Lycopene

Pronunciation

Lycopene (lie-koh-peen)

Summary

Lycopene is a non-provitamin A carotenoid that is responsible for the red and pink coloration of certain fruits, such as tomatoes, pink grapefruit, watermelon, papaya, and guava. Lycopene derived from tomato (Solanum lycopersicum) has been most widely studied source and accounts for significant portions of its dietary intake (71). Additionally, processed tomato products (e.g. ketchup, tomato juice, sauces) containing lycopene are often highly consumed in the U.S. (86). Of note, processed products such as ketchup, tomato paste, and spaghetti sauce contain 16-17mg/100g, fresh tomatoes contain 12 mg/100g (2).

Lycopene is most commonly recognized as an antioxidant with roles in preventing oxidative stress in cardiovascular disease, male infertility, osteoporosis, hypertension, neurodegenerative diseases, and inflammatory diseases (9). Studies have also demonstrated its potential use in prostate conditions (96), though the limited evidence is not conclusive in its effectiveness (35, 36).

Main Medical Uses

Lycopene supplementation can decrease biomarkers of oxidative stress observed in diseases such as CVD or cancer (4, 7, 10, 17, 18, 46, 55, 72, 100). Evidence supports tomato intake and the use of lycopene supplementation in lowering cardiovascular risk factors in cardiovascular disease (11, 12, 26, 58, 67), coronary heart disease (60) and metabolic syndrome (80). Lycopene may be used in treating benign prostatic hyperplasia (79), asthma (64, 97), hypertension (22, 70), hyperlipidemia (60), leukoplakia (83, 98), and oral submucous fibrosis (41, 49, 77), as well as in managing type II diabetes (65, 91), and infertility (24, 30, 62, 66). While animal and in vitro studies demonstrate the potential benefits of lycopene for eye health (e.g. 28, 29, 31, 37), conflicting epidemiological evidence exists for its use in eye-related conditions, such as age-related macular degeneration (25, 57) and cataracts (16, 19).

Dosing and Administration

For an explanation of the classes of evidence, please see the Rating Scales for Evidence-Based Decision Support.

Adverse Effects

The observed level of safety for lycopene has been described at 75mg per day, though higher concentrations have been ingested without adverse effects (81). Doses of lycopene as high as 120 mg per day have been ingested without adverse effects in healthy subjects (21) and has been shown to be safe at this dose after a year of consumption (13). Rare instances of allergic skin reactions have been reported (18).

Proprietary Extracts

Associated Interactions and Depletions

For an explanation of the classes of evidence, please see the Rating Scales for Evidence-Based Decision Support.

Pharmacokinetics

Absorption

Approximately 10-30% of lycopene is absorbed after oral intake (9) via passive diffusion in the intestine and into enterocytes across the apical membrane (86). This process may be facilitated with the scavenger receptor class B type I (SR-BI) cholesterol membrane transporter (63). After absorption into the enterocytes, carotenoids are transported across the basolateral membrane via chylomicrons and enter the lymphatic system for eventual transport in the blood (21, 86). Lycopene absorption is saturable (21). Regardless of the dose, 80% of subjects were reported to absorb less than 6 mg, while average absorption ranged between 1.78-14.28 mg, suggesting large interindividual variability for lycopene absorbability (21).

Distribution

The SR-BI cholesterol membrane transporter also located in the liver, adrenals, ovaries, placenta, kidneys, prostate, and brain (95). Lycopene is distributed in highest concentrations to the testes, and then sequentially to the adrenals, liver, prostate, breast, pancreas, skin, colon, ovaries, lungs, stomach, kidney, adipose tissues, and cervix, thereafter (9). Lycopene’s peak serum concentration is achieved within 24-48 hours and has a half-life of 2-3 days (84).

Bioavailability

A number of factors affect the bioavailability of lycopene. Lycopene can exist in all-trans, cis, or tetra-cis conformations (86). Cis-isomers appear to be the most bioavailable (14, 89). Uptake of cis-isomers have been shown to be significantly greater than all-trans lycopene and this may be due to its greater micellization (23). Post-ingestion, all-trans-lycopene can be converted to cis-lycopene (75). Bioavailability can increase when lycopene is derived from processed sources (eg.. tomato paste, ketchup, etc) compared with fresh tomatoes (3, 27), or when lycopene is co-ingested with dietary lipid sources (8, 88). Acute administration of lycopene with other carotenoids can diminish its absorption into chylomicrons, but this attenuates with longterm co-ingestion (87).

Metabolism

Lycopene neither induced CYP1A2, CYP2D6, and CYP3A4 (47), nor had activity with CYP3A4, CYP2C9, CYP2C19, CYP2D6 or P-gp, but moderately inhibited CYP2E1 in vitro (48). Whole tomato powder has been shown to decrease CYP2E1 proteins levels that were previously increased by alcohol in rats. However, this effect was not observed with tomato extract and purified lycopene (85). Another in vitro study indicated that lycopene inhibited recombinant CYP1A1 and CYP1B1 and increased microsomal uridine diphosphate (UDP)-glucuronosyltransferases (UGT) activity, indicating that lycopene may play a role in inhibiting phase I and increasing phase II enzymatic metabolism (94).

β-carotene 9′,10′-oxygenase (BCO2) appears to be the enzyme involved in the metabolism of lycopene. Cleavage by BCO2 can produce the apo-10′-lycopenal intermediate, which can then, in turn, be oxidized to apo-10′-lycopenoic acid or reduced to apo-10′-lycopenol using NAD+ or NADH as co-factors (95). Evidence suggests that lycopene may also be metabolized to CO2 via B-oxidation and metabolites excreted in urine (75).

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