Lycopene

Lycopene: A Comprehensive Reference

1. Identity and Chemical Characterization

Names and Classification

Lycopene (from New Latin: Lycopersicon, the name of a former tomato genus) is a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and vegetables. This organic compound is classified as a tetraterpene and a carotene. Lycopene is also known by the synonym psi-carotene and belongs to the family of organic pigments known as carotenoids. Its systematic IUPAC name is (6E,8E,10E,12E,14E,16E,18E,20E,22E,24E,26E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,8,10,12,14,16,18,20,22,24,26-dodecaene. With the molecular formula C₄₀H₅₆, it has a molecular weight of 536.85 g/mol and bears Chemical Abstract Service (CAS) Registry Number 502-65-8.

Molecular Structure

Lycopene belongs to the tetraterpenoid class of carotenoids, consisting of eight isoprene units held together by a tail-to-head configuration. It is an acyclic isomer of β-carotene and a highly unsaturated hydrocarbon containing 11 conjugated and 2 unconjugated double bonds. Lycopene is an isomer of the carotenes, both having the same molecular formula, C₄₀H₅₆, but differing in structure. The molecular mass and chemical formula are the same for lycopene and β-carotene, with the exception that lycopene lacks the β-ionone ring present in β-carotene's structure. Lycopene is soluble in fat, but insoluble in water, and eleven conjugated double bonds give it its deep red color.

Lycopene from natural plant sources exists predominantly in an all-trans configuration, the most thermodynamically stable form. In human plasma, lycopene is present as an isomeric mixture, with approximately 50% as cis isomers. Among the different carotenoids, lycopene has the highest singlet-oxygen (¹O₂) quenching ability, exceeding the antioxidant properties of carotene by at least twofold. The (Z)-isomers have the greatest antioxidant activity in scavenging lipid peroxyl radicals.

Relationship to Other Carotenoids

In plants, algae, and other photosynthetic organisms, lycopene is an intermediate in the biosynthesis of many carotenoids, including beta-carotene, which is responsible for yellow, orange, or red pigmentation, photosynthesis, and photoprotection. Unlike many carotenoids, lycopene has no vitamin A activity. Lycopene cannot be synthesized in the human body and therefore must be consumed in the daily diet.

2. Natural Sources

Lycopene is responsible for the red coloring of various foods like tomatoes, watermelon, papaya, pink grapefruit, and guava. Gac fruit has a high lycopene content derived mainly from its seed coats. Cara Cara navel oranges and other citrus fruit, such as pink grapefruits, also contain lycopene. Some foods that do not appear red also contain lycopene, e.g., baked beans. It is found in some non-red or non-orange plants, such as asparagus and parsley.

Tomato represents the most important lycopene source, as it is the cheapest raw material, supplying a large part of this carotenoid on the market; it is also the most ingested source, either in the form of fresh tomatoes or as processed products. Tomato products, including ketchup, tomato juice, and pizza sauce, are the richest sources of lycopene in the US diet, accounting for over 80% of the total lycopene intake of Americans. Average daily intake ranges from 5 to 10 mg in the US and Europe.

3. Historical Discovery and Traditional Context

Lycopene was isolated from the black bryony (Tamus communis), a European yam, in 1873, and from tomatoes in 1875. It was identified as a red pigment in tomato by Millardet in 1876. The name lycopene is derived from the tomato's scientific name, Solanum lycopersicum.

The history of lycopene is inseparable from the history of the tomato plant itself. Imported from the Andean region to Europe in the 16th century, the tomato is today widespread throughout the world and represents one of the most economically important vegetable crops. The tomato was already domesticated by the ancient Incan and Aztec civilizations before it came to Europe, where its breeding history began. While these civilizations used tomatoes extensively as food, the specific nutritional compound lycopene was not a recognized entity until the 19th century. Tomato was traded not only in the fresh market but also used in the processing industry in soups, pastes, concentrates, juices, and ketchup, and is an important source of nutrients such as lycopene, β-carotene, and vitamin C.

