The potential role of phytochemicals in wholegrain cereals for the prevention of type-2 diabetes.
ABSTRACT Diets high in wholegrains are associated with a 20-30% reduction in risk of developing type-2 diabetes (T2D), which is attributed to a variety of wholegrain components, notably dietary fibre, vitamins, minerals and phytochemicals. Most phytochemicals function as antioxidants in vitro and have the potential to mitigate oxidative stress and inflammation which are implicated in the pathogenesis of T2D. In this review we compare the content and bioavailability of phytochemicals in wheat, barley, rice, rye and oat varieties and critically evaluate the evidence for wholegrain cereals and cereal fractions increasing plasma phytochemical concentrations and reducing oxidative stress and inflammation in humans. Phytochemical content varies considerably within and among the major cereal varieties. Differences in genetics and agro-climatic conditions explain much of the variation. For a number of the major phytochemicals, such as phenolics and flavanoids, their content in grains may be high but because these compounds are tightly bound to the cell wall matrix, their bioavailability is often limited. Clinical trials show that postprandial plasma phenolic concentrations are increased after consumption of wholegrain wheat or wheat bran however the magnitude of the response is usually modest and transient. Whether this is sufficient to bolster antioxidant defences and translates into improved health outcomes is still uncertain. Increased phytochemical bioavailability may be achieved through bio-processing of grains but the improvements so far are small and have not yet led to changes in clinical or physiological markers associated with reduced risk of T2D. Furthermore, the effect of wholegrain cereals and cereal fractions on biomarkers of oxidative stress or strengthening antioxidant defence in healthy individuals is generally small or nonexistent, whereas biomarkers of systemic inflammation tend to be reduced in people consuming high intakes of wholegrains. Future dietary intervention studies seeking to establish a direct role of phytochemicals in mediating the metabolic health benefits of wholegrains, and their potential for mitigating disease progression, should consider using varieties that deliver the highest possible levels of bioavailable phytochemicals in the context of whole foods and diets. Both postprandial and prolonged responses in systemic phytochemical concentrations and markers of inflammation and oxidative stress should be assessed along with changes related to health outcomes in healthy individuals as well as those with metabolic disease.
- SourceAvailable from: Xochitl Aparicio[Show abstract] [Hide abstract]
ABSTRACT: The present study was conducted to analyze the chemical composition, total phenolics content and antioxidant capacity of two whole corn (Zea mays) based meals traditional from Mexico: “traditional pinole” and “seven grain pinole”; and compare it with information available from ready to eat cereal products based on refined corn and whole grain cereals. Proximate analyses (moisture, ash, fat, protein and fiber) were carried out according to the procedures of AOAC, sugars content was determined by HPLC method; calcium and iron were quantified using atomic absorption spectroscopy. Total phenolic compounds were determined by Folin-Ciocalteu spectrophotometric method; the antiradical capacity was determined by DPPH colorimetric method and total antioxidant capacity was determined by FRAP method. Traditional and seven grain pinole presented higher energy content and nutrient density (protein and fat) than processed cereals. Calcium content was higher in processed cereals than pinole; seven grain pinole presented the highest conentration of iron. Polyphenolic concentration was higher in both kinds of pinole compared to processed cereals; traditional pinole presented the highest antioxidant activity measured by DPPH and FRAP methods. The results provide evidence about the important nutrient and antioxidant content of traditional and seven grain pinole compared to processed cereals based on corn and other grains. It is recommended their incorporation in to regular diet as a healthy food, with a good protein level, low sugar content and good antioxidant capacity.Archivos latinoamericanos de nutrición 05/2014; 64(2):116-122. · 0.24 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To enhance the learner's competence with knowledge about studies that examined phytochemical use for assisting the body's healing processes.Advances in skin & wound care. 07/2014; 27(7):328-332.
- [Show abstract] [Hide abstract]
ABSTRACT: Abstract Whole wheat contains an array of phytochemicals. We quantified alkylresorcinols (AR), phenolic acids, phytosterols, and tocols in six whole wheat products and characterized their antioxidant capacity and ability to induce quinone reductase activity (QR). Total AR content ranged from 136.8 to 233.9 µg/g and was correlated with whole wheat content (r = 0.9248; p = 0.0083). Ferulic acid (FerA) was the dominant phenolic at 99.9-316.0 µg/g and mostly bound tightly to the wheat matrix. AR-C21 and total FerA predicted the whole wheat content in each product (R(2 )= 0.9933). Total phytosterol content ranged from 562.6 to 1035.5 µg/g. Total tocol content ranged from 19.3 to 292.7 µg/g. Phytosterol and tocol contents were independent of whole wheat content. Whole wheat biscuits and pasta were the most potent products to induce QR in Hepa1c1c7 cells. This study provides a platform to characterize the relationship between the phytochemical composition of whole wheat and products formulated with this whole grain.International Journal of Food Sciences and Nutrition 01/2015; · 1.20 Impact Factor
The potential role of phytochemicals in
wholegrain cereals for the prevention of
Damien P Belobrajdic1,2*and Anthony R Bird1,2
Diets high in wholegrains are associated with a 20-30% reduction in risk of developing type-2 diabetes (T2D), which
is attributed to a variety of wholegrain components, notably dietary fibre, vitamins, minerals and phytochemicals.
Most phytochemicals function as antioxidants in vitro and have the potential to mitigate oxidative stress and
inflammation which are implicated in the pathogenesis of T2D. In this review we compare the content and
bioavailability of phytochemicals in wheat, barley, rice, rye and oat varieties and critically evaluate the evidence for
wholegrain cereals and cereal fractions increasing plasma phytochemical concentrations and reducing oxidative
stress and inflammation in humans. Phytochemical content varies considerably within and among the major cereal
varieties. Differences in genetics and agro-climatic conditions explain much of the variation. For a number of the
major phytochemicals, such as phenolics and flavanoids, their content in grains may be high but because these
compounds are tightly bound to the cell wall matrix, their bioavailability is often limited. Clinical trials show that
postprandial plasma phenolic concentrations are increased after consumption of wholegrain wheat or wheat bran
however the magnitude of the response is usually modest and transient. Whether this is sufficient to bolster
antioxidant defences and translates into improved health outcomes is still uncertain. Increased phytochemical
bioavailability may be achieved through bio-processing of grains but the improvements so far are small and have
not yet led to changes in clinical or physiological markers associated with reduced risk of T2D. Furthermore, the
effect of wholegrain cereals and cereal fractions on biomarkers of oxidative stress or strengthening antioxidant
defence in healthy individuals is generally small or nonexistent, whereas biomarkers of systemic inflammation tend
to be reduced in people consuming high intakes of wholegrains. Future dietary intervention studies seeking to
establish a direct role of phytochemicals in mediating the metabolic health benefits of wholegrains, and their
potential for mitigating disease progression, should consider using varieties that deliver the highest possible levels
of bioavailable phytochemicals in the context of whole foods and diets. Both postprandial and prolonged
responses in systemic phytochemical concentrations and markers of inflammation and oxidative stress should be
assessed along with changes related to health outcomes in healthy individuals as well as those with metabolic
Keywords: Wholegrain, Phytochemical, Type-2 diabetes, Oxidative stress, Inflammation
* Correspondence: email@example.com
1Commonwealth Scientific & Industrial Research Organisation (CSIRO) Food
Futures National Flagship, GPO BOX 10041, Adelaide, SA 5000, Australia
2CSIRO Animal Food & Health Sciences, Adelaide, SA 5000, Australia
© 2013 Belobrajdic and Bird; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Metabolic disease and protective role
Type-2 diabetes (T2D) is a major health problem world-
wide. Rates are increasing alarmingly in many countries
and the global incidence is predicted to rise from 366
million people to about 552 million in the next two de-
cades [1,2]. It is a leading cause of death and disability
globally and carries a considerable socioeconomic bur-
den, especially in low and middle income settings [2-5].
Cost-effective mitigation strategies rather than contain-
ment are therefore of paramount importance. The initi-
ation and progression of T2D and related chronic
metabolic disorders is governed by a complex interplay
of genetic and multiple lifestyle influences of which diet
is a major and modifiable high exposure risk factor.
Dietary change has proven successful in both preventing
and managing diabetes and, when combined with other
lifestyle modifications, such as regular exercise and
weight loss, is more effective than pharmacological inter-
Dietary patterns featuring wholegrain cereals are asso-
ciated with reduced risk of T2D [7-10]. Systematic re-
views and meta-analyses of large, prospective studies
consistently demonstrate that frequent consumption of
wholegrain foods improves metabolic homeostasis and
delays or prevents the development of T2D and its com-
plications in a variety of cohorts, albeit mostly of European
ancestry [11-18]. Two to three serves daily of wholegrain
foods reduced the risk of T2D by 20-30% compared to
about 1 serve a week [12,13,15,18]. Randomised, con-
trolled dietary studies in humans and other experimental
research provides evidence of a causal relationship be-
tween wholegrain consumption and diabetes prevention
[15,18]. Furthermore, wholegrain foods improve indices of
diabetes risk, including glycemic control, fasting plasma
insulin and glucose, and insulin sensitivity and also aid in
the management of those individuals with or at high risk
of developing T2D [13,16,19-21].
Mechanisms by which wholegrains might protect against
Understanding the mechanisms by which wholegrains
prevent or delay the onset and progression of T2D is
pivotal to developing effective diabetes prevention op-
tions. The components of wholegrains which are respon-
sible for protecting against diabetes have not been
clearly identified but the high nutrient and fibre contents
in general, as well as the physical structure of wholegrains
are considered leading contenders [15,22,23]. Prospective
studies show that T2D risk is inversely related to cereal
fibre intake  and that cereal fibre accounts for much of
the reduction in diabetes risk associated with wholegrain
intake . Dietary fibre is concentrated primarily in the
bran layer of grains and it is this fraction which is more
strongly associated with reduction in risk of T2D .
Most but not all wholegrains are high in fibre  and in-
dividual wholegrains differ markedly in the types and
hence physiological properties of fibres they contain. Vis-
cous soluble fibres, such as those in oats and barley, slow
available carbohydrate assimilation and dampen postpran-
dial glycemic and insulinemic responses . However
most observational studies provide evidence of a protect-
ive role for insoluble rather than soluble fibres . The
likely explanation is that insoluble fibre is simply serving
as a marker of an intact (grain) food structure. Foods and
diets rich in carbohydrates that are rapidly digested and
absorbed have adverse consequences for metabolic health
[28-33]. Refinement of cereal grains removes the protect-
ive bran layer and greatly increases starch availability.
However, not all wholegrain foods elicit a moderate gly-
cemic response . Although wholegrain foods may
contain intact, cracked, broken or flaked kernels, most
commercially processed cereal foods consist of ground
and reconstituted wholegrain products .
Wholegrains contain a plethora of minerals, vitamins
and phytochemicals  and it is often difficult to
ascribe protective effects on metabolic health to any one
particular constituent, such as fibre. One of the primary
pathogenic factors leading to insulin resistance, β-cell
dysfunction, impaired glucose tolerance and ultimately
T2D is oxidative stress [36-38]. This mechanism has
been implicated as the underlying cause of both the
macrovascular and microvascular complications associ-
ated with T2D . Furthermore, the cells and tissues of
people with metabolic syndrome and T2D have an im-
paired ability to cope with the burden of increased oxi-
dative stress [40-42]. Therefore, dietary components
including phytochemicals (non-nutritive, plant bio ac-
tives that reduce risk of chronic diseases ), and a
limited number of micronutrients that function as anti-
oxidants, may prevent the development and progression
of metabolic syndrome and T2D by reducing oxidative
stress . Furthermore, systemic, low grade inflamma-
tion, especially in adipose tissue, is a hallmark of many
chronic diseases, including T2D . In addition to their
antioxidant properties, some cereal phytochemicals have
thereby modulate diabetes risk by this mechanism as
Phytochemicals in whole grains
Wholegrains generally contain diverse combinations of
phytochemicals depending on the type of cereal, location
within the grain and how the grain has been processed.
The outer structures of grains, in particular the pericarp
seed coat and aleurone layers, contain much higher
levels of phytochemicals such as phenolic compounds,
phytosterols, tocols, betaine and folate, than the germ
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 2 of 12
and endosperm . Phenolic compounds are the most
diverse and complex class of phytochemicals in cereal
grains [35,49]. They include numerous derivatives of
benzoic and cinnamic acids as well as flavonoids, fla-
vones and flavanols, anthocyanidins, avenanthramides,
lignans and alkylresorcinols. In most grains phenolic
acids are concentrated in the bran and embryo cell walls
and exist mostly in an insoluble bound form, free and
soluble-conjugated forms being minor entities [25,48].
The phenolic acid content of wholegrains is considered
a major contributor to total antioxidant capacity .
Other major phytochemicals that occur in wholegrains
which may have a role in protecting against diabetes in-
clude various carotenoids, notably α- and β-carotene, lu-
tein, β-cryptoxanthin and zeaxanthin, all of which are
located mainly in the bran and germ fractions .
Aside from some having pro-vitamin A activity, they all
function as antioxidants. Other phytochemicals with
strong antioxidant capacities include phytate (which che-
lates prooxidant minerals) and various terpenes and ter-
penoids (phytosterols and tocols).
To render them palatable, grains are processed by
various means including milling, grinding and flaking.
Although these treatments may reduce content of phyto-
chemicals, their bioavailability is often increased [45,50,51].
Thermal and bioprocessing too can improve phytochem-
ical bioavailability, especially the latter method, although
the results are not always consistent.
Differences among the most economically important
cereals in their contents of various micronutrients and
phytochemicals are shown in Table 1. Note that the
phytochemical values refer to uncooked wholegrains.
Wholegrains are normally cooked and are rarely con-
sumed in their unprocessed or raw form. Cooking re-
sults in considerable reductions in their phytochemical
levels. For instance, quick-cooking wild rice had a much
lower total phenolic content (2076 mg ferulic acid
equivalent (FAE)/kg) than uncooked wild rice varieties
(2472 to 4072 mg FAE/kg) .
Variation in grain phytochemical content
Wheat, barley, rice, rye and oats vary markedly in the
types and amounts of phytochemicals they contain.
The antioxidant properties of wheat have been
attributed primarily to the high phenolic content,
principally alkylresorcinols and hydroxycinnamic
acids (ferulic, sinapic, and ρ-coumaric acids) that are
concentrated in the bran fraction [49,75-77]. The
flavonoid concentration in the bound fraction of
wheat cultivars has been shown to vary from 97 ±
4 μmol catechin equivalents/100 g (Roane) to 139 ±
17 μmol catechin equivalents/100 g (Superior) .
However, there is less variation in total flavonoid
content (122 ± 10 μmol catechin equivalents/g
(Roane) to 149 ± 17 μmol catechin equivalents/100 g
(Superior) ) whereas tocopherols and tocotrienols
levels vary more than 2-fold (28 to 80 μg/g) among
175 different wheat genotypes from all over the world
grown at the same site in Europe . Even greater
variation (up to 10-fold variation) was seen in
Table 1 The type and concentration of phytohcemicals in a range of wholegrain cereals
PhytochemicalWheatBarley Rice RyeOat
Methionine (g/100g) [48,53-56]0.17 – 0.240.03 – 0.080.18 – 0.210.180.18
Cystine (g/100g) [48,53-56]0.19 – 0.400.06 – 0.2 0.11 – 0.160.180.18
Selenium (mg/100g) [48,57-60]0.0003 – 3 0.002 – 0.030 0.0002 – 1.370.00014< 0.10 – 3.3
Folate (mg/100g) [60,61]0.01 – 0.090.5 – 0.8 0.0160.55 – 0.800.05 – 0.06
Choline (mg/100g) [48,62]27 – 195 6.9 – 11UnknownUnknown2.0 – 2.6
Tocopherols + tocotrienols [48,63-67]2.3 – 8.0 4.7 – 6.8 0.4 – 0.9 0.4 – 0.7 0.05 – 4.8
Carotenoids (total) (mg gallic acid eq./100g) [48,60]0.04 – 0.630.015 – 0.105 0.014 – 0.077 Unknown0.031
Polyphenols (mg/100g) 70 – 145950 – 19654 – 313 125 – 255 9 – 34
Phenolic acids (total) (μg/g) [61,64,68]200 – 900 100 – 550 Unknown200 – 1080350 – 874
Phenolic acid (free) (ug/g) [61,64,68] 5 – 395 – 23Unknown10 – 3550 – 110
Ferulic acid (total, mg/100g) [48,69]16 – 213110 – 12030 3.9 – 5.02.1 – 2.4
Flavanoids (total, mg/100g) [48,69]30 – 4312 – 18Unknown6.7 – 7.55.6 – 8.2
Alkylresorcinols μg/g [61,70]200 – 7500 – 150Not present570 – 3220Not present
Avenanthramides (mg/100g [71,72]Not presentNot presentNot present Not present4.9 – 27.5
Betaine (mg/100g) [48,60,62,73]22 – 29140 – 760.5 (brown) Unknown11.3 – 100
Phytosterols (mg/100g) [48,74]
57 – 9890 – 115UnknownUnknownUnknown
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 3 of 12
α-tocopherol levels measured in several hundred
wheat cultivars grown in the United States .
The major phytochemicals in barley are phenolics,
tocols and folate. Analysis of a selection of 10 barley
lines showed a large variation in the concentration
of total phenolics (100 to 550 ug/g) but only
minimal variation in folate (500 to 800 ug/g) and
total tocols (45 to 70 ug/g) . Our group has
recently developed a new variety of barley,
BARLEYmax®  that has a range of substantiated
nutritional and health benefits [82,83]. It has a
phenolic content (5 mg/g) which is 40% greater than
that of standard cultivars such as Golden Promise
(2.9 mg/g) and Torrens (3 mg/g). It also contains
levels of tocopherol and tocotrienols (125 μg/g)
which are nearly 5 times those of other barley grain
varieties (McInerney, JK, Morell, MK and Bird, AR
Brown rice generally is a good source of lipid-soluble
antioxidants including ferulated phytosterols (i.e.
