Wellness Foods Europe Anti-cancer effect of carrots

Anti-cancer effect of carrots Wellness Foods Europe

Carrots prevent the development of cancer, but why?

by Lars P. Christensen, Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Denmark

It is well known from various epidemiological studies that diets rich in fruits and vegetables protect against the development of diseases such as cancers and cardiovascular diseases (13). The health promoting effects of fruit and vegetables has for many years primarily been ascribed to their contents of vitamins, minerals, bres (prebiotics) and antioxidants, but still the mechanisms and which compounds that in fact are responsible for this protection are almost unknown. The answer is probably not simple and may be due to a combination of many factors. However, if we look at the health promoting effects of specic vegetables, it may sometimes be pos38 | Wellness Foods Europe June 2006

sible to give a more unambiguous answer on their health promoting effects. This is, for example, the case with the carrot root (Daucus carota), which has a preventive effect on the development of cancer. Health effects of vegetables > Vegetables contain approximately 90 % water. They contain very low amounts of fat and proteins, but instead a wide range of important vitamins, minerals, prebiotics as well as antioxidants and other bioactive compounds. In the last twenty-years focus has mainly been on antioxidants, such as polyphenols, avonoids, phenolic acids and carotenoids,

as the primarily explanation for the health effects of vegetables. The antioxidant hypothesis is built on the assumption that antioxidants to a large extent are able to neutralize reactive-oxygen species (ROS) that are generated constantly in the body. ROS may react with vital compounds such as DNA, RNA and lipids, and therefore if the number of ROS exceeds the capacity of the antioxidant defence system in the body this may lead to serious oxidative damages, which in the end can result in the development of cancer and other diseases. The natural content of antioxidants, such as vitamin C and E, that is mainly provided through vegetables and fruits seem to offer a good protection against ROS. However, it has so far not been proven that other antioxidants such as plant phenols and carotenoids that we obtain through our diet provide further protection against ROS in vivo (4). In most cases where these antioxidants have shown some effect against diseases such as cancer, their mode of action is probably not related to their antioxidant activity. So in order to explain the health promoting effects of vegetables, in particular the anti-cancer effect, we also have to focus on other groups of bioactive compounds with other mode of actions. Some of these bioactive compounds are toxic in high concentrations but may have benecial effects in low concentrations. Carrots contain a group of highly bioactive polyacetylenes that are present in low concentrations, which may explain some of the health promoting effects of this vegetable. Polyacetylenes in carrots > The concentration of the main polyacetylenes in carrots, falcarinol, falcarindiol and falcarindiol 3-acetate, has been shown to be quite variable depending on factors such as genotype, growing conditions, root size, storage conditions and processing (5, 6). In an investigation of 6 genotypes of the Nantes type the content of falcarinol, fal-

carindiol and falcarindiol 3-acetate varied signicantly between 616 mg/kg fresh weight (FW), 1954 mg/kg FW and 919 mg/kg FW, respectively (table 1) (5). The carrot genotypes grown on location 1 had a signicant higher content of polyacetylenes than those grown on location 2 (table 1). The concentration levels of polyacetylenes were within the levels previously reported in carrots (68). Some of the largest changes in polyacetylene content of carrots occur, however, during heat treatments. The content of polyacetylenes in carrots has been shown to be reduced with more than 50 % during blanching/boiling (9). The results, however, shows that processed carrots are still a source of bioactive polyacetylenes.

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Wellness Foods Europe Anti-cancer effect of carrots

Anti-cancer effect of carrots Wellness Foods Europe

Table 1. The content of falcarinol, falcarindiol, falcarindiol 3-acetate in six carrot genotypes of the Nantes type grown at two locations. Data are means of two replications (5).

Genotype

Falcarinol (mg/kg FWa) 1 08.7 15.0 06.0 07.3 15.5 05.5 09.7 03.1 2 4.4 12.5 07.3 07.2 10.3 05.4 07.9 02.0 1

Falcarindiol (mg/kg FW) 2 19.3 36.4 29.1 27.9 25.1 22.8 26.8 05.1

Falcarindiol 3-acetate (mg/kg FW) 1 13.8 14.1 10.9 18.7 12.2 12.6 13.7 04.4 2 08.9 13.5 11.0 16.3 08.5 09.7 11.3 04.3

