Before we begin…….

Which of the B vitamins is the other name for Niacin?

a) B1b) B3c) B5d) B7

Which of the B vitamins is the other name for Niacin?

a) B1b) B3c) B5d) B7

Which amino acid can Niacin be synthesized from?

a) Prolineb) Alaninec) Tryptophand) Tyrosine

Which amino acid can Niacin be synthesized from?

a) Prolineb) Alaninec) Tryptophand) Tyrosine

Niacin deficiency can lead to:a) Anemiab) Seizuresc) Scurvyd) Pellagra

Niacin deficiency can lead to:a) Anemiab) Seizuresc) Scurvyd) Pellagra

Niacin

Kirsten Boestfleisch, Lindsay Edmonds,Lena Husnay, Sarah Johnson

NiacinVitamin B3 or nicotinic acidInositol hexaniacinate is also another

formDirectly converted to nicotinamideNiacin, nicotinic acid, and

nicotinamide are cofactors for:NAD+

NADP+

*Both are involved in energy productionWater soluble (body does not store it)Highest concentrations are found in

the liver as NAD+

Niacincommons.wikimedia.org

Nicotinamide

Food SourcesPlant products

Wheat branCornEnriched breads and cerealsLegumesNuts

Meat products – NAD+ and NADP coenzymesReleased during cooking

Need fortification

Why is Niacin Necessary?Necessary for the metabolism of

carbohydrates into glucose, which is used for energy

Helps the body use fat and proteinBoost immune system to fight disease Healthy liverProper function of the nervous systemImproves circulation

Synthesis from TryptophanNicotinamide can be synthesized from

tryptophanInefficient process: 1 mg of niacin needs 60

mg of tryptophanNiacin deficiency oftentimes results when

both niacin and tryptophan levels are insufficient

Major Functions1. Energy metabolism – NAD+ is reduced to NADH in several reactions:

Glycolytic reactionsOxidative decarboxylation of pyruvateOxidation of acetate in the TCA cycleOxidation of alcoholBeta oxidation of fatty acids Many other cellular oxidation reactions

Oxidation of NADH allows transfer of electrons in the electron transport chain to produce ATP.

Major Functions Continued2. NADP+ is reduced to NADPH

Pentose phosphate pathway Malate-pyruvate shuttle (crosses

mitochondrial membrane)

NADPH becomes a reducing agent for many cellular macromolecules, manufacture of

deoxyribonucleotides, cholesterol synthesis, and fatty acid production.

Major Functions Continued3. Poly(ADP-ribosyl)ation reactions

DNA metabolism and genomic stability

4. Mono(ADP-ribosyl)ation reactionsADP-ribose attaches to amino acid side

chains to make mono(ADP-ribose)Aids cyclic ADP-ribose and NAADP formationAllows control of intracellular calcium levels

= cellular signaling

Major Functions Continued*Cyclic ADP-ribose

Synthesis: ADP-ribose attaches to an internal ribose linkage

Important regulator of the CICR (calcium-induced calcium release)

Other regulators of calcium release:Inositol-1,4,5-triphosphate (IP3) - a type of

calcium channel NAADP (a contaminate of NADP found to

mobilize calcium)

Major Functions continued5. SIR2 (rats)/SIRT1 (humans) deacetylation reactions

Involved in genomic stability and expression particularly through:

Histones – involved in DNA transcriptionProtein p53 – tumor suppressor

A deficiency in niacin could result in a more active gene expression in DNA, making DNA

more susceptible to structural damage.

Specific AbsorptionSome in stomach liningMostly in small intestineAt low concentrations:

Sodium-dependent facilitated diffusionCarrier-mediated transportAnion antiporters

Transport MechanismPortal circulation

Facilitated diffusion into erythrocytes Nicotinic acid or nicotinamide

Liver Formation of NAD from tryptophan,

nicotinamide, or nicotinic acid Products for urinary excretion

Mechanism of Action on Various Tissues

1 & 2: Niacin Action in the Adipose TissueAffects: adipocyteTargets: HCAR2 receptor Leads to:

Decreased lipolysisDecreased VLDL and triglycerides

3 & 4: Niacin Action in the ArteryAffects: endotheliumTargets:

NAD+ phosphate Lowers LDL oxidation –

Decreases vascular inflammationRedox sensitive genes

Lowers MCP-1 and VCAM-1 – Decreases vascular inflammation

5-7: Niacin Action in the LiverAffects: hepatocyteTargets:

Enzyme/receptor DGAT2 Decreases triglyceride synthesis and Apo B

secretion – Lowers VLDL and triglycerides, Apo B, and increases LDL particle size

Beta-chain ATP synthase Lowers HDL catabolism –

Increases lipoprotein A-1 and HDL2

ToxicityShort-term:

VasodilationFlushing Burning in the face

and handsNausea and vomiting

*High dose is considered over 100mg per day

Long-term:HyperpigmentationAbnormal glucose

toleranceHyperuricemiaPeptic ulcersHepatomegalyJaundice

DeficiencySymptoms of mild deficiency: indigestion,

fatigue, canker sores, vomiting, depressionPellagra is associated with severe deficiency

Characterized by the four D’s:DiarrheaDementia Sun-sensitive dermatitis Even death

Associated with AIDS, alcohol abuse, anorexia nervosa, cancer patients

Pellagra Continued“Casals Necklace”Widespread in Europe in the 18th centuryHigh incidence in SE states of the US

During the early 20th century associated with new imports of corn from

EuropeAny guesses why?

Led to fortification of nicotinic acid and tryptophan in many foods

www.odermatol.com

Forms of Niacin as SupplementsNiacin used to treat:

Hartnup’s disease, poor glucose tolerance, IDDM, atherosclerosis, schizophrenia, hyperlipidemia, skin disorders

*Lipid soluble derivative of nicotinic acid for hyperlipidemia

Niacinamide used for:Chemotherapy and also IDDM

Tablet or capsuleRegular or extended-released (fewer side effects but

increased risk of liver damage)*When supplementing with niacin, it is recommended

that liver function tests be performed periodically

Clinical InteractionsAntibiotics (tetracycline)AspirinAnti-seizure medicationAnti-coagulants (blood thinners)Blood pressure medications (Alpha-blockers)Cholesterol-lowering medicationsStatinsDiabetes medicationsIsoniazid (INH)Nicotine patches

Take AwayNiacin supplies NAD+ to be reduced to NADHDeficiencies lead to PellagraNiacin can improve cardiovascular health by

increasing HDL and lowering LDL

References Brandt, Mark. “Vitamins and Coenzymes.” Chemistry and Biochemistry. Rose-Hulman

Institute of Technology, n.d. Wed. 18 Nov. 2013. <http://www.rose-hulman.edu/~brandt/Chem330/Vitamin.pdf>.

“B-Vitamins and Folate.” Eat Right. Academy of Nutrition and Dietetics, n.d. Web. 17 Nov. 2013. <http://eatright.org/Public/content.aspx?id=6793>.

Creider JC, Hegele RA, Joy TR. Niacin: another look at an underutilized lipid-lowering medication. Nat Rev Endocrinol. 2012;8(9):517-28.

Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B-26B.

Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol. 2013;61(4):440-6.

“New Lowdown on Cholesterol.” Havard Health Publications. Havard Medical School, n.d. Web. 18 Nov. 2013. <http://www.health.havard.edu/newsweek/New_lowdown_on_cholesterol.htm>.

“Niacin.” Medline Plus. National Institutes of Health, n.d. Web. 19 Nov. 2013. <http:/www.nlm.nih.gov/medlineplus/ency/article/002409.htm>.

“Niacin.” NMS Labs. Tox Wiki, n.d. Web. 20 Nov. 2013. <http://toxwiki.wikispaces.com/Niacin>.

Rhodes T, Norquist JM, Sisk CM, et al. The association of flushing bother, impact, treatment satisfaction and discontinuation of niacin therapy. Int J Clin Pract. 2013;67(12):1238-46.

“Vitamin B3 (Niacin).” University of Maryland Medical Center. N.p., 20 June 2013. Web. 17 Nov. 2013. <http://umm.edu/health/medical/altmed/spplement/vitamin-b3--niacin>.

Zempleni J, Rucker RB, McCormick DB, Suttie JW. (2007) Handbook of Vitamins, pp. 1-570. CRC Press, Boca Raton FL.