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Bovine Secretory Immunoglobulin A (sIgA)
Immunoglobulin Stability in the Digestive Tract
Glutathione and Colostrum


Derivatives - A


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Derivatives - B


Bovine Secretory Immunoglobulin A (sIgA)

Introduction
The beneficial aspects of milk and colostrum in maintaining health and well being are well established. In humans it has been shown that the incidence of common infections of the intestinal and respiratory systems is significantly reduced in breast fed infants when compared to non-breast fed infants.

The protective effect of human milk has been attributed to its immunoglobulin content, primarily secretory IgA, whereas in most other animals it is primarily IgG. Other non-specific factors have also been implicated, including lactoferrin and lyzozyme.

The pharmacological action of milk and colostrum lies in its ability to function as an antibacterial, anti-inflammatory, and possibly as an anti-viral agent. All these activities have been attributed to secretory IgA. The fact that secretory IgA is a normal constituent of milk and that it is found in relatively high concentration in bovine colostrum suggests that this natural food product is an ideal candidate for a natural food ingredient supplement.

Ant-Bacterial/Anti-Viral Activity
Secretory IgA is the predominate immunoglobulin in seromucousal secretions such as colostrum, milk, saliva, tears, nasal mucous, tracheobronchial secretions and genito-urinary secretions (1,2).

Structurally secretory IgA consists of two monomeric IgA molecules linked by disulfide bonds to a joining chain (J-chain) and one molecule of secretory component. The main features distinguishing secretory IgA from the other immunoglobulins is that function predominately in mucosal immunity and that the molecule is protected from proteolytic degradation by its association with secretory component.

Secretory IgA can be regarded functionally as "antiseptic paint" providing a first line of defense which prevents infectious organisms from entering the body proper. It is probably most important early in life where it may limit the extent of infection and give the newborn's system time to mature.

Adherence to epithelial cells of mucous membranes is essential for viral infection and bacterial colonization. Secretory IgA functions to inhibit the adhesion of these pathogens thus limiting disease. In addition secretory IgA functions to neutralise the toxins and virulence factors from microbial pathogens by immuno-agglutination.

The leading cause of death to newborns in developing countries has been attributed to infantile diarrhea (3). This is also true of domestic animals where scours (enteric dysentery) is the major cause of mortality in newborn calfs (4). The enterotoxigenic form of Escherichia coli is one of the pathogens most frequently associated with this disease state (4-7). Secretory IgA has been shown to neutralise this toxin, as well as enterotoxins of Vibrio cholererae, Shigella, and Salmonella (8-11).

Anti-Inflammatory Activity
Inflammation is a complex localized event in response to either injury, invasive foreign substance (pathogen) or in some instances to internally produced substances (rheumatoid arthritis).

This is a protective adaptation that serves to isolate, destroy, and rid the infected area of both the injurious agent and the injured tissue. Inflammation is characterized by an increase in vascular permeability and vasodilation with a subsequent migration of leukocytes into the inflammed area. Clinically inflammation is associated with pain, swelling, tenderness, redness, and general discomfort. Prostaglandin’s (PG) and leukotrienes (LT) play an important role in mediating the process of inflammation by increasing histamine-mediated vascular permeability. It is predominately this action, which causes the discomfort, associated with inflammation.

The common anti-inflammatory analgesic and antipyretic drugs, such as corticosteroids, aspirin, and indomethacin, inhibit PG and or LT synthesis. In fact most, if not all, of the anti-phlogistic actions of steriodal and non-steroidal anti-inflammatory drugs action by inhibiting prostaglandin synthesis. The anti-inflammatory effect of aspirin and indomethacin is inhibition of cyclooxygenase, whereas those of corticosteoids are thought to inhibit the release of fatty acids from phospholipids either by inhibition of phospholipase A2 or by interfering with the release of membrane phospholipids.

