Stevia

Stevia (Stevia rebaudiana Bertoni)

1. Identity: Botanical Names, Natural Source, and Common Forms

Taxonomy and Botanical Identity

Stevia is a genus of about 240 species of herbs and shrubs in the sunflower family (Asteraceae), native to subtropical and tropical South America and Central America. The species Stevia rebaudiana Bertoni, commonly known as sweet leaf, sugarleaf, or simply stevia, is widely grown for its sweet leaves. It is a small perennial shrub native to South America, particularly Brazil and Paraguay, where it is known as "stevia" or "honey leaf" for its powerful sweetness. The genus was named for the Spanish botanist and physician Pedro Jaime Esteve (Petrus James Stevus, 1500–1556), a professor of botany at the University of Valencia. The species epithet rebaudiana honours the Paraguayan chemist Ovidio Rebaudi, who was among the first to chemically characterise its sweet constituents.

Natural Source and Cultivation

Stevia is extracted from the leaves of Stevia rebaudiana, a plant native to areas of Paraguay and Brazil. Nowadays, stevia is commercially cultivated in Paraguay, Brazil, Central America, China, Thailand, and the USA. Stevia has been widely used in Japan as a sweetener for decades.

Common Forms and Preparations

Stevia is available and consumed in several distinct forms, each with different compositional profiles:

• Whole dried leaf: The raw or dried leaf, used as a tea additive or ground to powder. Whole stevia leaves and crude stevia leaf extracts are not approved food additives because there is not enough toxicological information available, according to the FDA; however, the use of stevia leaves and crude stevia leaf extracts in dietary supplements are not subject to FDA food additive regulations.
• Stevioside powder: A purified crystalline extract, which has been used in clinical trials, commonly in capsule form at doses of 500 mg per capsule.
• High-purity steviol glycoside extracts: Purified forms of individual glycosides (primarily rebaudioside A, also known as Reb A), approved for food use in multiple jurisdictions. In 2008, the FDA made its first GRAS determination on a stevia sweetener, rebaudioside A, purified from Stevia rebaudiana (Bertoni).
• Liquid drops: Concentrated aqueous solutions of steviol glycosides used as tabletop sweeteners; also employed in clinical research settings.
• Steviol glycosides produced by fermentation or enzymatic modification: Steviol glycosides may be extracted from Stevia leaves, synthesized by enzymatic processes, synthesized by chemical syntheses, or produced by fermentation.

Steviol glycosides are heat-stable, pH-stable, and do not ferment. The taste of stevia has a slower onset and longer duration than that of sugar, and at high concentrations some of its extracts may have an aftertaste described as licorice-like or bitter.

2. Traditional and Historical Use

Indigenous Guaraní Use

The plant Stevia rebaudiana has been used for centuries by the Guaraní peoples of South America, who called it ka'a he'ê ("sweet herb"). The leaves have been used traditionally for hundreds of years in both Paraguay and Brazil to sweeten local teas, and as a "sweet treat." The name Ka'a he'ê, which means "sweet grass" in Guaraní, has been part of Paraguay's Pãi Tavyterã indigenous people's lives for centuries.

These native people knew the leaves of the wild stevia shrub (a perennial indigenous to the Amambay Mountain region) to have a sweetening power unlike anything else; they commonly used the leaves to enhance the taste of bitter mate (a tea-like beverage) and medicinal potions, or simply chewed them for their sweet taste. The widespread native use of stevia was chronicled by the Spaniards in historical documents preserved in the Paraguayan National Archives in Asunción. Historians noted that indigenous peoples had been sweetening herbal teas with stevia leaves "since ancient times."

In Guaraní culture, stevia is a key ingredient in treating digestive problems and discomfort during menstrual cycles. They also consume it as a tea and to sweeten beverages. Among its many uses, anecdotal evidence suggests that Guaraní women employed stevia as a fertility regulator. According to ethnobotanical accounts, they prepared a decoction by boiling powdered stevia leaves in water and consumed it daily as a contraceptive. These claims regarding fertility effects are not corroborated by robust clinical human evidence.

Scientific Discovery and Formal Documentation

In 1887, Italian-Swiss botanist Moisés Santiago Bertoni began exploring the forests of eastern Paraguay, where local guides introduced him to Stevia rebaudiana and its remarkable properties. Bertoni conducted systematic studies on the plant, formally describing it and noting its exceptional sweetness in detail by 1901, which marked the modern scientific recognition of its potential as a sweetening agent. He named the species Stevia rebaudiana in 1905, honouring chemist Ovidio Rebaudi, and emphasized its non-sugar-derived taste in his botanical writings.

