Watermelon

Watermelon (Citrullus lanatus), botanically considered as a fruit, belongs to the family Cucurbitaceae ¹. It is native to Kalahari desert of Africa but nowadays, it is also cultivated in tropical regions of the world. In the pages of history, watermelon first harvest was documented 5000 years ago in Egypt that later spread to other part of the world. Presently, China is the top producer followed by Turkey, United States, Iran and Republics of Korea ². Watermelon is a valued source of natural antioxidants with special reference to lycopene, ascorbic acid and citruline. These functional ingredients act as protection against chronic health problems like cancer insurgence and cardiovascular disorders ³, ⁴. Lycopene is characterized by its distinctive red color in fruits and vegetable ⁵.

During the last few decades, presence of appreciable quantity of lycopene in watermelon has motivated the farmers/growers to cultivate high red flesh varieties. Overall, twelve hundred cultivars of watermelon are produced worldwide while the four most promising cultivars are picnic, icebox, yellow flesh and seed less ⁶, ⁷.

Watermelon nutrition facts

Watermelon fruit is 92% water, contains 7.55 % of carbohydrates out of which 6.2 % are sugars and 0.4 % dietary fiber. It is enriched with carotenoid, vitamin C, citrulline, carotenoids and flavonoids and fat and cholesterol free, thus considered as low caloric fruit ⁸. Additionally, watermelon is rich source of ß-carotene acts as an antioxidant and precursor of vitamin A.

In a 100 gram serving, watermelon fruit supplies 30 calories and low amounts of essential nutrients (Table 1). Only vitamin C is present in appreciable content at 10% of the Daily Value. Watermelon pulp contains carotenoids, including lycopene.

Besides the presence of lycopene, watermelon is a source of B vitamins, especially B1 and B6, as well as minerals such as potassium and magnesium ⁹. Watermelon contains phenolics quite comparable with that of other fruits ¹⁰. It is an inexpensive and nutritious source that is readily available to all socio-economic groups and its consumption depends on number of factors e.g. availability, income, age, gender, racial and ethnic norms. In this context, per capita consumption in Asian communities is almost 3 times greater as compared to other part of globe ¹¹.

The amino acid citrulline is produced in watermelon rind.

Table 1. Watermelon nutrition facts (raw)

[Source: United States Department of Agriculture Agricultural Research Service ¹²]

Health Benefits of Watermelon

Earlier, only tomato and its products were considered as potential sources of lycopene but now there are proven facts that watermelon also contains appreciable amount of cis-configured lycopene. Thus consumer is gradually shifting towards watermelon and its allied products for their health concerns. Nevertheless, the quantity of lycopene varies depending upon the variety and growing conditions ¹³. Overall, lycopene ranges from 2.30-7.20 mg/100 g fresh weight bases, present in crystalline form in cell ¹⁴. More interestingly, lycopene contents of red fleshed watermelon are almost 40 % higher than tomato i.e. 4.81 and 3.03 mg/100 g, respectively. However, yellow orange and yellow colored fleshed have relatively less lycopene content i.e. 3.68 and 2.51 mg/100 g, respectively ¹⁵. In tomato, lycopene is available in relatively higher quantity after heat treatment due to break down of protein-carotenoid complex. In contrast, lycopene from watermelon is available directly to the human body just after consumption ¹⁶.

Storage conditions are also important that significantly affect the concentrations of lycopene, phenolics and vitamin C contents. The higher ratio of lycopene to carotene in watermelon i.e. 1:12 yields remarkable antioxidant capacity ¹⁷. Owing to this specific characteristic, foods high in lycopene contents are referred as functional foods ¹⁸.

Lycopene

Lycopene is a vibrant tetrapenic carotenoid with molecular formula of C40H56 (Figure 1) and contains 11 conjugated and 2 unconjugated double bonds ¹⁹. It is an acyclic isomer and open-chain analogue of β-carotene that undergoes cis-trans isomerization when interact with light, temperature and chemicals ²⁰. A great majority of studies have demonstrated that human blood serum contains both cis- and trans-isomeric forms of lycopene whereas the plants have only trans-configuration except watermelon ²¹. Some isomeric forms of lycopene are also depicted in Figure 1. Among different configurations, 5-cis form is more stable with strong antioxidant potential as compared to all-trans, 7-cis, 9-cis, 11-cis, 13-cis and 15-cis ²².

