“Good” Cholesterol?

EUROPEAN WAPF LONDON 2014

“Good” Cholesterol?

“Bad” Cholesterol?

Spot the Difference


An Infamous Hypothesis

1961 Time Magazine

Dr Ancel Keys asserted that

saturated fats and cholesterol were the

causes of CVD


An Alternative Hypothesis

Professor John YudkinPublished in 1972

Sugar is a leading cause of diabetes and heart disease

Hypothesis became Dogma

Friday January 14th 1977 “Dietary Goals for the United States”

Senate Select Committee on

Nutrition and Human Needs Senator George McGovern

Carbohydrates arePlentiful and Cheaper

for theGrowing Population


OBESITY trend kicks upward withEat more carbs less fat policy

Introduction of HFCS (Fructose Syrup)Low Fat (High Sugar) Processed Foods


Keys’ - CVD Deaths & Dietary Fat

Dr Uffe Ravnskov “The Cholesterol Myths” ISBN 0-96708-970-0

Data SelectedTo fit Hypothesis?

Data Available to Keys

Yerushalmy and Hilleboe 1957 NY State Journal of Medicine

Violent Deaths StudyRegardless of age group they found

no association between degree of

atherosclerosis & blood cholesterolPathologist Kurt Lande & Biochemist Warren SperryArch. Pathol. Vol. 22,

301-312, 1936Department of Forensic Medicine New York University

Cholesterol & Athero-sclerosis

Solberg L A et al

Lab Invest

1985 Dec; 53(6):648-55.

PMID: 4068669

50 middle-aged menPost-Mortem Study

There is no correlationbetween ‘cholesterol’ and atherosclerosis


Is your language a risk factor ?

80% of Americans who have had heart attacks are

‘English’ Speaking --------------------

Statistical Associationis NOT

Proof of Causation

EUROPEAN CONFERENCE WAPF LONDON 2014

CholesterolWhat is it?

What does it do?Glyn Wainwright

www.lizscript.co.uk/glyn (web pages)@Cholesterol_OK (on twitter)

The Anecdotal Biochemist (on tumblr)

Chole = LiverSterol = Steroid Alcohol –OH

Water soluble & Fat soluble


"Let's do the good cholesterol, bad cholesterol bit.”Cartoonist: Tom Cheney New Yorker


“Good” Cholesterol?

“Bad” Cholesterol?

Spot the Difference

A Misleading and Unscientific ‘Marketing Concept’


• Steroid Hormones & Vitamin D•Cell Wall: Integrity, Form & Function•Fat soluble nutrients (Blood Lipids)•Packaging for Neuro-transmitters•Neural Insulation & Protection•Anti-oxidant

Always Good, Never Bad Cholesterol is VITAL

Cholesterol’s Roles


Other

Protein Water

Lipids

What are we made of ?

Liver makes

Cholesterol3.5 g per day

Brain5% of body

25% of body Cholesterol

Includes <1% Carbohydrate

4:1 Molecular RatioFat & Cholesterol


Cell Lipid Membranes4:1 Fat : Cholesterol


Cell Lipids Nutrition and Signalling

Requires20%

MolecularCholesterol


Inhibition of cholesterol biosynthesis impairsInsulin secretion and voltage-gated calcium channel

function in pancreatic beta-cells (Xia et al. Endocrinology 2008)Lowering Cholesterol

- Inhibits Insulin Secretion- Leading to T2 Diabetes

Insulin and Beta Cells• 10% depletion of Cholesterol

inhibits insulin release from pancreatic beta cells - Xia et al in late 2008

• Jupiter Trial – increased Type II diabetes in the statin group

• 6 out of 7 Clinical Trials reported Poorer Glucose Control

• Statin use has also been separately associated with raised fasting plasma glucose


Cholesterol Lowering Therapies & Membrane CholesterolWainwright G Mascitelli L & Goldstein M R

Archives of Medical Science Vol. 5 Issue 3 2009

“What ‘s the effect of Cholesterol Loweringon our cell-membranes?”


