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Dietary Supplements, Selenium and Chronic Disease Prevention

Dietary Supplements, Selenium and Chronic Disease Prevention. Saverio Stranges, MD, PhD Clinical Sciences Research Institute University of Warwick Medical School, UK. Outline. Context on Dietary Supplements Physiological Role of Selenium Selenium and Human Health Perspectives.

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Dietary Supplements, Selenium and Chronic Disease Prevention

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  1. Dietary Supplements, Selenium and Chronic Disease Prevention Saverio Stranges, MD, PhD Clinical Sciences Research Institute University of Warwick Medical School, UK

  2. Outline • Context on Dietary Supplements • Physiological Role of Selenium • Selenium and Human Health • Perspectives

  3. Dietary Supplement “A dietary supplement is a preparation intended to supply nutrients (such as vitamins, minerals, or amino acids) that are missing or not consumed in sufficient quantity in a person's diet”

  4. 1990: “Nutrition Labeling and Education Act” 1994: “Dietary Supplement Health and Education Act” Context: Dietary Supplement Use in US 1997-onwards: Dramatic increase in supplement sales $18.8 billion in 2003 1999/2000: 52% of US adults take some type of dietary supplements (NHANES)

  5. Any dietary supplement Multivitamin/multimineral Vitamin E Selenium Dietary Supplement Use in US Adults (≥ 20 ys) NHANES 1999-2000. Am J Epidemiol. 2004; 160:339-49

  6. Trends in Daily Use of Vitamin/Mineral Supplements - US Adults (≥ 18 ys) National Health Interview Survey. J Am Diet Assoc. 2004; 104:942-950

  7. 2002: Directive 2002/46/EC - Food Supplements Directive • 2004: Decreto Legislativo 169/2004(Italy) • 150 millions euros/year in dietary supplements (Italy) • 20-30% dietary supplement users (among adults) in Europe Context: Dietary Supplement Use in Europe

  8. Dietary Supplements in the Market

  9. Why Do People Take Dietary Supplements? • Balance a poor diet/promote optimal health, fitness • Prevent/manage minor ailments or chronic disease • Distrust of conventional medicine • Media pressure • Co-responsibility of health professionals…

  10. Supplements are good for health? Access is very important Supplements are adequately tested Stop using if ineffective Social Perception of Dietary Supplement Use Blendon JB et al. Arch Intern Med. 2001; 161:805-810

  11. Any Vitamin E Vitamin C β Carotene Use of “Antioxidants” among Physicians… Am J Cardiol. 1997; 79:1558-60

  12. It won’t hurt and might help, so why not take it? Doctor, why should I take this pill? BUT…

  13. The Beta-Carotene and Retinol Efficacy Trial Beta Carotene + Retinol (Vitamin A) Lung Cancer Incidence Mortality CARETrial. N Engl J Med. 1996; 334:1150-5

  14. Vitamin E Supplementation and Mortality Miller ER et al. Ann Intern Med 2005;142:37-46

  15. Mortality in Randomized Trials of Antioxidant Supplements * * * * *P < .05 Bielakovic G. JAMA. 2007; 297:842-857

  16. …Selene, Moon Goddess…

  17. Physiological Role of Selenium • Selenium is an essential trace mineral • Selenium is incorporated as seleno-cysteine (Sec) • At least 25 seleno-proteins in humans • Complex genetic mechanism encoded by the UGA codon

  18. Selenium Metabolism Papp LV. Antioxid. Redox Signal. 2007; 9:775-806

  19. Physiological Functions of Selenium • Redox Homeostasis (e.g., glutathione peroxidases, thioredoxin reductases ) • Thyroid Hormone Metabolism (iodothyronine 5’-deiodinase) • Reproduction/Testosterone Biosynthesis • Membrane Integrity • Immune Function/Prostacyclin Production

  20. Bioavailability of Selenium • Geographical variations in soil selenium content • Plant foods are the major dietary sources • Meats, seafood, and bread are common sources • 55 µg/day: recommended intake (RDA) to optimize GPx activity • 70-90 µg/L: plasma Se levels to optimize GPx activity • 400 µg/day: tolerable upper intake level (UL) • Increasing use of Se-enriched foods and fertilizers

  21. Dietary Sources of Selenium High Good http://dietary-supplements.info.nih.gov/factsheets/selenium.asp

  22. …Strategies to Increase Selenium Intake…

  23. Dietary Selenium Intake Worldwide (90’s) Optimal GPx activity Rayman MP. Lancet 2000; 356:233-241

  24. Selenium Status in Italy 118.8 μg/L Sesana G et al. Sci Total Environ. 1992 ;120:97-102.

  25. Plasma Selenium and Selenoproteins μg selenium/L plasma US Average 100 µg Se/day RDA 55 µg Se/day China 10 µg Se/day High-Dose (UL) 400 µg Se/day Modified from Burk RF. Nutr Clin Care. 2002; 5:75-79

