Stevia

Stevia is a naturally occurring low-calorie sweetener. Stevia can be helpful for hypertension, diabetes, fatty liver and weight loss.

Introduction

Stevia was originally called Eupatorium rebaudiana bertoni in honor of Rebaudi, who was the first chemist to study the chemical characteristics of the plant’s extracts (R).

It was originally used as a sweetener in herbal fusions by the Guarani people of South America, but Japan was the first Asian country to market steviol glycosides in the food and drug industry.

Now, cultivation of the plant has expanded to regions like China, Malaysia, Singapore, South Korea, Taiwan, and Thailand. The plant is a long-lasting shrub that is over 100-300 times sweeter than table sugar and has no calories (RR2).

Traditional uses of Stevia

Indigenous people of South America, particularly in Paraguay and Brazil, have used stevia as a sweetener for hundreds of years. For example, the Gurani Indians of Paraguay have an age-old practice of using stevia to sweeten their Yerba Mate tea.

South American populations also have a long history of using stevia medicinally, as a tonic for heart problems, obesity, high blood pressure and heartburn.

Stevia was first noticed by the outside world in the sixteenth century when Spaniards discovered the widespread use of stevia in South America.

In recent years, a growing need to find new, naturally sweet, calorie-free alternative to sugar has led to greater interest in the “sweet herb” from nutritional researchers and commerce (R).

Health Benefits of Stevia

1) Stevia Helps Protect the Heart

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Stevia Reduces High Blood Pressure (hypertension)

Stevia has blood pressure lowering qualities.

A meta-analysis study found that steviol glycoside causes a considerable decrease in the diastolic blood pressure and fasting blood sugar (a determinative element of diabetes and prediabetes).

The blood pressure reduction due to steviol glycoside can help decrease the number of strokes one suffers and can be a preventive measure for managing hypertension and diabetes (R).

Systolic blood pressure is minimally affected by steviol glycoside compared to placebos. The results were most effective when observed over a long period of time.

A study conducted on women found that rebaudioside A caused no significant changes in systolic, diastolic blood pressure, or cardiovascular risk. The blood pressure readings were monitored over a four-week period, during the morning, day, and night (R).

Stevia Inhibits Atherosclerotic Plaque Development

Atherosclerosis is when the arteries harden.

Stevioside is able to reduce the occurrence of atherosclerosis through multiple mechanisms.

It has the ability to inhibit atherosclerosis in the heart by reducing macrophages, oxidized low-density lipoprotein (ox-LDL), and lipids. This reduces plaque.

Stevioside also proved to decrease the production of the inflammatory protein Nf-kB by increasing the production of Nfkbia (R).

2) Stevia Helps Lower Blood Sugar

Stevia contains bio-molecules that stimulate beta cells in the pancreas to release insulin. This can lead to the improvement of carbohydrate metabolizing enzymes, which can lower blood sugar levels.

Stevia can also cause insulin secretion by increasing PPARy. This also normalizes blood sugar levels and monitors insulin release from the pancreas.

Component of stevia, rebaudioside A, stevioside and steviol can all increases insulin secretion by stimulating pancreatic beta cells (R, R).

Antioxidative properties of stevia can also cause an increase in insulin from the pancreas and reduce deterioration caused by chronic pancreatitis (R).

Stevia can also increase insulin sensitivity  in animal models. For example, stevioside was found to increase insulin sensitivity in rats fed a high fructose diet (R).

Similarly, a human study found that post-meal blood sugar levels were lower in stevia consumers than sucrose or aspartame consumers (R).

Stevia glycosides can also act like insulin in stimulating uptake of glucose into cells (R).

Steviosides cause an inhibition of glucagon release (in certain animal models), which can lower blood glucose.

Steviosides also causes an increase in carnitine palmitoyltransferase 1 (CPT 1) which plays an important role in burning fatty acids in the mitochondria (R).

3) Stevia Inhibits the Growth of Non-human Rotavirus

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Stevia has been proven to have an inhibitory effect against non-human rotavirus infection. This is due to stevia having a negatively charged ionic polysaccharide (R).

When using Stevia in conjunction with Sophora flavescens, it enhances the inhibitory ability against rotavirus replication.

Studies showed that the combination causes a decrease in the average concentration of sophora flavescens needed to get a result of 50% replication inhibition.

However, the combination only fights against replication, not attachment. The combination of sophora flavescens and stevia can cure severe diarrhea and intestinal lesions, caused by rotavirus, better than sophora flavescens by itself (R).

4) Stevia Inhibits Tumor Growth and May Prevent Cancer

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Stevia Inhibits the Formations of Skin Tumors Induced by Chemicals

Steviol, stevioside, and isosteviol were found to inhibit the formation of benign tumors (papillomas) caused by cancer-causing and tumor-causing elements such as DMBA  (12-dimethylbenz[a]anthracene) and TPA (12-o-tetradecanoylphorbol-13-acetate).  

The three stevia extracts suppress the promotion stage of tumor production (tumorigenesis), caused by DMBA, by reducing the rapid accumulation of abnormal growth cells that can turn cancerous.

The three extracts also suppress the initiation stage of tumorigenesis induced by peroxynitrite, an oxidant, and nitrating element.

Steviol also has the ability to inhibit the activation of Epstein-Barr virus early antigen, which is a herpesvirus partly responsible for the infection of mononucleosis (a.k.a. mono) (RR2).

Studies conducted on F344 mice concluded that stevia extracts such as rebaudioside A and C, stevioside, and dulcoside have inhibited inflammation caused by TPA (12-O-tetradecanoylphorbol-13-acetate).

Rebaudiosides A and C and dulcoside A have anti-inflammatory promoting abilities that are comparable to the function of hydrocortisone. Stevioside was more effective than an anti-inflammatory drug called indomethacin.

Rebaudioside C prevented 50% of swelling with doses 10 times less than indomethacin and 100 times less than quercetin (an anti-tumor promoting agent).

Concentrations of stevioside were also found to have similar activity to the components: triterpenoids, heliantriol C, pachymic acid, 3-O-acteyl-16a-hydroxytrametenolic acid, and poricoic acid.

These are the most effective naturally occurring elements from plants and fungi that have anti-tumor promoting effects. Tests performed on mice found that utilizing a stevioside mixture reduced the formation of tumors caused by TPA and DMBA (7,12-dimethylbenz[a]anthracene) approximately 73-96%.

The effects depend on the concentration of stevioside used. The mixture also delayed the formation of tumors in the mice (R).

Stevia May Help Treat Breast Cancer

Studies show that Stevia lowers the presence of benign tumors (adenomas) in the breasts of mice compared to mice not treated with stevioside concentrations. These changes are linked to the reduction in body weight due to caloric restriction (R).

Stevioside also has strong inhibitory effects on MCF-7 breast cancer cells. It generates reactive oxygen species within MCF-7 cells which promotes cell signaling and homeostasis.

Free radicals are also generated by the treatment of stevioside which can accelerate cell death by damaging cellular components such as DNA, proteins, and lipid membrane (R).

5) Stevia Can be Used to Treat Acute Lung Injuries

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Treatments with stevioside can be utilized as therapy for acute lung injury.

Stevioside can lessen the lung damage caused by lipopolysaccharides by decreasing the wet-to-dry ratio in the lungs, pro-inflammatory cytokine production, and inflammatory cell migration into the lungs.

Acute lung injury can be linked to inflated expressions of iNOS (inducible nitric oxide synthase). Stevioside reduces the presence of nitrate and nitrite and also inhibits the expression of iNOS in the lungs.

Stevioside also has protective anti-inflammatory effects by decreasing the production of proteins (cytokines) (R).

6) Stevia Helps Prevent Fatty Liver

Stevioside, rebaudiosides A, and steviol has an effect on the metabolic pathways that involve high fat levels (lipotoxicity) such as deterioration (steatosis), hepatitis, and liver disease (steatohepatitis).

Obese and insulin-resistant mice were treated with stevioside, rebaudiosides A, and steviol, and the results exhibited a significant decrease in liver steatosis levels.

Hepatic steatosis occurs when liver cells are invaded with fat. The reduction in hepatic steatosis levels is due to the improvement of sugar metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport by all the three steviol compounds.

Stevia derivatives also protect from the toxic effects abnormal placement of fat build up in the liver which contributes to obesity (R).

7) Stevia May Help Reduce Kidney Damage

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Concentrations of stevioside have been used to reduce the severity of chronic kidney disease (nephropathy).

According to one study in streptozocin-induced diabetic rats, stevia leaves could reduce the risk of oxidative stress and thus reduce kidney damage (R).

In another study, Stevia leaves were more effective than I-NNA (N-nitro-L-arginine) in managing diabetes-induced kidney disorders in rats (R).

8) Effects of Stevia on Fertility

Many studies have been conducted regarding the effects of stevia on fertility. Tukey and Mann-Whitney tests were used to determine how stevia impacts male reproductive organs.