Numerous publications have reported that the amount of lycopene affected significantly as a function of storage time and temperature of watermelon. It has been observed that the lycopene content at storage temperature of 5 °C varied from 7.8 to 8.1 mg/100 g that increased to 8.1 to 12.7 mg/100 g at 20 °C ¹⁵. Data from various studies have shown an increasing trend of lycopene and β-carotene contents of watermelon at higher storage temperatures. It has been suggested that the carotenoids producing enzymes pathways are sensitive to temperature ²³.

Figure 1. Lycopene chemical structure

[Source ²⁴]

Lycopene efficiently absorbs when supplemented with fat owing to its lipophilic characteristics ²⁵. Its assimilation is dependent on chylomicron micells mediated mechanism, facilitates its movement from gastrointestinal tract towards body tissues. The isomeric form of lycopene also affects the absorption e.g. trans-isomeric form is less adsorbed as compared to cis-isomeric configuration ²⁶. Presences of fat as well as cis-isomeric forms facilitate lycopene absorption afterwards, it resides in the adipose tissues, liver, prostate and adrenal glands. After ingestion of lycopene-based food, disruption carotenoids occur within the low pH environment of stomach where lycopene get attached to the protein to pass through intestinal leumen. The resultant lycopene-protein complex breakdown and lycopene joins chylomicron in blood stream from where it goes to target tissue via hepatic pathway ²⁷. The detailed mechanism of lycopene absorption and its storage is described in Figure 2.

Figure 2. Lycopene absorption

[Source ²⁴]

Lycopene Health Claims

Lycopene has potential to prevent various chronic ailments like dyslipidemia, diabetes, oncogenesis, neurodegenerative diseases, osteoporosis etc. The protective aspects are ascribed to the singlet oxygen scavenging ability. Numerous metabolic syndromes arise due to high free radicals formation reacting with macromolecules thus oxidizing proteins, lipids and DNA. Lycopene protects humans from various pathogenic attacks responsible for an array of diseases ²⁸. Several authors have reported that lycopene holds nutraceutical potential and being antioxidant provides protection against free radicals and oxidative damage ²⁹, ²⁵, ³⁰. Free radicals are produced in the body during oxidation reduction reaction however, excessive production deteriorates body defense mechanism, cell membrane and organelles. These degenerative processes resulted in life threatening ailments ³¹. The presence of large number of double bonds is responsible for its fairly high free radical scavenging or singlet oxygen quenching ability even better than α- and ß-carotene, lutein and α-tocopherol ³². Lycopene provides protection against degenerative disorders via mechanisms like gap-junction communication, gene function regulation, phase II drug-metabolizing pathways and carcinogenic metabolism ³³. It has been established through epidemiological studies that lycopene plays a role in maintaining normal cellular differentiation and division ³⁴. Lycopene scavenges free radicals at cellular level due to its attachment in cell membrane thereby may prevent hypercholesterolemia and hyperglycemia along with allied dysfunctions ³⁵.

a. Oxidative stress

Oxidative stress is an etiological factor in the onset of various metabolic dysfunctions. There are proven facts that uncontrolled oxidation leads to generate excessive reactive oxygen species (ROS), causative agent of many ailments that can address through antioxidants/phytochemicals rich diets ³⁶. Excessive production of free radicals leads to atherosclerosis by inactivation of nitric oxide and impairment of endothelium dependent vasodilatation. The reactive oxygen species (ROS) are produced continuously in normal metabolic pathways. The diet, smoking, exercises and environmental variables may enhance the production of reactive oxygen species (ROS) ³⁷. Despite, antioxidants have ability to start repairing through chain-chain interaction with oxidized biomolecules ³⁸. Diet based therapy indicated a significant role of lycopene in the reduction of oxidative damage of DNA and lymphocytes and short term improvement in LDL oxidation ³⁹.

