International Geology Review, Vol. 49, 2007, p. 374–388. Copyright © 2007 by V. H. Winston & Son, Inc. All rights reserved. Review of the Lithium Isotope System as a Geochemical Tracer YAN-JIE TANG,1 HONG-FU ZHANG, AND JI-FENG YING State Key Laboratory of Lithospheric Evolution, Institute of Geology and Geophysics, Chinese Academy of Sciences,
Easternbotanicals.careturn to itm online CHECKING FOR POSSIBLE HERB-DRUG by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon The issue of herb-drug interactions looms large over the practice of herbal medicine. Up to now there have been very few incidents recorded of herb-drug interactions, but since the first such reports emerged a decade ago,a concern has been raised: that we know so little about herbs and their potential for interaction with drugs thatthese incidents could be just the "tip of the iceberg." Virtually all medical writers who review the literatureacknowledge the small number of reports, but conclude that the issue of herb-drug interactions is a serious onethat must be pursued. In a few instances, the interactions may have been responsible for severe consequences.
As described in a previous article (The interactions of herbs and drugs, 2000 START Manuscripts), the nature of herb-drug interactions is not a chemical interaction between a drug and an herb component to producesomething toxic. Instead, the interaction may involve having an herb component cause either an increase ordecrease in the amount of drug in the blood stream. A decrease in the amount of drug could occur by herbcomponents binding up the drug and preventing it from getting into the blood stream from the gastrointestinaltract, or by stimulating the production and activity of enzymes that degrade the drug and prepare it for eliminationfrom the body. An increase in the drug dosage could occur when an herb component aids absorption of the drug,or inhibits the enzymes that break down the drug and prepare it for elimination. A decrease in drug dosage byvirtue of an interaction could make the drug ineffective; an increase in drug dosage could make it reach levels thatproduce side effects. Alternatively, an herb might produce an effect that is contrary to the effect desired for thedrug, thereby reducing the drug effect; or, an herb might produce the same kind of effect as the drug and give anincrease in the drug effect (without increasing the amount of the drug).
Examples of concerns about herb-drug interactions that have been raised are that an herb might: increase or decrease the effect of a blood thinner such as Warfarin and lead to either a bleedingepisode or formation of a dangerous clot;decrease the effect of a blood pressure medication, leading to high blood pressure and a stroke;decrease the effect of an anti-infection agent, letting the infection get out of control; orincrease the effect of an anti-diabetes drug and plunge blood sugar to dangerously low levels.
Such responses can occur with drug-drug interactions and with food-drug interactions, so the finding of some instances of herb-drug interaction would not be surprising.
In China it is common for herbs to be combined with drugs. Their combination is sometimes incidental, but is often intentional and based on a prevalent favorable theory about using herbs and drugs. The general sense ofthe situation among Chinese doctors has been that herbs reduce the side effects of drugs and help them to performtheir function better; in turn, drugs will make an herb formula work more strongly and quickly. Together, herbsand drugs may produce a more desirable result than either taken alone. As an outcome of working within thisscenario, little attention has been paid to adverse herb-drug interactions.
The Chinese culture is one in which herbs were a dominant medical therapy during the 20th Century, and drugs were a relatively recent addition to the medical field. The situation was different in the West. Herbs hadbeen almost entirely replaced by drugs during the 20th Century, and were later reintroduced once drugs hadbecome a dominant feature of modern health care. In the West, the replacement of herbs by drugs took place overa period of many decades during which there was a prevailing attitude that drugs were more reliable than herbs.
The re-introduction of herbs brings with it suspicions and concerns about their unreliability and the lack ofadequate knowledge about them.
