Review Article
Lycopene: A Potent Antioxidant with Multiple Health Benefits

Mercy Omoye Shafe ,1,2 Nontobeko Myllet Gumede,3 Trevor Tapiwa Nyakudya,3

and Eliton Chivandi1

1School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown,
Johannesburg 2193, South Africa
2Department of Human Physiology, Faculty of Basic Medical Sciences, College of Medicine and Allied Health Sciences,
Bingham University, P.M.B. 005, New Karu, Nasarawa 961002, Nigeria
3Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Gezina,
Pretoria 0031, South Africa

Correspondence should be addressed to Mercy Omoye Shafe; 2404174@students.wits.ac.za

Received 27 December 2023; Revised 14 May 2024; Accepted 20 May 2024

Academic Editor: Toshikazu Suzuki

Copyright © 2024 Mercy Omoye Shafe et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato-based products. Like other phy-
tochemicals, it exhibits health benefcial biological activities that can be exploited when it is used as a dietary supplement. In vitro
and in vivo, lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions and diseases including
infammation, obesity, and diabetes mellitus. Lycopene has been shown to alleviate metabolic diseases that afect the bone, eye,
kidney, liver, lungs, heart, and nervous system.Tis review presents the state of the art regarding lycopene’s health benefts and its
potential applications in health system delivery. Furthermore, lycopene’s protective efects against toxins, safety in its use, and
possible toxicity are explored.

1. Introduction

Te use of medicinal plants has deep historical roots,
ingrained in the traditional healing practices of diverse
cultures worldwide [1]. Troughout centuries, in-
digenous communities and ancient civilizations have
harnessed the therapeutic properties of plants, passing
down invaluable knowledge through generations [2].
Ethnomedicine, a feld dedicated to study traditional
medicinal practices, has played a crucial role in doc-
umenting this wealth of wisdom. Te efectiveness of
ethnomedicinal plants in disease management is at-
tributed to their constituent bioactive phytochemicals,
such as carotenoids, which are known to have multiple
health benefts [3]. Lycopene, a fat-soluble carotenoid, is
one of the most abundant and important carotenoids [4].
It has potent antioxidant activity [5]. Tis carotenoid,
a bioactive organic pigment, is found in pink grapefruit,
papaya, guava, apricot, watermelon, and vegetables but is

highly concentrated in tomatoes and tomato-derived
products [6]. It has been reported to be one of the
strongest antioxidants among carotenoids [7]. As one of
the most potent antioxidants, its capacity to neutralise
singlet oxygen is double that of β-carotene, ten times
greater than that of α-tocopherol, and one hundred and
twenty-fve times more efective than glutathione [5].
Lycopene, isolated from Lycopersicum esculentum (to-
mato) in 1903, was named after the fruit from which it
was isolated [8]. More than 85% of the lycopene in the
diet is derived from tomatoes and tomato-based products
[8]. In addition to fruits and vegetables, lycopene is also
found in some food ingredients, as shown in Table 1
[9, 10]. While overall tomatoes are a good source of
lycopene, research has demonstrated that diferent to-
mato and other fruit varieties have diferent lycopene
content [7]. In addition to varietal diferences, the mi-
croenvironment in which the tomato and or other
lycopene-containing fruit are grown, for example,

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Journal of Nutrition and Metabolism
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temperature, humidity, edaphic conditions, and fruit
maturity status at harvest also infuence lycopene content
[11]. Where the soil microbiome has favourable mi-
crobes, a 36% increase in lycopene has been
reported [11].

Several studies have investigated the potential of lyco-
pene to mitigate risk factors for obesity, type 2 diabetes
mellitus, and cardiovascular diseases, conditions charac-
terised by dyslipidaemia, oxidative stress, and infammation
[12]. Tese studies have shown that lycopene improved
outcomes of these metabolic diseases [13]. Lycopene, known
for its antioxidant properties, has been found to reduce
oxidative stress, a signifcant contributor to the development
of metabolic diseases [14]. In addition, it has been shown to
mitigate infammation and dyslipidaemia, thereby reducing
the risk of cardiovascular diseases and insulin resistance
[15, 16]. Research suggests that regular consumption of
lycopene as a dietary supplement can potentially remediate
insensitivity to insulin, hypertension, and obesity-related
metabolic complications [17, 18].

2. Lycopene: Biochemistry and
Physical Properties

In nature, over 750 carotenoids have been identifed [19].
About 40 to 50 are found in the human diet, and lycopene
is the sixth most common carotene in food products
[20, 21]. Two main categories of carotenoids exist: hy-
drocarbon carotenoids and xanthophylls. Hydrocarbon
carotenoids such as α-, β-, and c-carotene lycopene are
made up of hydrogen and carbon, while xanthophylls, for
example, lutein, β-cryptoxanthin, and zeaxanthin, contain
oxygen along with carbon and hydrogen [4, 22]. Lyco-
pene, as an aliphatic straight-chain hydrocarbon, contains
two unconjugated double bonds and 11 conjugated bonds
[23]. Its conjugated double bonds are subject to isom-
erization through heat, light, and chemical reactions [20].
Lycopene is found in trans- and cis-isomers, but the cis-
isomers are better absorbed and have greater bio-
availability than trans-lycopene [24, 25]. All-trans, 5-cis,

9-cis, 13-cis, and 15-cis are the most common forms of
lycopene isomers, and the 5-cis isomer is the most stable
isomer [26, 27]. Te molecular structure and physical
properties of lycopene are shown in Figure 1 [28] and
Table 2, respectively [8, 29].

3. Lycopene: Absorption, Transportation,
and Distribution

Following ingestion, lycopene released from the food
matrix combines with micelles-containing bile salts,
cholesterol, and fatty acids [30] and is then absorbed. Due
to its hydrophobicity, the dissolution of lycopene within
micelles in the small intestines facilitates its absorption [5]
through the passive difusion of lipids across the unstirred
water layer in the enterocytes [31]. Inside the absorptive
enterocyte, lycopene, together with free fatty acids,
monoglycerides, and fat-soluble vitamins, is packaged
into chylomicrons and released into the lymphatic system
for transportation into the bloodstream and liver [23]. A
fbre-rich diet has been proven to decrease the absorption
of lycopene. Such fbrous diets also mediate the absorption
of lycopene, resulting in over 40% reduction in plasma
lycopene [32]. Several factors, among these, alcohol,
smocking, gender, age, hormonal status, and other dietary
elements, afect the absorption of lycopene [32]. As
healthy individuals grow older, the bioavailability of ly-
copene tends to decrease, possibly due to age-related
structural changes in the gastrointestinal tract that re-
sult in reduced absorptive efciency [33]. Humans absorb
about 10% to 30% of dietary lycopene; the rest is excreted
through faeces [8, 33]. Te lycopene in heated and pro-
cessed tomato products is better absorbed compared to
that from fresh, unprocessed tomatoes [20]. Termal
exposure during cooking and processing of lycopene-
containing foods breaks the food matrix and converts
the natural (all-trans) lycopene structure to its cis geo-
metric isomer, which is 2.5 times better absorbed from the
gastrointestinal tract [34, 35]. Following its absorption
from the small intestines, lycopene is distributed to the
various body tissues [33]. Te assimilation of lycopene by
the tissues from lipoproteins is mediated by certain
membrane receptors known as scavenger receptor class B
type 1 (SR-B1) and cluster of diferentiation 36 (CD36)
[4]. In humans, the concentration of lycopene in the testes
is ten times greater than that found in other tissues [8].
Tis high concentration in the testes is followed by its
concentration in the adrenal gland, liver, prostate, breast,
pancreas, skin, colon, ovary, lung, stomach, kidney, adi-
pose tissue, and cervix [8]. However, cis-lycopene is
mainly distributed in the liver and adipose tissue [24].
Table 3 illustrates the concentration of lycopene in various
human tissues [36, 37]. Lycopene, the primary carotenoid
found in human plasma, exhibits a half-life of approxi-
mately 2 to 3 days. Its concentration in plasma and tissues
ranges between 0.2–21.4 nmol/g and 0.15–21.36 nmol/g,
respectively [8, 36]. In their study, Zaripheh et al. [38]
reported that in rats, lycopene was most concentrated in
the liver, adipose tissue, adrenal tissue, and spleen.

Table 1: Lycopene concentration in fresh fruits and processed food
products.

Fruit/processed food product Lycopene content (mg/100 g)
Apricot and fresh tomatoes 0.11–5.3
Carrot 0.65–0.78
Cooked tomatoes 3.70
Fresh tomatoes 0.72–4.2
Ketchup 9.90-13.44
Papaya 0.11–5.3
Pink grapefruit 0.35–3.36
Pink guava 5.23–5.5
Pumpkin 0.38–0.46
Rosehip 0.68–0.71
Sweet potato 0.02–0.11
Tomato paste 5.40–150
Tomato sauce 6.20
Watermelon 2.30–7.20
Source: [9, 10].

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4. Lycopene Autoxidation

Known to be thermolabile, lycopene undergoes autoxi-
dation when exposed to both light and oxygen [23]. Te
heat-, light-, and oxygen-induced lycopene degradation
gives rise to acetone, methyl-heptenone, laevulinic alde-
hyde, and glycoxal, a colourless compound that produces
a grass-like smell [23]. In addition to the attractive colour
of the fnal lycopene degradation products, their bio-
degradation also afects their favour and nutritive
value [39].

5. Biological Activities of Lycopene

Te meta-analyses and clinical trials of lycopene in human
studies are shown in Table 4.

5.1. Antiobesity Efects. Obesity results from an excessive
buildup of body fat. It has a detrimental efect on a person’s
metabolic health and overall well-being [66]. Te develop-
ment of obesity is infuenced by a variety of factors with
complicated origins that involve psychological, environ-
mental, socioeconomic status, and biological components
[67–69]. Te risk of cardiovascular diseases, cancer, de-
pression, dyslipidaemia, type 2 diabetes mellitus, non-
alcoholic fatty liver diseases (NAFLD), and hypertension is
heightened in obese individuals [70–73]. Obesity elevates the
prevalence of oxidative stress by disrupting the balance
between oxidants and antioxidant activity [74], which leads
to the presence of “unpaired mitochondria” (individual
mitochondria within a cell that have not fused or aligned
with others to form interconnected networks) and an up-
surge in reactive oxygen species [75]. Consequently, the
normal functioning of the adipose tissue is disrupted,
resulting in an increased production of adipocytokines and
a reduction in adiponectin levels, which contribute to the
occurrence of metabolic syndrome [76, 77]. Numerous
studies have reported on the health benefcial antioxidant
activity of lycopene. InmaleWistar rats exposed to a high-fat
diet for 12weeks, supplementation with lycopene at 25mg/
kg body weight for a period of 4 weeks was shown to reduce
plasma interleukin 6 (IL-6), tumour necrosis factor alpha
(TNF-α), leptin, very low-density lipoprotein (VLDL), low-
density lipoprotein (LDL), and total cholesterol (TC), but it
elevated plasma high-density lipoprotein (HDL) levels [78].
Te supplemental lycopene also reduced malondialdehyde
(MDA) concentration but increased hepatic superoxide
dismutase (SOD) and catalase (CAT) activities in the liver
tissue, demonstrating that it (lycopene) potentially is a po-
tent antioxidant that decreases hepatic oxidative stress by
increasing systemic antioxidant and enzyme activities [78].
Pre- and/or postweaning supplementing Sprague–Dawley
rat pups whose dams were fed a high-fat diet with lycopene
at 1% improved the ofspring’s brown adipose tissue (BAT)
development, reduced accumulation of white adipose tissue
(WAT), and enhanced serum antioxidant capacity and
blood glucose homeostasis [79]. In mice fed a high-fat diet,
lycopene was shown to improve glucose and lipid meta-
bolism and decrease body weight gain by stimulating WAT
browning and activating BAT through modulation of per-
oxisome proliferator-activated receptor gamma (PPARG)
[24]. In another study, where lycopene was administered at
25 and 50mg/kg body weight for 3months to male Wistar
rats, results showed increased HDL, improved antioxidant,
and oxidant biomarkers, decreased triglycerides (TG), LDL,
apolipoprotein-B (Apo-B), and β-hydroxybutyrate, but
boosted hepatic PPARG levels [80]. Furthermore, tomato
oleoresin, which contains 10mg/kg body weight of lycopene,
when orally administered to male Wistar rats for 6 weeks,
mediated a signifcant increase in the expression of

