Artificial and natural sweetener; how sweetness is measured commercially;bioacative steviol glycosides properties besides sweetness; stevia has been shown to reduce body weight, lower blood sugar, lipids, blood pressure and alter gut microbiome

1. NATURAL SUGAR SUBSTITUTE:
STEVIA,
NO 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 webinar presentation for HealthCare Professional Feb 2021

2. Lecture Outline
▪ Artificial and natural sweeteners
▪ Taste sensation, measurement and perception
▪ What is stevia
▪ History
▪ Production
▪ Composition of stevia leaves
▪ Pharmacology of stevia glycosides
▪ Clinical studies
▪ Safety

3. Timeline of artificial and natural sweeteners

4. What is Stevia?
▪ Stevia is a sugar substitute derived from the leaves of the plant
species Stevia rebaudiana, native to Brazil and Paraguay.
▪ The active compounds are steviol glycosides, which are 30 to
300 times the sweetness of sugar.
▪ Stevia is a white powder, freely soluble in water, insoluble in oils,
heat-stable, pH-stable, and not fermentable.

5. TASTE SENSATION AND PERCEPTION

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

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

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

9. How is sweetness commercially measured?
relative sweetness is represented on a scale of 100, where sucrose has a value of 100
▪ Sucrose 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 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. Relative sweetness of artificial sweeteners:
Sucrose is given a value of 1.0 and the remaining sugars are rated in
comparison to the value of 1.0 for sucrose.
Stevia sweetness=300

12. HISTORY

13. Discovery of Stevia
▪ In 1899, Swiss botanist Moisés Santiago Bertoni,
while conducting research in eastern Paraguay,
first described the plant and the sweet taste in
detail.
▪ In 1931, two French chemists Bridel and Lavielle
isolated the glycosides that give stevia its sweet
taste.
Moisés Santiago Bertoni

14. Historical use of Stevia
▪ The plant Stevia rebaudiana has been used for more than
1,500 years by the Guaraní peoples of South America, who
called it ka'a he'ê ("sweet herb").
▪ The leaves have been used traditionally in both Brazil and
Paraguay to sweeten local teas and medicines, and as a
"sweet treat".
▪ The active compounds are steviol glycosides (mainly
stevioside and rebaudioside), which have 30 to 300 times the
sweetness of sugar
▪ In the United States, high-purity stevia glycoside extracts
have been generally recognized as safe (GRAS) since 2008,
and are allowed in food products,
https://www.google.com/search?q=history+of+stevia&rlz=1C1CHBF_enUS863US863&oq=hi
story+of+stevia&aqs=chrome..69i57j0j0i22i30j0i390l3.5539j0j7&sourceid=chrome&ie=UTF-8

15. PRODUCTION & CULTIVATION
CLASSIFICATION
SCIENTIFIC STUDIES

16. Countries where Stevia Rebaudiana is cultivated
It is cultivated in
• China
• Taiwan
• Thailand
• Malaysia
• Korea
• India
• Brazil
• Canada
• California
• Hawaii

17. Scientific classification of Stevia Rebaudiana
https://plants.usda.gov/java/ClassificationServlet?source=display&classid=STRE2

18. Number of articles on “stevia” in PubMed from
1968 to 2020
https://pubmed.ncbi.nlm.nih.gov/?term=Stevia

19. COMPOSITION OF STEVIA

20. Nutrient compositions of dried Stevia leaves
63-73%
4-6%
12-14%
4-5%
4-12%
Trop J Pharm Res, January 2014;13 (1):

21. Stevia glycoside composition (≈40) in stevia leaves
https://www.sciencedirect.com/science/article/abs/pii/S0308814618310641#:~:text=1%2C%
20Stevia%20leaves%20contain%20a,2013%2C%20Prakash%20et%20al.%2C

22. STEVIA GLYCOSIDE

23. What is a glycoside?

24. Two most studied glycosides of Stevia rebaudiana

25. Sweetness (50-450) of selected Steviol glycosides (≈40) in
leaves of Stevia rebaudiana
https://www.whatsugar.com/stevia-buying-guide

26. PHARMACOLOGY

27. Scientific studies on stevia besides sweetness

28. Effect of diet and supplementary SGs (stevia glycosides) on
appetite regulatory biomarkers in
High-Fat Fed STZ-Induced Diabetic Rats (2021)
Inhibit hunger
Regulate glucose levels
Hunger hormone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823366/

29. Effect of diet and supplementary SGs (stevia glycosides) on
(A) fasting glucose concentration, (B) insulin concentration, (C) insulin resistance index,
(D) β-cell function index and (E) quantitative insulin sensitivity check index in rats (2021)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823366/
(A) GLU: fasting glucose concentration,
(B) INS: insulin concentration,
(C) HOMA-IR: insulin resistance index,
(D) HOMA-β: β-cell function index and
(E) QUICKI: the quantitative insulin
sensitivity check index in rats

30. Effect of diet and supplementary SGs (stevia glycosides)on
lipid profile indices of rats (2021)
(A) TG: serum triacylglycerols,
(B) TC: serum total cholesterol,
(C) HDL: serum high-density lipoproteins,
(D) LDL: serum low density lipoproteins and
(E) HDL/LDL ratio in serum of experimental rats.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823366/

31. Effect of Stevia aqueous extract on the glycosylated hemoglobin
(HbA1c) level of Streptozotocin-induced diabetes in rats(2018)
https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-018-2245-2
diabetic
non-diabetic

32. Stevia alters microbiota in the rat intestine (2019)
Nutrients 2019, 11, 1248

33. Final body weight, feed intake and body weight gain % in rats
treated with administration of stevia sweetener after 12 weeks.
https://www.sciencedirect.com/science/article/pii/S0570178315000561#f0010

34. Anti-inflammatory and immunomodulatory activities of
stevioside and steviol on colonic epithelial cells (2013)
▪ Background: Stevioside is a natural non-caloric sweetener isolated from Stevia rebaudiana
Bertoni leaves. We have proposed its effect on attenuation of tumour necrosis factor α (TNF-
α) and interleukin 1β (IL-1β) release in lipopolysaccharide (LPS)-stimulated monocytes. In this
study, the anti-inflammatory and immunomodulatory activities of stevioside and its
metabolite, steviol, on human colon carcinoma cell line (Caco-2) were evaluated.
▪ Results: Stevioside and steviol, in the doses used in this study, had no cytotoxicity on Caco-2
cells. Anti-inflammatory activities of these two compounds were observed by potentially
suppressed LPS-mediated TNF-α, IL-1β and IL-6 release. In addition, stevioside and steviol
showed immunomodulatory effects on IκBα activation and nuclear factor kappa B (NF-κB)
suppression in western blotting.
▪ Conclusion: Stevioside and steviol attenuate LPS-induced pro-inflammatory cytokine
productions by affecting cytokine gene expression via IκBα/NF-κB signalling pathway.
▪ Keywords: Caco-2 cells; NF-κB; inflammatory cytokine; steviol; stevioside.
https://pubmed.ncbi.nlm.nih.gov/23794454/

35. PHARMACOKINETICS

36. Degradation of steviol glycoside in human
glucose

37. Mean pharmacokinetic parameters for steviol glucuronide
in men (2008)
https://cspinet.org/sites/default/files/attachment/stevia-report_final-8-14-08.pdf

38. CLINICAL STUDIES

39. Clinical studies of stevia
▪ Obesity
▪ Diabetes
▪ Hypertension
▪ Lipids
▪ Gut microbiome

40. Effects of stevia, aspartame, and sucrose on
postprandial glucose and insulin levels (2010)
postprandial glucose insulin levels
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900484/

41. Effects of Stevia Extract on Postprandial Glucose Response, Satiety and Energy Intake:
A Three-Arm Crossover Trial (2019)
https://www.mdpi.com/2072-6643/11/12/3036/htm

42. Effect of non-sugar sweetener intake on
weight change (kg) in adults (2018)
https://www.bmj.com/content/364/bmj.k4718

43. Effect of Steviol Glycosides on fasting blood glucose
(FBG, mg/dL) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

44. Effect of Steviol Glycosides on glycated hemoglobin
(HbA1c, %) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

45. Effect of Steviol Glycosides on Basal Metabolic Index (BMI kg/m2):
randomized controlled trials (2019)
https://www.mdpi.com/2072-6643/11/9/1965/htm
SG=steviol glycosides

46. Effect of Steviol Glycosides on systolic blood pressure
(SBP, mmHg) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm
Non-diabetic
Diabetic
Total

47. Effect of Steviol Glycosides on diastolic blood pressure
(SBP, mmHg) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

48. Effect of Steviol Glycosides on low-density lipoprotein cholesterol
(LDL-C, mg/dL) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

49. Effect of Steviol Glycosides on high-density lipoprotein cholesterol
(HDL-C, mg/dL) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

50. Effect of Steviol Glycosides on triglycerides
(TAGs, mg/dL) 2019
https://www.mdpi.com/2072-6643/11/9/1965/htm

51. Summary of effects of stevia glycosides on
cardiovascular risk factors (2010)
https://www.mdpi.com/2072-6643/11/9/1965/ht
https://www.bmj.com/content/364/bmj.k4718

52. SAFETY

53. Safety
▪ In 2007, JECFA (Joint FAO/WHO Expert Committee on Food
Additives) specified that steviol glycoside sweeteners must be
composed of at least 95% of the known steviol glycosides.
▪ In December 2008, the FDA declared Stevia GRAS (generally
recognized as safe).
▪ The acceptable daily intake of stevia is 4 mg/kg.
▪ No serious adverse reactions have been documented

54. STEVIA PRODUCTS
SUMMARY

55. Varieties of Commercial Stevia Sweeteners
https://www.whatsugar.com/stevia-buying-guide

56. Summary
▪ Stevia is an extract derived from the leaves of Stevia rebaudiana.
▪ It contains a mixture of macronutrients, micronutrients and bioactive chemicals.
▪ The bioactive chemicals comprise about 40 steviol glycosides with sweetness
ranging from 30 to 300,
▪ Besides sweetness, stevia contains polyphenols and flavonoids which are beneficial
for health.
▪ Stevia has been shown to reduce body weight, lower blood sugar, lipids, blood
pressure and alter gut microbiome..
▪ However, the clinical results are mixed. More studies are needed.
▪ Meanwhile, the use of stevia as natural sweetener continues worldwide.

57. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
57