**5. Role of tomato carotenoids in chronic disease prevention**

Consumption of fruits and vegetables with beneficial health properties has been exploited for their ability to treat or prevent several chronic diseases [60]. There is an inverse relationship between the balanced consumption of tomatoes and tomatoderived products and the incidence of chronic diseases such as CVDs and various forms of cancers. These beneficial effects are attributed to carotenoids and phenolic compounds, which have high antioxidant capacities [48].

#### **5.1 Oxidative stress**

Oxidative stress plays an essential pathophysiological role in various chronic diseases such as CVDs, diabetes, neurodegenerative diseases, and cancer [60]. Free radicals, or other reactive oxygen- or nitrogen-containing species, are responsible for oxidative stress [48]. Oxidative stress occurs when there is a relative excess of ROS when compared with antioxidants [61]. ROS are reduced oxygen metabolites characterized by strong oxidizing capabilities. They are deleterious to cells at high concentrations but at low concentrations, they play a major role in cellular signaling and function [62]. ROS are formed as a by-product of mitochondrial respiration or metabolic activities (such as breathing, digesting food, metabolizing alcohol and drugs, and turning fats into energy) or by enzymes, such as superoxide dismutase, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases [60, 63]. Cells possess complex biochemical and genetic mechanisms to maintain ROS at physiologically normal concentrations, and deregulation in this balance has detrimental health effects [61, 62]. This is because abnormally high ROS levels may attack certain biomolecules (DNA, RNA, proteins lipids, and carbohydrates) causing damage to cells, tissues, and organs. [64]. The continuous production of free radicals in humans must be equivalent to the rate of antioxidant intake/synthesis [60]. Molecules such as ascorbate, a-tocopherol, and carotenoids are examples of antioxidants that are capable of quenching ROS. The structural properties of carotenoid molecules, particularly the presence of conjugated carbon–carbon double bonds enable the quenching of ROS and subsequently a reduction in ROS levels [19]. Tomato and related products contain carotenoids, particularly lycopene, one of the most potent

## *Potential of Carotenoids from Fresh Tomatoes and Their Availability in Processed Tomato-Based… DOI: http://dx.doi.org/10.5772/intechopen.103933*

antioxidants that have been found to protect against these chronic diseases by mitigating oxidative damage and improving the oxidative status [20, 48, 65]. Lycopene exerts strong antioxidant activity because it contains many double-conjugated bonds (11 conjugated double bonds and two unconjugated double bonds), which explains why lycopene can quench ROS and efficiently scavenge free radicals [7]. A study demonstrated that a long-term tomato-rich diet consisting of tomato juice, tomato sauce, tomato paste, ketchup, spaghetti sauce, and ready-to-serve tomato soup can reduce oxidative stress, this was attributed to an increase in serum lycopene levels from 181.79 ± 31.25 to 684.7 ± 113.91 nmol/l, as well as an increase in total antioxidant potential from 2.26 ± 0.015 to 2.38 ± 0.17 mmol/l Trolox equivalent [65]. The level of oxidative stress induced by in-vitro X-ray exposure in healthy adults was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG), and plasma reactive oxygen metabolite-derived compounds (d-ROMs), the results suggested that continuous tomato juice consumption could decrease extracellular 8-oxo-dG and d-ROMs [66]. Previous studies have shown that tomato extracts containing 6% lycopene, other tomato carotenoids (phytoene and phytofluene above 1%, beta-carotene above 0.2%), can prevent oxidative stress-induced damage to fibroblast skin cells [67].

