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, after an oral dose of 500 mg, the Cmax was 0.06 µg/mL; after an oral dose of 1000 mg, the Cmax was 2.42 µg/mL; and after an oral dose of 1500 mg, the Cmax was 4.22 µg/mL. The Tmax was 3.0 hours after an oral dose of 1000 mg or 1500 mg. After an oral dose of 500 mg, the AUC was 1.44 µgh/mL; after an oral dose of 1000 mg, the AUC was 6.66 µgh/mL; and after an oral dose of 1500 mg, the AUC was 12.41 µgh/mL. These values were not significantly different in patients requiring dialysis. 69.5% of the Nicotinic acid dose is excreted in the urine. Of the recovered dose, 37.9% was N-methyl-2-pyridone-5-carboxamide, 16.0% was N-methylnicotinamide, 11.6% was nicotinic acid, and 3.2% was nicotinic acid. Data regarding the volume of distribution of nicotinic acid are not yet available. Data regarding the clearance rate of nicotinic acid are not yet available. /Breast Milk/ Nicotinic acid is distributed in human breast milk. After oral administration, nicotinic acid is rapidly and extensively absorbed (60-76% of the absorbed dose). After oral administration of immediate-release (Niacor) or sustained-release (Niaspan) nicotinic acid formulations, peak plasma nicotinic acid concentrations are typically reached within 30-60 minutes or 4-5 hours, respectively. The bioavailability of one tablet of a fixed-release combination of 1 gram of sustained-release Nicotinic acid and 40 mg of lovastatin (Advicor 1 g/40 mg) differs from that of two tablets of a fixed-release combination containing 500 mg of sustained-release Nicotinic acid and 20 mg of lovastatin (Advicor 500 mg/20 mg). …After oral administration of Niaspan sustained-release tablets, the peak plasma concentrations of Nicotinic acid and its metabolites appear to be slightly higher in women than in men, possibly due to metabolic differences. Limited data suggest that women may have a stronger lipid-lowering response to Nicotinic acid than men, possibly due to sex differences in drug metabolism rate or volume of distribution. Nicotinic acid is primarily distributed in the liver, kidneys, and adipose tissue. Nicotinic acid and its metabolites are rapidly excreted in the urine. After single or multiple oral administrations of immediate-release (Niacor) or sustained-release (Niaspan) Nicotinic acid formulations, approximately 88% and 60-76% of the dose, respectively, are excreted in the urine as unchanged drug and inactive metabolites. For more complete data on the absorption, distribution, and excretion of Nicotinic acid (10 types), please visit the HSDB record page. Metabolism/Metabolites: While the metabolism of Nicotinic acid is poorly described in the literature, metabolites such as nicotinamide, nicotinamide N-oxide, nicouric acid, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-5-carboxamide, and trigonelline have been identified in human urine. …Nicotinamide is the primary precursor transported between different tissues. It is involved in the synthesis of adenine dinucleotide (NAD). The liver, kidneys, brain, and erythrocytes tend to use Nicotinic acid as a precursor for NAD synthesis, while the testes and ovaries tend to use nicotinamide. NAD nucleosidases cleave NAD, and nicotinamide is one of the products. Nicotinamide can be deamidated to nicotinic acid (and reconverted to NAD), or it can be methylated and excreted in the urine. Compared to Nicotinic acid, nicotinamide (and its metabolites) tends to be excreted more extensively. Nicotinic acid is rapidly metabolized and undergoes extensive first-pass metabolism. The drug is converted into several metabolites, including nicotinic acid (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). At doses used to treat hyperlipoproteinemia, the major metabolic pathway appears to be saturated, and nicotinic acid is thought to exhibit nonlinear, dose-dependent pharmacokinetic characteristics. Nicotinamide does not appear to have lipid-lowering effects; the activity of other metabolites on lipoprotein components is currently unclear. In four subjects, after administration of 100 mg of nicotinic acid (total dose 200 mg), the excretion of alkaline-hydrolyzed nicotinic acid derivatives and N1-methylnicotinamide in urine increased from 6.0 mg to 14.6 mg and from 2.8 mg to 5.7 mg, respectively, 3 hours later. Chromatographic analysis showed that the major metabolite in urine was nicotinic acid urate, accounting for 92-99% of the alkaline-hydrolyzed derivatives. Nicotinamide (1-4%) was another metabolite. Except for one subject who experienced skin flushing shortly after taking nicotinic acid, free nicotinic acid was undetectable in the urine of the remaining subjects. The excretion of N1-methylnicotinamide was significantly increased in these four subjects, ranging from 6.9 to 16.6 mg/3 hours. The slight increase in tertiary nicotinamide derivatives (0.9 to 1.8 mg) was entirely attributable to nicotinamide, as no other nicotinamide compounds were detected in the paper chromatogram. The mean N1-methylnicotinamide content in the urine of subjects who did not take nicotinic acid was 0.53 mg/3 hours. The total content of tertiary nicotinamide hydrolysis derivatives of nicotinic acid ranged from 0.2 to 0.3 mg over 3 hours. N1-Methyl-4-pyridone-3-carboxamide is the major metabolite of nicotinic acid and nicotinamide and has been found to be synthesized from N1-methylnicotinamide. For more complete metabolite/metabolite data on nicotinic acid (a total of 8 metabolites), please visit the HSDB record page. Nicotinic acid is rapidly metabolized and undergoes extensive first-pass metabolism in the liver. The drug is converted into multiple metabolites, including Nicotinic acid urate (NUA), nicotinamide, and nicotinamide adenine dinucleotide (NAD). At doses used to treat hyperlipoproteinemia, the major metabolic pathway appears to be saturated, and Nicotinic acid is thought to exhibit nonlinear, dose-dependent pharmacokinetic characteristics. (L1323)
Half-life: 20–45 minutes.