  26. Keshan Selenium and Human Health Where Did it Begin…? Keshan Disease Research Group. Chin Med J. 1979; 92:471-476

  27. Keshan Disease, Endemic Cardiomyopathy

  28. Diseases Related to Selenium • Selenium Deficiency • Keshan disease (endemic cardiomyopathy) • Viral Infections (HIV) and immune disease • Reproduction-related disorders (miscarriage, male infertility) • Selenium Status/Supplements and Chronic Disease • Cancer, all-cause mortality • Cardiovascular disease • Metabolic disease: type 2 diabetes, serum lipids

  29. Cancer Incidence- Mortality

  30. Geographic Studies: Selenium Levels in Forage Crops* 10% higher cancer mortality for major cancer sites in low-Se areas *L C Clark et al., 1991

  31. Selenium Supplementation and Chronic Disease Prevention The Nutritional Prevention of Cancer (NPC) Trial Clark LC et al. JAMA 1996; 276: 1957-1963 Arizona Cancer Center

  32. NPC Study Population • Multi-center, double-blind, randomized, placebo-controlled • 1,312 residents from Eastern United States • Previous history of non-melanoma skin cancer • Mean age, 63 years; range, 18-80 years; ¾ males • 200 μg selenium per day (as selenium yeast)or placebo • Blinded phase of the trial: 1983-1996 • Compliance: 79.3%

  33. NPC Endpoints • Primary Endpoint • Recurrent skin basal (BCC) and squamous cell (SCC) carcinomas • Secondary Endpoints • All-cause mortality • Total cancer mortality • Total and site-specific cancer incidence (lung/prostate/colorectal) • Cardiovascular disease (CVD) incidence and mortality • Type 2 diabetes

  34. Plasma Selenium Concentrations during NPC

  35. NPC Findings: Cancer Incidence (1983-1996, 7.4 years follow-up) Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639

  36. NPC Findings: Cancer-Specific (1983-1996, 7.4 years follow-up) *adjusted for age, gender, and smoking status at randomization Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639 Duffield-Lillico AJ et al. J Natl Cancer Inst. 2003; 95:1477-81

  37. Cases NPC - Total Cancer Incidence (1983-1996, 7.4 years follow-up) Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639

  38. Cases NPC - Total Cancer Incidence (1983-1996, 7.4 years follow-up) *adjusted for age, gender, and smoking status at randomization Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639

  39. SUMIVAX Trial, France7.5 years follow-up, n=13,017 100 μg Selenium + 120 mg Vitamin C, 30 mg Vitamin E, 6 mg of β-carotene, 20 mg of zinc Hercberg S et al. Arch Intern Med. 2004;164:2335-2342

  40. Selenium Status and Cancer MortalityNHANES III, 13,887 US adults Bleys J et al. Arch Inter Med. 2008; 168:404-410

  41. Selenium Status and All-Cause MortalityNHANES III, US Bleys J et al. Arch Inter Med. 2008; 168:404-410

  42. CVD Incidence/Mortality

  43. Low serum selenium (<45μg/l) Serum selenium (≥45μg/l) Selenium Status and CVDEastern Finland * * * *P < 0.001 Salonen JT et al. Lancet. 1982; 2:175-9

  44. Selenium Status and CVD MortalityNHANES III, 13,887 US adults Bleys J et al. Arch Inter Med. 2008; 168:404-410

  45. Antioxidant Supplementation and CHD IncidenceSUMIVAX Trial, France, 7.5 years follow-up 100 μg Selenium + 120 mg Vitamin C, 30 mg Vitamin E, 6 mg of β-carotene, 20 mg of zinc Hercberg S et al. Arch Intern Med. 2004;164:2335-2342

  46. Selenium Supplementation and CVD Incidence/MortalityNPC Trial (1983-1996) Participants without prevalent CVD at randomization (n = 1,004) Mean follow-up: 7.6 years *adjusted for age, gender, and smoking status at randomization Stranges S et al. Am J Epidemiol 2006; 163:694-699

  47. Selenium Supplementation and Recurrent CVDNPC Trial (1983-1996) Participants with prevalent CVD at randomization (n = 246) Mean follow-up: 5.5 years *adjusted for age, gender, and smoking status at randomization Stranges S et al. Am J Epidemiol 2006; 163:694-699

  48. Meta-analysis of Trials on Selenium and CHD Mateo GF et al. Am J Clin Nutr 2006; 84:762-773

  49. Type 2 Diabetes/Lipids

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