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Common Name

Nonprovitamin A carotenoid

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Clinical Summary

A natural pigment synthesized by plants and microorganisms, lycopene is used primarily as an antioxidant and also to prevent and treat cancer, heart disease, and macular degeneration. Lycopene has antioxidant activity and is classified as a nonprovitamin A carotenoid, other examples being lutein and zeaxanthin. Alpha-carotene, beta-carotene, and beta-cryptoxanthin are classified as provitamin A carotenoids because they can be converted into retinol. Small clinical trials suggest possible benefit against exercise-induced asthma (1), benign prostatic hyperplasia (BPH) (2), and cancer, but no optimal dosage has been established.

Lycopene enhanced docetaxel’s antitumor efficacy against prostate cancer in animal studies (22). Epidemiologic studies suggest an inverse relationship between lycopene consumption and risk of cancer (3), particularly lung (4), stomach (5), prostate (6), estrogen receptor (ER) and progesterone receptor (PR)-positive breast cancers (7). Consistent association between lycopene consumption and endometrial cancer risk has not been detected (8) (9).
Low intake of tomato sauce may be associated with advanced prostate cancer in patients with low-grade cancer at diagnosis (10) although data from other studies indicate that lycopene or tomato-based regimens does not prevent prostate cancer (11) and variable results were reported for lycopene supplementation in prostate cancer patients (12). A recent study did not find any association between levels of serum lycopene and risk of prostate cancer (23).

High doses of lycopene plus alcohol induced cytochrome P450 (CYP) 2E1 expression (13). An analysis of six commercially available brands revealed that lycopene content varied from the labeled dosage by as much as 43% (14).

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Food Sources

Tomatoes and tomato products, watermelon, guava, rose hips, and pink grapefruit
(15)

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Purported Uses
  • Asthma
  • Cancer prevention
  • Cancer treatment
  • Cardiovascular disease
  • Macular degeneration
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Mechanism of Action

Lycopene is a natural pigment synthesized by plants and microorganisms. Referred to as a nonprovitamin A carotenoid, it is not known to have any vitamin A activity. Biological actions include antioxidant activity via singlet oxygen quenching and peroxyl radical scavenging, induction of cell to cell communication, and growth control, although less efficiently than beta-carotene (15). Proposed mechanisms of action in cancer prevention include inhibition of cancer growth, induction of differentiation by modulation of cell cycle regulatory proteins, alterations in insulin-like growth factor-1 (16) or vascular endothelial growth factor (17) levels, prevention of oxidative DNA damage, and possible enhancement of carcinogen metabolizing enzymes (18). Other possible actions for all carotenoids include immunoenhancement, inhibition of mutagenesis and transformation, and inhibition of premalignant lesions. Carotenoids have also been associated with decreased risk of macular degeneration and cataracts, decreased risk for some types of cancers, and decreased risk of some cardiovascular events (19).

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Pharmacokinetics

Absorption:
Intestinal absorption of carotenoids, including lycopene, is facilitated by the formation of bile acid micelles containing carotenoids. The presence of fat in the small intestine stimulates the secretion of bile acids from the gall bladder and improves the absorption of carotenoids by increasing the size and stability of the micelles, thus allowing more carotenoids to be solubilized. Bioavailability of lycopene is affected by the dose and presence of other carotenoids such as Beta carotene (20).
Distribution:
Concentrations of lycopene in serum and body tissues are highly variable and are dependent on food source, efficiency of absorption, and amount of fat in the diet. The serum concentration after a single dose peaks at 24 to 48 hours post dose (21). Lycopene is primarily stored in adipose and liver. In both serum and tissue storage, lycopene cis-isomers constitute greater than 50 percent of the total lycopene present.
Metabolism/Excretion:
It is assumed that lycopene is excreted through the bile and kidneys (20).

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Warnings
  • A recent analysis of six commercially available brands revealed actual lycopene content to vary considerably from the labeled dosage, from 62% to 143% of the stated amount (14).

A possible interaction between lycopene and alcohol consumption was reported, indicating that cytochrome P450 (CYP) 2E1 expression (13) is induced by high doses of lycopene plus alcohol.

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Adverse Reactions

No adverse effects have been reported at normal doses.
(20)
Toxicity: Lycopenodermia has resulted following chronic ingestion of large quantities of lycopene-rich foods (i.e. tomato products) and is characterized by a deep orange discoloration of the skin.

