Popular Herbal and Dietary Supplements Monograph 7

A continuing
pharmacy
education activity
for pharmacists
Supported by an
independent educational
grant from
Provider: American Pharmacists Association
Target Audience: Pharmacists
Release Date: July 30, 2010
Expiration Date: July 30, 2013
Activity Preview
Americans spend an estimated $15 billion each year on herbal
products and other nonvitamin, nonmineral dietary supplements.
Many consumers view dietary supplements as milder, safer
alternatives to conventional prescription and nonprescription
medications; few are aware that dietary supplements are
not subject to the same standards of safety and efficacy as
conventional medications. As the health care professional most
likely to be accessible at the point of purchase, pharmacists are
well positioned to talk with consumers about dietary supplements,
provide evidence-based recommendations for the use of dietary
supplements, and discourage the use of potentially unsafe
products and practices.
This monograph addresses the use of herbal products
and other nonvitamin, nonmineral dietary supplements that are
available without a prescription. The regulation and marketing of
dietary supplements is reviewed and contrasted with regulations
governing prescription and nonprescription medications. A
framework for engaging patients in productive, evidence-based
discussions about dietary supplement use is presented. The
monograph concludes with an overview of selected dietary
supplements that are used widely in the United States.
Learning Objectives
At the completion of this activity, the pharmacist will be able to:
1. Summarize federal regulations governing dietary
supplements.
2. Identify common misperceptions concerning the extent of
regulation regarding the safety and efficacy of dietary
supplements.
3. Outline a strategy for guiding patient selection and use of
dietary supplements.
4. Provide examples of reputable sources of evidence-based
information about dietary supplements.
5. Discuss the efficacy and safety of popular dietary
supplements, including black cohosh, coenzyme Q10,
echinacea, evening primrose oil, fish oil, garlic, ginkgo,
ginseng, kava, melatonin, phytoestrogens, probiotics,
St. Johns wort, and saw palmetto.
Advisory Board
Bella Mehta, PharmD
Associate Professor of Clinical Pharmacy
Director, Clinical Partners Program
The Ohio State University
College of Pharmacy
Columbus, Ohio
Carol Rollins, MS, RD, PharmD, BCNSP
Associate Clinical Professor
Coordinator, Nutrition Support Pharmacy
University Medical Center
University of Arizona
College of Pharmacy
Tucson, Arizona
ACPE Number: 202-000-10-151-H01-P
CPE Credit Hours: 2.5 hours (0.25 CEUs)
ACPE Activity Type: Knowledge-based
Fee: There is no fee associated with this activity.
Accreditation Information
The American Pharmacists Association is
accredited by the Accreditation Council for
Pharmacy Education as a provider of continuing
pharmacy education (CPE). The ACPE Universal
Activity Number assigned to this activity by
the accredited provider is 202-000-10-151-H01-P. To obtain
2.5 hours of CPE credit (0.25 CEUs) for this activity, complete
the CPE exam and submit it online at www.pharmacist.com/
education. A Statement of Credit will be awarded for a passing
grade of 70% or better. You have two opportunities to successfully
complete the CPE exam. Pharmacists who successfully complete
this activity before July 30, 2013, can receive credit.
Your Statement of Credit will be available online immediately
upon successful completion of the CPE exam.
Development
This home-study CPE activity was developed by the American
Pharmacists Association.
Support
This activity is supported by an independent educational grant
from Procter & Gamble.
Disclosures
Bella Mehta, PharmD, declares that her husband owns stock in
Pfizer Inc.
Carol Rollins, MS, RD, PharmD, BCNSP, declares no conflicts of
interest or financial interests in any product or service mentioned
in this activity, including grants, employment, gifts, stock holdings,
and honoraria.
APhAs editorial staff declares no conflicts of interest or financial
interests in any product or service mentioned in this activity,
including grants, employment, gifts, stock holdings, and
honoraria.
This publication was prepared by Cynthia Knapp Dlugosz,
BPharm, of CKD Associates, LLC, on behalf of the American
Pharmacists Association.
Introduction
The term complementary and al-
ternative medicine (CAM) refers to a
group of diverse medical and health
care systems, practices, and prod-
ucts that are not generally considered
to be part of conventional medicine.
Complementary medicine is used as
an adjunct to conventional medicine,
whereas alternative medicine is used
in place of conventional medicine.
This monograph addresses one
aspect of CAM: the use of herbal
products and other nonvitamin, non-
mineral dietary supplements that are
available without a prescription. Ac-
cording to data from the 2007 National
Health Interview Survey, Americans
spent an estimated $14.8 billion
on nonvitamin, nonmineral dietary
supplements during the previous
12 monthsan amount equivalent to
approximately one third of total out-
of-pocket spending on prescription
medications (Figure 1). An analysis of
earlier National Health Interview Sur-
vey data found that nearly one in five
adults in the United Statesmore than
38 million peopleused an herbal
product for health promotion or treat-
ment of a specific health condition.
Regulation and
Marketing of Dietary
Supplements
Many consumers view dietary
supplements as substitutes for con-
ventional prescription and nonpre-
scription medications. Unfortunately,
consumersas well as many health
care professionalsoften are un-
aware of important differences be-
tween these categories of products.
acids, and substances such as en-
zymes, organ tissues, glandulars,
and metabolites. A new dietary in-
gredient is a dietary ingredient that
was not sold as a dietary supplement
in the United States before October
15, 1994. Manufacturers may market
a combination of dietary ingredients
as a proprietary blend.
The DSHEA places dietary
supplements in a special category
under the general umbrella of foods,
not drugs. Within the U.S. Food and
Drug Administration (FDA), dietary
supplements fall under the purview
of the Center for Food Safety and
Applied Nutrition. As a result, dietary
supplements are excluded from the
strict standards applied to prescrip-
tion and nonprescription medications
regulated through the Center for Drug
Evaluation and Research.
Under the DSHEA, firms that
manufacture or distribute a dietary
supplement are responsible for:
Determining that the product is
safe.
Figure 1. Total 2007 Out-of-Pocket Health Care
Costs for Conventional Health Care and
Complementary and Alternative Medicine
Ensuring that any representations
or claims made about the product
are substantiated by adequate
evidence to show that they are not
false or misleading.
In stark contrast to prescription and
nonprescription medications, dietary
supplements do not need to be
approved by the FDA before they
are marketed. Thus, firms are not
required to submit or disclose any
of the evidence used to substantiate
product safety or claims either before
or after a product is marketed, unless
the product contains a new dietary
ingredient.
Manufacturers or distributors of
dietary supplements that contain new
dietary ingredients must notify the
FDA of the intent to market the prod-
uct 75 days in advance; they also
must submit a premarket safety re-
port establishing that the new dietary
ingredient is reasonably expected to
be safe under the conditions recom-
mended or suggested in the label-
ing. However, because there is no

Dietary Supplement Health and

Education Act of 1994
The Dietary Supplement Health
and Education Act of 1994 (DSHEA)
amended the Federal Food, Drug,
and Cosmetic (FD&C) Act to create
a distinct regulatory framework for
dietary supplements. The DSHEA
defines a dietary supplement as a
product taken by mouth that contains
a dietary ingredient intended to
supplement the diet. Dietary ingre-
dients include vitamins, minerals,
herbs or other botanicals, amino

OTC Advisor: Popular Herbal and Dietary Supplements 1

authoritative list of dietary ingredients
that were available before October
15, 1994, the responsibility for deter-
mining whether a product contains
a new dietary ingredient lies with the
manufacturer or distributor. Moreover,
there are no specific criteria for what
constitutes acceptable evidence that
a new dietary ingredient poses no
significant or unreasonable risk.
Labeling of Dietary
Supplements
The labels of dietary supple-
ments are not required to provide the
comprehensive user information that
appears on labels of nonprescription
medications. Information that must
appear on a dietary supplement label
includes:
The name of the product and
identification of the product as a
dietary supplement.
The name and place of business
of the manufacturer, packer, or
distributor.
A complete list of ingredients.
The net contents of the product.
Most dietary supplements also
must include a Supplement Facts
panelsimilar to the Nutrition Facts
panel on foodsthat identifies each
dietary ingredient contained in the
product. Botanical dietary supple-
ments should indicate the scientific
(i.e., Latin binomial) name of the plant
as well as the specific plant part
used (e.g., Echinacea purpurea aerial
parts, which refers to the above-
ground parts of the plant).
For proprietary blends of dietary
ingredients, the DSHEA requires
that the product label include the
total weight of the blend and the
components of the blend, in order of
predominance by weight. The actual
quantity of each ingredient need not
be disclosed.
Dietary Supplement Claims
In the United States, only pre-
scription and nonprescription drugs
may legally claim to diagnose, cure,
mitigate, treat, or prevent illness. The
DSHEA permits three types of claims
on the labels of dietary supplements:
nutrient content claims, health claims,
and structure/function claims.
Nutrient content claims describe
the amount of a nutrient or dietary
2 American Pharmacists Association
substance in a product. They must be
made in accordance with the FDAs
authorizing regulations.
Health claims describe a relation-
ship between a dietary ingredient and
a disease or health-related condi-
tion. These claims also are subject to
FDA review and authorization; diets
high in calcium may reduce the risk
of osteoporosis is an example of an
authorized health claim.
Structure/function claims describe
the role of a dietary ingredient in
maintaining normal healthy structures
or functions of the body. For example,
echinacea may claim to support the
healthy defense mechanisms of the
body. These claims are not subject
to FDA review and authorization; the
manufacturer is responsible for ensur-
ing the accuracy and truthfulness of
Homeopathy
Homeopathy is a distinct system of
medicine with its own pharmacopoeia
and philosophy of practice. It is based
on the principle of like cures like,
or the law of similars. This principle
states that if a substance produces a
specific symptom or set of symptoms
when administered in large doses to a
healthy person, that same substance can
cure the specific symptom or symptoms
when administered in a very minute
dose. A second principle holds that as
a substance becomes more dilute, it
becomes more potent.
Unlike herbs and dietary supplements,
homeopathic preparations are not
regulated under the Dietary Supplement
Health and Education Act. Instead,
substances included in the Homeopathic
Pharmacopoeia of the United States
are recognized as drugs under the
Federal Food, Drug, and Cosmetic Act.
Because homeopathic products contain
little or no active ingredient, they do
not have to undergo the same safety
and efficacy testing as prescription and
nonprescription medications.
Homeopathic preparations can be sold
over the counter if they are intended
to treat self-limiting conditions such
as headaches or the common cold.
Preparations that are intended to treat
serious conditions such as cancer must
be obtained by prescription from a
licensed practitioner.
these claims. Manufacturers must
submit the text of structure/function
claims to the FDA within 30 days af-
ter marketing a dietary supplement.
When a structure/function claim is
made, the product label also must
include the following disclaimer: This
statement has not been evaluated
by the Food and Drug Administra-
tion. This product is not intended to
diagnose, treat, cure, or prevent any
disease.
The FDA and the Federal Trade
Commission (FTC) work together to
enforce regulations governing dietary
supplement claims. The FDA has
primary responsibility for regulating
claims found on packaging, package
labeling, inserts, and other promo-
tional materials that are distributed at
the point of sale. The FTC has prima-
ry responsibility for advertising claims
made though print and broadcast
advertisements, infomercials, cata-
logs, and other direct marketing ma-
terials. The FTCs truth-in-advertising
law requires that advertising claims
must be truthful and not misleading.
In addition, claims about the efficacy
or safety of dietary supplements
must be supported by competent
and reliable scientific evidence.
This evidence is defined as tests,
analyses, research, studies, or other
evidence based on the expertise of
professionals in the relevant area, that
have been conducted and evaluated
in an objective manner by persons
qualified to do so, using procedures
generally accepted in the profession
to yield accurate and reliable results.
Manufacturers who make dietary
supplement health claims sometimes
ignore the regulations established by
the FDA and FTC and market prod-
ucts using false or misleading claims.
Manufacturers of dietary supplements
for weight loss are frequent culprits.
The FTC consumer publication
Weighing the Evidence in Diet Ads
(available at www.ftc.gov/bcp/edu/
pubs/consumer/health/hea03.shtm)
provides examples of some common
false and misleading claims that pa-
tients may encounter.
Quality Control Considerations
Although the DSHEA required the
establishment of Current Good Manu-
facturing Practice (CGMP) standards
for dietary supplements, the FDA did
not issue a final rule until June 2007,
and manufacturers were not required
to comply with the standards until
June 2008 or later. (The standards
were implemented in a rolling fashion;
companies with 500 or more em-
ployees were given 1 year to comply,
companies with 20 to 500 employees
had 2 years, and companies with few-
er than 20 employees had 3 years.)
Before this final rule went into effect,
many dietary supplements were
found to have significant variability in
content, purity, potency, consistency,
and actual identity. In just one recent
example, a widespread outbreak of
acute selenium poisoning that began
in March 2008 in the United States
was traced to a liquid dietary supple-
ment that contained 200 times the
labeled concentration of selenium.
The final rule requires certain ac-
tivities in the manufacturing, packag-
ing, labeling, and holding of dietary
supplements to ensure that products
(1) contain what they are represented
to contain (i.e., are not misbranded)
and (2) are not contaminated with
harmful or undesirable substances
(i.e., are not adulterated). The final
rule further requires certain activities
intended to ensure the identity, purity,
quality, strength, and composition of
dietary supplements. The CGMPs es-
tablished by the final rule apply to all
domestic and foreign manufacturers,
as well as any company involved in
the testing, quality control, packaging
and labeling, or distribution of dietary
supplements in the United States.
Before the FDA issued its final
rule, several organizations developed
voluntary programs for verifying and
certifying the quality of dietary sup-
plement products. These organiza-
tions include the U.S. Pharmacopeia
(USP), ConsumerLab.com, NSF In-
ternational, and the Natural Products
Association. The programs adminis-
tered by these organizations remain
active; they address product quality
only, not the safety or efficacy of spe-
cific dietary supplement ingredients.
USP Programs
USP offers two programs for di-
etary supplements and each awards
a distinctive USP Verified Mark (Fig-
ure 2). These programs encompass
OTC Advisor: Popular Herbal and Dietary Supplements
Adulteration and Contamination of Dietary Supplements
According to the Dietary Supplement Health and Education Act, a dietary supplement is
considered to be adulterated if it:
Presents a significant or unreasonable risk of illness or injury when used in accordance
with the suggested labeling (or, if unlabeled, under ordinary conditions of use).
Is a new entity and lacks adequate evidence to ensure its safety of use.
Has been declared an imminent hazard by the Secretary of the Department of Health
and Human Services.
Contains a dietary ingredient that is present in sufficient quantities to render the product
poisonous or deleterious to human health, as described for adulterated foods in the
Federal Food, Drug, and Cosmetic Act.
Adulteration of dietary supplements may be intentional or unintentional. Unintentional
adulteration often reflects contamination of products by substances such as natural toxins,
bacteria, pesticides, glass, or heavy metals (e.g., lead) that are introduced at the time of
cultivation or during manufacturing processes. It also is possible for a dietary supplement
to be cross-contaminated by chemicals, drugs, or dietary ingredients present at the
manufacturing site.
Intentional adulteration is a deliberate act. For example, a manufacturer may use a
different substance in place of a dietary ingredient that is in short supply or is too
expensive. Alternatively, a manufacturer may choose to add an ingredient to intensify
a specific pharmacologic effect. In one notable case, a manufacturer allegedly added
pharmaceutical-grade ephedrine and caffeine to a dietary supplement that was
represented to contain ma huang and kola nut (and concealed the addition by falsifying
records). If only ma huang and kola had been used, the volume of those ingredients
needed to achieve the labeled strength of the supplement would have resulted in capsules
too large to ingest by mouth.
finished products (i.e., marketed ment Ingredients Program verifies
dietary supplement products pur- active and inactive ingredients used
chased by consumers) and ingredi- in the dietary supplement manufac-
ents (i.e., ingredients used to manu- turing process. It ensures that ingre-
facture dietary supplement products). dients are consistent in quality from
The program for finished prod- batch to batch; meet label or certifi-
ucts is the USP Dietary Supplement cate of analysis claims for identity,
Verification Program. It verifies the strength, purity, and quality; are pre-
quality, purity, and potency of dietary pared in accordance with accepted
supplement products through com- manufacturing processes; and meet
prehensive laboratory testing, review requirements for acceptable limits of
of manufacturing and quality control contamination. Verified ingredients
documents, on-site manufacturing fa- may carry the USP Verified Dietary
cility audits, and random off-the-shelf Supplement Ingredient Mark on their
testing. Finished products that meet containers.
the programs stringent criteria are
permitted to display the USP Dietary ConsumerLab.com Programs
Supplement Verification Program ConsumerLab.com, LLC, is a
certification mark. These products privately held company that provides
are certified to contain the listed in- test results and information to help
gredients in the indicated amounts, to consumers and health care profes-
be bioavailable, to be free of contami- sionals evaluate health, wellness, and
nants, and to have been manufac- nutrition products, including dietary
tured under appropriate conditions. supplements. Products are tested
A list of USP Verified dietary supple- through two programs: (1) Product
ments also is maintained on the USP Reviews and (2) a Voluntary Certifica-
tion Program for manufacturers and
Web site (www.usp.org/USPVerified/
dietarySupplements/supplements. distributors.
Product Reviews are independent
html).
The USP Verified Dietary Supple- tests of multiple brands of dietary
3

