Top Herbal Products: Efficacy and Safety Concerns

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Selection from: Top Herbal Products: Efficacy and Safety Concerns

http://www.medscape.com/viewarticle/568235

Introduction

A recent survey estimated that more than 38 million adults in the

United States used herbal products and dietary supplements in 2002.

[1] More than half of those users said that these products were

important to their health and well-being, yet only one third told a

conventional healthcare provider about their use.

Other reports have estimated that 25% of patients who seek medical

attention for a serious medical problem are using " unconventional "

therapies, and 70% of those patients do not disclose those practices

to their physician.[2,3] One survey estimated that about 18% of the

US population uses herbal therapy on a regular basis.[4]

Herbal products and dietary supplements are widely available in

supermarkets and other retail outlets, as well as by mail order. In

fact, only a small percentage of these products (4.5%) are actually

sold in pharmacies.[5] Many patients believe they derive health

benefits from these herbal preparations, yet some remain skeptical

and may seek advice from health professionals prior to use. Thus, it

is important for all health professionals to be informed about

available products and to be aware of any potential problems

associated with their use.

Concerns About Herbal Products and Dietary Supplements

Unlike prescription and over-the-counter drugs, herbal products are

not regulated by the US Food and Drug Administration (FDA) to

determine purity or potency.[6] In fact, some products may contain

contaminants, and their potency is dependent on many factors, such

as the climate and soil conditions where they are grown, harvested,

and stored.[7] Some herbal preparations have even been found to

contain prescription drugs and heavy metals as unlabeled

ingredients, and in some cases, these contaminants have resulted in

toxicities.[8-17]

The labeling of herbal products is regulated by the Dietary

Supplement Health and Education Act of 1994 (DSHEA).[18] Under this

law, manufacturers may only make general claims about a supplement's

effect on the structure or function of the human body (eg, " supports

the immune system " ). They must include the following statement in

their labeling: " This product is not intended to diagnose, treat,

cure, or prevent any disease. "

The labels on herbal products are designed to promote product use

and not necessarily to inform the consumer, so health professionals

should be equipped with a general understanding of popular herbs and

supplements, including knowledge of efficacy, common side effects,

risks, and interactions. In addition, they should prospectively seek

information regarding their patients' use of unconventional

medicines to avoid adverse consequences.

Consumers should be advised that manufacturers of herbal supplements

are not required to demonstrate safety or efficacy prior to

marketing. Before the FDA can remove a product from the market, the

agency must prove that the product is unsafe or ineffective. Recent

examples of this include the ban on products containing ephedra due

to adverse cardiovascular effects,[19] and the prohibition of kava

amid concerns about hepatotoxicity.[20]

Patients with medical illness should not use herbs and dietary

supplements without medical supervision. As will be discussed, some

herbal products have adverse effects and may interact with

prescribed medications. Furthermore, many conditions that patients

try to diagnose or treat themselves may be serious, requiring a

careful history and examination by a healthcare professional. For

example, unsupervised use of saw palmetto for urinary symptoms may

delay a diagnosis of prostate cancer.[21] Similarly, patients with

symptoms such as chronic insomnia, anxiety, and depressed mood

should see their health provider. Patients with cardiovascular

disease, hypertension, heart failure, and hyperlipidemia should be

under a healthcare professional's care and receive appropriate

prescription drugs.

The following is an overview of some of the most commonly used

herbal products, including important clinical considerations in the

use of these products.

Echinacea for Fighting Cold Symptoms, Boosting Immunity

Echinacea is one of the most popular herbs in the United States,

extracted from the purple coneflower that is native to North

America. Species include Echinacea purpurea, Echinacea angustifolia,

and Echinacea pallida. It has been studied as an adjunct therapy to

enhance the immune system, mostly in upper respiratory tract

infections, and these studies have produced mixed results.[22,23]

A recent meta-analysis concluded that standardized extracts of

echinacea were effective in the prevention of common cold symptoms

after clinical inoculation, when compared with placebo.[23] The

authors of that study concluded that the likelihood of experiencing

a cold was 55% higher with placebo than with echinacea (P < .043).

