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Bread, Oldest Man-made Staple Food in Human Diet. Bread intake is integral to good health and whole grain cereals beneficial against chronic diseases

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Abstract

ABSTRACT Bread is the most important staple food of humans from the prehistoric time. Baked bread is integral to human health with plenty of major nutrients, antioxidants and vitamins. After thousands of years, it remains the most regularly consumed food in the world, due to its convenience, portability, nutrition, and taste. Archaeological studies found that prehistoric human food hunter-gatherers started baking bread at least 30,000 years ago. Annual global wheat production is around 700 million tons. Over the same period the global average production of rice was 704 mt and for maize 874 mt. In the last decades a large number of scientific studies analysed wheat grain composition, protein content, essential amino acids, carbohydrates, mono- and oligo- saccharides, starch, vitamins, minerals, metals, dietary fibers, polyphenols, protenoids and carotenoids. All these components of wheat grain have direct relevance to human nutrition and health because they provide nutritional quality, energy and essential micro nutrients. Beneficial health effects from whole grain bread and other cereals have been studied by a large number of epidemiological and dietary studies. Most of the results found that consumption is associated with reduction of chronic diseases, such as coronary heart and cardiovascular diseases (CVDs), colon and breast cancers, obesity, type 2 diabetes and gastrointestinal diseases. It has been proved that whole grains help maintain human weight and enhances weight loss in obese individuals. In addition whole-grain fiber maintains optimum health due to the antioxidant phytochemicals and vitamins. Fiber intake from bread lowers blood pressure and serum cholesterol levels, increases soluble fiber improving glycemia and insulin sensitivity in non-diabetic individuals and diabetics. Also, reduces gastrointestinal disorders, such as gastroesophageal reflux disease, duodenal ulcer, constipation and hemorrhoids. Prebiotic fibers of whole grain cereals appear to enhance immune function. This review presents the most important studies in the last decade on the subject of wheat grain, and selected epidemiological and dietary research investigations on the health benefits of bread consumption in relation to reduction of CVDs, certain types of cancer, diabetes and obesity.
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WEBSITE: www.chem-tox-ecotox.org/ScientificReviews 15/11/2018
SCIENTIFIC REVIEWS
Bread, Oldest Man-made Staple Food in Human Diet
Bread intake is integral to good health and whole grain cereals
beneficial against chronic diseases
Athanasios Valavanidis
Department of Chemistry, National and Kapodistrian University of Athens, University
Campus Zografou, 15784 Athens, Greece
ABSTRACT
Bread is the most important staple food of humans from the prehistoric
time. Baked bread is integral to human health with plenty of major nutrients,
antioxidants and vitamins. After thousands of years, it remains the most regularly
consumed food in the world, due to its convenience, portability, nutrition, and
taste. Archaeological studies found that prehistoric human food hunter-gatherers
started baking bread at least 30,000 years ago. Annual global wheat production is
around 700 million tons. Over the same period the global average production of
rice was 704 mt and for maize 874 mt. In the last decades a large number of
scientific studies analysed wheat grain composition, protein content, essential
amino acids, carbohydrates, mono- and oligo- saccharides, starch, vitamins,
minerals, metals, dietary fibers, polyphenols, protenoids and carotenoids. All these
components of wheat grain have direct relevance to human nutrition and health
because they provide nutritional quality, energy and essential micro nutrients.
Beneficial health effects from whole grain bread and other cereals have been
studied by a large number of epidemiological and dietary studies. Most of the
results found that consumption is associated with reduction of chronic diseases,
such as coronary heart and cardiovascular diseases (CVDs), colon and breast
cancers, obesity, type 2 diabetes and gastrointestinal diseases. It has been proved
that whole grains help maintain human weight and enhances weight loss in obese
individuals. In addition whole-grain fiber maintains optimum health due to the
antioxidant phytochemicals and vitamins. Fiber intake from bread lowers blood
pressure and serum cholesterol levels, increases soluble fiber improving glycemia
and insulin sensitivity in non-diabetic individuals and diabetics. Also, reduces
gastrointestinal disorders, such as gastroesophageal reflux disease, duodenal ulcer,
constipation and hemorrhoids. Prebiotic fibers of whole grain cereals appear to
enhance immune function. This review presents the most important studies in the
last decade on the subject of wheat grain, and selected epidemiological and dietary
research investigations on the health benefits of bread consumption in relation to
reduction of CVDs, certain types of cancer, diabetes and obesity.
2
Introduction: bread in prehistoric human societies
Bread is the most important staple food of early prehistoric human
societies. Bread from domesticated wheat led to changes of nomadic lifestyle of
hunter-gatherers and started the first revolutionary agricultural civilization. It was
discovered recently that baked bread was used for the diet of hunter-gatherers
before the development of farming. In September 2018 archaeologists discovered
the oldest direct evidence of baked bread in archaeological history, dating back an
astounding 14,400 years, in Jordan. The research paper was published in the
prestigious journal Proceedings of the National Academy of Sciences, USA (15 Sept.
2018).1 Researchers found flatbreads that was baked by a group of hunter-
gatherers called the Natufians in a firepit at Shubayqa 1, an excavation site located
about 200 km northeast of the Jordanian capital of Amman. Its exceptional age is
significant because it predates the First Agricultural Revolution took place at around
10,000-12,000 B.C. in the region of Fertile Crescent (called also the "Cradle of
Civilization"). The region is in the intersection of the rivers Euphrates, Tigris and Nile
(Mesopotamia, ancient Egypt), through modern-day southern Iraq, Syria, Lebanon,
Jordan, Israel and northern Egypt. The discovery suggests that hunter-gatherers
produced bread by harvesting wild cereals. Baking with these untamed grains may
have inspired prehistoric humans to cultivate the earliest farms in historyan
innovation at the root of modern civilization. The bread production was identified
with the help of advanced scientific techniques and ashy bread remnants recovered
from Shubayqa 1 (Jordan) were analysed by scanning electron microscopy.1
There are recently many studies pushing back the timeline of bread-baking.
Some research suggested humans experimented with proto-flour more than 30,000
years ago. This doughy foodstuf the
first sedentary urban settlements. Archaeological discoveries provided crucial
insights into the staple food that founded the modern world. Researchers have
assumed that humans were foraging for fruits, nuts and roots long before 100,000
years ago, but cereal grains are quite a new addition to the early prehistoric
gastronomic picture. The inclusion of cereals in human diet is considered an
3
important step in human evolution because of the technical complexity and the
culinary manipulation that are required to turn grains into staples. Descendent of
the wild sorghum found on the tools still makes up a large portion of modern diets
in sub-Saharan products including breads, porridge and even beer.2
The Fertile Crescent
The Natufian region (Jordan)
Figure 1. The Fertile Crescent (known as "cradle of civilization") in the Mesopota-
mia region where agriculture started (10,000-12,000 BC). There is evidence for the
earliest human agricultural civilization with first plant cultivations and animal
herding. The Natufian culture (region of Jordan) existed in late Paleolithic period.
Natufians were hunter-gatherers that foraged for food (wheat, barley and
almonds), and hunted deer, cattle, horse, and other wild animals.
A scientific group investigated remnants of starch grains on 30,000-year-old
grinding stones. The discovery indicated that prehistoric man may have dined on an
early form of flat bread, contrary to the popular image as primarily a meat-eater.
The findings, published in PNAS (2010) indicate that Palaeolithic Europeans ground
down plant roots similar to potatoes to make flour, which was later whisked into
dough. The discovery changes the assumed subsistence of Paleolithic Europeans
that was based on animal protein and fat, whereas evidence for plant consumption
was rare. A group of scientists found starch grains from various wild plants on the
surfaces of grinding tools at the sites of Bilancino II (Italy), Kostenki 16Uglyanka
(Russia), and Pavlov VI (Czech Republic). The 3 sites suggested that vegetal food
processing, and possibly the production of flour, was a common practice,
widespread across Europe from at least ~30,000 y ago. It is likely that high energy
4
content plant foods were available and were used as components of the food
economy of these mobile huntergatherers.3
Figure 2. The site of Shubayqa (Jordan) showing Structure 1 and one of the
fireplaces (the oldest one) where the bread-like remains were discovered [Arranz-
Otaegui A, et al. Archaeobotanical evidence reveals the origin of bread 14,400 years
ago in northeastern Jordan. Proc Natl Acad Sci USA 115(31):7925-7930, 2018].
