Risks of Mixing Drugs and Herbal Supplements: What Doctors and Patients Need to Know
DGNEWS
Herbal, dietary, and energy or nutritional supplements can have harmful and even life-threatening effects when combined with commonly used medications. Clinicians need to educate their patients about the potential risks of mixing supplements and therapeutic agents, since their interaction can diminish or increase drug levels. This topic is explored in an article recently published in Alternative and Complementary Therapies.
(See complete article below from the Alternative and Complementary Therapies).
"'Natural' does not equal 'safe,'" and the effects and interactions of herbal or dietary supplements and functional foods such as energy drinks or nutritional bars can be difficult to predict, says Catherine Ulbricht, PharmD, Pharmacy, Massachusetts General Hospital, Boston, Massachusetts. "If something has a therapeutic action in a human body, this substance can also cause a reaction or an interaction."
The risk for interactions is greatest in younger and older people and in individuals with multiple health conditions or who take multiple medications, explains Dr. Ulbricht in the article "What Every Clinician Should Know About Herb–Supplement–Drug Interactions." She describes in detail some of the most common side effects that result from interactions between herbal supplements and therapeutic drugs, and provides guidance to clinicians on how to decrease the risk of harmful interactions in their patients and what resources are available for obtaining accurate information and reporting patient reactions.
Common examples include an increased risk of significant bleeding associated with garlic, ginkgo, ginger, and saw palmetto supplements; decreased blood sugar as a result of chromium, cinnamon, whey protein, and others; hormonal effects of dong quai, black cohosh, kudzu, and saw palmetto; and elevated blood pressure caused by bloodroot, green tea, hawthorn, and maté.
What Every Clinician Should Know About Herb–Supplement–Drug Interactions
Catherine Ulbricht, PharmD
Download PDF Here
ALTERNATIVE AND COMPLEMENTARY THERAPIES DOI: 10.1089/act.2012.18202 • MARY ANN LIEBERT, INC. • VOL. 18 NO. 2
APRIL 2012
Q: What should clinicians know about the level of risk for herb, supplement, and drug interactions?
Dr. Ulbricht: Any items that a person takes orally on a supplemental basis—whether they be herbs, dietary supplements,other natural products, or functional foods such as energy drinks and nutritional bars—can interact with each other and with medications. We know that these interactions may have harmful or beneficial effects and can increase or potentiate levels of other therapeutics and/or decrease levels of other therapeutics.
Dietary supplements can also interact with diagnostic test results and laboratory assays.It is important to note that interactions caused by supplements can be hard to predict due to a lack of clinical research,
compared to reactions caused by drugs, because many products are not standardized to specific ingredients or amounts, and herbal constituents may differ depending on what plant parts the constituents are derived from, for instance, petals, seeds,stems, roots, or leaves. Unlike a prescription drug, for which one can definitively draw the chemical structure graphically,measure it, weigh it, and see it under a microscope, this is more difficult when dealing with natural products.
We have all heard that “natural” does not equal “safe,” butthis is really true. If something has a therapeutic action in a human body, this substance can also cause a reaction or an interaction.
Supplements are not 100% receptor-specific to only have one effect and no other effects, and what might help one person might hurt another person, just like medications do.
But, remember that not all interactions are bad. Some interactions may be beneficial. An example is if one therapy increases the benefit of another or affects electrolyte levels or liver-function test results in a beneficial way. One therapeutic might interact with another in a good way in that it decreases a side-effect or allows a dose of another therapeutic to be lowered,and, therefore, a person experiences a lesser side-effect risk from both therapeutics. Also, a socioeconomic benefit maybe, if one purchases or perhaps grows a natural ingredient in a garden, that might be more cost-effective than the alternatives.
Purchasing without a prescription may keep insurance costs down over time. I think it is critical that clinicians consider herbs and supplements as therapeutic options. But, whether we are trained about this in medical school or not, I feel that we have a professional responsibility to educate ourselves and our patients or consumers about the potential for various types of interactions.
Q: How common are these types of interactions?
Dr. Ulbricht:It is really disparate. Unfortunately, there is not one driving channel or one centralized area to collect such information. The bottom line is that such interactions are likely to be much higher than any of us knows. Based on animal and laboratory research, we know that such products can alter blood sugar and blood pressure [BP], and affect the coagulation cascade and liver enzymes—to name a few effects. It is very difficult to do risk calculations per se, because many people need polypharmacy, and many supplement products are not standardized and may have many ingredients. But, again, with the lack of centralized reporting, we do not know exactly how many people are being affected by interactions.
