Keto Info Week 3/8

[spEEdfrEEk]

CATEGORY: diseases/allergy

TECHNICAL: **

SUMMARY:

This document was one of the reasons I gave up most

grain completely, and only consume rice and oats (whole grains)

only once a week. Pay careful attention to some of the diseases

being attributed to gluten intolerance (something all humans have

to one degree or another). It's scary. I also liked the way

this paper puts forth the paleo-neo-timeline so easily. I'll

forward other documents in the future that detail the shift of

humans from hunter-gatherer to agrarian. Also take note of the

B8 gene - this mutation, along with blood type differences, can

be attributed to agrarianism and grain consumption.

The most important part of the document, though, is the

part that discusses the genetic singularity in today's grain. Many

people believe that older grains (like spelt) are better than wheat,

but in fact, they are just as "man-made" (in the sense that man

genetically altered them by cross breeding). The note even mentions

lactose intolerance and the fact that, genetically, we are not

well adept at consuming the milk of other animals.

There really is so much info here. One thing I often tell

people is that expectant mothers, and infants should avoid these

foods as well too. Take a look below at the discussion of infant

mortality rates and you'll probably agree. The note even briefly

discusses the importance of breast feeding, but I have more complete

info on this subject that I will send later.

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From the Neolithic Revolution to Gluten Intolerance

_________________________________________________________________

Table Of Contents

* Why So Many Intolerant To Gluten ? by Luigi Greco, D.C.H.,

M.Sc.(MCH), M.D., Department of Pediatrics, University of Naples

30.06.1995

+ Hunters, Fishers and Gatherers

+ The Great Revolution: The First Farmers

+ The Expansion Of The Farmers

+ The Evolution Of Cereals

+ The Rise Of The Intolerance To Gluten

+ Hints On The Epidemiology Of Gluten Intolerance

+ Gluten Sensitive Versus Gluten Intolerant

+ References

_________________________________________________________________

Why So Many Intolerant To Gluten ?

We have recently reported on Lancet (1) a consistent cohort of

patients affected by drug-resistant epilepsy with cerebral

calcifications, half of which were cured by a gluten-free diet. All had an

atrophic jejunal mucosa, which recovered on a gluten free diet. Gluten

intolerance is now a recognized cause of brain calcifications and

epilepsy, of dementia, of psychiatric disturbances: many researchers

believe that, in genetically predisposed subjects, gluten is not healthy

for the brain function (2).

This is just too much.

Having had over 25 years of variegated experience with gluten

intolerance I find hard to imagine that the single most common food

intolerance to the single most diffuse staple food in our environment

might provoke such a complexity of severe adverse immunemediated

reactions in any part of the human body and function. The list is

endless, but malignancies, adverse pregnancy outcome and impaired brain

function are indeed complications above the tolerable threshold of this

food intolerance.

On the other end today we know very well that the majority (as many

as 9 to 1) of gluten intolerant subjects, identified by familial or

population screening, do not manifest any complaint, although they do have

a flat intestinal mucosa (3).

In conclusion a sizable proportion of our population (from 0.3 to 1%)

is gluten intolerant and reacts with a wide spectrum of symptoms from no

apparent reaction to severe life-threatening diseases.

This intolerance is strongly linked to specific genetic markers

which have indeed required thousands years to develop and be selected: the

'population genetic' time is of this dimension, while the changes in the

environment and in the food we eat, require centuries or less.

Where did they come from?

_________________________________________________________________

Hunters, Fishers and Gatherers

Human beings have been on Earth for over 3 millions year, but Homo

Sapiens Sapiens, our nearest parent, is only 100,000 years old. For ninety

thousand years he conducted a nomadic life getting food by hunting,

fishing and collecting fruits, seeds, herbs and vegetables from nature.

Only quite recently (about 10.000 years ago) did some nomadic tribes start

to have stable settlements because they developed the ability to gather

enough food to be stored. The cultivation of wild seeds begun.

Ten thousand years ago the last glaciation came to an end: a

Neo-thermal period ensued which marked the passage from the Paleolithic to

the Neolithic age. Ices melted gradually from the equator to the poles

over several thousands years when new fertile and humid lands were

uncovered in South East Asia all of Europe was still covered with ice and

Northern Countries had to wait up to 4000 years more to get out from a

frozen environment.

