(CHINESE) HERB NEWS
Herbs in this issue:
A Note From Dr. Leung
Time flies! It has been 5 years since the first issue of this Newsletter was published in September 1996. Originally, one of my objectives was to offer my readers a glimpse of the vast field of herbal information existing in the Chinese literature. This has not changed. Also, my intention of pointing out some of the unethical practices and sheer ignorance in the Chinese herbal field in North America, including disinformation and misinformation, continues, though this has been extended to the dietary supplements and herbal products field in general. Since this Newsletter has gradually evolved from dealing with only Chinese herbs to other herbs and related issues, we have changed our title to Leung’s (Chinese) Herb News to reflect the no-longer-exclusive Chinese herb nature of this Newsletter.
During the past 5 years, much has happened in the herbal/dietary supplements business. Companies came and went, with some unscrupulous marketers among them. The herbal market
Dr. Leung is author of the Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics (Wiley-Interscience), which was published in 1980 and revised in 1996. He is also creator of PHYTOMED, a prototype computer database on Chinese herbal medicine developed under contract with the National Cancer Institute.
became really hot and then turned very cold. Some shrewd promoters made a bundle for themselves while their pharmaceutical clients and/or their employees and the public got burned. Their company stock values plummeted when they declared bankruptcy. This caused massive layoffs of employees and at the same time their stockholders lost everything, while the key executives exited with millions. When you think about it, this doesn’t seem to be anything new. It’s just that I saw this coming with one of these companies formed and run by a ‘wall-street’ type and I actually warned a couple of my colleagues who worked there about this a few years prior to its collapse and metamorphosis. On the one hand, a certain segment of the herbal industry has become quite knowledgeable in herbs, while others still continue to engage in spreading disinformation to promote dubious products, drawing continued flak from the conventional medical establishment and consumer groups. There is now talk of amending the DSHEA that has obviously been proven inadequate in handling herbal drugs (ephedrine, synephrine, huperzine A, ginsenosides, etc.) being sold as dietary supplements. All the above has been frequently treated in past issues of this Newsletter. In the current 5th-anniversary issue and the next, I want to reproduce some of the ‘hot’ topics treated in previous issues. If you were not one of the original subscribers, you will find that some of the current ‘hot’ issues had already been dealt with in this Newsletter 2 to 3 years earlier. Although I can’t take major credit in having brought these issues to the forefront, I hope I can at least claim to have a hand in doing so. The reason is that this Newsletter reaches many of the movers and shakers in the herbal medicine and dietary supplement field who hold key positions in industry, government, and academia, some of whom have given me encouragements to keep on trucking.
The following comments relating to standardization issues are reprinted from Issue 13 (March/ April 1998) of this Newsletter
“Standardization” – a Wolf in Sheep’s Clothing?
The danger of including treatment herbs and their contained chemicals as dietary supplements is that we are basically introducing new classes of drugs into our food supply, which do not have the documented safe-use history enjoyed by foods and herbal tonics. Even with tonics and certain foods, we may have a problem with their safety, now that widespread and arbitrary standardization is being actively promoted. This will allow chemical producers to use the reputation and safety of an herb to isolate specific chemicals (some in trace amounts) from it for their specific effects, which may have no relevance to the properties and safe uses of the original herb. I can see it happening already. It is a free-for-all! The herbal extraction industry and the chemical industry both will have a lot to gain. The losers are the consumers who expect wholesome natural products but instead will more and more have their choice limited to chemicals isolated out of context or downright synthetically produced. Instead of getting the benefits from a good wholesome extract of an herb/food they will increasingly get purer and purer chemicals isolated from it. The culprit is “standardization.” There are currently no standards in “standardization.” It is a truly Wild West situation in this area. For any given herb, each chemical and extract supplier has its own “standardized” extracts. The more commonly promoted Western herbs with their standards include: echinacea (4% phenols), valerian (0.8% valerenic acid), feverfew (0.2% parthenolide), kava (10-40% kavalactones), and St. John’s wort (0.3% hypericins). As the standardized chemicals are usually not the only active components (in fact, some may not even be active), they can only serve as markers for the extracts. In principle, it is supposed to be just that. However, in practice, it will not happen. Once a chemical or extraction company is used to the profits of marketing such highly concentrated chemical fractions, whether genuinely extracted or synthetically produced and added, there would be no incentive to go back to develop new assays to include the truly active components. And when toxic incidents or ineffectiveness occurs as a result of these highly purified chemicals, the herb will get blamed.
