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Homocysteine – The “H factor”
Dr. Furquan Alam
MD (Biochemistry)
Assistant Professor
Glocal Medical College, SSH & RC, Sah...
Why it is
important to
discuss?
07 March 2017 Dr. Furquan Alam 2
07 March 2017 Dr. Furquan Alam 3
• High levels of homocysteine, or a high "H
Score," predicts the risk of more than 100
diseases and medical conditions inc...
Factors affecting blood Homocysteine Level
07 March 2017 Dr. Furquan Alam 5
What is
homocysteine?
07 March 2017 Dr. Furquan Alam 6
Introduction
• Homocysteine (Hcy), a sulphur containing amino acid
with a molecular weight of 135.2 Dalton.
• Derived from...
07 March 2017 Dr. Furquan Alam 8
9
Homocysteine
Three forms in plasma/serum
Sulfuration
07 March 2017 Dr. Furquan Alam
• Varying forms
• 1% free
• 70-80% bound to albumin via a disulfide link
• 20-30% either as a homocysteine dimer or a
cyst...
Homocysteine
• Normal levels :
• In serum: 13-18 µmol/L
• In plasma: 10- 15 µmol/L
• In pediatric patients: 3.7-10.3 µmol/...
Hyperhomocysteinemia
07 March 2017 Dr. Furquan Alam 12
Methionine
Homocysteine
Cystathionine
Cysteine
Cystathionine synthase
Cystathioninase
Vitamin B6
Vitamin B6
Methyl transfe...
07 March 2017 Dr. Furquan Alam 14
Increase Homocysteine concentration
Methionine
Homocysteine
Cystathionine
Cysteine
Cystathionine synthase
Cystathioninase
...
Etiology of Hyperhomocysteinemia
• Genetic mutations
• Nutritional deficiencies
• Disease states
• Drugs
07 March 2017 Dr....
Genetic Mutations
5-methyleneterahydrofolate reductase (MTHFR)
polymorphism due to a point mutation on chromosome 1.
Preva...
Nutritional deficiencies
• Folate deficiency
• Vitamin B12 (Cobalamine) deficiency
• Vitamin B6 (Pyridoxine) deficiency
07...
Disease states
• Cystathione β-synthase deficiency
• Homocysteinuria
• Methionine synthase deficiency
* Both are rare auto...
Drugs That Raise Homocysteine Levels
• A number of prescription drugs and natural compounds
can elevate blood levels of ho...
Drugs
• Cholestyramine (reduces cholesterol in blood)
• Impairs folate absorption
• Methotrexate (treatment of psoriasis)
...
Who should have their
Homocysteine level tested?

07 March 2017 Dr. Furquan Alam 22
Sample Collection & Patient Preparation
Sample type: Blood (Serum/Plasma)
It can be measured at any time of day but prefer...
How is the Homocysteine level measured ?
Currently, there are three main tHcy test methods
available to the clinical labor...
Advantages and Disadvantages of these
tHcy test methods:
07 March 2017 Dr. Furquan Alam 25
http://www.who.int/mediacentre/factsheets/fs310/en/
07 March 2017 Dr. Furquan Alam 26
Hyperhomocysteinemia and CVD
Cardiovascular Disease is the world’s
number one killing disease.
constituting about 30% of a...
The right idea but the wrong era
Dr Kilmer McCully, a researcher who graduated
from Harvard Medical School in the mid-1960...
Prevalence of hyperhomocysteinemia is
not insignificant:
• General population: 5 - 10%
• Elderly population: 30 - 40%
• Pt...
Why is Homocysteine harmful?
Experiments on arteries of both animals
and humans with an elevated level of
homocysteine sho...
Homocysteine and disease
Bipolar Disorder
PCOS
07 March 2017 Dr. Furquan Alam 31
Risk Factors for CVD
Non-modifiable
Advancing age
Heredity or family
history
Gender
Ethnicity or race
Major modifiable
Hig...
What Homocysteine Does to Arteries
Homocysteine Lysyl residues of collagen
Interferes collagen crosslinking & bind to fibr...
