encyclopedia

Lycopene

Natural Sources:
Watermelon, tomatoes, tomato products, and apricots.

Forms:
Standardized lycopene extracts from tomatoes; fresh tomato; freeze-dried, powdered tomato; Standardized natural mixed-carotenoid capsules, tablets and liquids including lycopene; ‘Greens’ supplements including tomato extracts.

Therapeutic Uses:
– Anti-aging
– Antioxidant
– Cancer Prevention
– Cellular Regeneration
– Cervical Disorders
– Detoxifying
– Eyesight Disorders
– Immune System Disorders
– LDL Cholesterol Oxidation
– Lung Disease
– Pancreatic Disorders
– Prostate Disorders
– Respiratory Diseases
– Vascular Disorders
– Vitamin A Deficiency (RDA=4.6-15.6mg/day)

Overview:

Lycopene is a red carotenoid found in vegetables and fruit, particularly concentrated in tomatoes and watermelon. Lycopene acts as an antioxidant, protecting cells against free radicals. Numerous studies have documented the benefits of lycopene for prostate health, particularly for preventing prostate cancer. Dietary consumption of lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been found, although the effects of lycopene seem to be stronger. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha- or beta-carotene. Dietary differences are believed to explain why the incidence of prostate cancer is 120 times greater in the United States than in China, where fatty foods are not part of the general diet. A nine-year study published in 1995 suggests that tomato-based products protect against prostate cancer. Significant results have also been found in a clinical trial to assess the effects of lycopene supplementation in patients with prostate cancer. Twenty-six men with newly diagnosed, clinically localized prostate cancer were randomly assigned to receive 15 mg of lycopene (15 patients) twice daily or no supplementation (11 patients) for 3 weeks before radical prostatectomy. Eleven (73%) subjects in the intervention group and two (18%) subjects in the control group had no involvement of extra-prostatic tissues with cancer (significant). Diffuse involvement of the prostate by ‘intraepithelial neoplasia’ was present in 10 (67%) subjects in the intervention group and in 11 (100%) subjects in the control group (also significant). Plasma prostate-specific antigen levels decreased by 18% in the intervention group, whereas they increased by 14% in the control group. The results suggest that lycopene supplementation may decrease the growth of prostate cancer. Tomatoes are also linked to significantly lower rates of pancreatic and cervical cancer.

Lycopene � Recent Positive Clinical Results:
A recent prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. Based on plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene, subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. Researchers quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Lycopene was the only antioxidant found at significantly lower mean levels in men with prostate cancer than in matched controls. In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. None of the lycopene associations were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results agree with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. This study provides further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

Chemistry:
Lycopene, the major red pigment of tomatoes, is a common carotenoid also found concentrated in watermelon. Carotenoids are natural fat-soluble pigments found principally in plants, algae, and photosynthetic bacteria, where they play a critical role in the photosynthetic process. Tomatoes contain lycopene; cis-5-lycopene; cis-5, cis-5-lycopene; lycophyll; lycoxanthin; and the lycopene precursor, phytofluene. Other carotenoids often found with lycopene include alpha-carotene, beta-carotene, gamma-carotene, beta-chryptoxanthin and lutein. Carotenoids are defined by their chemical structure and are chemically described as terpenes made of isoprene subunits. The majority of carotenoids are derived from a 40-carbon polyene chain, which could be considered the backbone of the molecule. This chain may be terminated by cyclic end-groups (rings) and may be complemented with oxygen-containing functional groups. The hydrocarbon carotenoids are known as carotenes, while oxygenated derivatives of these hydrocarbons are known as xanthophylls. All are powerful antioxidants. The distinctive pattern of alternating single and double bonds in the polyene backbone of carotenoids is what allows them to absorb excess energy from other molecules (antioxidant activity), while the nature of the specific end groups on carotenoids may influence their biological activity through their interaction with cell membranes. Carotenoids are always present in a living plant and decompose very slowly as compared to chlorophyll.

