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  1. 1. The Story of Hyperhomocysteinemia “ A Discovery from Rediscovery” [email_address]
  2. 2. The 'homocysteine story' <ul><li>A remarkable example of – </li></ul><ul><li>Medical sleuthing </li></ul><ul><li>Discovery </li></ul><ul><li>Solutions </li></ul><ul><li>Acclaim </li></ul><ul><li>Establishment </li></ul><ul><li>Rejection </li></ul><ul><li>AND decades later 'rediscovery' </li></ul>[email_address]
  3. 3. First, what is 'homocysteine' <ul><li>Protein in the body is made up of many different amino acids, like carriages of a train. </li></ul><ul><li>Some amino acids we can make and others we depend on getting them from diet - they are the 'essential' amino acids. </li></ul><ul><li>Homocysteine is produced from the amino acid methionine, which is found in normal dietary protein. </li></ul>[email_address]
  4. 4. First, what is 'homocysteine‘ (contd…) <ul><li>The trouble is, if you don’t have optimal amounts of B vitamins in your diet, the enzymes that turn homocysteine into either glutathione (an important antioxidant), or SAMe (s-adenosyl methionine) (an important biological agent in the human body, participating in over 40 essential biochemical reactions),don’t work efficiently, so blood homocysteine levels increase. </li></ul><ul><li>Also, it has been discovered that one in ten people have an inherited genetic mutation that makes them more prone to high homocysteine. </li></ul><ul><li>This is because the MTHFR enzyme that converts homocysteine into SAMe doesn’t work so well. </li></ul><ul><li>For these individuals to stay healthy, larger daily intakes of vitamin B12 and folic acid are necessary. </li></ul>[email_address]
  5. 5. A young Dr. Kilmer McCully… <ul><li>noted the 1933 landmark case of young 8 year old boy who died from atheroma-blocked arteries. </li></ul><ul><li>Then another case in 1965 of a 9 year old girl who had a newly discovered disease called 'homocysteinuria' where large amounts of a normal amino acid was found in the urine and blood - causing mental retardation and other problems. </li></ul><ul><li>It turned out that it was her uncle who was that 8 year old boy and homocysteine was a common factor . </li></ul>[email_address]
  6. 6. Homocysteine - the link to atheroma? <ul><li>By 1965 McCulley submitted his research paper suggesting the link between homocysteine and atheroma in children. </li></ul><ul><li>There were three types of homocysteinuria, all concerning problems converting homocysteine to methionine...leading to a toxic protein buildup of homocysteine. </li></ul><ul><li>Three common vitamins were needed yet they were either deficient or not being processed properly - B6, B12 and Folic acid. </li></ul>[email_address]
  7. 7. Homocysteine - the link to atheroma? Groundbreaking news <ul><li>At the time this caused great excitement in the medical research community. </li></ul><ul><li>His discovery was being confirmed in other centres. </li></ul><ul><li>There was also research showing a link with homocysteine in adult onset atheroma too. </li></ul><ul><li>But McCulley also proposed through his research that 'cure' was possible by treating with relatively high doses of one or combinations of folic acid, B6 and B12. </li></ul><ul><li>Perhaps this was to be his big mistake, he should have found a drug cure..... </li></ul>[email_address]
  8. 8. Cholesterol wins <ul><li>However, the cholesterol causation theory was deeply entrenched, and had been since the early 1900's. </li></ul><ul><li>Puzzling was the fact that a great proportion of heart victims had normal cholesterols! </li></ul><ul><li>Still, there was a link between high cholesterol and advanced atherosclerosis, that cant be denied. </li></ul><ul><li>But other more powerful factors seemed to be at play. </li></ul>[email_address]
  9. 9. Cholesterol wins... <ul><li>Policy decisions were made at the highest level that the way forward was to back the 'cholesterol cause' as the key to prevent and treat heart disease. </li></ul><ul><li>McCully's work was pushed aside as was he personally. </li></ul><ul><li>His career of 28 years at Harvard University was over. </li></ul><ul><li>Pharmaceutical industries then worked frantically to discover or improve lipid (fat) lowering drugs - and to this day. </li></ul><ul><li>Sure, they have their place and can be very effective in lowering your cholelsterol (lipid lowering drugs are covered elsewhere). </li></ul>[email_address]
