The Paleo Diet and Crohn's Disease

Q: Can you comment on any reported results in curbing the symptoms of Crohn's Disease with the Paleo Diet. As I am a sufferer, I would love to know.

Thank you,
Shannon

A: Dear Shannon,

Indeed, inflammatory bowel disease (Ulcerative Colitis & Crohn's Disease) patients usually do very well with The Paleo Diet, as nutrients are one of the main environmental triggers of this condition. Crohn's disease is an autoimmune disease where the immune system mounts an attack against its own tissues - in this case the cells lining the intestine.

For an autoimmune disease to occur we need a genetic predisposition and an environmental trigger. The genetic predisposition depends on genes coding for the Human Leukocyte Antigen (HLA) system. One of the environmental triggers may be nutrition, besides infections, geography (vitamin D deficiency), physical trauma or vaccination.

One of the key points in this process is increased intestinal permeability. This means that the gut barrier allows increased passage of bacterial or food proteins (antigens) into peripheral circulation, skipping a process known as oral tolerance. Once antigens come in contact with the immune system located in the gut associated lymphoid tissue, they may elicit a T-cell mediated immune response against those antigens.

If the molecular structure of the dietary or bacterial antigens is similar to that of the HLA system (part of the immune system representing cellular mechanisms), chances are that a cross reaction between foreign antigens and self antigens (produced by T-cells) occur. This is termed molecular mimicry, and leads to self injury by the adaptive immune system.

Hence, decreasing intestinal permeability is one of the treatment targets. There are several nutrients known to increase intestinal permeability that you may want to avoid, at least until symptoms subside. Here is a list, with the noxious substances in parentheses:

• Cereal grains (lectins and gliadin)
• Legumes, including soya and peanuts (lectins and saponins)
• Tomato (tomato lectin and alpha-tomatin)
• Potato (lectins and saponins)
• Chili (capsaicin)
• Quillaja (foaming substance)
• Quinoa (saponins)
• Egg white (lysozyme)
• Alfalfa sprouts (saponins)
• Amaranth (saponins)
• Alcohol

Moreover, some nutrients exert an adjuvant-like activity (they stimulate the immune system), which is something you don't want to if you are suffering from an autoimmune disease. Nutrients containing adjuvants:

• Quillaja extract, found in root beer
• Tomato alpha-tomatine

Dairy products and vegetable oils also have deleterious effects upon your immune system.

I hope this helps.
Maelán

Lysozyme from Egg Whites Article

Dear Readers,

This past week our newsletter (The Paleo Diet Update, volume 6, issue 4) featured an article by Dr. Cordain on Lysozyme and Egg Whites, and autoimmune disease. Readers who are not yet newsletter subscribers may obtain a free subscription on our web site to The Paleo Diet Update.

Readers who would like to obtain a copy of volume 6, issue 4 of The Paleo Diet update may purchase a copy of this and other back issues from our web store.

Paleo Diet Q & A - Epigenetics, Flaxseed Oil

Epigenetics

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

Thanks a lot, Michael

A: Dear Michael,

Epigenetics is defined as the science studying changes in phenotype or gene expression by mechanisms other than changes in DNA nucleotide sequence¹. The phenotype is someone's appearance which it's determined by the genotype (stable and heritable) and the environment (nutrition and other lifestyle factors) which give place to the epigenotype (heritable, labile and rapid)¹. Epigenetic changes are controlled, among other mechanisms, by methylation and histone modification. Altered methylation pattern and histone modification may lead to increased susceptibility to disease. E.G. cancer is associated to generalized hypomethylation and localized promoters hypermethylation¹. Histone manipulation may also increase or decrease disease susceptibility².

Both, methylation and histone manipulation are under the control of dietary substances. For example, methylation depends on SAMe availability, which in turn is influenced by vitamin B6, vitamin B12 and folate intake³, and long chain polyunsaturated fatty acids such as DHA⁴. On the other hand, certain substances such as garlic, horseradish, fiber, blueberries, apple, onion, nuts, berries, red grapes, broccoli, etc. are known nutrients involved in histone modification².

