Lycopene

Nutritional, Medicinal and Therapeutic Properties

V R Preedy, Ronald R. Watson, V R Preedy, Ronald R. Watson

• Publisher: CRC Press
• Year: 2019
• eBook ISBN:
  9780429526657
• Topic: Medicine
• Subtopic: Oncology

Tomatoes have become a dietary staple for humans in many parts of the world. The characteristic deep red color of the ripe tomato fruit and related products is mainly due to lycopene. Lycopene is the predominant carotenoid in tomatoes, followed by a-carotene, b-carotene, g-carotene, and phytoene, as well as by several other minor carotenoids. Tomat

Part 1

Caracterization of Lycopene from Chemistry to Basic Physiological Functions

1.1

Lycopene Overview: What It Is and What It Does

¹Robert M. Diener and ²Mildred S. Christian

¹ 185 Aster Court, Whitehouse Sta., NJ 08889, U.S.A.

² 933 Horsham Road, Horsham, PA 19044, U.S.A.

ABSTRACT

Lycopene is the bright red carotenoid phytochemical that gives tomatoes and other red fruits their color. Because of its predominance in tomatoes, it derives its name from the Latin genus name for tomatoes. Lycopene also serves as a potent antioxidant in humans and is said to lower the risk of a variety of cancers. Information about its chemistry, safety (absence of toxicity), availability and pharmacokinetics, actions and mechanisms of action and anticarcinogenic properties, as well as results of various human clinical trials, are summarized in this overview.

Introduction

Lycopene is a fat-soluble, bright red carotenoid pigment, a phytochemical found in tomatoes and other red fruit. Other major sources of lycopene are watermelons, pink grapefruit, guava, papaya and rosehip.

The name is derived from the tomato’s species classification, Lycopersicon esculentum. The importance of the tomato as a source of lycopene in Western diets is confirmed in US Department of Agriculture (USDA) data, which indicate that the average annual American per capita consumption of fresh and processed tomatoes in 2004 was 19.1 and 69.8 pounds, respectively. In the fresh state, only onions (19.3 pounds), head lettuce (21.3 pounds) and potatoes (45.6 pounds) exceeded the consumed amounts of fresh tomatoes, while processed tomato consumption far exceeded that of other processed vegetables (USDA 2005).

Unlike vitamins, lycopene content is increased in processed products, as summarized in Table 1.

Table 1 Lycopene content in raw and processed tomato products.

Tomato products	Lycopene content (μg/100 g)
Raw tomatoes	2,573
Tomato juice	9,037
Tomato sauce	15,152
Ketchup	17,007

Source: USDA data cited by Campbell et al. 2004.

Lycopene is the most common, and one of the most potent, carotenoid antioxidants in the human body. It also has been shown to be the most efficient quencher of singlet oxygen and free radicals among the common carotenoids in vitro (Di Mascio et al. 1989). Increased intake or blood levels of lycopene have also been associated with a lowered risk of a variety of cancers in humans, but a direct effect of lycopene has yet to be proven, for the beneficial effects have been achieved predominantly by the intake of tomatoes or tomato products rather than purified lycopene (Basu and Imrhan 2007, Giovannucci 1999).

Chemistry

Lycopene is a 40 carbon atom, open-chain polyisoprenoid with 11 conjugated double bonds. Each double bond reduces the energy required for electrons to transition to higher energy states, thus allowing the molecule to absorb visible light of progressively longer wavelengths, which makes it appear red. Its molecular weight is 536.88 daltons. The structural formula of lycopene is illustrated in Fig. 1 (PDRhealth 2007).

Fig. 1 Molecular formula of lycopene.

Chemically, lycopene is an acyclic isomer of beta-carotene. Beta-carotene, which contains beta-ionone rings at each end of the molecule, is formed in plants, including tomatoes, via the action of the enzyme lycopene beta-cyclase. All-trans lycopene is the predominant geometric isomer found in plants, although cis isomers of lycopene are also found in nature, including 5-cis, 9-cis, 13-cis and 15-cis isomers. However, the trans form of lycopene found in tomatoes is largely converted to the cis form by the crushing and temperature changes involved in making processed foods, such as tomato juice, ketchup, paste and sauce. As a result, the lycopene found in human plasma is a mixture of approximately 50% cis lycopene and 50% all-trans lycopene (PDRhealth 2007).

Toxicity

A number of recent publications have reported on the safety of ingested lycopene from a variety of sources. Results from these studies are summarized in Table 2.

Table 2 Toxicity studies conducted in animals to determine the safety of lycopene.

Jonker et al. (2003) fed lycopene derived from a fungal biomass (Blakeslea trispora) and suspended in sunflower oil (20% w/w) to groups of 20 Wistar male and female rats for 90 d. The diet contained lycopene concentrations of 0, 0.25, 0.50, and 1.0%, and lycopene intake was calculated to be 0,145, 291 and 586 mg/kg body weight/day in male rats, and 0,156, 312, and 616 mg/kg bw/d in female rats, respectively. Clinical and neurobehavioral observations, body weight and feed consumption measurements, ophthalmoscopic examinations, clinical pathology, organ weights, and gross pathology and histopathology failed to detect signs of toxicity in any of the groups of rats. The no-observed-effect level was 1.0% in the diet, the highest dietary concentration tested.

Lycopene from synthetic sources, which provide an alternative to extracts and can be used in dietary supplements, has been extensively tested in vitro and in vivo. Lycopene is commercially available only in formulated forms containing antioxidants, which prevent the degradation of lycopene and other excipients that provide for water dispersibility. Improperly stored, unformulated crystalline lycopene can degrade if exposed to light and air. McClain and Bausch (2003) reported on the safety of synthetic lycopene as a water-dispersible beadlet formulation containing antioxidants. In single doses, lycopene had a low order of toxicity. In repeated doses, no significant toxic effects were observed in rats treated with the lycopene beadlet formulation in the diet at doses of up to 500 mg/kg bw/d for 14 wk or 1000 mg/kg bw/d for 4 wk. The lycopene beadlets produced no teratogenic effects at dietary concentrations of 1000 ppm in a two-generation rat study or at gavaged doses of 1000 mg/kg bw/d in a rat teratology study. No genotoxic effects were observed in a comprehensive battery of mutagenicity studies. Exploratory short-term studies revealed that lycopene (in synthetic and natural form) accumulates in hepatocytes and to a lesser extent in the spleen, but the pigment accumulation was reversible in about 13 wk and produced no histopathological changes.

Results from another 13 wk toxicology study in Wistar rats were reported by Meliert et al. (2002). BASF Lycopene 10 CWD and Lyco Vit 10% formulated products, each containing approximately 10% synthetic lycopene (67% trans, 30.3% cis isomers), were evaluated for toxicological and behavioral effects at gavaged dosages of 0,500,1,500 and 3,000 mg/kg bw/d Lycopene 10 CWD and 3,000 mg/kg bw/d Lyco Vit 10%. No statistically significant, dose-related effects on body weight, feed consumption, hematology, urinalysis, clinical chemistry, gross and microscopic tissue examination or behavioral and sensimotor parameters were observed after 13 wk of treatment. No deaths attributed to the lycopene formulations occurred during the study; the only finding at terminal necropsy was the presence of red pigment in the feces and gastrointestinal tract, due to the red-pigmented test materials. The no-observed-adverse-effect level for this study was concluded to be 3,000 mg/kg bw/d for both Lycopene 10 CWD and Lyco Vit 10%.