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Biological half-life
The half-life of Nicotinic acid is 0.9 hours, Nicotinic acid urate is 1.3 hours, and nicotinamide is 4.3 hours.
/The author/ describes a case of oral Nicotinic acid overdose that resulted in severe, persistent hypotension without skin flushing. …A 56-year-old male with a history of schizophrenia was brought to the emergency department after ingesting 11,000 mg of Nicotinic acid. …At 48 and 96 hours post-ingestion, serum Nicotinic acid levels were 8.2 μg/mL and 5.6 μg/mL, respectively, with an apparent half-life of 87 hours. ...
The half-life is approximately 45 minutes.
It has been reported that the plasma half-life of Nicotinic acid is 20-60 minutes.

Hepatotoxicity
Daily intake of more than 500 mg of Nicotinic acid can cause transient, asymptomatic elevations in serum transaminase levels in up to 20% of patients. These elevations rarely exceed three times the upper limit of normal and usually resolve spontaneously with continued use. This effect is partly dose-related and is more common at daily doses exceeding 3 grams. In some patients, the total amount of serum proteins synthesized by the liver decreases, and in some cases, coagulation disorders occur, manifested as prolonged prothrombin time and decreased serum albumin, coagulation factors, and apolipoprotein levels. These changes resolve rapidly upon discontinuation of the drug and may not recur at lower doses. Nicotinic acid can also cause serious hepatotoxicity, but this is uncommon. High doses of extended-release Nicotinic acid are particularly prone to causing serious hepatotoxicity. In many cases, liver damage manifests with dose increases or after switching from a standard crystalline formulation to an extended-release formulation. The damage pattern is primarily hepatocellular, but cholestatic cases have also been reported. Patients may experience symptoms such as jaundice, itching, nausea, vomiting, and fatigue. When liver injury is caused by switching from a crystalline to a sustained-release formulation, the injury may develop acutely over days or weeks, with prodromal symptoms of nausea, vomiting, and abdominal pain, followed by jaundice and itching. Serum transaminase levels are very high in the early stages of injury, usually decreasing rapidly upon discontinuation or dose reduction. The clinical phenotype resembles acute liver necrosis, suggesting direct toxicity. Liver imaging may show low-density areas (“starry liver”), interpreted as focal fatty infiltration, which resolves upon discontinuation of the drug. Liver biopsy typically shows varying degrees of centrilobular necrosis with only mild inflammation. Probability score: A [HD] (a known cause of clinically significant liver injury at high doses). Protein binding data regarding Nicotinic acid protein binding are unclear.

[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 slightly acidic taste. Its saturated aqueous solution has a pH of 2.7, and a 1.3% solution has a pH of 3-3.5. (NTP, 1992)
Nicotinic acid is a pyridine monocarboxylic acid, where the hydrogen atom at position 3 of the pyridine molecule is replaced by a carboxyl group. It has multiple functions, including as an antidote, lipid-lowering agent, vasodilator, metabolite, EC 3.5.1.19 (nicotinamide enzyme) inhibitor, E. coli metabolite, mouse metabolite, human urine metabolite, and plant metabolite. It is a vitamin B3, a pyridine monocarboxylic acid, and a pyridine alkaloid. It is the conjugate acid of Nicotinic acid.