The Paleo Diet is rich is all of these nutrients⁵, hence it may exert positive effects upon epigenetics machinery leading to decreased disease susceptibility. Decreased availability of micronutrients is associated to disease severity, probably, through complex epigenetic mechanisms, and supplementation could improve those symptoms³. Improved epigenetic is influenced by metabolic programming during foetal and early life. These two periods are crucial for the developing newborn and future adult's health. Hence, The Paleo Diet may confer protection against several diseases improving the epigenetic programming.

We hope this is helpful.

Maelán Fontes Villalba
Pedro Carrera Bastos

References:

1. van Vliet J, Oates NA, Whitelaw E. Epigenetic mechanisms in the context of complex diseases. Cell Mol Life Sci. 2007 Jun;64(12):1531-8.
2. Delage B, Dashwood RH. Dietary manipulation of histone structure and function. Annu Rev Nutr. 2008;28:347-66.
3. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.
4. Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem. 2006 Nov;17(11):717-27.
5. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O'Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54.
6. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA. Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):75-85.

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Flaxseed Oil

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

First, why are flaxseeds ok in the Paleo Diet but other grains (seeds) are not? My understanding for eliminating grains from the diet is the toxins that they contain, but flaxseed contains large amounts of cyanogenic glycosides, producing up to 139 mg/kg of hydrogen cyanide in raw human-grade flaxseed. I am sure flaxseeds are processed somehow before selling them but I don't know what process that is or what effect it has on the HCN concentration.

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

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

Sincerely,
Tim

A: Hi Tim,

We think your thoughts are on the right track.

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

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

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

1. Hunter-gatherers do not eat ALA from seeds or vegetable oils.
2. Nuts, green leafy vegetables and animal foods contain ALA.
3. The conversion of ALA to EPA+DHA is limited, due to low delta-6 and delta-5 activity, although ALA is highly oxidized (twice that of LA) (see paper by Freemantle et al). This means that at some point in history we included preformed sources of EPA and DHA and still need to do so. Animal foods (especially brain from wild ruminants and fish) are very good sources of these fatty acids.
4. The essentiality of LA & ALA in human metabolism has been questioned (see paper by Le et al.), as we relied almost on LCPUFA (Arachidonic Acid, EPA and DHA) during the Palaeolithic era (see Dr. Cordain’s papers on that here and here). Moreover, there is already some evidence showing that human metabolism could re-convert AA and DHA into LA and ALA respectively, hence AA and DHA would be the true essential fatty acids.
5. The possible toxicity from seeds and vegetable oils (HCN, saponins, lectins).
6. They are not used by current HG societies, and these populations show no signs of western disease, so this means that flax seeds are not necessary.
7. The well known positive health effects of fish oil supplementation (among other factors to improve omega-6/omega-3 ratio) in contrast with some possible adverse effects of flaxseed oil (like the epidemiological evidence that points towards increased risk of prostate cancer with flax oil consumption – see paper by Brouwer et al).

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

Hope this helps,
Maelán Fontes Villalba

Additional reading: Effectiveness of different processing methods in reducing hydrogen cyanide content of flaxseed, Feng, et al.

Paleo Diet Q & A - Saturated Fat

Dear Readers,

This question has come up several times in recent weeks. Maelán's response warrants breaking this out from among the other questions answered in the original post. Included in this post is a link to Dr. Cordain's paper on the subject.

Q: I wanted to ask you why it is that you discourage saturated fats in the paleo diet? From what I have read their are healthy saturated fats from coconuts that are used for around 17% of the Kitavan diet. Also, what about tubers such as sweet potato and yam, do you think that consuming these in moderate portions (small enough to keep a low glycemic load) could be detrimental?

A: Regarding saturated fats:

Saturated fatty acids intake and the risk of developing cardiovascular disease (CVD) is a topic with a lot of controversy. In recent years a wide body of research has suggested that increased consumption of certain saturated fatty acids (Lauric acid, myristic acid and palmitic acid)
down-regulate LDL receptor and thereby increase LDL plasma levels, and this has been associated to increased risk of CVD. On the other hand, stearic acid (a 18 carbon saturated fatty acid) has been shown to decrease LDL plasma levels. However, this view is too simplistic as they are several other factors contributing to CVD, such as smoking, exercise, trans-fatty acids, increased omega-6/omega-3 ratio, free-radicals, nutrient deficiency, homocysteine, alcohol intake and low-grade chronic inflammation among others.

