Tomato as medicine, solanum lycopersicum, bioactive compounds, lycopene, antioxidant, anti-inflammatory, anti-cancer, anti-hypertension, meta-analysis of clinical studies

1. FOOD AS MEDICINE:
TOMATO,
SOLANUM LYCOPERSICUM
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 Provider Seminar Nov. 2019

2. Outline of Lecture
▪ History of origin of tomato
▪ Production and consumption
▪ Scientific classification
▪ Anatomy, nutrient composition
▪ Lycopene
▪ Bioavailability
▪ Pharmacology
▪ Meta-analysis
▪ Summary

3. How did the tomato get its name?
▪ The tomato is the edible, red, berry of
the plant Solanum lycopersicum,
commonly known as a tomato plant.
▪ The species originated in western South
America and Central America.
▪ The Nahuatl (Aztec language) word
tomatl gave rise to the Spanish word
tomate, from which the English word
tomato derived.
https://en.m.wikipedia.org/wiki/Tomato

4. Milestones in the history of tomato
Adapted from https://en.wikipedia.org/wiki/Tomato

5. Number of publications on lycopene, lycopene-prostate,
lycopene-cancer and lycopene-cardiovascular in
PubMed from 1980 to 2018
https://www.ncbi.nlm.nih.gov/pubmed/?term=lycopene+cancer

6. World Map for Largest tomato producing countries
https://gardeningfan.com/top-10-tomato-producing-countries-tomato-production/

7. Top Tomato Consuming Countries in the World (2015)
https://www.indexbox.io/blog/which-country-consumes-the-most-tomato-in-the-world/

8. Top 10 vegetables sold in the U.S. 2018
https://www.pma.com/content/articles/2017/05/top-20-fruits-and-vegetables-sold-in-the-us
Tomato

9. Classification of Tomato (Solanum lycopersicum)
https://plants.usda.gov/java/ClassificationServlet?source=display&classid=SOLY2

10. What Are the Different Types of Tomatoes?
▪ Tomato plant sizes
▪ Indeterminate tomato plants: vining plants that continue
growing in length throughout the growing season.
▪ Determinate tomato plans: grow to a fixed mature size and ripen
all their fruit in a short period, usually about 2 weeks.
▪ Hybrid vs Heirloom
▪ Hybrid tomato plants: crossbreed plants made by man.
▪ Heirloom tomato plants: open pollinated plants.
https://www.slideshare.net/GrowYourOwnNevada/gr
ow-your-own-nevada-spring-2013-seeds-vs-starts

11. Difference between Determinate and Indeterminate Tomatoes
Determinate Indeterminate
https://www.thespruce.com/determinate-and-indeterminate-tomatoes-2540020

12. TOMATO FLOWER & FRUIT STRUCTURE
https://www.carlsonstockart.com/photo/tomato-flower-fruit-structure-fertilized-ovary/

13. Nutrient composition of raw ripe tomato
based on 100 g
https://fdc.nal.usda.gov/fdc-app.html#/food-details/342502/nutrients

14. Groups of bioactive compounds of tomatoes.
https://repositorio-aberto.up.pt/bitstream/10216/111142/2/257843.pdf
Leaf and stem

15. Phytochemical composition of raw ripe tomato
based on 100 g raw ripe tomato
https://fdc.nal.usda.gov/fdc-app.html#/food-details/342502/nutrients
Lycopene

16. Concentration of lycopene depending on
variety and stage of tomato maturity. (2018)
PROCEEDINGS OF THE LATVIAN ACADEMY OF SCIENCES. Section B, Vol.
72 (2018), No. 2 (713), pp. 85–90. DOI: 10.2478/prolas-2018-0014

17. Effects of heating method on lycopene content
in tomato waste
https://scialert.net/fulltext/?doi=ijps.2018.63.70

18. What is Lycopene?
▪ Lycopene is a chemical compound found in tomatoes, red fruits and vegetables.
▪ It is a bright red carotenoid hydrocarbon with no vitamin A activity.
▪ It is a key intermediate in the biosynthesis of many carotenoids.

