Herb-Drug Interactions: Coffee

Coffea L. species. (Rubiaceae)

Synonym(s) and related species

Arabian coffee is from Coffea arabica.

Robusta coffee is from Coffea canephora (Pierre ex Froehner) also known as Coffea robusta (Linden ex De Wild.).

Other species include Coffea liberica.

Constituents

The kernel of the dried coffee bean contains xanthine derivatives, the main one being caffeine (1 to 2%), with some theobromine and theophylline. It also contains polyphenolic acids such as chlorogenic acids and various diterpenes (e.g. kahweol, cafestrol).

Use and indications

Coffee has been used as a stimulant and diuretic. However, when roasted, coffee beans are most commonly used as a beverage.

Pharmacokinetics

The pharmacokinetics of caffeine are discussed under caffeine. Evidence suggests that chlorogenic acid is hydrolysed in the gastrointestinal tract to free caffeic acid, which is then conjugated to form the glucuronate or sulphate.

Interactions overview

Coffee contains significant amounts of caffeine, so the interactions of caffeine, are relevant to coffee, unless the product is specified as decaffeinated. By virtue of its caffeine content, coffee may also cause serious adverse effects if used with other drugs or herbs with similar effects, such as ephedra. Evidence is conflicting, but in general the long-term use of coffee does not appear to be detrimental to the control of diabetes; however, coffee may have a small adverse effect on blood pressure control. Coffee may reduce the absorption of iron and the absorption of nicotine from chewing gum, but does not appear to affect the absorption of aspirin or tetracycline. A case report describes mania in a patient who drank coffee and took phenylpropanolamine. For the possible increase in clozapine effects with caffeine, sometimes from coffee, see Caffeine + Clozapine.

Coffee + Antidiabetics

Evidence is conflicting, but in general the long-term use of coffee does not appear to be detrimental to the control of diabetes.

Evidence, mechanism, importance and management

There is a lot of epidemiological evidence that coffee consumption is associated with a reduced risk of type 2 diabetes (this has been the subject of a review). In addition, a large prospective cohort study in Finland found that coffee drinking was associated with reduced total and cardiovascular disease mortality.

In contrast, some short-term randomised studies have found that coffee consumption had detrimental effects on insulin sensitivity in healthy subjects (high consumption of filtered coffee over 4 weeks)and increased postprandial hyperglycaemia in patients with type 2 diabetes taking unnamed oral antidiabetic drugs (caffeine added to decaffeinated coffee, single dose).

The evidence is not conclusive, which makes it difficult to advise patients taking antidiabetics on use of coffee beverages or supplements. However the Finnish study does provides some reassurance that use of coffee may not be detrimental in the long term, and may even be beneficial.

Coffee + Antihypertensives

Coffee may have a small adverse effect on blood pressure control.

Clinical evidence

Limited data are available on the effect of coffee on blood pressure in patients taking antihypertensives. In one study, two 150-mL cups of coffee (made from 24 g of coffee) increased the mean blood pressure of 12 healthy subjects taking propranolol 240 mg, metoprolol 300 mg or a placebo. Mean blood pressure rises were 7%/22% with propranolol, 7%/19% with metoprolol and 4%/16°/o with placebo. The beta blockers and placebo were given in divided doses over 15 hours before the test. However, there are lots of short-term studies on the effect of coffee on blood pressure in healthy subjects or patients with untreated mild hypertension. In one meta-analysis of 18 randomised studies of coffee consumption, coffee drinking was associated with a very small 1.22/0.49 mmHg increase in blood pressure.

One study found that blood pressure was higher in untreated hypertensives who drank coffee (5 cups daily, each containing approximately 60 mg caffeine) than in untreated hypertensives who did not drink coffee. However, coffee drinking reduced the potentially detrimental post-meal postural drop in systolic blood pressure in patients taking unnamed antihypertensives.

The only long-term studies are of epidemiological type. In one large prospective cohort study in Finland, low-to-moderate daily consumption of coffee (2 to 7 cups daily) was associated with a small (about 24 to 29%) increased risk of requiring antihypertensive drug treatment. In the Nurses Health prospective cohort, coffee consumption was not associated with an increased risk of developing hypertension.

In contrast to some of the data on coffee, chlorogenic acids from coffee have been reported to reduce blood pressure. In one randomised study in patients with mild hypertension not receiving antihypertensives, green coffee bean extract 480 mg (containing 140 mg of chlorogenic acids) daily for 12 weeks was associated with a 10/7 mmHg reduction in blood pressure. A dose-related decrease in blood pressure with green coffee extract was seen in another study. Note that green coffee is not roasted, and may therefore contain different constituents and have different effects than the usual roasted coffee, although the importance of this remains to be demonstrated.

Experimental evidence

Because of the extensive clinical evidence available, experimental data have not been sought.

Mechanism

Acute intake of caffeine raises blood pressure, but partial tolerance to this effect might possibly develop with regular consumption, see also Caffeine + Antihypertensives. Polyphenolic compounds in coffee might improve endothelial function, and might therefore lower blood pressure.

Importance and management

The evidence presented here is conflicting; however, most of the studies suggest that coffee might have a small adverse effect on blood pressure. It is possible that this does not extend to green (unroasted) coffee, and therefore supplements containing green coffee extract might not be expected to have a negative effect on blood pressure. Further study is needed.