What Homocysteine Does to Arteries
It changes coagulation factor levels so as to encourage
blood clot formation
It causes ...
07 March 2017 35
If cholesterol and a high-fat diet are
the key culprits in heart disease,
why haven't we seen more of a
reduction in our n...
Homocysteine vs. Cholesterol
Researchers conclude that homocysteine
is up to 40 times more predictive than
cholesterol in ...
Abnormally raised insulin seen in
most diabetics stops the body from
lowering and maintaining a healthier
homocysteine lev...
07 March 2017 Dr. Furquan Alam 39
07 March 2017 Dr. Furquan Alam 40
• tHcy levels are highly elevated in renal failure
patients.
• Impaired renal excretion and/or tubular
metabolism of Hcy, ...
Homocysteine & Osteoporosis
An increased homocysteine level appears to be a
strong and independent risk factor for
osteopo...
Homocysteine & Pregnancy
Homocysteine conc. decreased in pregnancy due to
• Hemodilution
• Raised GFR
• Hormonal changes o...
Homocysteine & Pregnancy Complication
07 March 2017 Dr. Furquan Alam 44
Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 1...
Homocysteine & Pregnancy Complication
Values in Early Pregnancy are more reliable.
Folic acid supplements decrease homocys...
5,883 women in Norway were followed through
14,492 pregnancies with their outcomes and
complications recorded against thei...
Higher homocysteine level and % Rise in
Risk of Complications
0
20
40
60
80
100
120
Pre -
eclampsia Premature
Birth Very L...
Homocysteine & PCOS
• In PCOS early atherosclerosis is not exclusively
dependent on hyperinsulinemia and elevated
lipid pr...
Homocysteine and Alzheimer's Disease
People with the highest levels of blood homocysteine had
almost double the risk of Al...
Homocysteine and Alzheimer's Disease
07 March 2017 Dr. Furquan Alam 51
CANCER – CUT YOUR RISK BY A THIRD
Cancer is triggered by damage to DNA – and having
a high homocysteine level means your D...
REDUCE YOUR RISK OF DEATH FROM ALL
CAUSES
One of the best ways to extend your lifespan is by
reducing your homocysteine le...
07 March 2017 Dr. Furquan Alam 54
Homocysteine New studies
Raised Homocysteine levels are seen in sufferers
of chronic fatigue syndrome [CFS]
Homocysteine a...
Should Hyperhomocysteinemia Be Treated?
Arguments favoring treatment
Approximately 80 clinical and epidemiological studies...
Should Hyperhomocysteinemia Be Treated?
Arguments against treatment
Many prospective studies shows that
Lowering homocyste...
Reduction in Homocysteine Levels
• Supplementation of B vitamins
• Folate, B6, and B12
• Restriction of methionine contain...
Homocysteine and Nutrition:
The Vitamin Connection
Screening for HCY may indirectly assess a
patient’s vitamin B6, B12 and...
07 March 2017 Dr. Furquan Alam 60
Vitamins and Food sources
Folic acid - Green leafy vegetables (e.g.
spinach, broccoli), legumes (e.g. lentils,
chick peas,...
Folic acid fortification of enriched grain
products in the late 1990’s appears to
have resulted in a decline in stroke and...
RDA for Vitamins B6, B12 and Folate
Vitamin B6 2 mg
Vitamin B12 6 mcg
Folate 400 mcg
07 March 2017 Dr. Furquan Alam 63
Treatment of hyperhomocysteinemia
Recheck every 6
months
64
Take Home Message
The lower the Hcy level, the lower the risk of
developing coronary artery disease and
suffering fatal he...
Take Home Message
Hcy test is Costly but definitely not costlier than you
Life.
Tobacco, caffeine and excessive intake of
...