Recent scholarship suggests humans started baking bread at least 30,000
years ago. Prehistoric humans had already been making gruel from water and
grains, so it was a small step to starting cooking this mixture into a solid by frying it
on stones. Around 10,000 BC, with the dawn of the Neolithic age and the spread of
agriculture, grains became the mainstay of making bread. The earliest bread grains
would have been ground by hand with rocks. The Mesopotamians refined this
process around 800 BC, using two flat, circular stones, stacked on top one another
to grind the grain. These stones were continuously rotated by draft animals or
slaves. The milling created smooth, finely ground flour that quickly became prized
as a status symbol. 4
Also, is must be emphasized that the domestication of wheat around 10,000
years ago marked a dramatic turn in the development and evolution of human
civilization, as it enabled the transition from a hunter-gatherer and nomadic
pastoral society to a more sedentary agrarian one. Bread as a staple food, like rice
and soya, provided to humans an important source of carbohydrates (energy).
5
Cooked bread is also portable and compact, which helps to explain why it has been
an integral part of our diet for thousands of years.5
The origins of ancient wheat have been established by many archaeological
studies. Ancient wheat first occurred in parts of Turkey, Lebanon, Syria, Israel, Egypt
and Ethiopia. Domesticated Einkorn wheat in Turkey dates back to 9,000 BC,
whereas evidence of the existence of wild barley (Hordeum sp) goes as far back as
23,000 BC. Cultivation of wheat began to spread beyond the Fertile Crescent after
about 8,000 BC. Slow domestication of wheat and other cereals implies that after
cultivation began, wild cereals may have remained unchanged for a long period,
supporting claims that agriculture originated in the Near East approximately 10,500
years before the present 6,7
Wheat bread is widely consumed worldwide
Wheat bread is the third most widely consumed staple food, others are rice
and maize. The importance of wheat and its contribution to the diets of humans
and livestock cannot be disputed. Available figures of global wheat production
show an average annual production of 680 million tons (mt) (2008) over the last 5
years with almost 700 mt being produced in 2011 (Food and Agriculture
Organization of the United Nations, Rome, FAOStat http://faostat.fao.org/site/
291/default.aspx). Over the same period the global average production of rice was
704 mt and for maize 874 mt. However, wheat is unrivaled in its range of
cultivation, from Scandinavia and Russia to Argentina, including elevated regions in
the tropics and subtropics. Increasing global demand for wheat is based on the
ability to make unique food products (bread, baked good, pasta-macaroni, pastry,
pies, bisquit, etc) and the increasing consumption of these products with
industrialization and westernization of many developing countries.8
High levels of per capita consumption of bread and bread products (2016)
were recorded in the United Kingdom (96 kg/year), Spain (77 kg/year), Italy (65
kg/year), Germany (65 kg/year), Russia (61 kg/year), France (52 kg/year), USA (46
kg/year). Although per capita consumption in China was 7 kg/year and India 2
kg/year, it is possible that there are underestimated figures, because a large portion
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of bread-like product consumption may originate from home or small street
bakeries, which are not covered by the appropriate statistics. In the last decade
China and India showed a sharp rise in bread consumption mainly spurred by
confectionary products and sweet-type bakery items.9
According to a world bread and bakery report, the global bread and bakery
product market displayed sustainable growth increasing from 122,000 tons in 2007
to 129,000 tons in 2016. In value terms, global consumption of bread and bakery
products stood at $358 billion dollars in 2016.9 Based on the results for 2016, the
countries with the highest consumption were the U.S.A. (14.7 million tons), China
(9.3 mt), Russia (8.7 mt) the UK (6.2 mt), Germany (5.2 mt), Egypt (4.6 mt) and Italy
(3.9 mt), together accounting for approximately 41% of global consumption.9
Figure 3. The global production of wheat in 2011 was 700 million tons (mt), the
third most widely consumed after maize (874 mt) and rice (704 mt). Bread is the
staple food of the Middle East, Central Asia, North Africa, Europe, and in European-
derived cultures (North & South Americas, Australia and Southern Africa).
Essential nutrients from cereals to human diet
 the name of the Roman goddess
of agriculture and harvesting. The first cereal grains were cultivated almost 12,000
years ago by ancient farming communities dwelling in the Fertile Crescent area
(Mesopotamia-Egypt). The first Neolithic founder crops that actually initiated the
development of agriculture include einkorn wheat, emmer wheat, and barley.
7
Cereals have a long history of use as stable food products by humans. The most
important cereals are: wheat, corn, rye, rice, barley, oat, triticale, sorghum and
millets. Cereals are a fundamental dietary source of energy, carbohydrates,
proteins and fibre, as well as containing a range of micronutrients such as vitamin
E,most of the B vitamins, and dietary minerals, such as magnesium and zinc.10
Figure 4. The most familiar grains used for making the category of cereals include
rice, maize, corn, wheat, barley, sorghum, millets and oats.
Cereals provide almost 30% of total calories in a regular diet, and are
probably the most widely consumed caloric food in America. This percentage rises
in places like rural Africa and Asia where cereals are reported to supply almost 70 to
80% of energy requirements (since people in these regions cannot afford to eat
other food products like fruits, vegetables, meat, or milk products). Cereals provide
around 95% of useful and nutrient minerals as sulfates and phosphates of
Magnesium (Mg), Potassium (K), Sodium (Na) and Calcium (Ca). A good amount of
phosphorous, called phytin (phytates, the storage form of phosphorus) is present in
cereals. Also, cereals contain some of the most useful dietary minerals such as Iron
(Fe), Zinc (Zn), Copper (Cu), Selenium (Se), and Manganese (Mn) in small quantities.
Also, cereals contain Vitamin E and D (important antioxidants) and some important
B Vitamins, such as Folic acid or folate (B9), Niacin (B3), Thiamin (B1), Riboflavin
(B2), and Pyridoxine (B6). 11,12
8
Wheat grain composition in relation to human nutrition and health
In the last decades a large number of studies in the scientific literature were
published on wheat grain composition, protein content, quality, essential amino
acids, carbohydrates, mono- and oligo- saccharides, starch, vitamins, minerals,
metals, dietary fibers, polyphenols, protenoids, carotenoids, etc. The components
of wheat grain have direct relevance to human nutrition and health because they
provide nutritional quality, energy and essential micro nutrients.13-16
Protein content and quality of wheat grain
Wheat grain protein content is determined by genetic and environmental
factors, notably the availability of nitrogen fertilization. The protein content
(samples of U.S. Department of Agriculture, World Wheat Collection) has been
reported to range from 7% to 22% of the dry weight, but generally varies from
about 1015% of the dry weight for wheat cultivars grown under field conditions.17
Protein nutritional quality of various foods is determined by the proportions
of essential amino acids in their content, especially the ones which cannot be
synthesized by animals or humans. Food with essential amino acids is nutritionally
important and their quality very high. Note that if only one essential amino acid is
limiting, the others will be broken down and excreted resulting in restricted growth
in humans and loss of nutritional nitrogen present in the diet.18

* In nature there are 20 amino acids. But 9 amino acids called essential or
indispensable amino acids, cannot be synthesized de novo (from scratch) by the
biological organism and must be supplied by diet. Humans cannot synthesize 9
amino acids: phenylalanine, valine, threonine, tryptophan, methionine, leucine,
isoleucine, lysine, and histidine. Also, another 6 amino acids are considered
conditionally essential in the human diet because their synthesis in the human body
can be limited under special pathophysiological conditions: arginine, cysteine,
glycine, glutamine, proline, and tyrosine.
