Open access peer-reviewed chapter - ONLINE FIRST

Role of Carotenoids in Cardiovascular Disease

Written By

Arslan Ahmad, Sakhawat Riaz, Muhammad Shahzaib Nadeem, Umber Mubeen and Khadija Maham

Submitted: December 20th, 2021 Reviewed: January 18th, 2022 Published: April 13th, 2022

DOI: 10.5772/intechopen.102750

IntechOpen
Carotenoids - New Perspectives and Application Edited by Rosa María Martínez-Espinosa

From the Edited Volume

Carotenoids - New Perspectives and Application [Working Title]

Dr. Rosa María Martínez-Espinosa

Chapter metrics overview

27 Chapter Downloads

View Full Metrics

Abstract

Carotenes are fat-soluble pigments found in a variety of foods, the majority of which are fruits and vegetables. They may have antioxidant biological properties due to their chemical makeup and relationship to cellular membranes. And over 700 carotenoids have been found, with—carotene, lutein, lycopene, and zeaxanthin is the most significant antioxidant food pigments. Their capacity to absorb lipid peroxides, reactive oxygen species (ROS) and nitrous oxide is likely linked to their anti-oxidative properties (NO). The daily requirements for carotenoids are also discussed in this chapter. Heart disease is still a prominent source of sickness and mortality in modern societies. Natural antioxidants contained in fruits and vegetables, such as lycopene, a-carotene, and B-carotene, may help prevent CVD by reducing oxidative stress, which is a major factor in the disease’s progression. Numerous epidemiological studies have backed up the idea that antioxidants might be utilized to prevent and perhaps treat cardiovascular illnesses at a low cost. Supplements containing carotenoids are also available, and their effectiveness has been proven. This article provides an overview of carotenoids’ chemistry, including uptake, transport, availability, metabolism, and antioxidant activity, including its involvement with disease prevention, notably cardiovascular disease.

Keywords

  • carotenoids
  • antioxidants
  • cardiovascular disease
  • free radicals
  • CVD prevention

1. Introduction

There are presently around 700 carotenoids known, although only about 50 of them are being digested by humans [1, 2]. Carotenoids are present in large concentrations in adipose tissue (80–80% of total), liver (8–12%), and muscles (2–3%) in healthy adults, but in fewer amounts in all other areas [3]. overall amount and levels of various carotenoids inside a person’s bloodstream are mostly determined by their daily average diet. Carotenoids and polyenes are abundant in green leafy vegetables and various multicolored fruits [4]. The bulk of dietary carotenoids is digested by the stomach and enters the bloodstream in humans. People’s blood contains B-carotene, a-carotene, cryptoxanthin, lycopene, and lutein [5]. Carotenoids circulate in the circulation alongside lipoproteins, notably LDL (low-density lipoprotein fraction) [6]. However, a large amount of ingested B-carotene and other provitamins. A carotenoid is transformed to the retina, primarily in the gut wall, but also some proportion in the stomach and intestines [7]. In the human diet, fresh vegetables are currently the primary source of carotenoids [8, 9, 10]. Lutein might perform an important role in hypertension and symptoms of acute permeability in those with heart problems, high cholesterol, and/or hyperglycemia, according to a literature review and meta-analysis [11].

Carotenoids may be found in a variety of fruits and are also available as a nutritional supplement [12, 13]. Cardiovascular abnormalities have subsequently been a major source of worry across the world since they affect a large portion of the global population, and an elevated death rate has been reported in individuals aged 30 and above [14, 15]. Numerous researches have looked at carotenoids’ possible cardioprotective and antioxidant capabilities [16, 17]. Individuals with cardiovascular disease may benefit from the anti-inflammatory properties of lutein, which may help to alleviate their symptoms [18]. ROS-induced reactive damage can arise in lipid peroxidation products, this may hasten the onset of atherosclerosis, the condition that causes heart attacks and ischemic strokes [19].

Advertisement

2. Chemistry of carotenoids and their dietary sources

Carotenoids can be found in a variety of foods, although the majority of carotenoids in the diet are derived from strongly colored vegetables, fruits, and juices. Carotenes supplied as food colorings to foods during the process, milk and dairy fat-containing meals, eggs, seafood, and carotenoids provided as food colorings to foods during handling can also supply trace amounts. The principal sources of carotenoids in the United States are shown in Figure 1. The data is derived from Median values using current HPLC procedures [20].

Figure 1.

United States donators of carotenoids rich foods and per capita.

B-cryptoxanthin is present in orange fruits, lutein in green leafy vegetables, and lycopene in tomatoes and tomato derivatives, while B-carotene and a-carotene are both found in yellow-orange veggies and fruits. Multicomponent or mixed meals (e.g., soup, stew) generally contain a considerable proportion of carotenoid-rich foods, which is a practical element to address in dietary evaluation [21, 22]. Seasonality may be a key factor of the kind and amount of dietary carotenoids consumed in populations or cultural groups that consume fruits and vegetables in seasonal patterns [23, 24]. Most carotenoids have a polyisoprenoid structure, which means they have a lengthy connected network with the double bonds and are essentially bilaterally symmetrical around the central doubled bond [25]. Multiple carotenoids are generated by cyclizing the end groups and adding oxygen functionalities to the basic structure, which gives them their distinctive hues and antioxidant characteristics. The structure of several carotenoids is shown in Figure 2.

Figure 2.

Chemical structure of common carotenoids.

Advertisement

3. Carotenoids and cardiovascular health

3.1 Lycopene

The most frequent pigment present in human blood is lycopene. That’s just a non-cyclic-carotene analog with 11 linked doubled bonds and two distinct doubling bonds arranged in a linear arrangement [25]. This natural pigment is produced by bacteria and plants. Tomatoes are one of the most potent antioxidants, having a respiration activity that is greater than the total beta-carotene and 10 twice that of -tocopherol [26]. This is owing to the high quantity of linked diamines in the product. The adrenals, testicles, liver, and sex organs all contain lycopene [27]. Unlike some other carotenoids, lycopene content in the blood and organs does not correspond well with the total fruit and veggies diet [28].

According to the oxidative hypothesis, preventing LDL from being damaged is the first stage in the production of fibrils and atherosclerosis plaques, which leads to its absorption by monocytes inside the artery wall and the formation of plaque [29]. Oxidative alterations include triglyceride destruction, phospholipid oxidation, and subsequent oxidation of Apolipoprotein B, in addition to unsaturated fatty acids [30].

3.2 Lycopene absorption

Lycopene can mainly be found in its all-trans stereoisomer”s natural form [31]. Lycopene is perhaps the most abundant pigment in blood serum, with a duration of 2–3 days [32].

Fragmentation of the lycopene-rich feed solution, cooking temperature, and the incorporation of lipids as well as other fat compounds, such as other carotenoids, all impact lycopene absorption from food components. Carotenoids, like other lipid-soluble medicines, are digested via a chylomicron-mediated process in the gastrointestinal system [33]. Humans absorb 10–30% of the lycopene they eat in their diet [34, 35]. Sauce, tomato puree, and tomato aqueous extracts capsules all absorb lycopene as well [34, 36]. Lycopene levels are greatest in the testicles, adrenals, prostate, chest, and liver in humans [37, 38]. Lycopene is metabolized and broken down in the tissues. Many oxidizing lycopene forms, as well as polarized intermediates, have recently been isolated and identified [39]. Table 1 shows the lycopene content of several foods [37, 40]. According to studies, 10–30% of lycopene taken in the diet is absorbed in the body [41].

Table 1.

Fruits and vegetables with high lycopene content [37, 40].

