Scientific Name(s): psi , psi-carotene
Common Name(s): Lycopene
Uses of Lycopene
The scientific literature documents the antioxidant activity of lycopene and its use in cancer prevention and cardiovascular disease.
Lycopene administered as a pure compound has been studied in clinical trials at dosages of 13 to 75 mg/day. Lycopene is mostly available in capsule and softgel form, with dosage guidelines from manufacturers ranging from 10 to 30 mg taken twice daily with meals. Lycopene is also incorporated in multivitamin and multimineral products.
Avoid with hypersensitivity to lycopene or to any of its food sources, especially tomatoes. Tomato-based products are acidic and may irritate stomach ulcers.
Information regarding safety and efficacy during pregnancy and lactation is lacking. The amount of lycopene in foods is assumed to be safe. Tomato consumption does increase lycopene concentrations in the breast milk and plasma of lactating women.
Lycopene interacts with some cancer chemotherapy agents, as well as with ciprofloxacin and olestra.
Lycopene Adverse Reactions
In general, tomato-based products and lycopene supplements are generally well tolerated. The scientific literature documents some GI complaints, such as diarrhea, dyspepsia, gas, nausea, and vomiting. One trial documented a cancer-related hemorrhage in a patient taking lycopene, although causality is unclear.
No toxic effects were observed in rats treated with lycopene 2,000 mg/kg/day for 28 days, an intake similar to approximately 200 mg of lycopene per kg of body weight per day in humans. Another 13-week toxicity study generated similar results.
Lycopene is a common carotenoid compound found in fruits, vegetables, and green plants 1 that is responsible for the red plant pigment found primarily in tomatoes. Other sources include apricot, cranberry, grapes, pink grapefruit, guava, papaya, peaches, and watermelon. 2
In North America, nearly 85% of dietary lycopene is derived from tomatoes and tomato-based products. 1 Tomatoes have been cultivated since the 16th century as a food source. In some countries, the tomato was considered poisonous and used for decorative purposes only. Columbus may have learned of the nutritional benefits of fruits and tomatoes, until then unknown in the European diet, from the inhabitants of the New World. 3 There is a large body of evidence documenting the health benefits of lycopene, as well as its biological activity in numerous human diseases. 1 , 2 , 3
Lycopene is a 40 carbon acyclic carotenoid containing 11 conjugated double bonds, with a molecular mass of 536. 2 , 4 , 5 It consists of only hydrogen and carbon atoms and is one of 600 carotenoids synthesized by plants and photosynthetic microorganisms. 2 , 4 The biochemistry of lycopene is unique because it has no pro-vitamin A activity, as compared with other carotenoids, such as alpha-carotene and beta-carotene. Lycopene is lipophilic and, thus, insoluble in water. Lycopene is the most abundant carotenoid in tomatoes (0.9 to 4.2 mg per 100 g), followed by beta-carotene, gamma-carotene, phytoene, and other minor carotenoids. 4 It is touted as the highest overall single oxygen-quenching carotenoid, double that of beta-carotene. 6
Lycopene is relatively resistant to heat-induced geometrical isomerization in the processing of tomatoes. 7 Processed tomato products are actually a better source of lycopene than fresh tomatoes 8 and are more bioavailable. 9 In addition, human uptake of lycopene is greater from heat-processed tomato juice than from unprocessed tomato juice. 10 Tomato sauce and ketchup contain lycopene 33 to 68 mg per 100 g, and raw tomatoes contain lycopene 3.1 mg per 100 g. 4 , 6 Mechanical treatment with heat helps release lycopene from the tomato matrix, improving bioavailability (as seen with processed commercial tomato products versus fresh tomatoes). Fat also enhances the absorption of lycopene. Natural sources primarily contain the all-trans form of lycopene; the cis form of lycopene is more bioavailable and is less likely to precipitate and form the crystals affecting solubility. 11 , 12
Lycopene Uses and Pharmacology
There are numerous studies on the use of lycopene in cancer and cardiovascular disease, as well as its antioxidant and anti-inflammatory activity.Antioxidant
