Lycopene

Lycopene/Drug Interactions:

  • Alcohol (ethanol)Alcohol (ethanol): The serum concentrations of some carotenoids are influenced by alcohol consumption, and it has been theorized that lycopene may also be subject to this interaction. However, a study in 12 healthy, nonsmoking men found that the intake of red wine, beer, or spirits lacked significant effect on serum lycopene levels (92; 93).
  • AndrogensAndrogens: In animal research, tomato carotenoids altered androgen status (94).
  • AntiasthmaticsAntiasthmatics: In preliminary research in asthmatic humans, daily consumption of lycopene-rich tomato extract and tomato juice reduced airway neutrophil influx and sputum neutrophil elastase activity (60), although the effects of lycopene alone are unclear. However, in healthy humans with exercise-induced breathing difficulties, lycopene-rich tomato extract (Lyc-O-Mato?) lacked evidence of benefit on various lung function parameters, including forced vital capacity (FVC), FEV1, and peak expiratory flow (75).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro and in clinical research, tomato-based foods prevented platelet aggregation and thrombosis (44; 45).
  • AntihypertensivesAntihypertensives: In humans, Lyc-O-Mato? tomato extract decreased systolic and diastolic blood pressure (41; 42; 52). Similarly, in primigravida women given oral lycopene, pre-eclampsia developed in significantly fewer women, and mean diastolic blood pressure was shown to be significantly higher in the placebo group (80). Conversely, in another human study, a reported initial diagnosis of hypertension occurred following the administration of 15mg of lycopene daily (47).
  • Anti-inflammatory agentsAnti-inflammatory agents: In clinical research, lycopene demonstrated anti-inflammatory activity (95; 48; 96).
  • AntilipemicsAntilipemics: In humans, lycopene and lycopene-rich foods reduced lipids (97; 63; 98; 69). Bile acid sequestrants such as cholestyramine (Questran?, Prevalite?, LoCHOLEST?) and colestipol (Colestid?) may reduce serum levels of lycopene (99). It has been theorized that cholestyramine caused a 30% decrease in serum lycopene levels, attributed to impaired gastrointestinal absorption and decreased serum cholesterol levels. It is unclear if these changes in carotenoid levels were harmful, beneficial, or neither, and supplementation was not given to patients. Therefore, although lycopene supplementation may offset these observed reductions, the potential outcome of such supplementation is unclear.
  • AntineoplasticsAntineoplastics: In vitro, in vivo, and in clinical research, lycopene has demonstrated antineoplastic effects (100; 101; 102; 103; 104; 105; 90; 106; 107; 83; 81; 108). These effects may be due to its antioxidant activity (90; 109; 110). Lycopene modulated intercellular communication, induced differentiation, altered gene expression, prevented DNA damage, and inhibited DNA synthesis (104; 105; 106; 111; 112).
  • ArsenicArsenic: In cellular research, lycopene was undetectable in the epidermis of patients suffering from chronic arsenic poisoning (2). Study investigators suggested that arsenic exposure reduces carotenoid concentration in the skin.
  • Bile acid sequestrantsBile acid sequestrants: Bile acid sequestrants such as cholestyramine (Questran?, Prevalite?, LoCHOLEST?) and colestipol (Colestid?) may reduce serum levels of lycopene (99). It has been theorized that cholestyramine caused a 30% decrease in serum lycopene levels, attributed to impaired gastrointestinal absorption and decreased serum cholesterol levels. It is unclear if these changes in carotenoid levels were harmful, beneficial, or neither, and supplementation was not given to patients. Therefore, although lycopene supplementation may offset these observed reductions, the potential outcome of such supplementation is unclear.
  • Cardiovascular agentsCardiovascular agents: According to a review and in human research, an incidence of heart attack has been reported following lycopene supplementation (39), and chest pain was reported following LycoRed? administration (43).
  • CreatineCreatine: In humans, changes in plasma lycopene concentration were lacking following creatine supplementation (113).
  • Fertility agentsFertility agents: In humans, lycopene improved sperm concentration and sperm motility of males with idiopathic infertility (74).
  • Gastrointestinal agentsGastrointestinal agents: Nonspecific adverse gastrointestinal effects have been reported in human research following LycoRed? administration (57). According to review studies, incidences of abdominal distension, anorexia, diarrhea, dyspepsia, flatulence, indigestion, nausea, and vomiting have been previously reported (39; 40).
