What are the best No Calorie Sugar replacements

artificial-sweeteners
Excessive sugar consumption is suspected to be one of the main causes of obesity.

Rather than making the effort to eat healthy whole foods, many people look for an easy solution like popping some Garcinia Cambogia pills,using zero-calorie (non-nutritive) sweeteners instead of added sugar.

They are supposed to provide a sweet taste without any of the adverse health effects associated with too much sugar. Nonetheless, their safety is debated.

A recent article summarized the available evidence on the effects of non-nutritive sweeteners on glucose metabolism and appetite hormones. Here is a detailed summary.

Article Reviewed

This was a systematic review that included 44 human studies on the effects of non-nutritive sweeteners on glucose metabolism and appetite hormones.

Effects of the Non-Nutritive Sweeteners on Glucose Metabolism and Appetite Regulating Hormones: Systematic Review of Observational Prospective Studies and Clinical Trials.

What Are Non-Nutritive Sweeteners?

Non-nutritive sweeteners (NNS), often referred to as artificial sweeteners, are food additives that imitate the sweet taste of sugar without any calories.

Six NNS are currently approved for use in the US and Europe:

  • Acesulfame-K.
  • Advantame.
  • Aspartame.
  • Neotame.
  • Saccharin.
  • Sucralose.

There is also growing interest in naturally-derived NNS, such as steviol glycosides(stevia) and luo han guo extract.

The following sections summarize the available evidence on the health effects of some of these NNS.

Bottom Line: Non-nutritive sweeteners, most of which are artificial sweeteners, imitate the taste of sugar without any additional calories.

Acesulfame K

Härtel BG, et al. The influence of sweetener solutions on the secretion of insulin and blood glucose level. Ernährungsunschau, 1993.

This crossover study in 14 healthy people compared the effects of 165 mg of acesulfame K mixed in water to water only. Acesulfame K did not affect insulin or blood sugar levels.


Bryant CE, et al. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. European Journal of Clinical Nutrition, 2014.

This crossover study in 10 healthy individuals examined the effects of 85 mg of acesulfame K to 45 grams of glucose.

Consuming acesulfame K did not significantly affect glucose or appetite sensations, compared to glucose only.


Steinert RE, et al. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. The British Journal of Nutrition, 2011.

This crossover study in 12 healthy individuals compared the effects of an intragastric infusion to 50 grams of glucose, 25 grams of fructose or 220 mg of acesulfame K.

Acesulfame K did not affect glucose, insulin, glucagon-like peptide 1 (GLP-1), peptide YY, ghrelin or appetite sensations, compared to water.


Olalde-Mendoza L, et al. Modification of fasting blood glucose in adults with diabetes mellitus type 2 after regular soda and diet soda intake in the State of Queretaro, MexicoArchivos Latinoamericanos de Nutricion, 2013.

This randomized trial in 40 people with type 2 diabetes (T2D) showed that drinking 200 ml of diet soda containing a 40 mg mix of aspartame and acesulfame K did not affect glucose levels, compared to a regular soda.


Brown RJ, et al. Effects of diet soda on gut hormones in youths with diabetes.Diabetes Care, 2012.

This crossover study recruited 9 participants with T1D, 10 with T2D and 25 healthy individuals as a control.

The study showed that drinking 240 ml of a diet soda sweetened with sucralose and acesulfame K increased levels of glucagon-like peptide 1 (GLP-1) by 43% in people with T1D and 34% in healthy individuals.

No effects were seen in participants with T2D. Additionally, the diet soda didn’t affect levels of glucose, C-peptidegastric inhibitory polypeptide (GIP) or peptide YY.

Bottom Line: Human trials suggest that acesulfame K has no adverse effects on blood sugar control or appetite.

Aspartame


Nehrling JK, et al. Aspartame use by persons with diabetes. Diabetes Care, 1985.