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Herb-Drug Interactions

One large scale prospective cohort study in Netherland suggested alcohol comsumption may affect the chemopreventive properties of vitamin A.
(19)

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Literature Summary and Critique

Schwarz S, et al. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. Jan 2008;138(1):49-53.
Because epidemiological studies suggest that dietary intake of lycopene is associated with decreased prostate cancer risk, this study sought to determine if lycopene supplementation improved benign prostatic hyperplasia (BPH), which may be a risk factor for prostate cancer development. Forty participants with BPH received lycopene (15 mg/day) or placebo for 6 months after which prostate specific antigen (PSA) levels and prostate enlargement was assessed. Decreased PSA levels were detected in the intervention group whereas there were no changes in the placebo group. Furthermore, although prostate enlargement was detected in the placebo group, no changes from baseline measurements were seen in the lycopene group. Larger, long-term studies are necessary to determine if lycopene supplementation could influence prostate cancer in men with BPH.

Kucuk O, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 2001;10:861-8.
A prospective evaluation of 15 mg lycopene (n=15) or placebo (n=11), administered twice daily, in patients with localized prostate cancer undergoing radical prostatectomy 3 weeks following supplementation. Study endpoints included cell growth and differentiation, plasma levels of IGF-1 and PSA, and tumor pathology. There was no difference in baseline demographics between treatment groups. Following surgery and analysis of data, it was shown that serum levels of IGF-1 and involvement of surgical margins and/or extra-prostatic tissues with cancer was significantly lower in the lycopene group. No adverse events were noted. Although beneficial trends were seen for patients supplemented with lycopene, larger randomized studies are required to validate results.

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References
  1. Neuman I, Nahum H, Ben-Amotz A. Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy 2000;55:1184-9.
  2. Schwarz S, Obermuller-Jevic UC, Hellmis E, et al. Lycopene inhibits disease progression in patients with benign prostate hyperplasia.J Nutr. Jan 2008;138(1):49-53.
  3. Olmedilla B, et al. A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene; analysis of serum responses. Clin Sci (Lond) 2002;102:447-56.
  4. Gallicchio L, Boyd K, Matanoski G, et al. Carotenoids and the risk of developing lung cancer: a systematic review. Am J Clin Nutr. Aug 2008;88(2):372-383.
  5. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999;91:317-31.
  6. Etminan M, Takkouche B, Caamano-Isorna F. The role of tomato products and lycopene in the prevention of prostate cancer: A meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev 2004;13(3):340-345.
  7. Cui Y, Shikany JM, Liu S, et al. Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women’s Health Initiative Observational Study. Am J Clin Nutr. Apr 2008;87(4):1009-1018.
  8. McCann SE, Freudenheim JL, Marshall JR, et al. Diet in the epidemiology of endometrial cancer in western New York (United States).Cancer Causes Control. Dec 2000;11(10):965-974.
  9. Pelucchi C, Dal Maso L, Montella M, et al. Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study.Cancer Causes Control. Dec 2008;19(10):1209-1215.
  10. Giovannucci E, Liu Y, Platz EA, et al. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer. 2007;121(7):1571-8.
  11. Peters U, Leitzmann MF, Chatterjee N, et al. Serum Lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 2007; 16(5):962-8.
  12. Van Patten CL, de Boer JG, Tomlinson Guns ES. Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence. J Urol. Dec 2008;180(6):2314-2321; discussion 2721-2312.
  13. Veeramachaneni S, Ausman LM, Choi SW, et al. High dose lycopene supplementation increases hepatic cytochrome P4502E1 protein and inflammation in alcohol-fed rats.J Nutr. Jul 2008;138(7):1329-1335.
  14. Feifer AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease. J Urol 2002;168:150-4.
  15. Stahl W, Sies H. Lycopene: a biologically important carotenoid for humans? Arch Biochem Biophys 1996;336:1-9.
  16. Voskuil DW, Vrieling A, Korse CM, et al. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk. Nutr Cancer. May-Jun 2008;60(3):342-353.
  17. Grainger EM, Kim HS, Monk JP, et al. Consumption of dietary supplements and over-the-counter and prescription medications in men participating in the Prostate Cancer Prevention Trial at an academic center.Urol Oncol. Mar-Apr 2008;26(2):125-132.
  18. Kucuk O, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 2001;10:861-8.
  19. Schuurman A, et al. A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 2002;13:573-82.
  20. Institute of Medicine, Food and Nutrition Board. Beta-carotene and other carotenoids. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 2000:325-400.
  21. Stahl W, Sies H. Uptake of lycopene and its geometrical isomers is greater from heat processed than from unprocessed tomato juice in humans. J Nutr 1992;122:2161-6.
  22. Tang Y, Parmakhtiar B, Simoneau AR, et al. Lycopene enhances docetaxel’s effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels. Neoplasia. 2011 Feb;13(2):108-19.
  23. Kristal AR, Till C, Platz EA, et al. Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev. 2011 Apr;20(4):638-46.
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How It Works

