Nutraceutical Properties of Human and

Bovine Colostrum in Health and Disease

Harpal S. Buttar , D.V.M., M.Sc., Ph.D., FICN

Senior Scientist, Therapeutic Products Directorate,

Health Canada (Retd.)

Adjunct Prof., Dept. of Pathol. & Lab. Medicine,

University of Ottawa, School of Medicine, Canada

18th World Congress on Clinical Nutrition,

Ubon Ratchathani, Thailand, Dec. 1-3, 2014

COLOSTRUM

Colostrum - first mammary secretion that all

mammals provide for their newborns during the first

24-48 hours after parturition.

It creates the foundation of life-long immunity.

Colostrum contains various antibodies, and has lower

fat and higher protein content than ordinary milk.

COLOSTRUM

Colostrum has a nutrient profile and immunological

composition that differs substantially from mature

milk.

Colostrum contains macro- and micronutrients,

including vitamins and minerals. It contains higher

amounts of oligosaccharides, growth factors,

antimicrobial compounds, and immune regulators.

The nutrients in colostrum

contribute to the maturing

and development of the GI

tract in newborns.

Colostrum starts helping

GI tract to heal

immediately by lowering

pathogens, virus, bacteria,

fungus, yeast, mold etc.) in

the GI tract

Colostrum has been known for centuries for its health benefits.

Bovine Colostrum > potency than Human colostrum.

Humans can rely on bovine colostrum for their health benefit.

Another purported use of colostrum in the early 1950s was for treatment of rheumatoid arthritis.

English Colostrum

Marathi Chiik

(Kharwas)

Hindi Khiis

Tamil Seem paal

Telugu Junnu

Konkani Posu/Geen

Gujarati Bari

Punjabi Bauli

May increase lean muscle,

May decrease body fat levels,

May improve sprint performance,

May enhance anaerobic performance and buffers lactic acid build up,

May improve the recovery between bouts of exercise,

May enhance endurance performance,

Can improve immune function,

Growth factors in colostrum may enhance differentiation of bone marrow stem cells.

Some Physiological Effects of Colostrum

Because of the rapid gut cell turn over rate (cell replication),

colostrum supplements may help in curing mal-absorption of

nutrients due to GI tract problems such as chronic inflammatory

gut disorder, leaky-gut syndrome.

Several investigators have reported that the immune and growth

factors present in human and bovine colostrum may not only

benefit the newborn, but may also help the adult humans.

Since colostrum is a food rather than a drug, its adverse effects

are considered to be minimal, provided the product is obtained

from a reliable source and is prepared using good manufacturing

procedure.

Benefits of Colostrum Supplements

Colostrum

Ig G1, G2, A,M

PRP GF I, II Lactoferrin Leptin

Immunoglobulin Quantity

IgG1 35.0 (mg/ml)

IgG2 16.0 (mg/ml)

IgA 1.7 (mg/ml)

IgM 4.3 (mg/ml)

Lactoferrin 0.8 (mg/ml)

Different immunoglobulins present in bovine colostrum

Biological Activities of Colostrum

1 •Antimicrobial

2 •Antioxidant

3 •Anti-inflammatory

4 •Cardio-protective

Antimicrobial activity

Antimicrobial activity of colostrum was tested

using both Gram positive & Gram negative

strains.

Pour plate method was adopted, according to the

Indian pharmacopoeia 2010.

MIC of colostrum was calculated by serial dilution

in triplicate and it was found to be around

100µg/ml.

Antimicrobial activity of Colostrum

Minimum inhibitory concentration of colostrum was found to

be 100 µg/ml against:

• E. coli

• S. aureus

• P. vulgaris

• E. aerogenes

• S. typhi

From the result obtained, it can be concluded that

Colostrum is a potent antimicrobial agent.

• Lactoferrin contained in colostrum has strong antioxidant

characteristics which seem to act by two separate

mechanisms:

(i) binding catalytic iron generated during cell destruction,

(ii) and binding bacterial lipopolysaccharide (LPS) which

causes a decrease in LPS bioactivity, such as increasing

neutrophil O2 production.

