Abstract
The use of dietary supplements in North America has exploded over the last two decades. Some of the most commonly used supplements include multiple vitamins; B vitamins; vitamins C, E, and D; valerian; chamomile; garlic; ginkgo; St. John’s wort; evening primrose oil; soy; aloe; and echinacea. Many patients do not disclose their use of supplements to their healthcare providers. This is problematic because many supplements have the potential to interact with medications used during the perioperative period or in an acute care setting. Interactions can be either pharmacodynamic or pharmacokinetic. The level of evidence supporting these interactions varies substantially, ranging from in vitro studies to findings from reliable pharmacokinetic trials. In order to maintain patient safety, incorporating supplement-specific questions into patient interviews is crucial. Dietary supplements should be discontinued 2 weeks before elective surgical procedures to avoid potential perioperative complications.
Similar content being viewed by others
Keywords
- Dietary Supplement
- International Normalize Ratio
- Pharmacodynamic Interaction
- Bitter Melon
- CYP450 Isozyme
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Introduction
The Dietary Supplement Health and Education Act (DSHEA) of 1994 established the current regulatory framework for dietary supplements. This act opened the door for the explosion of dietary supplements to come to market with limited regulatory oversight by the US Food and Drug Administration (FDA). The Act defines dietary supplements as any products taken by mouth which contain a dietary ingredient intended to supplement the diet. A dietary ingredient can include vitamins, minerals, amino acids, enzymes or metabolites, and herbs or other botanical products. Dietary supplements may come in a variety of formulations (e.g., capsules, liquids, extracts), so long as the label on such products does not represent the supplement as a conventional food item [1]. The popularity of supplement use has grown considerably over the past two decades as evidenced by the multibillion dollar supplement industry [2]. Over 55 million US adults report using supplements in their lifetime, and a recent national survey found that nearly 18 % of the US adults use non-vitamin, non-mineral supplements each month [3, 4]. People most commonly report taking supplements because they are “good for you.” Additionally, many seek supplementation to prevent osteoporosis, improve memory, prevent colds and influenza, boost immunity, and increase energy among many other uses [5]. Unlike drugs, safety and effectiveness of dietary supplements are not required to be proven before marketing. However, some safety-focused regulations do apply to dietary supplements. As of 2006, post-marketing adverse event reports related to dietary supplements must be reported by manufacturers to the FDA [6]. This post-marketing surveillance has greatly increased the number of reports to the FDA, but the overall number is still relatively low.
The specific safety concerns of dietary supplement use in anesthesia, critical care, and pain management will be discussed in this chapter.
Commonly Used Dietary Supplements
Vitamins and minerals are the most commonly used supplements. This is true in the general population and the hospitalized and preoperative population [7–9]. The use of herbal and other dietary supplements is also common in the hospitalized and preoperative population [8–10]. The use of dietary supplements in hospitalized or perioperative patients is a significant concern due to potential interactions and other safety concerns. As many as 70 % of these patients do not disclose their use of these supplements if they are not specifically asked [11]. This is likely due to the perception that supplements are natural and therefore safe.
The most commonly used vitamins and minerals in the hospitalized or preoperative population include multiple vitamins, B vitamins, and vitamins C, E, and D [8]. The most common herbs used in this population include valerian, chamomile, garlic, ginkgo, St. John’s wort, soy, aloe, and echinacea (Tables 33.1, 33.2, and 33.3) [7, 8]. Most of these dietary supplements have a good safety record and are well tolerated by most patients. However, in many cases, evidence of clinically meaningful benefit is absent or contradictory. For several supplements, there are concerns about potential interactions or other safety concerns related to the use in the perioperative period. In these cases, the risk of using the supplement may significantly outweigh any known benefit of continuing to use the supplement.
Potential Drug-Supplement Interactions and Complications
Supplements interact with drugs through the same mechanisms as drugs interact with other drugs. These interactions can be categorized as either pharmacodynamic or pharmacokinetic. Pharmacodynamic interactions can often be predicted based on a supplement’s pharmacology. These types of interactions involve either additive or oppositional pharmacological effects. A pharmacodynamic interaction occurs, for example, when two or more substances are taken together that have similar pharmacological effects, resulting in additive or synergistic effects.
