Stockley’s Herbal Medicines Interactions, 2nd edition, by Elizabeth Williamson, Samuel Driver, and Karen Baxter. London, UK: Pharmaceutical Press; 2013. Hardcover, 512 pages. ISBN: 978-0857110268. $99.00.
The first edition of Stockley’s Herbal Medicines Interactions was published in 2009, and now, four years later, Pharmaceutical Press has issued a revised, expanded, and updated second edition. Inevitably, coming from the Stockley’s stable, the book’s approach is derived from their well-known Drug Interactions textbook — with consequent inbuilt limitations due to its pharmaceutical provenance and absence of botanically qualified co-authors. The original edition was reviewed in HerbalGram #87 by Francis Brinker, ND, and readers wholly unfamiliar with Stockley publications should refer to Dr. Brinker’s review, which summarizes the approach of the book and adds valuable commentary on its strengths and weaknesses that remain entirely relevant to the second edition. Indeed, in their preface to the new edition, the authors emphasize how it retains the structure, organization, and conceptual approach of the original. Here, I will focus more on the novel aspects of the second edition.
The page count has increased from 423 to 512 pages, primarily due to the addition of 40 new monographs. Two of these are actually nutritional agents — alpha-lipoic acid and “carnitine derivatives” — a continuation from the first edition’s incongruous inclusion of assorted nutritional dietary supplements among the herbs. For owners of the first edition, the addition of 38 new botanical monographs promises a significant increase in added value of the second edition over its predecessor. However, on closer inspection, 29 of the new herbs are listed as having “no interactions” at all, whilst several more document only one theoretical or clinically insignificant interaction each. In fact, the only new monograph of any substance is the one on kava (Piper methysticum, Piperaceae). Because such a large percentage of the new material actually contains no interactions data whatsoever, a purchaser updating their original edition would be justified in feeling some resentment at the lack of real informational value of the “new monographs.”
For the botanically trained reader, the rationale for including some of the new herbs seems curious. For example, does the addition of African potato (Hypoxis spp., Hypoxidaceae) imply a more inclusive ethnobotanical policy to the materia medica embraced by the text, or does it perhaps relate to the now bygone era of HIV/AIDS denialism in South Africa (since the only issue discussed is a clinically insignificant interaction between African potato and non-nucleotide reverse transcriptase inhibitors, a class of HIV medications)? Either way, African potato is hardly a common medicinal plant in Europe and North America, and despite the claim of “international relevance” made in the preface, several South African plants are the only representatives suggestive of a wider ethnobotanical approach.
There are also inconsistencies in the presentation of potential or theoretical interactions extrapolated from the known pharmacology of any given botanical. For example, among the new monographs are two antimuscarinic herbs in the Solanaceae family — Brugmansia spp. and henbane (Hyoscyamus niger) — and both are listed as having no known interactions. Apart from the fact that Brugmansia species rarely are used clinically compared to their cousin Datura stramonium (Solanaceae) — which is absent from the text — all of these plants are phytochemically dominated by the presence of the bioactive tropane alkaloids. It would therefore be relevant to at least discuss their potential interactivity with a variety of neurological and psychopharmaceutical drugs. Alternatively, since berberine has a separate entry from the berberine-containing herbs, and other secondary compounds such as “natural coumarins” [sic] also have their own monographs, it would have been consistent to have a similar entry for tropane alkaloids that exhibit clinically significant bioactivity. Many of the new herbs that have been added despite having no known interactions are reported as having a “bioflavonoid content,” and then the reader is referred to a general flavonoid monograph — presumably as a justification for including the “non-interactors” such as limeflower (Tilia spp., Malvaceae), raspberry (Rubus idaeus, Rosaceae) leaf, plantain (Plantago major, Plantaginaceae), and so on. This entirely begs the question of the actual effect of clinical exposure to any given flavonoid or combination of flavonoids in a given herb, extract, or formula, while many flavonoids are ubiquitous dietary ingredients. Such generic information lacks any real practical application.
In their preface to the second edition, the authors also state that there were substantial additions, revisions, and revalidations made to the existing monographs. A comprehensive evaluation of this claim for each herb is beyond the scope of this short review. However, since I have a clinical interest in and familiarity with interactions between herbs and oncological drugs, and because there has been recent discussion in the literature of a potentially important adverse interaction between green tea (Camellia sinensis, Theaceae) polyphenols and the proteasome inhibitor bortezomib (Velcade®), I used the tea monograph as a test case to check the authors’ claims about revision and revalidation of the monographs.
The monograph for “Tea” (which includes the isolated extracts of green tea polyphenols such as epigallocatechin gallate [EGCG]) actually lists no new interactions and critically omits any mention at all of the potential bortezomib-green tea interaction in which EGCG has been shown experimentally to irreversibly inactivate bortezomib,1 although preclinical data suggest this interaction may not be clinically significant at “normal” levels of green tea consumption.2 Equally concerning is that the only antineoplastic drug interaction mentioned is of a clinically insignificant effect on irinotecan (Camptosar®) metabolism. In fact, a PubMed search of the recent literature reveals a plethora of both adverse and beneficial interactions between green tea polyphenols and many anticancer drugs, including antitumor antibiotics, antimetabolites, alkylating agents, microtubule inhibitors, and small-molecule tyrosine kinase inhibitors. It is disconcerting to find such extensive omissions for a widely available and popular botanical, especially in relation to the oncology setting where patients and providers need to be well informed about potential herb-drug interactions.
Finally, the discussion in the front matter of the book of the different mechanisms underlying or causing interactions has not been updated and now represents very limited coverage of the topic. There is a wealth of relevant new molecular and pharmacogenomic data available on how drug-metabolizing enzymes are regulated by different nuclear receptors, as well as a detailed understanding of the way in which polymorphisms of enzymes and receptors influence individual variability of response. At the very least, this has a significant impact on both clinical study design for interactions research and on the evaluation of anecdotal interaction case reports. Meanwhile, the capacity of many herbal remedies to influence drug responses through broad physiological mechanisms, such as altering biliary secretion, renal diuresis, pH, protein binding, and so on, is not discussed at all.
It is difficult to avoid the conclusion that the second edition of this book fails to measure up to the claims of its authors that it provides substantive additional coverage and extensive revisions and updates to the first edition. As a reference text for clinicians lacking familiarity with herbs, the book presents some practical difficulties in ease of use due to inconsistent usage of botanical and pharmacopeial nomenclature. Admittedly, the authors offer a caveat on this point, but it would have been more helpful to provide an index of synonyms and botanical names at the front of the book. For example, a physician is unlikely to know that “ispaghula” is psyllium (P. ovata, Plantaginaceae), while there are separate entries for ribwort plantain (P. lanceolata) and plantain. Some of the common names used are not that common, such as karela for Momordica spp. (bitter gourd; Cucurbitaceae), and in some cases there are typographical errors that are confusing (for example, in the title on page 387, Asclepias tuberosa [Asclepiadaceae] is mistakenly listed as a synonym for the sugar cane-derived supplement policosanol).
In mitigation, the subject of herb-drug interactions is not a tidy topic. There is no single source of information or approach that provides definitive and authoritative coverage. While concerned clinicians might consider adding a copy of Stockley’s to their herb-drug-interactions library despite its flaws, owners of the first edition will find little benefit in this update.
—Jonathan Treasure, MNIMH, MCPP
- Golden EB, Lam PY, Kardosh A, et al. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood. 2009;113:5927-5937.
- Bannerman B, Xu L, Jones M, et al. Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother Pharmacol. 2011;68:1145-1154.