Download What are the perioperative risk benefits of garlic supplementation

1
What are the perioperative risk/benefits of garlic supplementation?
Zarinah Ali-Burford CRNA MSN
Major Peter Strube CRNA MSNA APNP ARNP
Rosalind Franklin University
2
TABLE OF CONTENTS
I. INTRODUCTION
Background …………………………………………………………………..4
Regulation …………………………………………………………………….5
History of Herbs……………………………………………………………….6
Garlic…………………………………………………………………………..7
II. REVIEW OF LITERATURE
Introduction……………………………………………………………………9
Garlic and Platelet Function…………………………………………………..10
Garlic and Blood Pressure Lowering Effects………………………………… 12
Garlic and Lipid Lowering Effects…………………………………………….13
III. METHODOLOGY……………………………………………………….15
IV. SUMMARY, CONCLUSIONS AND RECOMMENDATIONS
Conclusions…………………………………………………………………… 15
Recommendations……………………………………………………………...17
3
Abstract
Use of garlic for medicinal purposes dates backs to thousands of years. Garlic, one of the most
popular botanicals used today has been well-known in almost every known ancient civilization
as a part of the therapeutic regimen for treatment for a variety of ailments. Many patients use
garlic in conjunction with prescription medicines to treat hypertension, hyperlipidemia, and
cancer. In recent times, studies have been undertaken world-wide to identify the bioactive
substances in garlic and their underlying mechanism of action. The validity of ancient medicine
is now being assessed analytically in cell-free systems, animal models, and human populations.
Accordingly, there is a need to determine the safety and efficacy of garlic supplementation. The
immediate objective of this research project is to assess the effects garlic on blood pressure,
platelet function, and lipid levels. A search of the documented risk and benefits of garlic intake
during the perioperative period has also been undertaken.
4
Introduction
Background
The World Health Organization (WHO) estimates that about 80% of the world-wide
population relies on herbal medicines as a part of its healthcare regimen (Ehrlich, 2011). In the
last 30 years, the use of herbal supplements has increased dramatically in the United States
(U.S.) (Ehrlich, 2011). According to Barnes and Bloom (2008), approximately 38% of the adults
in the U.S. use complementary medicines in the form of nonmineral or nonvitamin
herbs/botanicals, acupuncture, and chiropractic/osteopathic manipulation. In 2007, the annual
expenditure on complementary medicine and products was $33.9 billion in the U.S. (Nahin,
Barnes, Stussman, & Bloom, 2009).
Lately, use of herbal supplementation has been found to be associated with health
concerns. Among various herbal supplements available today, some common herbals are
associated with the incidence of adverse reactions which include echinacea, ephedra (ma huang),
garlic, gingko, ginseng, kava, and St. John’s wort.
Garlic (Allium sativum, lily family) is a well known herb with profound medicinal uses
making it an important constituent in various herbal products (Castleman, 2009). Current
research suggests that garlic may possess risks and benefits during the perioperative period.
During the preanesthesia assessment for the patients scheduled to receive anesthesia, most
anesthesia providers inquire about patients’ prescription drug use. Due to limited clinical trials
providing evidence for specific adverse interaction between garlic and anesthetic drugs,
information regarding concomitant use of herbal/dietary supplement use is often overlooked
(Dotson, Wiener-Kronish & Ajayi, 2007).
5
Regulation Governing Marketing and Use of Herbal Supplements in U.S.
Herbal supplements or botanicals, being used for medicinal purposes for thousands of
years are not strictly regulated by the Food and Drug Administration (FDA) and are not
subjected to same scientific scrutiny as drugs or medications. Botanicals are regulated by the
FDA, but not as drugs or food; herbs are categorized as dietary supplements. FDA regulates
dietary supplements under the Dietary Supplement Health and Education Act (DSHE) (Food and
Drug Administration, 1994) according to which:
a) Manufacturers are not required to seek FDA approval before introducing the product
in the market. In addition, companies can claim that the product addresses a nutrient
deficiency, supports health or is linked to body function by including a supporting
research and or with a disclaimer that the manufacturers have not evaluated the claim.
b) Companies must follow Good Manufacturing Practices (GMP) to ensure that
supplements are processed consistently and meet quality standards. These regulations
are intended to keep out the wrong ingredients and contaminants, such as pesticides
and lead, and to make sure that the right ingredients are included in appropriate
amounts.
c) Once a dietary supplement is on the market, the FDA is responsible for monitoring its
safety. If the FDA finds a product to be unsafe and hazardous to public health, it can
take action against the manufacturer or distributor or both, and may issue a warning
requiring the product be withdrawn from the market.