Prevention is always better than cure
07 March 2017 Dr. Furquan Alam 67
07 March 2017 Dr. Furquan Alam 68
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Homocysteine: An Overlooked Biomarker in Clinical Medicine

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Homocysteine and its role as Preventive and prognostic Biomarker in Clinical Medicine

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Homocysteine: An Overlooked Biomarker in Clinical Medicine

  1. 1. Homocysteine – The “H factor” Dr. Furquan Alam MD (Biochemistry) Assistant Professor Glocal Medical College, SSH & RC, Saharanpur An Overlooked Biomarker in Clinical Medicine
  2. 2. Why it is important to discuss? 07 March 2017 Dr. Furquan Alam 2
  3. 3. 07 March 2017 Dr. Furquan Alam 3
  4. 4. • High levels of homocysteine, or a high "H Score," predicts the risk of more than 100 diseases and medical conditions including CVD, CVA, Diabetes, Renal Disease etc. • Elevated Plasma Homocysteine is an important, Strong, Graded and Modifiable Risk Factor. • ↑ Hcy at baseline also Predicts higher long term Mortality. 07 March 2017 Dr. Furquan Alam 4
  5. 5. Factors affecting blood Homocysteine Level 07 March 2017 Dr. Furquan Alam 5
  6. 6. What is homocysteine? 07 March 2017 Dr. Furquan Alam 6
  7. 7. Introduction • Homocysteine (Hcy), a sulphur containing amino acid with a molecular weight of 135.2 Dalton. • Derived from Methionine • First isolated from a urinary bladder stone in 1933 by Vincent du Vigneaud. • Later Vincent du Vigneaud received the Nobel Prize in chemistry in 1955. 07 March 2017 Dr. Furquan Alam 7
  8. 8. 07 March 2017 Dr. Furquan Alam 8
  9. 9. 9 Homocysteine Three forms in plasma/serum Sulfuration 07 March 2017 Dr. Furquan Alam
  10. 10. • Varying forms • 1% free • 70-80% bound to albumin via a disulfide link • 20-30% either as a homocysteine dimer or a cysteine-homocysteine-mixed disulfide. * The type(s) of species responsible for the CVD pathology have yet to be determined. 07 March 2017 Dr. Furquan Alam 10
  11. 11. Homocysteine • Normal levels : • In serum: 13-18 µmol/L • In plasma: 10- 15 µmol/L • In pediatric patients: 3.7-10.3 µmol/L • Desirable Serum Level: <10 µmol/lit, preferably between 7-8 µmol/lit.  Hyperhomocysteinemia: Mild • 15 – 30 µmol/lit Moderate • 30 -100 µmol/lit Severe • >100 µmol/lit 07 March 2017 Dr. Furquan Alam 11
  12. 12. Hyperhomocysteinemia 07 March 2017 Dr. Furquan Alam 12
  13. 13. Methionine Homocysteine Cystathionine Cysteine Cystathionine synthase Cystathioninase Vitamin B6 Vitamin B6 Methyl transferase Homocysteine metabolism S-Adenosyl methionine S-Adenosyl homocysteine Acceptor Methylated acceptor 【Remethylation】 【Trans-sulfuration】 B12 Methyl B12 Methyl THF THF 07 March 2017 Dr. Furquan Alam 13
  14. 14. 07 March 2017 Dr. Furquan Alam 14
  15. 15. Increase Homocysteine concentration Methionine Homocysteine Cystathionine Cysteine Cystathionine synthase Cystathioninase Vitamin B6 Vitamin B6 Methyl transferase 【Nutritional deficiencies, Life style , Drugs , Some diseases 】 【Genetic deficiency】 07 March 2017 Dr. Furquan Alam 15
  16. 16. Etiology of Hyperhomocysteinemia • Genetic mutations • Nutritional deficiencies • Disease states • Drugs 07 March 2017 Dr. Furquan Alam 16
  17. 17. Genetic Mutations 5-methyleneterahydrofolate reductase (MTHFR) polymorphism due to a point mutation on chromosome 1. Prevalence MTHFR 15% in European, Middle Eastern and Japanese 1.4% or less in African Americans. Mild to moderate condition Higher risk of neural tube defects and pregnancy loss Mother with the MTHFR mutation who have normal homocysteine levels are not at increased risk for clots. 07 March 2017 Dr. Furquan Alam 17
  18. 18. Nutritional deficiencies • Folate deficiency • Vitamin B12 (Cobalamine) deficiency • Vitamin B6 (Pyridoxine) deficiency 07 March 2017 Dr. Furquan Alam 18
  19. 19. Disease states • Cystathione β-synthase deficiency • Homocysteinuria • Methionine synthase deficiency * Both are rare autosomal recessive disorders that are correlated with Hyperhomocysteinemia and vascular thrombosis. • Chronic renal failure regardless of etiology, duration, or type of dialysis • Severe psoriasis • Possibly through increased cell turnover • Pernicious anemia • Cobalamine deficiency 07 March 2017 Dr. Furquan Alam 19
  20. 20. Drugs That Raise Homocysteine Levels • A number of prescription drugs and natural compounds can elevate blood levels of homocysteine by interfering with folate absorption or metabolism of homocysteine. Caffeine Niacin Cholestyramine Nitrous oxide Colestipol Pemetrexed Fenofibrate Phenytoin Levodopa Pyrimethamine Metformin Sulfasalazine Methotrexate Carbamazepine 07 March 2017 Dr. Furquan Alam 20
  21. 21. Drugs • Cholestyramine (reduces cholesterol in blood) • Impairs folate absorption • Methotrexate (treatment of psoriasis) • Depletes folate metabolites • Anti-epileptics (carbamazepine, phenytoin) • Lower folate concentrations Tobacco and caffeinated coffee 07 March 2017 Dr. Furquan Alam 21
  22. 22. Who should have their Homocysteine level tested?  07 March 2017 Dr. Furquan Alam 22
  23. 23. Sample Collection & Patient Preparation Sample type: Blood (Serum/Plasma) It can be measured at any time of day but preferably overnight fasting and morning Sample. No special preparations. Once blood is drawn, Serum should separated within 1 hour. serum or plasma is first treated with a reducing agent that converts all Hcy species into the reduced form which is measured either directly or after derivatization. Homocysteine levels increase ~10% for every hour the serum/plasma is not separated from the RBCs at room temperature. 07 March 2017 Dr. Furquan Alam 23
  24. 24. How is the Homocysteine level measured ? Currently, there are three main tHcy test methods available to the clinical laboratories. They include: • Chromatographic method (HPLC) : • developed in the early 1980s, and is mainly used in research laboratories. • Immunoassay method: • developed in the mid 1990s, and has been automated for special immunoassay instruments. • Enzyme cycling method: • Latest, developed in last few years, Used on any Automated clinical chemistry analyzer, and is quickly becoming the preferred method for clinical laboratories.07 March 2017 Dr. Furquan Alam 24
  25. 25. Advantages and Disadvantages of these tHcy test methods: 07 March 2017 Dr. Furquan Alam 25
  26. 26. http://www.who.int/mediacentre/factsheets/fs310/en/ 07 March 2017 Dr. Furquan Alam 26
  27. 27. Hyperhomocysteinemia and CVD Cardiovascular Disease is the world’s number one killing disease. constituting about 30% of annual worldwide deaths. Up to 80% of all heart attacks occur in people with normal cholesterol In 25% of adults, the first sign of heart disease is sudden death from a heart attack. Copyright 2010 - Drjoeesposito.com July, 2006 Vol. 3 No. 4 Homocysteine - Revisited 07 March 2017 Dr. Furquan Alam 27
  28. 28. The right idea but the wrong era Dr Kilmer McCully, a researcher who graduated from Harvard Medical School in the mid-1960s and came up with the hypothesis that moderate elevations of homocysteine could lead to heart attacks and strokes. It was the time that the cholesterol-heart-attack theory was gaining tremendous momentum and Mc Cully’s hypothesis clearly challenged its future. He found himself moved down to the basement, funding for his research dried up and he was eventually asked to leave Harvard. 07 March 2017 Dr. Furquan Alam 28
