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Beta Carotene -Therapeutic Potential and Strategies to Enhance its Bioavailability
Shankaranarayanan Jeyakodi1*, Arunkanth Krishnakumar1 and Dinesh Kumar Chellappan2
1ZeusHygia Life Sciences Private Ltd, India
2Department of Life Sciences, International Medical University, Malaysia
Submission: July 02, 2018;Published: September 07, 2018
*Corresponding author: Shankaranarayanan Jeyakodi, ZeusHygia LifeSciences Pvt Ltd, Department of Research and Development, TIE, Balanagar, Hyderabad, Telangana, India
How to cite this article: Shankaranarayanan J, Arunkanth K, Dinesh K C. Beta Carotene -Therapeutic Potential and Strategies to Enhance Its Bioavailability.
002 Nutri Food Sci Int J. 2018; 7(4): 555716. DOI:10.19080/NFSIJ.2018.07.555716.
Background: Beta-carotene is a natural carotenoid that usually occurs as pigments in the plant kingdom. Ample evidence is available in the literature suggesting beta-carotene could possibly lower the risk of stroke, heart diseases, aging, vascular and other metabolic diseases. This mini review in this direction, focusses on the biological importance of beta-carotene and the impact of various factors on their bioavailability.
Methods: The goal of this work is to do a mini review on the available literature for the various therapeutic properties of beta carotene and also the current strategies that exist to enhance the bioavailability of beta carotene. Electronically accessible databases were searched, and the findings were collated for analysis and interpretation of the results.
Results: Bioavailability of such substances has been a topic of interest for several decades. Digestive aids play a crucial role in increasing the bio-absorption for carotenoids like beta-carotene. Some of these are, the use of vesicular systems, alteration of the physical structure and nano-formulations.
Conclusion: Owing to its therapeutic potential, the bioavailability of carotenoids has recently been described by several authors. Various strategies and techniques have been proposed and developed which can enhance the systemic absorption of such compounds.
Over the years nutraceuticals always played significant roles in improving human health and wellbeing. Nutraceutical products attracted huge interest due to their potential nutritional and health benefits. Nutraceuticals could be used to prevent chronic diseases and is believed to increase our life expectancy. Nutraceuticals comprise of rich sources of bioactive molecules which directly or indirectly upregulate / downregulate the molecular signals and prevent or delay onset of chronic diseases like diabetes, cancer, infective diseases and cardiovascular diseases. Recent market analysis data of nutraceutical products reflects that, carotenoids occupy a significant market share. There are more than 600 known carotenoids, among which few are found in our regular diet, like beta-carotene, cryptoxanthin, lutein, lycopene, zeaxanthin, and astaxanthin . These group of compounds called carotenoids are primarily responsible for naturally painting certain vegetables and fruits with their rich, attractive eye-pleasing color.
Carotenoids are oil-soluble molecules. Most of these compounds are comprised of 40 branched carbon units bonded
together . Structurally, they're composed of conjugated double bonds. Carotenoids can absorb light and this property is depended on the chemical structure of the molecule. The amount of conjugated double bonds a carotenoid contain changes the wavelength of light that it can absorb and as a result it varies in color from red, orange, to yellow.
Carotenoids play a prominent role in protecting bodily cells and thereby act as powerful antioxidants. Moreover, they are proved to be vital for maintenance of proper eyesight and vision. There is a huge amount of published literature currently available on the mechanisms and roles of carotenoids in human health . One among these carotenoids, beta-carotene has been studied elaborately by several researchers. It is now known that beta-carotene is the primary precursor for Vitamin A in humans. Moreover, the positive roles of beta-carotene in maintaining a proper vision and its role in other degenerative diseases are now known. It is believed that consumption of required amounts of food products containing these carotenoids may help to deal with diseases concerned with deficiency of vitamin A . In addition to the above mentioned points, it is also worthwhile to mention here that several carotenoids are being currently developed as powerful
agents for the promotion of health and wellbeing.