Suggested Amount:
A clinical trial with prostate patients showing significant benefits used 30mg of lycopene daily (15 mg taken twice daily). Tomato products are generally included in the diet to obtain lycopene on a daily or regular basis. Tomatoes have 3.1 grams of lycopene per 100 grams and watermelon has 4.1 grams per 100 grams. USDA tests show that lycopene is not destroyed by cooking, canning or freezing. This is also true for other carotenoids found in vegetables and fruit, and for the colorful flavonoids called anthocyanins found in berries, fruit peels and flower petals. These are very stable compounds when kept within the normal pH range of foods (highly alkaline conditions can ‘bleach’ them away).

Drug Interactions:
None known.

Contraindications:
Tomatoes and tomato-based products are contraindicated in cases of nightshade-sensitive arthritis. In these cases, to obtain the benefits of tomatoes in the diet, it is advisable to use standardized lycopene extracts – free of trace levels of solanine.

Side Effects:
Some people who are sensitive to Solanaceae plants and may develop allergic reactions to products containing tomato extracts. In these cases, to obtain the benefits of tomatoes in the diet, it is advisable to use standardized lycopene extracts – free of trace levels of solanine. Weeds of the nightshade family containing the alkaloid, solanine, have been implicated in causing rheumatic disorders in livestock. Many people maintain that all members of the nightshade family (Solanaceae), including white potatoes, eggplants and garden peppers have a tendency to trigger arthritis symptoms in susceptible persons. A British study ranked tomatoes fourteenth out of twenty foods likely to trigger arthritis symptoms; tomatoes affected 22% of the study subjects. No other nightshade plant was on the list. Another report claims that nightshades contain toxins that attack the cells of susceptible individuals, which are estimated to be approximately 10 of the population. Using standardized lycopene extracts free of solanine would prevent these problems.

References:

Amir H, Karas M, Giat J, Danilenko M, Levy R, Yermiahu T, Levy J, Sharoni Y. 1999. Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells. Nutr Cancer. 1999; 33(1): 105-12.

Carper, J. 1993. Food Your Miracle Medicine. HarperCollins Publishers, 10 East 53rd Street, New York, New York 10022-5299. Pp. 378-379.

de la Taille A, Katz A, Vacherot F, Saint F, Salomon L, Cicco A, Abbou CC, Chopin DK. 2001. [Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants
and trace elements]. Presse Med. 2001 Mar 24; 30(11): 557-60. Review. French.

Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, Li YW, Banerjee M, Grignon D, Bertram JS, Crissman JD, Pontes EJ, Wood DP Jr. 2001. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev. 2001 Aug; 10(8): 861-8.

Pool-Zobel BL, Bub A, Muller H, Wollowski I, Rechkemmer G. 1997. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis 1997 Sep; 18(9): 1847-50

Watzl B, Bub A, Brandstetter BR, Rechkemmer G. 1999. Modulation of human T-lymphocyte functions by the consumption of carotenoid-rich vegetables. Br J Nutr 1999 Nov; 82(5): 383-9

Additional Information:

Int J Oncol 2003 Jan;22(1):5-13

Chemoprevention of prostate cancer by diet-derived antioxidant agents and hormonal manipulation (Review).

Pathak SK, Sharma RA, Mellon JK.

Cancer Biomarkers and Prevention Group, Department of Oncology, University of Leicester, Leicester, LE2 7LX, UK.

Cancer of the prostate is the most commonly diagnosed solid malignancy and the second leading cause of cancer-related death in men living in developed countries. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an increasing need to prevent the onset of cancer or delay the progression of carcinogenesis in this organ. Chemoprevention is the administration of pharmacological agents to prevent, delay or reverse carcinogenesis. An example is the reversal of high grade intraepithelial neoplasia by hormonal manipulation using anti-oestrogens in breast carcinogenesis or anti-androgens in prostate carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of certain dietary factors, particularly anti-oxidants, may be protective. These factors include the vitamins D and E, soy, lycopene and selenium. The administration of 5-alpha reductase inhibitors to patients with benign prostatic hyperplasia may also constitute a potentially chemopreventive intervention. The efficacy of chemopreventive agents needs to be investigated in randomised, placebo-controlled trials in suitable cohorts of high-risk individuals. In parallel, reliable assays of potential biomarkers of the efficacy of intervention need to be developed and validated rigorously.