The oxidative balance disrupts during production of reactive oxygen species (ROS) that successively generate double allylic hydrogen atom and initiate oxidation of lipid. Meanwhile, neutrophils catalyze the synthesis of hypochlorous acid that causes oxidative injury in terms of cellular damage. In this milieu, body produces defense enzymes i.e. superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Superoxide dismutase acts as first line defense by producing singlet oxygen into hydrogen peroxide. However, GSH-Px and catalase enzymes convert hydrogen peroxide into water. Generally, these enzymes work in harmony but in case of ROS over production, interruption may occur resulting necrosis or apoptosis. In such cases, dietary lycopene acts as a therapeutic agent to combat excessive ROS production ⁴⁰.

Oxidative stress plays a vital role in the prevalence of chronic diseases. Free radicals are linked with various disease pathogenesis as diabetes, cardiovascular complications, osteoporosis, cancer and cataracts ⁴¹. Lycopene significantly restored the antioxidant enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), reduced glutathione (GSH) whilst decreased the levels of lipid peroxide malondialdehyde (MDA) in hypertensive patients ⁴². Similarly, lycopene was found to be effective in reducing MDA and increasing GSH levels in coronary artery disease ⁴³. Later, Kim et al. ⁴⁴ examined the effect of lycopene in smoker men with low fruit and vegetable intake through a double blind randomized controlled study. They concluded that lycopene significantly reduces oxidative stress and ameliorates endothelial function ⁴⁵.

Various interventional studies have described the interaction between reduced dyslipidemia and lycopene consumption. The lycopene rich diets have potential to reduce lipid peroxidation, one of the leading factors of hypercholesterolemia. In a case study, Mackinnon et al. ⁴⁶ noticed an inverse association of dietary lycopene with oxidative stress and positive impact on bone integrity. Effect of no lycopene diet was determined in postmenopausal women of 50 to 60 years. Blood serum was analyzed for protein thiols and thiobarbituric-malondialdehyde reactive substances along with bone turn over markers; alkaline phosphatase and cross-linked N-telopeptide. Inferences of research indicated that dietary restrictions of lycopene for one month resulting tremendous increase in oxidative stress biomarkers with allied bone resorption.

Similarly, a study was conducted in human subjects to find out the role of lycopene enriched functional juice and vitamin C. The core objective was to measure the effect of lycopene (20.6 mg/day) and vitamin C (435 mg/day) against the biomarkers of inflammation and oxidative stress. Blood serum was examined for lipid status, thiobarbituric acid reactive substances and antioxidant capacity. The decrease in thiobarbituric acid reactive substances (19 to 22 %) and rise in glutathione value (17 to 20 %) was recorded. It has been observed that functional juice led to a decline in total cholesterol ⁴⁷. A completely randomized cross over study was conducted to probe the role of lycopene in suppression of oxidative stress using lycopene based capsules. Purposely, twelve healthy subjects were administrated on these capsules and a reduction in lipid oxidation was observed. The oxidative stress biomarkers i.e. thiobarbituric acid reactive substances and glutathione showed significant changes. The glutathione value raised up to 23.6 %, whereas, a decrease of 20 % in thiobarbituric acid reactive substances value was noticed ⁴⁸. Lycopene attenuates lifestyle related disorders without imparting any deleterious effects on hematological aspects. Accordingly, Jonker et al. ⁴⁹ conducted a three months study to investigate any toxic effect of lycopene in wistar rats. Blood assay was performed to evaluate the red and white blood cell count, hemoglobin, thrombocytes, neutrophils, lymphocytes and monocytes. The summary of hematological aspects revealed non-significant effect of lycopene supplementation. Moreover, histopathological examination did not reflect any adverse sign. The health benefits of lycopene are depicted in Figure 3.

Figure 3. Lycopene health benefits

[Source ²⁴]

Lycopene Health Benefits

Lycopene inhibits androgen receptor expression in prostate cancer cells in vitro and along with some of its metabolites, reduces prostate cancer cell proliferation and may modulate cell-cycle progression ⁵⁰.

