteine (NAC) promoted .
This study was done in mice that did not have functioning immune systems, allowing researchers to inject and study human tumor cells in a mouse model. Though the researchers used melanoma cells from human patients samples, observing what happens when they were transplanted into immunodeficient mice does not exactly correlate to what happens in human cancer patients with functional immune systems. In addition, the number of different patient samples used in this study was relatively low, which means that there is a possibility that the results the researchers see are unique to those tumors. Researchers did note that melanoma in the study mice is predictive of clinical outcomes—in other words, the cancer cells that metastasized in human patients also metastasized in the mice. While this may be true, it does not mean that the mechanism that the cells use to metastasize is exactly the same in the two species, or that a functional immune system may affect the process.
Not too long ago, the idea that antioxidants are beneficial was well received, and clinical trials looked at giving cancer patients supplementary antioxidants. Recently, however, this idea is being questioned. This study indicates that oxidative stress limits the ability of melanoma cells to metastasize; when researchers added antioxidants to relieve oxidative stress, more occurred. The antioxidant treatments used in these mouse studies may help us understand how cancer acts, but the path from antioxidant treatments in genetically altered mice to clinical application is a long one, and not all study results in mice hold true in human patients. More work needs to be done to fully understand this process and how it might impact cancer patients.
However, the data from previous clinical trials prompted the U.S. Preventive Services Task Force () to recommend against the use of Vitamin E and Beta-carotene (antioxidants) for the prevention of cardiovascular disease or cancer. The also says that there is not enough data to recommend for or against the use of multivitamins (which include antioxidants) for the prevention of cardiovascular disease or cancer.
It is also important to note that the antioxidants injected into mice in this study were pure, supplemental treatment antioxidants. They included much greater antioxidant levels than what a person would get from a normal, healthy diet. In the context of this study, a greater dose of treatment antioxidants promoted . People with cancer, and those who have a high risk of cancer, should continue to eat a healthy diet that includes a variety of fruits and vegetables.
National Comprehensive Cancer Network (NCCN) guidelines on survivorship include the following recommendations on dietary supplement use:
- Taking dietary supplements is not recommended for most cancer survivors unless a patient has a known nutritional deficit, an inadequate diet or other indication (for example, ).
- Little data exist to support the use of vitamins or other dietary supplements for cancer prevention, control or recurrence.
- Taking vitamin supplements does not replace the need for a healthy diet. Patients should try to get nutrients from the foods they eat and the beverages they drink.
- Providers should ask about supplement use at regular intervals, about a patient’s reasons for using supplements and the ingredients in those supplements.
- Survivors of certain cancers are at risk of vitamin deficiencies based on cancer treatment (e.g., gastric cancer patients who have had a gastrectomy may be at risk of vitamin B12 and iron deficiencies).
- NCCN recommends calcium and vitamin D supplements for people who have been prescribed denosumab or a bisphosphonate to treat bone or .
- Patients taking multiple supplements and those in need of nutritional support should be referred to a registered dietitian or nutritionist, preferably one who is trained in supporting oncology patients.
Nutrition for people diagnosed with cancer
The National Comprehensive Cancer Network (NCCN) recommends the following for cancer survivors:
- Think about your food choices and amount of fruits, vegetables and unrefined grains you eat compared with red and processed meats, alcohol, and foods or drinks with added fat or sugar.
- Think about your eating habits, including portion size, snacking, how often you eat out and use of added fats or sugars.
- All survivors should be encouraged to:
- Make informed choices about food to ensure variety and adequate nutrient intake.
- Limit refined sugars.
- Eat a diet that is at least 50% plant-based, consisting mostly of vegetables, fruit and whole grains.
- Track calorie intake; monitoring of calories is an effective way to manage weight.
- Minimize alcohol intake to no more than one drink per day for a woman and two drinks per day for a man.
- For patients desiring further dietary guidelines, the USDA approximate food plate volumes are:
- Vegetables and fruits should comprise half the volume of food on the plate
- Vegetables: 30% of plate; Fruits 20% of plate
- Whole grains: 30% of plate
- Protein: 20% of plate
- Recommended sources of nutrients:
- Fat: plant sources such as olive or canola oil, avocados, seeds and nuts, and fatty fish.
- Carbohydrates: fruits, vegetables, whole grains and legumes.
- Protein: poultry, fish, legumes, low-fat dairy foods, and nuts.
The Academy of Nutrition and Dietetics, the United States Office of Disease Prevention and Health Promotion and the American Institute for Cancer Research also publish expert guidelines on nutrition and health.
- Are there foods I should eat or avoid after I have had cancer?
- What level of antioxidants should I include in my diet?
- Are there supplements I should take or avoid?
- Can you refer me to a nutritionist?
The following are studies focused on nutrition for people diagnosed with breast cancer.
- NCT04000880: AMPLIFY: An Online Weight Loss Study Specifically for Cancer Survivors. AMPLIFY is a nation-wide, web-based diet and exercise study recruiting overweight survivors of breast, , ovarian, renal, colorectal, endometrial cancer and multiple myeloma in people age 50 and older who are interested in becoming more active, eating better and losing weight.
- NCT04298086: A Study of the Body's Response to Exercise and a Plant-Based Diet in Overweight Postmenopausal Women With Breast Cancer. This study is looking to find out what effects exercise and a plant-based diet have on aromatase levels in postmenopausal women who are overweight and being treated with an aromatase inhibitor for their HR+ breast cancer.
- NCT04365569 Evaluating the Effectiveness of an Individualized Nutrition and Physical Activity Counseling Program. This pilot study looks at whether a tailored in-person and telephone-based nutrition and exercise counseling program can help breast cancer patients improve weight and fitness and thus improve cancer outcomes.
Nutritionists and dieticians are experts in food and diet with a focus on helping people maintain or improve their health. Dieticians are experts who have received additional training and certification. You can find a registered dietician in your area through Eatright.org, the website for the Academy of Nutrition and Dietetics. You can search for nutritionists by specialty, including "cancer," "weight management" and "heart health."
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