Cell Lipids, Nutrition and Signalling

Lowering Membrane CholesterolFrom 20% molecular to 18%Shuts down cellular activity

In all tissue types


Neurons

Lowering Cholesterol damages- Myelin Protective Sheathing

-Neurotransmitter Vesicles- Synaptic Functions

• Highest cholesterol content in brain is found in myelin

• Experiments with genetically engineered mice show that myelination is severely perturbed if cholesterol is unavailable*

* Saher et al., Nat Neurosci, 8(4), 2005

Myelin Sheath

Cholesterol in Myelination & Multiple Sclerosis

• Klopfleisch et al 2008 • Statins & Oligodendrocytes• Statins and Multiple Sclerosis• Statins prevent myelin production• Anti-inflammatory effect of statins• Two competing ideas courting disaster?• Short term - stoppage of de-myelination?• Long term - stoppage of re-myelination?

Low Cholesterolmeans

No Myelin Repairs

Brain Cholesterol

• Antioxidant• Electrical insulator (ion leaks)• Structural scaffold (myelin)• Neural Membrane Rafts. • Neurotransmitter wrapper • Synapse Formation (Pfrieger)

Lower Cholesterol =Leaky Membranes

Activation Failure & ‘Runaway Burn’

Cholesterol stops LeakagesThomas H. Haines,

"Do Sterols Reduce Proton and Sodium Leaks through Lipid Bilayers?“

Progress in Lipid Research (2001)Vol. 40, pp. 299-324

Memory and Neural Cholesterol

1997-2003 - Frank W Pfrieger et al.

• Synaptogenesis - depends on cholesterol• additional cholesterol required from Glia cells• 10% drop in cholesterol stops synaptogenesis• New cholesterol required for neuron pores

Cholesterol – Memories are made of this!

Low Cholesterol and Aggression Cholesterol content was measured

in cortical and sub-cortical tissue of brains.

Violent suicides were found to have lower grey matter cholesterol

content overall compared with non-violent suicides and controls

Lalovic A et al. Cholesterol content in brains of suicide completers

Int J Neuropsychopharmacol 2007;10:159-66

Low CNS Cholesterol levelsare associated withViolent Behaviours

Neuro-Muscular Junctions Cholesterol Dependent

• neuro-muscular ADRs• myasthenia gravis • amyotrophic lateral sclerosis • Lrp4-Agrin Complex binds MuSK• Pre- and post- synaptic exo & endo cytoses

Low Cholesterol - Aches, Pains and

Mobility Problems


Cholesterol & Bone Remodelling Statin Studies are in conflict on bone benefits Osteoclasts - removal of bone mineral matrix Statins reduce bone loss by osteoclasts Osteoblasts – deposition of bone mineral matrix Statins reduce bone repairs by osteoblasts High serum levels of cholesterol protect post-

menopausal women from osteoporosis

Bone Maintenance stopswith low Cholesterol

Membrane Cholesterol & Immunology

The exocytosis of apolipoprotein B, VLDL and LDL secretions in skin protects against Staphylococcus aureus infection

Bacterial ‘quorum sensing’ receptors disabled Epidemiological associations have been made

between statins and MRSA

Low cholesterol impairs natural skin

protection

Lipids - Fats and Cholesterol

What are blood lipids and lipoproteins?

LDL (Bad?) HDL (Good?)

Why are abnormal lipid levelsassociated with poor health?


Blood Lipids in Circulation


Characterised by:•Protein labels •Droplet size

Blood Lipid Transport

• LDL Lipids carry vital fats & fat-soluble nutrients for the feeding and maintenance of all organs especially the brain

• AGE sugar-damages LDL protein label• Undelivered LDL fats backed-up in the blood• Organs starved of vital fats & fat-soluble nutrients


N.B. Fats are liquid at

body temperature!

Lipid Parcel Delivery


2014 Nobel Prize: James E. Rothman, Randy W. Schekman and Thomas C. Südhof.

Fatty Nutrient Cycles

Receptor Mediated LDL Supply


•What can go wrong?

Sugar-Damaged LDL Labels


Fructose & DementiaRaised LDL & Lower HDL


Healthy Outcomes Unhealthy Outcomes

Sugar-Damaged Lipid Labels?

High Cholesterol Paradox

No Yes

• Cells Function• Fat-Nourished Organs• Good HDL/LDL• Lower Risk of Disease• Longevity

• Cells Fail• Fat-Starved Organs• Raised LDL - Low HDL• High Risk of Disease (T2D, CVD, Dementia)

Seneff, Wainwright and Mascitelli

SUGAR-DAMAGED LIPIDS

Ending 40 years of confusion AGE - Advanced Glycation Endproducts


Sugar damages the

Lipid-Proteins controlling the

Blood Lipids (LDL and HDL)

AGEs – Sugar-Damaged Proteins

• Diabetes & Insulin Resistance – AGE receptors• Elevated Blood Pressure – Vascular AGE elastins• Infection – Immune cell AGE & Lipid Deficiencies• CVD & CHD, infection, vascular and blood cell AGEs• Skin Appearance & Elasticity• Joints and inflammations - the immune response• Micro-vascular inflammation damage• Central Visceral Fat Cell Obesity – LDL AGEs


AGE & RAGE in the Body


• Decades of Excess Sugars• All tissues affected by AGE• Collagens, Keratins & Elastins• Damaged - Receptors/Signals• RAGE- Inflammation & Repair • Critical Functions Damaged?

