The document provides information about monk fruit, a natural zero-calorie sweetener. It begins with an outline of the presentation topics, which include the historical use of monk fruit in China, its scientific name and cultivation, scientific studies on it, its nutrient composition and pharmacological properties. The document then discusses monk fruit's traditional use in China since 1862, its taste sensation and perception, scientific classification, composition analysis from studies. It reviews laboratory and clinical studies on the health benefits of monk fruit and mogrosides, including effects on blood sugar, anti-inflammatory and neuroprotective properties. In summary, the document presents an overview of monk fruit as a natural sweetener, discussing its history, composition and research on health benefits.

1. NATURAL SUGAR SUBSTITUTE:
MONK FRUIT,
ZERO-CALORIE SWEETENER
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL., USA
Email: kevinng68@gmail.com
A slide presentation for HealthCare Professional March, 2021

2. Presentation outline
▪ Historical use of monk fruit from medicine to sweetener
▪ Taste sensation and perception
▪ Origin of scientific name & cultivation
▪ Scientific publications in PubMed
▪ Nutrient composition of monk fruit
▪ Pharmacological studies
▪ Health benefits of monk fruit
▪ Summary

3. Traditional use of Luo Han Quo (Monk fruit) in China
since 1862 AD
Adapted from https://www.frontiersin.org/articles/10.3389/fphar.2019.01400/full

4. Timeline of artificial and natural sweeteners
Monk Fruit
sweetener

5. TASTE SENSATION AND PERCEPTION

6. Taste Sensation
https://kcaporellicc.wordpress.com/taste-sensation-and-perception/
umami
5th taste

7. Taste receptors
https://kcaporellicc.wordpress.com/taste-sensation-and-perception/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738222/
Receptor
umami

8. Taste Sensation and Perception
https://kcaporellicc.wordpress.com/taste-sensation-and-perception/
umami

9. How is sweetness commercially measured?
relative sweetness is represented on a scale of 100, where sucrose (5%) has a value of 100
▪ Sucrose (5%) is the standard to which all other
sweeteners are compared.
▪ Sucrose: 100
▪ High Fructose Corn Syrup: 120-160
▪ Glucose: 70-80
▪ Lactose: 20
Method #1

10. Relative sweetness of natural sweeteners:
Sucrose (5%) is given a value of 1.0 and the remaining sugars are rated in
comparison to the value of 1.0 for sucrose.
https://www.sciencedirect.com/topics/food-science/sweetener
Method #2

11. Comparison of sweetness of monk fruit with other sweeteners
sweetness

12. ● WHAT IS MONK FRUIT?
● CULTIVATION
● ORIGIN OF SCIENTIFIC NAME
● SCIENTIFIC STUDIES

13. What is a Monk fruit?
▪ Monk fruit, known in Chinese as Luo Han Guo, comes from a plant that belongs to
the Cucurbitaceae family.
▪ It’s a small, green gourd that looks like a melon.
▪ In 2010, monk fruit was approved by the US FDA as a natural sweetener.

14. Cultivation of monk fruit in Southern China

15. Origin of Scientific name of Monk fruit: Siraita grosvenorii
▪ Gilbert Hovey Grosvenor : FATHER OF PHOTOJOURNALISM
▪ The scientific name of monk fruit honors Gilbert Hovey
Grosvenor, who, as president of the National Geographic
Society, helped to fund an expedition in the 1930s to find
the living plant in China where it was being cultivated.

16. Scientific classification of Monk fruit (Luo han guo)

17. Number of articles on “monk fruit” and “siraitia grosvenorii” on
PubMed from 1990 to 2020
Monk fruit
Siraitia grosvenorii
https://pubmed.ncbi.nlm.nih.gov/?term=siriatia+grosvenorii

18. NUTRIENT COMPOSITION

19. Composition of fresh monk fruit (2020)
https://www.researchgate.net/figure/The-amino-acid-hydrolysate-and-
mineral-composition-of-fresh-monk-fruit-extract_tbl2_339106844
Macronutrients
Vitamins
Phytochemicals

20. Composition of fresh monk fruit (2020)
Amino acids & Minerals
https://www.researchgate.net/figure/The-amino-acid-hydrolysate-and-mineral-
composition-of-fresh-monk-fruit-extract_tbl2_339106844

