7 Stevia Side Effects: Is It Safe?

Stevia | Good or Bad | Keto | Fasting | Insulin | Side Effects

Fitness gurus especially endorse stevia as natural and healthy. According to this, stevia leaf extract is supposed to replace sugar without any side effects.

Moreover, people claim that stevia lowers calorie intake and blood sugar levels and is healthy for diabetics.

Nevertheless, there are concerns about the potential side effects of stevia. In this article, I examine stevia to determine if the plant-based sweetener is harmful.

Is Stevia Bad for You?

More than 200 years ago, indigenous peoples in South America’s jungles discovered a shrub with leaves with an incredibly sweet taste.

It was not until 1905 that this shrub, which belongs to the sunflower or Asteraceae family, was named Stevia rebaudiana.

The extract made from the sweet leaves of this plant became known over time as the sweetener stevia.

The indigenous people of South America consumed the calorie-free sugar substitute as a sweetener in tea or chewed the leaves as candy. Therefore, they called it candy leaf.

Due to steviol glycosides, pure stevia extract is about 250-300 times sweeter than the same amount of table sugar (Ashwell 2015¹).

Although the plant is experiencing its heyday as a sweetener in western countries, it was used primarily for contraception by the indigenous population in Paraguay, where it originated (Schvartzman et al. 1977²).

Accordingly, the exotic plant has quite a controversial application as an indigenous medicinal herb.

Is the sweetleaf, therefore, the dream of all those with a sweet tooth? Is it possible that Stevia extract is extremely sweet and healthy simultaneously?

What Is in Stevia?

The stevia plant contains the following steviol glycoside compounds that give its leaves the enormous sweetness, which is indicated here as many times that of sugar:

• Stevioside: 150-300
• Rebaudioside A to F: 50-400
• Rubusoside: 110
• Steviolmonoside: N/A
• Steviolbioside: 100-125
• Dulcoside A: 50-120

You can find rebaudioside A and stevioside in the most significant amounts in stevia leaves.

Refined stevia extract can consist of either one or a mixture of different steviol glycoside compounds that define its sweetness (Ashwell 2015³).

The end product of stevia metabolism is steviol. The metabolized components leave the body (Momtazi-Borojeni et al. 2017⁴).

Although stevia is extracted from a plant, it is not a thoroughly natural product as the food industry sells it to us.

Stevia, as we know it, is a highly-processed industrially-produced sweetener. Therefore, many people view stevia as an artificial sweetener as well.

Moreover, food authorities have only approved industrially isolated steviol glycosides as additives. In contrast, they did not approve stevia plants, leaves, or unrefined natural stevia as sweeteners (FDA 2018⁵).

Since the European Commission has approved it, you can find stevia extract in numerous processed foods (Denina et al. 2014⁶).

Therefore, you can also find stevia as additive number E960 on the packaging.

In this sense, there is no significant difference compared to table sugar, obtained from the natural sugar beet.

The main difference is that stevia has no calories or carbohydrates. Therefore, the sweetener should hardly increase blood sugar levels, which could be a fundamental advantage.

Due to the following questions people frequently ask in this context, we will look at blood sugar and insulin levels in more detail.

Is Stevia Keto?

You may wonder if stevia is so healthy in the end that it has no consequences for your diet.

One of the most common questions is whether the intense sweetness of steviol glycosides could throw you out of ketosis on a low-carb, high-fat diet.

Unfortunately, no direct research can answer this question unequivocally since stevia studies have been conducted mainly on laboratory mice.

In any case, keto exploits the fact that proteins and carbohydrates stimulate insulin, but fat hardly does.

But insulin storage hormone blocks the enzyme that breaks down body fat (Meijssen et al. 2001⁷).

Consequently, the ketogenic diet aims to keep insulin levels low to allow the body to empty carbohydrate stores.

Since the carbohydrates stored as glycogen represent the faster usable energy source, the body uses them first.

The body can tap into stored fat for energy production through ketosis.

In the context of stevia, what matters for ketosis is whether the sweetener can influence insulin levels. Moreover, we find a similar constellation in fasting.

