Stevia Summary:

Stevia rebaudiana, is just 1 of almost 200 different species of stevia, however, it's the only one with the desired qualities as a sweetener.

The intense sweetness of stevia comes from a very uniwue phytochemical makeup. These phytochemicals are referred to as "steviol glycosides", which are actually suggested to be up to 200 times sweeter than sucrose (table sugar) yet has very little calories. This sweetness doesn't bring with it the negative side effects of regular table sugar of which we are all familiar (diabetes, metabolic syndrome, cancer, and so on). In fact in many cases the opposite effects can be seen, where stevia can actually improve conditions like high blood pressure and diabetes.

 As such, stevia has become well known as a natural sugar alternative. Diabetics, and those looking to lose weight by cutting sugar, often use stevia as a way to add a sweeter flavour to their food, tea or coffee without adding to the underlying issue.

Stevia can be added as a liquid extract, added to tea raw, or concentrated into a powder and used in the same way as regular white sugar. 

The sweetness of stevia is slightly different in taste to sugar, which means that as a sugar substitute it may take a little while to become used to the flavour.


Botanical Name

Stevia rebaudiana

Family

Asteraceae

Part Used

Leaves

Herbal Actions:

  • Hypoglycemic
  • Non-caloric sweetener
  • Food additive
  • Hypotensive
  • Antinflammatory
  • Vasodilator
  • Anti-tumor
  • Antidiarrheal
  • Immunomodulator
  • Diuretic
  • Antibacterial
  • Antifungal
  • Antiviral
stevia rebaudiana monograph

Indications:

  • Skin disorders
  • Natural sweetener
  • Diabetes
  • Tooth decay
  • Hypertension
  • Wound healing
  • Blemishes
  • Weight management
  • As an antioxidant

Common Names:

  • Stevia
  • Sweet herb/sweet leaf
  • Caa-he-e/Ca-a-jhei/a-a-yupi
  • Kaa jhee
  • Azucacaa
  • Eira-caa
  • Capim
  • Doce
  • Honey yerba/honeyleaf
  • Yaa waan
  • Candy leaf

Traditional Use:

Stevia rebaudiana has traditionally been used by the Guarani Indians of Brazil and Paraguay as a treatment for diabetes and as a sweetener (Taylor L. 2005; V. Cekic et al., 2011).

The Guarani Indians of Paraguay have used it to sweeten their yerba mate (Illex paraguariensis), another traditional infusion of various Amazonian peoples. They have also used Stevia leaves to sweeten other teas, and have used it medicinally as a cardiotonic, and for heartburn, obesity, and hypertension (Taylor L. 2005).

Once the Europeans learned of this herb through its “discovery” by Spain's conquistadores sometime in the 16th century, it became a popular herb throughout Europe and Asia as a sweetener (Taylor L. 2005).


Botanical Description:

Stevia rebaudiana is a small perennial shrub native to Central, and Northern South America, that has been used as a sweetener for thousands of years (B. Rizzo et al., 2013). Currently it is still used in much the same way, as a non-caloric sweetener appropriate for those who can not consume sugar.

Stevia rebaudiana grows to about 1m in height, with 2-3 cm long leaves (Taylor L. 2005).

Some sources state that there are 150 known species of Stevia (N. H. Mohd-Radzman et al., 2013), with other sources listing 200-230 (Taylor L. 2005; P. Guleria and K. Yadav, 2013). All agree that Stevia rebaudiana Bertoni is the only one found to have certain desired properties including its potent sweet flavor despite containing no calories and posessing significant antidiabetic effects, and richness of certain metabolites such as beta-carotene, thiamine, and various terpenes and flavonoids (N. H. Mohd-Radzman et al., 2013; P. Guleria and K. Yadav, 2013).


Habitat, Ecology, Distribution:

Stevia rebaudiana is native to Brazil, Paraguay, and other parts of South America. More specifically, it is indigenous to the Rio Monday Valley of the Amambay mountain region at altitudes between 200 and 500 m (P. Singh and P. Dwivedi., 2014).


Harvesting, Collection, Preparation: 

Due to the well documented effects as a sweetener and it's acceptable use in the food industry as such, low cost of production, and its positive effects on diabetes and various metabolic disorders, there is no doubt that this plant will need to be cultivated in mass amounts to be able to keep up with demand. Issues with this involve Stevias poor seed viability, and low germination rate. This makes it challenging to produce this plant on a large scale by traditional means. Vegetative propagation also poses a problem, as very specific habitat conditions are necessary in order to successfully acclimatize the roots into soil. A third option, in vitro cultures or “plant tissue culture” offers a solution to these issues. In result of this, P. Singh and P. Dwivedi., (2014) have developed an efficient micropropagation protocol for Stevia rebaudiana. They also noted that in vitro grown plants had a much higher stevioside content than in vivo grown plants. This form of cultivation and propagation will likely be the norm for this botanical on large scale operations.

