Transcript Document

The current trends regarding significance of
vitamins in cardiovascular disease
Prof. Asma Shaukat
NIACIN (B3)
direct and noncompetitive inhibition hepatocyte
diacylglycerol acyltransferase-2, a key enzyme for
TG synthesis.
 accelerated intracellular hepatic apo B
degradation and the decreased secretion of VLDL
and LDL particles.
REFERENCE
Kamanna VS, Kashyap ML. Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach,
California. Am J Cardiol. 2008 Apr 17;101(8A):20B-26B.
Decreased HDL-apo A-I catabolism
 inhibits the hepatocyte surface expression of betachain adenosine triphosphate synthase (a recently
reported HDL-apo A-I holoparticle receptor), inhibits the
removal of HDL-apo A-I.
REFERENCE
Kamanna VS, Kashyap ML. Atherosclerosis Research Center, Department of Veterans Affairs Healthcare
System, Long Beach, California. Am J Cardiol. 2008 Apr 17;101(8A):20B-26B.
NIACIN AS ANTIHYPERLIPIDEMIC
1-3 g/day niacin increases HDL level by 10-30 %
making it most powerful agent to increase HDL
cholesterol.
Recommended form of niacin for raising HDL is
sustained release preparations.
REFERENCES
36:Rader, Daniel J. (2004). "Raising HDL in Clinical Practice". Raising HDL in Clinical Practice: Clinical Strategies to Elevate HDL.
http://cme.medscape.com/viewarticle/479499_5. Retrieved October 8, 2009.
Chapman, M. John; Assmann, Gerd; Fruchart, Jean-Charles; Shepherd, James; Sirtori, Cesare; European Consensus
Panel on HDL-C (2004). "Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of
nicotinic acid – a position paper developed by the European Consensus Panel on HDL-C". Current medical research and
opinion 20 (8): 1253–68
Meyers, C. Daniel; Carr, Molly C.; Park, Sang; Brunzell, John D. (2003). "Varying Cost and Free Nicotinic Acid Content in
Over-the-Counter Niacin Preparations for Dyslipidemia". Annals of Internal Medicine 139 (12): 996
Homocysteine
• Normal level is 10-15mmol/L in serum
• Classification of severity of high homocysteine.
Mild-----15-30mmol/L
Moderate----30-100mmol/L
Severe--->100mmol/L
• CHD pt with Hcy >15mmol/L belongs
to high risk group.
Path-physiological role of homocysteine in CHD
Atherogenic
• Induces vascular inflammation via expression of TNF
• Increased.oxidative stress.
• Promote oxidation of LDL.
• Increased uptake of modified LDL by macrophages.
Direct toxic injury to endothelial.
Path-physiological role of homocysteine in CHD
Thrombogenic.
• Enhances binding of lipoprotein (a) to fibrin
•
decreases cell surface thrombomodulin and protein-C activation
• Increases platelet aggregation.
• Impairs inactivation of factor Va by activated protein C
FOLIC ACID
Folic acid is itself not biologically active,
Biological importance is due to tetrahydrofolate
FUNCTIONS
The human body needs folate to:
 Synthesize DNA
Repair DNA
Methylate DNA
Cofactor in biological reactions involving folate.
Aiding rapid cell division and growth (infancy
and pregnancy).
Production of healthy red blood cells and to
prevent anemia.
The FDA’s implementation of mandatory fortification of
grains and cereals with folic acid on January 1, 1998 is a
direct result of research studies confirming
folate’s HCY-lowering effects,
References:
Tucker KL, Selhub K, et.al. Dietary intake pattern related to plasma folate and HCY concentrations in the Framingham Heart Study. J Nutr
1996;126:3025-3031.
Food and Drug Administration. Food Standards: amendment of standards of identity for enriched grain products to require addition of
folic acid. Federal Register. 1996;61(44):8781-97.
Riddell, LJ, Chisholm A, et.al. Dietary strategies for lowering HCY concentrations. Am J Clin Nutr. 2000; 71(6): 1448-54.
TRYPTOPHAN
N-FORMYLKYNURENINE
KYNURENINE
Xanthurenic
Acid
3-OH-KYNURENINE
Kynureninase (PLP)
3-OH ANTHRANILIC ACID
QUINOLINIC ACID
NIACIN
acetyl
CoA
acetoacetyl
CoA
B6 AND CHD
C-reactive proteins:
Low concentrations of pyridoxal-5'-phosphate
(PLP) are associated with high C-reactive protein
(CRP) levels.
Low PLP and elevated inflammatory markers, such
as high:sensitivity CRP (hs-CRP) and fibrinogen, are
related to a higher risk of CAD.
References:
Waldmann A, Koschizke JW, et.al. HCY and cobalamin status in German
vegans. Public Health Nutr. 2004 May;7(3):467-72
VITAMIN B12 AND HOMOCYSTEINE
VITAMIN B12 AND HOMOCYSTEINE
Ascorbic Acid
It was found out that serum ascorbic acid
levels were independently associated with
prevalence of coronary heart disease and
stroke;
 A 0.5-mg per dl increase in serum
ascorbic acid level was associated with
an 11% reduction in coronary heart
disease and stroke prevalence.
REFERENCE
Joel A. Simon, Esther S. Hudes and Warren S. Browner
Epidemiology Vol. 9, No. 3 (May, 1998), pp. 316-321
Vitamin C
•Reduces oxidation,
•Increase collagen for healing and
•Improve the health and strength of arteries,
 High dose Lysine destroys Lp(a) plaques.
REFERENCE
How to Live Longer and Feel Better
Linus Pauling
ROLE OF VIT C DEFICIENCY IN CHD:
 initiation of atherosclerotic plaque formation.
Vitamin C and amino acid lysine (LP(a) binding
inhibitors), prevent this molecule from binding to
the walls of damaged arteries.
These substances at high dosages are patented to
prevent and to destroy existing atherosclerotic
plaques.
REFERENCE
Joel A. Simon, Esther S. Hudes and Warren S. Browner
Epidemiology Vol. 9, No. 3 (May, 1998), pp. 316-321
VITAMIN D
•Vit D inhibits Renin Angiotensin System
• Vit D regulates vascular smooth muscle (VSMC) function.
– Presence of 25OHD 1-alphahydroxylase in smooth muscle.
• Vit D improves endothelial cell-dependent vasodilation.
• Vit D inversely associated with coronary artery calcification.
• Vit D inhibits myocardial cell hypertrophy.
• Vit D exhibits anticoagulant activity.
• Vit D exhibits anti-inflammatory properties.
Reference
Greenland, Susan R. Heckbert, Karen C. Johnson, JoAnn E. Manson,et al.
Calcium/Vitamin D Supplementation and Cardiovascular Events. Circulation 2007, 115:846-854
DIET FOR HEALTHY HEART
Vitamin E - 800 to 3200 iu
Vitamin A - 20,000 to 40,000 iu
Super B-Complex, esp. Vitamins B6 and B3
Magnesium (300 to 1500 mg) and avoid Manganese
Avoid refined carbohydrates
Amino acids Taurine, Arginine and Carnitine (1 to 3 g).
Add a good mineral/multivitamin.
REFERENCE
How to Live Longer and Feel Better
Linus Pauling
Thank You