_________________________________________________________________

The Great Revolution: The First Farmers

The discovery in the Neolithic age of ways to produce and store food

has been the greatest revolution mankind ever experienced. Passage from

collection to production originates the first system in which human labor

is transferred onto activities which produced income for long periods of

time. The principle of property was consolidated and fortifications to

protect the land and food stores were developed.

Archeological findings suggest that this revolution was not initiated

by the man hunter and warrior, but by the intelligent observations made

by the woman. The woman carried the daily burden of collecting seeds,

herbs, roots and tubers. Most probably she used a stick to excavate roots

and tubers: during this activity she observed the fall of grain seeds on

the ground and their penetration into the soil with rain. She may have

been surprised to find new plants in the places which she herself dug with

a stick, and made the final connection between fallen seeds and new

'cultivated' plants.

She was, for thousands years, the sole leader of the farming

practices and provided a more and more consistent integration to the

scanty products of the man hunter (6).

To our actual knowledge, the origin of farming practices should be

located in the 'Fertile Crescent': the wide belt of South East Asia which

includes Southern Turkey, Palestine, Lebanon and North Iraq. In the

highlands of this area abundant rainfall was caused by the neo-thermal

switch. In all of this area existed, and still exists, a wide variety of

wild cereals, sometimes in natural extended fields, induced by the

rainfalls. Triticum Dicoccoides (wheat) and Hordeum Spontaneum (barley)

were common and routinely collected by the local dwellers. The wild

cereals had very few seeds (2-4) which fell easily on the ground on

maturation.

The people from the Uadi el-Natuf Tell of South East Asia (7800 B.C.)

provided the first traces of the gradual shift from hunters to grain

cultivators. Their economy was based on the hunt of the gazelle, but

their diet also included collected grain seeds. These gradually came to

form a substantial proportion of their energy input, as cultivation

practices ensued. There were no grinding stones or mills and it was most

probable that gathering prevailed on cultivation. But during the

Proto-Neolithic superior a cuneiform mortar appeared. 1000-2000 years

later (5000 B.C.) wild animals, more rare due to incoming drought, formed

only 5% of the daily diet, while cereals and farmed animals become a

sizable part of it (4).

Stable settlements were founded: the village of CatalHuyuk in

Southern Turkey had a population of 5000 inhabitants 9000 years B.C. In

that area a collection of sickles was found with inserted oxidian blades,

smoothed by the routine contact with the siliceous stalk of cereals. The

sickles indicate that it was possible to collect seeds not only by picking

on the ground, but also by cutting stems of plants which were capable of

retaining the seed in an ear (5). 'Mesopotamic' populations, originated in

the first farmers, developed a great civilization with large cities and

powerful armies to defend their land property and food stores. In Egypt a

civilization based on farming practices developed in the 5th millennium:

they became specialists in the cultivation of wheat, barley (to produce

beer) and flax.

_________________________________________________________________

The Expansion Of The Farmers

While in South East Asia the progressive drought made hunting

difficult and encouraged farming, in Europe the Paleolithic culture of

hunters and gatherers persisted for 5000 years more, gradually

transforming into the Mesolithic age.

In the 'Fertile Crescent' the availability of food stores and the

gradual development of animal farming stimulated an unprecedented

demographic explosion. The nuclear family had had a small dimension for

hundreds thousands of years: the birth rate had been limited by nomadic

life. In transmigrations the mother had been able to carry one infant,

while the others had been obliged to walk and move on their own. Small

babies in between had less chances of surviving. Thus mankind remained of

approximately the same size during entire ages.

Farmers, on the contrary, were settlers, possessed food stores and

most probably took advantages in the farming practices of more hands in

the family. In this manner the family size exploded and, as a result, a

progressive continuous need to gain more lands ensued.

The farmer's expansion lasted from 9000 B.C. up to the 4000 B.C. when

they reached Ireland, Denmark and Sweden covering most cultivable lands

in Europe. The expansions followed the waterways of Mediterranean and of

Danube across the time of Egyptians, Phoenicians, Greeks and Romans (7).