In vitro data
Lycopene was 2- to 10-fold more efficient in quenching singlet oxygen than alpha-tocopherol and beta-carotene. 13 The antioxidant activity of lycopene may also be mediated by its bioactive metabolites. 14Clinical data
One study involving 20 patients found a correlation between skin roughness and lycopene dietary concentration. 15 In an 8-week, double-blind, randomized, placebo-controlled trial, lycopene supplementation decreased DNA oxidative damage. 16 Lycopene also may ameliorate the oxidative stress of cigarette smoke. 17 , 18Cancer
Human epidemiological evidence indicates that diets high in tomatoes may reduce the risk of cervical, colon, esophageal, rectal, prostate, and stomach cancers. 1 , 4 , 13 , 19 Several molecular mechanisms of actions 4 are documented for lycopene's anticancer activity, including the following: Antioxidant activity or reduction of free radicals; Antioxidant response element or stimulation of cells to produce enzymes to protect against free radicals; Apoptosis or elimination of unhealthy abnormal cells; Cell-cycle arrest or induction of cell death at the G1 phase; Affect growth factors and signaling pathways critical for cancer cell growth; and Antimetastatic and anti-invasion activity.In vitro and animal data
In one study, lycopene inhibited human colon carcinoma, myeloid leukemia, and lymphoma cell lines in a dose-dependent manner. 3 Lycopene and eicosapentaenoic acid (EPA) also suppressed signal transduction pathways in human colon cancer cells, thus inhibiting cancer cell growth. 20 Another study documented activity against a liver adenocarcinoma cell line and noncancerous lung cell line. 2 Lycopene prevented chemically-induced DNA and chromosome damage and tumor-promoting activity in liver cells through antioxidant activity and inhibition of growth factors and signaling pathways. 21 , 22 , 23Clinical data
In a clinical trial, lycopene supplementation (30 mg/day for 2 months) had beneficial effects in healthy women with a high risk of breast cancer but not in breast cancer survivors. 24
In a large case-control study covering 3 years, the risk of pancreatic cancer for men consuming lycopene was reduced 31%. Lycopene protected against cancer by activating cancer-preventive phase 2 enzymes. 19 , 25
Growing evidence exists for the use of lycopene in prostate cancer prevention. Although numerous animal studies exist, 4 only the clinical evidence will be reviewed here. In a review of epidemiologic studies, a diet rich in fresh tomatoes, tomato sauce, and pizza reduced the incidence of prostate cancer in a cohort of 40,000 men. 19 Increased consumption of tomatoes statistically lowered the risk of prostate cancer in a cohort of 14,000 Seventh-Day Adventist men. 4 , 26 A meta-analysis of 21 studies provided further evidence of diets rich in tomatoes providing protection against prostate cancer. 19 Lycopene was more efficient than any carotenoid in inhibiting insulin-like growth factor type 1 (ie, high levels of this growth factor are related to an increased risk of cancer) in patients with a higher risk of colorectal cancer. 27 , 28 Lycopene also inhibited the progression of benign prostate hyperplasia. 29 Lycopene concentrations changed rapidly in men with prostate cancer given lycopene supplements for several weeks prior to radical prostatectomy. Apoptotic activity was observed and may have been caused by lycopene. 30 Prostate volume was reduced in prostate cancer patients taking 30 mg/day of lycopene extract for 3 weeks prior to radical prostatectomy. 30
Oxidative stress is recognized as a major contributor to increased cancer risk. Lycopene's efficient absorption from tomato products facilitates its antioxidant effects and may also play an important role in cancer prevention. 31 Lycopene not only achieves high concentrations in the prostate, but also in the testes and adrenal glands. Lycopene intake and decreased cancer risk association has been observed in stomach cancers. 32 Lycopene's protective role in the early stages of cervical carcinogenesis was noted in 1 study. 33 Plasma levels of lycopene and other carotenoids were lower in women with cervical intraepithelial neoplasia and cervical cancer, suggesting a protective effect of higher lycopene concentrations. 34Cardiovascular disease
