An Appeal to Fellow Scientists and Colleagues – True Alternatives to Conventional Drugs are Needed!
You receive this document because of one or more of the following:
- You hold a key position in government, industry or academia who can make a difference if you want to;
- You are an authority on matters relating to herbs and science;
- You subscribed to, or received, my newsletter (Leung’s Chinese Herb News; ISSN# 1523-5017) while it was being published between 1996 and 2004; or
- You are my colleague, associate, or friend whom I respect.
The next page consists of my comments on a New York Times article on ‘gingko biloba’ research. I have decided to send them to you because I believe there is a better chance you can help rectify the issues regarding herbal product identity and quality than others. These comments also apply to most other herbs in the ‘alternative’ field.
Also attached is an article I had been invited to write, slated to be published in February by one of those new online journals by the OMICS group, but has not yet been published. Instead, it has been giving me one excuse or another, because I refused to pay a $900 publication fee that it had promised to waive when it solicited my manuscript. I have given the publisher the date of withdrawal of my paper as May 1, 2013. So, here it is. I believe my article is relevant to what I have been saying during the past 10 plus years about our failure to provide consumers with a true alternative to conventional modern drugs in the form of herbal supplements/medicines. Instead, what we are providing them are not true herbal products as traditionally used and documented. These so-called ‘alternative’ supplements or medicines are mostly chemical entities that are not much different than conventional pharmaceuticals or nutritional chemicals (e.g., vitamins & amino acids) except that they also contain unknown chemicals with no long-term safe-use tradition as the herbs from which they are derived. Their only connection to true alternative herbal medicines is that these herbs are used as raw materials for their isolation. Once these chemicals are identified or isolated, they are afforded the full treatment of modern drug protocol. Thus, without any historical connection to the traditional herbs from which these ‘alternative’ supplements/medicines are derived, how alternative can they be?
The problem is not just research on ginkgo biloba, ginseng, or a common item like coffee. It is a fundamental flaw in our research approach to natural products. So far, there is only one basic approach that applies to conventional drugs (single-chemical entities) without problems. But it has failed miserably when applied to complex multicomponent botanicals (especially traditional herbs), unless you only use the latter as raw materials from which to extract pure chemicals and develop them into drugs. Then the vicious cycle repeats and none of the alternative options is utilized. This is exactly what has been happening over the past several decades, with the alternative options being increasing pushed aside.
Despite many of you are aware of the issues, not much has been done on the R&D end, except that NCCAM several years back started to restrict funding of herb research projects to those that had sufficiently clear definition of their proposed test materials to meet the criteria and approval of expert reviewers who had the training and knowledge to make such decisions. [I don’t remember the exact wording.] Yet most of these experts are trained in pharmaceutical research technology as many of us, not paying attention to the fact that herbal materials cannot be treated as pure chemicals by simply assigning specific chemical(s) to a complex material and analyzing for them. Such a selected chemical often does not have the effects traditionally known and documented for its parent herb. For example, “caffeine” or “chlorogenic acid” is not coffee the bean, nor are ginsenosides equivalent to American ginseng or Asian ginseng with the latter’s effects.
On the commercial product end, my compliments to colleagues at the FDA for finally moving in the right direction to enforce clearer and more meaningful identification and definition of herbal materials, using an approach suitable for multicomponent materials, especially requiring companies to show more than the usual marker compounds with more practical and comprehensive techniques such as HPTLC. This technique can readily detect adulterants (both drugs & phytochemicals) or missing components as long as at least 2 solvent systems are used to separate nonpolar to polar compounds. After all, with current GMP regulations being promulgated, how good are they if the multicomponent herbal material is not at least defined to the point that it can reasonably be reproduced with consistency.
Al
Albert Y. Leung, Ph.D.
05152013
“New Doubts about Ginkgo Biloba” by Roni Caryn Rabin (NYTimes 4/29/2013)
Comments by Albert Y. Leung, Ph.D.
Most of my esteemed fellow scientists and colleagues seem to have missed the point. The issue here (as with all other herbal supplements) is not humans versus animals or the dosage but rather, the fundamental basics of good scientific practice. It is a basic issue of single-chemical drugs versus multicomponent natural products. If we are using the wrong (or ambiguous) test material, nothing else matters, because the results generated cannot be reproduced anyway. Drs. Varro (Tip) Tyler and Christine Swanson as well as I had written about these 10 to 12 years ago.
For the identification and quality control of single-chemical drugs, there are already well established analytical protocols. Not so for herbal supplements! Yet so far we still have barely started to deal with it, largely due to complacency, inertia and/or marketing pressure. Without clearly identifying a test material such as ginkgo extract (e.g., 1, 2, 3, or more of the ginkgolides, flavonoids & ginkgolic acids along with numerous others also potentially present but not analyzed), how can we expect to get any meaningful or reproducible results?
“Ginkgo Biloba” is not a single-chemical entity. We cannot apply current analytical protocols meant for pharmaceuticals to multi-component herbal products and expect to get consistent results. At present, the only appropriate and practical means to reasonably define a multi-component herbal supplement is to use multiple techniques that can give us a better picture of the material other than some arbitrary or irrelevant marker compound(s), disregarding other components (good or bad) that may also be present. These combination techniques (Phyto-True™ that includes TLC/HPTLC) are now available, which are practical, relatively inexpensive, and have the capability and versatility of showing better profiles (fingerprints) of broader spectra of phytochemicals than any other more expensive and advanced techniques; and they have already been routinely used for over 10 years. They not only can show what is claimed to be present in commercial herbal supplements but also other components that are (and should also be) naturally present or absent (adulterations), encompassing a broad profile of compounds (nonpolar to polar), including the ones not currently being routinely analyzed in the quality control of herbal supplements whether or not specified by official compendia.
This issue is not unique to ginkgo biloba because its identity is not clearly defined to the point of reasonable reproducibility. For example, its active chemicals responsible for its total effects (good or bad) are not clearly known, as it contains different groups of chemicals, some of which contribute to its alleged effects. These groups include flavonoids and terpenoids, in roughly 24% and 6%, respectively. At present, there is no legal requirements for producers and manufacturers to identify (or at least show most of) the flavonoids and terpenoids present in the 24% and 6%, or what else is present in the remaining 70% of the extract(s) used in ginkgo products. Nor has there been any published comparison between these extracts and the original one on which early studies in Europe showed the desired pharmacologic effects that led to ginkgo biloba’s commercialization. In short, the ‘gingko biloba’ supplements on the market can differ widely, not just in strength, but also in identity as opposed tosingle-chemical drugs like aspirin that can be easily identified and quantified, as aspirin is aspirin in aspirin products – same identity, only different strengths. And since there is no one uniform extraction process used by all producers, the commercial ginkgo extracts used can be very different indeed in their chemical composition with numerous (to many) active chemicals not routinely being analyzed in their quality control, leaving a big gap in our knowledge of the identity, quality, efficacy and safety of these products.
Unless there is a basic change in the understanding and research approach among experts in industry, government and academia relating to multicomponent herbs/supplements (ginkgo biloba, ginseng or coffee) versus single-chemical drugs (quercetin, gingkolides, ginsenosides, or caffeine), these inconsistent, erratic results and hence controversy will continue, needlessly continuing to waste much of our country’s human and financial resources. Other comments and critiques of research results on ginkgo are premature without first more clearly and reasonably defining what constitutes the entity ‘ginkgo biloba’ extract – not just as currently specified (24%/6%), but what else is also present in the remaining 70%.
05/10/2013