Editing Niacin (section)

===Adverse effects===
The most common adverse effects of medicinal niacin ({{nowrap|500–3000&nbsp;mg}}) are flushing (e.g., warmth, redness, itching or tingling) of the face, neck and chest, headache, abdominal pain, diarrhea, [[dyspepsia]], nausea, vomiting, [[rhinitis]], [[pruritus]] and rash.<ref name=lpi/><ref name="NIH Fact Sheet" /><ref name="ReferenceB"/> These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach.<ref name="ReferenceB"/>

The acute adverse effects of high-dose niacin therapy ({{nowrap|1–3&nbsp;grams per day}}) &ndash; which is commonly used in the treatment of [[hyperlipidemia]]s &ndash; can further include [[hypotension]], fatigue, [[glucose intolerance]] and [[insulin resistance]], heartburn, blurred or impaired vision, and [[macular edema]].<ref name=lpi/><ref name="NIH Fact Sheet" /> With long-term use, the adverse effects of high-dose niacin therapy (750&nbsp;mg per day) also include [[liver failure]] (associated with fatigue, nausea, and [[loss of appetite]]), [[hepatitis]], and [[acute liver failure]];<ref name=lpi/><ref name="NIH Fact Sheet" /> these hepatotoxic effects of niacin occur more often when extended-release [[dosage form]]s are used.<ref name=lpi/><ref name="NIH Fact Sheet" /> The long-term use of niacin at greater than or equal to 2&nbsp;grams per day also significantly increases the [[risk ratio|risk]] of [[cerebral hemorrhage]], [[ischemic stroke]], [[gastrointestinal ulcer]]ation and [[gastrointestinal bleeding|bleeding]], [[diabetes]], [[dyspepsia]], and diarrhea.<ref name="NIH Fact Sheet"/>

====Flushing====
[[Flushing (physiology)|Flushing]] &ndash; a short-term [[vasodilation|dilatation]] of skin [[arteriole]]s, causing reddish skin color &ndash; usually lasts for about 15 to 30 minutes, although sometimes can persist for weeks. Typically, the face is affected, but the reaction can extend to neck and upper chest. The cause is blood vessel dilation<ref name=lpi/><ref name="NIH Fact Sheet" /> due to elevation in prostaglandin GD<sub>2</sub> ([[PGD2]]) and [[serotonin]].<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S | title = GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing | journal = The Journal of Clinical Investigation | volume = 115 | issue = 12 | pages = 3634–40 | date = December 2005 | pmid = 16322797 | pmc = 1297235 | doi = 10.1172/JCI23626 }}</ref><ref>{{cite journal | vauthors = Benyó Z, Gille A, Bennett CL, Clausen BE, Offermanns S | s2cid = 30199951 | title = Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells | journal = Molecular Pharmacology | volume = 70 | issue = 6 | pages = 1844–9 | date = December 2006 | pmid = 17008386 | doi = 10.1124/mol.106.030833 }}</ref><ref>{{cite journal | vauthors = Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, Connolly DT | title = Langerhans cells release prostaglandin D2 in response to nicotinic acid | journal = The Journal of Investigative Dermatology | volume = 126 | issue = 12 | pages = 2637–46 | date = December 2006 | pmid = 17008871 | doi = 10.1038/sj.jid.5700586 | doi-access = free }}</ref> Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction.<ref name="ReferenceA">{{cite journal | vauthors = Papaliodis D, Boucher W, Kempuraj D, Michaelian M, Wolfberg A, House M, Theoharides TC | s2cid = 5609632 | title = Niacin-induced "flush" involves release of prostaglandin D2 from mast cells and serotonin from platelets: evidence from human cells in vitro and an animal model | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 327 | issue = 3 | pages = 665–72 | date = December 2008 | pmid = 18784348 | doi = 10.1124/jpet.108.141333 }}</ref> Flushing is sometimes accompanied by a prickly or [[itching]] sensation, in particular, in areas covered by clothing.<ref name="NIH Fact Sheet" />