Cancer Res 1999 Mar 15;59(6):1225-30

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis.

Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ.

Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA. pgann@nwu.edu

Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

J Nutr 2000 Sep;130(9):2200-6
Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men.

Bub A, Watzl B, Abrahamse L, Delincee H, Adam S, Wever J, Muller H, Rechkemmer G.

Institute of Nutritional Physiology, Federal Research Centre for Nutrition, D-76131 Karlsruhe, Germany.

Because of their antioxidant properties, carotenoids may have beneficial effects in preventing cancer and cardiovascular disease. However, in humans consuming carotenoid-rich vegetables, data concerning the antioxidant effects of carotenoids are rather scarce. A human intervention trial was conducted, therefore, to determine whether a moderately increased consumption of carotenoid-rich vegetables would influence the antioxidant status in 23 healthy men. This short-term feeding study lasted 8 wk during which the men consumed a low carotenoid diet. A 2-wk low carotenoid period was followed by daily consumption of 330 mL tomato juice, then by 330 mL carrot juice and then by 10 g of spinach powder, each for 2 wk. Antioxidant status [water-soluble antioxidants in serum, ferric reducing ability of plasma (FRAP) and antioxidant enzyme activities] and lipid peroxidation (plasma malondialdehyde and ex vivo oxidation of LDL) were determined. In a subgroup of 10 men, lipoprotein carotenoids were measured. The consumption of carotenoid-rich vegetables significantly increased selected carotenoids in lipoproteins but had only minor effects on their relative distribution pattern. Tomato juice consumption reduced plasma thiobarbituric acid reactive substances (TBARS) by 12% (P: < 0.05) and lipoprotein oxidizability in terms of an increased lag time (18%, P: < 0.05). Carrot juice and spinach powder had no effect on lipid peroxidation. Water-soluble antioxidants, FRAP, glutathione peroxidase and reductase activities did not change during any study period. In evaluating the low carotenoid diet, we conclude that the additional consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid concentrations, but only tomato juice reduced LDL oxidation in healthy men. : J Nutr 2000 Feb;130(2):189-92 Lymphocyte lycopene concentration and DNA protection from oxidative damage is increased in women after a short period of tomato consumption. Porrini M, Riso P. Department of Food Science and Technology, University of Milan, Italy. Several epidemiologic studies have suggested a role of tomato products in protecting against cancer and chronic diseases. In nine adult women, we evaluated whether the consumption of 25 g tomato puree (containing 7 mg lycopene and 0.3 mg beta-carotene) for 14 consecutive days increased plasma and lymphocyte carotenoid concentration and whether this was related to an improvement in lymphocyte resistance to an oxidative stress (500 micromol/L hydrogen peroxide for 5 min). Before and after the period of tomato intake, carotenoid concentrations were analyzed by HPLC and lymphocyte resistance to oxidative stress by the Comet assay, which detects DNA strand breaks. Intake of tomato puree increased plasma (P <0.001) and lymphocyte (P<0.005) lycopene concentration and reduced lymphocyte DNA damage by approximately 50% (P<0.0001). Beta-carotene concentration increased in plasma (P<0.05) but not in lymphocytes after tomato puree consumption. An inverse relationship was found between plasma lycopene concentration (r = -0.82, P<0.0001) and lymphocyte lycopene concentration (r = -0.62, P<0.01) and the oxidative DNA damage. In conclusion, small amounts of tomato puree added to the diet over a short period can increase carotenoid concentrations and the resistance of lymphocytes to oxidative stress. Carcinogenesis 1997 Sep;18(9):1847-50 Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Pool-Zobel BL, Bub A, Muller H, Wollowski I, Rechkemmer G. Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany. A human intervention study with vegetable products has been performed in twenty three healthy, non smoking males aged 27-40. It was the aim of the study to assess whether consumption of vegetables containing different carotenoids could protect against DNA damage and oxidative DNA damage. The subjects consumed their normal diets, but abstained from vegetables high in carotenoids throughout the study period. After a 2 week depletion period, they received daily 330 ml tomato juice with 40 mg lycopene (weeks 3 and 4), 330 ml carrot juice with 22.3 mg beta-carotene and 15.7 mg alpha-carotene (weeks 5 and 6), and 10 g dried spinach powder (in water or milk) with 11.3 mg lutein (weeks 7 and 8). Blood was collected weekly and DNA damage was detected in peripheral blood lymphocytes with the 'COMET' assay. Oxidised DNA bases were detected by including an incubation step with endonuclease III. The supplementation of the diet with tomato, carrot or spinach products resulted in a significant decrease in endogenous levels of strand breaks in lymphocyte DNA. Oxidative base damage was significantly reduced during the carrot juice intervention. These findings support the hypothesis that carotenoid containing plant products exert a cancer-protective effect via a decrease in oxidative and other damage to DNA in humans. Exp Biol Med (Maywood) 2002 Nov;227(10):894-9 Lycopene and the lung. Arab L, Steck-Scott S, Fleishauer AT. Department of Epidemiology, University of North Carolina, Suite 2105E, Mcgavren Greenberg Building, Chapel Hill, NC 27599-7435, USA. lenore@unc.edu The human lung, due to the oxidative and ozone stress to which it is exposed, is particularly vulnerable to oxidative damage. Concentrations of dietary antioxidants in the lung epithelial lining and lining fluids may provide protection against oxidative damage. A randomized clinical trial was conducted to study the effects of supplemental, carotenoid-rich vegetable juice (V-8) on lung function macrophage levels of carotenoids and in moderating ozone-induced lung damage. Healthy young adults (n = 23) were exposed to 0.4 ppm ozone in a chamber for 2 hr after either 2 weeks of antioxidant supplementation (including one can of V-8 juice daily) or placebo. Mean lung concentrations of lycopene increased by 12%, and lung epithelial cell DNA damage as measured by the Comet Assay decreased 20% in supplemented subjects. No change in peripheral blood lymphocyte DNA damage was observed as evidenced by no change in mean comet area or length in supplemented or placebo subjects. We were not able to separate the effects of lycopene from other carotenoids or antioxidants administered in this study; however, lycopene is the predominant carotenoid in V-8 (it represents 88% of total carotenoids). A review of the epidemiologic literature providing evidence for the effect of lycopene (diet or serum) or tomatoes on the risk of lung cancer reveals 27 observational epidemiologic studies (18 case-control and nine cohort studies) reporting relative risk (RR) estimates. RR estimates for cohort studies ranged from 0.63 to 1.24 (mean RR = 0.93, SD = 0.16). Odds ratios (OR) for case-control studies ranged from 0.27 to 0.93 (mean OR = 0.61, SD = 0.16). Both plasma levels (RR = 1.01, OR = 0.37) and estimated intakes of lycopene from dietary sources (mean RR = 0.93, RR range = 0.80-1.05; mean OR = 0.67, OR range = 0.27-0.93) were examined. Seventeen studies, three of which were cohorts, reported their results at the level of tomato consumption rather than, or in addition to, lycopene consumption (mean RR = 0.89, RR range = 0.63-1.24; mean OR = 0.61, OR range = 0.37-0.80). The published epidemiologic literature shows an interaction between study design and the relationship between lycopene and/ or tomatoes and risk of lung cancer. Overall, cohort studies did not show an association, whereas case-control studies showed a decreased risk with greater consumption of lycopene and tomatoes. Although lycopene can be found in the human lung, and there is evidence, albeit weak, for a protective association with lung cancer, its biologic role remains to be elucidated. Exp Biol Med (Maywood) 2002 Nov;227(10):886-93 Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis. Bowen P, Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, Kim HS, Christov-Tzelkov K, van Breemen R. Department of Human Nutrition and Dietetics, m/c 517, University of Illinois, 1919 West Taylor Street, Chicago, IL 60612, USA. pbowen@uic.edu As part of a randomized placebo-controlled study to evaluate the effect of lycopene supplementation on DNA damage in men with prostate cancer, a nonrandomized 5th arm using tomato sauce was included and reported here. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for 3 weeks (30 mg of lycopene/day) before their scheduled radical prostatectomy. Prostate tissue was obtained as biopsies at baseline and as resected tissue at the time of the prostatectomy. Serum and prostate lycopene, serum prostate specific antigen (PSA) concentrations, and leukocyte DNA 8-OH-deoxyguanosine/deoxyguanosine (8OHdG) were measured at baseline and at the end of the intervention. Cancer cells in paraffin sections of prostate biopsies and postintervention resected tissue were compared for 8OHdG staining and for apoptosis. Adherence to the daily consumption of tomato-based entrees was 81.6% of the intended dose, and serum and prostate lycopene concentrations increased 1.97- and 2.92-fold (P < 0.001), respectively. Mean serum PSA concentrations decreased by 17.5% (P < 0.002) and leukocyte 8OHdG decreased by 21.3% (P < 0.005) after tomato sauce consumption. Resected tissues from tomato sauce-supplemented patients had 28.3% lower prostate 8OHdG compared with the nonstudy control group (P < 0.03). Cancer cell 8OHdG staining of Gleason Score-matched resected prostate sections was reduced by 40.5% in mean nuclear density (P < 0.005) and by 36.4% in mean area (P < 0.018) compared with the presupplementation biopsy. Apoptotic index was higher in hyperplastic and neoplastic cells in the resected tissue after supplementation. These data taken as a whole indicate significant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte and prostate tissue. Whether reduction in DNA damage to prostate cancer cells is beneficial awaits further research, although reduction in serum PSA concentrations is promising. Eur J Nutr 2002 Jun;41(3):95-100 Spinach and tomato consumption increases lymphocyte DNA resistance to oxidative stress but this is not related to cell carotenoid concentrations. Porrini M, Riso P, Oriani G. Department of Food Science and Technology, Division of Human Nutrition, University of Milan, Via Celoria 2, 20133 Milano, Italy. marisa.porrini@unimi.it BACKGROUND: The increased consumption of fruit and vegetables has been linked to protection against different chronic diseases, but the dietary constituents responsible for this association have not been clearly identified. AIM OF THE STUDY: We evaluated the effect of spinach and spinach+tomato puree consumption on cell DNA resistance to an oxidative stress. METHODS: To this aim, in a dietary controlled intervention study, 9 healthy female volunteers consumed a basal diet low in carotenoids (< 600 microg/day) enriched with daily portions (150 g) of spinach (providing about 9 mg lutein, 0.6 mg zeaxanthin, 4 mg beta-carotene) for 3 weeks (from day 0 to day 21) followed by a 2 week wash-out period (basal diet) and finally another 3 weeks (from day 35 to day 56) of diet enriched with daily portions of spinach (150 g) + tomato puree (25 g, providing about 7 mg lycopene, 0.3 mg beta-carotene). At the beginning and the end of each period of vegetable intake, blood samples were collected for lymphocyte separation. Carotenoid concentrations of lymphocytes were determined by HPLC and DNA damage was evaluated by the comet assay following an ex vivo treatment with H(2)O(2). RESULTS: During the first period of spinach consumption, lymphocyte lutein concentration did not increase significantly (from 1.6 to 2.2 micromol/10(12) cells) while lycopene and beta-carotene concentrations decreased significantly (from 1.0 to 0.1 micromol/10(12) cells, P < 0.001, and from 2.2 to 1.2 micromol/10(12) cells, P < 0.05, respectively). Lutein and lycopene concentrations increased after spinach+tomato puree consumption (from 1.2 to 3.5 micromol/10(12) cells, P < 0.01, and from 0.1 to 0.7 micromol/10(12) cells, P < 0.05, respectively). The increase may be attributed to the addition of tomato puree to spinach; however, the different concentrations of carotenoids in lymphocytes registered at the beginning of the two intervention periods may have affected the results. DNA resistance to H(2)O(2) insult increased significantly after both the enriched diets (P < 0.01); however, no "additive effect" was seen after spinach + tomato puree consumption. In the spinach + tomato intervention period an inverse correlation was observed between lymphocyte lycopene concentration and DNA damage, but this seems not able to explain the protection observed. CONCLUSIONS: The consumption of carotenoid-rich foods even for a short period of time gives protection against oxidative stress. The results obtained seem to suggest that this protective role is not specifically related to carotenoids. However they may contribute together