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Global Journal of Medical research: k
Interdisciplinary
V
olume 14 Issue 3 Version 1.0 Year 2014
Type: Double Blind Peer Reviewed International Research Journal
Publisher: Global Journals Inc. (USA)
Online ISSN: 2249-4618 & Print ISSN: 0975-5888
Pote
ntial Health Benefits and Adverse Effects Associated with
Phytate in Foods: A Review
By
H
abtamu Fekadu Gemede
A
ddis Ababa University, Ethiopia
A
bstract-
P
hytate (myo-inositol (1,2,3,4,5,6) hexakis -
phosphate), a naturally compound formed during
maturation of plant seeds and grains is a common constituent of plant-derived foods. This paper is aimed
to review the scientific information concerning the potential health benefits and adverse effects associated
with phytate in foods. The adverse health effects of phytate in the diet is its effect on mineral uptake.
Minerals of concern in this regard would include Zn2+, Fe2+/3+, Ca2+, Mg2+, Mn2+, and Cu2+.
Especially zinc and iron deficiencies were reported as a consequence of high phytate intakes. In addition,
a the adverse effect on the nutritional value of protein by dietary phytate is discussed. Consumption of
phytate, however, seems not to have only adverse health effects but also potential benefits on human
health. Dietary phytate was reported to prevent kidney stone formation, protect against diabetes mellitus,
caries, atherosclerosis and coronary heart disease as well as against a variety of cancers.
Ke
ywords: antinutrient, phytate, health benefits, health effects, human nutrition.
GJMR-K C
lassification: NLMC Code: QU 50
PotentialHealthBe
nefitsandAdverseEffectsAssociatedwithPhytateinFoodsAReview
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2014. Habtamu Fekadu Gemede. This is a research/review paper, distributed under the terms of the Creative Commons
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P
otential Health Benefits and Adverse Effects
Associated with Phytate in Foods: A Review
Ha
btamu Fekadu Gemede
A
bstract-
P
hytate (myo-inositol (1,2,3,4,5,6) hexakis -
phosphate), a naturally compound formed during maturation
of plant seeds and grains is a common constituent of plant-
derived foods. This paper is aimed to review the scientific
information concerning the potential health benefits and
adverse effects associated with phytate in foods. The adverse
health effects of phytate in the diet is its effect on mineral
uptake. Minerals of concern in this regard would include
Zn2+, Fe2+/3+, Ca2+, Mg2+, Mn2+, and Cu2+. Especially
zinc and iron deficiencies were reported as a consequence of
high phytate intakes. In addition, a the adverse effect on the
nutritional value of protein by dietary phytate is discussed.
Consumption of phytate, however, seems not to have only
adverse health effects but also potential benefits on human
health. Dietary phytate was reported to prevent kidney stone
formation, protect against diabetes mellitus, caries,
atherosclerosis and coronary heart disease as well as against
a variety of cancers.
K
eywords
:
a
ntinutrient, phytate, health benefits, health
effects, human nutrition.
I.
I
ntroduction
hytate (is also known as Inositol hexakis -
phosphate (InsP6)) is the salt form of phytic acid,
are found in plants, animals and soil. It is primarily
present as a salt of the mono- and divalent cations K+,
Mg2+, and Ca2+ and accumulates in the seeds during
the ripening period. Phytate is regarded as the primary
storage form of both phosphate and inositol in plant
seeds and grains [1]. In addition, phytate has been
suggested to serve as a store of cations, of high energy
phosphoryl groups, and, by chelating free iron, as a
potent natural anti-oxidant [2,3].
Phytate is ubiquitous among plant seeds and
grains, comprising 0.5 to 5 percent (w/w) [1]. The
phosphorus bound to phytate is not typically bio-
available to any animal that is non-ruminant. Ruminant
animals, such as cows and sheep, chew, swallow, and
then regurgitate their food. This regurgitated food is
known as cud and is chewed a second time. Due to an
enzyme located in their first stomach chamber, the
rumen, these animals are able to separate, and process
the phosphorus in phytates. Humans and other non-
ruminant animals are unable to do so [4].
