Niacin (0-900 μM, 42 hours) dramatically raises GSH and lowers ROS levels, and it also influences the expression of genes linked to lipid metabolism and apoptosis [1]. Niacin (0–40 μM, 24 hours) has little effect on proliferation but at low concentrations can reduce cancer invasive activity [2].

In male C57BL/6 mice, niacin (subcutaneous injection, 3-300 mg/kg once) can cause vasodilation in a dose-dependent manner in a matter of minutes [3].

RT-PCR[1]
Cell Types: cumulus cells and oocytes of prepubertal sows
Tested Concentrations: 600 μM
Incubation Duration: 42 hrs (hours)
Experimental Results: Up-regulated the relative expression of anti-apoptotic gene BCL2 and lipid metabolism gene ACACA, down-regulated the pro-apoptotic gene Apoptosis gene BAX. Cell proliferation experiment [2]
Cell Types: AH109A rat ascites liver cancer cell line
Tested Concentrations: 0-40 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: 2.5 μM to 40 μM has no effect on AH109A cell proliferation, but inhibits cell invasion.

Animal/Disease Models: Male C57BL/6 mice [3]
Doses: 3-300 mg/kg
Route of Administration: subcutaneous injection;
Experimental Results:Induced vasodilation in a dose-dependent manner.

Absorption, Distribution and Excretion
In patients with chronic kidney disease, the Cmax is 0.06µg/mL for a 500mg oral dose, 2.42µg/mL for a 1000mg oral dose, and 4.22µg/mL for a 1500mg oral dose. The Tmax is 3.0 hours for a 1000mg or 1500mg oral dose. The AUC is 1.44µg\*h/mL for a 500mg oral dose, 6.66µg\*h/mL for a 1000mg oral dose, and 12.41µg\*h/mL for a 1500mg oral dose. These values did not drastically differ in patients requiring dialysis.
69.5% of a dose of niacin is recovered in urine. 37.9% of the recovered dose was N-methyl-2-pyridone-5-carboxamide, 16.0% was N-methylnicotinamide, 11.6% was nicotinuric acid, and 3.2% was niacin.
Data regarding the volume of distribution of niacin is not readily available.
Data regarding the clearance of niacin is not readily available.
/MILK/ Niacin is distributed in human milk.
Niacin is rapidly and extensively (60-76% of dose) absorbed following oral administration. Peak plasma concentrations of niacin following administration of an immediate-release (Niacor) or extended-release (Niaspan) niacin preparation generally are attained within 30-60 minutes or 4-5 hours after oral administration, respectively. The bioavailability of 1 tablet containing 1 g of extended-release niacin in fixed combination with 40 mg of lovastatin (Advicor 1 g/40 mg) differs from that of 2 tablets each containing 500 mg of extended-release niacin in fixed combination with 20 mg of lovastatin (Advicor 500 mg/20 mg). ... Peak plasma concentrations of niacin and metabolites following oral administration of Niaspan extended-release tablets appear to be slightly higher in women than in men, possibly because of differences in metabolism. Limited data suggest that women may exhibit greater antilipemic response to niacin than men, possibly because of gender-specific differences in the metabolic rate or volume of distribution of the drug.
Niacin is distributed mainly to the liver, kidney, and adipose tissue.
Niacin and its metabolites are rapidly excreted in urine. Following oral administration of single and multiple doses of an immediate-release (Niacor) or extended-release (Niaspan) niacin preparation, approximately 88 or 60-76% of the dose, respectively, was excreted in urine as unchanged drug and inactive metabolites.
For more Absorption, Distribution and Excretion (Complete) data for Nicotinic acid (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
The metabolism of niacin is poorly described in the literature, but the metabolites niacinamide, niacinamide N-oxide, nicotinuric acid, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-5-carboxamide, and trigonelline have been identified in human urine.
... Nicotinamide is the main substance that is transported between the different tissues as a precursor of nicotinamide adenine dinucleotide (NAD) synthesis. The liver, kidneys, brain and erythrocytes prefer nicotinic acid as a precursor for NAD synthesis, but testes and ovaries prefer nicotinamide. NAD nucleosidase cleaves NAD with nicotinamide as one of the products. This can be deamidated to form nicotinic acid (and re-converted to NAD) or methylated and released via urine. Excretion of the amide (and its metabolites) tends to be more extensive compared to the acid.
Niacin is rapidly metabolized and undergoes extensive first-pass metabolism. The drug is converted to several metabolites, including nicotinuric acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). At doses used to treat hyperlipoproteinemia, the principal metabolic pathways appear to be saturable, and niacin is thought to exhibit nonlinear, dose-dependent pharmacokinetics. Nicotinamide does not appear to exert antilipemic effects; the activity of other metabolites on lipoprotein fractions currently are unknown.
After doses of 100 mg of niacin (total dose of 200 mg), the urinary excretion of alkalihydrolyzable niacin derivatives and of N1-methylnicotinamide increased from 6.0 to 14.6 mg and from 2.8 to 5.7 mg after 3 hr in four human subjects, respectively. Chromatographic results showed the major metabolite in the urine to be nicotinuric acid, forming 92-99% of the alkalihydrolysable derivatives. Niacinamide (1-4%) was the other metabolite. There was no free niacin in the urine except in one subject who had intense flushing of the skin soon after ingesting the niacin. In these four subjects, there was a large increase in the excretion of N1-methylnicotinamide, which varied from 6.9 to 16.6 mg/3 hr. The small rise in the tertiary nicotinyl derivatives (0.9 to 1.8 mg) was solely due to niacinamide, since no other nicotinyl compound could be detected on the paper chromatograms. Urine from undosed subjects, averaged 0.53 mg N1-methylnicotinamide for a period of 3 hr. The total content of tertiary alkali-hydrolyzable derivative of niacin ranged from 0.2 to 0.3 mg within 3 hr.
N1-methyl-4- pyridone-3-carboxamide is a major metabolite of niacin and niacinamide which has been found to be synthesized from N1- methylnicotinamide.
For more Metabolism/Metabolites (Complete) data for Nicotinic acid (8 total), please visit the HSDB record page.
Niacin is rapidly metabolized and undergoes extensive first-pass metabolism in the liver. The drug is converted to several metabolites, including nicotinuric acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). At doses used to treat hyperlipoproteinemia, the principal metabolic pathways appear to be saturable, and niacin is thought to exhibit nonlinear, dose-dependent pharmacokinetics. (L1323)
Half Life: 20-45 minutes.

