THE PALEO DIET INSIDERCALCIUM AND OSTEOPOROSIS

THE

LOREN CORDAIN, PH.D.

Vol. 4, Issue 7

PALEO ON A BUDGET

FORMS AND FUNCTIONS OF

VITAMIN K

PALEO PORTIONS

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studies (such as the four-year study published by Dr. Bischoff-Ferrari and colleagues, in the June edition of American Journal of Clinical Nutrition)1 showing calcium has a positive effect on fracture risk, longer-term studies, such as the three Harvard studies (study one followed 77,761 women for 12 years, study two followed 43.063 men also for twelve years, and study three followed 77,337 women for 18 years), haven’t shown an association between calcium intake and fracture incidence2-4 , and a recent review (published in August 2008), by Dr. Reid of the University of Auckla nd, New Zealand, concludes:5

“...the present findings suggest that reliance in high-calcium intakes to reduce the risk of hip fracture in older women is not appropriate.”

This adds further support to the notion that osteoporosis is a multi-factorial disease, and hence should be given a multi-factorial solution. Thus, a therapeutic or preventative approach should be to address the key factors underlying the disease, and that was the main goal of our original article. Our non-pharmacological, general recommendations to prevent the risk of fractures are:

1. Maintain plasma levels of 250HD3 above 30 ng/ml,6 either sun exposure, fish consumption, or supplementation;

2. Engage in a supervised exercise program (which includes weight-bearing exercise);7

3. Adopt a Paleo-style diet:

-Providing all the micronutrients8-11 (including calcium, which can be obtained from green, leafy vegetables, such as broccoli and kale). It

CALCIUM AND OSTEOPOROSISPedro Bastos, MA MS Ph.D.

Dear Paleo Diet,

In a recent issue of the Paleo Diet Update, you stated “calcium intake doesn’t decrease the risk for fractures”. This was from a Bischoff- Ferrari etal. paper that was based on a meta-analysis involving a quarter of a million people and was published in the American Journal of Clinical Nutrition on December 7, 2007. In June 2008, the authors published another paper in the same journal dramatically changing their opinion and concluding that calcium supplementation may reduce the risk of bone fracture by 72%. I take PDU information and suggestions seriously. Please clarify.

Respectfully,

Charles Selwitz

Dear Charles,

We appreciate your letter and congratulate you for keeping up with the current scientific literature on nutrition.

Regarding our statement “Calcium doesn’t reduce the risk of fractures”, maybe we should have stated that calcium alone may not prevent the risk of fractures. Our main goal was to show readers that osteoporosis results from a discordance between our Paleolithic genome and the nutritional, cultural, and activity patterns in contemporary Western populations, and cannot be solved by simply increasing calcium intake.

Moreover, although there are short and median-term

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should be mentioned that broccoli and kale, when compared to dairy foods, have a more balanced calcium/magnesium ratio and provide much higher amounts of Vitamin K (recent research indicates that up to 1,000 mcg of Vitamin K may be necessary to fully activate Osteocalcin,12 which is essential to get calcium into the bone instead of soft tissues.)

-With enough fruits and vegetable to become net base yielding (a net acid yielding diet can cause calcium13 and magnesium losses14 ). It is important to mention that broccoli and kale are net base yielding, and milk, yogurt and cheese are net acid yielding15

-With sufficient protein (it increases intestinal calcium absorption16, 17 and has an anabolic effect on bone,16 particularly in the context of a net base yielding diet18)

-Providing a high intake of omega 3 fatty acids (a diet with high w6/w3 ratio can cause bone loss19, 20 and multiple studies have suggested that omega 3 fatty acids may have a preventative and therapeutic effect on osteoporosis)21 -28

-Which has a low glycemic load/insulintropic effect (high blood insulin levels cause calcium loss).29 As already mentioned in previous editions of the Paleo Diet newsletter, milk and yogurt elevate plasma levels of insulin as much as white bread, making vegetables (again) a safer source of calcium30-34)

If you currently have osteoporosis, these guidelines should be followed under the supervision of your physician.

