Lycopene is carotenoid which is present in vegetables, green plants, and red fruits such as tomatoes, watermelons, pink grapefruit, papaya, and red bell peppers. Lycopene is not found in cherries or strawberries (these and other berries contain anthocyanins).
Lycopene is one of the most potent antioxidants in the human diet. The antioxidant activity of lycopene is twice as high as that of beta-carotene and ten times higher than that of alpha-tocopherol.
Tomatoes are the greatest source of lycopene in the western diet (approximately 80%).1
Unlike many nutrients, cooking and processing of tomatoes increases the bioavailability of lycopene. Since lycopene is fat soluble, the presence of fats and oils in food is thought to increase absorption of lycopene from diet.
Lycopene is an acyclic isomer of beta-carotene and is synthesized by plants and microorganisms. Despite its similarity to beta-carotene, lycopene does not have any vitamin A activity.
Lycopene is a 40-carbon molecule which is highly unsaturated and contains 11 conjugated and 2 unconjugated double bonds. In nature, lycopene is predominantly found in an all-trans configuration.
Lycopene is the predominant carotenoid in human plasma. In human plasma, lycopene is present in an isomeric mixture, with apparoximately 50% as cis and 50% as trans isomers. In the gut, all-trans-lycopene is partially isomerized to cis-lycopene, a process which is dependent on both the pH and foods present in the gut.2
Lycopene is found concentrated in the adrenal glands, testes, lungs, liver, colon, and prostate gland.
Studies have investigated intake of lycopene-containing foods or high serum levels of lycopene for reduction of risk for cancer, cardiovascular disease, and macular degeneration.
No adverse effects from high tomato intake or high lycopene levels have been demonstrated. Tomatoes and tomato-based products are generally well-tolerated. Rare reports of diarrhea, nausea, stomach pain or cramps, gas, vomiting, or loss of appetite have been made for lycopene or other tomato-based supplements. People with allergies to tomatoes or other tomato-based products should not take lycopene supplements.
Lycopene is naturally present in red fruits and vegetables, including tomatoes, watermelons, pink grapefruits, apricots, and pink guavas. Processed tomato products such as juice, ketchup, paste, sauce, and soup are also good sources of lycopene. In comparing bioavailability values for lycopene, it appears that lycopene is more bioavailable from processed tomato products than from raw tomatoes. Estimating the average daily intake of lycopene has been difficult due to the variability in reported levels in different foods. In the United States it has been estimated that the average daily intake of lycopene is about 3.7 mg to 6.5 per day.3
A dose-response study on the effects of purified lycopene supplementation on biomakers of oxidative stress.
A randomized, placebo-controlled, double-blind study investigated the effects of lycopene supplements on oxidative stress in a group of healthy adults over the age of 40 years. Seventy-seven people participated in the 10 week trial. Participants consumed a lycopene restricted diet for two weeks and were then assigned to receive 0, 6.5, 15, or 30 mg lycopene daily as a supplement while continuing to consume the lycopene restricted diet. Participants consumed the supplements for eight weeks. Blood and urine samples were collected after the initial two week period and at the end of the trial. Lycopene supplements increased plasma lycopene levels significantly versus placebo, independent of dose (p < 0.05). Significant decreases in DNA damage (p = 0.007) and in urinary 8-hydroxy deoxoguanosine (8-OHdG; p = 0.0002) were revealed by ANOVA for the 30 mg lycopene/day group. Glucose, lipid profile, and markers of lipid peroxidation were not changed for any group during the trial. The results of this trial indicate that the lycopene supplement used was bioavailable and that lycopene supplements may decrease oxidative damage of DNA.4
Effects of lycopene sypplementation on oxidative stress and markers of endothelial function in healthy men.
A RCT investigated the effects of lycopene supplements on oxidative stress in healthy males aged 22-57 yrs; n = 116. Participants were frequent smokers or frequent consumers of alcohol. Participants were excluded if they consumed >3 servings of vegetables & fruit per day, or >1serving of lycopene-rich foods per week, took antioxidant, vitamin, or mineral supplements, had any history of chronic disease, or were taking lipid-lowering or antihypertensive medications. Participants received a placebo, 6 mg lycopene, or 15 mg lycopene daily for eight weeks. As expected, serum lycopene increased in a dose-dependent manner during the 8 week trial (P<0.001). Results for the 15 mg supplemented group: greater increase in plasma SOD activity than the placebo group; greater reduction in lymphocyte DNA comet tail length than the placebo group; significant decreases in hs-CRP, systolic blood pressure, sICAM-1, and sVCAM-1; a 23% increase in RH-PAT index from baseline & significant increases in beta-carotene & LDL-particle size. Changes in RH-PAT index correlated with SOD activity esp. in the 15 mg lycopene/day group, lymphocyte DNA comet tail moment, and hs-CRP. In addition, changes in lycopene correlated with hs-CRP (r=-0.230, P=0.016) & SOD activity (r=0.205, P=0.037). Conclusion: increases in serum lycopene reduce oxidative stress, which may improve endothelial function.5
Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women.