Figure 2. Logos Associated With Voluntary
Programs for Verifying and Certifying Dietary
Supplement Quality
USP Verified Dietary Supplement Mark
USP Verified Dietary Supplement
Ingredient Mark
Sample ConsumerLab.com Approved
Quality Product Seal
NSF Certification Mark
Natural Products Association GMP
Certification Program
GMP = Good Manufacturing Practice; USP = United States Pharmacopeia.
supplement products that claim to com Approved Quality Product Seal
have the same key ingredient. Consu- (Figure 2). Product Reviews typically
merLab.com purchases a sampling are updated every 24 to 36 months,
of products at the retail level (e.g., although the company states that it
stores, mail order, online) to reflect may retest brands at any time.
both popular brands and smaller Products in the Voluntary Cer-
brands; no samples are accepted tification Program undergo similar
from product manufacturers. Blind testing. Although test results are pro-
samples are sent to select commer- prietary to the manufacturer, products
cial and academic laboratories for that pass are listed in the respective
testing; products with questionable Product Review with a footnote indi-
results are retested in a different cating that they were tested through
laboratory using similar methods the Voluntary Certification Program.
and instrumentation. The results are Products that pass also are eligible
compiled in Product Reviews that are to carry the ConsumerLab.com Seal.
available to ConsumerLab.com Web
site subscribers (a 1-year subscrip- NSF International Dietary Supplements
tion costs approximately $30). Prod- Certification Program
ucts deemed to pass testing are NSF Internationaloriginally
permitted to carry the ConsumerLab. founded as the National Sanitation
4 American Pharmacists Association
Foundationis a not-for-profit, non-
governmental organization engaged
in standards development, product
certification, education, and risk man-
agement for public health and safety.
It offers a Dietary Supplements Cer-
tification Program to manufacturers
and suppliers on a voluntary, fee-for-
service basis. As part of the certifica-
tion process, NSF:
Reviews product formulations and
labels to determine appropriate
testing.
Inspects manufacturing facilities.
Obtains products and tests them
at NSF laboratories to verify
conformance to the NSF Dietary
Supplement Standard.
Products that meet all of the require-
ments are permitted to carry the NSF
Certification Mark (Figure 2). Certified
dietary supplements can be found
by searching the NSF listings at
www.nsf.org/Certified/Dietary/.
Natural Products Association
GMP Certification Program
The Natural Products Association
Good Manufacturing Practice (GMP)
Certification Program is designed to
verify that member companies manu-
facturing practices for dietary supple-
ments conform to a standardized set
of GMPs developed and approved by
the association. The Natural Products
Association GMPs meet or exceed all
current FDA requirements for dietary
supplements; they also incorporate
some industry best practices.
Certification is based on third-par-
ty inspection of manufacturing facilities
and review of GMP-related documen-
tation. The program represents facility
and process certification rather than
product certification. Companies that
achieve a high level of compliance are
permitted to use the Natural Products
Association GMP Certification Mark
(Figure 2). All companies are re-audit-
ed every 2 years.
Unsafe Dietary Supplements
and Adverse Event Reporting
The FDA is responsible for taking
action against any unsafe dietary
supplement product after it reaches
the market. However, the burden of
proof rests with the agency; the FDA
must be able to show that a dietary
supplement is unsafe before it can
restrict the products use or remove
the product from the marketplace.
Evidence that a product is unsafe
typically comes from sources such as
safety literature, adverse event re-
ports, and product information (e.g.,
labeling, claims, package inserts,
accompanying literature).
One example of an FDA action
against unsafe dietary supplements
is the 2004 market withdrawal of
ephedra and other products (e.g.,
ma huang) that contain ephedrine
alkaloids. On February 11, 2004, the
FDA published a final rule declaring
these products adulterated under the
Federal FD&C Act (and therefore ille-
gal to market). The final rule became
effective on April 12, 2004. Accord-
ing to the FDA, dietary supplements
containing ephedrine alkaloids are
adulterated because they present an
unreasonable risk of illness or injury
under the conditions of use recom-
mended or suggested in labeling, or
if no conditions of use are suggested
or recommended in labeling, under
ordinary conditions of use. The
agency based its action on the well-
known pharmacology of ephedrine
alkaloids, the peer-reviewed scientific
literature on the effects of ephedrine
alkaloids, and the adverse events
reported to have occurred in individu-
als following consumption of dietary
supplements containing ephedrine
alkaloids. Among the reported ad-
verse events subjectively determined
to be definitely, probably, or possibly
associated with ephedra use were 17
cases of hypertension, 13 cases of
palpitations or tachycardia, 10 cases
of stroke, and 7 cases of seizures.
Ten of these events resulted in death.
Under the DSHEA, the reporting
of adverse events associated with
the use of dietary supplements was
voluntary. Adverse event reporting
became mandatory when the Dietary
Supplement and Nonprescription
Drug Consumer Protection Act was
signed into law in December 2006.
Specifically, that law requires manu-
facturers, packers, and distributors
of dietary supplements to record,
investigate, and forward to the FDA
any reports they receive of serious
adverse events associated with the
use of their products that are reported
OTC Advisor: Popular Herbal and Dietary Supplements
to them directly. A serious adverse
event is an adverse event that:
Results in death, a life-threatening
experience, inpatient hospitaliza-
tion, a persistent or significant
disability or incapacity, or a con-
genital anomaly or birth defect.
Requires, based on reasonable
medical judgment, a medical or
surgical intervention to prevent
one of these outcomes.
The law also expands labeling re-
quirements for dietary supplements
to include a domestic address or
telephone number for reporting seri-
ous adverse events. Companies must
submit reports of serious adverse
events to the FDA no later than 15
business days after the report is re-
ceived. Consumers and health care
professionals also are encouraged to
report both serious and nonserious
dietary supplementrelated adverse
events through the FDA MedWatch
program (1-800-FDA-1088 or www.
fda.gov/Safety/MedWatch).
Dietary supplement alerts and
safety information are available on the
FDA Web site at www.fda.gov/Food/
DietarySupplements/Alerts/default.
htm.
Advising Patients About
Dietary Supplement Use
As few as one third of adults dis-
close their use of herbal and other
dietary supplements to conventional
health care providers, and only about
half (54.9%) use these products in
accordance with evidence-based
indications (ranging from a high of
68.0% for echinacea to a low of 3.8%
for ginseng). As the health care pro-
fessional most likely to be accessible
at the point of purchase, pharmacists
are well positioned to talk with con-
sumers about dietary supplements,
provide evidence-based recommen-
dations for the use of dietary supple-
ments, and discourage the use of
unsafe products and practices.
Ashar and Rowland-Seymour rec-
ommend the following six-step frame-
work for engaging patients in discus-
sions about dietary supplement use:
1. Inquire about supplement use.
2. Evaluate the supplement.
3. Discuss regulatory issues sur-
rounding dietary supplements.
4. Discuss the available safety and
efficacy data.
5. Compare risk/benefit of use to
available conventional therapies.
6. Monitor for adverse effects and
therapeutic response.
Key considerations for implementing
this framework are described below.
Set the Tone for a
Productive Interaction
Asking patients about their use
of herbal products and other dietary
supplements should be a routine part
of pharmacist-patient interactions.
Because it is more likely that patients
will disclose this information openly
if they feel comfortable, pharmacists
must recognize the importance of re-
specting the patients beliefs and val-
ues so that a trusting, nonjudgmental
relationship can develop. Examples
of questions that will assist in char-
acterizing the patients use of dietary
supplements are listed in Table 1.
Consider Possible Risks of
Dietary Supplement Use
Many patients consider dietary
supplementsherbal products in
particularto be natural and there-
fore milder and safer than prescrip-
tion and nonprescription medications.
Unfortunately, the fact that herbal
dietary supplements are derived from
natural sources does not guarantee
safety. Although adverse effects
sometimes are linked to product con-
taminants, they more frequently result
from the basic pharmacology of the
supplement or its biologically active
constituents. For example, the pyr-
rolizidine alkaloids present in comfrey
have been associated with hepatotox-
icity that may be rapidly progressive
and fatal.
Data from the 2002 National
Health Interview Survey showed that
more than 80% of respondents who
used herbal dietary supplements also
had used a nonprescription medica-
tion during the previous 12 months,
and 72% had used a prescription
medication. Patients generally are
unaware of the potential for interac-
tions between dietary supplements
and conventional medications. These
interactions may have either a phar-
macodynamic or pharmacokinetic
5

