Citrus and Health

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Provisional chapter
Citrus and Health
Javier Marhuenda, Begoña Cerdá, Débora Villaño,
Alejandro Galindo and Pilar Zafrilla
Additional information is available at the end of the chapter
© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
JavierMarhuenda, BegoñaCerdá, DéboraVillaño,
AlejandroGalindo and PilarZafrilla
Additional information is available at the end of the chapter
Abstract
Citrus has been proposed as an interesting ingredient in the elaboration of food products
as soft drinks due to its distinctive aroma and high nutritive value. It is a rich source
of nutrients that contains higher amounts of vitamin C, citric acid, minerals, and avo-
noids, especially avanones and avones (reaching values of 400–600 mg/L) and in lesser
amounts avonols and hydroxycinnamic acids. Citrus avonoids decrease capillary
permeability and are benecial in the treatment of vascular diseases. Scientic studies
suggest that the ingestion of food products based on citrus fruits improves the blood lipid
prole, reduces oxidative stress, prevents atherogenic modications of LDL and platelet
aggregation, as well as contributes to the improvement of HDL levels. Other benets
aributed to citrus are antiaging, anticancer, neuroprotective, and antidiabetic. The pres-
ent revision tries to empathize the most relevant studies regarding citrus and health.
Keywords: citrus, obesity, neurodegeneration, diabetes, cancer, cardiovascular diseases
1. Introduction
There are numerous evidences supporting the crucial inuence of diet in the prevention of
diseases related to oxidative and inammatory processes. Citrus are one of the most impor-
tant foods included in a healthy lifestyle, due to their composition in bioactive compounds.
The biological activity of citrus bioactive compounds is mainly their free radical scavenging
property, increasing the antioxidant activity which closely related to disease prevention.
Healthy properties of citrus have been linked to its high vitamin content C and avonoids,
mainly aributed to its antioxidant capacity. Citrus are considered adjuvant in the preven-
tion of cardiovascular diseases and metabolic diseases such as obesity, diabetes mellitus or
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

dyslipidemia, as well as certain types of cancer. In citrus (particularly lemon), more than 60
individual avonoids have been identied.
2. Citrus and their role in dierent pathologies
The health benets described with the consumption of these fruits are related to their complete
prole on nutrients, including simple sugars, ber, potassium, high contents of vitamin C and
phytochemicals as avonoids, particularly avanones that may act synergistically. They are
low in fat and proteins, ranging from 0.1 to 0.3 g and from 0.69 to 0.94 g/100 g fresh weight,
respectively. Citrus are particularly rich in vitamin C (ascorbic acid), providing amounts in the
range of 23–83 g/100 g fresh weight. Considering that the Recommended Dietary Allowance
(RDA) is set at 75–80 mg and a medium-sized orange or grapefruit contains from 50 to 70 mg
ascorbic acid, it is easy to provide the necessary quantities with these fruits in a daily dietary
paern [1].
Micronutrients are secondary metabolites synthesized in the plant as a defense mechanism
against pathogens, parasites, or to protect from UV radiation. We nd two main groups in
citrus fruits: terpenes and avanones.
Terpenes are present in the essential aromatic oil produced by cells in the avedo, and the
main compounds are limonene and citral (mixture of isomers geranial and neral) (Figure 1).
These volatile substances contribute to the avor of citrics; similar to the protection eect
against biotic stress in plants, they have shown antimicrobial activities interesting for food
preservation and medicinal purposes [2, 3].
Besides, citrus fruits are especially rich in the avanones hesperetin, naringenin, and eriodic-
tyol [4]. Flavanones have the characteristic 15-carbon backbone ring structure common in the
avonoids (C6▬C3▬C6), consisting of two aromatic rings linked by three carbon atoms in an
oxygenated structure as pirane derivative [5]. In particular, avanones have a further degree
of oxidation, with a ketone group at position C-4 in C-ring.
These compounds are mainly found glycosylated, with a disaccharide linked by glycosidic
bond; common positions are the hydroxyl groups of C3 and C7. The free form (aglycone)
can render dierent avanones, depending on the position and type of sugar linked. In this
sense, grapefruit is abundant in narirutin and naringin, which are both heterosides from
the aglycone naringenin, but the glucose moiety is dierent (rutinoside or neohesperoside,
respectively). Orange is rich in hesperidin, that is the glycoside of hesperetin, while lemon is
rich in eriocitrin that contains the aglycone eriodictyol [6].
Flavanones are not uniformly distributed in the fruit but are more abundant in the albedo.
Because this part is discarded in juice processing, the level of avanones is lower in citrus
juices than in the whole fresh fruit [7]. In fact, levels of in orange fruit range between 35
and 147 mg/100 g of total avanones and 44 and 106 mg/100 g of naringin and narirutin
Citrus - Health Benefits and Production Technology2

