After a diagnosis of cancer, patients often initiate or increase their use of vitamins and dietary supplements, and their use is prevalent among the 11.7 million adults in the United States living with cancer. Whereas 50% of healthy adults take 1 or more dietary supplements, between 64% and 81% of cancer survivors report that they use vitamin or dietary supplements.1 Reasons offered for using these alternative therapies include strengthening the immune system, increasing the chance to be cured, and gaining a sense of control over their disease.
Although the American Cancer Society says, “A daily, multivitamin supplement in amounts equivalent to 100% of the [US Department of Agriculture Recommended] Daily Value is a good choice for anyone… who cannot eat a healthful diet,”2 supplements do not come without risks. Because of limited US Food and Drug Administration regulations and published experience, little is known about how supplements interact with cancers and their treatments. For example, antioxidants might reduce the efficacy of radiation and chemo therapy by blocking reactive oxygen species3 and some vitamins could stimulate cancer cell growth.4
More than half of cancer patients taking supplements do not inform their physician.1 It is therefore important for all healthcare practitioners to be familiar with the current literature addressing vitamin and dietary supplement use in this patient population so they can assist physicians and help mitigate risks. In 2010, research literature included studies on multivitamins, selenium, and vitamin D. Caution should be taken when evaluating and applying literature to clinical practice. In addition to inconsistencies among these trials, some published reports rely on early-phase data.
To evaluate the effects of multivitamin use on survival in patients with stage III colon cancer, a prospective, observational study was conducted as a companion study to CALGB 89803.5 Patients were asked to complete a diet and lifestyle questionnaire midway through therapy and again 6 months after treatment ended. During treatment, 49.9% (518/1038) of patients said they used multivitamins. Use remained consistent after treatment, with 51.4% (416/810) of patients reporting that they took multivitamins. The hazard ratio (HR) for disease-free survival for multivitamin users compared with nonusers was 0.94 (95% confidence interval [CI], 0.77-1.15). Multivitamin use during or following chemotherapy was not associated with a significant increase in recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75-1.15) or overall survival (multivariate HR, 0.92; 95% CI, 0.74-1.16). Women, patients with higher household incomes, and physically active patients were more likely to report multivitamin use.
The proposed anticancer effects of selenium include supporting antioxidant status, increasing activity of proteins involved in apoptosis, and inhibiting transcription factors associated with carcinogenesis, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1.6,7 Common adverse effects of selenium supplementation include brittle nails and hair, liver and kidney function test abnormalities, and cataracts. Previous trials have shown conflicting results regarding the ability of selenium to reduce the risk of developing cancer.8,9
Stratton and colleagues conducted a phase 2 trial to assess whether selenium supplementation reduces prostate cancer progression as measured by prostate-specific antigen (PSA) velocity. 10 A total of 140 patients with localized non–high-grade prostate cancer were randomized to receive daily placebo (n = 46), selenium 200 μg (n = 46), or selenium 800 μg (n = 47). After adjusting for confounders, PSA velocity did not differ significantly between the 3 groups. A subgroup analysis for the quartile of men with the highest baseline selenium levels who were randomized to the selenium 800-μg arm showed that they had significantly higher PSA velocity than men taking placebo (P = .018). The authors concluded that selenium did not demonstrate a protective effect on PSA velocity and that high-dose selenium supplementation might negatively affect PSA velocity.
Vitamin D is a unique supplement, because daily intake is derived from diet and sun exposure. This nutrient regulates calcium and skeletal homeostasis and behaves like a hormone, regulating transcription of more than 200 genes. It is theorized that vitamin D might help prevent cancer by inducing cellular differentiation, inhibiting angiogenesis, and causing apoptosis. Observational studies have demonstrated a link between low levels of vitamin D and increased cancer incidence or poorer cancer prognosis.11-13
In November 2010, the Institute of Medicine (IOM) released a report proposing increases in the dietary reference intake values for calcium and vitamin D.14 IOM tripled the recommended daily allowance of vitamin D for adults aged 31 to 50 years and increased it by 50% for adults aged 51 to 70 years, advising that all healthy, noninfant children and adults aged ≤70 years get 600 IU daily of vitamin D. The IOM said evidence of improved bone health was the only health condition that informed the suggested increases and cited mixed and inconclusive research about the use of vitamin D in the prevention and treatment of cancer.
