About Dietary Supplements
Dietary supplements were defined in a law passed
by Congress in 1994. A dietary supplement must meet
all of the following conditions:
- It is a product (other than tobacco) intended
to supplement the diet, which contains one or more
of the following: vitamins; minerals; herbs or other
botanicals; amino acids; or any combination of the
above ingredients.
- It is intended to be taken in tablet, capsule,
powder, softgel, gelcap or liquid form.
- It is not represented for use as a conventional
food or as a sole item of a meal or the diet.
- It is labeled as being a dietary supplement.
It's important to know that just because an herbal
supplement is labeled "natural" does not
mean it is safe or without any harmful effects. For
example, the herbs kava and comfrey have been linked
to serious liver damage.
Herbal supplements can act in the same way as drugs.
Therefore, they can cause medical problems if not
used correctly or if taken in large amounts. In some
cases, people have experienced negative effects even
though they followed the instructions on a supplement
label.
Women who are pregnant or nursing should be especially
cautious about using herbal supplements, since these
products can act like drugs. This caution also applies
to treating children with herbal supplements.
It is important to consult your health care provider
before using an herbal supplement, especially if you
are taking any medications (whether prescription or
over-the-counter). Some herbal supplements are known
to interact with medications in ways that cause health
problems. Even if your provider does not know about
a particular supplement, he can access the latest
medical guidance on its uses, risks and interactions.
If you use herbal supplements, it is best to do so
under the guidance of a medical professional who has
been properly trained in herbal medicine. This is
especially important for herbs that are part of an
alternative medical system, such as the traditional
medicines of China, Japan or India.
Alternative medical systems are built upon complete
systems of theory and practice, and have often evolved
apart from and earlier than the conventional medical
approach used in the United States.
In the United States, herbal and other dietary supplements
are regulated by the U.S. Food and Drug Administration
(FDA) as foods. This means that they do not have to
meet the same standards as drugs and over-the-counter
medications for proof of safety, effectiveness and
what the FDA calls “Good Manufacturing Practices”.
The active ingredient(s) in many herbs and herbal
supplements are not known. There may be dozens, even
hundreds, of such compounds in an herbal supplement.
Scientists are currently working to identify these
ingredients and analyze products, using sophisticated
technology. Identifying the active ingredients in
herbs and understanding how herbs affect the body
are important research areas for the National Center
for Complementary and Alternative Medicine.
Published analyses of herbal supplements have found
differences between what's listed on the label and
what's in the bottle. This means that you may be taking
less — or more — of the supplement than
what the label indicates. Also, the word "standardized"
on a product label is no guarantee of higher product
quality, since in the United States there is no legal
definition of "standardized" (or "certified"
or "verified") for supplements.
Some herbal supplements have been found to be contaminated
with metals, unlabeled prescription drugs, microorganisms
or other substances.
There has been an increase in the number of Web sites
that sell and promote herbal supplements on the Internet.
The Federal Government has taken legal action against
a number of company sites because they have been shown
to contain incorrect statements and to be deceptive
to consumers. It is important to know how to evaluate
the claims that are made for supplements.
Fact Sheet: St. John's
Wort
Depression is a serious medical illness affecting
17 million Americans. But with recent advances
in both medications and psychotherapy techniques,
individuals with depression have over an 80%
chance of being successfully treated. Unfortunately,
a stigma still surrounds mental illnesses
that prevents many who may suffer from depression
from seeking treatment. This stigma can encourage
people to enthusiastically embrace self-help
remedies before sufficient evidence has pronounced
them effective or even safe.
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The herbal extract Hypericum perforatum, commonly
known as St. John's wort, has been promoted as an
alternative treatment for depression. Anecdotal evidence,
particularly from Germany (where nearly 3 million
prescriptions are written for the herbal extract each
year), points to the effectiveness of St. John's wort
in the treatment of mild to moderately severe depression.
But before St. John's wort gains formal acceptance
in this country as an "alternative" antidepressant,
it needs to be subjected to testing that follows rigorous
clinical guidelines.