Today, doctors and pharmacists are provided courses and educational materials outlining potential problems with herbs that their patients may be using. The matter of herb-drug interactions involves a considerable amountof speculation about what might happen, based on knowledge-which is also quite limited-about drug-druginteractions and food-drug interactions. An example presentation to doctors is the following chart, produced in1999 and presented by Jerry Cott, a neuropsychopharmacologist: This chart first divides interaction concerns into broad subgroups, the main ones being related to pharmacodynamic interactions (mostly involved with herbs and drugs yielding similar effects or counteractingone another) and pharmacokinetics (such as changing the rate of absorption or elimination of a drug). There arealso two specialty groups: therapies involving obstetric/gynecological/hormonal matters and Chinese herbs. Verylittle information about actual interactions is imbedded in the presentation. There is mention of "xanthines" (e.g.,caffeine) under neuroendocrine, reflecting the concern that caffeine containing herbs (e.g., coffee and tea) couldcounteract the action of sedatives or produce excessive stimulation with stimulant drugs. Under the cardiovascularheading, there is mention of "glycoside-containing." The intended meaning is the specific class of cardiac-glycosides, as there are abundant glycosides that don't have significant cardiac effects (whereas, the cardiacglycosides are often quite potent, and can not only enforce or counteract the action of cardiac drugs but canthemselves cause cardiac problems if the dosage is large). Generally, the field of herbal medicine has been purgedof ingredients with cardiac glycosides; there remains a concern that one of the cardiac glycoside-containing herbswill find its way into a product by mistake. Under the heading hematological, there is mention of "coumarincontaining," which makes reference to the fact that some herbs contain coumarins which might act along withWarfarin, a coumadin (binary coumarin, much more potent than coumarins), or along with other blood thinners.
The table also makes passing mention of tannins (an herb component with several health benefits that can bind updrugs in the intestinal tract and make them less available). Under Chinese herbs, there is mention of three issues:the possible interaction of Minor Bupleurum Combination (Xiao Chaihu Tang; in Japan: Sho Saiko To) withinterferon in treatment of hepatitis to cause an immune response leading to lung damage; the possible interactionof salvia (danshen) and Warfarin, leading to excessive blood thinning; and the possible interaction of aristolochicacid and diuretic drugs (or others) to cause renal failure. Other than these few specific examples (all of whichhave been addressed by previous START articles), the chart outlines areas of concern, but not necessarily knownproblems.
Due to the paucity of actual reports of herb-drug interactions, lists of herb-drug interactions are usually padded with other information, such as reports of simple adverse reactions (not involving interactions). A tableprovided to pharmacists of this nature is shown here; it is by Pharmacists Planning Service, Inc.
HERBALS AND DRUG INTERACTIONS
Name of Herb
Some Common Uses
Possible Side Effects or Drug Interactions
External: used for muscle spasm External: potential for skin ulceration and blisteringand soreness with greater than 2 days of use. Internal: overuse may Internal: GI tract disorders cause severe hypothermia.
Echinacea boosts the immune Echinacea may cause inflammation of the liver ifsystem and helps fight colds and used with certain other medications, such as anabolicflu. Aids wound healing.
steroids, methotrexate or others.
Ephedra is also called Ma-Huang. Ephedra may interact with certain antidepressantIt is used in many over-the-counter medications or certain high blood pressurediet aids as an appetite suppressant. medications to cause dangerous elevation in bloodIt is also used for asthma or pressure or heart rate. It could cause death in certain Feverfew is used to ward offf Feverfew may increase bleeding, especially in for patients already taking certain anti-clotting arthritis, rheumatic disease and medications.
Garlic is used for lowering blood Garlic may increase bleeding, especially in patients cholesterol, triglyceride levels and already taking certain anti-clotting medications.
Ginger is used for reducing nausea, Ginger may increase bleeding, especially in patientsvomiting and vertigo already taking certain anti-clotting medications.
Ginkgo, also called ginkgo biloba,is used for increasing blood Ginkgo may increase bleeding, especially in patients circulation and oxygenation and for already taking certain anti-clotting medications.
improving memory and mental Ginseng may cause decreased effectiveness of certain Ginseng increases physical stamina anti-clotting medications. Persons using ginseng seeand mental concentration.
increased heart rate or high blood pressure. It maycause bleeding in women after menopause.
Goldenseal is used aas a mild Goldenseal may worsen swelling and/or high blood reduces pressure.
Kava-kava may increase the effects of certain anti- Kava-kava is used for nervousness, seizure medications and/or prolong the effects ofanxiety or restlessness; it is also a certain anesthetics. it can enhance the effects ofmuscle relaxant.
alcohol. It may increase the risk of suicide for people with certain types of depression.
Licorice is used for treating Certain licorice compounds may cause high blood stomach ulcers.
pressure, swelling or electrolyte imbalances.
Saw Palmetto is used for enlarged People using saw palmetto may see effects with otherprostate and urinary inflammations. hormone therapies.