The mechanism of action may be associated with antioxidant activity as well as decreased cell surface adhesion molecule expression and intima-media thickness.In vitro and animal data
Lycopene suppressed tissue factor activation in vascular thrombosis in human endothelial cells. 35 Additional studies found that lycopene reduced expression of cell surface adhesion molecules and binding of monocytes. 36 , 37 Lycopene also bound and inhibited platelet-derived growth factor, which is associated with the development and progression of cardiovascular disease in rat smooth muscle cells. 38 One nutritional study in rabbits compared lycopene's action in reducing the formation of atherosclerotic plaques in the aorta with that of fluvastatin. 39 There are studies on the development of more efficient vehicles to deliver lycopene to adipocytes. 40Clinical data
In 19 subjects, lycopene supplementation decreased serum lipid peroxidation and low-density lipoprotein (LDL) oxidation, suggesting a decreased risk for coronary heart disease (CHD). 41 An epidemiological study in 10 European countries, known as the EURAMIC study, confirmed beneficial effects on the heart correlating with lycopene lipid levels and reduced risk of myocardial infarction. 42 The Austrian Stroke Prevention Study found that certain concentrations of lycopene and other antioxidants may protect against cognitive impairment. 43 Plasma LDL cholesterol concentrations were reduced 14% in 6 men consuming dietary supplements of lycopene at 60 mg/day for a 3-month period. 44 Twenty-four patients in a 6-week clinical trial receiving fresh tomato and tomato juice twice daily reported reduced triglyceride levels and LDL cholesterol and increased high-density lipoprotein cholesterol. 45Other pharmacologic effects
Literature addressing beta-carotene's positive outcomes in skin disorders, including cancer, pigment imbalance, and photodermatoses, is available, 48 , 49 , 50 , 51 but lycopene may not share these effects because of its structural configuration. One report finds beta-carotene to be active in wound healing when lycopene was inactive. 52 Other studies document that lycopene or tomato-derived products rich in lycopene provide photoprotective effects against ultraviolet light-induced erythema. 53 , 54 Higher levels of lycopene antioxidants in the skin effectively lead to lower levels of skin roughness. 15Diabetes
In some animal models, lycopene reduced diabetes-induced learning and memory impairment by reducing oxidative stress and inflammation. 55 Lycopene also may attenuate diabetic neuropathic pain by inhibiting action of tumor necrosis factor-alpha and nitric oxide. 56 Lycopene may be useful in patients with type 2 diabetes by suppressing oxidative stress and enhancing innate immunity or serum levels of immunoglobulin M. 57Disease prevention
Reports are available on the International Symposium on Lycopene and Tomato Products in Disease Prevention. 58 , 59 Reviews describing lycopene and disease prevention are also available. 60 , 61 , 62 , 63Inflammation
Some epidemiological studies document that lycopene decreased the inflammation marker C reactive protein. 13 The production of inflammatory mediators, such as tumor necrosis factor-alpha, was reduced in patients consuming a tomato-based drink. 64 Asthmatic adults receiving lycopene treatments experienced improvement in airway inflammation. Patients treated with the tomato extract also had reduced sputum neutrophil elastase activity. 65 In a murine model of asthma, lycopene (a) suppressed infiltration of inflammatory mediators and cells into the lung; (b) decreased airway hyper-responsiveness; and (c) inhibited cell infiltration and invasion. 66 Lycopene may also have a role in reducing rhinovirus-induced airway inflammation by potentially inhibiting the formation of reactive oxygen species and decreasing viral replication. 67
Lycopene administered as a pure compound has been studied in clinical trials at dosages of 13 to 75 mg/day. 68 , 69 , 70 , 71 , 72 Lycopene is mostly available in capsule and softgel form, with dosage guidelines from manufacturers ranging from 10 to 30 mg taken twice daily with meals. Lycopene is also incorporated in multivitamin and multimineral products.
