Garlic, allium sativum, food as medicine, historical medicinal use, nutrient composition, bioactive compounds, organosulfur compounds, chemistry, bioavailability, health benefits, clinical studies, meta-analysis, commercial garlic products

1. FOOD AS MEDICINE:
GARLIC,
ALLIUM SATIVUM
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 June 2019

2. Why do we need to talk about garlic?
▪Food
▪Flavor
▪Medicine

3. Outline of Lecture
▪ History: Old Testament, Hippocrates, meaning of Allium sativum.
▪ Scientific classification, production of garlic in United States.
▪ Anatomy of garlic, nutrient composition of garlic.
▪ Bioactive compounds of garlic.
▪ Organosulfur compounds, chemistry, bioavailability.
▪ Health benefits.
▪ Clinical studies and meta-analysis.
▪ Commercial garlic products.
▪ Summary

4. Historical Documentation of Garlic in
The Old Testament (1200-165 BC)
“We remember the fish which we did eat in Egypt,
the cucumber, melons, leeks, onions and garlic”
Numbers 11:4-6

5. Hippocrates (460-370 BC): Father of Western Medicine
▪ FatherofWestern Medicine
▪ Theoryof4HumorsinDisease
▪ SeparatedDiseasefrom ReligiousBelief
▪ AdvocatedFoodasMedicine
▪ “Letfoodbethymedicineand
Letmedicinebethyfood”

6. Some plants and herbs used by Hippocrates (460-370 BC)
▪ Rosemary
▪ Thyme
▪ Mint
▪ Fennel
▪ Caraway
▪ Rose
▪ Cinnamon
▪ Clove
▪ Anise
Hippocrates used approximately 250 plants from island of Kos to treat diseases.

7. History of Garlic in medicinal use over the last
5,000 years of human history
http://www.allicinfacts.com/garlic-history/

8. Meaning of garlic and allium sativum
▪ The English word, garlic, is derived from the Anglo-
Saxon “gar–leac” or spear plant referring to its
flowering stalk.
▪ The name “Allium sativum” is derived from the
Celtic word “all”, meaning burning or stinging and
the Latin “sativum” meaning planted or cultivated.
https://www.sciencedirect.com/science/article/pii/S1319016409000528

9. Scientific classification of garlic (Allium sativum)

10. Number of publications on ”garlic” in PubMed from 1892 - 2018
https://www.ncbi.nlm.nih.gov/pubmed/?term=garlic
5,849

11. Garlic production in the world 2005 & 2016
https://en.wikipedia.org/wiki/Garlic_production_in_China
2005: garlic output as a % of top producer China 2016

12. Garlic production (tonnes) by country 2016
http://www.factfish.com/statistic/garlic%2C%20production%20quantity

13. Top Garlic Consuming Countries in the World
https://www.indexbox.io/blog/which-country-eats-the-
most-garlic-in-the-world/
▪ China
▪ India
▪ Indonesia
▪ Bangladesh
▪ Republic of Korea

14. Top supplements used by U.S. households (1997)and adults (2017)
1997 2017
https://academic.oup.com/jn/article/131/3/955S/4687054
https://www.statista.com/statistics/308345/top-herbal-
and-botanical-supplement-types-used-by-us-adults/

15. Anatomy of a garlic bulb
https://www.bestfoodfacts.org/are-there-health-benefits-of-eating-garlic/

16. Varieties of garlic
▪ White (fresh)
▪ Black (processed)
▪ Purple (Las Pedroneras, Spain)
~

17. Aging process of black garlic from fresh garlic
http://herbnutritionals.com/herbal-extracts/fermented-black-garlic-extract

18. Nutrient composition of garlic
Macronutrient g/100g Micronutrient in mg/100g
Minerals
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366009/
31.2 mg
Micronutrient in mg/100g
Vitamins
https://www.natureword.com/properties-and-benefits-of-garlic/
nutritional-facts-garlic/

