One More Way Sugar Makes You Sick

It’s all about the gut.

In the excellent series The Miniaturist, a 17th century Dutch woman finds herself running an import business for her new husband. She is led through a room where the imported delicacy is stored.

The room is full of shelves bearing white cones. During one scene, she samples a bit of the mysterious, flaky substance, which has Amsterdam’s import community abuzz.

She immediately realizes she’s about to become a gazillionaire.

Once she tastes the stuff, her first thought is how her local bakery will never stop ordering it. Customers will come back for more cookies and cakes sweetened with pure sugar.

And here we are, 300 years later, addicted to cookies and soda.

But unlike the Dutch in 1686, we should know better.

A recent article about how sugar disrupts the gut lining, leading to intestinal permeability, is one more link in the argument against eating more than a modest amount of this sweet elixir.

Sugar Leads to Leaky Gut

In 2018, the journal Disease Models and Mechanisms published an article by Pereira, et al, in which fruit flies were exposed to various dietary additives. They also exposed human cells to the same additives — substances you might find in daily life.

The goal was to discover which additives led to “leaky gut,” a condition in which the intestinal lining is compromised.

Leaky gut is associated with autoimmune diseases (including Type 1 Diabetes, Hashimoto’s, and MS), Type 2 Diabetes, Celiac diseae, and a host of digestive ailments.

As the authors state:

“Increased intestinal permeability has been correlated with aging and disease….The prevalence of…ailments…has risen together with an increase in industrial food processing and food additive consumption.”

While the culprits would appear to be exotic, modern additives like Red Dye #5 or High Fructose Corn Syrup, the authors discovered sugar was the problem.

Sugar, no different from the 17th century kind imported to Amsterdam, is implicated as the main factor in creating a leaky gut, setting us up for chronic disease.

A Fly in the Ointment

The gut lining is what allows nutrients to reach cells, while it also acts as a barrier against toxic materials. A healthy gut doesn’t allow food particles into the bloodstream, which can wreak havoc.

The fruit fly digestive system is similar enough to the human one to carry out experiments, because fruit flies also use paracellular and transcellular transport of macromolecules. As with humans, increased gut permeability is also correlated with aging.

The authors summarize the established science:

The main function of the GI tract is to act as a selective barrier that protects against potentially harmful luminal content such as foreign antigens and toxins, while simultaneously allowing nutrients and water to pass through the epithelium and enter the circulation. The small intestine is the primary site of nutrient absorption….

Epithelial cells form tight junctions, which prevent foreign invaders from entering the bloodstream. Conveniently, fruit flies and humans have similar tight junctions, and fruit flies (Drosophilia melanogaster) have the added benefit of short life cycles, so they make excellent experimental subjects.

It may seem incredible that we have so much in common with tiny fruit flies, but according the authors note that in addition to more rapid aging, fruit flies and humans suffer similar diseases when the gut lining is compromised.

Previous studies have also shown that chronic inflammation, type 2 diabetes, reduced metabolic stores and increased bacterial load are also associated with aging in both humans (Cheng et al., 2013; Chung et al., 2009; López-Otín et al., 2013; Lusis et al., 2008) and Drosophila.

The In Vivo Experiment and Results

The researchers exposed fruit flies to several substances, then analyzed how the gut responded. Using an in vitro model, i.e. the living fruit fly, they introduced sucrose, TiO2 nanoparticles (NP), an emulsifier called TWEEN 20, and table salt.

TiO2NP is short for titanium dioxide nanoparticles, which represent the most common ultra-tiny particles used for consumer goods like medicines, paints, and cosmetics. They are widely used in science and engineering.

TWEEN 20 is a surfactant, often found on the surface of pills becuase it allows the pill to remain intact in the digestive system long enough to reach the small intestine, where it can be absorbed. Surfactants and emulsifiers are often used in processed foods.

With an in vivo model (a test performed outside the living organism), they exposed the gut lining to glucose and TiO2 NP.

With both models, the researchers fed a diet similar to one humans eat, with sugar concentrations ranging from 11% to 50% for some meals. (They noted “chronic high sugar feeding” also leads to insulin resistance in adult fruit flies.)

The researchers were mildly surprised to find one substance stood out: sugar had a much bigger effect on creating a leaky gut in both models.

“Sugar had the most dramatic effects, and sugar-dependent microbial influences were also observed in each model.”

For the in vivo experiments, they used a “Smurf assay,” in which the flies with leakier guts turned blue. Scientists observed both young and old flies turning bluer (“Smurfing”) prior to death on a high sugar diet.

Salt and TWEEN 20 (the emulsifier) did cause some Smurfing, but sugar was the worst offender.

The In Vitro Experiment and Results

For the in vitro experiment, the scientists seeded human intestinal cells in a semi-permeable membrane, adding Lucifer Yellow (LY) dye to see whether their was leakage between and across cells.

The researchers estimated a typical exposure of TiO2NP as well as a “worst case scenario” amount.

There were no changes to intestinal permeability (i.e. no LY leaking) through the membrane when this additive TiO2NP was introduced.

They next exposed the in vitro cells to glucose (HS, or “high sugar”), using an amount calculated based on normal, non-diabetic blood sugar in humans. They observed the following:

A significant increase in gut permeability was observed in the samples exposed to HS (25 mM glucose), compared to the control cells (exposed to 5 mM glucose and 20 mM mannitol) at both 2 hours and 24 hours following HS exposure.

Fly Survival on Salt, TWEEN, and Sugar

The researchers observed how long the fruit flies survived on various additives, and concluded that although sugar increased Smurfing (intestinal permeability), it didn’t have a significant impact on shortening lifespan.

In other words, sugar created chronic disease but didn’t kill flies any sooner.

TWEEN and salt, however, were a different story. Both led to significantly shorter lives.

They did note that Smurfing and early death are sometimes correlated, depending on other dietary factors, as other research has shown.

The Mechanism: Why is Sugar So Destructive?

The first thing sugar does is affect intestinal phosphatase activity (IAP). IAP is a gut mucosal defense system produced only in the small intestine that protects against inflammation and helps regular lipid absorption, among other roles.

Second, the researchers observed changes to the gut structure and function in fruit flies fed a high sugar diet. They concluded these changes would likely affect nutrient absorption.

A high sugar diet can alter bacterial exposure. The authors concluded sugar feeding led to an increase in at least one tight-junction protein (ZO-1).

Final Quasi-Scientific Thoughts

It doesn’t take a PhD in biochemistry to realize that sugar is hard on the body.

Unfortunately, sugar is hiding almost everywhere in even minimally processed foods. Most sauces, soups, and nut butters have sugar. It is added to myriad products to help with shelf life and palatability, and comes in dozens of forms.

It’s worth avoiding processed foods, including canned and boxed products, to cut down on sugar. Frozen veggies are safe, but they often have added salt.

The supermarket has turned into a nutritional minefield.

If you wonder whether to choose soda water or coke next time you shop, consider what you might have in common with the lowly fruit fly.

Don’t get Smurfed. Skip the sugar, in every form.

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