When it comes to harvesting this plant, it is the leaves that are harvested and processed. This is because the steviol glycosides desired for the sweet flavor and medicinal attributes are mainly in the leaves (P. Guleria and K. Yadav, 2013).

Currently, Stevia is being cultivated commercially in Brazil, Paraguay, Uruguay, parts of Central America, Israel, Thailand, and China (Taylor L. 2005).


Constituents:

Stevia rebaudiana is rich in flavanoids and terpenes.
Contains the diterpene steviol (ent-13-hydroxykaur-16-en-19-oic acid) (including its glycosides Rebaudiosides A, B, C, and D), dulcoside, (N. H. Mohd-Radzman et al., 2013; I. Prakash et al., 2012). Stevioside comprises roughly 6-18% of the leaf (Taylor L. 2005), and has been noted to be higher in plants propagated in vitro P. (Singh and P. Dwivedi., 2014). Another sweet component includes steviolbioside (Taylor L. 2005).

The main plant chemicals in stevia include: apigenin, austroinulin, avicularin, beta-sitosterol, caffeic acid, campesterol, caryophyllene, centaureidin, chlorogenic acid, chlorophyll, cosmosiin, cynaroside, daucosterol, diterpene glycosides, dulcosides A-B, foeniculin, formic acid, gibberellic acid, gibberellin, indole-3-acetonitrile, isoquercitrin, isosteviol, jhanol, kaempferol, kaurene, lupeol, luteolin, polystachoside, quercetin, quercitrin, rebaudioside A-E, scopoletin, sterebin A-H, steviol, steviolbioside, steviolmonoside, stevioside, stevioside a-3, stigmasterol, umbelliferone, and xanthophylls (Taylor L. 2005).  



Pharmacology and Medical Research:

+ Diabetes

Diabetes mellitus is a metabolic disorder consisting of high blood glucose levels, and is divided into two types. Type 1 diabetes refers to the inability of the pancreas to produce adequate amounts of insulin for glucose uptake and metabolism. N. H. Mohd-Radzman et al., (2013) reports that the insufficient insulin production is due to a destruction of the autoimmune response, which results in disruption of 𝛽-cells.

The second type is referred to as type 2 diabetes. This form of diabetes is due to insulin resistance, relating to an impairment of the insulin-signalling pathway. There is compelling evidence that this form of diabetes is due to a combination of genetic linkage, and poor lifestyle choices (N. H. Mohd-Radzman et al., 2013).

Diabetes mellitus is a serious global health issue that negatively affects both quality of life and longevity. (V. Cekic et al., 2011). It is a disease associated with various cardiovascular diseases, obesity, lowered sexual functioning, fatigue, lowered epithelial function, lowered immune function, and more. Alzheimer's and other neurodegenerative diseases have been reported to have a close correlation with the impaired functioning of glucose metabolism/uptake as well (B. Rizzo et al., 2013).

High glycemic diets, including natural sugars like fructose, have been shown to induce a number of metabolic conditions (hyperinsulinemia, hyperglycemia, hypertension, and insulin resistance), in animal models (S. D. Anton et al., 2010).

The excessive intake of high caloric and high glycemic food can result in exaggerated postprandial glucose and insulin levels. This exaggeration may lead to metabolic, and hormonal changes that can stimulate fat deposition and hunger (S. D. Anton et al., 2010).

In a study done investigating the effects of Stevia (steviosides), aspartame, and sucrose on postprandial insulin and glucose levels, researchers found that both aspartame and Stevia were able to reduce postprandial insulin and glucose. They noted that these effects were not solely due to the low caloric and carbohydrate levels of Stevia and aspartame compared to sugar, because while Stevia and aspartame were taken in equal caloric amounts, Stevia showed a much stronger effect. This study also found that people taking Stevia and aspartame preloads did not eat more at either lunch or dinner compared to the sucrose preload. (S. D. Anton et al., 2010). Stevioside (a diterpenoid glycoside) exhibits direct insulinotropic action in multiple in vitro cell lines, and produces anti-hyperglycemic effects and insulinotropic, and glucagonostatic effects in diabetic animals in vitro. This effect was noted to only be through adrenaline-induced hyperglycemia (V. Cekic et al., 2011).

