Herb-Drug Interactions: Kudzu

Pueraria montana (Lour.) Merr. (Fabaceae)

Synonym(s) and related species

Ge Gen.

Pueraria hirsuta (Thunb.) C. Schneider, Pueraria lobata (Willd.) Ohwi, Pueraria lobata (Willd.) Ohwi var. thomsonii (Benth.) Maesen, Pueraria thunbergiana (Sieb. & Zucc.) Benth., Dolichos lobatus Willd.

Other species used include Pueraria mirifica Airy Shaw & Suvatabandhu (Thai kudzu, Kwao Kreu Kao) and Pueraria phaseoloides (Roxb.) Benth. (Puero, Tropical kudzu).

Constituents

The major isoflavone constituent of the root of Pueraria lobata is puerarin, which is the 8-C-glucoside of daidzein, but there are many others, such as puerarin hydroxy- and methoxy- derivatives and their glycosides, daidzein and its O-glycoside daidzin, biochanin A, genistein and formononetin derivatives. Pterocarpans are also present, including medicarpin glycinol and tuberosin. The flowers contain the phytoestrogens kakkalide and tectoridin.

Pueraria mirifica root contains similar constituents to Pueraria lobata, the major difference being lower amounts of daidzein.

Much of the research carried out on kudzu has been on the effects of isolated puerarin.

Use and indications

Kudzu contains isoflavones and is used as a phytoestrogen for menopausal symptoms, with a particular emphasis on bone metabolism for use in postmenopausal osteoporosis. It also has a popular reputation for being able to lower alcohol consumption and to treat symptoms of alcohol intoxication. This effect has not been reported for other isoflavone-containing herbs and the possible mechanism of action is unknown. Kudzu has also been used for migraine and hypertension, pain and stiffness, and angina. The phytoes-trogenic properties are well known, and puerarin is thought to be the major component with this effect, which has been well documented in animals. For further details about the general and specific effects of isoflavones, see isoflavones.

Pharmacokinetics

No relevant pharmacokinetic data for kudzu found. For information on the pharmacokinetics of its main isoflavone constituent puerarin, see isoflavones.

Interactions overview

Studies in rats suggest that kudzu can increase the effects of methotrexate. Kudzu contains oestrogenic compounds and therefore it may interact with oestrogens and oestrogen antagonists. Potential interactions of isoflavone constituents of kudzu are covered under isoflavones; see antibacterials, antidiabetics, benzodiazepines, miscellaneous cardiovascular drugs, digoxin, fexofenadine, nicotine, paclitaxel, and theophylline.

Kudzu + Antibacterials

No data for kudzu found. For the theoretical possibility that broad-spectrum antibacterials might reduce the metabolism of the isoflavone constituents of kudzu, such as puerarin and daidzin, by colonic bacteria, and so alter their efficacy, see Isoflavones + Antibacterials.

Kudzu + Antidiabetics

No data for kudzu found. For comment on the blood-glucose-lowering effects of puerarin, a major isoflavone constituent of kudzu, see Isoflavones + Antidiabetics.

Kudzu + Benzodiazepines

No data for kudzu found. Puerarin, a major isoflavone constituent of kudzu, has been reported to be a weak benzodiazepine antagonist, see Isoflavones + Benzodiazepines.

Kudzu + Cardiovascular drugs; Miscellaneous

No data for kudzu found. For a discussion of the evidence that puerarin, an isoflavone present in kudzu, might inhibit platelet aggregation, see Isoflavones + Cardiovascular drugs; Miscellaneous.

Kudzu + Digoxin

No data for kudzu found. For the possibility that high-dose biochanin A, an isoflavone present in kudzu, might increase digoxin levels, see Isoflavones + Digoxin.

Kudzu + Fexofenadine

For the possibility that high-dose biochanin A, an isoflavone in kudzu, may slightly decrease fexofenadine levels in rats, see Isoflavones + Fexofenadine.

Kudzu + Food

No interactions found.

Kudzu + Herbal medicines

No interactions found.

