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Artificial Sweeteners

  • Jeonbuk National University, Iksan, South Korea

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Artificial Sweeteners provide the sweetness of natural sugar without the calories and produce a low glycemic response. These sweeteners are used instead of sucrose (table sugar) to sweeten foods and beverages. Consumers and food manufacturers have long been interested in dietary sweeteners to replace sucrose in foods. This article goes into a lot of details about the different types of sweeteners such as saccharin, acesulfame potassium, aspartame, neotame and sucralose, their uses, chemistry and their potential effects on health. These sweeteners form acute and chronic effects on human health.
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International Journal of Research & Review ( 120
Vol.6; Issue: 1; January 2019
International Journal of Research and Review E-ISSN: 2349-9788; P-ISSN: 2454-2237
Review Paper
Artificial Sweeteners
Anushkkaran Periyasamy
Department of Chemistry, Faculty of Science, University of Jaffna, Jaffna, Sri Lanka
Artificial Sweeteners provide the sweetness of natural sugar without the calories and produce a low
glycemic response. These sweeteners are used instead of sucrose (table sugar) to sweeten foods and
beverages. Consumers and food manufacturers have long been interested in dietary sweeteners to
replace sucrose in foods. This article goes into a lot of details about the different types of sweeteners
such as saccharin, acesulfame potassium, aspartame, neotame and sucralose, their uses, chemistry and
their potential effects on health. These sweeteners form acute and chronic effects on human health.
Keywords: Artificial sweeteners; adverse effects; potential toxicity
Artificial sweeteners are many times
sweeter than table sugar, smaller amounts
are needed to create the same level of
sweeteners, and which are either not
metabolized in the human body or do not
significantly contribute to the energy
content of foods and beverages. Those
provide the sweeteners of sugar without the
calories and produce a low glycemic
response. [1] Glycemic response to food is
the effect that food has on blood sugar
levels after consumption. [2] Consumers and
food manufacturers have long been
interested in dietary sweeteners to replace
sucrose in foods. Because recently these
products have received increased attention
due to their effects on glucose regulation.
These exceed the sweeteners of sucrose by a
factor of 30-13,000 times because of these
include substances from several different
chemical classes. [1] These sweeteners are
widely used in baked goods, carbonated
beverages, powdered drink mixtures, jams,
jellies and dairy products. [3] These are
regulated by the Food and Drug
Administration (FDA).
Sweeteners have been classified as
natural sweeteners and artificial sweeteners.
These artificial sweeteners further classified
as nutritive and non-nutritive sweeteners
depending on whether they are a source of
calories. The nutritive sweeteners include
the monosaccharide polyols (e.g., sorbitol,
mannitol, and xylitol) and the disaccharide
polyols (e.g., maltitol and lactitol). The non-
nutritive sweeteners are better to known as
artificial sweeteners. [1]
Artificial sweeteners have some
ideal requirements. They should provide
sweetness with no unpleasant aftertaste,
should have little or no calories, should be
economical to produce, should not be
degraded by heat when cooked and should
not be carcinogenic or mutagenic.
Carcinogenic is having the potential to
cause cancer, and mutagenic is a physical or
chemical agent that changes the genetic
material of the organism. [3]
The main reasons for using artificial
sweeteners are weight lose, dental care,
diabetes mellitus, reactive hypoglycemia
and low cost. [1] Dental caries are also
known as teeth decay or cavities.
Breakdown of teeth due to activities of
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bacteria. This occurs due to acid made from
sugar on the tooth surfaces. Simple sugars in
foods are the primary energy source of these
bacteria. [4] Reactive hypoglycemia refers to
low blood sugar that occurs after a meal
usually within 4 hours after eating. This can
occur in both people with and without
diabetes and is thought to be more common
in overweight individuals. Reactive
hypoglycemia is known as the result of too
much insulin being produced and released
by the pancreas following a large sugar or
carbohydrate based meals. [5] To reduce
these activities, most of the people are using
artificial sweeteners.
The main five sugar substitutes for
use in a variety of foods are saccharin,
acesulfame potassium, aspartame, neotame
and sucralose. Characteristic features of
these five artificial sweeteners are given in
the Table 1.