Stevioside specifically has been shown to enhance insulin sensitivity throughout the whole body, and improve glucose infusion rate (N. H. Mohd-Radzman et al., 2013). TNF alpha (a proinflammatory cytokine involved with the reduction of insulin sensitivity), was also significantly downregulated along with other proinflammatory and chemotactic cytokines (N. H. Mohd-Radzman et al., 2013).

B. Rizzo et al., (2013) found that Stevia extracts behave similarly to insulin and was stated to be as efficient as insulin at increasing glucose uptake. They also suggest through their study, the likelihood that stevioside exerts some of these actions on blood glucose through inhibiting gluconeogenesis in the livers of diabetic rats, and modulating GLUT translocation through the PI3K/Akt pathway. The human GLUT family is a set of membrane proteins crucial to the movement of glucose in and out of the cell. They also noted that many of the insulinotropic, glucagonostatic, and anti hyperglycemic actions (mainly for rebaudioside A) were plasma glucose dependant. Meaning that a high blood glucose was needed for many of these effects to take place.

Other factors contributing to the antidiabetic effects of the leaves of Stevia includes its antioxidant properties, mostly through its high phenol content (N. H. Mohd-Radzman et al., 2013).

It appears that Stevias effects against metabolic disorders including diabetes, is through multiple pathways, producing a synergistic effect on reducing hyperglycemia within the body. As N. H. Mohd-Radzman et al., (2013), more specifically suggests, new research should focus on “IRS1, its phosphorylation, the translocation of GLUT4, and the roles of cytokines such as TNF𝛼, not forgetting how PPAR𝛾, JNK, and IKK𝛽 contribute to insulin resistance”. This research would prove useful in determining Stevia and its various glycosides mechanism of actions better, in order to understand more about Stevia's use as a preventative, and treatment for various metabolic disorders.

+ Hypertension

Hypertension is considered a high risk factor for cardiovascular mortality and morbidity in epidemiological studies. There have been many improvements in the treatment and management of this condition, yet it still persists as a major public health issue (P. Chan et al., 2000). Hypertension is a chronic condition that usually requires long term, continuous treatment in order to control. Lifestyle changes including diet restrictions and increased exercise are often implemented. Pharmaceutical medicines such as ACE inhibitors, beta blockers, calcium channel blockers, diuretics, and Clonidine (inhibits nervous system in the brain) are also often prescribed to patients with high blood pressure, although they bring with them a myriad of other health issues resulting from their use. One of the major side effects from some of these medications is a lowered sexual functioning.

In a study done by P. Chan et al., (2000), researchers found stevioside to not only produce significant antihypertensive effects ,but also had no adverse effect on sexual function. They also reported that in most cases, the reduction in blood pressure was not noted until about day 7 of treatment.

The mechanism of action for these effects are not fully understood, however researchers suggest that it appears these actions are through a calcium antagonist mechanism, in a similar fashion to the pharmaceutical drug verapamil (used to treat angina and cardiac arrhythmias). Other studies suggest these effects depend on prostaglandin activity (P. Chan et al., 2000).

+ Inflammation

Stevioside has been shown to down regulate the nuclear factor K-light-chain (NF-kB) pathway. This plays an important role in the process of inflammation within the body. (N. H. Mohd-Radzman et al., 2013).

Stevioside has also been found to reduce TNF alpha expression, as well as other chemotactic and proinflammatory cytokines (N. H. Mohd-Radzman et al., 2013).

+ Natural Sweetener

Fructose, a natural sugar found in most fruits, many veggies, and honey, is a ketose which is combined with glucose (an aldose) to form the common sugar, sucrose. This sugar is also a common additive to soft drinks, grain products, and other foods as a sweetener.

Z. T. Bloomgarden, (2011) states that “Fructose is associated in epidemiologic studies with greater weight, triglyceride, blood pressure, and insulin resistance levels and in animal and human feeding studies with small dense LDL cholesterol, nonalcoholic fatty liver disease, and greater levels of protein glycation”. They also state that extremely high fructose intake is uncommon “in nature”, but is a common occurrence when consuming medium to large amounts soda, containing added fructose.

In fact, as referred to in an article by Z. T. Bloomgarden, (2011), Miller Jones states that “ [the] Ingestion of fructose in a normal, dietary manner . . . does not cause biologically relevant changes in triglyceride or body weight [even] when consumed at levels approaching 95th percentile estimates of intake”.