An important example of pharmacodynamic interactions related to supplements involves those supplements that affect blood clotting (Table 33.4). Over 90 supplements have the potential to affect platelet aggregation and blood clotting [13].
Glucosamine is one of the most commonly used dietary supplements on the market. It is typically used for symptoms of osteoarthritis. In 2008, it was recognized that glucosamine taken as a single ingredient or combined with chondroitin has the potential to affect platelet aggregation and interact with antiplatelet or anticoagulant drugs. The first report of this interaction was in 2004 [50]. However, in this instance, doubling the typical therapeutic dose of glucosamine combined with chondroitin was used, resulting in an increased international normalized ratio (INR) in a patient taking warfarin. Later reports described several cases of increased INR, bruising, and bleeding events in patients taking typical amounts of glucosamine alone or in combination with chondroitin [51, 52]. Chondroitin is a small component of a heparinoid compound with modest anticoagulant effects. How glucosamine might affect bleeding is a bit unclear. However, some animal model research suggests that it might have antiplatelet activity [13, 52].
Ginkgo is a common herbal supplement that has been linked with bleeding risk. Gingko is typically used to improve memory in otherwise healthy adults and for treating symptoms of dementia. Concerns about bleeding risk with ginkgo resulted from a multitude of case reports describing bleeding events, often in the perioperative period, in patients taking the supplement [53–58]. However, more recent evidence suggests that ginkgo might not have a meaningful effect on bleeding risk. Some clinical trials show no effect on platelet aggregation or on bleeding time [59]. Studies also show no effect of single doses of ginkgo on bleeding time when combined with clopidogrel (Plavix) or ticlopidine (Ticlid) [60, 61].
The case of ginkgo illustrates an important point to keep in mind when evaluating potential interactions between drugs and supplements. Roughly 30 % of potential interactions between supplements and drugs are based on in vitro or animal model research or case reports. By definition, this is preliminary and weak evidence. Even though this level of evidence raises important concerns about potential interactions, more reliable evidence is often needed to better understand the clinical significance of potential interactions.
In addition to potentially interacting with other antiplatelet or anticoagulant drugs, supplements that affect platelet aggregation may also present risk during the perioperative period. Some supplements such as gingko and saw palmetto have been linked to reports of perioperative bleeding events [13, 62]. Table 33.4 provides a list of selected supplements that have been shown to have antiplatelet or anticoagulant effects. These supplements have the potential to interact with other antiplatelet or anticoagulant drugs as well as adversely affect patients in the perioperative period.
Several supplements have the potential to cause central nervous system (CNS) depression (Table 33.5). Many of these are used as “sleepy time” teas such as chamomile, lavender, and lemon balm. Although there is often little to no evidence documenting sedative effects with these products, they clearly have a mild sedative effect in those who use them.
Other products have clearly documented sedative effects. Valerian is one of the most commonly used herbal supplements with sedative effects. Constituents in valerian seem to have benzodiazepine-like effects [13, 39]. Theoretically, combining valerian with other sedatives, especially benzodiazepines, might result in additive sedation. Valerian has also been shown to increase levels of alprazolam by 19 %. This is probably due to valerian inhibition of cytochrome P450 3A4 metabolism of alprazolam [63].
Similar to CNS depressant supplements, those with hypoglycemic effects have the potential to interact with other hypoglycemic agents and adversely affect patient outcomes during the perioperative period (Table 33.6). Several supplements have direct insulin-like or insulin-stimulating effects. These are the most likely supplements to result in hypoglycemic effects and adverse outcomes. Supplements with these effects include banaba, bitter melon, fenugreek, and gymnema [13]. Other supplements affect blood glucose levels through an insulin-sensitizing effect. Some of these include cinnamon, chromium, prickly pear cactus, and vanadium. Although these can still lower blood glucose levels, they are less likely to result in serious hypoglycemia [13, 62].
Several dietary supplements have blood pressure-lowering effects (Table 33.7). Most of these provide a modest effect on blood pressure which is likely to be clinically insignificant in many cases. There are no reports of perioperative complications in patients taking these supplements.
