Herb-Drug Interactions: Lycopene

Types, sources and related compounds

E160(d).

Pharmacopoeias

Lycopene (US Ph 32); Lycopene preparation (US Ph 32); Tomato extract containing lycopene (The United States Ph 32).

Use and indications

Lycopene is a carotenoid – a natural red pigment found in plants including some fruit and vegetables (such as tomatoes) – and is therefore eaten as part of a healthy diet, and is also used as a food colouring. It has been used for age-related macular degeneration and its antioxidant properties have been investigated for possible use in cardiovascular disease and cancer prevention, especially prostate cancer.

Pharmacokinetics

Lycopene is similar to betacarotene, the most widely studied carotenoid, but, unlike betacarotene, it is not a precursor to vitamin A. A study in 25 healthy men found that the amount of lycopene absorbed from a single dose of up to 120 mg was less than 6mg in 80% of subjects, regardless of dose.

Interactions overview

There is very little information on the interactions of lycopene supplements, but there is some information on dietary lycopene. Combined use with sucrose polyesters, colestyramine, probucol or betacarotene modestly reduces dietary lycopene absorption. Lycopene does not appear to affect the absorption of betacarotene. A low-fat diet does not alter dietary lycopene absorption when dietary intake is high. Colchicine and orlistat modestly reduce the absorption of the related carotenoid, betacarotene, probably because of their effects on fat absorption. If the mechanism is correct, lycopene levels could also be affected, see Betacarotene + Colchicine and Betacarotene + Orlistat.

Lycopene + Colchicine

Colchicine modestly reduces the absorption of the related carot-enoid, betacarotene, potentially because of its effects on fat absorption. Because lycopene levels tended to be lower in those taking low-fat diets (see food, below), if the mechanism is correct, lycopene levels may also be affected by colchicine, see Betacarotene + Colchicine.

Lycopene + Food

A low-fat diet is unlikely to alter the absorption of lycopene when the dietary intake of lycopene is high.

Clinical evidence

There do not appear to be any studies on the effect of food on the absorption of lycopene from supplements; however, there are studies on the effect of foods on absorption of dietary lycopene. In one crossover study in 13 healthy men eating a diet with a controlled carotenoid content and high in lycopene, there was no significant difference in the serum levels of lycopene between a high-fat monounsaturated-fatenriched diet, or a high-carbohydrate low-fat diet. Lycopene was consumed as 300 g tomato soup and 60 g of tomato paste every day for 14 days. Similarly, no change in serum lycopene levels or betacarotene levels were found in a 12-month study in women randomised to a control diet or a low-fat diet, although plasma lycopene levels tended to be lower in those on the low-fat diet.

Experimental evidence

In an experimental study in rats fed a diet including lycopene 250mg/kg for 3 weeks, food restriction of 20% significantly increased the accumulation of lycopene in the liver by about 70% and reduced the serum lycopene levels by about 90%.

Mechanism

Carotenoids are transported in plasma in lipoprotein cholesterol. The study in humans indicates that in situations of abundant lycopene intake, the fat content of the diet does not affect absorption. In a situation of food restriction, the distribution of carotenoids is also restricted because the circulating total lipid concentrations are reduced, thus resulting in a reduction in the serum levels and accumulation in the liver.

Importance and management

The available data suggest that diet, especially dietary fat, is unlikely to alter the absorption of lycopene when the dietary intake of lycopene is high. This might therefore apply to lycopene supplements, but further study is needed to confirm the absence of an effect of food on their absorption.

Lycopene + Herbal medicines; Betacarotene

The absorption of endogenous lycopene and lycopene given as a supplement may be altered by betacarotene supplementation. The absorption of betacarotene appears to be unaffected.

Clinical evidence

In a study in 10 healthy subjects, a single 60-mg dose of betacarotene given with a single 60-mg dose of lycopene appeared to significantly increase the AUC of lycopene by about fourfold when compared with lycopene given alone. Betacarotene levels remained the same when given alone and when given with lycopene. However, it was unclear whether absorption was complete by the 24-hour time point, and there was large variation in the absorption of the carotenoids between subjects in this study.