Investigating a Promising Alternative
Without question, there is cause for some excitement
that St. John's wort could be an effective remedy.
Preliminary findings indicate that it is of some benefit
in the treatment of mild to moderately severe depression
and is associated with only a few mild side effects.
However, it is not known exactly why this herbal remedy
is an effective antidepressant or what is the proper
amount to take. Also, it is important to note that
these early studies compared the effectiveness of
St. John's wort against that of placebo and older
antidepressant medications, often given at what would
be considered subtherapeutic doses. In general, these
reports also did not study the effectiveness of St.
John's wort in individuals with the formal diagnosis
of major depressive disorder, but rather included
subjects with depression of lesser severity. Comparisons
of St. John's wort against the newer and highly effective
class of antidepressants, the selective serotonin
reuptake inhibitors (or SSRIs, of which Prozac is
but one) in patients with major depressive disorder
have yet to be performed.
But one is underway. The National Institute of Mental
Health has begun a large-scale rigorous study to definitively
answer whether St. John's wort is superior to placebo.
Individuals formally diagnosed with major depressive
disorder will undergo an 8-week trial and receive
either placebo, St. John's wort, or an SSRI. After
the initial phase of the investigation is completed,
the subjects will be followed for months afterward
to study the long-term effects of taking St. John's
wort, which have not yet been examined.
Know the Whole Story
For many, the belief that St. John's wort is a safe
all-natural remedy for depression stems from what
they have learned from the media. Unfortunately, most
of the stories that have advocated St. John's wort
as a natural remedy for depression only cited the
positive aspects of this treatment approach. Only
a very few presented the possible side effects or
acknowledged that the early studies of St. John's
wort did not follow the same strict criteria required
in America to gain approval from the Food and Drug
Administration (FDA). These early stories also rarely
included warnings advising against the use of the
herbal remedy while taking other medications or during
pregnancy.
People may tend to believe that if something is found
in nature, no harm can result from its use. But no
real distinction can be made between "natural"
remedies and other drugs, since the origin of many
medications can also be traced to plants and other
naturally occurring elements. The plant itself does
not have medicinal properties; it is the chemicals
within the plant that have the curative effect. And
a chemical is a chemical, whether it occurs naturally
(as in plants) or not.
St. John's wort is marketed in this country as a
dietary supplement, so it is outside the regulatory
jurisdiction of the FDA, according to a law passed
by Congress in 1994. Because the FDA has limited authority
to challenge companies that produce herbal supplements,
manufacturers can claim that their products enhance
normal body functions without submitting scientific
evidence to support these claims. However, these manufacturers
are not allowed to state that dietary supplements
can be used to treat medical illnesses, such as depression.
The Dangers of Self-Diagnosing and Self-Medicating
No one who thinks he or she may be depressed should
self-medicate with St. John's wort or any other "alternative"
remedy. Many suitable, clinically approved, and highly
effective therapies are already available for the
treatment of depression. If you think you may be suffering
from depression, it is important to consult with a
physician. Symptoms of depression could be caused
by other illnesses or result from other causes, such
as substance abuse. Never self-medicate. The risk
of self-harm far outweighs the potential benefits
of self-help.
Ginkgo Biloba
Ginkgo biloba, a readily available natural product,
has been the focus of recent media reports as a potential
treatment for Alzheimer's disease. Although a 1997
study in the United States suggests that a ginkgo
extract may be of some help in treating the symptoms
of Alzheimer's disease and vascular dementia, there
is no evidence that ginkgo biloba will cure or prevent
Alzheimer's disease.
In addition, some recent case studies imply that
daily use of ginkgo biloba extracts may cause side
effects, such as excessive bleeding, especially when
combined with daily use of aspirin. Much more research
is needed before scientists will know whether and
how ginkgo biloba extracts benefit people.
Black Cohosh and the
Symptoms of Menopause
What Is Black Cohosh?