9
Essential amino acids in wheat grain
Various studies have analyzed the typical contents of essential amino acids
reported for whole grain wheat and white flour and compared with the minimum
physiological requirements of minimum essential amino acids for adults. The list of
amino acids recommended by WHO adult intake g/100 g protein, physiological
requirements of minimum for essential amino acids for adults: Tryptophan 0.6,
Threonine 2.3, Isoleucine 3.0, Leycine 5.9, Lysine 4.5, Methionine 1.6, Cysteine 0.6,
Phenylalanine and Tyrosine 3.8, Valine 3.9, Histidine 1.5 (g/100 g protein).19
Analytical studies compared the content of wholemeal and white flour in amino
acids and their values are very near the requirements for diet with plenty bread.
The data of most research supported the widely accepted view that the first
limiting amino acid in wheat grain is lysine, with other essential amino acids being
present in adequate amounts in wheat, at least for adults.20-21
The protein content and amino acid composition for 17 wheat-related
species (WRS) and three common wheats (control) were determined and analyzed,
and the essential amino acids (EAAs) in WRS were evaluated according to
FAO/WHO amino acid recommendations. The results showed that the mean protein
content for WRS was 16.67%, which was 23.21% higher than that for the control.
The mean contents (g 100 g protein) of most amino acids for WRS were lysine
2.74%, threonine 2.83%, phenylalanine 4.17%, isoleucine 3.42%, valine 3.90%,
histidine 2.81%, glutamic acid 29.96%, proline 9.12%, glycine 3.59%, alanine 3.37%,
and cysteine 1.57%, which were higher than those for the control. The contents of
the other 6 amino acids for WRS were lower than those for the control. Comparing
with FAO/WHO amino acid recommendations, the amino acid scores (AAS) of lysine
(49%), threonine (70%). and sulfur-containing amino acids (74%) were the lowest,
which were considered as the main limiting amino acids in WRS.22
Long time ago scientists proposed the fortification of bread with lysine.
Experimental results with mice found that, as far as rat growth is concerned, the
only amino acid deficiency in commercial white bread was lysine. But the
fortification scheme did not materialized since the human diet was improved with
greater variety of food rich in essential nutrients.23,24
10
The natural state of whole grains
In their natural state growing in the farming land, whole wheat grains are
the entire seed of a plant. This seed is made up of three key edible parts the bran,
the germ, and the endosperm protected by an inedible husk that protects the
kernel from assaults by sunlight, pests, water, and disease.
Figure 5. Wheat grains have three parts: the bran, germ and endosperm. Whole
grains or foods made from them contain all the essential parts and naturally-
occurring nutrients (protein, fiber, vitamins and minerals) of the entire grain seed
[Whole Grains Council/Oldways Preservation & Exchange Trust. Information on
whole grains, visit wholegrainscouncil.org. Boston MA. Graphics B Red Mill.

products in The United States].
The bran is the multi-layered outer skin of the edible kernel. It contains
important antioxidants, B vitamins and ber. The germ is the embryo which has the
potential to sprout into a new plant. It contains many B vitamins, some protein,
minerals, and healthy fats. The endosperm      
provides essential energy to the young plant so it can send roots down for water
          
endosperm is by far the largest portion of the kernel. It contains starchy
carbohydrates, proteins and small amounts of vitamins and minerals.25
The major phytochemicals are in the bran of cereal grains, such as phenolic
acids, flavones, phytic acid, flavanoids, coumarins, and terpenes. Cereal germs are
good sources of ferulic acid, phytic acid, glutathione, and phytosterols. In addition,
11
the cereal germ contains the vitamins E, B1, B2, and B3, the minerals P, K, Mg, Ca, Zn,
and S, and fiber. Because of its rich nutrient content, cereal germ would be a
valuable ingredient for production of functional foods. 26
The wheat bran is a concentrated source of insoluble fibre which has
substantial physiological effects on health benefits to human when is included in
daily diet. According to epidemiological studies (which are going to be presented in
detail in the article) wheat bran and its fiber play an important role in the
prevention of diseases such as colon and breast cancers, cardiovascular disease,
obesity and gastrointestinal diseases. In recognition of the weight of evidence, the
European Food Safety Authority (EFSA) has recently approved two health claims for
wheat bran and gastrointestinal health.27
Carbohydrates in wheat grains
The wheat grain consists of 85% (w/w) of carbohydrates at maturity of the
grains, which is starch (present only in the starchy endosperm). Starch from wheat
and other cereal grains is the predominant source of human dietary carbohydrate,
whereas the cell wall polysaccharides are the major components of DF which is
important for human health as well as having impacts on grain utilization and
.28
The carbohydrates in wheat grains are monosaccharides and
oligosaccharides. The low molecular mass carbohydrate fraction includes the
reducing aldohexose monosacchar  and its ketohexose isomer,
 and minor amounts of their phosphorylated forms. The most abundant
        
and fructans.29
In the case of fructans of the wheat grains there is extensive scientific
research on the beneficial effects in human health, because they have the ability to
absorb calcium. Also, other studies showed that fructans absorb iron, but the
evidence is less conclusive. The majority of studies indicate that inulin-type fructans
are promising substances that could help to improve the supply with available
12
calcium in human nutrition, important for bone health in humans. Also, recent
research in growing rats suggest that wheat bread is an adequate vehicle for
including calcium and inulin in healthy food.30,31
Starch in wheat grain
Starch constitutes about 6070% of the mass of wheat grain, and about 70
85%             
human nutrition, being the main source of dietary carbohydrate and energy.
Molecule of Amylose
Structure of Amylopectin
Figure 6. Starch or amylum is a polymeric carbohydrate consisting of a large
number of glucose units joined by glycosidic bonds. It is the most common
carbohydrate in human diets and is found in potatoes, wheat, corn (maize), rice,
and cassava. Starch, by convention, is 300-600 monomers long. Most green plants
use starch as their energy store.
Chemically, starch is composed of two different molecules, amylose and
amylopectin. In amylose, the glucose molecules are linked in a "linear" fashion;
however, the tetrahedral chemistry of carbon (and the bond angles that result from
this chemistry) gives amylose an overall spiral shape. Amylopectin, on the other
hand, has a linear arrangement of glucose molecules that includes, at regular
intervals, a different kind of linkage between two adjacent glucoses. Starch
molecules are broken down by enzymes known as amylases. The digestibility of a
specific starch is influenced by its physical form. In plants starch is present in
microscopic granules, which impair the enzymatic digestion of starch molecules
obtained from plants. Cooking starch-containing items results in the hydration of
13
starch molecules and swelling of starch granules, increasing the rate and enhancing
the enzymatic breakdown of starch. Amylases convert starch to glucose.32
Phytochemicals in wheat grain
Phytochemical content varies considerably within and among the major
cereal varieties. Differences in genetics and agro-climatic conditions explain much
of the variation. Phytochemicals, such as phenolics and flavanoids, in grains are in
high concentrations but because they are tightly bound to the cell wall matrix, their
bioavailability in humans is often limited.
