Abstract
Objective:
The present study aimed to develop a food for special medical purposes (FSMP) and to assess its efficacy as adjuvant therapy in patients with chronic hepatitis C virus (HCV).
Design:
Open randomized clinical trials with a tomato-based FSMP used as adjuvant treatment to the pharmacological therapy with pegilated interferon and ribavirin.
Subjects:
Eight healthy volunteers and 39 HCV patients.
Interventions:
For the bioavailability study, healthy subjects consumed 100 g/die FSMP for a week and their serum carotenoid profile at baseline, after the week of administration and 7 days later was determined. The same quantity of FSMP for 6 months by 20 of the 39 HCV patients was consumed in the clinical trial. Serum transaminase, haemoglobin (Hb) and hydroperoxide concentrations during the therapy were monitored in all patients.
Results:
FSMP consumption caused a fourfold increase of lycopene serum concentration in healthy subjects. A significant increase of carotenoids after 1 month of consumption also in patients with HCV was recorded. Transaminase and Hb serum levels, as well as therapeutic response, were not influenced by FSMP. The decrease in serum hydroperoxides was independent from FSMP consumption in long-term responder patients, whereas nonresponder (NR) patients of FSMP group showed higher reductions than NR patients of Control group.
Conclusions:
The FSMP was effective in improving carotenoid status in healthy subjects. In HCV patients, it did not influence the therapeutic response, but it prevented carotenoid serum depletion and it was effective in improving the oxidative status during antiviral therapy in NR patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bohm V, Bitsch R (1999). Intestinal absorption of lycopene from different matrices and interactions to other carotenoids, the lipid status, and the antioxidant capacity of human plasma. Eur J Nutr 38, 118–125.
Bub A, Watzl B, Abrahamse L, Delincee H, Adam S, Wever J et al. (2000). Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. J Nutr 130, 2200–2206.
Bui MH (1994). Simple determination of retinol, alpha-tocopherol and carotenoids (lutein, all-trans-lycopene, alpha- and beta-carotenes) in human plasma by isocratic liquid chromatography. J Chromatogr B Biomed Appl 654, 129–133.
Burney PGJ, Comstock GW, Morris JS (1989). Serological precursor of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Ame J Clin Nutr 49, 895–900.
Castenmiller JJ, West CE (1998). Bioavailability and bioconversion of carotenoids. Annu Rev Nutr 18, 19–38.
Crozier A, Lean MEJ, McDonald MS, Black C (1997). Quantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce, and celery. J Agric Food Chem 45, 590–595.
Di Mascio P, Murphy MC, Sies H (1991). Antioxidant defense systems, the role of caritenoid, tocopherol and thiols. Amer J Clin Nutr 53, 194S–200S.
Erdman Jr JW, Bierer TL, Gugger ET (1993). Absorption and transport of carotenoids. Ann N Y Acad Sci 691, 76–85.
Fielding JM, Li D, Stockmann R, Sinclair AJ (2004). The effect of different plant oils used in preparing tomato sauces on plasma concentrations of lycopene and oxidative status: a dietary intervention study. Asia Pac J Clin Nutr 13, S49.
Flora K, Hahn M, Rosen H, Benner K (1998). Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 93, 139–143.
Fogliano V, Vitaglione P (2005). Functional foods planning and development. Mol Nutr Food Res 49, 256–262.
Fotouhi N, Meydani M, Santos MS, Meydani SN, Hennekens CH, Gaziano JM (1996). Carotenoid and tocopherol concentrations in plasma, peripheral blood mononuclear cells, and red blood cells after long-term beta carotene supplementation in men. Am J Clin Nutr 63, 553–558.
Franceschi S, Bidoli E, La Vecchia C, Salamini R, D'Avanzo B, Negri E (1994). Tomatoes and risk of digestive-tract cancers. Int J Cancer 59, 181–184.
Furr HC, Clark RM (1997). Intestinal absorption and tissue distribution of carotenoids. J Nutr Biochem 8, 364–377.
Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1995). Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87, 1767–1776.
Graziani G, Pernice R, Lanzuise S, Vitaglione P, Anese M, Fogliano V (2003). Effect of peeling and heating on carotenoid content and antioxidant activity of tomato and tomato-virgin olive oil system. Eur Food Res Technol 216, 116–121.
Helzlsouer KJ, Comstock GW, Morris JS (1989). Selenium, lycopene, R-tocopherol, α-carotene, retinol, and subsequent bladder cancer. Cancer Res 49, 6144–6148.
