Posted on: Friday, January 6th 2017 (and 2014) at 7:15 pm
Written By:Sayer Ji, Founder
A groundbreaking new study published in the prestigious journal
Nature has revealed how non-caloric artificial sweeteners (NAS) drive obesity-
and diabetes-related changes in both mice and humans.
The study titled, "Artificial sweeteners induce glucose intolerance by
altering the gut microbiota," states:
"Here we demonstrate that consumption of commonly used NAS
formulations drives the development of glucose intolerance through induction of
compositional and functional alterations to the intestinal microbiota."
Part 1: Gut Bacteria Mediate Artificial Sweetener-Induced Blood
Sugar Disturbances
The researchers administered commercially available formulations
of saccharin (Sweet' N Low), sucralose (Splenda) or aspartame (Equal) in the
drinking water of 10-week old mice. The control group received I either glucose
or sucrose. After 11 weeks, the three artificial sweetener fed groups developed
"marked glucose intolerance," with saccharin having the most
deleterious effects followed by sucralose and aspartame.
Graph showing the effects of artificial
sweeteners on blood glucose levels.
The researchers hypothesized that since artificial sweeteners
pass through the gut mostly unabsorbed by the body that the microbiota may be
responsible for regulating their observed adverse effects on blood sugar.
To test their theory they administered antibiotics to mice while keeping them
on their diet and sweetener supplementation regimens. Their results indicate
that gut bacteria indeed drive the adverse effects of these sweeteners:
"Notably, after 4 weeks of antibiotic treatment, differences
in glucose intolerance between NAS-drinking mice and controls were abolished
both in the lean and the obese states. Similar effects were observed with the
Gram-positive-targeting antibiotic vancomycin ('antibiotics B',
0.5 g l−1). These results suggest that NAS-induced glucose
intolerance is mediated through alterations to the commensal microbiota, with
contributions from diverse bacterial taxa."
Finally, in order to test whether the role of microbiota in
upsetting blood sugar balance was 'cause and effect' they performed a fecal
transplant from mice receiving saccharin or glucose into germ-free mice
receiving the same normal-chow diet. Their results confirmed the crucial
role of the microbiota in inducing blood sugar disturbing effects:
"Notably, recipients of microbiota from mice consuming
commercial saccharin exhibited impaired glucose tolerance as compared to
control (glucose) microbiota recipients, determined 6 days following
transfer. Transferring the microbiota composition of HFD-consuming mice
drinking water or pure saccharin replicated the glucose intolerance phenotype.
Together, these results establish that the metabolic derangements induced by
NAS consumption are mediated by the intestinal microbiota."
Artificial Sweeteners Induce Negative Changes In Gut Bacteria
The researchers next performed an analysis of the changes
induced in the composition of microbiota by saccharin finding a widespread
reorganization:
"Compared to all control groups, the microbiota of
saccharin-consuming mice displayed considerable dysbiosis, with more than 40
operational taxonomic units (OTUs) significantly altered in abundance ."
Notably, the researchers found that many of the strains that
were increased in relative abundance belonged to the Bacteroides genus and
Clostridiales order, both of which contain members linked to obesity and
opportunistic infections. They also observed that these microbiota
changes lead to 1) increased lipopolysaccharide biosynthesis often found in
harmful bacteria overgrowth and linked to metabolic endotoxemia 2) increased
bacterial chemotaxis (an indication of increased bacterial activity;movement)
previously observed in obese mice. 3) increased microbial energy harvest (e.g.
increased carbohydrate metabolism and fatty acid biosynthesis) linked to
obesity and glucose intolerance.
They summarized their findings in the animal model as follows:
"Collectively, these results demonstrate that saccharin
directly modulates the composition and function of the microbiome and induces
dysbiosis, accounting for the downstream glucose intolerance phenotype in the
mammalian host."
Part 2: Artificial Sweeteners Drive Similar Adverse Changes in Humans
In order to confirm that artificial sweeteners also drive
adverse changes in humans, the researchers enrolled 381 non-diabetic
individuals (44% males and 56% females) in a clinical nutritional study. Their
results were reported as follows:
"We found significant positive correlations between NAS
consumption and several metabolic-syndrome-related clinical parameters ,
including increased weight and waist-to-hip ratio (measures of central
obesity); higher fasting blood glucose, glycosylated haemoglobin (HbA1C%) and
glucose tolerance test (GTT, measures of impaired glucose tolerance), and
elevated serum alanine aminotransferase (ALT, measure of hepatic damage that is
likely to be secondary, in this context, to non-alcoholic fatty liver disease).
Moreover, the levels of glycosylated haemoglobin (HbA1C%), indicative of
glucose concentration over the previous 3 months, were significantly
increased when comparing a subgroup of high NAS consumers (40 individuals) to
non-NAS consumers (236 individuals)."