Polyphenoles, phenolic acids, lignans, terpenoids
Wheat grains contain two major groups of phytochemicals derived from
different biosynthetic pathways: phenolics and terpenoids. A range of health
benefits have been proposed for these components but few have been established
with sufficient scientific rigor to result in health claims approved by FDA or EFSA,
the main exceptions being tocopherols (vitamin E) which have a number of
established functions and plant sterols and stanol esters which have accepted
benefits in reducing blood cholesterol and therefore the risk of cardiovascular
disease. Phenolic acids are the major group of phytochemicals in wheat grain. They
contain a phenolic ring and an organic carboxylic function and fall into two groups,
which are derived either from cinnamic acid or benzoic acid. They also occur in
three forms, either as free compounds, as soluble conjugates bound to low
molecular weight compounds such as sugars, and as bound forms which are linked
to cell wall polysaccharides (particularly arabinoxylan in cereal grain) by ester
bonds.33,34
Lignans
Lignans are a group of diphenolic compounds that are concentrated in the
bran layer of cereal grain. The wheat grains contain lignans which are polyphenols
derived from phenylalanine via dimerization of substituted cinnamic alcohols, to a
dibenzylbutane skeleton.35 Experiments with cancer cells showed that lignans from
wheat bran had strong antioxidant activity and antimour potential for colon cancer.
14
Scientists concluded that inhibition of cancer cell growth by lignants sems to be
mediated by cytostatic and apoptotic mechanisms.36
Terpenoids
Terpenoids are important for plant survival and also possess biological and
pharmacological properties that are beneficial to humans because of their strong
antioxidant potential. 37
Figure 7. The structure of the main polyphenoles and phenolic compounds in wheat
grain. Cinnamic acid derivatives, flavones, anthocyanins, lignans
proanthocyanidins. All these compounds present strong antioxidant potential.35
Carotenoids and isoprenoids
Carotenoids in wheat grain 
xanthophylls (which include lutein and zeaxanthin) and the unoxygenated
carotenes (which include α βng
the carotenes, are converted to vitamin A (retinol) in mammals, and hence are also
referred to as provitamin A. The levels of carotenoids in cereal grain are generally
low, but are of particular interest in durum wheat where lutein in the major
determinant of the yellow color which is a quality trait for breeders and consumers.
Wheat grains contain also isoprenoids, which like carotenoids are primary
antioxidants which protect plants from oxidative damage under intense weather
conditions, excessive light, high temperatures and cold days.38-40
15
B vitamins and tocopherols in wheat grains
The B vitamin complex comprises of 8   
often occur together in the same foods and were initially considered to be a single
compound. Cereals are dietary sources of several B vitamins, particularly thiamine
(B1), riboflavin (B2), niacin (B3), pyridoxine (B6), and folates (B9). There has been
considerable debate on whether to introduce fortification of flour with folic acid or
folate (B9), on a voluntary or compulsory basis, with no internationally accepted
policy. The presence of vitamins of the B complex in wheat bread is considered very
important for the medicinal effect of bread. 41-43
Whole-grain bread and other cereals are considered valuable sources of
nutrients, such as dietary fiber, B vitamins, vitamin E, metals selenium (Se), zinc
(Zn), copper (Cu), and magnesium (Mg) and other phytochemicals, that together
play important roles in disease prevention.
Tocopherols are organic chemical compounds, many of which have Vitamin
E activity. There are alpha-, beta-, gamma- and delta-tocopherols. -Tocopherol is
the main source found in the European diet, where the main dietary sources are
olive and sunflower oils, while -tocopherol is the most common form in the
American diet due to a higher intake of soybean and corn oil.
Proposed and established health benefits of wheat grains
The importance of wheat grains in human diet inevitably attracted the
scientific interest of many research groups and dieticians to establish the health
benefits with clinical and epidemiological studies. There is a massive volume of
literature supporting the health benefits of wheat and especially the wheat fiber in
whole-grain bread. The results accumulated until now can be divided into:
proposed health benefits from positive results (antioxidant activity, reduced risk of
various diseases) but not very well documented and established health benefits
from high number and well researched data of clinical and epidemiological studies
with highly documented outcome. These two health benefits were proposed by the
16
well known wheat specialist Dr. Shewry PR (Dpt Plant Sciences, Rothamsted
Research, Harpenden, Hertfordshire, UK). [Shewry PR, Hey SJ. The contribution of
wheat to human diet and health. Food Ener Secur 4(3):178-202, 2015).8
1. Dietary fiber Reduces postprandial glycemic response (and risk of type 2
diabetes). Reduces intestinal transit time Increases fecal bulk. Reduces
cholesterol and risk of coronary heart disease. Yes
2. Reduces risk of colo‐rectal cancer. Reduces risk of breast cancer. Reduces risk
of stroke. Prebiotic effects stimulate immune responses. No
3. Resistant starch. Reduces postprandial glycaemic response. Other benefits
as part of dietary fiber above. Yes
4. Fructans. Prebiotic effects promote calcium (and iron?) absorption. No
5. Betaine. Normal homocysteine metabolism (reduced risk of coronary heart
disease). Yes (not for cereals),
6. Choline. Normal homocysteine metabolism (reduced risk CHD) coronary No
7. Phenolic acids. Improve vascular function. Antitumour properties
. No
8. Alkylresorcinols. Antimicrobial, . No
9. Lignans. Phytoestrogen, Antitumour, Antimicrobial. No
10. Sterols, stanols, and derivatives. Reduce serum cholesterol and risk of
coronary heart disease. Yes Anticancer effects. No
11. Tocopherols, Vitamin E activity. Yes. Prevention of neurodegeneration
Induction of immune responses anticancer cholesterol lowering,
. No
Health benefits of dietary fiber and whole-grain wheat
Wheat bran is a concentrated source of insoluble fiber. Fiber intake from
whole-grain bread and other cereals and beneficial effects on health has been
studied by a large number of epidemiological dietary studies. Most of the results
found prevention or reduction of diseases such as colon and breast cancers,
cardiovascular disease, obesity and gastrointestinal diseases. In recognition of the
17
weight of evidence, the European Food Safety Authority (EFSA) has recently
approved two health claims for wheat bran and gastrointestinal health.44
Studies showed that high-fiber foods such as whole-grain wheat and other
cereals help provide a feeling of fullness with fewer intake of calories. It has been
proved that whole grains for at least half of daily servings may help maintain human
weight and enhances weight loss in obese individuals. In addition to the basic
benefits of grains, fiber helps to maintain optimum health due to the antioxidant
phytochemicals it contains. Increasing fiber intake lowers blood pressure and serum
cholesterol levels. Increasing soluble fiber improves glycemia and insulin sensitivity
in non-diabetic individuals and diabetics. Fiber intake reduces gastrointestinal
disorders, such as gastroesophageal reflux disease, duodenal ulcer, diverticulitis,
constipation and hemorrhoids. Prebiotic fibers appear to enhance immune function
(not clearly established).45,46
The American Dietetic Association (ADA) recommends adequate amounts
of dietary fiber from a variety of plant foods, because populations that consume
more dietary fiber develop less chronic diseases. Although solubility of fiber was
thought to determine beneficial physiological effect, more recent studies suggest
other properties of fiber, perhaps fermentability or viscosity are important
parameters. High-fiber diets provide bulk, are more satiating, and have been linked
to lower body weights. The ADA and nutritional professionals propose increase in
consumption of high-fiber foods such as whole grains, legumes, fruits, and
vegetables.47
Physiological mechanism of action by dietary fiber
Scientists have investigated the physiological mechanisms (digestion, fecal
bulk, soluble fiber fraction, satiety, bacterial degradation, etc, in the gastro-
intestinal tract) of action of dietary fiber. The digestion of the dietary fiber influence
the rate and extent to which blood glucose increases after ingestion of a
carbohydrate food. Dietary fibers are not digested and absorbed in the small
intestine as other foods, but passes to the colon where it undergoes bacterial
18
degradation. Resistant starch in whole-meal bread refers to the portion of starch
that resist digestion as they pass through the gastrointestinal tract. The principal
types of dietary fiber are the non-starch polysaccharides, resistant starches, non--
glucan oligosaccharides (short chain carbohydrates) and some polyols and modified
starches. This physiological process of the dietary fiber in the digestive system
provides important health benefits because of the lower glycaemic response of the
foods in which it is present. Cereals and whole-meal wheat rich in dietary fiber
release glucose more slowly into the blood which is relevant to the prevention of
disorders such as obesity and diabetes. A significant proportion of dietary fiber that
enters the large bowel will be fermented by the commensal bacteria that live in the
colon. Foods containing high levels of fiber are often made from whole grains or
whole foods such as fruit and vegetables and are thus bulky with a low energy
density. This may promote satiety (*satiety definition: the state of being completely
satisfied, especially with food or pleasure, so that you could not have any more ) and
therefore may be expected to encourage weight loss, or prevent weight gain. A
further mechanism by which whole grain may influence body weight regulation is
via a prebiotic effect modulating the intestinal flora. The available evidence,
primarily from studies in animal models, suggests that the gut microbiota affect
nutrient acquisition and energy regulation.48-50
The human gastro-intestinal microbiota contains highly diverse microbial
communities that provide metabolic, immunologic, and protective functions that
play a crucial role in human health. The gastro-intestinal microbiota is influenced by
a number of factors (genetics, host physiology, medication). Diet is recognized as a
key environmental factor that mediates the composition and metabolic function of
the gastro-intestinal microbiota, of which dietary fiber and prebiotics, is an avenue
by which the microbiota can be modulated.51
…………………………………………………………….