Figure 1. Chemical structures of the main terpenes present in citrus essential oil.
Citrus and Health 3

in grapefruit [8]. By contrast, orange and grapefruit juices showed values between 10 and
80 mg/100 g of hesperidin and narirutin [9] and naringenin [10]. Therefore, the paern of
consumption of these fruits greatly aects the avanone total intake and further biological
activities. Moreover, the sugar moiety modies the in vivo pharmacokinetic properties of the
compound. Aglycones are more easily absorbed than their heterosides counterparts, as gly-
cosides are more hydrophilic and need active transport by proteins in gastrointestinal lumen
and/or hydrolysis by gut microora in order to be absorbed [11].
2.1. Citrus and cancer
Flavonoids are major compounds in citrus, and have been investigated since more than
20 years ago. Dietary avonoids have showed to be able to exert chemopreventive or anti-
cancer capacity [12]. Anticancer capacity of citrus avonoids takes place through three main
mechanisms: defense against DNA injury, inhibition of tumor growth, and inhibition of cell
proliferation [13].
The best anticancer compound must exert the most possible inhibition of tumor growth or
to able to destroy cancer cells, but origins minimum adverse health collateral eects [14].
Flavonoids are natural and considered innocuous and great compounds for the treatment of
cancerous processes [15, 16]. The synthetic molecules that can be used for the treatment of can-
cer are extremely noxious, and can be able to destroy healthy cells. Due to the safe long-term
consumption of avonoids, and their innate biological activity, avonoids can be considered
as good applicants regarding cancer treatment. In fact, scientic literature has revealed cyto-
toxic eects of citrus avonoids on cancer cells, with slightest adverse health eects.
That fact has led the research in order to implement avonoid-based cancer treatments [17].
As other polyphenols, the presence of aromatic rings in avonoids leads to pro- and antioxi-
dant capacity that can be useful for chemotherapies [18]. Cancerous cells show an increment
on oxidative stress, which leads to the possibility to be aacked by a substance that improves
reactive oxygen species level as avonoids do [19, 20]. As dened by Pacico et al. [21], pro- or
antioxidant capacity of citrus avonoids is dependent on the concentration, type of cell, and
culture condition (in vitro models).
Flavonoids exert DNA protection by their ability to absorb ultraviolet light. Some experiments
on a UV-irradiated model of plasmidic DNA indicate protecting capacity of naringenin and
rutin against UV-induced damage of DNA [22]. Indeed, naringin plays an important role in
regulating antioxidative capacity by increasing superoxide dismutase and catalase activities
and by upregulating the gene expressions of superoxide dismutase, catalase, and glutathione
peroxidase in cholesterol-rich diet-fed rabbits [23].
Apart from UV protection, avonoids can also diminish tumor promotion at the beginning of
carcinogenesis by the intensication of the detoxication processes. In particular, citrus avo-
noids inhibit ornithine decarboxylase induction of skin tumor promotion, activating protein
kinase C [24, 25]. Miller et al. [26] studied the inhibition of oral carcinogenesis by citrus avo-
noids in hamsters and the antineoplastic activity, concluding that hesperetin, neohesperetin,
tangeretin, and nobiletin were ineective, while naringin and naringenin gave good results.
Citrus - Health Benefits and Production Technology4