Bottom Line: Diets that contain many fruits and vegetables rich in carotenoids like lycopene can help prevent some types of cancers and heart problems. However, not enough research has been done to say whether lycopene supplements have the same effect.

Lycopene is a natural pigment that is produced by plants and microorganisms. Laboratory experiments with lycopene confirm that it acts as an antioxidant and affects the way cells grow and communicate with each other, although it is not as potent as beta-carotene. Scientists have proposed several different mechanisms by which lycopene might fight cancer. These include inhibition of cancer cell growth, prevention of DNA damage, and enhancement of enzymes that break down cancer-causing products. Studies in healthy elderly patients suggest that consumption of lycopene or tomato juice does not stimulate the immune system. In general, diets rich in carotenoids like lycopene have been associated with decreased risk of macular degeneration, cataracts, some types of cancers, and some heart problems.

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Purported Uses
  • To prevent and treat cancer
    Lycopene is an antioxidant. One clinical trial suggested that preventative use of lycopene supplements reduces the spread of localized prostate cancer, but there is no other proof from clinical trials that lycopene can treat cancer. Diets rich in carotenoids like lycopene are generally associated with a decreased risk of certain types of cancers.
  • To treat asthma
    One clinical trial showed that daily lycopene supplementation protected against exercise-induced asthma, but no additional studies have been performed to confirm this.
  • As an antioxidant
    Laboratory studies support this use.
  • To treat heart disease
    Diets rich in carotenoids like lycopene are generally associated with a decreased risk of some cardiovascular events. However, there is no proof that lycopene supplements have the same effect.
  • To prevent and treat macular degeneration
    Diets rich in carotenoids like lycopene are generally associated with a decreased risk of macular degeneration. However, there is no proof that lycopene supplements have the same effect.
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Research Evidence

Prostate cancer:
A small clinical trial examined the use of lycopene supplements in patients with localized prostate cancer who planned to undergo radical prostatectomy. For three weeks before surgery, 15 men received 15 mg of lycopene daily, while 11 received a similar-looking placebo. At the time of surgery, it was found that men who had been taking lycopene had less cancer spread to areas surrounding the prostate. No side effects of lycopene were reported. Though these results are promising, they need to be validated by larger studies in which the patients are randomly assigned to take lycopene or placebo.

Benign prostatic hyperplasia (BPH):
Forty participants with BPH received lycopene or placebo for 6 months. Symptoms of BPH including prostate specific antigen (PSA) levels and prostate enlargement were measured. Patients who took lycopene had decreased PSA levels and no further prostate enlargement. Patients given placebo had no changes in their PSA levels and further prostate enlargement. Larger, long-term studies needed to validate whether lycopene supplementation is useful for BPH treatment.

Asthma:
The role of lycopene in preventing exercise-induced asthma was studied in a clinical trial with 20 patients. Patients were randomly assigned to receive 30 mg of lycopene or placebo pill daily for one week. After four weeks of a “wash-out” period, patients were switched to the other group for another week of treatment. Their lung function after exercising was measured before and after each week of treatment, and it was found that lycopene was able to protect against exercise-induced asthma in 11 patients when compared to the placebo pill. This study is too small to inform us of the effects of lycopene in the general population.

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Patient Warnings
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
  • A recent analysis of six commercially available brands revealed that their actual lycopene content varied considerably from the labeled dosage. Brand-name vitamins contained as little as 62% of the claimed dosage to as much as 143% over the stated amount.
  • A large study in the Netherlands suggested that alcohol consumption may affect the anti-cancer properties of lycopene.
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Side Effects
  • No adverse effects have been reported at normal dosages.
  • After long-term ingestion of large quantities of lycopene-rich foods (i.e. tomato products), some individuals may develop lycopenodermia, a deep orange discoloration of the skin.
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Last updated: July 18, 2011
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