Bogus “Standardized” and “High-Strength” Extracts
The nature of an extract depends on what solvent(s) one uses. In an earlier issue of this newsletter (Issue 9, p. 2), I have already discussed the potential abuse by suppliers offering both traditional (based on strengths) and standardized extracts. By now, this practice is probably widespread.
If you are a manufacturer, it is important for you to know the solvents used for producing the extracts you receive from your suppliers, as it can explain a lot about whether the extract is genuine and how good it is.
There are two basic types of herbal extracts being used today in the manufacture of dietary supplements: those with fairly well established active constituents and those whose activities do not reside in a single chemical compound or group of compounds. The first includes such herbal extracts as ginkgo leaf (flavoneglycosides & terpenoids), hypericum (hypericins), kava (kavalactones), senna (sennosides), cascara bark (cascarosides), saw palmetto (lipids), milk thistle (silymarin), mahuang (ephedrine, pseudoephedrine, etc.), guarana (caffeine), etc., whose active principles are the ones mainly responsible for the intended effects of these herbs. The second type includes such extracts as echinacea (phenols, isobutylamides, polysaccharides), eleuthero (eleutherosides: phenylpropanoids, lignans, coumarins, triterpenoids, sterols; polysaccharides), danggui (ferulic acid, ligustilide, butylidene phthalide, polysaccharides), cured fo-ti (anthraquinones?, phosphatides?), astragalus root (triterpene glycosides, polysaccharides, flavonoids, free amino acids, phenolics, betaine, choline, folic acid, etc.), lycium fruit (polysaccharides, amino acids, betaine, b-carotene, etc.), and ginseng (ginsenosides, polysaccharides, sterols, choline, etc.). This group all has multiple active components, and no single one component can claim to represent the total activities of the herb. Yet one frequently comes across commercial standardized extracts of these herbs high in a particular chemical marker. The following are a few examples:
(1) Echinacea extract is widely sold standardized to >4% polyphenols, using chlorogenic acid as a standard. Do these extracts also contain the proportional amounts of polysaccharides and/or alkylamides from the original herb? If not, an unethical or greedy supplier must be adding this ubiquitous phytochemical to the extract simply to meet the assay. Who started promoting this marker/assay in the first place? Obviously not someone who knows both herbs and chemistry. And why have all those new experts/consultants in the industry kept quiet on such an elementary issue? And why do prominent industry analytical chemists still continue to develop and promote methods for analyzing phenolics in echinacea?! I would like to know if some company has been sneakily pushing a hidden agenda. If you have first-hand information on this, I would like to hear from you. I have been wrong before, and I won’t hesitate to admit it if I am proven wrong again.
(2) Here is another extract offered by certain companies – astragalus extract standardized to 10% amino acids and 0.5% of an isoflavone glycoside. Why these two, especially since they don’t even represent astragalus’ chemistry, nor its traditional properties? Polysaccharides and saponins or flavonoids are fine, but amino acids and a flavonoid? Come on! What is the hidden agenda? Both decoctions and alcoholic extracts, as well as astragalus powder itself, have exhibited the multifunctional effects traditionally attributed to astragalus. Their major active components have so far been found to include triterpene glycosides, polysaccharides, and flavonoids. There are many other chemical compounds also present, each has its own biological activity, and each in minor concentration, including individual flavonoids, amino acids, phenolic acids (including, yes, chlorogenic acid), trace minerals, choline, folic acid, and betaine. If you are interested in a specific chemical compound for its specific effect, and not in astragalus per se, do go ahead and isolate that chemical in high concentration and develop or use it as a new drug. However, if you want astragalus extracts for their well-known traditional properties and uses, you should use the extracts prepared according to traditional methods, with water and/or alcohol as the solvents. These extracts contain the full spectrum of components from the herb, not simply artificially high concentrations of amino acids or a particular trace flavonoid. The best way for manufacturers to control their quality is by TLC pattern coupled with a quantitative assay of one or two of their major active components (saponins, polysaccharides, flavonoids, or even chlorogenic acid, betaine, and amino acids). As long as the chemical pattern is consistent, the marker(s) can be any compound(s) present. This is the only way to avoid being sold extracts that are “formulated” to contain the arbitrary chemical, against which these extracts are “standardized;” these extracts may not contain the truly important and active components.
(3) There is a “strength contest” going on among certain extract suppliers. An increasing number of extracts of common traditional Chinese herbs is claiming unusually high strengths. Here are three that immediately caught my attention because they are obviously anything but genuine extracts: an astragalus powdered extract of 15:1 strength, Siberian ginseng (eleuthero) extracts of 28:1 and 35:1 strengths, and a fo-ti powdered extract of 12:1 strength. The astragalus extract is offered at $38/kg, the eleuthero extracts at $33/kg (28:1) and $38/kg (34:1), and the fo-ti extract at $60/kg. All these prices are considerably below the cost of raw materials. If these extracts were genuine, the companies who sell them must be charitable organizations disguised as extract suppliers! I have written about this type of problem in the herbal industry before (Issue 4, p.3 & Issue 9, p. 1). Let us analyze what these extracts possibly are. First of all, we can rule out that they are genuine total extracts prepared with traditional solvents (alcohol, water, or their mixtures). There are two possibilities that this kind of strength can be obtained. To refresh your memory regarding strengths of extracts: a 4:1 extract means 4 kg of crude herb, after exhaustive extraction followed by concentration, yield 1 kg of extract. The lesser amount being extracted from the herb, the higher the resulting strength. Thus, if only 1 kg is extracted from 100 kg of an herb, the extractives are very low (only 1%), but the strength of the resulting extract is very high (100:1). Normal genuine wholesome extracts don’t have this kind of strength. The only way such a high strength can be achieved is by using relatively non-polar solvents (hexane, isopropyl alcohol, petroleum ether, etc.) that are normally used for extracting specific chemicals or chemical fractions. Hence, if astragalus and eleuthero were extracted with isopropyl alcohol, you might end up with only 2.85% to 6.67% extractives, which would yield extracts of high strengths (35:1 to 15:1) as the ones being currently offered. Are these extracts good extracts? Certainly not, because they don’t contain the most important known active components! Since only such minor amounts of materials had been extracted from the herbs, what happened to the rest? Normally, when astragalus and eleuthero are extracted with water and/or alcohol, the yield of extractives is 10% to 33% (representing 10:1 to 3:1 in strength). After the isopropyl alcohol extraction, the remaining plant materials could be further extracted with water or alcohol (ethanol) to produce an extract that would still contain much of the polysaccharides, glycosides, betaine, and choline. What is missing in this partial extract is some of the less polar components. Under the current “Wild West” atmosphere, anything could happen with such an extract. Most likely it would be standardized against a marker and sold as such. In this manner, a single batch of herb could yield 2 mislabeled extracts – a “high-strength” extract and a “standardized” extract. There are just too many such opportunities to be “creative.” You can draw your own conclusions.
I have written about the difference between raw and cured fo-ti many times, in this Newsletter (Issue 3, p. 3; Issue 7, p.2) and elsewhere. It seems that one or two of my lay colleagues still haven’t got it straight, continuing to disseminate misinformation in popular herb magazines, treating fo-ti as they treat most Western herbs – simply as a plant species, with no regard to the importance of processing. It is this kind of misinformation that has probably led to the production and marketing of the fo-ti extract with the 12:1 strength. It is a water-soluble extract. But there is no indication as to what type of fo-ti (raw or cured) is used. Interestingly, the plant source is Brazil. Does that mean it is also a native of Brazil? If that is the case, the mystery may have been solved, because a cold water or hydro-alcoholic extraction (in typical Western tradition, based on misinformed scientific rationale) would not yield much of the extractives and thus could result in a high-strength extract. However, if this were supposed to be a Chinese herb grown in Brazil, the producer of the extract is totally misinformed. What is this cold extract used for, as a tonic or as a laxative? Was it prepared from raw root or from cured root? In either case, this extract is not an extract of the Chinese herb, fo-ti (heshouwu – Polygonum multiflorum), because traditional extraction would not yield such a high-strength extract. This is another typical case of misinformation leading to wrong products. Or could it be just a simple case of adulteration or dishonest marketing, with the marketers simply grabbing high numbers from thin air, believing the higher the number (in strength), the better the extract?