A single-arm, phase 2 trial evaluated the palliative benefit of high-dose vitamin D3 (cholecalciferol) on pain scores and bone resorption markers in 38 patients with breast cancer and evidence of bone metastases.15 Every day for 4 months, patients took 10,000 IU of oral vitamin D3 and 1000 mg of calcium. Pain response was measured using 2 validated questionnaires, which were administered at baseline and repeated monthly. All patients continued on previously prescribed bisphosphonate therapy. No significant changes from baseline in pain score or daily morphine-equivalent analgesia use were observed, although there was a significant reduction in number of pain sites. In addition, daily use of high-dose vitamin D3 and calcium did not significantly reduce levels of urinary bone resorption markers. The authors concluded that although the combination of daily high-dose vitamin D3 and calcium appeared safe, it did not offer significant palliation or reduce bone resorption.
Vitamin and mineral supplementation are often used to treat oncology patients. Emerging literature suggests a role for vitamin D in the prevention and treatment of cancer, but studies have failed to show any benefit with multivitamin and selenium use. Vitamin supplementation remains a promising area for research, but because of the risks and the inconsistent and conflicting data, it is important for healthcare professionals to evaluate the information carefully. This, in turn, allows medical professionals to assist cancer survivors in making appropriate treatment decisions.
- Velicer CM, Ulrich CM. Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J Clin Oncol. 2008;26:665-673.
- Doyle C, Kushi LH, Byers T, et al; for the 2006 Nutrition, Physical Activity and Cancer Survivorship Advisory Committee; American Cancer Society. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin. 2006;56:323-353.
- Lawenda BD, Kelly KM, Ladas EJ, et al. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Ins. 2008;100:773-783.
- Giovannucci E, Chan AT. Role of vitamin and mineral supplementation and aspirin use in cancer survivors. J Clin Oncol. 2010;28:4081-4085.
- Ng K, Meyerhardt JA, Chan JA, et al. Multivitamin use is not associated with cancer recurrence or survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. 2010;28:4354-4363.
- Stratton MS, Reid ME, Schwartzberg G, et al. Selenium and inhibition of disease progression in men diagnosed with prostate carcinoma: study design and baseline characteristics of the “Watchful Waiting” Study. Anticancer Drugs. 2003;14:595-600.
- Thompson IM. Chemoprevention of prostate cancer: agents and study designs. J Urol. 2007;178(3 pt 2):S9-S13.
- Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301:39-51.
- Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutrition Prevention of Cancer Study Group [published correction appears in JAMA. 1997;277:1520]. JAMA. 1996;276:1957-1963.
- Stratton MS, Algotar AM, Ranger-Moore J, et al. Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer. Cancer Prev Res (Phila). 2010;3:1035-1043.
- Chung M, Balk EM, Brendel M, et al. Vitamin D and Calcium: A Systematic Review of Health Outcomes. Evidence Report no. 183. Rockville, MD: Agency for Healthcare Research and Quality; 2009. AHRQ publication no. 09-E015.
- Drake MT, Maurer MJ, Link BK, et al. Vitamin D insufficiency and prognosis in non-Hodgkin’s lymphoma. J Clin Oncol. 2010;28:4191-4198.
- Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757-3763.
- Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academics Press; 2011.
- Amir E, Simmons CE, Freedman OC, et al. A phase 2 trial exploring the effects of high-dose (10,000 IU/day) Vitamin D3 in breast cancer patients with bone metastases. Cancer. 2010;116:284-291.