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Coenzyme Q10, Red Yeast Rice and Chitosan

Coenzyme Q10, Red Yeast Rice and Chitosan. Presented by: Confidential Group Members and Kaitlin Deason. Objectives. Discuss: Properties Pharmacokinetics Drug nutrient interactions Current research Indications. COEZYME Q10. Brief History of CoQ10.

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Coenzyme Q10, Red Yeast Rice and Chitosan

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  1. Coenzyme Q10, Red Yeast Rice and Chitosan Presented by: Confidential Group Members and Kaitlin Deason

  2. Objectives • Discuss: • Properties • Pharmacokinetics • Drug nutrient interactions • Current research • Indications

  3. COEZYME Q10

  4. Brief History of CoQ10 • First discovered by Prof. Fredrick L. Crane and co- workers in 1957. • Chemical structure was identified by Dr. Karl Folkers in 1958. • Chemical structure of Coenzyme Q10 is similar to vitamin K but it classified as a lipid. • Coenzyme Q10 known as CoQ10, ubiquinone, ubidecarenone

  5. Brief History of CoQ10 con’t. • In early seventies, CoQ10 was introduced into clinical therapy in Japan. • In mid eighties CoQ10 was further classified in the group of cardiovascular drugs for metabolic disturbances in Japan. • CoQ10 was effective used for mild congestive heart failure, symptoms such as edema, lung congestion and swollen liver.

  6. Description: • Coenzyme Q10 (2, 3 dimethoxy-5 methyl -6-decaprenyl bezoquinone) is further abbreviated as CoQ10, where Q is refers to the quinone chemical group and 10 refer to the number of isoprenyl groups associated with the center molecule

  7. Biosynthesis of CoQ10 • The biosynthesis of CoQ10 involves three steps: • 1. formation of benzoquinone structure. • 2. synthesis of the isoprene side chain. • 3. combining of these two substrates. • CoenzymeQ10 synthesizes through the mevalonate pathway • Biosynthesis of CoQ10 begins to decline at the age of twenty and further decreases rapidly after the age of forty

  8. CoQ10 • CoQ10 is found all the tissues in the body • Concentrations are relatively high in organs with high – energy turnover such as • Heart • Liver • Kidney • Pancreas

  9. Dietary sources of CoQ10 • Red meat products • Especially organ meats such as liver and heart • Oily fish such as salmon and tuna • Whole grain • Rapeseed oil

  10. Functions of Coenzyme Q10 • It plays a critical role during cellular respiration and ATP formation. • Functions as endogenous antioxidant by accepting electrons from free radicals • Acts as a proton translocator • Antioxidant activity of vitamin E also depends on the availability of CoQ10.

  11. CoQ10 Supplement • Third most popular dietary supplement in USA is CoQ10 behind Omega 3’s and Multivitamins • Coenzyme Q10 is artificially manufactured by fermenting beets and sugar cane with special strains of yeast Popular Brand names: • Co-Q-Max • Co-Q-Omega • Co-Q Max Daily • Co-Q-Rescue Serum

  12. Claims of CoenzymeQ10 • acts as an energy booster • acts as an antioxidant • strengthens the immune systems • counteracts muscle pain • improves heart function • maximizes oxygen uptake • increases exercise performance in cardiac patients. • used to treat gum disease

  13. Clinical studies also suggest: • CoQ10 supplementation may lower high cholesterol levels compared to healthy individuals of the same age • Increases sperm motility leading to enhanced fertility • Improves immune function in individuals with immune deficiencies (HIV/AIDS).

  14. Dosage forms • Tablets (chewable and non chewable). • Powder-filled capsules. • Soft gel containing oil suspension. • Oral spray • Ingredient for various cosmetic products such as: • Facial cream • Skin lotions

  15. Recommended dosages • Adults (above 18 years) is 30-100mg/day. • Therapeutic doses for adults generally range from 100-300mg/day. • High doses ranging from 1200-3000mg/day have also been used under medical supervision to treat early Parkinson’s disease.

  16. Possible side effects of CoQ10 supplements Side effects are mild and brief. Rxns may include: • Nausea • Vomiting • Stomach upset • Heartburn • Irritability • Diarrhea • Skin itching • Rash

  17. Pharmacokinetics of coenzymeQ10 Routes of Administration: • Enteral route (orally) • Bio availability CoQ10 is largely determined by the rate of absorption in the gastrointestinal tract. • Absorption of dietary CoQ10 is slow and limited due to its higher molecular weight and poor water solubility. • Rate of absorption can be enhanced by interaction with food or food component. • Parentaral route (topically)

  18. Pharmacokinetics of CoQ10 • Plasma peak of CoQ10 can be observed 2-6 hours after the oral administration. • Elimination half life is about 33 hours. • Data on metabolism of CoQ10 is limited. • Major routes of elimination are biliary excretion and fecal excretion.

  19. Drug Interactions • Certain cholesterol-lowering drugs or statins such as atorvastatin, cerivastatin and lovastatin tend to decrease the natural levels of CoQ10 in the body by decreasing the bio-synthesis. • CoQ10 has been shown to decrease the anti-coagulant effect of Warferin (Coumadin), resulting in higher dosage requirements for Warferin.

