Benefits of Selenium Against Cancer

I recommend all adults and more children to take selenium 200 mcg/d. Lower risk of cancer is one of the major benefits.

Bladder Cancer: Selenium Not Associated: No association was found between toenail selenium levels and bladder cancer risk. Michaud DS, Hartman TJ, et al. Cancer Epidemiol Biomarkers Prev 2002 Nov;11(11):1505-6

Bladder Cancer: Linked to Low Selenium: Prediagnostic selenium concentrations in archived toenails were inversely associated with bladder cancer risk in women (P=0.02), but not in men, in a nested case-control study of 338 cases and 341 matched controls. Toenail selenium concentrations and bladder cancer risk in women and men. Michaud DS, et al. Harvard. British Journal of Cancer (2005) 93, 804-806. 

Bladder Cancer: Low Selenium Associated: In 120,000 adults in a prospective study with 431 developing bladder cancer, the toenail clippings of the cancer victims vs. 2,459 controls found a 40% decreased risk for the three highest quintiles (RR = 0.60 vs. 1.00 and 1.09 for two lowest quintiles; p<.01 for inverse trend). Prediagnostic toenail selenium and risk of bladder cancer. Zeegers MP, et al. Cancer Epidemiol Biomarkers Prev 2002 Nov;11(11):1292-7

Bladder Cancer: Cigarettes Markedly Increase; Fruits Somewhat Decrease; Vitamin E Possibly and Selenium Probably Moderately Decrease: In a review of the research, The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. Zeegers MP, Kellen E, et al. World J Urol. 2003 Dec 17

Breast Cancer Not Helped by Mega-dose Selenium-A-C-Niacin-Q10-Zn: 90 unilateral non-metastatic breast cancer patients given mega-doses of beta-carotene, vitamin C, niacin, selenium, coenzyme Q10, and zinc in addition to standard therapies were compared with matched controls. The 90 treated patients were prescribed combinations from three to six of the vitamins and minerals listed above. The controls were matched (2:1) to the vitamin/mineral patients for age at diagnosis, presence of axillary lymph node metastasis, tumor stage, grade, estrogen receptor status, year of diagnosis, and prescription of systemic therapy. Median follow-up of surviving patients was 68 months. Breast cancer-specific survival (p = 0.19) and disease-free survival (p = 0.08) times for the vitamin/mineral treated group were nonsignificantly shorter, not longer. The hazard ratios for the vitamin/mineral treated group versus the control group were estimated at 1.75 for disease-specific survival and 1.55 for disease-free survival. Overall survival was similar. U Victoria. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Lesperance ML, Olivotto IA, et al. Breast Cancer Res Treat 2002 Nov;76(2):137-43. Ed: Many studies have found that vitamin A causes a higher death rate.  Whether it was the problem in this study is unknown.

Cancer: Selenium Level Linked to Increased Longevity: In the 9-year follow-up EVA study of 1389 adults ages 60-70, 101 study participants died. Baseline plasma selenium was higher in individuals who were alive at the end of follow-up [1.10 micromol/L] than in those who died during the follow-up [1.01 micromol/L; P <10(-4)]. Mortality rates were 56% higher in individuals with low selenium [relative risk (RR) = 1.56]. After controlling for various potential confounding factors, mortality rates were 54% higher in individuals with low selenium [RR = 1.54]. Cancer-related mortality was most significant [adjusted RR = 1.79]. Selenium and Mortality in the Elderly: Results from the EVA Study. Akbaraly NT, et al. Universite Montpellier I, France. Clin Chem. 2005 Aug 25

Cervical Cancer Not Influenced by Selenium: Cancer Causes Control 2002 Aug;13(6):517-26. This study found no difference in serum selenium levels between various degrees of invasiveness of cancer.

Colon Adenomas: Selenium Lowered Colon Adenoma Risk in Smokers and in those Low in Selenium: Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. In a DB PC study of 598 adults who underwent endoscopic screening at follow-up, 160 had adenomas. Those on 200 mcg of selenized yeast had 33% lower risk of developing adenomas, although this was not quite statistically significant. The primary benefit was for those in the lowest tertile of baseline selenium (OR = 0.27) and current smokers (OR = 0.27) who each had significant 73% reductions in risk. Selenium supplementation and colorectal adenomas: An analysis of the nutritional prevention of cancer trial. Reid ME, et al. Roswell Park Cancer Institute, Buffalo, NY. Int J Cancer. 2005 Oct 10.

Colon Adenomas: Benefit Primarily for Smokers: In a study of serum selenium and advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the multivariable odds ratio (OR) comparing participants in the highest quintile of serum selenium with those in the lowest quintile was 0.76 [P = 0.01]. The inverse association between serum selenium and advanced colorectal adenoma was significant among recent smokers (OR, 0.53; P = 0.008). Serum selenium was unrelated to adenoma risk in nonsmokers and former smokers who quit smoking > or = 10 years ago. High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program. Peters U, et al. National Cancer Institute, Rockville, Maryland. . Cancer Epid Biomarker Prev 2006 Feb;15(2):315-20.