Although, the regulations provide assurance that the herbal supplements meet certain quality
standards and the FDA can intervene to remove hazardous products from the market, the rules do
not guarantee the safety of a particular herbal supplement for common use. Many herbal
6
supplements contain active ingredients that may exert powerful effects on the body, exposing it
to unexpected risks. For instance, taking a combination of herbal supplements or using
supplements together with prescribed medications could lead to harmful, life-threatening results.
According to the DSHEA of 1994, once on the market manufacturers are not required to
report any possible adverse events associated with the use of the herbal products to the FDA or
to prove the quality of the product. In 2006, mandatory adverse reporting was implemented
through the Dietary Supplement and Nonprescription Drug Consumer Protection Act. The
burden of the assessment of safety and possible risks and health hazards rests on the FDA.
As
a result, among the thousands of herbal preparations available, only a few result in documented
harmful effects, either by intrinsic toxicity or pharmacokinetic and pharmacodynamic
interactions (Rosow & Wilton, 2009). Seldom a herbal supplement is withdrawn (i.e. ephedra,
androstenedione, and PC‐SPES) from the market.
The United States Pharmacopeia (USP) offers voluntary verification services to ensure the
quality of herbal supplements (Dlugosz, 2010). The USP offers two different programs for
herbal supplements – finished products and ingredients (Dlugosz, 2010). The finished products
program verifies quality, potency, and purity through various methods. The ingredient program
verifies active and inactive ingredients used in the manufacturing process of herbal supplements.
These programs guarantee consistency, bioavailibity, and overall quality of herbal supplements;
safety and efficacy are not addressed (Dlugosz, 2010). Botanical products which meet these
stringent criteria are awarded the distinctive USP Verified Mark appearing on the products label.
This label serves as a marker for consumers and retailers signaling enhanced product quality.
7
History of Herbs
In 1820, the U.S. established the first pharmacopeia, an authoritative book containing a
list of medicinal drugs (Hairston, 2009). By the 1920’s, synthetic drugs began to replace natural
products (Hairston, 2009). A resurgence in the use of natural products was evident in the 1960’s
(Hairston, 2009). In recent times, use of herbal supplements has regained popularity not only in
the U.S. but also worldwide (Cavaliere, Rea, Lynch & Blumenthal, 2009). Garlic is among the
top five natural products used in the U.S. today (Barnes, Powell-Griner, McFann, and Nahin,
2004).
Garlic (Allium Sativum)
For at least 5,000 years, garlic remained the remedy of choice to treat a variety of illness
(Armstrong, 2001). Many ancient textbooks and manuscripts from Egypt, India, China, Greece,
and Rome document garlic as an integral part of their medicinal regimen (Castleman, 2009).
Ancient Egyptians fed garlic to their slaves who built pyramids. Garlic also constituted as an
important part of the cuisine of ancient Olympic Greek athletes (Armstrong, 2001). The
Egyptians were named “the stinky ones” by Greek writers because of their garlic breath
(Castleman, 2009). In 1874, the world’s oldest surviving text, Ebers Papyrus, dating back to
1500 B.C., discovered by Georg Ebers, a German Egyptologist, in the Valley of the Tombs near
Luxor revealed garlic as an important herb among 876 herbal formulations. (Castleman, 2009).
Garlic, a member of the lily family, contains organosulfur compounds, adenosine, trace
minerals, and amino acids (Tang Center for Herbal Medicine and Research, 2003). Fresh garlic
contains alliin, which is a sulfoxide. When fresh garlic is cut or crushed, the component alliin
8
combines with the enzyme allinase and the resulting mixture is allicin (“Garlic”, 2003). Allicin is
the component responsible for the distinctive “garlic” smell, and is the most active ingredient
present in the garlic (Aggarwal, 2011). Allicin transforms into organosulfur compounds, which
are responsible for minimizing oxidation, inflammation, and other cell-destroying processes
(Aggarwal, 2011).