Table 1. Assessing
Dietary Supplement
Use By Patients
What are the patients goals for using
a dietary supplement?
Is the product being used to treat a
specific condition or symptom?
Is the product being used for
possible preventive purposes?
What benefit or effect does the patient
expect from the dietary supplement?
Is the patient currently taking a
nonprescription or prescription
medication for the same condition or
purpose?
Is there a cultural context that needs to
be understood?
basis. Pharmacodynamic interactions
are possible when a supplement aug-
ments or antagonizes the activity of
a medication the patient is taking; for
example, both St. Johns wort and
l-tryptophan increase the levels of
circulating serotonin and have been
linked to reports of serotonin syn-
drome in patients taking psychotropic
medications. Pharmacokinetic inter-
actions are caused by changes in
the absorption, distribution, metabo-
lism, or excretion of the supplement,
the medication, or both, resulting
in more pronounced or diminished
pharmacologic activity. For example,
St. Johns wort induces multiple cy-
tochrome P450 (CYP) isoenzymes
and has been reported to induce the
metabolism of drugs such as oral
contraceptives, protease inhibitors,
and cyclosporine.
Consult Reliable Sources
of Information
The safety and efficacy of most
dietary supplements sold in the
United States have not been well es-
tablished. Although the body of infor-
mation is growing, the overwhelming
majority of dietary supplements have
not been studied using modern sci-
entific techniques, and it remains
unlikely that definitive evidence will
be available anytime soon. There is
limited government funding available
to conduct high-quality clinical trials,
so the pace of research is slow. There
also are few incentives for manu-
facturers or scientists to conduct ef-
6 American Pharmacists Association
ficacy or safety studies. Companies
cannot obtain patents on existing
dietary ingredients and thus have
little possibility of market exclusivity.
Researchers seeking National Insti-
tutes of Health funding to assess the
efficacy of a dietary supplement in
treating or preventing a specific dis-
ease or condition would need to file
an investigational new drug applica-
tion. To do so, the researcher would
need to obtain manufacturer support
and detailed analytical information
about the specific supplement, which
the manufacturer may or may not be
willing to provide.
To help patients make informed
choices about dietary supplement
use, pharmacists need to be aware of
and have access to reliable sources
of product information. Examples of
popular resources are described in
this section.
Office of Dietary Supplements
The DSHEA authorized the estab-
lishment of the Office of Dietary Sup-
plements (ODS) within the National
Institutes of Health in 1995. The main
purposes of the ODS are to:
Explore more fully the potential
role of dietary supplements as a
significant part of the efforts of the
United States to improve health
care.
Promote scientific study of the
benefits of dietary supplements in
maintaining health and preventing
chronic disease and other health-
related conditions.
The ODS Web site includes a
library of Dietary Supplement Fact
Sheets that are suitable for distribu-
tion to patients (although not all of
these sheets would be appropriate
for patients with low literacy). The
Web site (http://ods.od.nih.gov) also
serves as a portal to the International
Bibliographic Information on Dietary
Supplements database, which pro-
vides access to bibliographic cita-
tions and abstracts from published,
international, and scientific literature
on dietary supplements.
National Center for Complementary
and Alternative Medicine
The National Institutes of Health
National Center for Complementary
and Alternative Medicine (NCCAM)
was created by Congress in 1998.
The mission of NCCAM is to explore
complementary and alternative
healing practices in the context of
rigorous science, train CAM research-
ers, and disseminate authoritative
information to the public and profes-
sionals. Accordingly, the NCCAM
Web site offers extensive information
about dietary supplements for both
consumers and health care practi-
tioners, including a list of clinical tri-
als. The Web site (http://nccam.nih.
gov) also includes a link to CAM on
PubMed, which automatically limits
literature searches to the CAM subset
of PubMed citations.
Cochrane Reviews
Cochrane Reviews are systematic
reviews of research in health care
and health policy, including research
about dietary supplements. Each
review provides detailed information
about the trials that were included
and excluded from analysis, summa-
rizes the results of included studies,
and offers the authors evidence-
based conclusions. The Cochrane
Library Web site (http://thecochrane
library.com) offers free access to the
abstracts and, where available, the
plain language summaries of all Co-
chrane systematic reviews. Access to
the full reports is available for a fee;
some pharmacists may have access
to the full reports through institutional
subscriptions.
ConsumerLab.com
In addition to the Product Reviews
described earlier, subscribers to the
ConsumerLab.com Web site have
access to an encyclopedia of natu-
ral and alternative treatments. Each
entry contains a brief summary of
what the herb or supplement is used
for, the evidence supporting its use,
the usual dosage, and safety issues.
Both English and Spanish versions
are available.
Natural Medicines Comprehensive
Database
The Natural Medicines Compre-
hensive Database at www.natural
database.com is a subscription ser-
vice from the company that publishes
Pharmacists Letter and Prescribers
Letter. The database consists of more
than 1,100 detailed, evidence-based
monographs on individual natural in-
gredients; each monograph provides
ratings of the safety of the ingredient
as well as its effectiveness for spe-
cific indications. In addition, possible
interactions with other dietary supple-
ments, drugs, foods, laboratory tests,
and diseases and conditions are
rated as major, moderate, or minor.
Products that have been awarded the
USP Dietary Supplement Verification
Program certification mark are identi-
fied with this mark next to their listing
in the database. The online mono-
graphs include links to a list of brand
name products that contain the ingre-
dient, as well as to patient handouts
in English and Spanish. Downloads
for personal digital assistant (PDA)
and print options are available.
A consumer version of the data-
base is available at www.naturaldata
baseconsumer.com.
Natural Standard
Natural Standard is an inter-
national research collaboration that
aggregates and synthesizes data
on complementary and alternative
therapies. The Natural Standard elec-
tronic database on foods, herbs, and
supplements includes comprehen-
sive, evidence-based monographs
designed to facilitate clinical decision
making. The quality of the available
evidence supporting the efficacy of
each therapy for a given indication is
rated on a validated, five-point scale
(A = strong evidence, B = good evi-
dence, C = unclear or inconclusive
evidence, D = fair negative evidence,
F = strong negative evidence). Phar-
macists can access the database at
www.naturalstandard.com through
an individual or institutional subscrip-
tion (including abridged desktop and
PDA options). A number of print prod-
ucts also are available.
Weigh the Benefits and Risks
of Dietary Supplement Use
Once the pharmacist understands
a patients reasons for using (or want-
ing to use) a dietary supplement and
has consulted a reliable source of
information about the supplement, it
is possible to provide the patient with
an evidence-based recommenda-
tion (or explain when the available
OTC Advisor: Popular Herbal and Dietary Supplements
information is insufficient). A schema
that considers both the efficacy and
safety of a given therapy is presented
in Figure 3.
Very few dietary supplements
have conclusive evidence supporting
both safety and efficacy. Those that
do generally can be recommended to
patients, assuming that no risk
of drug or disease state interactions
exists.
Similarly, few dietary supplements
have conclusive evidence indicat-
ing a serious safety risk, complete
lack of efficacy, or both. When such
evidence does exist, pharmacists
should actively discourage patients
from using the product.
Most dietary supplements fall into
one of the remaining two categories:
There is evidence supporting
safety, but evidence regarding
efficacy is inconclusive.
There is evidence supporting
efficacy, but evidence regarding
safety is inconclusive.
In either case, use of the desired
product most likely is acceptable with
appropriate patient counseling and
monitoring. Following the framework
outlined by Ashar and Rowland-Sey-
mour, pharmacists should acquaint
patients with the regulatory issues
surrounding dietary supplements and
summarize what is known about the
efficacy and safety of the desired
product. Whenever appropriate,
Figure 3. Dietary Supplement Counseling Actions
Based on Evidence of Safety and Efficacy
Evidence supports
both safety and
efficacy
Recommend
Continue to monitor
Evidence supports
efficacy, but evidence
regarding safety is
inconclusive
Provide caution
Monitor closely
pharmacists also might discuss the
efficacy and safety data for related
prescription and nonprescription
treatment options to ensure that the
patient is fully informed about all
possible choices. As an example, a
patient intent on purchasing a weight
loss dietary supplement might in-
stead elect to try a course of therapy
with nonprescription orlistat.
The FDA offers two publications
that acquaint consumers with basic
issues related to dietary supplement
use. Tips for the Savvy Supplement
User: Making Informed Decisions
and Evaluating Information includes
links to a number of other online re-
sources; it is available at www.fda.
gov/Food/DietarySupplements/Con
sumerInformation/ucm110567.htm.
Tips for Older Dietary Supplement
Users is targeted to older adults, but
it contains information that would be
of value to any patient who is con-
sidering using dietary supplements.
It is available at www.fda.gov/Food/
DietarySupplements/ConsumerInfor
mation/ucm110493.htm#botline.
All patients who elect to use di-
etary supplements should be advised
to inform all of their health care pro-
viders of the products they are taking.
Assist Patients With Product
Selection and Use
If a patient decides to purchase a
dietary supplement, the pharmacist
Evidence supports
safety, but evidence
regarding efficacy is
inconclusive
Use more than likely
acceptable
Provide caution
Monitor closely
Evidence indicates
serious safety risk,
lack of efficacy, or
both
Actively discourage use
7
should help the patient choose a qual-
ity product. In general, patients should
be counseled to purchase products
that either (1) bear a certification mark
from one of the voluntary programs
discussed earlier or (2) meet their
content claim as assessed by
ConsumerLab.com. Pharmacists may
feel most comfortable recommending
products from large companies with
known reputations, or from companies
that also manufacture prescription or
nonprescription medications.
Once a quality product has been
selected, patients should continue to
purchase and use the same brand
and formulation. This approach
increases the likelihood of a con-
sistent active ingredient, dose, and
response. Patients who have not had
positive results with a specific dietary
supplement product might consider
a trial with a different brand before
concluding that the supplement is
ineffective.
Additional recommendations for
product counseling are presented in
Table 2.
Monitor for Adverse Effects
and Therapeutic Response
Patients should be advised to
monitor for short-term adverse events
for at least 2 weeks after initiating a
new dietary supplement and to con-
tinue monitoring for longer-term ad-
verse events while using the product.
Educating patients about anticipated
adverse effects will enable them to
recognize a problem and discontinue
product use early enough to minimize
harm.
Patients also should be educated
about the likely window for thera-
peutic response. For some chronic
conditions, dietary supplements may
not produce noticeable effects for
30 days or longer. Patients who are
unaware of the anticipated response
time frame may discontinue product
use prematurely.
Considerations for
Special Groups
A number of special popula-
tions provide unique challenges
when counseling patients about
dietary supplements. The lack of
data on safety and efficacy in these
8 American Pharmacists Association
populations underscores the need older adults about the use of dietary
for comprehensive assessment of supplements.
the patients health status and knowl-
edgeable counseling on dietary Children
supplement use. Body and organ functions are in
a continuous state of development in
Older Adults children. Especially in children young-
Older adults are more likely than er than 2 years of age, renal function
younger patients to have multiple is less developed, and the central
chronic diseases and to be taking nervous system may be uniquely
multiple prescription and nonpre- sensitive to many substances. In ad-
scription medications. Older adults dition, the pharmacokinetic proper-
also are likely to have age- and ties of dietary supplements may be
disease-related changes in physi- different in children and may undergo
ologic function (e.g., decreased renal rapid change as children grow and
function). Thus, the potential for drug mature. It may be difficult or impos-
interactions, age-related functional sible to determine an appropriate pe-
declines, and concomitant disease diatric dose of a dietary supplement.
must be considered when counseling
Table 2. General Recommendations for Advising
Consumers About Dietary Supplements
Appropriate Use
Read all labels carefully; never take more than the recommended amount.
Never share dietary supplements with others.
Do not select a product that lacks dosing recommendations on the label.
Avoid products that do not carry a lot number or expiration date.
Discard products 1 year from the date of purchase if no other expiration date is present.
Select products that list the manufacturers name, address, and telephone number.
Store products in a dry environment out of direct sunlight and humidity, and away from
young children and pets.
Special Groups
Always seek the advice of a pediatrician before using dietary supplements in children.
Avoid dietary supplements if you are pregnant or nursing, or trying to become
pregnant.
Speak to your health care professional if you are trying to treat a life-threatening
condition, such as cancer or human immunodeficiency virus infection.
Adverse Effects
The term natural does not mean safe; be diligent and report any unusual experiences to
your physician and pharmacist.
If you are allergic to plants, weeds, and/or pollen, ask your health care provider about
dietary supplements before using these products.
Interactions
If you are taking a prescription medicine, do not take a dietary supplement for the same
condition.
When possible, avoid taking multi-ingredient preparations; select single-ingredient
products that list the strength per dose.
Do not take these products with alcohol until you know it is safe to do so, or you are
familiar with the effects.
Check with your health care provider if you are taking blood thinning drugs; some
dietary supplements may interact with the drugs.
Always inform your health care provider of the products you are taking; keep a list if
necessary or bring them with you to your appointment.
Expectations
Never use these products in place of proper rest and nutrition; eat a balanced diet.
Do not expect a cure or unrealistic results; these agents are not cure-alls.
If it sounds too good to be true, it probably is; use discretion when evaluating claims.
Keep a diary to track dietary supplement effectiveness and side effects.
Pregnant Women
Little information exists about
the safety of dietary supplement use
during pregnancy. This is of par-
ticular concern because as many as
395,000 births in the United States
each year involve antenatal exposure
to at least one herbal supplement.
Of the 4,239 women included in the
National Birth Defects Prevention
Study, 462 (10.9%) reported use
of an herbal product during the 3
months before or during pregnancy.
Among pregnant women, herbal use
was highest (6.9%) during the first
trimestera critical period of fetal
organ development.
Patients Undergoing Surgical
Procedures
Several different dietary supple-
ments may increase the risk of bleed-
ing before or after surgery; some
have the potential to affect the metab-
olism of anesthetic agents. It is pru-
dent for patients to discontinue use
of all dietary supplements at least 2
weeks before any scheduled surgical
procedure. Because some institutions
may have more stringent policies,
patients should check with all health
care providers involved in the surgery
regarding specific guidelines for dis-
continuation of dietary supplements.
Patients With Renal Disease
Many Americans have chronic re-
nal insufficiency or failure attributable
to systemic diseases such as diabe-
tes. Their renal systems may be un-
able to eliminate dietary supplements
appropriately, potentially resulting
in supratherapeutic concentrations.
In addition, herbs that possess anti-
platelet properties might increase the
risk of bleeding in adults with chronic
renal insufficiency.
Summaries of Selected
Dietary Supplements
Literally thousands of different
dietary supplements are available on
the market today. This section pro-
vides an overview of selected nonvi-
tamin, nonmineral supplements that
are used widely in the United States.
Because this monograph covers only
a small subset of dietary supplements
and their uses, pharmacists are en-
OTC Advisor: Popular Herbal and Dietary Supplements
couraged to consult any of the more
comprehensive resources discussed
earlier to obtain additional information
about the products discussed here
or to learn about other products that
their patients use.
Black Cohosh
Black cohosh (Actaea racemosa
or Cimicifuga racemosa) is a peren-
nial plant and a member of the but-
tercup family native to North America.
Black cohosh should not be confused
with blue cohosh (Caulophyllum thal-
ictroides), a different herb with chemi-
cals that may damage the heart and
increase blood pressure. Prepara-
tions of black cohosh are made from
the roots and rhizomes (underground
stems) of the plant.
The mechanism of action of black
cohosh remains unclear. Although it
is possible that black cohosh exhibits
estrogenic activity, the evidence is
contradictory and the issue remains
controversial; it has shown no effect
on vaginal epithelium, endometrium,
or hormone concentrations.
Black cohosh is used most com-
monly to treat symptoms of meno-
pause. The usual dosage is 40 to 80
mg daily (as a standardized extract)
in one or two doses. Black cohosh al-
so is used in the treatment of premen-
strual syndrome and dysmenorrhea.
There is some evidence to support its
use for joint pain in rheumatoid arthri-
tis or osteoarthritis.
A 2005 review of five published
studies on the effectiveness of black
cohosh for the relief of menopausal
symptoms (including hot flashes, pro-
fuse sweating, insomnia, and anxiety)
concluded the herb was a safe and
effective alternative to estrogen re-
placement therapy, although the au-
thor acknowledged limitations in the
clinical studies reviewed. In a 2010
meta-analysis that included nine ran-
domized, placebo-controlled trials,
six of the trials were found to dem-
onstrate a significant improvement in
menopausal symptoms in the black
cohosh group compared with the
placebo group; aggregate data from
