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ApoA1

ApoA1

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ApoA1

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  1. Micronutrients and Apo A1 Nutrigenomics: Olivia Tong

  2. Apo A1 Apo A1: major protein of HDL (liver and intestine) Gene expression regulated at: a) Promoter region b) Transcription c) Post-transcription

  3. Micronutrients (Many well research on macronutrients, new; not exist) Nutrients essential for growth and development (< 100mg/d) • Vitamins - Vitamin A, B3, C, and E 2) Macro-minerals 3) Trace minerals - Zinc, copper and chromium 4) Organic Acids

  4. Background..Apo A1 and Diseases Heart disease (leading cause of death in many countries) -Cardiovascular disease (CVD) Plaques form (blood vessel damage) LDL free radicals oxLDL  HDL Lipid disorder Atherosclerosis  Apo-A1 LDL, Cholesterol, plaque forms

  5. Background…Increase Apo A1 • If…CASE 1 (increase apo A1) Increase Apo A1 is GOOD Apo-A1 reverse cholesterol transport at liver LDL, cholesterol Atherosclerosis

  6. Background…antioxidant vitamins If…Case 2 (stop free radicals) Antioxidant vitamins (tested to stop, propose CVD-cardioprotective properties) • Vitamin A (retinoic acid) • Vitamin C (ascorbic acid) • Vitamin E (tocopherol) Romance? Is that true? Damage artery wall artherosclerosis Free radicals

  7. Antioxidant Vitamins • Antioxidant: Prevent destructive oxidation in tissues • Antioxidant Cocktail: antioxidant vitamins (vit. A, C, E ) + Se (metabolic essential) • Failed consistent protective effects (clinical trial for anti-inflammatory) (reverse-even bad) • Not all antioxidant bad: Dimethyl sulfoxide (different pathway)

  8. Antioxidant Cocktail-Vitamin A • Fat-soluble • Retinoic acid/ retinol/ beta-carotene: carrot, spinach, etc • Essential: low light + Colour vision Recommended daily intake • Decrease in plasma Apo A1 ( with approx. 2400 μg/day)

  9. Antioxidant Cocktail-Vitamin E Fat-soluble- Tocopherol: vegetable oil Deficient: muscle weakness Recommended daily intake • Decrease Apo A1 promoter activity • ( Cell model: ~100 μmol/L <- reference: 12-46 μmol/L) )

  10. Antioxidant Cocktail-Vitamin C • Water-soluble • Ascorbatic acid: oranges, kiwifruit (metabolic reactions) • Deficient: Scurvy Recommended daily intake • Decrease Apo A1 promoter activity • ( Cell model: ~15 μmol/L <- reference: 0-114 μmol/L)

  11. Antioxidant Cocktail- Critique + quick conclude Critique: • Values and results inconsistent • Experimental model (either cells or animals, no human) Conclusion: -END OF ROMANCE- Antioxidant vitamins DOES NOT have cardioprotective effect, Instead It would DECREASE Apo A1 promoter activity.

  12. Vitamin B3- Niacin • Water-soluble-Niacin: chicken, avocades(metabolic roles-DNA repair) • Deficient: Pellagra • Side effect: Flushing (overcome- Extended-release niacin) Recommended daily intake • Increase Apo A1 promoter activity • ( Human: 2000mg/day extended-release niacin)

  13. Vitamins summary Therapies…for CVD • Antioxidant vitamins: bad- overestimate value • lovastatin + niacin: good- clinically proven, valuable Conclude: Niacin is a plausible solution for CVD prone patients (Genotype-GA)

  14. Chromium Supplement • Sugar and lipid metabolism: apple, potato, peas • Chromium Deficiency • Bind to insulin receptor ; perform Insulinomimetic action Recommended daily intake • Decrease/ Increase Apo A1 promoter activity • ( Cell: 0-3 mM-> reference range unavailable)

  15. Zinc • In enzymes and transcription factors: Beef, lamb and liver • Zinc deficiency: decrease appetite and growth • Recommended daily intake • Zinc Deficiency Decrease plasmaApo A1

  16. Copper • Vital to health- occurs in liver, muscle and bone • Copper deficiency: Hematological and neurological • Recommended daily intake • Copper Deficiency Increase plasmaApo A1

  17. Trace minerals quick conclude • Chromium supplement: decrease plasma Apo A1 (reliable) -> Advice: follow RDA (so minimal: no need to take supplement unless) • Zinc Deficiency: decrease plasma Apo A1 -> Advice: follow RDA- take sufficient ( not excess-> toxic; balance diet) • Copper Deficiency: Increase plasma Apo A1 -> Advice: follow RDA ( no human studies yet, don’t try to lower)

  18. Summary

  19. Take home message • Excess or insufficient intake of micronutrients would lead to decrease in Apo A1 activity Simply say: Follow the Recommended Daily Intake

  20. Personalize diet • Heart disease prone people (GA Genotype) should take more reasonable amount of extended-release niacin supplement to Increase Apo A1 gene expression, Thus increasing plasma HDL Simply say: Take more niacin to lower the CVD risk

  21. Open discussions • Real life paradox?

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