Despite a rich history, the exact pharmacokinetics of the active ingredients present in
garlic are not fully understood (“Garlic”, 2003). After consumption, the organosulfur compounds
that readily react with cysteine in the intestinal tract are largely unknown (“Garlic”, 2003). The
usual dosage of garlic is 4 grams (about 2 cloves) of fresh bulb or its equivalent as an extract or
tincture per day “(Garlic”, 2003). Proponents of garlic advocate much larger doses (up to 28
cloves/day), and the development of concentrated garlic preparations has made these doses
achievable (“Garlic”, 2003). Commercial garlic preparations may be standardized to a fixed
alliin and allicin content.
Garlic supplements can be classified into four different processing groups, 1: garlic
essential oil; 2. garlic oil macerated products; 3. garlic powder; and 4. garlic extract. The process
of producing garlic essential oil involves passing steam through garlic (Castleman, 2009).
Commercially available garlic oil capsules contain vegetable oil and only small amounts of
essential garlic oil due to its strong odor (Ross, Finley, & Milner, 2006). The production of garlic
oil macerate products includes encapsulated mixtures of whole garlic cloves ground into
vegetable oil (Ross et al., 2006). Garlic powder is produced by slicing or crushing garlic cloves,
then drying and grinding them into powder (Ross et al., 2006). Garlic extract is made from whole
9
or sliced garlic cloves that are soaked in an alcohol solution (an extracting solution) for varying
amounts of time (Ross et al., 2006).
Herbal and dietary supplements are generally perceived natural and safe by the general
public. There are numerous preparations of herbal supplements which are used for a variety of
medical conditions. As these supplements are required to demonstrate minimum evidence for
efficacy, purity, safety, or quality (Food Drug Administration, 1994), their active ingredients
vary within preparation. Several manufacturing problems may contribute to preparation
variability; including misidentification of plant name, lack of standardization of plant
components, contamination during processing or storage, adulteration of herbal preparations, and
improper preparation and dosage of herbal products (Drew & Meyers, 1997). The incidence of
undocumented adverse events and numerous reports of drug-interaction resulting from the
concomitant use of herbal and dietary preparations add to the difficulty in identifying specific
adverse reactions and drug interactions.
Literature Review
Garlic and Platelet Function
Various studies suggest that bioactive components of garlic have the potential to inhibit
platelet function. The dose of garlic which influences platelet function is unknown (Scharbert,
Kalb, Duris, Marschalek, & Kozek-Langenecker, 2007).
Understanding the significance of garlic on platelet function is vital during the
perioperative period. Various in-vitro studies reveal bioactive components of garlic to inhibit
10
platelet aggregation (Scharbert et al., 2007). Garlic-induced platelet inhibition may interfere with
the biosynthesis of prostaglandins via inhibiting cyclooxygenase-1 and directly interacting with
fibrinogen receptors. This mechanism of action is comparable to aspirin (Scharbert et al., 2007).
Studies also suggest that extracts of garlic inhibit platelet aggregation, promote adhesion to
fibrinogen, and cause thromboxane B2 secretion (Scharbert et al., 2007). According to Scharbert
et al. (2007), significant increases in antiatherosclerotic effects occur within five hours after
garlic intake. Presence of arachidonic acid, collagen, and epinephrine are indicative of
irreversible platelet inhibition induced by garlic (Scharbert et al., 2007).
A large number of patients consume garlic supplements for various medical indications such
as hypercholesterolemia and hypertension. These patients may also suffer from ailments like
deep vein thrombosis, which require anticoagulation therapy. Some practitioners may discourage
consumption of large amounts of garlic to patients on anticoagulation therapy. Garlic may
increase the risk of postoperative bleeding and spinal hematoma formation (Scharbert et al.,
2007). Some anesthesia providers advise avoiding garlic intake seven days prior to surgery,
especially if postoperative bleeding is a particular concern.
In the past, clinical trials have shown that processed garlic (i.e. garlic powders and
extracts) exhibits platelet inhibitory effects (Wojcikowski, Myers, & Brooks, 2007). Various
processing methods yield preparations with differing potency and chemical composition of garlic
components (Wojcikowski et al., 2007). Processing increases the potency and bioavailability of
garlic compounds (Scharbert et al., 2007). The different preparation methods influence its
potency and efficacy; cooking garlic destroys volatile and unstable components while boiled
garlic is not likely to exert any effect on platelet function (Cavagnaro, Camargo, Galmarini, &
11
Simon, 2012). There are limited clinical trials which examine raw garlic dosage (Scharbert et al.,
2007) The finding of the studies conducted on raw garlic suggests that intake of 10 grams of
fresh garlic daily for two months increases clotting times (Scharbert et al., 2007).