This study in 62 individuals with type 2 diabetes (T2D) showed that consuming 2.7 grams of aspartame every day for 18 weeks did not affect blood sugar levels or HbA1c, compared to a placebo.


Okuno G, et al. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics. Diabetes Research and Clinical Practice, 1986.

These were two small crossover trials. The first trial showed that a single 500 mg-dose of aspartame lowered blood sugar 2–3 hours afterward, compared to 100 grams of glucose.

The second study found that consuming 125 mg of aspartame for two weeks had no effects, compared to 50 grams of glucose.

In these studies, aspartame did not significantly affect insulin, glucagon, triglycerides, total cholesterol or HDL cholesterol.


Colagiuri S, et al. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus. The American Journal of Clinical Nutrition, 1989.

This small study in nine diabetics showed that taking 162 mg of aspartame every day for 6 weeks did not affect glucose, HbA1c, body weight, total cholesterol, HDL cholesterol or triglycerides, compared to taking 45 grams of sucrose.


Rodin J. Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrientintake. The American Journal of Clinical Nutrition, 1990.

This crossover trial included 12 overweight and 12 normal-weight adults. On separate visits, the researchers tested the effects of 50 grams of glucose, 50 grams of fructose or 250 mg of aspartame. They also consumed 500 ml of water.

They detected no significant differences in glucose, insulin, glucagon, free fatty acids or calorie intake (at a subsequent lunch) between groups, or compared to water only.


Melanson KJ, et al. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. The British Journal of Nutrition, 1999.

This small crossover study in 10 healthy men showed that drinking an aspartame-sweetened beverage reduced blood sugar levels in 40% of the participants, whereas they increased them 20% and remained stable in the rest.

Aspartame did not affect calorie intake at a subsequent meal.


Hall WL, et al. Physiological mechanisms mediating aspartameinduced satiety.Physiology & Behavior, 2003.

This small crossover trial in six participants investigated the effects of taking either 400 mg of aspartame, 176 mg of aspartic acid combined with 224 mg of phenylalanine or 400 mg of corn flour as a placebo.

The researchers found that levels of glucagon-like peptide 1 (GLP-1) were significantly lower after taking either aspartame or the amino acids (aspartic acid and phenylalanine).

However, aspartame did not affect glucose, insulin, gastric inhibitory polypeptide (GIP), cholecystokinin, gastric emptying or appetite.


Maersk M, et al. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. European Journal of Clinical Nutrition, 2012.

This crossover study in 24 adults with obesity investigated the effects of drinking a soda sweetened with 500 ml of aspartame.

Consuming an aspartame-sweetened beverage did not affect glucose, insulin, ghrelin, GLP-1, gastric inhibitory polypeptide (GIP), appetite sensations, thirst or calorie intake at a buffet four hours afterward.


Härtel BG, et al. The influence of sweetener solutions on the secretion of insulin and blood glucose level. Ernährungsunschau, 1993.

This crossover study in 14 healthy people compared the effects of 165 mg of aspartame to 330 ml of water.

The study showed that glucose levels were in some cases slightly lower after consuming aspartame, compared to water. However, the differences were not clinically relevant.


Bryant CE, et al. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. European Journal of Clinical Nutrition, 2014.

This crossover study in 10 healthy individuals examined the effects of 150 mg of aspartame to glucose.

Consuming aspartame did not significantly affect glucose or appetite sensations, compared to glucose only.


Steinert RE, et al. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. The British Journal of Nutrition, 2011.

This crossover study in 12 healthy individuals compared the effects of an intragastric infusion of 50 grams of glucose, 25 grams of fructose or 169 mg of aspartame.

Aspartame did not affect glucose, insulin, glucagon-like peptide 1 (GLP-1), peptide YY, ghrelin or appetite sensations, compared to water.


Horwitz DL, et al. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care, 1988.

This study compared the effects of a beverage sweetened with 400 mg of aspartame to an unsweetened placebo.