3.3 Lycopene and CVD

A lower incidence of cardiovascular disease has been attributed to the Mediterranean diet. Tomatoes, tomato derivatives, lycopene, and other pigments are abundant [42, 43]. In 499 patients with CVD (Mayo cordial infection, strokes, CVD mortality, or revascularization therapies), increased plasma lycopene levels were linked to a decreased risk of cardiovascular disease in the Physicians’ Health Study [44]. Lower blood lycopene levels were connected to an increased risk of death in a demographic study comparing Lithuanian and Swedish populations with different heart disease mortality rates [45]. Inflammation is considered to have a part in the development of atherosclerotic disease, which accounts for around 80% of all heart disease cases. In studies, high levels of cytokine production in blood plasma were associated with the onset of cardiac problems [46].

In a research of 139 sick people, oxygenated carotenoids (zeaxanthin, lutein, carotenoids, B-cryptoxanthin, a-carotene, and b-carotene) were found to be reduced in both patient groups (39 with acute illness, 50 with cardiovascular events, and 50 control participants) [47]. In a Japan inhabitants research of 3061 people, there was a link between high blood carotenoids (a-carotene, a-carotene, lycopene, total carotene levels) and a decreased hazard ratio for mortality risk [48]. Upon 60 days of tomato diet intake, a study of CHD (chronic heart disease) patients found a significant improvement in plasma key anti-oxidative enzymes (lipid oxidation rate, dismutase, glutathione peroxidase) compared with control, implying that or more elements of veggies could have medicinal beneficial health effects. In a 3-month study, six healthy guys were given 60 mg of lycopene each day. At the completion of the medication term, their plasma LDL cholesterol level had dropped by 14% [49]. For 1 week, 19 smoke-free healthy people (10 men, 9 women) received lycopene via normal tomatoes and nutraceuticals (20–150 mg/d) in a designed cross nutritional controlled trial [50]. The goal of Thiess and coworkers’ randomized clinical experiment was to see how lycopene consumption affected the levels of cardiovascular risk indicators in healthy people. According to the data, taking 10 mg of lycopene every day for 12 weeks did not influence raised blood concentrations. The levels of Apolipoprotein A-I and Apoprotein B-100 were constant. Although the findings were not significant, both the diastolic (DBP) and systolic (SBP) blood pressures were reduced by 3.2 and 0.3 mmHg, respectively [51].

3.4 B-carotene

This group includes the xanthophyll compounds lutein and zeaxanthin. Macula lutea pigments are made from the macula lutea plant’s natural dyes. Certain pigments seem to be essential for the physiological function of the eye. They protect against cataracts and macular degeneration caused by aging. These qualities are owed to their antioxidant properties first and foremost [52]. Figure 1 shows that zeaxanthin has the same composition as lutein and is its derivative. From one of the final b-ion rings, the placement of a double bond changes between the two compounds: zeaxanthin is between C50 and C60, whereas lutein’s is between C40 and C5. Leafy foods, along with colorful veggies, are high in lutein. Two of the most prevalent sources are spinach and greens. Lutein can also be present in egg yolks, thanks to the practice of feeding chickens plant-based foods. Corn and red peppers, for example, contain zeaxanthin [53, 54]. Xu and colleagues looked into the efficacy of lutein supplements here on activation of proinflammatory mediators and blood lipids in atherosclerotic subjects. The levels of monocyte chemotaxis protein type 1 in the blood of several individuals who received lutein at a dosage of 20 mg/d for 3 months were decreased (MCP-1). LDL blood cholesterol values were also found to be lower in these individuals [55]. The China Coronary Finding provides evidence that lutein has a protective effect on atherosclerosis. Patients with early stages of atherosclerosis had lower blood lutein concentrations than healthy individuals, according to the study. Plasma lutein content is seen to be negatively linked to the thickness of carotid endothelial tissue (CIMT). The high amount of zeaxanthin in the blood was also shown to be inversely related to right main aorta stiffness and pulse velocity (PWV), both of which are markers of cardiovascular risk [56]. In the 39,876 women who were investigated, there was no link between serum lutein and zeaxanthin contents but also cardiovascular events [57].

3.5 Beta carotene absorption

β-Carotene is a strong fat-soluble nutraceutical that may be found in many fruits and vegetables. β-carotene converts to two molecules of vitamin A, resulting in a higher vitamin A supply [58, 59]. Cardiovascular, cancer, neurological, immunological, rheumatoid arthritis, cataracts, and aging have all been proven to be prevented by β-carotene [60, 61, 62]. The effectiveness of tagged β-carotene absorption varies greatly between clinical investigations, ranging from 3 to 80%, but quite often around 10 and 30% [63, 64]. It might be related to β-carotene’s varied bioavailability, or it could be owing to the enterocyte’s delayed absorption or transit. It’s worth noting that the absorption of β-carotene was commonly evaluated after a little meal. In humans, though, our stomach may retain β-carotene from the initial meal for eventual release during the subsequent period [65].

On the other hand, carotenoid binding vehicles may impact carotenoid absorption routes. Blended micelles were most likely separated from the majority of the bolus in the unstirred water of such a glycocalyx region before touching the boundary layer, whereupon carotenoid could be ingested passively or via a transporter-dependent method [66]. Phytofluene, β-carotene, and lutein accumulation are comparable to as well as much bigger than phytoene ingestion in differentiated Caco-2 cell monolayers, albeit lycopene ingestion was the lowest [67, 68]. Uptake efficiency appears to be linked to carotenoid polarity and flexibility in the same manner as bioavailability is. This might be because hydrophilic, pliable pigments have such a stronger attraction for lipids carriers and plasma membrane, resulting in more absorption. According to an IOM report from 2001 [69], the Supplemental and dietary β-carotene absorbing rate ranges from 5 to 26% (spinach) (raw carrots). β-carotene and lycopene are the most abundant carotenoids in human adipocytes, accounting for 20.2 and 18.5% of total carotenoids, respectively, with substantial inter-individual variability [70].

3.6 Beta-carotene and CVD

In a recent meta-analysis of all-cause mortality in 25,468 men and women, the relative risk (RR) for those with the highest vs. lowest blood beta-carotene levels was 0.69 (95% confidence interval: 0.59–0.80). (6137 deaths) [71]. According to the NHANES III study of 16,008 people, some in the top tertile of serum beta-carotene seemed to have a 25% lower risk of mortality (95% CI: 10–37%) than those in the lowest quintile (4225 deaths) [72]. Many investigations, along with a recent meta-analysis, suggest that circulating beta-carotene and overall mortality are negatively correlated [73, 74, 75]. In contrast, a meta-analysis of observational studies found that supplementation with b-carotene raises the odds of cardiovascular mortality from a tiny proportion [76]. Increased nutritional consumption of a-carotene and b-carotene was linked to a reduced risk of CVD mortality in the Zutphen Elderly research [77]. High serum concentrations of a-carotene and b-carotene, lycopene, or carotenoids, according to Japanese population-based follow-up studies, can lower the risk of mortality rates [78, 79].

The development of cardiovascular disorders is undoubtedly aided by peroxidation and chronically low irritation in the cardiovascular system. This pathogenesis of CVD and coronary disease has been related to oxidatively damaged low-density lipoproteins. An injection of such a free radical source that promotes LDL oxidation into foam cells appears to cause thermogenesis. An injection of such a free radical source into foam cells that stimulates LDL oxidation appears to trigger thermogenesis. Antioxidants may prevent cholesterol levels from degradation, lowering the risk of cardiovascular diseases in humans. Because β-carotene and lycopene are mostly found in LDL, they have a significant role in preventing oxidation [80]. The addition of b-carotene to LDL in situ was already found to lower the oxidation sensitivity of LDL [81].

Carotenoids have antioxidant properties and promote lymphocyte proliferation, which would boost immunological activity. The modification of vascular NO bioavailability owing to carotenoids’ lowering action is another intriguing technique for explaining how carotenoids assist prevent CVD. In a model of vascular inflammation, high beta-carotene concentrations are connected to a large rise in NO level or absorption, as seen by an increase in cGMP level. In endothelial cells, increased NO release resulted in the enzyme inhibition of NF-kB-dependent binding proteins [82]. Endothelial NO bioavailability is therefore thought to be important to endothelial function and overall vascular health. In a rat model of atherosclerosis, further study reveals that a 9-cis-beta-carotene-rich diet can protect heart disease by lowering non-HDL plasma cholesterol levels, inhibiting liver fibrosis growth and inflammation [83].