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Biological Half-Life
The half life of niacin is 0.9h, nicotinuric acid is 1.3h, and nicotinamide is 4.3h.
/The authors/ describe a case of massive oral niacin overdose that resulted in severe persistent hypotension without the manifestation of cutaneous flushing. ... A 56-year-old male with a history of schizophrenia presented to the emergency department after orally ingesting 11,000 mg of niacin. ... Serum niacin levels were 8.2 ug/mL and 5.6 ug/mL at 48 and 96 hours post ingestion, respectively, giving an apparent half-life of 87 hours. ...
Half-life about 45 min.
The plasma half-life of niacin has been reported to range from 20-60 minutes.

Hepatotoxicity
Niacin in doses above 500 mg daily causes transient, asymptomatic elevations in serum aminotransferase levels in up to 20% of people. The elevations are rarely greater than 3 times the upper limit of the normal range and usually resolve spontaneously even with continuation of the drug. The effect is partially dose related and is more common with doses above 3 g/day. In some patients, there is an overall decrease in serum proteins synthesized by the liver and, in some instances, coagulopathy with an increase in prothrombin time and decline in serum albumin, coagulation factors and apolipoproteins. These changes resolve rapidly upon stopping therapy and may not recur with lower doses.
Niacin can also cause serious hepatotoxicity, but this is uncommon. Significant hepatotoxicity is particularly common with high doses of sustained release niacin. In many cases, the injury becomes apparent after a dose increase or after switching from the regular crystalline to a sustained release form. The pattern is primarily hepatocellular, although cases with a cholestatic pattern have been described. The patients present with jaundice, itching, nausea, vomiting and fatigue. When the injury is the result of switching from the crystalline to the sustained release form, the injury may present acutely within days or a few weeks with a prodromal period of nausea, vomiting and abdominal pain, that is followed by jaundice and pruritus. Early during the injury serum aminotransferase levels are very high and then usually fall rapidly with discontinuation or dose lowering. The clinical phenotype resembles acute hepatic necrosis, suggesting a direct toxic effect. Imaging studies of the liver may reveal areas of hypodensity ("starry sky liver") interpreted as focal fatty infiltration that resolves after stopping the drug. Liver biopsy typically shows varying degrees of centrolobular necrosis with only mild inflammation.
Likelihood score: A[HD] (well known cause of clinically apparent liver injury when given in high doses).

