Supplements & Cancer
By Carrie Dennett, MPH, RDN
Today’s Dietitian
Vol. 25 No. 8 P. 34
When are they beneficial, and when are they harmful?
In the United States, more than one-third (36%) of adults with cancer use some form of complementary and alternative medicine, which may include dietary supplements, according to the National Cancer Institute.1 A 2008 systematic review of studies assessing supplement use among cancer survivors found that between 14% and 32% of survivors began using dietary supplements after they received a cancer diagnosis, with breast cancer survivors reporting the highest use,2 and a 2022 study found that 19% of people in remission from cancer believe that dietary supplements reduce the risk of their cancer returning.3
“People take supplements for a variety of reasons. They either feel better or they think it’s going to help,” says Mary Marian, DCN, RDN, CSO, FAND, a professor of practice at the University of Arizona’s School of Nutritional Science and Wellness. She says cancer patients may have family and friends telling them they know someone whose cancer was cured because they took a certain supplement, which may cause the patient to consult alternative practitioners who recommend supplements or even sell them.
Because dietary supplements are regulated as food rather than as drugs, the FDA doesn’t evaluate or approve supplements unless they make specific claims about disease prevention or treatment. All supplements are considered “safe” by the government until they are proven unsafe. There’s also no guarantee that a supplement contains only the ingredients on the label or that it has the exact amount of nutrient, herb, or botanical in it that the label claims it has. In addition, the FDA hasn’t approved the use of dietary supplements as a treatment for cancer.
Marian Neuhouser, PhD, RD, head of the Cancer Prevention Program at Fred Hutchinson Cancer Research Center in Seattle, says one possible but often overlooked harm of turning to dietary supplements during cancer treatment is financial hardship. “Many people, including many cancer patients, often spend hundreds of dollars of months on supplements, and they already have a lot of out-of-pocket expenditures, they’re missing work, there may be caregivers who have to miss work to take people to appointments. There’s a lot of financial toxicity associated with cancer treatment.”
Neuhouser says another potential harm is that dietary supplements may offer a false sense of security for cancer patients that they’re going to improve their health or their outcomes. “That’s where the science doesn’t match up with the claims,” she says. “We really don’t have solid data on whether using all of these supplements on top of all of the different treatments actually improves the outcomes.”
Potential Supplement-Treatment Interactions
A 2023 study that used social media to recruit women undergoing breast cancer treatment to fill out an online questionnaire found that 89.5% of participants reported current vitamin/mineral use, especially calcium, multivitamins, and vitamins C and D.4 More than 67% reported current use of natural product-derived dietary supplements, especially probiotics, turmeric, fish oil/omega-3 fatty acids, melatonin, and cannabis. Around one-half of the women reported using at least three products concurrently, and 23% of women undergoing chemotherapy were using supplements with possible adverse effects.4
Even though dietary supplements aren’t drugs, people take them because they expect that they’ll have a positive effect. While some supplements, such as daily multivitamins, don’t appear to affect cancer survival or recurrence—or cancer treatment—elements in certain herbs and supplements may affect how the body processes chemotherapy drugs when taken at the same time. For example, some supplements can interfere with specific enzymes or other components of the drug that affect how the drug is transported and metabolized.1 In some cases, this can make the drugs less effective in fighting cancer cells. In other cases, it can make the drugs more toxic to the body than intended.
Researchers from Yale University’s Lifestyle Exercise and Nutrition study asked 151 breast cancer survivors who participated in the study about their dietary supplement use: 120 of the women (80%) were taking a dietary supplement, 72 women (60%) were taking three or more formulations, and 29 women (24%) were taking five or more. Of the 54 different supplement formulations reported, 33% had potential interactions with Tamoxifen or aromatase inhibitors—estrogen-blocking drugs taken as part of breast cancer treatment. Most of these potential interactions (87%) were associated with herbal preparations,5 which, along with higher-dose antioxidant supplements, are of most concern when used during cancer treatment.
Antioxidants
Because radiation, chemotherapy, and many other anticancer drugs generate reactive oxygen species, or free radicals—unstable molecules that react with other molecules in a cell, causing DNA damage—to kill cancer cells, many cancer patients take antioxidant nutrient supplements with the intention of protecting healthy cells and reducing treatment side effects. Common dietary antioxidants include vitamins A, C, and E; beta-carotene; and other carotenoids, glutathione, and flavonoids, such as those found in soy and green tea.