According to Scharbert et al. (2007), single consumption of fresh garlic (up to 4.2 gapproximately 1-2 garlic cloves) has no platelet inhibitory function. Within the broader body of
literature on garlic and platelet inhibition, garlic powder or processed garlic has effectively
exhibited anti-aggregatory effects. Garlic’s chemical complexity and diverse processing methods
may result in differing effectiveness and chemical compositions in garlic preparations. The
differing study results of raw and processed garlic may result from varying amounts and types of
bioactive garlic components that eventually reach the platelets (Scharbert et al., 2007).
Processing garlic increases the potency and bioavailability of garlic compounds when compared
with raw garlic.
Garlic and Blood Pressure Lowering Effects
In patients with untreated hypertension, garlic supplements exert clinically significant
blood pressure lowering effects. The hypotensive effect of garlic results from the stimulation of
intracellular nitric oxide (NO) and production of hydrogen sulphide (H2S) (Reid, Frank, &
Stocks, 2010). Garlic blocks the production of angiotensin II, which promotes vasodilation and
blood pressure reduction (Reid et al., 2010). The two recent meta-analyses showed an average
systolic blood pressure (SBP) reduction of 8 ± 3 mm Hg in garlic group than the control groups.
12
This reduction in blood pressure is comparable to current first line treatment with
antihypertensive medications and is clinically relevant; other studies also confirm a decrease in
systolic pressure by 5 mm Hg thereby reducing the risk of cardiovascular disease by 8-20%
(Reid et al., 2010).
While previous trial focused on the effects of garlic powder, current literature suggest
that aged garlic extract (AGE) is a more reliable treatment option (Reid et al., 2010). Studies
suggest that AGE is safer and more tolerable than garlic powder and exerts more
antihypertensive effects than other garlic forms (Reid et al., 2010). The active ingredient in AGE
is less volatile making it more standardized (Reid et al., 2010).
In addition, AGE has been found to be effective in lowering systolic blood pressure in
patients with treated but uncontrolled hypertension. The level of blood pressure reduction was
equivalent to that achieved with conventional antihypertensive medications (-10.2 ± 4.3mm Hg)
over 12 weeks in patients with SBP > 140 mm Hg (Reid, Frank, & Stocks, 2010). Additional
trials indicate no reduction in normotensive patients, consuming garlic supplements (Beate,
Melgaard, & Marckmann, 2004). A recent meta-analysis reveals that reduction in blood pressure
with garlic occurred in patients with elevated SBP and not in those without elevated SBP
(Reinhart, Coleman, Teevan, Vachhani, & White, 2008). In an investigation conducted by
Sobenin et al. (2009), time-released garlic powder effectively lowered SBP in patients with mild
to moderate hypertension.
Studies also reveal that garlic supplements in therapeutic dosages cause gastrointestinal
disturbances (Reid et al., 2010). Genetic variation and enzyme capacity affect the metabolism of
sulfur compounds contained in garlic; molybdenum and vitamin B12 levels affect enzyme
function (Reid et al., 2010). Gastrointestinal disturbances associated with sulfur-containing
13
foods, such as garlic, onions, and leeks may be reversed by administration molybdenum and
vitamin B12.
Garlic and Lipid Lowering Effects
Atherosclerosis is one of the most common causes of mortality worldwide (Sobenin,
Andrianova, Demidova, Gorchakova, & Orekhov, 2008). Clinical manifestations associated with
atherosclerosis include myocardial infarction (MI) and cardiovascular heart disease (CHD). The
development of atherosclerosis is due to various risk factors, such as alterations in plasma lipid
and lipoprotein levels, blood pressure, platelet function, glucose intolerance, and obesity. The
most significant risk factor associated with coronary artery disease is hyperlipidemia (Sobenin et
al., 2008). Current literature indicates that increased cholesterol levels are the most significant
risk factor for the development of CHD and death in both women and men (Sobenin et al., 2008).