  29. 29. Prevalence of hyperhomocysteinemia is not insignificant: • General population: 5 - 10% • Elderly population: 30 - 40% • Pts with vascular disease: 20 - 40%. Epidemiology Annu Rev Med 1998;49:31-62. HCY and cardiovascular disease. Refsum H, Ueland PM, et.al. Jacques PF, Bostom AG, Wilson PW, et.al. Determinants of plasma total HCY concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73:613- 621 07 March 2017 Dr. Furquan Alam 29
  30. 30. Why is Homocysteine harmful? Experiments on arteries of both animals and humans with an elevated level of homocysteine showed that homocysteine level in blood is an independent risk factor for atherosclerotic vascular disease affecting the coronary (arteries supplying the heart), cerebral (arteries supplying the brain) and peripheral arteries (supplying the rest of the body). Copyright 2010 - Jeremy E. Kaslow, M.D. - all rights reserved 07 March 2017 Dr. Furquan Alam 30
  31. 31. Homocysteine and disease Bipolar Disorder PCOS 07 March 2017 Dr. Furquan Alam 31
  32. 32. Risk Factors for CVD Non-modifiable Advancing age Heredity or family history Gender Ethnicity or race Major modifiable High blood pressure. Abnormal blood lipids Tobacco use. Physical inactivity Obesity Diabetes mellitus Unhealthy diets Novel Risk Factors Excess homocysteine in blood Inflammation e.g. CRP Abnormal blood coagulation: e.g. Fibrinogen Lp ( a) 07 March 2017 Dr. Furquan Alam 32
  33. 33. What Homocysteine Does to Arteries Homocysteine Lysyl residues of collagen Interferes collagen crosslinking & bind to fibrillin  endothelial dysfunction. Homocysteine thiolactone (free radical) Thiolates LDL particles Aggregate Endocytosed by macrophages ↑ed tendency for atherogenesis07 March 2017 Dr. Furquan Alam 33
  34. 34. What Homocysteine Does to Arteries It changes coagulation factor levels so as to encourage blood clot formation It causes the smooth muscle cells that support the arterial wall to multiply-part of the atherogenic process. Homocysteine  activation of Hageman factor  ↑platelet adhesiveness  life threatening intravascular thrombosis. The net result is a threefold increase in heart attack risk (Loscalzo et al., 1998;Maxwal., 2000 ) 07 March 2017 Dr. Furquan Alam 34
  35. 35. 07 March 2017 35
  36. 36. If cholesterol and a high-fat diet are the key culprits in heart disease, why haven't we seen more of a reduction in our number-one disease killer over these past several decades? 07 March 2017 Dr. Furquan Alam 36
  37. 37. Homocysteine vs. Cholesterol Researchers conclude that homocysteine is up to 40 times more predictive than cholesterol in assessing cardiovascular disease risk. Many studies concluded that the risk of arteriosclerotic vascular disease does in fact increase with the homocysteine level, regardless of whether cholesterol is normal or elevated. heart44; 11-01-2004 07 March 2017 Dr. Furquan Alam 37
  38. 38. Abnormally raised insulin seen in most diabetics stops the body from lowering and maintaining a healthier homocysteine level. One third of the diabetic patients had elevated blood Homocysteine Type 2 diabetic patients with elevated homocysteine levels are nearly 200% more likely to die from a heart attack within 5 years than those with normal Homocysteine levels Homocysteine & Diabetes Vasc Health Risk Manag. 2010; 6: 327–332. 07 March 2017 Dr. Furquan Alam 38
  39. 39. 07 March 2017 Dr. Furquan Alam 39
  40. 40. 07 March 2017 Dr. Furquan Alam 40
  41. 41. • tHcy levels are highly elevated in renal failure patients. • Impaired renal excretion and/or tubular metabolism of Hcy, and extra renal factors, like secondary vitamin deficiencies (e.g., in connection with hemodialysis), genetic causes and altered Hcy metabolism are among the reasons. Homocysteine & Renal Disease/Failure 07 March 2017 Dr. Furquan Alam 41
  42. 42. Homocysteine & Osteoporosis An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women high serum homocysteine concentration may weaken bone by interfering with collagen cross- linking, thereby increasing the risk of osteoporotic fracture N Engl J Med. 2004;350:2033-2041 07 March 2017 Dr. Furquan Alam 42
  43. 43. Homocysteine & Pregnancy Homocysteine conc. decreased in pregnancy due to • Hemodilution • Raised GFR • Hormonal changes of pregnancy • Increased fetal uptake 07 March 2017 Dr. Furquan Alam 43
  44. 44. Homocysteine & Pregnancy Complication 07 March 2017 Dr. Furquan Alam 44
  45. 45. Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004 The American College of Obstetricians and Gynecologists as accessed on 29th April 2012 NTDs Other congenital defects spontaneous miscarriage recurrent abortion IUGR Pre-eclampsia placental abruption Pre-term labour Intrauterine fetal death Hyperhomocysteinemia 07 March 2017 Dr. Furquan Alam 45
  46. 46. Homocysteine & Pregnancy Complication Values in Early Pregnancy are more reliable. Folic acid supplements decrease homocysteine levels during pregnancy and substantially reduce the risk of central nervous system malformations 2004 issue of "Clinical Chemistry 07 March 2017 Dr. Furquan Alam 46
  47. 47. 5,883 women in Norway were followed through 14,492 pregnancies with their outcomes and complications recorded against their homocysteine levels. The Hordaland Homocysteine Study. JAMA 1995;274:1526–33 07 March 2017 Dr. Furquan Alam 47
  48. 48. Higher homocysteine level and % Rise in Risk of Complications 0 20 40 60 80 100 120 Pre - eclampsia Premature Birth Very Low Birth Weight 32 38 101 07 March 2017 48
  49. 49. Homocysteine & PCOS • In PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile – PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk. Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome. Gynecologic and obstetric investigation. 2002 Jun 6;53(3):157-62. 07 March 2017 Dr. Furquan Alam 49
  50. 50. Homocysteine and Alzheimer's Disease People with the highest levels of blood homocysteine had almost double the risk of Alzheimer's and other dementia as compared to people with lower blood homocysteine. Increase of 5 micromoles of homocysteine per liter of blood increased the risk of Alzheimer's Disease by 40%. The mechanism linking Hcy and Alzheimer’s disease is poorly understood, it is possible that Hcy is toxic to brain cells, possibly by excessive stimulation, resulting in neuronal damage due to CNS ischemia. New England Journal of Medicine", 2002;346(7):466-468. :07 March 2017 Dr. Furquan Alam 50
  51. 51. Homocysteine and Alzheimer's Disease 07 March 2017 Dr. Furquan Alam 51
  52. 52. CANCER – CUT YOUR RISK BY A THIRD Cancer is triggered by damage to DNA – and having a high homocysteine level means your DNA is more vulnerable to damage homocysteine levels have been found to be a very good indicator of whether cancer therapies are working. The homocysteine level rises when tumours grow, and falls when they shrink. Cancer Council Victoria 2011 07 March 2017 Dr. Furquan Alam 52
  53. 53. REDUCE YOUR RISK OF DEATH FROM ALL CAUSES 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: A 49% reduced risk of death from all causes. A 50% reduced risk of death from cardiovascular disease . A 26% reduced risk of death from cancer . A 104% reduced risk of death from causes other than cancer or heart disease 2005 Orthomolecular conference 07 March 2017 Dr. Furquan Alam 53
  54. 54. 07 March 2017 Dr. Furquan Alam 54
  55. 55. Homocysteine New studies Raised Homocysteine levels are seen in sufferers of chronic fatigue syndrome [CFS] Homocysteine accelerates the aging process by shortening telomeres. RA patients are 20-30% more likely to have higher Homocysteine levels than the normal population In traditionally-treated dialysis patients, 91% of HD and 67% of PD patients have elevated Hcy levels Nutridisk 2011 07 March 2017 Dr. Furquan Alam 55
