Coenzyme Q10, Red Yeast Rice and Chitosan

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Presented by: Confidential Group Members and Kaitlin Deason

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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. - PowerPoint PPT Presentation

Transcript of Coenzyme Q10, Red Yeast Rice and Chitosan

Page 1: Coenzyme Q10, Red Yeast Rice and Chitosan

Presented by:Confidential Group Members and Kaitlin

Deason

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Discuss:PropertiesPharmacokineticsDrug nutrient interactionsCurrent researchIndications

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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

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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.

Brief History of CoQ10 con’t.

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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

Description:

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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

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CoQ10 is found all the tissues in the body Concentrations are relatively high in

organs with high – energy turnover such as Heart LiverKidney Pancreas

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Red meat productsEspecially organ meats such as liver and

heartOily fish such as salmon and tunaWhole grainRapeseed oil

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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.

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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-MaxCo-Q-Omega

•Co-Q Max Daily•Co-Q-Rescue Serum

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• 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

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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).

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Tablets (chewable and non chewable).Powder-filled capsules.Soft gel containing oil suspension.Oral sprayIngredient for various cosmetic products

such as: Facial cream Skin lotions

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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.

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Side effects are mild and brief. Rxns may include:

• Nausea• Vomiting• Stomach upset• Heartburn

IrritabilityDiarrheaSkin itchingRash

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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)

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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.

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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.

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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

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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.

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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.

Coenzyme Q10 in the treatment of hypertension con’t.

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• 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.

Coenzyme Q10 in the treatment of hypertension con’t.

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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.

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• 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.

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Results:Suggest that CoQ10, enhances the

exercise performance A decrease in the subjective fatigue

sensation was observed compared to the placebo group

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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

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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

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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

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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.

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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).

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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.

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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.

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http://a.abcnews.com/images/GMA/redyeastrice_090615_mn.jpg

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• 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

Red Yeast Rice History

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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.

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Red Yeast Rice is fermented riceFermented by a red colored yeast

called Monascus purpureus. It gives its distinct appearanceIt 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

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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.

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XMonacolin K or

Xhttp://www6.ufrgs.br/favet/imunovet/molecular_immunology/cholesterol_synthesis.gif

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Scientifically proven Lowers cholesterol in hyperlipidemia

patients claimsHelps blood circulation Treatment of dyslipidemia in HIV patients Indigestion. Diarrhea. Improving blood circulation. Spleen and stomach problems. Other conditions.

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Generic Names Chinese Red Yeast

RiceZhi TaiXuezhikangXZKAngkakMonascus Purpureus

WentRed Yeast

Brand Names Red Rice Yeast CholestinChol-Reg

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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

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Little is known at this timeIt 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.

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Minor Side EffectsUpset 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

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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

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May cause muscle problems when combined with:

Cyclosporine (immunosuppressant) Niacin (reduce cholesterol and TG) Gemfibrozil (lower lipid levels) Other Statins

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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.

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Taken with food increases absorptionGrapefruit juice decreases metabolism of

RYRAlcohol may cause liver damage

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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

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Citrinin Byproduct and contaminant of RYR

fermentationNephrotoxin -may cause kidney failure

Variability of monacolin K in RYRAn 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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Women who are pregnant or breastfeeding

People with asthmaKidney diseaseRecent surgeryOrgan transplantPeople who >2 alcohol beverages per dayPeople with liver disease

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Venero, C.V., Venero, J.V., Wortham, D.C., & Thompson, P.D. (2010).

Lipid-lowering efficacy of red yeast rice in a population intolerant to statins. The American Journal of

Cardiology, 105(5), 664-666.

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PurposeObservational study evaluated the lipid-lowering

efficacy of RYR in patients intolerant to statins.

MethodsThey reviewed 1,400 medical charts and

assessed 25 patients with hyperlipidemia who were on RYR for >4 weeks.

They assessed the lipid levels before and after treatment with 1200 mg daily of RYR

Venero, Venero, Wortham & Thompson (2010).

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ResultsTreatment took place over a 74+39 day

period Average total cholesterol decreased by 15%LDL cholesterol decreased by 21%Triglycerides decreased by 6%, and HDL decreased by 0.5% Conclusion 92% tolerance for RYR, it may be a reliable

alternative for the treatment of hyperlipidemia when patients are intolerant to statin drugs.