The adverse side effects associated with certain anti-inflammatory agents limits their use. In the case of natural and synthetic corticosteroids the potential side effects include the elevation of blood pressure, water and salt retention, increased calcium and potassium excretion, gastric upset and possibly peptic ulceration. In addition, the use of these compounds may also aggravate diabetes mellitus.

The non-steroidal anti-inflammatory compounds (salicylates) are synthetic biochemical substances, which can be toxic at high doses. The possible side effects associated with these substances include gastric upset and gastric bleeding, prolonged clotting time, and hepatic injury. Though the number of various anti-inflammatory agents is great so are the potential side effects and adverse reactions associated with these compounds.

It has been shown by in vitro studies that the secretory component of secretory IgA inhibiting phospholipase A2 activity and therefore prostaglandin and leukotriene synthesis by limiting the release of arachidonic acid (12-14). This inhibition of prostaglandin and leukotriene synthesis thus gives supporting evidence that secretory component and secretory IgA possess anti-inflammatory properties.

Secretory IgA and secretory component are normal constituents of bovine colostrum are therefore are a natural food product. This fact that this natural protein possesses anti-bacterial and anti-inflammatory properties suggests that it would be an ideal candidate as a natural food ingredient supplement.

References
1. Tomasi, T. B., Jr., and Bienenstock, J. (1968), Advan. Immunol. 9,1.
2. Tomasi, T. B., Jr. (1970), Annu. Rev. Med. 21, 281 - 298.
3. Gordon, J. E. (1971), Ann. N.Y. Acad. Sci. 176, 9.
4. Oxender, W. D., Newman, L.E. and Morrow, D. A. (1973), Amer. Vet. Med. Assoc. 162, 458.
5. Black, R. E., Lopez de Romana, G., Brown, K. H., Bravo, N., Bazalar, O. G., Kanashiro, H. C. (1989), Amer. Jour. Epidemiol. 129, 785 - 799.
6. Black, R. E., Merson, M. H., Rahman, A. (1980), Jour. Infect Dis. 142, 660 -664.
7. Guerrant, R. L., Kirchhoff, L. V., Shields, D. S. et al. (1983), Jour. Infect. Dis. 148, 986 - 997.
8. Guerrant, R. L., Ribeiro, S. T. G., Vainstein, M. H., Ulhoa, C. J. (1995), Jour. Med. Microbiol. 42, 3 -9.
9. Stoliar, O. A., Pelley, R. P., Kaniecki-Green, E., Klaus, M. H., Carpenter, C. C. J. (1976), Lancet,2, 1258 -1261.
10. Holmgren, J., Hansen, L. A., Carlson, B., Lindblad, B. S., Rahimtoola, J. (1976), Scand. Jour. Immunol. 5, 865 - 871.
11. Allardyce, R. A., Shearman, D. J. C., McClelland, D. B. L., Marwick, K., Simpson, A. J., Laidlaw, R. B. (1974), Brit. Med. Jour., 3, 307 - 309.
12. Wilson, T., Liggins, G. C., Joe., L. (1989) Amer. Jour. Obstet. Gynecol. 160, 602 - 606.
13. Wilson, T., Liggins, G. C., Aimer, G. P., Skinner, S. J. M. (1985) Biochem. Biophys. Res. Comm., 131, 22 -29.
14. Wilson, T., Christie, D. L. (1991) Biochem. Biophys. Res. Comm., 176, 447 -452.

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Derivatives - C


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Derivatives - D


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Derivatives - E


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Derivatives - F


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Derivatives - G

GLUTATHIONE

A POWERFUL ANTIOXIDANT FOUND IN COLOSTRUM
Colostrum is the most significant food in the world. It was designed by natural to to protect the newborn. The significance of colostrum and the role it plays is best illustrated in the typical farm animal. Take the horse, cow, sheep, goat, cat, dog - unless these and most other animals receive colostrum in the first day or two of life they have a very significant chance not surviving.

