Editing High-density lipoprotein (section)

=== Pharmaceutical drugs and niacin ===

[[Pharmacological therapy]] to increase the level of HDL cholesterol includes use of [[fibrate]]s and [[Niacin (substance)|niacin]]. Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids.<ref>{{cite journal | vauthors = Benatar JR, Stewart RA | title = Is it time to stop treating dyslipidaemia with fibrates? | journal = The New Zealand Medical Journal | volume = 120 | issue = 1261 | pages = U2706 | year = 2007 | pmid = 17853928 | url = http://www.nzma.org.nz/journal/120-1261/2706/ | access-date = 2009-04-29 | archive-url = https://web.archive.org/web/20090706005219/http://www.nzma.org.nz/journal/120-1261/2706/ | archive-date = 2009-07-06 | url-status = dead }}</ref>

[[Niacin (substance)|Niacin]] (nicotinic acid, a form of [[vitamin B3]]) increases HDL by selectively inhibiting hepatic [[diacylglycerol acyltransferase]] 2, reducing [[triglyceride]] synthesis and [[VLDL]] secretion through a receptor HM74<ref>{{cite journal | vauthors = Meyers CD, Kamanna VS, Kashyap ML | title = Niacin therapy in atherosclerosis | journal = Current Opinion in Lipidology | volume = 15 | issue = 6 | pages = 659–65 | date = Dec 2004 | pmid = 15529025 | doi = 10.1097/00041433-200412000-00006 }}</ref> otherwise known as  [[niacin receptor 2]] and HM74A / GPR109A,<ref name="ReferenceA">{{cite journal | vauthors = Soudijn W, van Wijngaarden I, Ijzerman AP | title = Nicotinic acid receptor subtypes and their ligands | journal = Medicinal Research Reviews | volume = 27 | issue = 3 | pages = 417–33 | date = May 2007 | pmid = 17238156 | doi = 10.1002/med.20102 | s2cid = 20876888 }}</ref> [[niacin receptor 1]].

Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%,<ref>{{cite web |url=http://cme.medscape.com/viewarticle/479499_5 |access-date=8 October 2009 |title=Raising HDL in Clinical Practice |work=Raising HDL in Clinical Practice: Clinical Strategies to Elevate HDL |first=Daniel J. |last=Rader |year=2004 |archive-date=12 September 2019 |archive-url=https://web.archive.org/web/20190912024737/https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUub3JnL3ZpZXdhcnRpY2xlLzQ3OTQ5OV81&ac=401 |url-status=live }}</ref> making it the most powerful agent to increase HDL-cholesterol.<ref name="rhcrcr">{{cite web |title=Raising HDL-Cholesterol and Reducing Cardiovascular Risk: An Expert Interview With H. Bryan Brewer, Jr, MD |url=http://cme.medscape.com/viewarticle/520393 |access-date=8 October 2009 |first=H. Bryan |last=Brewer |date=27 December 2005 |archive-date=12 September 2019 |archive-url=https://web.archive.org/web/20190912024716/https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUub3JnL3ZpZXdhcnRpY2xlLzUyMDM5Mw==&ac=401 |url-status=live }}</ref><ref>{{cite journal | vauthors = Chapman MJ, Assmann G, Fruchart JC, Shepherd J, Sirtori C, ((European Consensus Panel on HDL-C)) | title = Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid—a position paper developed by the European Consensus Panel on HDL-C | journal = Current Medical Research and Opinion | volume = 20 | issue = 8 | pages = 1253–68 | date = Aug 2004 | pmid = 15324528 | doi = 10.1185/030079904125004402 | s2cid = 1009560 }}</ref> A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events.<ref name="ehjs">{{Cite journal|doi=10.1093/eurheartj/sul037 |title=Reducing risk by raising HDL-cholesterol: the evidence |year=2006 |last1=Drexel |first1=H. |journal=European Heart Journal Supplements |volume=8 |pages=F23–F29|doi-access=free }}</ref> Niacin products sold as "no-flush", ''i.e.'' not having side-effects such as "niacin [[Flushing (physiology)|flush]]", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation.<ref>{{cite journal | vauthors = Meyers CD, Carr MC, Park S, Brunzell JD | title = Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia | journal = Annals of Internal Medicine | volume = 139 | issue = 12 | pages = 996–1002 | date = Dec 2003 | pmid = 14678919 | doi = 10.7326/0003-4819-139-12-200312160-00009 | s2cid = 23980567 }}</ref> Both fibrates and niacin increase artery toxic [[homocysteine]], an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates.  A 2011 extended-release niacin (Niaspan) study was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke.<ref>{{cite web |url=https://www.npr.org/blogs/health/2011/05/28/136678665/study-boosting-good-cholesterol-with-niacin-did-not-cut-heart-risks?ps=sh_sthdl |title=Study: Boosting Good Cholesterol With Niacin Did Not Cut Heart Risks : Shots – Health News |publisher=NPR |date=2011-05-26 |access-date=2015-11-05 |archive-date=2015-03-27 |archive-url=https://web.archive.org/web/20150327121026/http://www.npr.org/blogs/health/2011/05/28/136678665/study-boosting-good-cholesterol-with-niacin-did-not-cut-heart-risks?ps=sh_sthdl |url-status=live }}</ref>