Ph
ytate works in a broad pH-region as a highly
negatively charged ion, and therefore its presence in the
diet has a negative impact on the bioavailability of dival -
ent, and trivalent mineral ions such as Zn2+, Fe2+/3+,
Ca2+, Mg2+, Mn2+, and Cu2+ [6]. Whe -ther or not
high levels of consumption of phytate-containing foods
will result in mineral deficiency will depend on what else
is being consumed. In areas of the world where cereal
proteins are a major and pred -ominant dietary factor,
the associated phytate intake is a cause for concern
[27].
Besides, phytate has also been reported to
form complexes with proteins at both low, and high pH
values. These complex formations alter the protein
structure, which may result in decreased protein solub -
ility, enzymatic activity, and proteolytic digestibility. The
phytate degrading enzyme, phytase, is in vogue for
degradating phytate during food processing, and in the
gastrointestinal tract. The major concern about the
presence of phytate in the diet is its negative effect on
mineral uptake [28]. Phytate markedly decrease Ca
bioavailability, and the Ca:Phy molar ratio has been
proposed as an indicator of Ca bioavailability. The
critical molar ratio of Ca: Phy is reported to be 6:1 [29].
In human studies, Phy:Zn molar ratios of 15:1 have been
associated with reduced zinc bioavailability, and the
molar ratio [Ca][Phy]/[Zn] is a better predictor of zinc
availability, because calcium exacerbates phytate’s
effect on zinc absorption, and if the values were greater
than 0.5 mol/kg, there would be interference with the
availability of zinc [30].
F
igure 1 : Structure of Phytate (Insp6), empirical
formula=C6P6O24H18
P
Global Journal of
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Research
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Year
2014
A
uthor : Center for Food Science and Nutrition, Addis Ababa
University, Addis Ababa, Ethiopia. Food Technology and Process
Engineering Department, Wollega University, Nekemte, Ethiopia.
e-mails:fekadu_habtamu@yahoo.com, simbokom@gmail.com
A
t the same time, phytate may have beneficial
roles as an Antioxidant, and Anticarcinogen [31]. The
outcome of surveillance of populations consuming veg -
etarian-type diets has shown lower incidence of Cancer,
which suggests that phytate has an Anticarcinogen
effect [32]. Dietary phytate may have health benefits for
Diabetes patients because it lowers the blood glucose
response by reducing the rate of starch digestion and
slowing gastric emptying. Likewise, phytate has also
been shown to regulate Insulin secretion [33]. It is
believed that phytate reduces Blood clots, Cholesterol,
and Triglycerides, and thus prevents Heart diseases. It
is also suggested that it prevents renal stone develop -
pment. It is used as a complexing agent for rem -oval of
traces of heavy metal ions [34].
Depending on the amount of plant-derived
foods in the diet, and the grade
of food processing, the
daily intake of phytate can be as high as 4500 mg. On
average, daily intake of phytate was estimated to be
2000–2600 mg for vegetarian diets as well as diets of
inhabitants of rural areas in developing countries, and
150–1400 mg for mixed diets [35, 37. 38]. Among the
cooking treatments boiling appeared effective to reduce
the phytate level, which could reduce as high as 20% of
phytate [36, 39]. However, the updated information on
health benefits and adverse effects of phytate in foods is
scant. Therefore, the objective of this review is to assess
updated scientific information of the potential health
benefits and adverse effects associated with phytate in
foods.
II.