Black cohosh (known as both Actaea racemosa
and Cimicifuga racemosa), a member of the
buttercup family, is a perennial plant that
is native to North America. Other common names
include black snakeroot, bugbane, bugwort,
rattleroot, rattletop, rattleweed and macrotys.
Insects avoid it, which accounts for some
of these common names.
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What Are Common Black Cohosh Preparations?
Preparations of black cohosh are made from its roots
and rhizomes (underground stems). One commercial standardized
black cohosh preparation is Remifemin®, which
contains black cohosh extract equivalent to 20 mg
of root per tablet. The manufacturer changed the formulation
of this preparation from a solution (root extracted
with ethanol, 60 percent by volume) to tablets (root
extracted with isopropyl alcohol, 40 percent by volume),
complicating the comparison of research results. Other
preparations of black cohosh have been less well studied
than Remifemin.
Extracts of black cohosh are standardized to 26-deoxyactein
content (erroneously reported in the scientific literature
as 27-deoxyactein [2]), a member of a group of chemicals
known as saponins. Commercially available preparations
of black cohosh usually contain 1 mg of total triterpene
saponins (expressed as 26-deoxyactein) in each 20-mg
dose of extract.
What Are the Historical Uses of Black Cohosh?
Black cohosh was used in North American Indian medicine
for malaise, gynecological disorders, kidney disorders,
malaria, rheumatism and sore throat [3]. It also was
used for colds, cough, constipation, hives and backache,
and to induce lactation [4]. In 19th-century America,
black cohosh was a home remedy used for rheumatism
and fever, as a diuretic and to bring on menstruation.
It was extremely popular among a group of alternative
practitioners who called black cohosh "macrotys"
and prescribed it for rheumatism, lung conditions,
neurological conditions and conditions that affected
women's reproductive organs (including menstrual problems,
inflammation of the uterus or ovaries, infertility,
threatened miscarriage and relief of labor pains)
[4].
What Clinical Studies Have Been Done on Black
Cohosh and Its Effect on Menopausal Symptoms?
Black cohosh is used primarily for hot flashes and
other menopausal symptoms. A number of studies using
various designs have been conducted to determine whether
black cohosh affects menopausal symptoms [5]. Few
studies were placebo controlled, and most assessed
symptoms by using the Kupperman index — a scale
that combines measures of hot flashes, insomnia and
depression but not vaginal dryness. Those with the
best study designs are described below.
A randomized, double-blind, placebo-controlled trial
was done in breast cancer survivors because most of
these women experience hot flashes and many use complementary
or alternative remedies [6]. The women were over age
18 and had completed breast cancer treatment at least
two months before the trial; 85 women (69 of whom
completed the trial) took one tablet of placebo or
40 mg/day of black cohosh (as 20 mg twice daily) for
two months to determine the effect on hot flashes,
excessive sweating, palpitations, headaches, poor
sleep, depression and irritability [J.S. Jacobson,
Columbia University, written communication, 2002].
Fifty-nine subjects were using tamoxifen (an antiestrogen
treatment for breast cancer); tamoxifen users were
distributed almost equally between the treatment and
control groups. The frequency and intensity of hot
flashes decreased in both groups, with no statistical
difference between the groups; excessive sweating
decreased significantly more in the treatment group
than the placebo group. Other symptoms improved equally
in both groups, and scores on a health and well-being
scale did not change significantly in either group.
A 24-week study in 60 women who had undergone hysterectomy
but retained at least one ovary compared the effects
of 8 mg/day of a black cohosh extract (as four 2-mg
tablets daily; isopropanol extract version of Remifemin)
with three estrogen regimens: estriol (1 mg/day),
conjugated estrogens (1.25 mg/day) and estrogen-progestin
therapy (one daily Trisequens® tablet containing
2 mg estradiol and 1 mg norethisterone acetate) [7].
In all groups a modified Kupperman index measuring
additional physical symptoms was significantly lower
four, eight, 12 and 24 weeks after treatment began.
Black cohosh decreased symptoms similarly to the other
treatments, but this study was not placebo controlled.
