Herb-Drug Interactions: Ginger

Zingiber offidnale Roscoe (Zingiberaceae)

Synonym(s) and related species

Gan Jiang, Zingiber.

Not to be confused with the wild gingers, which are Asarum canadense L. and Asarum europaeum L.

Pharmacopoeias

Ginger (British Ph 2009, European Ph 2008, US Ph 32); Ginger Capsules (US Ph 32); Ginger Tincture (US Ph 32); Powdered Ginger (The United States Ph 32).

Constituents

The constituents of ginger vary depending on whether fresh or dried forms are used. Generally, ginger rhizomes contain volatile oils of which zingiberene and bisabolene are major components: zingerone, zingiberol, zingiberenol, curcumene, camphene and linalool are minor components.

The rhizomes also contain gingerols and their derivatives, gingerdiols, gingerdiones and dihydrogingerdiones. Sho-gaols are formed from gingerols during drying, and together these make up the pungent principles of ginger.

Ginger extracts have been standardised to contain a minimum of 15mL/kg of essential oil with reference to the dried drug.

Use and indications

Ginger is thought to possess carminative, anti-emetic, anti-inflammatory, antispasmodic and antiplatelet properties. Both fresh and dried ginger are mainly used to settle the stomach, to alleviate the symptoms of motion sickness and to relieve morning sickness. Ginger has also been used in the treatment of osteoarthritis and rheumatoid arthritis, and for migraines.

Ginger is also an important culinary spice and the pungent properties of ginger have also been exploited for use in cosmetics and soaps.

Ginger is a constituent of Trikatu, a medicine used in Ayurvedic medicine in a ratio of 1:1:1 with Piper nigrum and Piper longum, see pepper.

Pharmacokinetics

Detailed information on the pharmacokinetics of ginger in humans is scarce but what has been found, in animals, is that gingerol, a major constituent of ginger, is rapidly cleared from plasma and elimination by the liver is involved. Gingerol is also a substrate of several UDP-glucuronosyl-transferases, which are major phase 2 metabolic enzymes responsible for the metabolism of several drugs. Gut flora also play a part in the metabolism of gingerol.

Interactions overview

There are isolated cases of ginger increasing the response to anticoagulant treatment with warfarin and related drugs, but a controlled study did not confirm an interaction. A small study showed antiplatelet effects for ginger that were synergistic with those of nifedipine, but any effect needs confirming.

For the interactions of ginger as a constituent of Trikatu, a medicine used in Ayurvedic medicine, see Pepper + Isoniazid, Pepper + NSAIDs, and Pepper + Rifampicin (Rifampin). For the interactions of ginger as a constituent of Chinese herbal medicines, see under bupleurum9.

Ginger + Anticoagulants

Evidence from pharmacological studies suggests that ginger does not increase the anticoagulant effect of warfarin, nor does it alter coagulation or platelet aggregation on its own. However, two case reports describe markedly raised INRs with phenprocoumon and warfarin, which were associated with eating dried ginger and drinking ginger tea. A prospective, longitudinal study also reports an increased risk of self-reported bleeding events in patients taking warfarin and ginger.

Clinical evidence

In a randomised, crossover study in 12 healthy subjects, 3 ginger capsules taken three times daily for 2 weeks did not affect either the pharmacokinetics or pharmacodynamics (INR) of a single 25-mg dose of warfarin taken on day 7. The brand of ginger used was Blackmores Travel Calm Ginger, each capsule containing an extract equivalent to 400 mg of ginger rhizome powder. Moreover, ginger alone did not affect the INR or platelet aggregation.

However, a case report describes a rise in INR to greater than 10, with epistaxis, in a woman stabilised on phenprocoumon several weeks after she started to eat ginger regularly in the form of pieces of dried ginger and tea from ginger powder. She was eventually restabilised on the original dose of phenprocoumon, and was advised to stop taking ginger. Another very similar case has been described in a woman taking warfarin.

Moreover, in a prospective, longitudinal study of patients taking warfarin and a herbal product or dietary supplement, there was a statistically significant increased risk of self-reported bleeding events in patients taking warfarin and ginger (7 bleeds in 25 weeks, none of which was major: odds ratio 3.2). No elevated INRs were reported for the combination. Note that the number of patients taking ginger was not reported, except to say it was less than 5% of 171 – so it was less than 8 patients. Also, the ginger products used were not mentioned and some patients were taking more than one potentially interacting supplement.