A
d
ver
s
e
H
e
al
th
E
ffe
ct
s
of
P
h
yta
te
T
he major concern about the presence of phytate in
the diet is its negative effect on mineral uptake. Minerals
of concern in this regard would include Zn2+,
Fe2+/3+, Ca2+, Mg2+, Mn2+, and Cu2+ [13,14], but
also a negative effect on the nutritional value of protein
[5,7].
a)
E
f
fect
on mineral uptake
Phyta
te forms complexes with numerous
divalent and trivalent metal cations. Stability and solu -
bility of the metal cationphytate complexes depends on
the individual cation, the pH-value, the phytate:cation
molar ratio, and the presence of other compounds in the
solution [15]. Phytate has six reactive phosphate groups
and meets the criterion of a chelating agent. In fact, a
cation can bind to one or more phosphate group of a
single phytate molecule or bridge two or more phytate
molecules [3, 40]. Most phytates tend to be more
soluble at lower compared to higher pH-values [16].
Solubility of phytates increase at pH-values lower than
5.5-6.0 with Ca2+, 7.2-8.0 with Mg2+ and 4.3-4.5 with
Zn2+ as the counter ion. In contrast, ferric phytate is
insoluble at pH values in the range of 1.0 to 3.5 at
equimolar Fe3+ : phytate ratios and solubility increases
above pH 4 [17]. Another important fact is the
synergistic effect of secondary cations, among which
Ca2+ has been most prominently mentioned [18, 41].
Two cations may, when present simultaneously, act
jointly to increase the quantity of phytate precipitation.
For example, Ca2+ enhanced the incorporation or
adsorption of Zn2+ into phytate by formation of a
calcium-zinc phytate. The effect of Ca2+ on the amount
of Zn2+ co-precipitating with phytate is dependent on
the Zn2+ : phytate molar ratio. For high Zn2+ : phytate
molar ratios, Ca2+ displaces Zn2+ from phytate bin -
ding sites and increases its solubility. The amount of
free Zn2+ is directly proportional to the Ca2+-conce -
ntration. For low Zn2+: phytatemolar ratios, Ca2+
potentiate the precipitation of Zn2+ as phytate. Thus,
higher levels of Ca2+ result in a more extensive
precipitation of the mixed phytates. Mg2+ also has
been shown in vitro to potentiate the precipitation of
Zn2+ in the presence of phytate, however, Mg2+ has
been found to exert a less pronounced effect on Zn2+-
solubility than Ca2+ [18, 42].
The knowledge about the interaction of partially
phosphorylated myo-inositol phosphates with different
cations is limited. Recent studies have shown that myo-
inositol pentakis-, tetrakis- and trisphosphates have a
lower capacity to bind cations at pH-values ranging from
5.0 to 7.0 [19 ]. The capacity to bind cations was found
to be a function of the number of phosphate groups on
the myo-inositol ring. The cation-myo-inositol phosphate
complexes are more soluble as the number of phos -
phate groups decreases. There is also some evid -ence
for weaker complexes when phosphate groups are
removed from phytate. In addition, the binding affinity of
cations to myo-inositol phosphates has been shown to
be affected by the distribution of the phosphate residues
on the myo-inositol ring.
The formation of insoluble metal cation-phytate
complexes at physiological pH-values is regarded as
the major reason for a poor mineral availability, because
these complexes are essentially non-absorbable from
the gastrointestinal tract. Most studies have shown an
inverse relationship between phytate content and
mineral availability, although there are great differences
in the behaviour of individual minerals. Zn2+ was
reported to be the essential mineral most adversely
affected by phytate [13,14]. Zn2+ deficiency in humans
was first reported in 1963 in Egyptian boys whose diets
consisted mainly of bread and beans [20, 43]. These
patients, who were characterised by dwarfism and hy -
pogonadism, showed a response to dietary Zn2+
supplementation. It became accepted that the presence
of phytate in plant-based foods is an important factor in
the reduction of Zn2+ absorption.
