Stevia

Restless legs syndrome associated with use of stevia nonnutritive sweetener

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Abstract

Restless legs syndrome is a common sensorimotor movement disorder affecting an estimated 15–20% of the general adult population in the United Sates. Several drugs and drug classes have been shown to either cause and/or exacerbate symptoms of restless legs syndrome. With the epidemic of obesity and the heightened awareness of the harmful effects of added sugars, the consumption of low and no-calorie sweeteners has substantially increased. We report a case where the patient developed restless legs syndrome symptoms with the use of a stevia extract–based no calorie sweetener. To our knowledge, this is the first case report of restless legs syndrome possibly associated with low or no-calorie sweetener use.

Citation:

Goswami U, Pusalavidyasagar S. Restless legs syndrome associated with use of stevia nonnutritive sweetener. J Clin Sleep Med. 2020;16(10):1819–1821.

INTRODUCTION

Restless legs syndrome (RLS) is a common1 sensorimotor disorder characterized by an unpleasant sensation in the legs during periods of rest or inactivity, with an urge to move them to obtain relief, resulting in difficulty initiating or maintaining sleep. Lower limbs, particularly the upper calves and legs, are most commonly affected, but the sensations can either spread to or be confined to other parts of body including buttocks, groin, back, abdomen, trunk, chest, neck, and face.2

RLS can be either primary (idiopathic) or secondary to iron deficiency associated with renal failure or pregnancy, rheumatoid arthritis, diabetes mellitus, and use of certain medications. Several drug classes including tricylic antidepressants, selective serotonin or norepinephrine reuptake inhibitors, antipsychotics, antihistamines, antiemetics, and antiepileptics have been shown to either cause and/or exacerbate RLS symptoms. With the epidemic of obesity and the heightened awareness of the adverse metabolic effects of added sugars, the consumption of nonnutritive (low-calorie or no-calorie) sweeteners has substantially increased.3 We report a case where the patient developed RLS symptoms with the use of a stevia extract.

REPORT OF CASE

A 54-year-old man with obstructive sleep apnea (apnea-hypopnea index, 40.9 events/hr; nadir SpO2, 86%), treated with autotitrating continuous positive airway pressure at 15–20 cmH2O pressure, was seen in the sleep clinic for follow-up of his obstructive sleep apnea. His other comorbidities included revascularized coronary artery disease; end-stage kidney disease secondary to diabetes mellitus type 2 and possible IgA nephropathy, treated with a living donor kidney transplant 15 years before; polyneuropathy; mild major depression; and generalized anxiety disorder.

He reported excellent control of obstructive sleep apnea symptoms, and continuous positive airway pressure adherence was confirmed with objective compliance measures showing 10 hours of average nightly use. During the visit, patient reported new concern for restlessness in both arms and neck, feeling of jitteriness in both legs before bedtime at night, improved only with movement of the affected body parts but returning with cessation of the movement and interfering with his ability to fall asleep. These symptoms were suggestive of a likely RLS diagnosis, estimated to be of moderate severity with a score of 20 on the International RLS Rating Scale. A thorough review of medications did not yield any potential causes. He had a history of anemia from chronic renal disease, with hemoglobin levels stable at 11.5–12 g/dL over the last 2 years. His iron function tests obtained approximately 1 year before the visit showed serum ferritin level of 22 μg/dL (reference range, 8–250 μg/dL), serum iron level of 66 μg/dL (reference range, 35–180 μg/dL), iron-binding capacity level of 344 μg/dL (reference range, 240–430 μg/dL), and iron saturation index of 19% (reference range, 15–46%). He had been maintained on an iron supplementation dose of ferrous sulfate 325 mg with vitamin C 500 mg twice daily without any changes for the last 1 year. A repeat measurement of the level of serum ferritin was 60 μg/dL. His diabetes mellitus was inadequately controlled, with a hemoglobin A1C value of 7.4%. He had a previous history of severe length-dependent sensorimotor polyneuropathy involving the bilateral sural nerve, right ulnar digit V, and right median and superficial radial sensory nerves. A traumatic accident several years before had resulted in a left leg injury that caused permanent left footdrop. The chronic symptoms of his polyneuropathy included numbness, tingling, and sharp pain in both feet and minimal numbness in both hands on awakening in the morning. The pattern of the current symptoms did not match with his neuropathic symptoms. On examination, he had normal muscle strength in the upper extremities and proximal lower extremities with left footdrop and atrophy of the left anterior compartment. Distal lower extremities sensation was reduced, particularly on the dorsum of the left foot, and ankle jerks were absent. The remainder of the detailed neurologic examination was unremarkable.

While reviewing for lifestyle changes, the patient reported switching to using a stevia sugar substitute for use with his morning coffee in the previous few weeks. The timing of onset of RLS symptoms correlated with the initiation of stevia use. He was instructed to discontinue the use of this supplement and monitor his symptoms. On 3-week follow-up, the patient reported complete resolution of symptoms with discontinuation of stevia. A brief trial of reintroduction of stevia a few months later resulted in recurrence of original RLS symptoms within 2 days. These again resolved with discontinuation of use.

DISCUSSION

The prevalence of diabetes mellitus and cardiovascular disease has increased with the global epidemic of obesity. The American Association of Clinical Endocrinologists recommends reduction in total caloric intake as one of the main components of any weight-loss intervention.4 Various studies have pointed to added sugars as a determinant of body weight.5 The consumption of nonnutritive sweeteners, both artificial (eg, aspartame, sucralose) and natural (eg, stevia), has substantially increased. The prevalence of low-calorie/no-calorie sweetener consumption, assessed using the National Health and Nutrition Examination Survey data from 2009 to 2012, showed 25% children and 41% adults consuming these agents, with higher consumption reported in those who were overweight or obese.3 Use of low-calorie sweeteners is associated with an approximate 10% reduction in daily energy intake and modest weight loss (0.80 kg).6

Stevia is a bio-sweetener, extracted from the leaves of the plant species Stevia rebaudiana Bertoni, native to Brazil and Paraguay. It produces a taste up to 400 times sweeter than sucrose with no nutritional value.7 Stevioside and rebaudioside A are the most common steviol glycosides and are used in beverages as a sugar substitute. Stevia has also been shown to have antioxidant, antihyperglycemic, antihypertensive, anti-inflammatory, hypolipidemic, antitumor, and immunomodulatory effects.7,8 The high-purity extracts of stevia glycoside have received generally recognized as safe designation in the United States since 2008 and are allowed as ingredients in food products.

This case demonstrates the possible association of stevia use to RLS symptoms. To the best of our knowledge, such an association has never been reported. Given that RLS is a diagnosis based primarily on clinical criteria, a thorough evaluation of differential diagnoses focused on patients’ comorbidities and their pharmaceutical treatment is essential. This patient had several potential causes of confusing symptoms, such as sensorimotor polyneuropathy that may resemble RLS. Demonstration of improvement in symptoms with movement of the affected body regions and pattern of symptoms different from the preexisting polyneuropathy suggested RLS as the likely diagnosis in this case. Also, known iron deficiency may independently result in emergence of RLS; however, because the patient showed significant improvement in serum ferritin level with previously prescribed oral iron supplementation, new-onset RLS is less likely to be precipitated by iron deficiency. Moreover, reemergence of RLS with a second trial of stevia strongly supports this possible correlation.9

The effects of stevia on the dopaminergic system and iron metabolism, the 2 primary pathways implicated in pathophysiology of RLS, need further evaluation. Although there are no studies to date on the effects of nonnutritive sweeteners on dopamine levels in humans, Garcia et al10 recently demonstrated a reduction in the dopamine levels in corpus striatum and a concurrent increase in antioxidants such as glutathione and lipoperoxidation levels after oral administration of stevia for 5 days in young male rats. Similar effects were not seen with a sucralose-based artificial sweetener. This suggests that the effects on brain dopamine levels resulting in RLS may be unique to stevia and not seen with other nonnutritive sweeteners. No evidence of effects of stevia on iron absorption or utilization in the brain is available.

CONCLUSIONS

As demonstrated by this case, use of the nonnutritive supplement stevia possibly results in emergence of RLS, putatively because of its effects on reduction of dopamine levels in selective brain regions. It is important to consider changes in dietary habits and use of supplements or medications when evaluating patients with new-onset RLS symptoms. This is of particular importance in patients with comorbid conditions, such as obesity and diabetes, who are attempting to lose weight by substituting their sugar source with low-calorie/no-calorie sweeteners. As in the case of medication-induced RLS, discontinuation of the offending agent is the main stay of treatment.

Stevia Has Potential Side Effects on Gut Microbiome and Brain, but Experts Explain Bottom Line

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The sugar substitute is known for its potential to lower blood pressure and blood sugar, but some research suggests it may disrupt more than the gut microbiome.

Stevia Has Potential Side Effects on Gut Microbiome and Brain, but Experts Explain Bottom Line

Stevia, known for its zero calories and potential benefits, such as lowering blood pressure and blood sugar, is often considered an excellent substitute for sugar. However, is this sweetener—used by Paraguayans for over a thousand years and by the Japanese for several decades—truly free from side effects?

Stevia Is Excreted, but Liver Problems May Pose Issue

Generally, stevia is thought to be metabolized and excreted without accumulating in the body.

Stevia’s sweetness comes from steviol glycosides. Steviol glycosides are a group of substances, among which stevioside and rebaudioside A are the two most common in commercial products.

Our stomachs and upper small intestines cannot break down or absorb steviol glycosides. Therefore, ingested steviol glycosides enter the lower gastrointestinal tract intact. In the colon, gut bacteria break down steviol glycosides into steviol, a process completed within 24 hours. Subsequently, most of the steviol is rapidly absorbed into the bloodstream through the intestinal wall, while any unabsorbed steviol is excreted in feces. The steviol entering the bloodstream is further metabolized into steviol glucuronide in the liver and ultimately excreted in the urine. This is why human experiments have shown no detectable levels of steviol in the blood after consuming steviol glycosides, while steviol glucuronide is detected in urine, and steviol is found in the feces.

“Factors like diet, medication use, or individual differences could potentially impact the metabolism of stevia and its metabolites,” said Lisa Young, an adjunct professor of nutrition in the Department of Nutrition and Food Studies at New York University and a registered dietitian nutritionist, in an email interview with The Epoch Times. She noted that while rare, some individuals may experience adverse reactions or intolerance to steviol, which “could cause gastrointestinal symptoms, allergic reactions, or other health concerns.”

Additionally, she emphasized the crucial role of the liver in the metabolism of stevia, indicating that liver diseases or impaired liver function may impact this process. “Individuals with liver diseases or those taking medications that affect liver function may need to exercise caution regarding the consumption of stevia.”

