Issue 13 - October 2003

Addressing patient concerns
A close look at herbal product quality
By Kerry Bone

Herbal supplements can be a natural compliment to your practice, but incorporating the best-quality products is essential if you want to achieve desired results.

When a patient asks, “What’s the difference between the herbal supplements you carry and those I can get at the corner store or through the Internet?” a good answer is, “Quality.”

Since herbs were once living organisms, they pose some unique manufacturing quality-control challenges since they can be misidentified, can come with an unwanted history (such as contamination with heavy metals) vary from harvest to harvest and batch to batch.

In addition to these variables, various manufacturing procedures can either preserve or damage the delicate chemical complexity of an herbal extract.

Probably the most commonly documented reason for toxic or serious adverse reactions to herbal products is the presence of adulterants. In this context the term “adulterant” can be defined as the presence — intentional or unintentional — of undeclared ingredients that impact adversely on the safety of the product.

Adulteration may be due to:

• The unintentional or intentional substitution of one or more herbal ingredients with toxic species;

• The intentional addition of a conventional chemical drug, either of natural or synthetic origin; or

• Environmental contamination of the herb with a chemical or pathogen.

These problems can generally be overcome by responsible manufacturing, comprehensive and stringent testing and — above all — a commitment to pharmaceutical level good manufacturing practice (GMP).

Good manufacturing practice — a specialized system of quality assurance which is extremely exacting and comprehensive at the pharmaceutical level — is legally required for the manufacture of herbal products in many countries, such as Australia, Japan, Canada and Germany. Eventually, some level of pharmaceutical GMP will be required for dietary supplements manufactured in the United States.

However, it must be stressed that GMP is only a code of practice. A manufacturer’s level of compliance with GMP must be high, in order to avoid some of the pitfalls described below and they must have an expert knowledge of the specific quality issues that apply to herbal products.

Some of the more common types of noncompliance issues that affect quality include:

• Toxic substitutions. The most infamous and tragic example, is commonly referred to (perhaps incorrectly) as Chinese herbs nephropathy (CHN).

In Belgium, a group of medical doctors running a slimming program decided to include herbs in their treatment. One of the herbs they wished to include was Stephania tetrandra, but many patients actually received Aristolochia fangchi which contains aristolochic acid.1, 2 This substitution is relatively common and has been attributed to the herbs having the same Pin Yin name: Fang Ji.3

However, the result of the substitution in this product was that many women developed renal failure and urothelial carcinoma.4

Herb substitution with toxic consequences has also occurred in the western world. One that is relatively common is the substitution of the hepatotoxic herb germander (Teucrium species) for skullcap (Scutellaria lateriflora). One case of hepatotoxicity in the United Kingdom which was supposedly associated with skullcap was verified to have resulted from the intake of the substitute herb Teucrium canadense (which has the common name pink skullcap).5

• Synthetic drug contamination. Adulteration of herbal products with synthetic drugs is also a relevant issue. The most cautionary tale is that of PC-SPES. PC-SPES was an herbal formulation specifically targeted at the treatment of prostate cancer (hence PC), developed and patented in the early1990s by a research chemist.6 It contained seven Chinese herbs and one American herb (saw palmetto: Serenoa repens).

In February 2002 the FDA alerted consumers to stop taking PC-SPES because the California Department of Health Services had detected the presence of warfarin. Another product called SPES from the same corporation had been found to contain the anti-anxiety drug alprazolam.7 The manufacturer undertook a voluntary recall and PC-SPES was subsequently withdrawn from the market.

• Intentional substitutions. Golden seal is a very expensive and endangered herb, so a temptation exists to substitute it with other, less expensive species. A recent survey of eight golden seal root samples and two products in the United States found that neither of the products contained hydrastine (the characteristic marker phytochemical of golden seal) and only five of the eight root samples.8 Hence, of the 10 “golden seal” products or samples, only five were authentic.

• False labeling. Many more subtle quality issues can impact on the safety or efficacy of an herbal product. To some authorities, standardized extracts are considered to be a significant development in the evolution of high quality herbal products. However, many products sold as standardized extracts do not comply with this lofty goal because they simply do not contain the claimed level(s) of marker compound(s).