Citrus avonoids can inhibit invasion, by rat malignant cells, in cardiac and hepatic tissue of
syngenetic rats [27]. Hydroxycinnamates, glycosylated avonoids, and the polymethoxylated
avones have shown inhibitory activity on several tumoral cell line proliferations [13]. Other
studies showed eriocitrin and its aglycone, eriodictyol, as potent inhibitors of lipoxygenases,
which are involved in the biosynthesis of various bioregulators that are closely related to
the pathogenesis of several diseases such as allergy and atherosclerosis and cancer [28].
Hesperidin in dierent citrus juices also showed antiproliferative activity [29], reporting
lemon in particular potent antiproliferative activities on HepG2 human liver-cancer cell in a
dose-dependent manner [30].
Also, the positive eect of vitamin C in reducing the incidence of stomach cancer has been
studied, being most probably due to the inhibitory action in the generation of nitrous com-
pounds by interrupting the reaction between nitrites and amine groups [31], although it has
recently shown that this eect may be due to a cytotoxic eect of vitamin C on human gastric
cancer cell line AGS [32]. Consistent protective eect of vitamin C has also been found in lung
and colorectal cancer [33].
One stretched revision done by Turati [34] reported a diminution on cancers of the digestive
tract and larynx regarding high intake of citrus. That eect was found to be due to the content
on vitamin C, avanones, and other compounds with antioxidant, antimutagenic, and antip-
roliferative properties [35]. Subjects consuming more than one portion of citrus fruit per week
showed OR between 0·42 and 0·82 for oral cavity and pharyngeal cancer, esophageal cancer,
stomach cancer, colorectal cancer, and laryngeal cancer. However, despite the good results
obtained, no correlation was found for other neoplasms, including cancers of breast, ovary,
endometrium, prostate, or kidney [35].
The most recent and huge research about citrus and cancer was published in 2016. An adap-
tive meta-analysis of cohort studies revealed that regular dietary intake of citrus prevents the
development of gastric cancer, particularly cardia gastric cancer [36].
2.2. Citrus and cardiovascular diseases
Cardiovascular diseases (CVD) are one of the main causes of illness and death in Western
countries, and cardiovascular drugs are the most commonly used medications. There are two
types of factors involved in the development of CVD. Some factor can be modied, like life
style, diet, environment, or smoking. Other cannot be modied: genetic factors, gender, his-
tory, or age. Atherosclerotic plaque formation is the most common phenomenon involved in
CVD [37].
Consumption of citrus is inversely associated with incidence of CVD, due to the presence of
bioactive compounds like avonoids. Current research has focused on diet containing bioac-
tive compounds, as an alternative to pharmaceutical medication. It can be concluded from the
analysis of multiple studies that as the mean consumption of avonoids increases, mortality
due to CVD decreases. Epidemiological evidence of clinical and preclinical studies suggest
that avanones present in the citrus fruits positively inuence cardiac and metabolic param-
eters, preventing CVD [38].
Citrus and Health 5

A study performed on approximately 70.000 women highlighted an inverse correlation
between the intake of avanones and the risk of suering a cerebral ischemia, which is sig-
nicantly dierent when contemplate women who consume high levels of avanones [39].
Another recent meta-analysis study of three randomized clinical trials, including 233 patients,
demonstrated a correlation between avanones intake and a reduction in blood pressure [40].
Another recognized cardiovascular risk factor is metabolic syndrome, characterized by
altered glucose metabolism, elevated blood pressure, dyslipidemia, and obesity. In 2016, a
study on 10,000 subjects demonstrated an inverse association between polyphenols and meta-
bolic syndrome, which was particularly signicant in individuals with the highest intake of
polyphenols [41].
Several studies carried out so far support a preventive role of citrus fruits on the main risk
factors of CVD, such as hypertension, dyslipidemia, overweight, and hyperglycemia. Among
CVDs, the eect of avonoids on stroke is not clear. Mursu et al. [42] studied the association
between intake of avonoid and risk of stroke and mortality caused by stroke and concluded
that a greater intake of avonoids decreases the chances of ischemic stroke as well as mortal-
ity caused by CVD.
Chronic inammation is caused by the excessive production of chemokines and cytokines.
Cytokines and chemokines act as regulatory proteins under normal physiological conditions,
but their excessive production disrupts the gradient balance and more reactive oxygen species
(ROS) are produced. It has been shown that the grape avonoids control chronic inamma-
tion by reducing ROS level and by modulating pathways of inammation. As avonoids are
natural compounds, they can target multiple steps in the inammation pathway as compared
to monotargeted synthetic anti-inammatory drugs [43].
Atherosclerosis, characterized by the plaque formation in arteries, is one of the major factors
contributing to incidence of stroke and myocardial infarction. It is caused by high level of
lipoprotein and cholesterol in plasma [37]. High intake of citrus avonoids reduces several
risk factors for development of atherosclerosis including: high tolerance to glucose, maintain-
ing good body mass index, and lowering blood pressure [44].
In another study, patients with metabolic syndrome had reduced cholesterol and ApoB due
to the intake of a supplement of hesperidin for 3 weeks [45]. Furthermore, in a 2012 clinical
study performed in our laboratory on patients with metabolic syndrome diagnosed, after 4 or
6 months drinking a citrus fruit juice, the glycemic prole was unchanged but the lipid prole
improved, as observed by decrease in the cholesterol, LDL-C, and C-reactive protein [46].
Naringenin plays an important role to overcome the metabolic problem that is connected to
dyslipidemia and resistance to insulin. It was shown to prevent atherosclerosis development
in mice fed a high fat diet. Naringenin treatment aenuated the adverse eects caused by
hyperinsulinemia and hyperlipidemia which was induced by western style diet. In mice that
were fed a western diet, hyperlipidemia led to development of atherosclerosis in the aortic
sinus evidenced by the development of plaque is that increased 10 times as compared to chow-
fed animals. Naringenin treatment decreased the incidence of atherosclerosis by 70% [44].
Citrus - Health Benefits and Production Technology6