*Definitions for prebiotics and probiotics
Prebiotics, special form of dietary fiber that acts as a fertilizer for the good bacteria
in gut. Probiotics are live bacteria that can be found in yogurt and other fermented
foods.
19
There is a large number of research evidence to show that dietary fiber can
significantly decrease the rate and extent of nutrient bioaccessibility, digestion and
absorption in the upper gastro-intestinal tract, although the degree to which this
occurs is variable and highly dependent on the structure and properties of the fiber
source. Recent results from in vitro and in vivo studies highlight the significant role
played by structurally intact cell walls of edible plants in impeding the digestion of
intra-cellular starch and lipids.52
There is increasing scientific evidence that dietary fiber and be beneficial to
the function of the immune system in humans. There is evidence that 
βans are able to regulate the immune responses that are involved in fighting
infection, attacking tumours and various inflammatory conditions. A review (2002)
collected scientific evidence for the immune-enhancing effects of dietary fibers.
Results showed that changes in the intestinal microflora as a result of the
consumption of prebiotic fibers may potentially mediate immune changes via: the
direct contact of lactic acid bacteria or bacterial products with immune cells in the
intestine; the production of short-chain fatty acids from fibre fermentation; or by
changes in mucin production. Reviewers concluded that although further work is
needed to better define the changes, mechanisms for immunomodulation and
impact on immune health, there is convincing preliminary data to suggest that the
consumption of dietary fiber and prebiotics can modulate immune parameters in
gut-associated lymphoid tissues, secondary lymphoid tissues and peripheral
circulation.53 Scientists propose that changes in diet and associated changes in the
gut microbiota are driving the increasing incidence of inflammatory disease .54
Epidemiological studies and health benefits of whole grain bread
Until the 1990s there were very few investigations of the beneficial effects
of bread and whole grain cereals. But in the last decade numerous prospective
epidemiological and feeding studies initiated in order to find actual health
benefits of whole cereal grain foods (which include the bran, germ, and
endosperm in their naturally occurring proportions), especially for prevention of
atherosclerotic diseases, CVDs, gastro-intestinal cancers and type 2 diabetes.55
20
In 2016 a group of well known epidemiologists (from Norway, Harvard
University, TH Chan School of Public Health, Tish Cancer Institute New York,
Epidemiology and Biostatistics from Imperial College and Leeds University, UK)
collected 45 studies on the intake of specific types of whole grain bread (whole
grain breakfast cereals, added bran, total bread) by a large number of people. The
aim of the review was to quantify dose-response relation between consumption of
whole grain and the risk of cardiovascular disease, total cancer, and all cause
specific mortality. Researchers concluded that the meta-analysis provided further
evidence that whole grain intake is associated with a reduced risk of coronary heart
disease (CHDs), cardiovascular disease (CVDs), total cancer, mortality from all
causes, respiratory diseases, infectious diseases, diabetes, and all non-
cardiovascular, non-cancer causes. These findings support dietary guidelines that
recommend increased intake of whole grain cereals to reduce the risk of chronic
diseases and premature mortality.56
In developed countries there is a wide variety of opinions and perceptions
among consumers and varied evaluations of commercial bread types from a health
perspective. A recent (2018) mixed-mode survey was contacted in Sweden (1,134
respondents) with open-ended questions and an elicitation task with pictures of
commercial breads for responders to observe. The responses were analysed: 844
people knew of breads they considered healthy    
 The breads were perceived as healthy mainly because they "contain fiber,"
have good "satiation" and beneficial "glycemic properties." Difficulties identifying
healthy bread were perceived as a barrier for consumption especially among
consumers with a lower education level.57
Bread, whole grain consumption and cardiovascular diseases
There are many prospective studies in the last decades evaluating the
effects of bread and in particular the types of whole-grain bread and cereals on
risk from coronary, myocardial infraction and in general cardiovascular diseases.
A prospective study (Denmark, 2016) included 54,871 Danish adults aged
50-64 years, of whom 2,329 individuals developed myocardial infarction (after 13.6
21
year of follow-up). Detailed information on daily intake of whole-grain products was
available from a self-administered food-frequency questionnaire. The association
between intake of whole grains and risk of myocardial infarction was examined
with the use of a Cox proportional hazards model adjusted for potential
confounders. For both men and women with total whole-grain intake in the highest
quartile, lower risks of myocardial infarction were shown (HR=hazard ratio): HRs:
0.75 (men) and 0.73 (women) compared with individuals with intake in the lowest
quartile. For total whole grain products, significantly lower myocardial infarction
risks were seen with higher intakes in both men and women. Rye bread (in men and
women) and oatmeal (in men) were associated with significantly lower risk of
myocardial infarction.58
A prospective cohort study in 2017 (Harvard University and Peking
University) examined the association of higher intake of whole grains and lower risk
of ischemic stroke. The research group analyzed whole grain consumption in
relation to ischemic stroke among 71,750 women from the Nurses' Health Study [a
series of prospective studies that examine epidemiology and the long-term effects
of nutrition, environment, and nurses' work-life on health and disease
development, for Harvard affiliated hospitals] and 42,    
Professionals Follow-up Study who were free of cardiovascular disease, diabetes
mellitus, and cancer at baseline through 2010 using a Cox proportional hazards
model. Validated semiquantitative food frequency questionnaires were used to
assess consumption of whole grain intake. During the follow-up in the 2 cohorts,
2,458 cases of ischemic stroke were identified and confirmed. Intake of total whole
grains was not associated with risk of ischemic stroke after adjustment for
covariates: the pooled hazard ratio (HR) comparing extreme intake level was 1.04.
However, intake of whole grain cold breakfast cereal and total bran was inversely
associated with ischemic stroke after multivariate adjustment: the pooled hazard
ratios were HR = 0.88 and 0.89 respectively. Other whole grain foods were not
associated with a lower risk of ischemic stroke. Scientists concluded that although
overall consumption of whole grains was not associated with lower risk of ischemic
22
stroke, greater consumption of whole grain cold breakfast cereal and bran was
significantly associated with a lower risk of ischemic stroke.59
These types of epidemiological studies started from the 1980s in the USA
(particularly in Harvard Medical School, Boston, USA) with the objectiv e to
evaluate whether high whole-grain intake reduces risk of coronary heart disease
(CHD) in women. In 1984, 75,521 women aged 38-63 years with no previous history
of CHDs or diabetes completed a detailed, semiquantitative food-frequency
questionnaire and followed for 10 years. During this period documented 761 cases
of CHD (208 of fatal CHD and 553 of nonfatal myocardial infarction). Results were
adjusted for age and smoking and increased whole-grain intake was associated with
decreased risk of CHD. The inverse relation between whole-grain intake and CHD
risk was even stronger in the subgroup of never smokers. The lower risk associated
with higher whole-grain intake was not fully explained by its contribution to intakes
of dietary fiber, folate, vitamin B-6, and vitamin E.60
The same group of researchers examined the hypothesis that higher whole
grain intake reduces the risk of ischemic stroke in women. They used the cohort of
75,521 U.S, women aged 38 to 63 years    without previous
diagnosis of diabetes mellitus, coronary heart disease, stroke, or other
cardiovascular diseases (CVDs) in 1984, who completed detailed food frequency
questionnaires in 1984, 1986, 1990, and 1994, and were followed up for 12 years.