Antioxidants have well-defined anticancer effects that theoretically make them a promising way to reduce the initiation, progression, and spread of cancer cells. Antioxidants were initially studied in cancer patients for their potential to improve outcomes and reduce oxidative damage to healthy cells from chemotherapy and radiotherapy, potentially allowing for higher doses. However, what researchers started to find was that in higher therapeutic doses, antioxidants might instead promote cancer progression and increase overall mortality in some patients—and that antioxidants’ ability to reduce the toxicity of chemotherapy and radiotherapy may also make treatment less effective by counteracting the reactive oxygen species that are supposed to be killing cancer cells.6
The results of a Phase III breast cancer drug trial published in 2020 found that patients who reported taking any antioxidant supplement—carotenoids, coenzyme Q10, or vitamins A, C, and E—both before and during postsurgical chemotherapy were 41% more likely to have their breast cancer return. This association was not seen with multivitamin use, likely because the amounts of individual antioxidants are lower than they are in single-nutrient supplements.7 However, a 2021 meta-analysis of more than 17,000 breast cancer survivors found that postdiagnosis use of antioxidant supplements wasn’t associated with overall mortality.8
A 2017 review authored by Marian looked at the research on dietary supplements commonly used by cancer survivors.9 She wrote that it’s difficult to determine the true impact of using antioxidant supplements during treatment because most studies have used various types and doses of antioxidants and have included patients undergoing a variety of treatment regimens with numerous types of cancer.
Herbs and Nutraceuticals
Some herbal medicines and other nutraceuticals—foods or parts of foods that allegedly provide the body with health benefits beyond basic nutritional value—can interfere with cancer treatment in another way by altering how the liver metabolizes chemotherapy drugs. For example, St. John’s Wort—an “herbal antidepressant” also commonly used by cancer patients—has been shown to inhibit tumor growth in triple-negative breast cancer10 and colorectal cancer in rodents11 as well as suppress cell proliferation and/or increase cell death in lab samples of human breast cancer cells12 and metastatic melanoma cells,13 to cite a few examples. However, it’s well established that in humans, St. John’s Wort increases the production of the cytochrome P450 isoenzyme 3A4 (CYP3A4), a liver enzyme that breaks down certain chemicals and toxins—including agents used in some chemotherapy drugs, including imatinib, docetaxel, and irinotecan. Taking St. John’s Wort concurrently with these drugs can decrease their bioavailability by 12% to 42%.14
Other herbs that may have a significant adverse effect on how the body metabolizes chemotherapy drugs include garlic, ginkgo, echinacea, ginseng, and kava. In addition, polyphenols found in many herbs and teas may affect enzymes that help process chemotherapy drugs, which can cause resistance to drugs such as vincristine, vinblastine, taxanes, anthracyclines, tamoxifen, and tyrosine kinase inhibitors.15 A 2021 review found potential interactions between 261 herbs, foods, and dietary supplements and 117 anticancer drugs via interactions with various cytochrome P450 isoenzymes.16
A 2018 review concluded that melatonin is the only compound whose use is supported by sufficient safety and efficacy data from randomized controlled trials to prolong survival in patients with advanced cancer. The authors wrote that other supplements, including curcumin, green tea, EPA, DHA, and artemisinin, are well-tolerated and potentially effective in combination with conventional treatments, but large randomized controlled trials are needed to fully investigate these supplements’ role within complex drug treatment strategies for cancer.17
Honoring the Uncertainty
“We just don’t know, especially with some of the newer immunotherapies, how taking all of these myriad supplements will result in benefits or harms,” Neuhouser says.
Marian says some of her patients have brought bags full of supplements they’re taking to their appointments. She says the large quantity of supplements is concerning, given the unknowns about how supplements may interact with their treatment and how the supplements may interact with each other. “I think when there’s the unknown, you have to be super cautious about the potential for adverse effects, even if we don’t know whether they could happen or not, because the fact that we don’t know is something to be concerned about.”
Food vs Supplements
While adequate macro- and micronutrients, along with beneficial food compounds such as flavonoids, curcumin, epigallocatechin gallate from green tea, resveratrol, and quercetin can support the body during cancer treatment, more isn’t necessarily better, and may even be worse.
The World Cancer Research Fund states that there’s no strong evidence that dietary supplements, apart from calcium for colorectal cancer, can reduce cancer risk. Both the World Cancer Research Fund and the American Institute for Cancer Research recommend meeting nutritional needs from diet alone, stating that a healthful diet is more likely to protect against cancer than dietary supplements, because eating whole foods allows the body to absorb a whole range of vitamins, minerals, and antioxidants that work together to protect health.18-20
Despite uniform recommendations from major cancer organizations, cancer patients continue to use supplements during treatment, sometimes without their health care providers knowing. One 2008 systematic review found that up to 68% of physicians are either unaware of supplement use in their cancer patients, or they’re aware but didn’t record that information in patients’ charts.2 Is the message not getting out, are providers not asking the right questions, or are patients ignoring evidence-based advice because they’re scared and want to throw everything they have at this major health crisis?