3.7 Astaxanthin absorption

Astaxanthin, or 3,3′-dihydroxy-, ′ β-carotene-4,4′-dione, is a red-orange marine carotenoid present inside a wide range of microorganisms and marine animals [61, 62]. Soft gels, capsules, lotions, energy beverages, oils, and extracts containing astaxanthin have already entered the market as nutritional supplements [84]. As for other liposome carotenoids, astaxanthin is considered to go through a complicated digesting and absorption process that includes liberation from food material, transport to a stomach organic phase, creation into micelles under solvation via pancreas hydrolases but also bile acids, transit through the villi, uptake by enterocytes, and inclusion into chylomicrons allowing transportation to the lymphatic vessels and bloodstream [58, 85]. The gastrointestinal system, particularly the duodenum, absorbs almost no carotenoids into enterocytes, and bioavailability refers to the fraction of the ingested dosage retained into micelles. [86].

However, because of its weak water solubility and corrosiveness, oral astaxanthin’s bioavailability is restricted. The pharmacokinetics of astaxanthin in rats were dose-independent between 100 and 200 mg/kg. Oral astaxanthin intake in the gastrointestinal tract followed a flip-flop pattern, according to Choi et al. [87]. The structure of astaxanthin has a role in its bioavailability. In vitro and rat, experiments demonstrated that a single ingestion of 100 mg mixed isomers resulted in a greater plasma level of cis-astaxanthin, particularly the 13-cis isomer, than diet [88, 89, 90]. Osterlie et al. looked at the dispersion of astaxanthin in different lipid fragments and found that 36–64% plasma astaxanthin accumulated in chylomicron-containing very-low-density lipoproteins, with the rest distributed almost evenly between low-density lipoprotein 29% and high-density lipoprotein 24% [90].

3.8 Astaxanthin and CVD

Microalgae, plankton, krill, fish, and other seafood are all members of the xanthophyll family. Microalgae, plankton, krill, fish, and other seafood contain astaxanthin, a red soluble pigment. In the marine environment, it can be found in microalgae, plankton, krill, fish, and some other seafood. It’s the pigment that gives salmon and crustaceans their characteristic colors [91]. Even though chronic damage is still a biomarker conducted in a range of diseases, astaxanthin has shown promise in the prevention and treatment of malignancies, inflammatory diseases, metabolic disease, kidney disease, nephropathy, spleen, and digestive diseases, neurodegenerative diseases, and even cardiovascular disease. According to Pashow et al., astaxanthin might help with myocardial injury, oxidation LDL, re-thrombosis following angioplasty, or other cardiac issues including fibrillation. Astaxanthin is a strong anti-oxidant and FR’s remover, and a reactive oxygen species (ROS) and nitrogen-oxygen species (NOS) quencher (NOS) [92]. During an eight-week study, Park looked at the effects of astaxanthin supplementation (0, 2, and 8 mg per day) on oxidative stress. People taking 2 mg a day for 8 weeks had a decreased hs-CRP, a primary predictor of heart disease. After 4 weeks of therapy, DNA damage as determined by serum 8-hydroxy-2?-deoxyguanosine was also reduced [93].

3.9 Lutein and zeaxanthin carotene absorption

The xanthophyll pigment astaxanthin (AST) is present in a variety of marine animals and microalgae [28]. Anti-inflammatory and antioxidant capabilities, as well as the ability to improve cardiovascular and immune system health, as well as prevent diabetes and neurological illnesses, are all found in AST [94, 95, 96, 97, 98]. In green foods, the lutein-to-zeaxanthin ratio ranges from 12 to 63, with kale having the highest concentration, whereas the ratio in yellow-orange fruits and vegetables is between 0.1 and 1.4 [99]. Dark green algae, that are consumed by fish, are rich in astaxanthin and fucoxanthin. Capsanthin is most commonly found within the pepper. β-Cryptoxanthin is a provitamin A that may be found inside a variety of vegetables, but it’s especially abundant in corn, oranges, peaches, papaya, watermelon, and egg yolk. [100, 101].

Carotenoids should be digested then delivered into the blood to assert and provide their physical effects. Carotenoids seem to be either lipid-soluble or hydrophilic, indicating they are accessible in fats and immiscible, just like the human digestive tract. When compared to the hydrocarbon carotenoids (α-, β-carotene, and lycopene), lutein and zeaxanthin have hydroxyl groups and are thus polar molecules. To calculate the advantages, a thorough understanding of carotenoid release, absorption, transit, and storage in the eye is required. The quantity and type of dietary fat, that assists in the solvation of releasing carotenoids, and also phospholipids, soluble fiber, and indeed the nature of carotenoids, are all key determinants in lutein and zeaxanthin absorption from food [102, 103, 104]. Many phases are engaged in the intake of carotenoids released from food: (i) dispersion inside the stomach colloid so it can be integrated into fat droplets, (ii) followed by translocation to micelles holding bile salts, biliary phospholipids, dietary lipids, as well as other substances. The intestinal cell collects the dissolved carotenoids and distributes them into the blood. In vitro transfer of lutein, zeaxanthin, and β-cryptoxanthin from fruits (orange, kiwi, grapefruit, and sweet potato) was nearly 0%, compared to 19 and 38%, respectively, from spinach and broccoli [105]. The primary carotenoids detected in maize milling fractions are lutein and zeaxanthin, which account for nearly 70% of total carotenoids [106]. Table 2 lists foods that are high in lutein and zeaxanthin [107, 108, 109, 110].

Food itemLutein μg/gZeaxanthin μg/g
Parsley64.0–106.564.0–106.5
Red pepper2.5–85.15.9–13.5
Corn chips61.192.5
Corn21.910.3
High lutein bread36.73.3
High lutein muffin26.13.7
Durum wheat5.40.5

Table 2.

Lutein and zeaxanthin sources [107, 108, 109, 110].

3.10 Zeaxanthin and CVD

With a 40-carbon hydroxylated structure, zeaxanthin is just an oxygenation non-provitamin A carotenoid [111]. The macular lutea, a yellow-colored region of the retina that supports the central vision and includes lutein and zeaxanthin, is a yellow-colored section of the retina that contains lutein and zeaxanthin. Zeaxanthin may protect proteins, lipids, or DNA from oxidative stress via influencing various cellular antioxidant mechanisms, in addition to immediately reducing superoxide radicals. Glutathione is a potent antioxidant found within tissues that defends them from oxidation [112]. Taking supplements with zeaxanthin or a-tocopherol lowers metabolized glutathione (GSSG) levels while raising internalized reduced glutathione (GSH) levels and the GSH/GSSG ratio, particularly during redox balance. By regulating glutathione production and hence glutathione levels, zeaxanthin functions as an antioxidant, either directly or indirectly. As a result, the internal redox state improves in oxidative stress, and susceptibility to H2O2-induced cell death decreases [113].

Beta-carotene and zeaxanthin, which are inversely related to right main artery stiffness, pulse speed, and deformability, are implicated in both ocular and cardiovascular health. Both the Beijing and Los Angeles atherosclerosis studies discovered an opposite relation between serum lutein and initial CVD, although subsequent follow-up trials revealed that greater serum zeaxanthin concentrations may defend from early arteriosclerosis [114]. Zeaxanthin may help vascular health, according to these studies.

