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==What is Vitamin B3 (Niacin)?==

==What is Vitamin B3 (Niacin)?==

Vitamin B₃, also called niacin, is an essential '''water-soluble''' vitamin that participates as a [[Nutrition Glossary#Cofactor|cofactor]] in [[Sugars - Nutrition|glucose]], [[Fatty Acids Overview - Nutrition|fatty acid]] and [[Amino Acids Overview - Nutrition|amino acid]] metabolism. The term niacin is used to describe a number of compounds that have biological activity associated with nicotinamide, including nicotinic acid, and a variety of pyridine nucleotide structures. Nicotinic acid and nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are metabolized to nicotinamide within the intestinal lumen and absorbed across the intestinal mucosa by either carrier-mediated transport or passive diffusion. Once in the enterocyte nicotinamide is either released as free nicotinamide or converted to NAD for use by the cell. Niacin derivatives are filtered by the [[Nephron Microscopic Anatomy#Proximal Tubule|renal tubules]], with some active reabsorption during periods of low intake.<ref name="McCormick">McCormick DB. (2000) '''Niacin, Riboflavin, and Thiamin. In Biochemical and physiological aspects of human nutrition. '''2000 ''Philadelphia, PA: WB Saunders Company'' p. 459-468.</ref>  

Vitamin B₃, also called niacin, is an [[Nutrition Glossary#Essential Nutrients|essential]] '''water-soluble''' vitamin that participates as a [[Nutrition Glossary#Cofactor|cofactor]] in [[Sugars - Nutrition|glucose]], [[Fatty Acids Overview - Nutrition|fatty acid]] and [[Amino Acids Overview - Nutrition|amino acid]] metabolism. The term niacin is used to describe a number of compounds that have biological activity associated with nicotinamide, including nicotinic acid, and a variety of pyridine nucleotide structures. Nicotinic acid and nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are metabolized to nicotinamide within the intestinal lumen and absorbed across the intestinal mucosa by either carrier-mediated transport or passive [[Diffusion - Physiology|diffusion]]. Once in the enterocyte nicotinamide is either released as free nicotinamide or converted to NAD for use by the cell. Niacin derivatives are filtered by the [[Nephron Microscopic Anatomy#Proximal Tubule|renal tubules]], with some active reabsorption during periods of low intake<ref name="McCormick">McCormick DB. (2000) '''Niacin, Riboflavin, and Thiamin. In Biochemical and physiological aspects of human nutrition. '''2000 ''Philadelphia, PA: WB Saunders Company'' p. 459-468.</ref>.

Like most animals, '''dogs can synthesise a certain amount of niacin from the essential amino acid [[Tryptophan - Nutrition|tryptophan]]'''. The tryptophan metabolite α-amino-β-carboxymuconic-ε-semialdahyde can be utilized in one of two pathways; it can be degraded by picolinic carboxylase to form acetyl-CoA and CO₂ or it can be used to produce nicotinamide. '''Cats, unlike dogs, are unable to synthesise significant levels of niacin from tryptophan''' because they have very high activity of the enzyme picolinic carboxylase which results in rapid catabolism of trypophan to acetyl-CoA and CO₂.<ref name="NRC">National Research Council (NRC) (2006)''' Vitamins. In Nutrient Requirements for Dogs and Cats.''' 2006 ''Washington, DC: National Academies Press ''p.220-223.</ref> As such, cats require preformed niacin in the diet.<ref name="Morris">Morris, J.G. (2002) '''Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations.''''' Nutr Res Rev ''2002;15; 153-168.</ref>

Like most animals, '''dogs can synthesise a certain amount of niacin from the essential [[Amino Acids Overview - Nutrition|amino acid]] [[Tryptophan - Nutrition|tryptophan]]'''. The tryptophan metabolite α-amino-β-carboxymuconic-ε-semialdahyde can be utilized in one of two pathways; it can be degraded by picolinic carboxylase to form acetyl-CoA and CO₂ or it can be used to produce nicotinamide. '''Cats, unlike dogs, are unable to synthesise significant levels of niacin from tryptophan''' because they have very high activity of the enzyme picolinic carboxylase which results in rapid catabolism of trypophan to acetyl-CoA and CO₂<ref name="NRC">National Research Council (NRC) (2006)''' Vitamins. In Nutrient Requirements for Dogs and Cats.''' 2006 ''Washington, DC: National Academies Press ''p.220-223.</ref>. As such, cats require preformed niacin in the diet<ref name="Morris">Morris, J.G. (2002) '''Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations.''''' Nutr Res Rev ''2002;15; 153-168.</ref>.