They recorded 352 confirmed incident cases of ischemic stroke among the cohort.
The results of the study observed an inverse association between whole grain
intake and ischemic stroke risk, which was also consistently observed among
subgroups of women who never smoked, did not drink alcohol, did not exercise
regularly, or who did not use postmenopausal hormones. Scientists concluded that
higher intake of whole grain foods was associated with a lower risk of ischemic
stroke among women, independent of known CVD risk factors.61
A Norwegian County Study (2001) examined men and women who were
whole-grain bread eaters. The study collected details of 16,933 men and 16,915
women (all residents aged 3556 years) were not disabled and free of CVDs.
Norwegian whole grain bread eaters were less likely to be smokers, were more
23
physically active, had lower serum cholesterol and systolic blood pressure, and
ate less total and saturated fat as a proportion of energy intake than white bread
eaters. After adjustment for age, energy intake, sex, serum cholesterol, systolic
blood pressure, smoking, body mass index, physical activity at leisure and work,
and use of cod liver oil or other vitamin supplements, hazard rate ratios (HRR) for
total mortality were inverse and graded across whole grain bread score
categories. Researchers concluded that whole grain intake prevents chronic
diseases.62
Figure 8. The most famous researcher on the subject is Prof. Walter Willett.
Professor of Epidemiology and Nutrition, Harvard University, USA. He started in
1980 with -up
Study. Together, these cohorts that include nearly 300,000 men and women with
repeated dietary assessments, are providing the most detailed information on the
long-term health consequences of food choices. Prof. W. Willett has published over
1,700 original research papers and reviews, primarily on lifestyle risk factors for
heart disease, cancer, and other conditions. Prof. W. Willett has written the
renowned textbook, Nutritional Epidemiology, published by Oxford University Press
(3rd edition, 2012, pp 552).
The Atherosclerosis Risk in Communities Study (ARIC) is a prospective
epidemiologic study (started 1987) conducted in four U.S. communities to
investigate the etiology and natural history of atherosclerosis. A group of
researchers (2003) assessed the relations of whole grain, refined-grain, and fruit
and vegetable intakes with the risk of death and the incidence of Coronary Artery
24
Diseases (CAD) and ischemic stroke, with adjustment for age, sex, ethnicity, energy
intake, and cardiovascular disease risk factors. Dietary intakes were assessed by
using a food-frequency questionnaire. Over an 11-years follow-up period, whole-
grain intake was inversely associated with total mortality and incident CAD. An
inverse association between fruit and vegetable intake and CAD was observed
among African Americans but not among whites. The risk of ischemic stroke was
not significantly related to whole-grain, refined-grain, or fruit and vegetable
consumption.63
A review of 17 papers analysed data from prospective epidemiologic and
feeding studies for whole grain consumption and risk of atheroscletoric
cardiovascular diseases and type 2 diabetes. The whole cereal grain foods in
these studies had natural proportions of bran, germ and endosperm. The results
showed 20-40% reduction in long-term risk for CVDs and diabetes when
compared to consumers who rarely eat these foods. The review examined also
12 studies that found similar risk reduction in association with the amount of
cereal fiber consumed, as well as feeding studies with analogous results. 64
A prospective cohort study (Department of Nutrition, Harvard School of
Public Health, Boston , MA) examined 42,850 male health professionals aged 40-75
years at baseline in 1986, who were free from cardiovascular disease (CVDs),
cancer, and diabetes. The study recorded daily whole-grain, bran, and germ intakes
(g/day) through a detailed semiquantitative dietary questionnaire. The follow-up
was for 14 years. During this period the study documented 1,818 incident cases of
coronary heart diseases (CHD). After CVDs risk factors and the intakes of bran and
germ added to foods were controlled for, the hazard ratio (HR) of CHD between
extreme quintiles (higher or lower 1/3) of whole-grain intake was 0.82 (beneficial
association). The hazard ratio of CHD in men with the highest intake of added bran
was 0.70 compared with men with no intake of added bran.65
A paper in 2010 summarized beneficial mechanisms of whole grain cereals.
All epidemiological studies have clearly shown that whole-grain cereals can protect
against obesity, type 2 diabetes, CVD and cancers. Nutrition investigations propose
that health protective mechanisms are the result of the specific constituents and
25
fibers in cereals. Whole grain bread has better glycaemic homeostasis through
increased insulin secretion, antioxidant and anti-carcinogenic properties of
numerous bioactive compounds, especially those in the bran and germ (minerals,
trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols). Recent
findings have led to the beneficial involvement of polyphenols in cell signalling and
gene regulation, and of sulfur compounds, lignin and phytic acid in antioxidant
protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes
(methionine, betaine, choline, inositol and folates) that may be involved in
cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation.
There is also evidence for potential protective effects of bound phenolic acids
within the colon, the B-complex vitamins on the nervous system and
oligosaccharides as prebiotics.66
Whole grain consumption and reduction of cancer risk
Mounting evidence from epidemiologic studies in the last decade suggested
that whole grains are protective against cancer, especially gastrointestinal cancers
such as gastric and colonic, and hormonally-dependent cancers including breast and
prostate. The mechanisms of protective effects of whole grains is believed to be the
results of its fermentation of carbohydrates in the colon, resulting in the
production of short chain fatty acids that lower colonic pH and serve as an energy
source for the colonocytes. Also, the antioxidant phytochemicals in whole grain play
a crucial anticancer role. Whole grains are significant sources of phytoestrogens
that have hormonal effects related to cancer protection. Finally, whole grains
mediate glucose response, which has been proposed to protect against colon and
breast cancer.67
A recent review (2016) examined 43 longitudinal studies conducted in
Europe and North America that reported multivariable-adjusted risk estimates for
whole grains (14 studies), cereal fiber (23 studies), or both (6 studies) in relation to
lifestyle-related cancers. The review recorded the study location, follow-up
duration, sample, dietary assessment method, risk estimates, and confounders.
26
From the 43 studies, 20 examined whole grains intake and cancer, 6 studies
reported a statistically significant 6%-47% reduction in risk, but 14 studies showed
no association. 29 studies investigated cereal fiber intake in relation to cancer, 8
showed a statistically significant 6%-49% reduction in risk, whereas 21 studies
reported no association. Scientists concluded that most studies were suggestive of
a null association (a null result is a result without the expected content: that is, the
proposed result is absent, i.e. reduction of cancer risk). Whole grains and cereal
fiber may protect against gastrointestinal cancers, but these findings require
confirmation in additional studies.68
Various epidemiological diet studies in the past suggested that whole grain
intake may reduce the risk for pancreatic cancer. In 2016 scientists conducted a
meta-analysis on the subject. Searching various scientific databases (for the period
1980-2015) they collected 8 studies regarding whole grain intake and risk of
pancreatic cancer. They calculated the Odds Ratios (ORs, odds ratio is a measure of
association between an exposure and an outcome) for pancreatic cancer using
random-effects model meta-analysis. The pooled OR of pancreatic cancer for those
with high versus low whole grain intake was 0.76. Scientists concluded that intake
of whole grains was associated with a reduced risk of pancreatic cancer, but further
prospective studies are needed to ensure conclusions.69
The European Prospective Investigation into Cancer and Nutrition (EPIC) is
an ongoing multi-centre prospective cohort study designed to investigate the
relationship between nutrition and cancer. The study currently includes 519,978
participants (366,521 women and 153,457 men, mostly aged 35-70 years) in 23
centres located in 10 European countries (Denmark, France, Germany, Greece,
Italy, The Netherlands, Norway, Spain, Sweden, and the United Kingdom).
