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The Cholesterol Conundrum: Final Cut

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An Engineering Analysis of the Human Cholesterol Control System, covering the core Biochemistry, control mechanisms, correlative analysis, mechanistic physics, and importantly - the experimental inferences that illustrate root causes of dysfunction.

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The Cholesterol Conundrum: Final Cut

  1. 1. The Cholesterol Conundrum What does the Latest Science Say? Ivor Cummins BE (Chem) May 19th 2014 2013 Ivor Cummins BE(Chem) MIEI
  2. 2. What happened since Oct 2013 Seminar…? At last, The unbiased experts are stepping up to the plate: • Six teaspoons max in 24 hours? • That’s less than a single can of your favorite sugary beverage, and assumes NO other added sugar for the rest of the day? Mmmmn…. • Looks like the Emperor’s suit is getting frayed…..but is anyone listening? 2013 Ivor Cummins BE(Chem) MIEI
  3. 3. 2013 Ivor Cummins BE(Chem) MIEI 1. The Key Molecules 2. The Key Particles 3. The Common Enemy 4. How the Cholesterol Processing System Works – High Level 5. The Risk Factors 6. The $1M Question – What Drives up the Risk Factors? The Conundrum Content:
  4. 4. 2013 Ivor Cummins BE(Chem) MIEI 1. The Key Molecules
  5. 5. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements Cholesterol – for Life Itself 2013 Ivor Cummins BE(Chem) MIEI
  6. 6. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist Cholesterol – for Life Itself 2013 Ivor Cummins BE(Chem) MIEI
  7. 7. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system Cholesterol – for Life Itself 2013 Ivor Cummins BE(Chem) MIEI
  8. 8. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. Cholesterol – for Life Itself 2013 Ivor Cummins BE(Chem) MIEI
  9. 9. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself 2013 Ivor Cummins BE(Chem) MIEI
  10. 10. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself • Triglyceride (aka Triacylglycerol) is a form of fat Trigylceride – for Energy 2013 Ivor Cummins BE(Chem) MIEI
  11. 11. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself • Triglyceride (aka Triacylglycerol) is a form of fat • Is three Fatty Acids on a glycerol (sugar-like) backbone Trigylceride – for Energy 2013 Ivor Cummins BE(Chem) MIEI
  12. 12. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself • Triglyceride (aka Triacylglycerol) is a form of fat • Is three Fatty Acids on a glycerol (sugar-like) backbone • Enters the body via fat-containing food Trigylceride – for Energy 2013 Ivor Cummins BE(Chem) MIEI
  13. 13. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself • Triglyceride (aka Triacylglycerol) is a form of fat • Is three Fatty Acids on a glycerol (sugar-like) backbone • Enters the body via fat-containing food • Is also synthesized by the body (neolipogenisis) for various reasons Trigylceride – for Energy 2013 Ivor Cummins BE(Chem) MIEI
  14. 14. Cholesterol and Triglyceride • Cholesterol is a Sterol Molecule that is used to build cells, hormones and other core physiological elements • Is critical, and fundamental for life to exist • Is a key element of your bodies damage repair system • Is a precursor to the synthesis of Vitamin D, which in turn is one of the most important agents for mortality deferral – we’ll look at this later…. • Finally, cholesterol generally gets blamed for disease pretty much as a paramedic on the scene might be blamed for the car crash Cholesterol – for Life Itself • Triglyceride (aka Triacylglycerol) is a form of fat • Is three Fatty Acids on a glycerol (sugar-like) backbone • Enters the body via fat-containing food • Is also synthesized by the body (neolipogenisis) for various reasons • Can be good or bad: depends on source, location and quantity…. Trigylceride – for Energy 2013 Ivor Cummins BE(Chem) MIEI
  15. 15. 2013 Ivor Cummins BE(Chem) MIEI 2. The Key Particles
  16. 16. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes…. 2013 Ivor Cummins BE(Chem) MIEI
  17. 17. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron 2013 Ivor Cummins BE(Chem) MIEI
  18. 18. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron  VLDL is made in the liver to ferry Trigs and Chol… VLDL 2013 Ivor Cummins BE(Chem) MIEI
  19. 19. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron  VLDL is made in the liver to ferry Trigs and Chol… LDLVLDL 2013 Ivor Cummins BE(Chem) MIEI  LDL (from VLDL) is the so-called “BAD Cholesterol”
  20. 20. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron sdLDL  VLDL is made in the liver to ferry Trigs and Chol… LDLVLDL 2013 Ivor Cummins BE(Chem) MIEI  LDL (from VLDL) is the so-called “BAD Cholesterol”  Oxidized LDL is the real “BAD Cholesterol”
  21. 21. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron sdLDL  VLDL is made in the liver to ferry Trigs and Chol… HDLLDLVLDL 2013 Ivor Cummins BE(Chem) MIEI  HDL is the so-called “GOOD Cholesterol”  LDL (from VLDL) is the so-called “BAD Cholesterol”  Oxidized LDL is the real “BAD Cholesterol”
  22. 22. 2013 Ivor Cummins BE(Chem) MIEI And now, a word from our “Sponsor”…..