Table 1. Characteristic features of artificial sweeteners [1]
Brand names
Number of times
sweetener than
Common uses
Sweet’N Low
Sweet Twin
Necta Sweet
Soft drinks, Tabletop sweetener, Jams, Chewing gum, Baked
Sweet One
Tabletop sweeteners, Candies, Chewing gum, Dairy products
Nutra Sweet
Soft drinks, Yoghurt, Pharmaceuticals
Baked goods, Soft drinks, Chewing gum, Jams, Jellies, Puddings,
Processed fruit and fruit juices
Frozen deserts, Fruit juices, Chewing gum, gelatins
1.1 Structural requirements for sweetness
The generally accepted theory for the
phenomenon of sweetness was developed
by Shallenberger and Acree. According to
this theory, a molecular system of a proton
donor and proton acceptor is necessary.
Changes in the distance between groups, as
well as changes in electronic structure
influence the occurrence of the sweet taste
and may change the general taste
perception, sometimes eliminating
sweetness totally, or changing it to
bitterness. [6]
1.2 General Uses
1.2.1 Foods and Beverages
Foods and beverages are the most
important fields of application of artificial
sweeteners, with calorie reduction being the
main goal. Single sweeteners or
combinations with other sweet substances.
Artificial sweeteners can be used in diabetic
foods and beverages; depending on the type
of product, either as single sweetening
agents or combined with bulk sugar
substitutes suitable for diabetic
consumption. Beverage uses of artificial
sweeteners account for more than 50% of
human consumption; sugar replacement by
artificial sweeteners is simple, as
carbohydrates do not play any important
functional role in beverages. Other
important applications are fruit flavored
dairy products and desserts. [7]
1.2.2 Tabletop sweeteners
For household use, artificial sweeteners are
formulated into table-top sweeteners, such
as sweetener tablets, powders and spoon-by-
spoon products, and liquids.
1.2.3 Pharmaceuticals
Artificial sweeteners are used to mask
undesired flavors and tastes of active
pharmaceutical ingredients, e.g., bitterness,
whenever the pharmaceuticals are intended
for use by diabetics. Sweeteners are used in
syrups, and soluble tablets and powders.
1.2.4 Cosmetics
Several types of cosmetics, especially oral
hygiene products, are sweetened to make
them more pleasant for consumers. For oral
hygiene products (e.g., toothpaste,
mouthwash, etc.), noncariogenic ingredients
have to be used. The desired sweetness level
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is adjusted with an additional quantity of
artificial sweetener.
1.3 Saccharin
Saccharin is the first and oldest artificial
sweetener that has been used for over a
century to sweeten foods and beverages
without adding calories. Saccharin has been
approved by FDA for use in more than 100
countries. [3]
1.3.1 History
Saccharin was discovered by Fahlberg &
Remsen in 1879 at John Hopkins
University. This was found after those
chemists were researching the oxidation
mechanisms of toluene sulfonamide. They
were working with coal-tar derivatives.
During their research, a substance
accidentally splashed on Fahlberg’s finger
and he noticed the substance had a sweet
taste, which he traced to the chemical
commonly known as saccharin. Saccharin
enjoyed great commercial success in periods
of short sugar supply, e.g., during world
wars I and II. [8]
In 1997, the FDA proposed a ban on
saccharin because of concerns about rats
that developed bladder cancer after
receiving high doses of saccharin. Foods
containing saccharin were required to carry
a label warning that sweetener could be a
health hazard and that it was found to cause
cancer in laboratory animals. That label
contains “use of this product may be
hazardous to your body”. In 2000, the
National Toxicology Programme
determined that saccharin should no longer
be listed as a potential cancer-causing agent
because mechanistic studies have shown
that these results apply only to rats.
Mechanistic studies that examine have a
substance work in a body. Human
epidemiology studies have shown no
consistent evidence that saccharin is
associated with bladder cancer incidence.
Because the bladder tumors in the rats are
due to a mechanism not relevant to human
and there is no clear evidence that saccharin
causes cancer in humans. Epidemiology
studies are that studies of patterns, causes
and control of disease in groups of people.
