Lycopene

What Is It?

Lycopene, a naturally occurring red compound, is a member of a plant pigment family known as ‘carotenoids’$^{1}$. Lycopene is predominantly found in tomatoes, but it can also be found in watermelons and papayas, and it is responsible for the characteristic coloration of these fruits and vegetables$^{2}$. This plant pigment has been shown to be a potent antioxidant, a discovery which has consequently drawn significant interest in the potential for lycopene to ameliorate chronic diseases where oxidative stress is an underlying factor, such as cancer and cardiovascular disease$^{2}$. Carotenoids: Lycopene vs Beta-Carotene The carotenoid family can be divided into two main types: hydrocarbons (compounds consisting of only carbon and hydrogen), and xanthophylls (compounds containing carbon, hydrogen, and oxygen)$^{2}$. Both lycopene and beta-carotene belong to the hydrocarbon carotenoids subfamily, and they are commonly mistaken to be the same compound. However, unlike beta-carotene, lycopene does not possess pro-vitamin A activity$^{1,3}$. Evidently, each of these micronutrients offer uniquely different benefits for human health, and it is thus important to be mindful of these distinctions in order to obtain the nutrient that is right for you.

What Are Its Other Names?

Lycopene is sometimes referred to as rhodopurpurin or a non-provitamin A carotenoid$^{4}$. The IUPAC name for lycopene is 6E,8E,10E,12E,14E,16E,18E,20E,22E,24E,26E)-2,6,10,14,19,23,27,31-octamethyldotriaconta-2,6,8,10,12,14,16,18,20,22,24,26,30-tridecane$^{5}$.

What Foods Have It?

Lycopene is found in a variety of fruits and vegetables, with tomatoes and tomato-derived products containing the highest amount of lycopene. The following table highlights different types of produce and their respective lycopene content.

It is essential to note that the lycopene content may be presented as a range since the amount of lycopene can differ greatly based on the produce’s variety and origin.

What Are Its Main Benefits?

Benefits for Cancer Prevention Lycopene has recently become the subject of immense scientific scrutiny for its potential beneficial effects against several different types of cancer, most notably prostate cancer. Numerous studies have reported a negative correlation between lycopene consumption and prostate cancer incidence$^{8-11}$. For instance, one clinical trial involving 26 prostate cancer patients found that, in addition to decreasing the levels of prostate-specific antigen (PSA) – which is a prostate gland-specific protein that is typically elevated in prostate cancer, lycopene intake also resulted in tumour regression$^{8,12}$. Several other studies have also described a similar relationship between lycopene intake and PSA levels in prostate cancer$^{9,10}$. A separate study demonstrated that besides lowering PSA levels and diminishing tumours, lycopene can also upregulate insulin-like growth factor binding protein 3 (IGFBP-3) and subsequently decrease the risk of prostate cancer$^{11}$. However, the same study also found that lycopene led to an overexpression of two genes that are implicated in cancer metastasis, c-fos and uPAR, and this therefore highlights the potential pitfalls of lycopene consumption$^{11}$. In addition to preventing prostate cancer, lycopene supplementation has also demonstrated promising outcomes in reducing the risk of several other types of cancer, such as breast cancer. One randomized controlled trial evaluated the effect of lycopene intake in women with a prior history of breast cancer or at a high risk of developing the disease, and found that lycopene decreased IGF levels (primary markers of breast cancer risk in this study) in healthy women, but not in breast cancer survivors$^{13}$. This therefore underscores the potential of lycopene in preventing breast cancer. Besides prostate and breast cancer, lycopene supplementation has also been linked to a potentially decreased risk of cancer, irrespective of the specific cancer type$^{14}$. In one study, it was found that lycopene reduced oxidative stress in vivo, consequently reflecting its ability to lower the risk of cancer in general$^{14}$. Benefits for Cancer Recurrence Prevention In addition to preventing primary cancers (the initial cancer that forms in the body), lycopene has also displayed potential in suppressing cancer recurrence. It accomplishes this by a complete or partial regression of secondary tumours as outlined in one clinical trial involving 54 prostate cancer patients$^{10}$. While these results are promising, more studies are required to elucidate the relationship between lycopene consumption and cancer recurrence prevention. Benefits for the Side-Effects of Cancer Beyond cancer prevention, lycopene may also be effective in improving the side effects of cancer, such as cancer-related fatigue that is commonly observed in patients with breast cancer$^{15}$. In one randomized controlled trial, it was shown that a fatigue-reduction diet which contained lycopene among other nutrients was effective in ameliorating cancer-induced fatigue experienced by these patients$^{15}$. However, it is unclear whether these effects can be solely attributed to lycopene given the presence of other nutrients in this fatigue-reduction diet. Benefits for Cardiovascular Disease Prevention in High-Risk Individuals Lycopene’s potent antioxidant effects have also been shown to impart this micronutrient with a unique ability to minimize the risk of cardiovascular diseases (CVD). Several studies highlighted that lycopene intake can decrease abdominal visceral fat (fat surrounding organs) or downregulate pro-inflammatory molecules, and thus inhibit the progression of cardiovascular disease$^{16-18}$. However, despite the reported benefits of lycopene for CVD, it is essential to highlight that these studies were conducted in patients who have a high risk of developing CVD$^{17,18}$. Furthermore, there were similar studies evaluating lycopene’s cardioprotective effects that found that it was ineffective in preventing CVD in healthy individuals$^{19,20}$. Consequently, this implies that lycopene’s potential to reduce CVD development may only be limited to individuals with a predisposition to this medical condition, instead of healthy individuals.