γ-oryzanol), tocopherols and tocotrienols, although
the levels of these phytochemicals vary widely
among rice varieties . For instance, tocol
concentration ranged from 90 to 220 nmol/g in six
varieties of rice . Brown rice may also be a good
source of phenolic acids as suggested by the levels
reported for the botanically related wild rice
(Zizaniae palustris and Zizaniae aquatica; 2472 to
4072 mg of ferulic acid equivalent (FAE)/kg). These
values are substantially higher than that of the
mixed sample of white rice, basmati rice and wild
rice (1460 mg of FAE/kg) . The total phenolics
content of these rices was directly related to their
in vitro antioxidant capacity, which was 30 times
higher for wild rice than the control (white) rice .
Rye contains more alkylresorcinols (568 to 3220 μg/g)
than the other major cereal varieties (0 to 750 μg/g).
The concentration of alkylresorcinol in rye [70,84] is
related to the high level of folate in the grain (0.55 to
0.80 mg/100 g) . Select varieties of rye also contain
very high levels of total phenolics (up to 1080 μg/g)
but the content of free phenolics is quite low
(between 10 to 35 μg/g) . Other phytochemicals,
including tocols, polyphenols and ferulic acid are
found at low levels in rye .
The major phytochemicals present in oats include
tocopherols and tocotrienols, phenolic acids, sterols,
selenium and avenanthramides (a group of
N-cinnamoylanthranilate alkaloids, unique to oats)
[85,86]. Tocol levels differ greatly (5 to 48 μg/g)
[61,65,66] among oat varieties but generally are
comparable to those found in rice and rye (4 to
9 μg/g) and also to the higher levels found in wheat
and barley (23 to 80 μg/g) . The range in the
total phenolic levels of oats are also similar to those
in wheat and rye, however oats contains up to
10-fold higher levels of free and conjugated
phenolics. Other phytochemicals, including folate,
polyphenols, ferulic acid and flavonoids are present
at low levels in oats.
Major regulators of phytochemical content of cereals:
genetics and agro-climatic conditions
The phytochemical content of cereal grains is influenced
considerably by genetics and a variety of agro-climatic
factors. In rice, the growing environment had a greater
effect on tocol and/or sterol esters of ferulic acid levels
than did genotype [87,88]. In wheat, genetic variation
and agro-climatic conditions are both important but the
extent of their influence depends on the phytochemical
concerned. In an assessment of over 200 lines of wheat,
α-tocopherol levels were influenced by not only varietal
differences but also crop year and production site .
Fertilization practices, soil type and wheat variety had
no influence . Additionally, when eight selected win-
ter wheat genotypes were grown under controlled condi-
tions α-tocopherol levels varied by as much as 3-fold,
highlighting the significant contribution of genetic vari-
ation . However, studies in Europe show that toc-
opherol and tocotrienol levels in some wheat varieties
are more susceptible to seasonal variation than others
. This greater susceptibility to seasonal variation and
growing location is also evident in some wheat geno-
types for free and conjugated phenolic levels . How-
ever, bound phenolics which comprise the greatest
proportion of total phenolic acids in wheat, are mostly
stable across different growing conditions. Thus, the
total phenolic acid content of wheat is mostly influenced
by genotype, for instance winter varieties contain up to
2-fold more total phenolic acids (1171 μg/g) than the
average level of 175 wheat genotypes (658 μg/g) .
Bioavailability refers to the fraction of ingested phyto-
chemical (or other dietary constituent) which reaches
the systemic circulation. More commonly it is defined as
the fraction which is absorbed in the gastrointestinal
tract. Tracer methods, in which atoms or molecules of
the phytochemical within the grain are labelled with an
intrinsic radioactive or stable marker, provide the only
means for accurately determining bioavailability. Given
the challenges of labelling cereal phytochemicals intrin-
sically, this technique has not been used to measure bio-
availability of phytochemicals in cereals. Simpler indirect
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 4 of 12
measures are more commonly used, such as the balance
method (intake minus fecal output), incremental area
under the postprandial serum concentration curve and
incremental urinary excretion. Numerous in vitro methods
have also been published however they, understandably,
have many limitations  aside from questionable valid-
ity, and so provide at best only a guide to the bioacces-
sibility of a phytochemical.
a. Absorption from the small intestine
Bioavailability varies markedly among the different
types of phytochemicals. Folate and α-tocopherol are
readily absorbed from the small intestine and their
bioavailability is independent of dietary fibre content
(Table 2) [94,95]. The majority of polyphenols
however, are tightly bound to cell walls within the
grain matrix thereby greatly limiting their
bioavailability in the upper gut . Even if
polyphenols are released from the grain matrix
during digestion it is unlikely that they will be
absorbed in the small intestine as they are too
hydrophilic to cross the epithelium by passive
diffusion . It is possible that there are apical
membrane carriers that facilitate polyphenol
absorption however the intestinal transport
processes remain largely unknown . Oats
contain the highest levels of free, or unbound,
phenolics (up to 30% of total phenolics) whereas
wheat, barley and rye contain only very low levels
(as little as 1.6%) . Thus specific varieties of oats
have the greatest potential to raise postprandial
plasma phenolic concentration and antioxidant
Wholegrain consumption elicits only minimal
increases in systemic levels of phytochemicals in
humans. Consumption of 100 g of boiled wheat bran
increased postprandial plasma phenolic
concentration by 5 μmol (60 min post ingestion)
which represented <2% increase over baseline levels
. As these changes in circulating phenolic levels
are minimal and of short duration it is unlikely that
high intakes of wholegrains such as wheat can
modulate systemic levels. Alternatively,
alkylresorcinols, a class of phenolic lipids found at
high levels in wheat and rye are relatively well
absorbed within the small intestine (about 58%) ,
and as they are primarily transported in the serum
in lipoproteins  they have a half life in serum of
5 h . However, alkylresorcinols are rather weak
antioxidants per se  and do not affect the
susceptibility of LDL to oxidation ex vivo .
Wholegrains wheat, oats and barley are good dietary
sources of betaine which can also contribute to
improving antioxidant status as well as acting possibly
as a methyl donor (transmethylation) and lipotrope
[48,104,105]. The bran and aleurone layers of wheat
are concentrated sources of betaine (~1% w/w)
[104,106] and there is evidence in humans that the
latter source is readily bioavailable .
It is important to consider how components of the
diet may affect phytochemical bioavailability because
cereal products are rarely consumed alone. Non-
heme iron when consumed with cereals reduced the
absorption of phenolics . Milk may also reduce
the absorption of phenolics , however other
studies have also shown no impairment [109-111].
Flavonol absorption (in particular quercetin and its
metabolites) may also be affected by a variety of
dietary constituents such as ethanol, fat, and
emulsifiers , but this observation is based on
evidence from in vitro and animal studies and
further research in humans is required.
Table 2 Major wholegrain phytochemicals, factors affecting their bioavailability and suggested mechanisms for
Phytochemical Major grain
sourcesaffecting bioavailabilityenhance bioavailability
Food & dietary factorsOther factors thatPotential mechanisms of action
freeOatsMilkUnknownIncrease plasma total antioxidant capacity to directly mitigate
Heme ironUnknownIndirect through cell signalling
Grain structureBio-processing of grainIncrease plasma total antioxidant capacity to directly mitigate
Indirect through cell signalling
Flavanoids Wheat, barleyGrain structureUnknown Increase plasma uric acid levels which has reducing and free
radical scavenging activities
Improve glutathione radical scavenging system
Not relevant as
Not relevant as
A cofactor for glutathione peroxidase, an enzyme that
quenches reactive oxygen species
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 5 of 12
b. Cereal bioprocessing for improving phytochemical
Cereal bioprocessing is receiving increasing attention
as a technique for purportedly improving the
bioavailability of bound phytochemicals in grains.
This technique utilises hydrolytic enzymes or
enzyme cocktails to selectively release
phytochemicals from the bran layer. However, there
is very little evidence that cereal bioprocessing
actually improves phytochemical bioavailability in
humans. Recently Anson and colleagues 
developed a bioprocessing technique whereby wheat
bran undergoes a yeast fermentation and enzyme
treatment procedure. When this wheat bran was
incorporated into a wholemeal bread and consumed
by volunteers the plasma concentrations of ferulic,
vanillic and sinapic acids, and 3,4-dimethoxybenzoic
acid were 2- to 3-fold higher than in the control
bread . Ferulic acid in particular increased in
plasma to a maximal level of 2.5 μmol/L, which is
considerably higher than baseline levels reported
previously (5 to 30 nmol) . The relevance of
these changes in circulating phytochemical levels to
metabolic health impact has yet to be demonstrated.
c. Phytochemical bioavailability in the large intestine:
role of the microbiota
Microbial fermentation of cereal grains has the
potential to increase the bioavailability of
phytochemicals bound to the fibre matrix [114-117].