Modern treatment for atherosclerosis includes reduction of various risk factors
simultaneously, including blood pressure and lipid levels. Medications used to lower cholesterol
levels include statins and 3-hydroxy-3methyl-glutaryl coenzyme A (HMG-CoA). Many studies
have proven the effectiveness of statins in lowering cholesterol. Statins are associated with many
adverse affects including hepatotoxicity, myopathy, etc. (Higashikawa, Noda, Awaya, Ushijima,
and Sugiyama, 2012). Many patients prefer to use dietary supplements with milder benefits and
fewer adverse affects than commonly prescribed medications which are used to treat
hyperlipidemia.
Several clinical trials indicate that the garlic inhibits key enzymes involved in cholesterol
and fatty acid synthesis (Sobenin et al., 2008). Studies investigating the antiatherosclerotic and
cardiovascular protective effects of garlic report that garlic-based preparations may normalize
14
plasma lipid levels, enhance fibrinolytic activity, inhibit platelet aggregation and lower blood
pressure (Sobenin, Pryanishnikov, Kunnova, Rabinovich, Martirosyan, & Orekhov, 2010).
In addition, garlic also inhibits human squalene monooxygenase and HMG-CoA reductase,
enzymes involved in cholesterol biosynthesis (Sobenin et al, 2010).
Garlic preparations may be promising modalities for multifunctional risk reduction and
cardioprotective effects. In a study conducted by Sobenin et al. (2010), a 12-month treatment
with garlic tablets resulted in a significant reduction in cardiovascular risk by 1.5 fold in men and
1.3 fold in women. Based on the results, a decrease in LDL cholesterol contributed most in
cardiovascular risk reduction in men and women (Sobenin et al., 2010). Also, men were found to
be more benefited from garlic’s lipid lowering effects.
Methodology
A comprehensive search of the Cochrane Library, PubMed, MEDLINE, electronic
publishing sites, reference lists of relevant papers, and manual searches of relevant journals was
performed. The researcher conducted computer searches on manufacturers, regulation, and
distributors of garlic products to identify additional studies. The researcher included randomized
controlled trials of garlic that evaluated the effects of garlic on cholesterol levels, blood pressure
and platelet aggregation. Data was extracted, and trial quality was assessed.
Conclusions and Recommendations
Conclusion
A central theme existed when evaluating the cardioprotective effects of garlic from all of
the previous studies mentioned in the review of literature - the lack of standardized dosages and
preparations for garlic supplementation. While the results of several studies on garlic and platelet
aggregation may be inconsistent, differences may occur from the use of different preparations
15
and dosages. As discussed earlier, processed garlic powder may contain different products which
may display different efficacy as compared to raw garlic. Current preoperative suggestions
include advising patients to avoid any form of garlic consumption before surgery.
Scharbert et al (2007) conclude that socially acceptable doses of raw garlic (4.2 g) in
prepared dishes are not associated with platelet inhibition, and therefore safe. Safe practice may
include identifying patients with inherited or acquired platelet dysfunction and raw garlic
consumption during the perioperative period and closely monitor coagulation function. Patients
undergoing surgeries associated with significant blood loss may be advised to omit processed
garlic before surgery. The use of herbal supplements as either sole or adjunctive therapy in the
treatment of hypertension has many financial and clinical practice applications. Nurse
anesthetists must be aware that garlic may also contribute to hypotension intraoperatively and
provide prompt intervention. Further studies are needed to explore dose-response relationships,
the effects when combined with blood pressure medication classes, and the impact on diastolic
hypertension. The results of Sobenin et al. (2010) conclude that time-released garlic has lipid
lowering effects; previous studies on garlic powder showed conflicting results in garlic’s ability
to normalize lipid levels. In a meta-analysis study conducted by Koo & Azizi (2009), the authors
examined the effects of various preparations of garlic, but the dosages varied. The discrepancies
may result from lack of dosage consistency, standardized garlic-based preparations, and duration
of treatment. Garlic’s preparation/manufacturing method can affect the composition of the garlic
compound. The effectiveness of garlic supplementation as an adjunctive therapy in the
prevention of CHD may be beneficial. Further studies are needed to determine the effect of
different preparations and therapeutic dosages.
16
Clinical manifestations associated with atherosclerosis include myocardial infarction
(MI) and CHD. Current preoperative suggestions to prevent intraoperative myocardial ischemia
include identification of patients at risk and continuation of beta blocker therapy. Sobenin et al.