• Colostrum lactoferrin also inhibits the production of

inflammatory cytokines.

• Proline rich peptides (PRP) in colostrum also act as an

oxidative stress inhibitor.

Anti-inflammatory Actions of Colostrum

• Colostrum has anti-inflammatory activity.

• Tumor necrosis factor-α (TNF-α) present in colostrum

bind with the cytokine receptors which control the

inflammatory cytokine cascade, effectively turning off

inflammation at its source.

• Colostrum also contains interleukin-1, the IL-1 receptor

protein, which also acts to inactivate the inflammatory

activity of IL-1.

• Colostrum may be beneficial in chronic inflammatory

diseases, such as various forms of arthritis and Crohn’s

disease, which has been linked to gut inflammation.

Anti-inflammatory Actions of Colostrum

Research suggests that to enhance supporting

performance, a minimum dose of 20 mg/day is

required, and this may take up to 8-weeks to have a

beneficial effect. It is not clear whether lower doses

(e.g. 10 g/day) would also be effective.

Note: Colostrum appears to be well tolerated. However, some

people may experience gastrointestinal problems such as

flatulence and nausea.

Athletic Benefits of Colostrum Supplements

Biochemical Components of Colostrum

Components Uses

1) Nutritional components

• Vitamins (A, B12 and

E)

• Minerals

• Amino Acids

• Essential fatty acids

Promote Health, Vitality,

and Growth of

the Newborn

Biochemical Components of Colostrum

Components Uses

2) Immune Factors

• Proline-Rich Polypeptide

(PRP)

• Immunoglobulins (A, D, E, G

and M)

• Lactoferrin

Regulate the thymus gland

IgG neutralizes toxins and

microbes

IgM destroys bacteria

IgE and IgD are highly antiviral

A nti-viral, anti-inflammatory and

anti-bacterial iron-binding protein

with therapeutic effects in cancer,

HIV etc.

Biochemical Components of Colostrum

Components Uses

3) Growth Factors

• Epithelial growth factor

(EGF)

• Insulin-like growth factor-I

and II (IGF-1 and IGF-II)

• Fibroblast growth factor

(FgF)

• Platelet-derived growth

factor (PDGF)

• Transforming growth factors

A (TgA) and B (TgB)

• Growth hormone (GH)

Help in enhancing cell and

tissue growth by stimulating

DNA formation

Comparison of Human, Cow, Buffalo & Goat Colostrum

Constituents Human Cow Buffalo Goat

Fat 3-5% 6.7% 7.56%-

11.31%

4.1%

Protein 0.8-0.9% 14.9% 4.3% 3.4%

Lactose 6.9-7.2% 2.5% 4.7% 4.7%

• Fat content in Buffalo Colostrum is higher than other species.

• Protein in Cow Colostrum is higher than other species.

• Lactose content in Human Colostrum is higher than other

species.

Water Soluble

Vitamin

Constituents

Human (mg/100

ml)

Cow (µg/ml) Buffalo (µg/ml) Goat

(µg/ml)

Niacin 0.02 0.34 - Approximately 0.6 µg/ml water soluble

vitamins are present.

Thiamine 0.017 0.90 -

Riboflavin 0.04 4.55 3.4

Vitamin B12 0.03 0.60 1.59

Pyridoxal - 0.15 -

Pyridoxamine - 0.21 -

Pyridoxine - 0.04 3.25

Comparison of water soluble vitamin and mineral contents in

Human, Cow, Buffalo & Goat Colostrum

Fat soluble vitamins Quantity

Retinol (vitamin A)

Tocopherol (vitamin E)

Beta-carotene

4.9 (µg/g)

2.9 (µg/g)

0.7 (µg/g)

Fat soluble vitamins present in bovine colostrum

Mineral Constituents Human (mg/100 ml) Cow (mg/kg) Buffalo (mM) Goat (g/kg)

Calcium 33 4716 47.1 0.65

Phosphorus 13-16 4452 27.7 0.36

Magnesium 4 733 7.3 -

Sodium 50 1058 20.3 1.44

Potassium 74 2845 28.7 3.38

Zinc 0.53 38 147-728 -

Iron 0.15 5.3 42-152 -

Copper 0.04 0.3 7 -

Sulphur - 2595 15700 0.2

Manganese - 0.1 38.2 -

The level of water soluble Vitamin content and Mineral constituent is much

higher in Cow Colostrum.