St. John's Wort is used for mild to St. John's Wort may prolong the effect of certain moderate depression or anxiety and anesthetic agents.
St. John's Wort
Valerian is used as a mild sedative Valerian may increase the effects of certain anti-or sleep-aid. It is also a muscle seizure medications or prolong the effects of certainrelaxant.
References to what the herbs "may" do when combined with certain drug groups, (e.g., valerian may increase the effects of certain anti-seizure medications or prolong the effects of anesthetic agents) often refer topharmacology studies rather than actual clinical experience. For example, when one wishes to demonstrate thatvalerian, used traditionally for seizures and for analgesic effects, is likely to accomplish what has been claimed,laboratory animal studies are conducted. A standard procedure is to test the herb extract alone and to also test itwith drugs that cause the same effect. If the drug effect is increased or prolonged by the herb, it is implied that theherb has a similar effect, even though it may have a different mechanism. Thus, a study intended to demonstratethat a traditional claim for an herb is true turns out to be a source of worry about herb-drug interactions. However,the amount of herb used in the pharmacology experiments of this type is often far higher than the amountnormally used in clinical practice; the likelihood of herb-drug interactions occurring with normal use of the herbmay be minimal. Still, if one wishes to consider possible herb-drug interactions under a variety of scenarios,including excessive use of the herb and use of the herb by individuals who are more sensitive to the possibleinteraction, then such data must be included.
When published reports alluding to adverse herb reactions (but not interactions) and to pharmacology studies only are eliminated, one is left with few instances of reported herb-drug interactions. This is likely due to the lowdose of any individual herb component usually consumed and the simple absence of significant interaction at anyreasonable dose. To help illustrate the low frequency of clinical reports, the following abstract of a recentpublication will be informative: Drug-herb interaction among commonly used conventional medicines: a compendium for healthcare professionals.
Brazier NC, Levine MA.
Center for Evaluation of Medicines and McMaster University, Hamilton, Ontario, Canada.
In: American Journal of Therapeutics 2003; 10(3): 163-169.
The objective of the review was to consolidate the clinical and pharmacologic aspects of drug-herbinteractions to develop a compendium of information to provide prescribers with a measure of the riskof interactions, a description of the clinical consequences, and an assessment of the quality (i.e.,validity) of evidence. A variety of electronic databases and hand-searched references were used toidentify documentation of interactions between herbal products and drugs from the most commonlyused therapeutic classes. MEDLINE, Allied and Complementary Medicine Database, CINHAL,HealthSTAR, and EMBASE were searched from 1966 to the present. One hundred sixty-two citationswere identified. Only 22 citations met the inclusion criteria. Using a matrix of 165 possible drug-herbinteraction pairs (15 therapeutic drug classes by 11 herbal products), we identified 51 (31%)interactions discussed in the literature. Twenty-two of these 51 drug-herb pairs (43%) were supportedby randomized clinical trials, case-control studies, cohort studies, case series, or case studies. Theremaining interaction pairs reflected theoretic reasoning in the absence of clinical data. Mostinteractions were pharmacokinetic, with most actually or theoretically affecting the metabolism of theaffected product by way of the cytochrome P450 enzymes. In this review, Warfarin was the mostcommon drug and St. John's Wort was the most common herbal product reported in drug-herbinteractions. To create a comprehensive and valid list of herb-drug interactions would require asubstantial increase in research activities in this area. Improvements in the quality of methodologyused are also necessary.
Put simply, there were very few well-supported interactions detected: namely 22 that involved more than an individual report, or a simple pharmacologystudy, or a mere suggestion of potential interaction. Not surprisingly, the maindrug of concern is Warfarin, which displays substantial sensitivity tointeractions with foods and drugs, and which is very widely used (givingmore opportunities to note interactions), while the primary herb involved isSt. John's Wort, one with unique constituents (here is a chemical diagram ofhypericin, one of the components) known to affect the drug metabolizingenzymes (such as cytochrome P450, mentioned in the abstract). Use of St.
John's Wort declined dramatically after revelations that it could cause herb-drug interactions along with reports questioning its effectiveness.
