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.

REFERENCEKamanna 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 beta-chain adenosine triphosphate synthase (a recently reported HDL-apo A-I holoparticle receptor), inhibits the removal of HDL-apo A-I.

REFERENCEKamanna 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.

REFERENCES36: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): 1253–68Meyers, 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 belongsto 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 DNARepair DNAMethylate 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

3-OH-KYNURENINE

3-OH ANTHRANILIC ACID

QUINOLINIC ACID

NIACIN

XanthurenicAcid acetyl

CoA

acetoacetylCoA

Kynureninase (PLP)

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 AcidIt 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.

REFERENCEJoel A. Simon, Esther S. Hudes and Warren S. BrownerEpidemiology 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 BetterLinus 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.

REFERENCEJoel A. Simon, Esther S. Hudes and Warren S. BrownerEpidemiology 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.

ReferenceGreenland, 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 HEARTVitamin E - 800 to 3200 iuVitamin A - 20,000 to 40,000 iuSuper B-Complex, esp. Vitamins B6 and B3Magnesium (300 to 1500 mg) and avoid ManganeseAvoid refined carbohydratesAmino acids Taurine, Arginine and Carnitine (1 to 3 g).Add a good mineral/multivitamin.

REFERENCE

How to Live Longer and Feel BetterLinus Pauling

Thank You