Herb-Drug Interactions: Rhodiola

2011

Rhodiola rosea L. (Crassulaceae)

Synonym(s) and related species

Arctic root, Golden root, Rodiola, Rose root.

Sedum rosea (L.) Scop., Sedum roseum (L.) Scop.

Other Rhodiola species may also used, particularly in Chinese medicine.

Constituents

The main active constituents of rhodiola rhizome and root are thought to be the rosavins (a complex series of monoterpene alcohol and phenylpropanoid glycosides such as rosin, rosarin and rosavin), rosiridin and tyrosol. Rhodiola also contains flavonoids such as kaempferol and its glycoside derivatives, sterols (beta-sitosterol), tannins, and rhodiolosides or salidrosides (a series of hydroxylated, methoxylated and methylated octadienyl and octenyl glucosides). There is also a small amount of essential oil (about 0.05%).

Use and indications

Rhodiola is widely used throughout the world, and the different species are used for similar purposes. It is considered to be an adaptogen, used for coping with stress, improving mood and alleviating depression. There is a large amount of pharmacological evidence available in support of its use and studies have shown that it can improve both physical and mental performance, reduce fatigue and prevent altitude sickness. However the evidence is of variable quality and the clinical efficacy of rhodiola remains to be conclusively demonstrated.

Pharmacokinetics

An in vitro study found that an extract of rhodiola root inhibited the cytochrome P450 isoenzyme CYP3A4; the extent of the inhibition increased with increasing concentrations of rosarin. The manufacturer of a licensed rhodiola product reports that in an in vitro study, a rhodiola extract 10 micrograms/mL inhibited CYP2C9 and CYP2C19. However, in another study, an extract of rhodiola did not affect the metabolism of warfarin, which is a substrate of CYP2C9. Rhodiola did not affect the metabolism of theophylline, and therefore seems unlikely to affect the metabolism of other drugs that are substrates of CYP1A2. For information on the pharmacokinetics of individual flavonoids present in rhodiola, see under flavonoids.

Interactions overview

Rhodiola does not appear to affect the pharmacokinetics of theophylline or warfarin. The concurrent use of pepper may diminish the antidepressant effects of rhodiola. For information on the interactions of individual flavonoids present in rhodiola, see under flavonoids.

Rhodiola + Food

No interactions found.

Rhodiola + Herbal medicines; Pepper

The interaction between rhodiola and warfarin is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

A study in rats found that the addition of piperine, an alkaloid found in pepper, to an extract of rhodiola (SHR-5, containing rhodioloside 2.7%, rosavin 6% and tyrosol 0.8%), unexpectedly reduced the antidepressant activity of rhodiola. The maximum plasma concentration of rhodioloside was reduced by 22%, and the AUC and maximum plasma concentration of rosavin were increased by 33% and 82%, respectively.

Mechanism

The exact constituents of rhodiola that are responsible for antidepressant activity are not fully established. Rhodioloside alone possesses some antidepressant activity. Although rosavin alone does not appear to be an antidepressant, when given in combination with other rhodiola constituents including rhodioloside the antidepressant effects are enhanced. Changes in the pharmacokinetics of the constituents of rhodiola by piperine may have diminished its antidepressant activity. The authors suggest that this may be due to the inhibition of the cytochrome P450 isoenzyme CYP1A1 by piperine.

Importance and management

Evidence is limited to one experimental study and extrapolating these findings to a clinical setting is difficult. Although the effect of using both of these herbal medicines in humans is unknown, due to the unpredictable effects that may occur when piperine is taken with rhodiola, notably a reduction in antidepressant effects, the authors of this study suggest that concurrent use should be avoided. Given that the outcome of concurrent use is likely to be opposite to the desired effects, this seems a reasonable recommendation.

Rhodiola + Theophylline

The interaction between rhodiola and theophylline is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a study, rats were given a standardised rhodiola extract (SHR-5, containing rhodioloside 2.7%, rosavin 6% and tyrosol 0.8%) twice daily for 3 days with a single dose of aminophylline, given one hour after the last dose of rhodiola extract. The pharmacokinetics of theophylline were only slightly affected by the rhodiola extract (less than 15% decrease in AUC and maximum levels).

Mechanism

Unknown.

Importance and management

Information appears to be limited to this one study in rats, which may not necessarily extrapolate directly to humans. However, what is known suggests that rhodiola extract is unlikely to have a clinically significant effect on the pharmacokinetics of theophylline.

Rhodiola + Warfarin

The interaction between rhodiola and warfarin is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a study, rats were given a standardised rhodiola extract (SHR-5, containing salidroside 2.5%, rosavin 3.9% and tyrosol 0.8%) twice daily for 3 days with a single dose of warfarin, given one hour after the last dose of rhodiola extract. The maximum levels of warfarin were increased by a modest 34%, but the AUC and half-life were not altered by rhodiola. Furthermore, the anticoagulant effects of warfarin (assessed by monitoring PTT) were unaffected.

Mechanism

Unknown. In other in vitro studies, rhodiola inhibited the activity of the cytochrome P450 isoenzyme CYP2C9, which metabolises the S-warfarin isomer. See Pharmacokinetics.

Importance and management

Information appears to be limited to this one study in rats, which may not necessarily extrapolate directly to humans. However, what is known suggests that rhodiola extract is unlikely to affect the response to treatment with warfarin.