Kudzu + Methotrexate

The interaction between kudzu and methotrexate is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a pharmacokinetic study in rats, the use of a kudzu root decoction significantly decreased the elimination and resulted in markedly increased exposure to methotrexate. Animals were given methotrexate, orally or intravenously, alone or with the decoction. Giving the decoction at a dose of 4 g/kg and 2 g/kg significantly increased the AUC of oral methotrexate by about 3-fold and 2.3-fold, respectively. This resulted in high mortality rates (57.1% and 14.3%). With intravenous methotrexate, the concurrent use of the kudzu decoction at 4 g/kg increased the half-life by 54% and decreased the clearance by 48%.

Mechanism

Kudzu markedly reduces the elimination of methotrexate. This might occur because of competition for renal of biliary excretion, possibly via organic anion transporter (OAT).

Importance and management

Evidence is limited to data in rats, and the doses of kudzu used in this study are very high. Nevertheless, the findings suggest that kudzu might markedly increase the effects of methotrexate. Until more is known, caution might be appropriate on concurrent use. The risks are likely to be greatest with high-dose methotrexate (for neoplastic diseases) and in patients with impaired renal function, but less in those given low doses (5 to 25 mg weekly) for psoriasis or rheumatoid arthritis and with normal kidney function. Note that the use of methotrexate requires routine monitoring (e.g. of LFTs), and patients should be advised to report any sign or symptom suggestive of infection, particularly sore throat (which might possibly indicate that white cell counts have fallen) or dyspnoea or cough (suggestive of pulmonary toxicity).

Kudzu + Nicotine

For discussion of a study showing that daidzein and genistein present in kudzu caused a minor decrease in the metabolism of nicotine, see Isoflavones + Nicotine.

Kudzu + Oestrogens or Oestrogen antagonists

Kudzu contains oestrogenic compounds. This may result in additive effects to oestrogens or it may oppose the effects of oestrogens. Similarly, kudzu may have additive effects to oestrogen antagonists or oppose the effects of oestrogen antagonists (e.g. tamoxifen).

Evidence, mechanism, importance and management

Kudzu has a long history of use for menopausal symptoms, and is known to contain isoflavones (plant oestrogens). Numerous in vitro and animal studies have demonstrated oestrogenic effects for the herb (too many to cite here). However, few clinical studies have been conducted. In one study, Pueraria mirifica alleviated menopausal symptoms in perimenopausal women, but in another study in postmenopausal women, Pueraria lobata did not alter menopausal symptoms or lipids or hormone levels, and was less effective than conventional HRT.

Theoretically, the isoflavones from kudzu might have oestrogen antagonistic effects when they are given with potent oestrogenic drugs, as their oestrogenic effects are weaker and they might competitively inhibit the conventional oestrogenic drugs. Conversely, because of their oestrogenic effects it is possible that they might reduce the efficacy of potent oestrogen antagonists.

Although many studies have been carried out, clinical information on the potential interaction of kudzu with oestrogens or oestrogen antagonists is sparse. On the basis of the postulated oestrogenic effects of kudzu and the theoretical mechanisms of antagonism, some have recommended caution if kudzu is given with other oestrogens including hormonal contraceptives, or with oestrogen antagonists such as tamoxifen. However, isoflavones from plants are widely consumed as part of the traditional diet in many parts of the world, and there is no clear evidence that this affects response to hormonal contraceptives or oestrogen antagonists such as tamoxifen. For further information on the oestrogenic effects of isoflavone supplements, see Isoflavones + Tamoxifen.

Kudzu + Paclitaxel

No data for kudzu found. For the possibility that the isoflavones biochanin A and genistein present in kudzu might increase paclitaxel levels, see Isoflavones + Paclitaxel. Note that paclitaxel is used intravenously, and the effect of biochanin A on intravenous paclitaxel does not appear to have been evaluated.

Kudzu + Theophylline

No data for kudzu found. For the possibility that high doses of daidzein present in kudzu might modestly increase theophylline levels, see Isoflavones + Theophylline.