Potential Impact of Stevia on Gut Microbiome

Some in vitro and animal experiments have found that stevia or steviol may potentially impact the gut microbiome.

An animal study published in Nutrients in 2019 revealed that, compared to those only drinking water, rebaudioside A consumption altered the gut microbiome composition in mice. However, Ms. Young noted that while the hindgut microbiome of mice and humans share some similarities, many bacteria present in the mouse gut are absent in humans. Therefore, there are certain limitations to animal studies.

Stevia May Kill Lyme Disease Pathogens: Study

A study conducted by Israeli scientists in 2020 revealed that stevia and steviol do not possess bactericidal properties. However, they may potentially interrupt communication among Gram-negative bacteria in the gut, leading to gut microbial imbalance. Additionally, steviol may also exhibit inhibitory effects on the competition among gut bacteria.

Lactobacillus reuteri is often incorporated into food as a probiotic. In an earlier study, stevioside and rebaudioside A were found to inhibit the growth of six strains of Lactobacillus reuteri, with the inhibitory effects varying depending on the specific strain.

An in vitro experiment published in the journal Genes in 2019 suggested that in a simulated human intestinal environment, steviol decreased the population of Bifidobacteria (healthy bacteria), hindered the degradation of bacterial food, and concurrently led to an increase in colonic pH.

Another in vitro experiment, published in the Journal of Agricultural and Food Chemistry in 2019, demonstrated that sweetener products containing steviol glycosides and erythritol altered the structure and diversity of the human gut microbiome to some extent. However, the study concluded that, overall, there was no negative impact on the gut microbial community due to the consumption of stevia.

A review published in Microbiology in 2022 indicated that current knowledge about stevia’s impact on the gut microbiome has primarily come from in vitro and animal studies. Due to a lack of randomized clinical trials conducted in human populations, there is no definitive evidence to elucidate how stevia influences the gut microbiome, and further research is needed.

Ms. Young noted that the impact stevia has on the gut microbiome remains an active area of research, and conclusions may vary. However, she emphasized that “most studies face limitations in terms of biological relevance because it is challenging to directly apply tested concentrations to human exposure levels.”

Gastrointestinal Discomfort Caused by Stevia-Based Products

The adverse effects of stevia-based products often do not stem from steviol glycosides.

As steviol glycosides are several hundred times sweeter than sucrose, most stevia-based products on the market are not 100 percent pure steviol glycosides. Instead, they often consist of a blend of steviol glycosides and some sugar alcohols. For example, you might find a combination of 1 percent steviol glycosides and 99 percent erythritol. These products are commonly found in supermarkets, usually as white crystalline powders, their appearance resembling that of granulated or powdered sugar.

Ms. Young stated that erythritol, present in stevia-based products, is recognized by the U.S. Food and Drug Administration (FDA) as generally recognized as safe (GRAS). However, excessive consumption can result in side effects such as bloating, cramps, flatulence, or diarrhea. Additionally, the inclusion of other substances like sugar alcohol in stevia products may also cause adverse effects, especially for individuals sensitive to these additives.

There are eight types of sugar alcohols approved by relevant regulatory authorities for use as sweeteners in food, including erythritol, hydrogenated starch hydrolysates, lactitol, isomalt, mannitol, maltitol, sorbitol, and xylitol. Some individuals may experience various gastrointestinal discomforts after consuming these substances.

Specifically, sugar alcohol substances may increase gas production after fermentation by bacteria in the gut, contributing to bloating in the gastrointestinal tract. Additionally, these substances can lead to the retention of water in the small intestine, causing abdominal discomfort. Sugar alcohols also impose a greater osmotic load on the gut, leading to increased water concentration in the colon and resulting in loose stools. Moreover, the fermentation of sugar alcohols in the gut may impact the intestinal environment by altering the gut microbiome and its metabolism, influencing the intestinal immune barrier, and potentially increasing the risk of a so-called “leaky gut.”

However, it is important to note that there is a significant variation in symptoms among those who consume sugar-alcohol substances. Factors such as the type of sugar alcohol, the amount ingested, the consumption of food alongside the substance, and the intestinal ability to reabsorb water can all lead to different outcomes. Moreover, people with lower gastrointestinal tolerance or those with intestinal diseases tend to experience more symptoms than healthy people.

The substances present in stevia-based products may also impact cardiovascular health.

A review published in Nature Medicine in 2023 highlighted a link between erythritol consumption and an increased risk of adverse cardiovascular events (including death or nonfatal heart attacks or strokes) and the formation of thrombosis. The researchers stated that further research on the long-term safety of erythritol is warranted. However, it is important to note that some controversy surrounds this study.

Potential Impact of Stevia on the Brain and Nervous System

Scientists have also assessed the potential impact of stevia and its metabolites on the brain and nervous system. However, due to medical ethical considerations, these studies are primarily conducted through animal experiments.

The previously mentioned 2019 animal study suggested that the consumption of stevia may impact the dopamine reward system in the brain.

In 2020, two clinical doctors jointly published a case report, suggesting for the first time a potential association between the symptoms of restless legs syndrome (RLS) and the consumption of stevia. A patient developed symptoms of RLS while using stevia, and these symptoms resolved after discontinuation. Several months later, upon a trial reintroduction of stevia, the RLS symptoms reappeared within two days. The doctors proposed that stevia might selectively reduce dopamine levels in specific regions of the brain, or the intake of stevia could affect iron absorption. Both factors are considered significant contributors to RLS.

In addition to potentially affecting the dopamine system, animal experiments have shown that stevia may also influence memory.

Researchers at the University of Southern California published a study in 2022 where they provided juvenile rats with either artificial sweeteners or water with added stevia for a month and then tested their memory. The results revealed that both artificial sweeteners and stevia impaired the rats’ memory compared to those only drinking water. These rats were less likely to remember objects or navigate through mazes successfully. A study conducted by Filipino researchers in 2015 revealed that mice consuming stevia or two other artificial sweeteners (aspartame and sucralose) showed no significant difference in their learning ability in a water maze compared to mice drinking only water. However, mice consuming stevia exhibited higher levels of cell death in the hippocampus. Another study also conducted in the Philippines in 2014 found that mice with a higher intake of stevia, compared to those only drinking water, exhibited a longer duration of reaction when subjected to heat, suggesting that stevia might inhibit the sensitivity of the mice’s nervous system.

Stevia May Disrupt Endocrine Function and Affect Immunity

In the body, steviol glycosides are first metabolized into steviol, which possesses a steroid-like structure. Therefore, researchers suspect that stevia may act as an endocrine disruptor.

For instance, a cell experiment demonstrated that a certain concentration of steviol could disrupt the endocrine function of human sperm cells and also impact cell viability.

Another study found that stevia consumption led to changes in the number of immune cells in the lymph nodes of mice. Compared to mice drinking only water, those consuming stevia showed an increase in the count of two types of immune cells and a decrease in another type. Additionally, there were varying degrees of changes in some hormones within the mice’s bodies.

In 2020, Brazilian researchers published an in vitro study in Immunopharmacology and Immunotoxicology, revealing that exposure to steviol led to a decrease in human lymphocyte quantity, accompanied by gradual DNA damage and structural changes. Therefore, the study proposed that, under certain concentrations and conditions, steviol exhibits cytotoxic, genotoxic, and mutagenic effects. An earlier study also suggested that, although steviol glycosides seem not to exhibit cytotoxicity, steviol itself possesses mutagenic properties.

Safety of Stevia in Human Studies

However, the experiments mentioned above, which indicate the effects of stevia or its metabolites, were not conducted on humans. In other words, the experimental conditions and subjects differ from those of the human body.

Per Bendix Jeppesen, who is currently studying stevia extract as an anti-diabetic drug and as a healthy sweetener and is an associate professor in the department of endocrinology and diabetes at Aarhus University in Denmark, told The Epoch Times that stevia is safe, stating, “It is the most researched sweetener in the world.” He elaborated: “The European Food Safety Authority (EFSA) are using 10 years to go through all materials. All kinds of studies and publications have been really looked into and they gave this permission (to use stevia).”

Mr. Jeppesen also pointed out, “Cell studies will never be able to replace in vivo studies as animal or human intervention studies.” This is because, in in vivo studies, the human body functions as a whole organism, with different organs working together, whereas in cell studies, it typically involves cells from a specific organ and cannot fully reflect the overall complexity of the organ.

Jan Geuns, a professor in the Department of Biology at Katholieke Universiteit Leuven in Belgium, who has researched stevia for many years, expressed in an email to The Epoch Times that extensive experiments have been conducted on animals as well as healthy subjects. Throughout the process, “we hoped to find other metabolites than steviol or steviol glucuronide. However, no other metabolites could be found.” He also pointed out that steviol glycosides and their metabolites do not accumulate in the human body.

Mr. Geuns also mentioned that “steviol glycosides are not easily absorbed in cells and, therefore, cell studies have nothing to do with the way steviol glycosides behave in man.” Additionally, he explained that once excreted from the body, steviol glucuronide continues to be further degraded by microorganisms, including those in the soil, and does not accumulate in the environment. “This cannot be said about compounds like sucralose, which has recently been proven to be carcinogenic and which is accumulating in surface waters and occurs in tap water.

“I think that sufficient studies have been done on the safety of steviol glycosides (and stevia),” he concluded.

A 2021 review recognized the safety of stevia, citing as primary evidence its historical use in the Paraguayan population for over 1,500 years and decades-long consumption by the Japanese without any reported side effects.

A study published in Nutrition Today in 2015 proposed that there were over 200 studies at that time confirming the safety of stevia. Additionally, a review published in 2023 in the journal Molecules also asserted that most existing human experiments suggest the safety of stevia consumption for the general population—“Although neither the applicability of stevioside in children, pregnancy, nor lactation has been evaluated, preclinical and clinical evidence of its safety allows it to be recommended, respecting the [acceptable daily intake].”

Study suggests that stevia is the most brain-compatible sugar substitute

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Study suggests that Stevia is the most brain-compatible sugar substitute
Credit: Jiang et al.

Given the known risks of consuming high amounts of sugar, today many people are looking for alternative sweeteners that produce a similar taste without prompting significant weight gain and causing other health issues. While research suggests that the brain can tell the difference between different sweet substances, the neural processes underlying this ability to tell sweeteners apart remain poorly understood.

Researchers at University of Shanghai for Science and Technology, the Chinese Academy of Sciences (CAS), and other institutes in China recently carried out a study aimed at better understanding what happens in the brain of mice when they are fed different types of sweeteners. Their findings, published in Neuroscience Research, suggest that the response of neurons to sucrose and stevia is similar, suggesting that stevia could be an equally pleasant but healthier sugar substitute.

