Medscape Diabetes & Endocrinology
COMMENTARY
Brandy W. Root, RDN
DISCLOSURES | August 16, 2024
Commercial sugar substitutes have been used since the late 1800s when saccharin was accidentally developed by a chemist at Johns Hopkins University. Due to widespread sugar rationing during World Wars I and II, saccharin grew in popularity.
In more recent times, the US Food and Drug Administration has approved six synthetic nonnutritive sweeteners as being “generally recognized as safe”: saccharin, aspartame, sucralose, neotame, acesulfame-K, and stevia. Several sugar alcohols (types of carbohydrates derived from fruit and vegetables) and naturally occurring low-calorie sweeteners extracted from monk fruit, licorice root, and other sources have saturated the market further.
As rates of obesity, type 2 diabetes, and metabolic syndrome have steadily grown, consumers have increasingly turned to artificial sweeteners as seemingly healthier alternatives to sugar, but ongoing research suggests that some of these products may not be as safe as initially suspected.
Microbiome-Altering Sugar Substitutes
Investigators have begun to elucidate the pathways by which diet, among other factors, can negatively affect gut microbiota and cause chronic inflammation. Certain research has linked widespread use of sugar substitutes with this process, which can eventually result in the development of several proinflammatory disease states.
Although some sugar substitutes have no perceived concerns, others have been shown to promote gut dysbiosis, causing chronic low-grade inflammation and contributing to insulin resistance and increased intestinal permeability. Other results have linked their use with increased mutations of Escherichia coli and increased rates of antibiotic resistance.
One study found that noncaloric artificial sweeteners, including saccharin and sucralose, contributed to intestinal dysbiosis and poor glycemic control even in short-term trials with healthy participants who didn’t normally use such sweeteners. This is of particular concern, given that these products are often used by consumers seeking to decrease their sugar intake to improve glycemic control.
Sucralose is commercially available and more commonly known as Splenda. Splenda contains sucralose and maltodextrin which, together, have been linked to a significant decrease in beneficial microbes in the intestines of rats. Sucralose alone has been shown to decrease the presence of intestinal bacteria and amino acid synthesis and to increase inflammation in animals.
Sucralose-6 acetate, an intermediary of sucralose found in commercial samples, was recently discovered by researchers to be genotoxic. Exposure in rats was shown to break DNA strands, whereas exposure in humans was shown to significantly increase expression of genes associated with inflammation, oxidative stress, and cancer.
Sucralose is also known to cross the placenta and is passed into breast milk. The presence of sucralose in the diet of pregnant and breastfeeding mothers is linked to an increase in Methanobrevibacter species, which has also been connected to obesity in children.
Although sucralose may have the largest body of research against its use, saccharin use has also led to concerns regarding its effect on the microbiome and gastrointestinal health.
Commercially available as Sweet’N Low, saccharin was previously thought to cause an uptick in bladder cancer in rats, which has since been debunked by further studies in humans. However, saccharin exposure continues to be linked to altered gut microbiota and poor response of intestinal epithelium.
Sugar Substitutes That Positively Affect the Gut Microbiome
Glycyrrhizin, an extract of licorice root, has long been used in Eastern medicine for its antimicrobial properties. It is available for commercial use as a sweetener and as a supplement from some health food stores. Glycyrrhizin has also been shown to have anticarcinogenic, anti-inflammatory, antiviral, antioxidant, and hepatoprotective benefits, and has been suggested to increase protective bacteria in the gut with regular use under 100 mg daily. However, more studies are needed regarding response of the microbiota to its presence. The use of glycyrrhizin may be limited by its strong licorice taste and propensity to induce hypertension in those who regularly use 100 mg or more daily.
Erythritol naturally occurs in a variety of fruits and some fermented foods. It is commercially found in many sugar-free products like chewing gum, candies, and sodas and is commonly used in Japan. It is also found in many health food stores.
Erythritol is nonfermentable, with no known effect on the gut microbiota. It has been shown to improve glucose tolerance and decrease rates of obesity and intestinal inflammation. However, research indicates that high levels of erythritol circulating in the blood can contribute to increased rates of heart attack and stroke by promoting platelet aggregation and blood clot development, and so it should be used with caution.
Counseling Patients to Decrease Sugar Intake
Although certain substitutes may positively affect the microbiome, I find that patients see the best results with weight loss, blood sugar control, and decreased inflammation by limiting sugar and sugar substitutes altogether.
Patients can become easily frustrated at first, because the most problematic sugar substitutes seem to be the ones most readily available at grocery stores, restaurants, coffee shops, and in diet drinks. However, decreasing sugar intake can increase perception of sweetness.
One study published in The American Journal of Clinical Nutrition found that participants who decreased intake of calories from simple sugars by 40% found the taste of sucrose-sweetened foods to be too intense or overwhelming, and they preferred the flavor of lower-sucrose options only 2 months into the study.
I usually recommend that patients decrease their preferred sugar substitute over several weeks. This can be done more easily at home, but when dining out, different strategies may be needed. For example, patients can mix sweetened and unsweetened beverages. The taste may be bitter initially, but patients should adjust within a few weeks. Trying other beverages, like hibiscus or jasmine tea, can also help to bridge the gap, as they may not be as bitter or bland as black tea or water.
This gradual approach to decreasing overall sugar intake rather than substituting sugar alternatives could better address patient blood sugar and weight concerns without swapping high blood glucose for increased intestinal inflammation and gut dysbiosis.
By addressing the root cause — patient preference for sweets — we can better address overall health and ideally prevent prediabetes and metabolic syndrome, or even prevent the development of diabetes altogether.
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