Type 2 Diabetes and Endotoxemia

by Maelán Fontes

Currently there’s an epidemic of type 2 diabetes (T2D) worldwide, especially in Westernized countries. T2D is characterized by persistent elevated glucose levels due to disrupted insulin action or an alteration in pancreatic insulin production¹.

It was estimated that 171 million people were suffering from T2D in 2001, with a total overall population prevalence of 6%. More alarming is the fact that in Caucasian adolescents 4% suffer from T2D and 25% are glucose intolerant¹. However, T2D prevalence in hunter-gatherer societies is low^2-6, and even nonexistent in the island of Kitava in Trobiand Islands in Papua New Guinea³.

Genetics does not seem to explain the difference, because when these populations are Westernized they suffer even more from diseases of civilization such as T2D, obesity, myocardial infarction and stroke among others^7-10 than original Western populations. Furthermore, there’s evidence showing that hunter-gatherer populations can reverse T2D when they are resettled in their ancient habitat⁸, a fact that has been demonstrated in two recent clinical trials conducted on Western populations^{11, 12}.

Insulin resistance seems to be one of the factors involved in T2D which is caused, by low-grade chronic inflammation^13-15 among other factors. Interestingly, low-grade chronic inflammation is a hallmark^16-19 in T2D patients.

Considering these factors, it seems plausible that the nutrition introduced with the agricultural revolution 10,000 years ago played an important role in the current diabetes epidemic in Westernized populations. Western foods are overload with antinutrients, namely lectins, saponins and gliadin, which may explain the great disparity between paleolithic and modern Western food when it comes to metabolic syndrome (a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes). There is evidence showing that antinutrients act as endocrine disrupting substances, promoting metabolic syndrome²⁰. On the other hand, antinutrients may elicit their negative health effects through increased intestinal permeability²¹. However, scant evidence exists regarding the role of antinutrients in the aetiology of Western diseases.

Gliadin and increased intestinal permeability

One of the most studied foods in the recent years is wheat, which contains a protein called gliadin, and is part of the gluten protein family²². Gliadin increases gut permeability by means of Zonulin production (a protein that regulates in tight junctions between cells in the wall of the digestive tract) in the gut enterocytes (epithelial cells found in the small intestines and colon). Zonulin binds the CXCR3 chemokine receptor leading to intracellular signalling cascades, mediated by protein kinase C (PKC), which ultimately causes disruption of the tight junction proteins which maintain the gut barrier function, and lead to increased gut permeability^{23, 24}.

In addition, when intestinal permeability is increased, gliadin - which is resistant to heat and digestive enzymes - is able to interact with gut associated lymphoid tissue (GALT) stimulating the innate immune system, leading to low-grade chronic inflammation^{22, 24}. Several studies have demonstrated that gliadin induces the production of pro-inflammatory cytokines (a small protein released by cells that has a specific effect on the interactions between cells, communications between cells or the behavior of cells), independent of one’s genetic predisposition to celiac disease – which is virtually everyone^{23, 25, 26}.

Lectins and increased gut permeability

Lectins are a family of glycoproteins (a complex protein containing a carbohydrate combined with a simple protein) found in the plant kingdom, including grains, legumes and solanacous plants (tomatoes, potatoes, eggplants and peppers)^{21, 27}. Lectins also have the ability to bind sugar containing molecules. They were first studied for their ability to agglutinate (cause to adhere) red blood cells by binding to their cell membranes. Many lectins present in other foods are harmless, but some lectins found in grains, legumes and solanaceous plants have been shown to be harmful to human physiology²⁸. Lectins are resistant to heat (unless cooked by pressure cooking)²⁹ and digestive enzymes³⁸, and therefore arrive intact when they reach the intestinal epithelium, passing through the intestinal barrier into peripheral circulation. Lectins are able to bind peripheral tissues, producing many deleterious health effects²¹. Furthermore, lectins disrupt intestinal barrier and immunological function when they bind surface glycans (a carbohydrate polymer containing simple sugars) on gut epithelial cells, causing cellular disruption and increasing gut permeability. Lectins also facilitate the growth of certain bacteria strains, stimulate T-cell proliferation, increase intercellular adhesion molecules (ICAM), stimulate production of pro-inflammatory cytokines (IL-1, TNF-alpha, etc.), and amplify HLA class II molecules expression, among other effects²¹.

