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Oh the cruel, cruel irony of it all.

Oh the cruel, cruel irony of it all.

Today’s post is inspired by an Israeli paper published in the journal Nature that studied the effects on glucose metabolism and gut flora from ingesting three popular artificial sweeteners. What they found is of more than passing interest in this calorie-obsessed age. (1)

I spend a lot of time on this website writing about the importance of diet to gut and overall health. What you put in your mouth does indeed affect the trillions of bacterial species that call your digestive tract home, whether you chose to believe it or not.

Feed friendly members of this community with the foods they thrive on, and they’ll increase in number while simultaneously inhibiting the growth of unfriendly gut critters that could impair well-being. Conversely, ingest foods that promote growth of gut pathogens, and you’ll increase their numbers at the expense of the beneficial organisms that have evolved over millennia to keep you healthy.

Said another way, if you put food on your lawn that appeals to rabbits and other grass-destroying organisms, while repelling their competitors, don’t be shocked when that once verdant expanse morphs into an overgrazed deadscape. Those metaphorical coyotes are truly vital for maintaining health.

In the over two years I’ve pounded out these posts, I’ve told you about several dietary substances that when eaten in excess, and without the soluble fiber beneficial gut flora obviously enjoy, turn your internal “lawn” into a diseased, immune-provoking (and cortisol generating) weed patch. Among these are omega 6 vegetable oils (actively promoted by the “nonprofit” American Heart Association), refined fructose, alcohol and gluten grains. Today’s post suggests that some artificial sweeteners should also be inducted into this Gut Dysbiosis Hall of Fame.

The non-caloric artificial sweeteners studied were saccharin, sucralose and aspartame. These are familiar to most of you under the brand names Sweet’N Low ®, Splenda ® and Equal ®.

However, to avoid unnecessarily suffering the slings and outrageous arrows of litigation, I must tell you that the actual brands used in this study were Sucrazit ®, Sucralite ® and Sweet’n Low Gold ®, all Israeli equivalents of the same.

Now that I’ve (hopefully) dispensed with any legal challenges to my good name, it’s time to dive into the cloying sweetness of today’s topic.

First off, these scientists put one of each sweetener in the drinking water of lean, ten-week old C57B1/6 mice separated into three corresponding groups. All mice were fed a regular rodent chow during this leg of the study.

As for their controls, three other sets of mice were given either water (always a recommended beverage by yours truly), water with glucose or water with sugar, also served with a delectable side of regular mouse chow. Do recall, dear reader, that sugar is composed of 50% glucose and 50% fructose.

For future reference, both experimental and control mice in this arm of the trial were labeled group a.

At eleven weeks, all control mice, and yes that includes those imbibing the beverage equivalent of unflavored Koolaid ®, showed normal glucose metabolism. However, this was not the case for our furry little friends trying desperately to avoid stinging humiliation at the weekly weigh-in. No, they all developed dysregulation of blood glucose.

Because saccharin exerted the worst effect of the three sweeteners (aspartame had the least negative effect with sucralose falling in the middle), this sweetener was used in the next series of experiments.

The next set of mice (group b), were fed water containing saccharin, but this time in conjunction with a high-fat diet.

Please keep in mind that the saccharin dose was adjusted for the body size of these mice using FDA maximum daily intake guidelines for humans. So this isn’t one of those studies where mice are fed a ridiculous dose of something that has absolutely no relation to what a normal human would ever be exposed to.

And again, those mice fed the high-fat diet with saccharin exhibited worse glucose control than a control group of mice fed the same high-fat diet, but accompanied with water containing just glucose. But this time the worsening in glucose parameters took only five weeks to become evident, making the combination of a high-fat diet and this artificial sweetener especially noxious.

As is true for most of these high-fat rodent diets, 60% of calories were from fat, with the majority of those coming from lard, a predominantly monounsaturated fat.

These results were duplicated using another strain of mice known as Swiss Webster mice (group d) also consuming their saccharin-infused water with the same high-fat diet. They too showed a worsening in glucose tolerance by the same five-week endpoint.

These researchers now wanted to see whether changes in gut flora could explain what was happening, so they gave all the mice in the first experiment (group a) antibiotics that specifically targeted gram-negative bacteria. As you remember, it’s gram-negative bacteria that contain lipopolysaccharides (LPSs).

