Annurca Apple Polyphenols Reduce Cholesterol by Boosting Mitochondrial Activity

Written by Angeline A. De Leon, Staff Writer. Annurca polyphenol extract effectively lowers cholesterol and fatty acid synthesis by reprogramming hepatic cell metabolism and promoting mitochondrial respiration, lipolysis, and fatty acid beta-oxidation.

The prevention of cardiovascular disease (CVD), an epidemic accounting for about 30% of global deaths among men and women ¹, involves a focus on the reduction of cholesterol and blood pressure levels through a combination of healthy lifestyle changes and statin use. While statins, a lipid lowering medication, are the most commonly prescribed drugs for high cholesterol prevention ², nutraceuticals with cholesterol-lowering properties show the ability to prevent CVD ³ without the side-effects commonly associated with statins. More specifically, polyphenols such as procyanidin B2 demonstrate protective effects against two leading causes of CVD: metabolic disorder and atherosclerosis ⁴. Research indicates that dietary intake of Malus Pumila Miller cv Annurca, a native Italian apple with one of the highest contents of procyanidin B2 ⁵, is linked to reduced total cholesterol and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) ⁶). Tenore and colleagues (2017) ⁷ found that 800 mg of Annurca polyphenolic extract (AAE) was equally effective at improving cholesterol levels as Atorvastatin and Simvastatin, two commonly prescribed statins ⁸. While as effective as statins, it is unclear whether the cholesterol-lowering effects of polyphenols involve a similar molecular mechanism. In a 2019 study published in Nutrients, researchers at the University of Salerno in Italy performed a metabolic profiling of in vitro human liver cells (hepatocytes) treated with AAE in order to elucidate its mechanism of action.

The AAE used in the study was a non-standardized industrial procyanidinic extract of Annurca apple produced in Turin, Italy. Human hepatoma cells were cultured and cultivated in a medium supplemented with deuterium oxide (a form of water whose increased abundance indicates the biosynthesis of cholesterol). 400 mg/L AAE (an amount equivalent to the daily dosage recommended for human consumption), 10 µm Atorvastatin, 10 µm Simvastatin, or a vehicle solution (dimethylsulfoxide) of the same volume was then added to the cultures for 72 hours. In vitro mitochondrial staining of cells, Gas chromatography-mass spectrometry analyses were carried out to identify mitochondrial metabolite signals.

Analyses confirmed that AAE lowers cholesterol through an inhibition of cholesterogenesis in hepatoma cells: AAE treatment produced a reduction in total cholesterol levels (0.48 +/- 0.05 fold, p < 0.001), comparable to the lowering effects of Atorvastatin and Simvastatin (0.55 +/- 0.09 fold, p < 0.001; 0.52 /- 0.06, p < 0.001, respectively). AAE was also found to reduce the intensity of peaks corresponding to deuterated cholesterol molecules, indicating inhibition of newly synthesized cholesterol. Metabolite profiling revealed that AAE significantly elevated levels of intracellular free fatty acids, including palmitic acid (p < 0.001), oleic acid (p < 0.001), and stearic acid (p < 0.05), in the absence of evidence of deuterium incorporation, suggesting that AAE was not inducing the production of new fatty acids, but was inducing their release from intracellular lipid stores (lipolysis of membrane lipids). Finally, metabolic profiling indicated increased citrate (necessary for production of cholesterol) levels in AAE cells (1.86 +/- 0.06 fold, p < 0.001), which is associated with increased mitochondrial respiration (cellular energy production, adenosine triphosphate, ATP). This was confirmed by increased levels of fumarate (an intermediate of the Krebs cycle, the process of ATP production) in AAE treated cells (1.32 +/- 0.12 fold, p < 0.05), as well as immunofluorescence imaging which showed that cells treated with AAE had significantly increased mitochondrial activity, relative to vehicle cells (1.22 +/- 0.02 fold, p < 0.01).

Results of the study offer insight into the mechanism by which apple polyphenols induce their cholesterol-lowering effects. While statins reduce cholesterol levels by selectively inhibiting a key enzyme involved in cholesterol biosynthesis (hydroxymethyl glutaryl coenzyme A reductase), AAE appears to lower cholesterol by diverting the use of intermediate metabolites (citrate) for lipogenesis and cholesterogenesis to the Krebs cycle, promoting mitochondrial respiration and preventing synthesis of cholesterol. AAE was also associated with lipolysis of membrane lipids and greater overall mitochondrial activity. Based on findings, researchers conclude that AAE’s beneficial effects on cholesterol levels involve a different pathway than that of statins, one that influences the entire metabolic process of hepatoma cells. Results confirm AAE as one of the most potent nutraceuticals with cholesterol-lowering capabilities, making it a promising candidate for the prevention of CVD and other cardiometabolic disorders.

Source: Sommella E, Badolati N, Riccio G, et al. A boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells. Nutrients. 2019; 11: 163. DOI: 10.3390/nu11010163.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Posted March 11, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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