Stevia - More Than Super Sweet: More Scientific Evidence, More Potential Implications for Weight Loss & -Maintenance, Anti-Diabetic & -Autoimmune and Even Pro-Anabolic Effects

Image 1: Stevia is sweeter than sugar, healthier than sugar and could even help reverse some of the damage sugar may already have done to your pancreas.

I know that a few of you were almost furious, when I had the audacity to mention the case-report on the pro-cortisol effects of stevia in the On Short Notice post on Saturday, August 18, 2012; and though I did emphasize that this was most likely something like an allergic reaction and/or an issue with solvents, heavy metals (click here for data on heavy metals in stevia leaves; based on Das. 2012), or whatever else may have been in the specific stevia product the lady used; I suspect that you will like today's blogpost which is basically an update on the beneficial effects stevia could have on your overall and metabolic health, much better.

So what's the latest about stevia, then?

Previous studies have already hinted at the fact that the benefits of the use of stevia go well beyond a mere reduction in energy intake and the overall glucose load the average sweet tooth is exposing her- / himself to. Against that background, the results of a recent publication from the School of Pharmacy in Madhya  Pradesh in India are actually not really surprising.

Figure 1: Blood glucose response (mg/ml) to oral glucose load (left) and superoxide dismutase (SOD) levels in mice treated with 250mg/kg (HED: 20mg/kg; ~1.4-2.0g) stevia extract/day (right; data based on Sharma. 2012)

With most previous studies being conducted on isolated pancreatic islet cells in the petri dish, this is however one of the few studies, which in which the scientists were able to observe a robust in-vivo effect from the administration of no more than 250mg/kg of stevia extract (Herbocal) to alloxan-diabetic (this is a model of type II diabetes that is induced by the injection of the drug Alloxan aka 2,4,5,6-pyrimidinetetrone, an oxygenated pyrimidine derivative) and healthy rodents for 28days - with benefits for both, the sick (normalization of blood glucose and restoration of endogenous antioxidants) and the healthy animals (no drop of blood glucose to hypoglycemic levels and increases in SOD above baseline!)

Could stevia not just ameliorate, but actually "heal" diabetes?

Figure 2: It takes it's time but stevia appears to (fully?) restore pancreatic function!

What's also intriguing are the time-course and general trend of the beneficial effects on blood glucose levels in the diabetic group. If you take a closer look at the data in figure 2 you could even speculate that another four weeks later the blood glucose levels would have totally normalized! And if that were the case, this would mean that the steviosides and rebaudiosides, the active molecules in stevia extracts, could actually have the ability to restore or repair the pancreatic beta cells that have been destroyed by either years of high blood glucose (normal type II diabetics) or the assault of the toxic sugar equivalent alloxan (in the study at hand). and protect healthy individuals against future damage by increasing the endogenous antioxidant system (as can be seen by the allegedly non-significant, but probably still physiologically relevant increase in SOD in figure 1, right)

"But this won't work in humans, will it?"

The above is certainly a good question, but in view of the fact that the short term benefits (e.g. +40% increase in insulin response in type II diabetic with -18% reduced postprandial glucose AUV with 1g of stevia in Gregersen et al. 2004), of which the Hermansen group at the Aarhus University Hospital in Aarhus, Denmark, argues that they are based on the interaction of rebaudioside A (cf. table 1) with the ATP-sensitive K-channels of the pancreatic cells in healthy and its glucagon (and thus gluconeogenesis) inihibiting effects in diabetic individual (Abdula 2004 & 2008; Jeppesen. 2007), have already been reproduced in human trials, I would say that it is more than likely that we will see similar effects in humans, as well, once the correct dosing has been established

Note: especially if you use those combination products of stevia + sugar alcohol you are very unlikely to get sufficient amounts of stevia to elicit those restorative effects; this does not mean that this is a better alternative than aspartame or cyclamate, but in those tiny amounts stevia is a sweetener, not a substance with almost drug-like effects.

Table 1: What's in stevia leaves?
(based on Yadav. 2012)

The latter is by the way all the more likely in view of the fact that Maryam Mohammadi-Sichani and her colleagues from the Falavarjan Branch-Islamic Azad University and the Esfahan University of Medical Sciences in Iran found that stevia extracts will also kill S. mutans, a common bacteria in your mouth that has its share in the development of dental caries and shows, irrespective of generally lower caries rates in type I diabetics, a hitherto not fully explained correlation with (poorly controlled) type I diabetes (Siudikiene. 2006).