Lycopene may also affect the insulin-like growth factor (IGF) intracellular pathway in prostate cancer cells.

Results from several in vitro and animal studies have indicated that lycopene may have chemopreventive effects for cancers of the prostate, skin, breast, lung, and liver; however, human trials have been inconsistent in their findings.

The recommended intake is at least 10mg of lycopene per day—from food. And tomato-based products do, give you the most bang for your buck.

Clinical trials utilizing lycopene in prostate cancer patients with various different clinical presentations (e.g., early stage, prostate-specific antigen (PSA) relapse, advanced disease) have yielded inconsistent results.

The U.S. Food and Drug Administration (FDA) has accepted the determination by various companies that their lycopene-containing products meet the FDA’s requirements for the designation of Generally Recognized as Safe (GRAS). In clinical trials involving prostate cancer patients, doses ranging from 10 to 120 mg/d have been well tolerated, with only occasional mild-to-moderate gastrointestinal toxicities.

Lycopene Possibly Ineffective ⁵¹ for:

• Bladder cancer. Research suggests that there is no link between lycopene consumption in the diet or lycopene blood levels and the risk for bladder cancer.

• Diabetes. Research suggests that increased lycopene consumption in the diet does not decrease the risk of developing diabetes.

Insufficient evidence to rate effectiveness ⁵¹ for:

• Age-related eye disease (age-related maculopathy). Research on the effect of lycopene in age-related eye disease is inconsistent. Some evidence suggests that people with low lycopene levels are almost twice as likely to develop age-related eye disease compared to people with high levels. However, other research suggests that there is no link between lycopene levels or lycopene intake and the risk of age-related eye disease.

• Asthma. Research on the effects of lycopene in people with asthma is inconsistent. Taking lycopene does not seem to reduce asthma symptoms in adults with stable asthma. However, in people with a history of exercise-induced asthma, taking a specific lycopene product (LycoMato, LycoRed Corp., Orange, NJ) seems to improve lung function after exercise.

• Hardening of the arteries (atherosclerosis). There is some evidence showing that higher lycopene blood levels is associated with a reduced risk of hardening of the arteries. There is also early evidence that higher lycopene blood levels can reduce the risk of heart disease associated with hardening of the arteries. However, there does not appear to be a link between lycopene levels and stroke risk.

• Enlarged prostate (benign prostatic hypertrophy). Early research shows that taking lycopene can slow the progression of prostate enlargement and can improve symptoms in people with this condition. However, other research found no link between lycopene intake in the diet and the development of an enlarged prostate.

• Breast cancer. Research about how lycopene affects breast cancer risk is inconsistent. Some evidence suggests that having higher lycopene blood levels is associated with a lower risk of breast cancer. However, other research shows that neither lycopene intake nor lycopene blood levels are linked to breast cancer risk.

• Heart disease. Some research shows that women with higher levels of lycopene in their blood have a lower risk of developing heart disease. However, other research shows no link between lycopene intake and the risk of heart attack or stroke in women. Also, increasing dietary lycopene does not seem to prevent heart attacks in men at low risk for heart disease.

• Cataracts. One study suggests that higher lycopene blood levels are associated with a lower risk of developing cataracts. However, other studies have found no link between lycopene intake or lycopene blood levels and the risk of developing cataracts.

• Cervical cancer. Research about how lycopene affects the risk of cervical cancer is inconsistent. Some evidence suggests that higher lycopene blood levels or higher lycopene intake in the diet is linked to a lower risk of cervical cancer. Other studies have not found this link.

• Colorectal cancer. Research about how lycopene affects the risk of colorectal cancer is inconsistent. Some research suggests that people with high lycopene intake in the diet are less likely to develop colorectal cancer than those with low intake. However, other research shows no link between lycopene intake and the risk of colorectal cancer.