By the 1800s, daily stevia consumption had become well entrenched throughout the region — not just in Paraguay, but also in neighboring Brazil and Argentina.

Commercial Adoption in Japan

Stevioside, a natural glycoside isolated from the plant Stevia rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and Brazil for more than 20 years (as of 2003). Japan's adoption of stevia from the 1970s onwards represented the first large-scale commercial application outside South America.

3. Key Constituents and Active Compounds

Steviol Glycosides: Structure and Diversity

Steviol glycosides are the chemical compounds responsible for the sweet taste of the leaves of the South American plant Stevia rebaudiana (Asteraceae) and the main ingredients (or precursors) of many sweeteners marketed under the generic name stevia and several trade names.

The major and minor steviol glycosides include stevioside, steviolbioside, rebaudioside A (RA), rebaudioside B (RB), rebaudioside C (RC), rebaudioside D (RD), rebaudioside E (RE), rebaudioside F (RF), rebaudioside M (RM), rubusoside, and dulcoside A (DA), among others. The term "steviol glycoside" refers to a glycoside of steviol, a diterpene compound. Steviol glycosides are comprised of steviol molecules glycosylated at the C13 and/or C19 position(s).

Based on the type of sugar (glucose, rhamnose/deoxyhexose, xylose/arabinose), steviol glycosides can be grouped into three families: (1) those with glucose, (2) those with glucose and one rhamnose or deoxyhexose moiety, and (3) those with glucose and one xylose or arabinose moiety.

Steviosides and rebaudiosides are the major constituents of glycosides found in the leaves of the stevia plant. Rebaudioside D exhibits an increased sweetness and weaker bitter taste compared to other steviol glycosides.

Sweetness Intensity

Steviol glycosides from Stevia rebaudiana have been reported to be between 30 and 320 times sweeter than sucrose, although there is some disagreement in the technical literature about these numbers. Higher-purity extracts, particularly rebaudioside A, approach the upper end of this range.

Non-Glycoside Constituents

In addition to sweet compounds, Stevia leaves contain many other biologically active substances which have beneficial effects for human health. In particular, the anti-diabetic, antihypertensive, antitumor, anti-cariogenic, anti-inflammatory, and bactericidal effects of the herb have been studied. These non-glycoside constituents include flavonoids, phenolic acids, chlorophyll, and other polyphenols present in the leaf matrix but not typically present in highly purified steviol glycoside extracts.

Metabolism and Caloric Value

Steviol glycosides do not induce a glycemic response when ingested, because humans cannot metabolize stevia. The metabolism of steviol glycosides is dependent upon gut microbiota, which breaks down glycosides into steviol that can be absorbed by the host. Stevia compounds are not digested by the host but are metabolized by microbiota and absorbed into circulation, where they are ultimately excreted in urine.

4. Mechanisms of Action

Glycemic Regulation

Stevia's anti-hyperglycemic effects involve mechanisms such as enhanced insulin secretion and modulation of glucose transporters. Stevioside has been shown to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner in preclinical models. These agents have demonstrated the ability to modulate key metabolic pathways, enhance tissue insulin sensitivity, reduce oxidative stress, and support pancreatic β-cell function.

Antihypertensive Mechanisms

Although the mechanism underlying the antihypertensive effect of stevioside is not fully clear, it has been demonstrated that the hypotensive response to stevioside appears to occur through a calcium antagonist mechanism similar to that of verapamil. However, other studies have shown that the blood pressure lowering effect of stevioside probably also depends on prostaglandin activity. Stevioside was also found to inhibit Ca²⁺ influx into blood vessels through vasorelaxation. Antihypertensive actions are linked to vasodilation and angiotensin-converting enzyme (ACE) inhibition.

Anti-Inflammatory Mechanisms

In vitro, stevioside has been shown to inhibit the synthesis of inflammatory factors stimulated by lipopolysaccharide by inhibiting the NF-κB signaling pathway and reducing the secretion of TNF-α through the TLR-4 pathway.

Antimicrobial Mechanisms

In vitro studies have shown that S. rebaudiana stops the growth of Streptococcus mutans, S. sobrinus, and Lactobacillus acidophilus. These bacteria are associated with the development of caries. Further studies showed that stevia extract significantly inhibited the growth and acid production of Streptococcus mutans, altered biofilm structure, and reduced biofilm viability and extracellular polysaccharide production.

