Food as Medicine; formation and functions of whey ,caseins and their bioactive compounds,;Benefits of fermented cheese and clinical studies.

1. FOOD AS MEDICINE:
CHEESE
BIOACTIVE COMPOUNDS
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 Providers May, 2020

2. Outline of lecture
▪ What is cheese
▪ History
▪ Cheese making process
▪ Nutrient composition
▪ Functions of bioactive compounds
▪ Clinical studies
▪ Summary

3. What is cheese ?
▪ Cheese is a milk product caused by
bacterial fermentation and coagulation of
the milk protein casein.
▪ It comprises proteins and fats from milk,
usually the milk of cows, buffalo, goats, or
sheep.
▪ There are over 1832 specialty cheeses
from 74 countries in the world.

4. Brief history of cheese making in the United States
Adapted from https://world-cheese-map.com/cheese/history-of-cheese/

5. Characteristic length scales in cheese.
HFG = homogenized fat globules, CGJ = curd granule junction.
https://www.journalofdairyscience.org/article/S0022-0302(17)30942-6/fulltext

6. Laser scanning microscopy images (100 µm × 100 µm) of
Cheddar cheese (age: 12 wk) at 3 different fat levels (8.5, 20.3, and 33.3%).
https://www.journalofdairyscience.org/article/S0022-0302(17)30942-6/fulltext
Column A shows the confocal laser scanning microscopy
images (100 µm × 100 µm) of Cheddar cheese (age: 12 wk)
at 3 different fat levels (8.5, 20.3, and 33.3%).
Column B is the schematic representation of Cheddar
cheese microstructure, with intact fat globules, aggregated
fat globules, coalesced fat globules, and nonglobular fats.
The dark and gray areas represent fat globules and protein
network within the cheese matrix, respectively.
Fat

7. The Basic Process of Turning Milk Into Cheese
▪ There are six important steps in cheesemaking:
1. Bacterial inoculation
2. Coagulation with rennet
3. Separating curds and whey
4. Salting
5. Shaping
6. Ripening.
▪ While the recipes for all cheeses vary, these
steps outline the basic process of turning milk
into cheese and are also used to make cheese
at home.

8. Major cheese producing countries in 2019
(in 1,000 metric tons)
https://www.statista.com/statistics/195809/cheese-production-in-selected-countries-2009/

9. Leading U.S. states in total cheese production in 2019
(in 1,000 pounds)
https://www.statista.com/statistics/195764/top-10-us-states-for-cheese-production-2008/

10. The most popular cheese by U.S. Region
https://ninateicholz.com/most-popular-cheese-state/

11. Classification of cheese
▪ Rennet-coagulated cheeses:
▪ Cheddar,
▪ Gouda,
▪ Mozzarella,
▪ Swiss,
▪ Blue,
▪ Camembert.
▪ Acid-coagulated cheeses:
▪ Cottage cheese
▪ Quark
▪ Processed cheese: mixture of milk powders, casein
products, flavors, colors, preservatives and
stabilizers: e.g. American cheese
▪ Imitation cheese: cheese-like products formulated
from casein powder and butterfat or a vegetable oil.

12. Varieties of cheese
Cheddar, Gouda, Mozzarella, Swiss, Blue, White Camembert.
Cottage cheese, Quark
American cheese
Shredded Imitation Cheddar

13. Types of Cheese
https://www.pinterest.ca/pin/545498573591587439/

14. Differences between cheeses
▪ country of origin,
▪ type of milk used,
▪ species of animal
▪ fat content,
▪ moisture content,
▪ texture,
▪ whether mould ripened or not,
▪ cheese making process used,
▪ moisture in the non-fat solids
https://www.dummies.com/food-drink/cooking/ingredients-for-cooking/a-few-good-cheeses/

15. Nutrient and bioactive compositions of cheese

16. Macronutrients (g) of common cheeses per 100 g
https://en.wikipedia.org/wiki/Cheese

17. Micronutrient (Vitamin) contents in %DV of common cheeses
per 100 g
https://en.wikipedia.org/wiki/Cheese

18. Micronutrient (Mineral) contents in %DV of common cheeses
per 100 g
https://en.wikipedia.org/wiki/Cheese

19. Composition of branded cheese
http://www.rroij.com/open-access/modelling-the-grade-value-of-cheese.php?aid=34167

20. Bacterial types commonly associated with milk.
http://phd.lib.uni-corvinus.hu/303/1/pasztorne_huszar_klara.pdf

21. Bacteria contents in some cheeses
https://www.slideshare.net/oneraltinsoy/cheese-50041398

22. The formation of volatile flavor compounds in cheese.
https://www.sciencedirect.com/topics/food-science/cheese-flavor