They also observed significant changes in the bacterial
composition in those subjects consuming artificial sweeteners, with a shift
towards the Enterobacteriaceae
family, the Deltaproteobacteria class and the Actinobacteria phylum.
In order to ascertain whether non-caloric artificial consumption
and blood glucose control is causative they followed seven healthy volunteers
(5 males and 2 females, aged 28-36), who do not normally consume artificial sweeteners (or
foods containing them) for 1 week. Starting on day 2 until day 7, participants
consumed the FDA's maximum acceptable daily intake (ADI) of saccharin (5 mg per
kg (body weight)) in 3 divided doses equivalent to 120 mg and were monitored
for glucose tolerance. A significant adverse effect was observed:
"Notably, even in this short-term 7-day exposure period,
most individuals (4 out of 7) developed significantly poorer glycaemic
responses 5–7 days after NAS consumption (hereafter termed 'NAS
responders'), compared to their individual glycaemic response on days
1–4."
Finally, the researchers took fecal samples from subjects with
artificial sweetener induced adverse bacterial changes (dysbios) and
transplanted them into germ-free mice, resulting in impaired glucose tolerance
and some replication of the adversely altered microbiome within the mice –
confirming that micobiota mediate the adverse effects of artificial sweeteners
on metabolism.
The Tip of the Toxic Artificial Sweetener Iceberg
This latest study provides a physiological basis for the
observed blood sugar impairing and weight-promoting properties of artificial
sweeteners, and may help to explain why we have a burgeoning epidemic of pre-
and type 2 diabetes, overweight and obesity, and related metabolic syndrome
associated conditions in countries where artificial sweeteners are found
everywhere.
Blood sugar problems and obesity, however, are only a small part
of far more serious health conditions linked to this category of chemicals...
Last year, for instance, sucralose (Splenda)
was found to impair blood sugar
in a human study, adding to a laundry list of its decades old experimentally confirmed adverse effects,
including neurotoxicity, carcinogenicity
(possibly due to dioxin formation when heated),
and perhaps even
leukemia generating properties.
The heightened sweetness of these synthetic chemicals also makes them highly
addictive, with one recent animal study showing saccharin may be more addictive than cocaine.
Aspartame has also been linked to
neurotoxicity and carcinogenicity – two adverse effects
than may combine to increase brain cancer risk.
Ultimately, tricking the body with chemicals made to taste like
nutrients is simply not a good strategy. The taste for sweetness is as ancient
as biological time itself, and even from our first taste of breast milk, it is
imprinted deeply into the human psyche. The key, perhaps, is moderation and
training the palate to respond to natural sweetness found in wholesome fruits,
berries, and honey – which is so much healthier than sugar
– and evading the ever-present meme of a chemically dependent society that
thinks it can outsmart nature.
For more research on blood sugar imbalances and obesity consult
our health guides on the topic:
Splenda Suppresses Thyroid Function, Promotes Weight Gain
Is sucralose (aka Splenda) really as safe a sugar alternative as
its manufacturers and advertisers claim, or is it really a toxic chemical
causing a wide range of health problems including thyroid suppression and
weight gain? New research sheds light on this question.
A concerning new study published in the European Journal of Nutrition
entitled, "Type of sweet flavour carrier affects thyroid axis
activity in male rats,” is the first study of its kind to
evaluate the effects of Splenda (Sucralose) on mammalian thyroid function and
metabolism. Their findings reveal that sucralose has endocrine disruptive
properties on the hypothalamic-pituitary-thyroid axis (HPA axis),
resulting in thyroid hormone suppression, increased appetite, and weight gain.
The Many Documented Harms of Sucralose (aka Splenda)
Before we delve into the details of the new paper, it is
important for our readers to understand that this study is not novel in finding
harm. There is, in fact, an accumulating body of research on sucralose showing
this chemical marketed as an artificial sweetener is causing a wide
range of adverse health effects. For instance, our sucralose research portal reveals 15
different signals of harm linked to this artificial sweetener, such as neurotoxicity.
When you add to this well-established body of research the
recent discovery that sucralose produces carcinogenic dioxins
when heated, the bitter truth about this
artificial sweetener, namely, that it is a chemical in the same
class as highly toxic pesticides like DDT, comes to light.
This is all the more disturbing when you consider that Splenda
is regularly advertised to consumers as a safe sugar alternative specifically
for baking applications. For instance, have you seen the TV ads where parents
are encouraged to use it presumably to keep their kids healthier than if they
used natural sweeteners? If not, you can visit the Splenda Baking and Cooking
page which features a picture of a woman holding her son while
baking. Also consider that a recent government-funded study found
sucralose contaminated 65% of all breast milk samples assayed.
In other words, the use of this toxicant is so prevalent that even our most
vulnerable populations are incapable of opting out of being exposed to it.
