Dietary Supplements, Selenium and Dietary Supplements, Selenium and Chronic Disease Prevention Chronic Disease Prevention Saverio Stranges, MD, PhD Saverio Stranges, MD, PhD Clinical Sciences Research Institute Clinical Sciences Research Institute University of Warwick Medical University of Warwick Medical School, UK School, UK
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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. - PowerPoint PPT Presentation
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Dietary Supplements, Selenium and Dietary Supplements, Selenium and
Plasma Selenium Concentrations during NPCPlasma Selenium Concentrations during NPC
Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639
NPC Findings: Cancer Incidence NPC Findings: Cancer Incidence (1983-1996, 7.4 years follow-up)(1983-1996, 7.4 years follow-up)
Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639Duffield-Lillico AJ et al. Duffield-Lillico AJ et al. J Natl Cancer Inst. 2003; 95:1477-81J Natl Cancer Inst. 2003; 95:1477-81
*adjusted for age, gender, and smoking status at randomization*adjusted for age, gender, and smoking status at randomization
NPC Findings: Cancer-Specific NPC Findings: Cancer-Specific (1983-1996, 7.4 years follow-up)(1983-1996, 7.4 years follow-up)
NPC - Total Cancer Incidence NPC - Total Cancer Incidence (1983-1996, 7.4 years follow-up)(1983-1996, 7.4 years follow-up)
Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639
NPC - Total Cancer Incidence NPC - Total Cancer Incidence (1983-1996, 7.4 years follow-up)(1983-1996, 7.4 years follow-up)
Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639Duffield-Lillico AJ et al. Cancer Epidemiol Biomarkers Prev. 2002; 11:630-639
Cases
Adjusted* HRAdjusted* HR 95% CI95% CI PP P trendP trend
>121.6 (ng/ml)>121.6 (ng/ml) 0.760.76 0.50–1.160.50–1.16 0.200.20*adjusted for age, gender, and smoking status at randomization*adjusted for age, gender, and smoking status at randomization
Int.Int. PlaceboPlacebo RRRR 95% CI95% CI PP P, intP, int
Antioxidant Supplementation and CHD IncidenceAntioxidant Supplementation and CHD Incidence SUMIVAX Trial, France, 7.5 years follow-upSUMIVAX Trial, France, 7.5 years follow-up
Hercberg S et al. Arch Intern Med. 2004;164:2335-2342Hercberg S et al. Arch Intern Med. 2004;164:2335-2342
100 μg Selenium +120 mg Vitamin C, 30 mg Vitamin E, 6 mg of β-carotene, 20 mg of zinc
Stranges S et al. Am J Epidemiol 2006; 163:694-699Stranges S et al. Am J Epidemiol 2006; 163:694-699
Selenium Supplementation and Selenium Supplementation and CVD Incidence/MortalityCVD Incidence/Mortality
NPC Trial (1983-1996)NPC Trial (1983-1996)
*adjusted for age, gender, and smoking status at randomization*adjusted for age, gender, and smoking status at randomization
Selenium Supplementation Selenium Supplementation and Incidence of Type 2 Diabetes and Incidence of Type 2 Diabetes
NPC Trial (1983-1996)NPC Trial (1983-1996)
• To examine the efficacy of selenium supplementation in To examine the efficacy of selenium supplementation in
the primary prevention of type 2 diabetesthe primary prevention of type 2 diabetes
• 1,202 participants free of type 2 DM at randomization1,202 participants free of type 2 DM at randomization
• Self-reported diagnosis/medical records for type 2 DM Self-reported diagnosis/medical records for type 2 DM
ascertainment (for both incident and prevalent cases)ascertainment (for both incident and prevalent cases)
• 200 μg of selenium/day (n=600) or placebo (n=602)200 μg of selenium/day (n=600) or placebo (n=602)
No difference between treatment groups was statistically significant (P ≤ 0.05)No difference between treatment groups was statistically significant (P ≤ 0.05)
Characteristics of Participants at RandomizationCharacteristics of Participants at Randomization
CharacteristicsCharacteristics SeleniumSelenium PlaceboPlaceboParticipants randomized (no.)Participants randomized (no.) 600600 602602Age, yearsAge, years 63.4 (10.2)63.4 (10.2) 63.0 (9.9)63.0 (9.9)Education, yearsEducation, years 12.9 (3.4)12.9 (3.4) 12.9 (3.3)12.9 (3.3)Gender, males (%)Gender, males (%) 7474 7575Body mass index, kg/mBody mass index, kg/m22 25.6 (3.9)25.6 (3.9) 25.5 (4.1)25.5 (4.1)Smoking status (%)Smoking status (%)
Never Never 34.034.0 30.030.0 FormerFormer 39.039.0 40.040.0 CurrentCurrent 27.027.0 30.030.0Pack-years of smokingPack-years of smoking 56.8 (40.3)56.8 (40.3) 56.6 (39.0)56.6 (39.0)Plasma selenium, ng/mlPlasma selenium, ng/ml
Mean Mean 114.4 (22.6)114.4 (22.6) 114.0 (21.5)114.0 (21.5) 3333rdrd 105.6105.6 104.8104.8 5050thth 113.6113.6 113.2113.2 6666thth 122.4122.4 121.2121.2
Selenium
Placebo
Log-rank test p value = 0.050
0.0
00
.05
0.1
00
.15
Incid
ence
0 5 10 15Years of follow-up
Cumulative Incidence of Type 2 DiabetesCumulative Incidence of Type 2 Diabetes
Stranges S et. al. Ann Intern Med 2007; 147:217-223
Incidence of Type 2 DM by Baseline CharacteristicsIncidence of Type 2 DM by Baseline Characteristics
*mutually adjusted for other baseline covariates*mutually adjusted for other baseline covariates
Antioxidant Supplementation and Antioxidant Supplementation and Glucose LevelsGlucose Levels SUMIVAX Trial, France, 7.5 years follow-up, n=3,146SUMIVAX Trial, France, 7.5 years follow-up, n=3,146
Czernichow S et al. Am J Clin Nutr. 2006; 84:395-399Czernichow S et al. Am J Clin Nutr. 2006; 84:395-399
100 μg Selenium +120 mg Vitamin C, 30 mg Vitamin E, 6 mg of β-carotene, 20 mg of zinc
Antioxidant Supplementation and Antioxidant Supplementation and LipidsLipids SUMIVAX Trial, France, 7.5 years follow-up, n=12,741SUMIVAX Trial, France, 7.5 years follow-up, n=12,741
Hercberg S et al. Lipids. 2005; Hercberg S et al. Lipids. 2005; 40:335-4240:335-42
100 μg Selenium +120 mg Vitamin C, 30 mg Vitamin E, 6 mg of β-carotene, 20 mg of zinc
LipidsLipids Suppl vs. PlaceboSuppl vs. Placebo PP
Mean CholesterolMean Cholesterol No differenceNo difference
HypercholesterolemiaHypercholesterolemia Higher in Suppl (women)Higher in Suppl (women) <0.05<0.05
Mean triglycerides Higher in Suppl (both sexes)Higher in Suppl (both sexes) <0.05<0.05
HypertriglyceridemiaHypertriglyceridemia Higher in Suppl (men)Higher in Suppl (men) <0.05<0.05
Selenium Status and Selenium Status and LipidsLipids NHANES III, 5,452 US adultsNHANES III, 5,452 US adults
Bleys J, Navas-Acien A, Stranges S et al. Am J Clin Nutr. 2008; 88:416-23 Bleys J, Navas-Acien A, Stranges S et al. Am J Clin Nutr. 2008; 88:416-23
Total CholesterolApolipoprotein A1LDL-cholesterolTriglyceridesApolipoprotein BHDL-cholesterol
……Diabetes and Prostate Cancer Risk…Diabetes and Prostate Cancer Risk…
Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev. 2006; 15:1977-83 Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev. 2006; 15:1977-83
*P < 0.001
****
**- 47%- 47%- 28%- 28%
……Diabetes and Prostate Cancer Risk…Diabetes and Prostate Cancer Risk…
Hsing AW et al. Am J Clin Nutr 2007;86:843S-857SHsing AW et al. Am J Clin Nutr 2007;86:843S-857S
SelSeleniumenium and Vitaminand Vitamin EE CCancer Preventionancer Prevention TTrialrial (SELECT) (SELECT)
Review of Prostate Cancer Prevention Study Shows No Benefit for Use of Selenium and Vitamin E Supplements
Initial, independent review of study data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health shows that selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer.
The data also showed two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the over 35,000 men age 50 and older in the trial taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium.
Because this is an early analysis of the data from the study, neither of these findings proves an increased risk from the supplements and both may be due to chance.
Keshan
The Nutritional Prevention of The Nutritional Prevention of Cancer (NPC) TrialCancer (NPC) Trial