“I think the message isn’t getting out there from providers and dietitians,” Neuhouser says. “The supplement industry is very powerful. The advertising is powerful. There are more supplements for sale than types of foods. They’re a very prolific industry and marketing works. And cancer is a very scary diagnosis, as we all know, so it’s easy for patients to want to do everything they can to improve their outcomes. But what they may not realize is that not only is this a very expensive way to do it but it may not be effective and it may cause harm.”
When Are Supplements Needed?
Some dietary supplements may be beneficial during cancer treatment. For example, some cancer treatments can lead to calcium loss or otherwise contribute to bone loss, so doctors may prescribe supplemental calcium and vitamin D.21 Some patients may find it difficult to meet their nutrient needs from food—this includes patients who have trouble eating due to nausea or lack of appetite, or difficulty swallowing due to radiation around the mouth or neck, as well as those who have absorption difficulties due to the surgical removal of part of their stomach or intestines, and those who follow a strict vegan diet and may be deficient in vitamin B12.23
Neuhouser says the patient’s nutritional status when they enter cancer treatment is a key consideration. “An elderly person may already have low oral intake, possibly due to poor dentition or low appetite. They may be a little underweight, then add chemo and/or radiation on top of that. Or maybe they come into cancer treatment with a preexisting condition that may make it difficult to manage both conditions simultaneously. I think having a comprehensive nutrition assessment when someone starts treatment is important, so the type of nutrition plan that’s recommended may be tailored.”
Marian says that if someone’s going through treatment and they’re not eating well and possibly losing weight, a multivitamin may help them. “Maybe they tolerate the treatment better. Maybe their white blood cell count comes up faster. Those things are hard to measure as far as outcomes, but maybe they’re worth thinking about.”
Neuhouser says there’s nothing to contraindicate a multivitamin or multivitamin with minerals, especially during treatment when oral intake may be impaired. In fact, observational data from colorectal and breast cancer cohorts in which 50% to 72% of patients were self-prescribing multivitamins showed neither beneficial nor harmful effects of these supplements on toxicity or survival.6 “A multi will have antioxidants in the appropriate amounts,” Neuhouser says. “Formulations that combine herbs with vitamins or minerals … those are the ones where we don’t have the data to confirm benefits or harms.”
How to Counsel Patients
Marian says she always asks about supplements when first meeting with a patient. “I kind of just roll in the supplements right after asking about the medication so it’s not a judgmental kind of thing. I’m just eliciting information from them,” she says. “I think sometimes they just feel better taking their supplements. I ask, ‘How would you feel if I recommend that you don’t take all of these? Are you going to be at loss because you feel like it’s providing you some benefit?’ I think it’s really important to establish what’s the bond with the supplement use when you’re counseling people.”
Neuhouser suggests dietitians ask patients to bring in their supplements, so they can do a thorough assessment. “Ask if any supplement use has changed since they started treatment. Ask them, ‘Why are you taking these?’ and ‘What do you hope to get from them?’ Do some additional probing to find out what the motivation is to take additional supplement during treatment,” she says. “Dietitians can also try to point out to patients how much they’re spending on these supplements and what else they could spend that money on. Maybe they are finding it hard to cook and they could use that money to get meals delivered.”
Marian says, “Let’s say a head and neck cancer patient is taking high doses of vitamin C and says, ‘Oh, well, my oncologist didn’t say there was a problem with that.’ I’ll explain to them what the potential problem is, but I’ll also say, ‘Well, I would just go back and ask your oncologist again,’ because you know I want them to feel comfortable in the information that their oncologist is giving them. And if the radiation oncologist, who knows more about the radiation side of things, really feels like vitamin C isn’t going to be a problem, then who am I to say that it’s going to be? But the oncologist isn’t going to do a diet history and say, ‘Let’s see how much vitamin C you’re getting from other things.’ It’s just complicated. You have to be up to date on the literature and look at the whole picture and know what potential micronutrient deficiencies can arise and what potential complications are of having too much or too little of something and kind of balance your suggestions on that.”
— Carrie Dennett, MPH, RDN, is the nutrition columnist for The Seattle Times, owner of Nutrition By Carrie, and author of Healthy for Your Life: A Non-Diet Approach to Optimal Well-being.
References
1. Cancer therapy interactions with foods and dietary supplements (PDQ)—health professional version. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/cam/hp/dietary-interactions-pdq. Updated May 26, 2022.
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10. You M, Lee YH, Kim HJ, Kook JH, Kim HA. St. John's Wort suppresses growth in triple-negative breast cancer cell line MDA-MB-231 by inducing prodeath autophagy and apoptosis. Nutrients. 2020;12(10):3175.
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18. Supplements & cancer: accept no substitutes. American Institute for Cancer Research website. https://www.aicr.org/cancer-prevention/healthy-eating/supplements-nutrients/
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