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Scientific Association for Research and Education
in the field of food-intolerances
Newsletter Q1/2014
Artificial Sweeteners & Sugar Substitutes – Sweet Risk?
Sugar substitutes are becoming more and more relevant for the food and pharmaceutical
industry. These substances induce a sweet taste when ingested, but are not fermentable and
exhibit only minute influence on blood sugar levels.
Sugar substitutes are sugar alcohols, especially Isomalt, Erythritol and Sorbitol. They are
being metabolized independently or with little influence on insulin secretion and additionally
do not lead to tooth decay. If more than 30g per day are ingested, sugar alcohols can induce
intestinal discomfort due to their high water retention capacity.
Xylitol, a sugar alcohol exhibiting a sweetening power of 1 (same as in Sucrose) is often used
in chewing gum as it is the only sugar alcohol which is not only unfermentable to the
cariogenic bacterium Streptococcus mutans, but also actively inhibits its growth [1].
Fig.1 Xylitol
Artificial sweeteners are even more important. These molecules present both high
sweetness and low caloric value. Sweetness is determined relative to sucrose. Taking the
example of Aspartame, after weighing in an equal amount of Aspartame and Sucrose, after
dissolution in water, the Aspartame containing solution has to be further diluted 18x to
exhibit the equal relative sweetness as in sucrose.
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Scientific Association for Research and Education
in the field of food-intolerances
Saccharin is one of the oldest artificial sweeteners, being in use for over 100 years. Briefly
the substance was banned in the 1970ies, after a single study reported the occurrence of
bladder tumours in rats.
Fig. 2 Saccharin
This however could be explained by both an unusually high experimental dose of Saccharin
as well as a particularity of the rat physiology: The very low pH of rat urine led to coprecipitation of Saccharin and Calcium in the bladder; these crystals would constantly irritate
the epithelium thus provoking tumorgenesis [2]. This would not happen in humans [3].
Mixed with Cyclamate 1:10 Saccharin’s typical metallic aftertaste can be mediated, and the
composition is often sold as sweetener for tea and coffee, due to its heat stability.
Aspartame, belonging to the family of dipeptide-sweeteners, is characterized by its intense
sweetness and low caloric value. It unsuitable for cooking, as continued heating will
inactivate the sweetener. Often used in soft drinks, Aspartame is mixed with Acesulfame
potassium to mediate the bitter, metallic aftertaste.
Fig. 3: Aspartame
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Scientific Association for Research and Education
in the field of food-intolerances
Aspartame is subject to a multiplicity of urban legends, rivalling those about the moon
landing and Kennedy assassination in numbers. Valid without a doubt are the dangers of
Aspartame to those suffering from phenylketonuria, an autosomal-recessive metabolic
disorder with a incidence rate of 1:8000. Here the amino acid phenylalanine cannot be
properly metabolized to tyrosine, so important mediators such as melanin or dopamine
cannot be synthesised from tyrosine; in addition the accumulation of alternative
phenylalanine metabolites induces severe intellectual disabilities and seizures in children.
Today new-borns are being screened for this disorder (Gurthie test) and those affected have
to maintain a strict diet greatly reduced in phenylalanine and fortified with tyrosine. As
every molecule of Aspartame harbours one molecule of phenylalanine, those afflicted with
phenylketonuria are required to avoid foods and beverages containing Aspartame. This is
endorsed by labels on those products stating “Phenylketonurics: Contains Phenylalanine”.
A further argument often found on the internet is a potential Aspartate excitotoxicity [4]. In
excitotoxicity neurons are killed by excessive stimulation with neurotransmitters. It may
happen in the context of neurodegenerative ailments such as Alzheimer’s, Parkinson’s, as
well as during acute alcohol or benzodiazepine withdrawal; this was demonstrated in one
animal study with Aspartame. Irrespective from the fact that this result could not be
reproduced in several successive studies, the amount of aspartate taken up with the normal
diet is several magnitudes larger than that taken up with artificially sweetened food.
An argument which continuously arises in the context of Aspartame intake is the potential
generation of the toxic chemical methanol during its metabolic breakdown by the cleavage
of the methyl group attached to aspartate. This in itself is not incorrect, however the
effective concentration of methanol in the circulation is physiologically irrelevant; even if
Aspartame intake is among the 99th percentile (up to 36mg/kg/day), the amount of
methanol released maxes at 3.7mg/kg/day, which is below detection limit in whole blood
[4]. This illustrates how desperately proponents are reaching for arguments supporting
Aspartame toxicity.
The most recent exponent of the family of artificial sweeteners is Stevia, a plant originally
home to the amazon region. The Glycostevioside has become a registered novel food within
the European Union in 2011. This has been preceded by an unparalleled grass-roots
campaign to allow the official sale of Stevia based sweeteners. Prior to that, Stevia tinctures
of greatly diverging product quality have been sold as “bath salts” on the internet and fairs.
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Scientific Association for Research and Education
in the field of food-intolerances
Stevia has adequate heath stability; however its use is characterized by a bitter aftertaste.
Added to sugar-reduced foods, this unpleasant taste is masked by sugar.
Fig. 4: Stevioglycoside
This exemplifies that if negative health effects are being fished for actively enough, they will
eventually be discovered. Due to unfit model systems or readily escalating toxicological
doses effects can be uncovered which would not occur in common everyday doses of these
substances. If dietary sugars were be assayed this rigorously, results would likewise be
worrying.
What is the gist for the physician who is prescribing drugs with artificial sweeteners or for
the pharmacist, selling these drugs, or - last, but not least - for the consumer? At any rate
one can confirm with clear conscience that from a scientific point of view, there are not valid
reasons to judge intake of those products harmful within the specified limits. Whether the
patient or customer acknowledges this, remains to be seen.
There is a defined niche for artificial sweeteners and sugar substitutes, however they will not
constitute the magic bullet in the dietary war against overweight and obesity. Without a
specifically adapted diet a permanent reduction in weight due to artificial sweeteners cannot
be substantiated by epidemiological studies [5]. However undisputed are the advantages of
sweeteners for diabetics and people following low-carb diets.
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Scientific Association for Research and Education
in the field of food-intolerances
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Mickenautsch, S. and V. Yengopal, Anticariogenic effect of xylitol versus fluoride - a
quantitative systematic review of clinical trials. Int Dent J, 2012. 62(1): p. 6-20.
Whysner, J. and G.M. Williams, Saccharin mechanistic data and risk assessment: urine
composition, enhanced cell proliferation, and tumor promotion. Pharmacol Ther, 1996. 71(12): p. 225-52.
Takayama, S., et al., Long-term feeding of sodium saccharin to nonhuman primates:
implications for urinary tract cancer. J Natl Cancer Inst, 1998. 90(1): p. 19-25.
Magnuson, B.A., et al., Aspartamee: a safety evaluation based on current use levels,
regulations, and toxicological and epidemiological studies. Crit Rev Toxicol, 2007. 37(8): p.
629-727.
Swithers, S.E., Artificial sweeteners produce the counterintuitive effect of inducing metabolic
derangements. Trends Endocrinol Metab, 2013. 24(9): p. 431-41.
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