ESPEN Congress Leipzig 2013

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1 ESPEN Congress Leipzig 2013 From A to Zinc: the evolving concept of micronutrient supplementation Micronutrients and cancer prevention T. Grune (DE)

2 Micronutrients and Cancer Prevention Tilman Grune Institute of Nutrition 2

3 Micronutrients and Metabolism Hormonal Regulation Sensoric Functions Enzym Cofactors Micronutrients Intermediate Metabolism Cell physiologie Redoxregulation

4 Micronutrients and Metabolism Hormonal Regulation Sensoric Functions Enzym Cofactors Micronutrients Intermediate Metabolism Cell physiologie Redoxregulation

5 Oxidative Stress Disturbance of the antioxidant and prooxidant system in favor of the prooxidants (Sies, 1985) Oxidative Stress Oxidants Antioxidants At least two major problems are associated with manipulating the redox status.

6 Antioxidative Defenses Problem 1 6 Non-enzymatic: a) Low molecular hydrophilic Vitamin C Urate Glutathion lipophilic Carotinoids Vitamin E b) Proteins Metall-binding Enzymatic: SODs (CuZn, Mn) Peroxidases Catalase GSH-Peroxidases Peroxiredoxins Reductases GSSG-Reductase Glutaredoxin Thioredoxin/-reductase Phase I- and Phase II-enzyms NQOR1 GSH-transferases... Repair enzymes

7 Problem 1 Low molecular weight antioxidants Endogenic: Uric acid Bilirubin Glucose Proteins Fe- and Cu- binding Exogenic: Vitamins (ß-Carotin, E, C) Carotinoids Ubichinon Lipoic acid Flavonoids, Polyphenols 7 7

8 Low molecular weight antioxidants Concentrations Problem 1 Antioxidans Plasmagehalt (µm) Hydrophil Ascorbat Glutathion 1-2 Urat Bilirubin 5-20 Lipophil (mit Lipoproteinen assoziiert) -Tocopherol Tocopherol 3-5 -Carotin Carotin Lycopin Lutein Zeaxanthin Ubichinol from: Sies et al., Ann N Y Acad Sci 669: 7-20, 1992

9 Antioxidant Interaction Metabolism Low molecular weight antioxidants Problem 1 Interactions LOO Uric acid Vitamin E Coenzym Q -Lipoic acid Vitamin C Glutathion NAD(P) 9

10 Problem 2 Micronutrients and Redox Regulation Oxidants Xenobiatica (Irradiation) Food Proteins Oxidants and Radicals ER / CyP Metabolism Lipids Chromatin

11 Problem 2 Micronutrients and Redox Regulation Food Oxidants Xenobiatica (Irradiation) Antioxidants Antioxidants Proteins Oxidants and Radicals ER / CyP Metabolism Lipids Chromatin

12 Problem 2 Micronutrients and Redox Regulation Food Oxidants Xenobiatica (Irradiation) Antioxidants Antioxidants Proteins Oxidants and Radicals ER / CyP Metabolism Lipids Blocking of regulatory effects!!!! Chromatin

13 Why micronutrient supplementation?

14 Why micronutrient supplementation? Primary food components Processing Storage Preparation Secundary food components Primary food components Taste changes Macro-nutrients Energy density Micronutrients Disbalance / no evolutionary adaptation to food processing Requirement of supplements / measurements by biomarkers

15 Risk of Insufficiency Antioxidant supplementation Adequate Risk of Overdose Risk Dose Vitamin supplementation helps if nutrition is not adequate. Is there an additional benefit of higher doses? 15

16 Antioxidant supplementation Vitamin supplementation helps if nutrition is not adequate. Is there an additional benefit of higher doses? High vitamin doses might be not healthy or have side effects. High antioxidant supplementation might suppress redox regulation. Research: moderate multiviatmins might be more effective. Studies: testing often single (high dosis) vitamins 16

17 Micronutrients and Cancer Gaziano et al. JAMA

18 Micronutrients and Cancer Gaziano et al. JAMA

19 Micronutrients and Cancer Gaziano et al. JAMA 2012 Design: - Male physicians (N=14642) years treatment - age: years (baseleine) cancer cases (1373 prostate cancer) - Mutivitamins: Vit E 400 IU (until 2007) Vit C 500 mg (until 2007) beta carotin (until 2003)(Lurotin/BASF 50mg) 19

20 Micronutrients and Cancer Gaziano et al. JAMA 2012 Importance: - large scale - randomized - long-term - multivitamins 20

21 Micronutrients and Cancer Metaanalyses Metaanalysis Studies N Mortality 21 Baldwin et al., ( 2012) Oral nutritional interventions in malnourished patients with cancer Macpherson et al. (2013) Multivitaminmultimineral supplementation and mortality Bjelokovic et al. (2008) Antioxidants in preventing gastrointestinal cancer Bjelakovic et al. (2012) Antioxidant supplements for prevention of mortality in patients with various diseases Bjelakovic et al. (2010) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases Bjelakovic et al. (2007) Gastrointestinal cancers / Chochrane Stratton/Goldwin (2011) The effect of supplemental vitamins and minerals on the development of prostate cancer Chang et al. (2011) Effects of vitamin treatment..on skin cancer No effect (RR 1.06; p=0.43) No effect (RR 0.96) No effect / selenium? (RR 1.02) No effect (RR 1.02) ->VitE/b-Car tendency to increase cancer No effect (RR 1.02) No effect. 14 No effect. 10 No effect (RR 0.98)

22 Micronutrients and Cancer Metaanalyses Metaanalysis Studies N Mortality 22 Baldwin et al., ( 2012) Oral nutritional interventions in malnourished patients with cancer Macpherson et al. (2013) Multivitaminmultimineral supplementation and mortality Bjelokovic et al. (2008) Antioxidants in preventing gastrointestinal cancer Bjelakovic et al. (2012) Antioxidant supplements for prevention of mortality in patients with various diseases Bjelakovic et al. (2010) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases Bjelakovic et al. (2007) Gastrointestinal cancers / Chochrane Stratton/Goldwin (2011) The effect of supplemental vitamins and minerals on the development of prostate cancer Chang et al. (2011) Effects of vitamin treatment..on skin cancer No effect (RR 1.06; p=0.43) No effect (RR 0.96) No effect / selenium? (RR 1.02) No effect (RR 1.02) ->VitE/b-Car tendency to increase cancer No effect (RR 1.02) No effect. 14 No effect. 10 No effect (RR 0.98)

23 Micronutrients and Cancer Metaanalyses Bjelakovic et al. JAMA 2007 Design: - 68 studies participants - mortality 23

24 Micronutrients and Cancer Metaanalyses Bjelakovic et al. JAMA 2007 Design: - 68 studies participants - mortality 24

25 Micronutrients and Cancer Metaanalyses Bjelakovic et al. JAMA 2007 Design: - 68 studies participants - mortality 25

26 Micronutrients and Cancer Metaanalyses Biesalski et al. Nutrients, 2010 Design: - same 68/66 studies / participants - primary end-point (+1/0/-1) 26

27 Micronutrients and Cancer Metaanalyses Biesalski et al. Nutrients, 2010 Design: - same 68/66 studies / participants - primary end-point (+1/0/-1) 27

28 Micronutrients and Cancer Metaanalyses Biesalski et al. Nutrients,

29 Micronutrients and Cancer Gaziano et al. JAMA 2012 More such studies are needed. 29

30 Thank you! 30

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