23. The formation of flavor compounds in cheese (2013)
https://www.researchgate.net/figure/Main-pathways-for-the-formation-of-flavour-compounds-in-cheese-Volatile-compounds-are_fig1_263353422

24. The aromatic profile of goat’s cheese during ripening (2013)
#1
https://www.researchgate.net/figure/2-Main-volatile-ketones-and-esters-identified-in-goat-cheeses_tbl1_263353422

25. The aromatic profile of goat’s cheese during ripening (2013)
#2
https://www.researchgate.net/figure/2-Main-volatile-ketones-and-esters-
identified-in-goat-cheeses_tbl1_263353422

26. Cheese making: protein contents in cow’s milk
https://www.robertbarrington.net/the-composition-of-whey-protein/
20%
80%

27. What is the difference between whey and casein protein?
https://www.quora.com/What-is-the-main-difference-between-casein-and-whey

28. What is Whey?
▪ Whey is a mixture of proteins isolated as liquid material from cheese production
▪ There are four main classes of proteins in whey:
▪ β-lactoglobulin
▪ α-lactalbumin
▪ serum albumin
▪ immunoglobulins
https://pubs.rsc.org/en/content/articlelanding/2015/gc/c5gc01428j#!divAbstract

29. Typical composition and physical properties of whey proteins
https://www.researchgate.net/figure/Typical-composition-and-physical-properties-of-whey-proteins_tbl1_305344169

30. What is casein?
▪ Casein is a family of related phosphoproteins (αS1, αS2, β, κ).
▪ These proteins are commonly found in mammalian milk, comprising c. 80% of the
proteins in cow's milk and between 20% and 45% of the proteins in human milk.
▪ Sheep and buffalo milk have a higher casein content than other types of milk with
human milk having a particularly low casein content

31. Structure of casein
http://iosrjournals.org/iosr-jac/papers/vol12-issue7/Series-1/C1207012325.pdf

32. Structure of the Caseins
Backbone asymmetric structure of a casein
submicelle with water molecules from droplet algorithm,
i.e., 2,823 water molecules:
k -casein in blue ,
αs1-casein in red ,
β-casein in magenta ,
oxygen from droplet waters in cyan
https://www.researchgate.net/publication/278659526_Higher_Order_Structures_of_the_Caseins_A_Paradox

33. Four different types of cow casein
https://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/enzyme-reagents/casein.html
1
2
3
4
+

34. Some physico-chemical characteristics of the caseins
https://www.sciencedirect.com/topics/food-science/gamma-casein

35. Simplified view of the biochemical changes that lead to
bioactive compounds, texture and flavor changes in cheeses.

36. The role of lactic acid bacteria during the fermentation or
ripening process of cheese. #1
https://www.sciencedirect.com/science/article/pii/S0022030218301462
Targets
Bacteria

37. The role of lactic acid bacteria during the fermentation or
ripening process of cheese. #2
https://www.sciencedirect.com/science/article/pii/S0022030218301462
Targets
Enzymes
Bacteria

38. The role of lactic acid bacteria during the fermentation or
ripening process of cheese. #3
https://www.sciencedirect.com/science/article/pii/S0022030218301462
Bioactive compds
Enzymes
Targets
Bacteria

39. In vitro actions of bioactive compounds in cheese
Adapted fromhttps://www.sciencedirect.com/science/article/pii/S0022030218301462

40. Health benefits of cheese
▪ Bone health
▪ Dental health
▪ Blood pressure
▪ Healthy blood vessels
▪ Gut microbiota and cholesterol
▪ Healthy weight
▪ Omega-3 fatty acid
▪ Healthy cells
https://www.medicalnewstoday.com/articles/299147#8-health-benefits-of-cheese

41. Scientific articles on “cheese” in PubMed from
1863 to 2019
Total 13,3343
https://pubmed.ncbi.nlm.nih.gov/?term=cheese%2C%20&timeline=expanded

42. Scientific studies on cheese
Cells
Antibacterial
Animals
Antioxidant
Hypertension
Opioid
Diabetes
Inflammation
Human
Lipids
Glucose
Blood pressure
Obesity