  23. 23. 2013 Ivor Cummins BE(Chem) MIEI And now, a word from our “Sponsor”….. 3. The Common Enemy
  24. 24. Atherosclerosis and CVD Mechanism 2013 Ivor Cummins BE(Chem) MIEI
  25. 25. Atherosclerosis and CVD Mechanism  Ingress of Lipoprotein Particles through Endothelium (inner wall) The Disease Sequence: TgCh ChCh B100 2013 Ivor Cummins BE(Chem) MIEI
  26. 26. Atherosclerosis and CVD Mechanism  Ingress of Lipoprotein Particles through Endothelium (inner wall)  Uptake of these by immune system Macrophage The Disease Sequence: + Macrophage TgCh ChCh B100 2013 Ivor Cummins BE(Chem) MIEI
  27. 27. Atherosclerosis and CVD Mechanism  Ingress of Lipoprotein Particles through Endothelium (inner wall)  Uptake of these by immune system Macrophage  Subsequent transformation into “Foam Cells” and buildup of Plaque The Disease Sequence: + Ch Ch Ch Macrophage = FOAM CELL TgCh ChCh B100 2013 Ivor Cummins BE(Chem) MIEI
  28. 28. Atherosclerosis and CVD Mechanism  Ingress of Lipoprotein Particles through Endothelium (inner wall)  Uptake of these by immune system Macrophage  Subsequent transformation into “Foam Cells” and buildup of Plaque  Ultimately a decline in vascular health, then breakouts, blockages….. The Disease Sequence: + Ch Ch Ch Macrophage = FOAM CELL TgCh ChCh B100 2013 Ivor Cummins BE(Chem) MIEI
  29. 29. Atherosclerosis and CVD Mechanism  Ingress of Lipoprotein Particles through Endothelium (inner wall)  Uptake of these by immune system Macrophage  Subsequent transformation into “Foam Cells” and buildup of Plaque  Ultimately a decline in vascular health, then breakouts, blockages….. The Disease Sequence: + Ch Ch Ch Macrophage = FOAM CELL  The Million Dollar Question: What mediates this inflammatory process? TgCh ChCh B100 2013 Ivor Cummins BE(Chem) MIEI End
  30. 30. 2013 Ivor Cummins BE(Chem) MIEI 4. How the Cholesterol Processing System Works - High Level
  31. 31. The Lipoprotein Particles – Boats for Cargo Trigylceride/ Cholesterol An Apo- Lipoprotein Phospholipids  The LIPOPROTEIN PARTICLES are transport vessels (“boats”) created in the body to deliver Triglyceride and Cholesterol (“cargo”), for energy transfer, critical synthesis, and healing purposes….  The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing Chylomicron sdLDL  VLDL is made in the liver to ferry Trigs and Chol… HDLLDLVLDL 2013 Ivor Cummins BE(Chem) MIEI  HDL is the so-called “GOOD Cholesterol”  LDL (from VLDL) is the so-called “BAD Cholesterol”  Oxidized LDL is the real “BAD Cholesterol” 1 2 3
  32. 32. 2013 Ivor Cummins BE(Chem) MIEI 4. Lipoprotein Type 1 of 3 : The CHYLOMICRON (for Dietary Fat and Cholesterol Transport…)
  33. 33. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg TgCh Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  34. 34. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg TgCh Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  35. 35. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg TgCh Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  36. 36. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgE Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  37. 37. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgE Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  38. 38. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgELDLR SR-B1 Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  39. 39. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgELDLR SR-B1 Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  40. 40. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgE Ch Ch Ch LDLR SR-B1 Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI
  41. 41. CHYLOMICRON: for dietary Fat and Chol Dietary Fats Triglycerides Cholesterol E C II CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg CHYLOMICRON B48 TgTgCh TgTgTg Tg Tg Tg Tg Tg Tg Tg Tg Tg B48 CHYLO REMNANT Ch TgTg TgE Ch Ch Ch LDLR SR-B1 Ch Tg Tg Tg 2013 Ivor Cummins BE(Chem) MIEI SYSTEM MANUAL: “Important: For Correct Operation, Insulin must be kept low” End
  42. 42. 2013 Ivor Cummins BE(Chem) MIEI 4. Lipoprotein Type 2 of 3 : The LDL Species (Created by your Liver, for Triglyceride and Cholesterol Delivery…)
  43. 43. VLDL, IDL,LDL…..and Small Dense LDL LDLR SR-B1 Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI
  44. 44. VLDL, IDL,LDL…..and Small Dense LDL LDLR VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 SR-B1 Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI
  45. 45. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 SR-B1 Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI
  46. 46. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 SR-B1 Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI
  47. 47. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 SR-B1 HL Ch Ch Ch Tg 2013 Ivor Cummins BE(Chem) MIEI
  48. 48. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 HL Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI Tg
  49. 49. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 HL Ch Ch Ch Ch Ch To tissues and cells 2013 Ivor Cummins BE(Chem) MIEI Tg
  50. 50. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 HL Ch Ch Ch 2013 Ivor Cummins BE(Chem) MIEI Ch Tg Ch To tissues and cells
  51. 51. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 TgCh ChCh B100 LDL SD HL HL Ch Ch Ch TgCh ChCh B100 LDL OX 2013 Ivor Cummins BE(Chem) MIEI Tg Ch Ch To tissues and cells Gluc
  52. 52. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 TgCh ChCh B100 LDL SD HL Ch Ch Ch TgCh ChCh B100 LDL OX 2013 Ivor Cummins BE(Chem) MIEI Tg Ch Ch To tissues and cells HL Gluc
  53. 53. VLDL, IDL,LDL…..and Small Dense LDL C II LDLR C II LPL VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 IDL TgTg Tg Ch Ch Ch Ch E B100 TgCh ChCh B100 LDL SR-B1 TgCh ChCh B100 LDL SD HL Ch Ch Ch Ch Ch Ch IMMUNE SYSTEM MACROPHAGE / FOAM CELL TgCh ChCh B100 LDL OX 2013 Ivor Cummins BE(Chem) MIEI Tg Ch To tissues and cellsCh HL Gluc End
  54. 54. 2013 Ivor Cummins BE(Chem) MIEI 4. Lipoprotein Type 3 of 3 : The HDL Species (For Cholesterol Management, and a few other important things…)
  55. 55. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch A HDL Tg E 2013 Ivor Cummins BE(Chem) MIEI
  56. 56. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch A HDL Tg E Ch Adrenal Cortex and Gonads 2013 Ivor Cummins BE(Chem) MIEI
  57. 57. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch A HDL Tg E Ch Adrenal Cortex and Gonads Ch From tissues and cells ABC A1 ABC G1 LCAT 2013 Ivor Cummins BE(Chem) MIEI
  58. 58. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch A HDL Tg E Ch Adrenal Cortex and Gonads Ch ABC A1 ABC G1 LCAT Ch Ch Ch IMMUNE SYSTEM MACROPHAGE / FOAM CELL ABC A1 ABC G1 From tissues and cells 2013 Ivor Cummins BE(Chem) MIEI LCAT
  59. 59. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch Ch Ch IMMUNE SYSTEM MACROPHAGE / FOAM CELL Ch A HDL Tg E Ch ABC A1 ABC G1 LCAT LCAT ABC A1 ABC G1 Ch Adrenal Cortex and Gonads From tissues and cells 2013 Ivor Cummins BE(Chem) MIEI + Antioxidant Action….!
