Stevia (Stevia rebaudiana)

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Stevia Summary

Stevia rebaudiana contains a series of glycosides that are up to 200 times as sweet as sucrose (table sugar). Despite the intensity of the sweet flavor, stevia is considered a "non-caloric sweetener." This means that the sweetening effects of stevia do not evoke an insulin response in the body.

In the developed world, overconsumption of sweeteners and carbohydrates has lead to widespread diabetes and metabolic disorders all over the world. If insulin spikes too many times each day for several years, the body will begin to become resistant to its effects. This is the pathophysiology of type II diabetes. Food is eaten, and sugar goes into circulation, but the insulin can no longer drive the sugar into the cells to be used as energy. As a result blood, sugar levels rise, and the cells begin to starve for energy leaving us fatigued and at risk for much more severe health effects like cardiovascular disease or renal failure.

Stevia offers a multifaceted and unique approach to combatting these effects and is a popular treatment for diabetics and prophylactic for pre-diabetics or those at risk of developing the disease. The sweet glycosides can be used to replace sugar, eliminating much of the sugar and insulin spikes that follow a meal. Stevia also directly improves insulin sensitivity within the cells to ameliorate the effects of insulin resistance.

In a world ravaged by diabetes, stevia is likely to become a staple herb in every household.

 

Indications

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

Contraindications

  • None noted

Herbal Actions:

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

What is Stevia Used For?

Stevia is mainly used as a non-caloric sweetener for people with diabetes. The glycosides contained in the plant are up to 160 times sweeter than sucrose. These glycosides are also useful for regulating blood sugar on their own and can be used as a prophylaxis treatment for those at risk for diabetes or metabolic syndrome.

 

Traditional Uses of Stevia

Stevia rebaudiana has traditionally been used by the Guarani Indians of Brazil and Paraguay as a treatment for diabetes and as a sweetener [10, 11].

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 [10].

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 [10].

 

Stevia Monograph

Weekly Dose

Part Used

  • Leaves

Family Name

  • Asteraceae

Distribution

  • Central & South America

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Constituents of Interest

  • Steviosides
  • Rebaudiosides A, B, C, and D
  • Steviol
  • Apigenin

Common Names

  • Stevia
  • Sweet herb
  • Sweet leaf
  • Kaa jhee
  • Azucacaa
  • Eira-caa
  • Capim
  • Doce
  • Yaa Waan
  • Honey yerba
  • Candy leaf

CYP450

Unknown

Nature/Taste

Sweet

Pregnancy

No adverse effects expected.

Duration of Use

  • Long term use of stevia is acceptable.
 

Botanical information

Stevia is a member of the Asteraceae family of plants. This is one of the largest family of flowering plants in the world, only smaller in diversity than Orchidaceae.

There are another 200 species of Stevia — however, Stevia rebaudiana is the only species with the sweet glycoside that has made this plant so useful.

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 [2]. 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 [10].

Some sources state that there are 150 known species of Stevia [5], with other sources listing 200-230 [8, 10]. All agree that Stevia rebaudiana Bertoni is the only one found to have specific desired properties including its strong sweet flavor despite containing no calories and possessing significant antidiabetic effects, and richness of particular metabolites such as beta-carotene, thiamine, and various terpenes and flavonoids [5, 8].

 

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 [6].

 

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 impact 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 reduced 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 to acclimatize the roots into the soil successfully. A third option, in vitro cultures or "plant tissue culture" offers a solution to these issues. In result of this, a group of researchers have developed an efficient micropropagation protocol for Stevia rebaudiana [6].

They also noted that in vitro grown plants had a much higher stevioside content than in plants cultivated in vivo. 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 [8].

Currently, Stevia is being cultivated commercially in Brazil, Paraguay, Uruguay, parts of Central America, Israel, Thailand, and China [10].

 

Pharmacology & Medical Reesearch

+ 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. Recent research suggests that insufficient insulin production is due to a destruction of the autoimmune response, which results in disruption of 𝛽-cells [5].

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-signaling pathway. There is compelling evidence that this form of diabetes is due to a combination of genetic linkage, and poor lifestyle choices [5].

Diabetes mellitus is a serious global health issue that negatively affects both qualities of life and longevity [11]. It is a disease associated with various cardiovascular diseases, obesity, lowered sexual functioning, fatigue, lowered epithelial function, reduced 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 [2].

High glycemic diets, including natural sugars like fructose, have been shown to induce several metabolic conditions (hyperinsulinemia, hyperglycemia, hypertension, and insulin resistance), in animal models [9].

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 [9].

In a study done investigating the effects of Stevia (stevioside), 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. [9].

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 [11].

Stevioside has been shown to enhance insulin sensitivity throughout the whole body, and improve glucose infusion rate [5].

TNF alpha (a proinflammatory cytokine involved with the reduction of insulin sensitivity), was also significantly downregulated along with other proinflammatory and chemotactic cytokines [5].