• Gingivitis. Early research shows that taking a specific lycopene supplement by mouth (LycoRed, Jagsonpal Pharmaceuticals) for 2 weeks or receiving a single injection of lycopene gel into the gums reduces gingivitis.

• Brain tumor (giloma). Early research shows that taking lycopene by mouth for 3 months does not improve the response to radiotherapy and chemotherapy in people with brain tumors.

• Ulcers caused by H. pylori infection. Early research shows that taking lycopene by along with antibiotics does not help treat H. pylori infection compared to taking antibiotics alone.

• Human papilloma virus (HPV) infection. Women with higher levels of lycopene in their blood seem to recover from cancer-associated HPV infection faster than women with lower lycopene blood levels.

• High cholesterol. Early research shows that taking a specific lycopene supplement (LycoRed, Jagsonpal Pharmaceuticals) by mouth daily for 6 months lowers total cholesterol and low-density lipoprotein (LDL or “bad”) cholesterol, and increases high-density lipoprotein (HDL or “good”) cholesterol. However, other evidence suggests that lycopene does not affect cholesterol levels in healthy adults or in those with heart disease.

• High blood pressure. Early research shows that taking a specific lycopene product (LycoMato, LycoRed Corp., Organge, NJ) daily for 8 weeks lowers blood pressure in people with high blood pressure. However, other research suggests that there is no link between lycopene blood levels and the risk of developing high blood pressure.

• Lung cancer. Research about how lycopene affects the risk of lung cancer is inconsistent. Some research shows that lower lycopene intake in the diet is linked to an increased risk of lung cancer. However, other research suggests that there is no link between lycopene consumption in the diet or lycopene blood levels and lung cancer risk.

• Male fertility problems. Early research shows that taking lycopene by mouth daily for 3 months improves sperm quality in some men with fertility problems due to unknown causes.

• Menopausal symptoms. Early research shows that taking a specific product containing lycopene, calcium, vitamin D3, astaxanthin, and citrus bioflavonoids daily for 8 weeks reduces menopausal symptoms including hot flashes, joint pain, anxiety, and depression.

• White pre-cancerous patches in the mouth (oral leukoplakia). Early research shows that taking a specific lycopene supplement by mouth twice daily improves white pre-cancerous patches in the mouth.

• Ulcers and swelling in the mouth (oral mucositis). Early research shows that taking lycopene by mouth daily for 2 months improves ulcerations in the mouth in people with oral mucositis.

• Ovarian cancer. There is inconsistent evidence about the effect of lycopene on ovarian cancer risk. Some research shows that a diet rich in carotenoids, including lycopene, seems to help prevent ovarian cancer in young (premenopausal) women. However, other research shows that the risk of developing ovarian cancer is not linked to lycopene blood levels.

• Pancreatic cancer. Some early research shows that a diet high in lycopene, primarily from tomatoes, seems to lower the risk of developing pancreatic cancer.

• High blood pressure during pregnancy. Research on the effect of lycopene for preventing high blood pressure during pregnancy is unclear. Some research shows that taking a specific lycopene supplement twice daily starting between weeks 16 and 20 of pregnancy and continuing until delivery lowers blood pressure and reduces associated complications. However, other research suggests that lycopene does not affect blood pressure during pregnancy.

• Prostate cancer. Research on the effects of lycopene for preventing or treating prostate cancer is inconsistent. Some research suggests that increasing lycopene consumption in the diet, or higher lycopene blood levels, is linked with a lower risk of developing prostate cancer. However, other research shows no link between lycopene intake or blood levels and prostate cancer risk. In addition, early research in men with precancerous changes in their prostate shows that taking lycopene supplements might delay or prevent the progression to prostate cancer. However, in other research, taking lycopene daily for up to one year did not seem to help treat prostate cancer.

• Prostate swelling and pelvic pain. Early research shows that taking a specific combination of lycopene, selenium, and saw palmetto by mouth for 8 weeks reduces pain in men with prostate swelling and pelvic pain compared to saw palmetto alone.

• Kidney cancer (renal cell carcinoma). Early research shows no link between lycopene consumption in the diet and the risk of developing kidney cancer.

