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Transcript
Niacin (Vitamin B3)
NUTR 624 – Vitamin Metabolism
6/25/2014
Chantal Otelsberg
Niacin (B3)
In terms of dietary intake, the combination of nicotinic
acid and nucleotide-bound nicotinamide=niacin status
Tryptophan is the third form of B3 that that is a precursor
to for NAD (essential amino acid)
Nicotinomide is the form of Niacin in supplements
Where do I find Niacin?
Historical Anecdotes
Based on niacin deficiency, corn
contains niacin
Corn is a tightly bound structure,
which is heat stable and is sensitive
to alkaline treatment
Native Americans developed various
alkaline processing techniques to
release existing niacin
Importance of process not
recognized when Columbus brought
corn to Europe
Pellagra outbreak occurred in outdoor
labor workers, where sun-induced
lesions occurred among those niacin
deficient
Similar outbreaks in Spain, Italy, and
Egypt during 1700s and 1800s
Nicotonic Acid first isolated in 1867,
active role of vitamin was not identified
until 1937
1906-NAD+ identified in yeast extracts
Redox capabilities understood in 1936
1915-Dr. Joseph Goldberger:
Conducted clinical trials on pellagra
induced prison populations
Pellagra cured/prevented through
balanced diet and yeast supplements
1949-NADH formation with ATP
production understood
1966-first publication on ATP-ribose
formation, which aided in
understanding pellagra
Digestion of Niacin
NAD and NADP needed to enable absorption, both present
in food
B6(pyrophosphatase) required for phosphate hydrolysis
of NADP
Due to negative electron charge of phosphate
•
Nicotinomide and nicotinic acid absorbed in stomach
•
More readily absorbed in the small intestine (sodium
dependent facilitated diffusion)
•
High concentration of Niacin, passive diffusion
Absorption
• Nicotinamide and nicotinic acid formed slowly in
stomach lining
• Absorption in small intestine more rapid
• Mechanisms of absorption not clear in current
research
• Nucleotides degraded in upper small intestine to form
free nicotinamide
• Low concentrations absorbed by sodium- dependent
faciliated diffusion/proton cotransportors/anion
antiporters
• Higher concentrations absorbed by passive diffusion
Absorption
Absorbed through brush
border in small intestine
Nicotinamide converted to
NADportal circulation
Liver takes up remaining
nicotinic acid from portal
blood
Nicotinic Acid and
Tryptophan converted to
NAD once in the liver
Transport
In plasma-niacin found in nicotinic amide bloodand
nicotinic acid
1/3 of nicotinic acid (plasma) bound to plasma
proteins
bloodnicotinamide and acidcell membrane by
simple diffusion
Nicotinic acid transport kidney tubules and red
blood cells require carrier
Metabolic Function
Coenzyme
Transfer H electrons
from one part of cell to
another
Provide energy to fuel
metabolic reactions
Aiding electron
transport chain
Non-redox Roles
NAD acts as donor to form
ADP-ribose and of
modification of proteins
associated with
chromosomes
Needed for DNA repair,
replication, and
transcription
Niacin Deficiency
Originally thought to be caused by disruptions in redox
cycling (only metabolic role of niacin at the time)
Due to ADP-ribosylation functions of NAD
Deficiency mainly caused by NAD+ pool depletion
Malabsorption
Increased sensitivity to DNA damage
Cancer
Bone Marrow
Esophagitis and Esophogeal ulcerations
Deficiency
Four D’s of deficiency:
1.
Dermatitis
•
•
2.
Dementia/Delerium
•
•
•
3.
Headache/apathy
Loss of memory
confusion
Diarrhea
•
4.
Pellagra – “rough skin”
Similar to sunburn
Gastrointestinal
manifestations
Death
•
If left untreated
Treatment
500 mg of nicotinamide
daily –several weeks
Possible riboflavin
supplementation to oral
lesions
Possible thiamin
supplementation for
treatment of peripheral
nerve problems
DRI/RDI/AI
Infants
0 - 6 months: 2* milligrams per day
(mg/day)
7 - 12 months: 4* mg/day
*Adequate Intake (AI)
Children
1 - 3 years: 6 mg/day
4 - 8 years: 8 mg/day
9 - 13 years: 12 mg/day
Adolescents and Adults
Males age 14 and older: 16 mg/day
Females age 14 and older: 14 mg/day
Tolerable Upper Limit
Children – 10-20 mg/d
Adults – 35 mg/d
*vasodilatory effects
Assessment
Urinary metabolites through urinalysis
Serum and red blood cell indicators due to NAD
concentrations related to NAD:NADP concentration
in erythrocytes
Interactions
Niacin synthesized in body from tryptophan
Scientists are currently debating how important the
tryptophan to niacin pathway is in human nutrition
Process requires vitamin B6 to occur
Therefore, tryptophan and vitamin B6 could increase
deficiency of niacin
Primary Research
Majewski, M., & Lebiedzinska, A. (2014). The evaluation of selected
shellfish as a source of niacin in nutrition and therapy of modern
human. Polish Annals of Medicine, 69.
•
Niacin analysis that was conducted showed differences between
the various types of seafood
•
•
•
•
Microbial method
Vitamin extracted using enzymatic hydrolysis – papain and diastase
Used 100g of seafood for DRI for men and women
Among the analyzed seafood, the best source of niacin came from
the 100 g of oyster meat (containing 1.16 mg niacin)
•
Determined that increased consumption of seafood might contribute
to reduce the risk of civilization diseases morbidity,
Critical Thinking
Diagram/Describe the several
general areas of metabolism in
which NAD(NADH) and
NADP(H)-dependent enzymes
are involved.
References
Majewski, M., & Lebiedzinska, A. (2014). The evaluation of selected shellfish as a source of
niacin in nutrition and therapy of modern human. Polish Annals of Medicine, 69.
Gropper, S. A., Smith, J. L., & Groff, J. L. (2009). Advanced nutrition and human metabolism.
Australia: Wadsworth/Cengage Learning.
Shils, M. E., & Shike, M. (2006). Modern nutrition in health and disease. Philadelphia:
Lippincott Williams & Wilkins.
Deficiency Diseases (History of Medicine). (n.d.). Retrieved from
http://www.blatner.com/adam/consctransf/historyofmedicine/5-deficiencydiseases/5deficdis.html
Guide to Vitamn B3-Niacin (Nicotinic Acid). (n.d.). Retrieved from
https://www.meschinohealth.com/books/vitamne_b3_niacin#vit2
Niacin: MedlinePlus Medical Encyclopedia. (n.d.). Retrieved from
http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm
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