  60. 60. HDL…..and Reverse Cholesterol Transport LDLR SR-B1 Ch Ch Ch Ch A HDL Tg E Ch Adrenal Cortex and Gonads Ch ABC A1 ABC G1 LCAT Ch Ch Ch IMMUNE SYSTEM MACROPHAGE / FOAM CELL ABC A1 ABC G1 From tissues and cells 2013 Ivor Cummins BE(Chem) MIEI LCAT + Antioxidant Action….!
  61. 61. HDL…..and Reverse Cholesterol Transport LDLR VLDL Tg Tg Tg Tg Tg Tg Tg Tg Ch Ch Ch Ch E C II B100 TgCh ChCh B100 LDL SR-B1 Ch Ch Ch Ch Ch Ch IMMUNE SYSTEM MACROPHAGE / FOAM CELL Ch A HDL Tg E Ch ABC A1 ABC G1 LCAT LCAT Ch Ch Tg Tg ABC A1 ABC G1 Ch Adrenal Cortex and Gonads From tissues and cells 2013 Ivor Cummins BE(Chem) MIEI + Antioxidant Action….! IDL TgTg Tg Ch Ch Ch Ch E B100 Ch Tg End
  62. 62. 2013 Ivor Cummins BE(Chem) MIEI 5. The Risk Factors
  63. 63. Key Predictors of Mortality –Dysfunctional Lipoprotein Status • LDL/HDL Ratio (or better still, ApoB/ApoA Ratio) • High Serum Triglyceride Levels, larger VLDL particles… • Small Dense LDL and associated LDL Particle COUNT (ApoB) 2013 Ivor Cummins BE(Chem) MIEI
  64. 64. Key Predictors of Mortality –Dysfunctional Lipoprotein Status • LDL/HDL Ratio (or better still, ApoB/ApoA Ratio) • High Serum Triglyceride Levels, larger VLDL particles… • Small Dense LDL and associated LDL Particle COUNT (ApoB) –Insulin Levels and Insulin Resistance Status 2013 Ivor Cummins BE(Chem) MIEI
  65. 65. Key Predictors of Mortality –Dysfunctional Lipoprotein Status • LDL/HDL Ratio (or better still, ApoB/ApoA Ratio) • High Serum Triglyceride Levels, larger VLDL particles… • Small Dense LDL and associated LDL Particle COUNT (ApoB) –Insulin Levels and Insulin Resistance Status –Blood Glucose Level and HbA1C 2013 Ivor Cummins BE(Chem) MIEI
  66. 66. Key Predictors of Mortality –Dysfunctional Lipoprotein Status • LDL/HDL Ratio (or better still, ApoB/ApoA Ratio) • High Serum Triglyceride Levels, larger VLDL particles… • Small Dense LDL and associated LDL Particle COUNT (ApoB) –Insulin Levels and Insulin Resistance Status –Blood Glucose Level and HbA1C –High Blood Pressure • generally driven by the same root causes that drive the above 2013 Ivor Cummins BE(Chem) MIEI
  67. 67. Key Predictors of Mortality –Dysfunctional Lipoprotein Status • LDL/HDL Ratio (or better still, ApoB/ApoA Ratio) • High Serum Triglyceride Levels, larger VLDL particles… • Small Dense LDL and associated LDL Particle COUNT (ApoB) –Insulin Levels and Insulin Resistance Status –Blood Glucose Level and HbA1C –High Blood Pressure • generally driven by the same root causes that drive the above –Other markers of Systemic Inflammation • GGT, CRP, Serum Ferritin, etc 2013 Ivor Cummins BE(Chem) MIEI
  68. 68. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. 2013 Ivor Cummins BE(Chem) MIEI Increasing Cholesterol IncreasedRisk
  69. 69. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. IncreasedRisk 2013 Ivor Cummins BE(Chem) MIEI  Increasing Cholesterol = lower risk Key Takeaways: Increasing Cholesterol
  70. 70. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. IncreasedRisk 2013 Ivor Cummins BE(Chem) MIEI  Increasing Cholesterol = lower risk Key Takeaways: Increasing Cholesterol Engineering Explanations for the mistake:
  71. 71. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. IncreasedRisk 2013 Ivor Cummins BE(Chem) MIEI  Increasing Cholesterol = lower risk  Age Confounding was a serious issue Key Takeaways: Increasing Cholesterol Engineering Explanations for the mistake:
  72. 72. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. IncreasedRisk 2013 Ivor Cummins BE(Chem) MIEI  Increasing Cholesterol = lower risk  Age Confounding was a serious issue Key Takeaways:  Non-Representative populations, inclusion of Hypercholesteremia cases Increasing Cholesterol Engineering Explanations for the mistake:
  73. 73. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 ALL CAUSE DEATH…. IncreasedRisk 2013 Ivor Cummins BE(Chem) MIEI  Increasing Cholesterol = lower risk  Age Confounding was a serious issue  Endemic Research Bias Key Takeaways:  Non-Representative populations, inclusion of Hypercholesteremia cases Increasing Cholesterol Engineering Explanations for the mistake:
  74. 74. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5  Increasing Cholesterol = lower risk  Age Confounding was a serious issue  Endemic Research Bias ALL CAUSE DEATH…. IncreasedRisk Key Takeaways: In short, Total Cholesterol effectively not considered any more by the leading edge researchers in the field  Non-Representative populations, inclusion of Hypercholesteremia cases 2013 Ivor Cummins BE(Chem) MIEI Engineering Explanations for the mistake: Increasing Cholesterol
  75. 75. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years Increasing LDL (the “Bad Cholesterol”) Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old 2013 Ivor Cummins BE(Chem) MIEI Decreasing HDL (the “Good Cholesterol”)
  76. 76. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old 2013 Ivor Cummins BE(Chem) MIEI Increasing LDL (the “Bad Cholesterol”) Decreasing HDL (the “Good Cholesterol”)
  77. 77. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important  The benefit of LDL being low………totally depends on the HDL status Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old 2013 Ivor Cummins BE(Chem) MIEI Increasing LDL (the “Bad Cholesterol”) Decreasing HDL (the “Good Cholesterol”)
  78. 78. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important  The benefit of LDL being low………totally depends on the HDL status  Risk is determined primarily by the RATIO of these parameters Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old 2013 Ivor Cummins BE(Chem) MIEI Increasing LDL (the “Bad Cholesterol”) Decreasing HDL (the “Good Cholesterol”)
  79. 79. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important  Risk is determined primarily by the RATIO of these parameters  Diagnosing via LDL is minimally useful in the face of the current science Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old 2013 Ivor Cummins BE(Chem) MIEI Increasing LDL (the “Bad Cholesterol”) Decreasing HDL (the “Good Cholesterol”)  The benefit of LDL being low………totally depends on the HDL status
  80. 80. Decreasing HDL (the “Good Cholesterol”) LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important  Risk is determined primarily by the RATIO of these parameters  Diagnosing via LDL is minimally useful in the face of the current science Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old XXX 2013 Ivor Cummins BE(Chem) MIEI Guess Who?  The benefit of LDL being low………totally depends on the HDL status Increasing LDL (the “Bad Cholesterol”)
  81. 81. LDL & HDL as predictive factors? Diagram adapted from article in Journal of Cardiovascular Medicine 2011, Vol 00, No 00 2.58 4.13 5.68 HDL=0.65 HDL = 1.16 HDL = 1.68 HDL = 2.20 RiskofHeartDiseaseafter4Years  HDL being adequate/higher is VERY important  Risk is determined primarily by the RATIO of these parameters  Diagnosing via LDL is minimally useful in the face of the current science Heart Disease Risk Vs LDL & HDL Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old XXX 2013 Ivor Cummins BE(Chem) MIEI And this Guy?  The benefit of LDL being low………totally depends on the HDL status Increasing LDL (the “Bad Cholesterol”) Decreasing HDL (the “Good Cholesterol”)
  82. 82. Key Predictors of Mortality Ready for more of the REAL Engineering? 2013 Ivor Cummins BE(Chem) MIEI
  83. 83. SERUM TRIGLYCERIDE as a Predictive Factor Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737. Data from the PROCAM Munster Study  Blood Triglyceride Levels are an important Risk Factor for Coronary Disease  However, they should not be judged alone – vital to balance with other factors  Again we see the importance of LDL/HDL Ratios and interactions with Trigs Key Takeaways: 2013 Ivor Cummins BE(Chem) MIEI
  84. 84. SERUM INSULIN as a Predictive Factor Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737. Data from the PROCAM Munster Study (from "Interesting slideset around…):  Insulin is fundamental to Coronary Disease and Mortality Risk  Insulin has been grossly underemphasized as a risk factor for decades  Triglyceride risk totally outgunned by Insulin Status here Key Takeaways: 2013 Ivor Cummins BE(Chem) MIEI Data from the Quebec Study Cardiovascular Study: Despres JP, et al. N Engl J Med. 1996;334:952-957.