Enrollment of participants took place between 1992 and 2000. EPIC plans to follow-
up the study participants for the next ten years at least, continuing to study the role
of nutrition and lifestyle in cancer development and other chronic diseases. 70
One EPIC study was in the city of Potsdam (Germany). A scientific group
gathered data from 23,153 German participants aged 35 to 65 years. The
participants were examined for high intake of fruits, vegetables, whole grain bread
27
and low meat consumption and data were analysed during the follow-up for
confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and
cancer. The participants were adhering to 4 healthy principles: no smokers, their
body mass index lower than 30 (weight in kg divided by height in m squared),
performing 3.5 hours/week or more of physical activity, and adhering to healthy
dietary principles. The follow-up was 7.8 years, 2,006 participants developed new-
onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%).
After adjusting for age, sex, educational status, and occupational status, the hazard
ratio (HR) for developing a chronic disease decreased progressively as the number
of healthy factors increased. Participants with adhering to all 4 factors at baseline
had a 78% lower risk of developing a chronic disease (diabetes 93%, myocardial
infarction 81%, stroke 50% and cancer 36%) compared to participants who did not
followed the 4 healthy lifestyle factors.71
The association of whole grain consumption and reduction of colorectal
cancer (CRC) has been explored by a small number of studies. The basic hypothesis
is that whole grains contain dietary fiber, a range of micronutrients and bioactive
compounds, which can play a crucial role in the reduction of carcinogenic risk in the
colon. An investigation in Norway (2016) used 78,254 Norwegian women
(prospective cohort study of the Norwegian Women and Cancer Study) of median
age 55 years old. Dietary intake was estimated from the food-frequency
questionnaires, and these women were then followed up for 9 years for colorectal
cancer incidence. The results, 795 women were diagnosed with CRC (316 proximal,
193 distal, 218 rectal). When compared to the low consumption group, the hazard
ratio (HR) for CRC was 0.89 for the high consumption group and 0.86 for the
medium consumption group in a multivariable model. Scientists concluded that
overall, no association between whole grain bread consumption and CRC was
found.72
Breast cancer risk and consumption of whole grain foods was another
hypothesis that was investigated Prof. W. Willett research team in Harvard
University. The research evaluated individual grain-containing foods and whole and
refined grain intake during adolescence, early adulthood, and premenopausal years
28
in relation to breast cancer risk in the Nurses' Health Study II. Grain-containing food
intakes were reported on a baseline dietary questionnaire (1991) and every 4 years
thereafter. The study followed 90,516 premenopausal women (27-44 years old),
and during the follow-up to 2013 identified 3,235 invasive breast cancer cases. Also,
44,263 women reported their diet during high school (from 1998 to 2013), the
study identified 1,347 breast cancer cases. Cox proportional hazards regression was
used to estimate relative risk (RR). The average of adolescent and early adulthood
whole grain food intake was suggestively associated with lower premenopausal
breast cancer risk (highest vs lowest quintile: RR 0.74). The research group
concluded that high whole grain food intake may be associated with lower breast
cancer risk before menopause. Also, they concluded that fiber in whole grain foods
may mediate the association with whole grains.73
An investigation in the Scandinavian countries focused in the association
between whole grain consumption and incidence of oesophageal cancer. The
HELGA prospective cohort study is from Norway, Sweden and Denmark (113,993
participants, follow-up 11 years). Information for whole grain consumption was
collected by food frequency questionnaires. The study indentified 112 oesophageal
cancer cases through national cancer registries. Cox proportional hazards ratios
(HR) were calculated for risk. When comparing the highest tertile (33%) (tertile
definition two points that divide an ordered distribution into three parts, each
containing a third of the population) of whole grain intake with the lowest, the
oesophageal cancer risk was approximately 45 % lower. Inverse associations were
also found in continuous analyses. Whole grain wheat was the only grain associated
with lower risk. Also, the lower oesophageal cancer risk was seen in both
histological subtypes, but particularly for squamous cell carcinomas.74
A meta-analysis of prospective cohort studies investigated the association of
dietary whole grain intake and risks for cancer, CVD and all-cause mortality.
Pertinent studies were identified in the MEDLINE and EMBASE (11 prospective
studies found including 2016). The 11 studies included a total of 816, 599 subjects
and 89,251 cases of all-cause mortality. On the basis of the highest vs. the lowest
categories of intake, whole grains may be associated with a lower risk of mortality.
29
For all causes mortality, summary relative risk (SRR, for CVD SRR was 0.81
and SRR for all cancers was  For each 3 servings/day increase in whole-grain
intake, there was a 19 % reduction in the risk of all-cause mortality, a 26% reduction
in CVD mortality and a 9 % reduction in cancer mortality.75
In 2017, Dr McRae published an umbrella review of all published meta-
analyses (for the period 1980-2016) on the effectiveness of whole grain as a
therapeutic agent in CVDs, cancer, obesity, and type 2 diabetes. The review
recorded 21 meta-analyses which reported statistically significant positive benefits
for reducing the incidence of: CVDs (relative risk, RR=0.63-0.79), colorectal,
pancreatic and gastric cancers (RR= 0.57-0.94), type 2 diabetes (RR= 0.68-0.80), and
a modest effect on obesity (body weight, waist circumference, body fat). The
results of this study suggested that the consumption of 2 to 3 servings per day (~45
g) of whole grains have beneficial effects on health.76
Whole grain consumption and reduction of type 2 diabetes
In the last decades there was strong evidence from epidemiological studies
for the beneficial effects of whole grain bread and other cereals for the reduction of
type 2 diabetes. Searches of bibliographic databases found 8 prospective
observational studies with 15,573 cases of type 2 diabetes (T2D) among 316,051
participants. Quantitative meta-regression demonstrated a significant linear inverse
relationship between whole grain intake and T2D occurrence, with an overall
absolute reduction of 0.3% in the T2D rate for each additional 10 g of whole grain
ingredient consumed daily. It was estimated that consuming 3 servings of whole
grain foods (45 g) daily would induce a 20% relative reduction in the T2D risk as
compared to consuming a half serving (7.5 g of whole grain ingredients).77
Scientists in the US performed a comprehensive search of human
prospective studies on the association of consumption of whole grain and food with
more that 25% bran (for the period 1965-2010) and reduction in risk for type 2
diabetes (T2D), CVDs and obesity. All prospective studies consistently showed a
reduced risk of T2D with high intakes of cereal fiber or mixtures of whole grains and
30
bran. A limited number of prospective studies showed reductions on body weight
and for CVDs reduced risk was associated high intakes of whole grain
consumption.78
Scientists in Commonwealth Scientific & Industrial Research Organisation-
CSIRO (Australia) contacted a review of studies which found that whole grain
consumption are associated with a 20-30% reduction in risk of developing type 2
diabetes (T2D). Researchers attributed the beneficial effects in the variety of whole
grain components, notably dietary fiber, vitamins, minerals and antioxidant
phytochemicals. They compared 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. These
effects are responsible for reducing the risk for type 2 diabetes. They suggest that
future dietary intervention studies must establish a direct role of phytochemicals in
mediating the metabolic health benefits of whole grains, and their potential for
mitigating disease progression for type 2 diabetes.79
All studies emphasize the fact that lifestyle intervention, especially diet, can
reduce the risk of type 2 diabetes (T2D). An electronic search by scientists in the
Department of Geriatrics and Metabolic Diseases, Second University of Naples
(Italy) collected 10 large prospective studies (scientific literature up to 2009)
comprising more than 190,000 subjects free of diabetes at baseline, followed for a
time ranging from 2 to 23 years, and 8,932 cases of incident diabetes. All studies
showed consistent results: Relative risk reduction of T2D ranged from 83% to 15%.