Saponins and increased gut permeability

Saponins are glycoalkaloids (a family of poisons commonly found in the plant species Solanum dulcamara - nightshades) produced by plants, technically known as steroid glycosides or triterpenoids, are formed by a sugar compound (glucuronic acid, glucose or galactose, among others) and aglycone (non-sugar molecule) portion^30-32. The aglycone portion binds the cholesterol molecule on gut cell membranes. When certain amounts of saponins bind cell membrane cholesterol molecules of the intestinal epithelial cells at a 1:1 ratio, the sugar portion of the saponins bind together, resulting in a complex molecule consisting of cholesterol and saponins. This new molecule disrupts the gut barrier and increases intestinal permeability. This has been shown in humans who consume a diet rich in alpha-solanine and alpha-chaconine - two of the saponins found in potatoes³¹.

On the other hand, saponins have adjuvant-like activity, which means that they are able to affect the immune system leading to pro-inflammatory cytokine production^{33, 34}, ultimately inducing insulin resistance.

Intestinal permeability and endotoxemia

Intestinal epithelia act as a physical barrier between the outside and the inside of the body, meaning that the intestinal lumen is technically outside the organism. When the intestinal barrier is disrupted, it allows increased passage of gut luminal antigens derived from food, bacteria and viruses into the organism²¹. In case of bacteria derived antigens, lipopolysaccharide (LPS) is the most commonly studied and utilized antigen to induce acute immune stimulation, this is known as endotoxemia (the presence of endotoxins - a toxin that forms an integral part of the cell wall of certain bacteria - in the blood which may cause hemorrhages, necrosis of the kidneys, and shock)³⁵. In addition, endotoxemia is associated with low-grade chronic inflammation, insulin resistance and T2D^{13, 18, 36}. In a recent human study it was demonstrated that LPS induced low-grade chronic inflammation in adipose tissue in T2D³⁶ humans.

LPS-TLR4 interaction and low-grade chronic inflammation

The innate immune system is localised in the GALT. When luminal antigens pass through the intestinal barrier, they are phagocited (consumed) by dendritic cells or macrophagues, key components of the innate immune system. Dendritic cells or macrophagues recognize antigens through a family of receptors known as Toll-like receptors (TLR). The best studied and known antigens from gram negative bacteria are LPS which interact with toll-like receptors-4 (TLR4), inducing the production of pro-inflammatory cytokines and ultimately insulin resistance and T2D³⁵. Interestingly, a recently published study demonstrated increased TLR4 expression in T2D humans, contributing to an increased inflammatory state³⁷.

In summary, antinutrients introduced with the agricultural revolution 10,000 years ago may be one of the causal factors in the epidemic of obesity, (as well as T2D) in Western countries. Lectins, saponins and gliadin increase intestinal permeability and allow increased passage of gut bacteria from intestinal lumen to peripheral circulation. LPS - an antigen found in gram-negative bacteria cell membranes - interacts with TLR-4, leading to inflammatory cytokine production and low-grade chronic inflammation, which is at the root of insulin resistance. Insulin resistance is recognised to induce the metabolic syndrome, including T2D. Endotoxemia-induced insulin resistance in T2D patients may be exacerbated, in part, by antinutrients.

References:

1. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005;365(9467):1333-46.
2. Joffe BI, Jackson WP, Thomas ME, Toyer MG, Keller P, Pimstone BL. Metabolic responses to oral glucose in the Kalahari Bushmen. British medical journal 1971;4(5781):206-8.
3. Lindeberg S, Eliasson M, Lindahl B, Ahren B. Low serum insulin in traditional Pacific Islanders--the Kitava Study. Metabolism: clinical and experimental 1999;48(10):1216-9.
4. Merimee TJ, Rimoin DL, Cavalli-Sforza LL. Metabolic studies in the African pygmy. The Journal of clinical investigation 1972;51(2):395-401.
5. Spielman RS, Fajans SS, Neel JV, Pek S, Floyd JC, Oliver WJ. Glucose tolerance in two unacculturated Indian tribes of Brazil. Diabetologia 1982;23(2):90-3.
6. Zimmet P. Epidemiology of diabetes and its macrovascular manifestations in Pacific populations: the medical effects of social progress. Diabetes care 1979;2(2):144-53.
7. Cruickshank JK, Mbanya JC, Wilks R, Balkau B, McFarlane-Anderson N, Forrester T. Sick genes, sick individuals or sick populations with chronic disease? The emergence of diabetes and high blood pressure in African-origin populations. International journal of epidemiology 2001;30(1):111-7.
8. O'Dea K. Marked improvement in carbohydrate and lipid metabolism in diabetic Australian aborigines after temporary reversion to traditional lifestyle. Diabetes 1984;33(6):596-603.
9. O'Dea K, Spargo RM, Akerman K. The effect of transition from traditional to urban life-style on the insulin secretory response in Australian Aborigines. Diabetes care 1980;3(1):31-7.
10. O'Dea K, Spargo RM, Nestel PJ. Impact of Westernization on carbohydrate and lipid metabolism in Australian Aborigines. Diabetologia 1982;22(3):148-53.
11. Jonsson T, Granfeldt Y, Ahren B, et al. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovascular diabetology 2009;8:35.
12. Lindeberg S, Jonsson T, Granfeldt Y, et al. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia 2007;50(9):1795-807.
13. Fernandez-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Trends in endocrinology and metabolism: TEM 2008;19(1):10-6.
14. Reyna SM, Ghosh S, Tantiwong P, et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 2008;57(10):2595-602.
15. Song MJ, Kim KH, Yoon JM, Kim JB. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochemical and biophysical research communications 2006;346(3):739-45.
16. Duncan BB, Schmidt MI. The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. Diabetes technology & therapeutics 2006;8(1):7-17.
17. Kimberly MM, Cooper GR, Myers GL. An overview of inflammatory markers in type 2 diabetes from the perspective of the clinical chemist. Diabetes technology & therapeutics 2006;8(1):37-44.
18. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes care 2004;27(3):813-23.
19. Spranger J, Kroke A, Mohlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003;52(3):812-7.
20. Jonsson T, Olsson S, Ahren B, Bog-Hansen TC, Dole A, Lindeberg S. Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance? BMC endocrine disorders 2005;5:10.
21. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. The British journal of nutrition 2000;83(3):207-17.
22. Fasano A. Surprises from celiac disease. Scientific American 2009;301(2):54-61.
23. Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scandinavian journal of gastroenterology 2006;41(4):408-19.
24. Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Annals of the New York Academy of Sciences 2009;1165:195-205.
25. Bernardo D, Garrote JA, Fernandez-Salazar L, Riestra S, Arranz E. Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut 2007;56(6):889-90.
26. Rakhimova M, Esslinger B, Schulze-Krebs A, Hahn EG, Schuppan D, Dieterich W. In vitro differentiation of human monocytes into dendritic cells by peptic-tryptic digest of gliadin is independent of genetic predisposition and the presence of celiac disease. Journal of clinical immunology 2009;29(1):29-37.
27. Kilpatrick DC, Pusztai A, Grant G, Graham C, Ewen SW. Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects. FEBS letters 1985;185(2):299-305.
28. Cordain L. Cereal grains: humanity's double-edged sword. World review of nutrition and dietetics 1999;84:19-73.
29. Grant G, More LJ, McKenzie NH, Pusztai A. The effect of heating on the haemagglutinating activity and nutritional properties of bean (Phaseolus vulgaris) seeds. Journal of the science of food and agriculture 1982;33(12):1324-6.
30. Francis G, Kerem Z, Makkar HP, Becker K. The biological action of saponins in animal systems: a review. The British journal of nutrition 2002;88(6):587-605.
31. Patel B, Schutte R, Sporns P, Doyle J, Jewel L, Fedorak RN. Potato glycoalkaloids adversely affect intestinal permeability and aggravate inflammatory bowel disease. Inflammatory bowel diseases 2002;8(5):340-6.
32. Keukens EA, de Vrije T, van den Boom C, et al. Molecular basis of glycoalkaloid induced membrane disruption. Biochimica et biophysica acta 1995;1240(2):216-28.
33. Oda K, Matsuda H, Murakami T, Katayama S, Ohgitani T, Yoshikawa M. Adjuvant and haemolytic activities of 47 saponins derived from medicinal and food plants. Biological chemistry 2000;381(1):67-74.
34. Pickering RJ, Smith SD, Strugnell RA, Wesselingh SL, Webster DE. Crude saponins improve the immune response to an oral plant-made measles vaccine. Vaccine 2006;24(2):144-50.
35. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57(6):1470-81.
36. Creely SJ, McTernan PG, Kusminski CM, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. American journal of physiology 2007;292(3):E740-7.
37. Dasu MR, Devaraj S, Park S, Jialal I. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes care;33(4):861-8.
38. Pusztai A and Grant G. Assessment of lectin inactivation by heat and digestion. From Methods in Molecular Medicine. Vol 9 Lectin methods and protocols. Edited by J M Rhodes and J D Milton Humana Press Inc. Totowa, NJ.

Paleo Diet Q & A - Sprouted Legumes

Q: Hi, the Paleo Diet makes a lot of sense to me and I very much appreciate the research that's gone into it. However, am I right in thinking that any diet we are adapted to may nevertheless not be an ideal diet? We adapted to a diet that enabled us to be healthy enough to live long enough to reproduce healthy enough offspring.

If I understand correctly, couldn't certain foods could make that basic diet even healthier? For example, I have The Paleo Diet for Atheletes out from the library right now and I see that you believe that the life of an athlete requires departure from a strict paleolithic diet. Couldn't properly treated grains and legumes be beneficial additions to the diet? (i.e. soaked/sprouted to reduce/eliminate anti-nutrients?)

I am waiting to receive The Paleo Diet from the library (I'm on a long waiting list, which is good news I guess!) so maybe you address this issue in the book, in which case, I apologize. But if not, I would appreciate knowing your views on soaking/sprouting grains and legumes, and the reasons behind those views.

Thanks so much,
Zena

A: Dear Zena, first of all - thanks for supporting our work.

Lectins, one of the known antinutrients in cereal grains and legumes¹, have been demonstrated to exert several deleterious effects upon human physiology¹, (especially for those with autoimmune diseases) by increasing intestinal permeability². Their function is to protect the plant against attacks by plant-eating animals by using several toxic substances, such as lectins³. There is a growing body of evidence showing that both the root and the sprout of wheat kernels have significant amounts of wheat germ agglutinin (WGA), one of the most studied lectins. Indeed, WGA originates in the wheat kernel, especially during germination and growth⁴, and the highest concentrations are found in young plant roots, seeds, and sprouts.

Lectins are resistant to digestive enzymes, and are found intact in peripheral circulation, as shown by Wang et al (1998)⁵. Furthermore, they are deposited in the internal organs⁶.

As stated by Pusztai et al⁷, lectins are heat stable, and normal cooking does not completely eliminate these toxic compounds unless they are pressure cooked^8-11. The best way to reduce lectins' adverse health effects is to limit their intake.

In addition, saponins - another type of toxic/antinutritive compound - exist in legume sprouts. Saponins have been shown to affect the gut barrier and by extension immune system function¹². They may also increase the risk of autoimmune diseases in genetically susceptible individuals¹³. Soaking, sprouting or cooking legumes, does not reduce their saponin content^{14, 15}.

In addition, a peptide fraction from gluten proteins called gliadin is found in wheat. Gliadin is resistant to digestive enzyme degradation¹⁶, arrives intact when it comes into contact with intestinal epithelial cells¹⁷, and increases intestinal permeability. Increased intestinal permeability may be at the root of autoimmune diseases such as Celiac Disease and Type 1 Diabetes¹³.

Phytate, the main form of phosphorus storage in many plants (especially bran and seeds) is classified as an antinutrient because is a chelator of iron, magnesium, calcium and zinc¹. Phytate ingestion inhibits the intestinal absorption of those minerals. Phosphorus from phytate is unavailable to humans, as we do not produce the phytase enzyme necessary to break down phytate - unlike ruminants, who do produce phytase, and are able to digest phytate¹⁸. Yeast fermentation in bread reduces phytate content¹⁹. Furthermore, addition of ascorbic acid counteracts the inhibitory effects of phytate upon iron absorption²⁰. Soaking and fermentation reduces the phytate content of grains and legumes as indicated in several studies^{21, 22, 23, 24}.

Having said that, Dr. Cordain in his first book talks about the 85:15 rule, where he explains that 85% of caloric intake from modern paleolithic-like foods is still more healthy than the typical western diet, where more than 70% of caloric intake comes from foods introduced in the human food chain after the agricultural revolution²⁵.

The bottom line is that our metabolism is perfectly adapted to the nutrition that shaped our genome during million of years of evolution. Therefore, any nutrient introduced after the agricultural revolution may not be compatible with our ancient genome. We believe that anyone engaged in athletic activities could do very well on a diet based on 85% paleolithic nutrients, which are preferable to the nutrients found in the typical western diet.

I hope this is helpful.
Maelán Fontes

References:

1. Cordain L. Cereal Grains: Humanity’s Double-Edged Sword. World Rev Nutr Diet. Basel, Karger,
   1999, vol 84, pp 19–73.
2. Cordain L. et al. Modulation of immune function by dietary lectins in rheumatoid arthritis. British
   Journal of Nutrition (2000), 83, 207–217.
3. Chrispeels, M.J. & Raikel, N.V. (1991) Lectins, lectin genes, and their role in plant defense. Plant Cell 3, 1-9.
4. Miller, R., & Bowles, D. (1982). A comparative study of the localization of wheat-germ agglutinin
   and its potential receptors in wheat grains. Biochem. J., 206, 571-576.
5. Wang Q, Yu LG, Campbell BJ, Milton JD, Rhodes, JM. Identification of intact peanut lectin in peripheral
   venous blood. Lancet 1998;352:1831-32.
6. Caron, M. & Steve, A.P. (2000) Lectins and Pathology, Taylor & Francis, London.
7. Pusztai A and Grant G. Assessment of lectin inactivation by heat and digestion. From Methods
   in Molecular Medicine. Vol 9 Lectin methods and protocols. Edited by J M Rhodes and J D Milton Humana
   Press Inc. Totowa, NJ.
8. Grant G, More LJ, McKenzie NH, Pusztai A. The effect of heating on the haemagglutinating activity
   and nutritional properties of bean (Phaseolus vulgaris) seeds. J Sci Food Agric 1982;33: 1324-1326.
9. Boufassa C, Lafont J, Rouanet J M, Besancon P 1986 Thermal inactivation of lectins (PHA)isolated
   from Phaseolus vulgaris. Food Chem 20 295-304.
10. Buera M P, Pilosof A M R, Bartholomai G B 1984 Kinetics of trypsin inhibitory activity loss in
    heated flour from bean Phaseolus vulgaris. J Food Sci 49 124-126.
11. Collins J L, Beaty B F 1980 Heat inactivation of trypsin inhibitor in fresh green soybeans and
    physiological responses of rats fed the beans. J Food Sci 45 542-546.
12. Patel B, Rober S, Sporns P, et al. potato glycoalkaloid adversely affect intestinal permeability
    and aggravate inflammatory bowel disease.
13. Visser J, Rozing J, Sapone A et al. Tight junctions, Intestinal permeability and Autoimmunity.
    Ann. N. Y. Acad. Sci. 1165: 195-205 (2009).
14. Ruiz RG, Price K, Rose M, Rhodes M, Fenwick R. A preliminary study on the effect of germination
    on saponin content and composition of lentils and chickpeas. Z Lebensm Unters Forsch 1996;203:366-369.
15. Ruiz RG, Price KR, Arthur AE, Rose ME, Rhodes MJ, Fenwick RG. Effect of soaking and cooking on
    the saponin content and composition of chickpeas (Cicer arietinum) and lentils (Lens culinaris).
    J Agric Food Chem 1996;44:1526-1530.
16. Shan L, Qiao SW, Arentz-Hansen H, et al. Identification and Analysis of Multivalent Proteolytically
    Resistant Peptides from Gluten: Implications for Celiac Sprue. J Proteome Res. 2005 ; 4(5): 1732–1741.
17. Drago S, Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac
    intestinal mucosa and intestinal cell lines. Scandinavian Journal of Gastroenterology,
    2006; 41:408/419.
18. Klopfenstein, TJ et al. "Animal Diet Modification to Decrease the Potential for Nitrogen and
    Phosphorus Pollution". Council for Agricultural Science and Technology 21.
19. Reinhold JG. Phytate destruction by yeast fermentation in whole wheat meals. J Am Diet Assoc 1975;66:38-41.
20. Hallberg L, Brune M, Rossander L. Iron absorption in man: ascorbic acid and dose-dependent inhibition
    by phytate. Am J Clin Nutr 1989;49:140-4.
21. Chen LH, Pan SH. Decrease of phytates during germination of pea seeds (Pisium Sativa). Nutr Rept Int.
    1977;16: 125-131.
22. Walker KA. Changes in phytic acid and phytase during early development of phaseoleus vulgaris beans.
    Planta 1974;116:91-98
23. Bain, J. M., Murcer, F. V.: Changes in phytic acid and acid-soluble phosphorus in maturing pinto beans.
    J. Sci. Fd. Agric. 20, 82–84 (1966).
24. Jennings, A. C., Morton, R. K.: Changes in nucleic acids and other phosphorus-containing compounds of
    developing wheat grain. Aust. J. Biol Sci. 16, 332–341 (1963b).
25. Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the western diet: health implications
    for the 21st century. Am J Clin Nutr 2005;81:341–54.

Paleo Diet Q & A - 11.25.09

Dear Readers,

We hope you find the daily Q & A from the Paleo Diet community useful and insightful in your efforts to meet your health and nutritional requirements.

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Q: I've read your books The Paleo Diet and The Paleo Diet for Athletes, and I find them very interesting. I am a 22 year old full time athlete from Norway, and my goal is to compete in the World Championship in Cross country skiing in 2011. Last year I got to represent Norway in the U23 WC in France, and now I put all of my energy in taking new steps towards my goals every day!

But.. I have a problem, that doesn't seem to go away. And it frustrates me!

After a lot of stomach trouble as a junior (18-19 years old), I've been focusing a lot on what to eat, and after reading your books, I think I've found the answer.

The doctors told me back then that I had an inflammation in my rectum (about 4 years ago). They gave me some medication and told me that it would go away, and it did. For a while... When it came back it got gradually worse, and I was pretty depressed at the moment. (My athletic performance wasn't very good either.) I became aware of what different foods do to your body, and a long story short, I cut out dairy products, wheat and rye. (I also started taking NDS probiotic.) Now I am mutch better, but not completely well. Sometimes I'm good, and sometimes I have symptoms again. And it wears me out!

Therefore I want to follow the guidelines of the Paleo Diet, given that I probably have a chronic inflammatory condition, and see if I can take out the rat once and for all! I hope you can be so kind to give me answers to a few questions that I have:

• You say in your book that lectins from grains, dairy and legumes may be a "villain" in my situation. When I train a lot, I need to get some protein in step 3 (food system in The Paleo Diet for Athletes). Now I have soy protein powder and pea protein powder. Is there lectins in these products? And do you know of any other products to replace them?
• When I train alot, I need a satisfying amount of carbohydrates. Is it ok to use potatoes and white rice (and starch/syrup)?
• Is corn ok? And corn products (starch and syrup)? I read something about avoiding corn in the book.
• I've cut out normal table salt, and replaced it with Himalaya salt (I'm told it contains more minerals). Should I also cut that out?
• I have been making bread from amaranth, quinoa and other naturally gluten-free flours. Do these products also contain lectins, or other bad sources?
• And at last: Would it be necessary to completely avoid grains, dairy and legumes if I want to get rid of this plague? Or can I sometimes, for example with friends, enjoy a pizza or a beer?

PS: Are there anything else I should be aware of?

A: Thanks for your interest in the Paleo Diet and I wish you well in your quest to compete in the World Cross Country Skiing championship.

Diet can have an impact upon athletic performance, and in my book, The Paleo Diet for Athletes, we show how a 1-2% performance difference can make or break whether or not an athlete places in a race. Gastrointestinal problems certainly can adversely affect performance,and as you have outlined in your case, a number of foods and food groups may promote GI upset. We do not recommend that dairy, grains or legumes be consumed by normals as well as athletes because of the numerous potential adverse health effects that these foods may elicit -- including GI inflammation and distress.

Whole grains and legumes contain not only lectins, but also saponins which adversely affect human gastrointestinal physiology as well as that in animal models. In my book, The Paleo Diet for Athletes, we recommend that in order for you to get sufficient carbohydrates in your diet you replace grains with high glycemic fruits including bananas, raisins, dates, dried fruit, and fresh fruits. Yams and sweet potatoes are also a good source of vegetable high glycemic load carbs. White potatoes can be problematic as they contain high concentrations of saponins which may exacerbate GI tract problems. Of all grains, rice seems to be the least problematic in terms of interacting with the immune system and GI function. Do I recommend it? Try it & see how you feel -- same advice for all dietary suggestions -- listen to your body -- it is the final judge. Corn and corn products also have been shown to adversely affect human GI tract function & you may want to experiment with eliminating these products. Endurance athletes in training may need additional sources of dietary salt to prevent hyponatremia (low blood salt) -- see my book for recommendations. Amaranth and Quinoa may contain high concentrations of saponins which as I pointed out with potatoes have the potential to adversely affect GI tract function by increasing intestinal permeability. These grains are also net acid yielding -- root foods like sweet potatoes or yams are better choices as are bananas and other fresh fruits and fruit juices. Food supplements containing soy or legumes should be avoided as they contain high concentrations of both saponins and lectins, which have been demonstrated in human and animal models to increase intestinal permeability, which concomitantly increases low level gut inflammation.

Yes, go out with your friends and enjoy a pizza and beer occasionally. It will do your spirit well. Life is also about fun and enjoyment. But know that when these foods become staples, your health may suffer. I suggest red wine and smoked salmon rather than beer and pizza. SALUD!!

Dr. Cordain

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Q: I recognize that I feel much better on small amounts of lean meats with lots of veggies and some fruit.......but I become very constipated on this........how can I correct this and stay on the Paleo Diet?

A: It is quite strange to suffer from constipation eating a lot of veggies as they are the biggest fiber source. However, you can help your gut health with some supplements until constipation improves:

• Probiotics: between 6-9 billion bacteria/day during one month, then cut down to 4-5 billion.
• Prebiotics: 4-6 grams a day during one month (if you do not improve with 4 grams increase up to 6 grams). Then cut down to 2 grams a day.
• Coconut oil (a good source of Medium Chain Fatty Acids): a tablespoon per day.
• Drink 1.5 liter of water a day.
  

Answers to Questions Posted by Blog Readers - 11.23.09

Dear Readers,

Thank you for your comments and questions! Our team is working to review your Paleo Diet-related questions and provide you with answers. We read all comments, and we are very interested in hearing your thoughts, learning about your experiences, and understanding what questions you have.

The Paleo Diet Team

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Blog Q: Ok, so I am just starting the diet and have just a few questions. I know processed grain/rice is a no but what about wild rice? I'm from Minnesota and my dad and I harvest our own rice from wild patches that grow in lakes. The rice is just then shaken and boiled and not processed so would this be an acceptable food?

Second question: my friend is the one who started me on this diet and she said that the only cheese that is OK is goat cheese. I know goat cheese is still dairy so I just wanted to confirm that it's a no-go and also if there are any cheese or cheese like substitutes.

A: Virtually all grains contain harmful substances namely lectins, alkylresorcinols, alpha-amylase inhibitors and protease inhibitors, independent of whether or not they are refined or whole grains. However, we believe that rice is probably the less harmful grain and wheat, barley, rye and maize the worst ones.

Regarding your second question, goat cheese is still a dairy product. Cow milk proteins are well studied and have been consistently demonstrated to be harmful to humans, but there's not enough literature to scientifically demonstrate that dairy products derived from goats have the same deleterious health effects. We think that because goat milk contain proteins from a different species it may have immunity stimulating proteins, and may therefore increase the risk of allergies or autoimmune diseases.

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Blog Q: I have been doing the paleo diet for a few months now, prior to this I followed
the Zone diet for 12 years. I have a mild autoimmune condition (lupus) ANA positive 1:64 speckled pattern. I used to get swollen knees, and a sore neck, but not any more using paleo foods combined with zone balance and added Omega 3 and vitamin D.

Other problems that are completely resolved are PMS (breast pain, but no more now), Severe menstrual pain (virtually none now with paleo, exercise and omega 3), Constipation (none now with paleo).

A couple of months ago I had blood tests and found a few problems. Thyroid: TSH slightly high 5.1, T4 okay. Also borderline low B12 and folic acid. Both of which I get plenty of in food and a supplement. I also have Raynauds (not very severe though).

Dr thinks they are all related to the auto immune problems. I would like to resolve the B12 and thyroid problem. I was using a little soy milk, but I've cut that out 6 weeks ago. I've started
taking iodine tabs (Kelp) and had to have a vitamin B12 injection. I would like to know what factors might be causing me not to absorb B12 and folic acid. Also how can I improve thyroid function.

No other health problems, I'm at my ideal weight, do CrossFit for exercise. I'm 50.

Julianne

A: Your thyroid problems might be caused by an autoimmune reaction. Many Celiac Disease patients also suffer from Autoimmune Thyroid Disease and the former disease is triggered by grains containing gluten such as wheat, rye and barley. Hence, avoiding foods containing gluten may decrease the risk of an autoimmune reaction against your thyroid gland.

Legumes, cereal grains, eggs, tomatoes, potatoes, chili peppers, quinoa, amaranth, and root beer are foods containing lectins and saponins. Lectins and saponins, along with gluten, increase intestinal permeability, allowing the increased passage of bacterial, viral or food antigens into peripheral circulation. Some of these antigens may have molecular similarity (molecular mimicry) with certain self antigens, like thyroglobulin, and therefore can trigger an autoimmune reaction of T-Lymphocytes against our own tissues.

Iodine supplementation is a good intervention since it is needed for T3 production. Selenium supplements can also help because it is needed for T3 (the active form of thyroxin) production. Selenium deficiency is common because the soil where vegetables are grown nowadays are empty of selenium.

Regarding B12, a substance known as Intrinsic Factor is needed in order to absorb B12. Intrinsic Factor is produced in a healthy GIT, hence a Paleo Diet devoid of saponins, lectins and gluten can improve the production of Intrinsic Factor and therefore B12 absorption.

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Blog Q: What is Dr. Cordain’s current recommendation regarding supplements? His books indicate supplementing certain vitamins (E, D, C, etc.) along with Selenium but I’m concerned that advice might be outdated. Recent literature (my apologies for not referencing them) along with some mainstream Dr’s--such as Dr. Dean Adel--indicate recent studies suggest supplements may be dangerous and to remove them all from your diet. Any comments or recent recommendations?

Similar Blog Q: In regards to the question on seafood, doesn't the recommendation to take supplements conflict with a recent newsletter that said vitamins aren't necessary? And that the human body wasn't meant to receive vitamins/antioxidants in pure form?