Table 2: Physical properties of lycopene.

Property Value/normal range
Boiling point 660.9°C at 760mmHg

Crystal form Long red needles separate from a mixture of
carbon disulfde and ethanol

Density 0.889 gm/cm3

Flash point 350.7°C
Main hazards Combustible
Melting point 172–175°C
Molecular weight 536.85Da
Powder form Dark reddish-brown
Refractive index 1.531

Solubility

Soluble in chloroform, hexane, benzene,
carbon disulfde, acetone, petroleum,

tetrahydrofuran, carbon disulfde, ether, and
oil; insoluble in water, ethanol, and methanol

Stability Sensitive to light, oxygen, high temperature,
acids, catalyst, and metal ions

Vapour pressure 1.33·10−16mmHg (25°C)
Source: [8, 29].

Table 3: Lycopene concentration in some human tissues.

Tissue Lycopene (nmol/g wet weight)
Adipose 0.2–1.3
Adrenal 1.9–21.6
Brainstem Non detectable
Breast 0.8
Colon 0.3
Liver 1.3–5.7
Lung 0.2–0.6
Ovary 0.3
Prostate 0.8
Skin 0.4
Stomach 0.2
Testis 4.4–21.4
Source: [36, 37].

H3C

H3C

CH3

CH3 CH3 CH3

CH3 CH3 CH3

CH3

Figure 1: Molecular structure of lycopene.

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s and C

onditions (https://onlinelibrary.w
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/term
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messenger RNA (mRNA) of adiponectin, forkhead box 01
(Fox01), fatty acid translocase/cluster of diferentiation 36
(FAT/CD36), and sirtuin 1 (SIRTI), but downregulated
PPARG expression in the adipose tissue of obese rats [81].

5.2. Antioxidant Efects. Oxidative stress is recognised as
a signifcant contributing factor to an increased risk of
cancer, the onset and progression of various metabolic
and chronic disorders [82]. Te concept of oxygen radicals
has been established for the past 50 years; however, its role
in the advancement of diseases was discovered in the past
two decades [83]. In several biological processes that are
vital for life, free radicals play an important role, such as
the destruction of intracellular bacteria by phagocytes
such as macrophages and granulocytes [82]. Excessive
production of reactive oxygen species (ROS) causes
protein, deoxyribonucleic acid (DNA), and lipid damage
[84]. Damage to these cellular molecules leads to tissue
injury and interruption in vital cellular processes [85].
Consuming diets rich in antioxidants or supplementing
with bioactive molecules such as vitamins, tannins, and
carotenoids may ofer protection against oxidative dam-
age [86]. Carotenoids such as lycopene are potent anti-
oxidants that inhibit or hinder the advancement of diverse
disorders triggered by ROS [5]. Carotenoid antioxidant
activity has been investigated in multilamellar liposomes
by measuring the inhibition of the formation of thio-
barbituric acid-reactive substances. Lycopene was shown
to be the most potent antioxidant in the sequence: ly-
copene, Υ-tocopherol, astaxanthin, canthaxanthin,
α-carotene, β-carotene, bixin, zeaxanthin, lutein,
α-tocopherol, glutathione, cryptoxanthin, crocin, and
lipoic acid [8, 87]. Lycopene attenuates ROS efects
through radical addition or adduct formation, electron
transfer to the radical, and allylic hydrogen abstraction
[6], and radical addition and allylic hydrogen abstraction
contribute to its antioxidant efects [88]. Lycopene has
been reported to enhance the status of enzymatic (catalase,
superoxide dismutase, and peroxidase) and nonenzymatic
antioxidants such as vitamins C and E from their radicals
by increasing the cellular antioxidant defence system [33].
In addition, lycopene acts as an antioxidant in systems
that produce singlet oxygen but behaves as a pro-oxidant
in systems that create peroxide [89]. In low doses, it acts as
an antioxidant, but at high doses, it acts as a pro-oxidant
[90]. Factors such as lycopene concentration, tissue ox-
ygen tension, and interaction with other antioxidants have
been reported to infuence the pro-oxidant potency of
lycopene [6]. In situation where there is an imbalance
between antioxidant defences and ROS production, such
as during infammation or exposure to environmental
toxins [91], lycopene may switch from its antioxidant role
to a pro-oxidant role [89]. Under these conditions, ly-
copene radicals may contribute to oxidative stress by
reacting with cellular components and promoting further
ROS generation [92]. Studies have suggested that under
conditions of low oxygen levels, its antioxidant properties
predominate [93, 94].