3.11 Lutein and CVD

With chemically similar formulas, it’s an isomer of the carotenoid zeaxanthin. It, like zeaxanthin, is exclusively found in foods like yellow maize, egg yolk, orange juice, honeydew melon, and other fruits, and must be gotten by supplements or diet [113]. The ubiquitous nuclear transcription factor NF-kB, which is implicated in a range of pathogenic reactions, is blocked by lutein [115], as well as the kB inhibitor’s degradation (I-kB) [48]. It also has a significant potential to scavenge ROS [116, 117]. NF-kB can begin to migrate into the nucleus when I-kB is released from the NF-kB complex by lutein, reducing inducible transcription of genes and the activation of cytokines markers such cytokines, chemokines, and iNOS [118]. Lutein inhibits the production of TNF-alpha, interleukin 6 (IL-6), prostaglandin 2 (PGE-2), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 2 (MIP-2) [119].

According to this study, plasmatic lutein shows a negative correlation with oxidative stress, implying that it has significant oxidative and anti-inflammatory effects on aortic tissue, potentially preventing atherosclerotic [120]. Several studies have found that lutein levels in individuals with atherosclerosis were considerably lower than in normal and that they were indirectly correlated to arterial tightness [121]. The cardiac and blood vessel preventive actions of lutein have also been connected to the management of hypertension. A rise in systolic blood pressure and unintentional hypertension was often negatively proportional to a larger amount of this carotenoid. Some with greater lutein values had lower serum blood pressure but a decreased risk of future hypertension, independent of whether or not they smoke [122]. By lowering peroxidation and myocyte apoptosis, lutein prevents the myocardium from ischemia damage [123]. By avoiding contractile dysfunction, limiting myocardial damage may lower CAD morbidity and mortality [124].

3.12 Oxidative stress and antioxidants activity

The onset and evolution of a range of disorders, including cardiovascular issues, have been related to oxidative stress. ROS are important biological variables that can influence a wide range of physiological and disease-related conditions [125]. Cancer, reactive arthritis, osteoarthritis, aging, neurological, and cardiac illnesses are all connected to oxidative stress. Given the evidence linking oxidative stress to a wide range of human illnesses, measuring oxidative stress biomarkers is critical for assessing health and detecting the onset of oxidative stress-related disorders [126]. Hypercholesterolemia is also a disease that is closely connected to peroxidation. FH individuals reported greater levels of reactive oxygen species than normolipidemic patients, as per an inter observational study involving 132 individuals with high cholesterol (FH). MDA concentration seems to be much higher in FH, suggesting a higher oxidative stress state, according to the International Federation of Clinical Chemists (IFCC) standard range (>1.24 g/L) [127]. Various demographic studies have examined the association between higher nutritional carotene intake and thus the environment’s effects on cardiovascular disease prevention [128, 129, 130, 131].

Circulating carotenoid concentrations, for example, have been associated with inflammatory markers, increased lipid peroxidation, and vascular dysfunction, that has all been connected to CVD [132, 133, 134]. Secondly, pigments and minerals have a phytonutrient-like impact on endothelial dysfunction and irritation, decreasing the risk of atherosclerosis. [135]. The finding of a link between carotene, peroxidation, and inflammation has been aided by several in vitro studies, notably those that used subsystem [136]. Carotenoids exhibit anti-oxidant and anti-inflammatory properties in vascular cells, as shown in Figure 3.

Figure 3.

Carotenoids have a beneficial effect on endothelial dysfunction and overall vascular health [137].

Nitrogen oxide may combine with O2− to generate peroxynitrite (ONOO-) under oxidative conditions, resulting in decreased NO bioavailability, vascular dysfunction, increased lipid oxidation, and chronic inflammatory responses. Nitrogen oxide may combine with oxygen to generate peroxynitrite (ONOO-) during oxidative conditions, resulting in decreased NO bioavailability, vascular dysfunction, increased lipid oxidation, and chronic inflammatory responses. All of these actions create a negative cycle, and the antioxidant and anti-inflammatory capabilities of carotenoids may be harmed as a result. TNF-, tumor necrotic lesions factor-alpha; NF-B, nuclear factor kappa-light-chain-enhancer of activated B cells; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; TNF-, tumor necrosis factor-alpha; NF-B, nuclear factor kappa-light-chain-enhancer of activated B cells; ICAM-1, intercellular adhesion molecule 1; TNF-, tumor necrosis factor-alpha; NF-B, nuclear factor kappa-light-chain-enhancer of activated B cells; ICAM-1, intercellular adhesion molecule 1; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; O2-, superoxide anion; ONOO-, peroxynitrite; eNOS, endothelial nitric oxide synth cGM.

Antioxidants are chemicals that prevent or restrict oxidative damage by inhibiting the action of reactive oxygen species. Intrinsic antioxidant components present in body cells include chronic damage, catalase, and glutathione peroxidase. Antioxidants found in foods include vitamin C, vitamin C, polyphenols, and carotenoids [138]. To help avoid chronic diseases like cancer and cardiovascular disease, current dietary guidelines recommend consuming more antioxidant-rich plant foods like fruits and vegetables [139].

3.13 ROS and RNS production by nitric oxide synthases

The conversion of L-arginine to L-citrulline and nitric oxide is catalyzed by nitric oxide synthases (NOS)., but they can create superoxide under uncoupling conditions:

NOS + L-arginine + O2 + NADPH − → NO + citrulline + NADP+ NOS(Fe(II)heme) + O2 − → NOS(Fe(III)heme) + O2 •− [140].

Two NOS isoforms, neuronal NOS (NOS1) and endothelial NOS (eNOS, NOS3), are generated in cardiomyocytes constantly, whereas inducible NOS (NOS2) is lacking in the healthy heart but can be triggered by pro-oxidants [141]. It was discovered that hypertrophied myocytes had a higher amount of iNOS [142]. Because NOSs may produce both RNS and ROS, their effects on the cardiovascular system can be complex—they can enhance or reduce heart damage. Because nitric oxide is an EDRF (endothelium-derived relaxing factor), its effects must primarily benefit the heart. The diffusion-controlled interaction of nitric oxide with superoxide, on the other hand, produces the very reactive peroxynitrite. To avoid heart damage, the equilibrium of superoxide/nitric oxide must be maintained. During pathological changes in the heart, the interplay of major enzymatic ROS generators contributes to this balance. In dogs with pacing-induced heart failure, NO synthases and xanthine oxidase was shown to be important in the modulation of myocardial mechanical efficiency, and overexpression of XO relative to NOS contributed to mechanoenergetic uncoupling [143].

Advertisement

4. Conclusion

Fruits and vegetables are rich in carotenoids. Carotenoids have long been regarded to be beneficial to one’s health. Nearly 700 carotenoids have been discovered. The most regularly referenced carotenoids in this chapter were a-carotene, b-carotene, lutein, lycopene, and zeaxanthin. Their absorption, transportation, needs, and chemistry were all discussed. Cardiovascular diseases are a significant public health issue. Carotenoids-rich meals may help to reduce the progression of coronary heart disease, according to the study reviewed in this chapter. Oxidative stress is responsible for a wide range of degenerative diseases, including cardiovascular issues. The pathogenesis of CVD is heavily influenced by oxidative stress. We looked at the significance of carotenoids in endothelial function and vascular health in general in this chapter. We also discussed how carotenoids may be obtained from a variety of fruits and vegetables. The etiology of atherosclerosis is aggravated by oxidative stress. Throughout this chapter, we looked at the significance of carotenoids in endothelial function and vascular health in general.

Advertisement

Acknowledgments

We thank the digital library GCUF for providing access to the publication.

Advertisement

Conflict of interest

There is no conflict of interest as declared by all authors.