  85. 85. SERUM INSULIN and LDL Particle Count Data from the Quebec Study Cardiovascular Study: Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.  Again Insulin is key, but significant interaction with LDL Particle Count (ApoB)  LDL Particle Count tracks with Small Dense LDL – I’ll explain this shortly!  Interaction is the operative word – synergy closely follows Key Takeaways: 2013 Ivor Cummins BE(Chem) MIEI Lamarche B, et al. Circulation. 1997;95:69-75.
  86. 86. Small Dense LDL as a Predictive Factor Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.  Small Dense LDL and associated LDL Particle Count are Key  These, along with Insulin / Insulin Resistance Status, are Master Markers Key Takeaways: 2013 Ivor Cummins BE(Chem) MIEI Reprinted from St-Pierre AC, et al. Circulation. 2001;104: 2295–2299, with permission from Wolters Kluwer Health.
  87. 87. Data taken from Table 2: Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk Kay-Tee Khaw, MBBChir, FRCP; Nicholas Wareham, MBBS, FRCP; Sheila Bingham, PhD; Robert Luben, BSc; Ailsa Welch, BSc; and Nicholas Day, PhD Glucose Levels Anyone? - HbA1c as a Risk Factor Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.  HbA1c is the alteration of Red Blood Cells driven by blood glucose levels  This again is closely related to Insulin & Insulin Resistance Status  HbA1c from this particular study is also an independent risk factor Key Takeaways: 2013 Ivor Cummins BE(Chem) MIEI
  88. 88. 2013 Ivor Cummins BE(Chem) MIEI 6. The $1M Question – What Primarily Drives up the Risk Factors???
  89. 89. Improving the Total Chol / HDL RatioTotCholesterol/HDL 2013 Ivor Cummins BE(Chem) MIEI  Tot Chol / HDL is a good metric  Increasingly Lower Carb delivers dose-response increased improvement  Low Carb exceeds benefits of low fat regime – even with NO dieting  Even during the starvation period, Low Fat regime struggles Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia1–3 Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams Data adapted from from Jeff Volek Summary of:
  90. 90. Improving the LDL / HDL Particle Ratio Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia1–3 Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams Data adapted from from Jeff Volek Summary of: ApoB/ApoA  LDL / HDL key (here we have even better metric – the particle COUNT ratio)  Increasingly Lower Carb delivers dose-response increased improvement 2013 Ivor Cummins BE(Chem) MIEI  Low Carb far exceeds benefits of low fat regime – even with NO dieting  Even during the starvation period, Low Fat regime fails
  91. 91. Improving the Serum Triglyceride Level TrigReduction 2013 Ivor Cummins BE(Chem) MIEI  Serum Triglyceride – important to keep this down  Increasingly Lower Carb delivers dose-response increased improvement  Even during the starvation period, Low Fat regime fails Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia1–3 Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams Data adapted from from Jeff Volek Summary of:  Low Carb far exceeds benefits of low fat regime – even with NO dieting
  92. 92. Improving LDL Particle DiameterLDLParticleDiameter 2013 Ivor Cummins BE(Chem) MIEI  LDL Particle Diameter is a serious metric  Increasingly Lower Carb delivers dose-response increased improvement  Low Carb far exceeds benefits of low fat regime, especially if you don’t diet  Even during the starvation period, Low Fat regime struggles Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia1–3 Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams Data adapted from from Jeff Volek Summary of:
  93. 93. Improving HDL LevelsHDL“good”Chol 2013 Ivor Cummins BE(Chem) MIEI  HDL – the higher the better  Increasingly Lower Carb delivers dose-response increased improvement  Low Carb far exceeds benefits of low fat regime, again even with no dieting  Even during the starvation period, Low Fat regime fails Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia1–3 Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams Data adapted from from Jeff Volek Summary of:
  94. 94. Another Recent Trial xxxxx.  ALL markers better with Low Carb regime – including all Inflammatory ones!  Only Low Carb enhances HDL, improves small LDL, and ApoB/ApoA ratio  Scientifically this appears to be a fundamental rule, but rigorously challenged? 2013 Ivor Cummins BE(Chem) MIEI HIGH CARB, LOW FATHIGH FAT, VERY LOW CARB
  95. 95. 2013 Ivor Cummins BE(Chem) MIEI (Richard David Feinman summary of referenced Studies) Another of Many….  ALL markers better with Low Carb / High Fat regime  Only Low Carb enhances HDL, though low GI has a go (!)  Scientifically this appears to be a fundamental rule, but rigorously challenged? HIGH CEREAL JENKINS LOW GLYCEMIC INDEX WESTMAN LOW GLYCEMIC INDEX WESTMAN LOW CARB HIGH FAT Jenkins DJ, Kendall CW, McKeown-Eyssen G, Josse RG, Silverberg J, Booth GL, Vidgen E, Josse AR, Nguyen TH, Corrigan S et al: Effect of a low-glycemic index or a high- cereal fiber diet on type 2 diabetes: a randomized trial. JAMA 2008, 300(23):2742-2753 Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR: The Effect of a Low-Carbohydrate, Ketogenic Diet Versus a Low-Glycemic Index Diet on Glycemic Control in Type 2 Diabetes Mellitus. Nutr Metab (Lond) 2008, 5(36).