5.3. Hypocholesterolaemic Efects. An imbalance in the level
of cholesterol in the body results in a lipid disorder known as
hypercholesterolemia, a notable risk factor for atheroscle-
rosis and related conditions such as coronary and cere-
brovascular diseases [95, 96]. Several animal and human
trials have investigated the association between lycopene and
cholesterol. Male broiler chickens fed a standard grower diet
supplemented with lycopene at 100mg/kg body weight for
3 weeks had signifcantly reduced serum total cholesterol,
triglyceride, very low-density lipoprotein, and increased
high-density lipoprotein content compared to counterparts
fed the control diet [97]. In apolipoprotein E knockout mice
fed a high-fat diet and lycopene supplementation at 60mg/
kg body weight daily for 14weeks, the administered lyco-
pene signifcantly decreased both total cholesterol and tri-
glycerides, beginning from the sixth week to the end of the
experiment [98]. Similarly, male Wistar rats given a high-fat
diet and 50mg/kg body weight of lycopene daily for
3months had signifcant reductions in plasma total cho-
lesterol, triglycerides, and low-density lipoprotein levels but
increased high-density lipoprotein cholesterol compared to
the group given a high-cholesterol diet [99]. Te reported
cholesterol-lowering efects of lycopene are attributed to
reduce cholesterol synthesis through the inhibition of the
expression and activity of 3-hydroxy-3-methylglutaryl co-
enzyme A (HMG-CoA) reductase and the modulation of
LDL receptor activity [100]. Te fndings obtained from
human studies have been inconsistent. In a systematic re-
view and meta-analysis of 12 and 11 trial arms consisting of
781 and 854 participants, respectively, supplementation of
lycopene signifcantly increased HDL-cholesterol levels
when compared to the control group; however, no signif-
cant diference was observed in the triglyceride levels [101].
Te conficting fndings observed from human studies could
be attributed to the diferences in the study design, char-
acteristics of the populations under investigation, and the
source and dose of lycopene utilised [16, 102].

5.4. Hepatoprotection. In a healthy human adult, the liver
weighs approximately 1.5 kg and is the largest gland and
visceral organ [103]. It plays a vital role in metabolic pro-
cesses such as bile production, digestion, detoxifcation of
xenobiotics, metabolism of lipids, proteins, carbohydrates,
immune regulation, and storage of vitamins [104, 105].
Among the major causes of global mortality is liver disease
[106]. Liver diseases may be caused by several factors, viral
infections, ischemia, alcohol-induced damage, autoimmune
diseases, and genetic defects such as alpha-1 antitrypsin
defciency, hereditary hemochromatosis, citrin defciency,
hereditary fructose intolerance, cystic fbrosis, cholesteryl
ester storage disease, type IV glycogen storage disease, and
Wilson disease [107–109]. Nonalcoholic fatty liver disease
(NAFLD) is the most prevalent liver disease [110]. Globally,
the prevalence of NAFLD is about 25%, in Africa, it is 13%
while in Europe, the rate is 23% and the highest at 32% in the
Middle East [111]. Tis disease is characterised by the ac-
cumulation of macrovesicular steatosis in ≥5% of hepato-
cytes without secondary causes such as alcohol intake, drugs,

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or liver diseases [111, 112]. Patients with type 2 diabetes,
dyslipidaemia, and obesity are at increased risk of de-
veloping NAFLD [113]. Recent studies have shown that
consumption of carotenoids such as lycopene can re-
markably reduce the chances of developing liver diseases
such as NAFLD [90]. In their study, Li et al. [114], using
beta-carotene-15,15′-oxygenase and beta-carotene-9′,10′-
oxygenase double knockout mice, the oral administration of
lycopene at 2.3mg/g for 24weeks resulted in signifcantly
decreased severity of hepatic steatosis and triglyceride levels
but signifcantly increased sirtuin 1 and fatty acid oxidation
compared to control counterparts fed a high-fat diet. Fur-
thermore, lycopene mediated a decrease in infammation. In
a tramadol-induced hepatotoxicity rat model, supplemental
lycopene at 15mg/kg body weight for 15 days mitigated the
hepatotoxicity by increasing antioxidant activity, reducing
fatty acid breakdown and necrosis, lipid peroxidation,
inhibiting DNA fragmentation, and apoptosis [115]. Lyco-
pene administered at 5, 10, and 20mg/kg body weight for
6weeks in a rat model of NAFLD was shown to mediate
hepatoprotective efects, as seen with reduced activities of
aspartate transaminase and alanine transaminase and con-
comitant reductions in malondialdehyde, free fatty acids,
and LDL-cholesterol concentrations [116]. Tese fndings
were associated with elevated hepatic superoxide dismutase
and glutathione concentrations, but with reduced cyto-
chrome P450 2E1 and tumour necrosis factor-alpha ex-
pression and decreased hepatic fat [116]. Te
abovementioned experimental studies provide a clear insight
that the administration of lycopene not only inhibits ROS
but also improves the activity of antioxidant enzymes,
thereby providing benefcial efects against NAFLD.

5.5. Renoprotection. Chronic kidney diseases (CKD) have
become a global public health issue, afecting more than 200
million people worldwide [117]. Chronic kidney disease is
a common term used to describe diferent disorders that
permanently afect the structure and function of the kidneys
for over a period of 3 months [118]. Tis can be diagnosed
when the abnormalities in the kidney or glomerular fltration
rate are lower than 60ml/min/1.73m2 and albuminuria is
characterised by an albumin to creatinine ratio above
30mg/g [119]. Patients with CKD are more prone to develop
end-stage renal disease, a condition that requires expensive
management by either dialysis or kidney transplantation
[76]. Patients sufering from CKD commonly display a high
incidence of arrhythmias, venous thromboembolism, heart
failure, and ischemic heart disease, which signifcantly in-
creases mortality [120, 121].Te increase in the prevalence of
cardiovascular disease (CVD) in CKD patients is associated
with oxidative stress, chronic infammation, and vascular
endothelial dysfunction [122]. Tese three factors create an
intricate cycle, resulting in pathological variations and
playing a crucial role in the initiation and progression of
CVD in CKD patients [123, 124]. Among these factors,
oxidative stress is a key mediator in the intricate pathways
linked to the progression of CKD [124]. As a result, the
utilisation of antioxidant therapy is one of the signifcant