In an earlier survey of similar nature (1), an intensive search of the literature and evaluation of reports of herb-drug interactions yielded the following: "108 cases of suspected interactions were found: 68.5% wereclassified as 'unable to be evaluated,' 13% as 'well-documented' and 18.5% as 'possible' interactions. Warfarinwas the most common drug (18 cases) and St. John's Wort the most common herb (54 cases) involved." Thus, 14cases were well-documented in this report published about 2 years earlier than the new report which found 22reasonably supported cases. The same drug and herb emerged as problematic. The rate of well-documented herb-drug interactions has been about 4 per year. No doubt, many more instances occurred and were not reported dueto their minor nature or uncertainty about the cause. Even so, the numbers should be kept in perspective: thenutriceutical industry estimated (1999) that about 45 million American adults use an herbal supplement at leastonce per year, and that 21 million adults are regular users of herbal remedies.
If a patient merely asks you to assure that the herbs you prescribe will not interact or be a problem with a drug
regimen being used at the same time, it is not possible to give such assurances. It is reasonable to relay the low
incidence of herb-drug interactions and to offer the methods of minimizing herb-drug interactions (e.g., not taking
the herbs and drugs at the same time; monitoring for potential interactions by maintaining routine testing, such as
blood coagulation tests given to users of Warfarin). However, a practitioner with internet access can also offer tocheck the most recent literature for reported herb-drug interactions. To do so will require an accurate listing of thedrugs being used.
Not all suspected cases of herb-drug interactions are published. However, in order for a suspected case to be published, it usually has to be formally written up by a doctor involved in the case, submitted to a journal, andreviewed by other doctors or researchers who are familiar with this subject area. Publication of a suspected casedoes not mean that the herb-drug interaction definitely occurred, but it does mean that the case was presented in amanner considered consistent with the modern standards for reporting such incidents. Current standards for manyjournal reports are inadequate, as indicated by the literature reviews.
All major medical journals, and many minor medical journals, have their articles listed-and often abstracted- in a huge database maintained by the National Center for Biotechnology Information (NCBI) of the NationalLibrary of Medicine (NLM), a division of the National Institutes of Health (NIH). The information is posted foreasy access on the internet, and this type of posting was one of the original uses of the internet (the earlierdesignation for the main part of the service was MedLine). The website where one accesses the information isnow called Entrez-PubMed and its access address is: This site (which can also be accessed through any search engine by typing in Entrez-PubMed and then following the first link) will provide a space into which the user may type the search terms, to yield a series ofabstract titles, with access to abstracts (or fuller reference information when abstracts are not available). Theprocedure for checking herb-drug interactions is to type in: [name of the drug], herb-drug interactions As an example, one can type in: Cyclosporin, herb-drug interactions Upon hitting the return button of the keyboard or clicking on the "go" icon on the screen, the search is rapidly completed. In the example cited here, there are three abstracts-two reviews and one specific article-allmentioning the same herb. The relevant abstract is this one: Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with theimmunosuppressant cyclosporin.
Mai I, Kruger H, Budde K, Johne A, Brockmoller J, Neumayer HH, Roots I.
Institute of Clinical Pharmacology, Charite University Medical Center, Humboldt University of Berlin,Germany.
International Journal of Clinical Pharmacology and Therapeutics 2000; 38(10: 500-502.
Contrary to common belief, over-the-counter herbal remedies may cause clinically relevant druginteractions. With the enclosed report we would like to alert other physicians that herbal extracts ofSaint John's Wort (Hypericum perforatum) may cause a sudden remarkable decrease of cyclosporintrough concentrations. A kidney transplantation patient treated with 75 mg bid doses of cyclosporin formany years experienced a sudden drop in her cyclosporin trough concentrations. This change was intemporal relationship to hypericum extract co-medication, and a re-challenge gave similar results….The potential clinical consequence of this pharmacokinetic herb-drug interaction is apparent, sincelow cyclosporin levels are associated with an increased risk of rejection after organ transplantation andare usually not suspected upon intake of plant products….
In most instances, when checking a drug for interactions, the page will display the following: No items found.
