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UK Journal of Pharmaceutical and Biosciences Vol. 4(4), 01-11, 2016 REVIEW ARTICLE
Assessment of the Health implications of Synthetic and Natural Food Colourants –
A Critical Review
Sunday N. Okafor1*, Wilfred Obonga1, Mercy A. Ezeokonkwo2, Jamiu Nurudeen3, Ufoma Orovwigho3,
Joshua Ahiabuike
1Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria
2Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria
3Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria
Article Information
Received 15 March 2016
Received in revised form 25 June 2016
Accepted 29 June 2016
Abstract
Several types of dyes are available in the market as colouring agents to food commodities.
Some commonly used synthetic food dyes include: brilliant blue, indigo carmine, citrus red,
fast green, erythrosine, allura red, tartrazine and sunset yellow. The main food biocolorants
are carotenoids, flavanoids, anthocyanidins, chlorophyll, betalain and crocin. There has been
a rising concern over the health implications of the use of food dyes in human diets. How
safe are these food colourants? This has led to a lot of studies, both by individual
researchers, corporate organization-sponsored and even government-sponsored researches,
to authenticate the benefits or risks associated with the use of food colourants (synthetic and
natural). This review critically evaluated scientific researches from various published journal
articles and reports, with a view of clarifying the health implications of using these food dyes.
Various studies have shown that synthetic food colourants have considerable toxicological
effects, including but not limited to carcinogenicity, hypersensitivity reactions, and behavioral
effects. However, natural food colourants have been found to be relatively safe to humans.
Besides the colouring property, they have been found to possess a number of
pharmacological properties like strong antioxidant, antimutagenic, anti-inflammatory,
antineoplastic and antiartheritic effects.
Keywords:
Food colourants,
Synthetic, natural,
Health benefits,
Toxicological effects
Corresponding Author:
E-mail : sunday.okafor@unn.edu.ng
Mob.: +2348036556699
1 Introduction
The natural and synthetic color additives were used extensively
to color foods, drugs and cosmetics1. This was largely due to
their cost effectiveness and tinctorial power2. Food
Manufacturers have used food colourants as a means of
ascertaining the level of acceptability of processed food by
consumers 3,4. The flavor perception of a food or beverage has
been shown to have a direct correlation to its colour5. Therefore,
it has appeared fashionable to use them in various food
materials.
Possible reasons for use of colorants in food substances are
enumerated (FNB, 1971):
To maintain the original food appearance even after
processing and during storage;
To assure the color uniformity for avoiding seasonal
variations in color tone;
To intensify normal color of food and thus to maintain its
quality;
To protect the flavor and light susceptible vitamins making
a light-screen support; and
To increase acceptability of food as an appetizing item6.
The demand for food color in global market in 2000 was 2400
Metric Tons (MT) which increased to 3000 MT by the year 2005
and further to increase to 8000 MT by the year 2010 and is
UK Journal of Pharmaceutical and Biosciences
Available at www.ukjpb.com
ISSN: 2347-9442
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 2
expected to increase to 15000 MT by the year 20157. Also,
Revanker and S. S. Lele, (2007) reported that because of the
wide applications of these clourants, the total world colorant
production is estimated to be 8,000,000 tons per year8.
There are varieties of colours. Because of the ability of these
food colours to influence or stimulate appetite and make it
appeal to consumers more strongly thereby influencing their
judgement, food manufacturing companies have explore this as
a major strategy in food marketing. Food colors can be grouped
divided into four categories: a) natural colors, b) nature-identical
colors, c) synthetic colors and d) inorganic colors5,9.
There is an increasing worries over the safety of the synthetic
food colourants. In 1820, English chemist Friedrich Accum was
the first to bring this growing problem to the public’s attention
with his publication of A Treatise on Adulterations of Food and
Culinary Poisons10. The book lists countless examples of
contemporary foods that either using poisonous dyes or any
colorant that masked the true nature of the product.
In the past few years, people are becoming increasingly aware
of the use of natural colorants11. Many of the approved artificial
dyes are being delisted because of consumer preference as
well as legislative action12. Consequently, there is a growing
demand of natural food colours as against the synthetic colours.
About US $ 1 billion has been invested to increase the supply of
these natural food colours6.
2 Chemistry of coloured compounds
Dyes are organic compounds with characteristic colours. The
compounds owe these characteristic colours due to their ability
to13:
1. absorb light in the visible spectrum (400–700 nm),
2. have at least one chromophore (colour-bearing group),
3. have a conjugated system, i.e. a structure with alternating
double and single bonds, and
4. exhibit resonance of electrons, which is a stabilizing force
in organic compounds.