Phytate affects Zn2+ absorption in a dose-
dependent manner. There is, however, some lack of
agreement among studies, particularly with respect to
specific foods and their individual components. In
addition, phytate was shown not only to depress the
P
otential Health Benefits and Adverse Effects Associated with Phytate in Foods: A Review
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Medical
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a
vailability of dietary Zn2+, but also to affect Zn2+
homeostasis negatively [15]. A great deal of controversy
exists regarding the effect of phytate on the availability
of dietary iron [14, 21]. Much of this controversy may be
due to the low absorption of iron in general, the
presence of different iron-phytates with different solu -
bility, and the existence of two types of food iron, heme
and nonheme iron.
Heme iron is better absorbed and its absorption
is little affected by dietary factors; nonheme iron,
however, is less easily absorbed, and its absorption is
affected by other dietary factors. Since many human
studies indicate that phytate has a very strong inhibitory
effect on iron absorption, it is well accepted today, that
phytate appears to be the major but not the only
contributor to the reduction in iron availability in man [22,
44]. Human studies also indicated that phytate inhibits
Ca2+ absorption, but the effect of phytate on Ca2+
availability seems to be less pronounced compared to
that on the availability of iron and particularly Zn2+ [7,
14]. This may be due to the relatively high Ca2+ content
of plant-based foods, the capability of the bacterial flora
in the colon to dephosphorylate phytate and the fact,
that Ca2+ could be absorbed from the colon [23].
Relatively few studies have dealt with the effects of
phytate on dietary Cu2+, Mn2+ and Mg2+ utilisation.
Phytate has been shown to decrease their bioavailability
in in vivo studies, but it appears that the effect of phytate
on Cu2+, Mn2+ and Mg2+ availability is less marked
than those for some other essential elements [13,14].
The fact that phytate phosphorus is poorly
available to single stomached living beings including
man was already demonstrated [24, 25]. Phosphorus is
absorbed as ortho-phosphate and therefore the utilis -
ation of phytate-phosphorus by single-stomached living
beings will largely depend on their capability to
dephosphorylate phytate. It was already shown, that the
human small intestine has only a very limited capability
to hydrolyse phytate [26] due to the lack of endogenous
phytate-degrading enzymes (phytases) and the limited
microbial population in the upper part of the digestive
tract.
b)
E
ff
e
ct on protein digestibility
Ph
ytate
interactions with proteins are pH-
dependent [5, 7]. At pH-values below the isoelectric
point of the protein, the anionic phosphate groups of
phytate bind strongly to the cationic groups of the
protein to form insoluble complexes that dissolve only
below pH 3.5. The α-NH2 terminal group, the ε-NH2 of
lysine, the imidazole group of histidine and guanidyl
group of arginine have been implicated as protein bin -
ding sites for phytate at low pH-values. These low pH
proteinphytate complexes are disrupted by the comp -
etitive action of multivalent cations. Above the isoelectric
point of the protein, both protein and phytate have a neg
-ative charge, but in the presence of multivalent cations,
however, soluble protein-cation-phytate complexes
occur. The major protein binding site for the ternary
complex appears to be the nonprotonated imidazole
group of histidine, but the ionized carboxyl group of the
protein are also suggested sites. These complexes may
be disrupted by high ionic strength, high (pH> 10), and
high concentrations of the chelating agents.
Phytate is known to form complexes with
proteins at both acidic and alkaline pH [5]. This inte -
raction may effect changes in protein structure that can
decrease enzymatic activity, protein solubility and
proteolytic digestibility. However, the significance of
protein-phytate complexes in nutrition is still under
scrutiny. Strong evidence exists that phytate-protein
interactions negatively affect protein digestibility in vitro
and the extent of this effect depends on the protein
source [5]. A negative effect of phytate on the nutritive
value of protein, however, was not clearly confirmed in
studies with simple-stomached animals [7, 45]. While
some have suggested phytate does not affect protein
digestibility, others have found an improvement in amino
acid availability with decreasing levels of phytate. This
difference may be at least partly due to the use of
different protein sources. Of nutritional significance
might be also the inhibition of digestive enzymes such
as α-amylase [46,47], lipase [48] or proteinases [49,51],
such as pepsin, trypsin and chymotrypsin, by phytate as
shown in in vitro studies. The inhibitory effect increases
with the number of phosphate residues per myo-inositol
molecule and the myo-inositol phosphate concentration.
