Is Steviol Glycosides Safe?

Stevia, commonly known as stevioside[1], is extracted from the herb stevia, which is native to Paraguay, Brazil, Argentina and other places in South America. Stevioside is 200 to 350 times sweeter than sucrose, but only 1/300 as high in calories. It is a new, natural sweetener that is high in sweetness and low in calories, and also has health benefits.

Stevioside has the characteristics of low calorie, high sweetness, good taste, high temperature resistance, and good stability. It does not leave residues in the human body, is safe and non-toxic, and is beneficial for regulating blood sugar and promoting mental activity. It is also beneficial for the treatment of cardiovascular cardiovascular disease, obesity, and diabetes patients have adjuvant therapeutic functions, and it is also helpful in preventing and treating tooth decay and can be used as a sugar substitute for phenylketonuria (PKU) patients [2-4]. In addition, it is also heat-resistant, stable, and antiseptic, so when added to food, it is not easily denatured or deteriorated. It is not strict about the pH requirement, has a long shelf life, and does not clump or brown. Therefore, it is widely used in the confectionery, beverage, food, pharmaceutical and other industries in many countries (regions) at home and abroad. It is known as the “best natural sweetener” and is the third natural sugar substitute with development value and health benefits after cane sugar and beet sugar. It is internationally known as the “third sugar source” [5-6].

1 Overview of steviol glycosides

1.1 Basic properties of steviol glycosides

Steviol glycosides are white to slightly yellow crystalline powders or granules with a cool, sweet taste. They have the molecular formula C38H60O18, are easily soluble in water and ethanol, have good heat resistance and stability, are non-fermentable substances, and do not cause the Maillard browning reaction.

Extensive research has confirmed that the sweetening component in stevia is a glycoside, the aglycone of which is a tetracyclic diterpene compound, and the glycosyl group has eight main glycosides such as glucose (-G) and rhamnose (-Rh).

1.1.1 Low-calorie

Steviol glycosides are linked by a β(2-1) bond and are not digested or absorbed in the upper gastrointestinal tract. In the lower gastrointestinal tract, they are mainly broken down by microorganisms in the caecum into steviol, which is partially absorbed. It is then excreted via the bile, enters the enterohepatic circulation, and is ultimately excreted in the faeces, mostly in the form of steviol, with only a very small proportion being excreted in the urine [7]. The calories are indirectly produced by the fermentation of the short-chain fatty acids produced by the colonic intestinal microorganisms, which is about 6.3 kcal/g. Stevioside is a low-calorie ingredient, so it does not cause problems and diseases caused by excess calories such as obesity in the human body. It is used in many countries to replace sugar to reduce the calories in dairy products, ice cream, candy, and baked goods.

1.1.2 Safety

Stevia is native to Paraguay and Brazil in South America, and the local people have been consuming it for more than 400 years without any harmful effects being detected. Japan and South Korea have a 40-year history of consuming stevia, and to date, no cases of illness caused by stevia consumption have been found. Long-term consumption of stevia has a preventive and adjuvant therapeutic effect on hypertension, diabetes, obesity, heart disease, atherosclerosis, and childhood dental caries, with no side effects.

Stevioside does not participate in metabolism in the body, does not accumulate, has no toxic effects, and is not teratogenic, mutagenic or carcinogenic. As a sweetener, it does not cause allergic reactions and is a “very low toxicity” sweetener. Its safety has been recognized by international organizations such as the FAO and WHO. The Japan Food Additives Group has long since determined that stevioside is a sweetener that does not require special limits on its use. The Ministry of Health of the People's Republic of China approved stevioside as a natural sweetener and pharmaceutical sweetener excipient for unrestricted use in 1985 and 1990, respectively.

The results of the acute oral toxicity study in rodents are shown in Table 1. No lethal damage was found after 14 days, and no clinical signs of toxicity or morphological or histopathological changes were found [8-9].

In a long-term feeding test with rats using different doses of stevioside, the no-observed-effect level (NOEL) for the first three months of feeding was used as the basis for the recommendation of an acceptable daily intake (ADI) of 7.9 mg/kg for humans [10]. Toyoda [11- 12] and others found that stevioside, with a purity of 95.6%, did not cause cancerous lesions in Fischer 344 rats when added to the feed at different ratios.

1.1.3 Stability

Under normal food and beverage processing conditions, steviol glycosides are quite stable, which is beneficial for reducing viscosity, inhibiting bacterial growth, and extending the shelf life of the product.