References

  1. 1. Krinsky NI. Actions of carotenoids in biological systems. Annual Review of Nutrition. 1993;13:561-587
  2. 2. Crews HA, Link G, Andersen R, Bradesco V, Holst B, Maiani G, et al. A critical assessment of some biomarker approaches linked with dietary intake. The British Journal of Nutrition. 2001;86:5-35
  3. 3. Olson JA. In: Porter JW, Spurgeon SL, editors. Formation and Function of Vitamin a. Biosynthesis of Isoprenoid Compounds. Vol. 2. New York: Wiley & Sons; 1983. pp. 371-412
  4. 4. Parker RS. Carotenoids in human blood and tissues. The Journal of Nutrition. 1989;119:101-104
  5. 5. Khachik F, Beecher GR, Whittaker NF. Separation, identification, and quantification of the major carotenoid and chlorophyll constituents in extracts of several green vegetables by liquid chromatography. Journal of Agriculture Food Chemistry. 1986;34:603-661
  6. 6. Mathews-Roth MM, Gulbrandsen CL. Transport of beta-carotene in serum of individuals with carotenemia. Clinical Chemistry. 1974;20:1578-1579
  7. 7. Olson JA. The provitamin a function of carotenoids: The conversion of beta-carotene into vitamin a. The Journal of Nutrition. 1989;119:105-108
  8. 8. Mangels AR, Holden JM, Beecher GR, Forman MR, Lanza E. Carotenoid contents of fruits and vegetables: An evaluation of analytical data. Journal of the American Dietetic Association. 1993;93:284-296
  9. 9. Johnson EJ. The role of carotenoids in human health. Nutrition in Clinical Care. 2002;5(2):47-49
  10. 10. Agarwal S, Rao AV. Carotenoids and chronic diseases. Drug Metabolism and Drug Interactions. 2000;17(1-4):189-210
  11. 11. Leermakers ETM, Darweesh SKL, Baena CP, Moreira EM, Van Lent DM, Tielemans MJ, et al. The effects of lutein on cardiometabolic health across the life course: A systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2016;103(2):481-494. DOI: 10.3945/ajcn.115.120931. Retrieved from
  12. 12. Ravikrishnan R, Rusia S, Ilamurugan G, Salunkhe U, Deshpande J, Shankaranarayanan J, et al. Safety assessment of lutein and zeaxanthin (LutemaxTM 2020): Subchronic toxicity and mutagenicity studies. Food and Chemical Toxicology. 2011;49(11):2841-2848. DOI: 10.1016/j.fct.2011.08.011. Retrieved from
  13. 13. Vijay K, Sowmya PRR, Arathi BP, Shilpa S, Shwetha HJ, Raju M, et al. Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells. Food and Chemical Toxicology. 2018;118:675-690. DOI: 10.1016/j. fct.2018.06.027. Retrieved from
  14. 14. Zaccara G, Lattanzi S, Cincotta M, Russo E. Drug treatments in patients with cardiac diseases and epilepsy. Acta Neurologica Scandinavica. 2020;142(1):37-49. DOI: 10.1111/ane.13249. Retrieved from
  15. 15. Albert CM, Deo R. Epidemiology and genetics of sudden cardiac death. Circulation. 2012;125(4):620-637 Retrieved from.http://circ.ahajournals.org/cgi/doi/1 0.1161/CIRCULATIONAHA.111.023838%5Cnpapers3://publication/DOI/10.1161/CIRCULATIONAHA.111.023838
  16. 16. Maria AG, Graziano R, Nicolantonio DO. Carotenoids: Potential allies of cardiovascular health? Food and Nutrition Research. 2015;59(1):26762. doi: 10.3402/fnr.v59.26762
  17. 17. Ribeiro D, Freitas M, Silva AMS, Carvalho F, Fernandes E. Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food and Chemical Toxicology. 2018;120:681-699. DOI: 10.1016/j.fct.2018.07.060. Retrieved from
  18. 18. Chung RWS, Leanderson P, Lundberg AK, Jonasson L. Lutein exerts anti-inflammatory effects in patients with coronary artery disease. Atherosclerosis. 2017b;262:87-93. DOI: 10.1016/j.atherosclerosis.2017.05.008. Retrieved from
  19. 19. Heller FR, Descamps O, Hondekijn JC. LDL oxidation: Therapeutic perspectives. Atherosclerosis. 1998;137(Suppl):S25-S31
  20. 20. Mangels AR, Holden JM, Beecher GR, Forman MR, Lanza E. Carotenoid content of fruits and vegetables: An evaluation of analytic data. Journal of the American Dietetic Association. 1993;93:284-296
  21. 21. Chug-Ahuja JK, Holden JM, Forman MR, Mangels AR, Beecher GR, Lanza E. The development and application of a carotenoid database for fruits, vegetables, and selected multicomponent foods. Journal of the American Dietetic Association. 1993;93:318-323
  22. 22. Hankin JE, Le Marchand L, Kolonel LN, Wilkens LR. Assessment of carotenoid intakes in humans. Annals NY Academy Science. 1993;691:68-75
  23. 23. Olmedilla B, Granado F, Blanco I, Rojas-Hidalgo E. Seasonal and sex-related variations in six serum carotenoids, retinol, and alpha-tocopherol. The American Journal of Clinical Nutrition. 1994;60:106-l 10
  24. 24. Rautalahti M, Alhanes D, Huakka J, Roos E, Gref CG, Virtamo J. Seasonal variation of serum concentrations of beta-carotene and alpha-tocopherol. The American Journal of Clinical Nutrition. 1993;57:551-556
  25. 25. Britton G. Structure and properties of carotenoids about function. The FASEB Journal. 1995;9:1551-1558
  26. 26. Miller NJ, Sampson J, Candeias LP, et al. Antioxidant activities of carotenes and xanthophylls. FEBS Letters. 1996;384:240-246
  27. 27. Stahl W, Schwarz W, Sundquist AR, et al. Cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Archives of Biochemistry and Biophysics. 1992;294:173-177
  28. 28. Michaud DS, Giovannucci EL, Ascherio A, et al. Associations of plasma carotenoid concentrations and dietary intake of specific carotenoids in samples of two prospective cohort studies using a new carotenoid database. Cancer Epidemiology, Biomarkers & Prevention. 1998;7:283-290
  29. 29. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994;344:793-795
  30. 30. Witztum JL. Role of oxidized low-density lipoprotein in atherogenesis. British Heart Journal. 1993;69:S12-S18
  31. 31. Clinton SK. Lycopene: Chemistry, biology, and implications for human health and disease. Nutrition Reviews. 1998;1:35-51
  32. 32. Stahl W, Sies H. Lycopene: A biologically important carotenoid for humans? Archives of Biochemistry and Biophysics. 1996;336:1-9
  33. 33. Parker RS. Absorption, metabolism, and transport of carotenoids. The FASEB Journal. 1996;10:542-551
  34. 34. Gartner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato ¨ paste than from fresh tomatoes. The American Journal of Clinical Nutrition. 1997;66:116-122
  35. 35. Rao AV, Agarwal S. Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: A review. Nutrition Research. 1999;19:305-323
  36. 36. Rao AV, Agarwal S. Bioavailability and antioxidant properties of lycopene from tomato products. Nutrition and Cancer. 1998;31:199-203
  37. 37. Rao AV, Mira MR, Rao LG. Lycopene. Advances in Food and Nutrition Research. 2006;51:99-164
  38. 38. Jain CK, Agarwal S, Rao AV. The effect of dietary lycopene on bioavailability, tissue distribution, in-vivo antioxidant properties, and colonic preneoplasia in rats. Nutrition Research. 1999;19:1383-1391
  39. 39. Khachik F, Carvallo L, Bernstein PS, Muir GJ, Zhao DY, Katz NB. Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health. Experimental Biology and Medicine. 2002;227(10):845-851
  40. 40. Rao AV, Rao LG. Lycopene and human health. Current Topical Nutrition Research. 2004;2:127-123