Location Bolero Duke Express Fancy Line 1 Cortez Mean LSDb

a

39.0 44.3 30.4 53.6 49.4 30.1 41.1 12.7

rot. This is the intake level of fruit and vegetables recommended by many ofcial agencies responsible for food safety and quality, to decrease the risk of cancer and other diseases. After 18 weeks the animals were euthanized and the colon examined for tumours and abnormal groups of cells that may lead to cancer (15). The results of this rat study showed that the number and size of tumours and groups of abnormal cells were signicantly lower in the rats that received one of the two experimental treatments, as compared to the control. Thus the results support the hypothesis that falcarinol is one of the main protective substances in carrots than can explain their anti-cancer effect. Falcarinol is also present in other root vegetables such as parsnip (Pastinaca sativa) and celeriac (Apium graveolens var. rapaceum) in concentrations corresponding to approximately 160 mg/kg FW and 300 mg/kg FW, respectively (7). It is therefore expected that these vegetables also have anti-cancer properties. Possible mode of action of polyacetylenes > The possible mode of action of falcarinol is not known but may be related to its hydrophobicity and its reactivity towards proteins and other biomolecules (15). The potential anti-cancer effect of falcarinol could be due to (i) enhancement of the immune system stimulating the production of T-lymphocytes, (ii) inactivation of proteins/enzymes responsible for the proliferation of cancer cells and/or (iii) direct interaction with cancer cells. A similar mode of action is also possible for falcarindiol and falcarindiol 3-acetate, although their reactivity is less compared to falcarinol in accordance with their signicant lower bioactivity compared to falcarinol (15). However, the carrot polyacetylenes may also interact with each other in both a synergistic or antagonistic manner thereby affecting their effectiveness (15). If the health benets of falcarinol and other carrot polyacetylenes are

conrmed in clinical studies, a more thorough investigation of their toxicity will be needed, to ensure that there are not some overlooked risks associated with their presence in relative high concentrations in food, which could reduce or maybe even eliminate a net health promoting effect. Bitter off-taste of carrots > Bitter taste in vegetables often causes consumer rejection and is one of the main reasons for low preferencescores in sensory evaluations of carrots (16). Carrots are able to produce sporadic bitterness when exposed to stress during growing, harvesting, transportation, storage, and processing. Recently it has been shown that polyacetylenes, and in particular falcarindiol, have a major impact on bitter taste in carrots and carrot products (6, 17). Falcarindiol and falcarindiol 3-acetate are primarily locat-

FW = fresh weight, bLSD = least signicant difference at P 0.05.

Anti-cancer effect of carrots > Several epidemiological studies have implied specically that carrots have anti-cancer effect and many studies have been based on the hypothesis that the antioxidant -carotene, abundantly present in the traditional orange carrot, was responsible for this effect. However, since several intervention studies have shown that a high intake of -carotene increase the risk of cancer (1012) focus is now on the polyacetylenes, in particular falcarinol, as potential anti-cancer principles in carrots. In an in vitro study, falcarinol was shown to stimulate differentiation of mammalian cells in concentrations between 150 ng/ml, while toxic effects were found above 100 ng/ ml (9). Ingestion of carrot juice by human volunteers resulted in a plasma concentration of falcarinol of 23 ng/ml for several hours, 40 | Wellness Foods Europe June 2006

well within the range where a physiological effect would be expected (13). Earlier studies have demonstrated that falcarinol has a pronounced cytotoxic activity against human tumour cell lines in vitro in physiological relevant concentrations (14). To document the anti-cancer effect of falcarinol in vivo we examined its effect on rats (BDIX rat model) induced with colectoral cancer (15). Three groups of rats, with 8 rats in each group, were fed the standard rat feed Altromin supplemented with either 10 % (w/w) freezedried carrots with a natural content of 35 g falcarinol/g, 10 % maize starch to which was added the same amount of puried falcarinol as in the carrot supplement, or 10 % maize starch (control). The amount of carrot provided in the carrot diet corresponds to a daily human consumption of 400600 g FW of car-

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Wellness Foods Europe Anti-cancer effect of carrots

Anti-cancer effect of carrots Wellness Foods Europe

ed in the periderm tissue of the carrot root whereas falcarinol is mainly present in the phloem tissue where they protect the carrot root from fungal attack (5). This distribution of polyacetylenes in carrots means that it is possible to remove most of the bitter taste of falcarindiol by peeling the carrot, and at the same time to maintain the health promoting effects of falcarinol. Future challenges > To nd the optimal concentration of polyacetylenes in carrots and related root vegetables where maximal health effects are obtained without affecting the taste signicantly seems to be one of the future challenges. However, we also need more information on how the content of polyacetylenes are affected by genotype, cultivation, storage, freezing, and processing/preparation in order to produce new healthier and better tasting root vegetables and to develop new healthier food products. References > 1. M. Maynard, D. Gunnell, P. Emmett, S. Frankel, G. D. Smith. Fruit, vegetables, and antioxidants in childhood and risk of adult cancer: the Boyd Orr cohort. Journal of Epidemiology and Community Health 57, 218225 (2003). 2. P. M. Kris-Etherton, T. D. Etherton, J. Carlson, C. Gardner. Recent discoveries in inclusive food-based approaches and dietary patterns for reduction in risk for cardiovascular disease. Current Opinion in Lipidology 13, 397407 (2002). 3. P. Greenvald, C. K. Clifford, J. A. Milner. Diet and cancer prevention. European Journal of Cancer 37, 948965 (2001). 4. M. N. Clifford. Diet-derived phenols in plasma and tissues and their implications for health. Planta Medica 70, 11031114 (2004). 5. U. Kidmose, S. L. Hansen, L. P. Christensen, M. Edelenbos, E. Larsen, R. Nrbk, Effects of genotype, root size, storage, and processing on bioactive compounds in or42 | Wellness Foods Europe June 2006