The scientific investigation of lycopene as a distinct bioactive compound began in earnest in the 20th century. Ernest is credited with discovering lycopene in 1959, and the compound was named "lycopin" by Schnuck, while Escher proposed its chemical structure. Interest in lycopene as a potential health-promoting substance accelerated considerably from the 1990s onward, driven by epidemiological observations linking tomato-rich diets to reduced disease risk. Lycopene does not feature in established traditional medicine systems (such as Ayurveda, Traditional Chinese Medicine, or European herbalism) as an isolated compound; its use was always as an integral part of tomato-rich foods rather than as a targeted remedy.

4. Key Constituents, Forms, and Preparations

Commercial and Supplemental Forms

Lycopene is widely used in the food industry as a coloring agent, usually in the form of oleoresin — a suspension in natural lipids. In this form, lycopene oxidation (crystalline lycopene being highly unstable) and bacterial degradation are prevented, most likely due to the lipids and natural antioxidants present. Owing to its strong color, lycopene is used as a food coloring, registered in the European Union as E160d.

As a dietary supplement, lycopene is available in several forms. Tomato-derived oleoresin extracts are the most common supplement form. The product Lyc-O-Mato (Lycored) is among the most widely studied standardized extracts, typically formulated as softgels due to its greasy consistency. Other preparations have been developed for improved bioavailability, including lycosome-formulated preparations and lactolycopene (where lycopene is entrapped with whey proteins). The molecular structure of carotenoids is highly sensitive, and lycopene is particularly prone to photodegradation and breakdown under light exposure (especially UV exposure), high temperatures, and the presence of oxygen — meaning carotenoids are easily degraded when exposed to light, heat, and oxidizing agents.

Isomeric Considerations in Preparations

The predominant all-trans form in raw foods has an estimated absorption rate of only 10–30%, while cis-isomers exhibit higher absorption rates of 40–50%, owing to their greater solubility in bile acid micelles and reduced tendency to crystallize. Cooking and food processing enhance bioavailability by inducing isomerization from the less-absorbable all-trans form to more bioavailable cis-isomers, without substantially reducing total lycopene content.

5. Mechanisms of Action

Antioxidant Activity

Lycopene is one of the most potent antioxidants among dietary carotenoids. It has a singlet-oxygen-quenching ability twice as high as that of β-carotene and 10 times higher than that of α-tocopherol, and is the most predominant carotenoid in human plasma. Rather than its low bioavailability, lycopene has twice more significant free radical scavenging potential than pro-vitamin A (β-carotene) and ten times more than vitamin E. The extended conjugated double-bond system is the principal structural basis for this antioxidant potency.

Anti-inflammatory Mechanisms

Lycopene positively affects inflammation as it activates the expression of antioxidant genes and regulates the signaling pathways responsible for inducing inflammatory mediators. Specifically, lycopene exerts anti-inflammatory activity through several pathways: downregulation of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α; reduction of other pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression; and inhibition of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase in macrophages.

Lycopene can also inhibit the nuclear factor kappa B (NF-κB) signaling pathway — known as a central driver of inflammatory responses — via attachment to the IκB protein (inhibitor of nuclear factor kappa B), maintaining its attachment to NF-κB and preventing its translocation to the nucleus.

Nrf2 Pathway Activation

Lycopene induces the nuclear translocation of Nrf2. One possible mechanism involves the direct interaction of lycopene with the cysteine residues of Keap1, which triggers the release of Nrf2 from the complex. Lycopene-generated metabolites can also activate a wide variety of kinases, which can further induce the release and nuclear translocation of Nrf2. Nrf2 activation promotes transcription of cytoprotective and antioxidant genes, including heme oxygenase-1 (HO-1) and glutathione-synthesizing enzymes.

