The Cholesterol Conundrum: Final Cut

The Cholesterol Conundrum
What does the Latest Science Say?
Ivor Cummins BE (Chem)
May 19th 2014
2013 Ivor Cummins BE(Chem) MIEI

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?

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:

1. The Key Molecules

Cholesterol and Triglyceride
• Cholesterol is a Sterol Molecule that is used to build
cells, hormones and other core physiological elements
Cholesterol – for Life Itself

• 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

• Triglyceride (aka Triacylglycerol) is a form of fat
Trigylceride – for Energy

• 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

• Is also synthesized by the body (neolipogenisis) for
various reasons
• Can be good or bad: depends on source, location and
quantity….

2. The Key Particles

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….

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
 The Chylomicron is the big one, created to ferry
dietary fat and cholesterol, for energy and healing
Chylomicron

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
Chylomicron
 VLDL is made in the liver to ferry Trigs and Chol…
VLDL

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
Chylomicron
LDLVLDL
 LDL (from VLDL) is the so-called “BAD Cholesterol”

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
Chylomicron sdLDL
LDLVLDL
 Oxidized LDL is the real “BAD Cholesterol”

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
Chylomicron sdLDL
HDLLDLVLDL
 HDL is the so-called “GOOD Cholesterol”

And now, a word from
our “Sponsor”…..

And now, a word from
our “Sponsor”…..
3. The Common Enemy

Atherosclerosis and CVD Mechanism

 Ingress of Lipoprotein Particles through Endothelium (inner wall)
The Disease Sequence:
TgCh
ChCh
B100

 Uptake of these by immune system Macrophage
+
Macrophage
TgCh
ChCh
B100

 Subsequent transformation into “Foam Cells” and buildup of Plaque
+ Ch
Ch Ch
Macrophage
=
FOAM CELL
TgCh
ChCh
B100

 Ultimately a decline in vascular health, then breakouts, blockages…..
+ Ch
Ch Ch
Macrophage
=
FOAM CELL
TgCh
ChCh
B100

 Ultimately a decline in vascular health, then breakouts, blockages…..
+ 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

4. How the Cholesterol
Processing System
Works - High Level

Trigylceride/
Cholesterol
An Apo-
Lipoprotein
Chylomicron sdLDL
HDLLDLVLDL
 HDL is the so-called “GOOD Cholesterol”
1 2 3

4. Lipoprotein Type 1 of 3 :
The CHYLOMICRON
(for Dietary Fat and Cholesterol
Transport…)

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

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

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

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

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

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
SYSTEM MANUAL:
“Important: For Correct Operation,
Insulin must be kept low”
End

The LDL Species
(Created by your Liver, for Triglyceride
and Cholesterol Delivery…)

VLDL, IDL,LDL…..and Small Dense LDL
LDLR
SR-B1
Ch
Ch
Ch

LDLR
VLDL
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Tg
Ch
Ch
Ch
Ch
E
C II
B100
SR-B1
Ch
Ch
Ch

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

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

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

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
Tg

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
Tg

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
Tg
Ch
To tissues
and cells

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
Tg
Ch
Ch
To tissues
and cells
Gluc

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
Tg
Ch
Ch
To tissues
and cells
HL
Gluc

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
Tg
Ch
To tissues
and cellsCh
HL
Gluc
End

The HDL Species
(For Cholesterol Management, and a few
other important things…)

HDL…..and Reverse Cholesterol Transport
LDLR
SR-B1
Ch
Ch
Ch
Ch
A
HDL
Tg
E

LDLR
SR-B1
Ch
Ch
Ch
Ch
A
HDL
Tg
E
Ch Adrenal Cortex and
Gonads

LDLR
SR-B1
Ch
Ch
Ch
Ch
A
HDL
Tg
E
Gonads
Ch
From tissues and cells
ABC A1
ABC G1
LCAT

LDLR
SR-B1
Ch
Ch
Ch
Ch
A
HDL
Tg
E
Gonads
Ch
ABC A1
ABC G1
LCAT
Ch
Ch Ch
IMMUNE SYSTEM
ABC A1
ABC G1
LCAT

LDLR
SR-B1
Ch
Ch
Ch
Ch
Ch Ch
IMMUNE SYSTEM
Ch
A
HDL
Tg
E
Ch
ABC A1
ABC G1
LCAT
LCAT
ABC A1
ABC G1
Gonads
+ Antioxidant
Action….!

LDLR
SR-B1
Ch
Ch
Ch
Ch
A
HDL
Tg
E
Gonads
Ch
ABC A1
ABC G1
LCAT
Ch
Ch Ch
IMMUNE SYSTEM
ABC A1
ABC G1
LCAT
+ Antioxidant
Action….!

