Botanicals in diabetes treatment: A look at stevia

Medicinal plants and drugs of biological origin have a place in the treatment of chronic diseases. Drugs of biological origin such as penicillin, morphine, and caffeine have been used consistently and are still in use globally in medical and pharmaceutical practices. Other drugs, such as vinca alkaloids, taxanes, and insulin preparations, are largely biosynthesized from natural sources. A significant number of antimicrobial agents, including vancomycin, griseofulvin, streptomycin, erythromycin, and gentamycin, originated from natural sources.

Stevia is a medicinal plant belonging to the botanical family Asteraceae. The leaf extracts of Stevia rebaudiana Bertoni contain eight potent diterpene glycosides - stevioside, rebaudiosides A to E, steviolbioside, and dulcoside A - which have been studied extensively for use as sweeteners.

Three of the stevia glycosides listed above (stevioside, rebaudoside A, and rebaudoside D) are well-studied and recognized to be 250–300 times sweeter than sucrose.

Properties

Studies of rats, dogs, and mice have examined the pharmacological and toxicological properties of stevia glycosides.

In “An evidence-based systematic review of stevia by the Natural Standard Research Collaboration” (NIH), Ulbricht C, Isaac R, Milkin T, et al assessed the effects of stevia on two indications: hypertension and hyperglycemia.¹ Results of two long-term studies showed that stevia possesses hypoglycemic and BP-lowering effects in mammals.

Shibata H, Sawa Y, Oka T, et al have postulated that the anti-diabetic effects of stevioside may result from a suppression of glucagon secretion from the alpha cells of the pancreas².

Wheeler A, Boileau AC, Winkler PC, et al (2008), have conducted human studies showing similar but different metabolic and elimination pathways for rebaudoside A and stevioside.³

In The U.S, FDA granted purified forms of rebaudoside A GRAS (Generally Recognized as Safe) status.⁴ Under the brand names of low-calorie sweeteners, they are marketed as natural sugar substitutes for use by people living with diabetes, for obese patients on strict diets/exercise regimen, and for patients diagnosed with pre-diabetes and or metabolic syndrome.

Extracts of natural stevia leaf are obtainable as dietary supplements and may not be used as food additives in commercial beverages, although current research is evaluating stevia’s potency in diabetes, obesity, and hypertension. In regard to diabetes, some studies have identified stevia’s trophic effects on pancreatic beta cells, insulin secretion and insulin sensitivity in rats.⁵

Safety

Stevia is not recommended for pregnant patients, and its effect is not yet evaluated in juveniles. It is inapplicable in type 1 diabetes, since its potential effects appear connected to functional pancreatic cells. In one case report of adverse reactions, four patients who were given 500 mg of stevia powder experienced symptoms of abdominal fullness, nausea, asthenia, and myalgia, but their symptoms disappeared after one week of treatment.

In vitro studies show marked anti-inflammatory and antibacterial properties of stevia glycosides, although there have been warnings of weak mutagenic activity in laboratory animals given high doses.⁶

According to the Joint FAO/WHO Expert Committee on Food Additives (JECFA), brand-name products labeled as stevia sweeteners must contain at least 95% of the stevia glycoside  rebaudoside A, and the suggested acceptable daily intake, per JECFA, is 0–2 mg/kgbw/day of a steviol content that is equivalent to 0–6 mg/kgbw/day of rebaudoside A.⁷

Stevia glycosides are metabolized initially in the gut to steviol (the aglycone moiety) and are excreted in the urine as steviol glucuronide.

Stevia was shown to have additive antihypertensive effects with verapamil, as well as blood-sugar-lowering effects with antidiabetic drugs; therefore, caution must be exercised in its use and recommendation for patients taking prescription drugs for chronic ailments.⁸

Section 201(ff){1} of the Federal Food, Drug & Cosmetic Act permits the sale of stevia leaf extracts in the United States as dietary supplements only, and not for the treatment of any manner of disease.

Stevia shows promise as a potential source of important phytochemical ingredients that may serve as precursors of new drugs for diabetes, just as a derivative of guanidine extracts from Galega officinalis (goat’s rue or French lilac), galegine, became the precursor of metformin.

References

1. Ulbricht, C; Isaac, R; Milkin, T; Poole, EA; Rusie, E. et al. (April 2010). An evidenced-based systematic review of stevia by the Natural Standard Research Collaboration. Cardiovascular Hematol Agents Med Chem. 8(2): 113–127. PMID 20370653.

2. Shibata H, Sawa Y, Oka T, et al. Steviol and steviol glycosides: Glucosyl tranferase activities in stevia rebaudiana Bertoni : Purification and partial characterization. Arch Biochem Biophys. 1995; 321(2): 390–396.

3. Wheeler A, Boileau AC, Winkler PC, et al. Pharmacokinetics of rebaudoside A and stevioside after a single dose in healthy men. Food Chem Toxicology, 2008:04.041.

4. FDA GRAS notification database; Stevia search in FDA GRAS Database.

5. Chen TH, Chen SC, Chan P, et al. Mechanism of the hypoglycemic effect of stevioside, a glycoside of stevia rebaudiana. Planta Med. 2005; 71(2):108–113.

6. Koyama, E, Kitazawa K, Ohori Y, et al. In vitro metabolism of the glycosidic sweeteners in stevia mixture and enzymatically modified stevia in human intestinal microflora. Food and Chemical Toxicology. 41.3(2003)359–374.

7. Joint FAO/WHO Expert Committee on food additives, 69th Meeting. World Health Organization, July 4, 2008.

8. Melis, MS, Sainati AR. “Effect of calcium and verapamil on renal function of rats during treatment with stevioside” : J. Etnopharmacol. 1991;33(3):257–262.

Oluwole Williamspractices pharmacy in the Philadelpha, Penn. area. Contact him at pharmwillie@yahoo.co.uk.