The compound (dye) loses its colour when any of these features
is lacking from the molecular structure. Some of these dyes can
also contain colour helpers group(s) called auxochromes. Their
role is to shift the colour of thedye and influence their solubility.
Examples of such group include hydroxyl, carboxylic acid,
sulfonic acid and amino groups. Table 1 show the relationships
between wavelength of visible and colour absorbed/observed
(Table 1). Tables 2 and 3 show examples of natural and
synthetic food dyes containing chromophoric groups.
3 Health implications of synthetic food colourants
Sahar and Manal (2012)14 conducted a research to investigate
the effect of using colour foods [(Colour fruit juice for 6 - 12 hr)
on the serum biochemical, and on the liver and kidney of rats for
13 weeks. Tomato ketchup potato chips, TKPC (30%) showed a
significant increase in total cholesterol (TC) and triacyl- glycerol
(TG). The level of ALT and AST was significant increase of rat’s
administration color fruit juice (for 12 hr) and TKPC at 30%.
Table 1: Wavelength of light absorption versus colour in
organic dyes
Wavelength
Absorbed (nm)
Colour
Absorbed
Colour
Observed
400–435
435–480
480–490
490–500
500–560
560–580
580–595
595–605
605–700
Violet
Blue
Green-Blue
Blue-Green
Green
Yellow-Green
Yellow
Orange
Red
Yellow-Green
Yellow
Orange
Red
Purple
Violet
Blue
Green-Blue
Blue-Green
There was also a significant increase in serum creatinine and
albumen. Both low and high colour foods consumed exhibited
significant decrease in liver GSH. The study also revealed that
high concentration of colour foods lead to increased number of
WBC as the result to the response of the immune system to the
inflammation. Their findings showed that color fruit juice
containing sunset yellow, tartazine and carmosine lead to
significant increase in ALT of serum rats. Therefore, they
concluded that the synthetic colours used in their research have
adverse effects on some of the serum biochemical, liver and
kidney.
These results were well supported by the data reported by
Mekkawy et al.15, and Amin et al.16, who indicated that rats
which consumed high dose synthetic color (Tartarzine,
Carmoisin, sunset yellow and fast green) showed a significant
increase in serum ALT and AST when compared to control rats.
A significant increase in serum ALT and AST may attribute
those changes in liver function to be hepatocellular impairment
level of intracellular enzymes into the blood17. This was more
evident in the histopathological studies. At low dose synthetic
color, the liver revealed a disruption of hepatic cells near the
central vein and hepatocellular damage. These results are in
agreement with the Sharma et al.18 who reported that synthetic
colours have adverse effect on vital organs. The release of a
normally high level of specific tissue enzymes into blood stream
is dependent on both the degree and type of damage exerted
by the toxic compound administration19,20. Furthermore, there
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 3
was a significant increase in the serum creatinine. It is believed
that the significant elevation in creatinine level is closely related
to the impairment of renal function.
Table 2: Examples of Natural food dyes containing chromophoric groups
Class
Example
E
Number
Structure
Flavonoids
Quercetin
Luteolin
Anthocyanidin
Pelargonidin (R1,
R2=H)
Cyanidin(R1=
OH, R2=H)
Delphinidin(R1,
R2=OH)
E 163
Terpenoid
(Carotenoid)
Beta Carotene
E 160a
Terpenoid
(Carotenoid)
Lycopene
E 160d
Terpenoid
(Carotenoid)
Canthaxanthin
160g
Terpenoid
(Carotenoid
Zeaxanthin
Lutein
E 161b
Capsanthin
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 4
Curcumin
E 100
Chlorophyll
E 140
Table 3: Some examples of Synthesis Food Colourants
Dye
Code
Structure
Brilliant Blue
Blue #1
(Indigo
Carmine)
Blue #2
Citrus
Red #2
Fast Green
Green #3
Erythrosine
Red #3
Allura Red
Red #40
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 5
Tartrazine
Yellow #5
Sunset Yellow
Yellow #6
Carmoisine
E122
The present findings are in accordance with data reported by
Ashour and Adelaziz21, who observed a significant elevation in
serum creatinine and urea level of rats doses with azo dye (fast
green) orally for 35 days. The group administrated with
chocolate and sweet colored at low and high concentrations
witnessed a significant increase in triglycerides. These results
again are in accordance with the results obtained by Abou El-
Zahab et al.22, and Himiri et al.23, who observed significant
increase in serum triglycerides of rats treated with synthetic
color (tartrazine) and chocolate color A and B that containing
tartrazine and Carmoisne.
