(CHINESE) HERB NEWS
Topics in This Issue:
Abuse of DSHEA
Abuse of standardization
A Note From Dr. Leung
Since the passage of the Dietary Supplement Health and Education Act (DSHEA) in October 1994, the herbal business has literally exploded, and the business climate is equivalent to what amounts to a Wild West atmosphere. The almighty American marketing has taken over. The public is bombarded with terms like “nutraceutical,” “phytonutrients,” “phytochemicals,” “phytopharmaceuticals,” “thermogenics,” “standardization,” etc., giving the impression that these are scientific breakthroughs, which are somehow highly desirable. But in fact they are nothing but fancy terms to describe nutrients, chemicals, drugs, or concepts. During the past two years, “experts” and “quality” companies seem to materialize from nowhere, promoting their products with shameless vigor, disguising their efforts in “consumer education” or “scientific information” and “technical seminars.” Typically, publications and events are sponsored by companies with a specific agenda and involve the same groups of “experts” in diverse areas whose loyalty has all been spoken for or bought.
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.
Promotion and marketing is one thing, but promoting and marketing products that pose a danger to consumer health is downright irresponsible and often unethical, even though it may be perfectly legal. I am talking about marketing products like ephedrine (in the form of mahuang) as an appetite suppressant or an “energy” booster (due to its central stimulant effect) while promoting it as a daily supplement. The fact is that mahuang, in its entire 2,000 plus years of documented use history, has never been used daily to supplement one’s diet. Rather, it has always been used to treat specific conditions (colds, asthma, etc.) and for short periods of time only. There is nothing wrong if it were promoted and sold as a medicine. But to sell mahuang or ephedrine products as if they were food products in the same vein as vitamins and minerals, is irresponsible. The problem is that there is such a huge market for weight-reducing as well as “energy” (something-to-get-high) products. And ephedrine foots both bills. After several well-publicized deaths due to mahuang products, the rush has been on to find substitutes. There are always fast-buck artists waiting in the wings using their imagination and marketing skills to capitalize on any obscure information. One of these people must have learned that tangerine peel or related products contain phenethylamine derivatives very closely related in structures and pharmacological activities to ephedrine and amphetamine. It doesn’t matter to these people if the concentrations of these biogenic amines in the herb are only in trace amounts. What matters to them is that the herb contains these ephedrine-like chemicals at all, because, now, this herb can serve as a vehicle and excuse to carry these adrenergic amines in high concentrations to serve as central stimulants, appetite suppressants, or fat-burners (thermogenics) in commercial “herbal” products, sold as dietary supplements. And I would not be surprised if extracts of this herb were simply artificial blends of ephedrine or amphetamine analogs, including synephrine, tyramine, N-methyltyramine, hordenine, and octopamine. During the past year, especially in recent months, there has been heavy promotion of precisely one such extract, supposedly from the well-known Chinese herb, zhishi (immature fruit of Citrus aurantium L. or bitter orange, that contains minor amounts of some of these adrenergic amines) to replace mahuang extracts. These zhishi extracts contain up to 8% synephrine. One recently formed company actually promotes an extract that contains a total of 6% of a blend of above alkaloids. It claims that this blend is proprietary and is derived from specially harvested and extracted fruits of the bitter orange, which works as well as ephedrine in burning fat, but without the undesirable central stimulant and cardiovascular effects of ephedrine. I have serious doubts about that. But let’s see some clinical results or use data! Also, an accompanying booklet by a naturopathic doctor claims that zhishi has been used for 2,000 years in China with no adverse side effects. I agree with its long-use history, but to say that zhishi has no side effects is pure fiction. On the contrary, the contraindications or cautions for zhishi have been well documented, in classic herbals, as well as in the current Chinese Pharmacopoeia: pregnant women and persons with weak constitution are advised to use it with caution. Who are more likely to have a weak constitution than obese people or people who frequently use drugs to get high? What a product to promote to them! The fact is that these amines are no better than ephedrine in their potential danger to the public. Also, how do we know that these are not simply a bunch of synthetic amphetamine-type compounds mixed in with a token plant extract? The marketers seem to have preplanned it all, because like someone invoking the Fifth, they claim their extract is proprietary, hence they don’t have to show us anything, and the average consumer would never know. For your information, the total alkaloid content in Citrus aurantium products ranges only from 0.05% to 0.41%. A total extraction normally will yield a minor amount of the alkaloids, a fraction of what is present in the zhishi extracts being offered to manufacturers.
The above is just one example of potential abuse of DSHEA by certain marketers. Totally new drugs isolated from “herbs” can be legally introduced to the public as dietary supplements. With increasingly powerful analytical techniques, trace chemicals can be found in an herb, isolated, concentrated, standardized, and marketed as herbal supplements just as the amphetamine-like compounds in zhishi, even though these chemicals have absolutely no relevance to the nature and uses of the herb. Due to greed, certain herbal companies have taken the drug route – marketing isolated or concentrated specific chemicals from herbs as dietary supplements with no regard to the their traditional practice.
Now that “standardization” is aggressively being promoted by chemical companies or certain extraction companies, I foresee much more abuse in the natural products field in the years ahead, unless manufacturers and consumers are alerted to the hidden agenda of the current push towards “standardizing” herbal extracts against specific chemicals.
What is an Herbal Supplement?
One of the major reasons behind the passage of DSHEA is that consumers wanted more natural products for their health. They didn’t want to have more new chemical drugs whose long-term safety is still unknown. Chemicals like ephedrine, and other amphetamine-like compounds, whether isolated from nature or synthesized, are not equivalent to the herbs from which they are derived. They are drugs and should be considered and regulated as such, and not as dietary or herbal supplements! Our current law does not distinguish herbs that are used solely to treat illnesses from others that have traditionally been used as foods or tonics. Both can legally be sold as dietary supplements. The former usually have toxic side effects and are meant only for short-term use, while the latter have hundreds or thousands of years of documented safe-use history and have traditionally been used as supplements to our diet. Hence the latter are true herbal supplements while the former are not. The former includes mahuang, ephedrine, N-methyltyramine, synephrine, feverfew, and St. John’s wort; the latter includes tea, ginseng, watercress, licorice, hawthorn, ginger, Job’s tear, lycium, and astragalus.
“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.
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.
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.