Product Safety: Miraculin: in vitro digestibility / allergenicity
Miraculin was shown to be fully and rapidly digested by pepsin in an in vitro digestibility assay. A
proteomic analysis of the digestibility assay indicated that it is highly unlikely that any of the protein will
remain intact within the gastrointestinal tract following digestion and therefore it is unlikely to be
absorbed intact into the body. The potential allergenicity and toxigenicity of miraculin was assessed
using a computerized model (in silico bioinformatic analyses). The results were that miraculin does not
represent a risk of allergy or toxicity to humans and has a low potential for cross-reactivity with other
allergens. A sensory study that characterizing the taste receptor activity of miraculin indicated that the
taste-modifying effect of miraculin at the concentration intended for product development has a rapid
onset and disappearance with no desensitizing impact on the receptor. The study authors concluded
that the use of miraculin to impact the sensory qualities of orally administered products with a
bitter/sour taste profile is not associated with any safety concerns.

Acute & 28-day toxicology studies - methanolic extracts
An acute toxicity study of a methanol extract of S. dulcificum pulp was conducted in rats. Cleaned, airdried fruit pulp was soaked in methanol at room temperature before filtration and the solvent evaporated to dryness. A total of 22 albino rats were used in a two-phase study. In phase I, three groups of 6 rats were orally administered with the extract (10 mg/kg, 100 mg/kg, and 1,000 mg/kg respectively for each group) by means of polythene cannula. The rats were monitored for 24 h for mortality and general behavior. In phase II, after 24 h, 3 individual rats were given three different concentrations (1600 mg/kg, 2900 mg/kg and 5000 respectively) orally, by means of polythene cannula. The fourth rats
received distilled water which served as control. The rats were monitored for 24 h for lethality and
general behavior. No mortality was observed, even at the highest dose of 5,000 mg/kg of the extract.
The report also detailed biochemical and histopathological examinations. In this part of the study, 24
albino rats, divided into 4 groups of 6 animals each, were orally administered saline, 100 mg, 200 mg
and 500 mg extract/kg body weight. Biochemical parameters including liver function enzymes, kidney
function parameters, serum electrolyte levels, serum total protein, serum total albumin, blood glucose
levels, serum lipid profile and lipid peroxidation were observed after 14 and 28 days. The livers and
kidneys of the animals were removed for histopathological studies. No negative effects on the health of
the rats were observed at any dose, the highest being 500 mg extract per kg body weight for 28 days.
A subacute toxicity study in rats was conducted using a methanolic extract of the fresh fruits of S.
dulcificum.19 The fruit was weighed, deseeded and homogenized (613 g) in 80% methanol left for 48 h
before filtrate collection. The filtrate was concentrated, and then lyophilized, resulting in a yield of 8.2%
extract (w/w). Male Wistar albino rats weighing 200-220 g were randomly divided into five groups with
five animals in each group. Group I served as the control and received distilled water. Group II-V
received oral administration of 25 mg, 50 mg, 100 mg and 200 mg/kg extract/body weight respectively,
once daily for 14 consecutive days. Blood samples were analyzed for the presence of liver enzymes and
bilirubrin. The livers of the animals were homogenized and measured for levels of total protein content,
malondialdehyde and glutathione as well as the activities of catalase, glutathione-S-transferase and
glutathione peroxidase. No signs of liver toxicity were observed. Lower doses of 50-100 mg/kg were
associated with decreases in serum total bilirubin and hepatic malondialdehyde levels and an elevation
of glutathione-S-transferase activity. The author of the study opined that the results of the study
indicated that the extract at these doses might boost antioxidant defense and have hepatoprotective
properties. The top dose of 200 mg/kg extract was associated with an increase in hepatic
malondialdehyde and a decrease in glutathione levels and might indicate a decrease in antioxidant
defenses.

Product Safety: Minor irritation at usage site.
Results from the device may exacerbate eating disorders in individuals prone to them.