  56. 56. Should Hyperhomocysteinemia Be Treated? Arguments favoring treatment Approximately 80 clinical and epidemiological studies suggest that elevated homocysteine is a risk factor for coronary heart , cerebro vascular, and peripheral vascular diseases Risk factor treatment of cardiovascular disease is an accepted clinical practice Treatment is inexpensive and unobtrusive under medical supervision Coronary Heart Disease ,Homocysteine,heart disease and stroke 2008 07 March 2017 Dr. Furquan Alam 56
  57. 57. Should Hyperhomocysteinemia Be Treated? Arguments against treatment Many prospective studies shows that Lowering homocysteine with folic acid supplementation is safe, but does not reduce the risk of vascular events The American Heart Association has not yet called hyperhomocysteinemia (high homocysteine level in the blood) a major risk factor for cardiovascular disease. Coronary Heart Disease ,Homocysteine,heart disease and stroke 2008 07 March 2017 Dr. Furquan Alam 57
  58. 58. Reduction in Homocysteine Levels • Supplementation of B vitamins • Folate, B6, and B12 • Restriction of methionine containing substances • Sesame seeds, brazil nuts, fish, meats • Exercise 07 March 2017 Dr. Furquan Alam 58
  59. 59. Homocysteine and Nutrition: The Vitamin Connection Screening for HCY may indirectly assess a patient’s vitamin B6, B12 and folate status, thus offering a useful window into the patient’s nutrition profile. Total homocysteine measurements are now recommended to screen for vitamin deficiency in both the general and high risk populations. Homocysteine may, in fact, be a more sensitive marker of Vitamin B12 , B6 or folate deficiency and… may precede deficiency of circulating vitamins. Screening for vitamin B12 and folate deficiency in older persons. Am J Clin Nutr 2003; 77: 1241-7. 07 March 2017 Dr. Furquan Alam 59
  60. 60. 07 March 2017 Dr. Furquan Alam 60
  61. 61. Vitamins and Food sources Folic acid - Green leafy vegetables (e.g. spinach, broccoli), legumes (e.g. lentils, chick peas, lima beans), orange Vitamin B6 - Meat, poultry, fish, green leafy vegetables, legumes, seeds, potatoes, cantaloupe, milk, egg yolks, cereals, grains, wheat, wheat germ. Vitamin B12 - Beef, poultry, fish (particularly crab, oyster, salmon and herring), liver, kidney, soy, fruit juice, dairy products, egg yolks, fortified cereals, breads 07 March 2017 Dr. Furquan Alam 61
  62. 62. Folic acid fortification of enriched grain products in the late 1990’s appears to have resulted in a decline in stroke and ischemic heart disease deaths. There has been evidence of three-fold acceleration in the decline of stroke related mortality that has been temporarily related to folic acid fortification. American Journal of Clinical Nutrition, Vol. 86, No. 5, 1563S-1568S, November 2007 07 March 2017 Dr. Furquan Alam 62
  63. 63. RDA for Vitamins B6, B12 and Folate Vitamin B6 2 mg Vitamin B12 6 mcg Folate 400 mcg 07 March 2017 Dr. Furquan Alam 63
  64. 64. Treatment of hyperhomocysteinemia Recheck every 6 months 64
  65. 65. Take Home Message The lower the Hcy level, the lower the risk of developing coronary artery disease and suffering fatal heart attacks and strokes . Your Homocysteine level is excellent single indicator of whether you are going to live a long and healthy life, or die young. A high Homocysteine level is a greater risk factor for many health problems Without any doubt, the demand for plasma homocysteine testing will increase soon, perhaps explosively. 07 March 2017 Dr. Furquan Alam 65
  66. 66. Take Home Message Hcy test is Costly but definitely not costlier than you Life. Tobacco, caffeine and excessive intake of Methionine rich diet (Meat, Fish etc.) should be avoided. 07 March 2017 Dr. Furquan Alam 66
  67. 67. Prevention is always better than cure 07 March 2017 Dr. Furquan Alam 67
  68. 68. 07 March 2017 Dr. Furquan Alam 68

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