the cholesterol conundrum: final cut
DESCRIPTION
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.TRANSCRIPT
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The Cholesterol Conundrum
What does the Latest Science Say?
Ivor Cummins BE (Chem)
May 19th 2014
2013 Ivor Cummins BE(Chem) MIEI
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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
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2013 Ivor Cummins BE(Chem) MIEI
1. The Key Molecules2. The Key Particles3. The Common Enemy4. How the Cholesterol Processing
System Works – High Level5. The Risk Factors6. The $1M Question – What Drives up
the Risk Factors?
The Conundrum Content:
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2013 Ivor Cummins BE(Chem) MIEI
1. The Key Molecules
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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2013 Ivor Cummins BE(Chem) MIEI
2. The Key Particles
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The Lipoprotein Particles – Boats for CargoTrigylceride/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
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The Lipoprotein Particles – Boats for CargoTrigylceride/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
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The Lipoprotein Particles – Boats for CargoTrigylceride/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
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The Lipoprotein Particles – Boats for CargoTrigylceride/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”
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The Lipoprotein Particles – Boats for CargoTrigylceride/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”
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The Lipoprotein Particles – Boats for CargoTrigylceride/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”
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2013 Ivor Cummins BE(Chem) MIEI
And now, a word from our “Sponsor”…..
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2013 Ivor Cummins BE(Chem) MIEI
And now, a word from our “Sponsor”…..
3. The Common Enemy
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Atherosclerosis and CVD Mechanism
2013 Ivor Cummins BE(Chem) MIEI
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Atherosclerosis and CVD Mechanism
Ingress of Lipoprotein Particles through Endothelium (inner wall)
The Disease Sequence:
TgChChCh
B100
2013 Ivor Cummins BE(Chem) MIEI
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Atherosclerosis and CVD Mechanism
Ingress of Lipoprotein Particles through Endothelium (inner wall)
Uptake of these by immune system Macrophage
The Disease Sequence:
+Macrophage
TgChChCh
B100
2013 Ivor Cummins BE(Chem) MIEI
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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:
+ ChCh Ch
Macrophage
=FOAM CELL
TgChChCh
B100
2013 Ivor Cummins BE(Chem) MIEI
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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:
+ ChCh Ch
Macrophage
=FOAM CELL
TgChChCh
B100
2013 Ivor Cummins BE(Chem) MIEI
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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:
+ ChCh Ch
Macrophage
=FOAM CELL
The Million Dollar Question: What mediates this inflammatory process?
TgChChCh
B100
2013 Ivor Cummins BE(Chem) MIEI End
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2013 Ivor Cummins BE(Chem) MIEI
4. How the Cholesterol Processing System Works - High Level
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The Lipoprotein Particles – Boats for CargoTrigylceride/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
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2013 Ivor Cummins BE(Chem) MIEI
4. Lipoprotein Type 1 of 3 :
The CHYLOMICRON(for Dietary Fat and Cholesterol
Transport…)
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
TgCh
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
TgCh
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
TgCh
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO REMNANT
Ch TgTg TgE
Ch
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO REMNANT
Ch TgTg TgE
Ch
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO REMNANT
Ch TgTg TgELDLR
SR-B1
Ch
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO REMNANT
Ch TgTg TgELDLR
SR-B1
Ch
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO REMNANT
Ch TgTg TgE
Ch
Ch
Ch
LDLR
SR-B1
Ch
Tg Tg Tg
2013 Ivor Cummins BE(Chem) MIEI
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CHYLOMICRON: for dietary Fat and Chol
DietaryFats
Triglycerides
Cholesterol
E
C II
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
CHYLOMICRONB48
TgTgChTgTgTg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
B48CHYLO 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
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2013 Ivor Cummins BE(Chem) MIEI
4. Lipoprotein Type 2 of 3 :
The LDL Species (Created by your Liver, for Triglyceride
and Cholesterol Delivery…)
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VLDL, IDL,LDL…..and Small Dense LDL
LDLR
SR-B1Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
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VLDL, IDL,LDL…..and Small Dense LDL
LDLR
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
SR-B1Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
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VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
SR-B1Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
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VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
SR-B1Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
