Is the amount of stevia used in your products safe?
Too much of any substance, solid or liquid may be toxic if too much is consumed. The term, LD50, describes the oral dose required to kill 50% of the lab animals. Let's compare the LD50 of these common substances:
SUBSTANCE-----LD50 GRAMS PER KILOGRAM BODYWEIGHT
Vitamin C----------------12.0 grams/kilogram
Sodium Chloride--------3.0 grams/kilogram
Note: For a 165-lb/75-kg athlete that translates to 1125 grams (1,125,000 mg) of steviosides.
1) Akashi and Yamamoto reported a Stevia-LD50 was 15g/kg in oral administration (1975). 15g/kg means 15 grams of Stevioside for every 1 kg (2.2 lbs.) of body weight.
Considering the safety record of stevia, plus the fact that its LD50 is 5x higher than salt, and even higher than vitamin C, the tincture of stevioside formulated in Hammer Nutrition products should not be of any concern.
First, it's important to mention that any metabolic sequence is always possible when dose is exaggerated and all conditions met. In other words, a variety of chemical conditions must be imposed before natural metabolites in stevioside may impose mutagenic effects. To reproduce mutagenic effects, you would first need to generate aglycone from stevoside. Next, the human enzymatic system would need to activate a number of bioactivities with certain microbes such as salmonella.
Steviol, the aglycone of stevioside, was found to be highly mutagenic when evaluated in the presence of a 9000 X g supernatant (floating above or on the surface) fraction derived from the livers of Aroclor 1254-pretreated rats. Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active.
That said, Brown in 1980 reported, "Two classes of common phenolic plant pigments, the anthraquinones and the flavonols, contain many members mutagenic in the Salmonella/mammalian microsome assay."(A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds. Mutat Res. 1980 May;75(3):243-77. Review. PMID: 6770263 - PubMed - indexed for MEDLINE).
There are several classes of natural compounds that can in extreme overdose in the presence of certain chemical reactions from human enzymes on certain microbes create a mutagenic reaction.
Stevioside is a natural sweetener extracted from leaves of Stevia rebaudiana (Bertoni) Bertoni. The literature about Stevia, the occurrence of its sweeteners, their biosynthetic pathway and toxicological aspects are discussed. Injection experiments or perfusion experiments of organs are considered as not relevant for the use of Stevia or stevioside as food, and therefore these studies are not included in this review. The metabolism of stevioside is discussed in relation with the possible formation of steviol. Different mutagenicity studies as well as studies on carcinogenicity are discussed.
Acute and subacute toxicity studies revealed a very low toxicity of Stevia and stevioside
Fertility and teratogenicity studies are discussed as well as the effects on the bio-availability of other nutrients in the diet. The conclusion is that Stevia and stevioside are safe when used as a sweetener. It is suited for both diabetics, and PKU patients, as well as for obese persons intending to lose weight by avoiding sugar supplements in the diet. No allergic reactions to it seem to exist .
Four steviol (ent-kaurene-type diterpenoid) glycosides, stevioside, rebaudiosides A and C, and dulcoside A, have been isolated from Stevia rebaudiana BERTONI. These compounds showed strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 54.1-291.6 micro g/ear. Furthermore, at 1.0 and 0.1 mg/mouse of stevioside mixture, the mixture of these compounds markedly inhibited the promoting effect of TPA (1 micro g/mouse) on skin tumor formation initiated with 7,12-dimethylbenz[a]anthracene (50 micro g/mouse)  .
Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. Consistent with reports in the literature, we have found that stevioside is not mutagenic as judged by utilization of Salmonella typhimurium strain TM677, either in the presence or in the absence of a metabolic activating system. Similar negative results were obtained with several structurally related sweet-tasting glycosides.
However, steviol, the aglycone of stevioside, was found to be highly mutagenic when evaluated in the presence of a 9000 X g supernatant fraction derived from the livers of Aroclor 1254-pretreated rats.
Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active. The structurally related species, isosteviol, was not active regardless of metabolic activation. Similarly, chemical reduction of the unsaturated bond linking the carbon-16 and -17 positions of steviol resulted in the generation of two isomeric products, dihydrosteviol A and B, that were not mutagenic. In addition, ent-kaurenoic acid was found to be inactive.
It is therefore clear that a metabolite of an integral component of stevioside is mutagenic; structural features of requisite importance for the expression of mutagenic activity include a hydroxy group at position 13 and an unsaturated bond joining the carbon atoms at positions 16 and 17. A potential metabolite of steviol, steviol-16 alpha,17-epoxide, was synthesized chemically and found to be ineffective as a direct-acting mutagen.
Thus, although stevioside itself appears innocuous, it would seem prudent to expeditiously and unequivocally establish the human metabolic disposition of this substance .
Am I saying you can catch cancer from a stevia sweetener? No, likely, and certainly it is not established in the literature's mixed results. In my (Dr. Bill Misner's) opinion it is a completely safe natural nutrient and is a much better choice than sugar added to sweeten foods. I can find 688 references on Medline to imply a carcinogenic relationship of cancer to dietary sugar, yet the FDA considers sugar GRAS. Go figure?
1) Geuns JM. Stevioside. Phytochemistry. 2003 Nov;64(5):913-21. Review. PMID: 14561506 [PubMed - indexed for MEDLINE]
2) Yasukawa K, Kitanaka S, Seo S. Inhibitory effect of stevioside on tumor promotion by 2 -O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Biol Pharm Bull. 2002 Nov;25(11):1488-90. PMID: 1241996
3) Pezzuto JM, Compadre CM, Swanson SM, Nanayakkara D, Kinghorn AD. Metabolically activated steviol, the aglycone of stevioside, is mutagenic. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2478-82. PMID: 3887402 [PubMed - indexed for MEDLINE]- index
4) FOOTNOTE: This response is based on a personal interpretation of formal postgraduate studies and personal research. Application of any information provided is subject to the approved review of each individual's authorized licensed health care practitioner.