In contrast, while the use of [[statin]]s is effective against high levels of [[Low-density lipoprotein|LDL]] cholesterol, most have little or no effect in raising HDL cholesterol.<ref name="rhcrcr" /> [[Rosuvastatin]] and [[pitavastatin]], however, have been demonstrated to significantly raise HDL levels.<ref>{{cite web|url=http://www.cholesteroladvice.net/treatment-high-cholesterol-level/ |title=When is treatment indicated for high cholesterol level? |url-status=dead |archive-url=https://web.archive.org/web/20120730073614/http://www.cholesteroladvice.net/treatment-high-cholesterol-level/ |archive-date=30 July 2012 |df=dmy }}</ref>

[[Lovaza]] has been shown to increase HDL-C.<ref>[http://us.gsk.com/products/assets/us_lovaza.pdf]  {{webarchive|url=https://web.archive.org/web/20120301074136/http://us.gsk.com/products/assets/us_lovaza.pdf|date=1 March 2012}}</ref> However, the best evidence to date suggests it has no benefit for primary or secondary prevention of cardiovascular disease.

The [[peroxisome proliferator-activated receptor|PPAR]] modulator [[GW501516]] has shown a positive effect on HDL-C<ref>{{Cite journal|title=Effects of peroxisome proliferator-activated receptor alpha/delta agonists on HDL-cholesterol in vervet monkeys. | pmid=15716581 | doi=10.1194/jlr.M500002-JLR200 | volume=46 | issue=5 |vauthors=Wallace JM, Schwarz M, Coward P, Houze J, Sawyer JK, Kelley KL, Chai A, Rudel LL| journal=J Lipid Res | pages=1009–16 | year=2005| doi-access=free }}</ref> and an antiatherogenic where LDL is an issue.<ref>{{Cite journal|title=Sirtuin 1 Mediates the Actions of Peroxisome Proliferator-Activated Receptor δ on the Oxidized Low-Density Lipoprotein-Triggered Migration and Proliferation of Vascular Smooth Muscle Cells. | pmid=27573670 | doi=10.1124/mol.116.104679 | volume=90 | issue=5 |vauthors=Hwang JS, Ham SA, Yoo T, Lee WJ, Paek KS, Lee CH, Seo HG| journal=Mol Pharmacol | pages=522–529 | year=2016| doi-access=free }}</ref> However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats.<ref>{{cite conference | conference = 48th Annual Meeting of the Society of Toxicology | location = Baltimore | url = http://www.toxicology.org/AI/Pub/Tox/2009Tox.pdf | archive-url = https://web.archive.org/web/20150504013406/http://www.toxicology.org/AI/PUB/Tox/2009Tox.pdf | archive-date = 2015-05-04 | title = PS 895 - Rat carcinogenicity study with GW501516, a PPAR delta agonist | vauthors = Geiger LE, Dunsford WS, Lewis DJ, Brennan C, Liu KC, Newsholme SJ | date = 2009 | publisher = [[Society of Toxicology]] | page = 105 }}</ref><ref>{{cite conference | conference = 48th Annual Meeting of the Society of Toxicology | location = Baltimore  | url = http://www.toxicology.org/AI/Pub/Tox/2009Tox.pdf | archive-url = https://web.archive.org/web/20150504013406/http://www.toxicology.org/AI/PUB/Tox/2009Tox.pdf | archive-date = 2015-05-04 | title = PS 896 - Mouse carcinogenicity study with GW501516, a PPAR delta agonist. | vauthors = Newsholme SJ, Dunsford WS, Brodie T, Brennan C, Brown M, Geiger LE | date = 2009 | publisher = [[Society of Toxicology]] | page = 105 }}</ref>