![Page 47: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/47.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
SR-B1
HL
Ch
Ch
Ch
Tg
2013 Ivor Cummins BE(Chem) MIEI
![Page 48: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/48.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
HL
Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
Tg
![Page 49: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/49.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
HL
Ch
Ch
Ch
Ch
ChTo tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
Tg
![Page 50: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/50.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
HL
Ch
Ch
Ch
2013 Ivor Cummins BE(Chem) MIEI
Ch
Tg
Ch
To tissues and cells
![Page 51: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/51.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
TgChChCh
B100 LDLSD
HL
HL
Ch
Ch
Ch
TgChChCh
B100 LDLOX
2013 Ivor Cummins BE(Chem) MIEI
Tg
Ch
Ch
To tissues and cells
Gluc
![Page 52: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/52.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
TgChChCh
B100 LDLSD
HL
Ch
Ch
Ch
TgChChCh
B100 LDLOX
2013 Ivor Cummins BE(Chem) MIEI
Tg
Ch
Ch
To tissues and cells
HL
Gluc
![Page 53: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/53.jpg)
VLDL, IDL,LDL…..and Small Dense LDL
C II
LDLR
C II
LPL
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
IDLTgTg
TgChCh
ChCh
E
B100
TgChChCh
B100 LDL
SR-B1
TgChChCh
B100 LDLSD
HL
Ch
Ch
Ch
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
TgChChCh
B100 LDLOX
2013 Ivor Cummins BE(Chem) MIEI
Tg
Ch
To tissues and cellsCh
HL
Gluc
End
![Page 54: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/54.jpg)
2013 Ivor Cummins BE(Chem) MIEI
4. Lipoprotein Type 3 of 3 :
The HDL Species (For Cholesterol Management, and a few
other important things…)
![Page 55: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/55.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
2013 Ivor Cummins BE(Chem) MIEI
![Page 56: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/56.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
Ch Adrenal Cortex and Gonads
2013 Ivor Cummins BE(Chem) MIEI
![Page 57: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/57.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
Ch Adrenal Cortex and Gonads
Ch
From tissues and cells
ABC A1ABC G1
LCAT
2013 Ivor Cummins BE(Chem) MIEI
![Page 58: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/58.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
Ch Adrenal Cortex and Gonads
ChABC A1ABC G1
LCAT
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
ABC A1ABC G1
From tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
LCAT
![Page 59: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/59.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
Ch
A HDLTg
ECh
ABC A1ABC G1
LCAT
LCAT
ABC A1ABC G1
Ch Adrenal Cortex and Gonads
From tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
+ Antioxidant Action….!
![Page 60: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/60.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
Ch Adrenal Cortex and Gonads
ChABC A1ABC G1
LCAT
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
ABC A1ABC G1
From tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
LCAT
+ Antioxidant Action….!
![Page 61: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/61.jpg)
HDL…..and Reverse Cholesterol Transport
LDLR
VLDLTg
Tg
Tg
Tg
Tg
Tg
Tg
TgChCh
ChCh
E
C II
B100
TgChChCh
B100 LDL
SR-B1Ch
Ch
Ch
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
Ch
A HDLTg
ECh
ABC A1ABC G1
LCAT
LCAT
Ch
Ch
Tg
Tg
ABC A1ABC G1
Ch Adrenal Cortex and Gonads
From tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
+ Antioxidant Action….!
IDLTgTg
TgChCh
ChCh
E
B100
Ch
Tg
End
![Page 62: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/62.jpg)
2013 Ivor Cummins BE(Chem) MIEI
5. The Risk Factors
![Page 63: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/63.jpg)
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
![Page 64: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/64.jpg)
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
![Page 65: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/65.jpg)
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
![Page 66: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/66.jpg)
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
![Page 67: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/67.jpg)
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
![Page 68: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/68.jpg)
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 CAUSEDEATH….
2013 Ivor Cummins BE(Chem) MIEI
Increasing Cholesterol
Incr
ease
d R
isk
![Page 69: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/69.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
2013 Ivor Cummins BE(Chem) MIEI
Increasing Cholesterol = lower risk
Key Takeaways:
Increasing Cholesterol
![Page 70: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/70.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
2013 Ivor Cummins BE(Chem) MIEI
Increasing Cholesterol = lower risk
Key Takeaways:
Increasing Cholesterol
Engineering Explanations for the mistake:
![Page 71: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/71.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
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:
![Page 72: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/72.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
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:
![Page 73: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/73.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
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:
![Page 74: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/74.jpg)
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 CAUSEDEATH….