Dietary supplements with stimulant effects can increase both heart rate and blood pressure. Examples of these include ephedra, bitter orange which contains synephrine, and dimethylamylamine (DMAA), among others (Table 33.8). While ephedra and bitter orange have not been linked to serious complications during anesthesia, the products have been implicated in other serious spontaneous adverse events including stroke, myocardial infarction, QT interval prolongation, and arrhythmia [13].
A number of supplements have the potential to impact neurotransmitters such as serotonin. Because of this, blood pressure and vascular activity may be affected in patients taking these products [62]. St. John’s wort, for example, has been linked to cardiovascular collapse during anesthesia induction [64]. Additionally, the use of St. John’s wort in combination with meperidine has led to serotonergic crisis according to anecdotal reports [65]. Other dietary supplements with serotonergic properties include SAMe, 5-HTP, and L-tryptophan (Table 33.9). The use of these products in combination with other serotonergic drugs may increase the risk of serotonergic side effects and serotonin syndrome. These products should be avoided in the perioperative period if possible [62].
In addition to the pharmacodynamic interactions listed previously, it is important to consider pharmacokinetic interactions between dietary supplements and drugs when assessing the safety of supplement use in anesthesia, critical care, and pain management. Pharmacokinetic interactions are those which impact the means by which the body absorbs, distributes, metabolizes, and excretes drugs or dietary supplements. The most common pharmacokinetic interactions are metabolic interactions involving the cytochrome P450 (CYP450) system (Table 33.10). Because many of the drugs utilized in anesthesia, critical care, and pain management are metabolized by this system, it is important to identify which supplements can lead to changes in metabolism of these drugs. Concomitant use of supplements which inhibit CYP450 isozymes can increase the plasma levels and duration of effect of drugs metabolized by these enzymes. Conversely, concomitant use of supplements which induce CYP450 isozymes can decrease the levels and duration of effect of drugs metabolized by these isozymes.
More than 50 % of all marketed drugs are metabolized to some degree by CYP450 isozyme 3A4 (CYP3A4). Thus, supplements which inhibit or induce CYP3A4 are of particular concern [66]. St. John’s wort, for example, is a potent inducer of this isozyme. A number of case reports show a pharmacokinetic interaction between cyclosporine and St. John’s wort in organ transplant patients. The supplement has been shown to reduce plasma cyclosporine levels by up to 70 %, leading to subtherapeutic drug levels and, ultimately, acute organ rejection [67–69]. St John’s wort has a large potential for drug interactions, and thus determining safe yet effective doses of drugs which interact with this supplement can be difficult [70].
In addition to St. John’s wort, some garlic preparations have been shown to induce CYP3A4, while other formulations have not [71]. Furthermore, clinical evidence suggests garlic may reduce the activity of CYP2E1 by up to 40 % [70]. Because anesthetics such as enflurane, halothane, isoflurane, and methoxyflurane are metabolized by this isozyme, patients taking garlic supplements may require smaller doses of the aforementioned drugs [13].
Kava impacts CYP2E1 in a similar fashion to garlic and thus may prolong the effects of certain anesthetics [72]. Additionally, both kava and valerian inhibit CYP3A4. Because of this, they can potentially increase plasma concentrations of drugs metabolized by CYP3A4. Examples of these include alfentanil, alprazolam, amlodipine, clarithromycin, ketoconazole, lidocaine, midazolam, verapamil, and serotonin receptor antagonists, among many others. It should be noted, however, that the interaction potential of both kava and valerian with drugs metabolized by CYP3A4 is based on in vitro data. This is weaker evidence than that supporting the St. John’s wort and garlic interactions [11, 13].
Other Safety Concerns
One of the biggest problems plaguing the dietary supplement industry is the issue of adulteration and contamination. Adulteration occurs if a dietary supplement contains an ingredient which is present in sufficient quantities to be poisonous or harmful to human health. Contamination on the other hand can be defined as any foreign substance which would make a product tainted. Therefore, a contamination is a form of adulteration [73]. When the FDA or Health Canada recognizes a risk with a dietary supplement, such as adulteration, they post an alert to the public on their website. According to the authors’ research (unpublished data, April 2013), from 2005 to 2012, a total of 1,356 dietary supplement alerts were posted through either the FDA or Health Canada. The most common reason for these alerts was a contaminant, and the most common contaminant reported was a pharmaceutical product (65 %) followed by a heavy metal contaminant (9 %), bacterial contaminant (5 %), and fungal contaminant (1 %). Of the pharmaceutical contaminants identified, the most common group of compounds that was noted was phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) which accounted for approximately 53 % of all pharmaceutical contaminants. The second most common pharmaceutical contaminant noted was sibutramine which accounted for 32 % of all pharmaceutical contaminants. Overall, dietary supplements marketed for weight loss and sexual enhancement accounted for over a half of all dietary supplement alerts from 2005 to 2012 and suggest that these types of products warrant the most concern for patient safety.
Supplement quality programs such as the US Pharmacopeia (USP) review dietary supplements to ensure that products contain what is stated on the label to help to quality control dietary supplements. Participation in these programs is voluntary. To date, relatively few manufacturers participate in these quality assurance programs. Table 33.11 describes three well-known supplement quality programs.
Guidelines
Most patients do not voluntarily disclose their use of dietary supplements to their physician or any other health professional. This is why it is extraordinarily important that dietary supplements are mentioned by name upon hospital admittance and/or in the preoperative patient interview. Patients should be asked to use specific terminology about the use of “dietary supplements,” “food supplements,” “nutritional supplements,” “herbal products,” “herbal teas,” “vitamins,” etc. Using these different terms will help patients recognize the kinds of products you are asking about. Additionally, patients should be encouraged to bring in the containers of the supplements they are taking in order to generate a reliable, comprehensive list of products and their ingredients [66, 74].
Since many dietary supplements have meaningful pharmacological effects, there is potential for them to interact with anesthesia or other medications used in an acute care setting and potentially result in harm to the patient. For most supplements, there is little or no harm in discontinuing them temporarily. Therefore, discontinuation prior to hospital admission or a surgical procedure is often considered the most reasonable approach [13]. The American Society of Anesthesiologists currently recommends that all dietary supplements be discontinued 2 weeks prior to an elective surgical procedure [66, 74].
Nonetheless, in emergency situations, discontinuation may not be a possibility. In these cases, obtaining an accurate history is critically important so that any potential complications can be anticipated and addressed [74].
Summary
The use of dietary supplements continues to grow, and thus the challenge of managing anesthesia, critical care, and pain in patients taking these supplements remains. The first step in meeting this challenge requires gathering an accurate list of the supplements each patient is taking. For this to happen, an open line of communication must exist between patient and practitioner. Once supplements are identified, a decision to continue the supplements, discontinue the supplements, and/or modify drug therapy should be made. Understanding which supplements can impact coagulation, blood pressure, blood glucose, and the central nervous system will help with these decisions. Identifying the dietary supplements which can lead to increased or decreased levels of certain drugs via pharmacokinetic interactions is also very important. A general rule of thumb is to have patients discontinue nonessential dietary supplements at least 2 weeks prior to any surgical procedures they have scheduled.
References
Significant amendments to the FD&C Act: Dietary Supplement Health and Education Act of 1994. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148003.htm. Accessed 28 Mar 2013.
Consumer Union of US Inc. Dangerous supplements: what you don’t know about these 12 ingredients could hurt you. September 2010. Available at: http://www.consumerreports.org/cro/2012/05/dangerous-supplements/index.htm. Accessed 19 Jan 2013.
Wu CH, Wang CC, Kennedy J. Changes in herb and dietary supplement use in the US adult population: a comparison of the 2002 and 2007 National Health Interview Surveys. Clin Ther. 2011;33(11):1749–58.
Barnes PM, Bloom B. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008;12:1–23.
Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337–44.
Significant Amendments to the FD&C Act: Dietary Supplement and Nonprescription Drug Consumer Protection Act. U.S. Food and Drug Administration Web site. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148035.htm. Accessed 3 Apr 2013.
Kaye AD, Clarke RC, Sabar R, Vig S, et al. Herbal medicines: current trends in anesthesiology practice – a hospital survey. J Clin Anesth. 2000;12:468–71.