Types Colostrum powder

manufacturer

Colostrum capsule

manufacturer

Cow colostrum APS BioGroup APS BioGroup

Buffalo colostrum Biostrum Nutritech

Pvt. Ltd

Biostrum Nutritech

Pvt. Ltd.

Goat colostrum Mt. Capra Whole food

Nutritionals

Mt. Capra Whole food

Nutritionals

Manufacturers of colostrum-derived nutraceuticals

Conclusions

Colostrum acts as an anti-microbial, anti-oxidant, anti-

inflammatory and cardio-protective agent.

Colostrum concentrate was safe in athletes at 20 mg/day

dose.

Well designed placebo-controlled clinical trials are

required to access the safety and efficacy of colostrum

products.

Further studies are needed to understand the underlying

mechanisms by which colostrum acts as anti-microbial,

anti-inflammatory and cardio-protective agent.

Acknowledgement

I would like to acknowledge the collaboration of Dr.

Ginpreet Kaur, Assistant Professor at School of

Pharmacy &Technology Management, V. L. Mehta

Rd, Vile Parle (W) Mumbai, India.

“Leave your drugs in the chemist’s pot, if

you can heal the patient with food”

“Illness occurs when the body’s systems are

toxic and out-of-balance. One must treat the

body as a whole, rather than a series of

parts”

Hippocrates -

Father of Medicine

ca.460-370 B.C.

Antimicrobial plate of Enterobacter aerogenes

Enterobacter aerogenes

Code

Description

Centre Positive

control

1 Negative

control

2 Mixture of

sample

3 Colostrum

(100 ppm)

4 Amoxicillin

(10 ppm)

Zone of inhibition of

colostrum = 12 mm

Antimicrobial plate of Proteus vulgaris

Code

Description

Centre Positive

control

1 Negative

control

2 Mixture of

sample

3 Colostrum

(100 ppm)

4 Amoxicillin

(10 ppm)

Proteus vulgaris Zone of inhibition of

colostrum = 12 mm

Antimicrobial plate of Escherichia coli

Code

Description

Centre Positive

control

1 Negative

control

2 Mixture of

sample

3 Colostrum

(100 ppm)

4 Amoxicillin

(10 ppm)

Escherichia coli Zone of inhibition of

colostrum = 13 mm

Antimicrobial plate of Salmonella typhi

Code

Description

Centre Positive

control

1 Negative

control

2 Mixture of

sample

3 Colostrum

(100 ppm)

4 Amoxicillin

(10 ppm)

Salmonella typhi Zone of inhibition of colostrum =

11 mm

Antimicrobial plate of Staphylococcus aureus

Code

Description

Centre Positive control

1 Negative control

2 Mixture of sample

3 Colostrum (100 ppm)

4 Amoxicillin (10 ppm)

Staphylococcus aureus Zone of inhibition of colostrum =

11 mm

Antimicrobial activity of Colostrum

Zone of inhibition was measured in millimeter after 24 hours of incubation at 37 0C.

Free radical scavenging activity of colostrum by DPPH

Free radical scavenging activity of colostrum by DPPH

According to DPPH free radical scavenging activity

assay, Colostrum powder showed moderate activity

(47.07 %) at 200 µg/ml in comparison with Ascorbic

acid (89.72%).

The activity of colostrum was found to be

concentration dependent.

From the results obtained, it can be concluded that

Colostrum has moderate antioxidant activity in

comparison with standard ascorbic acid.

Lipid peroxidation inhibitory activity

Evaluation of lipid per oxidation inhibitory activity of

colostrum was performed on rat liver homogenate

using Thiobarbituric acid reacting substances

(TBARS) method.

In acidic condition, a pink colored complex was

formed, absorbance of which was measured at 532 nm

spectrophotometrically.

Colostrum showed dose-dependent increase in the

antioxidant activity. The average IC50 value was found

to be 180 ppm.