Current literature has provided enough evidence to support
the claim that carotenoids are effective antioxidants. The
effective roles of these substances in preventing degenerative
diseases and other metabolic syndromes have renewed the
interest in carotenoids (Figure 1).
Carotenoids are classified into two major groups of
substances (Figure 1). They are classified based on their basic
moieties into carotenes and xanthophylls. The major compound
among carotenes is beta-carotene, which are structurally
made of cyclic hydrocarbons as one of their main components.
On the other hand, a major example for xanthophylls will be
Among carotenoids, beta carotene is the most commonly
found substance in dietary supplements . Majority of the
colours in fruits and plants are primarily due to this particular
pigment. In Latin, the word ‘carotene’ stands for carrot. This is
the origin of the present name. Apart from this, beta-carotene
also is used as a coloring agent in several food products.
It is reported that these carotene compounds act as
primary products in our body to produce vitamin A. Thus,
these substances are also called as pro-vitamin A and thereby
function as precursors. Studies have found out that majority
of the vitamin A in our diet comes from these carotenoids
like beta-carotene. On the other hand, there are also other
sources for beta-carotene. This can be manufactured as a
synthetic compound in laboratories or also can be isolated
from different fungi or algal sources. Palm oil is another
rich product containing beta-carotene. There are several
glycoproteins that are formed from vitamin A, and these play
a major role in humans for proper vision and eyesight. From
these glycoproteins are then produced retinoic acid, which is
essential in normal growth and cellular differentiation (Figure
Although, vitamin A can be beneficial for better eyesight,
better night vision, for better immunity and for a glowing skin,
it could be dangerous if consumed in excess . Human bodies
have a threshold of how much vitamin A is manufactured.
This purely depends on the bodily and metabolic needs.
Not all carotenoids can give raise to vitamin A. A number of
carotenoids like lutein and lycopene cannot act as a precursor
for vitamin A. Several studies have shown that beta-carotene,
in addition to its effects on vision, also functions as a potent
free radical scavenger. It is now known that much of the damage
to the cells internally is caused by free radicals and sources of
free radicals through oxidative reactions. Chronic exposure to
damaging oxidative radicals can allow several diseases in the
body. A number of authors have mentioned that antioxidants
and free radical scavengers can enhance immunity and shield
our bodies from several diseases .
There has been an extensive number of studies carried
out and research papers published on the health benefits of
beta carotene. Some of the therapeutic benefits based on the
research data published have been summarized here. The
USFDA approved beta-carotene as an effective therapy for
erythropoietin protoporphyria. Several research studies
conducted on animals have reported the anticancer activity
of β-carotene [8-11]. There is plenty of evidence now that
suggests carotenoids or food products rich in carotenoids are
indeed beneficial in the prevention of several types of cancers
and malignancies. Certain types of cancers namely, the cancers
of prostate gland, urinary bladder and of the colon respond to
a natural substance called lycopene. This substance is found
in abundance in tomatoes. It was as early as in the 1960s when
the initial findings of vitamin A as an anticancer agent started
surfacing out. Subsequently, these findings led scientists and
researchers to investigate on the anticancer potential of betacarotene,
as this substance was the precursor. There are two
different studies that were conducted respectively in 1973
and in 1977, proved that beta-carotene itself had anticancer
properties. The first study carried out by Dorogokupla and the
second by Epstein, both showed that there was a reduction in
the tumor size when supplemented with beta-carotene. The
positive control groups and placebo groups which were not
administered with beta-carotene showed the reverse. Both
these studies were carried out on rodents. These studies
proved that beta-carotene was effective in controlling cancers.
Recent research conducted in the last two decades revealed the tumour controlling activity of beta-carotene in several tumor models that were tested. The mechanism of action of
beta-carotene was later hypothesized, suggesting that, these
substances bring about their therapeutic potential primarily
through their free radical scavenging activity. This also
corroborates with the earlier findings that suggested that
beta-carotene has potent antioxidant potential.
