What is Lycopene ? Lykopen?

Lycopene is a carotenoid pigment, found in tomatoes and other red fruits, like watermelon, papaya, pink grapefruit and pink guava. Its name is derived from the tomato’s species classification, Solanum lycopersicum. Lycopene, similar to other carotenoids, is a natural fat-soluble pigment (red, in the case of lycopene) which is synthesized by some plants and micro-organisms but not by animals, where it serves as an accessory light-gathering pigment and to protect these organisms against the toxic effects of oxygen and light.

 Carotenoids are the principal pigments responsible for the colors of vegetables and fruits: these include ß-carotene, lutein, zeaxanthin and lycopene which is responsible for the red color of red tomatoes and other fruits it is found in. Its colour is due to its many conjugated carbon double bonds: each double bond reduces the energy required for electrons to transition to higher energy states, allowing the molecule to absorb visible lengths of progressively longer wavelengths.

 Lycopene absorbs most of the visible spectrum, so it appears red. Lycopene is an acyclic isomer of ß -carotene. It is a 40 carbon atom, open chain polyisoprenoid with 11 conjugated double bonds. Its molecular formula is C40H56. The structural formula of lycopene is represented in the diagram above. (All-E)-lycopene is the predominant geometric isomer found in plants. (Z)-isomers of lycopene are also found in nature, including (5Z)-, (9Z)-, (13Z)- and (15Z)- isomers. Lycopene found in human plasma is a mixture of approximately 50% (Z)-lycopene and 50% (all-E)-lycopene. Lycopene in processed foods, is mainly in the form of (all-E)-lycopene. Lycopene is the most common carotenoid in the human body and is one of the most potent carotenoid antioxidants.

Lycopene is easily absorbed by the organism and is naturally present in human plasma and tissues in higher concentrations than the other carotenoids. Its level is affected by several biological and lifestyle factors. Because of its lipophilic nature, lycopene concentrates in low-density and very-low-density lipoprotein fractions of the serum. Lycopene is also found to concentrate in the adrenal, liver, testes, and prostate. However, unlike other carotenoids, lycopene levels in serum or tissues do not correlate well with overall intake of fruits and vegetables.

Lycopene and Tomatoes Fruits and vegetables that are high in lycopene include not only tomatoes, but watermelon, pink grapefruit, papaya, and rosehip. In the European diet, however, more than 90% of the lycopene intake comes from tomatoes and tomato products. Lycopene and other antioxidants are present in the red, ripe, tomatoes. Weather, soil, varieties, and agricultural practices all have an effect on the content of lycopene and other carotenoids in the fresh tomato and processing and storage conditions also affect the lycopene content in the final product as well as its bioavailability. Unlike other micronutrients, such as vitamin C, lycopene content does not decrease during processing.

In fact, processing of tomatoes increases the lycopene content because of the concentration operations and more importantly it makes it more bioavailable. Because lycopene is so insoluble in water and is so tightly bound to vegetable fiber, the bioavailablity of lycopene is increased by processing. For example cooking and crushing tomatoes (as in the canning process) and serving in oil-rich dishes (such as pasta sauce or pizza) greatly increases assimilation from the digestive tract into the bloodstream.Lycopene in tomato paste is four times more bioavailable than in fresh tomatoes. Thus processed tomato products such as tomato juice, soup, sauce, and ketchup contain the highest concentrations of bioavailable lycopene.

The physical disruption of the cell structure in processed tomato products (tomato juice, above right) compared to fresh tomatoes (above left) partially explains the difference in the bioavailability of lycopene. In Europe, and most of the developed countries, a large proportion of the tomato consumption is in the form of processed tomato products, with an average 18kg (fresh tomato equivalent) consumed annually per capita in the European Union, with variations between 5 kg in the Czech Republic and 30 kg in Italy.

Disease Prevention The following is taken from an interview of Dr. Venket Rao (University of Toronto) in Tomate et Santé magazine - Tomate et Santé: So, Dr. Rao, please tell us about this exciting new title, Tomatoes, Lycopene & Human Health: Preventing Chronic Diseases and how it will affect the way tomato products are viewed in the future… Dr. Venket Rao: In recent years there has been a dramatic increase in the availability of scientific and lay publications about the role of fruits and vegetables in human health.