For instance, microbial esterases hydrolyse
conjugated phenolic acids, such as those from wheat
bran [118,119], potentially improving their
absorption.. In addition, ferulic acid from wheat
bran has been shown to increase plasma antioxidant
activity more effectively than pure ferulic acid in rats
. This highlights the important function cereals
may have in delivering ferulic acid to the large bowel
whereby enzymes from the microbiota cause the
slow release of ferulic acid up to 24 h after its
consumption. However, in humans there is limited
evidence that large bowel fermentation contributes
significantly to plasma phytochemical levels in the
systemic circulation. A study by Kern et al. 
showed that the absorption of wheat bran phenolics
was limited essentially to the postprandial period.
Plasma phenolics and metabolites of ferulic acid
(hydroxycinnamic and diferulic acids) were at
baseline levels 6 to 24 h after wheat bran
consumption, suggesting that the microbial
fermentation of the ingested wheat bran did not
contribute to the systemic phenolic level. In
addition, the authors also showed that diferulic acids
(formed by microbial esterase digestion of ferulic
acid) or their reduced dimers (formed by colonic
microbiota hydrogenation reactions of diferulic
acids) could not be detected in plasma or urine
samples. In a study by Anson et al.  whole wheat
bread increased plasma concentrations of two
metabolites of ferulic acid (3-hydroxyphenylpropionic
acid and phenylpropionic acid) 9 to 24 h after
consumption by healthy volunteers. It is unlikely that
these metabolites exert any biological affects
systemically as the maximal plasma concentrations
reached were only in the nanomolar range (100 nmol/L
and 350 nmol/L respectively). The evidence suggests
that the colonic microbiota contribute little to
systemic levels of phenolic metabolites.
Impact of wholegrain phytochemicals on metabolic health
Various blood and urine biomarkers are routinely used
to determine the metabolic health benefits of wholegrain
phytochemicals. For instance, plasma and urine levels of
oxidised lipids provide an indirect measure of the capacity
of cereal phytochemicals to protect circulating lipids from
damage by reactive oxygen species. In addition, circulating
levels of C-reactive protein and pro-inflammatory cyto-
kines are indicative of low grade systemic inflammation, a
hallmark of many metabolic diseases.
a. Oxidised lipids
There is some evidence supporting a role for
wholegrain consumption in reducing oxidised lipids
in plasma or urine. Kim et al.  showed that a
mixture of brown and black rice when consumed for
6 wk by healthy adults reduced plasma
thiobarbituric acid reactive substance (TBARS)
levels. Jang et al.  also showed a reduction in
oxidised plasma malondialdehyde (MDA) and urine
8-epi-prostaglandin F2α when subjects with
coronary heart disease consumed a wholegrain
powder mix (70 g/d) for 4 mo. Two other studies of
shorter duration (2 and 6 wk) in which refined grain
foods were replaced with wholegrain foods (7 to
8 servings/d) did not show any improvements in
urinary levels of oxidised lipids.[123,124] LDL
susceptibility to oxidation was also similar when
healthy subjects consumed 250 g of rye or wheat
bran bakery products for 6 weeks . It is not
clear from these later studies [103,123,124] whether
the lack of an effect was due to the shorter duration
of the interventions, differences in wholegrain type
or differences in the type of biological fluid analysed
(urine was analysed rather than plasma).
b. Antioxidant defence
The most promising evidence for wholegrain-rich
diets improving blood-based antioxidant defence is
through modulation of the glutathione radical
scavenging system. This system utilises glutathione
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 6 of 12
peroxidase to metabolise hydrogen peroxide to water
by using reduced glutathione as a hydrogen donor
. The capacity for reduced glutathione to
quench free radicals can be impaired if oxidised
glutathione is not recycled back to glutathione by
glutathione reductase, or if glutathione peroxidase
activity is reduced . An increase in reduced
glutathione (21%) occurred 15 min after healthy
subjects consumed an oat extract containing 1 g
avenanthramide-enriched mixture and remained
elevated (by up to 14%) for 10 h , a dose which
far exceeds a level that could be achieved by
consumption of wholegrain oats.. Alternatively,
wholegrain dietary intervention studies showed that
plasma glutathione peroxidase activity increased by
15% when subjects consumed brown and black rice
for 6 wk  but decreased by 35% when subjects
consumed a phytochemical-rich diet containing
wholegrains for 4 wk . These studies suggest
that the type of wholegrain and duration of
consumption is important in regulating glutathione
enzyme status or redox state. A possible mechanism
explaining the effect of wholegrains on glutathione
balance comes from in vitro evidence that flavonoids
alter the expression of genes responsible for the
synthesis and regulation of glutathione (Table 2)
[128,129]. There is further evidence from a dietary
intervention study in humans that selenium
improves glutathione peroxidase activity .
Subjects consuming brown or wholemeal bread
made from wheat containing high levels of selenium
increased whole blood glutathione peroxidase levels
by 10% . As most people in European countries
have plasma selenium levels below the
recommended level , wholegrain cereals with
high selenium concentrations may offer an
opportunity to improve glutathione status.
Alternatively, Fardet  recently proposed that
wholegrain wheat may increase glutathione levels
through the supply of the sulfur amino acids
methionine and cystine, which are precursors of
glutathione. However, these amino acids are present
in wholegrain wheat at low levels (0.5% of protein)
, thus other dietary sources of sulphur amino
acids such as egg and meat would presumably have
a greater influence on circulating selenium levels.
There is limited evidence for whole grain-rich diets
affecting copper-zinc superoxide dismutase (SOD),
uric acid and tocopherol levels in the blood. Plasma
SOD levels were unaffected in a study where
subjects consumed black rice for 6 mo . In
contrast, another study showed that erythrocyte
SOD levels were reduced when healthy adults
consumed a phytochemical-rich diet containing
wholegrains for 4 wk . Plasma uric acid levels
were increased (by 9%) in subjects who had
consumed bread (200 g/d) made from inulin, linseed
and soya fibre for 5 wk . These findings are
biologically significant in that uric acid accounts for
up to 90% of plasma total antioxidant capacity .
Furthermore, high levels of flavanoids in some
wholegrains are responsible for increasing plasma
total antioxidant capacity as a result of stimulating
uric acid levels rather than through the direct
actions of flavonoids . However, further
research is required that investigates the impact of
flavanoid-rich cereal consumption on uric acid levels
and antioxidant status in healthy people as well as
those with metabolic syndrome and T2D. Plasma
α-tocopherol concentrations barely increase after
consumption of wholegrains suggesting that this
compound is of limited importance for the
prevention of T2D , In addition, α-tocopherol
contributes less than 2% of the antioxidant capacity
of plasma , and a wholegrain-rich diet cannot
provide the level of Vitamin E necessary to reduce
oxidative stress in people with T2D (> 200 mg/d)
 Furthermore, a review of human clinical trials
concluded that vitamin E, and other common
antioxidants, were not useful for managing diabetic
c. Antioxidant capacity of blood
Most dietary intervention studies on wholegrains
have used the ferric reducing antioxidant potential
(FRAP) assay to determine plasma total antioxidant
capacity. In two studies by the same group, meals
consisting of approximately 100 g of wheat bran
were fed to subjects and the postprandial change in
plasma antioxidant status measured [98,140]. Both
studies showed an increase but in the study by
Beattie et al.  the magnitude of the response
was only 4% (an increase of approximately 50 μmol
of FRAP/L from a baseline of 1,204 ± 57.5 μmol of
FRAP/L). It is not known whether this change is
sufficient to protect against oxidative stress, a
hallmark of metabolic syndrome and T2DM, and
many other chronic diseases. In a study of longer
duration (5 wk) fasted plasma FRAP levels did not
change when subjects consumed bread (200 g/d)
made with inulin, linseed and soya fibre, which had
a 50% higher α-tocopherol content than the control
German wheat-rye bread . Although these
studies show a somewhat promising result for wheat
bran in improving plasma antioxidant capacity, the
FRAP assay has some limitations. For instance, it
does not account for the antioxidant capacity
provided by blood proteins (as they too are
extracted in sample preparation) and the assay is
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 7 of 12
based on the reduction of iron which is considered
too slow a measure of antioxidant potential
[137,141]. Alternative antioxidant capacity assays,
such as the one for plasma total antioxidant capacity
(TAC), have been used to show an increase in
plasma antioxidant capacity in subjects with
coronary heart disease who consumed black rice for
6 mo . Other total antioxidant capacity assays,
such as the Oxygen Radical Absorbance Capacity
(ORAC) and Trolox Equivalent Antioxidant
Capacity (TEAC), may be useful for evaluating
radical scavenging, however they are not suitable for
assessing lipid peroxidation inhibition . Thus
future studies should deploy a combination of
different antioxidant capacity assays and the results
interpreted in the context of changes in plasma lipid
and protein oxidative stress biomarkers and clinical
d. Anti-inflammatory actions
There is growing evidence supporting a reduction in
pro-inflammatory markers in people consuming
higher levels of wholegrains and/or cereal fibre. For
instance, cereal fibre intakes (> 8.8 g/d), but not
total fibre, were associated with significantly lower
plasma cytokine levels in healthy adults .