21. MOGROL GLYCOSIDES
There are 66 known mogrosides

22. What is a mogrol glycoside?
There are about 66 glycosides
+

23. Structural formulas of Mogroside IIe and Mogroside V
Mogroside IIe Mogroside V
(bitter) (sweet)

24. How many Mogrosides are there in monk fruit?
▪ A mogroside is named by the number of molecules of glucose that are
attached using Roman numbers. Mogroside V has 5 molecules of glucose
attached.
▪ There are about 66 known mogrosides
▪ Mogroside V is the main component of Siraitia grosvenorii fruit, constituting
0.5% to 1.4% of the dried fruit
▪ The sweetness of the mogroside varies with the number of glucose attached
to Mogrol

25. The sweetness of some known cucurbitane glycoside compounds
isolated from monk fruit

26. PHARMACOLOGY OF MOGROSIDES
LABORATORY STUDIES
CLINICAL STUDIES

27. Laboratory studies of mogrosides

28. IC50 values of antioxidant tests of mogroside V
.
Molecules 2014, 19, 12676-12689;
doi:10.3390/molecules190812676
mixed saponin product (MSP)

29. Anti-hyperglycemic and anti-hyperlipidemic effects of a special
fraction of Luohanguo extract on obese T2DM rats (2020)
▪ Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung,
soothe the throat, restore the voice, and lubricate intestine and open the bowels.
▪ LHG has been utilized for the treatment of sore throats and hyperglycemia in folk
medicine as a homology of medicine and food. The hypoglycemic pharmacology of
LHG has attracted considerable attention, and mogrosides have been considered to
be active ingredients against diabetes mellitus.
▪ We have found that these mogrosides could be metabolized into their secondary
glycosides containing 1–3 glucose residues in type 2 diabetes mellitus (T2DM) rats in
previous studies. These metabolites may be the antidiabetic components of LHG in
vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides
containing 1–3 glucose residues.
https://pubmed.ncbi.nlm.nih.gov/31586692/

30. AMPK activation is involved in hypoglycemic and hypolipidemic activities of
mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on
high-fat diet/streptozotocin-induced diabetic mice (2019)
https://pubs.rsc.org/en/Content/ArticleLanding/2019/FO/C8FO01486H#!divAbstract
hypoglycemic and hypolipidemic activities of MGE are probably attributed to the attenuation of insulin resistance and activation of hepatic AMPK signaling.

31. Anti-inflammatory mechanisms of mogroside V on
LPS-induced acute lung injury in mice (2013)
https://www.tandfonline.com/doi/full/10.3109/13880209.2013.867451

32. Antiproliferative Activity of Triterpene Glycoside (Mogroside IV)
Nutrient from Monk Fruit in
Colorectal Cancer and Throat Cancer (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924201/

33. Effects of Siraitia grosvenorii Fruits Extracts (SGFE) on
Physical Fatigue in Mice (2013)
C: control,
LT: low-dose SGFE-treated (100 mg/Kg bodyweight);
MT: middle-dose SGFE-treated (200 mg/Kg bodyweight),
HT: high-dose SGFE treated (400 mg/Kg bodyweight).
*: p < 0.05 as compared with the control group
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813191/
These results indicated that Siraitia grosvenorii fruits extracts had significant
anti-fatigue effects on mice and these effects were dose-dependent.

34. Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by
Regulating Immune Dysfunction and Skin Barrier Abnormality (2020)
▪ Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit)
are used as a natural sweetener and as a traditional medicine for the treatment of asthma and
bronchitis.
▪ We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of
atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine
model and in vitro.
▪ Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell
infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity
score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin
(IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining
showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in
atopic dermatitis skin lesions.
▪ In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and
decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human
keratinocytes.
▪ Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed
the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that
NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.
https://read.qxmd.com/read/33256152/-siraitia-grosvenorii-residual-extract-attenuates-
atopic-dermatitis-by-regulating-immune-dysfunction-and-skin-barrier-abnormality