Lycopene absorption in humans is approximately 10% to 30%, with the remaining excreted. 1 The half-life elimination of lycopene in plasma was estimated to be 12 to 33 days, while a single-dose pharmacokinetic study documented 28 to 61 hours. 73 The estimated daily intake of the general population is 0.5 to 27 mg per person per day. 74 Factors affecting uptake and absorption of carotenoids have been reported. 75 Pharmacokinetic parameters of lycopene have been evaluated in humans. 34 , 76 , 77 , 78 , 79 , 80 , 81 , 82
Safety information on the use of lycopene supplements during pregnancy and lactation is lacking. The amount of lycopene in foods is assumed to be safe. Tomato consumption does increase lycopene concentrations in the breast milk and plasma of lactating women. 83
Lycopene helped to prevent cardiotoxicity and renal toxicity during adriamycin administration in rats. 84 Lycopene supplementation also partially alleviated bleomycin-induced pulmonary fibrosis in rats by suppressing oxidative stress and inflammatory mediators. 85 Lycopene inhibited reactive oxygen species generation in a dose-dependent manner 86 and also reduced chromosomal aberrations induced by cisplatin in rats. 87 Administering lycopene to rats protected against cardiomyocyte oxidative DNA damage caused by doxorubicin. 88 , 89Ciprofloxacin
Lycopene may have an additive effect when used in combination with ciprofloxacin. In rats treated for chronic bacterial prostatitis, bacterial growth and inflammatory changes with the combination of lycopene/ciprofloxacin were reduced, compared with ciprofloxacin or lycopene alone. 90Olestra
Because lycopene requires fat for absorption and transport, studies have documented that patients consuming olestra experienced reduced lycopene absorption. A reduction of nearly 30% over 16 weeks was noted for patients consuming olestra and lycopene. Consumption of lycopene and olestra should be separated by several hours. 91
Tomato-based products and lycopene supplements are generally well tolerated. The scientific literature documents some GI complaints, such as diarrhea, dyspepsia, gas, nausea, and vomiting. One trial documented a cancer-related hemorrhage in a patient taking lycopene, although causality is unclear. 92
Avoid use with hypersensitivity to lycopene or to any of its food sources, especially tomatoes. Tomato-based products are acidic and may irritate stomach ulcers.
No toxic effects were observed in rats treated with lycopene 2,000 mg/kg/day for 28 days, an intake similar to approximately 200 mg lycopene per kg of body weight per day in humans. 74 Another 13-week toxicity study generated similar results. Some studies document a protective effect against the oxidative stress of acetaminophen-induced acute hepatotoxicity and against amiodarone-induced lung toxicity. 93 Lycopene pretreatment in rats helped protect against aflatoxin toxicity by blocking metabolism and metabolic activation of aflatoxin. 94
Bibliography1. Rao AV, Ray MR, Rao LG. Lycopene. Adv Food Nutr Res . 2006;51:99-164.
2. Burgess LC, Rice E, Fischer T, et al. Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range. Toxicol In Vitro . 2008;22(5):1297-1300.
3. Salman H, Bergman M, Djaldetti M, Bessler H. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother . 2007;61(6):366-369.
4. van Breemen RB, Pajkovic N. Multitargeted therapy of cancer by lycopene. Cancer Lett . 2008;269(2):339-351.
5. Jackson H, Braun CL, Ernst H. The chemistry of novel xanthophyll carotenoids. Am J Cardiol . 2008;101(10A):50D-57D.
6. Murray M. Encyclopedia of Nutritional Supplements . Rocklin, CA: Prima Publishing. 1996;27-29.
7. Nguyen ML, Schwartz SJ. Lycopene stability during food processing. Proc Soc Exp Biol Med . 1998;218(2):101-105.
8. No authors listed. New study shows processed tomato products are a better source of lycopene than fresh tomatoes. Oncology (Williston Park) . 1997;11(12):1802.
9. Gärtner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr . 1997;66(1):116-122.
10. 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(11):2161-2166.
11. Ratnam DV, Ankola DD, Bhardwaj V, Sahana DK, Kumar MN. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release . 2006;113(3):189-207.
12. Unlu NZ, Bohn T, Francis DM, Nagaraja HN, Clinton SK, Schwartz SJ. Lycopene from heat-induced cis-isomer-rich tomato sauce is more bioavailable than from all-trans-rich tomato sauce in human subjects. Br J Nutr . 2007;98(1):140-146.
13. Erdman JW, Ford NA, Lindshield BL. Are the health attributes of lycopene related to its antioxidant function? Arch Biochem Biophys . 2009;483(2):229-335.
14. Lindshield BL, Canene-Adams K, Erdman JW Jr. Lycopenoids: are lycopene metabolites bioactive? Arch Biochem Biophys . 2007;458(2):136-140.
15. Darvin M, Patzelt A, Gehse S, et al. Cutaneous concentration of lycopene correlates significantly with the roughness of the skin. Eur J Pharm Biopharm . 2008;69(3):943-947.
16. Devaraj S, Mathur S, Basu A, et al. A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr . 2008;27(2):267-273.
17. Polidori MC, Mecocci P, Stahl W, Sies H. Cigarette smoking cessation increases plasma levels of several antioxidant micronutrients and improves resistance towards oxidative challenge. Br J Nutr . 2003;90(1):147-150.
18. Steinberg FM, Chait A. Antioxidant vitamin supplementation and lipid peroxidation in smokers. Am J Clin Nutr . 1998;68(2):319-327.
19. Singh P, Goyal GK. Dietary lycopene: its properties and anticarcinogenic effects. Comprehensive reviews in food science and food safety . 2008;7:255-270.
20. Tang FY, Cho HJ, Pai MH & Chen YH. Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem . 2009;20(6):426-434.
21. Huang CS, Fan YE, Lin CY, Hu ML. Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1. J Nutr Biochem . 2007;18(7):449-456.
22. Tharappel JC, Lehmler HJ, Srinivasan C, Robertson LW, Spear BT, Glauert HP. Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,3',4,4'-tetrachlorobiphenyl (PCB-77). Food Chem Toxicol . 2008;46(11):3467-3474.
23. Scolastici C, Alves de Lima RO, Barbisan LF, Ferreira AL, Ribeiro DA, Salvadori DM. Antigenotoxicity and antimutagenicity of lycopene in HepG2 cell line evaluated by the comet assay and micronucleus test. Toxicol In Vitro . 2008;22(2):510-514.
24. 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 . 2008;60(3):342-353.
25. Nkondjock A, Ghadirian P, Johnson KC, Krewski D; Canadian Cancer Registries Epidemiology Research Group. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr . 2005;135(3):592-597.
26. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood) . 2002;227(10):852-859.
27. Vrieling A, Voskuil DW, Bonfrer JM, et al. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. Am J Clin Nutr . 2007;86(5):1456-1462.
28. Graydon R, Gilchrist SE, Young IS, Obermüller-Jevic U, Hasselwander O, Woodside JV. Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial. Eur J Clin Nutr . 2007;61(10):1196-1200.
29. Schwarz S, Obermüller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr . 2008;138(1):49-53.
30. Gupta S. Prostate cancer chemoprevention: current status and future prospects. Toxicol Appl Pharmacol . 2007;224(3):369-376.