  41. 41. Palozza P, Catalano A, Simone R. E, Mele M, C, Cittadini a: Effect of lycopene and tomato products on cholesterol metabolism. Annals of Nutrition & Metabolism. 2012;61:126-134. DOI: 10.1159/000342077
  42. 42. Fuhramn B, Elis A, Aviram M. Hypocholesterolemic effect of lycopene and ß-carotene is related to the suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophage. Biochemical and Biophysical Research Communications. 1997;233:658-662
  43. 43. Agarwal S, Rao AV. Tomato lycopene and low-density lipoprotein oxidation: A human dietary intervention study. Lipids. 1998;33:981-984
  44. 44. Sesso HD, Buring JE, Norkus EP, et al. Plasma lycopene, other carotenoids, retinol and the risk of cardiovascular disease in men. The American Journal of Clinical Nutrition. 2005;81:990-997
  45. 45. Kristenson M, Zieden B, Kucinskiene Z, et al. Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: Concomitant cross-sectional study of men aged 50. BMJ. 1997;314:629-633
  46. 46. Mann DL et al. Targeted Anticytokine therapy and the failing heart. The American Journal of Cardiology. 2005;95(11, Suppl. 1):9-16
  47. 47. Lidebjer C, Leanderson P, Ernerudh J, et al. Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Nutrition, Metabolism, and Cardiovascular Diseases. 2007;17:448-456
  48. 48. Ito Y, Kurata M, Suzuki K, Hamajima N, et al. Cardiovascular disease mortality and serum carotenoid levels: A Japanese population-based follow-up study. Journal of Epidemiology. 2006;16:154-160
  49. 49. Bose KS, Agrawal BK. Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate, and lipide profile in coronary heart disease. Singapore Medical Journal. 2007;48:415-420
  50. 50. Rao AV, Agarwal S. Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutrition and Cancer. 1998;31:199-203
  51. 51. Thies F, Masson LF, Rudd A, Vaughan N, Tsang C, Brittenden J, et al. Effect of a tomato-rich diet on markers of cardiovascular disease risk in moderately overweight, disease-free, middle-aged adults: A randomized controlled trial. The American Journal of Clinical Nutrition. 2012;95(5):1013-1022. DOI: 10.3945/ajcn.111.026286
  52. 52. Leermakers ETM, Moreira EM, Kiefte-de Jong JC, Darweesh SKL, Visser T, Voortman T, et al. Effects of choline on health across the life course: A systematic review. Nutrition Reviews. 2015;73(8):500-522. DOI: 10.1093/nutrit/nuv010
  53. 53. Holden JM, Eldridge AL, Beecher GR, Buzzard IM, Bhagwat S, Davis CS, et al. Carotenoid content of U.S. foods: An update of the database. Journal of Food Composition and Analysis. 1999;12(3):169-196. DOI: 10.1006/jfca.1999.0827
  54. 54. Abdel-Aal E-SM, Akhtar H, Zaheer K, Ali R. Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients. 2013;5:1169-1185. DOI: 10.3390/nu5041169
  55. 55. Zou XR, Xiao ZYX, Huang YM, Wang X, Lin XM. Effects of lutein supplement on serum inflammatory cytokines, ApoE and lipid profiles in early atherosclerosis population. Journal of Atherosclerosis and Thrombosis. 2013;20(2):170-177
  56. 56. Zou Z, Xu X, Huang Y, Xiao X, Ma L, Sun T, et al. High serum level of lutein may be protective against early atherosclerosis. The Beijing Atherosclerosis Study. 2011;219(2):789-793
  57. 57. Sesso HD, Buring JE, Norkus EP, Gaziano JM. Plasma lycopene and the risk of cardiovascular disease in women. Journal of the American College of Cardiology. 2012;39:147
  58. 58. Donhowe GE, Kong F. Beta-carotene: Digestion, microencapsulation, and In vitro bioavailability. Food and Bioprocess Technology. 2014;7:338-354. DOI: 10.1007/s11947-013-1244-z
  59. 59. Loveday S, Singh H. Recent advances in technologies for vitamin a protection in foods. Trends in Food Science and Technology. 2008;19:657-668
  60. 60. Yi J, Lam T, Yokoyama W, Cheng L, Zhong F. Beta-carotene encapsulated in food protein nanoparticles reduces peroxyl radical oxidation in Caco-2 cells. Food Hydrocolloids. 2015;43
  61. 61. de Freitas Zômpero RH, López-Rubio A, de Pinho SC, Lagaron JM, de la Torre LG. Hybrid encapsulation structures based on β-carotene-loaded nanoliposomes within electrospun fibers. Colloids Surfaces B Biointerfaces [Internet]. 2015;134:475-482 Available from:http://www.sciencedirect.com/science/article/pii/S0927776515001496
  62. 62. Jain A, Thakur D, Ghoshal G, Katare OP, Shivhare US. Characterization of microcapsulated β-carotene formed by complex Coacervation using Casein & gum Tragacanth [internet]. International Journal of Biological Macromolecules. Elsevier B.V. 2016. DOI: 10.1016/j.ijbiomac.2016.01.117
  63. 63. van Lieshout M, West CE, van Breemen RB. Isotopic tracer techniques for studying the bioavailability and bioefficacy of dietary carotenoids, particularly beta-carotene, in humans: A review. The American Journal of Clinical Nutrition. 2003;77:12-28 [CrossRef]
  64. 64. Van Loo-Bouwman CA, Naber TH, van Breemen RB, Zhu D, Dicke H, Siebelink E, et al. Vitamin an equivalency and apparent absorption of beta-carotene in ileostomy subjects using a dual-isotope dilution technique. The British Journal of Nutrition. 2010;103:1836-1843 [CrossRef]
  65. 65. Borel P, Grolier P, Mekki N, Boirie Y, Rochette Y, Le Roy B, et al. Low and high responders to pharmacological doses of beta-carotene: Proportion in the population, mechanisms involved and consequences on beta-carotene metabolism. Journal of Lipid Research. 1998;39:2250-2260
  66. 66. Phan CT, Tso P. Intestinal lipid absorption and transport. Frontiers in Bioscience. 2001;6:D299-D319 [CrossRef] [PubMed]
  67. 67. During A, Hussain MM, Morel DW, Harrison EH. Carotenoid uptake and secretion by caco-2 cells: Beta-carotene isomer selectivity and carotenoid interactions. Journal of Lipid Research. 2002;43:1086-1095 [CrossRef]
  68. 68. Mapelli-Brahm P, Desmarchelier C, Margier M, Reboul E, Melendez Martinez AJ, Borel P. Phytoene and phytofluene isolated from a tomato extract are readily incorporated in mixed micelles and absorbed by caco-2 cells, as compared to lycopene, and sr-bi is involved in their cellular uptake. Molecular Nutrition & Food Research. 2018;62:e1800703 [CrossRef] [PubMed]
  69. 69. Institute of Medicine. Dietary Reference Intakes for Vitamin a, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academies Press; 2001
  70. 70. Parker RS. Carotenoid and tocopherol composition of human adipose tissue. The American Journal of Clinical Nutrition. 1988;47:33-36
  71. 71. Zhao LG, Zhang QL, Zheng JL, Li HL, Zhang W, Tang WG, et al. Dietary, circulating betacarotene and risk of all-cause mortality: A meta-analysis from prospective studies. Scientific Reports. 2016;6:26983
  72. 72. Goyal A, Terry MB, Siegel AB. Serum antioxidant nutrients, vitamin a, and mortality in u.S. adults. Cancer Epidemiology, Biomarkers & Prevention. 2013;22:2202-2211
  73. 73. Hashim D, Gaughan D, Boffetta P, Lucchini RG. Baseline serum beta-carotene concentration and mortality among long-term asbestos-exposed insulators. Cancer Epidemiology, Biomarkers & Prevention. 2015;24:555-560
  74. 74. Bates CJ, Hamer M, Mishra GD. Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: The national diet and nutrition survey of people aged 65 years and over. The British Journal of Nutrition. 2011;105:123-132
