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WHITES AND

LOREN CORDAIN, PH.D. EGG WHITES AND AUTOIMMUNE DISEASE By Loren Cordain, Ph.D., Professsor

In all three of my books, I have advocated egg are uniquely different from meats in that they consumption, particularly eggs that are produced with represent the reproductive endpoints of adult birds high omega 3 fatty acid contents. eggs are which exist outside their mother’s body in a semi generally a nutritious food and are a good source of permeable, warm compartment. As such, all eggs selenium, A, vitamin D and the B are particularly vulnerable to invasion, attack and and some minerals. Additionally, numerous recent destruction by microorganisms such as fungi, bacteria experimental and epidemiological studies (reviewed in and present in their nesting environment. 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, Figure 1. Anatomy of a chicken egg. although eggs are one of the most concentrated sources of dietary (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 Vitelline from the body)1 and reduce the highly atherogenic small dense LDL particles while simultaneously Membrane 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. Albumen Hence, pre-agricultural humans could have never (white) 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. Chalazae If we follow up on the clue from the evolutionary template and examine eggs more closely, they Air Cell maintain certain nutritional shortcomings that may be problematic, particularly for people suffering from autoimmune diseases and . Although eggs Outer Membrane are classified as animal food sources and are lumped Inner Membrane together with meats in the USDA My Pyramid,

2 The innermost yolk represents the growing So, from a nutritional perspective, appears which is anchored to the albumen or egg white by to be a healthful source with an structures called chalazae. Outward from the egg composition capable of stimulating rapid muscular white are the inner and outer membranes and then growth. As is almost always the case in nutrition the shell, all of which provide physical barriers to and medicine, the devil lies in the detail, and a closer infection from pathogens and microorganisms. The examination of egg white reveals that it is a complex egg white makes up about 58% of the total egg volume mixture of more than 40 , some of which may and contains about 50% of the total egg protein adversely affect human health.6-8 and is composed of 88.5% water, 10.5% protein and A chicken egg is the reproductive endpoint for adult 0.5% carbohydrate6. The function of the egg white birds and survives by living outside its mother’s body is threefold: 1) storage of nutrients for the growing in a semi permeable compartment that is essentially embryo (yolk), 2) protection of the egg from microbial immovable. Accordingly, it has no means of protecting attack, and 3) transport of nutrients into the growing itself from microorganisms or predation by physical embryo. escape or avoidance. For this reason, the evolutionary Most nutritionists and dieticians consider egg white strategy eggs have taken to protect themselves from to be one of the most healthful and complete dietary microbial invaders is to select for toxic substances in proteins because its amino acid composition promotes the egg white; mainly in the form of antimicrobial rapid growth in laboratory animals. Athletes and proteins. Table 2 lists the major proteins in egg body builders frequently consume huge quantities of whites and their likely functions. Note that except for dried egg white for its high concentrations of muscle ovalbumen which comprises 54% of the total protein stimulating branch chain amino acids (Table 1). in egg white, virtually all the other major proteins

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 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 & (n=10) 1119 1980 1491 4590