Blood samples were taken regularly for three hours after consuming each beverage. The researchers found no significant differences in the levels of glucose, insulin or glucagon at any point in time.


Temizkan S, et al. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. European Journal of Clinical Nutrition, 2015.

This crossover study included eight people newly diagnosed with T2D and eight healthy people. It compared the effects of consuming 200 ml of water to water combined with 72 mg of aspartame.

Aspartame did not affect glucose, insulin, C-peptide or glucagon-like peptide 1 (GLP-1), compared to water.

Bottom Line: Aspartame did not adversely affect blood sugar control or appetite. Some studies suggest that aspartame may be useful for diabetics.

Saccharin


Cooper PL, et al. Sucrose versus saccharin as an added sweetener in noninsulin-dependent diabetes: short- and medium-term metabolic effects.Diabetic Medicine: A Journal of the British Diabetic Association, 1988.

This crossover study in 17 people with non-insulin dependent diabetes showed that taking 30 grams of saccharin combined with starch every day for 6 weeks did not affect glucose, insulin or triglycerides.


Suez J, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 2014.

This small trial in seven people showed that taking saccharin (2.3 mg per pound, or 5 mg per kg, of body weight) every day for 6 days, increased blood sugar levels in four of the participants.

When the feces of some of these four participants were transplanted into mice, their blood sugar levels increased as well. However, this study didn’t include a control group and therefore doesn’t prove that saccharin caused these effects.


Härtel BG, et al. The influence of sweetener solutions on the secretion of insulin and blood glucose level. Ernährungsunschau, 1993.

This crossover study in 14 healthy people compared the effects of 75 mg of saccharin to 330 ml of water.

The researchers found that glucose levels were in some cases slightly lower after consuming saccharin, compared to water. However, the differences were not clinically relevant.


Bryant CE, et al. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. European Journal of Clinical Nutrition, 2014.

This crossover study in 10 healthy individuals compared the effects of 20 mg of saccharin to 45 grams of glucose.

Consuming saccharin did not significantly affect glucose or appetite sensations, compared to glucose only.


Horwitz DL, et al. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care, 1988.

This study tested the effects of a beverage sweetened with 135 mg of saccharin to an unsweetened placebo.

Blood samples were taken regularly for three hours after consuming the beverage. The researchers found no significant differences in the levels of glucose, insulin or glucagon at any time point.

Bottom Line: There is limited evidence that saccharin has adverse effects on blood sugar control or appetite. One study suggests that saccharin may increase blood sugar levels by affecting the gut microbiota.

Stevia


Gregersen S, et al. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism: Clinical and Experimental, 2004.

This crossover trial in 12 people with type 2 diabetes showed that 1 gram of stevioside added to a 412 calorie breakfast reduced the rise in blood sugar levels in 18% of the participants.

Stevioside also increased the ratio of insulin to glucose (the insulinogenic index). In contrast, stevioside did not affect insulin, glucagon, glucagon-like peptide 1 (GLP-1) or gastric inhibitory polypeptide (GIP).


Barriocanal LA, et al. Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics.Regulatory Toxicology and Pharmacology, 2008.

This was a randomized controlled trial in 76 people — 30 with T2D, 16 with T1D and 30 healthy individuals.

It showed that taking 250 mg of steviol glycosides every day for three months did not affect glucose, insulin or HbA1c, compared to a placebo.


Maki KC, et al. Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 2008.

This randomized controlled trial in 122 people with diabetes examined the health effects of taking 1000 mg of rebaudioside A (a steviol glycoside) for four months.

The study showed that rebaudioside A did not affect glucose, insulin, HbA1c, C-peptide, body weight, blood pressure or blood lipids.


Anton SD, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite, 2010.

This crossover study in 19 normal-weight and 12 obese adults examined the acute effects of tea sweetened with sucrose, stevia or aspartame. The quantity of each sweetener was not specified.