What Are Its Main Drawbacks?

Potential Adverse Events Several randomized controlled trials investigating the cancer-fighting properties of lycopene found no adverse events related to lycopene consumption$^{21,22}$. However, in one study, it was reported that lycopene supplementation led to gastrointestinal symptoms in two patients$^{23}$. Besides gastrointestinal symptoms, lycopene consumption may also result in lycopenemia, which is a benign condition characterized by orange pigmentation of the skin, as reported in two studies$^{24-26}$. However, it is essential to note that only a small number of patients experienced this skin condition, and once lycopene was removed from the affected individuals’ diets, they ultimately recovered without suffering from any long-term health effects. Overall, while there may be some side effects associated with lycopene supplementation, it is important to highlight that these are not only rare, but they are also relatively mild, as current evidence suggests that they have no lasting detrimental health implications. However, one should still exercise a certain degree of caution when considering lycopene supplementation. Possible Drug Interactions Lycopene may also hinder the process of blood clotting and promote bleeding, as it may interact with a specific class of drugs known as anticoagulants$^{26}$. However, there is currently limited data on these interactions, which thus warrant further investigation. Low Bioavailability Lycopene is a highly lipophilic compound as it has a strong affinity for lipids$^{27}$. This consequently hinders its ability to dissolve in aqueous media such as the blood in the systemic circulation, consequently lowering its bioavailability$^{28}$. Potential Metastasis-Promoting Effects As discussed in the subsection entitled ‘What Are Its Main Benefits: Benefits for Cancer Prevention’, there is some evidence linking lycopene supplementation to an increase in c-fos and u-PAR, which are genes implicated in cancer metastasis$^{12}$. Overall, it is essential to consult a healthcare provider in order to evaluate the suitability of lycopene supplementation for your individual needs, and to minimise the risk of potential harmful side-effects.

How Does It Work?

Lycopene utilizes a variety of pathways and mechanisms to elicit its anticarcinogenic effects, most notably, reducing oxidative stress to prevent DNA and cellular damage, inhibiting the PI3K/AKT and NF-kB pathways to hamper tumour formation, and suppressing angiogenesis.

What Are Its Mechanisms of Action?