A RCT investigated the effects of lycopene supplements or supplemented juice on oxidative stress and bone resorption markers in postmenopausal women. Sixty women aged 50-60 years participated in the four month trial. Participants consumed a lycopene-free diet for 1 month prior to the beginning of the supplement phase. Participants were randomly assigned to 1 of 3 groups: 0 mg lycopene/day (placebo capsules), 30 mg lycopene/day (either regular tomato juice or lycopene capsules), or 70 mg lycopene/day (supplemented tomato juice). Serum was collected from participants after the washout period, after 2 months, & after 4 months of supplements. Serum lycopene was significantly increased compared to placebo in the lycopene supplemented groups (those groups consuming juice or supplements; repeated measures ANOVA p<0.001). For those consuming juice or supplements, 4 months of supplements resulted in significantly increased total antioxidant capacity (p<0.05), decreased lipid peroxidation(LP) (p<0.001), decreased protein oxidation(PO) (p<0.001), and decreased cross linked aminoterminal N-telopeptide (p<0.001). Changes in LP, PO, and aminoterminal N-telopeptide crosslinking were different from placebo (p<0.05, p<0.005, and p<0.02, respectively). This study indicates that lycopene from food or supplemental sources is effective for reducing measures of oxidative stress and aminoterminal crosslinking of N-telopeptide (a marker of bone resorption).6
Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women.
A randomized, placebo-controlled, double-blind study evaluated the effects of carotenoid supplements on DNA damage due to oxidation. Thirty-seven healthy nonsmoking women participated in the 57 day trial. Participants were randomly assigned to a placebo group, a mixed carotenoid group (4 mg/day each of beta-carotene, lutein, and lycopene), or a single carotenoid group (12 mg/day of beta-carotene, lutein, or lycopene). Compared to baseline, all carotenoid-supplemented groups had significantly lower endogenous DNA damage after 56 days of supplementation (P<0.01). The placebo group had no change in endogenous DNA damage. Differences in DNA damage were evident as early as day 15 for the mixed carotenoid group (P<0.01) and beta-carotene groups (P<0.05). The results of this study indicate that carotenoid supplements reduce oxidative DNA damage, particularly mixed carotenoid supplements and beta-carotene.7
Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects.
A randomized, single-blind crossover-design trial investigated the effects of tomato paste supplementation on oxidative stress and endothelial dynamics in healthy adults. Nineteen men and women aged 39 ± 13 years participated in the trial. After a two week washout period, participants were randomly assigned to supplement their normal diet with 70 g tomato paste (33.3 mg lycopene) daily or no change to their normal diet. A second two week washout period followed the first trial period and then the groups crossed over. Flow-mediated dilatation (FMD) was increased compared to control by tomato supplementation (P=0.047 for repeated-measures 3x2 analysis of variance); at day 15, FMD was increased by 3.3% ± 1.4% in the tomato supplemented group but declined by -0.5% ± 0.6% in the control arm (P=0.03). After supplementation stopped, total oxidative status decreased compared to baseline values (P=0.038). FMD and oxidative status were improved by tomato paste supplementation in this short term study.8
Manipulating antioxidant intake in asthma: a randomized controlled trial.
A RCT investigated the effects of antioxidants & lycopene intake on asthma. Two phases: Phase 1 trialed 2 wks on a high-antioxidant (HA) or low-antioxidant diet (LA); the HA diet included 5 servings of vegetables and 2 servings of fruit daily & the LA diet included 2 or fewer vegetable servings & 1 serving of fruit daily. Phase 2 was a parallel-design, RCT supplementation study. Participants in the HA diet consumed a placebo. Those in the LA diet group received a placebo or a tomato extract supplement containing 45 mg lycopene daily. The entire trial lasted for 14 wks (or until an exacerbation of asthma occurred). n =137 adults with asthma. The participants in the LA diet group had lower percentage predicted forced expiratory volume (1 s) and vital capacity after 14 days & increased plasma C-reactive protein at wk 14. Time to exacerbation was greater in the HA group compared to the LA group. The LA diet group was more than twice as likely to experience an exacerbation of symptoms (2.26, 95% CI 1.04 – 4.91, P=0.039). Within the LA diet group, there was no difference in airway inflammation, systemic inflammation, or clinical outcomes between the lycopene & placebo subgroups. This study suggests that clinical asthma outcomes were improved by supplementation with lycopene containing tomato extract. Further trials are needed to clarify these results and determine their clinical relevance.9
Lycopene inhibits disease progression in patients with benign prostate hyperplasia.
