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].