This inhibition may be due to the non-specific nature of
phytateprotein.
interactions, the chelation of calcium ions which
are essential for the activity of trypsin and α-amylase, or
the interaction with the substrates of these enzymes.
The inhibition of proteases may be partly responsible for
the reduced protein digestibility. Phytate has also been
considered to inhibit α-amylase in vivo as indicated by a
negative relationship between phytate intake and blood
glucose response [50, 52].
III.
B
e
neficial
H
e
alth
E
ffe
cts of
P
h
yate
In the view of the above results, the evidence
seems overwhelming that high intakes of phytate can
have adverse effects on mineral uptake in humans. In
the last years, however, some novel metabolic effects of
phytate or some of its degradation products have been
recognised. Dietary phytate was reported to prevent
kidney stone formation [8], protect against diabetes
mellitus [9], caries [10], atherosclerosis and coronary
heart disease [11] as well as against a variety of cancers
[12]. The levels of phytate and its dephosphorylation
products in urine, plasma and other biological fluids are
fluctuating with ingestion or deprivation of phytate in the
human diet [53]. Therefore, the reduction in phytate
intake in developed compared to developing countries
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P
otential Health Benefits and Adverse Effects Associated with Phytate in Foods: A Review
m
ig
h
t be one factor responsible for the increase in
diseases typical for Western societies such as diabetes
mellitus, renal lithiasis, cancer, atherosclerosis and
coronary heart diseases. It was suggested that phytate
exerts the beneficial effects in the gastrointestinal tract
and other target tissues through its chelating ability, but
additional mechanisms have also been discussed.
Moreover, the potential beneficial effects of phytate in
the prevention of severe poisoning should be consi -
dered.
One to two percent calcium phytate in the diet
has been found to protect against dietary Pb2+ in
experimental animals and in human volunteers [54].
Furthermore, calcium phytate was capable of lowering
blood Pb2+ levels [7, 55]. Thus, phytate seems to be a
helpful means to counteract acute oral Pb2+ toxicity.
The effect of calcium phytate on acute Cd2+ toxicity is
still discussed controversially, but the majority of studies
point to an improved Cd2+ absorption in
the presence
of phytate [56,57]. This may result in a Cd2+ accum -
ulation in liver and kidney.
Diabetes mellitus is one of the most common
nutrition-dependent diseases in Western society. It may
be caused by hyper-caloric diets with high percentage
of quickly available carbohydrates. Foods that result in
low blood glucose response have been shown to have
great nutritional significance in the prevention and
management of diabetes mellitus. In this regard phytate-
rich foods are of interest, since a negative relationship
between phytate intake and blood glucose response
was reported [9,52]. For example, phytateenriched
unleavened bread based on white flour reduced the in
vitro starch digestibility besides flattening the glycemic
response in five healthy volunteers in comparison with
bread
without phytate addition [52]. The in vitro
reduction of starch digestion was positively correlated
with the myo-inositol phosphate concentration and
negatively with the number of phosphate groups on the
myo-inositol ring. It has to be noted, that there are also
studies which have not found an inhibition of α-amylase
and starch digestion by phytate.
a)
Ph
ytate and Coronary Heart Disease
H
eart disease is a leading cause of death in
Western countries, yet it is low in Japan and developing
countries. Elevated plasma cholesterol or more speci -
fically, elevated Low Density Lipoprotein chole -sterol
concentrations have been shown to be one of the risk
factors. It has been proposed that dietary fibre or more
specifically phytate, as a component of fibre, may influ -
ence the aetiology of heart disease [58]. Animal studies
have demonstrated that dietary phytate supplementation
resulted in significantly lowered serum cholesterol and
triglyceride levels [11]. This effect was accompanied by
decrease in serum zinc level and in zinc-copper ratio.