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

Fruits (n=20) 209 319 292 820

3 (~33% of the total) maintain one form or another of dissolving bacterial cell walls.13 is unusual antimicrobial activity. among the major egg white proteins in that it has an alkaline isoelectric point (pI), which means that it can Egg white in the general population varies form strong complexes with other egg white proteins between 1.6 – 3.2 % and is the second most common including , ovalbumen and 8 cause of in children next to (Table ovotransferrin.6, 13 Hence, even though lysozyme is 3). In children, usually develops within a benign produced in our own bodies, when the first two years of life and resolves itself by school we eat egg white lysozyme, it comes as a compound 8 age. For both adults and children one or more of attached to other egg white proteins foreign to our the following symptoms may occur: , atopic bodies. (red, flaky itchy skin), , runny nose, diarrhea, abdominal pain, rapid swelling of the skin In the human digestive tract, called proteases and mucosa, and anaphylactic shock which may be normally break down proteins into their constituent life threatening. The major in egg white are amino acids so that the amino acids can be absorbed , ovalbumen, ovotransferrin and lysozymes8 across the intestines. Because egg white protein (Table 2). So for the vast majority of children and contains high concentrations of protease inhibitors adults (98.4 – 96.8 % of the population), egg white (ovomucoid, ovoinhibitor, ovostatin, cystatin) (Table allergy is not a problem, and except for anaphylactic 2), the human gut proteases (trypsin and chymotrypsin shock is not a debilitating or life threatening condition. primarily) are less effective in degrading egg white proteins, and lysozyme/egg white protein complexes. The same conclusion may not be true for people Additionally lysozyme is stable in the acidic gut suffering from an autoimmune disease multiple environment13 and therefore arrives intact in the lower sclerosis, , ankylosing spondylitis, gastrointestinal tract. erythematosus and others), since egg white consumption may contribute to the origin and So what’s wrong if lysozyme/egg white protein progression of these diseases via a process of molecular complexes aren’t dissolved by normal digestive mimicry that I have previously outlined for dietary processes? Normally, large multifaceted proteins lectins found in , and other grains and such as these complexes don’t have a prayer of getting legumes.12 across the intestinal barrier and into the bloodstream where they can interact with the immune system. You can see from Table 2 that egg white protein is no Once again, lysozyme is an unusual protein because simple protein, but rather a conglomeration of multiple it rapidly breeches the gut barrier and enters human proteins which have been designed by natural selection circulation14. Lysozyme and the complexes it forms to cause toxic and lethal effects in bacteria and with other egg white proteins can cross the gut microorganisms reminiscent of food lectins found in barrier since lysozyme contains a sugar15,16 that 12 grains and legumes. In order for any food proteins to specifically binds a gut , the epidermal growth potentially cause or promote an autoimmune disease, it factor receptor (EGF-R) which allows these protein must: complexes to enter circulation. Remember that 1. Survive the human digestive processes intact lysozyme also binds gut bacterial cell walls, so that 2. Cross the gut barrier intact either alone or these peptides also can gain access to circulation via with other attached proteins this Trojan Horse mechanism. 3. 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

4 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 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

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 , 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.

5 Figure 2. Bacterial/Egg Peptides.

B/E B/E LYSO Bacterial/Egg Peptides B/E Lysozyme LYSO Gut Interior

EGF-R EGF-R

Into Lymph LYSO B/E Enterocyte Cytosol B/E EGF-R LYSO

Into Activate Circulation T-Cells

6 REFERENCES 14. Hashida S, Ishikawa E, Nakamichi N, Sekino H. Concentration of egg white lysozyme in the serum of healthy 1. Fernandez ML. Dietary cholesterol provided by eggs and subjects after oral administration. Clin Exp Pharmacol Physiol. plasma lipoproteins in healthy populations. Curr Opin Clin Nutr 2002 Jan-Feb;29(1-2):79-83. Metab Care. 2006 Jan;9(1):8-12. 15. Lerrer B, Gilboa-Garber N.Differential staining of western 2. Kritchevsky SB. A review of scientific research and blots of avian egg white using diverse lectins. recommendations regarding eggs. J Am Coll Nutr. 2004 Dec;23(6 Electrophoresis. 2002 Jan;23(1):8-14 Suppl):596S-600S. 16. Mega T, Hase S. Conversion of egg-white lysozyme to 3. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines a lectin-like protein with agglutinating activity analogous JA. Plasma and lipoprotein responses to dietary fat to wheat germ agglutinin. Biochim Biophys Acta. 1994 Aug and cholesterol: a meta-analysis. Am J Clin Nutr. 1997 18;1200(3):331-3. Jun;65(6):1747-64. Copyright © 2014. The Paleo Diet. All Rights Reserved. 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.

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