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Herbal Therapy
What Every Facial Plastic Surgeon Must Know
Edmund deAzevedo Pribitkin, MD;
Gregory Boger, MD
Arch Facial Plast Surg. 2001;3:127-132.
ABSTRACT
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Herbal medicine (phytomedicine) uses remedies possessing significant
pharmacological activity and, consequently, potential adverse effects and
drug interactions. The explosion in sales of herbal therapies has brought
many products to the marketplace that do not conform to the standards of safety
and efficacy that physicians and patients expect. Unfortunately, few surgeons
question patients regarding their use of herbal medicines, and 70% of patients
do not reveal their use of herbal medicines to their physicians and pharmacists.
All surgeons should question patients about the use of the following common
herbal remedies, which may increase the risk of bleeding during surgical procedures:
feverfew, garlic, ginger, ginkgo, and Asian ginseng. Physicians should exercise
caution in prescribing retinoids or advising skin resurfacing in patients
using St John's wort, which poses a risk of photosensitivity reaction. Several
herbal medicines, such as aloe vera gel, contain pharmacologically active
ingredients that may aid in wound healing. Practitioners who wish to recommend
herbal medicines to patients should counsel them that products labeled as
supplements have not been evaluated by the US Food and Drug Administration
and that no guarantee of product quality can be made.
INTRODUCTION
The use of herbal medicine is widespread and growing. The actual and
perceived relative safety of natural products is a major reason for their
popularity with the general public. In 1997, 60 million Americans spent $3.24
billion on herbs as medical therapy.1 In 1999,
US herbal sales were expected to exceed $5 billion.2
Unfortunately, the explosion in sales of herbs, vitamins, and supplements
has brought many products to the marketplace that do not conform to the standards
of safety and efficacy that physicians and patients expect. Internet searches
for any given herbal medicine routinely yield thousands of links, most of
which offer promotional literature and the opportunity to purchase remedies
at the click of a mouse button. Pharmacies struggling to profit from small
margins on prescription drugs consistently devote prime display space and
marketing dollars to high-profit herbal remedies. Naturally, reports have
begun to surface from poison control centers in various states detailing adverse
reactions to a broad range of herbal supplements.3-4
For example, severe toxic reactions have been reported with the use of chaparral,5 germander,6 and pennyroyal.7 Numerous studies have also demonstrated contamination
of herbal medicines with potent synthetic medications.8-9
Nonetheless, when considering outcomes for exposures involving dietary supplements
(including, but not limited to, herbal preparations) for any reasons (unintentional,
intentional, adverse reaction, or other) reported to poison control centers,
fewer than 7000 exposures were reported in 1998, compared with more than 1
million exposures reported for all pharmaceuticals.10
No deaths and only 19 major (0.3%) and 165 moderate (2.4%) effects were attributed
to dietary supplement exposures, whereas 868 deaths (0.09%), 13 197 major
(1.3%), and 58 188 moderate (5.8%) effects were attributed to all pharmaceutical
exposures.10
Unlike other forms of complementary and alternative medicine, herbal
medicine may be approached as conventional medicine.11
Many herbal remedies possess significant pharmacological activity and, consequently,
potential adverse effects and drug interactions. To paraphrase Simon Y. Mills,
PhD, of the University of Exeter, Exeter, England, "Skeptics need only take
a few doses of the botanical laxative senna to become convinced of the herb's
clinical efficacy" (personal communication, October 1999). Recent articles12-15 in
peer-reviewed medical journals have acknowledged herbal medicine's unique
position in the growing field of complementary and alternative medicine and
have provided a context in which clinicians may approach patients using herbal
medicines. Nonetheless, many facial plastic surgeons remain unaware of herbal
remedies. Indeed, few physicians question patients regarding their use of
herbal medicines, and 70% of patients do not reveal their use of herbal medicines
to their physicians and pharmacists.16 It would
be difficult to fashion a more dangerous prescription for disaster than that
pertaining to the current state of herbal therapy in the United States: physician
ignorance of widespread patient use of products with significant pharmacological
activity. In this article, we will define herbal medicine and discuss how
plants are processed into remedies. We will summarize the history, use, and
regulation of botanical medicine in the United States and explore the adverse
effects of common herbal remedies. Finally, we will discuss the potential
for drug-herb interactions and examine potentially beneficial herbal therapies.
DEFINING HERBAL MEDICINE (PHYTOTHERAPY)
Herbal medicines are medicinal products that
contain plant materials as their pharmacologically active components.17 For most herbal medicines, the specific ingredients
that determine the pharmacological activity of the product are poorly characterized.