Stevia reduced glucose and insulin levels, compared to sucrose. In contrast, there were no significant differences in hunger, satiety or fullness at a subsequent meal.

Bottom Line: Stevia may have benefits for blood sugar control, and there is no evidence of any harmful effects.

Sucralose

Mezitis NH, et al. Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care, 1996.

This crossover study included 13 people with type 1 diabetes and 13 with type 2 diabetes. On two separate visits, the participants took a single 1000 mg capsule of sucralose or a placebo, followed by a standard liquid breakfast.

Sucralose did not affect the levels of blood sugar or C-peptide for four hours afterward, compared to a placebo.


Grotz VL, et al. Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Journal of the American Dietetic Association, 2003.

This large randomized controlled trial recruited 128 participants with T2D. It showed that taking 667 mg of sucralose every day for 13 weeks did not affect glucose, C-peptide or HbA1c, compared to a placebo.


Ma J, et al. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. American Journal of Physiology Gastrointestinal and Liver Physiology, 2009.

This small crossover trial in seven healthy adults showed that intragastric infusions of up to 800 mg of sucralose did not affect glucose, insulin, GLP-1, gastric inhibitory polypeptide (GIP) or gastric emptying, compared to a saline solution.


Ma J, et al. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. The British Journal of Nutrition, 2010.

This study in 10 healthy people tested the effects of injecting 960 mg of sucralose into the duodenum. Sucralose infusion did not significantly affect glucose or glucagon-like peptide 1 (GLP-1), compared to saline.


Ford HE, et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. European Journal of Clinical Nutrition, 2011.

This small crossover study in eight healthy individuals examined the acute effects of 50 ml of water, sucralose or maltodextrin combined with sucralose.

Sucralose did not affect glucose, insulin, GLP-1, peptide YY, food intake, appetite or brain responses, compared to a placebo.


Brown AW, et al. Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women. Nutrition Research, 2011.

This small crossover study in eight women showed that consuming 6 grams of sucralose did not affect glucose, insulin, glucagon, triglycerides, ghrelin, appetite sensations or general wellbeing, compared to water.


Wu T, et al. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. The American Journal of Clinical Nutrition, 2012.

This crossover study in 10 healthy individuals showed that consuming 60 mg of sucralose did not affect glucose, insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP) or gastric emptying, compared to 40 grams of glucose.


Pepino MY, et al. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care, 2013.

This study in morbidly obese people showed that 48 mg of sucralose increased blood sugar and insulin levels and impaired insulin sensitivity by 23%.

In contrast, sucralose did not affect GLP-1, gastric inhibitory polypeptide (GIP), glucagon or the pancreatic response.


Steinert RE, et al. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. The British Journal of Nutrition, 2011.

This crossover study in 12 healthy individuals compared the effects of an intragastric infusion of 50 grams of glucose, 25 grams of fructose or 62 mg of sucralose.

Sucralose did not affect glucose, insulin, glucagon-like peptide 1 (GLP-1), peptide YY, ghrelin or appetite sensations, compared to water.


Temizkan S, et al. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. European Journal of Clinical Nutrition, 2015.

This crossover study included eight people newly diagnosed with T2D and eight healthy people. It compared the effects of consuming 200 ml of water to water combined with 24 mg of sucralose.

The researchers found that sucralose lowered glucose levels and increased glucagon-like peptide 1 (GLP-1) in healthy participants, compared to water. In contrast, sucralose did not affect insulin and C-peptide.

Bottom Line: There is no solid evidence that sucralose adversely affects blood sugar control or appetite. One study showed that sucralose impaired insulin sensitivity in severely obese people.

Observational Studies on the Total Intake of Non-Nutritive Sweeteners

Several observational studies have investigated the association of total non-nutritive sweetener intake (NNS) with metabolic disorders, mainly type 2 diabetes (T2D). Here are summaries of their results.