Nicotinic acid is a B vitamin used to treat vitamin deficiencies, hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarction.
Nicotinic acid is present in or produced by Escherichia coli (K12 strain, MG1655 strain).
Nicotinic acid is a nicotinic acid. Nicotinic acid, also known as nicotinic acid and vitamin B3, is a water-soluble essential B vitamin. When taken in high doses, it effectively lowers low-density lipoprotein (LDL) cholesterol and raises high-density lipoprotein (HDL) cholesterol, making it uniquely valuable in the treatment of dyslipidemia. Nicotinic acid can cause mild to moderate elevations in serum transaminases, and high doses or certain formulations of Nicotinic acid have been associated with clinically significant acute liver injury, which can be severe or even fatal. Nicotinic acid has been reported in Umbelopsis vinacea, Codonopsis pilosula, and several other organisms with relevant data. Nicotinic acid is a water-soluble vitamin belonging to the B vitamin group, found in many animal and plant tissues, and possesses lipid-lowering activity. Nicotinic acid can be converted into its active form, nicotinamide, which is a component of the coenzyme nicotinamide adenine dinucleotide (NAD) and its phosphate form NADP. These coenzymes play important roles in tissue respiration and the metabolism of glycogen, lipids, amino acids, proteins, and purines. While the exact mechanism by which Nicotinic acid lowers cholesterol is not fully understood, its mechanisms of action may include inhibiting the synthesis of very low-density lipoprotein (VLDL), inhibiting the release of free fatty acids from adipose tissue, enhancing lipoprotein lipase activity, and reducing the synthesis of VLDL-C and LDL-C in the liver. Nicotinic acid, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin. Its derivatives, such as NADH, NAD, NAD+, and NADP, play important roles in energy metabolism and DNA repair in living cells. Vitamin B3 also includes its amide form, nicotinamide or Nicotinic acidamide. Severe Nicotinic acid deficiency can lead to pellagra, while mild deficiency can slow metabolism and reduce cold tolerance. The recommended daily intake of Nicotinic acid is: 2-12 mg for children, 14 mg for women, 16 mg for men, and 18 mg for pregnant or lactating women. Nicotinic acid is found in various animal and plant tissues and has therapeutic effects on pellagra, vasodilators, and lipid-lowering agents. The liver can synthesize Nicotinic acid from the essential amino acid tryptophan (see below), but the synthesis process is extremely slow and requires vitamin B6; 60 mg of tryptophan are needed to synthesize 1 mg of Nicotinic acid. Intestinal bacteria can also convert it, but the efficiency is lower. Nicotinic acid is a water-soluble B vitamin found in various animal and plant tissues. The human body needs Nicotinic acid to synthesize the coenzymes NAD and NADP. It has therapeutic effects on pellagra, vasodilators, and lipid-lowering agents. Drug Indications Nicotinic acid is indicated for the prevention of vitamin deficiencies in children and adults receiving parenteral nutrition, who typically receive intravenous multivitamins. Nicotinic acid oral tablets can be used alone 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 infarction in patients with a history of myocardial infarction and hyperlipidemia. Nicotinic acid can also be used in combination with bile acid-binding resins to treat atherosclerosis in patients with coronary artery disease and hyperlipidemia, or to treat primary hyperlipidemia. Finally, Nicotinic acid is indicated for the treatment of severe hypertriglyceridemia.