seven of the trials indicated that black
cohosh improved symptoms overall
by 26% (95% confidence interval,
11%40%). However, the trials were
significantly heterogeneous, and the
Standardization of Herbal
Dietary Supplements
Herbs contain many active and inactive
constituents. The process known as
standardization involves identifying
specific chemicals or markers that are
thought to possess therapeutic activity,
isolating them, and then formulating them
into a final and consistent product.
Standardization can occur only if the
chemical markers that contribute to
the pharmacologic effect of a plant-
based dietary supplement have been
identified. For example, a Ginkgo
biloba product may indicate that it is
standardized to contain 6% terpene
lactones and 24% flavonoid glycosides,
whereas an echinacea product may not
list any standardized markers. In some
cases, the identified active chemical
markers change over time as new
pharmacologic research is performed.
This happened with St. Johns wort; the
active antidepressant marker was initially
thought to be hypericin but is now
thought to be hyperforin. St. Johns wort
products may list one or both of these
standardizations on the package label.
trial with the longest follow-up and the
highest dose of black cohosh (160
mg)a 1-year randomized, double-
blind, placebo-controlled trial (n =
351) funded by NCCAMdid not
demonstrate significant improvement
in the black cohosh group compared
with the placebo group.
The use of black cohosh for up
to 6 months generally is considered
to be safe. Common adverse effects
include gastrointestinal complaints,
headache, rash, and occasional
weight gain. In a review of more than
2,800 patients using black cohosh, the
incidence of reported adverse events
was only 5.4%, and most events were
minor. Hepatitis and liver failure have
been reported in patients taking black
cohosh, but the causal association is
unclear. Until more data are available,
pharmacists should advise patients
to inform their primary care provider
of any symptoms such as abdominal
discomfort, dark urine, or jaundice that
may indicate liver disease.
The use of black cohosh by
women who have had breast can-
cer appears to be safe but remains
controversial. In a 2007 study, 1,102
breast cancer survivors taking black
9
cohosh were followed over an aver-
age of 3.6 years; the study concluded
that black cohosh was not associated
with an increased risk of recurrence.
However, it may be best for women
with a history of breast cancer to
avoid black cohosh until its effects on
breast tissue are better understood.
Because of potential hormonal ef-
fects, the use of black cohosh during
pregnancy and breastfeeding should
be avoided.
Information about black cohosh,
including drug interactions, is sum-
marized in Table 3.
Coenzyme Q10
Coenzyme Q10 (CoQ10) is found
in every cell of the human body,
primarily in the mitochondria. It is a
cofactor in many functions associated
with energy production; it is the rate-
limiting cofactor in the formation of
mitochondrial adenosine triphosphate
(ATP). CoQ10 stabilizes membranes
and may have vasodilatory and ino-
tropic effects.
One CoQ10 preparation has FDA
orphan drug status for the treatment
of Huntingtons disease. As a dietary
supplement, CoQ10 is used as a
treatment for several cardiovascular
conditions, especially heart failure,
cardiomyopathy, and hypertension. It
also is used as a general antioxidant.
Some patients have a documented
CoQ10 deficiency and take supple-
ments to correct that deficiency.
Evidence for most uses of CoQ10
is contradictory or preliminary. Recent
studies in patients with heart failure
have demonstrated both positive and
negative results in outcomes such as
overall symptoms, ejection fraction,
and oxygen consumption. Nonethe-
less, the use of CoQ10 as an adjunc-
tive therapy is considered to be
acceptable because of its favorable
adverse effect profile. Nausea, gas-
trointestinal distress, anorexia, head-
ache, irritability, and dizziness have
occurred in less than 1% of patients.
CoQ10 is manufactured using a
beet and sugarcane fermentation
process. The chemically reduced
form is called ubiquinone. The usual
dosage of CoQ10 is 100 to 200 mg
daily; doses greater than 100 mg
generally are administered as divided
doses.
10
Information about CoQ10, includ- chlorogenic acid, cynarin), glyco-
ing drug interactions, is summarized proteins, isobutylamides, polyenes,
in Table 4. and polysaccharides. Although the
specific mechanism of action of echi-
Echinacea nacea preparations remains unclear,
Echinacea, or purple coneflower, its effects include increasing cytokine
is a member of the Asteraceae family. secretion, lymphocyte activity, and
Nine Echinacea species are indig- phagocytosis. Antiviral, antifungal,
enous to North America; the species and anti-inflammatory activity also
used most frequently in clinical trials have been observed.
are Echinacea purpurea, Echinacea The evidence supporting the abil-
angustifolia, and Echinacea pallida. ity of echinacea to prevent or treat the
The roots, leaves, and flowers all are common cold is inconclusive. A 2006
considered to be medicinally active. Cochrane review analyzed 16 ran-
Echinacea preparations typically domized, controlled trials that com-
are not standardized to a single ac- pared echinacea with a placebo, no
tive constituent. Products may contain treatment, or another treatment for the
more than one Echinacea species prevention or treatment of the com-
and more than one part of the plant; mon colda total of 22 comparisons.
it is not clear which single species or None of the three comparisons in the
combination may be most effective. prevention trials showed an effect
Because products differ appreciably over placebo; in the treatment trials,
in composition, each product has its a significant effect for echinacea
own dose and dosing regimen. over placebo was reported in nine
Echinacea is used primarily as comparisons, a trend in one, and no
an immune stimulant to prevent and difference in six. Conversely, a 2007
treat the common cold and other meta-analysis of 14 trials encompass-
respiratory infections. Components ing more than 2,900 participants
that target the nonspecific cellular found that echinacea decreased the
immune system have been identi- odds of developing the common cold
fied and include alkylamides, caffeic by 58% and the duration of a cold by
acid derivatives (e.g., chicoric acid, 1.4 days.
Table 3. Black Cohosh at a Glance
Most Common Uses
Menopausal symptoms
Usual Dosages
40 to 80 mg daily in one or two doses
Adverse Effects
Generally safe at recommended doses for use up to 6 months
Adverse effects may include occasional, mild gastrointestinal complaints; headache;
rash; weight gain
High doses may cause headache, dizziness, perspiration, visual disturbances
Controversial hepatic effects; approximately 30 case reports of acute hepatitis
Selected Drug Interactions
Possible interaction with medications metabolized by CYP2D6, such as tricyclic
antidepressants, -blockers, and antipsychotics; use cautiously or avoid
Possible additive estrogenic activity with hormone therapy or oral contraceptives
Possible interaction with tamoxifen, raloxifene
May increase toxicity of doxorubicin and docetaxel
May decrease effectiveness of cisplatin
Avoid concurrent use with hepatotoxic medications
Cautions
Avoid use during pregnancy and breastfeeding because of possible hormonal effects
Use in high-risk populations (e.g., women with a history of breast cancer) should be
supervised by a health care professional
American Pharmacists Association
 Echinacea appears to work best
when treatment is started at the first
sign of cold symptoms and continued
for 5 to 7 days. The existing evidence
does not support chronic use of
echinacea to prevent or reduce the
frequency of respiratory infections.
Echinacea products generally
are well tolerated. Adverse effects
may include mild gastrointestinal
discomfort, tingling sensation of the
tongue, and headache. Patients with
allergies to plants in the Asteraceae
or Compositae familyincluding rag-
weed, chrysanthemums, marigolds,
and daisiesare more likely to have
an allergic reaction to echinacea and
should avoid using these products.
Echinacea products also are best
avoided by patients with a history of
asthma, atopy, or allergic rhinitis.
Information about echinacea,
including drug interactions, is sum-
marized in Table 5.
Evening Primrose Oil
Evening primrose (Oenothera
biennis) is a member of the primrose
family Onagraceae. The oil from eve-
ning primrose seeds consists of at
least 85% to 92% unsaturated fatty
acids. The essential omega-6 fatty
acids cis-linoleic acid and cis-gam-
ma-linolenic acid (GLA) are the pri-
mary components; GLA is believed
to be the active constituent. The seed
oil also contains smaller amounts of
oleic, palmitic, and stearic acids.
Evening primrose oil has been
used for a wide range of symptoms
and conditions, including mastalgia,
premenstrual syndrome, menopausal
symptoms, preeclampsia, diabetic
neuropathy, chronic fatigue syn-
drome, and atopic dermatitis. High-
quality evidence for most of these
uses is lacking, and much of the evi-
dence that does exist is inconsistent
or inconclusive. A systematic review
of 11 randomized, controlled trials of
evening primrose oil in the treatment
of premenstrual syndrome found no
conclusive evidence for efficacy. In
a meta-analysis of English language
trials on mastalgia, evening primrose
oil was no better for pain relief than
placebo. Several studies support the
use of evening primrose for the treat-
ment of atopic dermatitis, but addi-
tional data from large, well-designed
OTC Advisor: Popular Herbal and Dietary Supplements
trials is needed. disorders, as well as patients being
Evening primrose oil generally is treated with medications that may
well tolerated. Adverse effects may lower the seizure threshold (e.g.,
include headache, nausea, diarrhea, phenothiazines).
and abdominal pain. Because there The usual dosage of evening
have been several reports of seizures primrose oil depends on the condition
in people using evening primrose being treated. For example, dosages
oil, these products are best avoided of 4 to 8 g daily in divided doses have
in patients with a history of seizure been used for atopic dermatitis; dos-
Table 4. Coenzyme Q10 at a Glance
Most Common Uses
Cardiomyopathy
Coenzyme Q10 deficiency
General antioxidant effects
Heart failure
Hypertension
Usual Dosages
100 to 200 mg daily; doses greater than 100 mg should be administered as divided
doses
Adverse Effects
Generally well tolerated
Nausea, gastrointestinal distress, anorexia, headache, irritability, dizziness have been
reported by less than 1% of patients
Selected Drug Interactions
Possible vitamin Klike procoagulant effects if taken with warfarin; monitor international
normalized ratio
Cautions
Safety during pregnancy and breastfeeding has not been determined
Table 5. Echinacea at a Glance
Most Common Uses
Prevention of common cold
Treatment of common cold (reduction in duration, severity of symptoms)
Usual Dosages
Echinacea preparations are not standardized to one active constituent; each product
has its own dosing regimen
Adverse Effects
Generally well tolerated
Adverse effects may include mild gastrointestinal discomfort, tingling sensation of the
tongue, headache
Selected Drug Interactions
Possible interactions with immunosuppressant agents (e.g., azathioprine, cyclosporine),
although none documented
Potential CYP3A4 inhibitor (in vitro data only)
Cautions
Avoid use in patients with:
Allergies to plants in the Asteraceae family
A history of asthma, atopy, or allergic rhinitis
11
ages of 3 g daily in divided doses
have been used for mastalgia.
Information about evening prim-
rose oil, including drug interactions, is
summarized in Table 6.
Fish Oil
Fish oiloil obtained from fish
that store lipid in their flesh or liver
(e.g., cod liver)is a rich source of
the essential omega-3 fatty acids
docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA). As
essential fatty acids, DHA and EPA
cannot be manufactured in the body;
preformed DHA and EPA must be
obtained from exogenous sources.
The American Heart Association
emphasizes obtaining omega-3 fatty
acids from dietary sources; the gen-
eral recommendation is to consume
at least two servings of a variety of
oily fish (salmon, tuna, mackerel, her-
ring, and trout) per week. Because
the requisite amount of fish intake
may be difficult for many people to
achieve and sustain over the long
term, fish oil may be consumed to
help ensure an adequate intake of
DHA and EPA. Fish oil also is used
for cardiovascular benefits (including
treatment of hypertriglyceridemia and
hypertension) or to improve a variety
of inflammatory conditions (e.g., rheu-
matoid arthritis).
In contrast to many other dietary
supplements, there is a strong body
of evidence to support the use of fish
oil. In epidemiological and clinical
trials, consumption of omega-3 fatty
acids from fish or fish oil supplements
has been shown to reduce both the
incidence of cardiovascular disease
and the rates of all-cause mortality,
cardiac and sudden death, and
possibly stroke. The evidence for
the benefits of fish oil is stronger in
secondary prevention than in primary
prevention. Fish oil supplements also
have been shown to reduce serum
triglyceride concentrations by 20%
to 40%, with little or no effect on total
cholesterol and low-density lipopro-
tein cholesterol concentrations. Mul-
tiple small clinical trials have reported
small reductions in blood pressure
with intake of omega-3 fatty acids;
however, because the results are
considered to be inconclusive, any
hypertensive effect should be consid-
12
ered a beneficial side effect of using
fish oil supplements rather than a pri-
mary reason for taking them. Clinical
trials that investigated the use of fish
oil for rheumatoid arthritis have dem-
onstrated beneficial anti-inflammatory
effects, with reductions in pain and
swelling, increased range of motion,
and the ability to reduce doses of
prescription medications.
Fish oil supplements are available
primarily in capsule and liquid formu-
lations, although novel dosage forms
(e.g., soft chews, squeeze packets)
are being introduced. DHA and EPA
account for approximately 30% of the
fatty acids in a typical fish oil prepa-
ration, with a standard 1 g capsule
providing about 300 mg of DHA plus
EPA. More concentrated versions
are available. The labeled strength
may reflect only the DHA plus EPA
content, or it may reflect the total fish
oil content (including omega-3 fatty
acids other than DHA and EPA); con-
sumers should be cautioned to check
the Supplement Facts label carefully
to ensure that they are getting the
desired amount of DHA plus EPA.
The primary adverse effect as-
sociated with fish oil supplements is
gastrointestinal upset, especially
belching with a fishy aftertaste.
Belching generally can be lessened
Table 6. Evening Primrose Oil at a Glance
Most Common Uses
Atopic dermatitis (eczema)
Chronic fatigue syndrome
Diabetic neuropathy
Mastalgia
Menopausal symptoms
Preeclampsia
Premenstrual syndrome
Usual Dosages
Depends on condition being treated; up to 8 g daily in divided doses
Adverse Effects
Generally well tolerated
Adverse effects may include headache, nausea, diarrhea, abdominal pain
Selected Drug Interactions
Possible additive effects if taken with other platelet-active drugs (e.g., warfarin) or
supplements
Seizures possible if taken with phenothiazines
Potential additive effects to antihypertensive agents
Cautions
May lower the seizure threshold in patients who have seizure disorders
by using enteric-coated products and
consuming doses with meals; storing
capsule formulations in the freezer
also may help. (Liquid formulations of
fish oil always should be stored in the
refrigerator.) Very high intake of ome-
ga-3 fatty acids (e.g., more than 3 g
of DHA plus EPA) may increase the
risk of bleeding, but there is little evi-
dence of significant bleeding risk at
lower doses. There is a potential, al-
beit unlikely, risk of increases in blood
glucose levels. Safety concerns that
apply to the consumption of oily fish
do not apply to fish oil supplements,
which are essentially mercury free.
Recommendations for daily intake
of DHA plus EPA for general good
health range from 200 mg to 2 g. A
dose of 1 g per day is recommended
for secondary prevention of cardiovas-
cular disease; doses of 2 to 4 g per
day are recommended for triglyceride
lowering. Doses of 2.5 g or more have
been used in rheumatoid arthritis
studies. Patients with coronary heart
disease, elevated triglycerides, or
rheumatoid arthritis should consume
supplemental fish oil only in consulta-
tion with their physician. A prescription
product (e.g., Lovaza, which contains
omega-3-acid ethyl esters) may be
more appropriate for some patients
with hypertriglyceridemia.
American Pharmacists Association
 Information about fish oil, includ-
ing drug interactions, is summarized
in Table 7.
Garlic
Garlic dietary supplements are
derived from dried or fresh bulbs of
garlic (Allium sativum)the same
plant that is used for cooking. Garlic
bulbs contain alliin, an odorless, sulf-
oxide amino acid derivative. Crushing
a bulb of garlic releases the enzyme
allinase, which converts alliin to allicin.
Allicin is the main component of gar-
lics pungent, volatile oil.
Garlic possesses hypolipidemic,
hypotensive, antiplatelet, and anti-
infective properties and may have
antioxidant activity. Most research
examining the effects of garlic has
been conducted using tablets or
capsules containing dehydrated,
powdered garlic standardized to an
allicin content of 1% to 1.6%, provid-
ing 3 to 5 mg of allicin per day. The
World Health Organization recom-
mends a dosage of 2 to 5 mg of allicin
per day (the equivalent of 25 g fresh
garlic, 0.41.2 g dried garlic powder,
25 mg oil, or 3001,000 mg extract).
Although allicin is used as the primary
standardization marker, other sulfur-
containing substances in garlic also
may exert pharmacologic activity.
Numerous studies of the hypo-
cholesterolemic effects of garlic have
yielded conflicting results. Positive
findings generally have been mod-
est, with the most rigorous studies
showing reductions in total cholesterol
of approximately 5% over the short
term (similar to the reductions attain-
able with dietary changes alone).
However, a recent parallel-design,
placebo-controlled trial of three garlic
preparations (i.e., fresh garlic, dried
powdered garlic tablets, and aged
garlic extract tablets) in adults with
moderate hypercholesterolemia found
no statistically or clinically significant
effects on total cholesterol, low-
density lipoprotein cholesterol, or
other plasma lipid concentrations.
Garlic also has been used to treat
hypertension and type 2 diabetes.
The clinical evidence for these uses is
considered to be preliminary.
Regular consumption of large
amounts of raw or cooked (dietary)
garlic may help to reduce the risk of
OTC Advisor: Popular Herbal and Dietary Supplements
developing several types of cancer, These compounds exhibit a complex
including gastric and colorectal can- pharmacologic profile that includes
cer. No clinical trials have been per- neuroprotective, antioxidant, and free
formed using garlic supplements. radical scavenger effects. Ginkgolide
Garlic supplements generally are B is a potent platelet-activating factor
well tolerated. Bad breath and body antagonist.
odor are the most common adverse Ginkgo is used commonly to treat
effects; enteric-coated products may dementia and to enhance memory.
help to prevent or lessen bad breath. Data from a well-controlled, prospec-
(So-called odorless products may tive study suggest that a patients
contain insufficient amounts of allicin.) baseline cognitive state may influence