B. Rizzo et al., (2013) found that Stevia extracts behaved similarly to insulin and was stated to be as efficient as insulin at increasing glucose uptake [2]. 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 antihyperglycemic actions (mainly for rebaudioside A) were plasma glucose dependant, which means that 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 include its antioxidant properties, mostly through its high phenol content [5].

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” [5].

This research would prove useful in determining Stevia and its various glycosides mechanism of actions better, 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 persists as a significant public health issue [7]. Hypertension is a chronic condition that usually requires long term, continuous treatment 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 significant side effects from some of these medications is 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 [7]. 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, similar to the pharmaceutical drug verapamil (used to treat angina and cardiac arrhythmias). Other studies suggest that these effects depend on prostaglandin activity [7].

+ Inflammation

Stevioside has been shown to down-regulate the nuclear factor K-light-chain (NF-kB) pathway. This plays a vital role in the process of inflammation within the body. [5].

Stevioside has also been found to reduce TNF alpha expression, as well as other chemotactic and proinflammatory cytokines [5].

+ 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” [12]. 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.

As referred to in an article by Z. T. Bloomgarden, (2011), Miller-Jones states that “ [the] Ingestion of fructose in a normal, dietary manner [12]. . . 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 a 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 impact on triglyceride levels [12]. 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 adverse effects on health, which will not be discussed in this paper.

It should be noted that studies involving 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% [12]. This highly complex pathway is responsible for the conversion of excess carbohydrates into fatty acids to be then 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 Rebaudioside 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 [4].

In a qualitative sensory evaluation of rebaudioside 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 [4]. 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 [3].

 

Phytochemistry

Stevia rebaudiana is rich in flavonoids 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 and has been noted to be higher in plants propagated in vitro [6]. Another sweet component includes steviolbioside [10].

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 [10].

 

Clinical Applications Of Stevia:

Stevia has shown reliability in treating both Type I and type II diabetes through a series of mechanisms. Initially through replacing sugar with a non-caloric, and non-insulin stimulating flavour, as well as through a directly insulin-sensitising, and glucose uptake modulation. It is useful for both prevention and treatment of metabolic conditions like diabetes and metabolic syndrome.

The antinflammatory effects of stevia make it useful for systemic inflammation, especially in relation to TNF-a and NF-kB.

Stevia is also useful for hypertension and cardiovascular disease through calcium antagonism in the smooth muscle of the vascular system.

 

Cautions:

Those with low blood sugar should use caution when using stevia due to its hypotensive effects.

 

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated may 2016)

 

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References:

  1. Sclafani, A., Bahrani, M., Zukerman, S., & Ackroff, K. (2010). Stevia and saccharin preferences in rats and mice. Chemical senses35(5), 433-443.

  2. Rizzo, B., Zambonin, L., Angeloni, C., Leoncini, E., Vieceli Dalla Sega, F., Prata, C., ... & Hrelia, S. (2013). Steviol glycosides modulate glucose transport in different cell types. Oxidative medicine and cellular longevity2013.

  3. Pope, E., Koren, G., & Bozzo, P. (2014). Sugar substitutes during pregnancy. Canadian Family Physician60(11), 1003-1005.Chicago

  4. Prakash, I., Campbell, M., & Chaturvedula, V. (2012). Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, rebaudioside B, rebaudioside C, and rebaudioside D and sensory evaluation of their reduced derivatives. International journal of molecular sciences13(11), 15126-15136.

  5. Mohd-Radzman, N. H., Ismail, W. I. W., Adam, Z., Jaapar, S. S., & Adam, A. (2013). Potential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review. Evidence-Based Complementary and Alternative Medicine2013.Chicago

  6. Singh, P., & Dwivedi, P. (2014). Two-stage culture procedure using thidiazuron for efficient micropropagation of Stevia rebaudiana, an anti-diabetic medicinal herb. 3 Biotech4(4), 431-437.Chicago

  7. Chan, P., Tomlinson, B., Chen, Y. J., Liu, J. C., Hsieh, M. H., & Cheng, J. T. (2000). A double‐blind placebo‐controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. British journal of clinical pharmacology50(3), 215-220.Chicago

  8. Guleria, P., & Yadav, S. K. (2013). Agrobacterium mediated transient gene silencing (AMTS) in Stevia rebaudiana: insights into steviol glycoside biosynthesis pathway. Plos One8(9), e74731.Chicago

  9. Anton, S. D., Martin, C. K., Han, H., Coulon, S., Cefalu, W. T., Geiselman, P., & Williamson, D. A. (2010). Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite55(1), 37-43.

  10. Taylor, L. (2005). The healing power of rainforest herbs: A guide to understanding and using herbal medicinals (pp. 214-216). New York: Square One Publishers.

  11. Cekic, V., Vasovic, V., Jakovljevic, V., Mikov, M., & Sabo, A. (2011). Hypoglycaemic action of stevioside and a barley and brewer’s yeast based preparation in the experimental model on mice. Bosnian journal of basic medical sciences11(1), 11.

  12. Bloomgarden, Z. T. (2011). Nonnutritive sweeteners, fructose, and other aspects of diet. Diabetes Care34(5), e46-e51.