approaches to avert and mitigate the advancement of CKD
[56]. Lycopene is a potent antioxidant and an efcient free
radical scavenger that has been investigated and shown to
protect the kidney against chemically induced damage
[125, 126]. In female Wistar rats fed a high-fat diet, the
supplementation of 200ml of lycopene extract twice a week
for 8weeks signifcantly reduced plasma creatinine, urea,
serum angiotensin-converting enzymes, renal tissue
malondialdehyde, and C-reactive protein levels but in-
creased total protein and tissue antioxidant enzyme levels
[127]. Tabrez et al. [128] observed that lycopene protected
against the advancement of diabetic nephropathy and im-
proved renal function by inhibiting the advanced glycation
product and its receptors’ (AGE-RAGE) pathway. Lycopene
has shown to inhibit LDL-cholesterol peroxidation, which
can damage the kidneys [56]. Furthermore, supplemental
lycopene has shown to decrease MDA, RAGE, and TNF-α
levels in the kidneys of maleWistar rats fed a high-fat diet for
6 weeks [129], and similarly, lycopene orally administered at
25 and 50mg/kg body weight daily for 3months protected
the kidneys of male Wistar rats fed a high-fat diet by
inhibiting the expression of nuclear factor kappa-B, in-
terleukin 1 beta, tumour necrosis factor alpha, decreasing
oxidative stress, increasing nuclear factor erythroid 2-related
factor 2, and stimulating B-cell lymphoma 2, hence shielding
the kidney tissue against damages [66].

5.6. Osteoprotection. Oxidative stress caused by reactive
oxygen species infuences the activity of both osteoclasts and
osteoblasts [130]. Tis is thought to impact the pathogenesis
of skeletal system disorders, including osteoporosis, the most
common skeletal metabolic disease [131]. Osteoporosis often
develops in older adults and is characterised by an alteration
of the bone microarchitecture, typifed by a decline in bone
mineral density, which contributes to an elevated risk of
fractures [132]. Such bone fractures notably occur at the distal
forearm, vertebral column, and proximal femur [133].
Complications associated with osteoporosis, particularly hip
fractures, result in a mortality rate that is 4 times higher in the
global adult population [132]. Despite its preponderance in
the elderly, osteoporosis has shown to impact individuals of
various age groups, but postmenopausal women are at high
risk [134, 135] due to a decrease in estrogen production which
results in increased oxidative stress and osteoclast-induced
bone resorption [136]. Studies have shown that children born
to parents with a history of osteoporosis and fractures are
more prone to the development of osteoporosis [137]. In
addition to genetic predisposition, poor nutrition, excessive
alcohol consumption, smocking, cafeine intake, and medi-
cation side efects, for example, glucocorticoids, can cause the
development of osteoporosis [138–141]. Lycopene has shown
to have an advantageous efect on the skeletal health [142]. It
has shown to play a vital role in protecting postmenopausal
women from experiencing bone loss by upregulating alkaline
phosphatase, type 1A collagen, runt-related transcription
factor 2, triggering the activation of the wingless-related in-
tegration site/beta-catenin and extracellular signal-regulated
kinase 1/2 pathways, and downregulating receptor activator

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of nuclear factor kappa-B ligand [143]. In mice fed a high-fat
diet, supplemental lycopene at 15mg/kg body weight for
10weeks increased serum levels of total antioxidant capacity
(T-AOC), SOD, and reduced the levels of MDA and AGEs,
RAGE, and NF-kB expressions in the tibias and femurs [144].
In male albino rats, orally administered lycopene at 30mg/kg
body weight once daily over an 8-week period mitigated
glucocorticoid-induced osteoporosis [145], and in diabetic
male rats, lycopene suppressed bone resorption, enhanced
osteopreotegerin and RANKL expression ratios by preventing
oxidative damage and reducing infammation [146]. Tese
research fndings demonstrate that lycopene has osteopro-
tective properties.

5.7. Anti-Infammatory Efects. Infammation is an immune
response mechanism that is triggered when exposed to
various harmful stimuli, such as damaged cells, microor-
ganisms, poisonous, and allergenic substances [147]. It
serves as a crucial stage in the process of tissue regeneration,
repair, and remodelling, as well as the restoration of tissue
haemostasis in impaired areas [148]. Infammatory media-
tors include the cytokines interleukin (IL)-1, IL-5, IL-6, IL-
12, IL-1β, TNF-α, and interferon c [149], and chemokines
such as IL-8, monocyte chemoattractant protein 1, cyclo-
oxygenase, vascular cell adhesion molecule 1, matrix met-
alloproteinase, free radicals, growth factors, and
prostaglandins serve as regulatory mediators in the process
of infammation [150]. On stimulation, these mediators
activate endothelial cells, causing increased vascular per-
meability and the deployment of neutrophils, eosinophils,
monocytes, and mask cells to the injury site, which helps
eliminate the harmful agents and facilitate the healing
process [151]. However, infammation is known to con-
tribute to the development and progression of various
diseases, including but not limited to CKD, cancer, diabetes
mellitus, cardiovascular disease, NAFLD, obesity, asthma,
rheumatoid arthritis, osteoporosis, autoimmune, and neu-
rodegenerative disorders [152–154]. Te consumption of
natural antioxidants for maintaining human health has
become popular, especially in developed nations [155]. In
a study using female Wistar rats, lycopene was shown to
alleviate palmitic acid-induced neuroinfammation by re-
ducing oxidative stress and inhibiting the toll-like receptor 4
(TLR4) and nuclear factor kappa-B p65 (NF-kB p65) sig-
nalling pathways [156]. Lycopene supplementation miti-
gated metalaxyl-induced liver damage in male albino rats by
restoring antioxidant status, improving liver function, and
alleviating liver injury-associated complications [157]. In
lycopene-treated endothelial cells, lycopene inhibited the
activation of TNF-α but enhanced the expression of heme
oxygenase-1 (HO-1) through the upregulation of nuclear
factor erythroid 2-related factor 2 signalling pathways [158].
Another experimental study reported that in male albino
rats, orally administered lycopene at 10mg/kg body weight
for 21 days efectively protected the colon epithelial mucosa
against acetic acid-induced colitis and oxidative injury [159].
In C57BL/6 mice chronically exposed to cigarette smoke for
60 days, lycopene has shown to restore redox status and