The small number of reports of specific herb-drug interactions is the reason for getting this as a typical result. Even if one enters: Warfarin, herb-drug interactions, one will find only a few responses: some review articles (including the two cited above), and a specific report, such as a case involving an apparentinteraction with boldo-fenugreek. The review articles indicate that interactions (increased blood thinning effect,with bleeding) are suspected or found for Warfarin with ginkgo (referring to the leaf), garlic, tang-kuei (danggui;sometimes spelled dong quai), and salvia (danshen). The potential for interactions has been confirmed withlaboratory studies. However, such interactions are dose dependent, and it remains unclear what dosage mightcause a problem. Since tang-kuei and salvia are widely used in Chinese medicine and used at widely varyingdosages (from a few milligrams of powder to several grams in decoction), it would be helpful to know what dosemight cause the effect; this remains undocumented. In a pharmacology study of salvia and Warfarin, the dose ofsalvia given to laboratory rats was 5 grams/kg body weight; this is a huge dosage. However, cases of patientsexperiencing bleeding when taking Warfarin and salvia have been informally reported.
If a report of interaction appears, it is important to check the abstract (when provided) for details to confirm that there is an actual report of herb-drug interaction (as with the St. John's Wort case above) rather than merely aconcern raised. Also, once an herb-drug interaction report is found in the first search, a new search should beperformed, specifying the herb and the drug in the search box (not just the drug name and general area of herb-drug interactions). For example, if one types in the entry-Warfarin, salvia-there are additional reviews, plus some reports on this specific interaction. One of the reviews expands the list of herbs that may reinforce theanticoagulant action of Warfarin to include ganoderma, papaw, ginseng, devil's claw, quinine, ginger, red clover,and horse chestnut. Two laboratory animal reports aimed at the study of Warfarin-salvia interactions appeared inthis search. No individual clinical reports of the interaction were among those listed, so it remains unclear whetherthe referenced cases of bleeding had been confirmed. If one tries the entry-cyclosporin, St. John'sWort-33 references replace the earlier search results of just 3. While many of the reports review the same cases, others are relevant to understanding the interaction, and still others mention additional cases of apparentinteractions. St. John's Wort has been blamed for several instances of transplant rejection due to its lowering ofcyclosporin concentrations.
There are more sophisticated searches that can be performed by listing more key words to try and capture more references on the first search. However, an easy method of pursuing the subject further is to click on thewords "related articles" posted next to each abstract title.
ADVICE TO PATIENTS
Once a search has been conducted, the following can be conveyed to patients:
1. A search was carried out, and no herb-drug interactions were found; or (if reports found), a search was conducted and a report about potential for herb-drug interactions was found; therefore, the herbsincluded in that report won't be included in your formulas (or won't be included above a certain smalllevel).
2. Absence of a report in the literature doesn't guarantee that there is no possibility of an herb-drug interaction. Therefore, we should continue to monitor your overall health and the conditions treated bythe drugs, and you should continue all scheduled blood tests that might help confirm that there havebeen no problems that might be attributed to herb-drug interactions (e.g., weekly blood coagulationtests, daily monitoring of blood sugar or blood pressure).
3. In China, it is routine practice to combine herbs and drugs to get the best therapy. Therefore, the prescribing of herbs as an adjunct to your drug therapy is consistent with practice there. We arefollowing a standard method, but there is little or no information on the specific details (i.e.,combining these specific drugs with these specific herbs). Therefore, we will continue the use of anherb formula only so long as it appears to be beneficial to do so, minimizing any unknown risks.
4. The herb that has been reported most frequently to cause interactions is St. John's Wort. You are advised not to use that herb while using other drug therapies. The drug that has been most frequentlyreported to interact with herbs is Warfarin (coumadin). You are advised to maintain weekly blood coagulation tests to assure that the effects of Warfarin remain in the proper range and to change alldietary and herbal regimens gradually. The issues most frequently raised about herb-drug interactionsare herbs potentiating an anticoagulant therapy or drug that has antiplatelet activity (e.g., aspirin usedfor pain) and herbs counteracting immunosuppressive therapy. Therefore, these will be the main focusof adjustment to any herb prescription provided.
It is not advisable to give firm assurances that there can be no problem, but it is also not advisable to overstate the concerns. Most doctors will be satisfied to know that the drugs they have prescribed to their patienthave been checked for herb-drug interactions by the herb prescriber. A good perspective has been offered in arecent abstract from an article about herb-drug interactions with cardiac drugs: The prevalence of herb-drug interactions has been exaggerated. Nonetheless, some herbs, includinggarlic, ginkgo, ginseng, and St. John's Wort, can have a significant influence on concurrentlyadministered drugs. Herbal medicines may mimic, decrease, or increase the action of prescribed drugs.