Lipid peroxidation inhibitory activity of colostrum by

TBARS

Sr.No Concentration (ppm) % Inhibition

1. 20 11.1

2. 40 22.4

3. 80 40.9

4. 160 46.4

5. 200 52.5

Lipid peroxidation inhibitory activity by TBARS

IC50 of colostrum was found to be 180 ppm

0

10

20

30

40

50

60

0 50 100 150 200 250

% I

nh

ibit

ion

Concentration (ppm)

% Lipid peroxidation inhibition

% Inhibition

Anti-inflammatory activity

Male Wistar rats were fasted for 12 h with free access to water.

Before any treatment, the average volume of the right paw of

each animal was determined using a plethysmometer

(Plethysmometer 520). Immediately after, the test substances

were administered.

The control group received only the vehicle. Sixty minutes later,

paw edema was induced by subcutaneous injection of 0.1 ml

carrageenan (0.1%) into the plantar surface of the right paw.

The volume of the paw of each rat was measured 1, 2, 3 and 4 h

after the injection of the control substance, inflammatory agent

or Sample Extract.

Evaluation of Anti-inflammatory Activity of Colostrum

Group I • Control group

Group II • Standard drug Diclofenac sodium (30 mg/kg)

Group III • Test substance Colostrum (500 mg/kg)

Group IV

• Test substance Colostrum (500mg/kg) + Diclofenac (10 mg/kg)

Four groups (N = 6)

Anti-inflammatory activity results of colostrum

Time

(hrs) Diclofenac Colostrum Colostrum + Diclofenac

0 46.25 ± 0.07*** 35.62 ± 0.03*** 21.67 ± 0.02***

1 64.56 ± 0.05*** 50.76 ± 0.02*** 37.49 ± 0.02***

2 77.33 ± 0.06*** 58.80 ± 0.01*** 49.38 ± 0.02***

3 76.23 ± 0.11*** 67.94 ± 0.02*** 59.53 ± 0.02***

4 67.38 ± 0.06*** 56.65 ± 0.02*** 48.83 ± 0.01***

Anti-inflammatory Activity Results

Anti-inflammatory Activity Results

The reduction was of the highest percent in Colostrum

alone group (67.94%) was observed at 3rd hr.

The second highest reduction (59.53%) was observed in

Colostrum with Diclofenac combination at 3rd hr.

It was concluded that Colostrum powder has

moderate anti-inflammatory activity in

comparison with Diclofenac.

Cardio protective activity of colostrum

MYOCARDIAL INFARCTION

The plaque deposited in the arteries hardens and when it cracks

clots are formed around the plaque.

Artery blockage and cessation of blood supply leads to damage

of the heart muscles (myocardial infarction)

Cardioprotective activity of colostrum

Isoproterenol (200 mg/kg)

Saline

Administered to Albino Wistar

rats subcutaneously

for 2 consecutive days

Induction of myocardial infarction

Animal Groups

• Seven groups each group containing six rats (150-250 g body wt.)

Group I • Rats received 1.0 ml water as a vehicle. Group I rats were referred as control rats.

Group II • Rats were administered the dose of isoproterenol

Group III • Rats were dosed with the test agent colostrum 250 mg/kg alone.

Group IV • Rats were treated with colostrum 250 mg/kg plus 0.25mg/kg enalapril

Group V • Rats received the test agent colostrum 500 mg/kg alone.

Group VI • Rats were treated with colostrum 500mg/kg + 0.25mg/kg enalapril

Group VII • Rats received dose of standard ACE inhibitor enalapril 0.25mg/kg alone.

Biochemical serum estimation of CK-MB and LDH

The isoproterenol-induced myocardial infarcted control group

had the highest CK-MB and LDH values indicating cardiac

damage.

Colostrum produced a dose-dependent decrease in the toxicity.

There was a significant reduction in cardiotoxicity after the

combined administration of 500 mg/kg of colostrum and

0.25mg/kg enalapril on comparison with the isoproterenol

myocardial infarcted group (Group II rats).

The increase in the CK-MB values and LDH indicate the extent

of isoproterenol-induced cardiotoxicity.