(2010) concludes that daily consumption of time-released garlic therapy for one year effectively
reduces the clinical manifestations associated with atherosclerosis, especially in men. Patients
that consume garlic and undergoing surgery may benefit from this adjunctive therapy. Garlic
preparations may be promising modalities for multifunctional risk reduction and cardioprotective
effects.
Recommendations
As previously stated, further studies are needed to determine the effect of different
preparations, therapeutic dosages, and concomitant use with other antiatherosclerotic
medications. Further investigation is warranted to determine the dose-response relationships, the
effects when combined with blood pressure medication classes, and the impact on diastolic
hypertension. Further research into patient use of herbal and dietary supplements and anesthesia
provider practice regarding herbal and dietary supplements is warranted. Additional research
studies identifying specific compounds found in dietary supplements to identify potential
interactions with anesthesia and other medications are necessary. As more research into the use
of herbal supplement use and the potential for interaction with anesthetics is completed,
continued improvements in anesthesia safety can be maintained.
17
References
Aggrawal, B. (2011). Healing Spices. NewYork, NY: Sterling.
Armstrong, D. (2001). Herbs that work. Berkley, California: Ulyses Press
Barnes, P. and Bloom, B. (2008). Complementary and alternative medicine use among adults and
children: United States. National Health Statistics Report. Dec 10;(12):1-23.
Barnes, P., Powell-Griner, E., McFann, K., & Nahin, R. (2004) Complementary and alternative
medicine use among adults: United States. AdvData 343,1–19.
Beate, T., Molgaard, C., & Marckmann, P. (2004). Effect of garlic (Allium Sativum) powder
tablets on serum lipids, blood pressure and arterial stiffness in normo-lipidaemic
volunteers: a randomized, double blind, placebo-controlled trial. British Journal of
Nutrition, 92, 701-706.
Cavaliere, C., Rea, P., Lynch, M., & Blumenthal, M. (2009). Herbal supplement sales experience
slight increase in 2008. Journal of the American Botanical Council, 78, 58-60.
Castleman, M. (2009). The New Healing Herbs (3rd Ed). London, UK:Rodale Inc.
Cavagnarom, P., Camargo, A., Galmarini, C., & Simon. P. (2012). Effect of cooking on garlic
(Allium sativum L.) antiplatelet activity and thiosulfinates content. Journal of Agricultural
Food Chemistry, 55(4), 1280-1288.
Dotson, R., Wiener-Kronish, J.P., & Ajayi, T. (2007). Preoperative Evaluation and Medication.
In Stoelting, R.K. & Miller, R.D. (Eds.) Basics in Anesthesia (5th edition, pp. 157-177).
Philadelphia, PA: Churchill Livingstone Elsevier.
Drew, A.K., & Meyers, S.P., (1997). Safety issues in herbal medicine: Implications for
healthcare professionals. Medical Journal of Austrailia, 166 (10), 538-534.
18
References
Dlugosz, C. K., (2010). Popular herbal and dietary supplements. OTC Advisor, 7, 1-30
Retrieved on Febuary 15, 2013 from
http://elearning.pharmacist.com/Portal/Files/LearningProducts/7bd326737b644fd28966ed5
def2ef7fb/assets/037_OTC%20ADV_Herbal%20and%20Dietary%20Supplements_New%
20Final%20072910.pdf
Ehrlich, S. (2011). Herbal Medicine. The University of Maryland Medical Center. Retrieved on
January 20, 2012 from http://www.umm.edu/altmed/articles/herbal-medicine-000351.htm.
Food and Drug Administration. Dietary Supplement Health and Education Act (DSHEA) of
1994. Public Law 103-417,103rd Congress. Retrieved on January 20, 2013 from
http:www.fda.gov/opacom/laws/dshea.html
Hairston, A. (2009). Common Herbs and Dietary Supplements. Duke University Health
system, Powerpoint Presentation.
Higashikawa, F., Noda, M., Awaya, T., Ushijima, M., & Sugiyama, M., (2012). Reduction of
serum lipids by the intake of the extract of garlic fermented with Monascus pilosus: A
randomized, double-blind, placebo-controlled clinical trial. Clinical Nutrition 31, 261-266.
Koo, Y.Z., & Azizi, Z. (2009). Garlic supplementation and serum cholesterol: meta-analysis.
Journal of Clinical Pharmacy and Therapeutics, 34, 133–145.