For sources see References: Section I

PALEO FAST FOOD? Nell Stephenson, BS USC EXSC

Yes, you read it correctly, and no, I’m not talking about the local burger joint! It is quite possible - easy, actually - to find ready-made foods that fit right into a Paleo nutritional plan in order to keep you on track while on the road or simply on the go.

Following are some suggestions of what you’re likely to find in places, ranging from the local supermarket to convenience stores, that are bound to keep you honest! Keep in mind that if you’re on the road in the middle of nowhere, the “pickin’s” may be slim, and quite possibly NOT organic. However, you’re still way ahead of the game than if you’d defaulted to a double cheeseburger and fries!

Grocery Stores:

*Find sliced turkey (read the package to see if you can find one without nitrates/nitrites and other offensive additives), a bag of pre-washed spinach, a small avocado and an orange, and then you’ll have a basic salad.

*A small bag of almonds goes great with an apple!

*Try a pre-cut veg with some canned tuna (while not the epitome of an ideal protein, it’s quick, fast and clean; hopefully, you can give it a quick rinse), a small container of tomato salsa and some berries to finish.

*Some stores may offer a salad bar. If so, load up on the fresh veggies, hard-boiled egg whites, sliced turkey, a sprinkling of raw nuts and a squeeze of lime. Stay clear of the cheese, croutons and creamy-dressings.

Convenience Stores:

*In a tight spot, I’ve managed to make a meal from items I literally found at a 7-11! They generally seem to stock hard-boiled eggs and fresh fruit, such as apples and oranges, as well as nuts. I’ve even found individual packages of sliced chicken and turkey (again-just be sure to read the label). Don’t forget your bottled water or perhaps an herbal tea. Another option is to buy a sandwich and discard that white, nutritionally lacking bun.

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Fast Food “Restaurants”:

*More places are at least trying to offer healthier fare than the typical burger and milkshake. McDonald’s now offers a few types of chicken salad (go with the grilled, not the “crispy” option) that if eaten without the dressing and croutons, will fit right into Paleo, for example.

*If you’re stuck at a place like your typical Denny’s, scour the menu for any hint of veg and lean protein being served. If you see a spinach salad, don’t be shy about asking the chef for a side of steamed spinach, to name one option. Ask for some sliced avocado or the olive oil cruet, and you’ve got your meal’s fat needs taken care of as well. If you’re polite while making your “creative” adjustments to your order, chances are that the server will be happy to accommodate.

You can always pack your own:

*Of course, you can’t be expected to pack several days worth of fresh meat and produce if you’re traveling by plane, car, etc., for several days on end. You can, however, keep a few essentials in your briefcase or suitcase. Keep a bag of raw almonds or walnuts with you. Don’t leave home without your bottle of water. You can also bring a few pieces of fruit that travel well, like apples, pears, or oranges; anything that’s not too delicate!

Finally, don’t be afraid to think outside the box and eat foods that you might classify as being appropriate only for breakfast and so on. As I’ve said before, what’s wrong with broccoli at breakfast?

Happy eating!

GLUTEN, DAIRY AND AUTO-IMMUNE DISEASESPedro Bastos, MA MS Ph.D.

Gluten is a water-soluble protein found in wheat, barley, rye and oats.1 It is composed of an insoluble fraction called glutenin and alcohol-soluble proteins (prolamines) called gliadin in wheat, hordein in barley, secalin in rye and avenin in oats.1 It is believed that the gliadin proteins constitute the fraction in gluten responsible for celiac disease (CD).1 CD is an autoimmune disease in which immune cells (T-lymphocytes) mount an attack on the small bowel mucosa1, causing atrophy of the lining (villi) of the mucosa, where the absorption of nutrients occurs. This has profound effects throughout the body, and if left untreated, is life threatening1. People with CD need to follow a lifelong gluten-free diet.2 In the last 40 years, science has revealed that gluten may also be involved in the development of other auto-immune diseases, such as auto-immune thyroid diseases,3-7