Growth Factor Signaling Modulation

PDGFR-, IGF-IR-, and VEGFR-mediated signal transduction pathways are possible targets for lycopene. These receptors are activated at the cell surface during tumorigenesis. Activation of these receptors induces several downstream signaling pathways — among them, the Ras-MAPK and PI3K-AKT pathways, which transduce signals into the nucleus to activate transcription factors that regulate genes important for proliferation, cell-cycle progression, apoptosis, inflammation, angiogenesis, invasion, and metastasis. Lycopene has been shown to inhibit IGF-induced activation of IGFR by increasing the expression of IGFBPs. Similarly, lycopene directly binds to PDGF to reduce the autophosphorylation of PDGFR and VEGFR.

Effects on Cell Cycle and Apoptosis

Lycopene induces cell-cycle arrest and apoptosis. The anticancer property of lycopene is also evidenced by its inhibitory potential of the Wnt/β-catenin signaling pathway, which is involved in cancer cell modulation and propagation. Lycopene also suppresses and neutralizes oxidative stress and reactive oxygen species (ROS)-induced DNA damage, thereby preventing gene mutation.

Cholesterol and Lipid Metabolism

Unlike other carotenoids, lycopene is not consistently lower among smokers than among nonsmokers, suggesting that any possible preventive activity is not solely as an antioxidant. Lycopene may have a cholesterol synthesis-inhibiting effect and may enhance LDL degradation.

Vascular Endothelial Effects

By blocking the angiotensin-converting enzyme (ACE), lycopene reduces the oxidative stress imposed by angiotensin II and, as a result, indirectly increases the synthesis of NO in the endothelium. It has been shown that lycopene suppresses the production of reactive oxygen species and induces the expression of heme oxygenase-1 (HO-1) in human endothelial cells, lowering ET-1 gene expression. As a result, it may help prevent endothelial dysfunction by encouraging direct antioxidative actions and increasing the expression of several genes.

6. Bioavailability and Absorption

Only 10–30% of dietary lycopene is absorbed through the intestinal lumen, due to the unavailability of fats and oils and interaction with dietary fiber and other carotenoids. Absorption of lycopene requires that it be combined with bile salts and fat to form micelles.

Multiple studies have shown that lycopene from thermally processed tomato products is more bioavailable than lycopene from fresh tomatoes. Cooking and crushing tomatoes (as in the canning process) and serving in oil-rich dishes such as spaghetti sauce or pizza greatly increases assimilation from the digestive tract into the bloodstream. Lycopene is fat-soluble, so dietary fat helps absorption.

Lycopene bioavailability is greatly affected by dietary composition. Given that lycopene is a lipid-soluble compound, consuming it with fat increases its bioavailability. For example, consuming salads with full-fat dressing results in higher blood carotenoid levels than eating salads with reduced-fat dressing. When salads were consumed without fat in one study, no measurable lycopene uptake occurred.

Lycopene bioavailability is greater from tomato paste and tomato purée than from raw tomatoes, and lycopene bioavailability from supplements does not appear to be different from processed tomato paste when consumed with a meal.

The structural localization of lycopene in the chloroplasts of fruit and vegetables is an important factor limiting bioavailability from dietary sources, since chloroplasts have high resistance to gastric and intestinal digestion. Thus, food matrix structure significantly predetermines the bioavailability of lycopene.

Once absorbed, the absorbed lycopene is mostly stored in the liver, adrenals, and prostate. It can also be found in other body parts such as the brain and skin in lower concentrations. Lycopene is typically the most abundant carotenoid in the diet and in the blood.

7. Scientific Evidence by Health Area

7.1 Cancer — Prostate Cancer

Prostate cancer has been the most intensively studied cancer in relation to lycopene. Dietary intake of tomatoes and tomato products containing lycopene has been shown to be associated with a decreased risk of chronic diseases such as cancer and cardiovascular disease. Serum and tissue lycopene levels have been found to be inversely related to the incidence of several types of cancer, including breast cancer and prostate cancer.

Epidemiological evidence: Lycopene has been identified as an antioxidant agent with potential anticancer properties, but studies investigating the relation between lycopene and prostate cancer risk have produced inconsistent results.