Grauer RP, Thomas RD, Tronson MD, Heard GC, Diacon M. Preoperative use of herbal medicines and vitamin supplements. Anaesth Intensive Care. 2004;32:173–7.
Norred CL. Complementary and alternative medicine use by surgical patients. AORN J. 2002;76:1013–21.
Lucenterforte E, Gallo E, Pugi A, Giommoni F, et al. Complementary and alternative drugs use among preoperative patients: a cross-sectional study in Italy. Evid Based Complement Alternat Med. 2012;2012:527238.
Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. 2001;286:208–16.
Denke MA. Dietary retinol–a double-edged sword. JAMA. 2002;287(1):102–4.
Jellin JM, Gregory PJ, eds. Natural Medicines Comprehensive Database. Therapeutic Research Center: Stockton, 2013. Available at: www.naturaldatabase.com. Accessed 28 Mar 2013.
Pohanka M, Pejchal J, Snopkova S, et al. Ascorbic acid: an old player with a broad impact on body physiology including oxidative stress suppression and immunomodulation: a review. Mini Rev Med Chem. 2012;12(1):35–43.
Herr C, Greulich T, Koczulla RA, et al. The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer. Respir Res. 2011;12:31.
Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, Saldeen T. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr. 2003;77(3):700–6.
Vermeer C, Schurgers LJ. A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin North Am. 2000;14:339–53.
Power ML, Heaney RP, Kalkwarf HJ, et al. The role of calcium in health and disease. Am J Obstet Gynecol. 1999;181(6):1560–9.
Vincent JB. The biochemistry of chromium. J Nutr. 2000;130:715–8.
Dallman PR. Biochemical basis for the manifestations of iron deficiency. Annu Rev Nutr. 1986;6:13–40.
Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A. Magnesium: an update on physiological, clinical, and analytical aspects. Clin Chim Acta. 2000;294:1–26.
Klein AD, Penneys NS. Aloe vera. J Am Acad Dermatol. 1988;18:714–20.
Wuttke W, Gorkow C, Seidlova-Wuttke D. Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Menopause. 2006;13:185–96.
Giacalone M, Di Sacco F, Traupe I, Topini R, Forfori F, Giunta F. Antioxidant and neuroprotective properties of blueberry polyphenols: a critical review. Nutr Neurosci. 2011;14(3):119–25.
Wang Y, Tang H, Nicholson JK, et al. A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. J Agric Food Chem. 2005;53:191–6.
Avallone R, Zanoli P, Puia G, et al. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol. 2000;59:1387–94.
Lee YL, Owens J, Thrupp L, Cesario TC. Does cranberry juice have antibacterial activity? JAMA. 2000;283:1691.
Duthie GG, Kyle JA, Jenkinson AM, et al. Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice. J Agric Food Chem. 2005;53:2897–900.
Barrett B. Medicinal properties of Echinacea: a critical review. Phytomedicine. 2003;10:66–86.
Guivernau M, Meza N, Barja P, Roman O. Clinical and experimental study on the long-term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. Prostaglandins Leukot Essent Fatty Acids. 1994;51:311–6.
Ali M, Thomson M, Afzal M. Garlic and onions: their effect on eicosanoid metabolism and its clinical relevance. Prostaglandins Leukot Essent Fatty Acids. 2000;62:55–73.
Kudolo G. Ingestion of Ginkgo biloba extract significantly inhibits collagen-induced platelet aggregation and thromboxane A2 synthesis. Altern Ther. 2001;7:105.
McElhaney JE, Gravenstein S, Cole SK, et al. A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J Am Geriatr Soc. 2004;52:13–9.
Vuksan V, Stavro MP, Sievenpiper JL, et al. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care. 2000;23:1221–6.
Park HJ, Lee JH, Song YB, Park KH. Effects of dietary supplementation of lipophilic fraction from Panax ginseng on cGMP and cAMP in rat platelets and on blood coagulation. Biol Pharm Bull. 1996;19:1434–9.
Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides. J Am Coll Nutr. 2004;23:248–58.
Calapai G, Crupi A, Firenzuoli F, et al. Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Pharmacopsychiatry. 2001;34:45–9.
Normen L, Dutta P, Lia A, et al. Soy sterol esters and B-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. Am J Clin Nutr. 2000;71:908–13.
Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol. 1999;51:505–12.
Montorsi F, Strambi LF, Guazzoni G, et al. Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology. 1994;44:732–6.
Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998;159:433–6.
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289:1681–90.
Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta. 2004;1660:171–99.
Nestel PJ. Fish oil and cardiovascular disease: lipids and arterial function (abstract). Am J Clin Nutr. 2000;71:228S–31.
Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res. 2001;21:309–41.
Sherman AL, Ojeda-Correal G, Mena J. Use of glucosamine and chondroitin in persons with osteoarthritis. PM R. 2012;4(5 Suppl):S110–6.
Gupta V, Garg R. Probiotics. Indian J Med Microbiol. 2009;27:202–9.
Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand. 1990;81:432–6.
Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside–molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002;76:1151S–7.
Rozenfeld V, Crain JL, Callahan AK. Possible augmentation of warfarin effect by glucosamine-chondroitin. Am J Health Syst Pharm. 2004;61:306–7.
Knudsen J, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database. Pharmacotherapy. 2008;28:540–8.
Yue QY, Strandell J, Myrberg O. Concomitant use of glucosamine may potential the effect of warfarin. The Uppsala Monitoring Centre. Available at: www.who-umc.org/graphics/9722.pdf. Accessed 28 Apr 2008.
Benjamin J, Muir T, Briggs K, Pentland B. A case of cerebral haemorrhage-can Ginkgo biloba be implicated? Postgrad Med J. 2001;77:112–3.
Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas with chronic Gingko biloba ingestion. Neurology. 1996;46:1775–6.
Miller LG, Freeman B. Possible subdural hematoma associated with Ginkgo biloba. J Herb Pharmacother. 2002;2:57–63.
Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med. 2005;20:657–61.
Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis. 2003;167:367.
Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet. 1998;352:36.
Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31:490–502.
Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol. 2007;63:333–8.
Kim BH, Kim KP, Lim KS, et al. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers. Clin Ther. 2010;32:380–90.
Gregory PJ. The perioperative use of natural medicines. Therapeutic Research Center: Stockton, 2012. Available at: www.naturaldatabase.com. Accessed 28 Mar 2013.
Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos. 2004;32:1333–6.
Irefin S, Sprung J. A possible cause of cardiovascular collapse during anesthesia: long-term use of St. John’s wort. J Clin Anesth. 2000;12:498–9.
Kaye AD, Baluch A, Kaye AM. Mineral, vitamin, and herbal supplements. In: Fleisher LA, editor. Anesthesia and uncommon diseases. 6th ed. Philadelphia: Elsevier; 2012. p. 477.
Kaye AD, Baluch A, Kaye AJ, Frass M, Hofbauer R. Pharmacology of herbals and their impact in anesthesia. Curr Opin Anaesthesiol. 2007;20:294–9.
Bauer S, Stormer E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St. John’s wort in renal transplant patients. Br J Clin Pharmacol. 2003;55:203–11.
Mandelbaum A, Pertzborn F, martin-Facklam M, Wiesel M. Unexplained decrease of cyclosporine trough levels in a compliant renal transplant patient. Nephrol Dial Transplant. 2000;15:1473–4.
Morschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St. John’s wort) after organ transplantation. Am J Kidney Dis. 2001;38:1105–7.
Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002;72:276–87.
Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002;34:234–8.
Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther. 2005;77:415–26.
Cole MR, Fetrow CW. Adulteration of dietary supplements. Am J Health Syst Pharm. 2003;60(15):1576–80.
Kaye AD, Kucera L, Sabar R. Perioperative anesthesia clinical considerations of alternative medicine. Anesthesiol Clin N Am. 2004;22:125–39.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Chemical Structures
Chemical structure 33.1
Glucosamine
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gregory, P., Abe, A., Hein, D. (2015). Herbal Medications and Vitamin Supplements. In: Kaye, A., Kaye, A., Urman, R. (eds) Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8948-1_33
Download citation
DOI: https://doi.org/10.1007/978-1-4614-8948-1_33
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-8947-4
Online ISBN: 978-1-4614-8948-1
eBook Packages: MedicineMedicine (R0)