Food and Drug Interactions for CoEnzyme Q10, Red Yeast Rice

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Presented by:
Confidential Group Members and Kaitlin Deason
 Discuss:
 Properties
 Pharmacokinetics
 Drug nutrient interactions
 Current research
 Indications
 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
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.
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
 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
 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
 Red meat products
 Especially organ meats such as liver and heart
 Oily fish such as salmon and tuna
 Whole grain
 Rapeseed oil
 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.
 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 Max Daily
•Co-Q-Rescue Serum
 Co-Q-Omega
• 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
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).
 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
 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.
Side effects are mild and brief. Rxns may
include:
• Nausea
 Irritability
• Vomiting
 Diarrhea
• Stomach upset
 Skin itching
• Heartburn
 Rash
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)
 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.
 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 anticoagulant effect of Warferin (Coumadin), resulting
in higher dosage requirements for Warferin.
 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
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.
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.
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.
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.
• 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.
 Results:
 Suggest that CoQ10, enhances the exercise
performance
 A decrease in the subjective fatigue sensation
was observed compared to the placebo group
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
 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
 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
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.
 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).
 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.
 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.
http://a.abcnews.com/images/GMA/redyeastrice_090615_mn.jpg
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 (13681644 AD) published claims:
–
–
–
–
Can be used to improve health
Treatment in mild gastric disturbance
Blood circulation
Improve spleen and stomach health
 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.
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
 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-3methylglutaryl-coenzyme reductase (HMGCR).
 HMGCR enzyme is the rate limiting step for cholesterol
synthesis.
Monacolin K or
X
X
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/cholesterol_synthesis.gif
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.
Generic Names
 Chinese Red Yeast Rice
 Zhi Tai
 Xuezhikang
 XZK
 Angkak
 Monascus Purpureus
Went
 Red Yeast
Brand Names
 Red Rice Yeast
 Cholestin
 Chol-Reg
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
 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.
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
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
May cause muscle problems when combined with:
 Cyclosporine (immunosuppressant)
 Niacin (reduce cholesterol and TG)
 Gemfibrozil (lower lipid levels)
 Other Statins
 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.
 Taken with food increases absorption
 Grapefruit juice decreases metabolism of RYR
 Alcohol may cause liver damage
 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
 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
 Women who are pregnant or breastfeeding
 People with asthma
 Kidney disease
 Recent surgery
 Organ transplant
 People who >2 alcohol beverages per day
 People with liver disease
Venero, C.V., Venero, J.V., Wortham,
D.C., & Thompson, P.D. (2010). Lipidlowering efficacy of red yeast rice in a
population intolerant to statins. The
American Journal of Cardiology, 105(5),
664-666.
Purpose
 Observational study evaluated the lipid-lowering
efficacy of RYR in patients intolerant to statins.
Methods
 They 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).
Results
 Treatment 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), 664666.
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.
Purpose
 The 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).
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).
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.
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 daily
 The 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).
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).
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.
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)
Methods
• They examined lovastatin, RYR, MK-free RYR,
pigment-rich fraction RYR (PF-RYR), monacolinrich 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)
Results:
 RYR and PF-RYR demonstrated the most antiproliferation 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)
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)
 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.
 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.
http://planning.up.nic.in/innovations/inno3/fi/chitosan.htm
 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)
 Water purification
 Soil enrichment
 Antioxidant properties to prolong shelf-life
 Serves as a functional food
 Controlled drug release
 Antitumor and wound healing
 Used much less as a supplement that for its other
uses
 Lowers cholesterol
 Reduces fat absorption  reduces weight
 Reduces dental plaque formation
 Available in 500 mg capsules
1.5 g per day
 Generic names: chitosan, chitin, and kitosan,
 Brand names: Chitosan Plus™, Fat Absorb™, and
Fat Blocker™
http://www.vitaminstoday.com.au/blocke
r-caps-p-683.html
http://www.womenbeautycare.com/2010/12/overweightwomen-develop-osteoporosis.html
http://www.a1nutrition.com/buyuniversal_nutrition-chitosan_plus-120caps/
 Recommended dosage usually around 1500 mg to
 May cause gas, constipation and nausea
 Should not be taken by:
 People with shellfish allergies (because derived from
shellfish)
 Pregnant or breast feeding women
 Children
 Those with malabsorptive disorders
 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
 Little information is known
 Similar in structure to cellulose and seems to
function like this
 Not absorbed by the intestines and is primarily
eliminated through the feces
 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
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.
 Purpose:
 To determine the effect of chitosan on fecal fat excretion
 Methods:
 12 men and 12 women completed 12-day trial
 Cross-over design
 5 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).
 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).
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 waterinsoluble drugs following oral
administration in rats. Biological and
Pharmaceutical Bulletin, 29(9), 1941-1946.
 Purpose:
 to determine how chitosan effects GI absorption of
the drugs indomethacin, griseofulvin,
acetaminophen, and cephalexin, in rats
 Background:
 Indomethacin and griseofulvin are water-insoluble
 Acetaminophen and cephalexin are water-soluble
drugs
Nadai et al., (2006).
 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 drugs
 Pre-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).
 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).
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.
 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 study
 Subjects 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).
 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).
 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).
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 highfat diets. Journal of Agricultural and Food
Chemistry, 58(8), 5187-5193.
 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
biotransformation
 Each of the enzymes play an important role in drug
metabolism, and without them oxidative stress
increases
Yao, Lii, Chou, Lin, Yang, & Chiang (2010).
 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).
 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).
 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).
 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
 No real benefit from chitosan
 Possible drug/nutrient interactions should be
conveyed to patients
 Should 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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