Selenium Fails to Protect Against Lung Cancer

Study suggests Selenium, in smoking populations, may actually increase lung cancer risk.

By Jacob Schor, ND, FABNO

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Karp DD, Lee SJ, Shaw Wright GL, et al. A phase III, intergroup, randomized, double-blind, chemoprevention trial of selenium (Se) supplementation in resected stage I non-small cell lung cancer (NSCLC). J Clin Oncol. 2010;28:18s.


A double-blind, placebo-controlled study. Participants were randomized 2:1 to receive selenium yeast (200 mcg daily) or placebo for 4 years.


1,522 patients with stage IA and IB non–small cell lung cancer (NSCLC). The participants had undergone surgical resection of their primary tumor, were cancer-free for at least 6 months after surgery, were not taking excessive vitamin supplements, and had normal liver function and normal chest x-ray.

Study Medication and Dosage

Patients took 200 mcg of selenium yeast daily for 4 years.

Primary Outcome Measures

Occurrence of a second primary tumor

Key Findings

The study was halted at the 4-year median mark because the participants receiving selenium showed a shorter progression-free survival (PFS) than those taking the placebo. Different recurrence rates occurred in less than 2.5 years. At the 5-year mark, 28% of those taking selenium had experienced a recurrence of their cancer while only 22% of those taking placebo had (P=0.15).

When the study was stopped 4.1% of those taking selenium had developed a second primary tumor while only 3.7% of those taking the placebo had. Overall survival was 5% lower in the selenium group.

Practice Implications

Approximately 80% of the study participants were smokers, and just as in the beta-carotene trial from 1996, the intervention predicted to provide protection against lung cancer failed.1

As advantageous as antioxidants appear to be in general, selenium may have a paradoxical effect and be dangerous for smokers.

As advantageous as antioxidants appear to be in general, selenium may have a paradoxical effect and be dangerous for smokers.

Preventive medicine practitioners have been big fans of selenium for years and often cite Clark et al’s 1996 Nutritional Prevention of Cancer (NPC) as the reason for their use of selenium in cancer prevention. The NPC study followed 1,312 patients who had had basal cell or squamous cell carcinomas of the skin. They were randomized to receive either 200 mcg of selenium yeast or placebo and followed from 1983 through 1991. While no difference in skin cancer recurrence was seen, the study was halted and the code broken early; the participants taking selenium had a lower overall risk of getting cancer (RR: 0.63; 95% CI: 0.47-0.85).2

Stranges et al reported in 2007 on a double-blind trial that investigated whether 200 mcg/day of selenium would prevent type 2 diabetes. No benefit was seen. Rather, participants who achieved the highest serum levels of selenium were more likely to develop diabetes.3

In 2008 Reid et al reported on a small (N=425) trial that took place in Georgia in which participants took 400 mcg of selenium per day. They saw no change in cancer rates.4

Selenium’s action on cancer is not as straightforward as we once thought. This current study by Karp et al suggests that selenium will not provide protection against a second lung cancer; it may actually increase the risk, at least in a population of current and former smokers.

For more research involving integrative oncology, click here

About the Author

Jacob Schor, ND, FABNO, is a graduate of National University of Naturopathic Medicine, Portland, Oregon, and recently retired from his practice in Denver, Colorado. He served as president to the Colorado Association of Naturopathic Physicians and is a past member of the board of directors of the Oncology Association of Naturopathic Physicians and American Association of Naturopathic Physicians. He is recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the International Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clinician's Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians. His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal, where he is the past Abstracts & Commentary editor.


1. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;88(21):1550-1559.

2. 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. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276(24):1957-1963.

3. Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147(4):217-223.

4. Reid ME, Duffield-Lillico AJ, Slate E, et al. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Nutr Cancer. 2008;60(2):155-163.