5. Scientific Evidence by Health Area

5.1 Blood Glucose and Diabetes

Evidence Summary: Low-to-moderate certainty evidence from meta-analyses of human clinical trials suggests some blood glucose-lowering effects, primarily in individuals with diabetes or elevated BMI. Effects on HbA1c and insulin are less established.

A systematic review and meta-analysis following PRISMA guidelines, including 26 studies with 1,439 participants (PROSPERO registration CRD42023414411), found that stevia consumption was associated with significantly reducing blood glucose levels (weighted mean difference: −3.84; 95% CI: −7.15, −0.53; P = 0.02, low certainty), especially in individuals with higher BMI, diabetes, and hypertension. Dose-response analysis revealed a decrease in blood glucose for ≥3,342 mg/day of stevia consumption.

Stevia consumption has been shown to reduce blood glucose levels within 1–4 months; however, stevia did not significantly affect insulin concentration or HbA1c levels (very low and low certainty, respectively). Low certainty evidence showed that stevia improved blood glucose control, especially when consumed for less than 120 days; however, more randomized trials with higher stevia dosages are required.

A double-blind randomized clinical trial compared the effects of stevia- and sucralose-sweetened teas in 39 eligible type-2 diabetic patients, who were randomly assigned into two groups (19 in stevia and 20 in control groups).

In preclinical research, the results of a meta-analysis of animal studies support the hypothesis that stevia leaf has an antihyperglycemic effect and reduces the blood glucose level at doses of 200, 300, and 400 mg/kg. More clinical trials on animals and humans are needed to investigate the antidiabetic and antihyperglycemic effects along with the efficacy and safety of these medicinal leaves.

Limitations: Many included studies are short-term, use varied preparations and doses, and some have methodological weaknesses. Effects in healthy normoglycemic individuals appear minimal.

5.2 Blood Pressure

Evidence Summary: There is moderate evidence from at least two randomized, double-blind, placebo-controlled trials showing that stevioside supplementation reduces blood pressure in patients with mild essential hypertension over periods of months to years. Evidence data are partly conflicting.

A multicenter, randomized, double-blind, placebo-controlled trial enrolled Chinese men and women aged between 20 and 75 years with mild essential hypertension (systolic blood pressure 140–159 mm Hg and diastolic blood pressure 90–99 mm Hg). Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years. Based on patients' records of self-monitored blood pressure, blood pressure-lowering effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study. There were no significant changes in body mass index or blood biochemistry, and the results of laboratory tests were similar in the two groups throughout the study. No significant difference in the incidence of adverse effects was noted between groups, and quality-of-life scores were significantly improved overall with stevioside compared with placebo (P < 0.001).

Intake of 750–1,500 mg/day of stevioside was reported to reduce 10–11 mmHg of systolic blood pressure and 6–14 mmHg of diastolic blood pressure within 7 days of consumption in referenced studies. Clinical studies have demonstrated that administering stevia glycoside (15.0 mg/kg/day) before lunch and dinner for six consecutive weeks significantly lowered blood pressure in patients with mild essential hypertension.

Although the hypotensive effect of stevioside was not better than other antihypertensive drugs, it appears comparable, and almost all the active treatment group patients showed significant lowering of blood pressure. One interesting phenomenon observed was that blood pressure began to decrease at about 7 days after taking stevioside capsules.

Limitations: Data regarding antihypertensive effects of stevioside are conflicting. Most robust trials have been conducted in Chinese populations with mild essential hypertension; generalizability to other populations is uncertain. Most studies have used stevioside specifically, not crude leaf preparations.

5.3 Body Weight and Energy Intake

Evidence Summary: Clinical evidence suggests stevia, as a non-nutritive sugar substitute, can modestly support weight maintenance and reduce energy intake by displacing caloric sugars. Evidence is generally preliminary and limited by short duration and small sample sizes.

In a 12-week randomized open-label trial, there was a significant main effect of group on body weight change: the stevia group maintained their weight as opposed to the control group (mean weight change at week 12: −0.22 kg, 95% CI [−0.96, 0.51] in the stevia group, versus +0.89 kg, 95% CI [0.16, 1.63] in the control group). Energy intake was significantly decreased between week 0 and 12 in the stevia group (p = 0.003). These results suggest that daily stevia consumption does not affect glycaemia in healthy individuals, but could aid in weight maintenance and the moderation of energy intake.

