THE PALEO DIET INSIDER

ARE SNAILS PALEO?

THE

Vol. 6, Issue 1

HOW TO GET ENOUGH CALCIUM

BENEFITS OF FLAXSEED

LYSOZYME FROM EGG WHITES

LOREN CORDAIN, PH.D.

Vol. 6 ◆ Issue 1

2

Archaeologists interpret that snails were eaten because their shells were found in huge heaps called middens, and frequently were charred from being cooked.5 Snail middens dating from 20,000 to 10,000 years ago and from 10,000 to 6,000 years ago are common in lands close to and surrounding the Mediterranean Sea.3, 5 The five most commonly consumed species of snails (Helix aspera, Helix melanostoma, Leucochroa candissima, Helicella setifensis, and Otala species) still occur in the Mediterranean region today.

If you don’t know, snail meat is considered a delicacy worldwide and is most commonly known from its French term, “escargot,” an appetizer typically cooked in a sauce of butter, garlic and parsley.6 Although three species of snails (Helix aspera, Helix pomatia) and the African snail (Achatina fulica) are most commonly consumed6, a large variety of snail species are eaten worldwide, depending upon location and availability. The cost of 1 kg of prepared snail meat is expensive and fluctuates between $5 - $137. Snail meat, like fish, is high in protein and low in fat, and contains significant amounts of iron (see Table below). Give escargot a try, it’s a great Paleo appetizer.

Q & A: SNAILSQ: Do you know if they ate snails in the paleo times?

Thank you,

Geha

A: Hi Geha,

The Paleolithic era stands for the “Old Stone Age” (Paleo means old; lithic means stone) and extended from 2.6 million years ago with the appearance of the first crude stone tools until the beginning of agriculture 10,000 years ago. During this period, it is estimated that at least 20 species of hominins (upright walking apes) existed1. Because all hominins were omnivorous opportunists,2 land snails were almost certainly consumed on an occasional basis throughout hominin evolutionary history.

However, having said this, the first direct evidence for land snail consumption does not appear in the fossil record until 31,000 years ago at the Mumba-Hohle site on the shores of Lake Eyasi in East Africa.3,

4 The earliest archaeological evidence for land snail consumption in the Middle East has been dated to 22,000 to 23,000 years ago at the Kvar ‘Aqil site near Beirut, Lebanon.3 The hominin that would have eaten these snails was our own species, Homo sapiens.

3

Nutrients Units of measurement Nutrient content for nutrients per 100 grams of snail

Water g 79.20 Energy kilocalorie 90.00 Protein g 16.10 Total lipid (fat) g 1.40 Ash g 1.30 Carbohydrate, by difference g 2.00 Fiber, total dietary g 0.00 Sugars, total g 0.00 MINERALS Calcium, Ca mg 10.00 Iron, Fe mg 3.50 Magnesium, Mg mg 250.00 Phosphorus, P mg 272.00 Potassium, K mg 382.00 Sodium, Na mg 70.00 Zinc, Zn mg 1.00 Copper, Cu mg 0.40 Selenium, Se mcg 27.4 VITAMINS Vitamin C mg 0.00 Thiamin mg 0.01 Riboflavin mg 0.12 Niacin mg 1.40 Vitamin B-6 mg 0.13 Folate, total mcg 6.00 Folic acid mcg 0.00 Folate, food mcg 6.00 Folate, DFE mcg_DFE 6.00 Vitamin B-12 mcg 0.50 Vitamin B-12, added mcg 0 .00 Vitamin A, IU IU 100.00 Vitamin A, RAE mcg_RAE 30.00 Retinol mcg 30.00 Vitamin E (alpha- tocopherol) mg 5.00 Vitamin E, added mg 0.00 Vitamin K (phylloquinone) mcg 0.10 LIPIDS Fatty acids,total saturated g 0.361 4:0 g 0.000 6:0 g 0.000 8:0 g 0.000 10:0 g 0.000 12:0 g 0.000 14:0 g 0.056 16:0 g 0.249 18:0 g 0.051

Vol. 6 ◆ Issue 1

4

Nutrients Units of measurement Nutrient content for nutrients per 100 grams of snail