ganically grown carrots (Daucus carota L). Journal of Food Science 69, S388S394 (2004). 6. A. Czepa, T. Hofmann. Quantitative studies and sensory analyses on the inuence of cultivar, spatial tissue distribution, and industrial processing on the bitter offtaste of carrots (Daucus carota L.) and carrot products. Journal of Agricultural and Food Chemistry 52, 45084514 (2004). 7. C. Zidorn, K. Jhrer, M. Ganzera, B. Schubert, E. M. Sigmund, J. Mader, R. Greil, E. P. Ellmerer, H. Stuppner. Polyacetylenes from the Apiaceae vegetables carrot, celery, fennel, parsley, and parsnip and their cytotoxic activities. Journal of Agricultural and Food Chemistry 53, 25182523 (2005). 8. J. Mercier, R. Ponnampalam, L. S. Brard, J. Arul. Polyacetylene content and UV-induced 6-methoxymellein accumulation in carrot cultivars. Journal of the Science of Food and Agriculture 63, 313317 (1993). 9. S. L. Hansen, S. Purup, L. P. Christensen. Bioactivity of falcarinol and the inuence of processing and storage on its content in carrots (Daucus carota L.). Journal of the Science of Food and Agriculture 83, 1010 1017 (2003). 10. E. R. Greenberg, J. A. Baron, M. R. Karagas, T. A. Stukel, D. W. Nierenberg, M. M. Stevens, J. S. Mandel, R. W. Haile. Mortality associated with low plasma concentration of -carotene and the effect of oral supplementation. Journal of the American Medical Association 275, 699703 (1996). 11. G. S. Omenn, G. E. Goodmann, M. D. Thornquist, J. Balmes, M. R. Cullen, A. Glass, J. P. Keogh, F. L. Meyskens Jr, B. Valanis, J. H. Williams Jr. Effects of a combination of -carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 334, 1150 1155 (1996). 12. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, The effect of vitamin E and -carotene on the incidence

of lung cancer and other cancers in male smokers. New England Journal of Medicine 330, 10291035 (1994). 13. K. Brandt, L. P. Christensen, J. HansenMller, S. L. Hansen, J. Haralsdottir, L. Jespersen, S. Purup, A. Kharazmi, V. Barkholt, H. Frkir, M. Kobk-Larsen. Health promoting compounds in vegetables and fruits. A systematic approach for identifying plant components with impact on human health. Trends in Food Science and Technology 15, 384393 (2004). 14. H. Matsunaga, M. Katano, H. Yamamoto, H. Fujito, M. Mori, K. Takata. Cytotoxic activity of polyacetylene compounds in Panax ginseng C. A. Meyer. Chemical and Pharmaceutical Bulletin 38, 34803482 (1990). 15. M. Kobk-Larsen, L. P. Christensen, W. Vach, J. Ritskes-Hoitinga, K. Brandt. Inhibitory effects of feeding with carrots or ()-falcarinol on development of
ALW_AZ_Fibre_Func_130x90_E

azoxymethane-induced preneoplastic lesions in the rat colon. Journal of Agricultural and Food Chemistry 53, 18231827 (2005). 16.C. Alasalvar, J. M. Grigor, D. Zhang, P. C. Quantick, F. Shahidi. Comparison of volatiles, phenolics, sugars, antioxidant vitamins, and sensory quality of different colored carrot varieties. Journal of Agricultural and Food Chemistry 49, 14101416 (2001). 17. A. Czepa, T. Hofmann. Structural and sensory characterization of compounds contributing to the bitter off-taste of carrots (Daucus carota L.) and carrot puree. Journal of Agricultural and Food Chemistry 51, 38653873 (2003).

The author: Prof Lars P. Christensen, Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark Phone: +45 89 99 3367, Fax: +45 89 99 3495, E-mail: larsp.christensen@agrsci.dk 16.05.2006 15:27 Uhr Seite 1

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