What Is the Connection Between Lycopene and Cancer?

A carotenoid found in plant foods is also a red pigment. Deep red needle-like crystals, soluble in chloroform, benzene and oil, but insoluble in water. It is unstable to light and oxygen and turns brown when iron is encountered. The molecular formula is C ₄₀ H ₅₆ and the relative molecular mass is 536.85. There are 11 conjugated double bonds and 2 non-conjugated double bonds in the molecular structure, and the composition is a straight-chain hydrocarbon. Does not have the physiological activity of vitamin A, but has a strong antioxidant function. The content of ripe red plants is higher, especially in tomato, carrot, watermelon, papaya and guava. It can be used as a pigment in food processing, and it is also often used as a raw material for antioxidant health foods. ^[1]

Chinese name: Lycopene
Foreign name: lycopene
CAS number: 502-65-8
Solubility: Soluble in chloroform, benzene and oil but insoluble in water

Health effect: Protect cardiovascular and cerebrovascular, enhance immunity, etc.
Application: Health products, food additives, beverage colors, etc.
Food source: Tomato, carrot, watermelon, papaya and guava
Features: Unstable to light and oxygen, turns brown with iron

Introduction to lycopene

Lycopene is widely found in tomatoes, tomato products, and fruits such as watermelon and grapefruit. It is the main pigment in mature tomatoes and one of the common carotenoids. In 1989, MASCIO found that lycopene had the highest quenching activity against singlet oxygen among all carotenoids. Subsequently, the research on the function of lycopene became a hot topic. The research involved the absorption and metabolism of lycopene, lycopene reduced the risk of various tumors and cardiovascular diseases such as prostate cancer, and the extraction of lycopene And measurement methods. At present, lycopene has not only been widely used as a natural pigment, but also has been increasingly used in functional foods, medicines and cosmetics. ^[2]

Physical and Chemical Properties of Lycopene

Lycopene is an unsaturated olefin compound, the main pigment in mature tomatoes, and one of the common carotenoids. Lycopene does not have the -caragone ring structure of -carotene, so it cannot be converted into vitamin A in the body, which does not belong to provitamin A. The molecular formula is C ₄₀ H ₅₆ and there are many cis-trans conformers. Lycopene is a fat-soluble substance, hardly soluble in water, methanol, and ethanol, soluble in ether, petroleum ether, hexane, and acetone, and soluble in organic solvents such as chloroform, carbon disulfide, and benzene. The lycopene molecule has 11 conjugated double bonds and 2 non-conjugated double bonds, so its stability is poor, and cis-trans isomerization and oxidative degradation are easy to occur. Factors affecting lycopene stability include oxygen, light, heat, acids, metal ions, oxidants and antioxidants. ^[2]

Lycopene absorption metabolism

Lycopene absorption

Lycopene absorption is higher than -carotene and -carotene, but it is also affected by many factors. The cis configuration is more easily absorbed than the trans configuration. Most of the naturally occurring lycopene is in the all-trans configuration, while most of the human tissue is in the cis configuration (> 50%), and the proportion of lycopene in the body does not vary with food. The lycopene configuration of the medium changed. It is currently believed that the lycopene in the trans configuration is mostly deformed into the cis configuration in the gastrointestinal tract before absorption. The protein-carotene complex in food, a large amount of soluble dietary fiber (if gum), a combination of cholesterol and resin, and a lack of iron, zinc, and protein, and intestinal diseases may interfere with the absorption of lycopene. Thermal processing can transform the trans-structure of some natural lycopene into cis-structure, and the lipids in the food matrix can promote the release of lycopene. Lycopene is more easily absorbed after adding fat to heat treatment than unprocessed . ^[2]

Different human experiments have reported that the half-life of lycopene can range from 2 to 3 days to 10 to 33 days. The lycopene nutrition status can generally be judged by the serum lycopene concentration. U.S. adults' serum lycopene content is mostly between 0.42 and 0.47 mol / L. However, the dietary structure and lycopene intake of China and European and American countries are quite different. The basic data of the system, there are reports in the literature of 69 adult adults aged 30 to 92 in a community in Shanghai. The average lycopene content is about 0.32 g / ml (about 0.59 mol / L). ^[2]