Most herbal preparations are marketed as dry or fluid extracts, which are
made from dried plant parts by maceration or percolation. Schulz et al17 compare the preparation of herbal medicines with
the preparation of wines. Although, generally speaking, a cabernet will be
a cabernet, cultivated medicinal plants will yield different vintages, as
do cultivated grapes. Naturally, just as processing of the same grapes can
yield dramatically different potencies and tastes, so can the processing of
medicinal plant extracts yield medicines of varying strength and purity. All
extracts are not the same, and commercially available extracts vary greatly
in their quality. For example, California investigators in 1998 found that
nearly one third of 260 imported Asian herbal remedies were either spiked
with drugs not listed on the label or contained harmful materials.3 The California Department of Health Services, Food
and Drug Branch, investigated these Asian patent medicines collected from
California retail herbal stores and found that 83 of 260 products contained
undeclared pharmaceuticals or potentially hazardous levels of lead, arsenic,
or mercury.4 When prescribing herbal medicines,
practitioners are advised to select manufacturers (typically European) who
use methods such as high-performance liquid chromatography to generate a characteristic
fingerprint spectrum, which they use to maintain consistency across batches.17 Practitioners should select manufacturers from countries,
including those in Europe, Japan, and Australia, where herbal medicines must,
by law, be made according to the code of pharmaceutical Good Manufacturing
Practice.18 This fail-safe system of quality
assurance and quality control includes high-performance liquid chromatography
and other state-of-the-art methods to ensure consistent quality.17
HISTORY OF HERBAL MEDICINES
The use of plants as medicines predates written human history. A 60 000-year-old
Neanderthal burial site in northern Iraq has yielded large amounts of pollen
from 8 plant species, 7 of which are used now as herbal remedies.19 Ancient Chinese,20
Egyptian,21 and Assyrian22
texts detail the use of herbal therapies. Hippocrates (c 460-c 375 BC) advised
the use of herbal medicines to help balance the humors by removing from the
body that which was excessive and augmenting that which was deficient.23 Finally, herbal medicine found systemized expression
in the first European herbal, De Materia Medica,
which was written by the Greek physician Pednios Dioscorides in the first
century AD and which remains an authoritative herbal reference to this day.17
Herbs, the first human healing system, remain the mainstay of indigenous
healing practices. The World Health Organization estimated in 1985 that 75%
of the world's population, or 4 billion people, rely on herbs for their medical
needs.24 In Germany, where herbs are regulated
as drugs, they have been used as adjuncts alongside conventional Western medical
therapies for many years and are commonly prescribed. The German Commission
E was created in 1988 to evaluate critically the safety and efficacy of herbal
medicines. This commission considers traditional herbal uses, assesses the
scientific basis for granting an authorized herbal claim, and specifies allowable
dosages and limitations on use. The German Commission E has published more
than 400 monographs25 and approved more than
200 herbs for use. Six of the top 100 prescribed medications in Germany are
herbal preparations, and the top 12 herbals account for 2.25% of all sales
of prescribed German medicines.
In contrast with Germany, no enlightened system of laws and regulations
governing the sale and use of herbal medicines exists in the United States.
The original Food and Drugs Act of 1906 abolished adulterated or misbranded
drugs but did not address drug safety or efficacy. As a result, in 1938, the
federal Food, Drug and Cosmetic Act required that all drugs sold in the United
States be proven safe. The 1962 Kefauver-Harris amendments to this act required
that all drugs marketed in the United States be proven safe and effective.