Over the last decade lycopene has been singled out as a significant factor and has received increasing amounts of attention on account of its potential role in the prevention of chronic diseases. This book is a direct result of this growing interest and sets out to summarize the current state of knowledge in this area. Tomatoes, Lycopene & Human Health provides, for the first time, comprehensive, up to date information on various aspects of tomato lycopene showing how we can protect our health simply through attention to our diet. Internationally recognized experts have contributed chapters to this book which will be of great interest to the scientific community, food related industries, government agencies and also consumers.

The book examines many aspects of tomato lycopene and human health including dietary guidelines recommending increased consumption of plant foods for the prevention of chronic diseases such as cancer, cardiovascular disease, osteoporosis and diabetes. Scientists are actively investigating the role of these nutrients in human health and how they can protect us. Much attention has been focused on oxidative stress-induced cellular damage which is recognized as leading to the progression of chronic diseases. Antioxidants play an important role in stopping the harmful effects of oxidative stress.

Tomate et Santé: Does this mean that simply consuming more tomato products such as sauces or soups can really protect our health? Dr. Venket Rao: The text shows how lycopene can now be referred to as a chemopreventive agent especially as new scientific evidence suggests the cancer preventing effects of lycopene may be the result of its synergistic interactions with other phytonutrients such as phytoene, phytofluenes and alpha-carotene found in tomatoes and tomato products. These positive interactions have led to the term ‘combination prevention’ of cancer.

There is growing evidence that a diet rich in carotenoids can protect against CVD. A review of epidemiological (population) studies provides convincing evidence in favor of a protective role for lycopene. This book discusses a new, five year science project called Lycocard which is devoting substantial resources to study the role of lycopene in the prevention of CVD. Lycocard is a multidisciplinary consortium of scientists, technologists, and patient organisations composed of fifteen partners from six European countries.

The result of the programme will lead to new dietary guidelines which propose a higher intake of foods rich in lycopene, especially tomato and tomato products. Tomate et Santé: Does the book cover any other areas of science which affect different aspects of human health? Dr. Venket Rao: Another chronic disease currently being investigated is osteoporosis, a major metabolic bone disease that primarily affects women and men over the age of 50.

One risk factor is oxidative stress caused by reactive oxygen species (ROS). Lycopene has been suggested in the prevention of osteoporosis in postmenopausal women based on epidemiological data. This is a new and very exciting area of study and could provoke serious dietary considerations for all people seeking to protect against this silent disease. There are also chapters on hypertension, a significant factor in coronary heart diseases with oxidative stress now recognized as a component and also on male infertility which is an important condition also addressed.

Due to its composition, sperm is highly vulnerable to oxidative damage. A recently completed study shows how lycopene acting as an antioxidant can improve sperm quality. A newer development is the application of lycopene is in cosmeceutical products. UV irradiation of human skin leads to photo-oxidative damage associated with adverse effects on skin health and appearance. Supplying the skin with micronutrients may produce a degree of photo-protection. in humans. It concludes that the health benefits of tomatoes and lycopene will have a significant positive impact on the tomato industry in the future. Tomate et Santé: so…. how much do we need to consume to really make a difference in protecting our health?

Dr. Venket Rao: Since humans do not synthesize lycopene, it has to be provided through diet. There is a general agreement among scientists that the average intake of lycopene is lower than required to obtain its beneficial effects. More recent studies show that a daily intake of 7-8 mg is enough to maintain sufficient levels of lycopene to fight oxidative stress and prevent chronic diseases. That’s one medium sized glass of tomato juice or a fair serving of a good tomato pasta sauce. Tomate et Santé: That all sounds amazing, but what about the future?

Dr. Venket Rao: While many great advances have been made over the past decade, several key areas remain to be explored. These include: Epidemiological studies to investigate the relationship between the consumption of tomatoes, tomato products and other sources of lycopene and cancer, cardiovascular diseases, osteoporosis, hypertension and neurodegenerative diseases. Research to develop tomato varieties with a high lycopene content that can be grown in high yield as well as being disease and pest-resistant.

Studies to investigate the beneficial interactions between lycopene and pharmaceutical drugs being used to treat chronic diseases. And best of all, expanding the scope of the effects of lycopene beyond disease prevention to the actual treatment of chronic diseases such as cancer and cardiovascular disease. Tomate et Santé: Dr. Rao, if you had to describe in simple non scientific terms what all of this really means, how would you do it? Dr. Venket Rao: Okay, here we go. I’ll provide you a list of terms and explanations which cover most of the science discussed in the book.

In simple terms, the best metaphor for describing what some of the terms contained in this volume mean is to describe the human body as a car. With a car, whatever the model, the same physical rules apply. The car will age with the passing of time and during this time it will be continuously attacked by exposure to the elements. Oxidative Stress: Quite simply we can describe oxidative stress (oxidation) as the rusting of the car.

The metal reacts with oxygen forming a brown coloured oxide which ruins the paint work and what you are left with is rust. Now if you allow that to continue it won’t be long before the continuous rusting action leaves an unsightly hole in the bodywork and its time for a new door panel and a re-spray. In human terms though we cannot simply go the body shop, we have to consider some other way to control the rusting action. Antioxidants: Anti-rust treatment for your body.

There are many nutritional elements which can do this but lycopene is one of the most effective. Tomatoes, especially processed tomato products also contain other nutrients which act and work together to increase their anti-rusting effects. Phytochemicals: This group of chemicals are the plant’s own self defence system against the sun and the elements. They are extremely potent and very effective and they also work for humans. Humans cannot make these chemicals in the body, they have to be ingested (eaten) as part of your healthy diet. Carotenoids: Essentially, the colour pigmentation of food as provided by Mother Nature. Lycopene is part of this family. Beta- carotene is what makes carrots orange and lycopene is what makes tomatoes red. Carotenoids are efficient free radical scavengers making them good for plants and good for us.

Free Radicals: These include oxy-radicals (or by another alias, singlet oxygen) and also ROS or reactive oxygen species. But not all free radicals are ROS and not all ROS are free radicals. It is these reactive molecules which cause the rusting action (oxidative stress). Free radicals effectively run around just looking for something to react with. That can be bad news if initiation, promotion or progress of a chronic disease is provoked. Antioxidants in the diet will find and quench (neutralize) these damaging molecules preventing further or ongoing harm.

They can be stopped and the easiest way is by including more antioxidant rich foods in your diet. Bioavailability: So how do we get the best from our dietary intake of foods which contain these chemicals? In the case of tomatoes, the heat from processing (effectively cooking) breaks open the cell matrix unlocking the most effective parts of the lycopene. This means you can absorb more of the right nutrients and enjoy an increased level of benefit to your health. This is bioavailability. Note, the same essential nutrients are found in fresh tomato but are much more available from processed. Therefore tomato juice or a good rich tomato pasta sauce provide some of the best ways to access these nutrients.

Tomate et Santé: Thank you Dr. Rao for taking the time to explain this complex and yet simple issue. It looks like this new book title will certainly change the way people look at tomato and tomato products in the future. This is a food which protects and heels, amazing!! The book is available from the Caledonian website at http://www.caledoniansciencepress.com Lycopene and Cardiovascular Diseases Böhm, V. Institute of Nutrition, Friedrich Schiller University Jena Dornburger Str. 25-29, 07743 Jena, Germany Volker.Boehm@uni-jena.de The risk factors that predispose one to cardiovascular diseases have been identified by means of several studies in well-defined population groups [1, 2]. Among the most important “cardiovascular risk factors” are cigarette smoking and serum cholesterol levels. Smoking has been reported to increase atherosclerotic diseases by about 50% and at least doubles the incidence of coronary artery disease. Moreover, considerable evidence supports the direct relation between cardiovascular diseases and increased levels of serum low-density lipoprotein (LDL) cholesterol.

There is now a scientific consensus that atherosclerosis represents a state of increased oxidative stress characterized by lipid and protein oxidation in the vascular wall. One initial step leading to the development of atherosclerosis might be the oxidation of unsaturated lipids in the LDL particles [3, 4]. Human LDL particles are heterogeneous in nature, and the smaller and denser particles are more prone to oxidation.