• Sunburn. Early research shows that taking lycopene by mouth, alone or together with other ingredients, might protect against sunburn.
• Other conditions.

More evidence is needed to rate lycopene for these uses.

Lycopene Health Benefits for Men

Past research, has shown that a diet rich in lycopene-containing foods may help lower the risk of prostate and other cancers. Now, in a report just published in the journal Neurology, a team of Finnish researchers has linked lycopene levels in the blood to stroke protection ⁵². They made this connection after following more than a thousand middle-aged men for 12 years. Men with the greatest amounts of lycopene in their blood had a 55% lower chance of having any kind of stroke. The lycopene connection was even stronger (59%) when it came to protecting against strokes due to blood clots (the most common kind) ⁵². The researchers suggested that lycopene, in addition to its ability to attack free radicals, may also reduce inflammation and cholesterol, improve immune function, and prevent blood from clotting. All of these may help reduce ischemic strokes, which are caused by clot-caused blockages in blood flow to the brain. How the added that larger studies are needed to confirm the findings and to figure out if the stroke protection is due to lycopene or healthy lifestyle habits, because a high lycopene consumer is likely to eat more vegetables and not be a smoker ⁵².

For cancers, as pointed by the FDA (see below), “there was no credible evidence to support qualified health claims for tomatoes or tomato-based foods and a reduced risk for lung, colorectal, breast, cervical, or endometrial cancer. FDA further concluded that there was no credible evidence to support qualified health claims for lycopene, as a food ingredient, component of food, or as a dietary supplement, and a reduced risk of any of these cancers. Thus, FDA denied these claims. FDA concluded that there was very limited credible evidence for qualified health claims for tomatoes and/or tomato sauce and a reduced risk for prostate, gastric, ovarian, and pancreatic cancers provided that the qualified health claims were appropriately worded so as to not mislead consumers” ⁵³.

Lycopene, Cancers and U.S. Food and Drug Administration (FDA) Conclusion

In 2004, FDA received two petitions for qualified health claims regarding tomatoes and/or lycopene and cancer risk reduction from The Lycopene Health Claim Coalition (consisting of H. J. Heinz Company, LycoRed Natural Products Industries, Ltd, The Morningstar Company, and The Prostate Cancer Foundation) and American Longevity, Inc. Both petitioners requested that FDA evaluate the relationship between tomato and/or lycopene consumption and prostate cancer risk. One petitioner also requested that FDA review the relationship between tomato and/or lycopene consumption and the risks of other forms of cancer, including lung, colorectal, gastric, breast, cervical, ovarian, endometrial, and pancreatic cancers. In response to these petitions, FDA evaluated evidence for associations between lycopene (a food component) and tomatoes (a food) separately and each form of cancer.

Based on the scientific evidence, FDA concludes that there is no credible evidence to support a qualified health claim for tomato lycopene; tomatoes and tomato products, which contain lycopene; lycopene in tomatoes and tomato products; lycopene in fruits and vegetables, including tomatoes and tomato products, and lycopene as a food ingredient, a component of food, or as a dietary supplement and reduced risk of prostate cancer ⁵⁴.

The FDA found no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer ⁵⁵. The FDA also found no credible evidence for an association between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer. The FDA found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers ⁵⁵.

On November 8, 2005, FDA issued letters of enforcement discretion for these qualified health claims ⁵³.

Prostate Cancer

“Very limited and preliminary scientific research suggests that eating one-half to one cup of tomatoes and/or tomato sauce a week may reduce the risk of prostate cancer. FDA concludes that there is little scientific evidence supporting this claim” ⁵⁴.

Gastric Cancer

“Four studies did not show that tomato intake reduces the risk of gastric cancer, but three studies suggest that tomato intake may reduce this risk. Based on these studies, FDA concludes that it is unlikely that tomatoes reduce the risk of gastric cancer.”

Ovarian Cancer

The qualified health claim for ovarian cancer was “One study suggests that consumption of tomato sauce two times per week may reduce the risk of ovarian cancer; while this same study shows that consumption of tomatoes or tomato juice had no effect on ovarian cancer risk. FDA concludes that it is highly uncertain that tomato sauce reduces the risk of ovarian cancer.”