During the next several decades, many over-the-counter prescription drugs,
including many herbal medicines, failed to receive US Food and Drug Administration
(FDA) approval for therapeutic purposes. The landmark Dietary Supplement Health
and Education Act of 1994, however, classified herbs as "dietary supplements,"
and made the FDA responsible for proving in federal court that a product was
unsafe before it could be removed from the market. The Dietary Supplement
Health and Education Act also allowed manufacturers to make claims of supplement
activity on the body's structure or function, provided these claims were truthful
and not misleading; were not claims for a cure, treatment, or prevention of
disease; and were based on scientific evidence in company files. Thus, herbal
remedies with structural or functional claims carry a disclaimer: "This statement
has not been evaluated by the Food and Drug Administration. This product is
not intended to diagnose, treat, cure, or prevent any disease."26(p3)
The United States Pharmacopeia (USP) and National Formulary
(USP24-NF19) work closely with the FDA and have published authoritative
standards for 8 botanical supplements: feverfew (Tanacetum
parthenium), garlic (Allium sativum), ginkgo
(Ginkgo biloba), Asian ginseng (Panax ginseng), chamomile (Matricaria chamomilla), saw palmetto, St John's wort (Hypericum perforatum), and powdered valerian. The USP is also
developing monographs for other herbal preparations. Physicians may advise
patients to purchase products carrying NF or USP on their labels. Federal law requires that products
with NF or USP on the label
comply with USP24-NF19 published standards. Unfortunately,
the use of herbal medicines in the United States has depended largely on popular
literature and has been driven by media and Web-based outfitters responding
to increasing levels of consumption. Because there is no direct FDA regulation
of herbs as drugs, there is no control over product standardization, in terms
of either potency or contamination. Each surgeon must take a focused, systematic
look at commonly used herbal products, their adverse reactions, and common
drug interactions.
ADVERSE REACTIONS
Bleeding
Facial plastic surgeons commonly question patients with regard to aspirin
use, yet few explore the use of herbals among their patients contemplating
surgery. All surgeons should ask patients about the use of the following common
herbal remedies, which may increase the risk of bleeding during surgical procedures:
feverfew, garlic, ginger (Zingiber officinale), ginkgo,
and Asian ginseng. A partial listing of other herbal medicines that may increase
bleeding time is provided in Table 1.
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Table 1. Some Medicinal Plants Potentially Associated With an Increased
Risk of Bleeding
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Feverfew, despite its name, has no fever-reducing powers and is most
commonly used for migraines. Feverfew has been shown to inhibit platelet activity27 and must be avoided in patients using warfarin sodium
or other anticoagulants. Patients should be advised to discontinue feverfew
use before surgery. Unfortunately, abrupt cessation of feverfew therapy may
result in a withdrawal syndrome characterized by nervousness, tension headaches,
insomnia, stiffness, joint pain, and tiredness.28
Garlic has been widely touted as a cure for colds, coughs, flu, chronic
bronchitis, whooping cough, ringworm, asthma, intestinal worms, fever, and
digestive, gallbladder, and liver disorders. Recent research has explored
its use as a treatment for mild hypertension29
and hyperlipidemia.30 Heavy consumption may
lead to elevated clotting times31 and spontaneous
hemorrhage.32 Numerous studies33-36
have documented garlic's inhibitory effect on platelet aggregation in humans,
which occurs within 5 days of oral administration.
Ginger has been used for millennia in China as a digestive aid and to
remedy stomach upset, gassy indigestion, bloating, and cramping. Recent studies37-39 have confirmed its
use as an antinauseant in motion sickness. Ginger is a potent inhibitor of
thromboxane synthetase and can theoretically prolong bleeding times with long-term
use.40
Use of ginkgo was recognized by the 1994 German Commission E for treatment
of cognitive disorders, including dementia, intermittent claudication, and
tinnitus or vertigo of vascular or involutional origin.25
Recent publicity about its use as a treatment for Alzheimer disease41 has boosted sales of standardized G biloba extract to unprecedented levels. Reports of spontaneous hyphema42 and of spontaneous bilateral subdural hematomas43 underscore ginkgo's potent inhibitory effect on platelet
activating factor and, consequently, on platelet aggregation.44
Asian ginseng has become popular as a key to vitality and longevity,
the herb to take in cases of physical or mental fatigue or lowered resistance
to infection.26 The herb exhibits antiplatelet
effects,45 and its concomitant use with warfarin,
heparin, aspirin, and nonsteroidal anti-inflammatory drugs should be avoided.13 This effect has not been shown with Siberian ginseng
(Eleutherococcus senticosus), which has also been
promoted for its adaptogenic properties.
Numerous plants contain salicylate and should be used with caution,
although some authors have contended that natural sources of salicylates seem
to lack aspirin's effect of inhibiting platelet aggregation.46
These plants include black cohosh rhizome (Cimicifuga racemosa), meadowsweet flower (Filipendula ulmaria
and Spiraea ulmaria), poplar bark or buds (Populus species), sweet birch bark (Betula lenta and Betula pendula), willow bark
(Salix species), and wintergreen leaves (Gaultheria procumbens).46 Other plants
contain coumarin, and their use should be strictly avoided perioperatively
(Table 1). Herbal medicines such
as chaparral5 and germander6
have also been associated with toxic effects in the liver, which can lead
to an altered clotting function. Finally, herbal medicines not known to cause
bleeding may be adulterated with synthetic agents known to increase the risk
of bleeding during surgical procedures.