A clinical study with 500 mg of naringin plus 800 mg of hesperidin did not show a signi-
cant improvement in the lipid prole in patients with moderate hypercholesterolemia. This
study suggests that citrus avonoids have no eect on LDL-C in humans, at least not when
consumed in a capsule format [47]. A plausible explication of this results could be the inter-
individuals variability of pharmacokinetic parameters. Despite preclinical results are clearer,
further clinical studies need to be performed.
2.3. Citrus and diabetes
Diabetes is a chronic disease in which metabolic alterations of multiple etiologies character-
ized by chronic hyperglycemia and disorders in the metabolism of carbohydrates, fats, and
proteins occur. These alterations are the result of defects in the secretion of insulin, in the
action itself or in both. The long-term manifestation of insulin results in damage and dysfunc-
tion of various organs like nerves, kidneys, eyes, blood vessels, and heart. People living with
diabetes have a higher risk of morbidity and mortality than the general population [48].
Diabetes is an important public health problem, one of four priority noncommunicable dis-
eases (NCDs) targeted for action by world leaders. Both the number of cases and the preva-
lence of diabetes have been steadily increasing over the past few decades [49].
A recent report on diabetes by the World Health Organization estimates that 422 million cases
in 2014 [49], and an expected number of nearly 650 million subjects in 2040 was estimated [48].
This dramatic rise is largely due to type 2 diabetes (T2D).
The treatment of diabetes consists of pharmacological, dietary, and lifestyle measures. Many
trials have eectively tested dierent lifestyle and pharmacological intervention methods
both in terms of prevention and treatment [50].
The use of plants with antidiabetic properties is widely known and described in the scientic
literature. A lot of studies have reported that either plant parts or extracts of plant parts pos-
sess antidiabetic properties. This antidiabetic activity of plants is due to the presence of phy-
tochemicals which are termed as avonoids. In this way, several studies reported antidiabetic
activities of avonoids [51, 52].
Citrus fruits are one of the most consumed fruits mainly as fresh or raw materials for juices.
Additionally, citrus fruits can also be used in the food, beverage, cosmetic, and pharmaceuti-
cal industries [53].
Citrus fruits show several bioactivities of vital importance to human health, like antioxidative
and anti-inammatory activity, cardiovascular protective eects, antidiabetic activity, among
others. Citrus species contain a number of secondary metabolites, such as avonoids, alka-
loids, coumarins, limonoids, carotenoids, phenol acids, and essential oils [53]. Of all of them,
avonoids (especially avanone, avanonol, and methoxylated avones) are more active
compared to other secondary metabolites in citrus for their remarkable various bioactivities.
There are a lot of studies where have been widely reported on plentiful bioactivities from
avonoids.
Citrus and Health 7