Macan H, Uykimpang R, Alconcel M, Takasu J, Razon R, Amagase H, & Niihara Y. (2006).
Aged garlic extract may be safe for patients on warfarin therapy. Journal of Nutrition, 136,
793S-795S.
19
References
Nahin, R.L., Barnes, P.M., Stussman, B.J., & Bloom, B. (2009). Costs of Complementary and
Alternative Medicine (CAM) and Frequency of Visits to CAM Practitioners: United
States. National Health Statistics Reports, 18, 1-14.
Reid, K., Frank, O.R., & Stocks, N.P. (2010). Aged garlic extract lowers blood pressure in
patients with treated but uncontrolled hypertension: a randomized controlled trial.
Maturitas, 67, 144-150.
Reinhart, K.M., Coleman, C.I., Teevan, C., Vachhani, P., & White, C. (2008). Effects of garlic
on blood pressure in patients with and without systolic hypertension: a meta-analysis.
Annals of Pharmacotherapy Journal, 42(12), 1766-1771.
Rosow, C. & Wilton, L. (2009). Drug interactions. In Barash, P.G., Cullen, B.F., Stoelting, R.K.,
Cahalan, M.K., & Stock, M.C., (Eds.). Clinical Anesthesia (6th ed. pp. 549-566).
Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins.
Ross S.A., Finley J.W., & Milner J.A. Allyl sulfur compounds from garlic modulate aberrant
crypt formation. Journal of Nutrition, 136, 852S–854S.
Scharbert, G., Kalb, M., Duris, M., Marschalek, C., & Kozek-Langenecker, S. (2007). Garlic at
dietary doses does not impair platelet function. Anesthesia Analgesia, 105(5), 1214-1218.
Sobenin, I., Andrianova, I., Demidova, O., Gorchakova, T., & Orekhov, A. (2008). Lipidlowering effects of time released garlic powder tablets in double-blinded placebo
controlled randomized study. Journal of Arthrosclerosis and Thrombosis, 15(6), 334-338.
Sobenin, I.A., Pryanishnikov, V.V., Kunnova, L.M., Rabinovich, Y.A., Martirosyan, D.M., &
Orekhov, A.N. (2010). The effects of time-released garlic powder tablets on
20
References
multifunctional cardiovascular risk in patients with coronary artery disease. Lipids in
Health and Disease, 9:119
Sobenin I.A., Andrianova I.V., Fomchenkov I.V., Gorchakova T.V., & Orekhov A.N. (2009).
Time-released garlic powder tablets lower systolic and diastolic blood pressure in men
with mild and moderate arterial hypertension. Hypertension Research Journal, 32(6),
433-437.
Tang Center for Herbal Medicine and Research. (2003). Garlic. Retrieved December 2012 from
http://tangcenter.uchicago.edu/herbal_resources/garlic.shtml
Wojcikowski K, Myers S, & Brooks L. (2007). Effects of garlic oil on platelet aggregation:
double-blind placebo-controlled crossover study. Platelets, 18 (1), 29-34.
21
Questions
1. Under the Dietary Supplement Health and Education Act of 1994, herbs and botanicals are regulated
as:
a: Dietary Supplements
b. Medical devices
c. Nonprescription medications
d. Prescription medications
2. The Dietary Supplement Health and Education Act states that the FDA:
a. Does not require manufacturers to seek FDA approval before introducing the product in the market.
b. Ensures companies must follow Good Manufacturing Practices (GMP) to ensure that supplements are
processed consistently and meet quality standards.
c. Can remove a dietary supplement from the market only after the product has been proven to be
unsafe
d. All of the above.
3. Which of the following claims are not permitted on a dietary supplement label?
a. Claims that the product addresses nutrient deficiency
b. Claims that the product effectively treats a specific disease
c. Claims that the product supports health
d. Claims that the product is linked to body function(s)
4. Which of the following pieces of legislation requires manufactures of dietary supplements to report
serious adverse events to the FDA?
a. Dietary Supplement Health and Education Act.
b. Dietary Supplement and Nonprescription Drug Consumer Protection Act.
22
c. Federal Food, Drug, and Cosmetic Act.
d. Adverse event report is not mandatory for dietary supplements.
5. Which statement is true regarding herbal supplements?
a. Adverse event reporting is not required for dietary supplements.
b. The burden to assess product safety and possible risks and health hazards rests on the manufacturers.
c.