Sucralose has already been demonstrated to promote weight gain
and diabetes which undermines its primary
marketed ‘benefit.’ Indeed, the new study also found that it promotes weight
gain in comparison to an equally sweet, isocaloric diet that only differed in
that the sweet sensation was produced by sugar. So, let’s get to the study
details now...
Splenda's Endocrine Disruptive Properties Revealed
The straightforward purpose of the study was described as
follows:
"Non-nutritive sweeteners are the most widely used food
additives worldwide. However, their metabolic outcomes are still a matter of
controversy and their effect on the thyroid activity, a key regulator of
metabolism, has not been previously studied. Therefore, we aim to determine the
influence of the sweet type flavour carrier on selected parameters of thyroid
axis activity."
In order to accomplish this, they studied 105
Sprague-Dawley rats, divided into 3 groups, who were fed at their will
(ad libitum) for 3 weeks one of the three different diets. The diets had
identical caloric content (isocaloric), comprised of starch (wheat
starch)differing in the following ways: Diet #1 contained no sugar. Diet
#2 contained 10% sucrose (10 grams). Diet #3 contained enough Sucralose (.0167
grams) to create the same sweet flavor intensity as Diet #2 (10%
sucrose).
"The results obtained indicate that both the presence and
the type of sweet taste flavour carrier affect thyroid axis activity both at
fasting and postprandial state. Compared to diet with sucrose which stimulates
thyroid axis activity, sucralose addition diminishes thyroid hormone synthesis
as thyroid peroxidase (TPO) activity, plasma thyroxine (T4), and
triiodothyronine (T3) concentration was lower than in SC [sucrose containing]
and NS [not sweet] while in non-sweet diet the lowest level of hepatic deiodinase
type 1 (DIO1) and the highest reverse T3 (rT3) level indicate on altered
thyroid hormone peripheral metabolism."
In other words, sucralose significantly altered the thyroid and
metabolic functions of the animals in a manner that could overlap with the
symptoms of hypothyroidism.
The researchers concluded:
"One principal finding of this study concerns the close
relationship between the sweet flavour carrier and the pituitary-thyroid axis
activity, which is involved in the meta]bolic adaptation to meal composition.
This effect may be observed at various levels. Sucralose intake seems to
diminish thyroid axis activity by decreasing TPO activity, TSH, and plasma
total TH concentrations, but at the same time, it increases both free T3 and T4
indexes. Those findings confirmed that sucralose is physiologically active and
may provoke disturbances in thyroid axis activity."
It is important to understand that this study proves sucralose
is not 'metabolically inert' as often claimed when questions of its toxicity are
raised. Sucralose also increased appetite and weight gain — two things that run
diametrically opposed to consumer perception and the irresponsible marketing of
its “benefits.”
The study provides more details:
"Both food intake and body mass gain were significantly
affected by the type of diet (for both p < 0.001). In total, the highest
food intake was recorded in the SU [sucralose] group. The average daily intake
of sucralose with the diet (14.2 ± 0.4 mg/kg body weight/day) did not exceed
the acceptable daily intake (ADI, 15 mg/kg body weight/day).
The food intake recorded during the meal before euthanasia did
not differ between NS [not sweet], SC [sucrose], and SU [sucralose], and was
3.98 ± 0.5, 4.22 ± 0.41, and 4.71 ± 0.5, respectively.
The total daily body weight gain in the SU group was
significantly higher than in SC and NS, which represented the lowest value (for
both p < 0.001). Therefore, the highest diet growth efficiency was also
recorded in SU, and there were no differences between NS and SC (Table 2).”
Because previous research has established that dietary
carbohydrates directly affect thyroid axis activity, the study was designed to
keep the carbohydrate content identical in order to isolate only the difference
between the artificial and natural sweetener. The results provide
compelling evidence that the difference in thyroid and metabolic effects
observed between the study groups were due entirely to sucralose's significant
and complex toxicological properties.
Of Mice and Men
The question often emerges following animal studies, as to
whether the findings can be extrapolated to humans. The study addresses this
point directly as follows:
"Despite the known species derived differences in thyroid
economy between humans and rodents [65, 66], it was demonstrated that total T4
levels in rodents are a valid indicator of thyroid function in relation to
effects in humans [67]. Moreover, humans and rats might be equally sensi-tive
to TH synthesis disruptors, and even though in rats the response occurs after a
shorter exposure time, the final effect could be the same."
So why are studies like this not regularly performed on humans
to remove nagging doubt about their relevance? One reason is the prohibitive
cost. Another, perhaps more significant hurdle, is that it is unethical to
test chemical safety on human subjects. This obviously makes for great
regulatory challenges in unequivocally proving human safety. So, how are
the majority of chemicals released onto the market tested for safety? Animals.