Beta-carotene is found in most vegetables and fruits. Thus
a number of studies have already been done on beta-carotene
as a free radical scavenging agent. The studies have proved
to be significant in terms of its antioxidant effect. Several in
vivo studies done on animal models and other in vitro studies
have shown that carotenoids as antioxidants have the ability
to prevent chronic conditions. It was also found that the free
radical scavenging activity of carotenoids was enhanced when
combined with several other antioxidants like vitamin E.
However, some studies involving animal models have reported
that the pattern of metabolizing such carotenoids are different
in animals from humans, and thus the findings may not be
One of the major vitamins that is required by our human
bodies is vitamin A. Beta-carotene acts as a precursor for the
production of vitamin A in our bodies. Thus it is also referred
to as provitamin A. Vitamin A plays a major role in the normal
functioning of our eyes, especially in the production of several
pigments in the retina that helps with photoreception and
night vision. Several problems arise when the body does not
get the required amounts of vitamin A. This could be ranging
from ocular degeneration to conditions like keratomalacia.
Carotenoids like beta-carotene and lycopene have also
been proved to prevent cardiovascular diseases. The risk of
developing a cardiovascular disease and stroke is drastically
reduced when sufficient vegetables and fruits rich in
carotenoids are incorporated in the daily diet . There are
extensive studies done on the effects of carotenoids on stroke.
However, there are no confirmatory studies or trials yet that
prove that carotenoids protect the body from stroke. There are
assumptions that carotenoids may protect the blood vessels
from stroke as several studies have reported the reduced
levels of homocysteine when tested with certain carotenoids
and vitamins. Currently there is a clinical trial that is been
carried out on a larger scale to study the effects of carotenoids
on brain health and stroke [14-18].
Beta-carotene has been also studied for treating
sun sensitivity. This condition called as erythropoietic
protoporphyria, causes severe sensitivity to sunlight, which is
painful. However, consuming large amounts of beta-carotene
will render people with a decreased sensitivity towards
sunlight. The consumption of beta-carotene is gradually
tapered down over a certain period of time duration .
In one of the studies conducted among elderly males,
it was found out that the ones who consumed a diet with
beta-carotene and other carotenoids had a very less risk
of developing diabetes and cardiovascular disorders. Such
disorders are categorized under an umbrella term called
metabolic syndrome. In general, this is defined as symptoms
that are caused by problems associated with our metabolism.
Metabolic syndrome primarily constitutes diabetes,
cardiovascular disorders and lipid issues in the body. From
the study it was also found that the participants had decreased
lipid levels .
In another study involving participants with a condition
termed as leukoplakia showed less number of symptoms
when they consumed beta-carotene. On the other hand,
people with same condition when they consumed placebo, the
effects were discouraging. Leukoplakia is a condition usually
found in people who are chronic smokers or alcoholics. It is
characterized by white lesions in the oral cavity. However, it
is cautioned that people should take the advice of a physician
before consuming beta-carotene for this condition, as this
could be associated with other risks as well .
Scleroderma is another condition which is portrayed by
skin that is hardened. The condition also affects the connective
tissues in the body. It is reported that this condition might arise
when the levels of beta-carotene in the body gets lower than
the required amounts. Researchers have significant evidence
to prove that beta-carotene products can help people with
this condition. However, more large scale studies are required
before this can be formalised .
In a study conducted at the Harvard Medical School,
involving 4,052 males, reported that longer consumption
of beta-carotene on a regular basis have resulted in less
probability for the participants to get mental slowdown
or retardation. However, these results are observed only
in participants who were on long term beta-carotene
consumption. On the other hand, short term consumption,
between the beta-carotene group and the placebo group, did
not show any significant changes .
There are various factors that come into play with regards
to the bio-absorption of beta-carotene. These include the
source of the product, process of extraction or isolation,
quality and purity of the final product, cross interactions
with other food substances in the system and the factors
concerning the individual . Carotenoids are known to
be absorbed by duodenal mucosal cells by passive diffusion.