Some antiviral and bacteriostatic properties have been demonstrated

in vitro, and the herb also appears to stimulate the production of

cytokines (interferon, tumor necrosis factor, and interleukins).[24]

Animal studies have revealed probable mechanisms of echinacea-

induced immune enhancement, such as increasing the number of

circulating white blood cells.[25]

Common side effects of echinacea supplements include unpleasant

taste and allergic reactions. Because the flower is related to

ragweed, cross allergenicity may occur in individuals allergic to

ragweed.[26,27]

Echinacea is not recommended in patients with progressive or

autoimmune disorders, including acquired immunodeficiency syndrome,

tuberculosis, multiple sclerosis, collagen disorders, and diabetes

mellitus. Theoretically, since echinacea alters the immune system,

these disorders may be exacerbated.[28,29] Persistent use of

echinacea has been associated with hepatotoxicity, so it should not

be taken by patients who are taking other known hepatotoxins such as

anabolic steroids, amiodarone, methotrexate, or ketoconazole.[30]

While not all randomized controlled trials performed to date have

shown benefit for Echinacea over placebo,[22,31] a Cochrane review

in 2006 concluded that the aerial parts of Echinacea purpurea might

be effective for early treatment of colds in adults.[32]

Unfortunately, the optimal dose of echinacea is unknown, and

multiple formulations exist, such as capsules, tinctures, teas, and

extracted plant juice. Recommended dosages vary widely; for

instance, capsules of Echinacea purpurea extract range from 100 to

500 mg, with manufacturers' suggested use ranging from 1 to 4 times

daily for common cold prevention.

Take-home message: Clinicians should inform patients that a wide

variety of Echinacea preparations and doses have been studied and

results are inconsistent, making it difficult to recommend specific

products. However, E. purpurea seems to be modestly effective for

preventing the common cold in those at risk (eg, sick contacts).

Evidence that the herb may reduce the duration of cold symptoms has

been mixed. Patients allergic to ragweed, with progressive

autoimmune disorders, and on hepatotoxic drugs should avoid

echinacea.

Garlic: Warding Off Cardiovascular Disease?

Allium sativum, commonly known as garlic, has been used for

centuries in cooking because of its flavoring properties. Today, it

is used therapeutically by many consumers to prevent heart disease

by controlling high cholesterol and high blood pressure. The

suggested active ingredients are allicin and alliin.Numerous

studies, however, have produced conflicting results regarding

garlic's ability to lower lipids.[33-40] Positive findings in 3

trials exhibited a lowering of cholesterol in the range of 6.1% to

11.5%, primarily due to the lowering of low-density lipoproteins.[33-

36] Other studies have yielded neutral or conflicting results.[37-

39] One 12-week study tested the use of garlic powder in ambulatory

patients, finding a 14% reduction of serum cholesterol.[40]

Garlic may have modest antihypertensive effects. Studies have

documented either a small decline in arterial pressure (5% to 7% mm

Hg) or no change at all.[41] A meta-analysis of 8 trials revealed 3

studies that concluded garlic significantly reduced systolic blood

pressure, and 4 studies that found reductions in diastolic blood

pressure in patients with mild hypertension.[42]

With regard to potential adverse effects, garlic has been shown to

inhibit platelet aggregation in vitro[43-45] and in vivo[46]; thus,

it should be used with great caution in individuals with bleeding

disorders or in those who are receiving antiplatelet therapy.[47]

There has been 1 report of a spontaneous epidural hematoma occurring

with garlic supplementation, but this appears to be an isolated case.

[48]

Garlic may also decrease warfarin concentrations.[49-51] Studies to

date have not confirmed this interaction[52,53]; but particularly

close monitoring of the international normalization ratio (INR) for

patients taking both garlic and warfarin is prudent. Patients taking

garlic supplements should discontinue use 7 to 10 days prior to

having surgical procedures to avoid the potential for prolonged

bleeding.[54]

The most prominent side effect of garlic supplementation is

malodorous breath and garlic-like body odor.

Take-home message: Garlic should be used cautiously in individuals

receiving antihypertensive medications, and blood pressure should be

monitored carefully; orthostatic hypotension is a rare complication

for those on antihypertensives.[55] Also, garlic should be avoided

in those with a history of orthostasis or unexplained dizziness as

well as in patients taking drugs that can increase bleeding, such as

aspirin, warfarin and ibuprofen. A lack of standardization of garlic

products and formulations makes it difficult to recommend a dose or

specific product. For dyslipidemia, patients may benefit from taking

600 to 1200 mg of garlic powder daily in divided doses, or up to 4 g

of raw garlic daily.

Ginkgo Biloba for Enhancing Memory, Combating Alzheimer's Disease

Ginkgo biloba is one of the oldest species of living trees, and

ginkgo supplements are derived from the tree's leaves. This herbal

remedy is marketed to improve memory, particularly in elderly

individuals. While its mechanism of action is not fully understood,

ginkgo contains flavonoids, terpenoids, and organic acids that are

believed to act as free radical scavengers. These constituents have

been shown to:

Inhibit platelet activation factor (reducing thrombosis);

Dilate arteries and capillaries; and

Block the release of chemotactic factors and inflammatory mediators.

