EGG WHITES AND AUTOIMMUNE DISEASE

LOREN CORDAIN, PH.D.

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In all three of my books, I have advocated egg consumption, particularly eggs that are produced with high omega 3 fatty acid contents. Chicken eggs are generally a nutritious food and are a good source of selenium, vitamin A, vitamin D and the B vitamins and some minerals. Additionally, numerous recent experimental and epidemiological studies (reviewed in references 1, 2) indicate that regular egg consumption (7 per week) does not increase the risk for coronary heart disease (CHD). As I have previously noted, although eggs are one of the most concentrated sources of dietary cholesterol (212 mg per egg), dietary cholesterol has a minimal effect upon blood cholesterol concentrations in most people.1, 3 Further, high cholesterol egg diets cause an increase in blood HDL particles (the good particles that remove cholesterol from the body)1 and reduce the highly atherogenic small dense LDL particles while simultaneously increasing the less atherogenic large, “fluffy” LDL particles.4, 5

So, should everybody include eggs in their diet on a daily basis? Not necessarily, particularly if we examine the evolutionary template. Without question our pre- agricultural ancestors would have collected and consumed eggs from birds’ nests whenever possible. However, in the wild, bird eggs only appear seasonally. Hence, pre-agricultural humans could have never consumed two eggs for breakfast every morning of the year similar to some westernized people, but rather only occasionally for a few brief weeks or months.

If we follow up on the clue from the evolutionary template and examine eggs more closely, they maintain certain nutritional shortcomings that may be problematic, particularly for people suffering from autoimmune diseases and allergies. Although eggs are classified as animal food sources and are lumped together with meats in the USDA My Pyramid,

EGG WHITES AND AUTOIMMUNE DISEASEBy Loren Cordain, Ph.D., Professsor

eggs are uniquely different from meats in that they represent the reproductive endpoints of adult birds which exist outside their mother’s body in a semi permeable, warm compartment. As such, all eggs are particularly vulnerable to invasion, attack and destruction by microorganisms such as fungi, bacteria and viruses present in their nesting environment.

Vitelline Membrane

Yolk

Albumen (white)

Air Cell

Chalazae

Inner MembraneOuter Membrane

Figure 1. Anatomy of a chicken egg.

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The innermost yolk represents the growing embryo which is anchored to the albumen or egg white by structures called chalazae. Outward from the egg white are the inner and outer membranes and then the shell, all of which provide physical barriers to infection from pathogens and microorganisms. The egg white makes up about 58% of the total egg volume and contains about 50% of the total egg protein and is composed of 88.5% water, 10.5% protein and 0.5% carbohydrate6. The function of the egg white is threefold: 1) storage of nutrients for the growing embryo (yolk), 2) protection of the egg from microbial attack, and 3) transport of nutrients into the growing embryo.

Most nutritionists and dieticians consider egg white to be one of the most healthful and complete dietary proteins because its amino acid composition promotes rapid growth in laboratory animals. Athletes and body builders frequently consume huge quantities of dried egg white for its high concentrations of muscle stimulating branch chain amino acids (Table 1).

Table 1. Branch chain amino acid (BCCA) content in egg white and other food sources.

1000 kcal sample Weight of sample (grams) Isoleucine (mg) Leucine (mg) Valine (mg) Total BCCA (mg)

Dried Egg White 262 12002 17915 13529 43446 (84% protein)

Egg white raw 2000 11880 17740 13400 43020

Whey Protein (80 % Protein) 250 9225 17192 8968 35385

Whey Protein (75 % Protein) 250 8812 16425 8570 33807

Meats (n=4) 6364 9283 14741 9671 33695

Soy Protein (70% Protein) 301 8864 14815 9232 32911

Seafoods (n=20) 7443 12852 8031 28326

Hard boiled egg 645 3897 4426 4948 13271

Milk (n=1) 1628 3239 5240 3581 12060

Beans (n=8) 3199 5249 3491 11939

Veggies (n=18) 2383 2879 2450 7712

Grains (n=8) 1305 3034 1727 6066

Nuts & Seeds (n=10) 1119 1980 1491 4590

Starcy Root Vegetables (n=6) 450 662 580 1692

Fruits (n=20) 209 319 292 820

So, from a nutritional perspective, egg white appears to be a healthful protein source with an amino acid composition capable of stimulating rapid muscular growth. As is almost always the case in nutrition and medicine, the devil lies in the detail, and a closer examination of egg white reveals that it is a complex mixture of more than 40 proteins, some of which may adversely affect human health.6-8