31. Rao AV, Agarwal S. Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr Cancer . 1998;31(3):199-203.
32. Gerster H. The potential role of lycopene for human health. J Am Coll Nutr . 1997;16(2):109-126.
33. Kanetsky PA, Gammon MD, Mandelblatt J, et al. Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-Hispanic, black women. Nutr Cancer . 1998;31(1):31-40.
34. Palan PR, Mikhail MS, Goldberg GL, Basu J, Runowicz CD, Romney SL. Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer. Clin Cancer Res . 1996;2(1):181-185.
35. Lee DK, Grantham RN, Mannion JD, Trachte AL. Carotenoids enhance phosphorylation of Akt and suppress tissue factor activity in human endothelial cells. J Nutr Biochem . 2006;17(11):780-786.
36. Martin KR, Wu D, Meydani M. The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells. Atherosclerosis . 2000;150(2):265-274.
37. Hung CF, Huang TF, Chen BH, Shieh JM, Wu PH, Wu WB. Lycopene inhibits TNF-alpha-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion. Eur J Pharmacol . 2008;586(1-3):275-282.
38. Lo HM, Hung CF, Tseng YL, Chen BH, Jian JS, Wu WB. Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling transduction pathway in rat smooth muscle cells. Biochem Pharmacol . 2007;74(1):54-63.
39. Hu MY, Li YL, Jiang CH, Liu ZQ, Qu SL, Huang YM. Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits. Nutrition . 2008;24(10):1030-1038.
40. Gouranton E, Yazidi CE, Cardinault N, Amiot MJ, Borel P, Landrier JF. Purified low-density lipoprotein and bovine serum albumin efficiency to internalise lycopene into adipocytes. Food Chem Toxicol . 2008;46(12):3832-3836.
41. Agarwal S, Rao AV. Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study. Lipids . 1998;33(10):981-984.
42. Kohlmeier I, Kark JD, Gomez-Gracia E, et al. Lycopene and myocardial infarction risk in the EURAMIC study. Am J Epidemiol . 1997;146(8):618-626.
43. Schmidt R, Hayn M, Reinhart B, et al. Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study. J Am Geriatr Soc . 1998;46(11):1407-1410.
44. Fuhrman B, Elis A, Aviram M. Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. Biochem Biophys Res Commun . 1997;233(3):658-662.
45. Shen YC, Chen SL, Wang CK. Contribution of tomato phenolics to antioxidation and down-regulation of blood lipids. J Agric Food Chem . 2007;55(16):6475-6481.
46. Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod . 2007;103(2):207-213.
47. Chandra RV, Prabhuji ML, Roopa DA, Ravirajan S, Kishore HC. Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial. Oral Health Prev Dent . 2007;5(4):327-336.
48. Pollitt N. Beta-carotene and the photodermatoses. Br J Dermatol . 1975;93(6):721-724.
49. Pietzcker F, Kuner-Beck V. Treatment of acral vitiligo with beta-carotin [in German]. Med Welt . 1977;28(35):1407-1408.
50. Pietzcker F, Kuner-Beck V. “Pigment balance” through oral beta carotene. A new therapeutic principle in cosmetic dermatology [in German]. Hautarzt . 1979;30(6):308-311.
51. Beta carotene to prevent skin cancer. N Engl J Med . 1991;324(13):923-925.
52. Lee KH, Tong TG. Mechanism of action of retinyl compounds on wound healing. Ι. Structural relationship of retinyl compounds and wound healing. J Pharm Sci . 1970;59(6):851-854.
53. Stahl W, Heinrich U, Wiseman S, Eichler O, Sies H, Tronnier H. Dietary tomato paste protects against ultraviolet light-induced erythema in humans. J Nutr . 2001;131(5):1449-1451.
54. Stahl W, Heinrich U, Aust O, Tronnier H, Sies H. Lycopene-rich products and dietary photoprotection. Photochem Photobiol Sci . 2006;5(2):238-242.