Venero, C.V., Venero, J.V., Wortham, D.C., & Thompson, P.D. (2010). Lipid-lowering efficacy of red yeast rice in a population intolerant to statins. The American Journal of Cardiology, 105(5), 664-666.

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Halbert , S. C., French, B., Gordon, R. Y., Farrar, J. T., Schmitz, K., Morris, P. B., Thompson, P. D., Rader, D.J., & Becker, D.J. (2010). Tolerability of red yeast rice (2,400 mg twice daily) versus Pravastatin (20

mg twice daily) in patients with previous statin intolerance. The American Journal of Cardiology,

105(2), 198-204.

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PurposeThe aim of this FDA approved study

was to compare the effects of RYR and Pravastatin on the rate of myalgia recurrence in subject with a history of Statin associated myalgia (SAM).

Methods For 12 weeks participants took either

2400 mg twice daily RYR, 20 mg twice daily of Pravastatin, or a placebo.

All were educated on the Therapeutic Lifestyle Changes diet.

Halbert et al., (2010).

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Results • Both treatments showed a low rate of recurrent

myalgia, and significantly lowered the amount of LDL, total cholesterol, triglycerides and slightly lowered HDL.

• There were some dropouts in both groups but was not considered statistically significant (p=0.99).

Conclusion • The low rate of side effects for RYR treatment

may be related to the natural low dose of MK (<10 mg/day).

• The other components of RYR lowered cholesterol to a greater degree than expected.

Halbert et al., (2010).

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Li, J. J., Lu, Z. L., Kou, W. R., Chen, Z., Wu, Y. F., Yu, X. H., & Zhao, Y. C. (2009). Beneficial impact of Xuezhikang on

cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction

from the China Coronary Secondary Prevention Study (CCSPS). Journal of Clinical Pharmacology, 49(8), 947-956.

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Purpose:To analyze the impact of Xuezhikang on

cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction (MI).

Method:Randomized, double blind, placebo

controlled, parallel-group clinical trial. The Xuezhikang group had 772 participants

who received 0.6 g twice dailyThe placebo group had 758 participants.Xuezhikang contained 2.5-3.2 mg/capsule of

MK, a small amount of LV hydroxyl acid, ergosterol and some other elements.

Li, Lu, Kou, Chen, Wu, Yu, & Zhao (2009).

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Results After an average of 4.5 years in the

intervention, the results showed that participants who were treated with RYR had less cardiovascular events than the placebo group. Xuezhikang therapy significantly reduced risk of

nonfatal MI by 53.4% and coronary death by 29.2% compared to placebo.

RYR therapy significantly reduced the total number of strokes, cancer death, and total cancer compared to placebo.

Conclusion Xuezhikang may effectively reduce

cardiovascular events and other morbidities in Chinese elderly hypertensive patients with previous MI. Li et al., (2009).

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Hong, M. Y., Seeram, N. P., Zhang, Y., & Heber, D. (2008) Anticancer effects of Chinese red

yeast rice versus monacolin K alone on colon cancer cells. Journal of Nutritional Biochemistry,

19(7), 448-458.

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Purpose: To examine the effects of RYR on two

types of colon cancer cells, HCT-116 and HT-29, related to cell proliferation.

Also to evaluate the colon cancer cells’ apoptosis, and transcription levels of HMGCR and sterol response element binding protein-2 (SREBP-2) with RYR.

Hong, Seeram, Zhang, & Heber (2008)

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Methods• They examined lovastatin, RYR, MK-free

RYR, pigment-rich fraction RYR (PF-RYR), monacolin-rich fraction RYR (MF-RYR) on colon cancer cell proliferation in vitro.

• Apoptosis was assessed by Cell Death Detection ELISA.

• RNA was extracted, reverse transcription was determined.

• Gene expression of HMGCR and SREBP-2 were determined quantitatively with a detector.

Hong, Seeram, Zhang, & Heber (2008)

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Results: RYR and PF-RYR demonstrated the most

anti-proliferation and pro-apoptosis activity in both cancer cells compared to other types of RYR and lovastatin.

RYR did not elevate the gene expression of HMGCR or SREBP-2 unlike lovastatin.

Hong, Seeram, Zhang, & Heber (2008)

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Conclusion:• Anti-proliferation and pro-apoptosis

activity may be related to monacolin K and pigment compounds found in RYR.

Further investigation is needed in animal models and ultimately human subjects to determine if RYR will in fact act as a possible treatment for colon cancer.