1. Reduce Oxidative Stress: Oxidative stress is an important hallmark of cancer because elevated levels of reactive oxygen species (ROS) can lead to DNA damage and contribute to the development of cancer. Lycopene has been shown to demonstrate remarkable antioxidant effects as it is able to decrease the levels of various ROS in the body$^{29}$. This micronutrient is associated with enhancing the action of catalase enzymes to decrease the levels of hydrogen peroxide, consequently preventing hydrogen peroxide from forming highly reactive hydroxyl radicals, which are a type of ROS$^{29,30}$. Furthermore, lycopene can also act as a scavenger of other types of ROS such as peroxyl radicals and hypochlorous acid, and thus hinder these free radicals from inducing cellular damage$^{29}$. Lycopene’s ability to diminish free radicals in the body has significant implications as high levels of ROS can not only disrupt cellular physiology, but also induce DNA damage, both of which can pave the way for cancer formation$^{31}$.
2. Inhibit PI3K/AKT Pathway: One study conducted on colon cancer cells demonstrated that lycopene could hinder tumour development by inhibiting a specific signalling pathway, known as the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway$^{32}$. Given that this pathway is responsible for regulating cellular processes such as cell proliferation, apoptosis, and angiogenesis, aberrant activation of this signalling pathway can thus lead to cancer$^{33}$. Therefore, by inhibiting the AKT pathway, lycopene is able to suppress any downstream processes that play a role in tumorigenesis, thus hampering the formation of tumours.
3. Inhibit NF-kB Pathway: An important pathway downstream of the PI3K/AKT pathway is the nuclear factor kappa B (NF-kB) transcriptional pathway$^{34}$. The NF-kB pathway is known to be a crucial player in the development of cancer as it is responsible for preventing Tumour Necrosis Factor-α-induced apoptosis, in addition to promoting cell proliferation by activating the expression of cyclin D1$^{34,35}$. However, lycopene is able to inhibit the NF-kB pathway, and subsequently downregulate cell proliferation while sensitizing cells to apoptosis$^{35}$.
4. Inhibit Angiogenesis: Lycopene may also interfere with angiogenesis, which is the process by which tumour cells form blood vessels to obtain essential nutrients$^{35}$. In one study, it was found that lycopene supplementation interfered with endothelial cell growth and migration, which are both instrumental in angiogenesis$^{36-38}$. Therefore, the inhibition of angiogenesis by lycopene can disrupt the supply of nutrients to tumour cells, preventing them from proliferating and metastasizing.

What Are Typical Doses and Durations?

Dosage Clinical studies that examine the effects of lycopene on cancer prevention have used a wide range of treatment doses. Across all studies, lycopene was administered orally, but the way in which oral lycopene was administered to subjects differed significantly across the studies. Some studies that examined the anticancer effects of lycopene alone administered the micronutrient in the form of a capsule with doses ranging from 2 mg/day to 30 mg/day, and these capsules were sometimes taken once daily or several times throughout the day$^{10,39,40}$. Meanwhile, there were also studies that administered lycopene in combination with other nutrients, in the form of processed vegetables such as pastes, juices, sauces, and soups. These studies expressed treatment doses as volume/day or g/day, with doses ranging from 118 mL/day to 335 mL/day or 5.7 mg/day to 150 mg/day$^{14,41,42,43}$. Furthermore, there were also studies that examined the effect of lycopene as part of a multivitamin supplement, with treatment doses of lycopene ranging from 5 mg/day to 35 mg/day$^{43,44}$. There were also several studies that investigated the association between natural lycopene intake and cancer prevention, in which case there was no treatment dose administered$^{45,46}$. Duration Most clinical studies investigating the anticarcinogenic properties of lycopene lasted anywhere between a week to several months$^{8,11,47}$. There were also a number of studies that lasted over a period of a few years, and these studies typically investigated the effect of a diet rich in lycopene on cancer prevention$^{15,45}$.

Summary of Data

A total of 15 randomized controlled trials were identified from the PubMed database that investigated the cancer-preventing effects of lycopene alone. A summary of the results for each cancer type is as follows:

📄 Detailed Lycopene (administered alone) human clinical trial study notes analyzed by Anticancer.ca

A total of 6 randomized controlled trials were identified from the PubMed database that investigated the cancer-preventing effects of lycopene as part of a multivitamin or multi-antioxidant supplement. A summary of the results for each cancer type is as follows:

📄 Detailed Lycopene (administered with vitamins) human clinical trial study notes analyzed by Anticancer.ca

A total of 7 randomized controlled trials were identified from the PubMed database that administered lycopene from lycopene-rich sources. A summary of the results for each cancer type is as follows:

📄 Detailed Lycopene (from lycopene-rich foods) human clinical trial study notes analyzed by Anticancer.ca

A total of 14 dietary intake association studies were identified from the database PubMed that investigated the relationship between lycopene consumption and cancer. A summary of the results for each cancer type is as follows:

📄 Detailed Lycopene dietary intake study notes analyzed by Anticancer.ca

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• Lycopene
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• How Does It Work?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer