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“Good” Cholesterol?

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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“Good” Cholesterol?

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  1. Spot the Difference “Good” Cholesterol? “Bad” Cholesterol? EUROPEAN WAPF LONDON 2014

  2. An Infamous Hypothesis • 1961 Time Magazine • Dr Ancel Keys • asserted that • saturated fats and cholesterol were the causes of CVD EUROPEAN WAPF LONDON 2014

  3. An Alternative Hypothesis Professor John Yudkin Published in 1972 Sugar is a leading cause of diabetes and heart disease EUROPEAN WAPF LONDON 2014

  4. 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

  5. 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

  6. 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

  7. Data Available to Keys Yerushalmy and Hilleboe 1957 NY State Journal of Medicine

  8. 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

  9. 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

  10. 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

  11. 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

  12. "Let's do the good cholesterol, bad cholesterol bit.” Cartoonist: Tom Cheney New Yorker EUROPEAN WAPF LONDON 2014

  13. Spot the Difference “Good” Cholesterol? “Bad” Cholesterol? A Misleading and Unscientific ‘Marketing Concept’ EUROPEAN WAPF LONDON 2014

  14. 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

  15. 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

  16. Cell Lipid Membranes 4:1 Fat : Cholesterol EUROPEAN WAPF LONDON 2014

  17. EUROPEAN WAPF LONDON 2014

  18. Cell Lipids Nutrition and Signalling Requires 20% Molecular Cholesterol EUROPEAN WAPF LONDON 2014

  19. 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

  20. 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

  21. “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

  22. 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

  23. Neurons Lowering Cholesterol damages - Myelin Protective Sheathing -Neurotransmitter Vesicles - Synaptic Functions EUROPEAN WAPF LONDON 2014

  24. 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

  25. 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

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

  27. 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

  28. 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!

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. Blood Lipids in Circulation • Characterised by: • Protein labels • Droplet size EUROPEAN WAPF LONDON 2014

  35. 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

  36. Lipid Parcel Delivery Fatty Nutrient Cycles 2014 Nobel Prize: James E. Rothman, Randy W. Schekman and Thomas C. Südhof. EUROPEAN WAPF LONDON 2014

  37. Receptor Mediated LDL Supply • What can go wrong? EUROPEAN WAPF LONDON 2014

  38. Sugar-Damaged LDL Labels Fructose & Dementia Raised LDL & Lower HDL EUROPEAN WAPF LONDON 2014

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

  49. 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

  50. 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

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