  20. Drug Interaction cont. • CoQ10 may enhance the effectiveness of certain blood pressure medications. • CoQ10 supplementation allows individuals to take lower doses of blood pressure medications such as Diltiazem (Cardizem), Metoprolol (Lopressor), and Enalapril (Vasotec). This should only be done under the observation of a medical doctor. • Coenzyme Q10 supplements may potentiate the effects of diuretic herbs such as licorice and horsetail by lowering blood pressure

  21. Article 1:Coenzyme Q10 in the treatment of hypertension. Coenzyme Q10 in the treatment of hypertension: a meta analysis of the clinical trials, Rosenfeldt, F.L., has, S.J., Krum, H., Hadj, A., Ng,K., Leong,J.Y., Watts, G.F. (2007), Journal Human hypertensions, 21(4), 297-306.

  22. Coenzyme Q10 in the treatment of hypertension con’t. Purpose : • To determine the effects of CoQ10 on hypertension by looking at several previously published clinical trials. Method : • Carried out a Meta analysis by reviewing and pooling the data of all the published clinical trials of CoQ10 for hypertension • Assessed the overall efficacy and consistency of therapeutic action and reported side effects.

  23. Coenzyme Q10 in the treatment of hypertension con’t. • Methods con’t • Twelve clinical studies, including three randomized controlled trials, one crossover study, and eight open label trials were used for this study. • Results: • After pooling the all published data authors concluded that CoQ10 decrease systolic blood pressure by up to 17mmHg, and diastolic blood pressure by up to 10mmHg without any significant side effects.

  24. Article 2:Antifatigue effects of coenzyme Q10 during physical fatigue. Antifatigue effects of coenzyme Q10 during physical fatigue, Mizuno, K., Tanaka, M., Nozaki, S., Mizuma, H., Ataka, S., Tahara, T., Sugino, T., Shirai, T., kajimoto, Y., kuratsune, H., kajimoto, O., Watanabe, Y. (2008), Nutrition, 24, 293-299.

  25. Antifatigue effects of coenzyme Q10 during physical fatigue • Purpose: • to investigate antifatigue effects of coenzyme Q10 during physical fatigue. • Method: • Seventeen healthy volunteers participated in a double blind, placebo controlled, triple crossover study. • Subjects were randomly administered oral CoQ10 (100 or 300mg/d) or placebo for eight days.

  26. Antifatigue effects of coenzyme Q10 during physical fatigue con't. • Results: • Suggest that CoQ10, enhances the exercise performance • A decrease in the subjective fatigue sensation was observed compared to the placebo group

  27. Article 3:Effects of acute and 14 day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. Effects of acute and 14 day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals, Cooke, M., Iosia, M., Buford,T., Shelmadine, B., Hudson,G.,Kerkisick, C., Rasmussen, C., Greenwood,M., Leutholtz, B., Willoughby, D., Kreider,R. (2008), Journal of the International society of sports nutrition,5:8, 251-258

  28. Coenzyme Q10 and exercise performance • Purpose: • To investigate the effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. • Method : • Twenty-two trained and nineteen untrained male and female subjects participated in a randomized, double blind, placebo controlled study. • Subjects were randomly administered either 100mg of a dextrose placebo or a fast melt CoQ10 supplement twice a day for 14 days

  29. Coenzyme Q10 and exercise performance con't. • Results: • Chronic and acute CoQ10 supplementation resulted in higher muscle concentration of CoQ10. • Both types of supplementation decreased oxidative stress • Tendency to increase the time to exhaustion of muscles during exercise was observed

  30. Article 4:Improvement of the oral bioavailability of coenzymeQ10. Improvement of the oral bioavailability of coenzymeQ10 by emulsification with fats and emulsifiers used in the food industry, Tanatukorn,P., Kawai, K., Hayanakawa, M., Hayashi, M., Kajiwara, K.(2009), Food Science & Technology,42,385-390.

  31. Improvement of the oral bioavailability of coenzymeQ10 • Purpose: • To investigate the effect of emulsification of CoenzymeQ10 on oral bioavailability by using five commercially available fats and four types of emulsifiers. • Methods: • Five healthy volunteers participated in this experiment and administered a model emulsified CoQ10 (100mg) product and commercially available product (100mg).

  32. Improvement of the oral bioavailability of coenzymeQ10 con't. • Methods: • Concentration levels of CoQ10 and cholesterol in plasma were determined using High Performance Liquid Chromatographic system • Conclusion: • The results suggest that the oral bio availability of the model emulsified product was slightly greater than that of commercially available product.

  33. Take home message • CoQ10 supplements can be used to increase the CoQ10 levels in various tissues in the body, although there is no adequate scientific evidence to prove the effectiveness of replacing of CoQ10 with supplements • As a dietitian it is important to be aware that there is not enough scientific evidence to prove the effectiveness CoQ10. However, if the body is deficient in CoQ10, it may be beneficial to bring up these levels. Other uses are not proven and are just claims.