Incr
ease
d R
isk
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
![Page 75: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/75.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 76: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/76.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 77: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/77.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 78: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/78.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 79: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/79.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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
![Page 80: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/80.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 81: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/81.jpg)
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
Ris
k o
f H
ear
t D
ise
ase
aft
er
4 Y
ear
s
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”)
![Page 82: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/82.jpg)
Key Predictors of Mortality
Ready for more of the REAL
Engineering?
2013 Ivor Cummins BE(Chem) MIEI
![Page 83: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/83.jpg)
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
![Page 84: The Cholesterol Conundrum: Final Cut](https://reader034.vdocuments.us/reader034/viewer/2022052522/54b5410f4a795907288b4594/html5/thumbnails/84.jpg)
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.
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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.
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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.
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Data taken from Table 2: Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in
Adults: The European Prospective Investigation into Cancer in NorfolkKay-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
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2013 Ivor Cummins BE(Chem) MIEI
6. The $1M Question –What Primarily Drives up the Risk Factors???
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Improving the Total Chol / HDL Ratio
Tot C
ho
lesterol/H
DL
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 onatherogenic dyslipidemia1–3Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams
Data adapted from from Jeff Volek Summary of:
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Improving the LDL / HDL Particle Ratio
Separate effects of reduced carbohydrate intake and weight loss onatherogenic dyslipidemia1–3Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams
Data adapted from from Jeff Volek Summary of:
Ap
o B
/ Ap
o A
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
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Improving the Serum Triglyceride Level
Trig Red
uctio
n
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 onatherogenic dyslipidemia1–3Ronald 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
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Improving LDL Particle DiameterLD
L Pa
rtic
le D
iam
eter
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 onatherogenic dyslipidemia1–3Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams
Data adapted from from Jeff Volek Summary of:
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Improving HDL LevelsH
DL
“go
od
” C
ho
l
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 onatherogenic dyslipidemia1–3Ronald M Krauss, Patricia J Blanche, Robin S Rawlings, Harriett S Fernstrom, and Paul T Williams
Data adapted from from Jeff Volek Summary of:
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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
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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. NutrMetab (Lond) 2008, 5(36).
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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.
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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.
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So, Driving Risk Factors: Where are you?Disease Risk
MarkerHigh CarbLow Fat
Low Carb /High Fat*
Is Lean / FitKcal Control / active
Carb Tolerant(~30% of people?)
Is Not Lean / Is Not FitHigh Kcal / Sedentary
Carb Intolerant(~70% of people?)
Enables:Lean / Fit
Kcal Control / ActiveHealth and Wellbeing
Visceral Fat: Waist+
HDL
Tot Chol / HDL
Serum Glucose
Serum Insulin
Blood Pressure
Serum Triglyceride
Inflammationmarkers various
LDL **
* Following Metabolic Adaptation period of 3 weeks to 2 months
** Not a primary marker, particularly requires analysis of other factors to interpret2013 Ivor Cummins BE(Chem) MIEI
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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
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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
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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
CExpt
35
530
230
Ferritin
>1.00mmol
/L
< 200approx
<4.0
<35approx
< 1.5mmol
/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…
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N=1 Continued….
Weight
81kg
95
5k run time
<24min
28
Waist
<32”
35
Sys BP
125
145
Dia BP
75
95
CExpt
Ideal ~82Kg
Ideal 32”
<80mmHg
<130mmHg
Avg of 20+ readings from same Equipment2013 Ivor Cummins BE(Chem) MIEI
Old Ivor, watching the fat…..duh! New Ivor, keeping the carb down…
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2013 Ivor Cummins BE(Chem) MIEI
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2013 Ivor Cummins BE(Chem) MIEI
Human Evolution, low Insulin Regime for ~1 Million Years to 1970….
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2013 Ivor Cummins BE(Chem) MIEI
Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
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2013 Ivor Cummins BE(Chem) MIEI
Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
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2013 Ivor Cummins BE(Chem) MIEI
Discussion / Questions
Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”
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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
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BACKUP
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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
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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
CardiovascularDeath
Incr
ease
d R
isk
Incr
ease
d R
isk
Ischemic HeartDisease Death
2013 Ivor Cummins BE(Chem) MIEI
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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
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VLDL to LDL SummaryVLDL 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
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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
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Why are we in this room today- How does this come about?
Academic /Educational History
Problem SolvingExperience / Aptitude
2013 Ivor Cummins BE(Chem) MIEI
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