Pancreatic Cancer

The qualified health claim for pancreatic cancer was “One study suggests that consuming tomatoes does not reduce the risk of pancreatic cancer, but one weaker, more limited study suggests that consuming tomatoes may reduce this risk. Based on these studies, FDA concludes that it is highly unlikely that tomatoes reduce the risk of pancreatic cancer.”

Lung Cancer

The evidence for a relationship between tomato or tomato-based foods intake and a reduced risk of lung cancer is from one cohort study, one sub-cohort study and one nested case-control study. None of these 3 studies supported a relationship between tomato or tomato-based food intake and lung cancer risk reduction. Based on the above, FDA concludes that there is no credible evidence supporting a relationship between tomato or tomato-based food consumption and lung cancer.

Breast Cancer

The evidence for a relationship between tomato intake and reduced risk of breast cancer is based on two case control studies. Neither of the studies found a relationship between tomato or tomato-based food intake and breast cancer risk. Based on the above, FDA concludes that there is no credible evidence supporting a relationship between tomato or tomato-based food consumption and breast cancer.

Colorectal Cancer

The evidence for a relationship between tomato or tomato-based food consumption and reduced risk of colorectal cancer is based on two case-control studies from the United States and Italy. Neither case-control study found a relationship between tomato or pizza consumption and colorectal cancer risk reduction. Based on the above, FDA concludes that there is no credible evidence supporting a relationship between tomato or tomato-based food consumption and colorectal cancer.

Endometrial Cancer

There were no studies that evaluated the relationship of tomatoes or tomato-based foods and endometrial cancer risk. Based on the above, FDA concludes that there is no credible evidence supporting a relationship between tomato or tomato-based food consumption and endometrial cancer.

Cervical Cancer

There was one observational study that showed that the consumption of tomatoes was not significantly different between control and cervical cancer cases and no studies showing a relationship between tomatoes or tomato-based foods and risk of cervical cancer. Therefore, FDA concludes that there is no credible evidence to support a relationship between the consumption of tomatoes or tomato-based foods and cervical cancer risk.

Lycopene supplement

Many studies suggest that eating lycopene-rich foods or having high lycopene levels in the body may be linked to reduced risk of cancer, heart disease, and age-related eye disorders. However, measures of lycopene intake have been based on eating tomatoes, not on the use of lycopene supplements.

Lycopene Supplements may give you a purified form of lycopene, but you’re not sure you’re getting what you get from food. Since tomatoes also contain other nutrients, such as vitamin C and potassium, the potential benefits of lycopene alone are still unclear. Furthermore, you may be getting the wrong form of lycopene in a supplement. There are also a lot of compounds in food that aren’t lycopene but that are similar, and some of those molecules may be part of what makes lycopene so beneficial ⁵⁶.

• Lycopene deficiency is not considered a medical condition. There is a lack of evidence on whether increasing low lycopene levels may benefit health.

The appropriate dose of lycopene depends on several factors such as the user’s age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for lycopene. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.

Lycopene is likely safe when taken by mouth in appropriate amounts. Daily supplements containing up to 120 mg of lycopene have been used safely for up to one year.

Doses of lycopene ranging between 8 mg and 45 mg administered over a period ranging from 3 weeks to 2 years have been reported to be safe in randomized clinical trials targeting the prostate. When adverse effects occurred, they tended to present as gastrointestinal symptoms and, in one study, the symptoms resolved when lycopene was taken with meals. Another study reported that one participant withdrew because of diarrhea.

As an antioxidant, lycopene has been taken by mouth in doses of 6.5, 15, and 30 milligrams daily for eight weeks. Lyc-O-Mato® capsules (each containing up to 15 milligrams) have been taken by mouth once daily for eight weeks and 26 days, or twice daily for four months. Two capsules of LycoRed® (each containing 15 milligrams of lycopene) have been taken by mouth once daily for 21 days ⁵⁷.