Interventional (RCT) evidence: A systematic review identified eight RCTs that met the inclusion criteria. All included studies were heterogeneous with respect to their design and implementation of lycopene. The methodological quality of three studies was assessed as posing a "high" risk of bias, two a "low" risk of bias, and the remaining three an "unclear" risk of bias. Meta-analysis of four studies identified no significant decrease in the incidence of BPH (RR = 0.95, 95% CI: 0.63–1.44) or prostate cancer diagnosis (RR = 0.92, 95% CI: 0.66–1.29) between men randomized to receive lycopene and the comparison group. However, meta-analysis of two studies indicated a decrease in PSA levels in men diagnosed with prostate cancer who received lycopene (MD = −1.58, 95% CI: −2.61 to −0.55).

Given the limited number of RCTs published, and the varying quality of existing studies, it is not possible to support, or refute, the use of lycopene for the prevention or treatment of BPH or prostate cancer based on RCT evidence alone.

In terms of treatment outcomes in existing prostate cancer: It was shown across multiple studies that lycopene improved the treatment outcomes of locally advanced prostate cancer, reduced prostate cancer-specific mortality in men at high risk for prostate cancer, delayed the progression of recurrent prostate cancer regardless of hormone sensitivity status, improved the response to docetaxel chemotherapy in advanced castrate-resistant prostate cancer, and stabilised the effect of orchidectomy in a group of patients with advanced metastatic prostate cancer. In addition, lycopene improved quality of life and provided relief from bone pain and control of lower urinary tract symptoms. In some studies, however, lycopene brought no benefit in the treatment of patients in the early stages of prostate cancer recurrence (biochemically relapsed prostate cancer) or in patients with advanced hormone-refractory prostate cancer.

Evidence strength: Mixed and preliminary at the RCT level. Epidemiological associations are suggestive but not conclusive. Larger, well-designed RCTs are needed.

7.2 Cancer — Other Cancer Types

Several clinical and randomized controlled trials have reported the effect of lycopene supplementation in the management of cancer, including breast cancer, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, skin cancer, oral cancer, liver cancer, gastric cancer, and kidney cancer, with outcomes including reduction of prostate-specific antigen (PSA) levels. However, the volume of high-quality human trial data for these other cancer types is substantially smaller than that for prostate cancer. Although the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial effects, evidence is accumulating to suggest that other mechanisms may also be involved.

Evidence strength: Largely preclinical (in vitro and animal) for most cancers other than prostate cancer. Human clinical data are limited and insufficient to draw firm conclusions for other specific cancer sites.

7.3 Cardiovascular Disease

Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular disease (CVD). Bioactive food ingredients, including lycopene, are important in their prevention, and lycopene is increasingly promoted in the diet of people with cardiovascular problems.

Epidemiological evidence: Epidemiological studies show a number of favorable associations between the consumption of lycopene in the diet and a reduced risk of cardiovascular disease. Available evidence suggests that intimal wall thickness and risk of myocardial infarction are reduced in persons with higher adipose tissue concentrations of lycopene.

RCT evidence (endothelial function): A notable double-blind, randomized controlled mechanistic trial at the University of Cambridge investigated lycopene's effect on vascular function. Thirty-six statin-treated CVD patients and 36 healthy volunteers were randomized in a 2:1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Endothelium-dependent vasodilatation (EDV) in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to endothelium-independent vasodilatation or basal NO responses. The trial demonstrated that lycopene improves endothelial function in CVD patients who demonstrated impaired function at baseline, despite optimal secondary prevention medication, but not in age-matched healthy volunteers.

RCT evidence (coronary vascular disease): A 30-day clinical trial in patients with coronary vascular disease investigated the pharmacokinetic parameters and impact of highly bioavailable lycopene on cardiovascular variables, markers of inflammation, and oxidation. Patients were randomized into two major groups and were supplemented with a single 7 mg daily dose of lycopene, ingested either in the form of lactolycopene (68 patients) or in the form of lycosome-formulated GA lycopene (74 patients).

Several reports have appeared in support of the role of lycopene in the prevention of CVD, mostly based on epidemiological studies showing a dose-response relationship between lycopene and CVD. Although promising data from epidemiological, as well as cell culture and animal, studies suggest that lycopene and the consumption of lycopene-containing foods may affect cancer or cardiovascular disease risk, more clinical trial data is needed to support this hypothesis.