55. Kuhad A, Sethi R, Chopra K. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sci . 2008;83(3-4):128-134.
56. Kuhad A, Sharma S, Chopra K. Lycopene attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur J Pain . 2008;12(5):624-632.
57. Neyestani TR, Shariatzadeh N, Gharavi A, Kalayi A, Khalaji N. Physiological dose of lycopene suppressed oxidative stress and enhanced serum levels of immunoglobulin M in patients with Type 2 diabetes mellitus: a possible role in the prevention of long-term complications. J Endocrinol Invest . 2007;30(10):833-838.
58. Hoffmann I, Weisburger JH. International symposium on the role of lycopene and tomato products in disease prevention. Cancer Epidemiol Biomarkers Prev . 1997;6(8):643-645.
59. Weisburger JH. International symposium on lycopene and tomato products in disease prevention: an introduction. Proc Soc Exp Biol Med . 1998;218(2):93-94.
60. Clinton SK. Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev . 1998;56(2 pt 1):35-51.
61. Krinsky NI. Overview of lycopene, carotenoids, and disease prevention. Proc Soc Exp Biol Med . 1998;218(2):95-97.
62. Singh DK, Lippman SM. Cancer chemoprevention. Part 1: Retinoids and carotenoids and other classic antioxidants. Oncology (Williston Park) . 1998;12(11):1643-1653,1657-1658,1659-1660.
63. Michaud I. Chemoprevention: future is here. In: ASHP Midyear Clinical Meeting . 1998;33(Dec):PI-95.
64. Riso P, Visioli F, Grande S, et al. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agric Food Chem . 2006;54(7):2563-2566.
65. Wood LG, Garg ML, Powell H, Gibson PG. Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept. Free Radic Res . 2008;42(1):94-102.
66. Lee CM, Chang JH, Moon DO, et al. Lycopene suppresses ovalbumin-induced airway inflammation in a murine model of asthma. Biochem Biophys Res Commun . 2008;374(2):248-252.
67. Saedisomeolia A, Wood LG, Garg ML, Gibson PG, Wark PA. Lycopene enrichment of cultured airway epithelial cells decreases the inflammation induced by rhinovirus infection and lipopolysaccharide. J Nutr Biochem . 2008;20(8):577-585.
68. Paetau I, Khachik F, Brown ED, et al. Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans. Am J Clin Nutr . 1998;68(6):1187-1195.
69. Paetau I, Rao D, Wiley ER, Brown ED, Clevidence BA. Carotenoids in human buccal mucosa cells after 4 wk of supplementation with tomato juice or lycopene supplements. Am J Clin Nutr . 1999;70(4):490-494.
70. Kucuk O, Sakar FH, Sakr W, et al. Phase ΙΙ randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev . 2001;10(8):861-868.
71. Corridan BM, O'Donoghue M, Hughes DA, Morrissey PA. Low-dose supplementation with lycopene or beta-carotene does not enhance cell-mediated immunity in healthy free-living elderly humans. Eur J Clin Nutr . 2001;55(8):627-635.
72. Wright AJ, Hughes DA, Bailey AL, Southon S. Beta-carotene and lycopene, but not lutein, supplementation changes the plasma fatty acid profile of healthy male non-smokers. J Lab Clin Med . 1999;134(6):592-598.
73. Gustin DM, Rodvold KA, Sosman JA, et al. Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects. Cancer Epidemiol Biomarkers Prev . 2004;13(5):850-860.
74. Jian WC, Chiou MH, Chen YT, et al. Twenty-eight-day oral toxicity study of lycopene from recombinant Escherichia coli in rats. Regul Toxicol Pharmacol . 2008;52(2):163-168.
75. Williams AW, Boileau TW, Erdman JW Jr. Factors influencing the uptake and absorption of carotenoids. Proc Soc Exp Biol Med . 1998;218(2):106-108.
