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Spot the Difference. “Good” Cholesterol?. “Bad” Cholesterol?. 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 Yudkin Published in 1972

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slide1

Spot the Difference

“Good”

Cholesterol?

“Bad”

Cholesterol?

EUROPEAN WAPF LONDON 2014

slide2

An Infamous Hypothesis

  • 1961 Time Magazine
  • Dr Ancel Keys
  • asserted that
  • saturated fats and cholesterol were the causes of CVD

EUROPEAN WAPF LONDON 2014

slide3

An Alternative Hypothesis

Professor John Yudkin

Published in 1972

Sugar is a leading cause of diabetes and heart disease

EUROPEAN WAPF LONDON 2014

hypothesis became dogma
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 are

Plentiful and Cheaper

for the

Growing Population

slide5

OBESITY trend kicks upward with

Eat more carbs less fat policy

Introduction of HFCS (Fructose Syrup)

Low Fat (High Sugar) Processed Foods

EUROPEAN WAPF LONDON 2014

slide6

Keys’ - CVD Deaths & Dietary Fat

Data Selected

To fit Hypothesis?

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

EUROPEAN WAPF LONDON 2014

data available to keys
Data Available to Keys

Yerushalmy and Hilleboe 1957 NY State Journal of Medicine

violent deaths study
Violent Deaths Study

Regardless of age group they found

no association between degree of

atherosclerosis & blood cholesterol

Pathologist Kurt Lande & Biochemist Warren Sperry

Arch. Pathol. Vol. 22,

301-312, 1936

Department of Forensic Medicine

New York University

slide9

Cholesterol & Athero-sclerosis

50 middle-aged men

Post-Mortem Study

There is no correlation

between ‘cholesterol’

and atherosclerosis

Solberg L A et al

Lab Invest

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

PMID: 4068669

slide10

Is your language a risk factor ?

80% of Americans who

have had heart attacks are

‘English’ Speaking

--------------------

Statistical Association

is NOT

Proof of Causation

EUROPEAN WAPF LONDON 2014

cholesterol what is it what does it do

CholesterolWhat is it?What does it do?

Chole = Liver

Sterol = Steroid Alcohol –OH

Water soluble & Fat soluble

Glyn Wainwright

www.lizscript.co.uk/glyn (web pages)

@Cholesterol_OK (on twitter)

The Anecdotal Biochemist (on tumblr)

EUROPEAN CONFERENCE WAPF LONDON 2014

slide12

"Let's do the good cholesterol, bad cholesterol bit.”

Cartoonist: Tom Cheney New Yorker

EUROPEAN WAPF LONDON 2014

slide13

Spot the Difference

“Good”

Cholesterol?

“Bad”

Cholesterol?

A Misleading and Unscientific

‘Marketing Concept’

EUROPEAN WAPF LONDON 2014

slide14

Cholesterol’sRoles

  • 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

EUROPEAN WAPF LONDON 2014

liver makes cholesterol 3 5 g per day brain 5 of body 25 of body cholesterol

What are we made of ?

Includes <1% Carbohydrate

Other

Lipids

4:1 Molecular Ratio

Fat & Cholesterol

Liver

makes

Cholesterol

3.5 g per day

Brain

5% of body

25% of body Cholesterol

Water

Protein

EUROPEAN WAPF LONDON 2014

slide16

Cell Lipid Membranes

4:1 Fat : Cholesterol

EUROPEAN WAPF LONDON 2014

slide18

Cell Lipids Nutrition and Signalling

Requires

20% Molecular

Cholesterol

EUROPEAN WAPF LONDON 2014

slide19

Inhibition of cholesterol biosynthesis impairs

Insulin 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

EUROPEAN WAPF LONDON 2014

insulin and beta cells
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
slide21

“What ‘s the effect of

Cholesterol Lowering

on our cell-membranes?”