Thus, the hypothesis was put forward that coronary
heart disease is predominantly a disease of imbalance
in regard to zinc and copper metabolism [59]. The
hypothesis is also based on the production of hyperch -
olesterolemia, which is a major factor in the aetiology of
coronary heart disease, in rats fed a diet with a high
ratio of zinc and copper [60]. It was thought that excess
zinc in the diets resulted in decreased copper uptake
from the small intestine, since both minerals compete
for common mucosal carrier systems. As phytate
preferentially binds zinc rather than copper [61], it was
presumed that phytate exerts its effect probably by
decreasing zinc without affecting copper absorption. It
should be pointed out that the support for the preventive
role of phytate in heart disease is based only on a few
animal and in vitro studies. Results from human studies
are
still lacking.
b)
Ph
ytate and Renal Lithiasis
The increase of renal stone incidence in
northern Europe, North America, and Japan has been
reported to be coincident with the industrial develop -
pment of these countries, making dietary intake suspect.
Epidemiological investigations found that there were
substantial differences in renal stone incidences
between white and black residents of South Africa [62].
The major dietary difference is that, compared to the
white population, blacks consumed large amounts of
foods containing high levels of fibre and phytate. Furthe
-rmore, a high phytate diet has been used effect -tively
to treat hypercalciuria and renal stone formation in
humans [7,
63]. In recent years, research on phytate as
a potent inhibitor of renal stone formation has been
intensified [8, 64,65]. By comparing a group of active
calcium oxalate stone formers with healthy people it was
demonstrated that urinary phytate was significantly
lower for stone formers [8]. Therefore, in vitro and in vivo
experiments as well as clinical studies clearly demon -
strate that phytate plays an important role in preventing
the formation of calcium oxalate and calcium phosphate
crystals, which function as nuclei for kidney stone devel
-opment. Because excretion of low phytate amounts in
the urine was shown to be an important risk factor in the
development of renal calculi and urinary excretion of
phytate decreased significantly after intake of a phytate-
free diet [64], the importance of dietary phytate in
maintaining adequate
urinary levels to permit effective
crystallization inhibition of calcium salts and conseq -
uently preventing renal stone development was demo -
nstrated.
c)
Ph
y
ta
te a
nd Cancer
T
he
frequency of colonic cancer varies widely
among human populations. It is a major cause of mor -
bidity and mortality in Western society. The incidence of
cancer, especially large intestinal cancer has been
associated principally with dietary fat intake and is
inversely related to the intake of dietary fibre. It was
further suggested that the apparent relationship bet -
ween fibre intake and rate of colonic cancer might arise
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otential Health Benefits and Adverse Effects Associated with Phytate in Foods: A Review
f
rom the fact that many fibre-rich foods contain large
amounts of phytate and that this latter might be the
critical protective element, since an inverse correlation
between colon cancer and the intake of phytate-rich
fibre foods, but not phytatepoor fibre foods has been
shown [66]. A high phytate intake may also be an
important factor in reducing the breast and prostate
cancer mortality in man [12]. Both in vivo and in vitro
experiments have shown striking anticancer effects of
phytate. It was demonstrated that phytate is a broad-
spectrum antineoplastic agent, affecting different cells
and tissue systems [12]. Phytate inhibited the growth of
human cell lines such as leukaemic haematopoietic K-
562 cell line [67,68 ], colon cancer HT-29 cell line [69],
breast cancer cell lines [70], cervical cancer cell lines
[71], prostate cancer cell lines [72,74], HepG2 haep -
atoma cell line [75], mesenchymal tumour cells [76],
murine fibrosarcoma tumour cells [76], and rhabdom -
yosarcoma cells [77] in a dose- and time-dependent
manner. However, cells from different origin have diff -
erent sensitivity to phytate, suggesting that phytate may
affect different cell types through different mechanisms
of action. It was also demonstrated, that phytate has the
portential to induce differentiation and maturation of
malignant cells, which often results in reversion to the
normal phenotype [68]. Phytate was further shown to
increase differentiation of human colon carcinoma HT-
29 cells [69,78], prostate cancer cells [72, 73], breast
cancer cells [70], and rhabdo -myosarcoma cells [77].