19. Two shapes of Lycopene
Shape bent straight
Absorption 55 x more needs solubilization
Tissue mostly cis form 95% in red tomatoes
https://www.aicr.org/cancer-research-update/2015/10_14/cru_Heat-Shape-and-Type-Increasing-Lycopene-Absorption.html

20. Isomer composition of lycopene from
various sources (as % of total lycopene)
http://www.fao.org/fileadmin/templates/agns/pdf/jecfa/cta/67/lycopene.pdf

21. Bioavailability and Kinetics of Lycopene (2017)
▪ The bioavailability of cis-isomers in food is higher than that of all-trans isomers.
▪ It is believed that lycopene was absorbed by passive diffusion as lipids.
▪ Once inside the enterocyte, lycopene is packaged with other dietary lipids into
chylomicrons and released into the lymphatic system for transport to the liver.
▪ It is transported by the lipoproteins into the plasma for distribution to the different
organs.
▪ The elimination half-life for total lycopene ranged from 28.1 to 61.6 h.
https://www.sciencedirect.com/topics/neuroscience/lycopene

22. Absorption and distribution of lycopene
Systemic
circulation
10 mg all-trans lycopene cis-lycopene > all-trans lycopene in tissues
Adapted from https://www.sciencedirect.com/topics/neuroscience/lycopene
10-30%
absorption

23. Metabolism of Lycopene
https://www.sciencedirect.com/science/article/pii/S2095882X18300665

24. Pharmacological actions of Lycopene (2018)
▪ Antioxidant
▪ Anti-inflammatory
▪ Anti-cancer
▪ Anti-diabetic
▪ Cardioprotective
▪ Endothelia function modulation
▪ Anti-hypertensive
▪ Anti-platelet aggregation
▪ Anti-hyperlipidemic
▪ Anti-atherosclerosis
Adapted from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974099/

25. Enhanced absorption of formulated LYSOSOME GA LYCOPENE
Enhanced absorption
https://onlinelibrary.wiley.com/doi/pdf/10.1002/fsn3.734
5X

26. Enhanced absorption of LYSOSOME GA LYCOPENE
suppressed inflammation and oxidized LDL
Enhanced absorption
https://onlinelibrary.wiley.com/doi/pdf/10.1002/fsn3.734
5X

27. Anti-inflammatory effects of lycopene on the mRNA expression of
TNF-α, IL-1β and IL-6 in LPS-stimulated SW480 cells (2017)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376536/

28. Lycopene reduces cholesterol absorption through the
downregulation of Niemann‐Pick C1‐like 1 in Caco‐2 cells (2015)
https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201500221
cholesterol
This study provides the first evidence that lycopene inhibits
cholesterol absorption in the intestinal cells
Caco-2 cells has been used as a model for intestinal absorption

29. Lycopene inhibition of molecular pathways involved in
cholesterol metabolism. (2012)
https://www.karger.com/article/pdf/342077

30. Lycopene suppresses inflammatory TNF-α in cancer cells
normal prostatic epithelial cells:
PrEC
carcinoma cancer cells :
LNCaP,
PC3,
DU145
http://www.ajandrology.com/viewimage.asp?img=AsianJAndrol_2019_21_1_80_240740_f2.jpg

31. Lycopene inhibits growth of human colon cancer cells via
suppression of the Akt signaling pathway. (2008)
https://www.ncbi.nlm.nih.gov/pubmed/18537129

32. Possible lycopene intervention in the carcinogenic process
Inflammatory cytokines
https://www.semanticscholar.org/paper/Multiple-Molecular-and-Cellular-Mechanisms-of-of-
in-Trejo-Sol%C3%ADs-Pedraza-Chaverri/c49c99c989ef65f2b4070d286837858e750db19f

33. TOMATO AND HUMAN HEALTH
▪ Tomato Consumption Improves the Oxidative Status
▪ Tomato Suppresses the NF-κB Activation and Reduces Inflammation
▪ Tomato Reduces Inflammation Linked to Obesity, Diabetes and Cholesterol
▪ Tomato Prevents Cardiovascular Diseases, Atherosclerosis and Hypertension
▪ Tomato has Antitumour and Anticarcinogenic Properties
▪ Tomato Protects Liver from Hepatotoxicity and Hepatocarcinogenesis
https://repositorio-aberto.up.pt/bitstream/10216/111142/2/257843.pdf