  96. 96. Let’s Cut to The Bottom Line….  Selection of people with Coronary issues and Pattern B tendencies – the perfect cohort to explore  Examined the effect of dietary carbohydrate on their true “Bad Cholesterol” proportion  Surprising Result? No… Rather the Expected Result.  “Pattern B” is the Small Dense Cholesterol profile I described earlier (The BAD) 2013 Ivor Cummins BE(Chem) MIEI Higher % Carb in Diet Krauss RM: Atherogenic lipoprotein phenotype and diet-gene interactions. J Nutr 2001, 131(2):340S-3S.
  97. 97. Let’s Cut to The Bottom Line….  So Type B (dysfunctional LDL pattern), lowers directly with lowered Carb in Diet  R = 0.95, i.e. direct dose-response improvement with low carb  Incredible evidence – but still rigorously ignored………how can this be?  Selection of people with Coronary issues and Pattern B tendencies – the perfect cohort to explore  Examined the effect of dietary carbohydrate on their true “Bad Cholesterol” proportion  Surprising Result? No… Rather the Expected Result.  “Pattern B” is the Small Dense Cholesterol profile I described earlier (The BAD) 2013 Ivor Cummins BE(Chem) MIEI  R = 0.95 - any engineers in the audience today?? Higher % Carb in Diet Krauss RM: Atherogenic lipoprotein phenotype and diet-gene interactions. J Nutr 2001, 131(2):340S-3S.
  98. 98. So, Driving Risk Factors: Where are you? Disease Risk Marker High Carb Low Fat Low Carb / High Fat* Is Lean / Fit Kcal Control / active Carb Tolerant (~30% of people?) Is Not Lean / Is Not Fit High Kcal / Sedentary Carb Intolerant (~70% of people?) Enables: Lean / Fit Kcal Control / Active Health and Wellbeing Visceral Fat: Waist+ HDL Tot Chol / HDL Serum Glucose Serum Insulin Blood Pressure Serum Triglyceride Inflammation markers various LDL ** * Following Metabolic Adaptation period of 3 weeks to 2 months ** Not a primary marker, particularly requires analysis of other factors to interpret 2013 Ivor Cummins BE(Chem) MIEI
  99. 99. Moderate High Metabolically Compromised/obese Athletes Naturally lean Overweight/obeseSlide from: Professor Jeff Volek “The Many Facets of Keto- Adaptation” Google the Youtube video of this – it’s superb
  100. 100. Evidence-Based Science Comeback 2013 Ivor Cummins BE(Chem) MIEI  Driven by a GP who did the work and figured out Root Cause: Dietary Carb  Reported to the Swedish Health Board to get her License Revoked  Real Science Wins Out…. in Sweden anyway  Exonerated by a 2 year investigation by a Government Panel of Doctors & PHD’s
  101. 101. N = 1 (But the Important One!) HDL 1.47 1.73 GGT 112 42 Trig 0.78 0.92 Trig/HDL 1.03 1.44 Tot Chol /HDL 3.5 4.5 C Expt 35 530 230 Ferritin >1.00 mmol /L < 200 approx <4.0 <35 approx < 1.5 mmol /L < 2.0 Note: converted from mmol/L to mg/dL to get ratio guidelines 2013 Ivor Cummins BE(Chem) MIEI Old Ivor, watching the fat…..duh! New Ivor, keeping the carb down…
  102. 102. N=1 Continued…. Weight 81kg 95 5k run time <24min 28 Waist <32” 35 Sys BP 125 145 Dia BP 75 95 C Expt Ideal ~82Kg Ideal 32” <80 mmHg <130 mmHg Avg of 20+ readings from same Equipment 2013 Ivor Cummins BE(Chem) MIEI Old Ivor, watching the fat…..duh! New Ivor, keeping the carb down…
  103. 103. 2013 Ivor Cummins BE(Chem) MIEI
  104. 104. 2013 Ivor Cummins BE(Chem) MIEI Human Evolution, low Insulin Regime for ~1 Million Years to 1970….
