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Stevia and Diabetes

Stevia and Blood Sugar

Stevia is a genus of about 240 species of herbs and shrubs in the sunflower family (Asteraceae), native to subtropical and tropical South America and Central America. The species Stevia rebaudiana, commonly known as sweetleaf, sweet leaf, sugarleaf, or simply stevia, is widely grown for its sweet leaves. As a sweetener and sugar substitute, stevia's taste has a slower onset and longer duration than that of sugar, although some of its extracts may have a bitter or licorice-like aftertaste at high concentrations.

With its extracts having up to 300 times the sweetness of sugar, stevia has garnered attention with the rise in demand for low-carbohydrate, low-sugar food alternatives. Medical research has also shown possible benefits of stevia in treating obesity and high blood pressure. Because stevia has a negligible effect on blood glucose, it is attractive as a natural sweetener to people on carbohydrate-controlled diets. However, health and political controversies have limited stevia's availability in many countries; for example, the United States banned it in the early 1990s unless labeled as a supplement. Stevia is widely used as a sweetener in Japan, and it is now available in Canada as a dietary supplement.

Rebiana is a trade name for a zero-calorie sweetener containing mainly the steviol glycoside rebaudioside A (Reb-A), which is extracted from stevia. Truvia is the consumer brand for a sweetener made of erythritol and Rebiana marketed by Cargill and developed jointly with The Coca-Cola Company. In December 2008, the United States Food and Drug Administration permitted Reb A based sweeteners as food additives. PureVia is the PepsiCo and Merisant brand of Reb A.

The genus Stevia consists of 240 species of plants native to South America, Central America, and Mexico, with several species found as far north as Arizona, New Mexico, and Texas. Human use of the sweet species S. rebaudiana originated in South America. The leaves of the stevia plant have 30-45 times the sweetness of sucrose (ordinary table sugar). The leaves can be eaten fresh, or put in teas and foods. In 1899, The Swiss botanist Moisés Santiago Bertoni first described the plant and the sweet taste in detail. But only limited research was conducted on the topic, until in 1931, two French chemists isolated the glycosides that give stevia its sweet taste These compounds were named stevioside and rebaudioside, and are 250-300 times sweeter than sucrose, heat stable, pH stable, and non-fermentable.

The exact structure of the aglycone and the glycoside were published in 1955. In the early 1970s, Japan began cultivating stevia as an alternative to artificial sweeteners such as cyclamate and saccharin, which were suspected carcinogens. The plant's leaves, the aqueous extract of the leaves, and purified steviosides are used as sweeteners. Since the Japanese firm Morita Kagaku Kogyo Co., Ltd. produced the first commercial stevia sweetener in Japan in 1971, the Japanese have been using stevia in food products, soft drinks (including Coca Cola), and for table use. Japan currently consumes more stevia than any other country, with stevia accounting for 40% of the sweetener market.

Today, stevia is cultivated and used in food elsewhere in east Asia, including in China (since 1984), Korea, Taiwan, Thailand, and Malaysia. It can also be found in Saint Kitts and Nevis, in parts of South America (Brazil, Colombia, Peru, Paraguay, and Uruguay) and in Israel. China is the world's largest exporter of stevioside. Stevia species are found in the wild in semi-arid habitats ranging from grassland to mountain terrain. Stevia does produce seeds, but only a small percentage of them germinate. Planting cloned stevia is a more effective method of reproduction.

Medicinal use
For centuries, the Guaraní tribes of Paraguay and Brazil used stevia, which they called ka'a he'ê ("sweet herb"), as a sweetener in yerba mate and medicinal teas for treating heartburn and other ailments. More recent medical research has shown promise in treating obesity, high blood pressure, and hypertension. Stevia has a negligible effect on blood glucose, even enhancing glucose tolerance; therefore, it is attractive as a natural sweetener to diabetics and others on carbohydrate-controlled diets. Possible treatment of osteoporosis has been suggested by observations that eggshell breakage can be reduced by 75% by adding a small percentage of stevia leaf powder to chicken feed, and that pigs given 2% stevia leaf powder in their feed experienced a doubling of serum calcium.[21]

Availability
Steviol glycosides were first commercialized as a sweetener in 1971 by the Japanese firm Morita Kagaku Kogyo Co., Ltd., a leading stevia extract producer in Japan. Stevia has been grown on an experimental basis in Ontario, Canada since 1987 for the purpose of determining the feasibility of growing the crop commercially. In the United States, Rebiana is generally recognized as safe as of December 2008, and stevia is also recognized as a dietary supplement. Stevia has also been approved as a dietary supplement in Australia, New Zealand and Canada. Since Jun 2008 it is approved as a sweetener for food and beverages in Australia and New Zealand. In Japan and South American countries, stevia may also be used as a food additive. Stevia is currently banned for use in food in the European Union. It is also banned in Singapore and Hong Kong.

The U.S. ingredient firm Blue California claims to have developed an economical industrial production process for isolating Rebaudioside A. The company expects to go into industrial scale production in 2008. The isolation process for Rebaudioside A results in a product that delivers the desired sweetness without a bitter aftertaste. In 2007, The Coca-Cola Company announced plans to obtain approval for rebiana for use as a food additive within the United States by 2009, as well as plans to market rebiana-sweetened products in 12 countries that allow stevia's use as a food additive. In May 2008, Coke and Cargill announced the availability of Truvia, a consumer brand stevia sweetener containing erythritol and Rebiana, which the FDA permitted as a food additive in December 2008. Coca-Cola announced intentions to release stevia-sweetened beverages in late December 2008. Shortly afterward, PepsiCo and Pure Circle announced PureVia, their brand of stevia-based sweetener, but withheld release of beverages sweetened with reb-A until receipt of FDA confirmation. Since the FDA permitted Truvia and PureVia, both Coca Cola and PepsiCo have announced products that will contain their new sweetener. Critics note that the FDA has not actually permitted the stevia plant itself to be used as a food additive, but only the Reb A extract.