Fatty acids, total monounsaturated g 0.259 16:1 undifferentiated g 0.048 18:1 undifferentiated g 0.211 20:1 g 0.000 22:1 undifferentiated g 0.000 Fatty acids, total polyunsaturated g 0.252 18:2 undifferentiated g 0.017 18:3 undifferentiated g 0.000 18:4 g 0.015 20:4 undifferentiated g 0.000 20:5 n-3 g 0.119 22:5 n-3 g 0.099 22:6 n-3 g 0.000 Cholesterol mg 50.000

CALCIUM FROM WHERE?Q: While this style of eating and living makes sense to me, I am still left with the question of how to meet the Recommended Daily Allowance (RDA) for calcium. From all I’ve read on the subject, it’s not possible to reach the RDA with vegetable sources (unless you include fortified soy or rice milk). Since dairy isn’t part of your scheme, how does a person meet the RDA? Or do you disagree with the RDA?

A: Indeed, we relieve the RDA is higher than what you would need in a Palaeolithic type diet, because:

1. The absorption rate from brassica vegetables (e.g. Kale) is slightly higher than from milk and as so (and also because they have

numerous health benefits), we advise the daily intake of these foods.

2. A diet with lots of vegetables and fruit is net base yielding and in contrast a diet high in grains, cheese and salt and low in fruits and vegetables (which is a characteristic of the American way of eating) is net acid yielding and this increases calcium excretion.

3. The Paleo Diet is a High protein diet and this increases intestinal calcium absorption1, 2 and has an anabolic effect on bone,3 particularly in the context of a net base yielding diet.3

4. By avoiding grains, you decrease anti-nutrient intake, such as phytates, which decrease magnesium.4 calcium5 and zinc5 absorption.

For sources see References: Section I

5

5. The Paleo Diet is a Low Glycemic Load diet and as so, it does not promote Hyperinsulinemia as a high grain diet. It has been known since the year I was born (1975) that high blood insulin levels cause urinary calcium loss.6

6. Milk has a high Insulinotropic effect, and as so it may lead to an increase in urinary calcium excretion, for the reason outlined in point.5

For sources see References: Section II

EPIGENETICSQ: What do you think about epigenetics? Many scientists (in Germany) believe that the concept of the Paleo Diet is no longer tenable.

Thanks,

Michael

A: Dear Michael,

Epigenetics is defined as the science studying changes in phenotype or gene expression by mechanisms other than changes in DNA nucleotide sequence1. The phenotype is someone’s appearance which it’s determined by the genotype (stable and heritable) and the environment (nutrition and other lifestyle factors) which give place to the epigenotype (heritable, labile and rapid)1. Epigenetic changes are controlled, among other mechanisms, by methylation and histone modification. Altered methylation pattern and histone modification may lead to increased susceptibility to disease. E.G. cancer is associated to generalized hypomethylation and localized promoters hypermethylation.1 Histone manipulation may also increase or decrease disease susceptibility.2

Both, methylation and histone manipulation are under the control of dietary substances. For example, methylation depends on SAMe availability, which in turn is influenced by vitamin B6, vitamin B12 and folate intake,3 and long chain polyunsaturated fatty acids such as DHA4. On the other hand, certain substances such as garlic, horseradish, fiber, blueberries, apple, onion, nuts, berries, red grapes, broccoli, etc. are known nutrients involved in histone modification.2

The Paleo Diet is rich is all of these nutrients5, hence it may exert positive effects upon epigenetics machinery leading to decreased disease susceptibility. Decreased availability of micronutrients is associated to disease severity, probably, through complex epigenetic mechanisms, and supplementation could improve those symptoms.3 Improved epigenetic is influenced by metabolic programming during foetal and early life. These two periods are crucial for the developing newborn and future adult’s health. Hence, The Paleo Diet may confer protection against several diseases improving the epigenetic programming.

We hope this is helpful.

Maelán Fontes Villalba, MS P.h.D.

Pedro Carrera Bastos, MA MS Ph.D.

For sources see References: Section III

FLAXSEED OILQ: I recently visited family and my brother is a new advocate of the paleo diet. For breakfast he made us “fakecakes” which had about 1-2 tablespoons of flaxseed in them that he ground in a coffee grinder. I had few a questions regarding the use of flaxseed in the Paleo Diet.