This can be especially important for drugs with narrow therapeutic windows and in sensitive patientpopulations such as older adults, the chronically ill, and those with compromised immune systems The herbs mentioned in this abstract are those suspected of interacting with Warfarin, a drug with a narrow therapeutic window often used by sensitive patient populations. These herbs are often provided in single-herbproducts where they are at a relatively large dosage. A small amount of ginseng-an herb that has not been clearlyimplicated in the Warfarin interactions-is unlikely to cause interactions.
APPENDIX: The Problem of Blood Thinning
As noted above, the drug with greatest concern for interactions is Warfarin, but there is also a concern for
interaction with any blood-thinning drug. The following report abstract describes a survey at one institution that
found some potential interactions between herbs and drugs, where blood thinning was the main issue:
Potential interactions between herbal medicines and conventional drug therapies used by olderadults attending a memory clinic.
Dergal JM, et al., Applied Research Unit, Baycrest Centre for Geriatric Care, TorontoIn: Drugs and Aging. 2002;19(11):879-886.
OBJECTIVE: Herbal medicines and conventional drug therapies are often taken in combination. Theobjective of our study was to identify the range of natural health products and conventional drugtherapies used by older adults (aged 65 years and over) attending a memory clinic, and to specificallyevaluate the frequency of potential interactions between herbal medicines and conventional drugtherapies. DESIGN: We interviewed consecutive patients attending the Memory Disorders Clinic atthe Baycrest Centre for Geriatric Care, a University of Toronto teaching hospital, between 4 July and15 August 2000. Patients were asked to bring to their appointment all natural health products (i.e.,herbal medicines, vitamins and minerals) and conventional drug therapies (i.e., prescription and over-the-counter) they were currently using. We collected information on current and previously-usednatural health products and current conventional drug therapies. Patients were classified as having thepotential for an interaction if they were using a current herbal medicine in combination with aconventional drug therapy and the interaction had been reported previously in the medical literature.
PARTICIPANTS: We interviewed 195 consecutive patients attending the Memory Disorders Clinic atthe Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada. RESULTS: Of the 195 patients inour sample, 33 (17%) were 'current users', 19 (10%) were "past users," and 143 (73%) were "neverusers" of herbal medicines. Among the 52 patients who were "current or past users," the mostfrequently used herbal medicines were ginkgo (Ginkgo biloba) [39 users], garlic (n = 10), glucosaminesulphate (n = 9), and echinacea (n = 8). Among the 33 patients who were current users, the mostcommonly-used herbal medicines were ginkgo (n = 22), glucosamine sulphate (n = 8) and garlic (n =6). Among the 33 current users, we identified 11 potential herb-drug interactions in nine patients. The11 herb-drug interactions we identified were between ginkgo and aspirin [n = 8], ginkgo andtrazodone (n = 1), ginseng and amlodipine (n = 1), and valerian and lorazepam (n = 1).
CONCLUSIONS: Herbal medicines are widely used. Almost one-third of current users of herbalmedicines were at risk of a herb-drug interaction. The most common potential herb-drug interactionwas between ginkgo and aspirin. This finding has important potential implications because both ofthese products are regularly used by older people. Physicians and other healthcare providers should beaware of potential herb-drug interactions and should monitor and inform their patients accordingly.
This report would seem to give a shocking result: that nearly one-third of herb users (at least, among this elderly population) were at risk for herb-drug interactions. Because these people were going to a memory clinicand because modern medicine has limited impact on memory disorders, many patients were taking ginkgo, whichis claimed to be a memory enhancing herb.
A brief literature search turned up no formal journal reports giving details of interactions between aspirin and ginkgo, but there was a review article-Herbal medication: potential for adverse interactions with analgesic drugs(2)-which indicated that: Non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interactwith herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry,dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin(chamomile, motherwort, horse chestnut, fenugreek and red clover) and with tamarind, enhancing therisk of bleeding. Acetaminophen may also interact with ginkgo and possibly with at least some of theabove herbs to increase the risk of bleeding." A mild antiplatelet activity for ginkgo has been proposed as one of its mechanisms for aiding circulation to the brain and, thereby, enhancing memory. The Complementary and Alternative Medicines Institute says of thepotential for herb-drug interactions with ginkgo that (3): Ginkgo inhibits platelet aggregation. Preferably avoid use in patients on antiplatelet (aspirin,dipyridamole, ticlopidine) or anticoagulant (Warfarin) therapy. Monitor bleeding time and prothrombintime (PT) if patient is taking ginkgo concurrently with antiplatelet or anticoagulant drugs. Ginkgo mayincrease the activity/toxicity of monamine oxidase inhibitors.