In 2001, saccharin was officially declared
safe and the ban was removed. [9]
1.3.2 Chemistry
Saccharin is formed by an initial
reaction between toluene and chlorosulfonic
acid. Synthesis of saccharin is explained in
Figure 1. [7]
Figure 1. Synthesis of saccharin (Remsen-Fahlberg synthesis)
After ingestion, saccharin is not
absorbed or metabolized. Instead, it is
excreted, unchanged via the kidneys. [1]
Slightly bitter taste and metallic taste and
for this reason is sometimes combined with
other sweeteners. For an example, saccharin
is often used with aspartame in diet
carbonated soft drinks. [3] The form used as
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an artificial sweetener is sodium salt and
calcium salt, especially by people restricting
their dietary sodium intake. [1]
1.3.3 Uses
Important fields of application are
soft drinks, tabletop sweeteners, and
desserts. For taste reasons, blends with other
artificial sweeteners, or combinations with
reduced sugar levels are preferred wherever
such blends are approved. In oral hygiene
products, saccharin masks undesired tastes
of other ingredients. In starter feed for
livestock, saccharin is used to avoid reduced
feed intake after weaning. Besides its
applications as an artificial sweetener,
saccharin is used in electrolytic nickel
deposition. Addition of saccharin to the
nickel salt solutions increases the hardness
and brightness of the nickel plate. This
effect is apparently specific to saccharin. [10]
1.3.4 Toxicology
Saccharin causes a headache, breathing
difficulties, skin eruptions and diarrhea.
1.4 Acesulfame potassium
This is a general purpose sweetener,
white crystalline structure, high-intensity,
non-nutritive sweetener, non-carcinogenic
and stable under high temperatures. So it
does not break down in heat, therefore often
used in baked products. It is used in over
4000 products in approximately 90
countries. The “K” refers to the mineral
potassium, which is naturally found in our
bodies. [3]
1.4.1 History
Acesulfame-K was discovered in
1967 by chemist Karl Clauss and Jensen
during investigations on oxathiazinone
dioxides. The sweet taste was found by
chance. Several other oxathiazinone
dioxides taste sweet but have less favorable
characteristics. Acesulfame-K was approved
in the United States in 1988 for specific
uses, including a tabletop sweetener. In
1998, the FDA approved acesulfame-K to
be use in beverages. In specially, it has been
used to decrease the bitter aftertaste of
aspartame. FDA continues to support the
use of acesulfame-K in diabetic and low-
calorie food. [1]
1.4.2 Chemistry
Acesulfame-K is formed by an
initial reaction between 4-chlorophenol and
sodium. Synthesis of acesulfame-K is
explained in Figure 2.
Figure 2. Synthesis of acesulfame-K
Acesulfame-K is not metabolized by
the body and is not stored in the body. It is
quickly absorbed and excreted in urine
without undergoing any modification.
Pharmacokinetic studies show that 95% of
the consumed sweeteners basically ends up
excreted in the urine. [11]
1.4.3 Uses
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Acesulfame K is used in all fields of
applications of artificial sweeteners.
Common applications are table-top
sweeteners; beverages; foods, such as dairy
products, desserts, bakery products,
confectionery, chewing gum, pickles, and
marinated fish; oral hygiene products and
pharmaceuticals. Owing to its synergistic
characteristics, acesulfame K is often used
in sweetener blends, and in combination
with bulk sweeteners in products requiring
good stability, e.g., confectionery or bakery
1.4.4 Toxicology
Acesulfame-K contains methylene chloride
which is a known carcinogen. Long-term
exposure to methylene chloride can cause a
headache, depression, nausea, mental
confusion, liver and kidney effects.
Acesulfame-K’s breakdown in the body
forms the byproduct acetoacetamide, which
is toxic at high doses and which has been
shown to cause tumor growth in the thyroid
gland in rats, rabbits and dogs. Only 1%
acetoacetamide is accumulated for three
months. [3]
1.5 Aspartame
One of the most debated sweeteners.