This phenomenon is due to a wonderful mechanism by which the mother can pass on her complement of antibodies on to her newborn and is known as passive transmission of immunity. Because of this significance and the role that colostrum plays in the newborn some other very important actions or properties associated with the biological function of colostrum have been over-looked.

One of these properties is the fact that Colostrum, in addition to all its other benefits, is a source of a wide range antioxidants.One such antioxidant - Glutathione - has been described as the "Ultimate Antioxidant". It is very well documented that glutathione and it's precursors are present in colostrum in relatively high levels. In this capacity glutathione and glutathione precursors play an important part in colostrum's role in overall health.

Glutathione also referred to, as GSH is a naturally occurring peptide or small protein, which has a primary function as an antioxidant. Linus Pauling was a leading advocate of antioxidants and their respective role in prevention of disease and the promotion of overall good health. Antioxidants for the most part are naturally occurring compounds that possess the ability to neutralize unstable "free radicals".

Unchecked these free radicals have been linked, at least in part, as the causative agents of a number of disease conditions including cancer, heart disease, stroke, and improper nervous & immune system function.

A growing number of scientific and medical research studies have successfully shown that that antioxidants can deactivate free radicals and thus limit the spread of certain disease states. Basically antioxidants act as free radical scavengers and thus removing them from the body before they can cause their harmful effects.

Many foods such as fruits, vegetables, grains, and oils contain vitamins and minerals that have antioxidant properties. Vitamin A, C & E, carotenoids, and flavonoids are probably the best known antioxidants. The growing body of scientific and medical research substantiates the significance glutathione and other antioxidants play in sustaining health and combating the disease state.

This mountain of evidence suggests that by simply increasing one's cellular levels of glutathione a corresponding increase of overall good health can be envisioned.

The development of cancer and disease for the most part is a long and slow process. One exception are childhood cancers, which are usually attributed to, inherited defective genes.

Cancer cells in adults contain a large number of mutations acquired over a lifetime's exposure to environmental carcinogens, toxins, and free radicals. These substances damage the bodies DNA - the blueprint of life. Antioxidants have been shown to protect the DNA from excessive damage and help in the synthesis and repair. In fact the cellular level of glutathione has been described as predictive factor in determining our life expectancy. Glutathione regulates the actions of other less effective antioxidants such as vitamins C & E.

It has been reported that low levels of cellular glutathione are associated with liver and immune system malfunction, heart disease, premature aging, and death.

Further, it has been reported that glutathione functions in not only detoxification of toxins but of also neutralizing carcinogens.

Glutathione has also been described as having potent anti-viral and anti-bacterial properties. Glutathione has also been shown to have a wide variety of functions that help boost the immune system.

Lymphocytes (T cells and B cells), so vital in the immune response have been shown to be dependent on glutathione for proper function. As we age our cellular levels of glutathione drop and it is these lower levels of glutathione that have been implicated in diseases associated with aging. Finally, glutathione has been shown to enhance athletic performance by increasing muscle strength and weight gain.

As an antioxidant glutathione helps protect the overall integrity of every cell and tissue against damage caused by free radicals and disease. Acting as a scavenger of free radicals glutathione helps to protect us from pollutants and other disease causing agents.

Glutathione is a trimer composed of three amino acid precursors - glycine, glutamic acid and cysteine. Though free glutathione is surely of benefit the main benefit comes from the internalization of it's precursors and subsequent assembly and action within the cell. In fact a recent investigation involving piglets it was revealed that intercellular glutathione was most exclusively from dietary consumption of glutathione precursors.

There are a number of products available that contain glutathione and it's precursors. For the most part they are derived from colostrum, milk, and or whey. They are typically referred to as whey protein isolates. A number of these are marketing the fact that their respective products are significantly higher in glutathione and it's precursors.