Since elderly patients are more susceptible to spontaneous bleeds due to weakness of capillaries as well as having a prolonged healing time for response to incidents, this caution would seem reasonable. However, unlessthe extent of anticoagulant activity of an herb is measured, it is difficult to know whether or not to prohibit use. Itis firmly established that increased blood coagulation is a problem in modern society, especially among theelderly, and this problem often accompanies other circulation-related disorders. As a result, herbs that have anti-coagulant properties are generally attractive (e.g., garlic, ginkgo).
Researchers who are working to demonstrate the potential health value of herbs may be drawn to demonstrating the anti-coagulation potential for herbs during laboratory animal studies. These studies may notaccurately reflect what happens in human clinical cases, because of dosage of herb (usually high in laboratorystudies of this type) or the model used (coagulation of blood under circumstances different that occurs naturally inhumans). Ginkgo antiplatelet activity cautions appear to be based on case reports that still require verification. Inthe review article Dietary Supplement-Drug Interactions (4), the author states: "several case reports documentbleeding complications with Ginkgo biloba, with or without concomitant drug therapy." The suggestion here isthat the antiplatelet activity of ginkgo is high enough that it can cause bleeding complications on its own. At leastthree cases of brain hemorrhage have been blamed on ginkgo (5).
To be safe, a practitioner would either not prescribe ginkgo to a regular user of NSAIDS, especially aspirin and particularly for the elderly patient. An added risk to the practitioner is that the patient would suffer a bleedthat would be blamed (rightly or wrongly) on the interaction, and the practitioner "should have known and shouldhave warned the patient." The problem of using herbs with anticoagulants was address by Robert Rountree in anarticle that appeared in Herbs for Health magazine (2001): The Herb-Drug Mix: Deciding What's Safe
Millions of people regularly take blood-thinning drugs such Warfarin, and even more take aspirin and similar medications to prevent heart attacks and strokes. At the same time, with the use of herbal medicines more popularnow than ever, surveys show that most people don't tell their physicians about their use of herbs or vitaminsupplements.
How Do Herbs & Blood Thinners Mix?
Herbs may interact with the blood thinning drugs in different ways, some of them beneficial, some of them
potentially harmful. Herbs that enhance the effect of the anticoagulants may have antiplatelet activity, meaning
that they keep platelets from forming clots, or anticoagulant activity, meaning that they increase the time it takes a
clot to form, usually because they contain a compound called coumarin. Other herbs may counteract the effect of
anticoagulants by decreasing blood-clotting time, most likely because they contain a coagulant compound called
Meanwhile, physicians are starting to realize that many herbs possess potent pharmacological activity.
Concerns have been raised in prominent medical journals that this activity could have detrimental effects,especially for patients taking certain types of medications. Cautious physicians have chosen the route of absoluteavoidance rather than risk an adverse reaction, they recommend that patients stop taking herbs altogether. Is thisrational policy? Or is there another approach somewhere in between? To better answer these question, let's lookmore closely at how anticoagulants, or blood thinners, work in the body.
Blood Thickening and Thinning
Warfarin is the most commonly prescribed anticoagulant drug. Doctors typically give anticoagulant to people with
high risk of blood clotting, such as those who have artificial heart valves, deep vein thrombosis (a large blood
clot) in the legs, or arterial fibrillation (a chronic irregularity in heart rhythm). The process by which blood
thickens into a clot involves a chain reaction: various proteins interact to produce thrombin, which then produces
fibrin, the protein material that forms the clot's core. Several of these interacting proteins are made in the liver,
where vitamin K is essential for their production. Warfarin inactivates vitamin K to limit clotting proteins, so it
increases the amount of time it takes for blood to clot. This effect can be monitored with a simple blood test
called the prothrombine time (PT).
Vitamin K is found in high concentrations in many foods, including dark green leafy vegetables (especially turnip greens), alfalfa sprouts, broccoli, asparagus, egg yolks and dairy products. Eating these foods increases thepotential for higher blood levels of vitamin K, which would interfere with the anticoagulants, a few herbs alsopromote clotting, most notably shepherd's purse, possibly because it contains vitamin K.