First, why are flaxseeds ok in the Paleo Diet but other grains (seeds) are not? My understanding for eliminating grains from the diet is the toxins that they contain, but flaxseed contains

Vol. 6 ◆ Issue 1

6

large amounts of cyanogenic glycosides, producing up to 139 mg/kg of hydrogen cyanide in raw human-grade flaxseed. I am sure flaxseeds are processed somehow before selling them but I don’t know what process that is or what effect it has on the HCN concentration.

So, secondly...do you know of any studies on the amount of HCN in meals containing ground flasxseed and the chronic oral exposure of those amounts on humans? My understanding here is the HCN that isn’t hydrolysed to formic acid in the stomach and doesn’t bind to hemoglobin is converted to thiocyanate which hinders thyroid function.

Thank you for your time and any information you can supply.

Sincerely,

Tim

A: Hi Tim,

We think your thoughts are on the right track.

When Dr. Cordain wrote The Paleo Diet book, the advice to consume flaxseed oil was an attempt to balance the increased omega-6/omega-3 fatty acid ratio due to the exaggerated intake of omega-6 vegetable oils, especially linoleic acid, in the typical western diet.

Nevertheless, animal foods (fish, muscle meat and organs from wild animals) are good sources of w3 fatty acids. Therefore, when people eat these foods regularly along with vegetables and nuts, and avoid vegetable oils (especially oils rich in Linoleic Acid – Omega 6), they get a balanced intake of omega 3, omega 6, monounsaturated and saturated fatty acids. In this situation, there is no need for flax seeds to provide Omega 3 fatty acids and balance the Omega 3/Omega 6 ratio.

Here are some facts that support the notion that animal foods, vegetables and nuts provide the necessary Omega 6 and Omega 3 fatty acids in the right proportion:

1. Hunter-gatherers do not eat ALA from seeds or vegetable oils.

2. Nuts, green leafy vegetables and animal foods contain ALA.

3. The conversion of ALA to EPA+DHA is limited, due to low delta-6 and delta-5 activity, although ALA is highly oxidized (twice that of LA) (see paper by Freemantle et al). This means that at some point in history we included preformed sources of EPA and DHA and still need to do so. Animal foods (especially brain from wild ruminants and fish) are very good sources of these fatty acids.

4. The essentiality of LA & ALA in human metabolism has been questioned (see paper by Le et al.), as we relied almost on LCPUFA (Arachidonic Acid, EPA and DHA) during the Palaeolithic era (see Dr. Cordain’s papers

7

on that here and here). Moreover, there is already some evidence showing that human metabolism could re-convert AA and DHA into LA and ALA respectively, hence AA and DHA would be the true essential fatty acids.

5. The possible toxicity from seeds and vegetable oils (HCN, saponins, lectins).

6. They are not used by current HG societies, and these populations show no signs of western disease, so this means that flax seeds are not necessary.

7. The well known positive health effects of fish oil supplementation (among other factors to improve omega-6/omega-3 ratio) in contrast with some possible adverse effects of flaxseed oil (like the epidemiological evidence that points towards increased risk of prostate cancer with flax oil consumption – see paper by Brouwer et al).

The bottom line from an evolutionary perspective is that flax seeds and/or flaxseed oil would not have been consumed by pre-agricultural humans. However, having said that, hunter gatherers always would have preferentially sought high oil plant foods as per optimal foraging theory. But, most high fat plant foods contain high MUFA (with the exception of coconut and palm oils).

Hope this helps,

Maelán Fontes Villalba, MS, P.h.D.

LYSOZYME FROM EGG WHITESLoren Cordain, Ph.D., Professor Emeritus

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, some minerals and lutein as Barbara indicated. 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 particles1 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 preagricultural 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, 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 semipermeable, 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.

The innermost yolk of a chicken egg represents the growing embryo which is anchored to the albumen or

Vol. 6 ◆ Issue 1

8

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 1 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 (~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

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.

As I have previously mentioned, a chicken egg is the reproductive endpoint for adult birds and survives by living outside its mother’s body in a semi

Table 1. major proteins and their properties found in egg whites (adapted from references 6-10.)