“Obesity is a significant issue worldwide, and the use of sweeteners as a substitute for sucrose is a current trend in the food industry,” Yingjie Zhu, co-author of the paper, told Medical Xpress. “Although they all possess sweetness, many sugar substitutes have noticeable differences compared to sucrose when consumed. Therefore, our initial idea was to investigate whether there would be a specific brain region in the central nervous system that could reflect the differences between these sugar substitutes and sucrose in real-time.”

Stevia is a widely used sweetener derived from leaves of a plant native to South America. Many dieticians recommend stevia as a sugar substitute, as it is very sweet but has fewer calories and minimal effects on blood glucose levels. The key objective of the recent work by Zhu and his colleagues was to investigate how the brain of mice responded after they had consumed stevia, sugar, or one of three other sweeteners (i.e., xylitol, glycyrrhizin, and mogroside).

The team hoped to unveil how neurons in the mouse brain responded to the consistent consumption of these different sweeteners over a six-week period. In addition, they were interested in determining whether any of the low-calorie sweeteners they examined elicited similar brain responses to sugar.

“Our previous research identified that the activity of neurons in the paraventricular nucleus of the thalamus (PVT) can track stimulus salience,” Zhu explained. “Therefore, as part of our new study, we recorded the activity intensity in the PVT of mice while they consumed various sweeteners and sucrose.”

The researchers fed mice six different diets for a period of six weeks. One group of mice was fed a so-called control diet (with a mixture of sweeteners), while the other groups were fed a diet with high amounts of sugar, stevia, xylitol, glycyrrhizin, or mogroside, respectively.

Zhu and his colleagues recorded the activity of neurons in the brain of the mice in real-time, using in vivo fluorescence calcium imaging. This an experimental technique that allows scientists to monitor changes in calcium levels within cells, which in turn unveils these cells’ activity patterns.

Interestingly, the team’s recordings revealed that compared to other sugar substitutes considered as part of this study, stevia induced activity in the PVT that more closely resembled that elicited by sugar intake. This suggests that stevia is the most “brain compatible” among most widely used sugar alternatives, most closely mirroring the perceived taste of sugar.

“We found that, given an abundance of food supply, compared to other sugar substitutes, the activity in the PVT brain region induced by stevia was most similar to that induced by sucrose,” Zhu said. “This suggests that stevia could potentially be the most brain-compatible sugar substitute. Therefore, in the relevant food and beverage industries, stevia should receive more attention.”

In the future, this recent study could encourage more food & drink producers to incorporate stevia in their products to reduce their calorie count. In addition, it could inspire other neuroscientists to further examine the neural underpinnings of stevia consumption.

“We were delighted to observe a high similarity in brain activity in mice when consuming stevia and sucrose,” Zhu added. “Consequently, we hope to investigate whether a similar phenomenon exists in the human brain using fMRI in future studies.”

Stevia, Artificial Sweeteners Do Not Increase Appetite

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Replacing sugar with sweeteners like stevia does not increase a person’s appetite and can even help reduce blood sugar levels, according to a new study.

Stevia, Artificial Sweeteners Do Not Increase Appetite: Study

Fans of stevia and other sugar alternatives get a sprinkle of sweet news. Replacing sugar with sweeteners like stevia does not increase a person’s appetite and can even help reduce blood sugar levels, according to new randomized controlled trial results.

The study, published by the SWEET consortium in The Lancet’s eBioMedicine, was led by the University of Leeds in the United Kingdom and the Rhône-Alpes Research Center for Human Nutrition in France. The SWEET consortium comprises 29 Europe-based research, consumer, and industry partners collaborating to research whether switching from sugar to other sweeteners would benefit the public.

The first-of-its-kind study included 53 adult men and women between the ages of 18 and 60 who were considered overweight or obese. It is considered first-of-its-kind because it focused on sugary foods rather than beverages. Between 2021 and 2022, participants consumed cookies that contained either sugar, stevia, or an artificial sweetener called Neotame over three two-week periods. Neotame (sold as Newtame) is an artificial sweetener that is up to 13,000 times sweeter than regular sugar. Participants tried each type of cookie but in a different order. Their glucose levels, insulin, and appetite-related hormones were recorded on the first and last day of each two-week period.

The researchers found no difference in appetite levels between participants who ate cookies with sugar and those who ate cookies with stevia or artificial sweetener. Additionally, they found no difference between appetite-related hormones like ghrelin, glucagon-like peptide 1 (GLP-1), or pancreatic polypeptide.

However, participants who ate cookies made with stevia or artificial sweetener had lower blood sugar and insulin levels than those who ate cookies made with sugar. Participants who ate cookies made with stevia showed the most statistically significant difference in blood sugar.

Sugar and Obesity

While dietary fat was once suspected to cause weight gain and obesity, the finger has shifted to point to sugar in recent decades. Being overweight or obese increases a person’s risk of developing diabetes. Diabetics have too much glucose, or blood sugar, in the bloodstream, so they must watch how much sugar they consume. Additionally, obesity can worsen diabetes.

The unofficial term “diabesity” refers to someone who is both obese and has diabetes. Explains Dr. Jay Waddadar from the Cleveland Clinic: “Diabesity is a disease with enormous potential to cause ill effects on the body in the long run. … Diabesity is a silent disease that damages your body if it’s not controlled, even while you feel fine.”

In the end, sugar is a culprit for both obesity and diabetes, two conditions that feed off of one another.

A Safe Alternative to Sugar? Questions Remain

To reduce the burden of metabolic-related diseases like Type 2 diabetes, a safe alternative to sugar becomes more necessary to reduce sugar intake, lead author Catherine Gibbons, associate professor at the University of Leeds’ School of Psychology, said in a press release. However, the World Health Organization (WHO) has yet to get behind stevia or artificial sweeteners for weight control or reducing the risk of metabolic disorders.

“The rationale behind the recommendation appears to be founded on the lack of robust evidence,” the researchers wrote in the study.

The new research contradicts previous studies from 2023 linking artificial sweeteners to health concerns like impaired glycemic response, toxicological damage to DNA, and increased risk of heart attack or stroke. The authors suggest that this previous research was of lower quality and that the WHO’s stance was perhaps premature. However, although the SWEET consortium’s study was double-blinded, randomized, and highly controlled, with only 53 subjects, it was also small.

Nonetheless, the study offers evidence that nonsugar sweeteners could be a valuable tool in reducing the amount of sugar consumed globally. As more people look for ways to manage their weight and blood sugar levels, sweeteners like stevia and artificial sweeteners could help satisfy a sweet tooth without increasing appetite.

Stevia Has Potential Side Effects on Gut Microbiome and Brain, but Experts Explain Bottom Line

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The sugar substitute is known for its potential to lower blood pressure and blood sugar, but some research suggests it may disrupt more than the gut microbiome.

Stevia Has Potential Side Effects on Gut Microbiome and Brain, but Experts Explain Bottom Line

Stevia, known for its zero calories and potential benefits, such as lowering blood pressure and blood sugar, is often considered an excellent substitute for sugar. However, is this sweetener—used by Paraguayans for over a thousand years and by the Japanese for several decades—truly free from side effects?

Stevia Is Excreted, but Liver Problems May Pose Issue

Generally, stevia is thought to be metabolized and excreted without accumulating in the body.

Stevia’s sweetness comes from steviol glycosides. Steviol glycosides are a group of substances, among which stevioside and rebaudioside A are the two most common in commercial products.

Our stomachs and upper small intestines cannot break down or absorb steviol glycosides. Therefore, ingested steviol glycosides enter the lower gastrointestinal tract intact. In the colon, gut bacteria break down steviol glycosides into steviol, a process completed within 24 hours. Subsequently, most of the steviol is rapidly absorbed into the bloodstream through the intestinal wall, while any unabsorbed steviol is excreted in feces. The steviol entering the bloodstream is further metabolized into steviol glucuronide in the liver and ultimately excreted in the urine. This is why human experiments have shown no detectable levels of steviol in the blood after consuming steviol glycosides, while steviol glucuronide is detected in urine, and steviol is found in the feces.

“Factors like diet, medication use, or individual differences could potentially impact the metabolism of stevia and its metabolites,” said Lisa Young, an adjunct professor of nutrition in the Department of Nutrition and Food Studies at New York University and a registered dietitian nutritionist, in an email interview with The Epoch Times. She noted that while rare, some individuals may experience adverse reactions or intolerance to steviol, which “could cause gastrointestinal symptoms, allergic reactions, or other health concerns.”

Additionally, she emphasized the crucial role of the liver in the metabolism of stevia, indicating that liver diseases or impaired liver function may impact this process. “Individuals with liver diseases or those taking medications that affect liver function may need to exercise caution regarding the consumption of stevia.”

Potential Impact of Stevia on Gut Microbiome

Some in vitro and animal experiments have found that stevia or steviol may potentially impact the gut microbiome.

An animal study published in Nutrients in 2019 revealed that, compared to those only drinking water, rebaudioside A consumption altered the gut microbiome composition in mice. However, Ms. Young noted that while the hindgut microbiome of mice and humans share some similarities, many bacteria present in the mouse gut are absent in humans. Therefore, there are certain limitations to animal studies.

Stevia May Kill Lyme Disease Pathogens: Study

A study conducted by Israeli scientists in 2020 revealed that stevia and steviol do not possess bactericidal properties. However, they may potentially interrupt communication among Gram-negative bacteria in the gut, leading to gut microbial imbalance. Additionally, steviol may also exhibit inhibitory effects on the competition among gut bacteria.

Lactobacillus reuteri is often incorporated into food as a probiotic. In an earlier study, stevioside and rebaudioside A were found to inhibit the growth of six strains of Lactobacillus reuteri, with the inhibitory effects varying depending on the specific strain.

An in vitro experiment published in the journal Genes in 2019 suggested that in a simulated human intestinal environment, steviol decreased the population of Bifidobacteria (healthy bacteria), hindered the degradation of bacterial food, and concurrently led to an increase in colonic pH.

Another in vitro experiment, published in the Journal of Agricultural and Food Chemistry in 2019, demonstrated that sweetener products containing steviol glycosides and erythritol altered the structure and diversity of the human gut microbiome to some extent. However, the study concluded that, overall, there was no negative impact on the gut microbial community due to the consumption of stevia.

A review published in Microbiology in 2022 indicated that current knowledge about stevia’s impact on the gut microbiome has primarily come from in vitro and animal studies. Due to a lack of randomized clinical trials conducted in human populations, there is no definitive evidence to elucidate how stevia influences the gut microbiome, and further research is needed.

