Lycopene-A Scientific Overview,What is Lycopene and its sources,Actions and Pharmacology.Tomato Extract Lycopene

Article Content:

Lycopene Actions and Pharmacology?

Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image Actions and Functions:

Lycopene may have anticarcinogenic and antiatherogenic activities.

The intake of tomato-based foods, especially processed tomato products, is associated with a significantly lower risk for prostate cancer, and also appears to be associated with a lower risk for lung cancer. The mechanism of the possible anticarcinogenic activity of lycopene is not well understood, but there are a few hypotheses. Cancer, as well as several other chronic diseases, is linked to oxidative stress. In vitro studies have demonstrated that lycopene has the highest antioxidant activity of all the carotenoids. It has the ability to quench singlet oxygen (more so than beta-carotene), to trap peroxyl radicals, to inhibit the oxidation of DNA, to inhibit lipid peroxidation, and in some studies, to inhibit the oxidation of low-density lipoprotein (LDL).

Functions of Lycopene:

Lycopene is a potent antioxidant and has been shown to suppress cancer cell growth. Also, lycopene has been demonstrated to be the most potent of all the carotenoids in quenching singlet oxygen, a highly-reactive and short-lived molecule capable of causing extensive cell damage. In vitro (outside the body) evidence suggests that lycopene has the potential to prevent cancer cells from dividing, an important mechanism in cancer prevention.

Absorption and Metabolism:

Carotenoids are absorbed like fats and transported via the lymphatic system into the liver. Absorption is dependent on the diet. Studies have demonstrated that higher fat diets increase lycopene absorption, while cholesterol-lowering drugs reduce its absorption. Also, lycopene from processed tomato products is more readily absorbed than that from raw tomatoes.

Structure, intake absorption, and transport:

Lycopene is defined chemically as an acyclic carotene with 11 conjugated double bonds, normally in the all-trans configuration. The double bonds are subject to isomerization, and various cis isomers (mainly 5, 9, 13, or 15) are found in plants and also in blood plasma. Since the human body is unable to synthesize carotenoids from endogenously produced biochemicals, the body is totally dependent on dietary sourced (exogenous) carotenoids. In general, tomato fruit and tomato-based food products provide at least 85% of dietary lycopene in humans. The remaining 15% are usually obtained from watermelon, pink grapefruit, guava, and papaya fruits that are dietary sources of lycopene, although at much lower levels than tomatoes.
Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image

Mechanism of Action:How does it work?

Non-antioxidant mechanisms have also been proposed. Failure of cell signaling may be a cause of cell overgrowth and eventually cancer. Lycopene may stimulate gap junction communication between cells. It is speculated that lycopene may suppress carcinogen-induced phosphorylation of regulatory proteins such as p53 and Rb antioncogenes and stop cell division at the G0-G1 cell cycle phase. One researcher has hypothesized that lycopene-induced modulation of the liver metabolizing enzyme cytochrome P450 2E1 may be the underlying mechanism of protection against carcinogen-induced preneoplastic lesions in the rat liver. Lycopene may also reduce cellular proliferation induced by insulin-like growth factors. There is some preliminary in vitro evidence for the latter proposal.

The mechanism of the possible antiatherogenic activity of lycopene is likewise unclear. Lycopene's antioxidant activity is a possibility. Lycopene has also been found to inhibit cholesterol synthesis, to inhibit HMG-CoA (hydroxymethylglutaryl coenzyme A) reductase activity and to upregulate LDL receptor activity in macrophages. A small preliminary study in humans, reported an LDL-cholesterol-lowering effect of lycopene.
Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image

How does it work?

Carotenoids work to protect against cancer and aging-related diseases by acting as an antioxidant to counteract damaging effects of free radicals in tissues. Lycopene is one of the major carotenoids found in human blood and tissues, and is found primarily in the testis, adrenal glands, liver, prostate, breast, colon, and lung. Because lycopene cannot be metabolized to Vitamin A, its biological effects in humans have been attributed to other mechanisms. Lycopene is currently considered one of the most efficient carotenoids at protecting against free radicals that damage critical parts of the cell, including lipids, membrane lipoproteins, proteins, and DNA

Lycopene is a red pigment found in plants and is part of a large class of plant compounds called carotenoids. Carotenoids are fat soluble and create yellow, orange or red colors in plants. Carotenoids are not made by humans. Lycopene is not found in high amounts in many plants. The greatest sources of lycopene in fresh fruits and vegetables are watermelon, tomato, red grapefruit and guava.

The red color found in strawberries, cherries, etc. is a water soluble pigment called anthocyanin, and is formed by a very different pathway from the carotenoids.

The primary role of carotenoids in plants is to neutralize compounds created during photosynthesis. These compounds are often hydrogen peroxide or singlet oxygen, both of which will attack and destroy cell membranes, ultimately damaging the cell. Singlet oxygen is oxygen with a higher energy charge because outer orbital electrons are spinning in opposite directions.

Humans breathe in oxygen as O2. The biological processes in the body use oxygen for reactions, frequently creating singlet oxygen as a byproduct. The singlet oxygen is very reactive (high electric charge) and therefore must be eliminated by the body before cell damage occurs. The body uses antioxidants, compounds that look for singlet oxygen and neutralizes it. Of the carotenoids, lycopene is the most effective oxygen scavenger because it can neutralize several singlet oxygen with one lycopene molecule. Other antioxidants are Vitamin C (ascorbic acid) and Vitamin E.
Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image

Lycopene function in the human body:What does it do?

Although not considered an essential nutrient, research has shown that lycopene may have various benefits for human health. As a major carotenoid in human blood, lycopene protects against oxidative damage to lipids, proteins, and DNA. Lycopene is a potent quencher of singlet oxygen (a reactive form of oxygen), which suggests that it may have comparatively stronger antioxidant properties than other major plasma carotenoids. Lycopene has been found to be a potent and specific inhibitor of cancer cell proliferation, which is regulated by an elaborated cellular process called cell cycle.?Rapid and uncontrolled cell division is a hallmark of cancer cell metabolism; lycopene activity in retarding cell cycle progression may explain its demonstrated activity in retarding the spread of certain types of cancer. Lycopene may prevent malignant transformation (the cellular process which describes the transformation of a normal cell into a cancer cell). Contact inhibition is one of the mechanisms that controls excessive cell division. By this mechanism, a cell, in crowded surroundings, will stop multiplying. Special structures in the cell membrane, termed a gap-junction, function as communication channels between cells. Normal cells are both contact-inhibited and have a functional gap-junction whereas most tumor cells exhibit fewer of these structures. Lycopene was found to induce the formation of the protein connexin, one of the major building blocks of these channels, and thereby to restore gap junctions. Lycopene induces Phase II enzymes which help to eliminate carcinogens and toxins from the body. The change of the levels of so many regulatory proteins is related to lycopene ability to modulate various transcription factors which are key players in the process of new cellular protein synthesis.
Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image

What does it do?

Lycopene, found primarily in tomatoes, is a member of the carotenoid family,which includes beta-carotene and similar compounds found naturally in food,and has potent antioxidant capabilities.

A study conducted by Harvard researchers examined the relationship between carotenoids and the risk of prostate cancer. Of the carotenoids studied, only lycopene was clearly linked to protection. The men who had the greatest amounts of lycopene in their diet (6.5 mg per day or more) showed a 21% decreased risk of prostate cancer compared with those eating the least. This report suggests that lycopene may be an important tool in the prevention of prostate cancer. This study also reported that those who ate more than ten servings per week of tomato-based foods had a 35% decreased risk of prostate cancer compared with those eating less than 1.5 weekly servings. When the researchers looked at only advanced prostate cancer, the high lycopene eaters had an 86% decreased risk (although this did not reach statistical significance due to the small number of cases).

Contrary to popular opinion, research suggests that there is no preferential concentration of lycopene in prostate tissue. Although prostate cancer patients have been reported to have low levels of lycopene in the blood, and lycopene appears to be a potent inhibitor of human cancer cells in test-tubes, evidence is conflicting concerning whether an increased intake of tomato products is protective against prostate cancer. Some studies, like the one discussed above, have reported that high consumption of tomatoes and tomato products reduces risk of prostate cancer. Other studies, however, are inconclusive, and some have found no protective association.