The effectiveness of phytate as a cancer preventive
agent was also shown in colon cancer induced in rats
and mice. Phytate was effective in a dose-dependent
manner given either before or after carcinogen admin -
istration.
The phytate-treated animals demonstrated a
significantly lower tumour number and size. Studies
using other experimental models showed that the
antineoplastic properties of phytate were not restricted
to the colon. Phytate significantly reduced experimental
mammary carcinoma [79,80, 83], skin papillomas [84],
tumour size of metastatic fibrosarcoma and exper -
imental lung metastases [76], growth of rhabdomyo -
sarcoma cells [77], and regression of pre-existing liver
cancers [75,85]. In addition synergistic cancer inhibition
by phytate when combined with inositol was demo -
nstrated in several cancers in experimental animals
[76,81,82,86]. The in vivo experiments were performed
either by adding phytate to the diet or by giving phytate
via drinking water. Comparable of even stronger tumour
inhibition was obtained with much lower concentrations
of phytate when it was given in drinking water.
d)
M
echanism of action
T
he m
echanisms involved in the anticancer
activity of phytate are not fully understood. It was sugg -
ested that phytate exerts the beneficial effects through
its chelating ability, but additional mechanisms have
also been discussed. Because several myo-inositol
phosphates, including phytate, are present as intra -
cellular molecules and because the second messenger
D-myo-inositol (1,4,5) trisphosphate is brin -ging about a
range of cellular functions including cell proliferation via
mobilising intracellular Ca2+ [87], phytate was propo-
sed to exert its anticancer effect by affecting cell
signalling mechanisms in mammalian cells [68]. About
35 of the 63 possible myo-inositol phos -phate isomers
were identified in different types of cells [87]. Depending
on cell type, that is different receptors, phosphatases,
and kinases, myo-inositol phosphates were linked with
different physiological effects, such as basic cell func -
tions like secretion and contraction as well as functions
like cell division, cell differentiation and cell death.
Therefore, practically every myo-inositol phos -phate
isomer extracellularly present and may have a metabolic
effect by activating receptors, by being meta -bolised by
phosphatases and kinases or
by acting as inhibitors of
these intracellular proteins after being internalised by
cells. An effect of extracellular phytate on the conce -
ntration of several in- tracellular myo-inositol phosphate
esters has already been demonstrated in human
erythroleukemia cells [68]. Furthermore, it has been
recently reported that highly negatively charged myo-
inositol polyphosphates can cross the plasma mem -
brane and be internalised by cells. Myo-inositol hexakis -
phosphate was shown to enter HeLa cells followed by
an intracellular dephosphorylation to partially phosph -
orylated myo-inositol phosphates [71], whereas myo-
inositol (1,3,4,5,6) pentakisphosphate showed a quite
slow turnover after internalisation by SKOV-3 cells [88]. It
was suggested that the anticancer activity of phytate is
actually due to its dephosp -horylation to lower forms.
Myo-inositol (1,3,4,5, 6) pentakisphosphate inhibits
specifically phosphatidylinositol 3-kinase, the enzyme
catalysing the phosphorylation of inositol phospholipids
at the D3 position to generate 3’-phosphorylated
phosphoinositides [89], which act by recruiting specific
signalling proteins to the plasma membrane [90].
Activation of phospha -tidylinositol 3-kinase is a crucial
step in some events leading to angiogenesis, the form -
ation of a mature vasculature from a primitive vascular
network [90, 91]. Angiogenesis is involved in
pathologies such as arteriosclerosis and tumour growth.