Ms. Young noted that the impact stevia has on the gut microbiome remains an active area of research, and conclusions may vary. However, she emphasized that “most studies face limitations in terms of biological relevance because it is challenging to directly apply tested concentrations to human exposure levels.”

Gastrointestinal Discomfort Caused by Stevia-Based Products

The adverse effects of stevia-based products often do not stem from steviol glycosides.

As steviol glycosides are several hundred times sweeter than sucrose, most stevia-based products on the market are not 100 percent pure steviol glycosides. Instead, they often consist of a blend of steviol glycosides and some sugar alcohols. For example, you might find a combination of 1 percent steviol glycosides and 99 percent erythritol. These products are commonly found in supermarkets, usually as white crystalline powders, their appearance resembling that of granulated or powdered sugar.

Ms. Young stated that erythritol, present in stevia-based products, is recognized by the U.S. Food and Drug Administration (FDA) as generally recognized as safe (GRAS). However, excessive consumption can result in side effects such as bloating, cramps, flatulence, or diarrhea. Additionally, the inclusion of other substances like sugar alcohol in stevia products may also cause adverse effects, especially for individuals sensitive to these additives.

There are eight types of sugar alcohols approved by relevant regulatory authorities for use as sweeteners in food, including erythritol, hydrogenated starch hydrolysates, lactitol, isomalt, mannitol, maltitol, sorbitol, and xylitol. Some individuals may experience various gastrointestinal discomforts after consuming these substances.

Specifically, sugar alcohol substances may increase gas production after fermentation by bacteria in the gut, contributing to bloating in the gastrointestinal tract. Additionally, these substances can lead to the retention of water in the small intestine, causing abdominal discomfort. Sugar alcohols also impose a greater osmotic load on the gut, leading to increased water concentration in the colon and resulting in loose stools. Moreover, the fermentation of sugar alcohols in the gut may impact the intestinal environment by altering the gut microbiome and its metabolism, influencing the intestinal immune barrier, and potentially increasing the risk of a so-called “leaky gut.”

However, it is important to note that there is a significant variation in symptoms among those who consume sugar-alcohol substances. Factors such as the type of sugar alcohol, the amount ingested, the consumption of food alongside the substance, and the intestinal ability to reabsorb water can all lead to different outcomes. Moreover, people with lower gastrointestinal tolerance or those with intestinal diseases tend to experience more symptoms than healthy people.

The substances present in stevia-based products may also impact cardiovascular health.

A review published in Nature Medicine in 2023 highlighted a link between erythritol consumption and an increased risk of adverse cardiovascular events (including death or nonfatal heart attacks or strokes) and the formation of thrombosis. The researchers stated that further research on the long-term safety of erythritol is warranted. However, it is important to note that some controversy surrounds this study.

Potential Impact of Stevia on the Brain and Nervous System

Scientists have also assessed the potential impact of stevia and its metabolites on the brain and nervous system. However, due to medical ethical considerations, these studies are primarily conducted through animal experiments.

The previously mentioned 2019 animal study suggested that the consumption of stevia may impact the dopamine reward system in the brain.

In 2020, two clinical doctors jointly published a case report, suggesting for the first time a potential association between the symptoms of restless legs syndrome (RLS) and the consumption of stevia. A patient developed symptoms of RLS while using stevia, and these symptoms resolved after discontinuation. Several months later, upon a trial reintroduction of stevia, the RLS symptoms reappeared within two days. The doctors proposed that stevia might selectively reduce dopamine levels in specific regions of the brain, or the intake of stevia could affect iron absorption. Both factors are considered significant contributors to RLS.

In addition to potentially affecting the dopamine system, animal experiments have shown that stevia may also influence memory.

Researchers at the University of Southern California published a study in 2022 where they provided juvenile rats with either artificial sweeteners or water with added stevia for a month and then tested their memory. The results revealed that both artificial sweeteners and stevia impaired the rats’ memory compared to those only drinking water. These rats were less likely to remember objects or navigate through mazes successfully. A study conducted by Filipino researchers in 2015 revealed that mice consuming stevia or two other artificial sweeteners (aspartame and sucralose) showed no significant difference in their learning ability in a water maze compared to mice drinking only water. However, mice consuming stevia exhibited higher levels of cell death in the hippocampus. Another study also conducted in the Philippines in 2014 found that mice with a higher intake of stevia, compared to those only drinking water, exhibited a longer duration of reaction when subjected to heat, suggesting that stevia might inhibit the sensitivity of the mice’s nervous system.

Stevia May Disrupt Endocrine Function and Affect Immunity

In the body, steviol glycosides are first metabolized into steviol, which possesses a steroid-like structure. Therefore, researchers suspect that stevia may act as an endocrine disruptor.

For instance, a cell experiment demonstrated that a certain concentration of steviol could disrupt the endocrine function of human sperm cells and also impact cell viability.

Another study found that stevia consumption led to changes in the number of immune cells in the lymph nodes of mice. Compared to mice drinking only water, those consuming stevia showed an increase in the count of two types of immune cells and a decrease in another type. Additionally, there were varying degrees of changes in some hormones within the mice’s bodies.

In 2020, Brazilian researchers published an in vitro study in Immunopharmacology and Immunotoxicology, revealing that exposure to steviol led to a decrease in human lymphocyte quantity, accompanied by gradual DNA damage and structural changes. Therefore, the study proposed that, under certain concentrations and conditions, steviol exhibits cytotoxic, genotoxic, and mutagenic effects. An earlier study also suggested that, although steviol glycosides seem not to exhibit cytotoxicity, steviol itself possesses mutagenic properties.

Safety of Stevia in Human Studies

However, the experiments mentioned above, which indicate the effects of stevia or its metabolites, were not conducted on humans. In other words, the experimental conditions and subjects differ from those of the human body.

Per Bendix Jeppesen, who is currently studying stevia extract as an anti-diabetic drug and as a healthy sweetener and is an associate professor in the department of endocrinology and diabetes at Aarhus University in Denmark, told The Epoch Times that stevia is safe, stating, “It is the most researched sweetener in the world.” He elaborated: “The European Food Safety Authority (EFSA) are using 10 years to go through all materials. All kinds of studies and publications have been really looked into and they gave this permission (to use stevia).”

Mr. Jeppesen also pointed out, “Cell studies will never be able to replace in vivo studies as animal or human intervention studies.” This is because, in in vivo studies, the human body functions as a whole organism, with different organs working together, whereas in cell studies, it typically involves cells from a specific organ and cannot fully reflect the overall complexity of the organ.

Jan Geuns, a professor in the Department of Biology at Katholieke Universiteit Leuven in Belgium, who has researched stevia for many years, expressed in an email to The Epoch Times that extensive experiments have been conducted on animals as well as healthy subjects. Throughout the process, “we hoped to find other metabolites than steviol or steviol glucuronide. However, no other metabolites could be found.” He also pointed out that steviol glycosides and their metabolites do not accumulate in the human body.

Mr. Geuns also mentioned that “steviol glycosides are not easily absorbed in cells and, therefore, cell studies have nothing to do with the way steviol glycosides behave in man.” Additionally, he explained that once excreted from the body, steviol glucuronide continues to be further degraded by microorganisms, including those in the soil, and does not accumulate in the environment. “This cannot be said about compounds like sucralose, which has recently been proven to be carcinogenic and which is accumulating in surface waters and occurs in tap water.

“I think that sufficient studies have been done on the safety of steviol glycosides (and stevia),” he concluded.

A 2021 review recognized the safety of stevia, citing as primary evidence its historical use in the Paraguayan population for over 1,500 years and decades-long consumption by the Japanese without any reported side effects.

A study published in Nutrition Today in 2015 proposed that there were over 200 studies at that time confirming the safety of stevia. Additionally, a review published in 2023 in the journal Molecules also asserted that most existing human experiments suggest the safety of stevia consumption for the general population—“Although neither the applicability of stevioside in children, pregnancy, nor lactation has been evaluated, preclinical and clinical evidence of its safety allows it to be recommended, respecting the [acceptable daily intake].”

Stevia Has Potential Side Effects on Gut Microbiome and Brain, but Experts Explain Bottom Line

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The sugar substitute is known for its potential to lower blood pressure and blood sugar, but some research suggests it may disrupt more than the gut microbiome

Stevia, known for its zero calories and potential benefits, such as lowering blood pressure and blood sugar, is often considered an excellent substitute for sugar. However, is this sweetener—used by Paraguayans for over a thousand years and by the Japanese for several decades—truly free from side effects?

Stevia Is Excreted, but Liver Problems May Pose Issue

Generally, stevia is thought to be metabolized and excreted without accumulating in the body.

Stevia’s sweetness comes from steviol glycosides. Steviol glycosides are a group of substances, among which stevioside and rebaudioside A are the two most common in commercial products.

Our stomachs and upper small intestines cannot break down or absorb steviol glycosides. Therefore, ingested steviol glycosides enter the lower gastrointestinal tract intact. In the colon, gut bacteria break down steviol glycosides into steviol, a process completed within 24 hours. Subsequently, most of the steviol is rapidly absorbed into the bloodstream through the intestinal wall, while any unabsorbed steviol is excreted in feces. The steviol entering the bloodstream is further metabolized into steviol glucuronide in the liver and ultimately excreted in the urine. This is why human experiments have shown no detectable levels of steviol in the blood after consuming steviol glycosides, while steviol glucuronide is detected in urine, and steviol is found in the feces.

“Factors like diet, medication use, or individual differences could potentially impact the metabolism of stevia and its metabolites,” said Lisa Young, an adjunct professor of nutrition in the Department of Nutrition and Food Studies at New York University and a registered dietitian nutritionist, in an email interview with The Epoch Times. She noted that while rare, some individuals may experience adverse reactions or intolerance to steviol, which “could cause gastrointestinal symptoms, allergic reactions, or other health concerns.”

Additionally, she emphasized the crucial role of the liver in the metabolism of stevia, indicating that liver diseases or impaired liver function may impact this process. “Individuals with liver diseases or those taking medications that affect liver function may need to exercise caution regarding the consumption of stevia.”

Potential Impact of Stevia on Gut Microbiome

Some in vitro and animal experiments have found that stevia or steviol may potentially impact the gut microbiome.