The cytotoxicity of 11 dyes, used as food dyes in Japan, on
cultured fetal rat hepatocytes was studied24. Xanthene dyes
containing halogen atoms in their molecules such as phloxin,
rose bengal, and erythrosine were more toxic than other groups
of food dyes. The effect of food dyes on the cell growth of
hepatocytes was also examined. The high hepatotoxicity of
phloxin to the cell growth, which was dose-dependent, was
observed when the dye was added 3 days after plating.
A double blind placebo controlled high dose azo dye challenge
in a highly selected group of children with behaviour disturbance
suggested a small adverse effect on the children’s behaviour
based on ratings on the Connor scale25. Bateman et al (2004)
carried out a work on the effects of artificial food colourings and
benzoate preservative challenge on hyperactivity in a general
population sample of preschool children26. They found out that
there is a general adverse effect of artificial food colouring and
benzoate preservatives on the behaviour of 3 year old children.
They concluded that children would benefit more if artificial food
colours and benzoate preservatives were removed from their
diet.
The studies carried out by the Center for Science in the Public
Interest (CSPI), on food dyes revealed that27, some of the most
commonly used food dyes may be linked to numerous forms of
cancer. CSPI reported:
"The three most widely used dyes, Red 40, Yellow 5, and
Yellow 6, are contaminated with known carcinogens … Another
dye, Red 3, has been acknowledged for years by the Food and
Drug Administration to be a carcinogen, yet is still in the food
supply."
In their 58-page report, ―Food Dyes: A Rainbow of Risks‖ CSPI
revealed that nine of the food dyes currently approved for use in
the United States are linked to health issues ranging from
cancer and hyperactivity to allergy-like reactions, and these
results were from studies conducted by the chemical industry
itself. For instance,
Red # 40, which is the most widely used dye, may
accelerate the appearance of immune system tumors in
mice, while also triggering hyperactivity in children.
Blue # 2, used in candies, beverages, pet foods and more,
was linked to brain tumors.
Yellow 5, used in baked goods, candies, cereal and more,
may not only be contaminated with several cancer-causing
chemicals, but it's also linked to hyperactivity,
hypersensitivity and other behavioral effects in children.
As CSPI reported28
"Almost all the toxicological studies on dyes were
commissioned, conducted, and analyzed by the chemical
industry and academic consultants. Ideally, dyes (and other
regulated chemicals) would be tested by independent
researchers. Furthermore, virtually all the studies tested
individual dyes, whereas many foods and diets contain mixtures
of dyes (and other ingredients) that might lead to additive or
synergistic effects. In addition to considerations of organ
damage, cancer, birth defects, and allergic reactions, mixtures
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 6
of dyes (and Yellow 5 tested alone) cause hyperactivity and
other behavioral problems in some children.
In a placebo-controlled study conducted in 2007 and published
in The Lancet journal29, the work critically evaluated the effects
of common food dyes found in many soft drinks, fruit juices and
salad dressings. The results showed that dyes studied caused
some children to be more hyperactive and distractible. As a
support to the findings in the Lancet, a research work reported
in the Annals of Allergy30 revealed that 73 percent children who
were suffering from ADHD responded favourably to a diet which
artificial colours have been removed. The Lancet study found
that E-numbered food dyes cause as much damage to the
children’s brains as lead in gasoline, leading to significant
reduction in their IQ. At the wake of these findings, the British
Food Standards Agency (FSA) issued advisory warning to
parents to limit their children’s intake of food additives. FSA also
advised the food industry to voluntarily remove the six food dyes
named in the study back in 2009, and replace them with natural
alternatives if possible. UK food dyes on which the Food
Standards Agency has called for a voluntary ban include:
Tartrazine, Quinoline Yellow, Sunset Yellow, Carmoisine,
Ponceau 4R, and Allura Red31.
According to the Washington Post32
“Beyond the behavioral problems and cancer risks, the greatest
hazard that dyes pose for children may also be the most
obvious: They draw kids away from nutritious foods and toward
brightly colored processed products that are high in calories but
low in nutrients, such as fruit-flavored drinks and snack foods.
Those types of foods are a major force in America’s obesity
epidemic.”