In addition, because of the lack of communication between providers and patients, patients might be having interaction effects, but clinicians do not know whether or not these effects are related to particular products. Unfortunately, many clinicians were not educated about interactions during their training and may not realize that a product is the potential culprit for their patients’ symptoms.
This is a big part of why the Natural Standard Research Collaboration was founded-to serve as an aggregator,to help consolidate postmarketsurveillance reports, and to urge clinicians to submit case reports to us and to academic journals. One of our goals is to get all of the information in one place, which, in the long run, will help us learn more about risk incidence and effects.
Q: What populations are at greatest risk for such interactions?
Dr. Ulbricht:People who are younger, people who are older,people with many conditions, and people who need polypharmacy are all at higher risk. As people get older, they tend to have many conditions, such as cardiovascular disease and diabetes, and are typically taking more medications,
which increase the risk of interactions with herbs and supplements. However, this may also be a time when these patients really need specific supplemental nutrients for optimal health.
Patients who are pregnant or breastfeeding also need to consult with their health care providers to ensure that the medications and supplements being taken are safe, both for themselves and for their fetuses and/or infants. The U.S. Food and Drug Administration [FDA] labels drugs Pregnancy Category A–D,as well as Pregnancy Category X, with the latter indicating that such agents are contraindicated in pregnancy. However,this is not the case with herbs and supplements.
Another at-risk population includes those people who are not communicating openly and honestly with their health care providers,or who are patients of health care providers who do not take the time or do not feel comfortable discussing natural therapies with their patients. Poor communication poses a higher risk,and it is really important that these things are discussed openly.
Patients are always encouraged before starting new diets or exercise regimens to check with their health care providers and to not adjust the doses of medications without checking with their health care providers as well. The same is true for dietary supplements. It is important for clinicians and patients to work together to develop integrative personalized health plans that are safe and effective, and to set up appropriate monitoring parameters for potential interactions and adverse effects. Healthcare providers should also do monitoring to see if they can help patients eliminate some of the drugs being taken or reduce medication doses, because such supplements have helped achieve these goals. But the key is that providers and patients need to do this together as a team.
Then, there are the people who believe that more is better and who are into megadosing. Aside from an increased risk of interactions, it has actually been shown that a person who takes megadoses of a vitamin, for instance, may ultimately show signs of deficiency if that person stops taking the vitamin abruptly.
Q: What are some of the top side-effects from herb–supplement–drug interactions for which clinicians should be especially aware?
Dr. Ulbricht:Let’s talk about five major types of effects that can occur and are particularly important to know about,because they may pose life-or-death issues. Clinicians should know that there are hundreds of herbs and/or supplements in each of these categories, which may have these effects. Remember that the risk for sequelae from these interactions is not as common when patients are appropriately monitored,and specific patients may be more at risk based on their medical histories.
Bleeding and coagulation—
Let’s start by looking at the risk of bleeding and coagulation abnormalities. A rule of thumb in“Interactions 101” training is that I always think of the “Gs.”So, big G, little S. . .big G makes me think of garlic [Allium sativum], ginkgo [Ginkgo biloba], ginger [Zingiber officinale],and the little S is saw palmetto [Serenoa repens] to me. All of these have been shown to increase the risk of bleeding and may have been shown to cause clinically significant bleeding in case reports. These specific supplements need to be discontinued at least 2 weeks prior to surgery, including dental surgery. We have actually seen people bleed out, and we have seen surgeries rescheduled because clinicians only find out on the day that patients are wheeled into the surgical suite that they have been taking supplements. This is a huge life-and-death issue and,certainly, a big financial issue to schedule a surgical room and a team and then have to cancel, and the patient may be at risk because he or she obviously needed the surgery.
But, in addition to the herbs just mentioned, hundreds of other herbs and dietary supplements may increase the risk of bleeding, based on evidence from basic science or animal studies,clinical acumen from practitioners who have been using hese in the field for some time, anecdotal reports, or in theory,based on the active ingredients.
There is also the possibility of procoagulant effects such as clotting, In some cases, a paradoxical effect occurs. Sometimes itis based on the amounts of the therapeutics that are ingested.
Possible procoagulant supplements that may decrease the anticoagulant effects of warfarin include melatonin and coenzymeQ10, as well as vitamin K and vitamin K-containing foods or supplements, such as spinach and broccoli.