Intervention trials provide evidence that plasma
cytokines or C-reactive protein were reduced after
consumption of bakery products containing rye bran
, bread made from whole wheat with
bioprocessed bran  or a black rice pigment
The fibre component of wholegrains is often
associated with having favourable effects on pro-
inflammatory markers including C-reactive protein
and interleukin-6 [145,146]. In particular, the
fermentation of cereal fibre in the large bowel
produces short chain fatty acids (SCFA) that bind to
G-protein coupled receptors, inhibiting transcription
factor Nfκβ and thereby increasing the threshold for
an inflammatory response in the colonic mucosa
. The anti-inflammatory actions of SCFA may
extend beyond the large bowel as these bacterial
metabolites are readily absorbed by colonocytes
. However, SCFA concentrations in the
systemic circulation are low (<0.2 mM) as most
SCFA absorbed from the lumen of the gut are
metabolised extensively by the gut mucosa and the
liver. Furthermore, consumption of fermentable
dietary fibres produces only a modest rise in plasma
SCFA levels . Whether these modest levels of
circulating SCFA are sufficient to prevent or
attenuate the elevated inflammatory status of
individuals with diabetes and related disorders is yet
to be established and deserves further investigation.
Dietary fibre may help prevent chronic inflammation
by also reducing circulating levels of
lipoplysaccharides (LPS), which are known to
contribute to the development of obesity-related
inflammatory liver diseases [150-152]. The
consumption of prebiotics has been shown to
restrict the translocation of LPS from the large
bowel of mice fed a high fat diet, resulting in
reduced markers of inflammation in adipose tissue
. However, the relevance of these findings for
humans is not yet clear.
Evidence from postprandial and medium-term intake
studies suggest that the phytochemical component of ce-
reals provides limited benefit for preventing oxidative
stress and development of T2D. Wholegrain consump-
tion may increase postprandial plasma phenolic levels
but the response is modest and transient. Whether this
effect is sufficient to bolster antioxidant defences and
improve health outcomes has not been established. Al-
though there is growing interest in the colonic micro-
biota and bio-processing for increasing phytochemical
bioavailability the improvements so far are small and
have not improved markers of clinical relevance for re-
ducing risk of T2D. Future dietary intervention studies
seeking to establish a direct role of phytochemicals in
mediating the metabolic health benefits of wholegrains,
and their potential for mitigating disease progression,
should consider using varieties that deliver the highest
possible levels of bioavailable phytochemicals in the con-
text of whole foods and diets. Both postprandial and
prolonged responses in systemic phytochemical concen-
trations and markers of inflammation and oxidative
stress should be monitored and along with changes re-
lated to health outcomes in healthy individuals as well as
those with metabolic disease.
FAE: Ferulic acid equivalent; FRAP: Ferric reducing antioxidant potential;
LPS: Lipopolysaccharide; MDA: Malondialdehyde; ORAC: Oxygen Radical
Absorbance Capacity; SCFA: Short chain fatty acid; SOD: Superoxide
dismutase; TAC: Total antioxidant capacity; TBARS: Thiobarbituric acid reactive
substance; TEAC: Trolox Equivalent Antioxidant Capacity; T2D: Type-2
There are no conflicts of interest.
DPB and ARB participated in the acquisition, analysis and interpretation of
data, and drafting of the manuscript. Both authors read and approved the
Received: 27 February 2013 Accepted: 24 April 2013
Published: 16 May 2013
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 8 of 12
1.Shaw JE, Sicree RA, Zimmet PZ: Global estimates of the prevalence of
diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010, 87:4–14.
2.Whiting DR, Guariguata L, Weil C, Shaw J: IDF diabetes atlas: global
estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res
Clin Pract 2011, 94:311–321.
3. Walgate R: Diabetes research for developing countries. N Biotechnol 2008,
4.Misra A, Singhal N, Khurana L: Obesity, the metabolic syndrome, and type
2 diabetes in developing countries: role of dietary fats and oils. J Am Coll
Nutr 2010, 29:289S–301S.
5. Fitzgerald MA, Rahman S, Resurreccion AP, Concepcion J, Daygon VD, Dipti
SS, Kabir KA, Klingner B, Morell M, Bird A: Identification of a major genetic
determinant of glycaemic index in rice. Rice 2011, 4:66–74.
6.Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker
EA, Nathan DM: Reduction in the incidence of type 2 diabetes with
lifestyle intervention or metformin. N Engl J Med 2002, 346:393–403.
7.Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA, Willett WC:
Whole-grain intake and the risk of type 2 diabetes: a prospective study
in men. Am J Clin Nutr 2002, 76:535–540.
8.Hodge AM, English DR, O'Dea K, Giles GG: Dietary patterns and diabetes
incidence in the Melbourne Collaborative Cohort Study. Am J Epidemiol
9.Brunner EJ, Mosdol A, Witte DR, Martikainen P, Stafford M, Shipley MJ,
Marmot MG: Dietary patterns and 15-y risks of major coronary events,
diabetes, and mortality. Am J Clin Nutr 2008, 87:1414–1421.
10. Nettleton JA, McKeown NM, Kanoni S, Lemaitre RN, Hivert MF, Ngwa J, van
Rooij FJ, Sonestedt E, Wojczynski MK, Ye Z, et al: Interactions of dietary
whole-grain intake with fasting glucose- and insulin-related genetic loci
in individuals of European descent: a meta-analysis of 14 cohort studies.
Diabetes Care 2010, 33:2684–2691.
11. Meyer KA, Kushi LH, Jacobs DR Jr, Slavin J, Sellers TA, Folsom AR:
Carbohydrates, dietary fiber, and incident type 2 diabetes in older
women. Am J Clin Nutr 2000, 71:921–930.
12.McKeown NM, Meigs JB, Liu S, Wilson PW, Jacques PF: Whole-grain intake
is favorably associated with metabolic risk factors for type 2 diabetes
and cardiovascular disease in the Framingham Offspring Study. Am J Clin
Nutr 2002, 76:390–398.
13.Pereira MA, Jacobs DR Jr, Pins JJ, Raatz SK, Gross MD, Slavin JL, Seaquist ER:
Effect of whole grains on insulin sensitivity in overweight
hyperinsulinemic adults. Am J Clin Nutr 2002, 75:848–855.
14.van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB: Dietary patterns
and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002,
15.Murtaugh MA, Jacobs DR Jr, Jacob B, Steffen LM, Marquart L:
Epidemiological support for the protection of whole grains against
diabetes. Proc Nutr Soc 2003, 62:143–149.
16.Venn BJ, Mann JI: Cereal grains, legumes and diabetes. Eur J Clin Nutr
17. de Munter JS, Hu FB, Spiegelman D, Franz M, van Dam RM: Whole grain,
bran, and germ intake and risk of type 2 diabetes: a prospective cohort
study and systematic review. PLoS Med 2007, 4:e261.
18.Priebe MG, van Binsbergen JJ, de Vos R, Vonk RJ: Whole grain foods for
the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev
19.Jang Y, Lee JH, Kim OY, Park HY, Lee SY: Consumption of whole grain and
legume powder reduces insulin demand, lipid peroxidation, and plasma
homocysteine concentrations in patients with coronary artery disease:
randomized controlled clinical trial. Arterioscler Thromb Vasc Biol 2001,
20.Lutsey PL, Jacobs DR Jr, Kori S, Mayer-Davis E, Shea S, Steffen LM, Szklo M,
Tracy R: Whole grain intake and its cross-sectional association with
obesity, insulin resistance, inflammation, diabetes and subclinical CVD:
The MESA Study. Br J Nutr 2007, 98:397–405.
21.Rave K, Roggen K, Dellweg S, Heise T, Tom Dieck H: Improvement of
insulin resistance after diet with a whole-grain based dietary
product: results of a randomized, controlled cross-over study in
obese subjects with elevated fasting blood glucose. Br J Nutr 2007,
22.Hallfrisch J, Fac N, Behall KM: Mechanisms of the effects of grains on
insulin and glucose responses. J Am Coll Nutr 2000, 19:320S–325S.
23. Slavin J: Why whole grains are protective: biological mechanisms. Proc Nutr
Soc 2003, 62:129–134.
Smith CE, Tucker KL: Health benefits of cereal fibre: a review of clinical
trials. Nutr Res Rev 2011, 15:1–14.
Jonnalagadda SS, Harnack L, Liu RH, McKeown N, Seal C, Liu S, Fahey GC:
Putting the whole grain puzzle together: health benefits associated with
whole grains–summary of American Society for Nutrition 2010 Satellite
Symposium. J Nutr 2011, 141:1011S–1022S.