Protein % Total Proteins Functions

Ovalbumen 54 Storage protein

Ovotrasferrin 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 1.0 Thiamin transport protein

Ovoflavoprotein/ 0.8 Riboflavin transport Riboflavin binding protein

Ovomacroglobulin 0.5 Protease inhibitor/antimicrobial activity? (Ovostatin)

Cystatin 0.05 Protease inhibitor/antimicrobial activity?

Avidin 0.05 Antimicrobial activity

Total 88.8

9

cause of food allergy in children next to milk.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 lysozyme8 (Table 1). 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 (e.g. 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.11

You can see from Table 1 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 legumes11 In order for any food proteins to potentially cause or promote an autoimmune disease, it must:

1. Survive the human digestive processes intact

2. Cross the gut barrier intact either alone or with other attached proteins

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 Nacetylhexosaminodase that is also found in many human tissues, including tears.12 The function of lysozyme in both egg whites and in human tears is to act as a potent bacterialcidal agent by binding and dissolving bacterial cell walls.12

Bacterial cell walls are called the murein or peptidoglycan layer which is a gigantic polymer of (N- acetylglucosamine and N-acetylmuyramic acid) polysaccharide strands cross linked through short peptide bridges at the lactyl groups of the muramic

acid residues. Lysozyme degrades bacterial cell walls by catalyzing hydrolysis of the beta (-1,4-) linkage between N-acetylglucosamine and N-acetylmuramic acid. Human cells do not maintain a murein (peptidoglycan) exterior lining. Consequently, dietary lysozyme from egg whites do no increase intestinal permeability by breakdown of intestinal cell membranes but rather lysozyme increases intestinal permeability by other means that I will explain. It is this increase in intestinal permeability or “leaky gut” that makes egg white consumption problematic for people with egg allergies or autoimmune disease.

Lysozyme is unusual among the major egg white proteins in that it has an alkaline isoelectric point, which means that it can form strong complexes with other egg white proteins including ovomucin, ovalbumen and ovotransferrin.6, 12 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 or to gut borne bacterial proteins foreign to our bodies.

In the human digestive tract, enzymes called proteases normally break down proteins into their constituent

Vol. 6 ◆ Issue 1

10

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 - see Table 1), 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 environment12 and therefore arrives intact in the lower gastrointestinal tract. It should also be mentioned that Lysozyme is heat stable, having been reported to withstand 100 degrees C with little loss of activity.13 Matsuoka et al14 reported lysozyme to be stable in acidic solution (pH 4.5, 100 degree C for 3 min; pH 5.29, 100 degree C, 30 min. So lysozyme would survive any normal cooking procedures used for eggs.

So what’s wrong if lysozyme/egg white protein/bacterial 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 circulation,15 due to its unusual chemical properties (a positively charged isoelectric point).16 Because lysozyme maintains a positive charge, it results in an electrostatic attraction to the negatively

charged proteoglycans (the glycocalyx) of intestinal epithelial cells which in turn allows lysozyme to be absorbed rapidly into circulation.16

Absorption of pure egg white lysozyme by itself into circulation is likely not problematic because lysozyme is an enzyme that the body naturally produces. Rather it is the complexes that lysozyme forms with other egg white proteins, gut borne bacterial peptides and food peptides that may adversely stimulate the immune system. When these chimeric (monster) molecules breech the gut barrier via their net positive charge and enter circulation, they have the capacity to promote allergy and autoimmune disease.

Just how autoimmune diseases are triggered by gut borne antigens from egg white lysozyme and other common foods (cereal grains, legumes, dairy and certain saponin containing foods) is another good story that our research group has been working on for the past decade.

For sources see References: Section IV

11

PRIMAL IN THE KITCHEN

SALMON CAESAR SALAD

4-6 oz salmon fillets, skin on 2 Tb. extra virgin olive oil 2 heads romaine lettuce, chopped 1/4 small red onion, diced 2 Tb. cold pressed flaxseed oil 1 garlic clove, crushed 1 t. crushed mustard seed 1 Tb. freshly squeezed lemon juice Freshly ground black pepper, to taste

Preheat oven to broil. Brush flesh side of salmon fillet with 1 tablespoon of olive oil. Place in baking pan flesh side down. Brush skin with the remaining tablespoon of olive oil. Broil for fifteen minutes. Remove from oven and set aside.