mitigate hepatic infammation [160]. In addition, Li et al.
[161] reported that lycopene mitigated the dysregulation of
lipid metabolism and the infammatory response induced by
lipopolysaccharide in the rat testes. Tus, evidence is
plentiful demonstrating the anti-infammatory efects of
lycopene both in vitro and in vivo.

5.8. Antidiabetic Efects. Diabetes mellitus (DM) causes
hyperglycaemia and, if inadequately managed, can result in
damage to the heart, eyes, and kidneys [162]. Te global
prevalence of diabetes is approximately 9.3%, which cor-
responds to about 463 million individuals. However, it is
predicted to rise by 25% in 2030 and 51% in 2045 [163].
Diabetes mellitus is classifed into three major types: type 1
(insulin-dependent), type 2 (noninsulin-dependent), and
gestational diabetes mellitus [164]. Among these, type 2
diabetes mellitus predominates and accounts for about 90%
in all cases worldwide [162].

Scientifc evidence shows that lycopene can potentially
be used to prevent and treat diabetes mellitus [24]. In
streptozotocin-induced diabetes model, dietary fortifcation
with lycopene mediated increased serum insulin concen-
trations, decreased urine and blood sugar concentrations,
and reduced diabetes-induced pancreatic injury [165]. In
diabetic Wistar rats, orally administered lycopene at 40mg/
kg body weight signifcantly decreased serumMDA, cortisol,
and blood glucose concentration but increased SOD, CAT,
and glutathione peroxidase (GSH-Px) activities at 10, 20, and
40mg/kg body weight [166]. Furthermore, supplemental
lycopene has shown to attenuate renal damage in diabetic
rats [167]. In STZ-induced diabetic rats, at 4mg/kg body
weight, lycopene-ameliorated B-cell lymphoma-extra-large,
and B-cell lymphoma 2 (Bcl-2) concentrations and reduce
the expression of Bcl-2-associated X-protein (BAX) in the
hippocampus [168]. Interestingly, orally administered ly-
copene has shown to increase SOD and GSH-Px activities
and lower MDA concentrations in rat pancreatic tissue
[169], but it mediated increased plasma insulin concentra-
tions and reduced blood and liver lipid content, fasting
blood glucose and glycosylated haemoglobin concentration,
and homeostatic model assessment for insulin resistance in
diabetic rats [169].

5.9. Anticancer Efects. Cancer is a major global health
challenge and is the second primary reason for mortality in
the United States [170]. Te ingestion of tomatoes and
tomato-based products has been associated with a reduced
occurrence of diferent types of cancer [171]. In vivo and
in vitro research has demonstrated that lycopene hinders the
growth and multiplication of prostate cancer cells, inhibits
the cell cycle, and induces apoptosis [172]. Dietary sup-
plementation with lycopene mitigated the growth of breast
cancer cells by suppressing the activity of the insulin-like
growth factor 1 receptor (IGF-1R) signalling pathway [151].
While research shows that the consumption of a lycopene-
rich diet could be benefcial in reducing the risk of pancreatic
cancer [131]. In a rat model, the consumption of lycopene
has shown to reduce the progression and proliferation of

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ovarian cancer [173], and in human studies, cisplatin-based
chemotherapy in combination with lycopene supplemen-
tation enhanced cervical cancer treatment [174]. Further-
more, in animal models of hepatocellular carcinoma,
administered lycopene suppressed the onset and develop-
ment of cancer [175]. In human colorectal adenocarcinoma
cell line, treatment with lycopene has shown to exhibit
genotoxicity, antiproliferative, and apoptotic efects [176],
a demonstration of its anticancer efects.

5.10. Gastroprotection. Te incidence of peptic ulcer disease
(PUD) has substantially increased, afecting approximately 5
to 10 percent of the general population [177]. Te corrosive
efects of acid and pepsin on the gastroduodenal mucosa
cause peptic ulceration through exposure of the mucosa’s
lining to gastric acid and digestive enzyme actions [178].
Peptic ulcer disease is primarily caused by the extensive use
of nonsteroidal anti-infammatory drugs (NSAIDS) and
Helicobacter pylori infection [179]. Other contributing fac-
tors include surgery, severe illness, burns, Zollinger–Ellison
syndrome, excessive alcohol intake, smoking, and psycho-
logical and physical stress [180–182]. Te excessive pro-
duction of ROS is the major factor in stress-induced ulcers
[183]. Tus, the utilisation of strong antioxidants may be
benefcial in the management of ulcers [184]. In male Albino
rats, lycopene administered at 200mg/kg body weight for
10 days has shown to protect against ethanol-induced mu-
cosal injury [185]. In their study, Chen et al. [186] found that
supplemental lycopene at 10, 50, 100, and 150mg/kg body
weight reduced gastric juice secretion in adult male
Kunming mice when compared to the gastric injury control
group. However, at high doses (150mg/kg body weight),
lycopene exacerbated absolute ethanol-induced acute gastric
mucosal injury. In addition to mediating for protection
against alcohol-induced gastrointestinal tract mucosal in-
jury, lycopene has shown to suppress gastric acid secretion
and combat infection by Helicobacter pylori [130].