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Sjögren’s syndrome,7-11 rheumatoid arthritis,12-14 IgA nephropathy,15 multiple sclerosis,15-17 psoriasis18,19 and type 1 diabetes (T1D). Regarding T1D, it is known that this disease progresses more rapidly in rats when gluten is incorporated into their diet early in life.20,21 In addition, Schmid and colleagues found that:

“Diabetes onset was delayed and diabetes incidence was significantly reduced in female mice that received the wheat and barley protein-free diet throughout life”.22

In humans, exposure to gluten before three months of age increases the risk for T1D.23 Likewise, a gluten-free diet in subjects with a high risk for T1D led to significant improvements in their insulin response during a glucose tolerance test.24

There is a very interesting report in the medical literature about an adolescent who had abnormal blood glucose and insulin levels. The adolescent tested positive for islet cell autoantibodies (a marker of T1D development) and celiac disease (diagnosed through small bowel biopsy). After following a gluten-free diet for six months, the adolescent became islet cell autoantibody negative and presented normal glycemia and insulinemia.25

Similarly to what happens with gluten, cow’s milk is also implicated in a number of auto-immune diseases, such as type 1 diabetes,26-33 rheumatoid arthritis,13 Crohn’s disease,34 multiple sclerosis,35-41 Sjögren’s syndrome42 and even celiac disease.43

Based on this evidence, it appears that people who have an elevated risk for auto-immune diseases or already have such diseases would benefit from a gluten and dairy free diet, which is one of the characteristics of The Paleo Diet.

For sources see References: Section II

PALEO ON A BUDGETNell Stephenson, BS USC EXSC

Does it seem like the only way you’re able to eat healthy is by spending too much at a health food store right after you get your paycheck? You may eat like the king or queen of the “organic” jungle for a week, but then find yourself resorting to boxed and canned things that have been in your pantry for who knows how long until your next paycheck!

No, no, no! It doesn’t have to be that way. In my personal opinion, food shouldn’t be where you have to cut corners and if you plan properly, you can eat healthily all the time.

For one thing, where it makes sense, you might want to buy in bulk. Things such as raw nuts, dried herbs and spices or tea are often much less expensive when you buy out of the bins instead of paying for the attractive packaging. A nice bonus to that is you’re being even greener!

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You can also use this “bulk” mentality when buying fruits, veggies and meat if you freeze them! You might come across some lovely peaches at the farmer’s market at a great price, but think to yourself, “What would I do with a dozen peaches that are ripe, NOW?” Eat one, then wash the rest, slice them and freeze them. Easy! Do this with many types of fruit, and they’re ready to use for a homemade smoothie or a healthy dessert.

The same goes for chicken, fish and other meat. Separate them into individual portions before you freeze so defrosting is less of a hassle. You might even want to throw in a quick marinade, and let it sit in the fridge for a day before you freeze it so you’re one step closer to a flavorful dish when you’re ready to serve it!

You don’t HAVE to buy ALL organic ALL the time. It would be wonderful if all our produce was guaranteed to be completely free of pesticides and chemicals, but unfortunately it is not. Buy organic if you can, but if the foods are simply too pricey, don’t make that a reason to skip the vegetables and fruit. Do some research as to which foods you think are the most important to have from an organic source and stick with those. Personally, it’s a priority for me to be sure all the meat is organic, as well as soft fruits like strawberries.

Pack, pack, pack your lunch - and your spouse’s - and your kid’s! While it might seem like you’re forking out

a larger than normal chunk of change up front, you’ll more than compensate for it when you compare how much you would have spent if you’d eaten out for each meal. Plus, you know exactly what you’re eating!

FORMS AND FUNCTIONS OF VITAMIN KPedro Bastos, MA MS Ph.D.

There are two different forms of vitamin K: Vitamin K1, or phylloquinone, is found in green plants such as green, leafy vegetables. Vitamin K2, more properly designated: menaquinones (MK), is bacterially synthesized forms of Vitamin K (especially anaerobic bacteria that is present in the lower bowel).

The main function of Vitamin K is to carboxylate or activate a class of proteins called Gla-proteins. Phylloquinone preferably carboxylates or activates clotting factors in the liver, and menaquinones preferably carboxylate or activate other Gla-proteins

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such as matrix-Gla protein (which prevents calcification of soft tissues such as arteries) and osteocalcin (which is responsible for depositing calcium in the bones where it belongs).

We know that some Vitamin K1 gets converted to menaquinones, although this conversion appears to be small. Hence, both K1 and K2 appear to be essential for overall good health.

Moreover, the current evidence indicates that the RDA for Vitamin K1 (which was based on a single function - coagulation) seems to be insufficient. In one study, for instance, it was found that the amount of phylloquinone necessary to fully carboxylate osteocalcin was 1000 mcg1, whereas the RDA is only 120 mcg for men and 90 mcg for women. To get such an amount of vitamin K1, eat vegetables as your main source of carbohydrates, especially green, leafy vegetables.

Many nutrition writers recommend cheese and fermented soy (natto) as food sources of menaquinones. While it is true that cheeses contain a significant amount of MKs (~50-70 mcg/100 g of MK-8 and MK-9), as does natto (~100 mcg /100 g of MK 7), these foods were not part of the ancestral human diet and may have adverse effects. For instance, milk, cheese and yogurt are associated with a big list of health hazards ranging from allergy2-7 to auto-immune diseases,8-17 acne,18-20 some types of cancer,21-29 and cardiovascular disease.30-45 We are now in the process of collecting scientific references to publish a review

paper on dairy in the future. We also recommend against consuming legumes for similar reasons.46

Liver and to a lesser extent meat also contain MKs and, as Dr. Cordain has explained on the website, organ meats were favoured parts of the animal so presumably this was one way our hunter-gatherer ancestors would have gotten their MKs. And, let’s not forget menaquinones from gut bacteria. Unfortunately, today that may not be as reliable a source for some since we now live in a world with the generalized use of antibiotics, which may destroy gut flora.

Therefore, it could be useful to include organic organ meats (such as liver) in your diet, to maintain a healthy gut bacteria flora by supplementing with a broad spectrum probiotic supplement when an antibiotic is needed, to eat enough soluble fibre found in vegetables and certain fruits (such as apples) and prebiotic containing vegetables (such as onions and garlic).

For sources see References: Section III

PALEO PORTIONSNell Stephenson, BS USC EXSC

Are you happily eating your meals of lean meats, fresh veg and raw nuts, but feeling a bit tentative about how much of each you actually need to be consuming?

Because there is SO much variability from person to person (such as gender, activity level, body size, and body composition), it would be quite tricky to give a blanket statement regarding how much of each

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macronutrient each individual should eat on a daily basis.

There’s a lot to be gained from at least becoming familiar with what a “portion” looks like, but you needn’t feel that it is necessary to turn your diet into a lab experiment by weighing and measuring every single morsel.

For most people, eating the Paleo Diet makes counting calories and measuring portions much less important. Your body learns to self-regulate, and you can simply eat until you are no longer hungry. Do you have some lean protein, some unprocessed carbohydrate and some healthy fat on your plate? If so, then you’re all set!

One of my favorite things about The Paleo Diet is that if you follow it correctly, keeping this balanced approach in mind, you’ll finish each meal with a satisfied (but not stuffed) feeling and constant high energy levels throughout the day.

If you are more of a “numbers” person (as I am!) and

you’d like to be a bit more technical, then buy a food scale, some measuring cups and spoons and take advantage of the many food caloric composition websites and books that are available. One that I use quite a bit is: http://www.nal.usda.gov/fnic/foodcomp/search/. This is the USDA’s Nutrient Data Laboratory. You simply type in the food, hit search, choose which variety of the food you’re about to eat, enter the weight and there you go!

Ultimately, it all comes back to the balance of healthy food eaten regularly throughout the day. Follow this approach and you’ll easily find yourself able to determine just how much is the right amount for you!