It was noted that replacing sugar with steviol glycosides reduced caloric intake by approximately 90 kcal/day (2,700 kcal deficit per month) in both groups, resulting in weight loss. A significant difference in body weight, waist circumference, and BMI was observed at Day 90 when compared to baseline in both overweight study groups. Subgroup analysis revealed that replacement of sugars with stevia-based tabletop sweeteners led to weight loss in 77.77% of the subjects, with a mean weight reduction of 2.12 kg and reduction in waist circumference in 71.11% of subjects.

When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload.

Visual analogue scale scores for hunger and desire to eat were lower following stevia preload compared to water (p < 0.05). Findings suggest that stevia has at least a neutral effect on short-term food intake and its consumption led to lower postprandial glucose levels compared to sucrose.

Limitations: Limited evidence is available on the effect of steviol glycosides on weight reduction in human subjects. Observed weight effects are likely largely attributable to caloric displacement (removing caloric sugar) rather than a direct pharmacological effect of stevia on body composition.

5.4 Cardiovascular and Anti-Inflammatory Effects

Evidence Summary: Preclinical studies (in vitro and animal) suggest anti-inflammatory, antioxidant, and cardioprotective properties. Human clinical evidence in this domain remains limited.

In vitro and in vivo studies showed that stevia has antiglycemic action and antioxidant effects in adipose tissue and the vascular wall, reduces blood pressure levels and hepatic steatosis, stabilizes the atherosclerotic plaque, and ameliorates liver and kidney damage. These findings derive primarily from preclinical models and should not be extrapolated directly to human clinical outcomes without further clinical trial evidence.

5.5 Renal (Kidney) Health

Evidence Summary: A limited number of clinical and preclinical studies suggest potential nephroprotective properties; the area remains under investigation.

A clinical trial aimed to investigate the kidney-protective effects of stevioside in CKD Stage I–III patients, exploring its impact on inflammatory markers, kidney function, and hematological parameters. Stevia treatment significantly reduced systolic blood pressure (p < 0.043), diastolic blood pressure (p < 0.001), microalbuminuria (p < 0.003), postprandial blood sugar (p < 0.001), erythrocyte sedimentation rate (p < 0.023), and high-sensitivity C-reactive protein (p < 0.007) levels at the second follow-up. During the washout period (with no stevia), most of these improved values trended back toward baseline in the stevia group, indicating a loss of the treatment effect upon withdrawal. This nine-month clinical investigation found that oral stevia can positively impact biochemical indicators in CKD patients, potentially mitigating the progression of the disease.

Limitations: This is a single trial conducted in Bangladesh; results require replication in larger, multi-centre studies.

5.6 Oral and Dental Health

Evidence Summary: In vitro evidence indicates anti-cariogenic and antimicrobial properties against oral pathogens. Animal and limited human data are promising but insufficient for clinical recommendations.

Critical analysis of the literature supports the anti-bacterial role of steviosides on oral bacterial flora. In vitro studies have shown that S. rebaudiana stops the growth of Streptococcus mutans, S. sobrinus, and Lactobacillus acidophilus — bacteria associated with the development of caries. Animal studies showed significant increases in caries and bacterial counts only in the sucrose group, while stevia extract and rebaudioside A did not cause dental caries compared to controls. A key limitation was the use of non-human subjects.

Stevia extract obtained through various solvent extractions was tested on 16 strains of Gram-positive bacteria (including Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus acidophilus). All extracts showed antimicrobial activity with minimum inhibitory concentration (MIC) range of 30–120 mg/mL.

Stevia extract mouthwash can reduce plaque and gingival index in adolescents; however, the effect of stevioside and its underlying mechanism on periodontitis remain unclear.

5.7 Gut Microbiota

Evidence Summary: Human and animal data on stevia's effects on the gut microbiome are mixed and still emerging. Both neutral and perturbing effects have been reported, and robust conclusions cannot yet be drawn.

The metabolism of steviol glycosides is dependent upon gut microbiota, which breaks down glycosides into steviol that can be absorbed by the host. Results from reviewed studies indicated that stevia consumption has a potential benefit on the microbiome's alpha diversity. Alterations in the colonic microenvironment may depend on the amount and frequency of stevia intake, as well as on the simultaneous consumption of other dietary components.

In a 12-week human study, stevia did not cause significant changes in alpha or beta diversity when compared to control groups. When the relative abundances of taxa were investigated, no clear differences were detected.