Lycopene distribution

Lycopene is mainly distributed in the human testis and adrenal glands, as well as in liver, adipose tissue, prostate and ovary. Lycopene was not detected in the brain tissue (indicating that it may not be able to cross the blood-brain barrier and enter the brain tissue). There was a positive correlation between lycopene concentration in blood and tissue within a certain dose range. About 50% of carotenoids in the human body are lycopene, and lycopene is also one of the main carotenoids contained in human milk. ^[2]

Lycopene metabolism and excretion

At present, little is known about the metabolites of lycopene in the body. Only two oxidative metabolites have been detected in human serum, skin and milk, namely 5,6-dihydroxy-5,6 dihydrolycopene and 1 , 5-dihydroxy-2,6-epoxylycopene. It is speculated that lycopene may first be oxidized to epoxide, and then reduced to form 5,6-dihydroxy-5,6-dihydrolycopene. Unabsorbed lycopene is mainly excreted through feces, and the part distributed in the skin can be lost due to keratinization and shedding of the epidermis. ^[2]

Biological effects of lycopene

The long-chain polyunsaturated olefin molecular structure of lycopene has a strong ability to eliminate free radicals and antioxidant capacity. At present, researches on its biological effects are mainly focused on antioxidants, reducing the risk of cardiovascular disease, reducing genetic damage, and inhibiting the development of tumors. ^[2]

Lycopene enhances oxidative stress and anti-inflammatory effects in the body

Oxidative damage is considered to be one of the main causes of increased incidence of cancer and cardiovascular and cerebrovascular diseases. The in vitro antioxidant capacity of lycopene has been confirmed by many experiments. The ability of lycopene to quench singlet oxygen is more than twice that of the commonly used antioxidant -carotene and 100 times that of vitamin E. ^[2]

Lycopene protects the cardiovascular and cerebrovascular

Lycopene can deeply remove vascular garbage, regulate plasma cholesterol concentration, protect low-density lipoprotein (LDL) from oxidation, repair and perfect oxidized cells, promote intercellular glial formation, and enhance vascular flexibility. A survey study showed that serum lycopene concentration was inversely related to the incidence of cerebral infarction and cerebral hemorrhage. Studies on lycopene anti-atherosclerosis in rabbits show that lycopene can effectively reduce the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in rabbits. The effect is comparable to fluvastatin sodium. Other studies have shown that lycopene has a protective effect on cerebral ischemia. It mainly inhibits the activity of glial cells and reduces the area of cerebral perfusion injury through antioxidant and scavenging free radicals. ^[3]

Lycopene protects the skin

Lycopene also functions to reduce skin damage from radiation or ultraviolet (UV) rays. When the skin is irradiated with UV, the lycopene in the skin is combined with the free radicals generated by the UV to protect the skin tissue from damage. Compared with the skin without UV, the lycopene is reduced by 31% to 46%, and the content of other ingredients is almost constant. Studies have shown that by ingesting foods that are rich in lycopene, UV can be prevented and erythema can be avoided by UV irradiation. Lycopene can also quench free radicals in epidermal cells, and it has a significant fading effect on age spots. ^[3]

Lycopene enhances immunity

Lycopene can activate immune cells, protect phagocytic cells from their oxidative damage, promote the proliferation of T and B lymphocytes, stimulate the function of effector T cells, promote the production of certain interleukins and inhibit the generation of inflammatory mediators. Studies have found that taking lycopene capsules at medium doses can improve the body's immunity and reduce the damage to the body's immunity from acute exercise. ^[3]