Prevention of flushing requires altering or blocking the prostaglandin-mediated pathway.<ref name="NIH Fact Sheet" /><ref name="kamanna">{{cite journal | vauthors = Kamanna VS, Kashyap ML | title = Mechanism of action of niacin | journal = The American Journal of Cardiology | volume = 101 | issue = 8A | pages = 20B–26B | date = April 2008 | pmid = 18375237 | doi = 10.1016/j.amjcard.2008.02.029 }}</ref> [[Aspirin]] taken half an hour before the niacin prevents flushing, as does [[ibuprofen]]. Taking niacin with meals also helps reduce this side effect.<ref name="NIH Fact Sheet" /> Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most people no longer experience flushing.<ref name="NIH Fact Sheet" /> Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects.<ref name=autogenerated1>{{cite book |author=Katzung, Bertram G. |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |isbn=978-0-07-145153-6 }}</ref><ref>{{cite journal | title = Options for therapeutic intervention: How effective are the different agents? | journal = European Heart Journal Supplements | volume = 8 | pages = F47–F53 | doi = 10.1093/eurheartj/sul041 | vauthors = Barter P | date = October 2006 | issue = F| doi-access = free }}</ref>

====Liver damage====
Niacin in medicinal doses can cause modest elevations in serum [[transaminase]] and unconjugated [[bilirubin]], both biomarkers of liver injury. The increases usually resolve even when drug intake is continued.<ref name=LiverTox2014>{{cite book |title = IN: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet) |chapter = Niacin |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31643504 |date=February 2014 |location = Bethesda, MD }}</ref><ref name="bil1" /><ref name="bil2" /> However, less commonly, the sustained release form of the drug can lead to serious [[hepatotoxicity]], with onset in days to weeks. Early symptoms of serious liver damage include nausea, vomiting and abdominal pain, followed by [[jaundice]] and [[Itch|pruritus]]. The mechanism is thought to be a direct toxicity of elevated serum niacin. Lowering dose or switching to the immediate release form can resolve symptoms. In rare instances the injury is severe, and progresses to liver failure.<ref name=LiverTox2014 />

====Diabetes====
The high doses of niacin used to treat [[hyperlipidemia]] have been shown to elevate [[blood sugar|fasting blood glucose]] in people with type 2 [[diabetes mellitus|diabetes]].<ref name=Ong2014>{{cite journal |vauthors=Ong KL, Barter PJ, Waters DD |title=Cardiovascular drugs that increase the risk of new-onset diabetes |journal=Am. Heart J. |volume=167 |issue=4 |pages=421–8 |date=April 2014 |pmid=24655688 |doi=10.1016/j.ahj.2013.12.025 |s2cid=205306912 |url=http://www.escholarship.org/uc/item/6gd606b1 |access-date=27 June 2020 |archive-date=28 June 2020 |archive-url=https://web.archive.org/web/20200628180527/https://escholarship.org/uc/item/6gd606b1 |url-status=live |hdl=1959.4/unsworks_43825 |hdl-access=free }}</ref> Long-term niacin therapy was also associated with an increase in the risk of new-onset type 2 diabetes.<ref name=Ong2014 /><ref name=Goldie2016>{{cite journal | vauthors = Goldie C, Taylor AJ, Nguyen P, McCoy C, Zhao XQ, Preiss D | title = Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials | journal = Heart | volume = 102 | issue = 3 | pages = 198–203 | date = February 2016 | pmid = 26370223 | pmc = 4752613 | doi = 10.1136/heartjnl-2015-308055 }}</ref>

====Other adverse effects====
High doses of niacin can also cause niacin [[maculopathy]], a thickening of the [[macula]] and [[retina]], which leads to blurred vision and blindness. This maculopathy is reversible after niacin intake ceases.<ref>{{cite journal |vauthors=Domanico D, Verboschi F, Altimari S, Zompatori L, Vingolo EM |title=Ocular Effects of Niacin: A Review of the Literature |journal=Med Hypothesis Discov Innov Ophthalmol |volume=4 |issue=2 |pages=64–71 |date=2015 |pmid=26060832 |pmc=4458328 }}</ref> Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time.<ref name=Niaspan />