Your gut starts in your mouth: The stevia - bacteria connection

These observations stand in line with previous results, of a whole host of peer-reviewed studies Yadav & Guleria summarize in a 2012 review that's about to be published in the November edition of Critical Revision of Food Science, as follows :

Image 2 (20th Century Fox): You better feed your gut bacteria right, otherwise they will disbehave just like the Alien in Ellen Ripley in Alien 3  - read more about the "Gut Type Diet" and how what you eat influences the bacterial composition of your gut on the SuppVersity

"[...] Different extracts showed differential inhibitory activity against various microbes. This experimentation confirmed the antibacterial as well as antifungal potential of Stevia leaf extract and documented that Stevia might be a source of new non-antibiotic antibacterial and antifungal agent. Its antifungal activity was estimated to be higher than the standard fungicide usually used against plant pathogens. Such extraordinary antimicrobial activity of Stevia has presented it as a potent non-antibiotic pharmaceutical and an efficient food preservative. Stevioside alone has been observed to significantly reduce the amount of inflammation mediators and activate cytotoxic cells of the host. These activities suggested that stevioside might play a synergistic role with the innate immunity of the host. Thus stevioside is antibacterial, antifungal, anti-inflammatory, anti-tumorous, and safe for use. While at the same time rebaudioside A has been reported to be clinically insignificant." (Yadav. 2012; my emphases)

In other words, stevia could exert part of it's beneficial effects via the immune-modulatory effects it exerts due to it's impact on the human gut microbiome, the contribution of which to the etiology of both diet-induced type II, but also auto-immune type I diabetes is getting more and more attention among researchers, as of late:

"[...] the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children." (Giongo. 2011; my emphases)

And even if the whole "bacteria theory" of autoimmune disease and inflammation turns out to be yet another sidetrack - you will always have the

• beneficial effects on skeletal muscle insulin sensitivity and glucose uptake that has been established by Lailerd et al. in insulin sensitive and resistant mice and the 
• hopefully physiologically relevant increase in satellite cell activity, Bunprajun et al. observed earlier this year in response to lower NF kappa-beta activity (=modulation of inflammation) in an in-vitro model (Lailerd. 2004; Bunprajun. 2012) 

as additional* arguments to satisfy your sweet tooth with stevia instead of sugar or artificial alternatives (*in addition to being able to avoid the "alternatives").

And as long as you keep an eye on the overall amount of food you consume, instead of simply stuffing yourself until you feel like there was no tomorrow, the previously discussed effects any sweetener - natural, artificial, or whatever else the future may hold - could have on your ability to sense the energy density of your foods should not be all too much of a problem problem (cf. "Sweeter Than Your Tongue Allows").

References:

• Abudula R, Jeppesen PB, Rolfsen SE, Xiao J, Hermansen K. Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency. Metabolism. 2004 Oct;53(10):1378-81.
• Abudula R, Matchkov VV, Jeppesen PB, Nilsson H, Aalkjaer C, Hermansen K. Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. Diabetes Obes Metab. 2008 Nov;10(11):1074-85. Epub 2008 Apr 22.
• Das, K., R. Dang, L. Hegde and A.S. Tripathi. Assessment of heavy metals in dried stevia leaves by Atomic Absorption Spectrophotometer grown under various soil conditions. Middle–East J. Sci. Res. 2011; 8: 107-113.
• Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, Drew JC, Ilonen J, Knip M, Hyöty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011 Jan;5(1):82-91.
• Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism. 2004 Jan;53(1):73-6.
• Jeppesen PB, Dyrskog SE, Agger A, Gregersen S, Colombo M, Xiao J, Hermansen K. Can stevioside in combination with a soy-based dietary supplement be a new useful treatment of type 2 diabetes? An in vivo study in the diabetic goto-kakizaki rat. Rev Diabet Stud. 2006 Winter;3(4):189-99. Epub 2007 Feb 10.
• Sharma R, Yadav R, Manivannan E. Study of effect of Stevia rebaudiana bertoni on oxidative stress in type-2 diabetic rat models Biomedicine & Aging Pathology. 2012 August 28.
• Siudikiene J, Machiulskiene V, Nyvad B, Tenovuo J, Nedzelskiene I. Dental caries and salivary status in children with type 1 diabetes mellitus, related to the metabolic control of the disease. Eur J Oral Sci. 2006 Feb;114(1):8-14.
• Yadav SK, Guleria P. Steviol Glycosides from Stevia: Biosynthesis Pathway Review and their Application in Foods and Medicine. Crit Rev Food Sci Nutr. 2012 Nov;52(11):988-98.