Several other physico-chemical factors namely, particle size,
flow properties, rheology, interaction with other additives and
complexation also affect the bioavailability of beta-carotene.
Biological barrier interactions also play a major role in the
uptake of these substances .
There are several other factors that can affect the
biosorption of beta-carotene. These could be the procedure or method how the food was prepared, and the ingredients used.
Other factors related to diet like the amount of beta-carotene,
amount of preformed vitamin A, presence of other carotenoids
while preparation also play a major role [23-26]. It is reported
that biosorption of beta-carotene is higher with fruits and
red palm oil, whereas, with food products containing complex
food matrices, the biosorption is observed to be lower . It
is worthwhile to note here that, for beta-carotene to be bioabsorbed,
it needs to be first dismantled and released from the
food matrix. Different cooking methods affect the release and
absorption of beta-carotene into the system. Bioavailability
can also be increased by making the food homogenized [27-29].
In human beings the bioavailability of pure beta-carotene
is reported to be in the range of 8.7% to 65%. The interactions
of plant material with micelle formation affects drastically
the bioavailability of beta-carotene from natural products
like fruits, vegetables and other natural sources. The first
assessment on the bioavailability of beta-carotene was done
on two hospitalized patients by administering them with
radiolabeled beta-carotene. Radioactivity was measured
later in these patients which gave an approximate idea on the
amount of bioavailability .
Cheng et al.,  have studied the possibility of an oral
delivery system in the form of a microemulsion that could
be suitable to deal with the difficulties and complications
of delivering poorly aqueous soluble beta-carotene .
Microemulsions are usually comprised of an oily phase like
natural oils, edible hydrocarbons or synthetic oil mixture
of triglycerides with various chain length and saturation
degrees. These also comprise of surfactants for which the
molecular structure is mainly composed of a hydrophilic
group, a hydrophobic group and a water phase, which include
water and aqueous co-solvents. Incorporating beta-carotene
into an oil-in-water ME as a functional beverage has several
(1) solubilizing the poorly water-soluble beta-carotene.
(2) protecting beta-carotene from enzymatic degradation
following oral administration.
(3) forming a thermo-dynamically stable product with a
(4) improving the beta-carotene bioavailability by
(5) enhancing epithelial permeability through the use of
surfactants such as medium-chain fatty acids .
In another work, researchers studied the possibility of
microencapsulation methods to improve the release and
bioavailability of beta carotene in vitro. In this study, alginate
and chitosan-based formulations were evaluated . A
double-blind crossover study involving human subjects was
studied for the effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98.0% pure alkaloid
piperine, for its ability to improve serum response of betacarotene
during oral supplementation . In another study,
the effect of citric pectin on the bioavailability of synthetic
beta-carotene was studied. The authors conclude that 7%
citric pectin in the rat diet decreased the bioavailability of
synthetic beta-carotene, reducing the liver reserves of vitamin
A and beta-carotene .
Beta-carotene contains 40 carbons with 15 conjugated
double bonds and 2 β-ionone rings at both ends of the molecule.
These structural properties make beta-carotene highly
hydrophobic and non-polar in nature.
In adult tissues, beta-carotene-15,15′-oxygenase (CMOI)
is the main cytosolic enzyme that cleaves β-carotene to
generate vitamin A in vivo [36-38]. Dietary fats, lipids and
lipid-soluble vitamins, including β-carotene, are absorbed
by the small intestine and then subsequently deliver them to
the peripheral tissues for consumption. Although, the human
intestines abundantly express the main β-carotene cleavage
enzyme CMOI, complete intestinal conversion of all of the
ingested β-carotene to vitamin A practically does not occur. As
discussed above, the bioavailability of β-carotene, apart from
genetic factors seems to be also affected by the nature of food
matrix, type of preparation, fat content of the diet, type of fat,
digestibility of fat-soluble components in the diet, bile acids,
interactions with other carotenoids and individual variations
due to endogenous activity of the digestive enzymes [39-42].