Is Stevia Safe for Fasting?

Although not all people may be aware of this, ketosis is also why fasting brings about weight loss.

Accordingly, fasting is the more radical ketogenic diet. If you don’t eat for long, your body will have to tap into its fat reserves sooner or later.

But that’s nothing else than a natural survival mechanism. Winter body fat has to have some real purpose, right?

When stevia causes an insulin response, the sweetener has the potential to break a fast. Therefore, our essential storage hormone is also the crux of the matter in this context.

For this reason, we need to look closely at stevia and insulin.

Does Stevia Spike Insulin?

In the context of sweeteners, most people only examine the glucose response. But this view is too limited to be meaningful.

Ultimately, insulin production is not only stimulated by blood glucose. And at the end of the day, insulin is crucial as a signaling agent for fat gain.

Researchers can already predict about 75% of the gain and loss in overweight people using insulin levels (Kong et al. 2013⁸).

So with this in mind, it is not enough for a sweetener to have no calories or carbohydrates. On that basis, we cannot determine if stevia is good or bad for you.

With countless studies concluding that sweeteners in diet soda are a cause rather than a remedy for the ongoing obesity epidemic, we need to examine stevia in this regard (Fowler et al. 2008⁹).

Does Stevia Have More Side Effects Than Other Sweeteners?

Many want to know if stevia is a safe sugar substitute in beverages. For this reason, I have compared stevia to all the other common sweeteners. Let’s see if stevia is the less harmful sugar based on science.

Stevia vs. Sugar

Unlike sucrose, stevia extract does not provide carbohydrates.

Therefore, stevia extract cannot raise blood sugar levels as abruptly as sugar. But this does not necessarily mean that the sweetener does not affect blood sugar and insulin levels.

According to a well-known study, many claim that stevia does not affect blood sugar or insulin levels.

Sugar indeed causes higher glucose and insulin spikes immediately after consumption.

But even the much-cited study shows that levels change after about 90 minutes. From then on, blood glucose and insulin levels are higher after stevia than after sugar consumption (Anton et al. 2010¹⁰).

In contrast, a more recent study came to a different conclusion, examining the period of three rather than two hours after ingestion. Moreover, it involved sweetened beverages – not food.

Although sugar initially caused higher responses, stevia triggered as much insulin over three hours.

Besides, it is perplexing that the stevia and sugar group’s average blood glucose levels were the same (Tey et al. 2017¹¹).

But it gets even more interesting, as another study states that steviol glycosides stimulate insulin release directly in the pancreas (Jeppesen et al. 2000¹²).

Furthermore, researchers have recently studied the molecular structure of steviol and stevioside. They concluded that steviol glycosides are confusingly similar to insulin.

Therefore, like insulin, they can signal cells to take up glucose (Bhasker et al. 2015¹³).

For this reason, people like to tout that stevia regulates blood glucose and thus could play a role in fighting diabetes (Mohd-Radzman et al. 2013¹⁴).

But there is a significant problem since people develop insulin resistance and diabetes due to consistently elevated insulin levels. Therefore, stevia might enhance the risk of developing metabolic disorders.

Aspartame vs. Stevia

As a decades-old ingredient in diet soda, aspartame, or E951, is the best-known synthetic sweetener. That’s why it sets the bar for its plant-based competitor.

One study compared blood sugar and insulin levels after consuming stevia, sugar, and aspartame during a meal.

In the process, synthetic aspartame increased insulin levels even more than table sugar.

Thirty minutes after consumption, the meal sweetened by aspartame caused an absolute peak level that conventional sugar could not reach.

Also, blood sugar was highest with aspartame after 30 minutes, although it did not initially rise as steeply as after sugar consumption.

In contrast, people who consumed stevia showed the weakest responses during the short period (Anton et al. 2010¹⁵).

A more recent study, as previously addressed, showed no significant differences among the three sweeteners over three hours after consumption of a sweetened beverage (Tey et al. 2017¹⁶).

In summary, aspartame is about as unhealthy as sugar.

Due to its lower peak levels, stevia performs better in direct comparison to aspartame and sugar.