They also gave these antibiotics to another set of mice, group c, that were fed either a high-fat chow with water, or the same chow with pure saccharin. In both groups a and c, four weeks of antibiotic treatment completely abolished the differences between experimental animals and controls, strongly implicating changes in gut flora as the causative factor for poor blood glucose control.

Here’s a representation of the study design showing when glucose tolerance tests were taken, when fecal bacteria was analyzed and which week blood sugar went to crap in the experimental groups. Bars in black represent mice in control groups, while blue represent mice given an artificial sweetener:

 

Courtesy: Artificial sweeteners induce glucose intolerance by altering the gut micorbiota.

Courtesy: Artificial sweeteners induce glucose intolerance by altering the gut micorbiota.

 

To test the hypothesis that a change in gut flora was behind these observations, the researchers transplanted fecal bacteria from mice eating normal chow and drinking water containing commercial saccharin (as well as bacteria from their controls) into germ-free mice that were also eating the same chow. Lo and behold, the mice that received gut flora from the saccharin-fed mice also exhibited the same impaired glucose tolerance as their donors. Imagine that!

Doing the same, but this time with bacteria from mice fed a high-fat diet with saccharin, also resulted in similar glucose impairment in the previously germ-free mice.

These scientists then examined the fecal bacteria from all groups using genomic sequencing. In comparison to control mice, the saccharin-consuming rodents showed considerable gut dysbiosis as seen by changes to more than forty bacterial groups. Increases in Bacteriodes genus were noted along with decreases in Lactobacillus reuteri, as well as several Clostridium organisms.

On the phylum level, there was a distinct increase in gram-negative Bacteroidetes and a concurrent reduction in the mostly gram-positive Firmicutes phylum. Or to be more precise, an increase in Bacteroidetes from 70% to 89%, and a reduction in Firmicutes from 22% to 6%.

One overrepresented species in the glucose-intolerant mice was Bacteroides vulgatus, a gram-negative bacteria and member of the Bacteroidetes family. A major underrepresented species was Akkermansia muciniphila, which is also a gram-negative bacteria, but a member of the Verrucomicrobia phylum. As I wrote here, having more of this bacteria in your gut is associated with a lean body type and healthy glucose control.

This all dovetailed with an increase in LPS synthesis, which is to be expected given the relative shift to more gram-negative gut flora. Metabolic endotoxin was therefore likely at play here.

While not specifically addressed in this paper, the impairment of glucose homeostasis speaks to activation of the HPA-axis and the cortisol-cortisone shunt as I explained here. This is an expected compensatory reaction to immune activation as a result of gram-negative bacteria leaching across the gut wall.

What is equally fascinating is that adding saccharin to an in vitro stool culture induced a change in bacteria similar to that seen in saccharin-fed mice. Transferring these organisms into germ-free mice resulted in the same glucose intolerance. The researchers noted:

“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.”

To see if these same observations would be evident in humans, they recruited seven healthy adults (two women and five men, ages 28 to 36) who had never consumed foods containing artificial sweeteners. All seven consumed the maximum allowed FDA daily dose (5 mg per kg of body weight) split into three doses of 120 mg each for seven days.

That works out to 360 mg per day. A typical packet of the pink stuff sold in the United States contains 36 mg, so that is equivalent to 10 packets a day, not an unusual number assuming the use of this sweetener in beverages and desserts.

By the end of the week, four out of seven developed poorer glucose control. None of the three non-responders experienced any improvement.

Fecal analysis also revealed changes to gut flora, but not in the non-responders. Transplanting fecal bacteria from the responders to germ-free mice resulted in significant glucose intolerance, once again implicating changes in gut flora for the derangement.

While no explanation is offered for why three out of the seven didn’t experience glucose dysfunction, it could be because the trial didn’t last long enough. Or maybe they ate a diet that countered the effects, for example one containing prebiotic fibers or resistant starch or both.

Whatever the reason, this study suggests that when it comes to satisfying your sweet tooth, you’re better off using moderate amounts of sugar than any of these imposters. I would also include raw honey and maple syrup as better alternatives.

Of course the best way of satisfying those sugar cravings is by consuming whole fruit. Not only will it make your mother very happy, it comes chock full of good things like vitamins, antioxidants and fiber. It’s this latter quality that makes beneficial gut flora dance with joy when they ferment it, although caution must be exercised with certain varieties if you’re currently on a FODMAP elimination diet.

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