AGE Sugar-Damage Chemistry

• The Browning Reaction in Cooking • Excess Sugars & Oxidative Stresses• Maillard Reaction• Fructose/Glucose Aldehyde • Attaches via Amino group NH2 • Lysine is a typical target


Fructose 7 x more reactive than Glucose

‘Is the metabolic syndrome caused by a high fructose, and

relatively low fat, low cholesterol diet?’

Seneff S., Wainwright G., and Mascitelli L.

DOI: 10.5114/aoms.2011.20598Archives of Medical Science Vol.

7 2011


Sugar-Damaged Proteins

Fructose & Metabolic Syndrome • Elevated blood Fats and LDL

cholesterol• Lower levels of HDL cholesterol• Central Obesity (Visceral Fat)• Insulin Resistance – Raised Glucose• Elevated Blood Pressure• Increased Risks


• Type 2 Diabetes -T2D

• Coronary Heart Disease - CHD • Cardio-Vascular Disease - CVD

‘Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet’

Seneff S., Wainwright G., and Mascitelli L.

DOI:10.1016/j.ejim.2010.12.017European Journal of Internal

Medicine 22 (2011)

Sugar-Damaged Proteins


Fructose Damage & Dementia

• The amyloid-β is not causal - drug-induced suppression of its synthesis led to further cognitive decline

• Mitochondrial dysfunction and brain insulin resistance are early indicators of Alzheimer's disease

• AGEs block LDL delivery of fats and cholesterol vital to Astrocytes & therefore to Neurons (Myelin)

• Cerebrospinal fluid of Alzheimer's brains is deficient in fats and cholesterol

• Dietary modification – fewer processed carbohydrates and relatively more fats and cholesterol is likely to be protective against Alzheimer's disease


A Sugar-Damage Protein Blood Test?• HbA1C sugar-damage in blood

Haemoglobin damage is linked to LDL damage

• 60 or more - Rising Health Risks (diabetes)

• 49 to 60 - Well Managed/At Risk?• 48 to 30 - Healthy? (Lower risks) • Counts damaged molecules per 1,000

(mmol/mol)


Summary All cholesterol molecules are valuable and vital Blocking cholesterol synthesis is damaging Sugar-damaged LDL build up in the blood Poor lipid profiles are improved by lower sugar Low fat processed foods are often sugar loaded Fructose is 7x more damaging than glucose CVD, Obesity, Dementia mature-onset diseases

are signs of sugar-damaged proteins (AGE) HbA1c testing can be surrogate for LDL damage


What is Cholesterol Sulphate ?

Dr Stephanie Seneff’s question provoked an amazing biochemical adventure involving thermodynamics,

volcanic vents, sewage research, and some fascinating insights into a world of oxygen

transports, the placenta, energy stores and sunbathing

‘Vestigial Sulphur Respiration’ still in use within us?The subject of the next session from Dr Seneff


A well timed silence hath more eloquence

than speech

Martin Tupper 19th Century Writer Inventor


Arrest Decline & Await Repairs• Reduce use of Carbohydrates low <100g per day• Get Energy from Fats not from Carbohydrates• Read Food Labels – per 100g of which Carbohydrates• Avoid the Hypoglycaemic bounce

• Diabetics on Medication • must take medical advice

• Hypoglycaemic risk on some medicines


What to Eat

Low Sugar animal derived foods:

Meat, Fish, Eggs, Full-Fat Dairy, Cheese

Low Sugar/Low Starch plant foods:

Vegetables, Leaves, Beans, Nuts...


Budgets & Targets• Budget Pasta, Rice, Bread

(foods from grass seeds) Sweet Fruits & Sweet Starchy Vegetables (<100g /day)

• Avoid Refined Sugars, Confectionary Processed Foods & Low Fat Foods that may have High Fructose Corn Syrup added


75% Cocoa OK

“Good” Cholesterol?

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