35. Neuroprotective effect of mogrol against Aβ 1-42 -induced memory
impairment neuroinflammation and apoptosis in mice 2019
▪ Objectives: Cognitive impairment is the main character of Alzheimer's disease (AD). This study
mainly focused on whether mogrol, a tetracyclic triterpenoids compound of Siraitia grosvenorii
Swingle, can ameliorate the memory impairment induced by Aβ1-42 .
▪ Methods: Memory impairment mice model was made by stereotactic intra-hippocampal
microinjection of Aβ1-42 (410 pm/mouse). Mogrol (20, 40, 80 mg/kg) was given to mice by
intragastric administration at 3 days after Aβ1-42 injection for totally 3 weeks. Morris water maze
test and Y-maze test were operated to evaluate the therapeutic effect of morgrol on Aβ1-42 -
induced memory impairments. Immunohistochemical analyses and Hoechst 33258 assay were
used to evaluate effect of morgrol on Aβ1-42 -induced microglia overactivation and apoptotic
response in hippocampus of mice. Western blotting assay was used to evaluate effect of mogrol on
the Aβ1-42 -activated NF-κB signaling.
▪ Key findings: Mogrol could significantly alleviate Aβ1-42 -induced memory impairments, inhibit
Aβ1-42 -induced microglia overactivation and prevent Aβ1-42 -triggered apoptotic response in the
hippocampus. Mogrol also could suppress Aβ1-42 -activated NF-κB signaling, reduce the
production of proinflammatory cytokines.
▪ Conclusions: This study suggested that mogrol would ameliorate the memory impairment induced
by Aβ1-42 , which is involved in anti-inflammation and anti-apoptosis in the brain.
▪ Keywords: Alzheimer's disease; NF-κB; apoptosis; inflammation; mogrol.
https://pubmed.ncbi.nlm.nih.gov/30585314/#

36. Pharmacological studies of mogrosides in human
Mixed results

37. Blood glucose changes over time after the ingestion of
either monk fruit or sucrose
https://monkfruitauthority.com/does-monk-fruit-affect-blood-sugar/

38. Blood insulin changes over time after the ingestion of
either monk fruit or sucrose
https://monkfruitauthority.com/does-monk-fruit-affect-blood-sugar/

39. Effects of monk fruit on and artificial sweeteners on
24-h glucose profiles (2017)
▪ Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve
glycaemic control.
▪ The objective of this study was to investigate the effects of consuming artificial NNS (that is,
aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h
glucose profiles.
▪ Ten healthy males took part in this randomised, crossover study with the following four treatments:
aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked
to consume the test beverage as a preload mid-morning.
▪ Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose,
incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-
h glycaemic variability.
▪ Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for
glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose
profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and
nutritive sweeteners.
▪ The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day
appears to have minimal effect on 24-h glucose profiles in healthy males.
https://pubmed.ncbi.nlm.nih.gov/28378852/#

40. Effects of monk fruit extract and artificial sweeteners on glycaemic
control (2019)
▪ Purpose of review: By replacing sugar, nonnutritive sweeteners (NNSs) are thought to aid in
weight management and decrease insulin resistance. We reviewed the latest randomized
clinical trials (RCTs) investigating the effects NNSs on glycaemic control.
▪ Recent findings: Six RCTs addressed this topic between 2017 and 2018; the majority tested
artificial NNS (sucralose or aspartame), with only one testing natural NNS (stevia and monk
fruit extract). Most found no effect of NNS on blood glucose, insulin, gastric inhibitory
polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels; however, two trials showed an
effect of sucralose on the acute insulin response.
▪ Summary: We are still incapable of reaching a definite judgement on which types of NNS, if
any, impact glycaemic control. There is a need for more research to overcome the limitations
of recent RCTs, related to sample size, intervention duration, dose, form of NNSs used, and
inclusion of males or female participants only. Future studies should also compare different
NNS types with each other, and include the increasingly popular 'natural' NNS.
https://pubmed.ncbi.nlm.nih.gov/31033578/#

41. Meta-analysis of non-nutritive sweeteners (NNS) on
health risks (2017)
▪ 372 studies were analyzed in healthy subjects on the following risk outcome:
▪ appetite and short term food intake
▪ risk of cancer
▪ risk of diabetes
▪ risk of dental caries
▪ risk of weight gain
▪ risk of obesity.
▪ Overall there is no conclusive evidence for beneficial and harmful effects on those
outcomes.
▪ In subjects with diabetes and hypertension, the evidence regarding health outcomes
of non-nutritive sweeteners (NNS) use is inconsistent.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591507/