Hong, Seeram, Zhang, & Heber (2008)

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RYR is prescribed for statin-intolerant patients may be well tolerated.

RYR may lower the chance of cardiovascular events in elderly with previous MI.

Inhibition of cancer cell proliferation and gene expression by RYR are still in its early stages of research.

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Red yeast rice may be sought out more for treatment of hyperlipidemia.

Red yeast rice recommendations should be used with caution.

It is important to inform patients of possible side effects, efficacy and safety with RYR use.

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http://planning.up.nic.in/innovations/inno3/fi/chitosan.htm

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Chitin and chitosan were discovered in 1982 during a project sponsored by The Ministry of Agriculture and Fisheries, in Japan.

Deacetylated form of chitin- isolated from mushrooms and the shells of crustaceans, including crabs, lobsters, and shrimp

Aside from cellulose, chitosan is the most abundant natural polymer

There are no significant dietary sources(http://www.chitopia.co.kr/e-book004.html)

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Water purification Soil enrichmentAntioxidant properties to prolong shelf-lifeServes as a functional foodControlled drug releaseAntitumor and wound healingUsed much less as a supplement that for

its other uses

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Lowers cholesterol

Reduces fat absorption reduces weight

Reduces dental plaque formation

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Available in 500 mg capsules Recommended dosage usually around

1500 mg to 1.5 g per day Generic names: chitosan, chitin, and

kitosan, Brand names: Chitosan Plus™, Fat

Absorb™, and Fat Blocker™

http://www.womenbeautycare.com/2010/12/overweight-women-develop-osteoporosis.html

http://ww

w.vitam

instoday.com.au/

blocker-caps-p-683.html

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May cause gas, constipation and nausea Should not be taken by:

People with shellfish allergies (because derived from shellfish)

Pregnant or breast feeding womenChildren Those with malabsorptive disorders

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Functions like fiber by trapping and eliminating fat and cholesterol

Chitosan gains a positively charged, free amino acid group allowing it to attach to negatively charged compounds

Chitosan binds to fatty acids, bile acids or salts, cholesterol, and other molecules causing decreased absorption and excretion of these compounds

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Little information is knownSimilar in structure to cellulose and seems

to function like thisNot absorbed by the intestines and is

primarily eliminated through the feces

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May decrease absorption of fat soluble vitamins

May slow gastric emptying leading to delayed absorption of nutrients and drugs

May interact with absorption and metabolism of some drugs

May alter activity of CYP 450

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Gades, M. D. & Stern, J. S. (2005). Chitosan supplementation and fat

absorption in men and women. Journal of the American Dietetic

Association, 105(1), 72-77.

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Purpose: To determine the effect of chitosan on fecal fat

excretion Methods:

12 men and 12 women completed 12-day trial

Cross-over design5 meals per day were provided. Ea.

contained at least 15g fat for men and 10g fat for women

Supplemented 6 days with 2.5 g chitosan. 500mg per meal

Gades & Stern (2005).

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Results:non-clinically significant increase in fecal

fat excretion in men but no change in women

no benefit from chitosan supplementation Conclusion:

Study is limited by short duration and small sample size

Chitosan is not an effective way to prevent fat absorption and does not aid in weight loss

Gades & Stern (2005).

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Nadai, M., Tajiri, C., Yoshizumu, H., Suzuki, Y., Zhao, Y. L., Kimura, M.,

Tsunekawa, Y., Hasegawa, T. (2006). Effect of chitosan on gastrointestinal absorption of water-insoluble drugs following oral administration in rats.

Biological and Pharmaceutical Bulletin, 29(9), 1941-1946.

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Purpose: to determine how chitosan effects GI

absorption of the drugs indomethacin, griseofulvin, acetaminophen, and cephalexin, in rats

Background:Indomethacin and griseofulvin are water-

insolubleAcetaminophen and cephalexin are water-

soluble drugs

Nadai et al., (2006).

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Methods:Eight to nine week old rats were pre-treated

with either 5 mg/kg of chitosan, 25 mg/kg of chitosan, or a control

After 15 minutes, one of the four drugs was administered. Cmax, Tmax, and AUC were measured

Results:No effect on absorption of water-soluble drugsPre-treatment with 25 mg/kg of chitosan

significantly delayed Tmax for the water-insoluble drugs. Cmax and AUC were unchanged compared to the control Nadai et al., (2006).