There is some evidence that lycopene may be helpful in the treatment of prostate cancer. In a preliminary trial, 26 men with prostate cancer were randomly assigned to receive lycopene (15 mg twice a day) or no lycopene for three weeks before undergoing prostate surgery. Prostate tissue was then obtained during surgery and examined. Compared with the unsupplemented men, those receiving lycopene were found to have significantly less aggressive growth of cancer cells. In addition, a case report has been published of a 62-year-old man with advanced prostate cancer who experienced a regression of his tumor after starting 10 mg of lycopene per day and 300 mg of saw palmetto three times per day. As saw palmetto has not been previously associated with improvements in prostate cancer, the authors of the report attributed the response to the lycopene.Long-term controlled studies are needed to confirm these promising initial reports.

There is no evidence that tomato intake has any effect on benign prostatic hyperplasia (BPH).

Another study found that for the 25% of people with the greatest tomato intake, the risk for cancers of the gastrointestinal tract was 30-60% lower, compared with those who ate fewer tomatoes. These reduced risks were statistically significant.15 A study of women found that the 75% who ate the least amount of tomatoes had between 3.5 and 4.7 times the risk for pre-cancerous changes of the cervix (cervical intraepithelial neoplasia).Other researchers have also reported evidence suggesting that high dietary lycopene may be linked to protection from cervical dysplasia. While preliminary evidence also links dietary lycopene with protection from breast cancer,another study did not find this link.

In a review of 72 studies,20 one researcher reported 57 associations between tomato intake or blood lycopene levels and decreased risk of cancer. Of these associations, 35 were statistically significant. The benefit was strongest for prostate, lung, and stomach cancers, although protective associations were also found for cancers of the pancreas, colon, rectum, esophagus, oral cavity, breast, and cervix. Because the data were from observational studies, a cause-and-effect relationship cannot be firmly established. However, the consistently lower risk of cancer associated with higher consumption of lycopene-containing tomatoes, provides a strong foundation for further research on lycopene.

In Europe, researchers have found a statistically significant association between high dietary lycopene and a 48% lower risk of heart disease.Lycopene supplementation has also boosted immune function in the elderly. In that trial, 15 mg of lycopene per day increased natural killer cell activity by 28% in 12 weeks.
Tomato Extract Lycopene Lycopersicum esculentum extract Natural Tomato Extract CAS:090131-63-8 502-65-8 photo picture image

Pharmacokinetics:

Lycopene is available in nutritional supplements in the form of an oleoresin, in phospholipid complexes and in oils. In foods, lycopene exists as part of a matrix (in chloroplasts or chromoplasts) within the vegetables or fruit. The efficiency of absorption of lycopene from supplements and foods is variable. The efficiency of absorption of lycopene from tomatoes, in which lycopene is tightly bound within the matrix, is low. It is much higher in processed tomato products. The improved availability of lycopene from processed foods is due to its release from the ruptured plant cells following the mechanical and thermal processing, as well as heat induced-trans to cis isomerization. Cis-lycopene is reported to be more bioavailable than trans-lycopene. Lipids increase the absorption of lycopene. For example, the combination of tomato sauce and olive oil delivers more absorbable lycopene than tomato sauce without oil.

Lycopene from supplements or from the matrices of foods is either solubilized in the lipid core of micelles (formed from bile salts and dietary fat) in the lumen of the small intestine or forms clathrate complexes with conjugated bile salts. Micelles and clathrate complexes deliver lycopene to the enterocytes.

Lycopene is released from the enterocytes into the lymphatics in the form of chylomicrons. Lycopene is transported by the lymphatics to the general circulation via the thoracic duct. In the circulation, lipoprotein lipase hydrolyzes much of the triglycerides in the chylomicrons, resulting in the formation of chylomicron remnants. Chylomicron remnants retain apolipoproteins E and B48 on their surfaces and are mainly taken up by hepatocytes and to lesser degrees by other tissues. Within hepatocytes, lycopene is incorporated into lipoproteins. Lycopene is released into the blood from the hepatocytes in the form of very-low density lipoproteins (VLDL) and low-density lipoproteins (LDL). In the plasma, VLDL is converted by lipoprotein lipase to LDL. Lycopene is transported in the plasma predominantly in the form of LDL.

There is much unknown about the pharmacokinetics of lycopene, in particular its distribution and its metabolism.