  75. 75. Kilander L, Berglund L, Boberg M, Vessby B, Lithell H. Education, lifestyle factors and mortality from cardiovascular disease and cancer. A 25-year follow-up of Swedish 50-year-old men. International Journal of Epidemiology. 2001;30:1119-1126
  76. 76. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: A meta-analysis of randomized trials. Lancet. 2003;361:2017e23
  77. 77. Buijsse B, Feskens EJ, Kwape L, Kok FJ, Kromhout D. Both alpha- and beta-carotene, but not tocopherols and vitamin C, are inversely related to 15-year cardiovascular mortality in Dutch elderly men. The Journal of Nutrition. 2008;138:344e50
  78. 78. Ito Y, Kurata M, Suzuki K, Hamajima N, Hishida H, Aoki K. Cardiovascular disease mortality and serum carotenoid levels: A Japanese population-based follow-up study. Journal of Epidemiology. 2006;16:154e60
  79. 79. Ito Y, Suzuki K, Ishii J, Hishida H, Tamakoshi A, Hamajima N, et al. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pacific Journal of Cancer Prevention. 2006;7:533e46
  80. 80. Tapiero H, Townsend DM, Tew KD. Dossier: Influence of alcohol consumption and smoking habits on human health, the role of carotenoids in the prevention of human pathologies. Biomed & Pharmacotherapy. 2004;58:100-110
  81. 81. Jialal I, Norkus EP, Cristol L, Grundy SM. Beta-carotene inhibits the oxidative modification of low-density lipoprotein. Biochem Biophys Acta. 1991;1086:1348
  82. 82. Aizawa T, Wei H, Miano JM, Abe J. Role of PDE-3 in NO/cGMP-mediated anti-inflammatory effects in vascular smooth muscle cells. Circulation Research. 2003;93:40613
  83. 83. Harari A, Harats D, Marko D, Cohen H, Barshack I, Kamari Y, et al. A 9-cis b-Caroteneenriched diet inhibits atherogenesis and fatty liver formation in LDL-R knockout mice. Journal of Nutrition Diseases. 2008;138:192330
  84. 84. Bogacz-Radomska L, Harasym J, Piwowar A. Commercialization aspects of carotenoids. Carotenoids: Properties, Processing, and Applications. 2020;10:327-357. DOI: 10.1016/B978-0-12-817067-0.00010-5
  85. 85. Saini RK, Nile SH, Park SW. Carotenoids from fruits and vegetables: Chemistry, analysis, occurrence, bioavailability, and biological activities. Food Research International (Ottawa, Ont.). 2015;76(Pt 3):735-750. DOI: 10.1016/j.foodres.2015.07.047
  86. 86. Sy C, Gleize B, Dangles O, Landrier JF, Veyrat CC, Borel P. Effects of physicochemical properties of carotenoids on their bioaccessibility, intestinal cell uptake, and blood and tissue concentrations. Molecular Nutrition & Food Research. 2012;56(9):1385-1397. DOI: 10.1002/mnfr.201200041
  87. 87. Choi HD, Youn YK, Shin WG. Positive effects of astaxanthin on lipid profiles and oxidative stress in overweight subjects. Plant Foods for Human Nutrition (Dordrecht, Netherlands). 2011;66(4):363-369. DOI: 10.1007/s11130-011-0258-9
  88. 88. Honda M, Murakami K, Osawa Y, Kawashima Y, Hirasawa K, Kuroda I. Z-isomers of astaxanthin exhibit greater bioavailability and tissue accumulation efficiency than the all-E-isomer. Journal of Agricultural and Food Chemistry. 2021;69(11):3489-3495. DOI: 10.1021/acs.jafc.1c00087
  89. 89. Yang C, Zhang H, Liu RH, Zhu HH, Zhang LF, Tsao R. Bioaccessibility, cellular uptake, and transport of astaxanthin isomers and their antioxidative effects in human intestinal epithelial Caco-2 cells. Journal of Agricultural and Food Chemistry. 2017;65(47):10223-10232. DOI: 10.1021/acs.jafc.7b04254
  90. 90. Osterlie M, Bjerkeng B, Liaaen-Jensen S. Plasma appearance and distribution of plasma lipoproteins of men after single-dose administration of astaxanthin. Journal of Nutritional Biochemistry. 2000;11(10):482-490. DOI: 10.1016/S0955-2863(00)00104-2
  91. 91. Schweigert F. Metabolism of Carotenoids in Mammals. Basel, Switzerland: Birkhauser Verlag; 1998
  92. 92. Nakano M, Onodera A, Saito E, Tanabe M, Yajima K, Takahashi J, et al. Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats. Journal of Nutritional Science and Vitaminology. 2008;54:32934
  93. 93. Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutrition and Metabolism. 2010;7:18
  94. 94. Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T. Dietary astaxanthin inhibits colitis and colitisassociated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chemico-Biological Interactions. 2011;193(1):79-87
  95. 95. Yang Y, Kim B, Lee JY. Astaxanthin structure, metabolism, and health benefits. Journal of Human Nutrition & Food Science. 2013;1:1003
  96. 96. Grimmig B, Kim SH, Nash K, Bickford PC, Shytle RD. Neuroprotective mechanisms of astaxanthin: A potential therapeutic role in preserving cognitive function in age and neurodegeneration. Geroscience. 2017;39(1):19-32
  97. 97. Visioli F, Artaria C. Astaxanthin in cardiovascular health and disease: Mechanisms of action, therapeutic merits, and knowledge gaps. Food & Function. 2017;8(1):39-63
  98. 98. Guan L, Liu J, Yu H, Tian H, Wu G, Liu B, et al. Water-dispersible astaxanthin-rich nanopowder: Preparation, oral safety, and antioxidant activity in vivo. Food & Function. 2019;10(3):1386-1397
  99. 99. Humphries JM, Khachik F. Distribution of lutein, zeaxanthin, and related geometrical isomers in fruits, vegetable, wheat, and pasta products. Journal of Agricultural and Food Chemistry. 2003;51:1322-1327
  100. 100. Chandrika UG, Jansz ER, Wickranasinghe SMDN, Warnasuriya ND. Carotenoids in yellow and red-fleshed papaya (Carcia papaya L). Journal of the Science of Food and Agriculture. 2003;83:1279-1282
  101. 101. United States Department of Agriculture. Nutritional data laboratory home page. USDA Nutritional database for standard reference release 22. 2009. Available online:http://www.ars.usda.gov/Services/docs.htm?docid=20960[Accessed November 24, 2012].
  102. 102. Van Het Hof KH, Weststrate JA, Hautvast JG. Dietary factors that affect the bioavailability of carotenoids. Nutrition Research. 1999;130:503-506
  103. 103. Castenmiller JJ, West CE. Bioavailability and bioconversion of carotenoids. Annual Review of Nutrition. 1998;18:19-38
  104. 104. Bohn T. Bioavailability of non-provitamin a carotenoids. Current Nutrition & Food Science. 2008;4:240-258
  105. 105. O’Connell OF, Ryan L, O’Brien NB. Xanthophyll carotenoids are more bioaccessible from fruits than dark green vegetables. Nutrition Research. 2007;27:258-264
  106. 106. Kean EG, Hamaker BR, Ferruzzi MG. Carotenoids bioaccessibility from whole grain and degermed maize meal products. Journal of Agricultural and Food Chemistry. 2008;56:9918-9926
  107. 107. Maiani G, Periago Caston MJ, Catasta G, Toti E, Cambrodon IG, Bysted A, et al. Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Molecular Nutrition & Food Research. 2009;53:S194-S218
  108. 108. Abdel-Aal E-SM, Young JC, Akhtar H, Rabalski I. Stability of lutein in wholegrain bakery products naturally high in lutein or fortified with free lutein. Journal of Agricultural and Food Chemistry. 2010;58:10109-10117
  109. 109. De La Parra C, Saldivar SOS, Lui RH. Effect of processing on the phytochemical profiles and antioxidant activity of corn for production of masa, tortillas, and tortilla chips. Journal of Agricultural and Food Chemistry. 2007;55:4177-4183