  10. 10. So what happened to Homocysteine? <ul><li>The cholesterol theory had failed also. </li></ul><ul><li>Heart disease dropped dramatically in the 60's after an escalation in the 20 years before that. </li></ul><ul><li>But there were no changes in population cholesterol profiles. </li></ul><ul><li>Another problem with the theory was the lack of correlation between dietary fat and LDL levels. </li></ul><ul><li>There have been vast numbers of trials since to try and establish causative factors. </li></ul><ul><li>Indeed, as the western population has gone 'low fat' and high carbs and sugar, it has grown obese and heart disease is rampant and victims younger. </li></ul>[email_address]
  11. 11. Homocysteine implications get worse!!! <ul><li>It turns out that homocysteine is linked to several diseases including atheroma, stroke, Alzheimers, depression and many others possibly!!! </li></ul>[email_address]
  12. 12. It gets rediscovered !!! <ul><li>Homocysteine has been 'rediscovered' 20 years later. </li></ul><ul><li>Its &quot;an atherogenic determinate that promotes oxidant stress, inflammation, endothelial dysfunction and cell proliferation&quot; according to the New England Journal of Medicine. </li></ul><ul><li>In fact elevated homocysteine is even worse for stroke risk. Homocysteine oxidises LDL (becomes biologically rancid and harmful). </li></ul>[email_address]
  13. 13. Current position on Homocysteine <ul><li>In Cardiology 2007, a study showed that there is a 2.5 factor increase in coronary events (heart attack) in people with existing heart disease and homocyteine level above average levels. </li></ul><ul><li>In 1992 a study of physicians with no history of heart disease and highly elevated homocysteine showed a 300% increase in heart attacks over a 5 year period. </li></ul><ul><li>Previous studies appeared to show that keeping homocysteine under 7 was the safest approach. </li></ul><ul><li>Certainly under 9 at least because from 9-15 there was a doubling of risk of dying of a heart attack; and from 15 up nearly 6.5 times the risk. </li></ul>[email_address]
  14. 14. HEART ATTACKS AND STROKES – REDUCE YOUR RISK BY 75 % <ul><li>The largest review of 92 studies by David Wald, specialist registrar in cardiology, and colleagues from the Department of Cardiology at Southampton General Hospital, examined the association between homocysteine levels and the risk for cardiovascular disease in 20,000 people. </li></ul><ul><li>They found that with every 5-unit increase in homocysteine measured in the blood, the risk for heart disease went up 42 per cent in those with the MTHFR gene mutation and 32 per cent in those without. </li></ul><ul><li>The risk for stroke went up 65 per cent in those with the genetic mutation and 59 per cent in those without. </li></ul><ul><li>The researchers concluded that these “highly significant results indicate strong evidence that the association between homocysteine and cardiovascular disease is causal.” </li></ul><ul><li>This means that having a high homocysteine level isn’t just associated with a greater risk of heart disease, it actually causes heart disease – a conclusion that is being reached by other research groups. </li></ul>[email_address]
  15. 15. HEART ATTACKS AND STROKES – REDUCE YOUR RISK BY 75 % <ul><li>While the average homocysteine level – or H score - is approximately 10 units, an ideal level is 6 units or below. </li></ul><ul><li>Those with a history of cardiovascular disease often have a homocysteine level above 15 units. </li></ul><ul><li>By lowering a high homocysteine level from 16 to 6 units, a 10-point drop, the risk of heart disease could be cut by 75 per cent! </li></ul><ul><li>This is not only a much more substantial risk reduction than can be achieved by lowering cholesterol, it’s also more attainable. </li></ul>[email_address]
  16. 16. CANCER – CUT YOUR RISK BY A THIRD <ul><li>Cancer is about 85 per cent preventable. </li></ul><ul><li>Research published in the New England Journal of Medicine, describing a study involving 45,000 pairs of twins, found that cancer is more likely to be caused by diet and lifestyle choices than by genes. </li></ul><ul><li>Identical twins, who are genetically the same, had no more than a 15 per cent chance of developing the same cancer. </li></ul><ul><li>This suggests that the cause of most cancers is about 85 per cent environmental – that is, down to factors such as diet, lifestyle and exposure to toxic chemicals. </li></ul><ul><li>This study found that choices regarding diet, smoking and exercise accounted for 58 to 82 per cent of cancers studied. (3) </li></ul>[email_address]