Tomato Red Vegetarian Source

Mammals cannot synthesize lycopene by themselves, they must be obtained from vegetables and fruits. Lycopene is mainly found in foods such as tomato, watermelon, grapefruit and guava. The content of lycopene in tomatoes varies with variety and maturity. The higher the maturity, the higher the lycopene content. The content of lycopene in fresh ripe tomatoes is generally 31 37mg / kg. The content of lycopene in tomato juice / sauce is usually about 93 290mg / kg according to the concentration and production method. Fruits with higher lycopene content are also There are guava (about 52mg / kg), watermelon (about 45mg / kg), grapefruit (about 14.2mg / kg) and so on. Carrot, pumpkin, plum, persimmon, peach, mango, pomegranate, grape and other fruits and vegetables can also provide a small amount of lycopene (0.1 ~ 1.5mg / kg). ^[2]

Evaluation of lycopene safety

Except for two cases of lycopene found in human experiments, there have been no reports of other adverse reactions caused by human intake of lycopene poisoning or excessive lycopene. The two cases of lycopene were both caused by long-term high-dose intake of tomatoes and foods rich in lycopene. The symptoms were mainly orange staining on the skin, and the symptoms gradually disappeared after stopping the intake. ^[2]

Lycopene is currently considered a reversible harmless effect by the Food and Nutrition Board (Institute of Medicine, 2000). ^[2]

In animal experiments, the oral median lethal dose (LD50) of natural lycopene was all> 5000 mg / kgBW. For synthetic lycopene, the highest dose of 1000 mg / kg BW for 4 weeks and 500 mg / kg BW for 13 weeks were not found. Rats were given a lycopene at a dose of 1000 mg / kg BW daily for 100 days, or a lycopene at a dose of 20 mg / kg BW daily for 200 days. No toxic reaction caused by the test substance was observed. Dogs were fed with lycopene at 100 mg / kg BW for 192 days. Except for slight pigmentation of the liver and kidney, no toxic reaction was observed. In the one-year feeding experiment of rats, the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) in the medium-dose group (50 mg / kg BW) were decreased, while the high-dose group (250 mg / kg BW) Both ALT and AST increased, and aspartate aminotransferase activity recovered after 13 weeks of ingestion, but alanine aminotransferase only partially recovered, so 50 mg / kg BW was set to a level where no harmful effects were observed (No Observed Adverse EffectLevel, NOAEL). No positive findings were found in reproductive and developmental toxicity studies using rats (up to 3000 mg / kg BW) and rabbits (up to 2000 mg / kg BW). Lycopene's genetic toxicity experiments (in vivo micronucleus experiments, TK gene mutation experiments, chromosomal aberration experiments, etc.) have shown that it has no mutagenicity. ^[2]

Application of lycopene

According to Minte's "Global New Product Database" (GNPD), from 2003 to 2010, a total of 418 new products containing lycopene were launched worldwide. These products cover the food, supplements and cosmetics sectors, with lycopene-containing supplements being the most popular products. ^[3]

Lycopene health products and sports supplements

GNPD data show that there are 177 new lycopene-containing supplement products worldwide. The State Food and Drug Administration (CFDA) can check that there are 31 types of lycopene health products that have obtained the national food health word, including 2 imported health products, and the rest are domestic health products. These 31 kinds of health products are mainly used for anti-oxidation, delaying aging, enhancing immunity, regulating blood lipids, etc. Among them, 2 are tablets, 1 oil, and the rest are capsules. ^[3]

Lycopene cosmetics

GNPD data show that there are 81 new skin care products containing lycopene, and 51 types of makeup. Typical products, such as lycopene moisturizing emulsion, have whitening and anti-aging effects. Domestic products include lycopene whitening essence application needles, which have anti-oxidant, anti-allergic and whitening effects. ^[3]

Lycopene food and drink

In the food and beverage sector, lycopene has obtained European "new food" approval and US GRAS (generally considered safe) status, with non-alcoholic beverages being the most popular. GNPD data show that there are 20 new products: 7 in the fields of bread and breakfast cereals; 7 in the field of processed meat, fish and eggs; 7 in the field of dairy products; 6 in the field of chocolates and sweets; sauces and seasonings 5 types; desserts and ice cream. Applying it to dairy products not only keeps the nutrition of the dairy products, but also enriches its health-care functions. ^[3]