The farmers' expansion was not limited to the diffusion of the

agricultural practices, but was a 'demic' expansion: that is a

substantial replacement of the local dwellers, the Mesolithic populations

of Europe, by the Neolithic from South East Asia. More than 2/3 of our

actual genetic inheritance originated in this new population, while the

native genetic background has been progressively lost or confined to

isolated geographical areas.

The genetic replacement of the native European population is marked

by the B8 specificity of the HLA system. Cavalli Sforza and coworkers

showed that the migration of farmers is paralleled by the diffusion of

B8. The frequency of B8 is inversely proportional to the time length of

wheat cultivation. In practice B8 appears to be less frequent in

populations which have lived on wheat for a longer time, as it is caused

by a negative genetic selection in wheat cultivators (7). We are aware

that in Ireland, where the wheat cultivation came only 3000 years B.C., a

very high frequency of gluten intolerance has been reported.

_________________________________________________________________

The Evolution Of Cereals

The early wild cereals, of the Triticum (wheat) and Hordeum (barley)

species were genetically diploid and carried few seeds, which usually fell

on the ground at maturation, making any harvest very difficult. A

chromosomes in ingle couples (diploidicity) allowed for a wide genetic and

phenotypic heterogeneity with remarkable variations in the content of

protein and starches. Poliploid plants occasionally originated in

nature, but they had few chances to survive, without artificial

(cultivation) practices and were usually lost (8).

The beginning of farming, with the use of irrigation, allowed the

survival, and the expansion, of poliploid grains. But the new poliploid

grains had substantially reduced genetic variations (since each gene is

represented in several copies) and more frequently autoimpollinate

themselves, causing remarkable increase of the genetic uniformity.

The first stable formation of poliploid grains is dated around 6000

years B.C.: the genetic uniformity caused a considerable rise in stability

and yield, convincing the early farmer to nduce a progressive and rapid

replacement of the wild species.

Genetic variability of grains was essential in order to adapt the

plant to the very different environmental conditions of different areas,

but the yield was generally low (9).

Triticum Turgide Dicoccoides was crossed with Triticum Fanschii to

originate the Triticum Aestivum, which is the progenitor of all our actual

wheat. The Aestivum is an esaploid wheat with 42 chromosomes, versus the

14 of the T. Monococcum. Such powerful grain replaced all existing

varieties to the point where genetic variability nowadays is lost: over

the world we have 20,000 cultivated species of the same unique T.

Aestivum wheat. The Triticum Turgidum Dicoccoides, progenitor of the

actual 'durum' wheat with which pasta is made, had just few seeds

encapsulated into a pointed and twilled kernel: at maturation the seeds

fell on the soil and penetrated into it with rain, eased by the

arrow-shaped structure of the kernel.

Ten thousand years ago it was difficult to pick them up: hence the

attempt, made by the Neolithics, to select varieties which could retain

the seed longer, in order to allow for an harvest.

Genetic variability was already substantially reduced in Roman times:

'farrum', i.e. spelt, (T. Dicoccoides) and 'Siligo' (T. Vulgaris) were

the common grains. Siligo was used for bread making and contained a

certain amount of gluten, while spelt, used mainly for soups, was poorer

in gluten content (10).

But cultivation of wheat and barley was not started or diffused in

the whole world: only a small geographic area (South East Asia) developed

gluten-containing cereals. In Asia rice was the cultivated species, while

in America maize prevailed and in Africa sorghum and millet. All these

plants were present in nature and were gradually cultivated in the

places of origin (7).

In our part of the world grains had for centuries been selected in

order to improve their homogeneity and productivity, but soon (Roman times

or before?) another desirable quality was preferred: the ability to stick,

to glue up a dough to improve bread making. Early bread making activities

pushed towards grains that contained greater amounts of a structural

protein which greatly facilitated the bread making: the gluten. Gluten was

not chosen because of its, at the time unknown, nutritional value (which

is not absolutely special, since it is a protein with relatively low

nutritional value), but for its commercial qualities.

Rice, maize, sorghum, millet do not contain gluten: no leavened

bread was prepared with them: the majority of mankind never lived on

bread, as we do know it.

Over the last 200 years of our modern age active genetic selection,

and actual genetic manipulation, have changed the aspect of the original

Triticacee enormously: from few grains and little gluten to great wheat

harvests very enriched in gluten (50% of the protein content), well

adapted to cultivation practices and ready to be handled by monstrous

machinery.