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Conclusion:The results indicate that chitosan may alter

(decrease) absorption of water-insoluble drugs but the mechanisms of action are still unknown

Effect in human model is yet to be determined, but this study provides good evidence that human studies are needed

Nadai et al., (2006).

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Tapola, N. S., Lyyra, M. L., Kelehamainen, R. M., Sarkkinen, E. S., & Schauss, A. G. (2008). Safety aspects and cholesterol-lowering

efficacy of chitosan tablets. Journal of the American College of

Nutrition, 27(1), 22-30.

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Purpose:To determine how fat-soluble vitamins and

cholesterol concentrations are effected by chitosan supplementation

Methods:56 individuals not previously taking cholesterol

lowering drugs participated in 8 week studySubjects were randomly assigned to receive 4.5 g

of chitosan (n=15), 6.75 g of chitosan (n=12), glocomannan, an active control (n=15), or a placebo (n=14)

Participants were instructed to take 6 tablets, 3x per day, 15 minutes before breakfast, lunch and dinner. No changes were made to the diet.

Tapola, Lyyra, Kelehamainen, Sarkkinen, & Schauss (2008).

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Methods con’t:Baseline weight, blood pressure, and blood

samples were collected and compared with weight, blood pressure, and blood samples collected at the conclusion of the trial.

Results:No significant changes in fat-soluble

vitamin levels, total cholesterol levels, LDL cholesterol levels, body weight, or blood pressure in either chitosan treatment group

There were no serious adverse events reported, and while some experienced nausea, constipation, and heartburn, these side effects were not statistically significant

Tapola, et al., (2008).

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Conclusion:The weaknesses of this study- the small

sample size, short duration, and the variability in participant diets. In addition, the actual amount of chitosan being consumed before each meal may not have been the same because some of the pills were placebos

The main findings indicate that chitosan supplementation is a safe supplement, but it is not effective in lowering cholesterol

Tapola, et al., (2008).

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Yao, H., Lii, C., Chou, R., Lin, J., Yang, H., & Chiang, M. (2010). Effect of

chitosan on hepatic drug-metabolizing enzymes and oxidative stress in rats fed low- and high-fat diets. Journal of Agricultural and

Food Chemistry, 58(8), 5187-5193.

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Purpose:To determine the effect of chitosan on the

enzymes CYP P450, GST, UGT, and oxidative stress in rats

Background:CYP 450 is a catalyst for phase I

biotransformation of drugs GST and UGT are catalysts for phase II

biotransformationEach of the enzymes play an important role

in drug metabolism, and without them oxidative stress increases

Yao, Lii, Chou, Lin, Yang, & Chiang (2010).

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Methods:6 week old Wistar rats were randomly

assigned to recieve one of four diets. a low fat (LF) diet with either chitosan or

a control (cellulose)a high fat (HF) diet with either chitosan

or a control Feeding occurred for 4 weeks and then the

rats were killed after a 12-hour fast. Blood samples were taken to determine

oxidative stress and the effect on the drug metabolizing enzymes. Several CYP enzymes were examined for expression and activity.

Yao et al., (2010).

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Results:Chitosan decreased the expression of total CYP,

and this was most prominent in the rats fed a HF diet

The activity of CYP 3A and CYP 1A1 were significantly decreased by chitosan, but no effect was seen on other CYP enzymes. In addition, chitosan with either diet significantly decrease activity of GST but not UGT

Chitosan increased oxidative stress, which is to be expected because there is less of an effect from the phase I and phase II enzymes resulting in more free radicals

Yao et al., (2010).

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Conclusion:Overall, this study provides important

evidence that chitosan may decrease drug metabolism, and people taking chitosan need to be advised about this possible drug interaction in order to prevent toxicity or further adverse effects.

However, studies in human models are needed to confirm the results of this study.

Yao et al., (2010).

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Studies indicate little effect from supplementation

Evidence that chitosan may interact with some drugs and nutrients by altering their absorption and/or metabolism

Chitosan is currently considered a safe, natural, nontoxic product

There is no regulation of this supplement by the Food and Drug Administration

There are no long-term studies regarding safety

Page 95: Coenzyme Q10, Red Yeast Rice and Chitosan

No real benefit from chitosanPossible drug/nutrient interactions should

be conveyed to patientsShould not be recommended until further

research is conducted. Especially because of study results from animal studies

It is important to stay up to date on new information regarding safety

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