A randomized, double-blind, placebo-controlled study investigated the effects of lycopene supplements for men with histologically confirmed benign prostatic hyperplasia (BPH) without prostate cancer. Forty men between the ages of 45 and 70 years participated in the six month trial. Participants were randomly assigned to receive a placebo or 15 mg synthetic lycopene per day in a hard gelatin capsule (77% all-trans and 23% total cis-lycopene). Lycopene supplements reduced serum PSA levels (P<0.05); no change was noted in the placebo group. Plasma lycopene concentration increased in the supplemented group, as expected (P<0.0001). Other plasma carotenoids were not affected by lycopene supplementation in this study. Progression of prostate enlargement occurred in the placebo group (P<0.05 for trans-rectal ultrasonography; P<0.01 for digital rectal examination). Enlargement of the prostate was not detected in the lycopene supplemented group. Lycopene supplements were found to inhibit progression of BPH in this study.10
Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients.
A randomized, placebo-controlled, double-blinded study investigated the affects of lycopene supplements (tomato extract) on insulin-like growth factor system components. Fifty-six people with colon cancer who were scheduled for colectomy partipated in the trial. Plasma lycopene was increased after supplementation with a tomato lycopene extract; a small, non-significant increase in plasma lycopene was recorded for the placebo group as well. Compared to placebo, plasma insulin-like growth factor I decreased significantly in the supplemented group (approximately 25% decrease, P<0.05). The insulin-like growth factor I to insulin-like growth factor I-binding protein 3 ratio decreased significantly (P<0.05). No changes were found for insulin-like growth factor II or insulin-like growth factor I-binding protein 3. High plasma levels of insulin-like growth factor-I have been found to be a risk factor for certain types of cancer. The results of this study suggest that lycopene extracted from tomatoes may reduce risk for colon cancer.11
Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk.
A randomized, placebo-controlled, double-blind, crossover design trial investigated the effects of lycopene supplementation on insulin-like growth factors in premenopausal women with a history of or high risk for breast cancer. Twenty-four women with a history of breast cancer and 36 women with a high familial risk for breast cancer participated in the trial. Participants were randomly assigned to receive 30 mg per day of lycopene from a tomato-derived supplement or a placebo for two months. When both groups are combined, lycopene supplementation did not alter total IGF-1 or other IGF system components. In the breast cancer survivor group, total IGF-I and IGFBP-3 were increased (total IGF-I=7.0%, 95% CI= -0.2 to 14.3%; IGFBP-3=3.3%, 95% CI=0.7-6.0%). In the family history population, free IGF-I was decreased (-7.6%, 95% CI= -14.6 to -0.6%). The results of this study suggest that lycopene supplements beneficially altered insulin-like growth factor components for women at high risk for breast cancer but not for breast cancer survivors.12
Tomato paste rich in lycopene protects against cutaneous photodamage on humans in vivo: a randomized controlled trial.
A randomized controlled trial investigated the efficacy of tomato paste for protection against photodamage. 20 healthy women with a median age of 33 years participated in the 12 week trial. Participants were randomly assigned to consume 55 g tomato paste (in olive oil, providing 16 mg lycopene) or olive oil alone daily for 12 weeks. Pre- and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument; Biopsies were taken from unexposed and UVR-exposed (3 × MED 24 h earlier) buttock skin pre- and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin-1 and matrix metalloproteinase (MMP)-1, and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion. Tomato paste supplementation resulted in a significantly higher mean erythemal D(30) (vs. baseline or control; baseline 26.5 ± 7.5 mJ/cm2; control 23 ± 6.6 mJ/cm2; tomato paste 36.6 ± 9.6 mJ/cm2; P=0.03). Minimal erythema dose was not different between groups. Compared to presupplementation values, ultraviolet radiation induced a smaller increase in MMP-1 and increased pCI deposition (P=0.05). The mtDNA deletion was significantly reduced in the tomato paste supplemented group (P=0.01). These results suggest that tomato paste providing 16 mg lycopene provided protection against acute photodamage and possibly provides longer-term protection against photodamage.13
The effect of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients.
A double-blind, placebo-controlled, crossover-design trial investigated the effects of tomato extract on hypertension. Fifty adults with treated but uncontrolled hypertension participated in the trial. Participants received either a standardized tomato extract or placebo for six weeks followed by a crossover into the other treatment. Tomato extract supplementation reduced systolic blood pressure in both groups (145.8 ± 8.7 to 132.2 ± 8.6 mmHg (p < 0.001) and 140.4 ± 13.3 to 128.7 ± 10.4 mmHg (p < 0.001)). Diastolic blood pressure was reduced in both groups with tomato paste supplementation (82.1 ± 7.2 to 77.9 ± 6.8 mmHg (p = 0.001) and from 80.1 ± 7.9 to 74.2 ± 8.5 mmHg (p = 0.001)). A statistically significant correlation between systolic BP and lycopene levels was identified (r = -0.49, p < 0.001). The results of this study suggest that lycopene supplements, especially from tomato paste, may positively benefit people with hypertension. Further studies may help to clarify relationships between lycopene and hypertension.14
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