Studies in the United States have found that ginkgo stabilized --

and in some cases improved -- cognitive function and socialization

in patients with Alzheimer's disease, although the clinical

significance of the improvement was not known.[56,57] LeBars and

colleagues[56] reviewed 2020 patients in an intention-to-treat

analysis that resulted in a 1.4-point advantage over placebo in the

Alzheimer's Disease Assessment Scale-Cognitive subscale.

In addition, studies have also demonstrated that the standardized

extract of ginkgo biloba (EgB) 761, is effective in reducing

symptoms of claudication, giving patients a 50% increase in pain-

free walking distance.[58]

In contrast, a recent clinical trial failed to demonstrate any

improvement in cognitive function or in the quality of life in

cognitively intact, older individuals.[59]

Ginkgo is considered relatively safe, although the leaves have been

associated with mild gastrointestinal side effects and headache.

Ingestion of ginkgo seeds may result in serious neurologic and

allergic reactions; therefore, they are not used for medical

purposes.[60,61] Ingestion of leaf-based extracts has been

associated with a spontaneous hyphema (blood in the anterior chamber

of the eye) in an elderly man,[62] and with spontaneous subdural

hematomas.[63] However, while some isolated adverse events such as

these exist, it is considered safe when used as directed.

Ginkgolide B, an active component of ginkgo biloba, is a potent

inhibitor of platelet-activating factor, which is necessary for

normal platelet aggregation. As with garlic, it should be avoided in

patients using anticoagulants or antiplatelet therapy, or in those

who have active bleeding such as peptic ulcer disease. Based on case

reports, ginkgo is not recommended in patients with seizure

disorders.[64-67]

Standardization of product and recommended dosing is lacking, but a

typical dose is 40 mg to 80 mg taken 3 times daily, standardized to

24% to 27% ginkgo flavone glycosides and 6% to 7% triterpines per

dose. A dose of ginkgo extract EGb 761 at 160 mg daily has shown

equivalent efficacy compared with donepezil 5 mg daily for the

treatment of Alzheimer's disease.[68]

Take-home message: Ginkgo is a reasonable therapeutic option in

patients with Alzheimer's disease who are also receiving medical

care, but providers should remember that the herb has antiplatelet

activity and thus may not be appropriate for patients with bleeding

disorder or on antiplatelet or anticoagulation agents.

St. 's Wort Used for Depression

This yellow flowering plant (Hypericum perforatum) is named after

St. the Baptist. Extracts of the flower have been used for

centuries to treat mental illnesses. The herbal product has 10

constituents, of which hypericin is believed to be the most active

ingredient in treating depression.St. 's wort has a high

affinity for gamma-aminobutyric acid, which, when stimulated,

produces an antidepressant effect.[69] Hypericin also appears to

activate dopamine receptors and inhibit serotonin receptor

expression. In vitro, it has been shown to block reuptake of

serotonin and norepinephrine.[70] These mechanisms may explain the

lag time associated with the effectiveness of the herb.

A number of studies have examined the effectiveness of St. 's

wort in depression.[71,72] A meta-analysis of 23 controlled trials

concluded that it was more effective than placebo in treating mild-

to-moderate depression.[72] In a 12-week study of 135 depressed

patients, the herbal extract (900 mg per day) was found to be more

effective than fluoxetine (20 mg per day).[73] Other investigators

have confirmed the herb's efficacy over placebo in mild-to-moderate

depression.[74]

Because of its pharmacology, St. 's wort should not be taken

with prescription serotonin uptake inhibitors, as symptoms of

serotonin syndrome have been observed with co-administration

(headache, sweating, dizziness, and agitation).[75-77, 85]

In terms of other contraindications, St. 's wort should be

avoided during pregnancy.[78,79] It has been associated with

photosensitivity.[80] Studies have shown that the herbal product can

reduce plasma concentrations of digoxin[77,81] and indinavir.

[77,82,83] There have been cases of heart transplant rejection

associated with the use of St. 's wort that resulted from a

reduction in cyclosporine plasma concentrations.[84,85] Breakthrough

bleeding and unwanted pregnancies have been reported in women on

concomitant therapy of oral contraceptives and St. 's wort

extract.[85,86] This is likely a result of St 's wort-induced

decreases in ethinyl estradiol or metabolite concentrations due to

the herb's ability to induce cytochrome P450 (CYP450)-3A4 isoenzyme.

Take-home message: Patients who are depressed should not take this

herb without medical supervision. St. 's wort should be reserved

for the mildly depressed patient with an aversion to prescription

medication. Clinicians who recommend this botanical should be

mindful of the numerous potential drug interactions arising from

enzyme induction. The most commonly studied dose for depression is

300 mg taken 3 times a day, standardized to 0.3% to 0.5% hypericin

per dose.