Blood sugar—
Products that affect blood-sugar regulation are the next big issue with respect to interactions. There are both hyperglycemic or hypoglycemic herbs and dietary supplements.
Some popular examples specific to this category are agave [Agavespp.], annatto [Bixa orellana], l-arginine, dehydroepiandrosterone [DHEA], flaxseed [Linum usitatissimum], stinging nettle Urtica dioica], and goldenseal [Hydrastis canadensis]—all of which can affect blood sugar. This is a very important issue, because, whether somebody has diabetes or not, glucose regulation may be disrupted.
Well-known herbs and supplements that have been shown to specifically decrease blood sugar are chromium, cinnamon Cinnamomum spp.], glucomannan, b-glucan, vanadium, whey protein, fenugreek [Trigonella foenum-graecum], and gymnema[Gymnema sylvestre], and these may potentiate the effects of hypoglycemic drugs in diabetic patients. Coca [Erythroxylum coca] and cocoa [Theobroma cacao], however, have been shown to increase blood sugar. Other popular supplements that have been shown to both raise and lower blood sugar are licorice [Glycyrrhiza glabra, Glycyrrhiza uralensis] and ginseng [Panax spp.].
Cytochrome P450—
There are a host of herbs that may induce or inhibit the cytochrome P450 system and affect liver enzymes and, therefore, affect the clearance of other therapeutics.
One can have high levels of a drug or another herb and supplement in one’s system that can cause interactions or adverse effects, because the product is cleared through the cytochrome P450 system.
Hormonal effects—
Herbs and supplements may have androgenic effects,antiandrogenic effects, estrogenic effects, antiestrogenic effects, and many other hormonal effects. Specific examples of well-known herbs and supplements with these types of hormonal effects that may thus interact with hormonal agents include dong quai [Angelica sinensis], black cohosh [Cimicifuga racemosa], chasteberry [Vitex agnus-castus], DHEA, kudzu [Pueraria lobata], peony [Paeonia lactiflora, Paeonia officinalis, Paeonia suffruticosa], red clover [Trifolium pratense], soy [Glycine max], and saw palmetto. Based on clinical research, saw palmetto may be equivalent to the antiandrogenic agent ProscarR [finasteride] for alleviation of several symptoms of benign prostatic hyperplasia.
Blood pressure—
There are many therapies that, while they may help treat BP, can also lead to hyper- or hypotension. We have all heard about the hypertensive risk with ephedra [Ephedra spp.], but bloodroot [Sanguinaria canadensis], green tea [Camella sinensis], hawthorn [Crataegus spp.], mistletoe [Viscum album], maca [Lepidium meyenii], and mate [Ilex paraguariensis]may also increase the risk of hypertension. Many other products—depending on the patient and amount ingested—can lower BP.
So if one takes green tea and also takes cola nut [Cola spp.] or coltsfoot [Tussilago farfara]—which have documented hypertensive effects—then taking these items with other therapeutics that may have a hypertensive effect will increase this risk.
However, this interaction could be beneficial if somebody has orthostatic hypotension or if one wants to increase or stabilize a patient’s BP. If a person takes ephedra, ginseng [Panax spp.] grapeseed [Vitis vinifera], and scotch broom [Cytisus scoparius],then that person is taking four things that might increase BP, so the risk significantly increases. But these mentioned herbs and supplements are only the tip of the iceberg because hundreds of herbs may affect BP.
I want to make the point that I do not want to heighten clinicians’ fears of using herbs and supplements above overthe-counter or prescription medications. But I do want to emphasize that herbs and supplements are just as likely to interact and cause side-effects in many cases, so clinicians need to screen their patients for what they are taking and monitor them appropriately.
Q: What can clinicians do to decrease the risk of such interactions in their patients?
Dr. Ulbricht:Clinicians should talk with their patients about what medications and supplements are being taken, and clinicians should educate themselves about interactions, have credible resources in hand, and involve pharmacists and dietitians in patient care.
Ideally, clinicians should be educated about this in undergraduate and graduate school, and clinicians should not wait until they are out in the field and faced with these issues. I think, historically, a lot of the information-gathering about supplement use was at arm’s length. Clinicians may have given the message to hospitalized patients, “we do not want to know what supplements you are taking. We do not want to talk about it. You are not allowed to use this while you are in the hospital.”
But, the patients that come in have these products in their systems anyway, and, even if patients do not take supplements in the hospital, their effects remain in the patient’s bodies. Then,when they leave, they are going to take supplements again. The utilization rates support this, so clinicians have to talk about this with their patients.