Both carotenes and xanthophylls are insoluble in water
whereas in fats and oils a likewise only low solubility is found.
This restricted solubility and also the high sensitivity to
oxidation are an obstacle to direct application of the relatively
coarse-grained products obtained by chemical synthesis
in the coloring of foods and feeds, since the substances in
coarsely crystalline form are not storage-stable and give only
poor coloring results. Beta-carotene holds unique properties
as a colorant, physiological antioxidant and provitamin A. This versatility means that it is used across many different segments, which include food, feed, supplements, cosmetics and
colorants. To overcome the drawbacks of pure beta-carotene
and make it viable commercially, various formulation designs
were developed ensuring the product stability, solubility and
bioavailability. Each segment demands different properties
and stability of the beta-carotene formulations, which has led
to the development of following major product groups like oil
suspensions, powders, beadlets and emulsions (Figure 3).
Oil suspensions of beta carotene formulation have
been widely used in the nutraceutical industry. Various
concentrations of oil suspensions like 30%w/w to 10%w/w
with bio-enhancers and solubilizers are marketed which
shows relatively higher bioavailability than the raw synthetic
beta carotene. These suspensions are manufactured with
micronized beta carotene suspended in natural oil along with
stabilizing and solubilizing agents.
Powders are another significant group of beta carotene
formulation commercially available. Powders carry the
handling advantages and ease of manufacturing compared to
oil suspensions. Fine micronized grade of beta carotene are
prepared majorly by adopting spray drying techniques.
Finely pulverulent carotenoid preparations are produced
by dissolving a carotenoid in a volatile water-miscible
organic solvent at elevated temperatures, if necessary at
elevated pressure, precipitating the carotenoid by mixing
the solution with an aqueous solution of a protective colloid
and subsequently spray drying the solution as disclosed in
European patent EP-B-0 065 193.
Most of the carotenoids, including beta-carotene and other
carotenes, are relatively water insoluble and have also have
high melting points. In the presence of an aqueous phase like
water, they become highly sensitive to oxidation. The usual
technique adapted to make it more water-dispersible is to
formulate beta-carotene as a water-dispersible beadlet. These
beadlets can be prepared by dissolving beta-carotene in a
water-miscible organic solvent . This could be followed by
mixing the dissolved beta-carotene with an aqueous solution
of a swellable colloid, like gelatin, then precipitating the
β-carotene in a colloidally dispersed form and finally drying
the colloidal dispersion.
Oil in water emulsions are another beta carotene
formulation system used in the food, beverages and diary
industries. Conventional homogenization techniques,
including high-speed shearing, ultrasonic treatment, high
pressure valve homogenization, etc. are widely applied to
make beta-carotene emulsions. Among all the techniques,
high pressure homogenization is the most used technique
both in laboratories and industries, and emulsions with
different particle size ranges can be produced depending on
the pressures that the homogenizers can generate.
The bioavailability of the ingested nutrient is partially
determined by its bio-accessibility, which is generally defined
as the fraction of the ingested nutrient that is incorporated into
the mixed micelles and thus becomes available for absorption
in the body. The bio accessibility of beta carotene formulations
is majorly influenced by the emulsion droplet size digestive
oils, emulsifying agents. Hence during the formulation these
factors are taken care of to ensure desired bioavailability.
Among the carotenoids, Beta-carotene is a precursor
for vitamin A and essential for human health. Beta-carotene
has been used widely in food, feed and other nutraceuticals
commercially. Amidst the various therapeutic benefits of betacarotene,
it has got many drawbacks like poor bioavailability
and its degradation tendency on exposure to light, heat and
oxygen. Abundant studies and research were carried out
to design delivery systems for beta-carotene to improve its
bioavailability and chemical stability, and finally to enhance
the functionality. However, the demands for beta-carotene
formulations are on the rise, so are the research to address its
functional draw backs.