  • HMG-CoA reductase inhibitors (statins)HMG-CoA reductase inhibitors (statins): In humans, lycopene and lycopene-rich foods reduced lipids (97; 63; 98; 69). Lycopene may act similarly to statin drugs and potentiate their effects, according to in vitro observations that lycopene reduces cellular cholesterol synthesis with a mechanism of action similar to fluvastatin (114). In addition, the use of statins may reduce serum lycopene levels; lycopene and other carotenoids are transported in human plasma primarily by lipoproteins (115). In individuals with mild-to-moderate hypercholesterolemia, simvastatin therapy reduced the level of carotenoids in the plasma (including lycopene); however, after taking into account lipid levels, this effect was in fact reversed (i.e., simvastatin increased plasma lycopene) (116). Studies have found plasma lycopene levels to be significantly correlated with plasma low-density lipoprotein (LDL) levels (117; 118; 119; 120). To a lesser extent, lycopene is transported via high-density lipoproteins (HDL) (121; 122). Lowering of LDL levels by statins or other drugs may result in lowering of serum lycopene levels.
  • ImmunostimulantsImmunostimulants: In clinical research, lycopene demonstrated immunomodulatory effects (48).
  • ImmunosuppressantsImmunosuppressants: In clinical research, lycopene demonstrated immunomodulatory effects (48).
  • Neurologic agentsNeurologic agents: According to secondary sources, lycopene may interact with neurologic agents.
  • NicotineNicotine: Conflicting evidence exists regarding the influence of cigarette smoking on lycopene levels (123; 124; 125; 126; 127). Though inconsistent, it appears that lycopene serum concentrations, unlike other carotenoids, are not influenced by cigarette smoking (125; 128; 129; 118; 130; 92).
  • Osteoporosis drugsOsteoporosis drugs: In vitro, lycopene had stimulatory effects on bone calcification (4). According to animal, in vitro, and human research, lycopene had a positive effect on bone in animals leading to higher bone mass, trabecular bone volume, number, and thickness, and increased bone strength (35). It was reported that the osteoprotective effects from lycopene were due to antioxidant or anti-inflammatory pathways, leading to mineralization of osteoblasts and inactivation of osteoclasts.
  • Photosensitizing agentsPhotosensitizing agents: In a 10-week clinical study, consumption of tomato paste (16mg of lycopene daily) with pasta and olive oil was associated with increased serum lycopene levels and a 40% reduction in skin erythema caused by ultraviolet (UV) light, when compared to controls (pasta and olive oil without tomato paste) (131). In other clinical research, skin levels of lycopene significantly decreased after exposure to UV light (132). Lycopene-rich tomato paste has also mitigated UVR-induced elevations in procollagen-I (pC) deposition and reduction in matrix metalloproteinase-1 (MMP-1) (87).
  • Probucol (available in Canada, not commercially available in the United States)Probucol (available in Canada, not commercially available in the United States): In clinical research, probucol administration was associated with a statistically significant decrease in serum carotenoid levels in 303 hypercholesterolemic patients (99). It is unclear if these changes in carotenoid levels were harmful, beneficial, or neither. Although supplementation with carotenoids such as lycopene may offset these observed reductions, the potential benefits of supplementation are unclear.
  • Respiratory agentsRespiratory agents: In preliminary human research, lycopene-rich tomato extract and tomato juice reduced airway neutrophil influx and sputum neutrophil elastase activity (60). However, the effects of lycopene alone are unclear.

    • Lycopene/Herb/Supplement Interactions:

  • AndrogenicsAndrogenics: In animals, tomato carotenoids altered androgen status (94).
  • AntiasthmaticsAntiasthmatics: In preliminary research in asthmatic humans, daily consumption of lycopene-rich tomato extract and tomato juice reduced airway neutrophil influx and sputum neutrophil elastase activity (60), although the effects of lycopene alone are unclear. However, in healthy humans with exercise-induced breathing difficulties, lycopene-rich tomato extract (Lyc-O-Mato?) lacked evidence of benefit on various lung function parameters, including forced vital capacity (FVC), FEV1, and peak expiratory flow (75).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro and in clinical research, tomato-based foods prevented platelet aggregation and thrombosis (44; 45).