An animal study published in Nutrients in 2019 revealed that, compared to those only drinking water, rebaudioside A consumption altered the gut microbiome composition in mice. However, Ms. Young noted that while the hindgut microbiome of mice and humans share some similarities, many bacteria present in the mouse gut are absent in humans. Therefore, there are certain limitations to animal studies

A study conducted by Israeli scientists in 2020 revealed that stevia and steviol do not possess bactericidal properties. However, they may potentially interrupt communication among Gram-negative bacteria in the gut, leading to gut microbial imbalance. Additionally, steviol may also exhibit inhibitory effects on the competition among gut bacteria

Lactobacillus reuteri is often incorporated into food as a probiotic. In an earlier study, stevioside and rebaudioside A were found to inhibit the growth of six strains of Lactobacillus reuteri, with the inhibitory effects varying depending on the specific strain.

An in vitro experiment published in the journal Genes in 2019 suggested that in a simulated human intestinal environment, steviol decreased the population of Bifidobacteria (healthy bacteria), hindered the degradation of bacterial food, and concurrently led to an increase in colonic pH.

Another in vitro experiment, published in the Journal of Agricultural and Food Chemistry in 2019, demonstrated that sweetener products containing steviol glycosides and erythritol altered the structure and diversity of the human gut microbiome to some extent. However, the study concluded that, overall, there was no negative impact on the gut microbial community due to the consumption of stevia.

A review published in Microbiology in 2022 indicated that current knowledge about stevia’s impact on the gut microbiome has primarily come from in vitro and animal studies. Due to a lack of randomized clinical trials conducted in human populations, there is no definitive evidence to elucidate how stevia influences the gut microbiome, and further research is needed.

Ms. Young noted that the impact stevia has on the gut microbiome remains an active area of research, and conclusions may vary. However, she emphasized that “most studies face limitations in terms of biological relevance because it is challenging to directly apply tested concentrations to human exposure levels.”

Gastrointestinal Discomfort Caused by Stevia-Based Products

The adverse effects of stevia-based products often do not stem from steviol glycosides.

As steviol glycosides are several hundred times sweeter than sucrose, most stevia-based products on the market are not 100 percent pure steviol glycosides. Instead, they often consist of a blend of steviol glycosides and some sugar alcohols. For example, you might find a combination of 1 percent steviol glycosides and 99 percent erythritol. These products are commonly found in supermarkets, usually as white crystalline powders, their appearance resembling that of granulated or powdered sugar.

Ms. Young stated that erythritol, present in stevia-based products, is recognized by the U.S. Food and Drug Administration (FDA) as generally recognized as safe (GRAS). However, excessive consumption can result in side effects such as bloating, cramps, flatulence, or diarrhea. Additionally, the inclusion of other substances like sugar alcohol in stevia products may also cause adverse effects, especially for individuals sensitive to these additives.

There are eight types of sugar alcohols approved by relevant regulatory authorities for use as sweeteners in food, including erythritol, hydrogenated starch hydrolysates, lactitol, isomalt, mannitol, maltitol, sorbitol, and xylitol. Some individuals may experience various gastrointestinal discomforts after consuming these substances.

Specifically, sugar alcohol substances may increase gas production after fermentation by bacteria in the gut, contributing to bloating in the gastrointestinal tract. Additionally, these substances can lead to the retention of water in the small intestine, causing abdominal discomfort. Sugar alcohols also impose a greater osmotic load on the gut, leading to increased water concentration in the colon and resulting in loose stools. Moreover, the fermentation of sugar alcohols in the gut may impact the intestinal environment by altering the gut microbiome and its metabolism, influencing the intestinal immune barrier, and potentially increasing the risk of a so-called “leaky gut.”

However, it is important to note that there is a significant variation in symptoms among those who consume sugar-alcohol substances. Factors such as the type of sugar alcohol, the amount ingested, the consumption of food alongside the substance, and the intestinal ability to reabsorb water can all lead to different outcomes. Moreover, people with lower gastrointestinal tolerance or those with intestinal diseases tend to experience more symptoms than healthy people.

The substances present in stevia-based products may also impact cardiovascular health.

A review published in Nature Medicine in 2023 highlighted a link between erythritol consumption and an increased risk of adverse cardiovascular events (including death or nonfatal heart attacks or strokes) and the formation of thrombosis. The researchers stated that further research on the long-term safety of erythritol is warranted. However, it is important to note that some controversy surrounds this study.

Potential Impact of Stevia on the Brain and Nervous System

Scientists have also assessed the potential impact of stevia and its metabolites on the brain and nervous system. However, due to medical ethical considerations, these studies are primarily conducted through animal experiments.

The previously mentioned 2019 animal study suggested that the consumption of stevia may impact the dopamine reward system in the brain.

In 2020, two clinical doctors jointly published a case report, suggesting for the first time a potential association between the symptoms of restless legs syndrome (RLS) and the consumption of stevia. A patient developed symptoms of RLS while using stevia, and these symptoms resolved after discontinuation. Several months later, upon a trial reintroduction of stevia, the RLS symptoms reappeared within two days. The doctors proposed that stevia might selectively reduce dopamine levels in specific regions of the brain, or the intake of stevia could affect iron absorption. Both factors are considered significant contributors to RLS.

In addition to potentially affecting the dopamine system, animal experiments have shown that stevia may also influence memory.

Researchers at the University of Southern California published a study in 2022 where they provided juvenile rats with either artificial sweeteners or water with added stevia for a month and then tested their memory. The results revealed that both artificial sweeteners and stevia impaired the rats’ memory compared to those only drinking water. These rats were less likely to remember objects or navigate through mazes successfully. A study conducted by Filipino researchers in 2015 revealed that mice consuming stevia or two other artificial sweeteners (aspartame and sucralose) showed no significant difference in their learning ability in a water maze compared to mice drinking only water. However, mice consuming stevia exhibited higher levels of cell death in the hippocampus. Another study also conducted in the Philippines in 2014 found that mice with a higher intake of stevia, compared to those only drinking water, exhibited a longer duration of reaction when subjected to heat, suggesting that stevia might inhibit the sensitivity of the mice’s nervous system.

Stevia May Disrupt Endocrine Function and Affect Immunity

In the body, steviol glycosides are first metabolized into steviol, which possesses a steroid-like structure. Therefore, researchers suspect that stevia may act as an endocrine disruptor.

For instance, a cell experiment demonstrated that a certain concentration of steviol could disrupt the endocrine function of human sperm cells and also impact cell viability.

Another study found that stevia consumption led to changes in the number of immune cells in the lymph nodes of mice. Compared to mice drinking only water, those consuming stevia showed an increase in the count of two types of immune cells and a decrease in another type. Additionally, there were varying degrees of changes in some hormones within the mice’s bodies.

In 2020, Brazilian researchers published an in vitro study in Immunopharmacology and Immunotoxicology, revealing that exposure to steviol led to a decrease in human lymphocyte quantity, accompanied by gradual DNA damage and structural changes. Therefore, the study proposed that, under certain concentrations and conditions, steviol exhibits cytotoxic, genotoxic, and mutagenic effects. An earlier study also suggested that, although steviol glycosides seem not to exhibit cytotoxicity, steviol itself possesses mutagenic properties.

Safety of Stevia in Human Studies

However, the experiments mentioned above, which indicate the effects of stevia or its metabolites, were not conducted on humans. In other words, the experimental conditions and subjects differ from those of the human body.

Per Bendix Jeppesen, who is currently studying stevia extract as an anti-diabetic drug and as a healthy sweetener and is an associate professor in the department of endocrinology and diabetes at Aarhus University in Denmark, told The Epoch Times that stevia is safe, stating, “It is the most researched sweetener in the world.” He elaborated: “The European Food Safety Authority (EFSA) are using 10 years to go through all materials. All kinds of studies and publications have been really looked into and they gave this permission (to use stevia).”

Mr. Jeppesen also pointed out, “Cell studies will never be able to replace in vivo studies as animal or human intervention studies.” This is because, in in vivo studies, the human body functions as a whole organism, with different organs working together, whereas in cell studies, it typically involves cells from a specific organ and cannot fully reflect the overall complexity of the organ.

Jan Geuns, a professor in the Department of Biology at Katholieke Universiteit Leuven in Belgium, who has researched stevia for many years, expressed in an email to The Epoch Times that extensive experiments have been conducted on animals as well as healthy subjects. Throughout the process, “we hoped to find other metabolites than steviol or steviol glucuronide. However, no other metabolites could be found.” He also pointed out that steviol glycosides and their metabolites do not accumulate in the human body.

Mr. Geuns also mentioned that “steviol glycosides are not easily absorbed in cells and, therefore, cell studies have nothing to do with the way steviol glycosides behave in man.” Additionally, he explained that once excreted from the body, steviol glucuronide continues to be further degraded by microorganisms, including those in the soil, and does not accumulate in the environment. “This cannot be said about compounds like sucralose, which has recently been proven to be carcinogenic and which is accumulating in surface waters and occurs in tap water.

“I think that sufficient studies have been done on the safety of steviol glycosides (and stevia),” he concluded.

A 2021 review recognized the safety of stevia, citing as primary evidence its historical use in the Paraguayan population for over 1,500 years and decades-long consumption by the Japanese without any reported side effects.

A study published in Nutrition Today in 2015 proposed that there were over 200 studies at that time confirming the safety of stevia. Additionally, a review published in 2023 in the journal Molecules also asserted that most existing human experiments suggest the safety of stevia consumption for the general population—“Although neither the applicability of stevioside in children, pregnancy, nor lactation has been evaluated, preclinical and clinical evidence of its safety allows it to be recommended, respecting the [acceptable daily intake

Low-Calorie Sweeteners

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sugar free label on a can of soda

The health effects of low-calorie/artificial sweeteners are inconclusive, with research showing mixed findings.

Low-calorie sweeteners (LCS) are sweeteners that contain few to no calories but have a higher intensity of sweetness per gram than sweeteners with calories—like table sugar, fruit juice concentrates, and corn syrups. Other names for LCS are non-nutritive sweeteners, artificial sweeteners, sugar substitutes, and high-intensity sweeteners.

LCS are found in many beverages and foods like frozen desserts, yogurt, candies, baked goods, chewing gum, breakfast cereals, gelatins, and puddings. Foods and beverages containing LCS sometimes carry the label “sugar-free” or “diet.” Some LCS can be used as general purpose sweeteners.

Because LCS are many times sweeter than table sugar, they can be used in smaller amounts to achieve the same level of sweetness as sugar. People may use LCS in place of sugar to consume fewer calories or less sugar or to better control their blood glucose if they have diabetes or prediabetes.