Application of lycopene in meat products

During processing and storage of meat products, changes in color, texture, and flavor occur due to oxidation. At the same time, with the increase of storage time, the proliferation of microorganisms, especially botulinum, will also cause the meat to spoil and deteriorate. Therefore, chemical preservatives nitrite are often used to inhibit the growth of microorganisms, prevent meat spoilage and improve the flavor and colour. However, research has found that under certain conditions, nitrite can combine with protein breakdown products to form carcinogen nitrosamines. Therefore, the addition of nitrite to meat has been controversial. Lycopene is the main component of red pigments in tomatoes and other fruits. It has strong antioxidant capacity and good physiological functions. It can be used as a freshener and colorant for meat products. In addition, the acidity of tomato products rich in lycopene will lower the pH value of meat and will inhibit the growth of spoilage microorganisms to a certain extent. Therefore, it can be used as a preservative for meat foods, and can partially replace nitrite. effect. ^[4]

Application of lycopene in edible oil

Oxidative deterioration is an adverse reaction that often occurs during the storage of edible oil, which not only causes the quality of edible oil to change or even loses its edible value, but also more serious is that long-term intake of degraded edible oil can cause various diseases. ^[4]

In order to delay the deterioration of edible oils, certain antioxidants are often added during processing. However, with the increase of people's awareness of food safety, the safety of various antioxidants has also been raised. Therefore, finding safe natural antioxidants has become a focus of food additives. Lycopene has superior physiological functions and strong oxidation resistance, can efficiently quench singlet oxygen and scavenge free radicals, and inhibits lipid peroxidation. Therefore, adding it to edible oil can alleviate the deterioration of fats and oils. ^[4]

Other applications of lycopene

Lycopene, as a carotenoid compound with great potential, cannot be synthesized by the human body. It must be obtained through dietary supplements. After discovering the physiological function of lycopene, Israel s Ly-cored Natural Products Industries Ltd. took the lead Development of lycopene products. In addition, Henkel Corporation in the United States and Makhtshim Corporation in Japan have produced drugs with lycopene as the main active ingredient. Their main functions include lowering blood pressure, treating hypercholesterolemia, hyperlipidemia, and reducing cancer cells, which have significant effects. . At present, there are few reports on the use of lycopene as a food or pharmaceutical raw material in China. ^[5]

Lycopene can be used as a nutritional supplement to maintain human health. Lycopene oleoresin made by the Japanese has been widely used in beverages, cold foods, meat products and baked goods. Due to the special function of lycopene, it is also a functional factor for the development of functional foods of modern significance, such as making antioxidant health capsules, or making it into medicated cans after being compatible with other medicinal plants. ^[5]

Application of lycopene in various countries

China has approved the synthesis of lycopene (INS No. 160d) as a colorant (GB 2760-2011 "Standards for the Use of Food Additives") for beverages (except packaged drinking water), with a maximum usage of 15mg / kg; candy, maximum use The amount is 60mg / kg; solid soup, the maximum usage is 390mg / kg; semi-solid compound seasoning, 40mg / kg (the above are all based on pure lycopene). Lycopene is also used in health foods with functions such as anti-oxidation and immunity enhancement. The Joint FAO / WHO Expert Committee on Food Additives (JECFA) in 2006 considered lycopene as a pigment and nutrient supplement. ^[2]

In 2008, the European Union classified food supplements containing non-vitamins and minerals into 6 categories (amino acids, enzymes, essential fatty acids, probiotics, plant-derived substances, other categories), and lycopene was classified as "other categories". In 2009, synthetic lycopene, natural lycopene, lycopene extracted from Blakesleatrispora were approved as new food ingredients, and lycopene extracted from tomatoes was also approved. Oil and fat products are new ingredients for special therapeutic foods. ^[2]

Australia / New Zealand considers that lycopene extracted from tomatoes is a non-traditional food or a new resource food, but it is determined that there is no safety issue. It has been approved as a food additive, numbered 160d, and can be used as a colorant and dietary supplement. ^[2]

Codex Alimentarius Commission (CAC) approved three sources of lycopene, namely tomato extract, Blastodium trispora extract, and synthetic lycopene (INS No. 160d) as food colorants, and did not consider it Need to determine its ADI value. ^[2]