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
Ch
A
HDL
Tg
E
Ch
ABC A1
ABC G1
LCAT
LCAT
Ch
Ch
Tg
Tg
ABC A1
ABC G1
Gonads
+ Antioxidant
Action….!
IDL
TgTg
Tg
Ch
Ch
Ch
Ch
E
B100
Ch
Tg
End

5. The Risk Factors

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

–High Blood Pressure
• generally driven by the same root causes that drive the above
–Other markers of Systemic Inflammation
• GGT, CRP, Serum Ferritin, etc

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….
Increasing Cholesterol
IncreasedRisk

ALL CAUSE
DEATH….
IncreasedRisk
 Increasing Cholesterol = lower risk
Key Takeaways:

ALL CAUSE
DEATH….
IncreasedRisk
Key Takeaways:
Engineering Explanations for the mistake:

ALL CAUSE
DEATH….
IncreasedRisk
 Age Confounding was a serious issue
Key Takeaways:

ALL CAUSE
DEATH….
IncreasedRisk
Key Takeaways:
 Non-Representative populations,
inclusion of Hypercholesteremia cases

ALL CAUSE
DEATH….
IncreasedRisk
 Endemic Research Bias
Key Takeaways:

 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

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
Decreasing HDL
(the “Good
Cholesterol”)

2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
 HDL being adequate/higher is VERY important
Decreasing HDL
(the “Good
Cholesterol”)

2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
 The benefit of LDL being low………totally depends on the HDL status
Decreasing HDL
(the “Good
Cholesterol”)

2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
 Risk is determined primarily by the RATIO of these parameters
Decreasing HDL
(the “Good
Cholesterol”)

2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
 Diagnosing via LDL is minimally useful in the face of the current science
Decreasing HDL
(the “Good
Cholesterol”)

Decreasing HDL
(the “Good
Cholesterol”)
2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
XXX
Guess Who?

2.58 4.13 5.68
HDL=0.65
HDL = 1.16
HDL = 1.68
HDL = 2.20
XXX
And this Guy?
Decreasing HDL
(the “Good
Cholesterol”)

Ready for more of
the REAL
Engineering?

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:

SERUM INSULIN as a Predictive Factor
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:
Data from the Quebec Study Cardiovascular Study:
Despres JP, et al. N Engl J Med. 1996;334:952-957.

SERUM INSULIN and LDL Particle Count
Data from the Quebec Study Cardiovascular Study:
 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:
Lamarche B, et al. Circulation. 1997;95:69-75.

Small Dense LDL as a Predictive Factor
 Small Dense LDL and associated LDL Particle Count are Key
 These, along with Insulin / Insulin Resistance Status, are Master Markers
Key Takeaways:
Reprinted from St-Pierre AC, et al. Circulation. 2001;104:
2295–2299, with permission from Wolters Kluwer Health.

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
 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:

6. The $1M Question –
What Primarily
Drives up the Risk
Factors???

Improving the Total Chol / HDL RatioTotCholesterol/HDL
 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:

Improving the LDL / HDL Particle Ratio
ApoB/ApoA
 LDL / HDL key (here we have
even better metric – the
particle COUNT ratio)
 Low Carb far exceeds
benefits of low fat regime –
even with NO dieting
period, Low Fat regime fails

Improving the Serum Triglyceride Level
TrigReduction
 Serum Triglyceride –
important to keep this down
benefits of low fat regime –
even with NO dieting

Improving LDL Particle DiameterLDLParticleDiameter
 LDL Particle Diameter is a
serious metric
benefits of low fat regime,
especially if you don’t diet
period, Low Fat regime
struggles

Improving HDL LevelsHDL“good”Chol
 HDL – the higher the better
benefits of low fat regime,
again even with no dieting

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?
HIGH CARB, LOW FATHIGH FAT, VERY LOW CARB

(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).

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)
Higher % Carb in Diet
Krauss RM: Atherogenic lipoprotein phenotype and diet-gene
interactions. J Nutr 2001, 131(2):340S-3S.

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)
 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.

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

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

Evidence-Based Science Comeback
 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

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
Old Ivor, watching the fat…..duh! New Ivor, keeping the carb down…

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
Old Ivor, watching the fat…..duh! New Ivor, keeping the carb down…

Human Evolution, low Insulin Regime for ~1 Million Years to 1970….

Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”

Discussion / Questions
Human Evolution, low Insulin Regime for ~1 Million Years to 1970…. High Carb “Science”

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….

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)

Cardiovascular
Death
IncreasedRisk
IncreasedRisk
Ischemic Heart
Disease Death

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….

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

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!
HDL’s other key role is in moderating oxidation in
general, and of LDL specifically

Why are we in this room today
- How does this come about?
Academic /
Educational History
Problem Solving
Experience / Aptitude

The Cholesterol Conundrum: Final Cut

The Cholesterol Conundrum: Final Cut

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