  105. 105. 2013 Ivor Cummins BE(Chem) MIEI Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
  106. 106. 2013 Ivor Cummins BE(Chem) MIEI Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
  107. 107. 2013 Ivor Cummins BE(Chem) MIEI Discussion / Questions Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
  108. 108. Future “Biochemistry for Life” Topics: • 25 Hydroxy Vitamin D  The history, latest science, and significant mortality implications of this critical agent • Insulin – a Billion Years in Service  The evolutionary importance and critical functionality of Insulin, increasingly dysfunctional and pathogenic in our modern environment • Keto-Adaptation  Living in an advantaged metabolic state – it’s much more than simply having an edge • Omega 6 Vegetable Oils  The interesting story of how a machine lubricant became a health food – but should have stayed in the machine…. 2013 Ivor Cummins BE(Chem) MIEI
  109. 109. BACKUP
  110. 110. Fundamental Truth • To successfully gain excellent health and years of extra life, I believe that you must actually understand this science to a reasonable degree, not just “follow the diet” • To achieve this understanding will likely be the best thing you ever do for yourself. • Also, everyone has a different genetic makeup, and this must be understood also – it’s not one size fits all – know your phenotype! (but the key drivers do have much commonality) 2013 Ivor Cummins BE(Chem) MIEI
  111. 111. Total Cholesterol as a predictive factor? Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants) Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3 Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5 Cardiovascular Death IncreasedRisk IncreasedRisk Ischemic Heart Disease Death 2013 Ivor Cummins BE(Chem) MIEI
  112. 112. Chylomicron Summary Dietary Fat and Cholesterol is packaged into the Large Chylomicrons (100-1000nm) The latter deliver Triglyceride Molecules For Energy Use in the Heart / Skeletal Muscles Following this energy transfer, the Chylomicron remnants have a short half-life of ~20min in the bloodstream, and are readily taken up by the liver, thus completing the cycle However, the latter description assumes moderate carbohydrate ingestion and insulin secretion….high carb will spike insulin, suppress Triglyceride utilization, and increase remnant residence time…. 2013 Ivor Cummins BE(Chem) MIEI
  113. 113. VLDL to LDL Summary VLDL is produced by the liver to transport Triglyceride cargo for energy uses, and Cholesterol for building tasks As Triglyceride is depleted, Apo CII is shed and the VLDL becomes an IDL; further depletion and shedding of Apo E results in an LDL particle with Apo B100 only LDL should deliver cholesterol and ideally be taken up by the liver receptors before it becomes sdLDL or is oxidized (bad boats, increasing numbers, more risk!) Oxidized LDL reduces take-up by liver – and enhances take-up by macrophage – inflammation and the disease process is augmented 2013 Ivor Cummins BE(Chem) MIEI
  114. 114. HDL Summary HDL has many functions, one of which is to remove Cholesterol excess from problematic areas Low / dysfunctional HDL relative ratios generally track with high blood triglyceride, higher sdLDL and higher inflammatory status Thus the various risk factors are connected and synergistic – and have common drivers We’ll see how to influence HDL health shortly – and it’s not as hard as you might think! 2013 Ivor Cummins BE(Chem) MIEI HDL’s other key role is in moderating oxidation in general, and of LDL specifically
  115. 115. Why are we in this room today - How does this come about? Academic / Educational History Problem Solving Experience / Aptitude 2013 Ivor Cummins BE(Chem) MIEI

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