with other substances present in vegetables to lymphocyte resistance to oxidative damage. Clin Sci (Lond) 2002 Apr;102(4):447-56 A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene: analysis of serum responses. Olmedilla B, Granado F, Southon S, Wright AJ, Blanco I, Gil-Martinez E, van den Berg H, Thurnham D, Corridan B, Chopra M, Hininger I. Unidad de Vitaminas, Seccion de Nutricion, Clinica Puerta de Hierro, C/San Martin de Porres 4, 28035-Madrid, Spain. bolmedilla@hpth.insalud.es Increased levels of oxidative stress have been implicated in tissue damage and the development of chronic diseases, and dietary antioxidants may reduce the risk of oxidative tissue damage. As part of a European multicentre project, several studies were undertaken with the aim of testing whether the consumption of foods rich in carotenoids reduces oxidative damage to human tissue components. We describe here the serum response of carotenoids and tocopherols upon supplementation with carotenoids from natural extracts (alpha-carotene+beta-carotene, lutein or lycopene; 15 mg/day) and/or with alpha-tocopherol (100 mg/day) in a multicentre, placebo-controlled intervention study in 400 healthy male and female volunteers, aged 25-45 years, from five European regions (France, Northern Ireland, Republic of Ireland, The Netherlands and Spain). Supplementation with alpha-tocopherol increased serum alpha-tocopherol levels, while producing a marked decrease in serum gamma-tocopherol. Supplementation with alpha- + beta-carotene (carotene-rich palm oil) resulted in 14-fold and 5-fold increases respectively in serum levels of these carotenoids. Supplementation with lutein (from marigold extracts) elevated serum lutein (approx. 5-fold), zeaxanthin (approx. doubled) and ketocarotenoids (although these were not present in the supplement), whereas lycopene supplementation (from tomato paste) resulted in a 2-fold increase in serum lycopene. The isomer distributions of beta-carotene and lycopene in serum remained constant regardless of the isomer composition in the capsules. In Spanish volunteers, additional data showed that the serum response to carotenoid supplementation reached a plateau after 4 weeks, and no significant side effects (except carotenodermia) or changes in biochemical or haematological indices were observed throughout the study. This part of the study describes dose-time responses, isomer distribution, subject variability and side effects during supplementation with the major dietary carotenoids in healthy subjects. J Nutr 2002 Mar;132(3):404-8 A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. Richelle M, Bortlik K, Liardet S, Hager C, Lambelet P, Baur M, Applegate LA, Offord EA. Department of Nutrition, Nestle Research Center, Lausanne, Switzerland. Myriam.Richelle@rdls.nestle.com Lycopene from fresh and unprocessed tomatoes is poorly absorbed by humans. Absorption of lycopene is higher from processed foods such as tomato paste and tomato juice heated in oil. The aim of the present study was to develop a food-grade lycopene formulation that is bioavailable in humans. A formulation of lycopene named "lactolycopene" has been designed in which lycopene is entrapped with whey proteins. Healthy subjects (n = 33; 13 men and 20 women) participated and were allocated randomly to one of the three treatment groups. After a 3-wk deprivation of dietary lycopene, subjects ingested 25 mg lycopene/d for 8 wk from lactolycopene, tomato paste (positive control) or a placebo of whey proteins while consuming their self-selected diets. Plasma lycopene concentrations reached a maximum after 2 wk of supplementation in both lycopene-treated groups and then a plateau was maintained until the end of the treatment. Increases in plasma lycopene at wk 8 were not different between supplemented groups (mean +/- SEM): 0.58 +/- 0.13 micromol/L with lactolycopene and 0.47 plus minus 0.07 micromol/L with tomato paste, although they were different from the control (P < 0.001). Similar time-concentration curves of lycopene incorporation were observed in buccal mucosa cells. Although lycopene was present mainly as all-trans isomers (>90%) in both lycopene supplements, plasma lycopene enrichment consisted of 40% as all-trans and 60% as cis isomers. The precursor of lycopene, phytofluene, was better absorbed than lycopene itself. The lactolycopene formulation and tomato paste exhibited similar lycopene bioavailability in plasma and buccal mucosa cells in humans.

