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Herbal Products and Uses
by Victoria E. Rand, M.D.
Geriatric Times September/October 2001 Vol. II Issue 5
As clinicians, we have become all too aware that a large number of our patients take herbal and other supplements in addition to prescription medicines. This year, an article in the Archives of Internal Medicine described an 80% increase--from $8.8 billion to $15.7 billion spent per year--in dietary supplement sales between 1994 and 2000 (Blendon et al., 2001). Based on published surveys, there are a considerable number of patients who are taking both supplements and prescription medicines, and only about half of these patients are telling their physicians (Hensrud et al., 1999).
The supplement industry does not follow the same regulations from the U.S. Food and Drug Administration as the pharmaceutical industry; rather, it follows FDA regulations for food products. While the FDA requires supplement manufacturers to have internal monitoring systems, it does not require that products be proven safe and effective before they are made available.
Therefore, as health care providers, we need to do a better job in asking our patients if and why they are taking these supplements. There are also a few basic pieces of advice that we can give our patients about purchasing herbal products. For example, the botanical name of the herb should appear on the label along with a batch or lot number, an expiration date, and the name and address of the manufacturer. Women of childbearing age should be cautioned regarding the use of supplements, and all patients should be counseled to discontinue supplements prior to elective surgery.
Some of the most commonly used herbal supplements among older Americans include Gingko biloba for the treatment and prevention of dementia, St. John's wort (Hypericum perforatum) for the treatment of mild to moderate depression and saw palmetto (Serenoa repens) for the treatment of mild to moderate prostate hypertrophy.
Gingko biloba. This supplement is currently used in the United States for Alzheimer's disease and multi-infarct dementia, peripheral vascular disease, erectile dysfunction, tinnitus, and other conditions. Gingko acts as a free radical scavenger, enhances vasodilatation and inhibits platelet aggregation. For the treatment of dementia, most studies have used a dose of 40 mg to 60 mg three times per day; EGb 761 is a standardized extract that is used in Europe and has been used in most U.S. trials. Although side effects are often mild, there have been cases of serious bleeding in patients who combined Gingko biloba and prescription blood thinners due to platelet activation inhibition.
Le Bars et al. (1997) compared Gingko biloba to placebo for the treatment of dementia in a 52-week study. Though there was a high dropout rate in both groups, intent-to-treat analysis showed significant improvement in cognitive scoring as well as activities of daily living. In 1999, Ernst and Pittler's systematic review concluded that Gingko biloba was more effective than placebo. Currently, there is a six-year, $15 million study at University of Pittsburgh School of Medicine examining Gingko biloba for the prevention of dementia. Clearly, more data are needed comparing this herb with standard prescription drugs.
St. John's wort. This herb has been used since ancient times to treat a variety of ailments. In the United States, it is most commonly used to treat mild to moderate depression. St. John's wort (SJW) comes in a standardized extract of 0.3% hypericin and is typically dosed at 300 mg orally three times per day. Although the bulk of the published literature supports products that are standardized to hypericin, there is new literature supporting other active ingredients (Chatterjee et al., 1998; Muller et al., 1998), and some products are standardized to hyperforan. Similar to standard agents used to treat depression, there may be a four- to six-week lag time before clinical benefits are seen. The exact mechanism of SJW's antidepressant activity is not entirely known. It appears to affect the serotonin, norepinephrine and dopamine neurotransmitter systems.
While SJW is well-tolerated, there have been case reports of mania (Moses and Mallinger, 2000; Nierenberg et al., 1999) and anxiety (Brown, 2000). Although earlier literature suggested that SJW can cause photosensitivity, in these studies the herb was administered intravenously and in high doses (Gulick et al., 1992). Most physicians recommend discontinuing SJW prior to elective surgery due to concerns raised in anesthesia literature (Ciordia 1998; Irefin and Sprung, 2000). The most important published information on SJW in recent years is on drug/herb interactions. St. John's wort is a potent inducer of cytochrome P450 enzyme system 3A4, and 50% of prescriptions are metabolized by this enzyme system. It can decrease levels of protease inhibitors (Piscitelli et al., 2000), cyclosporine (Neoral, Sandimmune) (Ruschitzka et al., 2000), theophylline (Nebel et al., 1999), warfarin (Coumadin) and birth control pills (Yue et al., 2000). St. John's wort can also affect digoxin (Lanoxin) levels by decreasing digoxin absorption from the gut (Johne et al., 1999).
St. John's wort efficacy has been well-studied, primarily in Europe. In a meta-analysis of over 1,700 patients in 23 trials comparing SJW to placebo as well as tricyclic antidepressants (TCAs), Linde et al. (1996) found that SJW was superior to placebo and as effective as TCAs for mild to moderate depression. Linde and Mulrow (2000) looked at 27 trials with over 2,200 patients. Again, SJW performed better than placebo, but there was inadequate evidence to establish whether it was as effective as other antidepressants.
A German trial comparing SJW to 20 mg/day of fluoxetine (Prozac) showed equivalent benefit with fewer side effects in the SJW-treated group for mild to moderate depression (Harrer et al., 1999). In patients with major depression, Shelton et al. (2001) found that SJW was not effective. More recently, results of the completed Duke University trial comparing SJW to a selective serotonin reuptake inhibitor have yet to be published.
Saw palmetto. This herb has become very popular in the United States over the past five to 10 years. In Germany, 90% of men with benign prostatic hypertrophy (BPH) elect to take it instead of prescription drugs. While its precise mechanism of action is still uncertain, in-vitro data support its action as a 5-
reductase inhibitor as well as an
Like SJW, most of the studies on saw palmetto have been conducted in Europe, and they show improvement in both objective and subjective measures of an enlarged prostate, along with fewer side effects than other medications. In 1998, Wilt et al. published results from a meta-analysis of 18 randomized trials on BPH and saw palmetto. Almost 3,000 men were included. Although there were improvements in nocturia and peak flow rates, the pooled findings were not statistically significant. However, another meta-analysis of 13 trials using the European brand of saw palmetto, Permixon, found significant improvements in subjective and objective measures (Boyle et al., 2000). Marks et al. (2000) studied the efficacy of an American herbal blend that included saw palmetto and did not find significant differences between the blend and the placebo groups. While trials of European products have clearly shown benefit in men with BPH (Wilt et al., 1998), more studies need to be done on U.S. products.
No drug interactions with saw palmetto have been reported. Reports of side effects, including headaches and gastrointestinal disturbances, have been rare. However, a recent case report associated severe intraoperative hemorrhage to a patient's taking saw palmetto (Cheema et al., 2001).
As more and more Americans are trying supplements, it is important that physicians learn as much as we can regarding them so we can properly counsel our patients. Without being experts in this field, we can minimize the overuse of supplements and prevent unwanted herb/drug interactions. (For more information on the interactions between prescription medications and these and other herbal remedies, please see this month's continuing medical education article "Interactions Between Prescription Drugs and Herbs or Other Natural Remedies"--Ed.)
Dr. Rand is assistant clinical professor in the division of general internal medicine at University of California, San Francisco.
References
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