Conversely, one study found that stevia consumption perturbed the gut microbiota, including reductions in diversity and alterations in specific bacterial populations, such as Lachnospiraceae and Ruminococcaceae. These changes were associated with modifications in the mesolimbic dopamine pathway, potentially influencing reward-related behaviours, highlighting the interplay between sweetener consumption, gut microbiota, and neurological functions.

Limitations: Due to the lack of randomized clinical trials in humans, most reviewed evidence was derived from in vitro studies using certain microbial strains and in vivo laboratory animal studies. Human findings are inconsistent across studies, and the clinical significance of observed microbiota changes remains uncertain.

6. Body Systems and Health Areas of Association

Based on the available research evidence (noting that much comes from preclinical studies), stevia and its constituents have been associated with the following body systems:

• Endocrine/Metabolic system: Blood glucose regulation, insulin secretion enhancement, postprandial glucose reduction, lipid metabolism.
• Cardiovascular system: Blood pressure reduction via calcium channel antagonism and ACE inhibition; vasodilation; anti-atherosclerotic effects in preclinical models.
• Renal system: Potential nephroprotective effects (reduction of microalbuminuria; preclinical hepatoprotective evidence).
• Gastrointestinal system: Traditional use for digestive complaints; interaction with gut microbiota as a substrate for bacterial metabolism.
• Oral/Dental system: Anti-cariogenic activity against key oral pathogens in vitro; potential antimicrobial mouthwash properties.
• Immune/Inflammatory system: Inhibition of NF-κB and TNF-α pathways (primarily preclinical); reported benefits include anti-hyperglycaemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions.
• Body weight and energy balance: Caloric displacement from sugar substitution; possible modest effects on appetite and satiety.

7. Dosage Forms and Dosages Reported in Clinical Studies

The following dosages are reported directly from peer-reviewed clinical studies and should not be interpreted as recommended doses:

• Stevioside capsules for hypertension (2-year trial): Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years (total: 1,500 mg/day).
• Stevioside for mild essential hypertension (short-term): Intake of 750–1,500 mg/day of stevioside was reported to reduce systolic blood pressure by 10–11 mmHg and diastolic blood pressure by 6–14 mmHg within 7 days of consumption.
• Stevia glycoside for hypertension (Brazil): Administering stevia glycoside at 15.0 mg/kg/day before lunch and dinner for six consecutive weeks.
• Stevia drops for weight and glycaemia (12-week trial): Healthy subjects with a normal BMI participated; the stevia group was asked to consume five drops of stevia twice daily.
• Stevia for body weight in overweight adults (NNS trial): NNS consumers were randomly assigned to the stevia group (0.375 mg/kg) or the sucralose group.
• Meta-analysis dose-response threshold: Dose-response analysis revealed a decrease in blood glucose for ≥3,342 mg/day of stevia consumption.
• Antihyperglycemic effects in animal studies: The results of the meta-analysis support the hypothesis that stevia leaf has an antihyperglycemic effect and reduces the blood glucose level at doses of 200, 300, and 400 mg/kg (in animal models).

8. Regulatory Status and Acceptable Daily Intake

Stevia sweeteners have been studied and reviewed by leading medical, scientific, and regulatory authorities, including the Joint Expert Committee on Food Additives (JECFA), the U.S. Food and Drug Administration, and the European Food Safety Authority. In response to Generally Recognized As Safe (GRAS) notifications submitted to the US FDA, the FDA has stated it has no questions regarding the conclusion of expert panels that stevia is GRAS for use as a general purpose sweetener in foods and beverages, excluding meat and poultry.

The European Food Safety Authority (EFSA) assessed the safety of steviol glycosides from stevia and established an Acceptable Daily Intake (ADI) of 4 mg/kg bw/day for their safe use. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established an ADI for steviol glycosides of 0–4 mg/kg bw per day, expressed as steviol.

JECFA based its ADI of 4 mg/kg bw on a no-observed-adverse-effect level of 970 mg/kg bw/day (383 mg/kg bw/day as steviol) from a 2-year study in rats and a safety factor of 100 to account for intra- and inter-species differences.

The European Union approved stevia additives in 2011. In the United States, extracts of certain high-purity steviol glycosides have been generally recognized as safe (GRAS) and may be lawfully marketed and added to food products, but stevia leaf and crude extracts do not have GRAS or FDA approval for use in food.

Since 2008, several US FDA GRAS notifications in relation to steviol glycoside preparations with major individual steviol glycosides (stevioside and rebaudiosides A, C, D, and M) received "No Objection" letters from the FDA.