4.2 Health benefits of natural food colourants
Natural food colourants (biocolorants) may also play an
important role in human health as they contain some biologically
active compounds, which possess a number of pharmacological
properties like strong antioxidant, antimutagenic, anti-
inflammatory and antiartheritic effects33-41. Carotenoids are also
used as vitamin supplements42, since β-carotene is the
precursor of vitamin A. The regular intake of carotene can help
prevent night blindness resulting from inadequate supply of
vitamin A. Carotenoids also act as biological antioxidants,
protecting cells and tissues from the damaging effects of free
radicals and singlet oxygen and also as a good source of anti-
tumor agent43.
Lycopene, is particularly effective at quenching the destructive
potential of singlet oxygen44. Lutein, zeaxanthin and
xanthophylls are believed to function as protective antioxidants
in the macular region of the human retina45-47. These
compounds also act against aging, mascular degeneration, and
senile cataracts48. Canthaxanthin also shows antioxidant
property49. Astaxanthin is another naturally occurring
xanthophyll with potent antioxidant properties44.
Food phenolic compounds, particularly flavonoids, are thought
to play important roles in human health50-52. A number of
studies, both in vivo and in vitro studies have demonstrated that
flavonoids have antioxidant and antimutagenic activities53 and
could be very useful in the reduction of the risk of developing
cardiovascular disease and stroke54. Flavonoids may act as
antioxidants to inhibit free-radical mediated cytotoxicity and lipid
peroxidation, as antiproliferative agents to inhibit tumor, growth
or as weak estrogen agonists or antagonists to modulate
endogenous hormone activity55. Flavonoids have been labeled
as ―high level‖ natural antioxidants on the basis of their abilities
to scavenge free radicals and active oxygen species56-58 as
result of the hydroxyl groups and the conjugated ring system
through halogenation or complexing with these oxidizing
species59,60. In these ways, flavonoids may confer protection
against chronic diseases such as atherosclerosis and cancer
and assist in the management of menopausal symptoms. Thus,
flavonoids have been referred to as semi-essential food
components61.
Consumption of quercetin may protect against cardiovascular
disease62 by reducing capillary fragility and inhibiting platelet
aggregation63. Several flavonoids such as catechin, apigenin,
quercetin, naringenin, rutin, and venoruton are reported for their
hapatoprotective activities64. Anthocyanins have drawn
increasing attention because of their preventive effect against
various diseases. Zhu et al.65 demonstrated that anthocyanin
cyanidin-3-O-β-glucoside (C3G) increases hepatic Gclc
expression by increasing cAMP levels to activate protein kinase
A (PKA), which in turn upregulates cAMP response element
binding protein (CREB) phosphorylation to promote CREB-DNA
binding and increase Gclc transcription. Increased Gclc
expression results in a decrease in hepatic ROS levels and
proapoptotic signaling. It was also shown that the C3G
treatment reduces hepatic lipid peroxidation, inhibits the release
of proinflammatory cytokines, and protects against the
development of hepatic steatosis65.
Other health benefits of biocolorants include enhancement of
immune system function66, protection from sunburn67, and
inhibition of the development of certain types of cancers68.
Lycopene prevents oxidation of low-density lipoprotein (LDL)
cholesterol and reduces the risk of developing atherosclerosis
and coronary heart disease69. Epidemiological studies have
revealed a correlation between the consumption of chlorophylls
and decreased risk of colon cancer70. They have also been
observed to possess antineoplastic, radiation-protective,
vasotonic, vasoprotective, anti-inflammtory and
hepatoprotective activities71. A flavaoured and brightly coloured
seed of Manikara obovate has been showed to have both
antioxidant and hepatoprotective activities72.
Table 4: Colour additives to avoid
Colour
Status worldwide:
Where found
Possible negative effects:
References
Erythrosine
FD&C Red
No. 3
Banned for use in cosmetics and
external drug, but not food and
ingested drugs in
the U.S.
Cocktail,
canned fruits
salads
confections
dairy products
snack foods.
Cancer
[32]
Tartrazine
(E102)
FD&C
Yellow No. 5,
Banned in Norway and Austria.
Ice cream
Carbonated drinks
Fish sticks
Hyperactivity, asthma, skin
rashes, and migraine
headaches.
[33]
Quinoline
yellow
(E104)*
Banned in Australia, Japan,
Norway and the U.S.
Restricted to max.
Permitted levels in U.K.