19. Bioactive organosulfur compounds of garlic
Organosulfur compounds

20. Allicin content in different forms of garlic
Adapted from https://www.tandfonline.com/doi/full/10.1080/10942910601113327?scroll=top&needAccess=true

21. Black garlic (made by enzymatic reaction over a period of time):
difference between fresh and black garlic
http://herbnutritionals.com/herbal-extracts/fermented-black-garlic-extract

22. Comparison between the components of fresh and black garlic
Adapted from https://www.sciencedirect.com/science/article/pii/S1021949816301727

23. Classification of garlic bioactive compounds by solubility

24. Classification of bioactive compounds by volatility
Adapted from https://core.ac.uk/download/pdf/55063732.pdf

25. Major bioactive compounds in raw garlic
Adapted from https://core.ac.uk/download/pdf/55063732.pdf
(odor)
key active ingredient

26. Organo-sulfur compounds present in
commercial garlic preparations (2017)
http://www.onlinepbe.com/index.php/PBE/article/view/220/html

27. Organosulfur compounds of garlic based on extraction process
https://www.sciencedirect.com/science/article/abs/pii/S0924224407002282

28. Major Organosulfur Compounds Present in Garlic.
http://eprints.umsu.ac.ir/122/1/Antileishmanial%20and%20Immunomodulatory%20Activity%20of%20Allium%20sativum%20
%28Garlic%29.%20A%20Review.pdf

29. Major organosulfur compounds in garlic
garlic odor precursor
precursor of glutathione
2 to 6 mg/g fresh garlic
6 to 14 mg/g fresh garlic
https://lpi.oregonstate.edu/mic/food-beverages/garlic
2 groupsAt least 33 compounds

30. Conversion of alliin (garlic odor precursor) to allicin
allicinalliin
odorless characteristic odor of garlic

31. Major bioactive compounds and their metabolites:
(1) alliin (2) ‫-ץ‬glutamyl-S-alk(en)yl-L-cysteine
allinase or
crushing
-
(1) alliin
(AM)
SAC contributes to health benefits of garlic: antidiabetic, antioxidant and anti-inflammatory activities

32. Site of origin of odoriferous breath gases after garlic ingestion. (1999)
Metabolism of 3 sulfur-containing gases (methanethiol, allyl mercaptan,
and allyl methyl sulfide) by different rat tissues:
duodenal mucosa (solid bar), stomach mucosa (open bar), cecal
mucosa (hatched bar), and liver (gray bar)
https://pdfs.semanticscholar.org/6d97/d8a2d39b595dd06e42f2581eea026a178b27.pdf?_ga=2.137281520.1738031391.1554530157-
220121597.1554530157
cecal mucosa

33. Major water-soluble derivatives of ‫-ץ‬glutamy-L-cysteine peptides
γ-Glutamyl-S-allyl-L-cysteine
SAC contributes to health benefits of garlic: antidiabetic,
antioxidant and anti-inflammatory activities

34. Typical concentration curve for breath AMS (allyl methyl sulfide) after
consumption of raw garlic homogenate. (2018)
analysis by HPLC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073756/

35. Plasma SAC content in human volunteers orally consuming
garlic supplement containing SAC (S-allylcysteine)
https://www.omicsonline.org/drug-metabolism-and-pharmacokinetics-of-organosulfur-compounds-from-garlic-2157-7609.1000159.php?aid=20147
half-life approx. 10 hr

36. Pharmacokinetic parameters of DADS (diallyl disulfide) and its
metabolites after a single oral administration of 200 mg Kg-1 in rats.
https://www.omicsonline.org/drug-metabolism-and-pharmacokinetics-of-
organosulfur-compounds-from-garlic-2157-7609.1000159.pdf

37. Cause of garlic odor in breath and skin

38. Comparison of allicin bioavailability and bioequivalence from garlic
supplements and garlic foods. (2018)
Adapted from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073756/