A randomized, double-blind, placebo-controlled trial
in 80 menopausal women compared 8 mg/day of a black
cohosh extract (as two 2-mg tablets of Remifemin twice
daily) with placebo or conjugated estrogens (0.625
mg/day) [8]. At 12 weeks, scores on the Kupperman
index and the Hamilton anxiety scale were significantly
lower in the treated groups than in the placebo group;
the scores of participants using black cohosh were
somewhat better than the scores of those receiving
the estrogen treatment. This is one of the few studies
in which hot flashes were scored separately from other
symptoms. Daily hot flashes decreased from 4.9 to
0.7 in the black cohosh group, 5.2 to 3.2 in the estrogen
group and 5.1 to 3.1 in the placebo group.
A randomized, 12-week study of 55 menopausal women
compared an ethanolic extract of black cohosh (40
drops twice daily) with conjugated estrogens (0.6
mg/day) or diazepam (2 mg/day) [9]. Regardless of
the treatment, all symptoms improved as measured by
the Kupperman index, a depression scale and an anxiety
scale. However, this was not a blinded, placebo-controlled
trial and diazepam is not a usual treatment for menopausal
symptoms.
Although some study results suggest that black cohosh
may help relieve menopausal symptoms, other study
results do not. Studies of black cohosh have yielded
conflicting data, in part because of lack of rigor
in study design and short study duration (six months
or less). In addition, interpretation of these studies
is complicated by the fact that different amounts
of black cohosh from different sources were used in
the various studies and their outcome measures were
different. To provide more definitive evidence on
the effects of black cohosh on menopausal symptoms,
the National Center for Complementary and Alternative
Medicine, part of the National Institutes of Health,
is funding a 12-month, randomized, placebo-controlled
study to determine whether treatment with black cohosh
is effective in reducing the frequency and intensity
of menopausal hot flashes. The study also will assess
whether black cohosh reduces the frequency of other
menopausal symptoms and improves quality of life.
The study will examine the possible mechanisms of
action of black cohosh. (Women who are interested
in participating in the study, which is at Columbia
University in New York City, can find out more at
www.clinicaltrials.gov or [212] 342-0110.)
How Does Black Cohosh Work?
How black cohosh works is not known. The
possibility that black cohosh exhibits estrogenic
activity has been studied but the evidence
is contradictory.
A compound recently identified in black cohosh
— fukinolic acid — was shown to
have estrogenic activity in vitro . Other
active compounds appear to include triterpene
glycosides (including actein and cimicifugoside),
resins (including cimicifugin), and caffeic
and isoferulic acids .
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Effect on Hormone Levels
Women who have reached menopause generally have lower
levels of estrogen and higher levels of two other
hormones — luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) — than do women who menstruate.
Three of four studies show that black cohosh does
not affect LH or FSH.
A study of 150 perimenopausal and postmenopausal
women using two different doses of black cohosh (Remifemin
tablets, 39 or 127.3 mg/day) found that six months
of treatment caused no changes in LH, FSH, prolactin,
estradiol or sex-hormone-binding globulin. Another
trial of black cohosh in women with breast cancer
found small but insignificant changes in LH levels
(in 18 subjects) and FSH levels (in 33 subjects) [6].
In the third study, Remifemin (8 mg/day given as four
2-mg tablets) did not affect LH or FSH levels in 15
women who had undergone a hysterectomy who were part
of a study comparing black cohosh with several estrogens.
The fourth study, which found an effect of black
cohosh on LH levels, was a trial in 110 women with
menopausal symptoms. Participants treated with Remifemin
(8 mg/day) for eight weeks had significantly lower
average LH levels than did a control group (FSH levels
were unchanged) . However, the report of this study
does not include the participants' hormone levels
before the study began, so the two groups may have
had different LH levels initially.