Evidence strength: Moderate epidemiological support; limited but mechanistically interesting RCT data, particularly regarding endothelial function. Clinical evidence is not yet sufficient for definitive therapeutic recommendations.

7.4 Bone Health

Lycopene has recently been shown to have a potential protective effect against bone loss. Several human epidemiological studies, supplemented by in vivo and in vitro studies, have shown decreased bone loss following the consumption of lycopene or tomato. However, there are still limited studies that have evaluated the effect of lycopene on the prevention of bone loss in postmenopausal women.

A 2025 systematic review (registered in PROSPERO, following PRISMA guidelines) that comprised a total of 21 studies meeting eligibility criteria — including 6 clinical trials and 15 animal studies — found that lycopene supplementation promotes an increase in bone mineral density, preserves trabecular microarchitecture, stimulates osteoblastic activity, and inhibits osteoblast apoptosis. The review concluded that lycopene supplementation promotes beneficial effects on both the formation and preservation of bone tissue, suggesting that this carotenoid may represent a potential adjuvant strategy in the management of osteometabolic disorders.

Evidence strength: Preliminary. Animal and preclinical evidence is substantial, but human clinical trial data remains limited. Evidence is promising but not yet conclusive.

7.5 Type 2 Diabetes Mellitus

Lycopene, a bright red carotenoid hydrocarbon, has been extensively studied for its biological activities and treatment efficiency in diabetes care. Epidemiological investigations indicate that lycopene has potential antioxidant properties, is capable of scavenging reactive species, and alleviates oxidative stress in type 2 diabetes mellitus (T2DM) patients. In vitro and in vivo, lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions and diseases including inflammation, obesity, and diabetes mellitus.

Evidence strength: Mostly preclinical (animal and in vitro). Human observational data exists but RCT evidence specifically for diabetes outcomes is limited and inconclusive.

7.6 Skin Health and Photoprotection

Lycopene has been found to be efficient in ameliorating cancer insurgences, diabetes mellitus, cardiac complications, oxidative stress-mediated malfunctions, inflammatory events, skin and bone diseases, hepatic, neural, and reproductive disorders. The carotenoid's role in photoprotection is supported by its strong singlet-oxygen quenching capacity, which helps neutralize UV-induced reactive oxygen species in skin tissue. However, most evidence for skin photoprotection is from cell culture and limited human experimental studies; large RCTs in this domain are lacking.

Evidence strength: Preliminary. Mechanistic plausibility is high based on antioxidant capacity, but clinical evidence in dermatology and photoprotection requires further investigation.

7.7 Neurological Health

In addition to a wide range of reported health benefits, lycopene is known to act as a natural neuroprotective agent. The therapeutic and brain-health benefits of lycopene are worth being further examined in neurological, cognitive, and psychobehavioral disease conditions. Epidemiological trials indicate that lycopene also protects against neurodegenerative diseases and other chronic diseases such as asthma, hypertension, and osteoporosis.

Evidence strength: Very preliminary. Evidence is largely preclinical (animal models of neurodegeneration). Human clinical data in neurology is insufficient to draw conclusions.

7.8 Oxidative Stress Biomarkers

In a clinical study, subjects consumed test tomato products providing 30 mg of lycopene per day for four weeks. At the end of treatment, serum lycopene level increased significantly, total antioxidant potential increased significantly, and lipid and protein oxidation was reduced significantly. The results suggest that a tomato-rich diet containing different sources of lycopene can increase serum lycopene levels and reduce oxidative stress effectively.