Eur J Nutr 1999 Feb;38(1):35-44

Plasma concentrations of carotenoids in healthy volunteers after intervention with carotenoid-rich foods.

Muller H, Bub A, Watzl B, Rechkemmer G.

Federal Research Center for Nutrition, Institute of Nutritional Physiology, Karlsruhe, Germany.

AIM OF THE STUDY: The present study was conducted to investigate changes in the plasma concentration of carotenoids and carotenoid oxidation products, vitamin A, alpha- and gamma-tocopherol, and ubiquinone-10 during a dietary intervention trial with 23 male healthy volunteers. METHOD: A two week carotenoid depletion period was followed by a daily consumption of 330 mL tomato juice (40 mg lycopene), then by 330 mL carrot juice (15.7 mg alpha-carotene and 22.3 mg beta-carotene), and then by a 10 g spinach powder preparation (11.3 mg lutein and 3.1 mg beta-carotene) served with main meals for two weeks, respectively. Blood samples were collected in the morning after an overnight fasting and carotenoids, vitamin A, tocopherols, and ubichinone were analyzed by reversed-phase HPLC. RESULTS: During the tomato juice intervention, plasma concentrations of trans- and cis-lycopene increased 3-fold compared to the depletion period. Lycopene oxidation products could be demonstrated in plasma and were significantly elevated compared to control (p < 0.001). After two weeks of carrot juice consumption, alpha-carotene and beta-carotene concentrations increased 8.6- and 3.2-fold, respectively. Finally, during the spinach consumption period the lutein concentration increased 2-fold, while the beta-carotene concentrations were still elevated 2-fold. CONCLUSIONS: The moderate change in dietary habits, e.g., the consumption of 330 mL of carotenoid-rich vegetable juices caused significant changes in the plasma carotenoid concentrations, indicating a high bioavailability of carotenoids from these processed vegetable products. The changes in plasma carotenoid concentrations reflected the carotenoid composition of the consumed foods. However, particularly during the tomato juice intervention period the occurrence of lycopene oxidation products and cis-lycopene isomers in plasma was eminent. The formation may be due to antioxidant reactions of lycopene in the organism. Carcinogenesis 1998 Dec;19(12):2159-62 Serum carotenoids and oxidative DNA damage in human lymphocytes. Collins AR, Olmedilla B, Southon S, Granado F, Duthie SJ. Rowett Research Institute, Bucksburn, Aberdeen, UK. a.collins@rri.sari.ac.uk Carotenoids are thought to act as antioxidants in vivo, decreasing oxidative damage to biomolecules and thus protecting against coronary heart disease and cancer. However, human intervention studies with beta-carotene have given equivocal results in terms of cancer incidence. In an alternative molecular epidemiological approach, we have employed the 'comet assay' (single cell alkaline gel electrophoresis) to measure strand breaks, oxidized pyrimidines and altered purines in the DNA of lymphocytes from volunteers supplemented with alpha/beta-carotene, lutein, lycopene or placebo. In addition, we measured concentrations of the main serum carotenoids, and vitamins E and C, by HPLC. We report a significant negative correlation between basal concentrations of total serum carotenoids and oxidized pyrimidines. A similar correlation was seen between individual carotenoids (notably lutein and beta-carotene) and oxidized pyrimidines. However, carotenoid supplementation did not have a significant effect on endogenous oxidative damage. This suggests that there are some factors in the basal diet, probably found in fruit and vegetables, that decrease oxidative damage to DNA. In this case, basal serum carotenoids may simply be markers of consumption of fruit and vegetables, they themselves having little or no protective value. Am J Clin Nutr 1997 Aug;66(2):315-9 Effects of 4 y of oral supplementation with beta-carotene on serum concentrations of retinol, tocopherol, and five carotenoids. Nierenberg DW, Dain BJ, Mott LA, Baron JA, Greenberg ER. Department of Medicine, Dartmouth Medical School, Hanover, NH. david.nierenberg@dartmouth.edu beta-Carotene has been studied widely as a potential cancer-preventing agent. Recent studies found that subjects who took beta-carotene supplements orally had increases in their serum concentrations of alpha-carotene and lycopene that were large (> 150% increase) and significantly greater than such increases in subjects who received placebo and that similar supplementation was associated with a decrease of approximately 37% in plasma lutein concentrations. A biologic interaction between beta-carotene and other carotenoids was suggested. We measured concentrations of retinol, alpha-tocopherol, and five carotenoids in serum specimens from a random sample of subjects enrolled in a clinical trial of the use of antioxidant vitamins in preventing colonic adenomas. We used serum specimens obtained at enrollment and after the subjects took placebo (n = 54) or 25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis, baseline serum concentrations of the analytes, sex, body mass index, diet, smoking status, and age were associated with variable changes in some analytes over the 4-y period but supplementation with beta-carotene was related only to a mean increase in serum beta-carotene itself of 151%. We excluded with 95% confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%, and a decrease in lutein > 14.7% in subjects given beta-carotene. These results confirm previous findings that supplementation with beta-carotene given orally does not alter serum concentrations of retinol or alpha-tocopherol. The findings also indicate that beta-carotene supplementation, which results in a moderate increase in serum beta-carotene concentration, does not significantly change serum concentrations of other carotenoids.