Flavonoids, a group of natural substances with variable phenolic structures, are well known
for their benecial eects on health. Flavonoids are now considered as an indispensable com-
ponent in a variety of nutraceutical, pharmaceutical, medicinal, and cosmetic applications
[54]. Flavonoids are distinct based on structural characteristics in the following six subclasses:
avonols, avones, isoavones, avanones, anthocyanins, and avanols (catechins and pro-
anthocyanidins) [6]. In Citrus genus, avanones comprise approximately 95% of the total
avonoids, and these foods are the main source of avanones [6].
Citrus avanones are glycosylated in vegetables. The same aglycone can be combined with
several glycosides to give dierent avanones; for example, the most representative a-
vanones in grapefruit are narirutin and naringin, those in orange fruit are hesperidin and
narirutin, and that in lemon is eriocitrin [6]. Naringin, naringenin, nobiletin, narirutin, and
hesperidin are the most important avonoids thus far isolated from citrus fruits [35].
There has been a substantial body of evidence suggesting that oxidative stress is a key
mechanism in pathogenesis of diabetes. Flavanones and avanones-rich botanical extracts
have been a subject of great interest for scientic research. Citrus avanones like naringin
and hesperidin exert a variety of biological activities such as antioxidant, anti-inammatory,
antihyperglycemic, antiapoptotic, etc. Naringin and hesperidin along with their respective
aglycones, naringenin, and hesperetin have been shown to aenuate diabetes and its related
complications [55]. In this way, Ashafaq et al. [56] demonstrated that hesperidin treatment
signicantly aenuated the altered levels of oxidative stress and neurotoxicity biomarkers.
Their results demonstrate that hesperidin exhibits potent antioxidant and neuroprotective
eects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model.
Iskuender et al. observed that after administration of hesperidin and quercetin in STZ-induced
diabetic rats, glucose levels increased and liver and kidney damage markers decreased sig-
nicantly [57]. In the same way, Akiyama et al. [50] demonstrated that hesperidin normalizes
blood glucose by altering the activity of glucose-regulating enzymes, and lowering serum and
liver lipid levels in STZ-induced marginal type 1 diabetic rats without any body weight loss
due to STZ injection. Thus, hesperidin showed both hypoglycemic and hypolipidemic eects.
In a study, Gupta et al. [58] demonstrate the dipeptidyl peprtidase-4 (DPP-4) inhibition activ-
ity of citrus bioavonoid nutraceuticals as compared to known gliptins (oral antidiabetic
agents). The naringin and hesperidin compounds have the best individual activity in com-
parison to that of the gliptins. Natural gliptin-like alternatives may make these supplements a
promising group of natural products for use in improving blood glucose levels in prediabetes
and early stages of type 2 diabetes.
The hypoglycemic eect of naringin and naringenin is very well documented in animal and
cell studies. So, naringin (30 mg/kg) and vitamin C (50 mg/kg) cotreatment ameliorated strep-
tozotocin-induced diabetes in rats by improving insulin concentration and prevented oxida-
tive stress [59]. Naringenin supplementation (0.2 g/kg of diet) improved glucose intolerance
and insulin resistance in a model of high-fat-diet-fed mice [59]. More research is needed to
determine the mechanism by which naringenin has hypoglycemic eect. So far, some authors
have suggested the following: that is mediated via uptake of glucose in the skeletal muscle
[60]; increased activities of hexokinase [61]; decreased production and expression of IL-1b,
IL-6, and MCP-1 [62].
Citrus - Health Benefits and Production Technology8