It is precisely this kind of abuse in extract strengths in the botanical industry that has led to the call for standardization. But can standardization solve the problem? Not if it is championed by people with the same self-interest as the original people in the industry that caused the problems in the first place. I personally think the only way to correct this abuse is for sincere quality-conscious manufacturers to work only with extract companies that are open and share information with them, not with those who do their extraction under secrecy or “proprietary” cover. Lastly, and most importantly, manufacturers and marketers interested in producing genuine unadulterated products need to further educate themselves on how commercial herbal extracts are prepared and quality controlled, by meaningful methods, not simply relying on HPLC and other sophisticated techniques that only give a limited view of the total picture. The bottom line: Herbal extracts normally contain multiple active ingredients. Sophisticated chemical analysis (e.g., HPLC) must be combined with other basic methods (e.g., TLC and colorimetry) to assure that high-quality genuine extracts are used.
Self-defense for Honest Manufacturers
For honest manufacturers of genuine herbal products, additional analyses can be performed to assure that the standardized extracts they obtain from their suppliers are genuine and of decent quality. High-performance liquid chromatography (HPLC) of single chemicals (or chemical groups) does not determine the quality of the extract. It only shows you that the particular chemicals (markers) are present at a predetermined level. Often, in order to reach artificially high preset levels of a marker, which does not need to be an active component (e.g., chlorogenic acid for echinacea), the supplier either has to add that chemical to the extract or selectively extract it in such a way that other active components are not extracted. For example, “ginseng extracts” with artificially high ginsenoside levels (>20%) cannot be good genuine ginseng extracts because they would be deficient in other active components, especially polysaccharides. And ginseng “extracts” containing excessive amounts of ginsenosides (e.g., 80% or 90%) should not be allowed to be labeled as ginseng extracts at all, but rather only as “ginsenosides” or “ginsenoside concentrates” because they contain little or no other active components from ginseng. Furthermore, I wouldn’t be surprised that ginsenosides from Gynostemma pentaphyllum (a much cheaper gourd plant) are now added to these extracts to meet the “standards.” In order to assure that a standardized extract indeed is genuine, which does not contain an artificially high amount of the standardized chemical, a manufacturer should use alternative methods to measure the presence of the other active components. A simple method is by thin-layer chromatography (TLC) which can give you a consistent pattern of the naturally occurring chemicals in a genuine herbal extract. A reference herbal extract can be prepared, in most cases, by using a methanol or a 50% ethanol extract of the authenticated herb. If the standardized commercial extract contains the required amount of the standardized chemical but does not show the usual chemical pattern of the reference extract, you don’t have a genuine extract. You may as well buy that chemical, at a much cheaper price, if that is what you want.
It has been three-and-a-half years since the above was published. I am pleased to report that the herbal industry (American Herbal Products Association) is now producing a white paper on standardization which will address most of the problems and issues described above. Although this is a giant step towards product definition and product quality, the ultimate challenge and goal for the industry is to forgo some profits and to put the words on paper into practice.
Varro E. (Tip) Tyler, Ph.D. (1926-2001)
A giant in our field (pharmacognosy, phytochemistry, phytomedicine, etc.) passed away last August 22nd. He is probably best known to the general public for his popular book titled The Honest Herbal. He was one of my most admired true experts in the modern phytomedicine field. A gentleman and a gentle man, Tip was one of the few scientists with integrity who spoke his mind and was not corrupted by commercial pursuits of him (not by him). He and I had our differences in opinion, especially regarding the relationship between tradition and science, but we respected each other’s views. Nevertheless, on the lack of precise definition of herbal medicines/supplements for scientific research and clinical trials, we held the same view. While I published my “Criteria for evaluating research on herbs and other natural products” in this Newsletter only a couple of months after I had written it, Tip published his “Product definition deficiencies in clinical studies of herbal medicines” in a peer-reviewed journal a year after.1,2 In either case, we both spoke our mind.
Although I can’t claim, like some others after his death, that Tip and I were close personal friends, we were nevertheless friends. At an American Society of Pharmacognosy meeting held in Tunica, Mississippi at the end of April of 1999, I found out he and his wife liked Chinese green tea, especially the Dragon Well brand, which is also my favorite brand. So, whenever I returned from a trip to China, I started sending him Dragon Well out of my deep respect for him. Always a gentleman who didn’t want to take advantage of anyone, he would send me, in return, copies of his newest books. I ended up owning duplicate copies of his works which I placed in different locations where I work. My close friends and colleagues still joke about how I was ‘taking advantage of’ Tip by an uneven exchange of gifts. We do so miss him!
(1) Leung’s Chinese Herb News, Issue 19, pp. 2-3 (1999); (2) Tyler, V.E., Scientific Review of Alt. Med. 4(2): 17-21(2000).