To treat asthma caused by exercise, 30 milligrams of lycopene in the form of Lyc-O-Mato® has been taken by mouth daily for one week ⁵⁷.

To treat coronary artery disease, 1.24 grams of six-percent lycopene oleoresin capsules (LycoRed®) has been taken by mouth daily for one week. Two LycoRed® softules (each containing 2,000 micrograms of lycopene) have been taken by mouth daily for six months. Lycopene has been taken by mouth in the form of tomato products, capsules, and Lyc-O-Mato® in doses of 39.2-80 milligrams for 1-12 weeks ⁵⁷.

To treat enlarged prostate, 15 milligrams of lycopene (LycoVit®) has been taken by mouth daily for six months ⁵⁷.

To treat brain tumors, eight milligrams of lycopene has been taken by mouth daily for three months ⁵⁷.

To treat heart disease, lycopene has been taken by mouth in the form of tomato products, capsules, and Lyc-O-Mato® in doses of 39.2-80 milligram doses daily for 1-12 weeks ⁵⁷.

To treat gum disease, LycoRed® (providing eight milligrams of lycopene) has been taken by mouth daily in divided doses for two weeks ⁵⁷.

To treat high blood pressure, lycopene has been taken by mouth in 4-44-milligram doses daily for up to six months. Lyc-O-Mato®, containing 15 milligrams of lycopene, has been taken by mouth daily for six weeks and eight weeks. A dose of 250 milligrams of Lyc-O-Mato® has been taken by mouth for eight weeks ⁵⁷.

To treat infertility, 2,000 micrograms of lycopene has been taken by mouth twice daily for three months ⁵⁷.

To lower lipid levels, lycopene has been taken by mouth in 4-44-milligram doses daily for up to six months. Two LycoRed® softules (each containing 2,000 micrograms of lycopene) have been taken by mouth daily for six months ⁵⁷.

To treat mouth sores, LycoRed®, containing 4-8 milligrams of lycopene, has been taken by mouth daily for three months in two divided doses ⁵⁷.

To treat inflammation of the mouth, 16 milligrams of lycopene has been taken by mouth daily in two divided doses for two months ⁵⁷.

To prevent ovarian cancer, 4,000 micrograms of lycopene has been taken by mouth daily ⁵⁷.

To treat high blood pressure associated with pregnancy, LycoRed® (containing two milligrams of lycopene per capsule) has been taken once or twice daily until delivery ⁵⁷.

• Pregnancy and breast-feeding: Lycopene is likely safe during pregnancy and breast-feeding when taken in amounts commonly found in foods ⁵¹. However, lycopene is POSSIBLY UNSAFE when taken as a supplement during pregnancy. A study using a specific lycopene supplement (LycoRed, Jagsonpal Pharmaceuticals) found that taking 2 mg daily, starting between weeks 12 and 20 of pregnancy and continuing until delivery, increased the rate of premature births and low-birth-weight babies. Not enough is known about the safety of lycopene supplements during breast-feeding ⁵¹. If you are pregnant or breast-feeding, avoid using lycopene in amounts greater than those typically found in foods.

To prevent or treat prostate cancer, two milligrams of lycopene has been taken by mouth twice daily, and four milligrams of lycopene has been taken by mouth twice daily for one year. Lyc-O-Mato®, containing up to 120 milligrams of lycopene, has also been taken by mouth in divided doses twice daily for periods of up to one year. LycoRed® softules, providing a total daily dose of 10 milligrams of lycopene, have been taken daily for three months.

• Prostate cancer: Developing laboratory research suggests lycopene might worsen established prostate cancer by increasing the spread of cancer without having any effect on cancer cell growth. Until more is known, avoid lycopene if you have a prostate cancer diagnosis ⁵¹.

To protect skin from sun damage, 55 grams of tomato paste in olive oil (providing 16 milligrams of lycopene) has been taken by mouth daily for 12 weeks ⁵⁷.

Children (younger than 18 years) : There is no proven safe or effective dose for lycopene in children ⁵⁷.

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