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PRIMAL IN THE KITCHEN

ROASTED TURKEY BREAST

4 Tb. cold pressed olive oil 1 Tb. chopped romsemary 1 Tb. chopped sage 1 garlic clove, crushed 1 bone-in, skin-on turkey breast, 2-3 lbs

Preheat oven to 325 degrees. Combine oil with rosemary, sage, and garlic. Rub into turkey flesh, both under and on the skin. Place turkey breast in a roasting pan and cover with foil. Cook for one hour. Remove from oven and let rest for five minutes before carving.

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

SUNCHOKE SAUTÉ

2 Tb. extra virgin olive oil 2 garlic cloves, diced 1 Tb. minced fresh basil 1 t. dried tarragon 8 oz. sunchokes peeled and cut into 1/2 inch slices (*also known as Jerusalem Artichokes) 1 t. freshly ground black pepper 4 fresh parsley sprigs

Heat oil in a cast iron skillet over medium heat. Add garlic, oregano, basil, and tarragon and stir for one minute. Add sunchokes and contine to stir for eight to ten minutes, or until tender. Remove from heat and sprinkle with pepper. Garnish with sprigs of parsley.

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

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Contributing writers from The Paleo Diet Team:

Pedro Bastos MA MS Ph.D. candidate in Medical Sciences at Lund University, Sweden; International College of Human Nutrition and Functional Medicine

Nell Stephenson, BS USC EXSC, ACSM H/FI, Paleo Nutritional Counselor, co-author of The Paleo Diet Cookbook, author of Paleoista, Gain Energy, Get Lean and Feel Fabulous

with the Diet You Were Born to Eat. Paleoista

REFERENCES: SECTION I1. Bischoff-Ferrari HA, Rees JR, Grau MV, Barry E, Gui J, Baron JA. Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. Am J Clin Nutr. 2008 Jun;87(6):1945-51.

2. Owusu W, Willett WC, Feskanich D, Ascherio A, Spiegelman D, Colditz GA. Calcium intake and the incidence of forearm and hip fractures among men. J Nutr 1997; 127:1782-7

3. Feskanich D, Willett W et al. Milk, Dietary Calcium, and Bone Fractures in Women: A 12-Year Prospective Study. Am J Public Health. 1997 Jun;87(6):992-7.

4. Feskanich D, Willett WC, Colditz GA. Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Am J Clin Nutr. 2003 Feb;77(2):504-11.

5. Reid IR, Bolland MJ, Grey A. Effect of calcium supplementation on hip fractures. Osteoporos Int. 2008 Aug;19(8):1119-23

6. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S

7. Borer KT. Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors. Sports Med. 2005;35(9):779-830.

8. Sojka JE, Weaver CM. Magnesium supplementation and osteoporosis. Nutr Rev. 1995 Mar;53(3):71-4

9. Abrams SA, Griffin IJ. Microminerals and Bone Health. In Holick MF, Dawson-Hughes B. Nutrition And Bone Health.

Humana Press, 2004, pp 377-387

10. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Jun 26;166(12):1256-61

11. Pols H, Yazdanpanah N, van Meurs J. Homocysteine, the vitamin B complex family and bone. 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 151-157

12. Binkley NC. A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am J Clin Nutr. 2002 Nov;76(5):1055-60.

13. Jajoo R, Song L, Rasmussen H, Harris SS, Dawson-Hughes B. Dietary Acid-base balance, bone resorption, and calcium excretion. J Am Coll Nutr. 2006 Jun;25(3):224-30.

14. Rylander R, Remer T, Berkemeyer S, Vormann J. Acid-base status affects renal magnesium losses in healthy, elderly persons. J Nutr. 2006 Sep;136(9):2374-7.

15. Frassetto L.A. et al. A practical approach to the balance between acid production and renal acid excretion in humans. J Nephrol. 2006 Mar-Apr;19 Suppl 9:S33-40

16. 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

17. 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

18. 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.

19. Weiss, l.A.; Barrett-Connor, E.; Von Muhlen, D. Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the

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Rancho Bernardo Study. Am J Clin Nutr; 2005;81(4):934-8.

20. Watkins, B.A.; Li, Y.; Seifert, M.F. Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats. J Nutr Biochem 2006; 17(4):282-9, 2006.