  110. 110. Abdel-Aal E-SM, Young JC, Rabalski I, Frégeau-Reid J, Hucl P. Identification, and quantification of seed carotenoids in selected wheat species. Journal of Agricultural and Food Chemistry. 2007;55:787-794
  111. 111. Pfander H. Carotenoids: an over-view. Methods in Enzymology. 1992;213:313
  112. 112. Giblin FJ. Glutathione: a vital lens antioxidant. Journal of Ocular Pharmacology and Therapeutics. 2000;16:12135
  113. 113. Gao S, Qin T, Liu Z, Caceres MA, Ronchi CF, Chen CYO, et al. Lutein and zeaxanthin supplementation reduces H2O2- induced oxidative damage in human lens epithelial cells. Molecular Vision. 2011;17:318090
  114. 114. Dwyer JH, Paul-Labrador MJ, Fan J. Progression of carotid intima-media thickness and plasma antioxidants: The Los Angeles atherosclerosis study. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:31319
  115. 115. Krishaswamy R, Devaraj SN, Padma VV. Lutein protects HT29 cells against Deoxynivalenol-induced oxidative stress and apoptosis: Prevention of NF-(B nuclear localization and downregulation of NF-(B and COX-2)) expression. Free Radical Biology & Medicine. 2010;49:5060
  116. 116. Dilsiz N, Sahaboglu A, Yildiz M, Reichenbach A. Protective effects of various antioxidants during ischemia-reperfusion in the rat retina. Graefe's Archive for Clinical and Experimental Ophthalmology. 2006;244:62733
  117. 117. Peng CL, Lin ZF, Su YZ, Lin GZ, Dou HY, Zhao CX. The anti-oxidative function of lutein: Electron spin resonance studies and chemical detection. Funct Plant Biology. 2006;33:83946
  118. 118. Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, et al. Negative feedback regulation of LPS-induced inducible NOS gene expression by HMOX-1 induction in macrophages. Molecular Immunology. 2008;45:210615
  119. 119. Jin XH, Ohgami K, Shiratori K, Suzuki Y, Hirano T, Koyama Y, et al. Inhibitory effects of lutein on endo toxin-induced uveitis in Lewis rats. Investigative Ophthalmology & Visual Science. 2006;47:25628
  120. 120. Kim JE, Leite JO, DeOgburn R, Smyth JA, Clark RM, Fernandez ML. A lutein-enriched diet prevents cholesterol accumulation and decreases ox-LDL and inflammatory cytokines in the aorta of Guinea pigs. The Journal of Nutrition. 2011;141:145863
  121. 121. Zou Z, Xu X, Huang Y, Xiao X, Ma L, Sun T, et al. High serum level of lutein may be protective against early ATS: The Beijing atherosclerosis study. Atherosclerosis. 2011;219:78993
  122. 122. Hozawa A, Jacobs JDR, Steffes MW, Gross MD, Steffen LM, Lee DH. Circulating carotenoid concentrations and incident hypertension: The coronary artery risk development in young adults (CARDIA) study. Journal of Hypertension. 2009;27:23742
  123. 123. Voutilainen S, Nurmi T, Mursu J, Rissanen TH. Carotenoids and cardiovascular health. The American Journal of Clinical Nutrition. 2006;83:126571
  124. 124. Adluri RS, Thirunavukkarasu M, Zhan L, Maulik N, Svennevig K, Bagchi M, et al. Cardio-protective efficacy of a novel antioxidant mix vitaepro against ex vivo myocardial ischemia-reperfusion injury. Cell Biochemistry and Biophysics. 2011;30:93007
  125. 125. Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian. Journal of Clinical Biochemistry. 2015;30:11-26 [CrossRef] [PubMed]
  126. 126. Katerji M, Filippova M, Duerksen-Hughes P. Approaches, and methods to measure oxidative stress in clinical samples: Research applications in the cancer field. Oxidative Medicine and Cellular Longevity. 2019;2019:29. DOI: 10.1155/2019/1279250
  127. 127. Rahman T, Hamzan NS, Mokhsin A, Rahmat R, Ibrahim ZO, Razali R, et al. Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: A case control study. Lipids in Health and Disease. 2017;16:81. DOI: 10.1186/s12944-017-0470-1
  128. 128. Kohlmeier L, Kark JD, Gomez-Gracia E, Martin BC, Steck SE, Kardinaal AF, et al. Lycopene and myocardial infarction risk in the EURAMIC study. American Journal of Epidemiology. 1997;146:618-626
  129. 129. Buijsse B, Feskens EJ, Schlettwein-Gsell D, Ferry M, Kok FJ, Kromhout D, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The survey in Europe on nutrition and the elderly, a concerted action (SENECA). The American Journal of Clinical Nutrition. 2005;82:879-886
  130. 130. Ciccone MM, Cortese F, Gesualdo M, Carbonara S, Zito A, Ricci G, et al. Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care. Mediators of Inflammation. 2013;2013:782137
  131. 131. Gajendragadkar PR, Hubsch A, Maki-Petaja KM, Serg M, Wilkinson IB, Cheriyan J. Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: A randomized controlled trial. PLoS One. 2014;9:99070
  132. 132. Fortmann SP, Ford E, Criqui MH, Folsom AR, Harris TB, Hong Y, et al. CDC/AHA workshop on markers of inflammation and cardiovascular disease: Application to clinical and public health practice: Report from the population science discussion group. Circulation. 2004;110:554-559
  133. 133. Blankenberg S, Rupprecht HJ, Bickel C, Peetz D, Hafner G, Tiret L, et al. Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation. 2001;104:1336-1342
  134. 134. Blake GJ, Ridker PM. Inflammatory biomarkers and cardiovascular risk prediction. Journal of Internal Medicine. 2002;252:283-294
  135. 135. van Herpen-Broekmans WM, Klöpping-Ketelaars IA, Bots ML, Kluft C, Princen H, Hendriks HF, et al. Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation. European Journal of Epidemiology. 2004;19:915-921
  136. 136. Kaulmann A, Bohn T. Carotenoids, inflammation, and oxidative stress--implications of cellular signaling pathways and relation to chronic disease prevention. Nutrition Research. 2014;34:907-929
  137. 137. Di Tomo P, Canali R, Ciavardelli D, Di Silvestre S, De Marco A, Giardinelli A, et al. Beta-carotene, and lycopene affect endothelial response to TNF-alpha reducing nitro-oxidative stress and interaction with monocytes. Molecular Nutrition & Food Research. 2012;56:217-227
  138. 138. Khansari N, Shakiba Y, Mahmoudi M. Chronic infl ammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Patents on Inflammation & Allergy Drug Discovery. 2009;3:73-80
  139. 139. Dietary guidelines for Americans. Home and Garden Bulletin no 232. 5th ed. Washington, DC: US Department of Agriculture, US Department of Health and Human Services; 2000
  140. 140. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM. Pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation. 2002;105(3):293-296
  141. 141. Umar S, Van Der Laarse A. Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Molecular and Cellular Biochemistry. 2010;333(1-2):191-201
  142. 142. Lijun DAI, Brookes PS, Darley-Usmar VM, Anderson PG. Bioenergetics in cardiac hypertrophy: Mitochondrial respiration as a pathological target of NO∗. American Journal of Physiology. 2001;281(6):H2261-H2269
  143. 143. Saavedra WF, Paolocci N, John MES, et al. Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart. Circulation Research. 2002;90(3):297-304

Written By

Arslan Ahmad, Sakhawat Riaz, Muhammad Shahzaib Nadeem, Umber Mubeen and Khadija Maham

Submitted: December 20th, 2021 Reviewed: January 18th, 2022 Published: April 13th, 2022