Harris KA, Kris-Etherton PM: Effects of whole grains on coronary heart
disease risk. Curr Atheroscler Rep 2010, 12:368–376.
Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing
H: Fiber and magnesium intake and incidence of type 2 diabetes: a
prospective study and meta-analysis. Arch Intern Med 2007, 167:956–965.
Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC:
Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J
Med 2001, 345:790–797.
Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I: Dietary glycemic
index: health implications. J Am Coll Nutr 2009, 28(Suppl):446S–449S.
Sluijs I, Beulens JW, der AD V, Spijkerman AM, Grobbee DE, Van der Schouw
YT: Dietary intake of total, animal, and vegetable protein and risk of type
2 diabetes in the European Prospective Investigation into Cancer and
Nutrition (EPIC)-NL study. Diabetes Care 2010, 33:43–48.
Barclay AW, Petocz P, McMillan-Price J, Flood VM, Prvan T, Mitchell P, Brand-
Miller JC: Glycemic index, glycemic load, and chronic disease risk–a
meta-analysis of observational studies. Am J Clin Nutr 2008, 87:627–637.
Halton TL, Liu S, Manson JE, Hu FB: Low-carbohydrate-diet score and risk
of type 2 diabetes in women. Am J Clin Nutr 2008, 87:339–346.
Livesey G, Taylor R, Hulshof T, Howlett J: Glycemic response and health–a
systematic review and meta-analysis: relations between dietary glycemic
properties and health outcomes. Am J Clin Nutr 2008, 87:258S–268S.
Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I: Carbohydrates–the
good, the bad and the whole grain. Asia Pac J Clin Nutr 2008,
Okarter N, Liu RH: Health benefits of whole grain phytochemicals. Crit Rev
Food Sci Nutr 2010, 50:193–208.
Ceriello A, Motz E: Is oxidative stress the pathogenic mechanism
underlying insulin resistance, diabetes, and cardiovascular disease? The
common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004,
Dandona P, Aljada A, Chaudhuri A, Mohanty P: Endothelial dysfunction,
inflammation and diabetes. Rev Endocr Metab Disord 2004, 5:189–197.
Robertson RP: Chronic oxidative stress as a central mechanism for
glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem
Brownlee M: Biochemistry and molecular cell biology of diabetic
complications. Nature 2001, 414:813–820.
Niedowicz DM, Daleke DL: The role of oxidative stress in diabetic
complications. Cell Biochem Biophys 2005, 43:289–330.
Cardona F, Tunez I, Tasset I, Montilla P, Collantes E, Tinahones FJ: Fat
overload aggravates oxidative stress in patients with the metabolic
syndrome. Eur J Clin Invest 2008, 38:510–515.
Pizent A, Pavlovic M, Jurasovic J, Dodig S, Pasalic D, Mujagic R:
Antioxidants, trace elements and metabolic syndrome in elderly
subjects. J Nutr Health Aging 2010, 14:866–871.
Levitan EB, Cook NR, Stampfer MJ, Ridker PM, Rexrode KM, Buring JE,
Manson JE, Liu S: Dietary glycemic index, dietary glycemic load, blood
lipids, and C-reactive protein. Metabolism 2008, 57:437–443.
Guo W, Kong E, Meydani M: Dietary polyphenols, inflammation, and
cancer. Nutr Cancer 2009, 61:807–810.
Anson NM, Aura AM, Selinheimo E, Mattila I, Poutanen K, van den Berg R,
Havenaar R, Bast A, Haenen GR: Bioprocessing of wheat bran in whole
wheat bread increases the bioavailability of phenolic acids in men and
exerts antiinflammatory effects ex vivo. J Nutr 2011, 141:137–143.
Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M,
Mykkanen H, Poutanen K: Impact of dietary polyphenols on carbohydrate
metabolism. Int J Mol Sci 2010, 11:1365–1402.
Salas-Salvado J, Martinez-Gonzalez MA, Bullo M, Ros E: The role of diet in
the prevention of type 2 diabetes. Nutr Metab Cardiovasc Dis 2011,
Fardet A: New hypotheses for the health-protective mechanisms of
whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010, 23:65–134.
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 9 of 12
49.Adom KK, Sorrells ME, Liu RH: Phytochemicals and antioxidant activity of
milled fractions of different wheat varieties. J Agric Food Chem 2005,
Slavin JL, Jacobs D, Marquart L: Grain processing and nutrition. Crit Rev
Biotechnol 2001, 21:49–66.
Bryngelsson S, Dimberg LH, Kamal-Eldin A: Effects of commercial
processing on levels of antioxidants in oats (Avena sativa L.). J Agric Food
Chem 2002, 50:1890–1896.
Qiu Y, Liu Q, Beta T: Antioxidant activity of commercial wild rice and
identification of flavonoid compounds in active fractions. J Agric Food
Chem 2009, 57:7543–7551.
Xu SY, Cheng HJ, Guo YY, Ding SR: Amino acid contents of barley grains
in relation to cultivars and cultivation conditions. Zhejiang Agricultural
Fickler J, Fontaine J, Heimbeck W: The amino acid composition of feedstuffs.
Ridgefield Park, NJ; 2001.
Lee TT, Wang MM, Hou RC, Chen LJ, Su RC, Wang CS, Tzen JT: Enhanced
methionine and cysteine levels in transgenic rice seeds by the accumulation
of sesame 2S albumin. Biosci Biotechnol Biochem 2003, 67:1699–1705.
Council NAoS-NR: Joint United States-Canadian tables of Feed Composition.
2nd edition. Washington, D.C; 1964.
Gibson C, Lyons G, Choi B, Park S, Stewart D: Selenium enriched barley.
Biofortification to improve human health. Hobart, Australia: 12th Australian
Barley Technical Symposium; 2005.
Williams PN, Lombi E, Sun GX, Scheckel K, Zhu YG, Feng X, Zhu J, Carey AM,
Adomako E, Lawgali Y, et al: Selenium characterization in the global rice
supply chain. Environ Sci Technol 2009, 43:6024–6030.
Eurola M, Hietaniemi V, Kontturi M, Tuuri H, Kangas A, Niskanen M,
Saastamoinen M: Selium content of Finnish oats in 1997–1999: effect of
cultivars and cultivation techniques. Ag Food Sci 2004, 13:46–53.
Fardet A, Llorach R, Orsoni A, Martin JF, Pujos-Guillot E, Lapierre C, Scalbert
A: Metabolomics provide new insight on the metabolism of dietary
phytochemicals in rats. J Nutr 2008, 138:1282–1287.
Ward JL, Poutanen K, Gebruers K, Piironen V, Lampi AM, Nystrom L,
Andersson AA, Aman P, Boros D, Rakszegi M, et al: The HEALTHGRAIN
Cereal Diversity Screen: concept, results, and prospects. J Agric Food
Chem 2008, 56:9699–9709.
Bruce SJ, Guy PA, Rezzi S, Ross AB: Quantitative measurement of betaine
and free choline in plasma, cereals and cereal products by isotope
dilution LC-MS/MS. J Agric Food Chem 2010, 58:2055–2061.
Britz SJ, Prasad PV, Moreau RA, Allen LH Jr, Kremer DF, Boote KJ: Influence
of growth temperature on the amounts of tocopherols, tocotrienols, and
gamma-oryzanol in brown rice. J Agric Food Chem 2007, 55:7559–7565.
Nystrom L, Lampi A-M, Andersson AAM, Kamal-Eldin A, Gebruers K, Courtin
CM, Delcour JA, Li L, Ward JL, Fras A, et al: Phytochemicals and Dietary
Fiber Components in Rye Varieties in the HEALTHGRAIN Diversity
Screen. J Agric Food Chem 2008, 56:9758–9766.
Barnes PJ: Cereal tocopherols. Amsterdam: Elsevier; 1983.
Lasztity R, Berndorfer-Kraszner E, Huszar M: On the presence and distribution
of some bioactive agents in oat varieties. New York: Academic Press; 1980.
Ehrenbergerova J, Belcrediova N, Pryma J, Vaculova K, Newman CW: Effect
of cultivar, year grown, and cropping system on the content of
tocopherols and tocotrienols in grains of hulled and hulless barley. Plant
Foods Hum Nutr 2006, 61:145–150.
Shewry PR, Piironen V, Lampi A-M, Nystrom L, Li L, Rakszegi M, Fras A, Boros
D, Gebruers K, Courtin CM, et al: Phytochemical and Fiber Components in
Oat Varieties in the HEALTHGRAIN Diversity Screen. J Agric Food Chem
Zilic S, Sukalovic VH, Dodig D, Maksimovic V, Maksimovic M, Basic Z:
Antioxidant activity of small grain cereals caused by phenolics and lipid
soluble antioxidants. J Cereal Sci 2011, 54:417–424.
Evans LE, Dedio W, Hill RD: Variability in the alkylresorcinol content of rye
grains. Can J Plant Sci 1973, 53:485–488.