9. Safety Considerations and Interactions

General Safety Profile

Leading global health authorities such as the European Food Safety Authority (EFSA) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) have concluded that high-purity steviol glycosides are safe for consumption within the acceptable daily intake (ADI) level. After reviewing the safety evidence, regulatory agencies like EFSA, FDA, and JECFA have determined that stevia sweeteners are safe for the general population, including pregnant and breastfeeding women, when consumed within the limits of the ADI.

No major contraindications, warnings, or adverse reactions have been documented for steviol glycosides consumed within the established ADI.

Interactions with Antidiabetic Medications

Some research shows that stevia might decrease blood sugar in people with type 2 diabetes. In theory, stevia might cause an interaction with diabetes medications resulting in blood sugar levels going too low; however, not all research has found that stevia lowers blood sugar. Therefore, it is not clear if this potential interaction is a concern.

Interactions with Antihypertensive Medications

Some research shows that stevia might decrease blood pressure. In theory, taking stevia along with medications used for lowering high blood pressure might cause blood pressure to go too low. However, some research shows that stevia does not affect blood pressure. Therefore, it is not known if this potential interaction is a major concern.

Interactions with Lithium

Stevia may have a diuretic effect (causing increased urination) which might reduce the excretion of lithium from the body. This could cause increased lithium levels in the blood and can lead to serious side effects.

Pharmacokinetic Drug Interactions

Drugs like quercetin, telmisartan, diclofenac, and mulberrin were found to inhibit the OAT3-mediated uptake of steviol glucuronide, potentially altering its renal clearance. Theoretically, given stevia's potential blood glucose– and blood pressure–lowering effects, co-administration of glucose-lowering drugs or antihypertensives could have additive effects.

Additionally, in vitro data indicate that steviol may interact with nuclear receptors involved in drug metabolism. Steviol moderately activated the pregnane X receptor (PXR) and aryl hydrocarbon receptor (AHR), resulting in the induction of their target genes including CYP3A4 and CYP1A2 in primary human hepatocytes. A weak inhibition of CYP3A4 and CYP2C9 with steviol was also found. These results provide mechanistic data indicating that stevioside and stevia sweeteners may have the potential to induce food-drug interactions, a finding that warrants future prospective clinical investigation.

Gut Microbiota and Long-Term Concerns

Although most studies have found a positive impact of stevia glycosides on metabolic parameters, doses in animal studies have greatly exceeded the adequate daily intake recommended by governing health agencies like Health Canada and the US FDA from ten- to one-hundred-fold. Results from supraphysiological doses in animals may therefore not apply to human use at ADI-equivalent levels.

Crude Leaf vs. Purified Glycosides

These forms of stevia (whole leaf and crude extracts) are different from certain highly purified steviol glycosides obtained from stevia leaves, which have been the subjects of GRAS notices; FDA has not objected to the use as sweeteners of these highly refined substances. The distinction between crude leaf preparations and purified glycosides is significant from a regulatory and toxicological standpoint; the evidence base for safety is substantially stronger for high-purity steviol glycoside preparations consumed within the ADI.

Pregnancy and Lactation

While no published research has examined possible effects of purified steviol glycosides on pregnant and lactating women, several landmark studies in animals have demonstrated no adverse reproductive or developmental effects on mothers or their offspring, even when animals were exposed to levels more than 100 times the ADI, every day, over long periods of time.

References

• Wikipedia – Steviol glycoside
• Wikipedia – Stevia
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• PMC – Effect of stevia leaves on diabetes: A systematic review and meta-analysis of preclinical studies
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• ScienceDirect – Efficacy and tolerability of oral stevioside in patients with mild essential hypertension (full text)
• PubMed – Antihypertensive effect of stevioside in different strains of hypertensive rats
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• PMC – Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels
• PMC – Effects of Stevia Extract on Postprandial Glucose Response, Satiety and Energy Intake: A Three-Arm Crossover Trial
• PMC – Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota
• PMC – The Effects of Stevia Consumption on Gut Bacteria: Friend or Foe?
• PMC – Low-Dose Stevia (Rebaudioside A) Consumption Perturbs Gut Microbiota and the Mesolimbic Dopamine Reward System
• PMC – Natural sweetener Stevia rebaudiana: Functionalities, health benefits and potential risks
• PMC – Is Stevia rebaudiana Bertoni a Non Cariogenic Sweetener? A Review
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