There are six LCS approved as food additives by the U.S. Food and Drug Administration (FDA). [1] Numerous studies have been conducted on each type to identify possible toxic effects. They are all sweeter than table sugar (sucrose) but contain few or no calories. They include:

Low-Calorie SweetenerBrand Names†Sweetness as compared with sugarAcceptable Daily Intake* (maximum number of tabletop sweetener packets per day)
AspartameEqual®, NutraSweet®, Sugar Twin®200 times sweeter than sugar75**
Acesulfame-KSunett®, Sweet One®200 times sweeter than sugar23
SaccharinSweet’N Low®, Sweet Twin®, Necta Sweet®200-700 times sweeter than sugar45
SucraloseSplenda®600 times sweeter than sugar23
NeotameNewtame®7,000-13,000 times sweeter than sugar23
AdvantameNo brand names20,000 times sweeter than sugar4,920

*An Acceptable Daily Intake is the maximum amount of a substance that can be consumed daily over the course of a person’s lifetime with no appreciable health risk, and is based on the highest intake that does not lead to observable adverse effects. Calculations are based on a 132 pound individual.
**People with a rare hereditary disease known as phenylketonuria (PKU) have difficulty breaking down phenylalanine, a component of aspartame, and should limit their intake of phenylalanine from all sources, including aspartame.
†The inclusion of brand-names on this list is for reference only and does not constitute an endorsement. The Nutrition Source does not endorse specific brands.

Two other LCS are permitted for specific conditions of use in the food supply through the FDA’s GRAS (“Generally Recognized as Safe”) notification program:

  • Certain Steviol Glycosides, which come from the South American Stevia plant, Stevia rebaudiana.
    • Steviol glycosides are found in foods and beverages in the U.S. under the names Rebaudioside A (or Reb A), Stevioside, Rebaudioside D, or steviol glycoside mixtures that contain Rebaudioside A and/or Stevioside as the main ingredients. Commercial brand names include Truvia® and PureVia®. At 200-400 times sweeter than sugar, the Acceptable Daily Intake is 9 packets daily.
    • Stevia leaf and unrefined stevia extracts are not considered GRAS and are not allowed in the U.S. for use as sweeteners.
  • Monk Fruit, also known as luo han guo or Siraitia grosvenorii Swingle fruit extract (SGFE), comes from a plant native to Southern China.
    • Monk fruit is 100-250 times sweeter than sugar.
    • An Acceptable Daily Intake has not yet been determined.

Sugar Alcohols

Sugar alcohols, or polyols, are not classified as LCS but have slightly less calories than table sugar. The sweetness of sugar alcohols varies from 25-100% as sweet as sugar. They do not promote tooth decay or cause sharp rises in blood glucose. Examples are sorbitol, xylitol, lactitol, mannitol, erythritol, and maltitol. They are found in sugar-free candies, cookies, ice cream, beverages, and chewing gums. They are also used in toothpastes and medicines like cough syrups.

In some people, eating high quantities of certain sugar alcohols can cause loose stools or diarrhea. They are absorbed slowly and may cause extra water to be drawn into the intestines. [2] With continued use, people may improve their tolerance.

More research is needed on the longer-term use of sugar alcohols. An observational three-year study found an association between erythritol as an added sweetener and cardiovascular disease (CVD) events, such as stroke and heart attack, in patients with heart disease or risk factors for CVD (e.g., diabetes, high blood pressure). [3] When comparing patients with the lowest and highest blood levels of erythritol, the latter had twice the risk of developing a CVD event. It is noted that the researchers only checked blood erythritol once at the start of the study. They further investigated with a separate lab study, and found that exposing human platelets to erythritol increased the risk of blood clot formation. Erythritol occurs naturally in small amounts in fruits, wine, and beer. But the amount of erythritol used as an additive in low-calorie beverages, ice cream, chewing gums, and candies is much higher.

Low-Calorie Sweeteners and Health

The health effects of LCS are inconclusive, with research showing mixed findings. Research is also looking at potential differences in effects from the various types of LCS. The following reviews research specific to LCS beverages.

  • A large observational study of French women showed that both sugar-sweetened beverages (SSBs) and LCS beverages were linked with an increased risk of developing type 2 diabetes. [4] The authors noted that a high intake of SSBs has been associated with weight gain, possibly due to lower satiety and increased blood sugar and insulin levels, leading to insulin resistance. LCS beverages may also cause weight gain by stimulating appetite and a sweet preference in some people.
  • With observational studies, it should be noted that the theory of reverse causation is also possible (for example, when people who are overweight or have prediabetes begin drinking LCS beverages to improve their blood sugar control, which produces a false association between higher LCS beverage intake and future risk of developing diabetes). Reverse causation may explain the finding from a meta-analysis of 17 cohort studies showing an 18% higher incidence of type 2 diabetes with SSBs and 25% higher incidence with LCS beverages, compared with no intake of these drinks. [5]
    • In a detailed analysis of data from the Health Professionals Follow-up Study, the positive association observed between LCS beverage intake and type 2 diabetes incidence was largely explained by higher baseline BMI and metabolic conditions, which might have led to increased use of LCS beverages in the first place. [6]
  • In three large prospective cohort studies of U.S. men and women, intake of SSBs was associated with an average 3-pound weight gain within each 4-year time period. Substituting the same amount of SSBs with water or LCS beverages was associated with less weight gain (about 1 pound) within each 4-year time span. [7]
  • For adults trying to wean themselves from sugary soda, diet soda is a possible short-term substitute, best used in small amounts over a short period of time. For children, the long-term effects of consuming LCS beverages are unknown, so it’s best for kids to limit their intake. [8]

Weight Control

Long-term observational studies show that regular consumption of LCS beverages reduces calorie intake and promotes less weight gain or weight maintenance, but other research shows no effect, and some studies even show weight gain. [9] Randomized controlled trials also show mixed findings, although most have shown a modest reduction in weight. [10] Most of these studies are short-term with a small number of participants, making it difficult to provide definitive conclusions on LCS beverages and weight control. Different comparisons among studies may also produce different results; for example, was LCS beverage intake being compared with SSBs, juice, or water?

The human brain responds to sweetness with signals to eat more. By providing a sweet taste without any calories, however, LCS beverages may cause us to crave more sweet foods and drinks, which can add up to excess calories. Although hypothetical and not proven in human studies, research is actively looking at proposed mechanisms of LCS beverages that may affect appetite and weight:

  • Do repeated exposures to the sweet taste of LCS promote a preference for sweets in the diet?
  • Does the sweet taste of LCS stimulate an insulin response even though blood glucose does not change, leading to an increased appetite and food intake?
  • If LCS beverages (as compared with SSBs) do not release hormones in the stomach that signal satisfaction, may a person increase their food intake due to hunger?
  • Animal studies have shown that LCS can change gut microbiota, leading to weight gain and increased blood glucose levels. Would a similar effect be found in human studies?

At the University of California-San Diego, researchers performed functional MRI scans as volunteers took small sips of water sweetened with sugar or sucralose. Sugar activated regions of the brain involved in food reward, while sucralose didn’t. [11] It is possible, the authors say, that sucralose “may not fully satisfy a desire for natural caloric sweet ingestion.” So, while sugar signals a positive feeling of reward, LCS may not be an effective way to manage a craving for sweets. LCS and Cancer?

Scientific Advisory

A 2011 statement from the American Heart Association and American Diabetes Association concluded that when used judiciously, non-nutritive sweeteners (including low-calorie sweeteners, artificial sweeteners, and non-caloric sweeteners) might help with weight loss or control, and could also have beneficial metabolic effects. The statement also points out, however, that these potential benefits will not be fully realized if there is a compensatory increase in energy intake from other sources—ultimately saying that at this time there is insufficient data to make a conclusive determination about using non-nutritive sweeteners; more research is needed. [18]

The American Heart Association and American Diabetes Association followed this with a 2018 scientific advisory specific to LCS beverages and cardiometabolic health. [8] The report cited the decline in consumption of both SSBs and LCS beverages in the United States, suggesting that it is possible to reduce SSBs without necessarily increasing LCS beverage intake. The advisory outlined the following summary points:

  • Children should not drink LCS beverages in the long-term because of unknown effects. If there is a potential increased risk in adults of metabolic syndrome, type 2 diabetes, and cardiovascular events with diet beverage intake, the risk could be heightened in a child due to their smaller body size and earlier exposure.
  • For adults who are regular high consumers of SSBs, LCS beverages may be a useful temporary replacement strategy to reduce intake of SSBs. This may be particularly helpful for those who are used to a sweet-tasting beverage and for whom water, at least initially, is an undesirable option.
  • Alternatives to LCS beverages and SSBs, such as plain, carbonated, or unsweetened flavored waters, should be encouraged for all.
  • The potential benefits from LCS beverages as replacements for SSBs will not be fully realized if their use is offset by an increase in calorie intake from other foods or beverages. Additionally, an overall healthful dietary pattern is recommended.
  • Further research on the effects of LCS beverages on weight control, cardiometabolic risk factors, and risk of cardiovascular disease and other chronic diseases is needed.

Stevia: A Popular Sweetener That Lowers Blood Sugar, Fights Diabetes

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Modern research has found that stevia exhibits anti-diabetic activity.

In this series, we will explore the good and bad sweeteners, uncover the unexpected outcomes of cutting out sugar, and discover the ultimate way to achieve this.

Stevia has recently become one of the most popular natural sugar substitutes. Sugar is known to raise blood sugar levels, but stevia can actually lower them. In fact, it was even used to treat diabetes in ancient times.

Stevia is also known as honey leaf, sweet leaf, or sweet herb. According to a paper published in Nutrition Today, it belongs to the sunflower (Asteraceae) family and is native to southern Brazil and northern Paraguay. The indigenous Guaraní people have been using stevia to sweeten their food and beverages for centuries. According to a 2019 meta-analysis published in Nutrients, they have also used it for medicinal purposes, such as treating diabetes.

Stevia’s sweetness mainly comes from steviol glycosides, which are about 200 to 300 times sweeter than sucrose.

High-purity stevia extracts contain 95 percent or more steviol glycosides, according to the Nutrition Today paper. A 2023 study published in Molecules found eight different types of steviol glycosides that occur naturally in stevia leaves, with stevioside being the most abundant.

Because of its commercial potential and pharmacological properties, stevia has attracted widespread attention from the food and scientific community. As a result, stevia plantations can now be found in many regions around the world.

Stevia’s glycemic index (GI) and calorie content are zero (pdf). The glycemic index measures how quickly and to what extent a food increases blood sugar levels, also called blood glucose levels, with glucose being the standard at a GI value of 100.

A Sweetener With Anti-Diabetic Properties

Modern research has found that stevia exhibits anti-diabetic activity

Stevia not only increases insulin secretion and activity but also reduces insulin resistance. It also inhibits or reduces the liver’s production of glucose, which helps maintain healthy blood sugar levels. Additionally, the stevioside and steviol found in stevia help to regulate the activity of certain enzymes, preventing blood sugar from dropping too low and causing hypoglycemia.

