FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

In continuation of my update on ezetimibe and atorvastatin
FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

Naringenin (grape fruits) initiates increased fatty acid oxidation, inhibits vLDL production...

Naringenin is a flavonoid that is considered to have a bioactive effect on human health as antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator. It is the predominant flavanone in grapefruit. It  has been shown to have an inhibitory effect on the human cytochrome P450 isoform CYP1A2, which can change pharmacokinetics in a human (or orthologous) host of several popular drugs in an adverse manner, even resulting in carcinogens of otherwise harmless substances. Naringenin has also been shown to reduce hepatitis C virus production by infected hepatocytes (liver cells) in cell culture. This seem to be secondary to Naringenin ability to inhibit the secretion of very-low-density lipoprotein by the cells.It has been reported that Naringenin,  lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet. 

Now interestingly, researchers from Hebrew University of Jerusalem and Massachusetts General Hospital (MGH) report that naringenin activates a family of small proteins, called nuclear receptors, causing the liver to break down fatty acids. In fact, the compound seems to mimic the actions of other drugs, such as the lipid-lowering Fenofibrate and the anti-diabetic Rosiglitazone, offering the advantages of both. If the results of this study extend to human patients, this dietary supplement could become a staple in the treatment of hyperlipidemia, type-2 diabetes, and perhaps metabolic syndrome.

The researchers demonstrated that the compound activates PPARα and PPARγ by dramatically increasing the levels of a co-activator peptide of both, called PGC1α. At the same time, naringenin bound directly to LXRα, blocking its activation. These effects culminated with increased fatty acid oxidation and the inhibition of vLDL ('bad cholesterol') production.  

"It is a fascinating find," says Yaakov Nahmias, PhD, of the Hebrew University of Jerusalem the paper's senior author. "We show the mechanism by which naringenin increases two important pharmaceutical targets, PPARα and PPARγ, while blocking a third, LXRα. The results are similar to those induced by long periods of fasting".

Authors claim that, it is a process which is similar to the Atkins diet, without many of the side effects and the liver behaves as if fasting, breaking down fatty acids instead of carbohydrates. 

"Dual PPARα and PPARγ agonists, like naringenin, were long sought after by the pharmaceutical industry," says Nahmias, "but their development was plagued by safety concerns. Remarkably, naringenin is a dietary supplement with a clear safety record. Evidence suggests it might actually protect the liver from damage."....

 Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012399

No Firm Conclusions About HDL Cholesterol Can Be Drawn from JUPITER Sub-Analysis

The European Society of Cardiology (ESC) is concerned that interpretations of a paper about cholesterol, published in the Lancet , could act to deter ongoing research efforts into developing new therapeutic strategies to increase high density lipoprotein (HDL) cholesterol. Caution, the ESC experts advise, should be displayed in the interpretation of the results.....

In the Lancet study, Paul Ridker and colleagues, from Brigham and Women's Hospital (Boston, MA, USA), undertook a retrospective post-hoc analysis of the JUPITER trial. The results show that if a normal, healthy individual has level of low density lipoprotein (LDL), known as "bad cholesterol", substantially lowered with a potent statin, then the level of HDL "good cholesterol" in that person no longer bears any relation to the remaining cardiovascular risk. More.....

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960713-1/fulltext