But is there another difference between plant-based and artificial sweeteners?

Sucralose vs. Stevia

Besides aspartame, there is another prominent and globally used artificial sweetener called sucralose. You can identify it among additives as E number 955.

It, too, has no carbohydrates, proteins, or calories.

A study published in the journal Diabetes Care compared drinking water with and without sucralose.

It found that drinking the sweetener increased glucose and insulin levels in the subjects (Pepino et al. 2013¹⁷).

In particular, the significant effect on blood glucose makes sucralose the worse option than stevia when losing weight.

Splenda vs. Stevia

Splenda is nothing more than a widely used sweetener based primarily on sucralose.

It is available in the form of yellow packets that resemble conventional sugar. Due to the reasons mentioned above, stevia is probably the better option for weight loss.

However, the manufacturer Splenda also recognized the hype surrounding the natural sweetener. For this reason, it has launched Splenda Naturals.

Ultimately, this sweetener veteran wants to profit from stevia’s plant-based and healthy image. But it is interesting to note that Splenda Naturals consists only partially of stevia extract.

On the other hand, the lion’s share is the sugar alcohol erythritol.

Erythritol vs. Stevia

Erythritol, like stevia, is sold as a natural sugar substitute. Nevertheless, it is produced from carbohydrates through industrial processes.

Sugar alcohols differ significantly from steviol glycosides in that they are not calorie-free. Instead, they represent dietary fiber and are labeled as such on the packaging.

The human body cannot absorb these anti-nutrients. However, intestinal bacteria can feed on them to a small extent.

Therefore, about 90% of the sweetener leaves the body unchanged (Noda et al. 1994¹⁸).

Also, no significant increase in glucose and insulin levels has yet been observed with erythritol over a more extended period after ingestion (Bornet et al. 1996¹⁹).

At first glance, this makes erythritol the better choice concerning insulin response.

However, since few researchers have studied erythritol, you should handle this information carefully.

Monk Fruit vs. Stevia

Monk fruit has a similar effect to stevia. As for the green leaves, monk fruit is extremely sweet and adds about 200 times the sweetness to beverages compared to sugar.

It also performed similarly in a recent study.

Over three hours after their ingestion, researchers could not find significant differences in glucose and insulin concentrations between beverages sweetened with monk fruit extract, stevia, and sugar (Tey et al. 2017²⁰).

Like stevia-, monk fruit extract can also cause cravings due to its intense sweetness (Yang 2010²¹).

The bottom line is that the two natural sweeteners are equally healthy regarding weight loss.

Truvia vs. Stevia

Truvia is nothing more than the name of a stevia product manufactured by an international soda pop giant.

The composition of the sweetener sold as natural is similar to that of Splenda Naturals. In addition to stevia extract, erythritol represents a significant portion of the sweetener.

For this reason, Truvia is not a zero-calorie sweetener, as its nutritional claims already indicate.

If we trust the low review of erythritol, Truvia may be a better option than stevia regarding insulin production and weight loss.

Since steviol glycosides are similar to insulin in chemical structure, they may dock directly to insulin receptors.

They may also increase insulin secretion, especially when blood glucose levels are high (Jeppesen et al. 2000²²).

While this helps to lower blood glucose again, it can promote fat gain.

For these reasons, stevia is not as well suited for ketogenic diets as its proponents claim.

Thus, the insulinotropic properties of steviol glycosides may kick you out of ketosis (Bhasker et al. 2015²³).

A sweetened beverage may not be enough for this. When used in a meal, this effect is more likely.

In my opinion, stevia might also be able to break a fast. For this reason, I would stick with unsweetened tea during fasting.

Like other sweeteners, stevia is therefore not healthy for weight loss, which we will see in detail in a moment in the context of potential side effects.

Side Effects of Stevia

In connection with insulin, we have already found that steviol glycosides have a hormone structure. That’s a property calling for a prescription rather than free availability in the supermarket.

Nevertheless, most toxicological studies state that stevia is safe (Momtazi-Borojeni et al. 2017²⁴).