The observed anticancer effects of phytate
could be mediated through several other mechanisms.
Besides affecting tumour cells, phytate can act on a
host by restoring its immune system. Phytate augments
natural killer cell activity in vitro and normalises the
carcinogen-induced depression of natural killer cell
activity in vivo [7, 92]. The anti-oxidant role of phytate is
known and widely accepted. The 1,2,3-trisphosphate
grouping in phytate has a conformation that uniquely
provides a specific interaction with iron to completely
inhibit its capability to catalyse hydroxyl radical form -
ation from the Fenton reaction [93]. Chelation of iron to
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he 1, 2, 3-trisphosphate grouping may also reduce the
P
otential Health Benefits and Adverse Effects Associated with Phytate in Foods: A Review
likeli
hood for ironcatalysed lipid peroxidation [94]. It is
as yet uncertain whether physiological intakes of phytate
can significantly improve the anti-oxidant
status in man.
The anticancer action of phytate may be further related
to mineral binding ability or other positively charged
compounds. By complexing Zn2+ and /or Mg2+, phy -
tate can affect activity of enzymes essential for DNA
synthesis. Due to inhibition of starch digestion in the
small intestine, undigested and unabsorbed starch will
reach the colon where it may either contribute to faecal
bulk and increase the dilution of potential carcinogens,
or it may be fermented to short-chain fatty acids, which
may subsequently decrease the colonic pH. The
increased production of shortchain fatty acid, partic -
ularly
butyrate, may play a protective role in colon
carcinogenesis, because butyrate has been shown in
several in vitro studies to slow down the growth rate of
human colorectal cancer cell lines [95,96]. Decreased
pH has been suggested to be protective of colon
carcinogenesis [97] by possibly causing alterations in
the metabolic activity of colonic flora, altering bile acid
metabolism and inhibiting ammonia production and
absorption [98, 99].
IV.
C
o
ncl
u
sion
Phytate is a principal chelating agent in cereal-
based foods and is capable of impairing divalent
mineral bioavailability through binding. Phytate has been
recognized as an antinutrient due to its adverse effects.
It reduced the bioavailability of minerals and caused
growth inhibition. Many studies reported that phytate in
plant foods binds essential dietary minerals in the
digestive tract, making them unavailable for absorption.
It forms insoluble complexes with Cu2+, Zn2+, Fe3+
and Ca2+ and as a result reduces the bioavailability of
these essential minerals. Many
animal feedings of plant
food trials reveal that lower bioavailability of zinc,
calcium, magnesium, phosphorus and iron are due to
the presence of phytate. This is the main reason why
phytate has been considered as an antinutrient.
Recent studies on phytate have shown its
beneficial effects such as decrease in blood lipids,
decrease in blood glucose response and cancer risk. In
addition, a high phytate diet is used in the inhibition of
dental caries and platelet aggregation, for the treatment
of hypercalciuria and kidney stones in humans, and as
antidote activity against acute lead poisoning. The
beneficial health effects of phytate are more significant
for populations in developed countries because of the
higher incidence of cancer especially colon cancer
which is associated with higher fat and lower fibre rich
food intakes. Such populations generally do not suffer
from mineral deficiencies. On the one hand, the
chelating ability of phytate is considered to be a
detriment to one’s health whilst, on the other hand,
many researchers consider this ability to bind with
minerals as its most powerful asset. Such a variant topic
signifies that more intensive studies are needed to
obtain better insight into the mechanism responsible for
the ‘‘friend or foe” challenge of phytate. Moreover,
regardless of a series of researches on the positive and
negative features of phytate, the information on the
dosage for humans eliciting positive or negative effects
is limited and the optimal dosage for clinical therapies is
yet to be determined.
V.
A
c
knowledgement
I acknowledge all the Authors I used as a refer -
ences in preparing this review paper. The
author have
no conflict of interests.
R
ef
er
en
ces
R
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