  • Antihypertensive herbs and supplementsAntihypertensive herbs and supplements: In humans, Lyc-O-Mato? tomato extract decreased systolic and diastolic blood pressure (41; 42; 52). Similarly, in primigravida women given oral lycopene, pre-eclampsia was shown to develop in significantly fewer women, and mean diastolic blood pressure was shown to be significantly higher in the placebo group (80). Conversely, in another human study, a reported initial diagnosis of hypertension occurred following the administration of 15mg of lycopene daily (47).
  • Anti-inflammatoriesAnti-inflammatories: In clinical research, lycopene demonstrated anti-inflammatory activity (48; 96).
  • AntilipemicsAntilipemics: In humans, lycopene and lycopene-rich foods reduced lipids (97; 63; 98; 69). Lycopene may act similarly to cholesterol-lowering herbs and supplements and potentiate their effects, according to in vitro observations that lycopene and mixed-ingredient lycopene such as LycoRed? reduced cellular cholesterol synthesis (114) and clinical findings that lycopene and lycopene-rich foods reduced lipid levels (97; 63; 98; 69). In addition, the use of cholesterol-lowering herbs and supplements may reduce serum lycopene levels; lycopene and other carotenoids are transported in human plasma primarily by lipoproteins (115). Studies have found plasma lycopene levels to be significantly correlated with plasma LDL levels (117; 118; 119; 120). To a lesser extent, lycopene is transported via HDL (121; 122). Lowering of LDL levels by cholesterol-lowering herbs and supplements may result in lowering of serum lycopene levels.
  • AntineoplasticsAntineoplastics: In vitro, in vivo, and in clinical research, lycopene has demonstrated antineoplastic effects (100; 101; 102; 103; 104; 105; 90; 106; 107; 83; 81; 108). These effects may be due to its antioxidant activity (90; 109; 110). Lycopene modulated intercellular communication, induced differentiation, altered gene expression, prevented DNA damage, and inhibited DNA synthesis (104; 105; 106; 111; 112).
  • AntioxidantsAntioxidants: A number of laboratory, animal, and clinical research have demonstrated that lycopene and mixed-ingredient lycopene such as Lyc-O-Mato? possess antioxidant properties (133; 134; 135; 136; 137; 138; 127; 139; 140; 141; 142; 49; 53; 3; 52).
  • AstaxanthinAstaxanthin: In humans, astaxanthin supplementation increased the plasma concentration of carotenoids (143).
  • Beta-caroteneBeta-carotene: There is conflicting evidence regarding the interaction of beta-carotene and lycopene. In human studies, concomitant ingestion of lycopene and beta-carotene has been reported to increase lycopene absorption (144; 145). Other investigations have found beta-carotene to lack an effect on lycopene serum levels (146; 147; 148; 132; 149; 150). In human research, subjects receiving beta-carotene supplements had a reduced concentration of lycopene in an assay of LDL (151). The precise nature of this potential interaction is unclear.
  • CanthaxanthinCanthaxanthin: Canthaxanthin, a carotenoid, inhibited lycopene uptake from dietary sources, which may result in decreased serum levels (152). The clinical implications of this finding are unclear.
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: According to a review and in human research, an incidence of heart attack has been reported following lycopene supplementation (39), and chest pain was reported following LycoRed? administration (43).
  • CarotenoidsCarotenoids: Lycopene may have additive effects when taken with other carotenoids. Canthaxanthin, a carotenoid, inhibited lycopene uptake from dietary sources, which may result in decreased serum levels (152).
  • Fertility agentsFertility agents: In humans, lycopene improved sperm concentration and sperm motility of males with idiopathic infertility (74).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Nonspecific adverse gastrointestinal effects have been reported in human research following LycoRed? administration (57). According to review studies, incidences of abdominal distension, anorexia, diarrhea, dyspepsia, flatulence, indigestion, nausea, and vomiting have been previously reported (39; 40).
  • ImmunomodulatorsImmunomodulators: In clinical research, lycopene demonstrated immunomodulatory effects (48).