Am J Clin Nutr 2002 Mar;75(3):526-34

Vegetable-borne lutein, lycopene, and beta-carotene compete for incorporation into chylomicrons, with no adverse effect on the medium-term (3-wk) plasma status of carotenoids in humans.

Tyssandier V, Cardinault N, Caris-Veyrat C, Amiot MJ, Grolier P, Bouteloup C, Azais-Braesco V, Borel P.

Unite Maladies Metaboliques et Micronutriments, INRA, Clermont-Ferrand/Theix, Saint-Genes-Champanelle, France.

BACKGROUND: The results of epidemiologic studies have consistently shown associations between dietary intake or plasma carotenoid status and incidence of cancers and cardiovascular and eye diseases. OBJECTIVE: The aim was to assess whether vegetable-borne carotenoids (lycopene, lutein, and beta-carotene) compete for intestinal absorption and whether this affects the plasma status of carotenoids in the medium term (ie, after 3 wk). DESIGN: During 3-wk periods separated by 3-wk washout periods, 20 women were supplemented with either 96 g tomato puree/d (14.98 mg lycopene + 1.50 mg beta-carotene), 92 g cooked chopped spinach/d (11.93 mg lutein + 7.96 mg beta-carotene), 96 g tomato puree/d + 92 g chopped spinach/d, 96 g tomato puree/d + 2 lutein pills (12 mg lutein), or 92 g chopped spinach/d + 1 lycopene pill (15 mg lycopene). Plasma carotenoids were measured before and after each supplementation period. The subjects also participated in postprandial experiments in which they ingested meals containing double amounts of the supplements described above. Carotenoids were measured in chylomicrons to assess the interaction of carotenoids on absorption. RESULTS: Adding a second carotenoid to a meal that provided a first carotenoid diminished the chylomicron response to the first carotenoid. However, cosupplementation with a second carotenoid of a diet supplemented with a first carotenoid did not diminish the medium-term plasma response to the first carotenoid. CONCLUSION: Consumption of carotenoids from different vegetable sources does not diminish plasma carotenoid concentrations in the medium term, despite the finding in postprandial testing of competitive inhibitory interactions among different carotenoids.