Steviol glycosides have a melting point of 198°C to 202°C and are relatively heat-resistant. They are stable in solutions with a pH of 3 to 9. At pH 3 (room temperature), there is basically no decomposition loss and no precipitation occurs after 180 days. The sweetness remains the same after heating at temperatures below 95°C for 2 hours. At a pH of 2.15 to 3.15 and a stevioside concentration of 0.105%, the stevioside is about 90%; when the pH is between 3.10 and 4.10 and the concentration is 0.1013%, the retention rate is about 90% after being stored at room temperature for 6 months [13]. In addition, stevioside is also very stable to light. A 0.11% stevioside solution placed in a glass container and exposed to sunlight for 7 months had a residual rate of over 90%. Stevia also has good tolerance, does not cause the Maillard browning reaction, and is not assimilated or fermented by microorganisms.

1.2 Physiological functions of stevioside

Many studies have shown that stevioside can promote the proliferation of bifidobacteria and lactobacilli in the human body. Bifidobacteria and lactobacilli can ferment carbohydrates in food to produce acetic acid, propionic acid, butyric acid and lactic acid, significantly reducing the pH of the intestines, inhibiting the growth of pathogenic bacteria such as Escherichia coli, Clostridium and Salmonella[14], reducing the production of putrefactive products, promoting intestinal peristalsis, relieving constipation, and having a preventive effect on intestinal diseases.

In addition, the indigestibility of stevioside means that its ingestion does not cause an increase in blood glucose concentration, nor does it promote an increase in insulin concentration in the blood, making it suitable for use by diabetics [15]. Jiangu Chen et al. [16] found in a clinical study that stevioside has the potential to improve insulin, especially for type 2 diabetes, and to resist hyperglycemia.

Many researchers have reported that stevioside can lower the levels of cholesterol and triglycerides in the blood, reduce the concentration of low-density lipoprotein (LDL) in the body, and not affect the concentration of high-density lipoprotein (HDL), resulting in an increase in the HDL/LDL ratio. The reason is thought to be that the structure of stevioside gives it the ability to adsorb lipids to a certain extent, so that it can adsorb bile acids in the intestine, and competitively inhibit the binding of the latter to cholesterol and fat, making cholesterol and fat in the monomeric state not conducive to the absorption of small intestinal villi absorption. In a study of the efficacy and tolerance of orally administered stevioside, Ming-Yi Hsieh et al. found that stevioside can effectively lower systolic and diastolic blood pressure (P<0.05) without significant toxic side effects.

Jin Chenyan (Japan) and others [17] found that fermented stevia extract has obvious antihistamine effects and may also reduce allergic rhinitis, urticaria, and asthma.

2 Stevioside applications

2.1 Stevioside applications in food products

Steviol glycosides are naturally non-toxic, have stable physical and chemical properties and excellent physiological properties, making them widely used in the food industry.

2.2 Steviol glycosides in compound sweeteners

Steviol glycosides are one of the most promising natural sweeteners in terms of production resources, sweetness, sweetness perception and price. However, the bitter taste of stevioside has always hindered its widespread use. For this reason, Japan, South Korea and China have used transferase and hydrolase methods to improve the aftertaste of stevioside; the downside is that the negative effect is often a decrease in the sweetness multiplier and an increase in cost. People have tried to extract and refine stevioside glycosides with higher A3 glycoside content, which can be up to 350-400 times sweeter, but the aftertaste of bitterness has increased correspondingly, making it difficult to use. However, even if the aftertaste problem is solved, the mellow, refreshing taste of sweetness can only be achieved through the chemical synergy of compounding.

Compound sweeteners can achieve the best effect of sweeteners, reduce costs, and maintain the special effects of single sweeteners. New compound sweeteners can be made by combining new flavor additives. By taking advantage of the synergistic effects and physiological characteristics of various sweeteners, they can reduce undesirable flavors, shorten the time it takes for the taste to develop, improve the stability and richness of sweetness, reduce the total amount of sweetener used, and lower costs.

Currently, the combination of natural sweeteners is increasingly in line with today's fashionable trend of natural, healthy, green, and slimming sweeteners. For example, the natural combination of erythritol and stevioside.

Erythritol is a natural filling sweetener with high tolerance. Its sweetness is 70% to 80% that of sucrose, and its pure sweetness is soft and refreshing. A 1% to 3% solution of erythritol can mask the unpleasant taste or flavor usually associated with high-potency sweeteners, significantly improving the taste characteristics. In addition, erythritol has a low caloric value (0 cal/g to 0.2 cal/g), only 5% to 10% of the energy of sucrose, and is difficult to metabolize, making it suitable for diabetics.

It can be seen that the combination of the two natural sweeteners stevioside and erythritol not only enhances the health benefits, but also complements each other to a certain extent. Erythritol can improve the undesirable taste caused by stevioside alone, and stevioside can reduce the cost of using erythritol alone. Therefore, the combination of the two must have broad application prospects.