  34. Red Yeast Rice http://a.abcnews.com/images/GMA/redyeastrice_090615_mn.jpg

  35. Red Yeast Rice History • Used for thousands of years in China dating back to the Tang Dynasty ~800 AD as a food colorant and preservative. • A pharmacist during the Ming Dynasty (1368-1644 AD) published claims: • Can be used to improve health • Treatment in mild gastric disturbance • Blood circulation • Improve spleen and stomach health

  36. Red Yeast Rice Today • Today, the growth of consumer spending on red yeast products for health use escalated nearly 80% in the United States from 2005 to 2008 reaching estimated sales of $20 million in 2008.

  37. What is Red Yeast? Red Yeast Rice is fermented rice • Fermented by a red colored yeast called Monascus purpureus. • It gives its distinct appearance • It is still found in some Asian foods and used as a dietary supplement for health purposes. Picture: http://a.abcnews.com/images/GMA/redyeastrice_090615_mn.jpg

  38. Red Yeast Rice • RYR is made of monacolins, isoflavonoids, monounsaturated fats, and sterols. • RYR has a “natural statin” similar to lovastatin called monacolin K • Monacolin K inhibits endogenous cholesterol synthesis by inhibiting enzyme 5-hydroxy-3-methylglutaryl-coenzyme reductase (HMGCR). • HMGCR enzyme is the rate limiting step for cholesterol synthesis.

  39. Red Yeast Rice’s Monacolin K: Mechanism of Action X Monacolin K or X http://www6.ufrgs.br/favet/imunovet/molecular_immunology/cholesterol_synthesis.gif

  40. Red Yeast Rice Uses Scientifically proven • Lowers cholesterol in hyperlipidemia patients claims • Helps blood circulation • Treatment of dyslipidemia in HIV patients • Indigestion. • Diarrhea. • Improving blood circulation. • Spleen and stomach problems. • Other conditions.

  41. Red Yeast Rice Generic Names • Chinese Red Yeast Rice • Zhi Tai • Xuezhikang • XZK • Angkak • Monascus Purpureus Went • Red Yeast Brand Names • Red Rice Yeast • Cholestin • Chol-Reg

  42. Red Yeast Rice Forms and Dosage Recommendations Red yeast rice is available in United States • In capsule and tablet form • Teas and tinctures (extract) • Each capsule or tablet usually contains 600 mg of RYR and may contain 5-10 mg of monacolin K • The recommended dosage for adults is 1200mg to 2400 mg once or twice daily • It is not recommended for children

  43. Pharmacokinetics RYR • Little is known at this time • It is theorized monacolin K may have similar absorption, metabolism and excretion as lovastatin. • Lovastatin is absorbed in intestines and metabolized by CYP3A4 in the liver and excreted in bile and urine. • Research is needed for the official pharmacokinetics of RYR.

  44. Red Yeast Rice Side Effect Minor Side Effects • Upset stomach, Heartburn, Gas, Bloating, • Headache, Dizziness and others. Severe Side Effects • Myalgia (muscle pain) • Rhabdomyolysis (muscle fiber breakdown) • Hepatoxicity (liver toxicity) • Kidney problems http://www.alcis.com/images/muscle_pain.jpg

  45. Drug-Supplement Interaction May cause hepatoxicity when combined with: • Acetaminophen (pain reliever) • Carbamazepine (anti-seizure) • Phenytoin (anti-seizure) • Isoniazid (treatment of TB) • Methotrexate (antimetabolite-tx of cancer) • Fluconazole (antifungal tx) • Erythromycin (antibiotic) • Other Statins

  46. Drug- Supplement Interaction May cause muscle problems when combined with: • Cyclosporine (immunosuppressant) • Niacin (reduce cholesterol and TG) • Gemfibrozil (lower lipid levels) • Other Statins

  47. Supplement- Supplement Interactions • RYR is also known to lower coenzyme Q-10 levels. • St. John’s Wort can lower serum levels of statin drugs and so it may reduce the effects of red yeast rice.

  48. Food- Supplement Interaction • Taken with food increases absorption • Grapefruit juice decreases metabolism of RYR • Alcohol may cause liver damage

  49. Controversy in Red Yeast Rice • In 2001, a RYR product called Cholestin, manufactured by a company called Pharmanex, was found to contain the drug lovastatins. • Because it contained lovastatin, it cannot be sold without a prescription. • In 2007, the FDA released a safety warning against three products: (1) Red yeast rice from Nature’s Value Inc. and (2) Red Yeast Rice/ Policosanol Complex from Kabco Inc., and (3) Cholestrix sold by Sunburst Biorganic. • May cause kidney or muscle problems

  50. Controversy in Red Yeast Rice cont. • Citrinin • Byproduct and contaminant of RYR fermentation • Nephrotoxin -may cause kidney failure • Variability of monacolin K in RYR • An analysis of 9 proprietary brands of RYR determined that different amount of monacolin K found in RYR products despite label information (0.15-3.37 mg MK /capsule). • Seven out of nine brands contained citrinin

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