Aspartame has a sugar-like taste. It can be
safely heated to high temperatures with
some loss of sweeteners. It has been used in
over 6000 different types of products. [12]
1.5.1 History
Aspartame was discovered in 1965
by G. D. Searle when he was studying new
treatments for gastric ulcers. Tetrapeptide is
normally produced in the stomach which
was used by the biologist to test new anti-
ulcer drugs. One of the most important steps
in the process was to make an intermediate,
aspartyl-phenylalanine methyl ester to
synthesis tetrapeptide. When chemist was
synthesis this tetrapeptide, accidentally, a
small amount of the compound landed on
the chemist’s hand. Without noticing the
compound, the chemist licked his finger and
discovered a sweet taste. After realizing it
was not likely to be toxic.
It was first approved by the FDA in
1981 as a tabletop sweetener; in 1996, it
was approved as a general-purpose
sweetener in all foods and drinks.
Aspartame is sometimes blended with more
stable sweetener saccharin. [13]
1.5.2 Chemistry
Aspartame is made by joining L-
phenylalanine or L-phenylalanine methyl
ester with L-aspartic acid. Synthesis of
aspartame is explained in Figure 3.
Figure 3. Synthesis of aspartame
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Aspartame breaks down into small
amounts of methanol, aspartic acid and
phenylalanine during the digestion.
Methanol is non-drinking alcohol, injecting
of that can lead to toxicity and death within
a few hours. The body also breaks down this
methanol into formaldehyde which turns
into formic acid in the liver. Formaldehyde
and formic acid both are toxic.
Our body produces formaldehyde in
amounts thousands of times greater than we
get from the sweetener which is used by the
body to make important substances. Formic
acid rarely builds up because the body uses
formaldehyde so quickly and if there were
an excess, it would be eliminated through
urine or broken down into CO2 and water.
Finally, the aspartame in diet produces so
little amount of ethanol. [14]
1.5.3 Uses
The sensory characteristics of
aspartame allow its use in all common
sweetener applications. Limitations are
imposed by its susceptibility to hydrolytic
decomposition and limited temperature
1.5.4 Toxicology
FDA has mandated packaging bear a
warning label to prevent individuals with
the rare genetic disorder phenylketonuria
from ingesting the aspartame.
Phenylketonuria is an inborn error of
metabolism that leads to attenuated
metabolism of the amino acid
phenylalanine. Phenylketonuria can lead to
behaviour problems and mental disorders.
Individuals who suffer from this disease
have an insufficient amount of the enzyme
phenylalanine hydroxylase which is
required to breakdown the phenylalanine.
Without the presence of this enzyme,
phenylalanine accumulates.
Due to the methanol, aspartic acid
and phenylalanine which came from the
digestion of aspartame can cause the
following symptoms: headache, blurred
vision, brain tumors, eye problems, memory
loss and nausea. [15]
The aspartame consists of aspartic
acid which is a well-documented
excitotoxin. 3 amino acids such as
glutamate, aspartate and cysteine that excite
our neurons can be called as excitotoxin.
These neurotransmitters (amino acids)
excessively stimulate the nerve cells to
either damage or kill. Excitotoxicity may be
involved in spinal cord injury, stroke and
hearing loss. [16]
1.6 Neotame
Neotame is the newest sweetener
and a derivative of aspartame. A t-butyl
group is added to the free amine group of
aspartic acid. This could be a super sweet
deal for food and beverage manufacturers,
all the sweetness of sugar without a metallic
after-taste plus at a fraction of the amount of
sweetener needed compared to other sugar
substitutes. The neotame was approved in
2002 as a general purpose sweetener,
excluding in meat and poultry by FDA. [1]
1.6.1 History
After the success of aspartame in the
market, there were calls for developing a
novel sweetener possessing additional
qualities such as higher heat stability, fewer
restrictions and higher sweetener potency
which means less amount to achieve the
same sweetness at a lower cost. Therefore
scientists synthesized thousands of
compounds based on the simple structure of
aspartame. End of the research, neotame
came up with the desirable qualities among
those synthesized compounds. Neotame was
approved by FDA for general use in 2002.