Herbal supplements removed from the market include ephedra, androstenedione, and
PC‐SPES.
d. There are many herbal supplments with documented harmful effects.
6. The following statement is incorrect regarding the U.S. Pharmacopeia (USP) organization:
a. Awards a USP certified mark for use on labels, packages and promotional materials
b.Consist of two programs – finished products and ingredients.
c.The USP is the only that offers involuntary verification services.
d. The USP does not guarantee safety or efficacy of products approved.
7. Which of the following herbal supplements is listed as one of the top five herbal supplements used in
the U.S.?
a.Grass
b. Garlic
c.Gentian seeds
d.Betony
8. Which of the following ancient civilizations is associated with garlic use?
a. Egypt
b. Persian
c. Babylonian
d. Cimmerian
23
9. Garlic is a member of which family class?
a. Nightshade family
b.Rose family
c. Berry family
d.Lily family
10. Which of the following is not a component of garlic?
a.Oorganosulfur compounds
b. Adenosine
c.Trace minerals
d.Amino acids
e. None of above
11. The active ingredient in garlic that is responsible for its “garlic” smell is?
a.Allinase
b. Alliin
c. Allicin
d. Aspirin
12. Which of the following statements about garlic is true?
a. Garlic supplementation is associated with no adverse effects.
b. Garlic is one of the most common herbal supplements used in presurgical patients.
c. Garlic supplementation is always safe since it is a natural product.
d. Garlic can only be used as an ingredient for cooking.
24
13. Garlic is associated with which of the following types of serious adverse effects?
a. Gastrointestional
b. Dermatologic
c. Respiratory
d. Renal
14. Match the proposed antiplatlet effects of garlic to the prescription drug with similar mechanism of
actions.
a. Garlic-induced platelet inhibition may interfere with the biosynthesis of prostaglandins via
inhibiting cyclooxygenase-1 and directly interacting with fibrinogen receptors – similar to
aspirin.
b. Garlic-induced platelet inhibition may block ADP receptors inhibiting platlets – similar to plavix.
c. Garlic- induced platelet inhibition by inhibiting glycoprotein IIb/IIIa receptors – similar to aspirin.
d. none of the above
15. Garlic may lower blood pressure by which mechanism of action? Select 2
a. By stimulating the alpha receptors, thereby producing vasodilation.
b. Stimulation of intracellular nitric oxide (NO) and production of hydrogen sulphide.
c. Garlic blocks the production of angiotensin II, which promotes vasodilation and blood pressure
reduction
d. Blocking the voltage-gated calcium channels, producing vasodilation
16. Which statement is true regarding garlic’s ability to lower blood pressure?
a. Some studies show garlic supplementaion lowers blood pressure comparable to some
antihypertensive prescription medications.
b. Garlic should be used as a first line modality in the treatment of hypertension.
c. Studies suggest garlic lowers diastolic blood pressure more than systolic blood pressure.
d. Garlic is more effective at lowering blood pressure in patients with severe high blood pressure than
those with mild hypertension.
25
17. The possible cardioprotective effects of garlic include:
a. Blood pressure elevation
b.Increase plasma lipid levels
c. Decrease fibrinolytic activity
d. Inhibit platelet function
18. Garlic may lower lipids levels by: ( select 2)
a. Garlic inhibits key enzymes involved in cholesterol and fatty acid synthesis.
b. Inhibits human squalene monooxygenase and HMG-CoA reductase, enzymes involved in
cholesterol biosynthesis
c. Garlic works in the intestine, where they bind to bile from the liver and prevent it from being
reabsorbed into the circulatory system
d.Reduce the production of triglycerides and can increase HDL cholesterol
19. Which of the following may contribute to the contradictory results of studies performed on the
cardioprotective effects of garlic?
a. Insufficient garlic supply
b.The lack of standardized dosages and preparations for garlic supplement use.
c. There are no contradictory study results, garlic is cardioprotective.
d. There are no contradictory study results, garlic is not cardioprotective.
20. The importance of evaluating patient herbal supplement use preoperatively includes:
a. To identify possible drug interactions with anesthetic medications.
b. To encourage the use of herbal supplementation.
c. There is no need to evaluate nonprescription medication use.
d. To teach patients the safety of herbal supplementation administration.
26