This tends to make a mockery of the concept and mitigates against the unquestioning acceptance of a product as high quality because it is “standardized”. The consumer is left confused and hoodwinked because they are unable to differentiate between products that meet their label claim and those that do not.

Several studies have been published, particularly in the United States, which have analyzed herbal products on the market and compared the findings against the levels stated on the label.

St. John’s wort, a popular herb, has received particular attention. Eight commercially available St. John’s wort products were assayed by a spectrophotometric method and found to contain hypericin concentrations that varied from 47 percent to 165 percent of the label claim.9

The Boston Globe sponsored a study of seven St. John’s wort products (January 10, 2000 edition). Six products claimed to contain 0.3 percent hypericin on their label, but only one did. Two products contained only 0.25 percent and one considerably less.

• Variations from same herb. Products supposedly made from the same herb can exhibit tremendous variations. For example, a recent U.S. study of 59 Echinacea-only products purchased in the Denver, Colo. area in 2000 found that 6 (10 percent) contained no measurable amount of Echinacea phytochemicals.10

The Echinacea species (E. angustifolia, E. pallida or E. purpurea) found in each product was consistent with the label claim in only 31 (52 percent) of the samples. Of the 21 products that were labeled as being standardized, only 9 (43 percent) met the quality standard designated on the label. In addition, the products labeled as standardized were not significantly more likely to contain the correct (labeled) species than those that were not.

It might be argued that the tests the scientists did were not valid or they made a mistake with their assays. But this argument does not carry much weight when we find that overseas studies have delivered a similar scorecard for Echinacea. For example, a survey of Echinacea products on the German market found wide variations in levels of tested phytochemical components.11 And even more disturbingly, large differences in quality were found between different batches of the same product.

Because of the complexities of the quality issues with herbs, consumers often unknowingly select products that will not only not deliver the required results, they may harm their health. It is the duty of healthcare professionals to guide their patients to select the highest quality, most efficacious products.

Kerry Bone, BSc (Hons), Dip Phyto, FNIMH, FNHAA, MCPP, was an experienced research and industrial chemist before studying herbal medicine full-time in the United Kingdom, where he graduated and joined the National Institute of Medical Herbalists. He is a practising herbalist and head of research and development at MediHerb and principal of the Australian College of Phytotherapy. He can be contacted at www.mediherb.com.

References
1 Vanherweghem JL, Depierreux M, Tielemans C et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 1993; 341: 387-391

2 Vanhaelen M, Vanhaelen-Fastre R, But P et al. Identification of aristolochic acid in Chinese herbs Lancet 1994; 343: 174

3 Chen JK. Nephropathy associated with the use of Aristolochia. HerbalGram 2000; 48: 44-45

4 Cosyns JP, Jadoul M, Squifflet JP et al. Urothelial lesions in Chinese-herb nephropathy. Am J Kidney Dis 1999; 33(6): 1011-1017

5 De Smet PAGM. Health risks of herbal remedies. Drug Safety 1995; 13(2): 81-93

6 Ochs R. Going to bat for prostate cancer herbs. Newsday.com October 8, 2002. Available online: Accessed October 10, 2002.

7 Reuters Health. Prostate herbals contain prescription drugs: FDA. February 8, 2002. Available online: Accessed February 14, 2002.

8 Govindan M, Govindan G. A convenient method for the determination of the quality of goldenseal. Fitoterapia 2000; 71: 232-235

9 Constantine GH, Karchesy J. Variations in Hypericin concentrations in Hypericum perforatum L. and commercial products. Pharmaceutical Biology 1998; 36(5): 365-367

10 Gilroy CM, Steiner JF, Byers T, Shapiro H, Georgian W. Echinacea and truth in labeling. Arch Intern Med 2003; 163(6): 699-704

11 Osowski S, Rostock M, Bartsch H-H et al. [Pharmaceutical comparability of different therapeutic Echinacea preparations]. Forsch Komplementärmed Klass Naturheilkd 2000; 7(6): 294-300