5.11. Neuroprotection. Neurodegenerative diseases (NDs)
are characterised by gradual loss of neurons and are asso-
ciated with the formation of protein aggregates [187]. Tese
diseases are considered a major medical challenge as it af-
fects millions of patients globally [188]. Alzheimer’s, Par-
kinson’s, Huntington’s, prion and motor-neural diseases,
amyotrophic lateral sclerosis, spinocerebellar ataxia, and
spinal muscular atrophy are common NDs [187, 189, 190].
Despite age being the leading factor in the onset of all
neurodegenerative disorders, recent discoveries indicate that
the combination of a person’s genetic makeup and envi-
ronmental infuences can contribute to an elevated risk of
developing NDs [191]. Regardless of the various factors
causing these NDs, a key feature common to all is the onset
and development of neuronal cell death [192]. Te pro-
gression of NDs is characterised by increased ROS pro-
duction, which causes oxidative stress [193]. Administered
lycopene has shown to attenuate memory loss due to age,
cognitive impairments, neuronal damage, and synaptic
dysfunctions in the brain [194]. In addition, lycopene was

observed to mitigate age-related oxidative stress by sup-
pressing lipid peroxidation and enhancing GSH, SOD, and
CAT activities [194]. Dietary fortifcation with lycopene was
demonstrated to decrease age-related neuroinfammation by
attenuating microgliosis and combating infammation [194].
Furthermore, lycopene mediated the reduction in the ac-
cumulation of amyloid beta 1–42 in the brains of aged CD-1
mice [194] and when used as a supplement, it upregulated
the mitogen-activated protein kinase (MARK)/extracellular
signal-regulated kinase (ERK) signalling pathway, inhibited
oxidative stress and neuronal apoptosis, and protected
against bisphenol-induced neurotoxicity in the hippocampi
of adult male rats [195]. It has also shown to decrease
palmitic acid-induced brain oxidative stress and neuro-
infammation and to inhibit the toll-like receptor 4 (TLR4)/
nuclear factor kappa-light chain enhancer of activated B cells
p65 (NF-kB-p65) pathway in female rats [156]. In mice with
Alzheimer’s disease induced by β amyloid, lycopene reduced
oxidative stress, decreased neuronal loss, improved synaptic
plasticity, and inhibited neuroinfammation [196].

5.12. Cardioprotection. Globally, cardiovascular diseases
(CVDs) stand at the forefront as the leading cause of human
mortality [16]. Studies have shown that in 2019, CVDs
caused 17.8 million fatalities, and this trend is projected to
increase by 2030 to 23 million [197]. Several epidemiological
studies have confrmed the signifcance of lycopene in
preventing CVDs [198]. For instance, lycopene supple-
mentation has shown to reduce C-reactive protein levels,
interleukin-6, pulse wave velocity, blood pressure, and in-
tercellular adhesion molecule 1 and enhance vascular health
through fow-mediated dilation of the endothelium [199].
Lycopene supplementation at a dosage of 5mg/kg body
weight for 21 days has shown to confer protection against
atrazine-induced cardiotoxicity in mice [200]. In
Brown–Norway/Lewis rat model, lycopene treatment was
demonstrated to have the potential to mitigate vascular
arteriosclerosis in allograft transplantation by inhibiting
Rho-associated kinases and by regulating the expression of
nitric oxide/cyclic guanosine monophosphate signalling
pathways [201], which indicates that lycopene has the po-
tential to alleviate vascular arteriosclerosis. In another study,
lycopene administered for 4weeks at 10mg/kg body weight
reduced infammation and apoptosis during postmyocardial
infarction remodelling by suppressing the NF-KB signalling
pathway in mice [202]. In addition, supplemental lycopene
improves endothelial function in individuals sufering from
CVDs [203].

5.13. Lung Protection. In male C57BL/6 mice, dietary ly-
copene supplementation at 25 or 50mg/kg body weight
mitigated cigarette smoke-induced pulmonary emphysema
[204]. Te literature shows that lycopene or matrine treat-
ment alone ofered minimal protection against
lipopolysaccharide-induced acute lung injury in mice, but
when coadministered, signifcant mitigatory efects were
observed [205]. Tese results indicate that lycopene and
matrine in combination may function as an alternative to

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glucocorticoid therapy in treating acute lung injury [205]. In
a study conducted byMustra Rakic et al. [206], supplemental
lycopene at 90mg/kg body weight for 22weeks efectively
suppressed tobacco carcinogen/cigarette smoke (NNK/CS)-
induced emphysema, chronic bronchitis, and preneoplastic
lesions. Furthermore, dietary lycopene signifcantly de-
creased NNK/CS-induced buildup of total cholesterol and
upregulated mRNA expression of peroxisome proliferator-
activated receptor alpha (PPARα), ATP-binding cassette
(ABC) transporters ABCA1 and ABCG1, and liver X re-
ceptor alpha (LXRα) in the lungs of the ferret model. Tese
fndings suggest that lycopene could act as a preventative
agent against the adverse efects of tobacco smoke on lung
health and lipid metabolism.

