Herb-Drug Interactions: Parsley

2011

Petroselinum crispum (Mill.) A.W.HiII (Apiaceae)

Synonym(s) and related species

Apium petroselinum L., Carum petroselinum (L.) Benth., Petroselinum peregrinum (L.) Lag., Petroselinum sativum Hoffm., Petroselinum vulgare Lag.

Constituents

All parts of the parsley plant contain similar compounds but possibly in different proportions. The most important constituents are the natural coumarins (furanocoumarins including bergapten, psoralen, 8- and 5-methoxypsoralen), and the phthalides Z-ligustilide, cnidilide, neocnidilide and senkyunolide. Flavonoids present include apigenin, luteolin and others. There is also a small amount of volatile oil present, in all parts but especially the seed, containing apiole, myristicin, eugenol, osthole, carotol and others.

Use and indications

Parsley root and seed are traditionally used as a diuretic, carminative and for arthritis, rheumatism and other inflammatory disorders. The leaves are used as a culinary herb in foods.

Pharmacokinetics

A small study in mice reported that a parsley root extract reduced the liver content of cytochrome P450 when compared with control animals. The general significance of this is unclear and further study is needed. For information on the pharmacokinetics of individual flavonoids present in parsley, see under flavonoids.

Interactions overview

A single case reports lithium toxicity in a patient who took a herbal diuretic containing parsley, among many other ingredients. A patient taking warfarin had an increase in his INR when he stopped taking a regular supplement containing various vitamin K-containing plants, including parsley. For information on the interactions of individual flavonoids present in parsley, see under flavonoids.

Parsley + Aminophenazone

The interaction between parsley and aminophenazone is based on experimental evidence only.

Evidence, mechanism, importance and management

A study in mice found that parsley (extracted from the rhizome and mixed with water and olive oil in a ratio of 4:3:3), given 2 hours before a single 60-mg/kg dose of aminophenazone, potentiated and prolonged the analgesic action of aminophenazone.

The authors of this study suggest that it is possible that the parsley extract reduced the metabolism of aminophenazone by cytochrome P450, as the overall content of cytochrome P450 in the livers of the mice given parsley was significantly reduced, when compared with the control group.

The clinical relevance of this small preliminary study is unclear and further study is needed, particularly as parsley is commonly used in food.

Parsley + Food

No interactions found. Parsley is commonly used in food.

Parsley + Herbal medicines

No interactions found.

Parsley + Lithium

A woman developed lithium toxicity after taking a herbal diuretic.

Evidence, mechanism, importance and management

A 26-year-old woman who had been taking lithium 900 mg twice daily for 5 months, with hydroxyzine, lorazepam, propranolol, risperidone and sertraline, came to an emergency clinic complaining of nausea, diarrhoea, unsteady gait, tremor, nystagmus and drowsiness, (all symptoms of lithium toxicity). Her lithium level, which had previously been stable at 1.1 mmol/L, was found to be 4.5 mmol/L. For the past 2 to 3 weeks she had been taking a non-prescription herbal diuretic containing corn silk, Equisetum hyemale, juniper, ovate buchu, parsley and bearberry, all of which are believed to have diuretic actions. The other ingredients were bromelain, paprika, potassium and vitamin B^.

The most likely explanation is that the herbal diuretic caused the lithium toxicity. It is impossible to know which herb or combination of herbs actually caused the toxicity, or how, but this case once again emphasises that herbal remedies are not risk free just because they are natural. It also underscores the need for patients to avoid self-medication without first seeking informed advice and monitoring if they are taking potentially hazardous drugs like lithium.

Parsley + Paracetamol (Acetaminophen)

The interaction between parsley and paracetamol (acetaminophen) is based on experimental evidence only.

Evidence, mechanism, importance and management

A study in mice found that parsley (extracted from the rhizome and mixed with water and olive oil in a ratio of 4:3:3), given 2 hours before a single 80-mg/kg dose of paracetamol, potentiated and prolonged the analgesic action of paracetamol to an extent that was statistically significant.

The authors suggest that it is possible that the parsley extract reduced the metabolism of paracetamol by cytochrome P450, as the overall content of cytochrome P450 in the livers of the mice given parsley was significantly reduced, when compared with the control group.

The clinical relevance of this small preliminary study is unclear and further study is needed, particularly as parsley is commonly used in food.

Parsley + Pentobarbital

The interaction between parsley and pentobarbital is based on experimental evidence only.

Experimental evidence, mechanism, importance and management

A study in mice found that parsley (extracted from the rhizome and mixed with water and olive oil in a ratio of 4:3:3), given 2 hours before a single 40-mg/kg dose of pentobarbital significantly extended the sleeping time, when compared with a control group of animals who received pentobarbital alone. This effect was not seen when the same parsley extract was given 30 minutes before pentobarbital.

The authors suggest that it is possible that the parsley extract reduced the metabolism of pentobarbital by cytochrome P450, as the overall content of cytochrome P450 in the livers of the mice given parsley was significantly reduced compared with the control group.

The clinical relevance of this small preliminary study is unclear and further study is needed, particularly as parsley is commonly used in food.

Parsley + Warfarin and related drugs

A man had a rise in his INR after stopping taking a herbal nutritional supplement (Nature’s Life Greens), which contained a number of plants including parsley.

Clinical evidence

A 72-year-old man stabilised on warfarin was found to have an INR of 4.43 at a routine clinic visit, which was increased from 3.07 six weeks previously. The patient had stopped taking a herbal product Nature’s Life Greens that month because he did not have enough money to buy it. He had been taking it for the past 7 years as a vitamin supplement because he had previously been instructed to limit his intake of green leafy vegetables. He was eventually restabilised on warfarin and the same nutritional product.

Experimental evidence

No relevant data found.

Mechanism

The product label listed 25 vegetables without stating the amounts or concentrations, but at least 5 of the listed ingredients are known to contain high levels of vitamin K1 including parsley, green tea leaves, spinach, broccoli, and cabbage. It is therefore likely that the supplement contained sufficient vitamin to antagonise the effect of the warfarin so that when it was stopped warfarin requirements fell and, without an appropriate adjustment in dose, this resulted in an increased INR.

Importance and management

The interaction of vitamin K1 from vegetables with warfarin is well established. However, the evidence suggests that, in patients with normal vitamin K1 status, in general, clinically relevant changes in coagulation status require large continued changes in intake of vitamin K1 from foods. It is unlikely that the parsley alone caused this effect, and there appear to be no other published cases of parsley reducing the efficacy of warfarin and related anticoagulants. 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.

Nevertheless, some consider that increased INR monitoring is required in any patient wanting to stop or start any herbal medicine or nutritional supplement.