Experimental evidence

See under Mechanism below.

Mechanism

Ginger (Zingiber officinale) has sometimes been listed as a herb that interacts with warfarin on the basis that in vitro it inhibits platelet aggregation. However, this antiplatelet effect has generally not been demonstrated in controlled clinical studies (three of which have been reviewed) although in one other study ginger had antiplatelet effects that were synergistic with those of nifedipine, see nifedipine, below.

Importance and management

Evidence from a controlled study suggests that ginger does not increase the anticoagulant effect of warfarin. Despite it being cited as a herb that inhibits platelet aggregation, there is limited evidence that it increases bleeding when given alone or with warfarin, and there are just two case reports of markedly raised INRs with phenprocoumon and warfarin, which were associated with ginger root and ginger tea. Because of the many other factors influencing anticoagulant control, it is not possible to reliably ascribe a change in INR specifically to a drug interaction in a single case report without other supporting evidence. It may be better to advise patients to discuss the use of any herbal products that they wish to try, and to increase monitoring if this is thought advisable. Cases of uneventful use should be reported, as they are as useful as possible cases of adverse effects.

Ginger + Caffeine

For mention that sho-saiko-to (of which ginger is one of 7 constituents) only slightly reduced the metabolism of caffeine in one study, see Bupleurum + Caffeine.

Ginger + Carbamazepine

For mention that saiko-ka-ryukotsu-borei-to and sho-saiko-to (of which ginger is one of a number of constituents) did not affect the pharmacokinetics of carbamazepine in animal studies, see Bupleurum + Carbamazepine.

Ginger + Food

No interactions found. Ginger is extensively used as a food ingredient.

Ginger + Herbal medicines

No interactions found.

Ginger + Isoniazid

For details of an animal study to investigate a possible interaction between isoniazid and Trikatu, an Ayurvedic medicine containing ginger, black pepper and long pepper, see Pepper + Isoniazid.

Ginger + Nifedipine

A small study found that antiplatelet effects for ginger were synergistic with those of nifedipine, but any effect needs confirmation.

Evidence, mechanism, importance and management

In a small study in 10 hypertensive patients and another in 10 healthy subjects, ginger 1 g daily for 7 days given with nifedipine 10 mg twice daily for 7 days inhibited platelet aggregation by up to three times more than nifedipine alone. In these studies, ginger alone had similar antiplatelet effects to aspirin 75 mg (used as a control), either alone, or given with nifedipine. Nifedipine alone also had antiplatelet effects, but these were not as great as aspirin 75 mg alone. The ginger used in this study was dried, but no other details about the preparation were given.

Calcium-channel blockers are not generally viewed as antiplatelet drugs, and the finding of synergistic antiplatelet effects between nifedipine and aspirin in this report and its clinical relevance needs further study. Furthermore, this study suggests that ginger alone may have similar antiplatelet effects to low-dose aspirin alone; however, this antiplatelet effect has generally not been demonstrated in other controlled clinical studies of ginger (three of which have been reviewed). Therefore, it is difficult to make any clinical recommendations on the basis of this one small study. Further study is clearly needed.

Ginger + NSAIDs

For details of an animal study to investigate a possible interaction between diclofenac and Trikatu, an Ayurvedic medicine containing ginger, black pepper and long pepper, see Pepper + NSAIDs.

Ginger + Ofloxacin

For mention that sairei-to and sho-saiko-to (of which ginger is one of a number of constituents) do not affect the pharmacokinetics of ofloxacin, see Bupleurum + Ofloxacin.

Ginger + Rifampicin (Rifampin)

For details of an interaction between rifampicin and Trikatu, an Ayurvedic medicine containing ginger, black pepper and long pepper, see Pepper + Rifampicin (Rifampin).

Ginger + Tolbutamide

For conflicting evidence from animal studies that sho-saiko-to (of which ginger is one of 7 constituents) might increase or decrease the rate of absorption of tolbutamide, see Bupleurum + Tolbutamide.