Holloway DE, Yang M, Paganga G, Rice-Evans CA, Bramley PM (2000). Isomerization of dietary lycopene during assimilation and transport in plasma. Free Radic Res 32, 93–102.
Houglum K, Venkataramani A, Lyche K, Chojkier M (1997). A pilot study of the effects of d-α-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 113, 1069–1073.
Hu X, Jandacek RJ, White WS (2000). Intestina absorption of beta-carotene ingested with a meal rich in sunflower oil or beef tallow: postprandial appearance in triacylglycerol-rich lipoproteins in women. Am J Clin Nutr 71, 1170–1180.
Jakus V, Lopuchova M (1999). Role of free radicals, oxidative stress and antioxidant systems in liver diseases. Bratisl Lek Listy 100, 548–559.
Jones BE, Czaja MJ (1998). Mechanisms of hepatic toxicity III. Intracellular signaling in response to toxic liver injury. Am J Physiol 275, 874–878.
Kaiano K, Sakaida I, Uchida K, Okita K (1998). Inibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells. J Hepatol 29, 642–649.
Kaplowitz N (2000). Mechanisms of liver cell injury. J Hepatol 32, 39–47.
Khachik F, Spangler CJ, Smith Jr. JC, Canfeld LM, Steck A, Pfander H (1997). Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. Anal Chem 69, 1873–1881.
Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N et al. (1981). Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1, 431–435.
Kohlmeier L, Kark JD, GomezGracia E, Martin BC, Steck SE, Kardinaal AFM et al. (1997). Lycopene and myocardial infarction risk in the EURAMIC study. Am J Epidemiol 146, 618–626.
Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ (2003). Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 38, 413–419.
Lavine JE (2000). Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 136, 734–738.
Lee A, Thurnham I, Chopra M (2000). Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma. Free Radical Biology & Medicine 29, 1051–1055.
Levin G, Benamotz A, Mokady S (1994). Liver accumulation of soluble all-trans or 9-cis beta-carotene in rats and chicks. Comp Biochem Phys A 107, 203–207.
Loguercio C, Nardone G, Sicolo P, Cuomo R, Del Vecchio Blanco C, Budillon G (1996). Intravenous load of fructose and fructose 1,6-diphosphate: effect on uricemia in patients with nonalcoholic liver disease. Am J Gastroenterol 91, 559–564.
Mato JM, Camara J, Fernandez de Paz J, Caballeria L, Coll S, Caballero A et al. (1999). S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 30, 1081–1089.
Micozzi MS, Brown ED, Edwards BK, Bieri JG, Taylor PR, Khachik F et al. (1992). Plasma carotenoid response to chronic intake of selected foods and α-carotene supplements in men. Am J Clin Nutr 55, 1120–1125.
Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA (1996). Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384, 240–242.
Mitsuyoshi H, Nakashima T, Sumida Y, Yoh T, Nakajima Y, Iscikawa H et al. (1999). Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants. Biochem Biophys Res Commun 263, 537–542.
Mori N, Hirayama K (2000). Long-term consumption of a methionine-supplemented diet increases iron and lipid peroxide levels in rat liver. J Nutr 130, 2349–2355.
Morisco F, Verde V, Fogliano V, Ritieni A, Marmo R, De Luise G et al. (2004). Oxidative status in chronic hepatitis C: the influence of antiviral therapy and prognostic value of serum hydroperoxide assay. Free Radic Res 38, 573–580.
Muller H, Bub A, Watzl B, Rechkemmer G (1999). Plasma concentrations of carotenoids in healthy volunteers after intervention with carotenoid-rich foods. Eur J Nutr 38, 35–44.
Ota Y, Sasagawa T, Suzuki K, Tomioka K, Nagai A, Niiyama G et al. (2004). Vitamin E supplementation increases polyunsaturated fatty acids of RBC membrane in HCV-infected patients. Nutrition 20, 358–363.
Ott M, Thyagarajan P, Gupta S (1997). Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors. Eur J Clin Invest 27, 908–915.
Par A, Roth E, Rumi G, Kovacs Z, Nemes J, Mozsik G (2000). Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C. Orv Hetil 141, 1559–1655.
Pares A, Planas R, Torres M, Caballeria J, Viver JM, Acero D et al. (1998). Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28, 615–621.
Parker RS (1996). Absorption, metabolism, and transport of carotenoids. FASEB J 10, 542–551.