Other common gastrointestinal ef- the clinical response to ginkgo; pa-
fects include nausea, vomiting, and tients with mild to moderate dementia
heartburn, all of which are more likely showed actual improvement, whereas
at higher doses. Some patients may those with more severe disease
experience allergic reactions to garlic. showed stabilization or a diminished
Because garlic has antiplatelet and rate of deterioration. Another random-
antithrombotic effects, bleeding is a ized, double-blind, placebo-con-
potentially serious adverse effect of trolled study comparing the efficacy
garlic use. of ginkgo with that of donepezil for
Information about garlic, including the treatment of Alzheimers dementia
drug interactions, is summarized in found they were equally effective.
Table 8. In contrast, a Cochrane review of
randomized, placebo-controlled,
Ginkgo double-blind trials examining the ef-
Ginkgo dietary supplements fects of ginkgo in patients with cogni-
are produced from the leaves of the tive impairment and dementia (of any
Ginkgo biloba tree. The standard- severity) concluded that the evidence
ized, concentrated (50:1) leaf extract for ginkgos benefit was inconsistent
contains diterpene lactones such as and unconvincing. The authors noted
ginkgolides (A, B, C, and M) and the that early trials used small populations
sesquiterpene bilobalide, as well as and less rigorous methodology.
bioflavonoids and flavone glycosides. Conflicting data continue to ap-
Table 7. Fish Oil at a Glance
Most Common Uses
Dietary supplementation of essential omega-3 fatty acids
Cardiovascular health
Secondary prevention of coronary heart disease
Treatment of hypertriglyceridemia
Inflammatory conditions (e.g., rheumatoid arthritis)
Usual Dosages
General good health: 200 mg to 2 g DHA + EPA daily
Secondary prevention of cardiovascular disease: 1 g DHA + EPA daily
Hypertriglyceridemia: 2 to 4 g DHA + EPA daily
Rheumatoid arthritis: 2.5 g or more DHA + EPA daily
Adverse Effects
Generally well tolerated
Adverse effects may include gastrointestinal upset, especially belching with a fishy
aftertaste (fish burps)
Selected Drug Interactions
Possible additive effects if taken with anticoagulant and antiplatelet therapy
Cautions
Increased risk of bleeding with very high intake (e.g., more than 3 g of DHA plus EPA)
DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid (EPA).
13
pear in the literature. One random-
ized, double-blind, placebo-controlled
trial used a special standardized
extract (EGb 761) to assess the ef-
fects of ginkgo in 400 patients 50
years of age or older with Alzheimers
disease or vascular dementia. EGb
761 proved to be superior to placebo
on all outcome measures. A second
randomized, double-blind, placebo-
controlled clinical trial assessed
cognitive function and quality of life in
90 healthy, cognitively intact persons
64 years of age or older. In this study,
ginkgo was not superior to placebo. In
the recently concluded Ginkgo Evalu-
ation of Memory (GEM) Study, ginkgo
120 mg twice daily was no more ef-
fective than placebo in reducing the
overall incidence rate of dementia,
reducing the incidence of Alzheimers
disease, or preventing cognitive de-
cline in more than 3,000 older adults
with either normal cognition or mild
cognitive impairment.
There is strong evidence support-
ing the use of ginkgo for the treatment
of intermittent claudication. Numerous
studies suggest that ginkgo supple-
ments cause small improvements in
leg pain that occurs with exercise or
at rest. However, ginkgo may not be
as helpful as either exercise therapy
or prescription medications.
Ginkgo supplements generally
are well tolerated. Mild gastrointes-
tinal effects, headache, dizziness,
and allergic skin reactions all have
been reported. There may be a risk
of seizure, particularly in patients with
a seizure disorder. Although most
reports of seizures have involved
eating ginkgo seeds (as opposed to
consuming the ginkgo leaf extract that
is used in most products), the use of
ginkgo is best avoided in patients with
a history of seizures and patients who
take medications that may lower the
seizure threshold.
Ginkgo use has been associated
with bleeding, with case reports rang-
ing from nose bleeds to life-threaten-
ing bleeds. Although standardized
ginkgo is unlikely to cause bleeding,
patients who take other platelet-active
medications or dietary supplements
(e.g., warfarin, garlic) should use
ginkgo with caution.
Use of ginkgo is not recommend-
14
ed during pregnancy and breastfeed- Information about ginkgo, includ-
ing because of the lack of information ing drug interactions, is summarized
about possible effects. in Table 9.
The usual daily dosage of ginkgo
is 80 to 240 mg of a 50:1 standard- Ginseng
ized leaf extract administered in two The term ginseng applies to
or three divided doses. Ginkgo prepa- several species of the genus Panax.
rations should be standardized to The two species used most com-
24% ginkgo flavones glycosides and monly in dietary supplements are
6% terpenoids. Panax ginseng (referred to as Asian
ginseng, usually from Korea or China)
Table 8. Garlic at a Glance
Most Common Uses
High cholesterol levels
Hypertension
Type 2 diabetes
Usual Dosages
0.4 to 1.2 g dried garlic powder daily (equivalent to 2 to 5 mg allicin per day)
Adverse Effects
Bad breath and body odor are common and expected
Gastrointestinal adverse effects (nausea, vomiting, heartburn) more common at higher
dosages
Allergic reactions possible
Selected Drug Interactions
Warfarin: increased international normalized ratio in case reports
Saquinavir: up to 50% decrease in serum levels, with possible reduction in efficacy
Decreased effectiveness of oral contraceptives
Possible alterations in serum levels of drugs metabolized through CYP3A4 and CYP2D6
Cautions
May cause bleeding (including bleeding after surgery and spontaneous bleeding)
Table 9. Ginkgo at a Glance
Most Common Uses
Dementia
Intermittent claudication
Memory enhancement
Usual Dosages
80 to 240 mg of a 50:1 standardized leaf extract administered in two or three divided
doses
Adverse Effects
Generally well tolerated
Adverse effects may include mild gastrointestinal complaints, headache, dizziness,
allergic skin reactions
Selected Drug Interactions
Platelet-active drugs: possible additive effect
Trazodone: case report of coma in patient taking low-dose trazodone
Avoid concurrent use in patients taking medications that may lower seizure threshold
Potential additive effects with antihypertensive agents
Cautions
Avoid use in patients with a history of seizures
Avoid using during pregnancy and breastfeeding
American Pharmacists Association
and Panax quinquefolia (referred to
as American ginseng). The roots and
rhizomes of Panax species are con-
sidered to be medicinally active.
Ginseng is considered to be an
adaptogena substance that in-
creases resistance to physical, chemi-
cal, and biological stress and has a
normalizing effect on the body. The
constituents believed to be respon-
sible for adaptogen activity are gin-
senosides, which are triterpenoid sa-
ponins. At least 30 ginsenosides have
been identified; Asian and American
ginseng contain different types and
ratios of ginsenosides, which ac-
counts in part for different physiologic
effects. Additional constituents in-
clude carbohydrates, B vitamins, and
flavonoids.
The plant sometimes referred to
as Siberian ginseng (Eleutherococ-
cus senticosus) is distinct from true
ginseng (Panax species) and is more
accurately referred to as eleuthero.
Although Siberian ginseng may be
included in commercially available
ginseng preparations, it does not con-
tain ginsenosides and therefore does
not offer benefits similar to Panax
species.
Asian ginseng is the best studied
of the various Panax species. It has
been investigated in a wide variety of
conditions, often in combination with
other botanicals; additional or higher-
quality studies are needed before
clear conclusions can be reached for
most uses. Currently, Asian ginseng
is used primarily to enhance immune
function and mental performance, to
improve cardiovascular health and
physical endurance, and to treat
mental and physical stress. Ameri-
can ginseng is recommended most
frequently to reduce postprandial
glucose elevations and to reduce the
severity of cold and upper respira-
tory infection symptoms. American
ginseng contains more nonsaponin
components (e.g., quinquefolans A,
B, and C) than other Panax species
do; there is speculation that these
nonsaponin components, or different
ginsenosides present in American
ginseng, are responsible for hypo-
glycemic effects.
Ginseng preparations generally
are well tolerated. Possible adverse
OTC Advisor: Popular Herbal and Dietary Supplements
effects include insomnia, headache, concentrations used doses of 1 to 3 g,
blood pressure changes, anorexia, 30 minutes before meals. Long-term
rash, mastalgia, and menstrual abnor- dosing generally should not exceed
malities. Large doses may cause gas- 1 g of dry root per day. Some practi-
tric upset and central nervous system tioners recommend discontinuing
stimulation. Ginseng should be used use of ginseng for 1 to 2 weeks after
with caution in patients with acute using it continuously for 2 to 3 weeks.
illness, cardiovascular disease, or Information about ginseng, includ-
diabetes. Because ginseng may have ing drug interactions, is summarized
estrogen-like effects, its use generally in Table 10.
should be avoided in patients with
hormone-sensitive conditions (e.g., Kava
breast cancer, endometriosis). Kava is derived from the roots
Ginseng has been used tradi- and rhizomes of Piper methysticum,
tionally in pregnant and breastfeed- a member of the black pepper family.
ing women. However, its use is not The pharmacologically active constit-
recommended because safety in uents are fat-soluble lactones referred
humans has not been clearly estab- to as kavalactones and kavapyrones.
lished. The mechanism of action includes
Most studies of Asian ginseng interacting with dopaminergic trans-
have used dosages between 100 and mission, inhibiting central monoamine
400 mg per day of extracts standard- oxidase-B, and modulating gamma-
ized to 4% ginsenosides. Some stud- aminobutyric acid-B receptors. Kava
ies have used powdered root in doses also may inhibit uptake of noradrena-
of 0.5 to 9 g. Trials of American gin- line and have antithrombotic activity.
seng that demonstrated positive re- Kava is used widely by Pacific
sults in reducing postprandial glucose Islanders as a social and ceremonial
Table 10. Ginseng at a Glance
Most Common Uses
Immune system enhancement
Improved mental and physical performance
Increased sense of well-being and stamina
Type 2 diabetes/glucose intolerance
Usual Dosages
Asian ginseng: 100 to 400 mg per day of extracts standardized to 4% ginsenosides
American ginseng: 1 to 3 g, 30 minutes before meals
Adverse Effects
Generally well tolerated
Adverse effects may include insomnia, headache, blood pressure changes, anorexia,
rash, mastalgia, menstrual abnormalities
Large doses may cause gastric upset and central nervous system stimulation
Selected Drug Interactions
Glucose-lowering medications: possible lowered blood glucose levels in type 2
diabetes
Phenelzine: possible headache, tremor, and mania in case report
Unpredictable effect on concurrent anticoagulant and antiplatelet therapy
Possible interference with antipsychotics and immunosuppressants
Possible inhibition of CYP2D6 (not clinically significant)
Cautions
Use with caution in patients with acute illness, cardiovascular disease, or diabetes
Avoid use in patients with hormone sensitive conditions (e.g., breast cancer,
endometriosis) because of possible estrogen-like effects
Avoid use during pregnancy and breastfeeding
Some practitioners recommend discontinuing use of ginseng for 1 to 2 weeks after
using it continuously for 2 to 3 weeks
15
tranquilizing beverage. As a dietary
supplement, kava is used most com-
monly to treat mild anxiety and sleep
disturbances. A number of small stud-
ies have shown kava to be superior to
placebo for the short-term treatment
of anxiety; efficacy similar to benzo-
diazepines and buspirone has been
reported.
Until recently, kava was gener-
ally thought to be safe, with dizziness
and drowsiness the most common
adverse effects. But as of 2004, at
least 78 cases of hepatotoxicity have
been associated with kava ingestion;
4 are probably linked to kava and 23
are potentially linked. Some of these
cases involved coadministration with
other products with known hepato-
toxic potential or consumption of large
quantities of alcohol. In other cases,
hepatotoxicity occurred in previously
healthy patients who were taking no
other medications and consuming
minimal amounts of alcohol. In one
case, symptoms of hepatitis resolved
spontaneously after the patient
stopped taking kava, then returned
after rechallenge with kava.
As a result of these reports, the
safety of kava is controversial. Many
natural medicine experts continue to
believe that kava is safe at recom-
mended doses. Conversely, several
European nations have restricted
the sale of kava products. Until the
potential for hepatotoxicity with kava
is characterized completely, phar-
macists should discourage patients
from using kava. Patients who insist
on using kava should do so only with
the knowledge and supervision of a
health care provider; patients who
have liver problems, take medications
with known liver toxicity, or consume
alcohol regularly should not use kava.
Typical dosages of kava prepa-
rations range from 50 to 280 mg of
kavalactones per day administered
at bedtime. Many clinical trials used
extracts standardized to 70% kavalac-
tone content at a dosage of 100 mg
two to three times daily. Because the
kavalactone content of products var-
ies, different dosages will be neces-
sary for various products.
Information about kava, including
drug interactions, is summarized in
Table 11.
16
Melatonin 5:00 pm and 10:00 pm local time),
Melatonin is an endogenous followed by 2 to 5 mg at bedtime for
hormone synthesized from trypto- the next 2 to 5 days.
phan via a serotonin pathway. It is Evidence for the efficacy of mela-
produced in the brain by the pineal tonin in the treatment of insomnia is
gland. Although its exact role has not not definitive. A number of studies
been characterized fully, melatonin is have demonstrated clinical benefits,
known to play a critical role in regu- such as increases in rapid eye move-
lating sleep and circadian rhythms. ment sleep, slightly faster sleep
Melatonin release is induced by dark- onset, increased duration of sleep,
ness and suppressed by light via a decreased daytime somnolence,
multisynaptic pathway that links the and more normal patterns of time
pineal gland and the retina. in sleep stages in healthy patients
Melatonin has FDA orphan drug with insomnia and in women with
status for the treatment of sleep dis- asthma. A meta-analysis of 17 trials
orders in blind patients. As a dietary (n = 284)conducted primarily in
supplement, synthetic melatonin healthy subjects and patients with
products are used primarily as a insomniasupports the claim that
sleep aid and for the prevention and melatonin has small but clinically
treatment of jet lag. When taken in significant benefits. Patients whose
doses of 0.3 to 5 mg, 30 minutes natural sleep patterns are disrupted
before bedtime, melatonin may make for physical reasons (e.g., ill health)
a patients attempt to sleep more suc- may derive the greatest benefit. There
cessful; it does not generally cause a is some evidence that melatonin may
feeling of drowsiness. The effects of be effective in healthy children 6 to 12
melatonin on jet lag may result from years of age with chronic sleep-onset
more rapid adjustment of circadian insomnia. (Children should take mela-
rhythm after changing time zones. tonin only under the advice and su-
The recommended dosing regimen pervision of a primary care provider.)
for jet lag is 2 to 5 mg on the day of The clinical evidence for the use
arrival at the destination (between of melatonin in preventing and treat-
Table 11. Kava at a Glance
Most Common Uses
Anxiety
Sleep disturbances
Usual Dosages
50 to 280 mg of kavalactones per day administered at bedtime
Adverse Effects
May cause serious hepatotoxicity; use of kava is best avoided until more information
is available
Adverse effects may include dizziness and drowsiness
Selected Drug Interactions
Do not use concurrently with medications or other dietary supplements that may
damage liver
Levodopa: reduced efficacy of levodopa
Possible increased sedative effect with alcohol and other central nervous system
depressants
Possible additive effects with other platelet-active medications or dietary supplements
Possible additive effects with monoamine oxidase inhibitors
Preliminary evidence suggests kava may inhibit CYP2C9, CYP2C19, CYP2D6,
CYP3A4 (significance unknown)
Cautions
Patients with liver problems and patients who consume alcohol regularly should not
use kava
Avoid use during pregnancy and breastfeeding
American Pharmacists Association
ing jet lag is more consistent than the
evidence for insomnia. A Cochrane
review concluded that melatonin can
decrease jet lag in people cross-
ing five or more time zones and has
greater benefit for eastward travel
than westward travel.
Of note, melatonin does not ap-
pear to be effective for treatment of
circadian rhythm disruption caused
by shift work.
Melatonin generally is well toler-
ated. Possible (albeit rare) adverse
effects include nausea and vomiting,
headache, tachycardia, irritability,
dysthymia and worsening of depres-
sive symptoms, and morning hang-
over effect. Long-term administration
is appropriate only under the direct
supervision of a primary care pro-
vider.
Use of melatonin is not recom-
mended during pregnancy and
breastfeeding because of possible
hormonal effects on the fetus.
Information about melatonin, in-
cluding drug interactions, is summa-
rized in Table 12.
gen (SPARE) study is examining the
efficacy of a purified soy isoflavone
supplement (administered in tablet
form) in preventing menopausal
symptoms and spinal bone loss in
the initial years of menopause. In a
recent Cochrane review of 30 trials
that investigated the use of phytoes-
trogens for vasomotor menopausal
symptoms, only five trials were suit-
able for meta-analysis, and all used
red clover extract. There was no sig-
nificant difference in those trials in the
frequency of hot flushes between red
clover and placebo.
Both soy and red clover are well
tolerated. Possible adverse effects
include gastrointestinal complaints,
headaches, and allergic reactions.
The long-term safety of phytoestro-
gens is not established, especially
with respect of estrogen-dependent
cancers and thromboembolic dis-
ease. Because the safety of phytoes-
trogen supplements in women with
estrogen receptorpositive breast
cancer is unknown, these supple-
ments should be avoided. Cou-
mestans in red clover may increase
the risk of bleeding, especially if
warfarin and similar drugs are taken
concomitantly.
A recommended dose of phy-
toestrogens has not been estab-
lished. Clinical studies of soy have
examined 40 to 120 mg of soy isofla-
vones taken daily for up to 6 months.
Clinical studies of red clover have
used widely varying doses.
Information about red clover and
soy, including drug interactions, is
summarized in Table 13.
Probiotics
Probiotics are nonpathogenic, liv-
ing microorganisms that have a ben-
eficial effect on the host when con-
sumed in adequate amounts. Most
probiotics are lactic acidproducing
bacteria, especially strains of Bifido-
bacterium or Lactobacillus species;
the yeast Saccharomyces boulardii
also is used widely. These microor-
ganisms do not permanently colonize