34. Dietary sources of lycopene
https://en.wikipedia.org/wiki/Lycopene

35. Recommended dosage of lycopene
▪ There is no recommended daily intake of lycopene
▪ Lycopene administered as a pure compound has been
studied in clinical trials at dosages of 8 to 75 mg/day.
▪ Lycopene is primarily available in capsule and softgel
form, with dosage guidelines from manufacturers ranging
from 10 to 30 mg taken twice daily with meals.
▪ The synthetic lycopene contains approximately 70% of
all-trans-lycopene, up to 23% of 5-cis-lycopene, and
minor quantities of other cis-isomers.
https://www.drugs.com/npp/lycopene.html

36. Meta-analysis of effect of lycopene on
cancer and chronic inflammatory diseases
▪ Prostate cancer
▪ Ovarian cancer
▪ Colorectal cancer
▪ Type 2 diabetes mellitus
▪ Hyperlipidemia
▪ High Blood pressure
▪ Cardiovascular disease

37. What is meta-analysis: evidence-based medicine
https://rdfeinman.files.wordpress.com/2015/08/meta-anal_whatis.png

38. Example of a Meta-analysis: Hierarchy of evidence in clinical studies
use of statistical methods to summarise the results of these studies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049418/
Example

39. Increased dietary and circulating lycopene are associated with reduced
prostate cancer risk: a systematic review and meta-analysis (2017)
https://www.nature.com/articles/pcan201725?draft=journal

40. Overall analysis of the association between tomato
consumption and prostate cancer risk. (2016)
https://www.nature.com/articles/srep37091

41. Association between blood α-carotene and lycopene levels and
risk of advanced Prostate Cancer (2015)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140415

42. The association between dietary lycopene and ovarian cancer (2014)
https://www.nature.com/articles/srep04885

43. Lycopene Consumption and Risk of Colorectal Cancer:
A Meta-Analysis of Observational Studies (2016)
https://www.ncbi.nlm.nih.gov/pubmed/27472298

44. Effect of lycopene on type 2 diabetes mellitus:
A meta-analysis (2011)
https://www.ncbi.nlm.nih.gov/pubmed/22411366

45. Effect of lycopene on serum cholesterol and blood pressure:
Meta-analyses of intervention trials (2010)
https://www.sciencedirect.com/science/article/abs/pii/S0378512210004469

46. Lycopene Supplement and Blood Pressure:
An Updated Meta-Analysis of Intervention Trials (2013)
Systolic blood pressure Diastolic blood pressure.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798929/
WMD=weighted mean difference

47. Dietary and circulating lycopene and stroke risk:
a meta-analysis of prospective studies (2014)
https://www.nature.com/articles/srep05031

48. Lycopene and tomato and risk of cardiovascular diseases:
A systematic review and meta-analysis of epidemiological evidence 2019
High-intakes or high-serum concentration of lycopene
are associated with significant reductions in the
▪ risk of stroke (26%),
▪ mortality (37%) and
▪ CVDs (14%).
https://www.tandfonline.com/doi/figure/10.1080/10408398.2017.1362630?scroll=top&needAccess=true

49. Lycopene status in Europe and the United States
▪ European Food Safety Authority concluded that evidence was insufficient
for lycopene having antioxidant effects in humans, particularly in skin,
heart function, or vision protection from ultraviolet light
▪ The US Food and Drug Administration (FDA) concluded that there was no
credible evidence supporting a beneficial relationship between lycopene
consumption and cancers.
https://en.wikipedia.org/wiki/Lycopene

50. Summary
▪ The tomato is the edible red, berry of the plant Solanum
lycopersicum, commonly known as a tomato plant.
▪ A raw ripe tomato contains macronutrients, micronutrients
(vitamins and minerals) and phytochemicals.
▪ Lycopene is the major phytochemical with antioxidant, anti-
inflammatory, anti-cancer, and cardioprotective properties.
▪ However, the results of clinical studies are mixed and no
conclusion has been provided by European Food Safety
Authority and the US Food and Drug Administration (FDA),

51. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
51