The fact is that in relation to New Zealand colostrum (low temperature processed) these products do not have significantly higher levels of either glutathione, glutathione precursors or other bioactives present in properly processed colostrum. In fact it has been recently reported that antioxidant activity of bovine colostrum is significantly greater as compared to number of such products, including whey protein hydrosylates. Figure 1 illustrates that lack of any significant difference between a whey protein isolate glutathione enriched product and a quality produced colostrum.

Of special significance are the glutathione precursors Glycine, Glutamic Acid, and Cystine (2 linked Cysteine molecules) and the relative values found in the respective products.

Figure 1.

Reported composition of a commercially available whey protein isolate which is reportedly enriched with glutathione & it's precursors and a quality processed New Zealand colostrum product.

Amino Acid Whey Derived Product NZ Colostrum 20% Ig's
Glycine 20mg/g protein 18.1 mg/g protein
Glutamic Acid 201 126.3
Cystine 24 16.8

Proteins
Lactoalbumin 9.7% 2%
lactoglobulin 59.1% 19%
lactoferrin 0.14% 0.15%

Total Immunoglobulins 24.6 25%

IGF-1 1000ng/g
IGF-2 250ng/g
TGF-B1 150ng/g
TGF-B2 950ng/g
EGF 250ug/100g

Vitamin
A 100 IU/100g
B1 1.5 - 2.0 mg/60g
B2 1.7 - 2.2 mg/60g 1.12 mg/100g
B6 0.03 mg/100mg
B12 13.6 ug/100g
C 2.5 mg/100g
D < .2ug/100g
E 130ug/100g

It is of interest that the whey protein isolate which is reportedly enriched with glutathione and it's precusors does not contain a significantly greater amount of glutathione precursors as compared to the quality colostrum product. This is also true of other constituents that make up the composition of the respective products. It is of interest that Cysteine has been reported to be a rate limiting amino acid for the biosynthesis of glutathione.

The fact that lactoglobulin and lactoalbumin are a rich source of this essential amino acid and they are found in relatively high amounts in colostrum should be noted.
Of outmost importance is the simple fact that if there is a substance that can improve the quality of life then this information should be available to and shared by everyone. The scientific and medical evidence generated from producers of whey protein isolate products is significant. However most if not all their claims based on their findings can and for the most part have been attributed to the same claims generated from investigations centering on colostrum.

Further the process of manufacturing whey protein isolated products for the most part includes ultrafiltration or microfiltration of raw material in order to concentrate the various constituents responsible for bioactivity. Typically this requires that this material is subjected to filtration through 10,000 molecular weight (Dalton) membrane.

Thus many small molecular weight molecules are removed from solution. These include many growth factors that are involved with the healing and recovery process, including growth factors and cytokines which have a wide variety of biological functions. This is most probably indicated by the fact the manufactures of whey protein isolates who claim enriched glutathione levels typically do not include growth factor and cytokine levels as part of their respective compositional information.

Colostrum is a magical substance composed of many, many substances that work together in a synergistic manner in such a way that the overall effect of colostrum is greater than the individual components. In regard to whey protein isolated products they have attributed the action to one constituent - glutathione. This is only part of the answer as many other bioactive molecules are involved - antibodies, immune factors, growth factors, cytokines, etc. In reality it is an "Ever Ending Story" with only part of the answer on how colostrum and in fact it's derivatives, such as whey protein isolates, actually function and work only partly known. The wonderful thing is that they actually do work and that this is backed by scientific and medical evidence.


REFERENCES

Glutathione - Alternative Health Care. Volume Two, Article Four, May 1999. http://www.healthalternative.org/vol2.htm 24 June 2002.

Petrosino SP. The Benefits of Glutathione (GSH) - The Nutrition Advisor. http://NutritionAdvisor.com . 20 June 2002.

Lands LC., Grey VL., and Smountas AA. The Effect of Supplementation With a Cysteine Donor on Muscular Performance. Journal of Applied Physiology, 87:4, 1999, 1381-1385.