At Natural Standard, we have conducted systematic reviews on thousands of ingredients and have compiled the data into charts and tables, which are very helpful. If, for instance, there is a patient who is prone to be at high risk for bleeding or clotting, the clinician can check quickly and see if any of those therapeutics are in that list.
Q: What resources can clinicians turn to for reporting interactions and for more information about interactions?
Dr. Ulbricht:Again, one centralized place for reporting is lacking at this time. Currently, clinicians can file any complaints with the Office of Dietary Supplements [ODS],FDA, Federal Trade Commission [FTC], and Better Business Bureau, as well as many lay sites, including social media sites,
blogs, and social health–related sites such as Quackwatch.
Social media, websites, and blogs have all become casual forms of reporting symptoms that may represent interactions. The FDA MedWatch reports product recalls. The FTC, National center for Complementary and Alternative Medicine, or ODS websites also have a button that reads: “Click here to communicate with us.”
Over time, increasing numbers of integrative or complementary and alternative medicine studies are being indexed in PubMed and MEDLINE,R which is very important, because this is a free and internationally renowned resource, and a lot of information on interactions, case reports, or adverse effects that are in journals are not yet MEDLINE-listed. It is important that quality case reports get indexed and done so retroactively to include prior issues of journals. There are some additional bibliographic databases—uch as EMBASE,IPA [International Pharmaceutical Abstracts], HerbMed, and CINAHL [Cumulative Index to Nursing and Allied Health Literature]—nd agricultural databases where people can get information about interactions.
Centralized postmarket surveillance of these therapeutics is important. At Natural Standard, we cull, collate, report, and cite information from all of these locations, and are signed up for hundreds of newsletters and RSS [Really Simple Syndication/RDF Site Summary] feeds from professional organizations, publications, and the lay press. Clinicians can go on to our website [www.naturalstandard.org and access databases where there are charts and tables that give great details about potential interactions. Specifically, a clinician can look at what supplements his or her patient is taking and put it in our interactions checker, and the checker will cross-search and identify potential interactions and the level of scientific support or risk for those interactions.
Continuing education [CE] programs for all disciplines are also excellent sources for learning about interactions.The American Pharmacists Association did a survey, and the number-one requested CE program was about dietary supplements due to the high utilization rates and the lack of formal education about dietary supplements. The American Academy of Family Physicians endorses Natural Standard as an evidencebased resource for continuing medical education courses.
Q: Do you have any final comments about how clinicians can help protect their patients and inform them about interactions?
Dr. Ulbricht:The biggest point is to keep the potential for interactions in mind. Clinicians should be mindful of what they are saying to their patients and what is being prescribed. Clinicians should make sure that they monitor patients’ medication profiles, which should include herbs and dietary supplements,and screen for interactions, including the main categories of side-effects mentioned. Remember that the risk of interactions is lower when patients are appropriately monitored and clinicians are educated about what is known about interactions.
A multidisciplinary approach is important. Clinicians are cross-trained to some extent, but cannot be “jacks of all trades,masters of none.” So, that is why people specialize. Physicians are diagnosticians. Pharmacists focus on therapeutics. Dietitians focus on diets. Physical therapists focus on exercises.Multidisciplinary teams should be used for patient care.
If a person comes in complaining of symptoms that a clinician cannot quite make sense of and that patient has just started taking new supplements and a new drug, then the clinician can use resources to determine if there is an interaction and document it. It is all about communication among providers and between providers and patients. Reporting concerns to product manufacturers is also recommended—whether the manufacturers report these things or not remains to be seen. Government agencies are working on how to deal with that and develop requirements for manufacturers in this industry.
Clinicians are also encouraged to publish in peer-reviewed journals, because those are the conduits to get this information out to scientists all over the world as opposed to just locally. In addition to simply reporting an adverse reaction,one can submit the case or information to a peer-reviewed journal, which helps spread the word. The key is to consolidate efforts and promote education and share resources across health care disciplines.
Catherine Ulbricht, PharmD, Is the co-founder of Natural Standard Research collaboration, is a senior attending pharmacist at Massachusetts General Hospital, and is an adjunct/assistant clinical professor at many universities.
To order reprints of this article, e-mail Karen Ballen at: Kballen@liebertpub.com or call (914) 740-2100.
http://online.liebertpub.com/doi/abs/10.1089/act.2012.18202
No comments:
Post a Comment