Dimberg LH, Molteberg EL, Solheim R, Frølich W: Variation in Oat Groats
Due to Variety, Storage and Heat Treatment. I: Phenolic Compounds.
J Cereal Sci 1996, 24:263–272.
Emmons CL DMP: Antioxidant activity and phenolic content of oat as
affected by cultivar and location. Crop Sci 2001, 41:1676–1681.
de Zwart FJ, Slow S, Payne RJ, Lever M, George PM, Gerrard JA, Chambers
ST: Glycine betaine and glycine betaine analogues in common foods.
Food Chem 2003, 83:197–204.
74. Andersson AAM, Lampi A-M, Nystrom L, Piironen V, Li L, Ward JL, Gebruers
K, Courtin CM, Delcour JA, Boros D, et al: Phytochemical and Dietary Fiber
Components in Barley Varieties in the HEALTHGRAIN Diversity Screen.
J Agric Food Chem 2008, 56:9767–9776.
Baublis AJ, Lu C, Clydesdale FM, Decker EA: Potential of wheat-based
breakfast cereals as a source of dietary antioxidants. J Am Coll Nutr 2000,
Mattila P, Pihlava JM, Hellstrom J: Contents of phenolic acids, alkyl- and
alkenylresorcinols, and avenanthramides in commercial grain products.
J Agric Food Chem 2005, 53:8290–8295.
Parikka K, Rowland IR, Welch RW, Wahala K: In vitro antioxidant activity
and antigenotoxicity of 5-n-alkylresorcinols. J Agric Food Chem 2006,
Adom KK, Sorrells ME, Liu RH: Phytochemical profiles and antioxidant
activity of wheat varieties. J Agric Food Chem 2003, 51:7825–7834.
Lampi A-M, Nurmi T, Ollilainen V, Piironen V: Tocopherols and Tocotrienols
in Wheat Genotypes in the HEALTHGRAIN Diversity Screen. J Agric Food
Chem 2008, 56:9716–9721.
Davis KR, Peters LJ, LeTourneau D: Variability of the vitamin content of
wheat. Cereal Foods World 1984, 29:364–370.
Clarke B, Liang R, Morell MK, Bird AR, Jenkins CL, Li Z: Gene expression in a
starch synthase IIa mutant of barley: changes in the level of gene
transcription and grain composition. Funct Integr Genomics 2008, 8:211–221.
Bird AR, Vuaran MS, King RA, Noakes M, Keogh J, Morell MK, Topping DL:
Wholegrain foods made from a novel high-amylose barley variety
(Himalaya 292) improve indices of bowel health in human subjects. Br J
Nutr 2008, 99:1032–1040.
King RA, Noakes M, Bird AR, Morell MK, Topping DL: An extruded cereal
made from a high amylose barley cultivar has a low glycemic index and
lower plasma insulin response than one made from a standard barley.
J Cereal Sci 2008, 48:526–530.
Ross AB, Aman P, Andersson R, Kamal-Eldin A: Chromatographic analysis of
alkylresorcinols and their metabolites. J Chromatogr A 2004, 1054:157–164.
Peterson DM, Qureshi AA: Genotype and environment effects on tocols of
barley and oats. Cereal Chem 1993, 70:157–162.
Peterson DM: Oat Antioxidants. J Cereal Sci 2001, 33:115–129.
Bergman CJ, Xu Z: Genotype and environment effects on tocopherol,
tocotrienol, and ç-oryzanol contents of southern U.S. rice. Cereal Chem
Miller A, Engel KH: Content of gamma-oryzanol and composition of steryl
ferulates in brown rice (Oryza sativa L.) of European origin. J Agric Food
Chem 2006, 54:8127–8133.
Moore J, Hao Z, Zhou K, Luther M, Costa J, Yu LL: Carotenoid, tocopherol,
phenolic acid, and antioxidant properties of Maryland-grown soft wheat.
J Agric Food Chem 2005, 53:6649–6657.
Lampi AM, Nurmi T, Piironen V: Effects of the environment and genotype
on tocopherols and tocotrienols in wheat in the HEALTHGRAIN diversity
screen. J Agric Food Chem 2010, 58:9306–9313.
Fernandez-Orozco R, Li L, Harflett C, Shewry PR, Ward JL: Effects of
Environment and Genotype on Phenolic Acids in Wheat in the
HEALTHGRAIN Diversity Screen. J Agric Food Chem 2010, 58:9341–9352.
Li L, Shewry PR, Ward JL: Phenolic Acids in Wheat Varieties in the
HEALTHGRAIN Diversity Screen. J Agric Food Chem 2008, 56:9732–9739.
Heaney RP: Factors influencing the measurement of bioavailability,
taking calcium as a model. J Nutr 2001, 131:1344S–1348S.
Riedl J, Linseisen J, Hoffmann J, Wolfram G: Some Dietary Fibers Reduce
the Absorption of Carotenoids in Women. J Nutr 1999, 129:2170–2176.
Fenech M, Noakes M, Clifton P, Topping D: Aleurone Flour Is a Rich Source
of Bioavailable Folate in Humans. J Nutr 1999, 129:1114–1119.
Scholz S, Williamson G: Interactions affecting the Bioavailability of dietary
polyphenols in vivo. Int J Vitam Nutr Res 2007, 77:224–235.
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L: Polyphenols: food
sources and bioavailability. Am J Clin Nutr 2004, 79:727–747.
Price R, Welch R, Lee-Manion A, Bradbury I, Strain JJ: Total phenolics and
antioxidant potential in plasma and urine of humans after consumption
of wheat bran. Cereal Chem 2008, 85:152–157.
Ross AB, Kamal-Eldin A, Lundin EA, Zhang JX, Hallmans G, Aman P: Cereal
alkylresorcinols are absorbed by humans. J Nutr 2003, 133:2222–2224.
100. Linko-Parvinen AM, Landberg R, Tikkanen MJ, Adlercreutz H, Penalvo JL:
Alkylresorcinols from whole-grain wheat and rye are transported in
human plasma lipoproteins. J Nutr 2007, 137:1137–1142.
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 10 of 12
101. Landberg R, Linko AM, Kamal-Eldin A, Vessby B, Adlercreutz H, Aman P:
Human plasma kinetics and relative bioavailability of alkylresorcinols
after intake of rye bran. J Nutr 2006, 136:2760–2765.
102. Kamal-Eldin A, Poruru A, Eliasson AC, Aman P: Alkylresorcinols as
antioxidants: hydrogen donation and peroxyl radical-scavenging effects.
J Sci Food Agric 2001, 81:353–356.
103. Harder H, Tetens I, Let MB, Meyer AS: Rye bran bread intake elevates
urinary excretion of ferulic acid in humans, but does not affect the
susceptibility of LDL to oxidation ex vivo. Eur J Nutr 2004, 43:230–236.
104. Craig SA: Betaine in human nutrition. Am J Clin Nutr 2004, 80:539–549.
105. Price RK, Keaveney EM, Hamill LL, Wallace JM, Ward M, Ueland PM, McNulty
H, Strain JJ, Parker MJ, Welch RW: Consumption of wheat aleurone-rich
foods increases fasting plasma betaine and modestly decreases fasting
homocysteine and LDL-cholesterol in adults. J Nutr 2010, 140:2153–2157.
106. Likes R, Madl RL, Zeisel SH, Craig SA: The betaine and choline content of a
whole wheat flour compared to other mill streams. J Cereal Sci 2007,
107. Hallberg L, Hulthen L: Prediction of dietary iron absorption: an algorithm
for calculating absorption and bioavailability of dietary iron. Am J Clin
Nutr 2000, 71:1147–1160.
108. Serafini M, Laranjinha JA, Almeida LM, Maiani G: Inhibition of human LDL
lipid peroxidation by phenol-rich beverages and their impact on plasma
total antioxidant capacity in humans. J Nutr Biochem 2000, 11:585–590.
109. van der Burg-Koorevaar MC, Miret S, Duchateau GS: Effect of milk and
brewing method on black tea catechin bioaccessibility. J Agric Food
Chem 2011, 59:7752–7758.
110. Reddy VC, Vidya Sagar GV, Sreeramulu D, Venu L, Raghunath M: Addition of
milk does not alter the antioxidant activity of black tea. Ann Nutr Metab
111. van het Hof KH, Kivits GA, Weststrate JA, Tijburg LB: Bioavailability of
catechins from tea: the effect of milk. Eur J Clin Nutr 1998, 52:356–359.
112. Anson NM, Selinheimo E, Havenaar R, Aura AM, Mattila I, Lehtinen P, Bast A,
Poutanen K, Haenen GR: Bioprocessing of wheat bran improves in vitro
bioaccessibility and colonic metabolism of phenolic compounds. J Agric
Food Chem 2009, 57:6148–6155.
113. Kern SM, Bennett RN, Mellon FA, Kroon PA, Garcia-Conesa MT: Absorption
of hydroxycinnamates in humans after high-bran cereal consumption.
J Agric Food Chem 2003, 51:6050–6055.