1.6.2 Chemistry
When we add the t-butyl group to
the free amine group of aspartic acid, it
leads to a second hydrophobic group and
results in a product that is 30-60 times
sweeter than aspartame. [18] Figure 4 shows
the synthesis of neotame.
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Figure 4. Synthesis of neotame
Neotame is rapidly metabolized by
hydrolysis of the methyl ester via esterase
present throughout the body. It forms a
minor amount of methanol that the body
absorbs. This process yields de-esterified
neotame. Neotame and de-esterified
neotame are rapidly clear from the plasma,
which is completely eliminated from the
body with recovery in urine and feces
within 72 hours. It is safe for who suffer
from phenylketonuria because t-butyl group
is added to the free amine group of aspartic
acid. This t-butyl group typically break the
peptide bond between the aspartic acid and
phenylalanine, thus reduce the availability
of phenylalanine which is responsible for
phenylketonuria. [19]
1.6.3 Toxicology
Neotame causes some of the toxic
effects in the human such as it to reveal
changes in body weight and food
consumption, headache and hepatotoxicity
at high dosages.
1.7 Sucralose
Sucralose is a sucrose molecule in which
three of the hydroxyl groups have been
replaced by Cl atoms. Sucralose is also heat
stable which quality makes it a superb
sweetener for cooking and baking. It retains
its sweeteners significantly longer than
aspartame. Figure 5 shows structures of
sucrose and sucralose.
Figure 5. Structures of sucrose and sucralose
1.7.1 History
Sucralose was accidentally
discovered by Tate & Lyle in 1976, was
looking for ways to use sucrose as a
chemical intermediate. Ironically, sucralose
states out as cane sugar but ends up 600
times sweeter than table sugar. It came on
the scene in 1976 and was approved by the
FDA in 1999 for use in 15 food categories.
After some laboratory experiments which
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changes the sugar molecule, its structure
now prevents it from being absorbed by the
body. [20]
1.7.2 Chemistry
Synthesis of sucralose is shown in the figure
Figure 6. Synthesis of sucralose
TrCl = triphenylmethyl chloride; DMAP = 4-dimethylaminopyridine
Sucralose is poorly absorbed in the human
and the majority of ingested sucralose
excreted unchanged in the feces.
1.7.3 Toxicology
Sucralose is responsible for the
shrunken thymus glands with diets of 5%
sucralose, and also it causes diarrhea and
Artificial sweeteners are not
carbohydrates. So generally they don’t raise
blood sugar levels and cause diabetes. They
have no calories. In distinction, every gram
of normal table sugar contains four calories.
They are suitable for obesity. They do not
promote dental caries. [1]
Saccharin, acesulfame-K and
aspartame induced DNA damage in human
peripheral lymphocytes. Sucralose has been
well-tried through scientific
experimentation to cause a decrease in
beneficial micro-organisms. Under acidic
conditions, acesulfame-K formed minute
quantities of acetoacetamide and
acetoacetamide-N-sulfonic acid. While
under basic conditions, acetoacetic acid and
acetoacetamide-N-sulfonic acid are formed.
These degradation products may cause
DNA strand breaks. [3]
Toxic potential of artificial sweeteners for
the human body are shown in the Table 2.
Table 2. Toxic potential of artificial sweeteners [1]
Nausea, vomiting, diarrhea
Low birth weight, bladder
cancer, hepatotoxicity
Thyroid tumors
Headache, dizziness, nausea, vomiting,
Headache, hepatotoxic at high doses
Lower birth rate, weight loss
Diarrhea, dizziness, stomach pain
Thymus shrinkage
ADI - Annual daily intake
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Aspartame hydrolyzes into its
components within the gut. The increase of
these components was considered a
possibility of gastrointestinal problems.
Aspartame has been thought to cause brain
damage because one of its hydrolyzed
components is phenylalanine. Phenylalanine
plays an important role in a neurotransmitter
regulation. [3]
Artificial sweeteners provide some
of the health benefits. However, commonly
these sweeteners are toxic at high
concentrations in the long term. Their
consumption has been shown to cause mild
to serious side effects ranging from
headaches to life-threatening brain damages.