Rutin is another avonoid present in citrus fruits to which many biological activities have
been aributed, among them having antihyperglycemic properties. In 2017, Ghorbani [63] in
a review discussed the antihyperglycemic property of rutin. Proposed mechanisms for this
eect include a decrease of carbohydrates absorption from the small intestine, inhibition of
tissue gluconeogenesis, an increase of tissue glucose uptake, stimulation of insulin secretion
from beta cells, and protecting Langerhans islet against degeneration. Rutin also decreases
the formation of sorbitol, reactive oxygen species, advanced glycation end product precur-
sors, and inammatory cytokines.
In conclusion, it can be armed that avonoids are useful in the prevention and treatment of
diabetes, especially in diabetes type 2, as Xu et al. [64] arm the meta-analysis of prospective
cohort studies carried out in 2018. Now, more studies are needed to elucidate the mechanism
or mechanisms by which they carry out this antidiabetic activity.
2.4. Citrus and neurodegenerative diseases
Neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease
represent rapidly growing causes of disability and death, which have profound economic and
social implications; nonetheless, only few eective disease-modifying therapies are available
for these diseases [65, 66].
Citrus avonoids exert lile adverse eect and have low or no cytotoxicity to healthy, nor-
mal cells. The main citrus avonoids can also traverse the blood-brain barrier; hence, they
are promising candidates for intervention in neurodegeneration and as constituents in brain
foods [67].
Assessment of cognitive performance in middle-aged individuals has indicated that con-
sumption of dierent polyphenols such as catechins, avonols, and hydroxybenzoic acids is
strongly associated with language and verbal memory. Hydroxycinnamates, phenolic acids,
and phenolic alcohol are also capable of inducing neuroprotective eects in the same way as
avonoids [68].
Naringenin and hesperidin are abundant polyphenols in citrus fruits and have been shown to
have protective eects in Huntington’s disease due to their mechanism of nitric acid against
3-nitropropionic acid, which presents neurotoxicity in experimental models with rats [69].
5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyavone (HHMF) from the Citrus genus and nobiletin,
the most abundant polymethoxyavone in orange peel extract are compounds that enhance
neuronal survival and exerted prosurvival action in PC12 cells [70].
Ushikubo et al. [71] demonstrated that 3,3′,4′,5,5′-pentahydroxyavone prevents Aβ bril for-
mation and that lowering bril formation decreases Aβ-induced cell death in rat hippocampal
neuronal cells. In another study, ursolic acid, p-coumaric acid, and gallic acid extracted from
Corni fructus plant were shown to aenuate apoptotic features such as morphological nuclear
changes, DNA fragmentation, and cell blebbing induced by Aβ peptide in PC12 cells [72].
The citrus avanones hesperidin, hesperetin, and neohesperidin are known to exhibit anti-
oxidant activities and could traverse the blood-brain barrier [73]. These authors showed
that hesperetin, hesperidin, and neohesperidin inhibited the decrease of cell viability (MTT
Citrus and Health 9

reduction), prevented membrane damage (LDH release), scavenged ROS formation, increased
catalase activity, and aenuated the elevation of intracellular free Ca2+, the decrease of mito-
chondrial membrane potential and the increase of caspase-3 activity in H2O2-induced PC12
cells. Meanwhile, hesperidin and hesperetin aenuated decreases of glutathione peroxidase
and glutathione reductase activities and decreased DNA damage in H2O2-induced PC12 cells.
These results rst demonstrate that the citrus avanones, such as hesperidin, hesperetin, and
neohesperidin, even at physiological concentrations, have neuroprotective eects against
H2O2-induced cytotoxicity in PC12 cells. These dietary antioxidants are potential candidates
for use in the intervention for neurodegenerative diseases.
Antunes et al. [74] demonstrated that hesperidin (50 mg/kg) treatment was eective in
preventing memory impairment in the Morris water maze test, as well as depressive-like
behavior in the tail suspension test. Hesperidin aenuated the 6-OHDA-induced reduction
in glutathione peroxidase and catalase activity, total reactive antioxidant potential, and the
dopamine and its metabolite levels in the striatum of aged mice. This study demonstrated a
protective eect of hesperidin on the neurotoxicity induced by 6-OHDA in aged mice, indicat-
ing that it could be useful as a therapy for the treatment of PD.
Chakraborty et al. [75] showed that hesperidin completely inhibits the amyloid bril forma-
tion which is further supported by atomic force microscopy. Hesperidin exhibited moderate
ABTS(+) radical scavenging assay but strong hydroxyl radical scavenging ability, as evident
from DNA nicking assay.
3. Conclusions
The Mediterranean diet, considered a good example of a prudent and healthy diet, has under-
gone important changes in recent years. Factors such as urbanization, pollution, economic
development, excessive working hours, and the adoption of inadequate lifestyles cause the
population to be exposed to environmental and nutritional factors associated with the onset
and progression of diseases related to aging. In this sense, citrus fruits are an important source
of bioactive compounds, powerful antioxidants whose health benets have been scientically
demonstrated in several studies for their protective role against oxidative damage. For this
reason, the regular consumption of citrus fruits should be promoted as part of a varied and
balanced diet. The absence of sucient scientic evidence and validated tests to reliably mea-
sure the antioxidant activity in vivo of the bioactive compounds present in citrus justies the
need of interventional studies in humans for the correct determination of bioactive properties
of citrus and their bioactive compounds.
Conict of interest
Authors declare that they do not have conict of interest.
Citrus - Health Benefits and Production Technology10

Author details
Javier Marhuenda*, Begoña Cerdá, Débora Villaño, Alejandro Galindo and Pilar Zafrilla
*Address all correspondence to: jmarhuenda@ucam.edu
Faculty of Health Sciences, Department of Pharmacy, UCAM, Murcia, Spain
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