  17. 17. CANCER – CUT YOUR RISK BY A THIRD <ul><li>So where does homocysteine come in to all this? </li></ul><ul><li>Cancer is triggered by damage to DNA – and having a high homocysteine level means your DNA is more vulnerable to damage, and poorly repaired once the damage has occurred. </li></ul><ul><li>At the other end of the scale, homocysteine levels have been found to be a very good indicator of whether cancer therapies are working. </li></ul><ul><li>The homocysteine level rises when tumours grow, and falls when they shrink. </li></ul><ul><li>Forms of cancer already clearly linked to high homocysteine include cancer of the breast and colon, and leukaemia, among others. </li></ul><ul><li>Low homocysteine is likely to reduce your risk of these cancers by a third. </li></ul>[email_address]
  18. 18. DIABETES – LOWER YOUR RISK <ul><li>Type 2 (non-insulin dependent) diabetes is highly preventable, yet more and more young people are developing it. </li></ul><ul><li>The obesity “epidemic” in the West has helped fuel this rise. </li></ul><ul><li>If you are obese, the risk of developing diabetes goes up 77 times! </li></ul><ul><li>Diabetics are at risk of having high homocysteine because it is now known that the abnormally raised insulin seen in most diabetics stops the body from lowering and maintaining a healthier homocysteine level. </li></ul><ul><li>By following a homocysteine-lowering diet, plus taking appropriate supplements, you will be able to reduce your risk of diabetes or, if you are diabetic, you’ll be able to help keep it under better control and reduce complications. </li></ul>[email_address]
  19. 19. ALZHEIMER’S DISEASE – HALVE YOUR RISK <ul><li>The evidence indicates that if you can lower your homocysteine level, you will significantly lower your risk of developing Alzheimer’s disease. </li></ul><ul><li>Homocysteine is strongly linked to damage in the brain. </li></ul><ul><li>The evidence – the higher the homocysteine, the greater the damage to the brain. </li></ul><ul><li>A recent study in the New England Journal of Medicine charted the health of 1,092 elderly people without dementia, measuring their homocysteine levels. </li></ul><ul><li>Within the following eight years, 111 were diagnosed with dementia. </li></ul><ul><li>Eighty-three of this group were diagnosed with Alzheimer’s. Those with high blood homocysteine levels (in this study, above 14 units) had nearly double the risk of Alzheimer’s. </li></ul><ul><li>These studies strongly suggest that following a homocysteine-lowering regime should, at the very least, halve your risk of developing Alzheimer’s disease in later life. </li></ul>[email_address]
  20. 20. HALVE YOUR RISK OF DEATH FROM ALL CAUSES <ul><li>One of the best ways to extend your lifespan is by reducing your homocysteine level. With every five-point decrease in your H score, you will gain: </li></ul><ul><li>A 49 per cent reduced risk of death from all causes </li></ul><ul><li>A 50 per cent reduced risk of death from cardiovascular disease </li></ul><ul><li>A 26 per cent reduced risk of death from cancer </li></ul><ul><li>A 104 per cent reduced risk of death from causes other than cancer or heart disease </li></ul>[email_address]
  21. 21. Testing homocysteine and the treatment decision <ul><li>Conventional blood test normal levels are said to be: </li></ul><ul><li>Normal 5 - 15 nmol/L </li></ul><ul><li>Moderate 16 - 30 </li></ul><ul><li>Intermediate 31 - 100 </li></ul><ul><li>Severe above 100 </li></ul>[email_address]
  22. 22. HIGH HOMOCYSTEINE RISK FACTORS <ul><li>Inherited genetic mutation (abnormal functioning of the MTHFR enzyme) </li></ul><ul><li>Family history of heart disease, stroke, cancer,Alzheimer’s disease, schizophrenia, diabetes </li></ul><ul><li>Folic acid deficiency </li></ul><ul><li>Increasing age </li></ul><ul><li>Male sex </li></ul><ul><li>Oestrogen deficiency </li></ul><ul><li>Excessive alcohol, coffee or tea intake </li></ul><ul><li>Smoking </li></ul><ul><li>Lack of exercise </li></ul><ul><li>Hostility and repressed anger </li></ul><ul><li>Inflammatory bowel diseases (coeliac disease, </li></ul><ul><li>Crohn’s disease, ulcerative colitis) </li></ul><ul><li>H.pylori-generated ulcers </li></ul><ul><li>Pregnancy </li></ul><ul><li>Strict vegetarian or vegan diet (due to a possible lack </li></ul><ul><li>of vitamin B12) </li></ul><ul><li>High fat diet, excessive red meat and/or dairy intake </li></ul><ul><li>High salt intake </li></ul>[email_address]
  23. 23. LOWERING YOUR HOMOCYSTEINE LEVEL <ul><li>THE TEN-STEP H FACTOR DIET </li></ul><ul><li>Eat Less Fatty Meat, More Fish and Vegetable Protein </li></ul><ul><li>Eat Your Greens </li></ul><ul><li>Have a Clove of Garlic a Day </li></ul><ul><li>Don’t Add Salt to Your Food </li></ul><ul><li>Cut Back on Tea and Coffee </li></ul><ul><li>Limit Your Alcohol </li></ul><ul><li>Reduce Your Stress </li></ul><ul><li>Stop Smoking </li></ul><ul><li>Correct Oestrogen Deficiency </li></ul><ul><li>Supplement a High-Strength Multivitamin and Mineral Every Day </li></ul>[email_address]
  24. 24. The discovery rediscovered… [email_address]
  25. 25. Thank you [email_address]