One report using data from a study including more than 70,000 women showed that a high intake of caffeinated, artificially sweetened beverages was associated with an increased risk of T2D (1).

However, this association was lost when the researchers adjusted for body mass index (BMI) and calorie intake. In other words, those who consumed the most NNS from caffeinated beverages had a higher BMI, explaining the links with T2D.


In another study based on data from the Nurses Health Study II, researchers found no significant association between NNS intake and T2D (2).


Similar studies have also investigated this association in men.

Data from the Health Professionals Follow-Up Study, including more than 40,000 men, showed that a high intake of NNS was significantly linked with an increased risk of T2D, but the association was lost after an adjustment for BMI (3).


The largest observational study examining the link between total NNS intake and T2D was the European Prospective Investigation into Cancer and Nutrition (EPIC) study. It was conducted in eight countries and included 340,234 subjects (4).

The study reported a significant association between NNS intake and T2D. But once again, this link was lost after an adjustment for BMI and calorie intake.


Several other smaller observational studies have investigated the links between NNS intake and metabolic disease.

The Black Women’s Health Study, which included 43,960 African American women, found no significant links between NNS intake and T2D (5).


Three studies showed that a high intake of NNS was associated with metabolic syndrome. However, they didn’t take BMI or fat mass into account (678).


One study found that drinking a lot of diet soda was linked with an increased risk of metabolic syndrome and T2D.

Again, the association with metabolic syndrome was lost after adjusting for BMI and waist circumference. However, while the link to T2D weakened after adjustment, it remained significant (9).


Another study in 66,118 French female teachers showed that drinking more than 20 oz of artificially sweetened beverages per week was linked with a higher risk of T2D, even after adjusting for BMI (10).


Among 2,337 Japanese factory workers, consuming one or more servings of diet soda per week was associated with a higher risk of T2D, compared to those who didn’t drink diet soda (11).

The association remained significant after adjusting for multiple variables.


In the EPIC-Norfolk Study, which included 24,653 adults, drinking more than 336 g of artificially sweetened beverages per day was associated with an increased risk of T2D (12).

However, this link was lost after adjusting for BMI and waist circumference.


Other studies looked at the links between obesity and NNS intake. They showed that obese people and those gaining weight were more likely to consume artificially sweetened beverages (13).


Two meta-analyses have examined the connection between drinking artificially sweetened beverages and T2D.

One analysis included four studies with healthy participants. It reported that drinking 330 ml of artificially sweetened beverages a day increased the risk of T2D.

However, the relative risk (RR) was small or only 1.13. In other words, those who consumed 330 ml of artificially sweetened beverages per day were only 1.13 times more likely to develop TD2, compared to those who didn’t consume them (14).

Another analysis included 10 studies. It found artificial sweeteners increased the risk of T2D (RR = 1.48). However, the association was lost after adjusting for BMI (15).

Bottom Line: Studies indicate people who consume NNS are at an increased risk of metabolic disease, but the link is usually lost after adjusting for fat mass.

Summary and Real-Life Application

Although some observational studies show a significant link between high intakes of NNS and type 2 diabetes, the association is generally lost after an adjustment for fat mass or BMI.

People who are overweight or obese and at risk of developing diabetes or metabolic disorders have a tendency to choose diet sodas sweetened with zero-calorie sweeteners. This likely explains the findings of many observational studies.

Accordingly, the majority of randomized controlled trials have not found any signs of adverse effects. However, many trials are small and flawed in design.

One study found that sucralose reduced insulin sensitivity in morbidly obese individuals. Further trials need to confirm its findings.

Additionally, a few trials found that artificial sweeteners lowered blood sugar or insulin levels, compared to sugar, which benefits people with poor blood sugar control.

Taken together, there is currently no strong evidence linking non-nutritive sweeteners (NNS) with adverse changes in glucose metabolism or appetite in humans when they are eaten in acceptable amounts.