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 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:


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



• 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 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 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 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






• Triglyceride (aka Triacylglycerol) is a form of fat

Trigylceride – for Energy





• Triglyceride (aka Triacylglycerol) is a form of fat• Is three Fatty Acids on a glycerol (sugar-like) backbone






• 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






• 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






• 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….




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….



An Apo-Lipoprotein


The Chylomicron is the big one, created to ferry dietary fat and cholesterol, for energy and healing

Chylomicron



An Apo-Lipoprotein



Chylomicron

VLDL is made in the liver to ferry Trigs and Chol…

VLDL



An Apo-Lipoprotein



Chylomicron


LDLVLDL


LDL (from VLDL) is the so-called “BAD Cholesterol”


An Apo-Lipoprotein



Chylomicron sdLDL


LDLVLDL



Oxidized LDL is the real “BAD 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:

TgChChCh

B100




Uptake of these by immune system Macrophage


+Macrophage

TgChChCh

B100





Subsequent transformation into “Foam Cells” and buildup of Plaque


+ ChCh Ch

Macrophage

=FOAM CELL

TgChChCh

B100






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


+ ChCh Ch

Macrophage

=FOAM CELL

TgChChCh

B100






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


+ ChCh Ch

Macrophage

=FOAM CELL

The Million Dollar Question: What mediates this inflammatory process?

TgChChCh

B100

2013 Ivor Cummins BE(Chem) MIEI End


4. How the Cholesterol Processing System Works - High Level


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

DietaryFats

Triglycerides

Cholesterol

CHYLOMICRONB48

TgTgChTgTgTg

Tg

Tg

Tg

Tg

Tg

Tg

Tg

Tg

TgCh

Tg Tg Tg



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



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



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



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



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



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



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



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


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-B1Ch

Ch

Ch



LDLR

VLDLTg

Tg

Tg

Tg

Tg

Tg

Tg

TgChCh

ChCh

E

C II

B100

SR-B1Ch

Ch

Ch



C II

LDLR

C II

LPL

VLDLTg

Tg

Tg

Tg

Tg

Tg

Tg

TgChCh

ChCh

E

C II

B100

SR-B1Ch

Ch

Ch



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



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



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


Tg


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


Tg


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

Tg

Ch

To tissues and cells


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


Tg

Ch

Ch


Gluc


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


Tg

Ch

Ch


HL

Gluc


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


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-B1Ch

Ch

Ch

Ch

A HDLTg

E



LDLR

SR-B1Ch

Ch

Ch

Ch

A HDLTg

E

Ch Adrenal Cortex and Gonads



LDLR

SR-B1Ch

Ch

Ch

Ch

A HDLTg

E


Ch

From tissues and cells

ABC A1ABC G1

LCAT



LDLR

SR-B1Ch

Ch

Ch

Ch

A HDLTg

E


ChABC A1ABC G1

LCAT

ChCh Ch


ABC A1ABC G1



LCAT


LDLR

SR-B1Ch

Ch

Ch

ChCh Ch


Ch

A HDLTg

ECh

ABC A1ABC G1

LCAT

LCAT

ABC A1ABC G1




+ Antioxidant Action….!


LDLR

SR-B1Ch

Ch

Ch

Ch

A HDLTg

E


ChABC A1ABC G1

LCAT

ChCh Ch


ABC A1ABC G1



LCAT



LDLR

VLDLTg

Tg

Tg

Tg

Tg

Tg

Tg

TgChCh

ChCh

E

C II

B100

TgChChCh

B100 LDL

SR-B1Ch

Ch

Ch

ChCh Ch


Ch

A HDLTg

ECh

ABC A1ABC G1

LCAT

LCAT

Ch

Ch

Tg

Tg

ABC A1ABC G1





IDLTgTg

TgChCh

ChCh

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 CAUSEDEATH….


Increasing Cholesterol

Incr

ease

d R

isk





ALL CAUSEDEATH….

Incr

ease

d R

isk


Increasing Cholesterol = lower risk

Key Takeaways:






ALL CAUSEDEATH….

Incr

ease

d R

isk



Key Takeaways:


Engineering Explanations for the mistake:





ALL CAUSEDEATH….

Incr

ease

d R

isk



Age Confounding was a serious issue

Key Takeaways:







ALL CAUSEDEATH….

Incr

ease

d R

isk




Key Takeaways:

Non-Representative populations, inclusion of Hypercholesteremia cases







ALL CAUSEDEATH….

Incr

ease

d R

isk




Endemic Research Bias

Key Takeaways:










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





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


Decreasing HDL(the “Good Cholesterol”)



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








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


The benefit of LDL being low………totally depends on the HDL status








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



Risk is determined primarily by the RATIO of these parameters








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



Diagnosing via LDL is minimally useful in the face of the current science










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






XXX


Guess Who?





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






XXX


And this Guy?





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

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:


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 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


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 Ratio

Tot C

ho

lesterol/H

DL


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



Ap

o B

/ Ap

o A

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

Even during the starvation period, Low Fat regime fails

Improving the Serum Triglyceride Level

Trig Red

uctio

n


Serum Triglyceride –important to keep this down





Low Carb far exceeds benefits of low fat regime –even with NO dieting

Improving LDL Particle DiameterLD

L Pa

rtic

le D

iam

eter


LDL Particle Diameter is a serious metric


Low Carb far exceeds benefits of low fat regime, especially if you don’t diet

Even during the starvation period, Low Fat regime struggles



Improving HDL LevelsH

DL

“go

od

” C

ho

l


HDL – the higher the better


Low Carb far exceeds 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. NutrMetab (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

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

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

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


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

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…



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


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….


BACKUP

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)






CardiovascularDeath

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Ischemic HeartDisease 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 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


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 SolvingExperience / Aptitude


Health & Medicine

The Cholesterol Conundrum: Final Cut