#### **5.2 Tomato consumption and cardiovascular diseases**

Worldwide, CVDs are an increasing concern due to the rising prevalence and consequent mortality and disability with a heavy economic burden since it is an important contributor to the cost of medical care [68, 69]. In 2019, 17.9 million people died from CVDs, representing 32% of all global deaths [70]. There is a growing body of epidemiological evidence that tomato and tomato products intake lower the risk of CVDs, through antioxidative, anti-inflammatory, and hypotensive effects [71]. The improvement of biomarkers associated with CVD development and the subsequent reduction in CVD risk has been ascribed to increased plasma lycopene levels. Moderate intake (2–4 servings) of tomato products such as soup, paste puree, juice, or any other tomato beverages, when consumed with the addition of dietary lipids, such as olive oil or avocados, leads to a rise in plasma carotenoids, particularly lycopene [72]. Dietary lycopene consumed as oil-based tomato products confers cardiovascular benefits. The consumption of ≥7 servings/week of tomato-based food products has been associated with a 30% reduction in CVD development in women [73]. Consumption of two glasses of tomato juice satisfies the recommended daily intake of lycopene (35 mg), [74]. **Table 4** shows the lycopene content of tomatoes and some frequently consumed tomato-derived products.

Epidemiological studies also suggest that the risk of myocardial infarction is lowered in individuals with higher lycopene content in adipose tissue. The EURAMIC (European community multicenter study on antioxidants, myocardial Infarction, and breast cancer) case–control study conducted in 10 European countries to assess the relations between antioxidant status and acute myocardial infarction, found lycopene concentration of adipose tissue to be independently protective against myocardial infarction [76]. A recent study by Cheng et al. [77] reported that higher intakes of lycopene or its high serum concentrate have been associated with significant reductions in the risk of stroke (26%) and CVDs (14%). Another carotenoid present in processed tomato products associated with CVD risk reduction is β-carotene [78].

Low levels of high-density lipoprotein (HDL) cholesterol and elevated LDL cholesterol are established CVD risk factors [79]. Pharmacological therapies aimed at LDL lowering have convincingly proven to reduce CVD disorders, such as coronary


#### **Table 4.**

*Lycopene content of tomatoes and processed tomato products.*

heart disease. Therefore, LDL cholesterol levels should be lowered as much as possible to prevent CVD [80, 81]. Lycopene may modulate the expression of adhesion molecules in human vascular endothelial cells and increase the expression of LDL receptors involved in the regulation of cholesterol metabolism [75]. Increasing the concentration of HDL can slow and even reverse the progression of coronary atherosclerosis (coronary heart disease) and reduce CVD risk in those with dyslipidemia (abnormal levels of blood lipids including cholesterol). Consumption of two uncooked tomatoes per day demonstrated a significant elevation of HDL levels in overweight women [79]. Michaličková et al. [71] conducted a randomized controlled study to examine the effect of tomato juice on LDL cholesterol. The intervention group was supplemented with 200 g of tomato juice for 4 weeks and a significant reduction in total cholesterol and LDL was observed [71] indicating that tomato and derivatives have favorable effects on lipid metabolism.

Systemic arterial hypertension is a condition in which an individual has abnormally high blood pressure (BP) and is a primary risk factor for CVDs [82]. BP above 140 mmHg systolic and/or 90 mmHg diastolic is considered hypertensive [83]. Several studies indicated that tomato products intake leads to a significant reduction in BP [84, 85]. A higher dosage of tomato-derived supplements (containing more than 12 mg lycopene per day) could significantly lower systolic blood pressure (SBP), particularly among populations with baseline SBP > 120 mmHg [84]. The effect of treatments with tomato nutrient complexes (containing 5, 15, and 30 mg lycopene) was compared with 15 mg of synthetic lycopene and a placebo over 8 weeks, significant reductions in mean SBP were noted in tomato nutrient complexes treatments with 15 or 30 mg of lycopene [86]. A recent trial highlighted the benefits of processed tomato products on BP management in overweight middle-aged adults. A lowered diastolic BP was observed in participants that consumed a high tomato diet consisting of approximately 200 g/day or 1400 g/week of tomato products [78]. In a quasi-experimental study, 32 type 2 diabetes patients consumed 200 g raw tomato daily for 8 weeks. A significant decrease in systolic and diastolic BP was noted at the end of the study compared with initial values [87]. Tomato consumption might be beneficial for reducing CVD risk in type 2 diabetic patients.