However, unlike other non-caloric sweeteners, studies suggest that stevia is biologically active (Ruiz-Ruiz et al. 2017²⁵).

From a pharmacological perspective, steviol glycosides are said to have numerous benefits. Accordingly, they may have the following effects (Momtazi-Borojeni et al. 2017²⁶):

• Anti-inflammatory
• Anticancer
• Antidiabetic
• Antimicrobial
• Antioxidant
• Blood pressure-lowering

However, the caveat is that further studies are needed to prove these potential effects and their magnitude.

Nevertheless, there are two sides to this coin as well. The stevia plant’s bioactive substances can not only be healthy but also induce dangers.

For this reason, legitimate questions arise regarding the potential side effects of stevia.

1. Cancer

Most toxicological studies state that stevia does not cause carcinogenic or malignant effects (Momtazi-Borojeni et al. 2017²⁷).

Nevertheless, isolated studies suggest that stevia extract may cause genetic mutations and increase cancer risk, even when high doses are used (Terai et al 2002²⁸).

In summary, the cancer risk from stevia appears to be relatively low compared to other artificial sweeteners.

2. Kidneys

Stevia is known to be a diuretic. Accordingly, it promotes the excretion of water and electrolytes through urine.

Although concerns have been repeatedly raised that stevia could be potentially harmful to the kidneys, a study reached a controversial conclusion.

According to the researchers, stevia is a legitimate candidate for a drug to treat kidney disease because it can reduce cyst growth in kidney cells (Yuajit et al. 2013²⁹).

3. Diabetes

Even supposedly natural sweeteners can affect metabolism.

When a sweet taste stimulates the reward center, the brain expects glucose, which does not enter the bloodstream with a calorie-free sweetener. As a result, sweeteners induce cravings for sweets (Yang 2010³⁰).

For this reason, long-term consumption of intense zero-calorie sweeteners like stevia can cause metabolic syndrome and type 2 diabetes (Swithers 2013³¹).

But isn’t stevia the sweetener said to help with diabetes?

This claim may be valid, but the devil is in the details here. According to studies, stevia consumption directly affects beta cells of the pancreas and, thus, insulin secretion (Jeppesen et al. 2000³²).

Accordingly, steviol glycosides enhance insulin secretion depending on the current blood glucose level (Abudula et al. 2008³³).

For this reason, stevia has a blood glucose-lowering effect similar to exogenous insulin injection in type 2 diabetics. Since people with type 1 diabetes lack beta cells due to the disease, stevia cannot affect them.

Thus, stevia alleviates a significant symptom of type 2 diabetes. However, high insulin levels cause type 2 diabetes and pre-disease insulin resistance.

For this reason, permanent consumption of stevia can aggravate type 2 diabetes. In contrast, only permanent lifestyle and dietary changes can reverse the disease.

4. Weight Gain

Since steviol and stevioside have a similar molecular structure to insulin, they might promote fat gain (Bhasker et al. 2015³⁴).

Finally, the storage hormone insulin signals muscle cells to consume glucose from the bloodstream and fat cells to store it as energy reserves.

And fat cells, of all things, cannot become insulin resistant. Therefore, stevia could support weight gain, especially for people who already suffer from pre-diabetes.

That stevia stimulates insulin secretion, especially when blood sugar is already high, and is also not conducive to weight loss (Jeppesen et al. 2000³⁵).

Since stevia is often used as a sugar substitute in baking, the sweetener usually enters the body in the company of large amounts of carbohydrates.

Due to the insulin spike, this use supports storage as body fat, which might significantly affect insulin resistance cases.

5. Fertility

Indigenous peoples of South America traditionally use stevia not as a sweetener but as a contraceptive (Schvartzman et al. 1977³⁶).

As early as 1968, researchers found that an aqueous solution prepared by decocting stevia leaves significantly reduced fertility in female rats.

In this regard, the reduction in fertility persisted for at least 50 to 60 days after ingesting the stevia water without affecting the animals’ health (Planas et al. 1968³⁷).