Parodi PW. Cow's Milk Components With Anti-Cancer Potential. Human Nutrition Program, Dairy Research and Development Corporation Correspondence to Peter W. Parodi. Australian Journal of Dairy Technology 2001; 56: 65-73.

Antioxidant Activity of Colostrum, http://www.docters-choice.com/activity.htlm , 22 June, 2002

Buescher ES., McIlheran SM. Antioxidant Properties of Human Colostrum. Pediatrics Research, 1988, July, 24(1)14-9.

Parodi PW. Cow's Milk Components With Anti-Cancer Potential. Australian Journal of Dairy Technology, 2001;56:65-73.

Reeds PJ., Burrin DG., Stoll B., Jahoor F., Wykes L., Henry J., Frazer M. Enteral Glutamateis the Preferential Source of Mucosal Glutathione Synthesis in the Piglet. Agricultural Research Services, United States Department of Agriculture. 1996. http://www.nal.usda.gov/ttic/tektran/data/000007/70/0000077019.html 24/6/02.

Health-Enhancing Properties of Dairy Ingredients - Composition of Whey. Dairy Council Digest. June 24, 2002. http://www.nationaldairycouncil.org/lvl04/nutrib/digest/dairydigest_722b.htm 24/6/02.

Bounous G. Whey Protein Concentrate (WPC) and Glutathione Modulation in Cancer Treatment. Anticancer, 2000, Nov-Dec;20 (6C):4785-92.

Micke P., Beeh KM., Sclaak JK.,Buhl R. Oral Supplementation With Whey Proteins Increases Plasma Glutathione Levels of HIV-Infected Patients. European Journal of Clinical Investigations, 2001,February;31(20):171-8.

Kennedyl RS., Konokil GP., Bounous G.,Baruchel S. The Use of a Protein Concentrate in the Treatment of Pathogens with Metastatic Carcinoma: A Phase I-ll Clinical Study. Anticancer Research. 1995, 15:2643-2650.

The-Analysis-Glutathione. http://www.digitailnaturoath.com/treat/treat/T147297.html , 24 June, 2002.
Kramer TR., Zhang YH., Taylor PR., Li JY., Blot WJ., Brown CC., Guo W., Dawsy SM., Li B. Effects of Micronutrient Intervention on Mitogenic Responsiveness of T-Lymphocytes in a Population at Risk of Esophageal Cancer. Agricultural Research Services, United States Department of Agriculture. http://www.nal.usda.gov//ttic/tektran/data/000006/41/0000064140.html


 

 

Derivatives - H


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Derivatives - I


Immunoglobulin Stability in the Digestive Tract

An important consideration is the stability of antibodies in the digestive tract. In a study conducted to ascertain the stability of bovine immunoglobulins to proteolytic digestion it was revealed that antibodies which possess specific activity can pass through the gastrointestinal tract of infants without being completely destroyed.

This indicates that the specific action of antibodies in the gastrointestinal tract is not adversely affected and that biological activity is retained. It is further suggested that the IgG in Colostrum manages to escape digestion because of a high buffering capacity of Colostrum. In addition, bovine Colostrum is also thought to contain a globulin-like protein which inhibits proteolytic enzymes - trypsin in particular.

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Derivatives - J


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Derivatives - K


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Derivatives - L


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Derivatives - M


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Derivatives - N


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Derivatives - P


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Derivatives - Q


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Derivatives - R


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Derivatives - S


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Derivatives - T


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Derivatives - U


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Derivatives - V


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Derivatives - W


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Derivatives - X


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Derivatives - Y


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Derivatives - Z


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DISCLAIMER:
The statements contained herein have not been evaluated by the Food And Drug Administration. It is not intended to diagnose, treat, cure or prevent disease. The statements are for informational purposes only and is it not meant to replace the services or recommendations of a physician or qualified health care practitioner. Those with health problems or pregnancy are specifically advised that they should consult their physician before taking colostrum or any nutritional supplement.


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