#### **5.3 Anti-cancer role of tomato carotenoids**

The consumption of tomatoes and tomato-derived products is inversely related to the incidence of different types of cancers, (prostate, stomach, and lung cancers) [7, 72, 88, 89]. A study on elderly patients in the US attributed a 50% reduction in mortality rates from cancer of all sites to a high intake of tomatoes [90]. Tomatoes and tomato products are typical components of the Mediterranean diet (MD).

*Potential of Carotenoids from Fresh Tomatoes and Their Availability in Processed Tomato-Based… DOI: http://dx.doi.org/10.5772/intechopen.103933*

The MD represents a dietary pattern suitable for the prevention of chronic diseases [91]. A meta-analysis of observational studies, which evaluated the effects of the adoption of the MD on incidence and mortality of different types of cancer, showed that the high adherence to this diet was associated with a significantly lowered risk of overall cancer, especially colorectal cancer, pharyngeal and esophageal cancer, and prostate cancer [92]. The protective role of tomatoes is predominantly ascribed to the carotenoid, lycopene [93]. Researchers found that there was a lower rate of mortality from cancer in the group of US adults with the highest tomato and lycopene intake (42.5% and 45.9%, respectively) [94].

Extensive research has been conducted on the role of lycopene in the prevention of prostate cancer, the second most frequent cancer (after lung cancer) diagnosed in men worldwide [7, 72, 95], with higher incidence and mortality observed in developed countries [96]. Findings from ecological and migrant studies suggest that the wide disparity in incidence rates of prostate cancer worldwide may be attributed to a "Westernized" diet and lifestyle in developed countries [97]. A study conducted in 2011 using DU145 cells (human prostate cancer cells), revealed that the proliferation of these cells was significantly inhibited by lycopene. The authors found that lycopene induced a reduction of the proliferation rate at concentrations of 15 and 25 μM, but not at physiological concentrations (>2 μM) [98]. The US health Professionals Follow-up Study investigated the relationship of various carotenoids and retinol consumption with the risk of prostate cancer. There was an inverse relationship between the estimated intake of lycopene and the risk of this cancer. This reduced incidence was not observed with any other carotenoid. A reduction in risk of almost 35% was observed for a consumption rate of 10 or more servings of tomato products per week, and the protective action was greater with more advanced or aggressive prostate cancer [95]. In a more recent study, there was an 18% lower risk of prostate cancer associated with adherence to the same recommended tomato intake [97].

Evidence pointing to the protective effect of tomato product consumption for other cancer sites other than the prostate is ambiguous [99]. Lung cancer is the leading cause of cancer death, with an estimated 1.8 million deaths (18%) [100]. Growing evidence suggests that tomato lycopene may be preventive against the development of this cancer [101]. In 2020, a study demonstrated that lycopene treatment may inhibit the growth of lung tumor cell line A549. Varying amounts of lycopene (2.5, 5, and 25 μL) were used to treat lung cancer cell cultures and higher lycopene concentrations were more damaging to cancer cell nuclei [102]. Among 14 case-control lung cancer studies, only 6 studies showed a statistically significant risk reduction for cancer incidence, averaging 51%. However, cohort studies showed no beneficial relation between lung cancer reduction and tomato product consumption [99]. According to epidemiological studies, higher lycopene intake is associated with either a reduced or no change in lung cancer risk when compared to lower intake levels [103]. Gastric (stomach) cancer remains one of the dominant causes of cancer mortality in the world [104, 105]. Tomato or lycopene intake has proven to reduce gastric cancer risk in a variety of populations [72, 95]. However, few studies have been conducted to date. A meta-analysis study consisting of 21 studies supports an inverse association between tomato consumption and risk of gastric cancer [106]. Previous research projects have reported a negative relationship between tomato intake and the risk of gastric cancer. A study conducted in Korea consisting of 1245 subjects (415 cases and 830 matched controls; 810 men and 435 women), highlighted that the consumption of tomatoes and tomato ketchup was inversely associated with GC risk in the overall subjects [107]. In a case-control study in Uruguay, tomato consumption had a strong inverse association

with gastric carcinogenesis. The carotenoids, α-carotene, and lycopene were strongly associated with this reduction in stomach cancer development [108].