Another aspect of blood clotting involves the clumping together of platelets: the combination of platelets clumps and the fibrin clot is what causes blood to thicken into full clots. Platelet function can be measured withthe test called the bleeding time. Many antiplatelet drugs are commonly used in medical practice, primarily toprevent strokes and heart attacks. Aspirin is the most common antiplatelet agent; others include dipyridamole(Persantine), sulfinpyrazone (Anturane), clopidogrel (Plavix), and ticlodipine (Ticlid). Many herbs also inhibitplatelet aggregation (see below). Undoubtedly the list will expand with further research.
Commonly Used Herbs*
chamomile, dong quai (tang-kuei), horse chestnut bilberry, bromelain, cayenne, feverfew, flaxseed oil, garlic, ginger, ginkgo, ginseng, green tea, meadowsweet, motherwort, and turmeric goldenseal, Oregon grape root, shepherd's purse *To expand the list of anticoagulant and antiplatelet herbs, the following are mentioned in Pharmacology and
Applications of Traditional Chinese Medicine (6): white atracytlodes, cnidium (chuanxiong), salvia, garlic,
zedoaria, pueraria, carthamus, lysimachia, cinnamon bark, tien-chi (sanqi), and capillaris (also listed: tang-kuei
If using anticoagulants has impaired a person's normal clotting mechanism, good platelet function is obviously an important backup system. Otherwise, a minor injury could lead to a severe hemorrhage. Or, if youare taking antiplatelet drugs everyday, the addition of ginkgo or one of the herbs listed in the first two sections ofthe chart above could lead to uncontrolled bleeding.
Deciding What's Safe
So what is an informed person to do? Well, there are several options, depending on the degree of effort one is
willing to put out. As a start, I propose the following step by step method.
If your doctor starts you on anticoagulant medication and your diet already includes vegetables rich invitamin K. (or a multivitamin that includes vitamin K), it's not necessary to make any dietary changes.
Instead allow your doctor to adjust the dose of medication based on the PT test. In this situation, it'smore important that if your diet changes, you inform your doctor so that the PT can be checked again.
While you're taking anticoagulants, avoid regular use of concentrated, standardized extracts of herbsthat are known to have antiplatelet activity, such as ginkgo, which is commonly sold as 50:1concentrate. While a daily cup of ginkgo tea or dropperful of tincture is unlikely to cause problems,the extract is much more potent. This same rationale applies to concentrated forms of any of theantiplatelet herbs, although it's probably safe to eat fresh ginger or garlic in food or to have a cup ortwo of green tea every day. If you feel that it's essential to your health to continue taking any of theanticoagulant or antiplatelet herbs listed in the chart along with prescription, there's another option.
Ask your doctor if he or she would be willing to monitor your bleeding time along with the PT. Ifyour bleeding time stays on normal range, you're less likely to have an unexpected hemhorrage.
If you are generally healthy and taking an antiplatelet drug such as aspirin for preventive purposes,you may want to try switching to ginkgo, which has many benefits. And consider that deep-sea fishoils (e.g., from salmon or cod) that have many of the same positive effects as aspirin, without therisks.
Given the increasingly large number of people taking complex mixtures of herbs, vitamins and drugs, it's probable
that we will see more reports of side effects and negative interactions. Some authorities are using these incidents
to discourage the public from taking herbs. But rather than turning back the clock on herbal medicine, I propose
learning from these examples and upgrading our database of medical information.
[end of article Rountree article] 1. Fugh-Berman A, Ernst E, Herb-drug interactions: review and assessment of report reliability, British Journal of Clinical Pharmacology 2001, 52(5): 587-595.
2. Abebe W, Herbal medication: potential for adverse interactions with analgesic drugs, Journal of Clinical Pharmacology and Therapeutics 2002; 27(6): 391-401.
3. Anonymous, Ginkgo, 2000 Complementary and Alternative Medicines Institute at the University of 4. Smolinske SC, Dietary supplement-drug interactions, Journal of the America Medical Woman's Association 1999; 54(4): 191-192, 195.
5. Cupp MJ, Herbal remedies: adverse effects and drug interactions, American Family Physician 1999.
6. Chang HM and But PPH (editors), Pharmacology and Applications of Chinese Materia Medica, (2 vols.), 1986 World Scientific, Singapore.
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