39. How to Get Rid of Garlic Breath
▪ Brush and floss
▪ Raw apples, parsley, spinach and mint
▪ Lemon juice and green tea
▪ Beverages or food with high water and/or fat content
https://ascientificcuriosity.wordpress.com/ever-wondered/why-garlic-makes-your-breath-smell/

40. Biological activities of organosulfur compounds in garlic
▪ Breath and body odor
▪ Flavoring agent
▪ Anti-microbial activity
▪ Anti-oxidant activity
▪ Anti-inflammatory activity
▪ Anti-diabetic
▪ Immuno-modulatory
▪ Cardiovascular protection:
▪ Inhibition of cholesterol synthesis
▪ Inhibition of platelet aggregation
▪ Inhibition of vascular smooth muscle cell (VSMC) proliferation
▪ Inhibition of vascular cell adhesion molecules
▪ Hydrogen sulfide-mediated vasodilatory activity
▪ Anti-cancer activity:
▪ Effects on carcinogen metabolism
▪ Induction of cell cycle arrest
▪ Induction of apoptosis
▪ Induction of angiogenesis
https://lpi.oregonstate.edu/mic/food-beverages/garlic#metabolism-bioavailability

41. Hypoglycemic effect of S-allyl-cysteine sulfoxide (alliin) in
mice (2018)
https://www.nature.com/articles/s41598-018-21421-x/figures/1
glucose tolerance test insulin tolerance test

42. Garlic as lipid lowering agent – a meta analysis
http://www.allicin-garlic-extract.com/garlic.asp

43. Effect of Raw Garlic vs Commercial Garlic Supplements on Plasma Lipid
Concentrations in Adults With Moderate Hypercholesterolemia
A Randomized Clinical Trial 2007
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/411743

44. Effect of garlic powder on C-reactive protein and plasma lipids in
90 overweight and smoking (> 10 cig) subjects age 40-75 y (2006)
▪ RTC trial: No significant differences between the garlic-treated and the placebo
groups.
▪ In contrast, compared with the placebo group, atorvastatin treatment resulted in
significantly lower plasma concentrations of
▪ C-reactive protein
▪ total cholesterol
▪ LDL cholesterol
▪ triacylglycerols
▪ tumor necrosis factor-α
▪ Conclusion: garlic preparation has no significant effect on inflammatory biomarkers,
endothelial function, or lipid profile in normolipidemic subjects with risk factors for
CVD.
https://pdfs.semanticscholar.org/478d/dbbc9f2bdc19ec7b2b5dc8ce142ed6b7cf02.pdf?
_ga=2.253332746.2067893108.1556763120-494571324.1556763120

45. Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis
Factor, and Interleukin-6 in Adults: (2019)
A Systematic Review and Meta-analysis of Randomized Controlled Trials
▪ 16 RCTs were included.
▪ Garlic doses ranged from 12 to 3600 mg/d, and
▪ Intervention duration ranged from 2 to 52 wk.
▪ Garlic administration significantly reduced serum
▪ C-reactive protein (CRP) (n = 13)
▪ IL-6 (n = 5)
▪ TNF (n = 7).
▪ However, the effect of garlic supplementation were not significant on serum:
▪ adiponectin (n = 3)
▪ leptin (n = 2)
▪ Conclusion: garlic supplementation reduced serum concentrations of CRP, TNF, IL-6, but
did not affect serum adiponectin and leptin in adults.
https://academic.oup.com/jn/article-abstract/149/4/605/5428122?redirectedFrom=fulltext

46. Garlic for the common cold (2015)
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006206.pub4/epdf/full

47. 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/

48. 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/

49. Garlic is an effective and safe approach for BP management:
meta-analysis (2015)
https://www.nutraingredients-usa.com/Article/2015/04/21/Great-economical-and-clinical-benefit-Garlic-is-an-effective-
and-safe-approach-for-BP-management-says-meta-analysis
favors garlic in BP management
systolic BP
diastolic BP