There is much debate about the antioxidant content of these particles, and carotenoids – mainly lycopene – may play a key role in protecting LDL particles. In addition to LDL oxidation, other oxidative events are involved in vascular diseases. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease, such as endothelial dysfunction and plaque disruption.

The contribution of antioxidants to cardiovascular diseases has been investigated to some degree; however, only scarce data are available about the specific effects of lycopene or tomato products [5-10]. Diet is believed to play a major role in the development of cardiovascular diseases. The gastric digestion of food containing oxidisable lipids and iron catalysts for peroxide decomposition (such as (met)myoglobin from muscle meat) can be accompanied by an extensive formation of potentially toxic lipid hydroperoxides which are implicated in the process of atherosclerosis.

Much interest and research are focused on identifying ways to prevent cardiovascular diseases through dietary changes. Primarily, epidemiological studies as well as some in vitro and limited in vivo experiments support the hypothesis that carotenoids, including β-carotene and lycopene, may protect lipoproteins and vascular cells from oxidation. In particular, lycopene is known to be an efficient scavenger of reactive oxygen species, including singlet oxygen (1O2) and other excited species [11, 12]. Lycopene also reduces the amount of oxidative DNA damage in cell culture and in rats in vivo [13, 14]. In addition, clinical studies demonstrated that a lycopene-rich diet protects against oxidative DNA damage in human leukocytes in vitro [15] and prostate tissue in vivo [16].

Several findings suggest that the redox properties of carotenoid molecules can deeply influence cell growth, by affecting molecular pathways involved in cell proliferation and apoptosis. A variety of animal and cell-culture studies also supports a role for lycopene in cell growth. All together, these findings suggest that lycopene can modify cell growth of smooth muscle cells present in the atheroma. Besides cardiovascular diseases, recent evidence points to carotenoids as effective antioxidants for inhibiting the development of degenerative diseases such as cancer, cataracts, etc. Intake of β-carotene has been inversely linked to incidence of lung cancer, as well as similar correlations between lutein and macular disease and between lycopene or tomato-based products and prostate cancer [17-19].

However, lycopene, being the strongest singlet oxygen quencher as well as a potent antioxidant compared to other carotenoids, has rarely been tested in studies for its role in cardiovascular disease prevention. Although some papers [20-22] reported inverse correlation between incidence for degenerative diseases and the consumption of fruit and vegetable instead of correlations to single ingredients of these foods, there is only scarce scientific knowledge on the interactions between different food components regarding their protective potential. Important points of bioavailability of lycopene as well as molecular mechanisms of its protective effects are not yet completely investigated.

 Lycopene is mainly contained in tomatoes, the second-most important vegetable in Europe (after potatoes) and in higher concentrations in processed tomato products like ketchup, tomato sauce/juice, as well as in red coloured fruits like water melon and guava. Accordingly, the main dietary source of lycopene in Europe and the US is mainly processed tomato products. Tomatoes and tomato products have been under investigation for their protective effects on health for many years. However, the scientific reasons for their positive effects are not yet completely clear.

Besides lycopene, which has been studied now for more than a decade, tomatoes contain other positive ingredients, including other carotenoids, ascorbic acid, tocopherols, folate, polyphenols, etc., whose interactions with lycopene have not yet been investigated in detail. Tomatoes have not been considered as an important source of folate in the diet, but due to their great consumption, the contribution of tomatoes to the total intake of folate might be relevant. A poor intake of folates in the diet has been associated with an increase of homocysteine level in human plasma, which is considered a risk factor in cardiovascular diseases.

This brief review has shown that there is a wealth of information about development of cardiovascular diseases as well as good evidence that certain foods – such as tomatoes – are healthy.

However, these two aspects are not sufficiently linked because research has lacked a “total food chain” approach. The missing link in the chain is the development of healthy new foods and nutritional guidelines that bring these two ends of the food chain together.