In a large bowl, mix together lettuce and onion. Combine flaxseed oil, garlic, mustard seed, and lemon juice in a small jar and shake well. Toss with lettuce and onion. Serve topped with salmon fillet and season with freshly ground pepper.

Copyright © 2011. The Paleo Diet Cookbook. All Rights Reserved.

Vol. 6 ◆ Issue 1

12

REFERENCES: SECTION I 1. Wood B. Hominid revelations from Chad.Nature. 2002 Jul 11;418(6894):133-5.

2. Cordain L. Saturated fat consumption in ancestral human diets: implications for contemporary intakes. In: Phytochemicals, Nutrient-Gene Interactions, Meskin MS, Bidlack WR, Randolph RK (Eds.), CRC Press (Taylor & Francis Group), 2006, pp. 115-126.

3. Lubell, D. Prehistoric edible land snails in the circum-Mediterranean: the archaeological evidence. In, J-J. Brugal & J. Desse (eds.), Petits Animaux et Sociétés Humaines. Du Complément Alimentaire Aux Ressources Utilitaires. XXIVe rencontres internationales d’archéologie et d’histoire d’Antibes, pp. 77-98. Antibes: Éditions APDCA, 2004.

4. Mehlman MJ. Mumba-Hohle revisited: the relevance of a forgotten excavation to some current issues in East African prehistory. World Archaelogy 1979;11:80-94.

5. Lubell, D. Are land snails a signature for the Mesolithic-Neolithic transition? In, M. Budja (ed.), Neolithic Studies 11. Documenta Praehistorica XXXI: 1-24.

6. Ozogogul, Y, Ozogul F, Olgunoglu AI. Fatty acid profile and mineral content of the wild snail (Helix pomatia) from the region of the south of the Turkey. Eur Food Res Technol 2006;221:547-549.

7. Zymantiene J et al. Selected features of vineyard snails shell, their movement and physic-chemical composition of foot meat. Biotechnol & Biotechnol Eq 2006;20:82-87.

REFERENCES: SECTION II1. Kerstetter JE, Gaffney ED, O’ Brien O, et al. Dietary Protein increases intestinal calcium absorption and improves bone balance: An hypothesis. In Burckhardt P, Heaney R, Dawson-Hughes B. Proceedings of the International Symposium on Nutritional Aspects of Osteoporosis, 4-6 May 2006, Lausanne, Switzerland. Elsevier, 2007, pp 204-216.

2. Dawson-Hughes B. Protein intake and calcium absorption

– Potential role of the calcium sensor receptor. In Burckhardt P, Heaney R, Dawson-Hughes B. Proceedings of the International Symposium on Nutritional Aspects of Osteoporosis, 4-6 May 2006, Lausanne, Switzerland. Elsevier, 2007, pp 217-227.

3. Sebastian A. Dietary protein content and the diet’s net acid load: opposing effects on bone health. Am J Clin Nutr. 2005 Nov;82(5):921-2.

4. Bohn T, Davidsson L, Walczyk T, Hurrell RF. Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans. Am J Clin Nutr. 2004 Mar;79(3):418-23.

5. Cordain L. Cereal grains: humanity’s double edged sword. World Rev Nutr Diet 1999; 84:19-73.

6. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975;55:845–55.

REFERENCES: SECTION III1. van Vliet J, Oates NA, Whitelaw E. Epigenetic mechanisms in the context of complex diseases. Cell Mol Life Sci. 2007 Jun;64(12):1531-8.

2. Delage B, Dashwood RH. Dietary manipulation of histone structure and function. Annu Rev Nutr. 2008;28:347-66.

3. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.

4. Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem. 2006 Nov;17(11):717-27.

5. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54.

6. Kemperman RF, Veurink M, van der Wal T, Knegtering H,

13

Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.

REFERENCES: SECTION IV1. 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 acidenriched 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. 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.

12. 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.

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

14. Matsuoka Y, Hidaka Y, Yashima M. Japanese Patent 41-150, 1966.

15. 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.

16. Nishikawa M, Hasegawa S, Yamashita F, Takakura Y, Hashida M. Electrical charge on protein regulates its absorption from the rat small intestine. Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G711-9.