Although a recent study found no significant impairment of pregnancies and births in rats that consumed stevia over an extended time, the above concerns argue against continued stevia consumption (Saenphet et al. 2006³⁸).

This might be more obvious when we look at the hormone level’s effects.

While stevia boosts the production of the hormone progesterone, it also blocks progesterone receptors.

Thus, the hormone can no longer deliver its message by binding to a receptor.

Therefore, although the sweetener is of natural origin, stevia cannot generally be considered safe, according to the researchers (Shannon et al. 2016³⁹).

Progesterone is essential for maintaining pregnancy and regulating the menstrual cycle and fertility.

Thus, stevioside and rebaudioside A are technically progesterone receptor antagonists. These substances are used clinically as contraceptives and to terminate a pregnancy.

For this reason, indigenous peoples in Paraguay and Brazil traditionally used the stevia plant as a contraceptive.

6. Testosterone

In the context of insulin and progesterone, we have already learned that stevia can interfere with the hormonal system.

Furthermore, stevia might affect not only female but also male fertility.

Accordingly, a study on male rats records that stevia consumption can negatively affect the development of sexual organs, sperm concentration, and testosterone levels (Melis 1999⁴⁰).

7. Gut Health

The antimicrobial properties of stevia are usually hailed as healthy (Momtazi-Borojeni et al. 2017⁴¹).

However, the bactericidal effects of steviol glycosides may also have drawbacks (Wang et al. 2018⁴²).

Recent studies show that stevia, like other artificial sweeteners, can alter the gut microbiome (Ruiz-Ojeda et al. 2019⁴³).

Furthermore, stevioside and rebaudioside A could dramatically reduce the growth and activity of six Lactobacillus reuteri strains (Denina et al. 2014⁴⁴).

Since these bacteria are essential probiotics, the effects of stevia on gut flora raise significant health concerns.

8. Diarrhea

Since many stevia products, such as Splenda Naturals or Truvia, contain sugar alcohols in addition to stevia extract, they can cause digestive problems.

In most cases, the sugar alcohols that can cause diarrhea and bloat are listed either by name or as dietary fiber on the package.

How Much Stevia Is Too Much?

According to the WHO, 4 milligrams of steviol per kilogram of body weight per day are the safe upper limit for stevia consumption.

Although this may seem minor at first glance, for a person weighing 70 kilograms, that’s about 40 packets of stevia sweetener per day.

Because 12 milligrams of highly concentrated stevia extract are needed to consume 4 milligrams of steviol, the result is pretty high (Ashwell 2015⁴⁵).

Since the acceptable intake of stevia per day, the WHO didn’t research what we would consider the most significant side effects today, 40 packets of stevia might be more than questionable.

Stevia Side Effects Can Be Bad for You

Unlike some artificial sweeteners, Stevia can most likely be neither carcinogenic nor harmful to the kidneys.

Nevertheless, one cannot deny the pharmacological effect of stevia.

Therefore, recent studies suggest that stevia may affect the following functions and components of the human body:

• Hormone balance
• Fertility
• Gut microbiome

Ultimately, no human studies examine the full range of stevia side effects – especially none that address fertility.

Although occasional consumption of small amounts of stevia is unlikely to cause severe side effects, I would not use the sweetener daily.

Stevia Side Effects FAQ

What are the negative effects of stevia?

The main disadvantages of stevia are that the sweetener can affect hormone balance, fertility, and intestinal flora.

Is stevia as bad as artificial sweeteners?

Stevia might be as bad as artificial sweeteners, especially for people with problems with hormone balance, fertility, or intestinal flora.

Is stevia safer than Splenda?

Stevia is probably safer than Splenda. But it might be the worse choice for people with hormone balance, fertility, or gut health issues.

Is stevia worse than sugar?

A general disadvantage of stevia 🍬 is that it can fuel cravings and alter the gut microbiome. From this point of view, it might be worse than sugar.

Studies

#1-7

¹Ashwell M. Stevia, Nature’s Zero-Calorie Sustainable Sweetener: A New Player in the Fight Against Obesity. Nutr Today. 2015 May;50(3):129-134. doi: 10.1097/NT.0000000000000094. Epub 2015 May 14. PubMed PMID: 27471327; PubMed Central PMCID: PMC4890837.