A chicken egg is the reproductive endpoint for adult birds and survives by living outside its mother’s body in a semi permeable compartment that is essentially immovable. Accordingly, it has no means of protecting itself from microorganisms or predation by physical escape or avoidance. For this reason, the evolutionary strategy eggs have taken to protect themselves from microbial invaders is to select for toxic substances in the egg white; mainly in the form of antimicrobial proteins. Table 2 lists the major proteins in egg whites and their likely functions. Note that except for ovalbumen which comprises 54% of the total protein in egg white, virtually all the other major proteins

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dissolving bacterial cell walls.13 Lysozyme is unusual among the major egg white proteins in that it has an alkaline isoelectric point (pI), which means that it can form strong complexes with other egg white proteins including ovomucin, ovalbumen and ovotransferrin.6, 13 Hence, even though lysozyme is a benign enzyme produced in our own bodies, when we eat egg white lysozyme, it comes as a compound attached to other egg white proteins foreign to our bodies.

In the human digestive tract, enzymes called proteases normally break down proteins into their constituent amino acids so that the amino acids can be absorbed across the intestines. Because egg white protein contains high concentrations of protease inhibitors (ovomucoid, ovoinhibitor, ovostatin, cystatin) (Table 2), the human gut proteases (trypsin and chymotrypsin primarily) are less effective in degrading egg white proteins, and lysozyme/egg white protein complexes. Additionally lysozyme is stable in the acidic gut environment13 and therefore arrives intact in the lower gastrointestinal tract.

So what’s wrong if lysozyme/egg white protein complexes aren’t dissolved by normal digestive processes? Normally, large multifaceted proteins such as these complexes don’t have a prayer of getting across the intestinal barrier and into the bloodstream where they can interact with the immune system. Once again, lysozyme is an unusual protein because it rapidly breeches the gut barrier and enters human circulation14. Lysozyme and the complexes it forms with other egg white proteins can cross the gut barrier since lysozyme contains a sugar15,16 that specifically binds a gut receptor, the epidermal growth factor receptor (EGF-R) which allows these protein complexes to enter circulation. Remember that lysozyme also binds gut bacterial cell walls, so that these peptides also can gain access to circulation via this Trojan Horse mechanism.

(~33% of the total) maintain one form or another of antimicrobial activity.

Egg white allergy in the general population varies between 1.6 – 3.2 % and is the second most common cause of food allergy in children next to milk8 (Table 3). In children, egg allergy usually develops within the first two years of life and resolves itself by school age.8 For both adults and children one or more of the following symptoms may occur: hives, atopic dermatitis (red, flaky itchy skin), asthma, runny nose, diarrhea, abdominal pain, rapid swelling of the skin and mucosa, and anaphylactic shock which may be life threatening. The major allergens in egg white are ovomucoid, ovalbumen, ovotransferrin and lysozymes8 (Table 2). So for the vast majority of children and adults (98.4 – 96.8 % of the population), egg white allergy is not a problem, and except for anaphylactic shock is not a debilitating or life threatening condition.

The same conclusion may not be true for people suffering from an autoimmune disease multiple sclerosis, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus and others), since egg white consumption may contribute to the origin and progression of these diseases via a process of molecular mimicry that I have previously outlined for dietary lectins found in wheat, peanuts and other grains and legumes.12

You can see from Table 2 that egg white protein is no simple protein, but rather a conglomeration of multiple proteins which have been designed by natural selection to cause toxic and lethal effects in bacteria and microorganisms reminiscent of food lectins found in grains and legumes.12 In order for any food proteins to potentially cause or promote an autoimmune disease, it must:

1. Survive the human digestive processes intact2. Cross the gut barrier intact either alone or with other attached proteins3. Interact with the immune system in a manner suspected of causing an autoimmune disease.

A number of egg white proteins fulfill these necessary steps. Most problematic is the egg white protein, lysozyme which is actually an enzyme known as N- acetylhexosaminodase that is also found in many human tissues, including tears.13 The function of lysozyme in both egg whites and in human tears is to act as a potent bacterialcidal agent by binding and

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Once the (lysozyme/egg white protein/bacterial cell wall protein) complex gains access to circulation, it has the potential to activate the immune system in a process called three way molecular mimicry.12 In genetically susceptible individuals, this process causes the immune system to lose the ability to recognize self proteins from foreign proteins in such a manner that the immune system ultimately destroys the body’s own tissues.