76. Johnson EJ, Qin J, Krinsky NI, Russell RM. Ingestion by men of a combined dose of beta-carotene and lycopene does not affect the absorption of beta-carotene but improves that of lycopene. J Nutr . 1997;127(9):1833-1837.
77. O'Neill ME, Thurnham DI. Intestinal absorption of beta-carotene, lycopene, and lutein in men and women following a standard meal: response curves in the triacylglycerol-rich lipoprotein fraction. Br J Nutr . 1998;79(2):149-159.
78. Talwar D, Ha TK, Cooney J, Brownlee C, O'Reilly DS. A routine method for the simultaneous measurement of retinol, alpha-tocopherol and five carotenoids in human plasma by reverse phase HPLC. Clin Chim Acta . 1998;270(2):85-100.
79. Johnson EJ. Human studies on bioavailability and plasma response of lycopene. Proc Soc Exp Biol Med . 1998;218(2):115-120.
80. Boucher BJ. Intestinal absorption of beta-carotene, lycopene, and lutein in men and women following a standard meal. Br J Nutr . 1998;80(1):115.
81. Mayne ST, Cartmel B, Silva F, et al. Effect of supplemental beta-carotene on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in humans. Am J Clin Nutr . 1998;68(3):642-647.
82. Yeum KJ, Ferland G, Patry J, Russell RM. Relationship of plasma carotenoids, retinol, and tocopherols in mothers and newborn infants. J Am Coll Nutr . 1998;17(5):442-447.
83. Alien CM, Smith AM, Clinton SK, Schwartz SJ. Tomato consumption increases lycopene isomer concentrations in breast milk and plasma of lactating women. J Am Diet Assoc . 2002;102(9):1257-1262.
84. Yilmaz S, Atessahin A, Sahna E, Karahan I, Ozer S. Protective effect of lycopene on adriamycin-induced cardiotoxicity and nephrotoxicity. Toxicology . 2006;218(2-3):164-171.
85. Zhou C, Han W, Zhang P, Cai M, Wei D, Zhang C. Lycopene from tomatoes partially alleviates the bleomycin-induced experimental pulmonary fibrosis in rats. Nutr Res . 2008;28(2):122-130.
86. Rios AdO, Antunes LM, de L.P. Bianchi M. Bixin and lycopene modulation of free radical generation induced by cisplatin-DNA interaction. Food Chem . 2008;113(4):1113-1118.
87. Sendão MC, Behling EB, dos Santos RA, Antunes LM, de Lourdes Pires Bianchi M. Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats. Food Chem Toxicol . 2006;44(8):1334-1339.
88. Ferreira AL, Yeum KJ, Matsubara LS, et al. Doxorubicin as an antioxidant: maintenance of myocardial levels of lycopene under doxorubicin treatment. Free Radic Biol Med . 2007;43(5):740-751.
89. Ferreira AL, Salvadori DM, Nascimento MC, et al. Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats. Mutat Res . 2007;631(1):26-35.
90. Han CH, Yang CH, Sohn DW, Kim SW, Kang SH, Cho YH. Synergistic effect between lycopene and ciprofloxacin on a chronic bacterial prostatitis rat model. Int J Antimicrob Agents . 2008;(31 suppl 1):S102-S107.
91. Koonsvitsky BP, Berry DA, Jones MB, et al. Olestra affects serum concentrations of alpha-tocopherol and carotenoids but not vitamin D or vitamin K status in free-living subjects. J Nutr . 1997;127(8 suppl):1636S-1645S.
92. Jatoi A, Burch P, Hillman D, et al. A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II study from the North Central Cancer Treatment Group. Urology . 2007;69(2):289-294.
93. Jamshidzadeh A, Baghban M, Azarpira N, Bardbori AM, Niknahad H. Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem Toxicol . 2008;46(12):3612-3615.
94. Tang L, Guan H, Ding X, Wang JS. Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats. Toxicol Appl Pharmacol . 2007;219(1):10-17.
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