In contrast, in a study in 5 healthy subjects (not taking any lycopene supplements), very high-dose betacarotene 300 mg daily for 21 days decreased the levels of endogenous lycopene by about 30%.

Experimental evidence

In a study in ferrets, although the serum levels of betacarotene following a single 10-mg/kg dose were reduced by a single 10-mg/kg dose of lycopene, the average reduction was not significant.

Mechanism

Unclear. There is some debate as to whether these two carotenoids share the same biochemical pathways and compete for absorption, or whether the chemical nature of the preparations in which the supplements are taken affects absorption kinetics.

Importance and management

The evidence is limited, but it suggests that absorption of betacarotene from supplements is affected only modestly, if at all, by lycopene supplements, whereas betacarotene supplements might increase absorption of lycopene supplements taken at the same time. However, the clinical relevance of this, if any, is uncertain. Note that the doses of betacarotene used in the studies are much higher than the maximum daily dose of supplements of 7mg recommended by the Food Standards Agency in the UK.

Lycopene + Lipid regulating drugs

Colestyramine and probucol reduce the serum levels of lycopene eaten as part of a normal diet.

Clinical evidence

There do not appear to be any studies on the effect of lipid regulating drugs on the absorption of lycopene from supplements; however, one 3-year study of 303 hypercholesterolaemic subjects given colestyramine in doses of 8 g to 16 g daily, according to tolerance, found that the serum levels of dietary-derived lycopene were reduced by about 30% after 2 months. When probucol 500 mg twice daily was then added, the serum levels of lycopene were reduced by another 30% after a further 2 months. After the initial 6-month period, patients were randomised to receive probucol or placebo, and all continued to take colestyramine. In those patients randomised to the placebo group, it took about 1 year for the lycopene levels to return to the pre-probucol level and, in those randomised to probucol, lycopene levels remained at the same low level and did not drop further.

Experimental evidence

No relevant data found.

Mechanism

Colestyramine and probucol are lipid regulating drugs that reduce the levels of low-density-lipoprotein-cholesterol and high-density-lipoprotein-cholesterol respectively. Colestyramine also reduces the intestinal absorption of lipids and the authors suggest that probucol may also displace lycopene from very-low-density-lipoprotein-cholesterol in the liver. All these factors may contribute to the reduction of lycopene serum levels because lycopene is fat soluble and therefore its absorption and distribution are dependent on the presence of lipoproteins.

Importance and management

This long-term study suggests that colestyramine and probucol reduce the serum levels of lycopene eaten as part of a normal diet. Supplemental lycopene does not appear to have been studied, but be aware that its desired effect may be reduced by colestyramine and probucol.

Lycopene + Orlistat

Orlistat modestly reduces the absorption of the related carotenoid, betacarotene, probably because of its effects on fat absorption. Because lycopene levels tended to be lower in those taking low-fat diets (see food) they may also be affected by orlistat, see Betacarotene + Orlistat.

Lycopene + Sucrose polyesters

Olestra reduces the serum levels of lycopene eaten as part of a normal diet.

Clinical evidence

There do not appear to be any studies on the effect of sucrose polyesters on the absorption of lycopene from supplements; however, in one study in 194 healthy subjects, the serum levels of dietary lycopene were reduced by up to about 30% by Olestra 18 g daily. Olestra is a sucrose polyester that is a non-absorbable, non-calorific fat ingredient in snack foods.

Experimental evidence

No relevant data found.

Mechanism

Olestra is thought to reduce the absorption of fat-soluble vitamins when present at the same time in the gastrointestinal tract.

Importance and management

Evidence is limited to data on dietary lycopene and it is not known whether Olestra or other sucrose polyesters will reduce the absorption of supplemental lycopene; however, it has been found that the baseline levels of vitamin A have been maintained when subjects take vitamin A supplements with Olestra, and theoretically, at least, this may also be the case with lycopene. The manufacturers of Olestra state that, because snacking is just a part of the normal balanced diet and because there is a lack of scientific agreement on the health benefits of carotenoids, it is not necessary to take carotenoid supplements with Olestra. It should also be pointed out that the intake of Olestra in this study is far higher than the average daily intake from snack foods. Nevertheless, separating the intake of lycopene and sucrose polyesters should be enough to avoid any possible interaction.