  • IsoflavonesIsoflavones: According to a clinical study, there may be a conflicting interaction between lycopene and soy isoflavones (46; 153). Vaishampayan et al. conducted a randomized controlled trial to examine the efficacy of lycopene alone, or in combination with soy isoflavones, on serum prostate-specific antigen (PSA) levels in men with prostate cancer (46). Serum PSA levels stabilized in 35 of 37 (95%) patients in the lycopene group. Because only 22 of 33 (67%) patients in the lycopene-and-soy-isoflavone group achieved stable PSA levels, a potential negative interaction between lycopene and soy isoflavones was proposed. However, results from a noncontrolled clinical study have suggested that combined lycopene and isoflavone supplementation in healthy long-distance runners reduced postexercise lipid peroxidation and increased plasma antioxidant defense (153).
  • LuteinLutein: In vitro, the combination of lutein and lycopene demonstrated more efficient antioxidant activity than either compound alone, suggesting synergy when lutein and lycopene are ingested together (140).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: According to secondary sources, lycopene may interact with neurologic agents.
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: In vitro, lycopene had stimulatory effects on bone calcification (4). According to animal, in vitro, and human research, lycopene had a positive effect on bone in animals, leading to higher bone mass, trabecular bone volume, number, and thickness, and increased bone strength (35). It was reported that the osteoprotective effects from lycopene were due to antioxidant or anti-inflammatory pathways, leading to mineralization of osteoblasts and inactivation of osteoclasts.
  • Palm oilPalm oil: According to secondary sources, red palm oil may increase blood levels of lycopene.
  • PhotosensitizersPhotosensitizers: In a 10-week clinical study, consumption of tomato paste (16mg of lycopene daily) with pasta and olive oil was associated with increased serum lycopene levels and a 40% reduction in skin erythema caused by ultraviolet (UV) light, when compared to controls (pasta and olive oil without tomato paste) (131). In other clinical research, skin levels of lycopene significantly decreased after exposure to UV light (132). Lycopene-rich tomato paste has also been shown to mitigate UVR-induced elevation in procollagen-I (pC) deposition and reduction in matrix metalloproteinase-1 (MMP-1) (87).
  • Respiratory herbs and supplementsRespiratory herbs and supplements: According to preliminary human research, lycopene-rich tomato extract and tomato juice reduced airway neutrophil influx and sputum neutrophil elastase activity (60). However, the effects of lycopene alone are unclear.
  • Saw palmettoSaw palmetto: According to a case study, combination lycopene and saw palmetto therapy lowered PSA level and improved bony metastases in a patient with progressive prostate cancer, previously unresponsive to conventional pharmacological interventions (154).
  • Tobacco or nicotine-containing herbs and supplementsTobacco or nicotine-containing herbs and supplements: Conflicting evidence exists regarding the influence of cigarette smoking on lycopene levels (123; 124; 125; 126; 127). While it is inconsistent, it appears that lycopene serum concentrations, unlike other carotenoids, are not influenced by cigarette smoking (125; 128; 129; 118; 130; 92). However, the inconsistency of study results leaves the concern that cigarette smoking may lead to decreased serum levels of lycopene (133).
  • Vitamin C (ascorbic acid)Vitamin C (ascorbic acid): According to limited human research, a synergistic antioxidant effect between lycopene and other phytonutrients commonly found in tomato-based products, including vitamin C, has been purported (155). In humans with type 1 diabetes, low serum lycopene was significantly associated with increased exercise-induced lipid hydroperoxides, compared to healthy controls (p<0.05) (8).
  • Vitamin D (calciferol)Vitamin D (calciferol): In vitro, lycopene has been shown to have synergistic effects on the inhibition of cellular proliferation of HL-60 promyelocytes when administered with 1,25-dihydroxy vitamin D3 (104).
  • Vitamin E (alpha-tocopherol)Vitamin E (alpha-tocopherol): In vitro, lycopene has been shown to act synergistically with alpha-tocopherol to inhibit the proliferation of prostate carcinoma cells (156). Beneficial effects were lacking in humans.

    • Lycopene/Food Interactions:

  • Carbohydrate-restricted dietCarbohydrate-restricted diet: According to limited research in humans, carbohydrate-restricted diets have been shown to lower both dietary and plasma lycopene levels (157).
