Editing Low-density lipoprotein (section)

====Not approved as drugs ====
* Several [[CETP inhibitor]]s have been researched to improve HDL concentrations, but so far, despite dramatically increasing HDL-C, have not had a consistent track record in reducing atherosclerosis disease events. Some have increased mortality rates compared with placebo.
* Some [[tocotrienol]]s, especially delta- and gamma-tocotrienols, are being promoted as statin alternative non-prescription agents to treat high cholesterol, having been shown in vitro to have an effect. In particular, gamma-tocotrienol appears to be another HMG-CoA reductase inhibitor, and can reduce cholesterol production.<ref>{{Cite journal |last1=Song |first1=B.L. |last2=DeBose-Boyd, R.A. |year=2006 |title=Insig-Dependent Ubiquitination and Degradation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Stimulated by Delta- and Gamma-Tocotrienols |journal=J. Biol. Chem. |volume=281 |issue=35 |pages=25054–25601 |doi=10.1074/jbc.M605575200 |pmid=16831864 |doi-access=free}}</ref> As with statins, this decrease in intra-hepatic (liver) LDL levels may induce hepatic LDL receptor up-regulation, also decreasing plasma LDL levels. As always, a key issue is how benefits and complications of such agents compare with statins—molecular tools that have been analyzed in large numbers of human research and clinical trials since the mid-1970s.{{cn|date=February 2025}}
* [[Phytosterol]]s are widely recognized as having a proven LDL cholesterol lowering efficacy'<ref>{{Cite web |last=European Food Safety Authority, Journal |year=2010 |title=Scientific opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations |url=http://www.efsa.europa.eu/en/efsajournal/pub/1813}}</ref> A 2018 review found a dose-response relationship for phytosterols, with intakes of 1.5 to 3&nbsp;g/day lowering LDL-C by 7.5% to 12%,<ref>{{Cite journal |last1=Trautwein |first1=Elke |last2=Vermeer |first2=Mario |last3=Hiemstra |first3=Harry |last4=Ras |first4=Rouyanne |date=7 September 2018 |title=LDL-Cholesterol Lowering of Plant Sterols and Stanols—Which Factors Influence Their Efficacy? |journal=Nutrients |publisher=MDPI AG |volume=10 |issue=9 |page=1262 |doi=10.3390/nu10091262 |pmc=6163911 |pmid=30205492 |doi-access=free}}</ref> but reviews as of 2017 had found  no data indicating that the consumption of phytosterols may reduce the risk of CVD.<ref>{{Cite journal |last1=Cabral |first1=Carlos Eduardo |last2=Klein |first2=Márcia Regina Simas Torres |year=2017 |title=Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases |journal=Arquivos Brasileiros de Cardiologia |publisher=Sociedade Brasileira de Cardiologia |volume=109 |issue=5 |pages=475–482 |doi=10.5935/abc.20170158 |pmc=5729784 |pmid=29267628}}</ref> Current supplemental guidelines for reducing LDL recommend doses of phytosterols in the 1.6-3.0&nbsp;grams per day range (Health Canada, EFSA, ATP III, FDA) with a 2009 meta-analysis demonstrating an 8.8% reduction in LDL-cholesterol at a mean dose of 2.15&nbsp;gram per day.<ref>{{Cite journal |last1=Demonty |first1=I. |last2=Ras |first2=R.T. |last3=van der Knaap |first3=H.C. |last4=Duchateau |first4=G.S. |last5=Meijer |first5=L. |last6=Zock |first6=P.L. |last7=Geleijnse |first7=J.M. |last8=Trautwein |first8=E.A. |date=Feb 2009 |title=Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. |journal=The Journal of Nutrition |volume=139 |issue=2 |pages=271–84 |doi=10.3945/jn.108.095125 |pmid=19091798 |doi-access=free}}</ref>