==Why is it Important?==

==Why is it Important?==

Niacin is used in oxidative-reduction reactions involving catabolism of glucose, fatty acids, ketone bodies, and amino acids. Chronic niacin deficiency results in a wide range of clinical signs from dermatitis and oral mucosa ulceration, to [[diarrhoea]] and death. This condition was originally called black-tongue in dogs and was used as a model to understand and prevent pellagra (i.e. niacin deficiency) in people.<ref>Lanska DJ. (2012)''' The discovery of niacin, biotin, and pantothenic acid. '''''Ann Nutr Metab ''2012;61:246-253.</ref>

Niacin is used in oxidative-reduction reactions involving catabolism of [[Sugars - Nutrition|glucose]], [[Fatty Acids Overview - Nutrition|fatty acids]], ketone bodies, and [[Amino Acids Overview - Nutrition|amino acids]]. Chronic niacin deficiency results in a wide range of clinical signs from dermatitis and oral mucosa ulceration, to [[diarrhoea]] and death. This condition was originally called black-tongue in dogs and was used as a model to understand and prevent pellagra (i.e. niacin deficiency) in people.<ref>Lanska DJ. (2012)''' The discovery of niacin, biotin, and pantothenic acid '''''Ann Nutr Metab ''2012;61:246-253.</ref>.

==Roles in the Body==

==Roles in the Body==

====Metabolic Function====

#'''Metabolic Function:''' The niacin derivatives, NAD and NADP, are required cofactors in dehydrogenase/reductase reactions. In general, NAD is used in catabolic reactions involving glucose, fatty acid, ketone, and amino acid metabolism while NADP is used in synthesis of [[Fat Overview - Nutrition|lipids and cholesterol]]<ref name="McCormick" />. Both NAD and NADP also act as electron donors to the riboflavin-derivative flavin adenine dinucleotide (FAD) in the mitochondrial electron transport chain during adenosine triphosphate (ATP) production.

The niacin derivatives, NAD and NADP, are required cofactors in dehydrogenase/reductase reactions. In general, NAD is used in catabolic reactions involving glucose, fatty acid, ketone, and amino acid metabolism while NADP is used in synthesis of [[Fat Overview - Nutrition|lipids and cholesterol]].<ref name="McCormick" /> Both NAD and NADP also act as electron donors to the riboflavin-derivative flavin adenine dinucleotide (FAD) in the mitochondrial electron transport chain during adenosine triphosphate (ATP) production.

#'''Therapeutic Uses:''' High dose niacin supplementation has been shown to reduce [[Nutrition Glossary#Low Density Lipoprotein|low-density lipoprotein]] (LDL) and [[Nutrition Glossary#Very Low Density Lipoprotein|very low-density lipoprotein]] (VLDL) while increasing [[Nutrition Glossary#High Density Lipoprotein|high-density lipoprotein]] (HDL) cholesterol concentrations in people.<ref name ="Xenoulis">Xenoulis PG and Steiner JM. (2010) '''Lipid metabolism and hyperlipidemia in dogs. '''''Vet J ''2010;183:12-21.</ref> Niacin supplementation has been suggested as a treatment to reduce hypercholesterolemia in dogs,<ref>Goldberg AC.(1998)''' Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. '''''Am J Cardiol ''1998;82:35U-38U</ref> and has been shown to decrease VLDL synthesis in obese dogs.<ref>Le Bloc’h J, et al.(2010)''' Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs. '''''J Pharmacol Exp Ther ''2010;334:583-589.</ref>

 

====Therapeutic Uses====

High dose niacin supplementation has been shown to reduce low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) while increasing high-density lipoprotein (HDL) cholesterol concentrations in people.<ref name ="Xenoulis">Xenoulis PG and Steiner JM. (2010) '''Lipid metabolism and hyperlipidemia in dogs. '''''Vet J ''2010;183:12-21.</ref> Niacin supplementation has been suggested as a treatment to reduce hypercholesterolemia in dogs,<ref>Goldberg AC.(1998)''' Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. '''''Am J Cardiol ''1998;82:35U-38U</ref> and has been shown to decrease VLDL synthesis in obese dogs.<ref>Le Bloc’h J, et al.(2010)''' Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs. '''''J Pharmacol Exp Ther ''2010;334:583-589.</ref>