²Schvartzman JB, Krimer DB, Moreno Azorero R. Cytological effects of some medicinal plants used in the control of fertility. Experientia. 1977 May 15;33(5):663-5. doi: 10.1007/BF01946562. PubMed PMID: 862810.

³Ashwell M. Stevia, Nature’s Zero-Calorie Sustainable Sweetener: A New Player in the Fight Against Obesity. Nutr Today. 2015 May;50(3):129-134. doi: 10.1097/NT.0000000000000094. Epub 2015 May 14. PubMed PMID: 27471327; PubMed Central PMCID: PMC4890837.

⁴Momtazi-Borojeni AA, Esmaeili SA, Abdollahi E, Sahebkar A. A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Curr Pharm Des. 2017;23(11):1616-1622. doi: 10.2174/1381612822666161021142835. Review. PubMed PMID: 27784241.

⁵FDA. Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States. Silver Spring: Food and Drug Administration, 2018. Retrieved 2021 Feb 22, from https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states.

⁶Deniņa I, Semjonovs P, Fomina A, Treimane R, Linde R. The influence of stevia glycosides on the growth of Lactobacillus reuteri strains. Lett Appl Microbiol. 2014 Mar;58(3):278-84. doi: 10.1111/lam.12187. Epub 2013 Nov 19. PubMed PMID: 24251876.

⁷Meijssen S, Cabezas MC, Ballieux CG, Derksen RJ, Bilecen S, Erkelens DW. Insulin mediated inhibition of hormone sensitive lipase activity in vivo in relation to endogenous catecholamines in healthy subjects. J Clin Endocrinol Metab. 2001 Sep;86(9):4193-7. doi: 10.1210/jcem.86.9.7794. PubMed PMID: 11549649.

#8-13

⁸Kong LC, Wuillemin PH, Bastard JP, Sokolovska N, Gougis S, Fellahi S, Darakhshan F, Bonnefont-Rousselot D, Bittar R, Doré J, Zucker JD, Clément K, Rizkalla S. Insulin resistance and inflammation predict kinetic body weight changes in response to dietary weight loss and maintenance in overweight and obese subjects by using a Bayesian network approach. Am J Clin Nutr. 2013 Dec;98(6):1385-94. doi: 10.3945/ajcn.113.058099. Epub 2013 Oct 30. PubMed PMID: 24172304.

⁹Fowler SP, Williams K, Resendez RG, Hunt KJ, Hazuda HP, Stern MP. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring). 2008 Aug;16(8):1894-900. doi: 10.1038/oby.2008.284. Epub 2008 Jun 5. PubMed PMID: 18535548.

¹⁰Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DA. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010 Aug;55(1):37-43. doi: 10.1016/j.appet.2010.03.009. Epub 2010 Mar 18. PubMed PMID: 20303371; PubMed Central PMCID: PMC2900484.

¹¹Tey SL, Salleh NB, Henry J, Forde CG. Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. Int J Obes (Lond). 2017 Mar;41(3):450-457. doi: 10.1038/ijo.2016.225. Epub 2016 Dec 13. PubMed PMID: 27956737.

¹²Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabolism. 2000 Feb;49(2):208-14. doi: 10.1016/s0026-0495(00)91325-8. PubMed PMID: 10690946.

¹³Bhasker S, Madhav H, Chinnamma M. Molecular evidence of insulinomimetic property exhibited by steviol and stevioside in diabetes induced L6 and 3T3L1 cells. Phytomedicine. 2015 Oct 15;22(11):1037-44. doi: 10.1016/j.phymed.2015.07.007. Epub 2015 Aug 14. PubMed PMID: 26407946.

#14-20

¹⁴Mohd-Radzman NH, Ismail WI, Adam Z, Jaapar SS, Adam A. Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review. Evid Based Complement Alternat Med. 2013;2013:718049. doi: 10.1155/2013/718049. Epub 2013 Nov 12. Review. PubMed PMID: 24324517; PubMed Central PMCID: PMC3845826.