#### **5.4 Tomato in protection against obesity and diabetes**

The incidence of type 2 diabetes (diabetes mellitus) and obesity has increased worldwide during the last century in both developed and developing countries [109]. Obesity is a chronic inflammatory disorder in which an increase in circulating inflammatory mediators is caused by an increase in body fat [20, 110]. Destructive mechanisms associated with obesity increase ROS and hamper the antioxidant status [111]. Individuals having a fasting blood sugar level of 126 mg/dl or higher on 2 separate days, will be diagnosed with type 2 diabetes [112]. The strong link between type 2 diabetes and obesity [113], with 80 percent of type 2 diabetes patients being overweight [112], was named "diabesity." According to the WHO, overweight and obesity account for 44% of diabetes cases. Therefore, it is necessary to develop therapeutic strategies favoring weight loss and blood glucose control (anti-obesity and antidiabetic treatment) [114].

A randomized controlled clinical trial was conducted on 64 overweight or obese demonstrated that tomato juice reduces oxidative stress in overweight females and may prevent the development of obesity-related diseases. In this study, the antioxidant parameters of study participants that ingested 330 ml/day of tomato juice for 20 days were analyzed at the beginning and after this period verifying an increase in plasma total antioxidant capacity (TAC) and erythrocyte antioxidant enzymes [115]. Ghavipour et al. [110] demonstrated that tomato juice consumption lowers inflammation in overweight and obese females. The predictive biomarkers of inflammation [tumour necrosis factoralpha (TNF-α) and interleukin 8 (IL-8)] were examined in study participants who drank 330 ml of tomato juice every day for 20 days. The serum levels of IL-8 and TNF- α were significantly lower in overweight people that consumed the tomato juice compared to the control group. The scientists concluded that eating more tomatoes may lower the risk of inflammatory disorders, such as CVDs and diabetes [110].

The goal of diabetes management is to maintain plasma glucose concentrations at near-normal levels [112]. According to the WHO, expected values for normal fasting blood glucose levels are between 70 mg/dl (3.9 mmol/l) and 100 mg/dl (5.6 mmol/l) [116]. Chemicals found in fresh or processed tomatoes have been shown to have antihyperglycemic properties that enable the lowering of glucose levels in the blood. In streptozotocin (STZ)-induced hyperglycemic rats, oral administration of tomato extract lycopene (90 mg/kg of body weight) resulted in a lower serum glucose level. The therapeutic amount of lycopene in humans is around 14.5 mg/kg of body weight. Lycopene's anti-diabetic properties may be linked to its antioxidant activity, which reduces the number of free radicals generated [117]. Another study indicated that fasting blood sugar levels decreased after drinking tomato juice for 3 weeks [112]. The reduction in fasting blood glucose levels was found to be an average of 9.00 mg/ dl (7.64%). Supplementation with β-carotene did not affect type 2 diabetes in randomized controlled trials [118, 119]. The impact of lycopene consumption on blood glucose concentration was analyzed, each 1 mg increase in lycopene consumption was associated with a 0·005 mmol/l decrease in fasting blood glucose concentration [120]. The effects of pre-prandial tomato intake on body weight, fat percentage, triglyceride, cholesterol, and blood sugar levels were evaluated in 35 young women aged 18 to 21 years. Participants ate raw, ripe tomatoes (90 g) before lunch each day for 4 weeks. At the end of the study, there were significant reductions in body weight (1.09 ± 0.12 kg), fat % (1.54 ± 0.52%), fasting blood glucose (5.29 ± 0.80 mg/dl),

*Potential of Carotenoids from Fresh Tomatoes and Their Availability in Processed Tomato-Based… DOI: http://dx.doi.org/10.5772/intechopen.103933*

triglycerides (8.31 ± 1.34 mg), and cholesterol (10.17 ± 1.21 mg/dl). Thus, tomato consumption before meals was positively correlated with body weight, fat %, triglycerides, blood sugar, and cholesterol levels in young adult women [121].