42. FATE OF MOGROSIDES IN THE BODY?

43. Mean plasma concentration–time profiles of rats after oral administration of
mogroside V (200 mg/kg) and LHG extract (12.5 ml/kg). 2019
https://www.frontiersin.org/articles/10.3389/fphar.2019.00915/full

44. Pharmacokinetic parameters of mogroside V (200 mg/kg) and
LHG extract (12.5 ml/kg) orally administered to
rats (n = 6 per time point). 2019
https://www.frontiersin.org/articles/10.3389/fphar.2019.00915/full

45. Metabolism of mogroside V and distribution of its metabolites
in rats by HPLC-ESI-IT-TOF-MSn (2015)
https://www.sciencedirect.com/science/article/abs/pii/S0731708515300789

46. The metabolism of a natural product mogroside V, in
healthy and type 2 diabetic rats (2018)
▪ Mogroside V, a natural compound isolated from the fruits of Siraitia grosvenorii (Swingle), is a promising candidate for anti-
diabetic activity.
▪ The present study aims to develop a simple and practical strategy for comparing the in vivo metabolite profiling of mogroside V in
healthy and type 2 diabetic (T2D) model rats.
▪ In this paper, a highly sensitive and rapid ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry
(UPLC-Q-TOF/MS) with MetaboLynx™ software combined with mass defect filtering (MDF) method was established and
successfully applied to detect and identify the metabolites in plasma, urine, bile and feces
▪ samples of healthy and model rats administrated with mogroside V.
▪ The distribution of metabolites in plasma, bile, urine and feces of healthy and model rats had obvious differences. A total of 23
metabolites were observed in healthy rats while 26 metabolites were detected in model rats.
▪ The results indicated that dehydrogenation, deoxidation, oxidation and isomerization were the major metabolic transformations of
mogroside V. Additionally, it was noticed that the peak areas of metabolites in T2D rat plasma samples were much larger than
those of metabolites in healthy rat plasma sample, whereas in T2D rat urine samples they were remarkably smaller compared with
healthy rat urine sample. These high blood concentrations of metabolites might be beneficial for the treatment of T2D.
▪ The results of this study are valuable and important in understanding the metabolic process and therapeutic mechanism of
mogroside V.
▪ Keywords: Comparative metabolism; Mass spectrometry; Mogroside V; Siraitia grosvenorii Swingle; Type 2 diabetes.
https://pubmed.ncbi.nlm.nih.gov/29428672/

47. BENEFITS
SIDE EFFECTS

48. Benefits of monk fruit
▪ Natural sweetener with no known side effects
▪ Antioxidant properties
▪ Anti-inflammatory properties
▪ Does not affect blood sugar
▪ May promote weight loss
▪ May have anticancer property
▪ Anti-tussive and phlegm reducing properties

49. Side effects of monk fruit sweeteners
▪ Monk fruit was approved by FDA in 2010.
▪ There are no known side effects.
▪ The FDA has deemed monk fruit “generally
recognized as safe (GRAS)” for everyone,
including pregnant women and children.

50. ACCEPTABLE DAILY INTAKE
COMMERCIAL PRODUCTS
SUMMARY

51. Non-nutritive sweeteners available in the USA and the European Union:
Acceptable Daily Intake levels, as defined by regulatory bodies
Mogrosides
Steviosides

52. Commercial products of monk fruit
▪ Dried monk fruit
▪ Monk fruit extract
▪ Liquid
▪ Powder
▪ Cubes
▪ Monk fruit blend with stevia

53. Summary
▪ Monk fruit, known in Chinese as Luo Han Guo, comes from a plant
that belongs to the Cucurbitaceae family.
▪ It has been used as a traditional medicine for cough and phlegm.
▪ The sweetness of monk fruit is due to the presence of 66 or more
mogrosides
▪ The sweetness of mogrosides varies with the number of glucose
molecules attached to the mogrol structure.
▪ The mogrosides are 250 to 350 times sweeter than sucrose (5%).
▪ The monk fruit sweeteners is generally recognized as safe (GRAS).
▪ There is no known side effects of monk fruits or its sweetness
content.

54. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
54