Soft drinks
Ice creams
Candies
Cosmetics
medications
Asthma, rashes and
hyperactivity. Potential
carcinogen in animals:
implicated in bladder and liver
cancer. Altered reproduction
in animals.
[34]
Sunset
yellow
(E110)*
Yellow FCF
Orange
Yellow S
Banned in Norway, Sweden and
Finland. Restricted to
maximum permitted levels in U.K.
Sweets
Snack foods
Ice-creams,
Yoghurts
Drinks
AVOID in allergies & asthma.
Cancer – DNA damage,
increases tumors in animals.
Growth retardation and
severe weight loss in
animals.
[34]
Carmosine
(E122)*
Banned in Canada, Japan, Norway,
Austria, Sweden
and the U.S. Restricted to
maximum permitted levels in U.K.
Yoghurts
Sweets
DNA damage and
tumours in animals.
[35]
Allura red
(E129)*
FD&C Red
No. 3
Banned in Denmark,
Belgium, France, Germany,
Switzerland, Sweden,
Austria and Norway
Carbonated drinks
Bubble gum, snacks,
Sauces, preserves,
Soups, wine, cider,
etc.
May worsen or induce
asthma, rhinitis (including
hayfever), or urticarial (hives).
[33]
Ponceau 4R
(E124)*
Conchineal
Banned in US, Canada, Norway,
Sweden and Japan. Restricted to
maximum permitted levels in the
UK
Carbonated drinks
Ice-creams
Confectioneries
Desserts
Cancer - DNA damage and
tumours in animals. Can
produce bad reactions in
asthmatics
[36]
Amaranth
(E123)
Banned in the U.S.
Alcoholic drinks
Fish roe
May worsen or induce
asthma, allergies or hives.
[37]
Okafor et al., Assessment of the Health implications of Synthetic and Natural Food Colourants
UK J Pharm & Biosci, 2016: 4(4); 8
Wine
Indigo
Carmine
(E132)*
Banned in the US, Japan, Australia
and Norway. UK use restricted to
maximum permitted levels
Ice-creams
Sweets
Baked goods
Confectionery items
Biscuits
May cause nausea,
vomiting, skin rashes, and
brain tumors. DNA
damage and tumors in
animals.
[38]
Brilliant
Blue
(E133)*
Banned in Austria, Belgium,
France, Norway, Sweden,
Switzerland and Germany.
Restricted to maximum
permitted levels in U.K.
Dairy products
Sweets
Drinks
Hyperactivity and skin
rashes. Listed as human
carcinogen by the US EPA.
Causes DNA damage and
tumors in animals
[38]
*All of these additives are considered the ―Dirty Dozen Food Additives‖ and are prohibited in the UK for foods marketed for children less than 36 months.
5 Recommendations
1. People should try to stick to unprocessed naturally
colored foods for their health
2. The food industry should voluntarily remove harmful
food dyes and replace them with natural alternatives if
possible
3. Foods that contain artificial food dyes should be
labeled with warning labels stating the food "may
have an adverse effect on activity and attention in
children."
4. Relevant Government agencies should issue an
immediate advisory to parents, warning them to
limit/avoid their children's intake of additives if they
notice an effect on behavior
5. Food and Drug regulatory agencies should ban food
dyes, which serve no purpose other than a cosmetic
effect,
6. Some laws making it difficult to ban certain food
colourants should be amended to make it no more
difficult to ban food colorings than other food
additives)
6 Conclusions
As a result of carcinogenicity, hypersensitivity reactions, and
behavioral effects and other toxicological considerations, food
dyes cannot be considered safe. We strongly advocate that
food and drug regulatory agencies of various countries should
rise up and ban food dyes, which serve no purpose other than a
cosmetic effect, borrowing a leave from Japan and all European
countries have banned trading of synthetic color made products.
In the meantime, food companies should voluntarily replace
dyes with safer, natural colorings, which has been found to be
relatively safe and with health benefits.
7 Acknowledgements
The Authors wish to acknowledge the supports from
Ogechukwu Ugwu, Uchechi Uchenyi, Gloria Eze, Ifudu Unoaku
and Glory James. We also wish to thank Young Researchers’
Forum of Nigeria for their encouragement and supports
throughout the period of this work.
8 Conflict of interest
We declare that there is no conflict of interest
9 Author’s contributions
SNO, JN, UU and JA contributed to the design, collection of
data, carried out literature review; SNO prepared the
manuscript; WO and MAE supervised the entire work. All
authors read and approved the final manuscript.
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