Safety of use of Monk fruit extract as a food additive in different food categories

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. 2019 Dec 11;17(12):e05921. doi: 10.2903/j.efsa.2019.5921

	Study type	Species	Substance/purity	Dosing	Samples analysed	Analysis	Results	Conclusions
Murata et al. (2010)	In vivo	Wistar rat	SG‐Gly powder with a MV content of 72%	Single oral dose of SG‐gly solution (117 mg/mL) with 65.5 μmol MV (about 300 mg/kg bw)	Small intestine (at 2 h), portal blood (at 2 h), faeces (at 24 h), and urine (?)	LC–MS/MS for MV, siamenoside I, M‐IV, III, IIE, IIA, IE and MO In blood and urine after enzymatic hydrolysis of glucuronides/sulfates	In small intestine: MV as major form, also metabolites present In portal blood: traces of M‐IE and MO; no MV detected In faeces: mostly MO, M‐IIA and IE; also other metabolites and some MV present In urine: triterpenoids not detected (no data shown)	Total amount of analytes in faeces is about 40 μmol which corresponds to 61% of administered MV (65.5 μmol) As only traces or no SG‐triterpenoids were detected in blood or urine, the absorbed amount of SG‐gly and its metabolites was very low; the ingested M‐V is partly converted by intestinal bacterial enzymes and excreted without being absorbed
Xu et al. (2015)	In vivo	Sprague–Dawley rats	M‐V (> 98%)	Oral in solution MV 50 mg/kg bw per day (on 3 days, after earlier collection of blank biosample)	Faeces and urine collected on 3 days; then 1 h after last MV administration blood collected heart, liver, spleen, lungs, kidneys, stomach, small intestine	HPLC‐ESI‐IT‐TOF‐MSⁿ for MV and in toto 77 metabolites; eight identified with standards; others were tentatively identified by MS data; quantified by peak areas	In plasma: M‐V and IIE and MO found in low levels In urine: mainly M‐V, also several of its metabolites In faeces: high levels of M‐IIA and IE1 plus MO metabolites In organs: M‐V found at low levels in all; most abundant metabolite is M‐IIE, in liver > heart > spleen> intestine > kidney > lung	The pattern of analytes differs between various biospecimen: M‐V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces Many M‐V metabolites that were not detected in plasma were detected in various organs The study results indicate absorption of MV and systemic bioavailability along with its extensive conversion by digestive enzymes and the intestinal microflora of rats
Luo et al. (2016a,b)	In vivo	SD rats, male	M‐V (> 98.5%)	Single dose of 2.0 mg/kg bw by i.v. injection or 5.0 mg/kg bw by oral dosing	Blood sampling at various time points after i.v. or oral dosing (up to 6 h)	LC–MS/MS analysis of M‐V and MO (no other products monitored)	Concentration‐time profiles for M‐V and MO in plasma after i.v. and oral dosing; kinetic parameters: t_1/2, C_max, AUC, clearance, and others; oral bioavailability	After i.v. injection elimination half‐life was 0.33 and 1.53 h for M‐V and MO, respectively. After oral dosing, only MO was found in plasma. The oral absolute bioavailability of M‐V was estimated to be 8.73 ± 1.46% and the elimination half‐life of MO was 2.46 ± 0.19 h in rat

Study type

Species

Substance/purity

Dosing

Samples analysed

Analysis

Results

Conclusions

Murata et al. (2010)

In vivo

Wistar rat

SG‐Gly powder with a MV content of 72%

Single oral dose of SG‐gly solution (117 mg/mL) with 65.5 μmol MV (about 300 mg/kg bw)

Small intestine (at 2 h), portal blood (at 2 h), faeces (at 24 h), and urine (?)

LC–MS/MS for MV, siamenoside I, M‐IV, III, IIE, IIA, IE and MO

In blood and urine after enzymatic hydrolysis of glucuronides/sulfates

In small intestine: MV as major form, also metabolites present

In portal blood: traces of M‐IE and MO; no MV detected

In faeces: mostly MO, M‐IIA and IE; also other metabolites and some MV present

In urine: triterpenoids not detected (no data shown)

Total amount of analytes in faeces is about 40 μmol which corresponds to 61% of administered MV (65.5 μmol)

As only traces or no SG‐triterpenoids were detected in blood or urine, the absorbed amount of SG‐gly and its metabolites was very low; the ingested M‐V is partly converted by intestinal bacterial enzymes and excreted without being absorbed

Xu et al. (2015)

In vivo

Sprague–Dawley rats

M‐V (> 98%)

Oral in solution

MV 50 mg/kg bw per day (on 3 days, after earlier collection of blank biosample)

Faeces and urine collected on 3 days; then 1 h after last MV administration blood collected

heart, liver, spleen, lungs, kidneys, stomach, small intestine

HPLC‐ESI‐IT‐TOF‐MSⁿ for MV and in toto 77 metabolites; eight identified with standards; others were tentatively identified by MS data; quantified by peak areas

In plasma: M‐V and IIE and MO found in low levels

In urine: mainly M‐V, also several of its metabolites

In faeces: high levels of M‐IIA and IE1 plus MO metabolites

In organs: M‐V found at low levels in all; most abundant metabolite is M‐IIE, in liver > heart > spleen> intestine > kidney > lung

The pattern of analytes differs between various biospecimen: M‐V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces

Many M‐V metabolites that were not detected in plasma were detected in various organs

The study results indicate absorption of MV and systemic bioavailability along with its extensive conversion by digestive enzymes and the intestinal microflora of rats

Luo et al. (2016a,b)

In vivo

SD rats, male

M‐V (> 98.5%)

Single dose of 2.0 mg/kg bw by i.v. injection or 5.0 mg/kg bw by oral dosing

Blood sampling at various time points after i.v. or oral dosing (up to 6 h)

LC–MS/MS analysis of M‐V and MO (no other products monitored)

Concentration‐time profiles for M‐V and MO in plasma after i.v. and oral dosing; kinetic parameters: t_1/2, C_max, AUC, clearance, and others; oral bioavailability

After i.v. injection elimination half‐life was 0.33 and 1.53 h for M‐V and MO, respectively. After oral dosing, only MO was found in plasma. The oral absolute bioavailability of M‐V was estimated to be 8.73 ± 1.46% and the elimination half‐life of MO was 2.46 ± 0.19 h in rat

M‐V: mogroside V; M‐IV: mogroside IV; M‐III: mogroside III; M‐IIE: mogroside IIE; M‐IIA: mogroside IIA; M‐IA: mogroside IA; MIE: mogroside IE; MO: mogrol; SG: Saraitia grosvenori Swingle; SG‐Gly: Saraitia grosvenori Swingle‐glycoside; LC–MS: liquid chromatography–mass spectrometry; HPLC: high‐performance liquid chromatography; HPLC‐ESI‐IT‐TOF‐MSⁿ: HPLC in tandem with an electrospray ionisation ion‐trap time‐of‐flight multistage mass spectrometry.