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How to cite this article: Periyasamy A. Artificial sweeteners. International Journal of Research
and Review. 2019; 6(1):120-128.
... Artificial sweeteners are many times sweeter than table sugar, smaller amounts are needed to create the same level of sweetness, and which are either not metabolized in the human body or do not significantly contribute to the energy content of foods and beverages. They provide the sweetness of sugar without the calories and produce a low glycaemic response [6]. ...
Full-text available
Aim: This study aimed at evaluating the influence of Sacoglottis gabonensis ethanolic extract on the electrolytes of swiss mice administered aspartame. Location and Duration of Study: The study was carried out in the green house of the Department of Animal and Environmental Biology, Rivers State University, Nkpolu-Oroworukwo, Port Harcourt, Nigeria (Coordinates 4o48’14”N 6o59’12”E). The experiment lasted for Ninety days. Experimental Design: A completely randomized experimental design employing relevant statistical tools for analysis and interpretation. Methodology: Ninety mice were assigned to six groups (A-F) of fifteen mice each. Group A was the negative control and so they were not given any treatment, but pellet and clean tap water. Group B was the positive control and received 50mg/kg/bw/day of aspartame alone. Group C received 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of ethanolic extract of Sacoglottis gabonensis leaf. Group D received 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of ethanolic extract of S. gabonensis bark. Group E received 50mg/kg/bw/day of aspartame and 250mg/kg/bw/day of a combination of bark and leaf extract. Group F received 50mg/kg/bw/day of aspartame and 500mg/kg/bw/day of a combination of bark and leaf extract. All the groups were exposed to their treatment by oral gavage for 30, 60 and 90days. Feed was withdrawn from the animals 24hours before the termination of experiment. Analysis of serum for electrolytes concentrations followed approved standard procedures. Results: There was a significant increase in potassium and chloride level across experimental duration compared with the control group. There was significant increase in sodium level in group B across the duration of experiment with the lowest value recorded in group D 30 days. The level of bicarbonate decreased in groups B and C at 30 days, D and F at 60 days and increased in B and C at 90 days. Calcium level increased significantly across experimental duration with the lowest value observed in group F. Conclusion: This study recorded alterations in the electrolyte concentrations in the serum of experimental mice especially group administered aspartame alone compared to the control group. However, these alterations reported in the level of electrolytes may lead to metabolic disorder in individuals exposed to frequent and high intake of aspartame. Therefore, moderate consumption of aspartame is advocated while the consumption of S. gabonensis is highly recommended.
Background With the features of safety, stabilization, and low/no calorie, natural sugar substitutes have been widely used in food and beverage industries. Nevertheless, the low abundance of natural sugar substances makes the traditional plant extraction process neither economical nor environmentally friendly. Thus, the bioproduction of natural sugar substitutes by microbial cell factories has received great attention. Scope and approach Natural sugar substitutes can be classified into five types: monosaccharides, oligosaccharides, sugar alcohols, glycosides, and sweet-tasting proteins. This review aims to comprehensively summarize the recent advances in the bioproduction of the first four natural sugar substitutes, including synthetic pathways, production routes, and metabolic engineering strategies used to construct natural sugar substitute cell factories. The challenges and perspectives of the bioproduction of natural sugar substitutes are also discussed. Key findings and conclusions The bioproduction of natural sugar substitutes driven by synthetic biology has made great progress, and the microbial production of some natural sugar substitutes has been commercialized at an industrial scale. However, several challenges, such as the low activity of key enzymes, imbalance of metabolic modules caused by the overexpression of heterologous genes, and unknown exporters of some sugar substitutes, still exist. The emergence of new synthetic biology tools, including machine learning-based computational biodesign of cell factories, clustered regularly interspaced short palindromic repeats-based genome editing technology, and genetic circuit-based multimodular ordered control of cellular metabolism, brings promising opportunities to overcome the above challenges and make more natural sugar substitutes produced by microbial cell factories on the market.