Pellegrini N, Re R, Yang M, Rice Evans C (1999). Screening of dietary carotenoid-rich fruit extracts for antioxidant activities applying 2,2′-azinobis (3-ethylenebenzothiazoline-6-sulfonic acid) radical cation decolorization assay. Methods Enzymol 299, 379–389.
Pellegrini N, Riso P, Porcini M (2000). Tomato consumption does not affect the total antioxidant capacity of plasma. Nutrition 16, 268–271.
Peterhans E (1997). Reactive oxygen species and nitric oxide in viral diseases. Biol Trace Elem Res 56, 107–116.
Pratico D, Iuliano L, Basili S, Ferro D, Camastra C, Cordova C et al. (1998). Enhanced lipid peroxidation in hepatic cirrhosis. J Investig Med 46, 51–57.
Rice-Evans CA, Sampson J, Bramley PM, Holloway DE (1997). Why do we expect carotenoids to be antioxidants in vivo? Free Radic Res 26, 381–398.
Sakamoto H, Mori H, Ojima F, Ishiguro Y, Arimoto S, Imae Y et al. (1994). Elevation of serum carotenoids after continued ingestion of tomato juice. J Jpn Soc Nutr Food Sci 47, 93–99.
Schierle J, Bretzel W, Buhler I, Faccin N, Hess D, Steiner K et al. (1996). Content and isomeric ratio of lycopene in food and human blood plasma. Food Chem 59, 459–465.
Schlenker T, Feranchak AP, Schwake L, Stremmel W, Roman RM, Fitz JG (2000). Functional interactions between oxidative stress, membrane Na permeability, and cell volume in rat hepatoma cells. Gastroenterology 118, 395–403.
Shuppan D, Ji-Dong J, Brinkhaus B, Hahn EG (1999). Herbal products for liver diseases: a therapeutic challenge for the new millenium. Hepatology 30, 1099–1104.
Sodergren E, Cederberg J, Basu S, Vessby B (2000). Vitamin E supplementation decreases basal levels of F2-isoprostanes and prostaglandin F2 α in rats. J Nutr 130, 10–14.
Steinberg FM, Chait A (1998). Antioxidant vitamin supplementation and lipid peroxidation in smokers. Am J Clin nutr 68, 319–327.
Stewart AJ, Bozonett S, Muller W, Jenkins GI, Lean MEJ, Crozier A (2000). Occurrence of flavonols in tomatoes and tomato-based products. J Agric Food Chem 48, 2663–2669.
Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago Y et al. (2003). Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis. Int J Vitam Nutr Res 73, 411–415.
Van den Berg H, Faulks R, Granado F, Hirschberg J, Olmedilla B, Sandmann G et al. (2000). The potential for the improvement of carotenoid levels in foods and the likely systems. J Sci Food Agric 80, 880–890.
VanEenwyk J, Davis FG, Bowen PE (1991). Dietary and serum carotenoids and cervical intraepithelial neoplasia. Int J Cancer 48, 34–38.
Verde V, Fogliano V, Ritieni A, Maiani G, Morisco F, Caporaso N (2002). Use of N,N-dimethyl-p-phenylenediamine to evaluate the oxidative status of human plasma. Free Radic Res 36, 869–873.
Vitaglione P, Monti SM, Ambrosino P, Skog K, Fogliano V (2002). Carotenoids from tomatoes inhibit heterocyclic amine formation. Eur Food Res Technol 215, 108–113.
Vitaglione P, Morisco F, Caporaso N, Fogliano V (2004). Dietary antioxidant compounds and liver health. Crit Revi Food Sci Nutr 44, 575–586.
Von Herbay A, Stahl W, Niederau C, Sies H (1997). Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized, double-blind, placebo-controlled study. Free Radic Res 27, 599–605.
Wasser S, Sian Ho JM, Khengm AH, Eng Looi TC (1998). Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats. J Hepatol 29, 760–771.
Yeum KJ, Ahn SH, Paiva SA, Lee-Kim YC, Krinsky NI, Russell RM (1998). Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer. J Nutr 128, 1920–1926.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vitaglione, P., Fogliano, V., Stingo, S. et al. Development of a tomato-based food for special medical purposes as therapy adjuvant for patients with HCV infection. Eur J Clin Nutr 61, 906–915 (2007). https://doi.org/10.1038/sj.ejcn.1602571
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejcn.1602571