Skin Reactions
Numerous herbal medicines may profoundly affect the skin and thereby
adversely interact with the facial plastic surgeon's efforts to improve skin
quality through resurfacing techniques. Kava (Piper methysticum) preparations are an herbal alternative to synthetic anxiolytics and
tranquilizers and are frequently found in "herb drinks."47
A characteristic "kava dermatopathy" may develop if the herb is used continuously
for several months.48 Symptoms include reddened
eyes, scaly skin eruptions, and a yellowish discoloration of the skin, hair,
and nails, attributed to 2 yellow pigments in the plant.49
Fortunately, these effects appear to be reversible on discontinued use of
the herb. St John's wort is licensed in Germany for the treatment of mild
depressive states, anxiety, nervous unrest, and sleep disorders.25
Sales of the herbal preparation have boomed because of the public's perception
that it is a safe alternative to prescription antidepressants. St John's wort
poses a risk of photosensitivity reaction attributed to its hypericin component.50 Concomitant use with other photosensitizing agents,
such as tetracycline hydrochloride, fluoroquinolones, and sulfonamides, should
be avoided. Retinoids, such as tretinoin, and similar dermal irritants should
be administered with caution in conjunction with St John's wort because of
the possibility of augmented phototoxic effects. Certain medicinal plants
of the carrot family (Apiaceae species) contain furocoumarins
and can also cause a photodermatitis in humans from sensitization of the skin
to UV light. Use of any herbal medicines containing furocoumarins (Table 2) should be avoided while undergoing
cosmetic UV light exposure or in conjunction with other photosensitizing agents
or dermal irritants.46
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Table 2. Some Medicinal Plants With Potential Photosensitizing Effect
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Estrogen Effects
Many facial plastic surgeons advise patients who are postmenopausal
to consult their primary care physicians regarding the risks and benefits
of estrogen replacement therapy. More than 500 plant species contain phytoestrogens,
naturally occurring substances functionally similar to estradiol.51 Phytoestrogens may potentiate or antagonize estrogen
effects. Accordingly, these compounds may contribute to changes in skin pigmentation
following resurfacing procedures. Moreover, use of some phytoestrogens in
conjunction with estrogen replacement therapies may result in symptoms such
as nausea, bloating, hypotension, breast fullness or tenderness, migraines,
and edema. Among the more commonly used phytoestrogen-containing herbs are
dong quai (Angelica sinensis), red clover (Trifolium pratense), alfalfa (Medicago
sativa var italica), licorice (Glycyrrhiza glabra), and black cohosh.52-53
POTENTIALLY BENEFICIAL WOUND HEALING HERBAL MEDICATIONS
Botanical remedies have long been used as topical preparations to enhance
wound healing. These topical preparations may be administered in vehicles
with high water content, such as moist compresses, hydrogels, and tinctures,
or may be applied in formulations with high fat content, such as lipophilic
creams and ointments. The German Commission E has approved 25 herbs for dermatologic
indications, including chamomile, witch hazel leaves and bark (Hamamelis virginiana), podophyllin (Podophyllum peltatum), calendula flowers (Calendula officinalis),
bittersweet (Solanum dulcamara), purple coneflower
(Echinacea purpureae), St John's wort oil, arnica
flowers (Arnica montana), and comfrey leaves and
root (Symphytum officinale).17
Facial plastic surgeons must be aware of arnica and comfrey, both of which
have a long tradition in European folk medicine for the treatment of posttraumatic
and postoperative discomfort, ecchymosis, and edema. In vitro studies have
demonstrated anti-inflammatory54 and antimicrobial55 effects attributable to arnica's helenalin component.