Food additives are the materials that are added in to the food product intentionally while processing or storage or transportation of food. They are added directly or indirectly in the food product. They may be either natural, nature identical or artificial. As per their purpose of addition in to food products they can be classified in to following four categories: i. Preservatives- They are added into the food product for particularly food preservation purpose. ii. Processing agents- They are added with the intention to maintain desired product property or aid the food processing. iii. Sensory agents- They improve the sensory properties of food products like food colour, flavour sweetener etc. iv. Nutritional additives- These additives are added during fortification or enrichment of food products to correct the dietary deficiency. The use of additives and preservatives increased with the growing need of processed food. Excessive use of many of these additives have health effects. So, there was a need for the toxicological study and regulation of these additives. The safety of food additives and its usage levels both are evaluated and recommended by some international body.
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Sugar gained a bitter name regards to health. Consumption of more sugars involves risk of more calories which leads to diseases like obesity, diabetes and cardiovascular problems in human body. These days food which is sugar free acquired much more reputation because of their low or no calorie content. So as a result many food industries use different low calorie artificial sweeteners instead of sugars. Food and Drug Administration (FDA or USFDA) accepted the use of six sugar substitutes (aspartame, saccharine, sucralose, neotame, acesulfame-k and stevia) safe human consumption. Advantame and extract from swingle fruit have recently discovered and added to the list of nonnutritive sweeteners. These artificial sweeteners or sugar substitutes are extensively applied in the fields of processed foods, dairy and therapeutic industries. The main aim of this review is to discuss the different types of artificial sweeteners, their history, synthesis, metabolism, uses, toxicity, therapeutic use, nontherapeutic use, health benefits and toxic effects.
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The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, and people are concerned about its negative effects. Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered, and these may be accredited to changes in regional brain concentrations of catecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.
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Reduction of dietary glycemic response has been proposed as a means of reducing the risk of diabetes and coronary heart disease. The impact of glycemic response on markers of health remains to be elucidated. We assessed the evidence relating the glycemic impact of foods to measures relevant for health maintenance and management of disease. This was a systematic review and synthesis of interventional evidence from literature reported on glycemic index and markers of health through the use of meta-analyses and meta-regression models. Data from 45 relevant publications were found to January 2005. Lower glycemic index (GI) diets reduced both fasting blood glucose and glycated proteins independently of variance in available and unavailable carbohydrate intakes. Elevated unavailable carbohydrate added to improvements in both blood glucose and glycated protein control. These effects were greater in persons with poor fasting blood glucose control. No effects were seen on fasting insulin<100 pmol/L; above this, study numbers were few but consistent with prevention of hyperinsulinemia in some but not all overweight persons. Insulin sensitivity according to a variety of measurement methods was improved by lower GI, higher unavailable carbohydrate interventions in persons with type 2 diabetes, in overweight and obese persons, and in all studies combined. Fasting triacylglycerol in addition to body weight reduction related more to glycemic load than to GI. Glycemic load reduction by >17 g glucose equivalents/d was associated with reduced body weight. Consumption of reduced glycemic response diets are followed by favorable changes in the health markers examined. The case for the use of such diets looks compelling. Unavailable carbohydrate intake is equally important.
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Since their discovery, the safety of artificial sweeteners has been controversial. Artificial sweeteners provide the sweetness of sugar without the calories. As public health attention has turned to reversing the obesity epidemic in the United States, more individuals of all ages are choosing to use these products. These choices may be beneficial for those who cannot tolerate sugar in their diets (e.g., diabetics). However, scientists disagree about the relationships between sweeteners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus. Recently these substances have received increased attention due to their effects on glucose regulation. Occupational health nurses need accurate and timely information to counsel individuals regarding the use of these substances. This article provides an overview of types of artificial sweeteners, sweetener history, chemical structure, biological fate, physiological effects, published animal and human studies, and current standards and regulations.
A study of several stereoselectively sweet amino acid molecules has led to a prediction of the presence and approximate location of a third structural feature, relative to the currently postulated A—H/B features in the glucophore. An examination of several unrelated sweet molecules supports this glucophore hypothesis. A relationship between a polarizability parameter and sweetness level in a series of substituted nitroanilines leads to the hypothesis that this third binding site may be involved in dispersion bonding with an appropriate receptor feature.