  • High-fat dietHigh-fat diet: Theoretically, because lycopene is a fat-soluble carotenoid, it may be absorbed better with the consumption of fatty foods; however, studies comparing the consumption of a full-fat diet to a reduced-fat diet lacked demonstrable effect on plasma lycopene levels (158; 159).
  • Mediterranean dietMediterranean diet: According to human research, increased plasma lycopene levels have been observed in type 2 diabetics following adherence to a traditional Mediterranean diet (160). In healthy females adopting a Mediterranean diet, increased plasma lycopene corresponded with increased plasma saturated fatty acids (161).
  • Olestra (Olean?)Olestra (Olean?): The fat substitute olestra decreased serum levels of lycopene by up to 30% (90; 162). Olestra is available commercially in many reduced-fat foods (indicated on product labels).
  • Palm oilPalm oil: According to secondary sources, red palm oil may increase blood levels of lycopene.
  • PhytosterolsPhytosterols: According to limited human research, phytosterols combined with a diet high in cholesterol and saturated fat lowered serum lycopene levels (163).
  • SoySoy: According to limited human research, lycopene negatively interfered with soy isoflavones (46).
  • Vegan dietVegan diet: According to limited research in humans, adherence to a very-low-fat vegan diet contributed to increased dietary intake of lycopene (164).
  • Vitamin C (ascorbic acid)Vitamin C (ascorbic acid): According to limited human research, a synergistic antioxidant effect between lycopene and other phytonutrients commonly found in tomato-based products, including vitamin C, has been purported (155). In humans with type 1 diabetes, low serum lycopene was significantly associated with increased exercise-induced lipid hydroperoxides, compared to healthy controls (p<0.05) (8).
  • Vitamin D (calciferol)Vitamin D (calciferol): In vitro, lycopene had synergistic effects on the inhibition of cellular proliferation of HL-60 promyelocytes when administered with 1,25-dihydroxy vitamin D3 (104).
  • Vitamin E (alpha-tocopherol)Vitamin E (alpha-tocopherol): In vitro, lycopene acted synergistically with alpha-tocopherol to inhibit the proliferation of prostate carcinoma cells (156). Beneficial effects are lacking in humans.

    • Lycopene/Lab Interactions:

  • Blood pressureBlood pressure: In humans, Lyc-O-Mato? tomato extract decreased systolic and diastolic blood pressure (41; 42; 52). Similarly, in primigravida women given oral lycopene, pre-eclampsia was shown to develop in significantly fewer women, and mean diastolic blood pressure was shown to be significantly higher in the placebo group (80). Conversely, in another human study, a reported initial diagnosis of hypertension occurred following the administration of 15mg of lycopene daily (47).
  • Coagulation panelCoagulation panel: In vitro and in clinical research, tomato-based foods prevented platelet aggregation and thrombosis (44; 45).
  • HormonesHormones: Lycopene may interact with estrogen due to a potential negative interaction between lycopene and isoflavones observed in human research (46). In animals, tomato carotenoids altered androgen status (94).
  • Insulin-like growth factor-1 (IGF-1)Insulin-like growth factor-1 (IGF-1): According to preliminary human research, increased serum lycopene levels have been associated with decreased serum insulin-like growth factor binding protein-3 (IGFBP-3) in women (165).
  • Lipid profileLipid profile: According to human research, lycopene and lycopene-rich foods reduced lipids and triglycerides (97; 98; 69; 166) and increased HDL (98; 167; 63). In clinical research, treatment with LycoRed? softules significantly decreased TC and LDL and increased HDL; however, triglyceride levels lacked a significant change at three months, and each group increased significantly at six months (63). Blum et al. reported a statistically significant increase in HDL following the consumption of 300g of tomatoes daily for one month (167).
  • Semen analysisSemen analysis: In humans, lycopene improved sperm concentration and sperm motility of males with idiopathic infertility (74). In limited clinical research, lycopene selectively decreased levels of soluble receptor for advanced glycation end products (sRAGE) in seminal, but not blood, plasma (168).
  • Serum PSA panelSerum PSA panel: In clinical research, lycopene reduced PSA levels in subjects with prostate cancer (46; 81; 86) and in men presenting with localized prostate cancer (PCa) scheduled for a radical prostatectomy (84). Schwarz et al. reported that lycopene supplementation prevented prostate enlargement and reduced serum PSA levels in men with benign prostate hyperplasia (65).