5.14. Sperm Quality Enhancement and Fertility Promotion.
Infertility is a prevalent health problem that afects roughly
48 million couples and 186 million individuals globally
[207]. ROS-induced oxidative stress is a primary contributor
to various reproductive complications [208]. In varicocele-
induced rats, supplemental lycopene has shown to protect
sperm against DNA damage by mediating upregulation of
antioxidant responses that quenched ROS, whichmanifested
with improved sperm viability, Johnson’s score, membrane
integrity, and the expression of B-cell lymphoma 2-
associated X-protein (BAX) [209]. Similarly, in men with
oligozoospermia, supplemental lycopene for 12weeks at
25mg/kg body weight attenuated oxidative stress and im-
proved sperm quality [52]. In their study, Yamamoto et al.
[210] observed that the consumption of tomato juice with
30mg of lycopene for a duration of 12weeks increased
plasma lycopene concentration and sperm motility and
decreased the white blood cell count in the seminal plasma of
the tomato juice group compared to the control group of
infertile men. Dietary supplementation with lycopene at
20mg per day for 3months prior to the scheduled in vitro
fertilization (IVF) treatment increased the arachidonic acid
to docosahexaenoic acid ratio in the seminal fuid and
resulted in 7 natural pregnancies in addition to 15 preg-
nancies following the IVF procedure [51]. In methotrexate-
induced ovarian damage, pretreatment with lycopene at
5mg/kg body weight for 5 days prevented infertility and has
shown to mediate increased GSH activity as well as de-
creased MDA and myeloperoxidase concentrations [211].
Tese fndings suggest that lycopene alleviates imbalances in
polyunsaturated fatty acids and can serve as a preventive
agent against infertility.

5.15. Protection of Skin Health. Te skin, constituting ap-
proximately 15% of the total body weight [20], plays a vital
role in preventing excessive water loss from the body and
maintaining the body temperature within an optimal range
[212]. It provides protection against toxic substances, free
radicals, physical damage, and ultraviolet radiation [213].
Te latter causes the development of skin conditions and
diseases through sunburn, photoaging, and excessive ROS
production within the skin, which damages DNA and causes
skin cancer [213–215]. Lycopene is extensively used as an

ingredient in cosmetic products due to its demonstrated
ability to protect the skin from aging and photodamage
[215]. Anbualakan et al. [216] showed that lycopene can
prevent and/or treat sunburn and photoaging and that it
could potentially be efective against UV-induced skin
cancers. As a dietary supplement, lycopene has been dem-
onstrated to improve skin appearance and pigmentation and
mitigate erythema [217].

5.16. Protective Efect on Vision. Age-related ophthalmic
conditions, inclusive of macular degeneration, glaucoma,
cataracts, and diabetic retinopathy, are key contributors to
gradual and permanent vision loss [218]. In diabetic patients,
serum lycopene concentration has been observed to be lower
than normal [114]. Importantly, due to its consistent lower
levels in diabetics, it has been suggested that serum lycopene
concentration might serve as a diagnostic tool for diabetic
retinopathy [114]. Using ARPE-19 cells derived from human
retinal pigment epithelium, Gong et al. [219] demonstrated
that lycopene suppressed growth of human RPE cells against
oxidative stress-induced cell loss fndings which suggests
that it (lycopene) may protect against RPE proliferative
disease and old-age related macular degeneration. Oxidative
stress and infammation have been shown to be associated
with the pathogenesis of eye-related conditions [220]. As
a dietary supplement, lycopene has been proven to mitigate
the risk of developing eye diseases associated with old age
[221]. Tis could be due to its demonstrated ability to
prevent cataract formation both in vitro and in vivo [131].

6. Lycopene: Protective Effects against Toxins

Toxins are natural and harmful chemical substances that
adversely impact health [222]. Tey cause specifc organ
toxicity, for example, skin, eye, kidney, liver, blood, car-
diovascular, respiratory, reproductive, endocrine, immune,
and nervous system damage [222, 223]. Trough their ac-
tions, toxins disrupt homeostasis, alter gene expression, and
cancer-related metabolic signalling pathways [224]. Re-
search has demonstrated that lycopene as a dietary sup-
plement efectively mitigates the deleterious efects of myco-,
bacterial, and chemical toxins [225] [125, 226, 227], fun-
gicides [228], pesticides [229], herbicides [230], and fuoride
[231]. It is hypothesised that lycopene mediates protection
against toxins through its potent antioxidant, chelating, and
antiapoptotic properties [224].

7. Lycopene: Safety and Potential Toxicity

Tere is no specifed daily prescription for dietary lycopene
intake, but epidemiological studies have recommended an
intake of 2 to 20mg daily of lycopene [93]. It has shown that
consumption of up to 100mg of lycopene daily does not
elicit adverse outcomes [5]. In a toxicological study con-
ducted on rats, feeding a diet fortifed with lycopene at 1%
(w/w) did not elicit any side efects [232]. Similarly, using
lycopene at 200mg/kg body weight per day as a dietary
supplement has also been shown not to negatively impact
animals [233]. Generally, it is asserted that lycopene can be

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used as a safe dietary supplement during pregnancy and
lactation [234]. Although in pregnant women, high dietary
intake of lycopene has shown to mitigate the risk of de-
veloping preeclampsia [235]. Imran et al. [7] reported that
excessive chronic consumption of tomato juice, a rich source
of lycopene, caused lycopenemia. Findings from both animal
and human studies suggest that although lycopene could
generally be used as a safe dietary supplement, some caution
must be exercised against excessive intake.

8. Conclusion

Te extensive studies carried out on lycopene highlight its
exceptional potential to promote overall health and well-
being. Its varied spectrum of benefts places it as a potent
natural compound which can contribute to the promotion of
health either as a prophylactic or ore therapeutic agent
against metabolic diseases. In order to fully exploit its po-
tential and increase its utility in health delivery, it is crucial
to undertake additional research to comprehensively elu-
cidate the health benefcial mechanisms underlying lyco-
pene’s medicinal properties. Furthermore, in order to enjoy
optimal utility from the use of lycopene, there is a need to
evaluate and recommend efective dosages for efcacy and
prevention of possible side efects of abnormally high doses.

Data Availability

Te data that support this systematic review come from
studies and datasets that were previously reported and cited
in this article.

Conflicts of Interest

Te authors declare that they have no conficts of interest.

Acknowledgments

Tis work was funded by the Faculty Research Committee
grant, Faculty of Health Sciences, University of the Wit-
watersrand, South Africa.

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