114. Rice-Evans C: Flavonoid antioxidants. Curr Med Chem 2001, 8:797–807.
115. Scalbert A, Morand C, Manach C, Remesy C: Absorption and metabolism
of polyphenols in the gut and impact on health. Biomed Pharmacother
116. Selma MV, Espin JC, Tomas-Barberan FA: Interaction between Phenolics
and Gut Microbiota: Role in Human Health. J Agric Food Chem 2009,
117. Hervert-Hernandez D, Goni I: Dietary Polyphenols and Human Gut
Microbiota: a Review. Food Reviews International 2011, 27:154–169.
118. Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa MT: Intestinal
release and uptake of phenolic antioxidant diferulic acids. Free Radic Biol
Med 2001, 31:304–314.
119. Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa MT: Esterase activity
able to hydrolyze dietary antioxidant hydroxycinnamates is distributed
along the intestine of mammals. J Agric Food Chem 2001, 49:5679–5684.
120. Kroon PA, Faulds CB, Ryden P, Robertson JA, Williamson G: Release of
covalently bound ferulic acid from fiber in the human colon. J Agric Food
Chem 1997, 45:661–667.
121. Rondini L, Peyrat-Maillard M-N, Marsset-Baglieri A, Fromentin G, Durand P,
Tomé D, Prost M, Berset C: Bound Ferulic Acid from Bran Is More
Bioavailable than the Free Compound in Rat. J Agric Food Chem 2004,
122. Kim SH, Lee SS, Kim JY, Kim JH, Lee Da H: Meal replacement with mixed rice is
more effective than white rice in weight control, while improving
antioxidant enzyme activity in obese women. Nutrition research (New York, NY)
123. Enright L, Slavin J: No effect of 14 day consumption of whole grain diet
compared to refined grain diet on antioxidant measures in healthy,
young subjects: a pilot study. Nutr J 2010, 9:12.
124. Andersson A, Tengblad S, Karlstrom B, Kamal-Eldin A, Landberg R, Basu S,
Aman P, Vessby B: Whole-grain foods do not affect insulin sensitivity or
markers of lipid peroxidation and inflammation in healthy, moderately
overweight subjects. J Nutr 2007, 137:1401–1407.
125. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J: Free radicals
and antioxidants in normal physiological functions and human disease.
Int J Biochem Cell Biol 2007, 39:44–84.
126. Chen CY, Milbury PE, Collins FW, Blumberg JB: Avenanthramides are
bioavailable and have antioxidant activity in humans after acute
consumption of an enriched mixture from oats. J Nutr 2007,
127. Bruce B, Spiller GA, Klevay LM, Gallagher SK: A diet high in whole and
unrefined foods favorably alters lipids, antioxidant defenses, and colon
function. J Am Coll Nutr 2000, 19:61–67.
128. Myhrstad MC, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JO: Flavonoids
increase the intracellular glutathione level by transactivation of the
gamma-glutamylcysteine synthetase catalytical subunit promoter.
Free Radic Biol Med 2002, 32:386–393.
129. Moskaug JO, Carlsen H, Myhrstad MC, Blomhoff R: Polyphenols and
glutathione synthesis regulation. Am J Clin Nutr 2005, 81:277S–283S.
130. Thomson CD, Ong LK, Robinson MF: Effects of supplementation with
high-selenium wheat bread on selenium, glutathione peroxidase and
related enzymes in blood components of New Zealand residents. Am J
Clin Nutr 1985, 41:1015–1022.
131. Barclay MNI, Macpherson A: Selenium content of wheat for bread making
in Scotland and the relationship between glutathione-peroxidase levels
in whole-blood and bread consumption. Br J Nutr 1992, 68:261–270.
132. Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst
R: Selenium in human health and disease. Antioxid Redox Signal 2011,
133. del Molino IMM, Rojo B, Martínez-Carrasco R, Pérez P: Varietal differences in
amino acid composition of wheat (Triticum aestivum L) grain. J Sci Food
134. Wang Q, Han P, Zhang M, Xia M, Zhu H, Ma J, Hou M, Tang Z, Ling W:
Supplementation of black rice pigment fraction improves antioxidant
and anti-inflammatory status in patients with coronary heart disease.
Asia Pac J Clin Nutr 2007, 16(Suppl 1):295–301.
135. Seidel C, Boehm V, Vogelsang H, Wagner A, Persin C, Glei M, Pool-Zobel BL,
Jahreis G: Influence of prebiotics and antioxidants in bread on the
immune system, antioxidative status and antioxidative capacity in male
smokers and non-smokers. Br J Nutr 2007, 97:349–356.
136. Lotito SB, Frei B: Consumption of flavonoid-rich foods and increased
plasma antioxidant capacity in humans: Cause, consequence, or
epiphenomenon? Free Radic Biol Med 2006, 41:1727–1746.
137. Erel O: A novel automated direct measurement method for total
antioxidant capacity using a new generation, more stable ABTS radical
cation. Clin Biochem 2004, 37:277–285.
138. Bartlett HE, Eperjesi F: Nutritional supplementation for type 2 diabetes: a
systematic review. Ophthalmic Physiol Opt 2008, 28:503–523.
139. Golbidi S, Ebadi SA, Laher I: Antioxidants in the treatment of diabetes.
Curr Diabetes Rev 2011, 7:106–125.
140. Beattie R, Lee A, Strain J: Evaluation of the in vivo antioxidant activity of
wheat bran in human subjects. Proc Nutr Soc 2003, 62:17A.
141. Ou B, Huang D, Hampsch-Woodill M, Flanagan JA, Deemer EK: Analysis of
antioxidant activities of common vegetables employing oxygen radical
absorbance capacity (ORAC) and ferric reducing antioxidant power
(FRAP) assays: a comparative study. J Agric Food Chem 2002,
142. Niki E: Assessment of antioxidant capacity in vitro and in vivo. Free Radic
Biol Med 2010, 49:503–515.
143. Chuang SC, Vermeulen R, Sharabiani MT, Sacerdote C, Fatemeh SH, Berrino
F, Krogh V, Palli D, Panico S, Tumino R, et al: The intake of grain fibers
modulates cytokine levels in blood. Biomarkers 2011, 16:504–510.
144. de Mello VD, Schwab U, Kolehmainen M, Koenig W, Siloaho M, Poutanen K,
Mykkanen H, Uusitupa M: A diet high in fatty fish, bilberries and
wholegrain products improves markers of endothelial function and
inflammation in individuals with impaired glucose metabolism in a
randomised controlled trial: the Sysdimet study. Diabetologia 2011,
145. Oliveira A, Rodriguez-Artalejo F, Lopes C: The association of fruits,
vegetables, antioxidant vitamins and fibre intake with high-sensitivity
C-reactive protein: sex and body mass index interactions. Eur J Clin Nutr
146. Herder C, Peltonen M, Koenig W, Sutfels K, Lindstrom J, Martin S, Ilanne-Parikka
P, Eriksson JG, Aunola S, Keinanen-Kiukaanniemi S, et al: Anti-inflammatory
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 11 of 12
effect of lifestyle changes in the Finnish Diabetes Prevention Study.
Diabetologia 2009, 52:433–442.
147. Al-Lahham SH, Peppelenbosch MP, Roelofsen H, Vonk RJ, Venema K:
Biological effects of propionic acid in humans; metabolism, potential
applications and underlying mechanisms. Biochim Biophys Acta 1801,
148. Roelofsen H, Priebe MG, Vonk RJ: The interaction of short-chain fatty acids
with adipose tissue: relevance for prevention of type 2 diabetes.
Benef Microbes 2010, 1:433–437.
149. Verbeke K, Ferchaud-Roucher V, Preston T, Small AC, Henckaerts L, Krempf
M, Wang H, Vonk RJ, Priebe MG: Influence of the type of indigestible
carbohydrate on plasma and urine short-chain fatty acid profiles in
healthy human volunteers. Eur J Clin Nutr 2010, 64:678–684.
150. Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG: Antibiotics prevent
liver injury in rats following long-term exposure to ethanol.
Gastroenterology 1995, 108:218–224.
151. Lichtman SN, Keku J, Schwab JH, Sartor RB: Hepatic injury associated with
small bowel bacterial overgrowth in rats is prevented by metronidazole
and tetracycline. Gastroenterology 1991, 100:513–519.
152. Lichtman SN, Sartor RB, Keku J, Schwab JH: Hepatic inflammation in rats
with experimental small intestinal bacterial overgrowth. Gastroenterology
153. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts
L, Naslain D, Neyrinck A, Lambert DM, et al: Changes in gut microbiota
control inflammation in obese mice through a mechanism involving
GLP-2-driven improvement of gut permeability. Gut 2009, 58:1091–1103.
Cite this article as: Belobrajdic and Bird: The potential role of
phytochemicals in wholegrain cereals for the prevention of type-2
diabetes. Nutrition Journal 2013 12:62.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
Belobrajdic and Bird Nutrition Journal 2013, 12:62
Page 12 of 12