¹⁵Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DA. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010 Aug;55(1):37-43. doi: 10.1016/j.appet.2010.03.009. Epub 2010 Mar 18. PubMed PMID: 20303371; PubMed Central PMCID: PMC2900484.

¹⁶Tey SL, Salleh NB, Henry J, Forde CG. Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. Int J Obes (Lond). 2017 Mar;41(3):450-457. doi: 10.1038/ijo.2016.225. Epub 2016 Dec 13. PubMed PMID: 27956737.

¹⁷Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013 Sep;36(9):2530-5. doi: 10.2337/dc12-2221. Epub 2013 Apr 30. PubMed PMID: 23633524; PubMed Central PMCID: PMC3747933.

¹⁸Noda K, Nakayama K, Oku T. Serum glucose and insulin levels and erythritol balance after oral administration of erythritol in healthy subjects. Eur J Clin Nutr. 1994 Apr;48(4):286-92. PubMed PMID: 8039489.

¹⁹Bornet FR, Blayo A, Dauchy F, Slama G. Plasma and urine kinetics of erythritol after oral ingestion by healthy humans. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S280-5. doi: 10.1006/rtph.1996.0109. PubMed PMID: 8933644.

²⁰Tey SL, Salleh NB, Henry J, Forde CG. Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. Int J Obes (Lond). 2017 Mar;41(3):450-457. doi: 10.1038/ijo.2016.225. Epub 2016 Dec 13. PubMed PMID: 27956737.

#21-28

²¹Yang Q. Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J Biol Med. 2010 Jun;83(2):101-8. PMID: 20589192; PMCID: PMC2892765.

²²Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabolism. 2000 Feb;49(2):208-14. doi: 10.1016/s0026-0495(00)91325-8. PubMed PMID: 10690946.

²³Bhasker S, Madhav H, Chinnamma M. Molecular evidence of insulinomimetic property exhibited by steviol and stevioside in diabetes induced L6 and 3T3L1 cells. Phytomedicine. 2015 Oct 15;22(11):1037-44. doi: 10.1016/j.phymed.2015.07.007. Epub 2015 Aug 14. PubMed PMID: 26407946.

²⁴Momtazi-Borojeni AA, Esmaeili SA, Abdollahi E, Sahebkar A. A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Curr Pharm Des. 2017;23(11):1616-1622. doi: 10.2174/1381612822666161021142835. Review. PubMed PMID: 27784241.

²⁵Ruiz-Ruiz JC, Moguel-Ordoñez YB, Segura-Campos MR. Biological activity of Stevia rebaudiana Bertoni and their relationship to health. Crit Rev Food Sci Nutr. 2017 Aug 13;57(12):2680-2690. doi: 10.1080/10408398.2015.1072083. Review. PubMed PMID: 26479769.

²⁶Momtazi-Borojeni AA, Esmaeili SA, Abdollahi E, Sahebkar A. A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Curr Pharm Des. 2017;23(11):1616-1622. doi: 10.2174/1381612822666161021142835. Review. PubMed PMID: 27784241.

²⁷Momtazi-Borojeni AA, Esmaeili SA, Abdollahi E, Sahebkar A. A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Curr Pharm Des. 2017;23(11):1616-1622. doi: 10.2174/1381612822666161021142835. Review. PubMed PMID: 27784241.

²⁸Terai T, Ren H, Mori G, Yamaguchi Y, Hayashi T. Mutagenicity of steviol and its oxidative derivatives in Salmonella typhimurium TM677. Chem Pharm Bull (Tokyo). 2002 Jul;50(7):1007-10. doi: 10.1248/cpb.50.1007. PubMed PMID: 12130868.

#29-35

²⁹Yuajit C, Homvisasevongsa S, Chatsudthipong L, Soodvilai S, Muanprasat C, Chatsudthipong V. Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. PLoS One. 2013;8(3):e58871. doi: 10.1371/journal.pone.0058871. Epub 2013 Mar 11. PubMed PMID: 23536832; PubMed Central PMCID: PMC3594167.