Although topical application may cause irritant or allergic dermatitis, arnica
may safely be recommended for use on unbroken skin to lessen posttraumatic
ecchymosis, inflammation, and edema. Undiluted arnica, however, is toxic if
taken internally, and the claim that homeopathic arnica is efficacious beyond
a placebo effect is not supported by rigorous clinical trials.56
Physicians should caution against use of comfrey because of the herb's constituent
pyrrolizidine alkaloids,57 which have shown
hepatotoxic,58 carcinogenic,59
and mutagenic59 properties in rats. Although
topical formulations have been approved by the German Commission E for short-term
use on unbroken skin, comfrey preparations in the United States are not standardized
and may contain high levels of pyrrolizidine alkaloids and contaminants such
as nightshade (Atropa belladonna) and foxglove (Digitalis purpurea).2
Numerous botanical remedies formulated as essential oils have been shown
to have antimicrobial and anesthetic effects, including tea tree oil (Melaleuca alternifolia), peppermint oil (Mentha piperita), and various conifer-derived oils. Tea tree oil's
primary antimicrobial ingredient has been identified as terpinen-4-ol,60 which has demonstrated in vitro efficacy against
numerous bacteria and fungi, including methicillin sodium–resistant Staphylococcus aureus.61
In a 1990 clinical study involving 124 individuals with mild to moderate acne,
5% tea tree oil in a water-based gel significantly reduced the mean number
of acne lesions by the end of 3 months, with fewer reported adverse effects
than those associated with 5% benzoyl peroxide lotion use.62
Peppermint oil has also demonstrated antibacterial,63
antiviral, and antifungal64 effects in several
in vitro studies. Numerous analgesic creams include peppermint oil or its
distillate menthol because of the oil's long-lasting cooling effect on the
skin.65 Surgeons should approach the use of
essential oils with caution, however, because they may irritate sensitive
skin and cause contact dermatitis.66
Aloe vera (Aloe vera) gel is commonly incorporated
in many cosmetic products for its wound-healing properties. Aloe vera gel,
or mucilage, is a thin, clear, jellylike substance obtained from the parenchymal
tissue making up the inner part of the A vera plant
leaf. It must not be confused with aloe juice (also known as latex), which is a cathartic, bitter yellow juice extracted from specialized
cells of the plant's inner leaf.2 Fresh aloe
vera gel promotes the attachment and growth of normal human cells in vitro
and enhances the healing of wounded monolayers of cells.67
Aloe vera contains several pharmacologically active ingredients, including
a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and
substances that inhibit the local vasoconstrictive effect of thromboxane in
vivo.68 Controversy exists as to whether these
wound-healing effects can be seen with commercially prepared products, many
of which contain minimal amounts of A vera. Quality
aloe vera gel products typically contain more than 95% pure A vera and have proven effective in preserving skin circulation following
frostbite injury69 and in accelerating wound
healing in patients who have undergone full-face dermabrasion.70
Aloe vera gel improves the anti-inflammatory effect of hydrocortisone acetate
when used as a vehicle for topical application on mice.71
In an excisional wound model in rats, aloe vera gel accelerated wound contraction
and neutralized the toxic effects of topical antimicrobials to fibroblasts
and keratinocytes. Consequently, aloe vera increased collagen activity and
enhanced the breaking strength of scars resulting from excisional wounds.72 Aloe vera gel may aid in superficial wound healing
(dermabrasion and minor surface wounds), although at least one study73 has indicated it may delay recovery in complex wound
healing by secondary intention. The evidence for a potential beneficial wound-healing
effect from aloe vera gel is sufficient to warrant the design and implementation
of well-controlled clinical trials. Several reputable suppliers produce a
stabilized aloe vera gel for use and are working toward isolating and eventually
providing verified active ingredients in dosable quantities.74
CONCLUSIONS
Facial plastic and reconstructive surgeons work with patients seeking
to maintain their appearance of health and vitality. Eisenberg et al note
that 58% of alternative therapies in 1997 were used, at least in part, to
"prevent future illness from occurring or to maintain health and vitality."75(p1574) Clearly, all patients should be asked about
the use of herbal medicines and should have their responses documented in
the medical record.76 Surgeons must be aware
of adverse reactions stemming from herbal medicine use, especially with regard
to perioperative bleeding. They must caution patients that lack of standardization,
quality control, and regulation may result in variability in herbal content,
efficacy, and frank contamination. Well-controlled clinical trials may yield
valuable new herbal medicines or validate ancient remedies, but each surgeon
should discuss proven treatment options with patients before consideration
of herbal therapies.
AUTHOR INFORMATION
Accepted for publication September 10, 2000.
Presented at the American Association of Facial Plastic and Reconstructive
Surgery Combined Spring Meeting, Orlando, Fla, May 13, 2000.
Corresponding author and reprints: Edmund deAzevedo Pribitkin, MD,
Department of Otolaryngology–Head and Neck Surgery, Thomas Jefferson
University, 925 Chestnut St, Sixth Floor, Philadelphia, PA 19107 (e-mail: Edmund.Pribitkin{at}mail.tju.edu).
From the Department of Otolaryngology–Head and Neck Surgery,
Thomas Jefferson University, Philadelphia, Pa.
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