It found that the cauda epididymis, seminal vesicle, and testis of male mice (treated with high concentrations of stevia) decreased in relative weight. The cauda epididymis also experienced a large decrease in spermatozoa.

These effects were believed to be caused by a reduction of plasma levels of androgen receptors (steroid hormones that promote certain male sex characteristics) (R).

However, other studies have found contrasting results. For instance, a more recent study proved that stevia has no effect on male reproduction by replicating the Tukey and Mann-Whitney tests that were previously used.

An extremely high concentration of stevia was used in the experiment, the amount is comparative to approximately 50% of the mice’s body weight.

Experiments were also performed on chicken embryos because they are highly susceptible to toxins. Broiler eggs were injected with stevioside then evaluated at hatch day and a week after.

The hatchlings developed normally with no effect on body weight, deformations, or irregular development of the gonads (RR2).

Dosage and Safety

Based on the published research, independent scientific experts in both the U.S and globally have concluded that stevia sweeteners are safe for people of all ages and an Acceptable Daily Intake (ADI) of 4mg/Kg body weight has been established (R).

The natural, whole stevia leaf has mostly been shown to be non-toxic and safe. Studies indicate that stevioside, the primary chemical that gives Stevia its sweetness, cannot cause cellular changes or affect fertility (R, R2).

Similarly, Stevioside was found to be non-toxic in rats fed with doses as high as 2000mg/kg.

However, there was one study on male rats that found that consumption of a water extract of the stevia leaf lowered testosterone levels and sperm count (R).

Fortunately, this result seems to be anomalous and probably due to the high levels of stevia used in the study.

Another study gave stevia extracts to 500 rats for two years, with stevia totaling 1% of their diet. The researchers found that there was no dose-related change in growth, organ health, appearance or other health parameters (R).

Some commentators have suggested that certain components of stevia can be converted by the body into compounds that cause DNA mutations and cancer.

However, researchers found that the potential of steviol glycosides to cause DNA mutation is 3000 times less than common compounds like diesel smoke or burnt meat.

Whilst Stevia has recently become widely used in many countries without indications of toxicity surfacing, until certain aspects of distribution and metabolism have been properly investigated in humans, any assumption of safety appears premature. This explains why the FDA has not approved crude or whole-leaf stevia as a safe food additive.

Adverse Effects

One piece of research discovered that 16% of infants with nasal allergies, 34% of infants with bronchial asthma, and 64% of infants with atopic eczema were allergic to stevia.

If you have an allergy to plants in the Compositae or Asteraceae families – such as chrysanthemums, marigolds, ragweed or daisies – then it’s entirely possible that you will have an allergic response to stevia.

Symptoms include swelling and itching of the oral area, hives, GI pain, nausea, and vomiting.

Constituents of Stevia

It is now known as Stevia rebaudiana or stevia, for short. The best known natural products derived from stevia rebaudiana are glycosides such as stevioside (9.1%), rebaudioside A (3.8%), rebaudioside C (0.6%), steviolbioside (a.k.a. steviol), dihydroisosteviol (a.k.a. isosteviol), rubusoside, and dulcoside (0.3%).

Stevia consists of approximately 80-85% percent water, protein, fiber, lipids, monosaccharides, essential oils, vitamin c, β-carotene, vitamin B2, and vitamin B1.

It also contains minerals like cobalt, magnesium, iron, potassium, and phosphorus. Certain antioxidant compounds are also elements in stevia.

Technical

  • Nfkb1 is a gene that is involved in inflammation, whereas, Nfkbia is an inhibitor of Nkfb1.
  • Steviol glycosides in stevia may help regulate blood sugar levels by modulating GLUT translocation through the PI3K/Akt pathway.
  • Stevia also blocks anti-VP7, which is a protein that plays a role in the cellular entry of anti-human rotavirus, from binding to MA104 cells in certain concentration (R).
  • Stevioside inhibits DNA combination, suppresses cell functionality, and causes self-destructive cell death (apoptosis) by mitochondrial apoptotic pathways.
  • Decreasing the wet-to-dry ratio could inhibit abnormally large amounts of fluid from accumulating in tissues and serious leakage of fluid into the lungs.
  • The wet-to-dry ratio is determined by removing the lungs and weighing them then drying the lungs for a certain amount of time and weighing them again.
  • Atherosclerosis is the condition of plaque build up inside blood vessels.
  • Hypoglycemia is when the body’s blood sugar levels drop too low to adequately support the need for energy and stability. It plays an important role in the development of diabetes.
  • Palmitates are saturated fatty acids found in natural oils and fats. They also cause triglyceride accumulation which affects cell metabolism.

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