Stevia

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 ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

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 ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

Diabetes mellitus is a serious global health issue that negatively affects both quality of life and longevity ^{11Reference 11Cekic et al. · 2011AnimalHypoglycaemic action of stevioside and a barley and brewer’s yeast based preparation in the experimental model on mice}. It’s 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 ^{2Reference 2Rizzo et al. · 2013Steviol glycosides modulate glucose transport in different cell types}.

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 ^{9Reference 9Anton et al. · 2010Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels}.

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 ^{9Reference 9Anton et al. · 2010Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels}.

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. ^{9Reference 9Anton et al. · 2010Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels}.

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 ^{11Reference 11Cekic et al. · 2011AnimalHypoglycaemic action of stevioside and a barley and brewer’s yeast based preparation in the experimental model on mice}.

Stevioside has been shown to enhance insulin sensitivity throughout the whole body, and improve glucose infusion rate ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

TNF alpha (a proinflammatory cytokine involved with the reduction of insulin sensitivity), was also significantly downregulated along with other proinflammatory and chemotactic cytokines ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

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 ^{2Reference 2Rizzo et al. · 2013Steviol glycosides modulate glucose transport in different cell types}. 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 ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

It appears that Stevia’s 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” ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

This research would prove useful in determining Stevia and its various glycosides’ mechanisms of action better, to understand more about Stevia’s use as a preventative, and treatment for various metabolic disorders.

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 ^{7Reference 7Chan et al. · 2000A double‐blind placebo‐controlled study of the effectiveness and tolerability of oral stevioside in human hypertension}. 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 ^{7Reference 7Chan et al. · 2000A double‐blind placebo‐controlled study of the effectiveness and tolerability of oral stevioside in human hypertension}. 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 ^{7Reference 7Chan et al. · 2000A double‐blind placebo‐controlled study of the effectiveness and tolerability of oral stevioside in human hypertension}.

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. ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

Stevioside has also been found to reduce TNF alpha expression, as well as other chemotactic and proinflammatory cytokines ^{5Reference 5Mohd-Radzman et al. · 2013ReviewPotential roles of Stevia rebaudiana Bertoni in abrogating insulin resistance and diabetes: a review}.

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” ^{12Reference 12Bloomgarden · 2011Nonnutritive sweeteners, fructose, and other aspects of diet}. They also state that extremely high fructose intake is uncommon “in nature,” but is a common occurrence when consuming medium to large amounts of 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 ^{12Reference 12Bloomgarden · 2011Nonnutritive sweeteners, fructose, and other aspects of diet}.. Does not cause biologically relevant changes in triglyceride or body weight [even] when consumed at levels approaching 95th percentile estimates of intake”.

It’s 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 ^{12Reference 12Bloomgarden · 2011Nonnutritive sweeteners, fructose, and other aspects of diet}. 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’s apparent that it’s 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% ^{12Reference 12Bloomgarden · 2011Nonnutritive sweeteners, fructose, and other aspects of diet}. 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 ^{4Reference 4Prakash et al. · 2012Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, rebaudioside B, rebaudioside C, and rebaudioside D and sensory evaluation of their reduced derivatives}.

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 ^{4Reference 4Prakash et al. · 2012Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, rebaudioside B, rebaudioside C, and rebaudioside D and sensory evaluation of their reduced derivatives}. 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 ^{3Reference 3Pope et al. · 2014Sugar substitutes during pregnancy}.