Niacin, nicotinic acid or vitamin B3, is a water-soluble B vitamin found naturally in some foods, and also sold as a supplement (or even certain medications). It is believed that niacin has antioxidant and anti-atherosclerotic properties through lipid modulation and release of prostaglandin D2. (6)
Niacin's Mechanism of Action
Drs Kamanna VS, and Kashyap ML. have a detailed description about the benefits and adverse side effects of niacin in a review article. Nicotinic acid (niacin) has long been used for the treatment of lipid disorders and cardiovascular disease. Niacin favorably affects apolipoprotein (apo) B-containing lipoproteins (eg, very-low-density lipoprotein [VLDL], low- density lipoprotein [LDL], lipoprotein[a]) and increases apo A-I-containing lipoproteins (high-density lipoprotein [HDL]). According to the review article, niacin directly and noncompetitively inhibits hepatocyte diacylglycerol acyltransferase-2, a key enzyme for triglyceride synthesis. The inhibition of triglyceride synthesis by niacin results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles. Previous human and test-tube studies findings indicate that niacin retards mainly the hepatic catabolism of apo A-I (vs apo A-II) but not scavenger receptor BI-mediated cholesterol esters. Decreased HDL-apo A-I catabolism by niacin explains the increases in HDL half-life and concentrations of lipoprotein A-I HDL subfractions, which augment reverse cholesterol transport. Initial data suggest that niacin, by inhibiting the hepatocyte surface expression of beta-chain adenosine triphosphate synthase (a HDL-apo A-I holoparticle receptor), inhibits the removal of HDL-apo A-I. Niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes, key cytokines involved in atherosclerosis.
The niacin flush (its major side effect) results from the stimulation of prostaglandins D(2) and E(2) by subcutaneous Langerhans cells via the G protein-coupled receptor 109A niacin receptor. Although decreased free fatty acid mobilization from adipose tissue via the G protein-coupled receptor 109A niacin receptor has been a widely suggested mechanism of niacin to decrease triglycerides, physiologically and clinically, this pathway may be only a minor factor in explaining the lipid effects of niacin. (1)
Niacin's Potential Health Benefits on Cardiovascular Diseases
In an article, Dr. Lardizabal and Deedwania, UCSF, explain that cardiovascular disease still ranks as the top cause of mortality worldwide. Lipid-modifying therapy has revolutionized the treatment of the disease and is partly responsible for the recent decline in deaths due to cardiovascular disease. Treatment strategies have evolved since the introduction of the earlier lipid-lowering agents (fibrates, niacin, bile acid resins) to the advent of statins, which have become the standard drugs in cholesterol therapy. (2)
In a rat study, the rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow and given 3% alcoholic water for 60 days. Two other groups fed with the same lipogenic diet and treated with chromium and niacin. Researchers found heart LPO, serum GGT activity and serum PCC
were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. [Hum Exp Toxicol. 2010 Dec 22. ] Similarly, in a clinical study, Insull W Jr. from Baylor College, Texas, found combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy in a study of patients with dyslipidemia. (3)
Niacin's Potential Benefits on Metabolic Syndrome
Patients with metabolic syndrome are at increased risk for cardiovascular disease. Niacin improves lipid abnormalities associated with metabolic syndrome, but is underused, mainly because of flushing (its side effect). Laropiprant reduces niacin-induced flushing and, in combination with extended-release niacin, improves lipid levels.
Niacin's Potential Benefits on Diabates - Reduced Risk in Cardiovascular Events Patients with type 2 diabetes have increased expression of cell adhesion molecules (CAMs). CAMs and monocyte adhesion mediate essential processes in atherogenesis. Dr Tavintharan S. and co-workers from Khoo Teck Puat Hospital found niacin 1500mg daily raised HDL- cholesterol from 0.8mmol/l (95% CI: 0.7-0.9) to 0.9mmol/l (95% CI: 0.8-1.1) and monocytes isolated from patients on niacin had reduced adhesion to endothelial cells. (4)
The Relationship of Niacin and Fat Cells
Niacin is converted to NAD and NADP in tissues, whose products are involved in a number of cellular processes; and it is associated with the regulation of adipogenesis. Dr. Fujimori K from Osaka University, Japan, found niacin promoted adipogenesis by suppressing the production of the anti-adipogenic PGF(2α) through down-regulation of C/EBPβ-activated cyclooxygenase-2 expression in adipocytes. (5) Adipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat.
A RECENT ARTICLE
Eric Chung, The University of Queensland, Australia, published an interesting article on the relationship between dietary niacin intake and erectile dysfunction: a population-based study. (6) He considers that niacin has antioxidant and anti-atherosclerotic properties through lipid modulation and release of prostaglandin D2,3,4 which may have indirect potential positive effects on erectile function. It appears that niacin is likely more effective in patients with dyslipidemia and cardiovascular disease. However, he also states, "it is likely that niacin alone is less likely to be effective in patients with severe or medically refractory ED.6 Furthermore, the exact causal effect of niacin on erectile function restoration and the safe threshold of niacin intake for maximum therapeutic remain unknown."
REFERENCES
1. Vaijinath S Kamanna , Moti L Kashyap Mechanism of action of niacin, Am J Cardiol. 2008 Apr 17;101(8A):20B-26B.
2. Joel A Lardizabal, Prakash Deedwania, Lipid-lowering therapy with statins for the primary and secondary prevention of cardiovascular disease, Cardiol Clin. 2011 Feb;29(1):87-103.
3. William Insull Jr et al, Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy, Vasc Health Risk Manag. 2010 Nov 24:6:1065-75.
4. S Tavintharan, Niacin results in reduced monocyte adhesion in patients with type 2 diabetes mellitus, Atherosclerosis. 2011 Mar;215(1):176-9.
5. Ko Fujimori 1, Fumio Amano, Niacin promotes adipogenesis by reducing production of anti-adipogenic PGF2α through suppression of C/EBPβ-activated COX-2 expression, Prostaglandins Other Lipid Mediat. 2011 Apr;94(3-4):96-103.
6. Chung, Eric, Commentary on “Relationship between dietary niacin intake and erectile dysfunction: a population-based study” Asian Journal of Andrology ():10.4103/aja202424, April 26, 2024.