Dietary Supplement
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Although no reports describing the use of stevia during human pregnancy have been located, this dietary supplement is consumed extensively throughout the world. Exposure in pregnancy is inevitable, but the lack of reports prevents a thorough assessment of the embryo–fetal risk. In Brazil, South Korea, and Japan, stevioside and highly refined extracts are routinely used as a low-calorie sweetener (1). Such use in the United States started in 1995 (1). Animal reproduction studies have not shown evidence of developmental toxicity except at very high doses. The benefits of stevioside as a dietary supplement have been listed as its being a stable, noncaloric product that maintains good dental health by reducing the intake of sugar, and can be used by diabetic and phenylketonuria patients (1). Moreover, stevioside, the major sweetening compound in stevia, either is not absorbed into the systemic circulation or the absorption is very low. Information on the other compounds such as the rebaudiosides is lacking. Nevertheless, the moderate use of stevia or stevioside as sweeteners appears to represent a low risk to the embryo–fetus, if it exists at all.
FETAL RISK SUMMARY
The perennial shrub Stevia rebaudiana Bertoni (stevia) is indigenous to South America but is grown commercially in areas such as Central America, Israel, Thailand, and China. The leaves have been used as a low-calorie sweetener for hundreds of years. The largest use of stevia appears to be in Japan where it is used to replace aspartame and saccharin (2). Oral stevia is also used as a weight-loss aid; for contraception and lowering uric acid levels; for the treatment of diabetes, hypertension, and heartburn; and as a cardiotonic and diuretic (3).
The sweetness of stevia is mainly due to stevioside, a sweet ent-kaurene glycoside that is 300 times sweeter than sucrose (0.4% solution). There also are several variants of rebaudioside, another ent-kaurene glycoside that is present in lower concentrations. Stevia leaves contain 6%–18% of stevioside. In addition to the glycosides, the leaves contain minor amounts of nonsweet sterols (stigmasterol, beta-sitosterol, and campesterol), vitamins (A, B, and C), electrolytes, minerals, and protein (1,2).
Reproduction and growth studies have been conducted with stevioside in male and female hamsters with daily oral doses up to 2.5 g/kg (4). No abnormalities in growth, fertility, or reproduction performance were observed through three generations. Moreover, histological examination of reproductive tissues revealed no evidence of stevia-induced abnormalities. The investigators briefly cited other studies that observed no toxic effects in mice and rats (4).
In a 2006 study, female rats before mating were given an aqueous extract of various mixtures of Aegle marmelos (6%), a Thai medicinal plant popularly consumed as a herbal tea, and stevia (0%–10%) (5). The rats then were mated with untreated males, and the effects on reproduction were examined at day 14 of pregnancy. Compared with untreated controls, there were no significant differences in terms of number of corpus lutea, implanted and dead fetuses, or fetal growth (5).
A 2003 review cited several other animal reproduction studies using stevia extracts that observed no developmental toxicity in chicken embryos, mice, rats, and hamsters (1). There also was no adverse effect on spermatogenesis or interstitial cell proliferation in male rats, except at very high doses.
A 1985 study found that stevioside was not mutagenic in Salmonella typhimurium, but that steviol, an aglycone metabolite of stevioside, was mutagenic when it was further metabolized (6). The clinical significance of this toxicity was unknown because the complete metabolic disposition of stevioside in humans had not been fully characterized. A review cited four studies that confirmed the mutagenicity but noted that the mutagenicity activity was low (1). In addition, the presence in blood of the steviol metabolites after feeding of stevioside has not been proven. Moreover, there is no evidence in animals or humans that stevioside is carcinogenic (1).
The pharmacology of stevia in animals and humans has been reviewed (1). The author concluded that the dietary supplement is safe when used as a sweetener. In humans, oral stevioside either is not absorbed or the uptake is extremely low. Even so, the European Commission refused to accept stevia or stevioside as a novel food because of inadequate or controversial studies on its safety (1). For the same reason, the FDA classifies stevia as an “unsafe food additive” (3).
BREASTFEEDING SUMMARY
Although the dietary supplement stevia is used extensively as a natural, low-calorie sweetener, no reports describing its use during lactation have been located. Stevioside, the major sweetening compound in stevia, is either not absorbed into the systemic circulation or the absorption is very low. However, information on the other compounds, such as the rebaudiosides, is lacking. Nevertheless, the risk to the nursing infant from maternal intake of stevia, if it exists, appears to be low.
References
1.Geuns JMC. Stevioside. Phytochemistry 2003;64:913–21.
2.Stevia. In: DerMarderosian A, Beutler JA, eds. The Review of Natural Products. St. Louis, MO: Wolters Kluwer Health. July, 2004.
3.Stevia. In: Jellin JM, ed. Natural Medicines Comprehensive Database. 10th ed. Stockton, CA: Therapeutic Research Faculty, 2008:1387–8.
4.Yodyingyuad V, Bunyawong S. Effect of stevioside on growth and reproduction. Hum Reprod 1991;6:158–65.
5.Saenphet K, Aritajat S, Saenphet S, Manosroi J, Manosroi A. Safety evaluation of aqueous extracts from Aegle marmelos and Stevia rebaudiana on reproduction of female rats. Southeast Asian J Trop Med Public Health 2006;37 Suppl 3:203–5.
6.Pezzuto JM, Compadre CM, Swanson SM, Nanayakkara NPD, Kinghorn AD. Metabolically activated steviol, the aglycone of stevioside, is mutagenic. Proc Natl Acad Sci USA 1985;82:2478–82.