For discussion of the adverse effect of caffeine on blood pressure, see Caffeine + Antihypertensives.

Coffee + Aspirin

Coffee does not appear to affect aspirin absorption.

Evidence, mechanism, importance and management

A study in 5 healthy subjects found that 200 mL of coffee had no effect on the rate and extent of absorption of a single 500-mg dose of aspirin, whereas 200 mL of milk reduced the bioavailability and maximum concentration of salicylates from the same dose of aspirin by a modest 30%.

No significant reduction in the bioavailability of aspirin would be expected with black coffee; however the addition of milk, depending on the quantity, may possibly reduce the absorption of aspirin.

Note that caffeine may enhance the analgesic effects of aspirin, see Caffeine + Aspirin or Diclofenac.

Coffee + Food

No specific interactions found; however, the effects of caffeine from coffee or a coffee-containing herbal medicine will be additive to those of other caffeine-containing foods or beverages.

Coffee + Herbal medicines

The caffeine content of coffee suggests that it may interact with other herbal medicines in the same way as caffeine, see Caffeine + Herbal medicines; Bitter orange, and Ephedra + Caffeine.

Coffee + Iron compounds

Coffee may possibly contribute towards the development of iron-deficiency anaemia in pregnant women, and reduce the levels of iron in breast milk. As a result their babies may also be iron deficient.

Clinical evidence

In a series of studies in healthy subjects, drinking 200 mL of coffee with various test meals containing radiolabelled iron resulted in a 39% to 83% reduction in the absorption of iron. No decrease was observed if the coffee was drunk one hour before the meal, but when the coffee was given one hour after the meal the reduction was the same as taking it simultaneously with the meal. With one meal, the effect of coffee was about half that of tea. In another study, a 275 mL serving of instant coffee reduced the absorption of radiolabelled iron from a 50 g bread roll, and this was not affected by milk.

A controlled study among pregnant women in Costa Rica found that coffee consumption was associated with reductions in the haemoglobin levels and haematocrits of the mothers during pregnancy, and of their babies shortly after birth, despite the fact that the women were taking ferric sulfate 200 mg and 500 micrograms of folate daily. The babies also had a slightly lower birth weight (3189g versus 3310g). Almost a quarter of the mothers were considered to have iron-deficiency anaemia (haemoglobin levels of less than 11 g/dL), compared with none among the control group of non-coffee drinkers. Levels of iron in breast milk were reduced by about one-third. The coffee drinkers drank more than 450 mL of coffee daily, equivalent to more than 10 g of ground coffee.

In a randomised study in Guatemalan infants, discontinuing coffee intake in those given an iron supplement led to a greater increase in serum ferritin than continuing coffee consumption (median 891 mL weekly). However, discontinuing coffee had no effect on changes in haemoglobin.

Experimental evidence

Because of the extensive clinical evidence available, experimental data have not been sought.

Mechanism

It is suggested that polyphenolics in coffee might interfere with the absorption of iron.

Importance and management

The general importance of these findings is uncertain, but be aware that coffee consumption may contribute to iron-deficiency anaemia. Note that coffee is not generally considered to be a suitable drink for babies and children, because of its effects on iron absorption. More study is needed. Consider also Tea + Iron compounds.

Coffee + Nicotine

Coffee drinking may reduce the absorption of nicotine from chewing gum.

Evidence, mechanism, importance and management

In a study in 8 otherwise healthy smokers, intermittent mouth rinsing with coffee substantially reduced salivary pH and nicotine absorption from nicotine polacrilex gum. Buccal nicotine absorption is best in an alkaline environment, which is provided by the buffering agents in the nicotine gum. Consumption of coffee reduces the pH and therefore nicotine absorption. The reduction in the absorption of buccal nicotine would apply only to beverages that affect buccal pH. Drinking coffee beverages during or immediately before nicotine gum use might therefore decrease the efficacy of this form of nicotine replacement therapy. See also Caffeine + Nicotine.

Coffee + Phenylpropanolamine

A case report describes mania in a patient who drank coffee and took phenylpropanolamine.

Evidence, mechanism, importance and management

A case report describes mania with psychotic delusions in a healthy woman (who normally drank 7 to 8 cups of coffee daily) within 3 days of her starting to take a phenylpropanolamine-containing decongestant. She recovered within one week of stopping both the coffee and the phenylpropanolamine. This appears to be the only case report of an adverse interaction specifically between coffee and phenylpropanolamine. However, case reports have described other severe reactions with caffeine, see Caffeine + Phenylpropanolamine.

Coffee + Tetracycline

Coffee does not appear to affect the absorption of tetracycline.

Evidence, mechanism, importance and management

A study in 9 healthy subjects found that 200 mL of coffee (milk content, if any, unstated) did not significantly affect the bioavail-ability of a single 250-mg dose of tetracycline.

Milk is well known to decrease the absorption of tetracyclines, and a study in 12 healthy subjects found that 16mL of evaporated milk added to 200 mL of coffee still significantly reduced tetracycline absorption (by roughly half). From the first study, it appears that coffee alone does not affect tetracycline absorption.