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Protein Binding
Data regarding the protein binding of niacin is not readily available.

[1]. Supplementation with Niacin during in vitro maturation improves the quality of porcine embryos. Theriogenology. 2021 Jul 15;169:36-46. doi: 10.1016/j.theriogenology.2021.04.005. Epub 2021 Apr 18.

[2]. Anti-invasive activity of niacin and trigonelline against cancer cells. Biosci Biotechnol Biochem. 2005 Mar;69(3):653-8.

[3]. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6682-7.

[4]. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010 Jun;210(2):353-61.

[5]. Pellagra: a review with emphasis on photosensitivity. Br J Dermatol. 2011 Jun;164(6):1188-200.

[6]. Pellagra among chronic alcoholics: clinical and pathological study of 20 necropsy cases. J Neurol Neurosurg Psychiatry. 1981 Mar;44(3):209-15.

Nicotinic acid is an odorless white crystalline powder with a feebly acid taste. pH (saturated aqueous solution) 2.7. pH (1.3% solution) 3-3.5. (NTP, 1992)
Nicotinic acid is a pyridinemonocarboxylic acid that is pyridine in which the hydrogen at position 3 is replaced by a carboxy group. It has a role as an antidote, an antilipemic drug, a vasodilator agent, a metabolite, an EC 3.5.1.19 (nicotinamidase) inhibitor, an Escherichia coli metabolite, a mouse metabolite, a human urinary metabolite and a plant metabolite. It is a vitamin B3, a pyridinemonocarboxylic acid and a pyridine alkaloid. It is a conjugate acid of a nicotinate.
Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions.
Nicotinic acid is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Niacin is a Nicotinic Acid.
Niacin, also known as nicotinic acid and vitamin B3, is a water soluble, essential B vitamin that, when given in high doses, is effective in lowering low density lipoprotein (LDL) cholesterol and raising high density lipoprotein (HDL) cholesterol, which makes this agent of unique value in the therapy of dyslipidemia. Niacin can cause mild-to-moderate serum aminotransferase elevations and high doses and certain formulations of niacin have been linked to clinically apparent, acute liver injury which can be severe as well as fatal.
Nicotinic acid has been reported in Umbelopsis vinacea, Codonopsis pilosula, and other organisms with data available.
Niacin is a water-soluble vitamin belonging to the vitamin B family, which occurs in many animal and plant tissues, with antihyperlipidemic activity. Niacin is converted to its active form niacinamide, which is a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and its phosphate form, NADP. These coenzymes play an important role in tissue respiration and in glycogen, lipid, amino acid, protein, and purine metabolism. Although the exact mechanism of action by which niacin lowers cholesterol is not fully understood, it may act by inhibiting the synthesis of very low density lipoproteins (VLDL), inhibiting the release of free fatty acids from adipose tissue, increasing lipoprotein lipase activity, and reducing the hepatic synthesis of VLDL-C and LDL-C.
Nicotinic acid, also known as niacin or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. The designation vitamin B3 also includes the amide form, nicotinamide or niacinamide. Severe lack of niacin causes the deficiency disease pellagra, whereas a mild deficiency slows down the metabolism decreasing cold tolerance. The recommended daily allowance of niacin is 2-12 mg a day for children, 14 mg a day for women, 16 mg a day for men, and 18 mg a day for pregnant or breast-feeding women. It is found in various animal and plant tissues and has pellagra-curative, vasodilating, and antilipemic properties. The liver can synthesize niacin from the essential amino acid tryptophan (see below), but the synthesis is extremely slow and requires vitamin B6; 60 mg of tryptophan are required to make one milligram of niacin. Bacteria in the gut may also perform the conversion but are inefficient.
A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties.