A: Dr. Cordain's current recommendations regarding supplements are based on the fact that our genome evolved in a diet rich in vitamins, mineral and phytochemicals compared to the typical western diet. In his scientific paper titled "The Nutritional Characteristics of a Contemporary Diet Based Upon Paleolithic Food Groups" he demonstrates that by eating a diet similar to what our ancestors did during 2.6 million years ago the amount of vitamins and minerals is much higher when compared to a typical western diet. This means that our "machinery", shaped by our ancient genome, needs high amount of vitamins, minerals and several other substances--not the ones recommended by current nutritional boards based on observations made in western populations. Hence, if you eat a Paleolithic diet you won't need to take supplements except for vitamin D, which is produced by the action of the sun in our skin. So, unless you have adequate exposure to sunlight (depending on season, latitude, skin color, etc.) you'll probably need to take vitamin D supplements.

In summary, if you've been eating a typical western diet, you are probably deficient in almost all vitamins and minerals, and will need to supplement them at least during a few months and cut them if you eat a Paleolithic diet most of the time. The ideal vitamins should be in their pure form.

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Blog Q: In the newsletter v5 #24, you recommend breastfeeding until at least 1-1.5 years.

Is there a chance that auto-antibodies can be passed on to the child through mothers milk so that the child has greater risk in developing autoimmune disease? If that is the case, is it better to stop breastfeeding and start giving solid paleo food earlier?

Do you know if auto-antibodies pass on to the child during pregnancy?

Sincerely, Ohana

A: Dear Ohana,

Mother's milk provides the breast-fed baby with what is called passive immunity, this means that the mothers antibodies pass through to the infant in order to protect it against infections. Hence, the infant is protected against the same bacteria or virus as the mother is. However, our team is not aware of any research demonstrating that this mechanism increases the risk of autoimmune diseases. What has been shown is that food peptides from the mother's gut can pass on to the breast milk and therefore to the breast-fed baby. This might increase the risk of autoimmune or allergy diseases.

The bottom line is to eat as Paleo as possible in order to not increase the risk of these possible mechanisms of disease.

Regarding your last question, yes, auto-antibodies pass on to the child during pregnancy.

Paleo Diet Q & A - 11.20.09

Dear Readers,

We hope you're continuing to experience the health benefits of eating Paleo. Here is today's edition of Paleo Diet Q & A. If you find that reading our Q & A raises new questions for you about the Paleo Diet please post a comment and our team will respond.

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Q: I have just started the diet. For years I have been using pan sprays without alcohol for cooking. With soy and soy oil being detrimental, how bad is soy lecithin? It's not only in pan sprays, but 9 out of 10 fish oil supplements.

I am the chef/owner of a Mediterranean restaurant. Eating a Mediterranean diet (and exercise) has made me healthier, but my triglycerides are way high--but then it appears to be genetic. Hoping the Paleo Diet will reverse this.

A: Yes, this diet should definitely lower your triglycerides. I do not know if soy lecithin contains lectins and saponins or not (two of the main problematic components of soy) – it is something we will have to look into, and perhaps cover in a future newsletter.

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Q: I first want to thank you and your research group immensely for doing the work you do. I have read The Paleo Diet and The Dietary Cure for Acne, which have made a great impact in my life (and some of my friends' as well!). I have suffered intense acne for years and have tried basically every acne medication out there without success; except for Accutane because of the possible side effects. After two months of being on the diet, I can see incredible progress in my complexion and continuously see improvements. I cannot express the astounding changes with words; my family and friends are amazed. Again, for this I thank you deeply. I have also cherished the changes the Paleo Diet has brought to different aspects of my life, one of these has been better racquetball performance (I'm a racquetball aficionado).

I do have a quick question. In The Dietary Cure for Acne you explain how teens are most susceptible to acne because the body normally increase the amount of insulin in the blood in order to facilitate the adolescent growth spurt. Since the Paleo Diet decrease this insulin, does it also put the body in a less favorable state to grow (height-wise) than the normal American diet? (Assuming that all other variables as nutrients, vitamins, etc are the same.) I have noticed that the hunter-gatherers living today have a lower average height than Americans/Europeans. Is this the reason?

Although I am past my growth spurt, I have not recommended this diet to young teens because I would like to let them know about this information as well, if my conclusions are true. If they are not, please explain to me why not.

A: Thanks for the feedback and congratulations on your success. Yes, because insulin is a pro-growth hormone, it is possible that the increasing height seen in many people today is the result of a high-glycemic diet. It is also possible that the same diet may increase their risk for certain cancers as they age. Epidemiological studies also support this notion.

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Q: I have read The Paleo Diet for Athletes and have put it into effect with excellent results. While obviously ground nuts should be a good substitute for flour, you don't mention chestnuts in your book. Are chestnuts and chestnut flour in the same category as almonds, walnuts, etc., or should they be avoided?

A: Yes, chestnut and chestnut flour are allowed in The Paleo Diet. Chesnuts belong to the nut family.