In vitro studies used to examine the effect of black
cohosh have given contradictory results. Black cohosh
had no activity in estrogen receptor (ER) binding
assays in Ishikawa (endometrial) and S30 (breast cancer)
cell lines. It did not show potent ER binding activity;
slightly enhanced the growth of ER-positive breast
cancer cells (T47D) but was not tested on ER-negative
cells. In another study, black cohosh inhibited the
growth of T47D (human breast cancer) cells . In ER-positive
breast cancer cell line 435, black cohosh resulted
in growth inhibition. In ER-positive breast cancer
cell line MCF-7, it inhibited estradiol-induced stimulation
of cell proliferation in one study but isolated constituents
of black cohosh increased proliferation in another.
Effect on the Vagina
Because of the marked changes in hormone levels in
women who have achieved menopause, numerous modifications
occur in the structure and activity of vaginal and
uterine tissues. Microscopically, vaginal cells look
different after menopause because of decreased estrogen.
Studies have been mixed on whether black cohosh affects
vaginal epithelium. One placebo-controlled, double-blind
trial of black cohosh showed estrogenic changes in
vaginal epithelium of menopausal women, but another
study of two Remifemin doses (39 or 127.3 mg/day)
found that six months of treatment in perimenopausal
and menopausal women caused no changes in vaginal
cytology .
Effect on the Uterus
Menopause is associated with a thinning of the uterine
lining (the endometrium). No human studies have adequately
evaluated the effect of black cohosh on uterine endometrium.
When uterine weight of immature female mice and growth
of ER-positive breast cancer cells (MCF-7) were used
to measure the estrogenic effect of black cohosh,
black cohosh caused an increase in uterine weight
and growth of cancer cells in culture, which the authors
said reflected an estrogenic effect . Black cohosh
did not exhibit estrogenic effects in a study that
measured uterine weight in immature mice and vaginal
cell cornification (conversion of cells from columnar
to squamous) in ovariectomized rats .
What Is the Regulatory Status of Black Cohosh
in the United States?
In the United States, black cohosh is sold as a dietary
supplement, and dietary supplements are regulated
as foods, not drugs. Manufacturers do not have to
provide the U.S. Food and Drug Administration with
evidence that dietary supplements are effective or
safe before marketing. Because dietary supplements
are not always tested for manufacturing consistency,
the composition may vary considerably from lot to
lot.
Can Black Cohosh Be Harmful?
Black cohosh can cause stomach discomfort and headaches
. Clinical trials comparing estrogens with black cohosh
preparations have shown a low incidence of adverse
effects associated with black cohosh; headaches, gastric
complaints, heaviness in the legs and weight problems
were the main adverse effects noted.
A published case of acute hepatitis involved a 47-year-old
woman who used black cohosh for symptoms of menopause.
She received a liver transplant three weeks after
she started taking the herb. The report indicated
the dose of black cohosh did not exceed the dosage
recommended on the package; but no other dosage information
was provided. No other cause for liver disease was
found.
Black cohosh usually has not been used for long periods,
and published studies have followed women for only
six months or less. Recently, a large study that followed
postmenopausal women taking combined estrogen and
progestin for an average of 5.2 years showed a small
but significant increase in the risk of certain diseases,
demonstrating the importance of long-term studies
in revealing risks that may not be apparent in shorter
studies. If black cohosh is estrogenic, long-term
use may adversely affect uterine or breast tissue.
No studies have been published on long-term safety
in humans, particularly regarding abnormal stimulation
of cells in the endometrium or breast.
There is a case report of neurological complications
in a postterm baby after labor induction with a mixture
of black cohosh and blue cohosh (Caullophylum thalictroides)
during a home birth .
Other cases of adverse outcomes experienced by neonates
born to women who reportedly used blue cohosh to induce
labor have been published in peer-review journals.
Who Should Not Take Black Cohosh?
The use of black cohosh during pregnancy has not
been rigorously studied. Thus, it would be prudent
for pregnant women not to take black cohosh unless
they do so under the supervision of their health care
provider.
Women with breast cancer may want to avoid black
cohosh until its effects on breast tissue are understood.
Does Black Cohosh Interact With Any Drugs or Laboratory
Tests?
Although black cohosh has not been reported to interact
with any drugs or to influence laboratory tests, this
has not been rigorously studied.