3 Current development and safety evaluation of stevioside

3.1 Current development of stevioside

Stevioside has been widely used in developed countries abroad. In Japan, 40% of foods already use stevioside as a sweetener, and stevioside is also widely used in medicine. In recent years, the use of stevioside in Japan has increased at a rate of 10% to 20%. The United States issued a stevioside permit relatively late. At the end of 2008, after the US Food and Drug Administration (FDA) passed the “generally recognized as safe” (GRAS) resolution on stevioside, Coca-Cola and PepsiCo launched stevia-sweetened products. Coca-Cola teamed up with the agricultural company Cargill to develop Truvia, and PepsiCo teamed up with EarthSweet to develop PureVia. This FDA decision enabled Coca-Cola and PepsiCo to launch drinks containing this sweetener, and the two companies also hope that this sweetener will promote the launch of their low-calorie drinks and increase product sales.

Judging from the situation in China, the use and production of synthetic food additives such as saccharin has been restricted by the state time and time again. People also hope that safe, natural health food additives will be introduced. Since stevioside was first used, it has been fully recognized and accepted by people. The market has passed the introduction period and is growing into a mature new product that is popular and favored by many people. China is not only a major stevia-growing country, but also a major stevioside-producing country and an even bigger exporter, responsible for supplying the world with stevioside. However, because stevioside is expensive, it is rarely used in domestic food products and is mostly exported. But you can still find traces of stevioside in potato chips, prawn crackers and instant noodles in supermarkets.

From the above analysis, it is not difficult to see that with the continuous progress of human society and improvement of living standards, as well as the development and popularization of nutrition and health science, in the near future, stevioside will not only completely replace various chemically synthesized sweeteners and enter thousands of households, but will also gradually replace sucrose and ultimately occupy the dominant position in the sweet world!

3.2 Safety evaluation of stevioside

The Joint Food and Agriculture Organization of the United Nations (WHO/FAO) Expert Committee on Food Additives (JECFA) conducted a safety evaluation of stevioside in 1998 and did not conclude that stevioside is harmful to human health. Current research reports also show that there is no evidence of direct harm to human health from stevioside. In 1984, China approved stevioside as a food additive and included it in the Hygienic Standards for Uses of Food Additives (GB2760), stipulating that stevioside can be used to include liquid and solid drinks, candies, pastries, etc. After 2000, it was approved to expand the scope of use to include fried snacks, seasonings, candied fruits and melon seeds, and to use it as needed for normal production. In the past 20 years of use, no safety problems have been found with steviol glycosides. At present, in addition to China, steviol glycosides have been approved for use as food additives in more than 20 countries, including Japan, Brazil, Malaysia, Argentina, and Paraguay.

The United States allowed stevia to be used as a dietary supplement in 1995, but since the 1980s, the FDA has always labeled stevia as an “unsafe food additive” [18]. It was not until the end of 2008 that it was announced that stevioside diastereoisomer A (derived from the plant stevia) was “generally recognized as safe” as a sweetener for general use.

The Scientific Committee for Food (SCF) of Europe accepted applications for stevioside as a sweetener in 1985 and 1997. The SCF believes that there is insufficient specification data on stevioside, and that the metabolite steviol exhibited mutagenicity in in vitro experiments and may also affect reproductive capacity, requiring further confirmatory studies. In addition, only data from rat carcinogenicity experiments with stevioside were provided, so the current safety data are also insufficient to support its use as a sweetener [19]. The application for the marketing of stevia plant bodies and dried leaves as food or food ingredients was rejected [20].

4 Prospects for stevioside

Stevioside is not only an ideal natural sweetener with high sweetness, low calorie, easily soluble, delicious, heat-resistant, stable, non-fermentable, safe and non-toxic properties, but also has many health-promoting functions. Therefore, it is widely used as a new food additive in the food, beverage, brewing, pharmaceutical, and household chemical industries, and has achieved certain results. However, at the same time, there are still many problems: for example, the conversion rate of the raw material is not high, and the purity of the product is not high enough. However, with the development of science and technology in China and people's increasing awareness of health care, stevioside products with high purity, low cost, and excellent performance that meet people's health needs will gradually be developed, ultimately contributing to improving people's health. As research on stevioside continues to deepen, the application prospects of stevioside will become more and more promising.

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[18]  Federal  Food,  Drug  and  Cosmetic  Act  of 1994 (  revised  April 2000).  [Z], Section 402(a)  (2)(c), Section 409 and 21 CFR 170 and21 CFR 189-1

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