Phytoestrogens Table 12. Melatonin at a Glance

(Red Clover and Soy)
A number of different plantsin-
cluding red clover (Trifolium pratense
L.) and soy (Glycine max [L.] Mer-
rill)contain compounds that are
believed to have estrogen-like effects
in the body. These compounds often
are referred to as phytoestrogens.
Phytoestrogens in soy include isofla-
vones such as genistein, daidzein,
and glycitein. Phytoestrogens in red
clover may include biochanin, genis-
tein, daidzein, and formononetin. All
of these compounds have multiple
complex effects that also may en-
compass antiestrogenic, antioxidant,
and anticancer activity.
Dietary supplements containing
red clover or soy are used primarily
for managing vasomotor symptoms
associated with menopause. The
evidence supporting the use of sup-
plements for this purpose is incon-
clusive. Studies involving soy have
been limited by poor design, small
sample size, or short duration; ad-
ditionally, many studies have focused
on dietary sources of soy rather than
supplements. The ongoing Soy Phy-
toestrogens As Replacement Estro-
Most Common Uses
Insomnia
Prevention and treatment of jet lag
Treatment of circadian rhythm disorders in blind patientsa
Usual Dosages
Insomnia: 0.3 to 5 mg, 30 minutes before bedtime
Jet lag: 2 to 5 mg in the evening on the day of arrival at the destination (between
5:00 pm and 10:00 pm local time), followed by 2 to 5 mg at bedtime for the next
2 to 5 days
Adverse Effects
Generally very well tolerated
Adverse effects may include nausea and vomiting, headache, tachycardia, irritability,
dysthymia and worsening of depressive symptoms, morning hangover effect
Selected Drug Interactions
Nifedipine: reduced delivery via the gastrointestinal therapeutic system (i.e., Procardia
XL)
Fluvoxamine, monoamine oxidase inhibitors, tricyclic depressants all may increase
melatonin levels
Benzodiazepines and sodium valproate may decrease nighttime melatonin levels
Verapamil may decrease melatonin levels
Caffeine, oral contraceptives have variable effects on melatonin levels
Possible interaction with immunosuppressant drugs as a result of immunostimulating
properties
Cautions
Avoid use during pregnancy and breastfeeding
Long-term use and use in children should be supervised by a primary care provider
a
Approved by the U.S. Food and Drug Administration as an orphan drug for this indication.