And so, the argument that animal studies are not sufficient to demonstrate
plausible toxicity in humans is absurd, given that the toxicological risk
assessments used to justify releasing chemicas like sucralose into the human
food supply are invariably based on animal studies. In fact, these animal
studies are used to determine an "acceptable level of harm" by
extrapolating from them to find the dose that would not cause overt morbidity
in a human. The notion, however, that the dose makes the poison, has been
completely undermined, given research on petrochemicals, low-dose radiation,
nanoparticles, and other non-linear dose responses observed following exposure
to extremely low concentrations of toxicants, whose effects are amplifed
because they mimic hormones (endocrine disruptors) or cause DNA damage and
subsequent cellular transformation into cancer instead of inducing cell death
(apoptosis). The most recent classical
example of this is the finding that glyphosate,
the main in the herbicide Roundup, exhibits estrogenic/carcinogenic/endocrine
disruptive properties in
the parts-per-trillion range.
Sucralose: A Sweetener or Pesticide?
Another highly concerning observation was that sucralose’s
effects are similar to those observed with other organochlorine chemicals in
its class, which include dangerous pesticides.
"[T]he pattern of HPT axis components—decreased TPO
activity, TSH, T4, and T3 plasma concentrations together with increased
free-to-total TH ratios in the group on the diet with sucralose—resembles some
effects evoked by organochlorine compounds documented in human and animal
studies. The inverse relationships between plasma levels of chloroorganic
compounds and TSH or the thyroid hormone have been observed [31–35]. The
association between high levels of fT4 and the consumption of fish exposed to
organochlorinated xenobiotics was found in adults from a certain area in East
Slovakia [36]. This could be explained by the binding of chloroorganic
compounds residues to transthyretin [37]. In the light of these parallels, our
results could raise questions about the physiological inertness of
sucralose."
In a previous article, we reported on
sucralose's relationship to organochlorine compounds like DDT, and how both
compounds have the potential of accumulating in the body and causing adverse
health effects:
"The makers of sucralose/Splenda argue that this
"remarkably stable" chemical passes unchanged into the urine and
feces, when in fact, up to 11% to 27% is absorbed into the body (FDA, 1999). In
fact, the varying degrees to which sucralose is absorbed is used as a marker
for gut and intestinal permeability to determine certain disease states. Once
absorbed, some portion of this chlorocarbon accumulates in the body (between
1.6% to 12.2%). What effects will these accumulated chemicals have? According
to James Bowen, M.D:
"Any chlorocarbons not
directly excreted from the body intact can cause immense damage to the
processes of human metabolism and, eventually, our internal organs. The liver
is a detoxification organ which deals with ingested poisons. Chlorocarbons damage
the hepatocytes, the liver's metabolic cells, and destroy them. In test animals
Splenda produced swollen livers, as do all chlorocarbon poisons, and also
calcified the kidneys of test animals in toxicity studies."
The Body Perceives Splenda To Be Toxic
The stiudy also noted that previous researchers have doubted the
safety of sucralose based on observations that sucralose intake alters
expression of both “rat intestinal P-glycoprotein (P-gp) and cytochrome
P-450 isozymes, which are key components of the detoxification system in
first-pass drug metabolism [38].” In other words, sucralose induced responses
in the body consistent with the perception that it was doing physical harm, and
needed to be removed from the body in the way other toxicants are handled.
Changes also observed consistent with sucralose as a toxicant
are: “Alterations in beneficial intestinal microflora and epithelial border
function after long-term sucralose ingestion were also recorded [38, 39].”
The researchers conjecture that sucralose’s adverse effects on
the thyorid axis would be reflected in “thyroid hisopathology,” i.e. thyroid
lesions/tumnors. Could this be one of the causes behind the mysterious global
uptick in thyroid cancer diagnoses?
Ditch The Chemicals
This study leaves far more questions than answers. First, why
are regulators turning a blind eye to the accumulating body of research
indicating that sucralose is a highly toxic chemical whose safety has not be
established? Second, why would anyone risk exposing themselves to a
chemical when the evidence indicates that artificial sweeteners of all kinds
promote weight gain, and increase appetitde -- the last two things those who
wish to lose weight, or "cut down on sugar" want?
Thankfully we live in an age where research like this is now
directly available online, the moment it is published. With greater access to
information, we can all better exercise informed consent and take control of
our health. We are also to better assess the health benefits of natural
substances that render the use of synthetic ones unnecessary, such as honey,
stevia, and xylitol. Use the GreenMedInfo.com Research Dashboard to
learn more about these alternatives.
Sayer Ji is founder of Greenmedinfo.com,
a reviewer at the International Journal of Human Nutrition and Functional
Medicine, Co-founder
and CEO of Systome Biomed, Vice Chairman of the
Board of the National
Health Federation, Steering Committee
Member of the Global Non-GMO Foundation.