FDA Label

Mechanism of Action

Nicotinic acid performs multiple functions in the body, and therefore its mechanisms of action are diverse, but not all mechanisms are fully elucidated. Nicotinic acid can reduce lipid and apolipoprotein B (apo B) levels by regulating triglyceride synthesis in the liver (a process that degrades apolipoprotein B (apo B)) or by regulating lipolysis in adipose tissue. Nicotinic acid inhibits hepatocyte diacylglycerol acyltransferase-2. This action prevents the final step in triglyceride synthesis in hepatocytes, thus limiting the triglycerides available for very low-density lipoprotein (VLDL). This activity also leads to intracellular apo B degradation and reduces the production of low-density lipoprotein (a catabolite of VLDL). Nicotinic acid can also inhibit high-density lipoprotein (HDL) catabolism receptors, thereby increasing HDL levels and prolonging its half-life. Long-term use of Nicotinic acid can have beneficial effects on plasma lipid and lipoprotein profiles, thus reducing the risk of cardiovascular disease (CVD). Short-term use of Nicotinic acid can inhibit the release of non-esterified fatty acids from adipocytes and stimulate the release of prostaglandins from Langerhans cells in the skin, but the short-term effects weaken with long-term use, while the long-term effects persist. To further understand the long-term effects of Nicotinic acid on adipocyte lipid metabolism, we used a mouse model with similar human lipoprotein metabolism and drug response [female APOE3-Leiden.CETP (apolipoprotein E3 Leiden cholesterol ester transfer protein) mice], treated with Nicotinic acid and without Nicotinic acid for 15 weeks. Gene expression profiles of gonadal white adipose tissue (gWAT) from Nicotinic acid-treated mice showed upregulation of the "unsaturated fatty acid biosynthesis" pathway, which was confirmed by quantitative PCR and gWAT fatty acid ratio analysis. Furthermore, adipocytes from Nicotinic acid-treated mice secreted more polyunsaturated fatty acid DHA in vitro. This resulted in increased fatty acid secretion profiles in adipocytes and elevated DHA/arachidonic acid (AA) ratios in plasma of Nicotinic acid-treated mice. Notably, the DHA metabolite 19,20-dihydroxyeicosapentaenoic acid (19,20-diHDPA) was also increased in the plasma of Nicotinic acid-treated mice. The elevated DHA/AA ratio and 19,20-diHDPA levels suggest anti-inflammatory properties and may indirectly promote improvements in the anti-atherosclerotic lipid and lipoprotein profiles associated with long-term Nicotinic acid treatment. This study aimed to investigate the effects of Nicotinic acid on adiponectin and adipose tissue inflammatory markers in an obese mouse model. Male C57BL/6 mice were divided into two groups, fed a control diet or a high-fat diet (HFD), which was maintained throughout the study. After 6 weeks of feeding the control or HFD diet, treatment with excipients or Nicotinic acid was initiated and continued for 5 weeks. Simultaneously, the same study was conducted in HCA2 (-/-) (Nicotinic acid receptor (-/-)) mice. Nicotinic acid increased the concentration of the anti-inflammatory adiponectin in the serum of wild-type mice fed a high-fat diet by 21%, but had no effect on lean wild-type mice or lean/high-fat HCA2 (-/-) mice. Nicotinic acid increased the expression of adiponectin gene and protein only in wild-type mice fed a high-fat diet. The increase in serum adiponectin concentration, gene, and protein expression was not associated with changes in the expression of PPARγC/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in adipose tissue. Furthermore, Nicotinic acid had no effect on the expression of ERp44, Ero1-Lα, or DsbA-L (key endoplasmic reticulum molecular chaperones involved in adiponectin production and secretion) in adipose tissue. However, Nicotinic acid treatment attenuated the increase in MCP-1 and IL-1β gene expression in the adipose tissue of wild-type mice fed a high-fat diet (HFD). Nicotinic acid also reduced the expression of CD11c, a marker of pro-inflammatory M1 macrophages, in wild-type mice fed with high-temperature diets (HFD). Nicotinic acid treatment alleviated obesity-induced adipose tissue inflammation by increasing the expression of adiponectin and anti-inflammatory cytokines and reducing the expression of pro-inflammatory cytokines in a Nicotinic acid receptor-dependent manner. Nicotinic acid (nicotinic acid) is a B vitamin that has been used as a lipid-lowering drug for nearly 50 years. The pharmacological effects of Nicotinic acid require doses far exceeding those provided by a normal diet. Its main action is to reduce lipolysis in adipose tissue by inhibiting hormone-sensitive triglyceride lipase. The anti-lipolytic effect of Nicotinic acid involves inhibition of adenylate cyclase mediated by G(i) proteins, thereby inhibiting the accumulation of cyclic adenosine monophosphate (cAMP) in adipose tissue. Previous studies have proposed the presence of a G protein-coupled receptor for Nicotinic acid in adipocytes. This study demonstrates that the orphan G protein-coupled receptor “interferon-γ upregulated protein in macrophages” (mouse PUMA-G, human HM74) is highly expressed in adipose tissue and is a Nicotinic acid receptor. Nicotinic acid binding to PUMA-G or HM74 leads to a decrease in G(i) protein-mediated cAMP levels. In PUMA-G-deficient mice, the Nicotinic acid-induced reduction in plasma free fatty acid (FFA) and triglyceride levels disappeared, indicating that PUMA-G mediates the anti-lipolytic and lipid-lowering effects of Nicotinic acid in vivo. Identification of the Nicotinic acid receptor may contribute to the development of novel drugs for the treatment of 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.)