“B” HealthyB Vitamins

Corporate Managers

Siddharth Bhalla Jennifer LimDianna Le Dana Shan

PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson

What are B vitamins?

A class of water-soluble vitamins that facilitate:

Physiological processes involved in making or extracting energy from food (metabolism)

RBC production

Cancer/disease prevention?

There are eight different types:➢B1 (thiamine)➢B2 (riboflavin)➢B3 (niacin)➢B5 (pantothenic acid)➢B6 (pyridine derivatives)➢B7 (biotin)➢B9 (folic acid) ➢B12(cyanocobalamin)

What are B vitamins?

Vitamin B3 (niacin)BOS-1T8

Niacin (nicotinic acid)

nicotinamide

NAD+ NADP+

niacin

General Function

➢ Synthesis of fatty acids and cholesterol (NADH)➢ Hydrogen carriers for reactions catalyzed by

dehydrogenase➢ Metabolism of carbohydrates, fats, proteins

(NAD+)➢ In non-redox reactions, NAD+ is a substrate for

mono-ADP-ribosyltransferases and poly-ADP-ribose polymerase

➢ Cytochrome P450 reactions

Sources

Pharmacological applications

Cholesterol: a review

Image retrieved from www.clinbiochem.info

Cholesterol: a review

Cardiovascular diseases cost the Canadian economy more than $20.9 billion per year

Gu-Cheng et al., 2013 Stroke. Image retrieved from http://vascularsurgeon-ny.com/doctor/

Anti-hyperlipidemic

Improves lipid and cholesterol profile➢Inhibits hydrolysis of triglycerides into free fatty acids➢Inhibits de novo synthesis of triglycerides➢Increases functional HDL

Slows and potentially reverses the progression of atherosclerosis

Anti-hyperlipidemic

Improves lipid and cholesterol profile➢Inhibits hydrolysis of triglycerides into free fatty acids➢Inhibits de novo synthesis of triglycerides➢Increases functional HDL

Slows and potentially reverses the progression of atherosclerosis

Anti-hyperlipidemic

Lukasova et al., 2011.

BOS-1T8

Anti-hyperlipidemic

Improves lipid and cholesterol profile➢Inhibits hydrolysis of triglycerides into free fatty acids➢Inhibits de novo synthesis of triglycerides➢Increases functional HDL

Slows and potentially reverses the progression of atherosclerosis

Anti-hyperlipidemic

Peripheral Tissues

LDL

HDL

Elimination

Anti-hyperlipidemic

Marsche et al., 2001.

Leukocyte myeloperoxidase (MPO):H2O2 + Cl- → HOCl (potent microbicide)

Anti-hyperlipidemic

Ganji et al., 2014.

Reduction in MPO activity attenuates HDL

degradation and dysfunction

Improves cholesterol clearance

Anti-atherothrombotic

➢ Attenuates systemic inflammation○ Improves endothelial dysfunction○ Decrease in C-reactive protein

➢ ↑ plaque stability → ↓ thrombosis

Dose and side effects

Dose to achieve lipid modifying effects:➢Minimal dose: 1 g/day➢Greatest efficacy: 2 g/day

Side effects➢Subcutaneous flushing through GPCR109A

Deficiency ➢Pellagra: four “Ds”

➢ Treat with nicotinamide

“B” Healthy!

ReferencesAntoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C.. 2009. Homocysteine and coronary atherosclerosis:

from folate fortification to therecent clinical trials. Eur Heart J 30(1):6-15.

Ganji SH, Kamanna VS, Kashyap ML. 2014. Niacin decreases leukocyte myeloperoxidase: mechanistic role of redox agents and Src/p38MAP kinase. Atherosclerosis 235(2):554-61.

Gu-Cheng X, Yu Y, Wang C. 2013. Surgical treatment for diffuse coronary artery diseases. INTECH open access publisher. Guthikonda S, Haynes WG. 2006. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep 8(2):100-6.

Harvard School of Public Health. Three of the B Vitamins: Folate, Vitamin B6, and Vitamin B12. Retrieved from http://www.hsph.harvard.edu/nutritionsource/vitamin-b/#introduction.

Heart & Stroke Foundation. 2008. Stroke. http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3483991/k.34A8/Statistics.htm#stroke.

Lukasova M, Hanson J, Tunaru S, Offermanns S. 20111. Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials. Trends Pharmacol Sci 31(12):700-7.

Marsche G, Hammer A, Oskolkova O, Kozarsky K, Sattler W, Malle E. 2002. Hypochlorite-modified High Density Lipoprotein, a High Affinity Ligand to Scavenger Receptor Class B, Type I, Impairs High Density Lipoprotein-dependent Selective Lipid Uptake and Reverse Cholesterol Transport. J Biol Chem 277(35):32172-9.

Sahebkar A, Chew GT, Watts GF. 2014. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog Lipid Res 56C:47-66.

Sauve AA. 2014. NAD+ and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther 324(3):883-93.

Si Y, Zhang Y, Zhao J, Guo S, Zhai L, Yao S et al. 2014. Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway. Mediators Inflamm 2014:263786.

ReferencesTiwari V and Khokhar M. 2014. Mechanism of action of anti-hypercholesterolemia drugs and their resistance. Eur J Pharmacol

741C:156-170.

[1] Avocado. Image retrieved from http://www.bjjscandinavia.com/2013/01/19/10-health-benefits-of-avocados/.

[2] Free range veal. Image retrieved from http://bffbeef.com/products-2/bff-free-range-veal/.

[3] Dates. Image retrieved from http://www.popsugar.com.au/fitness/photo-gallery/35024842/image/35024891/Dates.

[4] Sashimi combo. Image retrieved from http://www.sushikiku.com/location1takeout/sashimicombo/.

[5] Shiitake mushrooms. Image retrieved from http://drleonardcoldwell.com/2014/04/15/shiitake-mushrooms-can-help-prevent-cervical-cancer-study-finds/.

SummaryB vitamins

• Essential class: obtained from high-protein foods or supplements

• Functions: energy metabolism, RBC production

Niacin nicotinamide NAD+ and NADP+

–Redox functions: fatty acid/cholesterol synthesis; H carriers; metabolism

–Non-redox functions: cell signalling (G-proteins)

–Other: alter P450 activity

• Antihyperlipidemic effects

–Too much LDL leads to atherosclerosis and cardiovascular diseases

–Niacin slows and potentially reverses the progression of atherosclerosis•Inhibits hydrolysis of triglycerides into free fatty acids (GPCR109A, in adipocytes)•Inhibits de novo synthesis of triglycerides (DGAT2, in hepatocytes)•Increases functional HDL: improves cholesterol clearance

• Reduces activity of MPO, which reduces HOCl- production less HDL degradation

• Anti-atherothrombotic effects

–Decrease systemic inflammation

–Stabilize plaques

• Deficiency causes pellagra (4 “Ds”: dermatitis, diarrhea, dementia, death)

–Treat with high dose of nicotinamide