21. Watkins BA, Li Y, Lippman HE et al. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):387-98.

22. Sun D, Krishnan A, Zaman K et al. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res. 2003 Jul;18(7):1206-16.

23. Corwin RL. Effects of dietary fats on bone health in advanced age. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):379-86.

24. Reinwald S, Li Y, Moriguchi T et al. Repletion with (n-3) fatty acids reverses bone structural deficits in (n-3)-deficient rats. J Nutr. 2004 Feb;134(2):388-94.

25. Bhattacharya A, Rahman M, Banu J et al. Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids. J Am Coll Nutr. 2005 Jun;24(3):200-9.

26. Kruger MC, Schollum LM. Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability? Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):327-34.

27. Hasturk H, Kantarci A, Ohira T et al. RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J. 2006 Feb;20(2):401-3.

28. Shen CL, Yeh JK, Rasty J et al. Protective effect of dietary long-chain n-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats. Br J Nutr. 2006 Mar;95(3):462-8.

29. 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.

30. Gannon MC, Nuttall FQ, Krezowski PA, Billington CJ, Parker S. The serum insulin and plasma glucose responses to milk and fruit products in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1986 Nov;29(11):784-91.

31. Holt SH et al. An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods. Am J Clin Nutr. 1997 Nov;66(5):1264-76

32. Ostman EM, et al. Inconsistency between glycemic and insulinemic responses to regular and fermented milk products. Am J Clin Nutr 2001;74:96 –100.

33. Liljeberg Elmstahl H & Bjorck I. Milk as a supplement to mixed meals may elevate postprandial insulinaemia. Eur J Clin Nutr 2001; 55:994–999.

34. Hoyt G, Hickey MS, Cordain L. Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk. Br J Nutr. 2005 Feb;93(2):175-7

REFERENCES: SECTION II1. McGough N, Cummings JH. Coeliac disease: a diverse clinical syndrome caused by intolerance of wheat, barley and rye. Proc Nutr Soc. 2005 Nov;64(4):434-50

2. Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007 Jan;117(1):41-9

3. Toumi D, Mankai A, Belhadj R, Ghedira-Besbes L, Jeddi M, Ghedira I. Thyroid-related autoantibodies in Tunisian patients with coeliac disease. Clin Chem Lab Med. 2008;46(3):350-3.

4. Spadaccino AC, Basso D, Chiarelli S, Albergoni MP, D’Odorico A, Plebani M, Pedini B, Lazzarotto F, Betterle C. Celiac disease in North Italian patients with autoimmune thyroid diseases. Autoimmunity. 2008 Feb;41(1):116-21.

5. Iuorio R, Mercuri V, Barbarulo F, D’Amico T, Mecca N, Bassotti G, Pietrobono D, Gargiulo P, Picarelli A. Prevalence of celiac disease in patients with autoimmune thyroiditis. Minerva Endocrinol. 2007 Dec;32(4):239-43.

6. Ch’ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007 Oct;5(3):184-92.

7. Maclaurin BP, Matthews N, Kilpatrick JA. Coeliac disease associated with auto-immune thyroiditis, Sjogren’s syndrome, and a lymphocytotoxic serum factor. Aust N Z J Med. 1972 Nov;2(4):405-11. No abstract available.

8. Pittman Fe, Holub Da. Sjoegren’s Syndrome and Adult Celiac Disease. Gastroenterology. 1965 Jun;48:869-76.

9. Teppo AM, Maury CP. Antibodies to gliadin, gluten and reticulin glycoprotein in rheumatic diseases:elevated levels in Sjögren’s syndrome. Clin Exp Immunol. 1984 Jul;57(1):73-8.

10. Szodoray P, Barta Z, Lakos G, Szakáll S, Zeher M. Coeliac disease in Sjögren’s syndrome--a study of 111 Hungarian patients. Rheumatol Int. 2004 Sep;24(5):278-82.

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11. Lidén M, Kristjánsson G, Valtýsdóttir S, Hällgren R. Gluten sensitivity in patients with primary Sjögren’s syndrome. Scand J Gastroenterol. 2007 Aug;42(8):962-7.