Bottom line: If you suffer from an autoimmune disease such as multiple sclerosis, rheumatoid arthritis or others, I have previously recommended that you adopt a grain, dairy and legume free diet. To that list, you may also want to add eggs for the reasons I have described above. Eliminate all of these foods for an extended period and carefully monitor your symptoms. You may want to then gradually add single foods back into your diet to see if they cause problems to re-appear.

Table 2. Major proteins and their properties found in egg whites.6-10

Protein % total proteins Function(s)

Ovalbumen 54 Storage protein

Ovotransferrin 12 Iron binding with antimicrobial activity

Ovomucoid 11 Protease inhibitor/antimicrobial activity?

Ovomucin 3.5 Potent antiviral activity

Lysozyme 3.4 Antibacterial activity

G2 globulin 4.0? Antibacterial activity

G3 globulin 4.0? Antibacterial activity

Ovoinhibitor 1.5 Protease inhibitor/antimicrobial activity?

Ovoglycoprotein 1.0 ?

Thiamin binding protein 1.0 Thiamin transport

Ovoflavoprotein/Riboflavin 0.8 Riboflavin transport binding protein

Ovomacroglobulin (Ovostatin) 0.5 Protease inhibitor/antimicrobial activity?

Cystatin 0.05 Protease inhibitor/antimicrobial activity?

Avidin 0.05 Antimicrobial activity

Total 88.8

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Into Lymph

Into Circulation

Activate T-Cells

LYSOB/E

B/E B/E

B/ELYSO

Bacterial/Egg Peptides

EnterocyteCytosol

Lysozyme

Gut Interior

EGF-R EGF-R

EGF-R

LYSO

B/E

LYSO

Figure 2. Bacterial/Egg Peptides.

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REFERENCES1. Fernandez ML. Dietary cholesterol provided by eggs and plasma lipoproteins in healthy populations. Curr Opin Clin Nutr Metab Care. 2006 Jan;9(1):8-12.

2. Kritchevsky SB. A review of scientific research and recommendations regarding eggs. J Am Coll Nutr. 2004 Dec;23(6 Suppl):596S-600S.

3. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines JA. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am J Clin Nutr. 1997 Jun;65(6):1747-64.

4. Herron KL, Lofgren IE, Sharman M, Volek JS, Fernandez ML.High intake of cholesterol results in less atherogenic low-density lipoprotein particles in men and women independent of response classification. Metabolism. 2004 Jun;53(6):823-30.

5. Maki KC, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH.Lipid responses in mildly hypertriglyceridemic men and women to consumption of docosahexaenoic acid-enriched eggs. Int J Vitam Nutr Res. 2003 Oct;73(5):357-68.

6. Stevens L. Egg white proteins. Comp Biochem Physiol B 1991;100:1-9.

7. Szxena I, Tayyab S. Protein proteinases inhibitors from avian egg whites. Cell Mol Life Sci 1997;53:13-23.

8. Mine Y, Yang M. Recent advances in the understanding of egg allergens: basic, industrial and clinical perspectives. J Agric Food Chem 2008;56:4874-4900.

9. Wellman-Labadie O, Picman J, Hincke MT. Comparative antibacterial activity of avian egg white protein extracts. Br Poult Sci. 2008 Mar;49(2):125-32.

10. Takahashi K.G., Nakamura A., Mori K. Inhibitory effects of ovoglobulins on bacillary necrosis in larvae of the pacific oyster, Crassostrea gigas. J Invert Pathol 2000;75:212-217.

11. National Institute of Allergy and Infectious Diseases (July 2004). “NIH Publication No. 04-5518: Food Allergy: An Overview.

12. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17.

13. Proctor VA, Cunningham FE. The chemistry of lysozyme and its use as a food preservative and a pharmaceutical. Crit Rev Food Sci Nutr 1988;26:359-395.

14. Hashida S, Ishikawa E, Nakamichi N, Sekino H. Concentration of egg white lysozyme in the serum of healthy subjects after oral administration. Clin Exp Pharmacol Physiol. 2002 Jan-Feb;29(1-2):79-83.

15. Lerrer B, Gilboa-Garber N.Differential staining of western blots of avian egg white glycoproteins using diverse lectins. Electrophoresis. 2002 Jan;23(1):8-14

16. Mega T, Hase S. Conversion of egg-white lysozyme to a lectin-like protein with agglutinating activity analogous to wheat germ agglutinin. Biochim Biophys Acta. 1994 Aug 18;1200(3):331-3.

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