Researchers from the University of Florida conducted an experiment in which 31 adult participants fasted for 12 hours and ate the same breakfast. Twenty minutes before lunch and dinner, they were given tea and snacks containing sucrose, aspartame, or stevia, without knowing which type of sugar they were ingesting. They were then free to eat lunch and dinner as they wished.

Their hunger and satiety levels were evaluated hourly, and blood tests were conducted. All participants completed three days of food tests.

The results showed that participants who consumed stevia had significantly lower blood sugar levels right after lunch than those who consumed sucrose, and they had no significant fluctuations.

Consumption of stevia resulted in lower blood glucose levels right after lunch. (The Epoch Times)
Consumption of stevia resulted in lower blood glucose levels right after lunch. (The Epoch Times)

Additionally, after lunch, the insulin levels of participants who consumed stevia were overall lower than those of participants who consumed aspartame or sucrose.

Consumption of stevia resulted in lower insulin levels right after lunch. (The Epoch Times)
Consumption of stevia resulted in lower insulin levels right after lunch. (The Epoch Times)

“It would suggest that compared to other types of sweeteners, stevia could be beneficial in helping people keep their glucose levels under control or in a healthy range after eating,” study co-author Stephen Anton, a professor in the department of physiology and aging at the University of Florida who has a doctorate in clinical and health psychology, told The Epoch Times. “Compared to sucrose and aspartame, stevia could lead to better post-meal metabolic states.”

Moreover, participants who consumed stevia and aspartame had a significantly lower total caloric intake.

Although participants who consumed stevia before meals didn’t obtain calories from it, they didn’t compensate for the calorie difference by consuming more during lunch or dinner compared with those who consumed high-calorie sucrose. Furthermore, their satiety levels were similar.

A randomized, controlled trial on diabetic patients published in the Journal of the Science of Food and Agriculture in 2016 further demonstrated the blood sugar-lowering effect of stevia. Twenty patients with Type 2 diabetes were randomly divided into two groups, one taking 1 gram of dried stevia leaf powder daily and the other not taking any. The experiment was conducted over 60 days.

The results showed that taking dried stevia leaf powder significantly reduced the fasting and postprandial blood sugar levels of these diabetic patients.

Consumption of stevia resulted in lower fasting and postprandial blood sugar levels. (The Epoch Times)
Consumption of stevia resulted in lower fasting and postprandial blood sugar levels. (The Epoch Times)

“I see that using stevia as a sugar substitute can bring about a huge change,” said Per Bendix Jeppesen, an associate professor in the department of endocrinology and diabetes at Aarhus University in Denmark who is currently studying stevia extract as an anti-diabetic drug and as a healthy sweetener.

“It is a game changer,” he told The Epoch Times.

That’s because the main component of stevia has positive effects on the human endocrine system, especially for people with diabetes. In addition to studying stevia’s effectiveness and extraction techniques, Mr. Jeppesen is involved in related experiments on anti-diabetic drugs.

Modern people tend to engage in too little physical activity, consume too much food, and eat diets that are high in sugar and fat.

“Stevia could be a very good substitute for the sugar that we are consuming too much of,” Mr. Jeppesen said. “By adding stevia, it could really enhance public health, as the calorie intake would decrease when we consume less sugar.”

Effects on Metabolism, Blood Pressure, and Blood Lipids

In addition to controlling postprandial blood sugar and other anti-diabetic effects, stevia can lower blood pressure and blood lipids.

Steviol glycosides found in stevia can regulate the level of calcium in the blood, which can lead to vasodilation and reduced arterial contraction, both of which contribute to lowering blood pressure, according to the 2023 Molecules study.

Researchers in Taiwan conducted a randomized, double-blind, placebo-controlled trial on hypertensive patients in which 174 hypertensive patients were divided into two groups. One group took steviol glycoside capsules three times a day, each containing 500 milligrams of steviol glycoside, while the other group took a placebo. Two years later, those who took steviol glycoside showed significant improvements in their blood pressure. Their systolic blood pressure decreased from an average of 150 to 140 mm Hg, and their diastolic blood pressure decreased from an average of 95 to 89 mm Hg.

Notably, the beneficial effects of steviol glycosides on hypertensive patients were observed approximately one week after the start of the experiment and continued throughout the entire study. Additionally, the group taking steviol glycosides had significantly improved overall quality of life scores, as measured by a survey.

The Nutrients meta-analysis included seven studies and nine randomized controlled trials involving 462 participants. The analysis revealed that compared with taking a placebo, steviol glycosides significantly reduced systolic blood pressure by 6.32 mm Hg and diastolic blood pressure by 3.6 mm Hg. Additionally, there were nonsignificant reductions in body mass index, fasting blood sugar, and total cholesterol.

Stevia can also lower blood lipids. A review study showed that consuming stevia extract can significantly increase the level of high-density lipoprotein (“good” cholesterol) and reduce the levels of total cholesterol, triglycerides, and low-density lipoprotein (“bad” cholesterol).

Anti-Inflammatory and Antioxidant Properties

Stevia contains more than 100 compounds, many of which benefit our health. In addition to natural sweeteners and various trace elements, stevia contains terpenes, sterols, tannins, volatile acids, flavonoids, vitamins, enzymes, organic acids, and polysaccharides, all of which have biological activity.

According to the Molecules study, steviol glycosides have been found to suppress and control factors that trigger cell inflammation. They also play a protective role in the liver by preventing inflammation and have been shown to enhance the body’s innate immune system.

In addition, steviol glycosides exhibit antioxidant properties. The study published in Molecules in 2023 demonstrated that they can protect heart cells from damage caused by hydrogen peroxide, resulting in increased vitality and improved antioxidant capacity. They can also prevent oxidative DNA damage in the liver and kidneys.

Minimal Side Effects

According to a paper published in the Experimental and Clinical Sciences (EXCLI) Journal, Paraguayans have been consuming stevia continuously for more than 1,500 years with almost no adverse effects reported. Additionally, a review study indicates that most reports on stevia consumption don’t suggest any adverse events.

According to the U.S. Food and Drug Administration (FDA), highly purified steviol glycosides are generally recognized as safe (GRAS). But stevia leaf and crude stevia extract are not considered GRAS “due to inadequate toxicological information.” They are subject to food additive regulations, not dietary ingredients and dietary supplements, FDA said.

In other countries like Japan, Australia, and Brazil, stevia leaf-derived products are approved for use as sweeteners in food. They are used in a variety of foods, including teas.

The acceptable daily intake of steviol glycosides, as defined by the U.S. Food and Drug Administration and the European Food Safety Authority, is 4 mg per kg body weight, or about 1.8 mg per pound.

Mr. Jeppesen stated that these agencies took more than 10 years to conduct rigorous evaluations before listing stevia as a food additive. However, stevia extracts has been widely used as a sweetener in Japan since the 1980s.

An earlier rat study mentioned in the EXCLI Journal suggested that stevia might affect the fertility of experimental animals. However, Mr. Jeppesen said that the final results of these studies generally weren’t accepted.

Stevia plants. (casa.da.photo/Shutterstock)
Stevia plants. (casa.da.photo/Shutterstock)

How to Choose Stevia Sweetener

Despite stevia’s benefits, not all stevia products available for sale are high quality.

Some products have been found to contain artificial sweeteners sodium saccharin and sodium cyclamate. In addition, crude stevia extracts may have a higher allergenic potential than high-purity stevia sweeteners containing at least 95 percent of steviol glycosides.

Because stevia is so sweet, most stevia products found in supermarkets are blended formulas. Steviol glycosides generally account for only about 1 percent of powdered products, while the remaining ingredients are usually sugar alcohols such as erythritol and xylitol. Certain products may also contain a combination of steviol glycosides and cane sugar or raw sugar.

Liquid-based stevia products mainly contain water and may also contain some preservatives such as alcohol. Colorless and transparent products are formulated using steviol glycosides as raw materials; products that are green in color are more likely to be directly extracted from the stevia plant.

Mr. Jeppesen recommended choosing products that combine soluble fiber and steviol glycosides for a calorie-free sweet taste and additional fiber intake. Also, the application and preparation methods of these products are similar to those of sugar, making them a practical alternative for use in cooking.

Some stevia products have a metallic or bitter taste from the stevioside compound.

Mr. Jeppesen said that the taste of steviol glycoside products would continue to improve as extraction technology advances. In fact, the aftertaste of metallic or bitter flavors can now be eliminated. In the future, there’ll be more and more steviol glycoside products available to choose from.

Tips for Growing Stevia Plants at Home

How can stevia plants be grown at home?

Stevia is a hardy plant that will thrive under the right conditions. Provided with adequate light and well-draining, lightweight soil, stevia plants will produce more leaves with higher levels of steviol glycosides.

Stevia leaves contain eight different steviol glycosides, and rebaudioside A has been found to have a more pleasant taste than stevioside. Some high-quality stevia varieties with a higher content of rebaudioside A than stevioside have been developed in recent years.

When the stevia flowers blossom, the leaves are less sweet. According to a recent study published in Applied Microbiology and Biotechnology, this is because the levels of sweet compounds in stevia leaves will significantly decrease during the flowering process.

Stevia leaves contain eight different steviol glycosides. (Take Photo/Shutterstock)
Stevia leaves contain eight different steviol glycosides. (Take Photo/Shutterstock)

Adjusting watering levels and applying organic fertilizers based on temperature and humidity is also essential. Stevia is not cold tolerant, so it should be moved indoors during winter or have a thick layer of straw mulch added to its roots for insulation.

For inexperienced growers, starting with stevia seeds can pose obstacles, as they are quite difficult to germinate; it might be more convenient to propagate stevia through stem cuttings or purchase stevia seedlings directly.

Complete Guide to Diabetes-Friendly Sugar Substitutes

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Today, it is easier than ever to cook and bake with sugar substitutes thanks to the wide variety of products available.

It wasn’t so long ago that most available sugar substitutes had strong off-flavors or, even worse, unfortunate gastrointestinal effects. (Check out the hilarious and horrifying review comments on this Amazon listing for the maltitol syrup-sweetened sugar-free gummy bears to see why the fear is very real.)

Nowadays there are so many options that it’s tough to know where to begin. How do they impact blood glucose? Are they easy on one’s stomach?

Some of these sweeteners have been widely available for decades, and others have gained popularity only recently.

A note: we have excluded popular sugar alternatives like agave syrup and coconut sugar. These may or may not be healthier than pure sugar, but they definitely have an identical blood sugar impact. This article will concentrate on sweeteners that do not provoke a blood sugar increase, and are therefore of special interest for people managing diabetes. That said, some of the sweeteners on this list are more diabetes-friendly than others, depending on what your personal needs are.