Colon Cancer: Selenium May Protect Against Colon Cancer: An analysis of data from three randomized trials--the Wheat Bran Fiber Trial, the Polyp Prevention Trial, and the Polyp Prevention Study-- for colorectal adenoma prevention among participants who recently had an adenoma removed during colonoscopy found blood selenium levels in the highest quartile had lower odds of developing a new adenoma compared with those in the lowest quartile (OR = 0.66; P(trend) = .006). Selenium and colorectal adenoma: results of a pooled analysis. Jacobs ET, Jiang R, et al. University of Arizona. J Natl Cancer Inst. 2004 Nov 17;96(22):1669-75

Colorectal, Lung, and Prostate Cancers Decreased by Selenium in DB: 1312 Patients average age 63 with a history of skin cancer were randomized and treated for 4.5 years at 200 mg/day with 6.4 years total follow-up. There was no difference in skin cancer deaths but a decrease in total deaths 108 vs. 129. RR 0.83 with 29 vs. 57 cancer deaths (50% decrease!). Selenosis (excess selenium) symptoms are nail changes, brittle hair, garlic breath. There was no difference in cardiac or stroke deaths. The East coast has low selenium in soil and crops. Selenium was no benefit to breast, bladder, or leukemia. JAMA 12/25/96 p1957-63 & Med Klin 9/97. Benefit only for lowest 2/3rds in selenium serum levels. Upper 1/3 actually slight increase in CA RR 1.2. The argument for increasing selenium intake. Rayman MP, Rayman MP.

Colon Polyps Not Stopped But Adenomas Prevented by Vitamins A, C, and E, Calcium and Selenium Mixture: Mixture of Beta-carotene, C, E, Calcium, and Selenium was studied in a DB in patients with adenomas and polyps. It found no benefit preventing polyps growth although the mixture did help prevent new adenomas in those under 65 with no family history and not more than one adenoma at the start. Hofstad, Norway, Digestion ’98;59:148

Esophageal Cancer in Barrett’s High if Low Selenium: In a 399-patient endoscopy study, University of Washington researchers found serum selenium levels in the upper three quartiles (i.e., >1.5 micro M) were less likely to have high-grade dysplasia (OR = 0.5, 95% CI = 0.3 to 0.9) or aneuploidy (OR = 0.4). Serum Selenium Levels in Relation to Markers of Neoplastic Progression Among Persons With Barrett's Esophagus. Rudolph RE, Vaughan TL, et al. J Natl Cancer Inst 2003 May 21;95(10):750-7

Gallbladder Cancer Associated with Low Selenium, Zinc: Data supports an association between lower levels of selenium, zinc, vitamin E, and the risk of carcinoma of the gallbladder and suggest that Cu/Zn ratio could be a useful parameter in evaluating the patients of carcinoma of the gallbladder. J Surg Oncol. 2003 Sep;84(1):31-5

Gastric Cancer: Selenium Decreased in DB Study: In a 5-year DB PC study on allitridum and selenium in preventing cancer of digestive system, the accumulative mortality rate of all cancer, digestive system cancer and gastric cancer had decreased 45.5%, 41.2% and 63.3% in the intervention group. The effects in males were stronger than in females. Six to ten years later after the termination of intervention, the accumulative mortality rate and relative risk of all cancers in two groups became similar. Study on the long-time effect on allitridum and selenium in prevention of digestive system cancers. Zheng GH, et al. Shandong University, China. Zhonghua Liu Xing Bing Xue Za Zhi. 2005 Feb;26(2):110-2.

Gastric Cancer May be Decreased by Selenium, Zinc; Salt Increases It: incidence and mortality from gastric cancer in Japan are the highest in the world. This is thought to be due, in part, to dietary habit, including a high salt intake. Study of 14 minerals in water found low selenium and zinc associated with more gastric cancer. Relationship between mineral and trace element concentrations in drinking water and gastric cancer mortality in Japan. Nakaji S, Fukuda S, et al. Nutr Cancer 2001;40(2):99-102.

Gastric Cardia and Esophageal Cancer Lower with High Selenium, but High Selenium Not Associated with Lower Mortality: In an 1103 adult Chinese 15-year follow-up study with a representative sample found that the change in risk conferred by a 25% increase in serum selenium relative to the population distribution was significantly inversely associated between baseline serum selenium and death from esophageal cancer (RR: 0.83) and gastric cardia cancer (0.75). Trends toward inverse associations were noted for death from heart disease (0.89), but no association was noted for total death (0.96) or stroke (0.99). Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Wei WQ, Abnet CC, et al. Am J Clin Nutr. 2004 Jan;79(1):80-5

G Selenium Good; Vitamin A, E, and Carotene Bad for GI Cancers: Researchers analyzed 14 randomized trials (170,525 participants), assessing beta-carotene (9 trials), vitamin A (4 trials), vitamin C (4 trials), vitamin E (5 trials), and selenium (6 trials) for GI cancers. Neither the fixed effect (RR 0.96) nor random effects meta-analyses (RR 0.90) showed significant effects of supplementation with antioxidants on the incidences of gastrointestinal cancers. Among the seven high-quality trials reporting on mortality (131,727 participants), the fixed effect (RR 1.06) unlike the random effects meta-analysis (RR 1.06) showed that antioxidant supplements significantly increased mortality. Beta-carotene and vitamin A (RR 1.29) and beta-carotene and vitamin E (RR 1.100) significantly increased mortality, while beta-carotene alone only tended to do so (RR 1.05). In four trials, selenium showed significant beneficial effect on gastrointestinal cancer incidences. Antioxidant supplements for preventing gastrointestinal cancers. Bjelakovic G, Nikolova D, et al. Copenhagen, DENMARK. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004183

GI Cancer Chemotherapy Patients Selenium and Zinc Helped in DB: 60 patients were treated with selenium 200 mg./day and zinc 21 mg/day. 21/30 (70%) of those treated with Selenium and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs. 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index. U Naples. Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract. Federico A, Iodice P, Federico P, Del Rio A, Mellone MC, Catalano G, Federico P. Eur J Clin Nutr 2001 Apr;55(4):293-7

Head Neck Cancer Associated with Low Selenium, High Copper: 66 % of all patients have shown a decreased serum-concentration of selenium. These patients were additionally characterized by decreased activities of endogenous glutathionperoxiase. A third of all patients had decreased zinc and iron levels. Copper was found enhanced in 30%. In trend the malondialdehyde was increasing due to decreasing selenium levels. Head neck cancer patients show the same characteristic trace element status as other solid tumors: decreased selenium, zinc and iron, increased copper. The therapeutic consequences of these observations are still unclear. Laryngorhinootologie. 2003 Aug;82(8):573-7

Liver Cancer Linked to Low Selenium: In a nested case-control study comparing the Se content in toenail clippings of 166 adults with hepatocellular carcinoma (HCC) to 394 healthy controls in Haimen City, China, where HCC is a leading cause of mortality, the median toenail Se was lower for HCC cases than controls (p = 0.03). HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 , 0.83 and 0.50 (p for trend = 0.06). Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China. Sakoda LC, Graubard BI, et al. National Cancer Institute, Rockville, MD. Int J Cancer. 2005 Feb 9

Lung Cancer: Selenium May Decrease Lung Cancer Risk in Those with Low Intakes:  When all epidemiological studies were combined, the relative risk (RR) with higher selenium exposures was 0.74 or a 26% decrease in lung cancer rates. The risk for areas where selenium levels were low was 0.72, while the risk for areas where selenium levels were higher was 0.86. In both studies in high selenium areas, protective effects were only found when subjects in the lowest category of selenium exposure were considered. The risk was lower in studies assessing selenium exposure using toenails (RR 0.46) than in studies using serum selenium (RR 0.80) or studies assessing dietary intake (RR 1.00). Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Zhuo H, Smith AH, et al,   University of California, Berkeley,  Cancer Epidemiol Biomarkers Prev. 2004 May;13(5):771-8

M Selenium reduced pulmonary metastasis of melanoma cells in mice. Li D, et al. Creighton University J Nutr. 2004 Jun;134(6):1536-40

Non-Hodgkins Lymphoma Treatment Better if Higher Selenium: Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin's lymphoma. Last KW, Cornelius V, et al. London. J Clin Oncol. 2003 Jun 15;21(12):2335-41.

Skin Cancer Not Helped by Selenium Supplement in DB: 1312 patients with non-melanoma skin cancer (basal and squamous cell) took 200 microg/d. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. Duffield-Lillico AJ, Slate EH, et al; Nutritional Prevention of Cancer Study Group. J Natl Cancer Inst. 2003 Oct 1;95(19):1477-81

Total Cancer Deaths in Males Associated with Higher Selenium: In a small Belgium nested case-control study of 201 cancer deaths and 600 controls found the risk ratio for males with high selenium was 2.2 but for females was 0.8. Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population. Kornitzer M, Valente F, De Bacquer D, Neve J, De Backer G. Eur J Clin Nutr. 2004 Jan;58(1):98-104; Ed: This is certainly an odd result.  The study was small and case-control studies have less predictive power than double-blind studies.  The huge difference between males and females seems strange. Hopefully, it was a chance finding and does not represent a real relationship.  I don't know if they controlled for meat intake.  While meat is higher in selenium, it's relationship to higher levels of cancer is very likely due to other factors.

Selenium May Help by Protecting DNA From Alkylating Agents: Human exposure to alkylating agents metabolized from tobacco- and food-borne carcinogens occurs regularly. Dietary inorganic compounds such as selenium and vanadium have been chemoprotective benefits in rat and humans. Inorganic compounds to protect DNA from alkylation damage. An enzyme cleavage assay is used to observe alkylated DNA. Simple salts (e.g., NaCl or NiCl(2)) did not prevent DNA alkylation, whereas anionic oxo species (e.g., Na(2)SeO(4) or Na(3)VO(4)) did inhibit alkylation. Inhibition of DNA alkylation damage with inorganic salts. Hamilton EE, Wilker JJ. Purdue University. J Biol Inorg Chem. 2004 Sep 16. Ed: Selenium appears to protect against several cancers. This might be how.

Thomas E. Radecki, M.D., J.D.

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