Moreover, some studies have suggested that there’s not enough scientific data to support the view that increased total or LDL cholesterol is an independent risk factor for CVD, but rather oxidized LDL. Plaque production is mediated by oxidized LDL but not LDL. Oxidized LDL can produce shedding of the inner layer of the artery namely glycocalix. Then oxidized LDL infiltrates in the intima of the artery. Oxidized LDL is eaten by macrophagues, a process known as phagocytosis, and therefore macrophagues are transformed into foam cells which produce the fibrous cap.

Once the fibrous cap has been produced we need to break it down in order to produce an ischemic event. Lectins and low-grade chronic inflammation are involved in the activation of matrix metalloproteinases which break down the fibrous cap.

In summary, high total cholesterol or LDL levels do not increase CVD risk but rather oxidized LDL. To produce oxidized LDL we need the factors mentioned above. Hence, consumption of saturated fatty acids is not an issue if we control several other factors such as those mentioned before.

Dr. Cordain wrote a book chapter where he shows that saturated fat consumption in ancient hunter-gatherer populations were usually above recommended 10% (American Heart Association) of energy from saturated fats yet non atherogenic.

The bottom line is that we do not recommend cutting down saturated fatty acid intake but rather decrease high-glycemic load foods, vegetable oils, refined sugars, grains, legumes and dairy.

I hope this helps.
Maelán

Link to supporting paper.

Paleo Diet Q & A - Snails

Q: Do you know if they ate snails in the paleo times? Thank you, Geha

A: Hi Geha,

The Paleolithic era stands for the "Old Stone Age" (Paleo means old; lithic means stone) and extended from 2.6 million years ago with the appearance of the first crude stone tools until the beginning of agriculture 10,000 years ago. During this period, it is estimated that at least 20 species of hominins (upright walking apes) existed¹. Because all hominins were omnivorous opportunists², land snails were almost certainly consumed on an occasional basis throughout hominin evolutionary history.

However, having said this, the first direct evidence for land snail consumption does not appear in the fossil record until 31,000 years ago at the Mumba-Hohle site on the shores of Lake Eyasi in East Africa^{3, 4}. The earliest archaeological evidence for land snail consumption in the Middle East has been dated to 22,000 to 23,000 years ago at the Kvar ‘Aqil site near Beirut, Lebanon³. The hominin that would have eaten these snails was our own species, Homo sapiens. Archaeologists interpret that snails were eaten because their shells were found in huge heaps called middens, and frequently were charred from being cooked⁵. Snail middens dating from 20,000 to 10,000 years ago and from 10,000 to 6,000 years ago are common in lands close to and surrounding the Mediterranean Sea^{3, 5}. The five most commonly consumed species of snails (Helix aspera, Helix melanostoma, Leucochroa candissima, Helicella setifensis, and Otala species) still occur in the Mediterranean region today.

If you don’t know, snail meat is considered a delicacy worldwide and is most commonly known from its French term, "escargot," an appetizer typically cooked in a sauce of butter, garlic and parsley⁶. Although three species of snails (Helix aspera, Helix pomatia) and the African snail (Achatina fulica) are most commonly consumed⁶, a large variety of snail species are eaten worldwide, depending upon location and availability. The cost of 1 kg of prepared snail meat is expensive and fluctuates between $5 - $13⁷. Snail meat, like fish, is high in protein and low in fat, and contains significant amounts of iron (see Table below). Give escargot a try, it’s a great Paleo appetizer.

Table 1. Nutritional value of snails. USDA National Nutrient Standard Reference, release 19 (2006).

Nutrients	Units of measurement for nutrients	Nutrient content per 100 grams of snail
Water	g	79.20
Energy	kilocalorie	90.00
Protein	g	16.10
Total lipid (fat)	g	1.40
Ash	g	1.30
Carbohydrate, by difference	g	2.00
Fiber, total dietary	g	0.00
Sugars, total	g	0.00
Minerals
Calcium, Ca	mg	10.00
Iron, Fe	mg	3.50
Magnesium, Mg	mg	250.00
Phosphorus, P	mg	272.00
Potassium, K	mg	382.00
Sodium, Na	mg	70.00
Zinc, Zn	mg	1.00
Copper, Cu	mg	0.40
Selenium, Se	mcg	27.4
Vitamins
Vitamin C	mg	0.00
Thiamin	mg	0.01
Riboflavin	mg	0.12
Niacin	mg	1.40
Vitamin B-6	mg	0.13
Folate, total	mcg	6.00
Folic acid	mcg	0.00
Folate, food	mcg	6.00
Folate, DFE	mcg_DFE	6.00
Vitamin B-12	mcg	0.50
Vitamin B-12, added	mcg	0.00
Vitamin A, IU	IU	100.00
Vitamin A, RAE	mcg_RAE	30.00
Retinol	mcg	30.00
Vitamin E (alpha-tocopherol)	mg	5.00
Vitamin E, added	mg	0.00
Vitamin K (phylloquinone)	mcg	0.10
Lipids
Fatty acids,total saturated	g	0.361
4:0	g	0.000
6:0	g	0.000
8:0	g	0.000
10:0	g	0.000
12:0	g	0.000
14:0	g	0.056
16:0	g	0.249
18:0	g	0.051
Fatty acids, total monounsaturated	g	0.259
16:1 undifferentiated	g	0.048
18:1 undifferentiated	g	0.211
20:1	g	0.000
22:1 undifferentiated	g	0.000
Fatty acids, total polyunsaturated	g	0.252
18:2 undifferentiated	g	0.017
18:3 undifferentiated	g	0.000
18:4	g	0.015
20:4 undifferentiated	g	0.000
20:5 n-3	g	0.119
22:5 n-3	g	0.099
22:6 n-3	g	0.000
Cholesterol	mg	50.000

References:

1. Wood B. Hominid revelations from Chad.Nature. 2002 Jul 11;418(6894):133-5.
2. Cordain L. Saturated fat consumption in ancestral human diets: implications for contemporary intakes. In: Phytochemicals, Nutrient-Gene Interactions, Meskin MS, Bidlack WR, Randolph RK (Eds.), CRC Press (Taylor & Francis Group), 2006, pp. 115-126.
3. Lubell, D. Prehistoric edible land snails in the circum-Mediterranean: the archaeological evidence. In, J-J. Brugal & J. Desse (eds.), Petits Animaux et Sociétés Humaines. Du Complément Alimentaire Aux Ressources Utilitaires. XXIVe rencontres internationales d'archéologie et d'histoire d'Antibes, pp. 77-98. Antibes: Éditions APDCA, 2004.
4. Mehlman MJ. Mumba-Hohle revisited: the relevance of a forgotten excavation to some current issues in East African prehistory. World Archaelogy 1979;11:80-94.
5. Lubell, D. Are land snails a signature for the Mesolithic-Neolithic transition? In, M. Budja (ed.), Neolithic Studies 11. Documenta Praehistorica XXXI: 1-24.
6. Ozogogul, Y, Ozogul F, Olgunoglu AI. Fatty acid profile and mineral content of the wild snail (Helix pomatia) from the region of the south of the Turkey. Eur Food Res Technol 2006;221:547-549.
7. Zymantiene J et al. Selected features of vineyard snails shell, their movement and physic-chemical composition of foot meat. Biotechnol & Biotechnol Eq 2006;20:82-87.

Paleo Diet Q & A - Calcium from where?

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

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

1. The absorption rate from brassica vegetables (e.g. Kale) is slightly higher than from milk (see attached paper) and as so (and also because they have numerous health benefits), we advise the daily intake of these foods.


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


3. The Paleo Diet is a High protein diet and this increases intestinal calcium absorption^{1, 2} and has an anabolic effect on bone³, particularly in the context of a net base yielding diet³.


4. By avoiding grains, you decrease anti-nutrient intake, such as phytates, which decrease magnesium⁴, calcium⁵ and zinc⁵ absorption.


5. The Paleo Diet is a Low Glycemic Load diet and as so, it does not promote Hyperinsulinemia as a high grain diet. It has been known since the year I was born (1975) that high blood insulin levels cause urinary calcium loss⁶.


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

Links to Relevant Papers:

• RDA of calcium


• Dietary Acid-Base Balance


• Adverse Effects of Sodium Chloride on Bone


• Calcium absorption from kale


• Diet Evolution and Aging

References:

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


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


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


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


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


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