The potential oral developmental toxicity of the synthetic lycopene 10 CWD and LycoVit 10% was also studied in rats and rabbits (Christian et al. 2003). Gavaged dosages of 0, 500, 1,500 or 3,000 mg/kg/d were used for 10 CWD in rats and 0, 500, 1,500 or 2,000 mg/kg/d in rabbits (maximum dose because of viscosity). LycoVit 10% was tested in rats and rabbits only at the highest dosage levels of 3,000 and 2,000 mg/kg/d, respectively. Dosages were administered on gestation days 6 through 19 (rats) or gestation days 6 through 28 (rabbits). Feed consumption and weight gain were essentially unaffected in rats and rabbits, despite intubation problems in both species and reduced gastrointestinal motility and mortality in rabbits attributable to the physical properties (high viscosity) of the gels. Neither Lycopene 10 CWD nor LycoVit 10% caused direct maternal or developmental toxicity in rats or rabbits at dosages as high as 3,000 or 2,000 mg/kg/d, respectively.

Pharmacokinetics

The efficiency of lycopene absorption from supplements and foods is variable, and the optimal daily intake has not been established. In foods, lycopene is part of a matrix in chloroplasts or chromoplasts within the plant, and absorption of lycopene from raw tomatoes is low, because it is mostly in the trans isoform and is tightly bound within the matrix. In synthetic nutritional supplements, lycopene is in the form of an oleoresin embedded in phospholipid complexes and in oils, and marketed formulations (usually capsules) range in dose from 5 to 15 mg/d. In processed tomato products, absorption is much higher for a number of reasons. First, mechanical and thermal processing releases the lycopene from crushed or ruptured plant cells. Second, heat during processing induces the trans isoform to change to the cis isomer, which is more bioavailable. Third, the addition of lipids, such as vegetable oils, increases lycopene absorption because it is lipophilic (Shi and Maguer 2000).

Lycopene’s journey throughout the human body is long and complex, whether it originates from food matrices or synthetic supplements. Table 3 summarizes some of the physiological actions and chemical transformations that are given in greater detail elsewhere (PDRhealth 2007).

Studies have been conducted in rats and ferrets subjected to a 9 wk tomato oleoresin supplement to determine lycopene uptake and distribution in the body (Ferreira et al. 2000). After tissue saponification, the total lycopene levels in rats were found to be as follows: liver 14,213 nmol/kg, intestine 3,125 nmol/kg, stomach 79 nmol/kg, prostate 24 nmol/kg, and testis 3.9 nmol/kg. In ferrets, tissue content of lycopene after saponification was substantially lower than in rats, and prostate tissues had a higher content than stomach. Non-saponified extract was highest in the liver of both species. Results from this study indicate that lycopene is absorbed and stored primarily in the liver of both species, but rats absorb lycopene more effectively than ferrets.

Table 3 Lycopene pathway from ingestion to incorporation into tissues.

Lycopene is solubilized in the lumen of the small intestine by bile salts and fat. ↓ Soluble lycopene is taken up by enterocytes in the intestinal wall. ↓ Lycopene is delivered into lymphatics as chylomicrons. ↓ Chylomicrons enter the circulation and are hydrolyzed, producing chylomicron remnants. ↓ Remnants are taken up mainly by hepatocytes. ↓ Within hepatocytes, lycopene is incorporated into lipoproteins. i ↓ Low density and very low density lipoproteins enter the circulation. ↓ Lycopene incorporated mostly in low density lipoproteins enters various tissues

Zhao et al. (1998) studied lycopene uptake and tissue disposition in Fischer 344 rats after they had been on a diet supplemented with tomato oleoresin for 10 wk. Lycopene was present in lung (134-227 ng/g), mammary gland (174-309 ng/g) and prostate (47-97 ng/g). Serum levels ranged from 80 to 370 mg/mL in both sexes but were not reflective of dietary intake. Investigations in F344 rats by Boiliau ...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Dedication
• Foreword
• Preface
• Table of Contents
• List of Contributors
• Part 1 Characterization of Lycopene from Chemistry to Basic Physiological Functions
• Part 2 Biochemical and Physiological Features of Lycopene's Effects
• Part 3 Lycopene and Cancer
• Index