Nutritional Supplements: Counseling Points for Patients with Cancer

Although eating a healthy and balanced diet is considered the optimal approach for meeting nutritional needs and obtaining the recommended essential vitamins, minerals, and trace elements for good health, many individuals still find it difficult to do so. They may find it easier to meet their dietary needs by using nonprescription nutritional supplements.

The pharmacy shelves are lined with a plethora of nutritional supplements formulated as singleentity, combination, multivitamin, and mineral or all natural supplements, and the selection can be overwhelming for many patients. Generally, nutritional supplements are safe when used properly; however, many patients are often unaware of the potential for drug—nutrient interactions or contraindications, and sometimes they take more than the recommended daily amounts (RDAs) of these nutrients.

Pharmacists can be instrumental in assisting patients with properly selecting and using nutritional supplements. They can also help identify possible drug—micronutrient interactions and contraindications and can be an important resource in guiding patients with such medical conditions as cancer, especially when they are undergoing chemotherapy and radiation treatments. Patients with cancer frequently experience a number of symptoms related to the cancer as well as adverse effects (AEs) linked to chemotherapy and radiation therapy.¹ As a result, many patients with cancer may inquire about the use of nutritional supplements to boost their energy, improve their appetite, or enhance their immune systems.¹

The great debate about the use of nutritional supplements, especially in patients with cancer, continues, and several concerns have arisen among health care advocates regarding the use of nutritional supplements, especially in conjunction with other medications, including nonprescription and prescription, due to the potential for interactions that may cause toxicity or decrease therapeutic efficacy.^2,3

A study published in the Journal of the Academy of Nutrition and Dietetics reported that adults were 2.5 times more likely to take a nutritional supplement in conjunction with a prescription medication compared with adults without a diagnosed medical condition.^3,4 Additionally, many patients are motivated to start a regimen of nutritional supplements after receiving a cancer diagnosis, and cancer survivors frequently continue to use the supplements—for numerous reasons.^3,5

Results from a survey published in the Journal of Clinical Oncology showed that 14% to 32% of individuals started using nutritional supplements after being diagnosed with cancer. Many elect to use these supplements, including herbal products, to boost their health, improve their nutrition, or reduce AEs associated with cancer treatment.^6,7

Other reasons, as cited by an estimated 56.2% of surveyed patients with cancer, included that supplementation was something they could do to help themselves.⁷ Study results have also suggested that patients receiving chemotherapy were more likely to use nutritional supplements to relieve stress.^8-12

Results from a 2014 survey revealed that fewer than 50% of oncologists discuss the risks and benefits of supplement use with their patients.¹³ Many patients with cancer also use natural or alternative supplements without consulting their primary health care provider.^3,5 Further, only 23% of patients' supplements were reportedly recommended by a physician or other health care provider.^3,5 Results from a recent study similarly showed that because patients with chronic diseases or cancer may use nutritional supplements and are likely to take multiple medications, there is an increased risk for drug—supplement interactions.¹⁴ Such an interaction is considered clinically significant if it alters a pharmacotherapeutic response or compromises a patient’s nutritional status.¹⁵

Current expert guidelines from the American Cancer Society, the World Cancer Research Fund, and the American Institute for Cancer Research advise patients with cancer to not use supplements, to instead obtain nutrients from foods wherever possible; however, this is not always a feasible option.^16-18 Despite this recommendation, nutritional supplement use is extensive among patients with cancer, and some clinicians still recommend them when warranted and appropriate. Data collected between 2003 and 2010 within the Intergroup phase 3 Breast Cancer Chemotherapy trial stated that an estimated 48% of patients were taking multivi- tamins; 20%, supplements containing vitamin C, vitamin D, and n-3 oils; 15%, vitamin E, vitamin B6, and folic acid; and 34%, calcium.^16,19 Clinicians also advised 33% of patients to start taking a supplement during treatment, 10% to discontinue use of one, and 7% to stop all except a multivitamin; 51% of patients received no advice.^16,19

Unfortunately, there is a lack of proven clinical evidence regarding the benefits or risks associated with the use of nutritional supplements in patients with cancer, which may account for the inconsistent or lack of advice from clinicians regarding their use.¹⁶ Many clinicians recommend that patients only use multivitamin and mineral supplements that contain the RDA; however, an estimated 33% of the US population and an estimated 50% of patients with cancer use supplements that contain more than the RDA.^16,20 Other recent studies report that more than 80% of patients with cancer use nutritional supplements, with herbs and vitamins being the most popular choices, and that 75% of these patients never disclose this information to their oncologists.^8,21

What Clinical Studies Say

The results of various clinical studies on the use of nutritional supplements reveal they may have various effects on chemotherapy toxicity; unfortunately, no clinical data on outcome currently exist.¹⁶ In addition, because vitamin D deficiency is quite common among patients with cancer, ongoing phase 3 trials are exploring the effect of vitamin D on outcome and ideal vitamin D and calcium intakes for bone health.¹⁶