The study found that adherence to a healthy dietary pattern was associated with
reduced risk of developing T2D and was characterized by high consumption of fruit
and vegetables, whole grains, fish, and poultry, and by decreased consumption of
red meat, processed foods, and sugar-sweetened beverages.80
A cohort study in Finland (National Public Health Institute, Helsinki) followed
for 10-years a group of men and women who were initially free of diabetes. The
cohort study involved 2,286 men and 2,030 women aged 4069 years. Food
consumption data were collected from 1966 through 1972 with the use of a dietary
31
history interview. During a 10-year follow-up, incident type 2 diabetes cases were
identified in 54 men and 102 women from a nationwide register. The study found
that whole grain consumption was associated with a reduced risk of T2D. The
relative risk (adjusted for age, sex, geographic area, smoking status, body mass
index, energy intake, and intakes of vegetables, fruit) between the highest and
lowest quartiles of whole-grain consumption was 0.65. Cereal fiber intake was also
associated with a reduced risk of type 2 diabetes.81
Whole grain consumption and all-cause mortality
Numerous prospective studies in Europe and in the USA in the last decade
have examined the association between major food groups (vegetables, fruits, nuts,
legumes, eggs, dairy, fish, red meat, processed meat and sugary beverages) and risk
of all-cause mortality. Also, in these studies there was strong interest for dietary
whole grains and refined grains of cereals.
In 2017 a group of nutritionists and epidemiologists in Germany, Austria and
UK, published their findings in the form of a meta-analysis. They searched PubMed,
Embase, and Google Scholar databases for studies with the aim to produce a meta-
analysis about the relationship between intake of 12 major foods (including whole
grains) and risk of all-cause mortality. The risk reduction potential of foods was
calculated by multiplying the Relative Risk (RR) by optimal intake values (serving
category with the strongest association) for risk-reducing foods or risk-increasing
foods, respectively. With increasing intake the all-cause mortality decreased:
for whole grains RR: 0.92, for vegetables RR: 0.96, for fruits RR: 0.94, for nuts (RR:
0.76, and fish (RR: 0.93). Increases of all-cause mortality were found in higher
intake of red meat (RR: 1.10) and processed meat (RR: 1.23). Optimal consumption
of risk-decreasing foods results in a 56% reduction of all-cause mortality.82
Another meta-analysis (Department of Epidemiology-Cancer Institute,
Shanghai, China, and Department of Epidemiology and Biostatistics, University of
South Carolina, USA) summarized the evidence from cohort studies regarding the
association between whole grain intake and all-cause mortality. The study collected
32
11 pertinent prospective cohort studies (up to 2016) involving 101,282 deaths and
843,749 participants. The pooled relative risk (RR) of all-cause mortality for the
highest category of whole grain intake versus lowest category was 0.82. Scientist
concluded that higher intake of whole grain is associated with a reduced risk of all-
cause mortality. 83
A study in 2014 investigated the association of fiber intake and whole-grain,
fruit, and vegetable consumption with all-cause mortality in a Mediterranean
cohort of elderly adults at high cardiovascular disease (CVD) risk. The study
followed up 7,216 men (55-75 years old) and women (60-75 years old) at high CVD
       DIMED). The participants
answered a 137-item validated food-frequency questionnaire administered by
dietitians and was repeated annually to assess dietary exposures (fiber, fruit,
vegetable, and whole grain intakes). During the 8.7 years of follow-up, 425
participants died. Baseline fiber intake and fruit consumption were significantly
associated with lower risk of death, Hazard Ratio (HR) 0.63 (for fiber) (37% lower
risk) and HR 0.59 (for fruit) (41% lower risk).84
Two large prospective studies in the USA [74, 
Health Study (1984-2010) and 43,-Up
Study (1986-2010)] were used to evaluate total mortality (Hazard ratios, HR) with
whole grain consumption. Whole grain consumption was updated every 2 or 4
years by using validated food frequency questionnaires. The study documented
26, hs from the follow-up. Multivariate adjustments were used for
potential confounders (age, smoking, physical activity, body mass index, etc). The
study estimated that every serving (28 g/day) of whole grain consumption was
associated with a 5% lower total morality or a 9% lower CVD mortality. Researchers
concluded that higher whole grain consumption is associated with lower total and
CVD mortality in US men and women, independent of other dietary and lifestyle
factors.85
Whole grain intake and all-cause mortality gave in the past inconsistent
results, so a research team collected 14 studies and summarized their results by a
meta-analysis (2016). The research team searched for prospective cohort studies in
33
Medline, Embase, and unpublished results from the National Health and Nutrition
Examination Survey (NHANES) III and NHANES 1999 to 2004. The review combined
results from 14 studies conducted in the USA, the UK, and Scandinavian countries
with health and consumption information from over 786,000 participants. The
review recorded 97,867 total deaths, 23,957 deaths from CVDs and 37,492 deaths
from various cancers. Pooled relative risks (RR) comparing high intake of whole
grain versus low intake of whole grain was 0.84 for total mortality (decrease 16%),
0.82 for CVD mortality (decreased risk 18%), and 0.88 for cancer mortality
(decreased risk 12%). The research team concluded that the meta-analysis
demonstrated inverse associations of whole grain intake with total and cause-
specific mortality, and findings were particularly strong and robust for CVD
mortality. 86
Conclusion
Bread is considered as the oldest staple food of prehistoric humans that led
to fundamental changes of nomadic lifestyle of hunter-gatherers and started the
first revolutionary agricultural civilization of 10-12,000 years ago. In modern times
white bread was the preferred bread of the rich people, while the poor in industrial
and agricultural societies consumed cheaper dark colored, whole grain, bread.
However, in the late 20th century for most developed western countries (USA, W.
Europe, Canada, Australia, etc) there was a reversal in consumption with whole
grain bread becoming preferred as having superior nutritional and health value.
Starting in the 1980s dieticians, nutritionists and epidemiologists contacted
extensive prospective studies with thousands of participants who were followed for
many years through systematic diet questionnaires. The results of these studies
have established that consumption of whole wheat bread and other cereals is more
nutritional and healthier. Whole grain intake on a daily basis is lowering the relative
risks for chronic diseases common in the current era, such as cardiovascular
diseases (CVDs), various types of gastrointestinal cancer, type 2 diabetes (T2D),
hypertension and obesity. Also, whole grain consumption reduces risk of all-cause
mortality. All whole grain bread and cereals provide resistant bran and fiber which
34
slow the breakdown of starch into glucose (maintaining steady blood sugar), help in
lowering cholesterol and provide B vitamins, iron, copper, zinc, magnesium,
antioxidants, and useful phytochemicals. Whole grain fiber help prevent the
formation of small blood clots that can trigger heart attacks or strokes. All meta-
analysis that estimated the association of whole grain intake and reduction of all-
cause mortality, mostly in developed countries (USA, UK, Scandinavian countries)
found that people who ate 70 grams/day of whole grainscompared with those
who ate little or no whole grainshad around 20% lower risk of total mortality,
lower risk of CVDs and around 10% lower risk of cancer deaths.
The last meta-analysis (2018) of prospective cohort studies on the subject of
whole grain intake and mortality included 19 eligible studies with 1,041,692
participants and 96,710 total deaths. The pooled relative risk (RR) was 0.84 for total
mortality, 0.83 for CVD mortality and 0.94 for cancer mortality. These decreases
were the result of comparison among the participants with the higher intake of
whole grain with the lowest category. Each 28 g/day intake was associated with
14% lower CVD, 9% total mortality and 3% lower risk for cancer. Researchers
concluded that the results support current dietary guidelines for the intake of
whole grains in order to improve health and prevent premature morbidity and
mortality. Government officials, scientists and medical staff should take actions to
promote whole grains intake.87
35
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