In 2006, the Council for Responsible Nutrition (USA) conducted a risk assessment of lycopene and proposed an "Observed Safe Level (OSL)" of 75 mg / d. The assessment is based on more than 30 human intervention experiments that have been published and peer reviewed before 2006. In these experiments, the highest dose was 150 mg / d (intake for 7 consecutive days); followed by 75 mg / d (15 healthy adults for 28 days); the longest duration was 140 days (healthy adults 13.3 mg / d) No adverse effects were observed, so the Tolerable Upper Intake Level (UL) cannot be deduced. The OSL calculated from animal experimental data was 270 mg / d. ^[2]

Lycopene extraction and separation method

The extraction and separation methods of lycopene mainly include organic solvent extraction method, enzyme reaction method, microbial fermentation method, artificial synthesis method, supercritical CO ₂ extraction method, microwave method and the like. The most traditional method is the solvent extraction method (ie, the extraction method), but the traditional extraction method has the disadvantages of long extraction time, large labor intensity, large raw material and processing energy consumption, and easy destruction of heat-sensitive components. Chemically synthesized lycopene contains a variety of isomers and impurities, so it is banned from use in health products, and its market share has decreased sharply; while natural extraction methods are limited by raw materials, it is difficult to further reduce costs and production is significantly affected by the season. Therefore, the development of microbial fermentation production methods has shown obvious advantages in recent years. ^[5]

Lycopene is widely distributed in nature. At this stage, people are gradually aware of the harmfulness of synthetic pigments to the human body, so extracting lycopene from natural plants has become a more common method. ^[5]

Lycopene organic solvent extraction

Principle: Lycopene is an aliphatic hydrocarbon with 11 carbon-carbon unsaturated double bonds. It is insoluble in water, hardly soluble in methanol and ethanol, soluble in ether, petroleum ether, hexane and acetone, and easily soluble in chloroform. , Carbon disulfide, benzene and other organic solvents. Based on this property, lycopene can be extracted from tomatoes using a lipophilic organic solvent. ^[5]

Process flow: tomato mashed into mud drying crushing organic solvent extraction extraction solution filtration filtrate concentration crude product

Extraction pH, extraction temperature and extraction time are the most important factors affecting the extraction effect. The organic solvent extraction method has fewer equipment, simple processes, and convenient operations, but because tomatoes also contain other ingredients, and organic solvents will have traces of residues. Only solvent extraction alone is used to obtain products with generally low purity, lycopene content of about 5% to 15%, and usually does not produce lycopene crystals, but a kind of oily substance, namely lycopene oil Resin. ^[5]

CO2 Supercritical CO2 extraction of lycopene

Principle: Under higher pressure, the difference between the liquid phase and the gas phase shrinks. When a certain temperature and pressure are reached, the difference disappears and merges into a phase. This state becomes a critical point. The temperature and pressure at this time are called critical temperature and criticality, respectively. Pressure, when the temperature and pressure exceed the critical point, the properties of its fluid are between liquid and gas, which is called supercritical fluid. ^[5]

Supercritical fluid has the characteristics of gas-liquid duality. It has both high permeability and low viscosity equivalent to gas, and similar density to liquid and excellent dissolving ability to substances. It can extract useful ingredients from raw materials to achieve the required separation purpose, and is especially suitable for heat sensitive ingredients such as lycopene. ^[5]

Process flow: fresh red tomato raw material beating pressing filtration vacuum drying pulverizing screening weighing installation of extraction tank and sealing control proper working parameters static and dynamic extraction pressure reduction separation get tomatoes from separation column Red pigment product quality inspection ^[5]

Lycopene reaction

Principle: The enzyme reaction method mainly uses the enzyme contained in tomato skin to react to extract lycopene. The method is to react pectinase and cellulase in tomato skin under alkaline conditions to decompose pectin and cellulose, so that the lycopene protein complex is dissolved from the cells.