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Drug Indication
Niacin is indicated to prevent vitamin deficiencies in pediatric and adult patients receiving parenteral nutrition as part of multivitamin intravenous injections. Niacin oral tablets are indicated as a monotherapy or in combination with simvastatin or lovastatin to treat primary hyperlipidemia and mixed dyslipidemia. It can also be used to reduce the risk of nonfatal myocardial infarctions in patients with a history of myocardial infarction and hyperlipidemia. Niacin is also indicated with bile acid binding resins to treat atherosclerosis in patients with coronary artery disease and hyperlipidemia or to treat primary hyperlipidemia. Finally niacin is indicated to treat severe hypertriglyceridemia.
FDA Label

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Mechanism of Action
Niacin performs a number of functions in the body and so has many mechanisms, not all of which have been fully described. Niacin can decrease lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver, which degrades apo B, or by modulating lipolysis in adipose tissue. Niacin inhibits hepatocyte diacylglycerol acyltransferase-2. This action prevents the final step of triglyceride synthesis in hepatocytes, limiting available triglycerides for very low density lipoproteins (VLDL). This activity also leads to intracellular degradation of apo B and decreased production of low density lipoproteins, the catabolic product of VLDL. Niacin also inhibits a high density lipoprotein (HDL) catabolism receptor, which increases the levels and half life of HDL.
Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment.
/The study objective was/ to determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin receptor(-/-)) mice. Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARgamma C/EBPalpha or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lalpha, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1beta in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.
Nicotinic acid (niacin), a vitamin of the B complex, has been used for almost 50 years as a lipid-lowering drug. The pharmacological effect of nicotinic acid requires doses that are much higher than those provided by a normal diet. Its primary action is to decrease lipolysis in adipose tissue by inhibiting hormone-sensitive triglyceride lipase. This anti-lipolytic effect of nicotinic acid involves the inhibition of cyclic adenosine monophosphate (cAMP) accumulation in adipose tissue through a G(i)-protein-mediated inhibition of adenylyl cyclase. A G-protein-coupled receptor for nicotinic acid has been proposed in adipocytes. Here, we show that the orphan G-protein-coupled receptor, "protein upregulated in macrophages by interferon-gamma" (mouse PUMA-G, human HM74), is highly expressed in adipose tissue and is a nicotinic acid receptor. Binding of nicotinic acid to PUMA-G or HM74 results in a G(i)-mediated decrease in cAMP levels. In mice lacking PUMA-G, the nicotinic acid-induced decrease in free fatty acid (FFA) and triglyceride plasma levels was abrogated, indicating that PUMA-G mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid in vivo. The identification of the nicotinic acid receptor may be useful in the development of new drugs to treat dyslipidemia.

C6H5NO2

123.11

123.032

59-67-6

Niacin-d4;66148-15-0;Niacin-13C6;1189954-79-7;Niacin hydrochloride;636-79-3;Niacin-15N,13C3;2483829-87-2

938

White to off-white solid powder

1.473

292.5±13.0 °C at 760 mmHg

234-238 ºC

130.7±19.8 °C

0.0±0.6 mmHg at 25°C

1.571

0.15

1

3

1

9

114

0

PVNIIMVLHYAWGP-UHFFFAOYSA-N

InChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)

pyridine-3-carboxylic acid

NSC-169454; NSC 169454; Niacin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~406.14 mM)
H2O : ~10 mg/mL (~81.23 mM)

Solubility in Formulation 1: 2.08 mg/mL (16.90 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (16.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (16.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 110 mg/mL (893.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)