OTC Advisor: Popular Herbal and Dietary Supplements 17

the gastrointestinal tract beyond early
infancy, so they must be consumed
regularly to maintain their presence in
the colon. When a sufficient number
of these organisms are present, they
appear to reduce colonization by
pathogenic bacteria. The normaliza-
tion of gut flora decreases inflam-
matory responses, but probiotics
also have some immunomodulating
activity. Macrophage and lympho-
cyte activity are both affected, as are
various cytokines, such as increased
interferon-alfa and immunoglobulin
and decreased tumor necrosis factor.
Probiotics also stabilize the intestinal
barrier function by reducing intestinal
permeability.
Probiotics differ from prebiotics,
which are nondigestible food com-
ponents that stimulate the growth or
activity of the beneficial microorgan-
isms already in the colon. Inulin-type
fructans, including their partial hy-
drolysis product fructose oligosac-
charides, are the most common
prebiotics; they are found in many
edible plants (e.g., asparagus, ba-
nanas, chicory, Jerusalem artichoke,
leek, onion, soy, wheat) and may be
added to other foods as a source of
fiber. Products that contain both pro-
biotics and prebiotics are known as
synbiotics.
The proposed health benefits of
probiotics have undergone increas-
ingly rigorous scientific evaluation
in recent years, to the point that
there are well-established benefits
in a growing number of conditions
(primarily gastrointestinal condi-
tions such as constipation, diarrhea,
inflammatory bowel disease, and
irritable bowel syndrome). Probiotics
also show promise for the prevention
and treatment of atopic dermatitis in
children, as well as for the treatment
of allergic disorders in adults.
It is important to note that the ef-
fects of probiotics are specific to in-
dividual strains. Effects also may vary
in healthy patients versus those with
a disease, in different disease states,
and in different age groups. Thus,
the results of clinical trials that use
a certain probiotic strain in a certain
population should not be generalized
to other strains or other populations.
Pharmacists should consult pub-
18
lished studies, as well as emerging organisms per gram at the time of
meta-analyses, to determine the manufacture. Unfortunately, the value
particular strains and doses used. of the seal is limited because starter
Caution is urged when considering cultures for acid production are not
individual studies; many have inad- distinguished from probiotic bacte-
equate specification of the microor- ria. Liquid yogurt drinks (kefir) and
ganisms, variable preparations, small cultured fluid milk, such as sweet
patient populations, and imprecise acidophilus milk and buttermilk, can
endpoints. contain variable amounts of viable
Probiotics generally are well toler- organisms; however, most provide
ated. Gastrointestinal effects such as adequate amounts (108 viable organ-
gas and bloating are common and isms per gram), usually in the form
subside as therapy continues. There of Lactobacilllus acidophilus and Bi-
are a few reports of fungemia caused fidobacterium species. A few brands
by S. boulardii and bacteremia and of cottage cheese contain active cul-
endocarditis caused by lactoba- tures, but most do not. Other foods
cilli. Although all of these cases had containing probiotics include brined
complicating factors, it is prudent for olives, kimchi (Korean form of fer-
patients who are immunocompro- mented cabbage), miso, sauerkraut,
mised to avoid the use of probiotic tempeh, and some juices and soy
preparations. beverages.
Probiotics are available in foods Various probiotic supplements
and as dietary supplements. The ma- are available, containing one or
jor food source of probiotic bacteria multiple species; some examples
is dairy foods. Most major brands are provided in Table 14. Because
of yogurt contain probiotic bacteria, probiotic microorganisms should be
although viable cultures are not re- live, the quality of probiotic products
quired for yogurt in the United States is essential. Ideally, products should
and labels do not list the number of list the genus, species, and strain
viable probiotic organisms. The Live of the probiotics they contain. They
& Active Cultures seal of the Na- also should clearly state the number
tional Yogurt Association is allowed of colony-forming units (i.e., live mi-
on products containing 108 viable crobes) provided in each serving.
Table 13. Phytoestrogens (Red Clover and Soy)
at a Glance
Most Common Uses
Menopausal symptoms
Usual Dosages
Varies according to intended therapeutic use, specific product composition
Clinical studies of red clover have employed a wide range of doses
Clinical studies of soy have examined 40 to 120 mg of soy isoflavones taken daily for
up to 6 months
Adverse Effects
Generally well tolerated
Adverse effects may include gastrointestinal complaints, headache, allergic reactions
Selected Drug Interactions
Possible increased risk of bleeding in patients taking warfarin with red clover products
Genistein (an isoflavone found in red clover and soy products) may counteract the
beneficial effect of tamoxifen in slowing breast cancer growth
Daidzein (an isoflavone found in red clover and soy products) may inhibit the activity of
CYP1A2
Cautions
Women with estrogen receptorpositive breast cancer should not use supplements
containing phytoestrogens
Avoid use during pregnancy and breastfeeding because of possible hormonal effects
Long-term safety of phytoestrogens has not been established
American Pharmacists Association
 The optimum dose for a given
probiotic is not known. Usual doses
of S. boulardii are 250 to 500 mg two
to four times daily. Doses of Lacto-
bacillus and Bifidobacteria vary by
product, with most recommended
dosages ranging from 1 billion to
10 billion colony-forming units per
day.
St. Johns Wort
St. Johns wort is derived from
the flowers and leaves of Hypericum
perforatum, a perennial plant that
grows wild throughout Europe, Asia,
North America, and South America.
Potentially biologically active con-
stituents include hyperforin, hyperi-
cin, flavonoids, tannins, volatile oils,
and phenols. St. Johns wort may
modulate serotonin, dopamine, and
norepinephrine; it also may act as an
antagonist at various neuroreceptors.
St. Johns wort is used most
commonly for the treatment of mild to
Case 1. Drug-Dietary Supplement Interactions
HW, a 36-year-old woman, visits her primary care provider with a chief complaint of
anxiety. The primary care provider decides to initiate therapy with buspirone 7.5 mg
twice daily. The prescribing information states that buspirone is metabolized primarily
by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4
(CYP3A4).
The patient reports current use of garlic, ginseng, and St. Johns wort. Which of these
products would be least likely to interfere with buspirone therapy?
a. Garlic.
b. Ginseng.
c. St. Johns wort.
Case study responses appear on page 26.
moderate depression. It also some- Some short-term studies (12 weeks
times is used to treat pain, anxiety, or less) have found the benefits of
obsessive-compulsive disorder, and St. Johns wort to be comparable to
premenstrual syndrome. those of standard antidepressants
A growing body of evidence sup- (e.g., fluoxetine, sertraline, citalo-
ports the efficacy of St. Johns wort pram). However, because St. Johns
for mild to moderate depression. wort has the potential to interact with

Table 14. Examples of Probiotic Supplements

Product Name
(Manufacturer) Contents (Trade Name) Amount
AccuFlora (Northwest Natural Products Bifidobacterium bifidum 500 million CFU per capsule
Inc.) Lactobacillus acidophilus
Lactobacillus rhamnosus
Lactobacillus salivarius
Streptococcus thermophilus
Align (Procter & Gamble) Bifidobacterium infantis 35624 (Bifantis) 1 billion CFU per capsule
Culturelle (Amerifit Brands Inc.) Lactobacillus rhamnosus GG (LGG) 10 billion CFU per capsule
Florastor (Biocodex Inc.) Saccharomyces boulardii lyophilized 5 billion CFU per capsule
Pearls IC (Enzymatic Therapy) Bifidobacterium breve 1 billion CFU per capsule
Bifidobacterium bifidum
Bifidobacterium lactis
Bifidobacterium longum
Lactobacillus acidophilus
Lactobacillus rhamnosus
Sustenex (Ganeden Biotech Inc.) Bacillus coagulans GBI-30, 6086 (GanedenBC30) 2 billion CFU per capsule

VSL#3 (VSL Pharmaceuticals Inc.) Bifidobacterium breve 225 billion CFU per 2 capsules
Bifidobacterium infantis
Bifidobacterium longum 450 billion CFU per packeta
Lactobacillus acidophilus
Lactobacillus bulgaricus
Lactobacillus paracasei
Lactobacillus plantarum
Streptococcus thermophilus
a
Powder in individual packet should be mixed with at least 4 ounces of cold water and consumed immediately.
CFU = colony-forming units.