50. Effect of garlic on total cholesterol as compared with placebo
(2009)
https://www.researchgate.net/publication/26319823_The_impact_of_garlic_on_lipid_parameters_A_systematic_review_and_meta-analysis
Favors garlic

51. Epidemiological studies on Allium vegetables and cancer risk
cancer risk
▪ Stomach cancer ↓
▪ Colorectal cancer ↓
▪ Esophageal cancer ↓
▪ Prostate cancer ↓
▪ Oral cavity/pharynx, ↓
▪ Ovary and endometrium ↓
▪ Kidney, breast (No association)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366009/

52. Effect of garlic in gastric cancer prognosis:
a systematic review and meta-analysis (2018)
Forest plot for mortality rate in gastric cancer patients
with garlic usage in comparison with control.
Forest plot for Hazard ratio of gastric cancer patients
with garlic usage in comparison with control.
https://www.wcrj.net/article/1184
garlic intake in high doses could have a reducing effect on gastric cancer mortality.
mortality rate hazard ratio

53. Garlic consumption (highest vs lowest category)
reduces gastric cancer risk. (2011)
https://www.gastrojournal.org/article/S0016-5085(11)00441-0/pdf
LowHigh
favors high garlic consumption

54. Garlic consumption and colorectal cancer risk in man:
a systematic review and meta-analysis (2016)
Public Health Nutrition, Volume 19, Supplement 2
February 2016 , pp. 308-317
(a) case–control, (b) cohort and (c) supplement studies.

55. Garlic supplements: results of randomized controlled trials
• Garlic supplementation modestly improves serum lipid
profiles in individuals with elevated serum cholesterol.
• Garlic supplementation reduces blood pressure in
hypertensive subjects.
• Current evidence from observational studies does not
support an association between high intakes of garlic
and prevention of gastric and colorectal cancer.
• It is not known whether garlic-derived organosulfur
compounds may be effective in preventing or treating
human cancers.

56. Safety issues
▪ Dose: the following doses have been studied in scientific research:
▪ For diabetes: garlic powder 600-1500 mg daily in divided doses
▪ For high cholesterol: 600-900 mg of garlic powder daily in divided doses
▪ For high blood pressure: 300-1500 mg of garlic tablets in divided doses
▪ Adverse effects
▪ Breath odor
▪ Body odor
▪ Pregnancy and lactation
▪ No adverse effects have been reported
▪ Drug interactions
▪ Anticoagulant medication may increase risk of bleeding
▪ HIV protease inhibitors bioavailability decreased by garlic supplements
https://lpi.oregonstate.edu/mic/food-beverages/garlic#supplements

57. Recommended dosage of garlic and supplements
▪ Raw garlic: 4 grams (one to two cloves) per day
▪ Garlic powder tablet: 300 mg 2-3 times per day
▪ (standardized to1.2 percent alliin or 0.6 percent allicin
yield)
▪ Aged garlic extract: 7.2 grams per day
https://www.aafp.org/afp/2005/0701/p103.html

58. Commercial garlic products
▪ Fresh garlic
▪ Black garlic (aged garlic)
▪ Dehydrated garlic powder
▪ Distilled garlic oil
▪ Garlic capsule
▪ Alliin powder extract

59. Examples of some delicious garlic cuisine

60. Summary
▪ Garlic has been used as food and medicine for thousands of years.
▪ Study of its medicinal benefits began in the later half of the twentieth
century.
▪ The major bioactive compounds are alliin and -‫ץ‬ glutamyl-S-allyl-L-
cysteine.
▪ The conversion of alliin to allicin and its volatile products gives rise to
the flavor in cuisines and odor in the breath and skin.
▪ Scientific studies showed that garlic has anti-microbial, anti-oxidant,
anti-inflammatory, immunomodulatory, anticancer, anti-
hyperglycemia, anti-hyperlipidemia, and anti-hypertension properties.
▪ Current evidence from observational studies does not support an
association between high intakes of garlic and prevention of gastric
and colorectal cancer
▪ Garlic is safe for consumption and the adverse reaction is uncommon.