It is not merely high intake of fructose that delivers these adverse effects, but any sugar. In a study looking into the comparative effects of high fructose intake and high sucrose intake (25% of diet) in men, both sugars were found to have a similar effect on triglyceride levels (Z. T. Bloomgarden., 2011). These results suggest that the type of carbohydrate is likely not the main issue at hand here, but rather the amount of carbohydrate consumed.

In light of this, and copious other sources of information regarding this topic, it is apparent that it is necessary to either cut out foods with added sugar, or to replace this caloric sweetener with non-caloric forms such as aspartame, or glycosides such as those found in Stevia rebaudiana. It should also be mentioned that aspartame also has its own detriments, and negative effects on health, which will not be discussed in this paper.

It should be noted that studies done regarding fructose (and other carbohydrates) on rodents, may not be a good model representing the same effects on human health, as the de novo lipogenesis in rodents constitutes 60-70%, whereas humans are a mere 10-20% (Z. T. Bloomgarden, 2011). This highly complex pathway is responsible for the conversion of excess carbohydrates into fatty acids to then be esterified and stored as triacylglycerols. Therefore the effects of ingesting various amounts of carbohydrates in rodent bodies and humans are significantly different.

Stevia contains some well known and well studied glycosides such as Rebaudiosides B, C, and D, and Steviosides. Many of these glycosides are considered non-caloric sweeteners. Meaning they provide the desired sweet flavor, without adding caloric content, which in high amounts leads to obesity, and metabolic disorders such as diabetes, as mentioned earlier.

Rebaudioside B tastes about 150 times sweeter than sucrose. Rebaudioside C is about 20-30 times sweeter, And rebaudioside D is 200-220 times sweeter than sucrose. All of these glycosides are non-caloric. (I. Prakash et al., 2012).

In a qualitative sensory evaluation of rebaudiosides B, C, and D, all were deemed to have a slow onset of sweetness. B provided a lingering aftertaste, C was considered less sweet than sucrose in taste, and D was considered sweeter in taste than sucrose. (I. Prakash et al., 2012). P. Singh and P. Dwivedi., (2014) suggests that collectively the steviosides and rebaudiosides taste about 300 times sweeter than sucrose (p. 431).

As a food additive, Stevia was approved by Health Canada in 2012, and has since increased in popularity as an alternative to artificial sweeteners (E. Pope et al., 2014).

 

Toxicity

Steviol glycosides are not considered carcinogenic, genotoxic, or associated with any reproductive or developmental toxicity (B. Rizzo et al., 2013). Stevioside has been shown to be non-toxic in rabbit, guinea pig, bird, and rat toxicology studies (Taylor L. 2005).

The raw leaf has also showed no signs of mutagenic effects or toxic effects. One study was mentioned by Taylor. L (2005) that suggested Stevia lowers sperm count and testosterone levels in male rats, however multiple other studies have not been able to reproduce this and have instead shown that stevia has no effect on male or female fertility.

Due to Stevias hypotensive effects, people with low blood pressure should use Stevia with caution and avoid high doses of this herb. 

 

Synergy:

B. Rozzo et al., (2013), found that the co-treatment with insulin and Stevia extract caused a significantly higher rise in glucose transport, than was found with the treatment of insulin alone. The extracts obtained from Stevia have been shown to act similarly, and as efficiently as insulin at increasing glucose uptake. This suggests synergy between the two, and provides an area for closer study to find the best ratio between them. Perhaps this is a way to lower insulin injection doses or eliminate them completely in diabetic individuals.

Harmonic Arts Botanical Dispensary

Author:

Justin Cooke

The Sunlight Experiment

Updated: March 2017


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References:

  1. Anthony Sclafani, Mahsa Bahrani, Steven Zukerman, and Karen Ackroff. (2010). Stevia and Saccharin Preferences in Rats and Mice. Chem. Senses. 35. 433-443. doi:10.1093/chemse/bjq033
  2. Benedetta Rizzo, Laura Zambonin, Cristina Angeloni, Emanuela Leoncini, Francesco Vieceli Dalla Sega, Cecilia Prata, Diana Fiorentini, and Silvana Hrelia. (2013). Steviol Glycosides Modulate Glucose Transport in Different Cell Types. Oxidative Medicine and Cellular Longevity.
  3. Eliza Pope, Gideon Koren, Pina Bozzo. (2014). Sugar substitutes during pregnancy. Canadian Family Physician. 60.
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