Check them out:

The New Sugar Substitutes

If you’re new to low-carb, you might not be aware of how many good new options there are for sugar alternatives.

Allulose: 

Allulose may be our favorite zero-carb sweetener. The reasons are simple:

  1. Of every alternative sweetener we’ve tried, it tastes the best, which is to say that it tastes the most like true sugar. There is no aftertaste, no chemical flavor, no strange mouthfeel issues.
  2. It appears to have zero impact on blood sugar.

The science backs us up. In a 2018 study, allulose was actually found to slightly reduce the blood sugar of people with type 2 diabetes.

Allulose is not as sweet as sugar, but it works extremely well in baking recipes, and can even be turned into caramel.

Monk Fruit:

Monkfruit powder is another sugar alternative that we can recommend highly. It’s extremely popular in the keto community, especially when sold under the brand name Lakanto. The Lakanto company sells monk fruit sugar in multiple varieties, including brown sugar, granulated white sugar, powdered white sugar, and has a range of products, from maple sugar and chocolate sauce to brownie mixes.

Monk fruit comes from the lo han guo fruit, found in China. It does not impact blood glucose and does not seem to cause gastrointestinal symptoms in users. It’s much sweeter than sugar, so a little goes a long way. Low-carb bakers love the way it behaves in recipes.

Users should be aware that monk fruit products often contain a smaller amount of erythritol, for an improved flavor profile and usability.

Erythritol:

You’ll find this under many brands, most notably as Swerve. You can find granular, powdered, and brown sugar versions of erythritol, often formulated so as to offer a 1:1 replacement for sugar, making it easy to use for baking. Many popular low-carb or sugar-free recipes use Swerve.

Erythritol is a sugar alcohol. It is almost completely calorie-free and has no known impact on blood sugar.

PubChem states erythritol is two times as sweet as sucrose. While most people seem to tolerate it well, there are some reports of eaters experiencing gas or bloating, so it may be smart to watch how much you include in your diet.

Stevia:

Stevia is a newly popular alternative sweetener. You can find it in grocery stores as SweetLeaf, Pyure, Stevia in the Raw, and several other brands. Derived from the leaves of a plant native to South America, stevia is an all-natural sweetener that is several hundred times sweeter than sugar, according to the FDA. It is calorie-free and won’t raise blood sugar.

Stevia is divisive because many tasters find that it has a bitter aftertaste. Many low-carb eaters absolutely love it, though. If you’re buying low-sugar packaged foods that use stevia, be sure to check the ingredients, because it’s often combined with sugar.

There are actually different types of stevia, and one of our staff members strongly prefers a type called “Reb A,” which is made from only a certain extra-delicious part of the plant. If you’ve tried stevia and haven’t liked it, it might be worth looking for the Reb A variety.

Xylitol:

Xylitol is another sugar alcohol: it’s about as sweet as sucrose but lower in calories. It does raise blood glucose a little bit, which may make it a less optimal choice than its cousin erythritol. PubChem explains that xylitol is a five-carbon sugar alcohol that can be found naturally in many fruits and vegetables.

This sugar alcohol may cause gastrointestinal distress in some individuals at a certain threshold intake. It may be possible that once the body acclimates to the sweetener, more can be consumed with no unwanted side effects.

Xylitol is often found in candy and sugar-free gum because it inhibits the growth of bacteria in the mouth.

Beware: xylitol is extremely toxic to dogs, so probably not ideal for a pet owner.

Traditional Sugar Substitutes

You’re probably already familiar with the flavor of these – most of them have been ubiquitous for decades. In our opinion, the alternative sugars below are more likely to have strange flavors and chemically aftertastes, and they’re also less likely to be useful in low-carb baking recipes. But many people love them! And they also probably won’t raise your blood sugar.

Aspartame:

Found on the market as NutraSweet and Equal. According to the American Cancer Society, it is about 200 times sweeter than sugar and is not for those with phenylketonuria disease. It’s also calorie-free and does not raise blood sugar but is not recommended for use in cooking or baking.

Maltitol:

Maltitol is a sugar alcohol commonly used as a way to make foods “sugar-free.” It doesn’t make foods “carbohydrate-free” however, as it still affects blood glucose somewhat. An analysis on PubChem references a study that found that Malitol has 38% the blood sugar impact of pure sugar, and that it was absorbed more slowly. However, beware: this chemical is known to provoke gastrointestinal problems.

Saccharin:

Sold as Sweet and Low, Sweet Twin, Sweet’N Low, and Necta Sweet. According to the FDA, saccharin was discovered in 1879. It is 200-700 times sweeter than sugar and is not as popular as it used to be, due to its bitter aftertaste and difficulty for use in baking.

Sorbitol:

According to the PubChem Chemistry Database, “Sorbitol is a sugar alcohol found in fruits and plants with diuretic, laxative and cathartic property.” Also, it contains “one-third fewer calories and 60 % the sweetening activity of sucrose and is used as a sugar replacement in diabetes.” As you can see, sorbitol can be a laxative, and still raises blood sugar. Be aware of this when choosing sorbitol!

Sucralose:

This is most commonly known as the brand name Splenda. Sucralose is calorie-free and doesn’t raise blood sugar. It can be tricky to bake with due to how sweet it is (about 600 times sweeter than sugar).

Use What Works for You

When choosing a sugar substitute, your goal is to enjoy the flavor as much as possible while maintaining steady blood sugar levels and avoiding unpleasant side effects. Your own experience will be unique. Some people are sensitive to some of these sweeteners, and some are not, so individual results have to be prioritized. It’s also possible that you’ll have different blood sugar responses than predicted in this article. And in matters of taste, of course, there can be no disputes.

Alternative Sweeteners Can Alter the Gut Microbiome and Raise Blood Sugar Levels

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By Ross Wollen

August 24th, 2022

Are zero-calorie sweeteners really harmless? It’s a question of intense interest in the diabetes community, given how many of us rely heavily on diet soda, low-sugar meal replacements, stevia, allulose, and similar products.

These sugar alternatives bring a little sweetness to our lives without prompting significant or obvious blood sugar spikes, and they can be instrumental for happier, less stressful glucose control. These non-nutritive compounds are said to pass through the body without significant interaction with one’s metabolism. But more than a few studies have found that artificial sweeteners are associated with unfortunate metabolic outcomes like weight gain and poor glycemic control. Some of this evidence comes in the form of dubious observational research, but it’s still enough to make many of our readers nervous.

A new and high-quality study of the issue was published this month in Cell. A constellation of researchers have collaborated on a new randomized controlled trial (RCT) of four common sugar alternatives: aspartame, saccharin, sucralose, and stevia. The RCT is widely considered the gold standard of nutritional research: a costly and highly-controlled experiment that directly tests the effects of a food on human beings.

In the new trial, 80 healthy adults were split into groups of 20, and asked to eat six commercially available sweetener packets per day. An additional control group of 20 consumed only smaller amounts glucose, commonly used as a bulking agent in sweetener packets; a final control group of 20 had no sweeteners at all. The participants were very closely monitored throughout the experiment. They all wore continuous glucose monitors (CGMs) and took regular blood and glucose tolerance tests. The researchers even analyzed stool samples to check on any microbiome changes.

The results?

Two of the sweeteners, saccharin and sucralose, led to blood sugar spikes. When subjected to an oral glucose tolerance test, a test often used to diagnose diabetes, volunteers in the saccharin and sucralose groups had significantly steeper blood sugar rises. It appears that the sweetener itself did not necessarily raise blood sugar immediately, but instead that it significantly affected the ability to properly metabolize a sugary meal.

  • Saccharin is found in fewer food products these days, but it’s still the major component of pink packets of Sweet ‘N Low. It’s not listed as an ingredient in any of the major diet soda brands. For years it was thought that saccharin might cause cancer, for which the FDA once required warning labels.
  • Sucralose, most famously found in yellow packets of Splenda, is more common than saccharin. It’s an ingredient in certain diet soft drinks, including Diet Mountain Dew and Gatorade Zero and G2 drinks, as well as a variety of processed low-sugar foods and meal replacement powders.

The magnitude of these changes is unclear. The results were not reported in mg/dL or other measures familiar to people with diabetes, and analysis of CGM data had slightly different conclusions. None of the groups showed significant differences in A1C, blood pressure, or other metabolic parameters.

Although just two of the sweeteners affected glucose metabolism, all four were associated with significant changes in gut microbiome profiles, directly contradicting the idea that non-nutritive sweeteners are “inert” and pass through the body without interacting.

How can we know if the microbiome and blood sugar shifts were related to each other? To confirm a causal link between the two, the researchers took fecal samples from human participants and transplanted them into mice with completely sterile digestive tracts. The mice soon evinced extremely similar changes to their own blood glucose results. It’s a strong suggestion that the metabolic shifts resulting from sweetener consumption are a direct result of microbiome changes.

The study has already created something of a stir. Less scrupulous sources, like the New York Post, have announced in headlines that “artificial sweeteners could cause diabetes,” a contention that isn’t even remotely supported by the research itself.

Senior author Dr. Eran Elinav, an immunologist and microbiome researcher at the Weizmann Institute of Science and the German National Cancer Center (DKFZ), emphasized that the glycemic changes identified in the study occurred in “a highly personalized manner.” Different volunteers had different responses, and because we all have unique microbiomes, it’s impossible to predict exactly how any one of us might react to the same ingredients. The effects of the microbiome remain largely mysterious, and we are likely years away from the point where our unique colonies of microorganisms can be amended or harnessed in a targeted way.

As such, it’s difficult to know what to take away from the study. It’s possible that the results wouldn’t be the same in people with diabetes, and it’s possible that individual readers would not be among the “top responders” to saccharin or sucralose. The short duration of the study also limits its applicability. While the glucose-spiking effect was found to wear off in the week after volunteers stopped consuming their sweeteners, we don’t know what would happen after longer experiments, or whether a longer duration would result in more significant metabolic changes.

Non-nutritive sweeteners may be more impactful than originally suspected, but they certainly remain healthier than sugar. Dr. Elinav stressed that, despite the results of his study, sugar “is clearly most harmful to our metabolic health.” The study may reinforce readers already skeptical about sugar alternatives, or those that have already chosen natural alternatives like stevia, which was found to have no blood sugar impact.

Hopefully, future studies will subject trendy modern sugar alternatives like monkfruit and allulose to similar experiments. There is some preliminary evidence that allulose, one of our favorites, may actually reduce blood sugar levels.