43. CHEESE:
PRO-INFLAMMATORY vs ANTI-INFLAMMATORY

44. Distribution of the inflammatory markers measured in the 52 human
studies on “dairy products and inflammation”. (2014)
The x-axis presents the inflammatory markers.
The y-axis presents the number of study results reporting a specific analytical result with the corresponding inflammatory marker
• significant anti-inflammatory change (black bars),
• no significant change (grey bar),
• significant pro-inflammatory change (white bars).
https://www.tandfonline.com/doi/full/10.1080/10408398.2014.967385

46. Distribution of the study results labeled as “anti-inflammatory”,
“no effect”, and “pro-inflammatory”
for the entire data set composed of 78 study results
A) Number of study results labeled as “anti-inflammatory”,
“no effect”, “pro-inflammatory”
B) Distribution of the Inflammatory Score.
https://www.tandfonline.com/doi/full/10.1080/10408398.2014.967385

47. Distribution of the study results labeled as
“anti-inflammatory”, “no effect”, and “pro-inflammatory”
among the dairy product categories “high-fat” and “low-fat”
• significant anti-inflammatory change (black bars)
• no significant change (grey bars)
• Significant pro-inflammatory change (white bars)
https://www.tandfonline.com/doi/full/10.1080/10408398.2014.967385

48. Meta-analysis: Hierarchy of evidence in clinical studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049418/

49. Meta-analysis: Hierarchy of evidence in clinical studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049418/

50. Meta-analysis of prospective studies on cheese consumption
(high vs. low) and risk of all-cause mortality.
https://www.mdpi.com/2072-6643/9/1/63/htm

51. Relative risks of CVD for an increment of 10 g/day of cheese
https://pubmed.ncbi.nlm.nih.gov/28374228/?from_term=cheese%2C+meta-analysis&from_pos=4

52. Relative risk of all-cause mortality for an increment of
20 g/day of fermented dairy intake
https://pubmed.ncbi.nlm.nih.gov/28374228/?from_term=cheese%2C+meta-analysis&from_pos=4

53. Meta-analysis of cheese consumption of per 50 g/d and risk of
cardiovascular disease (CVD), coronary heart disease (CHD), and stroke
stroke
https://link.springer.com/article/10.1007/s00394-016-1292-z?referrer=yahoo

54. Consumption of dairy product and its association with
total and cause specific mortality :
A population-based cohort study and meta-analysis
on 636,726 participants. (2018)
▪ Higher total dairy consumption was associated with
lower total and cerebrovascular mortality,
▪ Higher milk consumption was associated with higher
risk of coronary heart disease.
▪ a significant inverse association between fermented
dairy products and total mortality
https://ars.els-cdn.com/content/image/1-s2.0-S0261561418325834-fx1_lrg.jpg
https://www.sciencedirect.com/science/article/abs/pii/S0261561418325834

55. Side effects of cheese
Cheese is a whole food with minor side effects
associated with:
▪ Lactose intolerance
▪ Allergy to casein protein
▪ High blood pressure due to high sodium
▪ Hyperlipidemia due to saturated fat
▪ Constipation due to absence of fiber

56. Pasteurization
▪ A number of food safety agencies around the world have warned of the risks of raw-
milk cheeses.
▪ The U.S. Food and Drug Administration states that soft raw-milk cheeses can cause
"serious infectious diseases including listeriosis, brucellosis, salmonellosis and
tuberculosis".
▪ It is U.S. law since 1944 that all raw-milk cheeses (including imports since 1951)
must be aged at least 60 days.
▪ There is a trend for cheeses to be pasteurized even when not required by law.
▪ Pregnant women may face an additional risk from cheese; the U.S. Centers for
Disease Control has warned pregnant women against eating soft-ripened cheeses
and blue-veined cheeses, due to the listeria risk, which can cause miscarriage or
harm the fetus.
https://en.wikipedia.org/wiki/Cheese

57. Summary
▪ Cheese is a milk derived food produced by bacteria, coagulation of
curds and ripening process of cheese.
▪ The process of fermentation and ripening leads to the generation of a
variety of bioactive compounds.
▪ Most of the scientific studies on the bioactive products were done on
laboratory animas.
▪ Studies of the bioactive compounds on human showed that the
fermented cheese is associated with anti-inflammatory activity.
▪ There is a marginally significant increased risk of all-cause mortality
due to the high content of saturated fat in cheese.

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