³⁰Yang Q. Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J Biol Med. 2010 Jun;83(2):101-8. PMID: 20589192; PMCID: PMC2892765.

³¹Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10. PubMed PMID: 23850261; PubMed Central PMCID: PMC3772345.

³²Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabolism. 2000 Feb;49(2):208-14. doi: 10.1016/s0026-0495(00)91325-8. PubMed PMID: 10690946.

³³Abudula R, Matchkov VV, Jeppesen PB, Nilsson H, Aalkjaer C, Hermansen K. Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. Diabetes Obes Metab. 2008 Nov;10(11):1074-85. doi: 10.1111/j.1463-1326.2008.00864.x. Epub 2008 Apr 22. PubMed PMID: 18435771.

³⁴Bhasker S, Madhav H, Chinnamma M. Molecular evidence of insulinomimetic property exhibited by steviol and stevioside in diabetes induced L6 and 3T3L1 cells. Phytomedicine. 2015 Oct 15;22(11):1037-44. doi: 10.1016/j.phymed.2015.07.007. Epub 2015 Aug 14. PubMed PMID: 26407946.

³⁵Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabolism. 2000 Feb;49(2):208-14. doi: 10.1016/s0026-0495(00)91325-8. PubMed PMID: 10690946.

#36-42

³⁶Schvartzman JB, Krimer DB, Moreno Azorero R. Cytological effects of some medicinal plants used in the control of fertility. Experientia. 1977 May 15;33(5):663-5. doi: 10.1007/BF01946562. PubMed PMID: 862810.

³⁷Planas GM, Kucacute J. Contraceptive Properties of Stevia rebaudiana. Science. 1968 Nov 29;162(3857):1007. doi: 10.1126/science.162.3857.1007. PubMed PMID: 17744732.

³⁸Saenphet K, Aritajat S, Saenphet S, Manosroi J, Manosroi A. Safety evaluation of aqueous extracts from Aegle marmelos and Stevia rebaudiana on reproduction of female rats. Southeast Asian J Trop Med Public Health. 2006;37 Suppl 3:203-5. PubMed PMID: 17547081.

³⁹Shannon M, Rehfeld A, Frizzell C, Livingstone C, McGonagle C, Skakkebaek NE, Wielogórska E, Connolly L. In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia. Mol Cell Endocrinol. 2016 May 15;427:65-72. doi: 10.1016/j.mce.2016.03.005. Epub 2016 Mar 8. PubMed PMID: 26965840.

⁴⁰Melis MS. Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol. 1999 Nov 1;67(2):157-61. doi: 10.1016/s0378-8741(99)00081-1. PubMed PMID: 10619379.

⁴¹Momtazi-Borojeni AA, Esmaeili SA, Abdollahi E, Sahebkar A. A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Curr Pharm Des. 2017;23(11):1616-1622. doi: 10.2174/1381612822666161021142835. Review. PubMed PMID: 27784241.

⁴²Wang QP, Browman D, Herzog H, Neely GG. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS One. 2018;13(7):e0199080. doi: 10.1371/journal.pone.0199080. eCollection 2018. PubMed PMID: 29975731; PubMed Central PMCID: PMC6033410.

#43-45

⁴³Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr. 2019 Jan 1;10(suppl_1):S31-S48. doi: 10.1093/advances/nmy037. PubMed PMID: 30721958; PubMed Central PMCID: PMC6363527.

⁴⁴Deniņa I, Semjonovs P, Fomina A, Treimane R, Linde R. The influence of stevia glycosides on the growth of Lactobacillus reuteri strains. Lett Appl Microbiol. 2014 Mar;58(3):278-84. doi: 10.1111/lam.12187. Epub 2013 Nov 19. PubMed PMID: 24251876.

⁴⁵Ashwell M. Stevia, Nature’s Zero-Calorie Sustainable Sweetener: A New Player in the Fight Against Obesity. Nutr Today. 2015 May;50(3):129-134. doi: 10.1097/NT.0000000000000094. Epub 2015 May 14. PubMed PMID: 27471327; PubMed Central PMCID: PMC4890837.