Niacin

Brandon M. Kistler, PhD, RD

Structure - Niacin
 Sources
• Best sources are fish and meat Food (serving) Niacin (mg)
Beef Liver (3oz) 15
• Plant products
– Enriched and fortified grain products, Tuna, Yellow Fin (3oz) 11.3
whole grains, legumes, coffee, tea
Salmon, Atlantic (3oz) 8.5
• Bacterial metabolism Beef, Sirloin (3oz) 7.6

• Supplements Chicken, Breast (3oz) 7.7

– Nicotinamide Pasta, Enriched, Cooked (1 c) 2.3

• Synthesis in liver Peanut Butter (2Tb) 4.3

– ~1 mg niacin from 60 mg dietary
Lentils (1/2 c) 1.1
tryptophan (only 3%)
 Digestion

• Animal sources • NADP (Pyrophosphatase) -> NAD

– Nicotinamide, NAD, NADP
• NAD (Glycohydrolase) -> Nictoniamide
• Plant Sources
– Nicotinic Acid
• Absorption of niacin
– Corn
• Niacytin (carbohydrate) – Small Intestine
• Niacinogens (peptide)
• Only 10% available for absorption • Occurs by:
from maize
– Sodium-dependent facilitated diffusion
• Lime water – frees niacin from [low]
carbohydrate structure
– Passive diffusion [high - supplement]
– High affinity carrier for nicotinic in colon
Metabolism

Tryptophan

B2, B6 & Iron

FAD, PLP

Niacin
 Functions
Over 400 enzymes require niacin coenzymes
– Coenzymes (H+ donor or electron acceptor)
• Oxidative reactions uses NADH (TCA, ETC—energy
release (ATP)
– Glycolysis, PDH reaction, TCA cycle, Beta-oxidation, ethanol
• Reductive biosynthesis uses NADPH (Fatty acids,
cholesterol & steroid H)
– Fatty acids, cholesterol, & steroid hormone synthesis
• Folate metabolism (coenzymes synthesis DHF and THF)

– Nonredox roles
• Act as a donor of ADP –ribose for the posttranslational
modification of proteins
• Important role in DNA repair & gene stability
 Recommended Daily Allowance - Niacin

Life Stage Age Males (mg/day)* Females (mg/day)*

Infants 0-6 months 2 (AI) 2 (AI)
Infants 7-12 months 4 (AI) 4 (AI)
Children 1-3 years 6 6
Children 4-8 8 8
Children 9-13 12 12
Adolescents 14-18 16 14
Adults 19+ 16 14
Pregnant All - 18
Breastfeeding All - 17
*Mg/day of Niacin Equivalents
 Clinical Relevance: Assessment
– Urinary excretion of niacin metabolites
• <0.8 mg/day of N’methyl nicotinamide suggestive of deficiency
• <0.5 mg N’methyl nicotinamide per 1 gm creatinine suggestive of deficiency
• N’methyl 2-pyridone 5-carboxamide to N’methyl nicotinamide: <1 suggestive of
deficiency

– Erythrocyte NAD concentrations

– Erythrocyte NAD to NADP ratio
 Clinical relevance: Pellagra (4 Ds)
• Pelle (skin) – agra (rough)
• Dermatitis
– Skin exposed to sunlight develops dermatitis
– Casal’s necklace

• Diarrhea (n&v), glossitis, cheliosis,

stomatitis

• Dementia
– Confusion, disorientation
– Other neurologic manifestations include headache,
fatigue, peripheral neuritis

• Death (if untreated)

 Clinical relevance: Hartnup Disorder
• Inherited metabolic disorder
• Defective gene, on chromosome 5
• Rare (recessive pattern of inheritance)

• Problem:
– Impaired absorption of tryptophan
– Impaired synthesis of niacin from tryptophan

• Treatment:
– High protein diet
– Niacin supplement
– Avoidance of exposure to sunlight
 Clinical Relevance: Toxicity
Age UL (mg/day)

0-12m Not established

1-3 yrs 10

4-8 15

9-13 20

14-18 30

19+ 35
 Additional roles that may be of clinical
significance
• Nicotinic acid and blood lipids (up to 6g/ day)
– Lower total cholesterol, TAGs, LDL, Lipoprotein a
– Increase HDL
– 1g + day nicotinic acid associated with flushing (redness), GI distress (N & V)
– Extreme cases = liver failure
– Extended release (Niaspan) or coupled with prostaglandin antagonist to reduce symptoms of
flushing

• In vitro (cell culture) data suggests NAD may be involved in cancer initiation

• Nicotinamide may protect Beta-cells early in Type I Diabetes and has been used for
skin conditions (acne)
– Does not improve blood lipids
 Drug Interactions
• Statins
– Rhabdomyolysis – breakdown of muscle, enzymes/electrolytes releases can
cause kidney damage
– Co- administering niacin enhances risk

• Chemotherapy agents
– Can cause symptoms of pellagra
– Supplementation may be warranted

• Sulfinpyrazone – promotes excretion of uric acid typically used in gout

– Reduce uric acid clearance

• Oral contraceptives (estrogen containing)

– Increase conversion from tryptophan (reduced dietary needs)