Process: Wash fresh tomatoes (roughly called) peel and peel at 100 ° C (completed in 5-7s) beat heat-passivating enzyme activity (85 ° C, 20min) cool to 55 ° C, adjust pH to about 4.5 (use Phosphoric acid and sodium hydroxide) Add pectinase and cellulase mixed enzyme (add 0.5g / 100g tomato, the ratio of the two enzymes is listed as 1: 2) for 2h coarse filter to remove the core add 2% dichloromethane Extraction of petroleum ether with a material ratio of about 1: 3 separation by separation tower finished product ^[5]

Compared with the traditional organic solvent extraction method, this method shortens the extraction time and improves the extraction rate significantly. ^[5]

Two-step saponification of lycopene

Principle: Firstly, use KOH solution to perform the first alkaline washing and saponification on the pretreated tomatoes to remove most of the fatty acid glycerides and various free fatty acids in the tomatoes, and then use organic solvents to obtain crude lycopene extracts. The product is subjected to secondary saponification to separate the proteins, fatty acids, and fatty acid glycerides in the tomato cell debris to form a water-soluble saponification, releasing the water-insoluble lycopene contained therein, and finally recrystallizing the method to obtain a higher purity tomato red Crystals. ^[5]

Process flow: fresh tomato washing freeze-drying organic solvent for pretreatment alkali saponification in water bath washing to neutral mixed solvent extraction obtaining lycopene-rich extract distillation under reduced pressure concentration lycopene oil Resin lycopene oleoresin and glycerin are mixed uniformly add KOH in ethanol solution, mix well after adding distilled water leave to separate, wash the oil phase to neutral wash with ethanol 2 to 3 times treatment The oleoresin was dissolved in acetone at 50 ° C to remove insoluble matters, and it was left at room temperature for 8 hours to obtain lycopene crystals.

During the saponification process, the saponification ratio significantly affects the yield, the saponification temperature and the saponification time also have an influence, but the degree of influence gradually decreases. ^[5]

Lycopene microwave method

Principle: During extraction, the microwave penetrates the extraction medium and penetrates deeply into the material cells, causing the polar molecules inside the material to collide and rub fiercely with the change of the external electromagnetic field, causing the temperature inside the material to rise rapidly, thereby causing cells Rupture, allowing the effective components in the cell to flow freely and be dissolved by the solvent.

Process flow: washing fresh tomatoes beating adding organic solvents for microwave heating extraction filtering vacuum evaporation of organic solvents finished products ^[5]

Lycopene microbial fermentation

In addition to extracting lycopene from tomatoes, algae and fungi and yeast fermentation can be used to prepare lycopene. Isopentene pyrophosphate (IPP), as the first more direct precursor in the lycopene synthesis pathway, is converted from glucose. Lycopene has been synthesized via isoprenoid metabolism

Biosynthetic pathway of lycopene The details are shown in the figure. ^[5]

The lycopene-containing genus Rhodobacterium is higher, but it has not yet been industrially produced. Lycopene can be produced by the fermentation of mold, but lycopene can form a variety of carotenoids through the action of cyclase, and the cyclization reaction needs to be avoided. ^[5]

The use of genetic engineering and biotechnology has been able to partially control the direction of precursor conversion during lycopene synthesis, such as enabling FPP to competitively shift from ergosterol production to lycopene. The technology of lycopene production by microbial fermentation has not reached the scale of industrial production at present, but the cost and pollution of the fermentation method are relatively low. If it can further improve the storage capacity and transformation power of the bacterial cells, it is economical and effective to achieve industrial production of lycopene. way. ^[5]

Lycopene prospect

As people pay more attention to dietary health, lycopene is more and more popular. In addition, it has also attracted much attention in terms of feed additives. Studies have shown that lycopene used in aquaculture can make aquatic animals bright in color and improve quality; mixed with lutein to make carotenoid preparations can prevent animal vitamin deficiency. At the current stage, lycopene is produced by microbial fermentation. The production cycle is short and it is not subject to site and season restrictions. Most of the raw materials used are low-cost food crops, which have low production costs and are safe and non-toxic. With the deepening of research and the continuous emergence of innovative products in various fields, lycopene has a good application prospect. ^[3]