OTC Advisor: Popular Herbal and Dietary Supplements 19

a large number of drugs, it is not an
appropriate choice for many patients.
An analysis of randomized trials
found rates of adverse effects in
patients taking St. Johns wort similar to
those in patients taking placebo, much
lower than those in patients taking old-
er antidepressants, and slightly lower
than those in patients taking selective
serotonin receptor inhibitors. Pares
thesias, headache, nausea, dry mouth,
agitation, and skin reactions have been
reported most commonly. The use
of St. Johns wort should be avoided
in patients with bipolar disorder and
schizophrenia. Photosensitivity reac-
tions have been reported, although
there also is evidence indicating no
effect. Until these results are sorted
out, people who take St. Johns wort
should limit their exposure to sun and
apply sunscreen. Abrupt discontinua
tion of St. Johns wort after chronic use
may result in withdrawal symptoms
similar to those seen when withdrawing
conventional antidepressants.
Use of St. Johns wort is not rec-
ommended during pregnancy and
breastfeeding because of the lack of
information about possible effects.
Unlike many herb-drug interac-
tions discussed in this monograph,
interactions with St. Johns wort are
well documented and clinically signif-
icant. St. Johns wort contains many
compounds that influence activities
of major human drug-metabolizing
enzymes, resulting in multiple phar-
macokinetic interactions. The specific
enzymes, the degree of influence of
hypericin versus hyperforin, and in vi-
tro analysis versus clinical outcomes
are still being studied. St. Johns wort
is a potent inducer of CYP3A4, result-
ing in significantly lower concentra-
tions of drugs
metabolized through this pathway,
including amitriptyline, benzodiaz-
epines, methadone, oral contracep-
tives, protease inhibitors, simvastatin,
and warfarin. St. Johns wort induces
CYP1A2 and CYP2C9 to a lesser ex-
tent and may induce P-glycoprotein
transport proteins, resulting in lower
serum concentrations of drugs such
as digoxin and fexofenadine. Many
drug interactions are based on
extrapolating across drug class or
metabolic pathway. Patients taking
20
other serotonergic drugs or natural It does not alter prostate volume or
products should avoid the use of St. prostate-specific antigen levels. Men
Johns wort because it may induce who have prostate symptoms should
serotonin syndrome. consult with a primary care provider
The recommended dosage of before self-treating with saw palmetto
St. Johns wort for adults with mild to to rule out prostate cancer.
moderate depression is 300 to 900 A number of clinical trials have
mg (standardized at 0.3% hypericin reported that saw palmetto improves
or 5% hyperforin) three times daily symptoms of benign prostatic hyper-
with meals. Because the content of plasia, including nocturia, urinary
hypericin and hyperforin varies in flow, and overall quality of life. In
commercial preparations, products some studies, the efficacy of saw
may not be interchangeable. As with palmetto was similar to that of finaste-
conventional antidepressants, the ride. However, an updated Cochrane
therapeutic effects of St. Johns wort review that incorporated data from
may not be evident for 3 to 4 weeks. nine recent trials involving 2,053
Information about St. Johns wort additional men concluded that saw
is summarized in Table 15. palmetto is no more effective than
placebo.
Saw Palmetto Saw palmetto generally is well
Saw palmetto (Serenoa repens) tolerated. Gastrointestinal complaints
is a dwarf palm tree native to the are the most commonly reported ad-
southeast coastal region of the United verse effects; stomach upset may be
States. The lipophilic extracts from reduced by taking doses with food.
the ripened fruit contain saturated There has been one case report of a
and unsaturated fatty acids and plant man who had intraoperative hemor-
sterols, which are believed to be rhage during surgery; although cau-
the source of the biologically active sality has not been established, saw
components. Saw palmetto inhibits palmetto should be used with caution
5-alpha-reductase and cytosolic an- in patients taking any medication or
drogen receptor binding. It has local dietary supplement that might pro-
antiestrogenic and anti-inflammatory long bleeding. Patients who already
effects on the prostate. take androgenic medications should
Saw palmetto is used primarily to avoid using saw palmetto.
treat urinary symptoms associated Saw palmetto is included in some
with benign prostatic hyperplasia.
Table 15. St. Johns Wort at a Glance
Most Common Uses
Treatment of mild to moderate depression
Usual Dosages
300 to 900 mg (standardized at 0.3% hypericin or 5% hyperforin) three times daily
with meals
Adverse Effects
Generally well tolerated
Adverse effects include paresthesias, headache, nausea, dry mouth, agitation, skin
reactions
Photosensitivity possible; advise patients to avoid sun exposure and use sunscreen
Selected Drug Interactions
Potent inducer of CYP3A4 and mild inducer of CYP1A2 and CYP2C9; use caution
when medications metabolized by these enzymes are administered concurrently
Possible increased risk of serotonin syndrome if taken with serotonergic medications
Cautions
Abrupt discontinuation after chronic use may precipitate withdrawal symptoms
Avoid use in patients with bipolar disorder and schizophrenia
Avoid use during pregnancy or breastfeeding
American Pharmacists Association
products intended for use by women.
Because saw palmetto inhibits
5-alpha-reductase, its use is contra-
indicated during pregnancy and
breastfeeding.
The usual dosage of saw palmet-
to is 160 mg twice daily or 320 mg
once daily. Products should contain
80% to 95% standardized fatty acids.
Information about saw palmetto,
including drug interactions, is sum-
marized in Table 16.
Summary
Herbal products and other di-
etary supplements are used widely in
the United States. Many consumers
are unaware of important differences
between the way medications and
dietary supplements are regulated;
as a result, they may take unintended
risks with products that seem natu-
ral and benign. Pharmacists can
help to ensure safe and effective use
of these popular therapies by engag-
ing patients in discussions about
dietary supplements and providing
evidence-based recommendations.
OTC Advisor: Popular Herbal and Dietary Supplements
Table 16. Saw Palmetto at a Glance
Most Common Uses
Treatment of urinary symptoms associated with benign prostatic hyperplasia
Usual Dosages
160 mg twice daily or 320 mg once daily; products should contain 80% to 95%
standardized fatty acids
Adverse Effects
Generally well tolerated
Gastrointestinal complaints most common
Selected Drug Interactions
Potential interaction with hormonal or antihormonal therapies
Possible additive effects when used with antiplatelet or anticoagulant agents
Cautions
Men who have prostate symptoms should consult with a primary care provider to rule
out prostate cancer
Use contraindicated during pregnancy and breastfeeding
Case 2. Saw Palmetto
LA, a 65-year-old man, was diagnosed recently with benign prostatic hyperplasia. He is
interested in using an herbal product to help alleviate his symptoms (increased frequency
of urination, nocturia, and reduced urinary flow). LA is aware of some prescription
medications for benign prostatic hyperplasia, but really would prefer something natural
so that he doesnt have to worry about side effects. His friend recommended that he
check out saw palmetto. LA asks your opinion about using saw palmetto instead of a
prescription medication.
A review of LAs medication history shows current use of metoprolol 50 mg twice daily,
hydrochlorothiazide 25 mg daily, simvastatin 40 mg at bedtime, and aspirin 81 mg
daily. He reports having suffered a mild heart attack 2 years previously.
Based on his medical history and profile, is the patient an appropriate candidate for a
trial of therapy with saw palmetto?
a. Yes.
b. No.
If the patient were to begin using saw palmetto, which of the following points should be
conveyed when educating him about proper use of the selected product?
a. He should take each dose with food or milk if stomach upset occurs.
b. He should discontinue use of the product immediately if symptoms of jaundice,
such as dark urine or yellowing of the eyes, occur.
c. He should discontinue use of the product immediately if he detects an increase in
blood pressure.
d. All of the above.
Case study responses appear on page 26.
21
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Kiefer D, Pantuso T. Panax ginseng. Am Fam
Physician. 2003;68:153942.
Vogler BK, Pittler MH, Ernst E. The efficacy of
ginseng. A systematic review of randomised
clinical trials. Eur J Clin Pharmacol. 1999;
55:56775.
24
Kava
Centers for Disease Control and Prevention.
Hepatic toxicity possibly associated with
kava-containing productsUnited States,
Germany, and Switzerland, 19992002.
MMWR Morb Mortal Wkly Rep. 2002;
51:10657.
Clouatre DL. Kava kava: examining
new reports of toxicity. Toxicol Lett.
2004;150:8596.
Pittler MH, Ernst E. Kava extract for treating
anxiety. Cochrane Database Syst Rev.
2003;(1):CD003383.
Melatonin
Brzezinski A, Vangel MG, Wurtman RJ, et al.
Effects of exogenous melatonin on sleep: a
meta-analysis. Sleep Med Rev. 2005;9:41
50.
Herxheimer A, Petrie KJ. Melatonin for the
prevention and treatment of jet lag. Cochrane
Database Syst Rev. 2002;(2):CD001520.
Phytoestrogens
Lethaby AE, Brown J, Marjoribanks J, et al.
Phytoestrogens for vasomotor menopausal
symptoms. Cochrane Database Syst Rev.
2007;(4):CD001395.
Levis S, Strickman-Stein N, Doerge DR, et al.
Design and baseline characteristics of the
Soy Phytoestrogens As Replacement Estrogen
(SPARE) study: a clinical trial of the effects
of soy isoflavones in menopausal women.
Contemp Clin Trials. March 15, 2010.
[Epub ahead of print]
Low Dog T. Menopause: a review of
botanical dietary supplements. Am J Med.
2005;118(suppl 12B):98108.
Probiotics
Boyle RJ, Robins-Browne RM, Tang MLK.
Probiotic use in clinical practice: what are the
risks? Am J Clin Nutr. 2006;83:125664.
Floch MH, Madsen KK, Jenkins DJA, et al.
Recommendations for probiotic use. J Clin
Gastroenterol. 2006;40:2758.
Huffnagle GB, Wernick S. The Probiotics
Revolution. New York, NY: Bantam Books;
2007.
International Scientific Association for
Probiotics and Prebiotics. Probiotics: A
Consumer Guide for Making Smart Choices.
March 11, 2009. Available at: http://
www.isapp.net/docs/Consumer_Guidelines-
probiotic.pdf. Accessed April 3, 2010.
Walker R, Buckley M. Probiotic Microbes:
The Scientific Basis. Report of an American
Society for Microbiology colloquium;
November 57, 2005; Baltimore, MD.
Available at: http://academy.asm.org/
index.php?option=com_content&view=
article&id=233:probiotic-microbes-the-
scientific-basis-june-2006&catid=40:browse-
all&Itemid=79. Accessed April 6, 2010.
Williams NT. Probiotics. Am J Health Syst
Pharm. 2010;67:44958.
St. Johns Wort
Knuppel L, Linde K. Adverse effects of St.
Johns wort: a systematic review. J Clin
Psychiatry. 2004;65:14709.
Linde K, Berner MM, Kriston L, et al. St.
Johns wort for major depression. Cochrane
Database Syst Rev. 2008;(4):CD000448.
Rahimi R, Nikfar S, Abdollahi M. Efficacy
and tolerability of Hypericum perforatum in
major depressive disorder in comparison
with selective serotonin reuptake inhibitors: a
meta-analysis. Prog Neuropsychopharmacol
Biol Psychiatry. 2009;33:11827. Epub
November 12, 2008.
Saw Palmetto
Bent S, Kane C, Shinohara K, et al. Saw
palmetto for benign prostatic hyperplasia.
N Engl J Med. 2006;354:55766.
Tacklind J, MacDonald R, Rutks I, et al.
Serenoa repens for benign prostatic
hyperplasia. Cochrane Database Syst Rev.
2009;(2):CD001423.
Willetts KE, Clements MS, Champion S,
et al. Serenoa repens extract for benign
prostate hyperplasia: a randomized
controlled trial. BJU Int. 2003;92:26770.
American Pharmacists Association
 Case Study Responses
Case 1. Drug-Dietary Supplement Interactions
The patient reports current use of garlic, ginseng, and St. Johns wort. Which of these products would be least
likely to interfere with buspirone therapy?
a. Garlic.
Incorrect. Garlic may induce CYP3A4 and thus could increase the rate of buspirone metabolism.
b. Ginseng.
Correct. Ginseng is not known to interact with buspirone.
c. St. Johns wort.
Incorrect. St. Johns wort is a potent inducer of CYP3A4 and thus would be likely to increase the rate of
buspirone metabolism.

Case 2. Saw Palmetto

Based on his medical history and profile, is the patient an appropriate candidate for a trial of therapy with saw
palmetto?
a. Yes.
Correct. The patient has no obvious contraindications to the use of saw palmetto.
b. No.
Incorrect. The patient has no obvious contraindications to the use of saw palmetto.

If the patient were to begin using saw palmetto, which of the following points should be conveyed when
educating him about proper use of the selected product?
a. He should take each dose with food or milk if stomach upset occurs.
Correct. Gastrointestinal complaints, including stomach upset, are the most common adverse effects
of saw palmetto and can be minimized by taking doses with food.
b. He should discontinue use of the product immediately if symptoms of jaundice, such as dark urine or
yellowing of the eyes, occur.
Incorrect. Saw palmetto is not associated with hepatotoxicity.
c. He should discontinue use of the product immediately if he detects an increase in blood pressure.
Incorrect. Saw palmetto is not known to increase blood pressure.
d. All of the above.
Incorrect.

OTC Advisor: Popular Herbal and Dietary Supplements 25

 CPE Exam
Instructions: The assessment questions printed below allow you to preview
the online CPE exam. Please review all of your answers to be sure you have
marked the proper letter on the online CPE exam. There is only one correct
answer to each question.
1. Under the Dietary Supplement
Health and Education Act of 1994,
dietary supplements are regulated
as:
a. Food.
b. Medical devices.
c. Nonprescription medications.
d. Prescription medications.
2. The Dietary Supplement Health and
Education Act states that the FDA:
a. Must evaluate the safety
of dietary supplements prior to
marketing.
b. Must regularly inspect
manufacturing facilities
of dietary supplements to
ensure compliance with Good
Manufacturing Practices.
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. Of the following quality assurance
programs for dietary supplements,
which certifies a companys
manufacturing practices rather than
specific dietary supplements?
a. ConsumerLab.com Approved
Quality Product Seal.
b. Natural Products Association
GMP Certification Program.
c. NSF International Dietary
Supplements Certification
Program.
d. USP Dietary Supplement
Verification Program.
26
4. The Current Good Manufacturing
Practices final rule for dietary
supplements should help to do all of
the following except:
a. Ensure that products are
not contaminated with harmful
substances.
b. Ensure that products contain
the stated amount of an
ingredient.
c. Ensure that the active
ingredients in products are
safe and effective.
d. Reduce the number of
misbranded products.
5. Which of the following claims is not
permitted on a dietary supplement
label?
a. Efficacy for treating a specific
disease.
b. Nutrient content of the
product.
c. The relationship between a
dietary ingredient and a
disease or health-related
condition.
d. Structure/function claims
related to health maintenance.
6. Which of the following pieces of
legislation requires manufacturers
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.
c. Federal Food, Drug, and
Cosmetic Act.
d. Adverse event report is not
mandatory for dietary
supplements.
7. Which of the following dietary
supplements has orphan drug status
for the treatment of Huntingtons
disease?
a. Coenzyme Q10.
b. Echinacea.
c. Garlic.
d. Ginkgo.
8. Which of the following dietary
supplements is identified in
this monograph as being well
documented for having the
potential to interact with a large
number of drugs, thereby rendering
it an inappropriate choice for many
patients?
a. Evening primrose oil.
b. Garlic.
c. Kava.
d. St. Johns wort.
9. Which of the following statements
about homeopathy and
homeopathic medications is true?
a. A guiding principle of
homeopathy states that
substances become more
potent as they become more
dilute.
b. All homeopathic medications
are available on a
nonprescription basis.
c. Homeopathic medications
are subject to the provisions of
the Dietary Supplement Health
and Education Act.
d. All of the above.
10. Black cohosh is used most
commonly to treat which of the
following conditions?
a. Heart failure.
b. Insomnia.
c. Mastalgia.
d. Menopausal symptoms.
American Pharmacists Association
 11. Both garlic and ginkgo are
associated with which of the
following types of potentially serious
adverse effects?
a. Dermatologic.
b. Gastrointestinal.
c. Hematologic.
d. Renal.
12. Evening primrose oil should not be
used by patients with:
a. A history of breast cancer.
b. A history of seizure disorders.
c. Allergies to ragweed or
chrysanthemums.
d. Diabetes.
13. Fish oil is considered to be a rich
source of which of the following
essential fatty acids?
a. Alpha-linolenic acid and
docosahexaenoic acid.
b. Arachadonic acid and linoleic
acid.
c. Docosahexaenoic acid and
eicosapentaenoic acid.
d. Gamma-linolenic acid and
linoleic acid.
14. Which of the following dietary
supplements is an adaptogen that
aids the body in adapting to stress?
a. Black cohosh.
b. Ginseng.
c. St. Johns wort.
d. Saw palmetto.
OTC Advisor: Popular Herbal and Dietary Supplements
15. Although kava may be effective for
the short-term treatment of anxiety,
its use is limited by concerns about:
a. Bleeding.
b. Drug interactions.
c. Hepatotoxicity.
d. Seizures.
16. No usual dosage is reported for
echinacea because:
a. Doses must be calculated
individually for each patient.
b. Dosing regimens are product-
specific, depending on the
component Echinacea species
and plant parts.
c. No dosage has been found to
be effective.
d. The usual dosage depends on
the condition being treated.
17. Which dietary supplement may be
effective for the treatment of urinary
symptoms associated with benign
prostatic hyperplasia?
a. Black cohosh.
b. Evening primrose oil.
c. Ginkgo.
d. Saw palmetto.
18. Which dietary supplement appears
to be effective for the prevention
and treatment of jet lag?
a. Coenzyme Q10.
b. Garlic.
c. Melatonin.
d. Saw palmetto.
19. Which of the following statements
about probiotics is true?
a. Probiotics are nondigestible
food ingredients that stimulate
the growth or activity of the
beneficial microorganisms
already in the colon.
b. Probiotics are nonpathogenic,
living microorganisms that are
consumed orally.
c. Probiotics permanently
colonize the gastrointestinal
tract.
d. The available probiotics all
have similar effects (i.e.,
effects are not specific to
individual strains).
20. Which of the following is identified
in this monograph as a factor
that makes it difficult to draw
conclusions about the efficacy of
soy supplements for managing
vasomotor symptoms?
a. Many of the available studies
have been limited by poor
design, small sample size, or
short duration.
b. Much of the existing evidence
comes from studies that
focused on dietary sources of
soy, not soy supplements.
c. Many of the existing studies
have proven to be unsuitable
for meta-analysis.
d. All of the above.
27
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