CKMB

0

500

1000

1500

2000

2500

Group I Group II Group III Group IV Group V Group VI Group VII

ckm

b IU

/l

Treatment Groups

CKMB

**

*** *** *** ***

Bars represented as Mean ± SEM, one way ANOVA followed by

Dunnett’s multiple comparison test. Significantly differ from

control Group 1, ** p<0.01 and ***p< 0.001.

LDH

0

200

400

600

800

1000

1200

1400

1600

1800

Group I Group II Group III Group IV Group V Group VI Group VII

LDH

(IU

/L)

Treatment Groups

LDH

***

*** ***

***

***

Bars represent as Mean ± SEM, one way ANOVA followed by

Dunnett’s multiple comparison test. Significantly differ from

control Group 1, ***p< 0.001.

Conclusion

Colostrum was found to act as an antimicrobial, antioxidant,

anti inflammatory and cardio protective agent.

Colostrum was safe till a 2g/kg dose.

Further studies to understand the underlying mechanisms by

which Colostrum acts in inflammation and cardio protection

are required.

Summary and Conclusions

Acute toxicity, antimicrobial, antioxidant, anti

inflammatory and cardio protective effects of Colostrum

were evaluated.

Colostrum was safe upto 2.0 g/kg dose.

MIC of Colostrum was 100 µg/ml.

DPPH free radical scavenging activity assay - 47.07 % at

200µg/ml.

Lipid peroxidation inhibitory assay - IC50 value was

found to be 180 ppm.

Summary and Conclusions

Colostrum alone reduced inflammation (67.94%)

compared to colostrum + diclofenac (59.53%).

Reduction could be due to an antagonistic effect.

Colostrum + enalapril reduced cardiotoxicity more

than colostrum alone.

Acknowledgement

I would like to acknowledge the

collaboration of Dr. Ginpreet Kaur,

Assistant Professor at School of

Pharmacy &Technology Management,

V. L. Mehta Rd, Vile Parle (W)

Mumbai, India.

“Leave your drugs in the chemist’s pot, if you

can heal the patient with food” “Illness occurs when the body’s systems are

toxic and out-of-balance. One must treat the

body as a whole, rather than a series of parts”

Hippocrates -

Father of Medicine

ca.460-370 B.C.

Thank you !!

References

1. Grivennikov SI, Sergei I, Greten FR, Karin M. Immunity, inflammation, and

cancer. Cell. 2010; 140(6): 883-99.

2. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications,

molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol

Rev. 2001; 65(2): 232-60.

3. Davies J. Inactivation of antibiotics and the dissemination of resistance genes.

Science. 1994; 264(5157): 375-82.

4. Brown MRW, Allison DG, Gilbert P. Resistance of bacterial biofilms to

antibiotics a growth-rate related effect?. J Antimicrob Chemother. 1988; 22(6):

777-80.

5. Neu HC. The crisis in antibiotic resistance. Science. 1992; 257(5073): 1064-73.

References

6. Demerec M. Origin of bacterial resistance to antibiotics. J Bacteriol. 1948; 56(1): 63-74.

7. Pakkanen R, Aalto J. Growth factors and antimicrobial factors in bovine colostrum.

International Dairy Journal. 1997; 7(5): 285-97.

8. Ogra SS, Ogra PL. Immunological aspects of human colostrum and milk. J Pediatr. 1978;

92(4): 550-55.

9. van Hoojidonk AC, Kussendrager KD, Steijns JM: In vivo antimicrobial and antiviral

activity of components in bovine milk and colostrum involved in non-specific defence. Br J

Nutr 2000; 84 Suppl 1: S127 -34.

10. Tokuyama H, Tokuyama Y, Migita S. Isolation of two new proteins from bovine

colostrum which stimulate epidermal growth factor-dependent colony formation of NRK-

49F cells. Growth Factors. 1990; 3(2): 105-14.

Thank you !!

59

OBJECTIVES

7) NDC Questions regarding Findings and Recommendations

Raphael, 1509, School of Athens, Causarum cognitio (Seek Knowledge of

Causes) “A Visualisation of Knowledge”