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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: