Wednesday, July 21, 2010

The Paleo Diet in the News

Dear Readers,

The Paleo Diet
and Dr. Cordain's work have been cited in recent articles in the following media:

Sunday, July 18, 2010

Consumption of Nightshade Plants paper now available

Dear Readers,

Dr. Cordain's newest paper "Consumption of Nightshade Plants" is now available from our web store.

Thank you for your continued readership.

Sunday, July 11, 2010

Protein Intake for Pregnant Women

by Loren Cordain, Ph.D., Professor

Q: Hello Dr. Cordain

I would like to know if you could direct me to any research that indicates what amounts of protein are necessary for pregnant women who live the Paleo Diet way. I am in my third trimester with my first child and have been living Paleo since I first heard you lecture on it back at Boulderfest before your book came out. I have been the picture of health and my pregnancy has been very easy. I am finding that my protein and fat requirements are significantly higher.

Is there any research you could direct me to regarding protein requirements for pregnancy based on trimester?

Thank you very much and I look forward to hearing from you.

Best Regards,

A: Hi Lynda,

This question has come up before and the bottom line is that your probably should increase your fat and carbohydrate consumption, and limit protein to about 20-25% of energy, as higher protein intakes than this may prove to be deleterious to mother and fetus for a variety of physiological reasons. In my next book, I have devoted a chapter to maternal nutrition before, during and after pregnancy and why protein must be limited during pregnancy.

My colleague John Speth (an anthropologist) at the University of Michigan wrote a paper on protein aversion in hunter-gatherer women during pregnancy. Listed below is the abstract: (note the 25% protein energy ceiling!!!)

"During seasonal or inter-annual periods of food shortage and restricted total calorie intake, ethnographically and ethnohistorically documented human foragers, when possible, under-utilize foods that are high in protein, such as lean meat, in favour of foods with higher lipid or carbohydrate content. Nutritional studies suggest that one reason for this behaviour stems from the fact that pregnant women, particularly at times when their total calorie intake is marginal, may be constrained in the amount of energy they can safely derive from protein sources to levels below about 25% of total calories. Protein intakes above this threshold may affect pregnancy outcome through decreased mass at birth and increased perinatal morbidity and mortality. This paper briefly outlines the evidence for the existence of an upper safe limit to total protein intake in pregnancy, and then discusses several facets of the issue that remain poorly understood. The paper ends by raising two basic questions directed especially toward specialists in primate and human nutrition: is this protein threshold real and demographically significant in modern human foraging populations? If so, does an analogous threshold affect pregnant female chimpanzees? If the answer to both of these questions is yes, we can then begin to explore systematically the consequences such a threshold might have for the diet and behaviour of early hominids."2

The physiological basis for this aversion stems from a reduced rate of urea synthesis during pregnancy that is evident in early gestation1 as well as increases in the stress hormone cortisol3. Hence, pregnant women should include more carbohydrate and fat (i.e. fattier meats) in their diets and limit dietary protein to no more than 20-25% of their total caloric intake.

Hope this helps!
Loren Cordain, Ph.D., Professor

  1. Kalhan, S. Protein metabolism in pregnancy. Am J Clin Nutr 2000;71 (suppl): 1249S-55S.
  2. Speth JD. Protein selection and avoidance strategies of contemporary and ancestral foragers: unresolved issues. Philos Trans R Soc Lond B Biol Sci. 1991 Nov 29;334(1270):265-9; discussion 269-70.
  3. Herrick, K., Phillips, D. I. W., Haselden, S., Shiell, A. W., Campbell-Brown, M., Godfrey, K. M., 2003. Maternal consumption of a high-meat, low-carbohydrate diet in late pregnancy: relation to adult cortisol concentrations in the offspring. J. Clin. Endocrinol. Metab. 88(8):3554-3560.

Sunday, July 4, 2010

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 low2-6, 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 others7-10 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 populations11, 12.

Insulin resistance seems to be one of the factors involved in T2D which is caused, by low-grade chronic inflammation13-15 among other factors. Interestingly, low-grade chronic inflammation is a hallmark16-19 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 permeability23, 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 inflammation22, 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 everyone23, 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) portion30-32. 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 production33, 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 T2D13, 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.

  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.

Thursday, July 1, 2010

Fundraiser for Documentary Series: In Search of the Perfect Human Diet™

Fund raising continues for The Ancestral Health Society & Foundation's post-production work on the international documentary series In Search of the Perfect Human Diet™. The four-part series features the world’s leading scientists and advocates in human evolutionary nutrition. For the first time a major television & DVD release will document proof of the Paleo Diet principles.

Donations of $100 or more will get a Special Edition DVD set and Film Credit for their support.

Distribution of this series will create important ongoing financial support for the Ancestral Health Society's non-profit foundation and educational mission via direct financial contributions from all DVD sales.

The four-part series features the world’s leading scientists and advocates in human evolutionary nutrition, including:
  • Dr. Loren Cordain (author of The Paleo Diet, Colorado State University)
  • Dr. Michael Richards (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany -Department of Human Evolution)
  • Dr. Jay Wortman (Inuit Diet research, Canada)
  • Dr. Steve Phinney (Professor Emeritus of Medicine, UC Davis)
  • Gary Taubes (New York Times science writer and author of Good Calories, Bad Calories)
  • Dr. Michael R. Eades (author of Protein Power)
  • Barry Sears Ph.D. (author of The Zone)
  • Dr. Leslie C. Aiello (President, Wenner-Gren Foundation for Anthropological Research, New York)
  • Robb Wolf (Research bio-chemist, author of The Paleolithic Solution)
  • Professor Richard D. Feinman, PhD (Downstate Medical Center (SUNY) in New York)
  • Professor Craig Stanford (Chair, Department of Anthropology, USC)
  • Dr. Lane Sebring (Sebring Clinic, Wimberley, TX)
  • Eric Schlosser (author of Fast Food Nation)
  • And many more…
This fundraiser will enable Hunt Thompson Media, LLC to finish the international documentary series post-production work by Thanksgiving 2010, and release it for the 2010 Christmas and the 2011 New Year's resolution season. For more information on the documentary series visit

To make a donation click the Chip In button below.