Cholesterol Lowering Therapies & Membrane Cholesterol

Wainwright G Mascitelli L & Goldstein M R

Archives of Medical Science

Vol. 5 Issue 3 2009

EUROPEAN WAPF LONDON 2014

slide22

Cell Lipids, Nutrition and Signalling

Lowering Membrane Cholesterol

From 20% molecular to 18%

Shuts down cellular activity

In all tissue types

EUROPEAN WAPF LONDON 2014

slide23

Neurons

Lowering Cholesterol damages

- Myelin Protective Sheathing

-Neurotransmitter Vesicles

- Synaptic Functions

EUROPEAN WAPF LONDON 2014

myelin sheath
Myelin Sheath
  • 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

cholesterol in myelination multiple sclerosis
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 Cholesterol

means

No Myelin Repairs

brain cholesterol
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
Lower Cholesterol =Leaky Membranes Activation Failure & ‘Runaway Burn’

Cholesterol stops Leakages

Thomas 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
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
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 levels

are associated with

Violent Behaviours

neuro muscular junctions cholesterol dependent
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

slide31

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 stops

with low Cholesterol

EUROPEAN WAPF LONDON 2014

membrane cholesterol immunology
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
Lipids - Fats and Cholesterol

What are blood lipids and lipoproteins?

LDL (Bad?)

HDL (Good?)

Why are abnormal lipid levels

associated with poor health?

EUROPEAN WAPF LONDON 2014

blood lipids in circulation
Blood Lipids in Circulation
  • Characterised by:
  • Protein labels
  • Droplet size

EUROPEAN WAPF LONDON 2014

blood lipid transport
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!

EUROPEAN WAPF LONDON 2014

lipid parcel delivery
Lipid Parcel Delivery

Fatty Nutrient Cycles

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

EUROPEAN WAPF LONDON 2014

receptor mediated ldl supply
Receptor Mediated LDL Supply
  • What can go wrong?

EUROPEAN WAPF LONDON 2014

sugar damaged ldl labels
Sugar-Damaged LDL Labels

Fructose & Dementia

Raised LDL & Lower HDL

EUROPEAN WAPF LONDON 2014

slide39

High Cholesterol Paradox

Sugar-Damaged Lipid Labels?

No

Yes

Healthy Outcomes

Unhealthy Outcomes

  • 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

EUROPEAN WAPF LONDON 2014

sugar damaged lipids

Sugar-Damaged Lipids

Sugardamages the

Lipid-Proteinscontrolling the

Blood Lipids (LDL and HDL)

Ending 40 years of confusion AGE - Advanced Glycation Endproducts

EUROPEAN WAPF LONDON 2014

ages sugar damaged proteins
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

EUROPEAN WAPF LONDON 2014

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

EUROPEAN WAPF LONDON 2014

age sugar damage chemistry
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

EUROPEAN WAPF LONDON 2014

sugar damaged proteins
Sugar-Damaged Proteins

‘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

EUROPEAN WAPF LONDON 2014

fructose metabolic syndrome
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

EUROPEAN WAPF LONDON 2014

sugar damaged proteins1
Sugar-Damaged Proteins

‘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.2010.12.017

European Journal of Internal Medicine

22 (2011)

EUROPEAN WAPF LONDON 2014

fructose damage dementia
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

EUROPEAN WAPF LONDON 2014

slide48

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)

EUROPEAN WAPF LONDON 2014

summary
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

EUROPEAN WAPF LONDON 2014

what is cholesterol sulphate
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

EUROPEAN WAPF LONDON 2014

slide51

Martin Tupper 19th Century Writer Inventor

A well timed silence hath more eloquence

than speech

EUROPEAN WAPF LONDON 2014

arrest decline await repairs
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

EUROPEAN WAPF LONDON 2014

what to eat
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...

EUROPEAN WAPF LONDON 2014

budgets targets
Budgets & Targets
  • Budget Pasta, Rice, Bread (foods from grass seeds) Sweet Fruits & Sweet Starchy Vegetables (<100g /day)
  • AvoidRefined Sugars, Confectionary Processed Foods & Low Fat Foods that may have High Fructose Corn Syrup added

75% Cocoa OK

EUROPEAN WAPF LONDON 2014