Plasma Clearance of Lovastatin Versus Chinese Red Yeast Rice in Healthy Volunteers

Objectives: It is now accepted that inhibition of cholesterol biosynthesis is effective in the primary and secondary prevention of heart disease. However, the perceived side-effects on muscle and liver reduce the general acceptance of statin drug therapy as well as compliance over the long term, which is necessary for prevention efforts to be successful. Chinese red yeast rice (CRYR) is a supplement containing lovastatin (monacolin K), eight other monacolins, pigments, tannins, and other phytochemicals. The authors previously reported on a double- blind placebo-controlled trial of CRYR supplement in 80 individuals demonstrating a significant decrease in cholesterol levels from 250 mg/dL to 210 mg/dL over 8 weeks independent of diet. The current study compared the pharmacokinetics of CRYR with lovastatin at the same bioeffective dose for lowering cholesterol. Methods: Eleven (11) healthy volunteers were randomized to a crossover study taking 2400 mg CRYR or 20 mg of lovastatin. Results: The Cmax and area under the curve (AUC) of lovastatin were 22.42 ng/mL, and 80.47 higher than CRYR (p = 0.001 and 0.002, respectively). The Cmax for lovastatin hydroxy-acid was 36.63 ng/mL higher than the Cmax of CRYR hydroxy-acid (p = 0.001). The AUC of lovastatin hydroxy-acid was 258.5 greater than that of CRYR (p = 0.001). Conclusions: The results suggested that the effect of CRYR on the cholesterol concentration might be caused by the additive and/or synergistic effects of monacolin K with other monacolins and substances in CRYR. It may lead to the ultimate development of a botanical supplement based on CRYR

Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice

Background: Ellagic acid (EA) and hydrolyzable ellagitannins (ETs) are dietary polyphenols found in fruits and nuts and implicated with potent antioxidant, anticancer and antiatherosclerotic biological properties. Unfortunately, there are no reports on bioavailability studies of EA or ETs in the human body. Therefore we conducted in vivo studies whereby a human subject consumed pomegranate juice (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins, the major fruit ellagitannin). Methods: A rapid plasma extraction procedure utilizing acidic precipitation of proteins, followed by HPLC-UV analyses was employed. Results: EA was detected in human plasma at a maximum concentration (31.9 ng/ml) after 1h post ingestion but was rapidly eliminated by 4h. The calibration curve for quantification of EA was linear (r2 = 0.9975) over the concentration range from 1000 to 15.6 ng/ml. Conclusions: Since EA has reportedly strong affinity for proteins and poor absorption in small animals, further studies to investigate whether the presence of free EA in human plasma may be due to its release from the hydrolysis of ETs, facilitated by physiological pH and/or gut microflora action, is warranted. EA can be considered as a biomarker for future human bioavailability studies involving consumption of ETs from food sources

Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectroscopy

Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, anticancer, antiatherosclerotic and anti-neurodegenerative properties. Identification of food phenolics is necessary since their nature, size, solubility, degree and position of glycosylation and conjugation influence their absorption, distribution, metabolism and excretion in humans. Freeze-dried whole strawberry fruit powder and strawberry fruit extracts were analyzed by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) methods. Phenolics were identified as ellagic acid (EA), EA-glycosides, ellagitannins, gallotannins, anthocyanins, flavonols, flavanols and coumaroyl glycosides. The anthocyanidins were pelargonidin and cyanidin, found predominantly as their glucosides and rutinosides. The major flavonol aglycons were quercetin and kaempferol found as their glucuronides and glucosides. LC-ESI-MS/MS methods differentiated EA from quercetin conjugates since both aglycons have identical molecular weights (302 g/mol). The identification of strawberry phenolics is necessary to generate standardized materials for in vitro and in vivo studies and for the authentication of strawberry-based food products

Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study.

Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism

Vertical Sleeve Gastrectomy Attenuates the Progression of Non-Alcoholic Steatohepatitis in Mice on a High-Fat High-Cholesterol Diet

ObjectiveTo determine whether vertical sleeve gastrectomy (VSG) attenuates fibrosis in mice on a high-fat high-cholesterol (HFHC) diet.BackgroundBariatric surgery mitigates non-alcoholic steatohepatitis in 85-90% of obese patients. While animal models demonstrate similar results on a high-fat diet, none have observed the effects of bariatric surgery on a combined HFHC diet.MethodsMice on a HFHC diet were used to confirm the development of hepatic fibrosis at 8 (n = 15) and 24 (n = 15) weeks. A separate cohort of mice on a HFHC diet for 12 weeks was subjected to either VSG (n = 18) or sham (n = 12) operations and remained on a HFHC diet for an additional 20 weeks. Changes in weight, dyslipidemia, and the development of steatosis and fibrosis were documented. Serum was obtained for bile acid analysis by liquid chromatography and mass spectrometry, while hepatic gene expression by RT-PCR was performed to evaluate intrahepatic lipid metabolism.ResultsHepatic steatosis and fibrosis developed after 8 weeks on the HFHC diet. After VSG, mice demonstrated a sustained decrease in weight with a significant decrease in fibrosis compared to sham mice. Serum total cholesterol, HDL, and LDL were significantly reduced following surgery, while serum bile acids were significantly elevated. Intra-hepatic cholesterol excretion was not upregulated based on hepatic gene expression of CYP7A1 and ABCG5/8.ConclusionsVSG attenuates the development of hepatic fibrosis in diet-induced obese mice, presumably through enhancement of cholesterol elimination at the intestinal level