Neotame (NTM) is a new nonnutritive sweetener. NTM is a derivative of aspartame (APM). NTM has a clean sweet taste and a good flavour profile. It is a high-potency sweetener; it is 6000–10 000 times sweeter than sucrose, and 30–60 times sweeter than APM. NTM is a noncaloric, noncariogenic sweetener. NTM has an extensive shelf life in dry conditions. In aqueous food systems, it presents the same functionalities as APM in acidic medium, but it is significantly more stable in neutral medium. Consequently, NTM should be a useful sweetener in baked goods. NTM is compatible with reducing sugars and aldehyde-based flavouring agents. It has flavour-enhancing properties. Its relative cost is expected to be lower than sucrose or APM at sweetness equivalence. A petition was filed in the USA in December 1998 for its approval as a general use sweetener; other regulatory activities are underway in several countries.
Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methyl ester) with a sweeting potential 180 to 200 times that of sucrose. Questions have been raised about potential toxic effects of its constituent amino acids, aspartate and phenylalanine when the compound is ingested in large amounts. Plasma and erythrocyte amino acid levels were measured in 12 normal subjects after administration of either Aspartame (34 mg/kg) or equimolar quantities of aspartate (13 mg/kg) in a crossover design. No changes in either plasma or erythrocyte aspartate levels were noted at any time after either Aspartame or aspartate ingestion. Plasma phenylalanine levels decrease slightly after aspartate loading, and increased from fasting levels (4.9 +/- 1 mumoles/100 ml) to 10.7 +/- 1.9 mumoles/100 ml about 45 to 60 minutes after Aspartame loading. Phenylalanine levels returned to baseline by 4 hours. Erythrocyte phenylalanine levels showed similar changes.
The controversy regarding the safety of saccharin for human consumption started shortly after its discovery over 100 years ago and has yet to subside appreciably. The consumption of saccharin, particularly in North America, began to escalate when the U.S. Food and Drug Administration set new standards of identity which allowed foods containing artificial sweeteners to be promoted as "nonnutritive" or "noncaloric" sweeteners for use by the general public. In 1969, when cyclamates were banned, at least 10 single-generation feeding studies were undertaken with saccharin to more accurately assess the potential toxicological consequences resulting from the anticipated increase in its consumption. None of these studies resulted in any overt regulatory action. Subsequently, the introduction of the two-generation chronic toxicity/carcinogenicity bioassay added a new tool to the toxicologist's arsenal. Three two-generation studies using saccharin have since been conducted. The results from these studies clearly show that when rats were exposed to diets containing 5 or 7.5% sodium saccharin from the time of conception to death, an increased frequency of urinary bladder cancers was found, predominantly in the males. While some study results suggested that impurities in commercial saccharin or the presence of urinary tract calculi may have been responsible for the observed bladder tumors, it now appears that these possibilities are highly unlikely. The mechanism by which saccharin elicited the bladder tumors using the two-generation experiment has not been ascertained.
The clinical characteristics and scores on the Minnesota Multiphasic Personality Inventory (MMPI) of 192 patients undergoing a five-hour oral glucose tolerance test (OGTT) for evaluation of reactive hypoglycemia were assessed. There were twice as many women as men. One hundred twenty-nine patients had spells of light-headedness, shakiness, diaphoresis, weakness, and fatigue. Hypoglycemic symptoms occurring during the test were not related to level of plasma glucose nadir or to rate of descent of glucose level. Hypoglycemia was not found when glucose levels were measured during occurrence of spontaneous symptoms in 86 patients. MMPI scores were significantly different from those of general medical patients. Both men and women evinced a conversion V profile. The five-hour OGTT seems unreliable for the diagnosis of reactive hypoglycemia, and most patients with symptoms suggestive of hypoglycemia may have emotional disturbances.
Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.
Ullmann's Encyclopedia of Industrial Chemistry
  • Von G W Rymonlipinski
  • Sweeteners
Von RymonLipinski. G. W. Sweeteners. Ullmann's Encyclopedia of Industrial Chemistry. 2000;35(1):543-564.