the cholesterol conundrum draft
Post on 21-Oct-2014
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A draft of another seminar I've prepared on a key topic - the video will follow, like/follow this and I'll make sure you get to have a look! (note: the slides without the narrative are in fairness limited in value, but might pique the interest)TRANSCRIPT
The Cholesterol Conundrum
What does the Latest Science Say?
Ivor Cummins BE (Chem)
March 21st 2014
2013 Ivor Cummins BE(Chem) MIEI
Why are we in this room today- How does this come about?
Academic /Educational History
Problem SolvingExperience / Aptitude
2013 Ivor Cummins BE(Chem) MIEI
Quick Update from my last 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 sugar for the rest of the day?
• Looks like the Emperor’s suit is getting frayed…..
• Gloves off lads, better pour some money into the lobbying chest, and shut this thing down quick
2013 Ivor Cummins BE(Chem) MIEI
2013 Ivor Cummins BE(Chem) MIEI
1. The Key Molecules2. The Key Particles3. Our Common Enemy4. The Risk Factors5. How the Cholesterol Processing
System Works – High Level6. The $1M Question – What Drives up
the Risk Factors?
The Conundrum Content:
2013 Ivor Cummins BE(Chem) MIEI
1. The Key Molecules
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
2013 Ivor Cummins BE(Chem) MIEI
2. The Key Particles
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….
HDL is the so-called “GOOD Cholesterol”
LDL (from VLDL) is the so-called “BAD Cholesterol”
The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing
Chylomicron100 to 1000nm
sdLDL<25nm
VLDL is made in the liver to ferry Trigs and Chol…
Small Dense LDL is the real “BAD Cholesterol”
HDL5-15nm
LDL>26nm
VLDL30 to 80nm
2013 Ivor Cummins BE(Chem) MIEI
2013 Ivor Cummins BE(Chem) MIEI
And now, a word from our Sponsor…..
2013 Ivor Cummins BE(Chem) MIEI
3. Our Common Enemy
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
2013 Ivor Cummins BE(Chem) MIEI
4. The Risk Factors
Key Predictors of Mortality
– Dysfunctional Lipoprotein Status• LDL/HDL Ratio• Serum Triglyceride Levels• Small Dense LDL and associated LDL Particle COUNT
– Insulin Levels and Insulin Resistance Status– Blood Glucose Level and HbA1C– High Blood Pressure (generally driven by the
above scenarios)– Other markers of Systemic Inflammation
2013 Ivor Cummins BE(Chem) MIEI
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
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
Age Confounding is a serious issue
US Versus Other Geographies is an issue
Diagnosing via Total Cholesterol no longer supported by the science
ALL CAUSEDEATH….
Incr
ease
d R
isk
Key Takeaways:
Total Cholesterol effectively not considered any more by leading edge researchers
Economics / Hubris retain bad science
2013 Ivor Cummins BE(Chem) MIEI
LDL-C & HDL-C 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
LDL (the “Bad Cholesterol”)
HDL being adequate/higher is VERY important
The benefit of LDL being low………depends on the HDL status
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
LDL-C & HDL-C 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
LDL (the “Bad Cholesterol”)
HDL being adequate/higher is VERY important
The benefit of LDL being low………depends on the HDL status
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?
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
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 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.
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
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.
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
So Let’s look at how it all works, shall we?
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.
2013 Ivor Cummins BE(Chem) MIEI
4. How the Cholesterol Processing System Works - High Level
(Hope appreciate the artwork here, it took me a while!)
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….
HDL is the so-called “GOOD Cholesterol”
LDL (from VLDL) is the so-called “BAD Cholesterol”
The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing
Chylomicron100 to 1000nm
sdLDL<25nm
VLDL is made in the liver to ferry Trigs and Chol…
Small Dense LDL is the real “BAD Cholesterol”
HDL5-15nm
LDL>26nm
VLDL30 to 80nm
2013 Ivor Cummins BE(Chem) MIEI
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
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
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
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
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
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
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
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
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
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
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
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
HSLXXX
Tg
Tg
2013 Ivor Cummins BE(Chem) MIEI
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
HSLXXX
Tg
Tg
2013 Ivor Cummins BE(Chem) MIEI
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
HSLXXX
Ch
Tg
Tg
ChTo tissues and cells
2013 Ivor Cummins BE(Chem) MIEI
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
HSLXXX
Ch
To tissues and cells
Tg
Tg
Ch
2013 Ivor Cummins BE(Chem) MIEI
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
HSLXXX
Ch
Tg
Tg
TgCh
TgChChCh
B100 LDLOX
To tissues and cells2013 Ivor Cummins BE(Chem) MIEI
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
HSLXXX
Ch
Tg
Tg
TgCh
TgChChCh
B100 LDLOX
To tissues and cells2013 Ivor Cummins BE(Chem) MIEI
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
ChCh Ch
IMMUNE SYSTEM MACROPHAGE / FOAM CELL
HSLXXX
Ch
Tg
Tg
TgCh
TgChChCh
B100 LDLOX
To tissues and cells2013 Ivor Cummins BE(Chem) MIEI
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!)
Oxidised LDL reduces takeup by liver – and enhances takeup by macrophage – inflammation and the disease process is augmented
2013 Ivor Cummins BE(Chem) MIEI
HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1Ch
Ch
Ch
Ch
A HDLTg
E
2013 Ivor Cummins BE(Chem) MIEI
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
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
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
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
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 Agents….!
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 Agents….!
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
2013 Ivor Cummins BE(Chem) MIEI
6. The $1M Question –What Primarily Drives up the Risk Factors???
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:
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
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
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:
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:
Another Recent Trial
xxxxx.
ALL markers better with Low Carb regime – including all Inflammation
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
2013 Ivor Cummins BE(Chem) MIEI
For ref....
Another of Many….
ALL markers better with Low Carb regime – including all Inflammation
Only Low Carb enhances HDL, though low GI has a go (!)
Scientifically this appears to be a fundamental rule, but rigorously challenged?
Moderate
High
Metabolically
Compromised/obese
Athletes
Naturally lean
Overweight/obeseSlide from:Jeff Volek - The Many Facets of Keto-AdaptationGoogle the Youtube video of this – it’s superb
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
Blood Pressure
Visceral Fat
LDL **
* Following Metabolic Adaptation period of 3 weeks to 2 months
** Not a primary marker, particularly requires analysis of other factors to interpret
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)
THE CRITICAL BIOCHEMISTRY OF VITAMIN D
• Content in this draft slidepack for latest science on 25 Hydroxy Vitamin D and related mortality statistics will follow …..