8. Body Systems and Health Areas of Association

• Cardiovascular system: Lycopene has been shown to alleviate metabolic diseases that affect the heart. Evidence includes epidemiological links to reduced CVD risk and mechanistic RCT evidence for improved endothelial function.
• Oncological: Associations with reduced risk of several cancers in epidemiological data; most intervention evidence centered on prostate cancer; PSA lowering observed in some trials.
• Skeletal system: Evidence from clinical trials and animal studies that lycopene supplementation promotes increases in bone mineral density, preserves trabecular microarchitecture, and stimulates osteoblastic activity.
• Metabolic/endocrine: In vitro and in vivo, lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions including inflammation, obesity, and diabetes mellitus.
• Integumentary (skin): Antioxidant-mediated UV protection via singlet-oxygen quenching; preliminary evidence from experimental and limited human studies.
• Nervous system: Lycopene has been shown to potentially alleviate metabolic diseases that affect the nervous system. Evidence is largely preclinical.
• Hepatic and renal: Lycopene has been shown to alleviate metabolic diseases that affect the kidney and liver. Primarily in vitro and animal evidence.

9. Dosage Forms and Doses Used in Studies

The following doses are reported as used in the cited scientific studies and are not recommendations:

• A double-blind randomized controlled trial in CVD patients and healthy volunteers used 7 mg of lycopene or placebo daily for 2 months.
• A 30-day clinical trial in coronary vascular disease patients used a single 7 mg daily dose of lycopene, administered as either lactolycopene (68 patients) or lycosome-formulated GA lycopene (74 patients).
• In a bioavailability study, healthy subjects (n = 33) ingested 25 mg lycopene per day for 8 weeks from either lactolycopene, tomato paste, or a placebo.
• In an antioxidant study, subjects consumed tomato products providing 30 mg of lycopene per day for four weeks.
• An average daily dietary intake of lycopene estimated from a food-frequency questionnaire was 25 mg/day, with processed tomato products accounting for 50% of total daily intake.
• In a randomized crossover clinical trial examining isomer bioavailability, subjects consumed two meals each delivering 10 mg lycopene, from either tangerine or red tomato juice.
• Use in an optimal dose of 12 mg/day to a very high 150 mg/100 g does not show any toxic effect in the populations assessed in the reviewed literature.

10. Safety, Tolerability, and Drug Interactions

General Safety Profile

Lycopene is non-toxic and commonly found in the diet, mainly from tomato products. Its use in a dose range from 12 mg/day up to 150 mg/100 g does not show any toxic effect in the populations assessed in the literature. In animal studies (rats, dogs, rabbits) and in vitro, which concerned the assessment of acute toxicity, genotoxicity, and metabolism of lycopene, negative effects of synthetic and natural lycopene (up to 3 g per body weight per day) were not observed.

Lycopenemia

Excess lycopene intake from dietary sources can result in a benign condition called lycopenemia, in which the skin acquires an orange-yellow discoloration due to the accumulation of the pigment in subcutaneous fat. This is reversible upon reduction of intake and is not associated with toxicity.

Gastrointestinal Effects

There are cases of intolerance or allergic reaction to dietary lycopene, which may cause diarrhea, nausea, stomach pain or cramps, gas, and loss of appetite.

Drug Interactions

Lycopene may increase the risk of bleeding when taken with anticoagulant drugs. Additionally, due to its potential HMG-CoA reductase-inhibiting properties, caution may be warranted in patients already on lipid-lowering therapy. As with most dietary supplements, the research on drug interactions with lycopene is incomplete, and the interactions between lycopene and medicines are not fully understood.

Regulatory and Acceptable Daily Intake Considerations

Based on evidence from human clinical trials, an upper level of supplements (ULS) of 75 mg per day has been proposed. According to EFSA's exposure assessment for lycopene as a food additive, the highest P95 intakes for children and adults when combined with natural occurrence and use of lycopene as a food color would exceed the established acceptable daily intake (ADI) for lycopene of 0.5 mg/kg body weight per day. EFSA has expressed concern regarding over-consumption of lycopene, and the safety of lycopene has been assessed by EFSA on several occasions.

Bioavailability-Related Safety Note

Lycopene bioavailability can be decreased by aging and by certain pathological states, such as cardiovascular diseases. Improper processing and storage — i.e., exposure to light and oxygen — may alter the ratio of lycopene isomers or degrade lycopene entirely, potentially reducing the biological value of food products.

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