References (1) W. B. Kannel, P. W. F. Wilson, An update on coronary risk factors, Med. Clin. North Am. 79 (1995) 951-971. (2) J. D. Neaton, D. Wentworth, Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease: overall findings and differences by age for 316.000 white men, Arch. Intern. Med. 152 (1992) 56-64. (3) R. A. Riemersma, Epidemiology and the role of antioxidants in preventing coronary heart disease: a brief overview, Proc. Nutr. Soc. 53 (1994) 59-65. (4) J. M. Gaziano et al., Supplementation with b-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation, Atherosclerosis 112 (1995) 187-195. (5) D. L. Morris, S. B. Kritchevsky, C. E. Davis, Serum carotenoids and coronary heart disease, J. Am. Med. Assoc. 272 (1994) 1439-1441. (6) L. Kohlmeier et al., Lycopene and myocardial infarction risk in the EURAMIC study, Am. J. Epidemiol. 146 (1997) 618-626. (7) V. P. Palace, N. Khaper, Q. Qin, P. K. Singal, Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease, Free Radical Biol. Med. 26 (1999) 746-761. (8) R. Bilton, M. Gerber, P. Grolier, C. Leoni (eds), The White Book on antioxidants in tomatoes and tomato products and their health benefits, 2nd rev. edition 2001, CMITI Sarl Avignon, ISSN 1145-9565. (9) J. K. Willcox, G. L. Catignani, S. Lazarus, Tomatoes and cardiovascular health, Crit. Rev. Food Sci. Nutr. 43 (2003) 1-18. (10) D. P. Vivekananthan, M. S. Penn, S. K. Sapp, A. Hsu, Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials, Lancet 361 (2003) 2017-2023. (11) W. Stahl, B. Junghans, E. S. de Boer, E. S. Driomina, K. Briviba, H. Sies, Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein, FEBS Lett. 427 (1998) 305-308. (12) A. A. Woodall, G. Britton, M. J. Jackson, Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: relationship between carotenoid structure and protective ability, Biochim. Biophys. Acta 1336 (1997) 575-586. (13) H. R. Matos, V. I. Capelozzi, O. F. Gomes, P. di Mascio, M. H. Medeiros, Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate, Arch. Biochem. Biophys. 396 (2001) 171-177. (14) H. R. Matos, P. di Mascio, M. H. Medeiros, Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in cell cultures, Arch. Biochem. Biophys. 383 (2000) 56-59. (15) B. L. Pool-Zobel, A. Bub, H. Müller, I. Wollowsky, G. Rechkemmer, Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods, Carcinogenesis 18 (1997) 1847-1850. (16) P. Bowen, I. Chen, M. Stacewicz-Sapuntzakis, C. Duncan, R. Sharifi, L. Ghosh, H. S. Kim, K. Christov-Tzelkov, R. van Breemen, Tomato sauce supplementation and prostate cancer: Lycopene accumulation and modulation of biomarkers of carcinogenesis, Exp. Biol. Med. 227 (2002) 886-893. (17) E. Giovannucci, E. B. Rimm, Y. Liu, M. J. Stampfer, W. C. Willet, A prospective study of tomato products, lycopene, and prostate cancer risk, J. Natl. Cancer Inst. 94 (2002) 391-398. (18) H. D. Sesso, J. E. Buring, E. P. Norkus, J. M. Gaziano, Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women, Am. J. Clin. Nutr. 79 (2004) 47-53. (19) D. A. Cooper, A. L. Elridge, J. C. Peters, Dietary carotenoids and certain cancers, heart disease, and age-related macular degeneration: A review of recent research, Nutr. Rev. 57 (1999) 201-214. (20) G. Block, B. Patterson, A. Subar, Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence, Nutr. Cancer 18 (1992) 1-29. (21) S. Bradley, R. Shinton, Why is there an association between eating fruit and vegetables and a lower risk of stroke?, J. Human Nutr. Diet. 11 (1998) 363-372. (22) S. Franceschi, M. Parpinel, C. La Vecchia, A. Favero, R. Talamini, E. Negri, Role of different types of vegetables and fruit in the prevention of cancer of the colon, rectum, and breast, Epidemiol. 9 (1998) 338-341.