The use of antioxidants has also been studied in patients with cancer to measure how their protective effects against cancer improve patient outcomes and decrease oxidative damage from chemotherapy and radiotherapy, as well as the dose-limiting toxicities of therapies.¹⁶ Moreover, results from large-scale, randomized cancer prevention trials have reported notable AEs and beneficial effects.16 These trials demonstrated that the use of beta-carotene may augment the risk of lung and stomach cancers, excessive doses of vitamin E may increase incidences of prostate cancer and colorectal adenoma, and selenium prevents gastric and lung cancers in patients with low selenium levels but increase rates of both in those with higher levels.^16,22 Another study’s results showed that although vitamin E and beta-carotene may diminish toxicity from radiotherapy among patients with head and neck cancer, they have been found to increase relapse, especially among smokers.¹⁶

In 2008, a review of results from published randomized clinical trials investigating antioxidants with radiation therapy or chemotherapy concluded that the use of megadoses of “supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.”²³

Even after more than 2 decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, debate remains about the efficacy and safety of supplementation remains.²³ Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related AEs.²³ Some data indicate that antioxidants may protect tumor cells and healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents.²³ Other data suggest that antioxidants can protect normal tissues from chemotherapy or radiation-induced damage without dimin- ishing tumor control.²³

Results from another study reported that megadoses of vitamin C may actually interfere with radiotherapy, while some supplements may increase the risk of bleeding during surgery.^8,24 According to the National Cancer Institute, study results have revealed that St. John’s wort, garlic extract, and echinacea are examples of those supplements believed to pharmacokinetically interact with chemotherapy agents (table 126,27).^25-27 Additionally, supplements containing Panax ginseng and green tea have been found to have toxicities and to interact with various medications, including chemotherapy agents.²⁵ The results of 1 study of patients with cancer estimated that 28% were at risk for nutrient interactions and that an estimated 46% of these patients were being treated with curative intent.^25,28 A more recent study of patients with ovarian cancer estimated that 40% were in jeopardy of an interaction between a supplement and their chemotherapy.^25,29

On the other hand, research from clinical trials reveals that nutritional supplements may aid in managing certain AEs related to chemotherapy.²⁹ For example, American ginseng and astragalus root, often used in traditional Chinese medicine, may aid in lessening some of the AEs associated with chemotherapy, such as fatigue,²⁹ and supplements like glutamine, vitamin B6, vitamin E, and omega-3 have been evaluated as potential treatments for peripheral neuropathy when appropriate; however, more research is needed.²⁹

What Patients With Cancer Should Know When Using Nutritional Supplements

Many patients with cancer who use nutritional supplements may not always be aware of the potential drug—nutrient interactions. However, because there is extensive supplement use among this patient population, there is a clear need for further research on the use of supplements and to increase awareness among health care professionals to seize every opportunity to talk to their patients about their proper use.⁸ The American Society of Clinical Oncology provides key elements that pharmacists and other health care professionals can relay to their patients on the use of nutritional supplements (see table 2).²⁹

The Role of the Pharmacist

Pharmacists should always advise patients with cancer to seek counsel from their oncologist before recommending nutritional supplements, including alternative supplements, to avoid potential drug—nutrient interactions and or contraindications. For example, some dietary supplements can cause skin sensitivity and severe skin reactions when taken during radiation treatment, and patients may not be aware of this.²⁹ Patients should be encouraged to have an open dialogue about the appropriateness of using nutritional supplements, especially during chemotherapy and radiation. Currently, the recommendation for patients with cancer is to only take moderate doses of supplements because evidence from human clinical studies that confirm their safety and benefits is limited.

Prior to recommending any nutritional supplements, it is imperative for pharmacists to evaluate a patient’s medical history and medication profile to screen for potential drug—nutrient interactions or contraindications. It is also crucial that patients be made aware of these potential interactions and AEs and that they understand the significance of notifying their primary health care provider of all supplements they are taking, including those labelled as “natural,” "alternative," and "complementary." Patients with cancer who elect to use nutritional supplements should be reminded to only use these supplements under the supervision of their oncologist and to always discuss the desire to use these supplements before actually using them, especially during chemotherapy and radiation. Pharmacists can also direct patients and other clinicians to the variety of resources available concerning the use of nutritional supplements in patients with cancer (online table 3).

References:

• Carr AC, Vissers MCM, Cook JS. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol. 2014;4:283. doi:10.3389/fonc.2014.00283.
• Sood A, Sood R, Brinker FJ, Mann R, Loehrer LL, Wahner-Roedler DL. Potential for interactions between dietary supplements and prescription medications. Am J Med. 2008;121(3):207-211. doi: 10.1016/j.amjmed.2007.11.014.
• Comments on NIH Office of Dietary Supplements re Strategic Plan Progress Report. Academy of Nutrition and Dietetics website. eatrightpro.org/resource/news-center/on-the-pulse-of-public-policy/regulatory-comments/comments-to-nih-office-of-dietary-supplements-re-strategic-plan-progress-report. Accessed November 25, 2016.
• Farina EK, Austin KG, Lieberman HR. Concomitant dietary supplement and prescription medication use is prevalent among US adults with doctor-informed medical conditions. J Acad Nutr Diet. 2014;114(11):1784-1790.e2. doi: 10.1016/j.jand.2014.01.016.
• Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults use dietary supplements. JAMA Intern Med. 2013;173(5):355-361. doi: 10.1001/jamainternmed.2013.2299.
• Velicer CM, Ulrich CM. Vitamin and mineral supplement use among US adults after cancer diagnosis. J Clin Oncol. 2008;26(4):665-673. doi: 10.1200/JCO.2007.13.5905.
• Ferrucci LM, McCorkle R, Smith T, Stein KD, Cartmel B. Factors related to the use of dietary supplements by cancer survivors. J Altern Complement Med. 2009;15(6):673-680. doi:10.1089/acm.2008.0387.
• Wong LYE, Leung PC, Tang J-L, Mercer SW. Use of dietary supplements by breast patients with cancer undergoing conventional cancer treatment. Patient Prefer Adherence. 2010;4:407-414. doi:10.2147/PPA.S13639.
• Owens B. A test of the self-help model and use of complementary and alternative medicine among Hispanic women during treatment for breast cancer. Oncol Nurs Forum. 2007;34(4):E42-E50. doi:10.1188/07.ONF.E42-E50.
• diGianni LM, Garber JE, Winer EP. Complementary and alternative medicine use among women with breast cancer. J Clin Oncol. 2002;20(suppl 18):34S-38S.
• Redd WH, Montgomery GH, DuHamel KN. Behavioral intervention for cancer treatment side effects. J Natl Cancer Inst. 2001;93(11):810-823.
• Boon HS, Olatunde F, Zick SM. Trends in complementary/alternative medicine use by breast cancer survivors: Comparing survey data from 1998 and 2005. BMC Womens Health. 2007;7:4. doi:1186/1472-6874-7-4.
• Lee RT, Barbo A, Lopez G, et al. National survey of US oncologists’ knowledge, attitudes and practice regarding herb and supplement use by patients with cancer. J Clin Oncol. 2014;32(36):4095-4101. doi: 10.1200/JCO.2014.55.8676.
• Wiley. Herbal and dietary supplements can adversely affect prescribed drugs, says extensive review. Science Daily website. sciencedaily.com/releases/2012/10/121024101754.htm. Published October 24, 2012. Accessed November 20, 2016.
• Boullata JI, Barber JR. A perspective on drug-nutrient interactions. In: Boullata JI, Armenti VT, eds. Handbook of Drug Nutrient Interactions. Totowa, NJ: Humana Press; 2004.
• Harvie M. Nutritional supplements and cancer: potential benefits and proven harms. Am Soc Clin Oncol Educ Book. 2014:e478-e486. doi: 10.14694/EdBook_AM.2014.34.e478.
• Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62(4):243-274. doi: 10.3322/caac.21142.
• World Cancer Research Fund and American Institute for Cancer Research. Cancer survivors. dietandcancerreport.org/cancer_prevention_recommendations/rec. Accessed November 20, 2016.
• Zirpoli GR, Brennan PM, Hong CC, et al. Supplement use during an intergroup clinical trial for breast cancer (S0221). Breast Cancer Res Treat. 2013;137(3):903-913. doi: 10.1007/s10549-012-2400-2.
• Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;159(12):824-834.
• Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18(13):2505-2514.
• Dolara P, Bigagli E, Collins A. Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary. Eur J Nutr. 2012;51(7):769-781.
• Lawenda B, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008;100(11):773-783. doi: 10.1093/jnci/djn148.
• Appadurai IR, Hanna CL. Concerns with complementary and alternative medicines. Eur J Anaesthesiol. 2006;23(5):441-442.
• Dietary supplements and cancer treatment: a risky mixture. National Cancer Institute website. cancer.gov/about-cancer/treatment/research/dietary-supplements. Published August 11, 2009. Accessed November 20, 2016.
• Furlow B. Understanding the interaction between food and treatment. Oncology Nurse Advisor website. oncologynurseadvisor.com/chemotherapy/understanding-the-interaction-between-food-and-treatment/article/177852/2/. Published August 1, 2010. Accessed November 20, 2016.
• McCune JS, Hatfield AJ, Blackburn AA, Leith PO, Livingston RB, Ellis GK. Potential of chemotherapy-herb interactions in adult patients with cancer. Support Care Cancer. 2004;12(6):454-462.
• Andersen MR, Sweet E, Lowe KA, Standish LJ, Drescher CW, Goff BA. Dangerous combinations: ingestible CAM supplement use during chemotherapy in patients with ovarian cancer. J Altern Complement Med. 2013;19(8):714-720. doi: 10.1089/acm.2012.0295.
• Bauer A. 5 things you should know about herbs and supplements. American Society of Clinical Oncology Cancer.Net website. cancer.net/blog/2015-04/5-things-you-should-know-about-herbs-and-supplements. Published April 16, 2015. Accessed November 20, 2016.