Herb-Drug Interactions: Cocoa

2011

Theobroma cacao L. (Sterculiaceae)

Synonym(s) and related species

Cacao, Chocolate, Chocolate tree, Theobroma.

Pharmacopoeias

Chocolate (US Ph 32); Cocoa Butter (US Ph 32); Theobroma Oil (British Pharmacopoeia 2009).

Constituents

Cocoa seeds contain xanthine derivatives, principally theobromine (1% to 4%), with small amounts of caffeine (up to about 0.4%) and other alkaloids. They are also rich in flavonoids from the flavanol and procyanidin groups, mainly catechin and epicatechin and their polymers. The nibs (cotyledons) are a rich source of cocoa butter (theobroma oil), which contains oleic, stearic, palmitic and linoleic acids.

Use and indications

The seeds roasted and powdered are the source of cocoa, which is mainly used as a food (in chocolate). Medicinal uses include as a stimulant and as a diuretic; effects that can be attributed to the xanthine content. However, note that theobromine is a much weaker xanthine than caffeine. Cocoa butter is used as an emollient and pharmaceutical excipient. More recently, there has been interest in the possible beneficial effects of cocoa consumption on cardiovascular health, because of its high content of flavonoids.

Pharmacokinetics

The pharmacokinetics of caffeine are discussed under caffeine. In one study, caffeine absorption from chocolate was slower with a lower maximum concentration than from capsules, whereas theobromine absorption was faster with higher maximum concentration than from capsules. For information on the pharmacokinetics of individual flavonoids present in cocoa, see under flavonoids.

Interactions overview

Although the use of cocoa supplements has been cautioned by some in diabetic patients, there seems little evidence to support this. Dark chocolate may slightly decrease blood pressure in hypertensive patients, but caffeine from cocoa may have the opposite effect. Famotidine and foods have no effect, or only modest effects, on the absorption of flavanols from cocoa. Cocoa may reduce the absorption of iron.

Cocoa contains small amounts of caffeine compared with some other caffeine-containing herbs. Although it contains high levels of theobromine, this has weak xanthine effects when compared with caffeine. Nevertheless, when taken in sufficient quantities, cocoa could produce levels of caffeine sufficient to cause interactions, see caffeine.

For information on the interactions of individual flavonoids present in cocoa, see under flavonoids. Of particular note are studies showing that cocoa flavanols, might have antiplatelet effects, and that these might be additive with aspirin, see Flavonoids + Anticoagulants or Antiplatelet drugs.

Cocoa + Anticoagulant or Antiplatelet drugs

For studies showing that cocoa flavanols might have antiplatelet effects, and that these might be additive with aspirin, see Flavonoids + Anticoagulant or Antiplatelet drugs.

Cocoa + Antidiabetics

Although the use of cocoa supplements has been cautioned by some in diabetic patients, there seems little evidence to support this.

Evidence, mechanism, importance and management

The traditional advice in diabetes is to avoid or limit intake of chocolate. This is principally because of the high calorific value of chocolate, and its high sugar content (particularly milk chocolates). In one study, an isomalt-based chocolate (about 45% w/w) had a lower glycaemic effect than a sucrose-based chocolate (about 45% w/w), which confirms the concerns regarding the sucrose content. Conversely, in animal studies, cocoa extract containing high levels of procyanidins had beneficial effects on blood-glucose levels. In addition, in one study in patients with untreated essential hypertension, an improvement in glucose and insulin responses was found during an oral glucose tolerance test, and a slightly lower fasting blood-glucose level was seen, after subjects ate 100 g of dark chocolate daily for 15 days (substituted for food of similar energy and macronutrient composition). This effect was not seen with 90 g of white chocolate daily. Taken together, the evidence suggests that cocoa in itself, and cocoa supplements, should not be a problem in diabetics and should not interfere with blood-glucose control.

Cocoa + Antihypertensives

Dark chocolate may slightly decrease blood pressure in hypertensive patients, but caffeine from cocoa may have the opposite effect.

Evidence, mechanism, importance and management

There has been some interest in the possible beneficial effects of cocoa consumption on cardiovascular health, because of its high content of flavonoids. In a meta-analysis of five short-term randomised controlled studies, daily consumption of high doses (46 to 100 g daily) of dark chocolate, or 105 g daily of milk chocolate, all containing high levels of flavonoids, caused a modest 4.7 and 2.8 mmHg reduction in systolic and diastolic blood pressure, respectively. Another study with a lower dose (6.3 g daily) showed a smaller effect (2.9/1.9 mmHg reduction).

These studies show that high doses of dark chocolate 100 g daily modestly decrease blood pressure, an effect attributed to its flavonoid content. This suggests that blood pressure control is unlikely to be significantly affected by cocoa supplements in patients with hypertension. None of the patients in these studies was taking antihypertensive medication so some caution would still be needed.

Theoretically, the caffeine content in cocoa could result in increases in blood pressure, and therefore large quantities of cocoa supplements could be inadvisable in patients with hypertension, see Caffeine + Antihypertensives.

Cocoa + Famotidine

Famotidine has no effect on the absorption of flavanols from cocoa.

Evidence, mechanism, importance and management

In a study in 6 healthy subjects, a single 20-mg dose of famotidine given one hour before consumption of sugar-free, flavanol-rich cocoa had no effect on the AUC of flavanols. It was concluded that alteration of gastric pH had no effect on flavanol absorption. No special precautions appear to be necessary.

Cocoa + Food

Food has no effect, or only modest effects, on the absorption of flavanols from cocoa.

Evidence, mechanism, importance and management

In a series of studies in 6 healthy subjects, high-carbohydrate foods (bread or sugar) increased the flavanol AUC by about 40% after consumption of 125 micrograms/kg of sugar-free, flavanol-rich cocoa. Lipid and protein-rich foods (butter or steak) and whole milk had little effect on flavanol absorption. Grapefruit juice had a minor effect (20% increase), which was attributed to its carbohydrate content.

This study demonstrated that carbohydrates can increase oral flavanol absorption from cocoa. However, the extent is modest, and probably of little clinical relevance.

Cocoa + Herbal medicines

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

Cocoa + Iron compounds

Cocoa may reduce the absorption of iron.

Clinical evidence

In a study in 10 healthy subjects a 275 mL serving of cocoa beverage reduced the absorption of radiolabelled iron from a 50 g bread roll by about 70%. In this study, the inhibitory effect of cocoa beverage on iron absorption was only slightly less that of black tea (Assam tea, Camellia sinensis). Note that black tea is known to inhibit iron absorption, see Tea + Iron compounds.

Experimental evidence

No relevant data found.

Mechanism

The polyphenols in cocoa may bind to iron in the gastrointestinal tract and reduce its absorption.

Importance and management

Evidence appears to be limited to this one study, but be aware that some beverages such as cocoa might reduce iron absorption similarly to conventional tea. See Tea + Iron compounds, for further discussion of the possible impact of this interaction.