==Consequences of Niacin Deficiency==

==Consequences of Niacin Deficiency==

Cats and kittens fed niacin deficient diets develop anorexia, fever, erythema of oral mucosa and tongue with eventual ulceration, weight loss, and death within the 2-3 weeks.<ref>Heath MK, ''et al.'' (1940)''' Feline pellagra.''''' Science ''1940;92:514;</ref><ref>Da Silva AC, ''et al.'' (1952)''' The domestic cat as laboratory animal for experimental nutrition studies. II Niacin requirement and tryptophan metabolism.''''' J Nutr'' 1952;1:26-32.</ref>

Cats and kittens fed niacin deficient diets develop anorexia, fever, erythema of oral mucosa and tongue with eventual ulceration, weight loss, and death within the 2-3 weeks.<ref>Heath MK, ''et al.'' (1940)''' Feline pellagra.''''' Science ''1940;92:514;</ref><ref>Da Silva AC, ''et al.'' (1952)''' The domestic cat as laboratory animal for experimental nutrition studies. II Niacin requirement and tryptophan metabolism.''''' J Nutr'' 1952;1:26-32.</ref>

Niacin is prone to degradation with heat processing. Conditions associated with diuresis (e.g., chronic disease, such as renal disease or [[Diabetes Insipidus|diabetes]], or therapeutic intervention, such as intravenous fluids or increased water intake with management of [[Cystitis|lower urinary diseases]]) can result in increased loss of niacin and may increase daily requirements. Patient on chronic haemodialysis are at an increased risk for developing a deficiency.  

Niacin is prone to degradation with heat processing. Conditions associated with diuresis (e.g. chronic disease, such as [[:Category:Kidney - Pathology|renal disease]] or [[Diabetes Insipidus|diabetes]], or therapeutic intervention, such as [[Fluid therapy|intravenous fluids]] or increased water intake with management of [[Cystitis|lower urinary diseases]]) can result in increased loss of niacin and may increase daily requirements. Patients on chronic haemodialysis are at an increased risk of developing a deficiency.

==Toxicity==

==Toxicity==

There are no published studies evaluating niacin toxicity in cats. In dogs one study reported bloody diarrhoea in 2 dogs that were fed approximately x250 the adult requirement, and chronic exposure (11 days) resulted in death.<ref>Chen KK, ''et al. ''(1938) '''Toxicity of nicotinic acid. '''''Proc Soc Exp Biol Med ''1938; 38: 241-245. </ref> In humans, where it is used to help manage hypercholesterolemia, a high intake niacin (x25 the minimum requirement)   can cause peripheral vasodilation (i.e., “flushing”).<ref name ="Xenoulis" /> This side effect of therapeutic niacin has not been evaluated in dogs.

There are no published studies evaluating niacin toxicity in cats. In dogs one study reported bloody diarrhoea in 2 dogs that were fed approximately x250 the adult requirement, and chronic exposure (11 days) resulted in death<ref>Chen KK, ''et al. ''(1938) '''Toxicity of nicotinic acid. '''''Proc Soc Exp Biol Med ''1938; 38: 241-245. </ref>. In humans, where it is used to help manage hypercholesterolemia, a high intake niacin (x25 the minimum requirement) can cause peripheral vasodilation (i.e. “flushing”)<ref name ="Xenoulis" />. This side effect of therapeutic niacin has not been evaluated in dogs.

==Dietary Sources==

==Dietary Sources==

Niacin is naturally occurring in muscle and organ meats and pulses (i.e., legumes). Dietary niacin is typically found in the form of nicotinic acid in plant based materials, and as NAD or NADP in animal based materials. Certain whole grains such as corn and sorghum have a relatively high niacin content, but in these foods niacin is concentrated in the bran and germ layers and has poor [[Nutrition Glossary#Bioavailability|bioavailability]] (i.e., highly bound within the cell), making them a poor source of dietary niacin. Niacin is also sensitive to degradation with heating and additional supplementation is required with commercial pet foods.  

Niacin is naturally occurring in muscle and organ meats and pulses (i.e. legumes). Dietary niacin is typically found in the form of nicotinic acid in plant based materials, and as NAD or NADP in animal based materials. Certain whole grains such as corn and sorghum have a relatively high niacin content, but in these foods niacin is concentrated in the bran and germ layers and has poor [[Nutrition Glossary#Bioavailability|bioavailability]] (i.e. highly bound within the cell), making them a poor source of dietary niacin. Niacin is also sensitive to degradation with heating and additional supplementation is required with commercial pet foods.

==Diagnosing Niacin Deficiency==

==Diagnosing Niacin Deficiency==

==References==

==References==

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[[Category:Vitamins]]

[[Category:Vitamins]]