Herb-Drug Interactions: Rooibos
Aspalathus linearis (Burm.f.) RDahlgren (Fabaceae)
Synonym(s) and related species
Red bush tea, Green red bush, Kaffree tea.
Constituents
The needle-like leaves and stems of rooibos contain polyphenolic flavonoids. The unfermented product remains green in colour and contains aspalathin, a dihydrochalcone, whereas the fermented product is red in colour due to oxidation of the constituent polyphenols. Oxidation of aspalathin produces dihydro-iso-orientin. Other flavonoids present in both green and red rooibos include rutin, isoquercetin, hyperoside and quercetin. Rooibos also contains volatile oils and minerals, but does not contain caffeine. The tannin content of rooibos tea is less than 5%.
Use and indications
Rooibos teas have been traditionally used in South Africa for a wide range of aliments including asthma, colic, headache, nausea, depression, diabetes and hypertension. Currently, rooibos is principally used to produce a tea-like beverage. In experimental studies, it has shown some antioxidant, chemopreventive and immunomodulating effects.
Pharmacokinetics
Rooibos appears to induce the cytochrome P450 isoenzyme CYP3A4, see midazolam. For information on the pharmacokinetics of individual flavonoids present in rooibos, see under flavonoids.
Interactions overview
Midazolam levels are reduced by rooibos tea in vitro and in rats, but clinical evidence for an interaction is lacking. Rooibos tea does not appear to affect iron absorption. For information on the interactions of individual flavonoids present in rooibos, see under flavonoids.
Rooibos + Food
No interactions found.
Rooibos + Herbal medicines
No interactions found.
Rooibos + Iron compounds
Rooibos tea does not appear to significantly reduce the absorption of iron.
Clinical evidence
In a parallel group study in healthy subjects, mean iron absorption after ingestion of radiolabelled iron 16 mg with a beverage was 7.25% with rooibos tea, 1.7% with tea and 9.34% with water. Note that tea is known inhibit iron absorption, see Tea + Iron compounds.
Experimental evidence
No relevant data found.
Mechanism
Rooibos does not appear to reduce the absorption of iron. It contains some polyphenolic flavonoids which might bind iron in the gut; however, these differ from the polyphenols found in tea, such as the catechins, which have reported to affect iron absorption. Tannins found in tea are also thought to reduce iron absorption, but rooibos tea has less than 5% tannins.
Importance and management
The evidence suggests that rooibos does not reduce the absorption of iron. No special precautions are likely to be required.
Rooibos + Midazolam
The interaction between rooibos tea and midazolam is based on experimental evidence only.
Clinical evidence
No interactions found.
Experimental evidence
An in vitro study investigating the effects of rooibos tea on midazolam pharmacokinetics found that a 10% solution of rooibos tea 4 g/L brewed for 5 minutes reduced the levels of the 4-hydroxy metabolite of midazolam to undetectable levels. A subsequent study in rats found that an unrestricted amount of rooibos tea given for 2 weeks reduced the AUC and maximum concentration of a single 20-mg/kg oral dose of midazolam by 70% and 64%, respectively. Intestinal metabolism appeared to be more affected than hepatic metabolism.
Mechanism
Midazolam is a substrate of the cytochrome P450 isoenzyme CYP3A4. These studies suggest that rooibos tea induces CYP3A4, mainly in the intestine, thereby increasing midazolam metabolism and decreasing its levels.
Importance and management
Although the data are limited and there appear to be no clinical studies, it would seem that rooibos tea may have the potential to significantly reduce the levels of midazolam, and therefore reduce its efficacy. However, the amount of rooibos tea required to significantly inhibit CYP3A4 in humans, and produce a clinically important reduction in drug levels, is unknown. Nevertheless, until more is known, it would seem prudent to monitor the outcome of concurrent use, being alert for a decrease in the efficacy of midazolam.
Midazolam is used as a probe drug for CYP3A4 activity, and therefore these results also suggest that a pharmacokinetic interaction between rooibos and other CYP3A4 substrates is possible. See the table Drugs and herbs affecting or metabolised by the cytochrome P450 isoenzyme CYP3A4 for a list of known CYP3A4 substrates.