Production
To produce rebaudioside A commercially, stevia plants are dried and subjected to a water extraction process. This crude extract contains about 50% rebaudioside A and is refined using natural crystallization and separation technologies to separate the various glycoside molecules in the extract. This allows the manufacturer to isolate pure rebaudioside A.

The National Research Council of Canada has patented a process for extracting sweet compounds from Stevia by column extraction at temperatures from 0-25°C , followed by purification by nanofiltration. A microfiltration pretreatment step is used to clarify the extract. Purification is by ultrafiltration followed by nanofiltration.

Controversies
Steviol is the basic building block of stevia's sweet glycosides: Stevioside and rebaudioside A are constructed by replacing the bottom hydrogen atom with glucose and the top hydrogen atom with two or three linked glucose groups, respectively.

Health controversy
A 1985 study reported that steviol, a breakdown product from stevioside and rebaudioside (two of the sweet steviol glycosides in the stevia leaf), is a mutagen in the presence of a liver extract of pre-treated rats- but this finding was criticized on procedural grounds that the data were mishandled in such a way that even distilled water would appear mutagenic.[35] Over the following years bioassay, cell culture, and animal studies have shown mixed results in terms of toxicology and adverse effects of stevia constituents, but in general, they have not been found to be harmful. While reports emerged that found steviol and stevioside to be weak mutagens, the bulk of studies show an absence of harmful effects. In a 2008 review, 14 of 16 studies cited showed no genotoxic activity for stevioside, 11 of 15 studies showed genotoxic activity for steviol, and no studies showed genotoxicity for Rebaudioside A. Nevertheless, even if a chemical can cause DNA damage in the controlled conditions of a bioassay (e.g., in bacteria, in mammalian cell cultures) it is a fundamentally different question whether it causes cancer in intact organisms (e.g., rodents, humans) or is teratogenic (i.e., causes birth defects). No evidence for stevia constituents causing cancer or birth defects has been found. Other studies have shown stevia improves insulin sensitivity in rats and may even promote additional insulin production,[41] helping to reverse diabetes and metabolic syndrome. Preliminary human studies show stevia can help reduce hypertension although another study has shown it has no effect on hypertension.[44] Indeed, millions of Japanese have been using stevia for over thirty years with no reported or known harmful effects. Similarly, stevia leaves have been used for centuries in South America spanning multiple generations in ethnomedical tradition as a treatment of type II diabetes.

In 2006, the World Health Organization (WHO) performed a thorough evaluation of recent experimental studies of stevioside and steviols conducted on animals and humans, and concluded that "stevioside and rebaudioside A are not genotoxic in vitro or in vivo and that the genotoxicity of steviol and some of its oxidative derivatives in vitro is not expressed in vivo. The report also found no evidence of carcinogenic activity. Furthermore, the report noted that "stevioside has shown some evidence of pharmacological effects in patients with hypertension or with type-2 diabetes"but concluded that further study was required to determine proper dosage. Whole foods proponents draw a distinction between consuming (and safety testing) only parts, such as stevia extracts and isolated compounds like stevioside, versus the whole herb. However, professionals in pharmacognosy, as well as physicians and science journalists disagree that whole foods are beneficial over extracted components, and may even be harmful.

Political controversy
The stevia plant may be grown legally in most countries, although some countries restrict or ban its use as a sweetener. In 1991, the United States Food and Drug Administration (FDA) labeled stevia as an "unsafe food additive" and restricted its import. The FDA's stated reason was "toxicological information on stevia is inadequate to demonstrate its safety." This ruling was controversial, as stevia proponents pointed out that this designation violated the FDA's own guidelines under which natural substances used prior to 1958, with no reported adverse effects, should be generally recognized as safe (GRAS) as long as the substance was being used in the same way and format as prior to 1958. Stevia occurs naturally, requiring no patent to produce it. As a consequence, since the import ban in 1991, marketers and consumers of stevia have shared a belief that the FDA acted in response to industry pressure. Arizona congressman Jon Kyl, for example, called the FDA action against stevia "a restraint of trade to benefit the artificial sweetener industry." Citing privacy issues, the FDA has not revealed the source of the original complaint in its responses to requests filed under the Freedom of Information Act. Stevia remained banned until after the 1994 Dietary Supplement Health and Education Act forced the FDA in 1995 to revise its stance to permit stevia to be used as a dietary supplement, although not as a food additive - a position that stevia proponents regard as contradictory because it simultaneously labels stevia as safe and unsafe, depending on how it is sold. Although unresolved questions remain concerning whether metabolic processes can produce a mutagen from stevia in animals, let alone in humans, the early studies nevertheless prompted the European Commission in 1999 to ban stevia's use in food in the European Union pending further research. Singapore and Hong Kong have banned it also. However, more recent data compiled in the safety evaluation released by the World Health Organization in 2006 suggest that these policies may be obsolete. In December 2008, the FDA gave a "no objection" approval for GRAS status to Truvia (developed by Cargill and The Coca-Cola Company) and PureVia (developed by PepsiCo and the Whole Earth Sweetener Company, a subsidiary of Merisant), both of which are wholly-derived from the Stevia plant.


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