12. Paimela L, Kurki P, Leirisalo-Repo M, Piirainen H. Gliadin immune reactivity in patients with rheumatoid arthritis. Clin Exp Rheumatol. 1995 Sep-Oct;13(5):603-7.

13. 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.

14. Hafstrom I, Ringertz B, Spangberg A, von Zweigbergk L, Brannemark S, Nylander I, Ronnelid J, Laasonen L, Klareskog L: A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford) 2001, 40:1175-1179.

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

16. Reichelt KL, Jensen D. IgA antibodies against gliadin and gluten in multiple sclerosis. Acta Neurol Scand. 2004 Oct;110(4):239-41

17. Pengiran Tengah CD, Lock RJ, Unsworth DJ, Wills AJ. Multiple sclerosis and occult gluten sensitivity. Neurology. 2004 Jun 22;62(12):2326-7.

18. Michaëlsson G, Gerdén B, Ottosson M, Parra A, Sjöberg O, Hjelmquist G, Lööf L. Patients with psoriasis often have increased serum levels of IgA antibodies to gliadin. Br J Dermatol. 1993 Dec;129(6):667-73.

19. Michaëlsson G, Gerdén B, Hagforsen E, Nilsson B, Pihl-Lundin I, Kraaz W, Hjelmquist G, Lööf L. Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet. Br J Dermatol. 2000 Jan;142(1):44-51.

20. Hoorfar J, Buschard K, Dagnaes-Hansen F. Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr. 1993 Mar;69(2):597-607.

21. Scott FW. Food-induced type 1 diabetes in the BB rat. Diabetes Metab Rev 1996;12:341–59.

22. Schmid S, Koczwara K, Schwinghammer S, Lampasona V, Ziegler AG, Bonifacio E. Delayed exposure to wheat and barley proteins reduces diabetes incidence in non-obese diabetic mice. Clin Immunol. 2004 Apr;111(1):108-18.

23. Ziegler A-G, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 2003;290:1721–8.

24. Pastore M-R, Bazzigaluppi E, Belloni C, Arcovio C, Bonifacio E, Bosi E. Six months of gluten-free diet do not influence antibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clin Endocrinol Metab 2003;88:162–5.

25 Banin P, Perretta R, Ravaioli E, De Sanctis V. Regression of autoimmunity and abnormal glucose homeostasis in an adolescent boy with silent coeliac disease. Acta Paediatr 2002;91:1141–3.

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30. Akerblom HK, Vaarala O, Hyöty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet. 2002 May 30;115(1):18-29.

31. Virtanen, S.M.; Knip, M. Nutritional risk predictors of beta-cell autoimmunity and type 1 diabetes at a young age. Am J Clin Nutr; 78:1053-67, 2003.

32. Knip M, Akerblom HK. Early nutrition and later diabetes risk. Adv Exp Med Biol. 2005;569:142-50.

33. Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36.

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40. Guggenmos J. Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis. The Journal of Immunology, 2004, 172: 661–668

41. Winer S et al. T cells of multiple sclerosis patients target a common environmental peptide that causes encephalitis in mice. J Immunol 2001;166: 4751-56

42. Lidén M, Kristjánsson G, Valtysdottir S, Venge P, Hällgren R. Cow’s milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren’s syndrome. Clin Exp Allergy. 2008 Jun;38(6):929-35.

43. Kristjansson G, Venge P, Hallgren R. Mucosal reactivity to cow’s milk protein in coeliac disease. Clin Exp Immunol 2007;147:449–55

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Vol. 4 ◆ Issue 7

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43. Tailford KA, Berry CL, Thomas AC, Campbell JH. A casein variant in cow’s milk is atherogenic. Atherosclerosis. 2003 Sep;170(1):13-9

44. Bell SJ, Grochoski GT, Clarke AJ. Health implications of milk containing beta casein with the A2 genetic variant. Crit Rev Food Sci Nutr. 2006;46(1):93-100

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46. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Brit J Nutr 2000, 83:207-217.