_________________________________________________________________

The Rise Of The Intolerance To Gluten

Did everybody adapt to such profound changes in the basic nutrition

over such a short period of time? South Eastern populations, presumably

well adapted to the new foods, grossly replaced the existing Mesolithic

European dwellers who still lived on hunting and gathering. But a

proportion of the local populations (or, rather, of their inheritance )

persisted beside the invaders. The feeding changes were not well tolerated

by everybody.

The best similar example is lactose intolerance: populations that

have more recently adapted to milk consumption, still lack the genetic

ability to digest lactose over the infancy period. Environment has

changed centuries before any change in the inheritance may have been

possible.

Similarly a considerable proportion of the hunters and gatherers of

the pre-Neolithic ages have not fully adapted to the great feed changes

induced by the cultivation of wheat. These people could not recognize

gluten as a 'tolerable' protein available for digestion and absorption:

they may have not have any problem or complaint for centuries, since the

content of gluten in the grains was very low, but when 'industrial'

quantities of gluten were induced by selection of wheat in order to

improve bread making, they were exposed to unbearable quantities of an

'intolerable' protein or peptide.

This population, genetically identifiable today by their specific

HLA pattern, did not recognized, through their HLA system, the gluten

peptide as a tolerable item, but, because of the similarity of some

sequences of gliadin peptides with several pathogenic viruses, they

generate a complex defense mechanism (an immune response) which does not

eventually find the pathogen to destroy, and most probably activate an

auto-immune response which ultimately is the origin of the damage to

their intestine and other organs.

These fierce descendants of hunters and fishers, exposed to this

subtle enemy, could not develop the defense of tolerance and, in the

attempt to fight the unknown, they ultimately develop a disease due to

excess defense. For centuries they underwent a negative selective

pressure, with less chances to survive, and then to be manifest (11).

In the last millennium gluten-intolerant children mostly had a harsh

time behind them: after weaning, malabsorption and malnutrition were the

underlying causes of poor defense to infections during infancy and early

childhood. Acute infectious diarrhea was the main killer of infants up to

50 years ago in Europe and up to 15 babies every thousand died for this

condition. In the suburbs of Naples, only 25 years ago, infectious

diarrhea was the main killer (25% on an infant mortality rate of 100 per

thousands live births) (12).

The vast majority of gluten intolerance occurred among these poor

infants. In my own clinical experience 25 years ago I observed several

fatal gastrointestinal infections in babies with the 'celiac crisis',

which has now disappeared from our wards.

Few chances to survive, few intolerant children that reached the

reproductive age, and become capable of transmitting the intolerance, few

adult cases. Then gluten intolerance may have become extinct, as was in

fact the case with several other pathogenic conditions? Not at all.

The intolerance most probably had some selective advantage which

counterbalanced the gluten intolerance: it is possible to suggest that

it was their very effective HLA Class II system that gave them a selective

advantage against infections, which compensated the disadvantage due to

gluten intolerance.

When, in the last 50 years, infantile infections greatly diminished,

the descendants of the hunters and gatherers with very active

immune-defense, 'over reacted' more frequently to the gluten than to their

ordinary enemy. Hence the rise of the cohort that now appears to manifest,

in different manners, a gluten intolerance.

However, not all populations of the world were ever exposed to such a

nasty protein: the vast majority of mankind, after the development of

agriculture, lived on maize, rice, sorghum and millet, tubers: all gluten

free. All of them did not underwent the selective pressure of gluten

intolerance and they may in fact have been the reservoir of wild genes.

Finally, breast feeding most probably played a major role in

preserving some children from the fatal infection of infancy (13). The

capacities of breast milk to protect against viral and bacterial attack,

the protection given by maternal antibodies and the delaying effect on the

manifestation of symptoms of gluten intolerance (in the predisposed

subjects) may all have protected the hunters and gatherers, who in this

manner avoided to develop fatal symptoms and managed to survive and

transmit their genes to our population.

_________________________________________________________________

Hints On The Epidemiology Of Gluten Intolerance

The epidemiology of gluten intolerance, as we know it today, is the

complex result of the apparition of the population of hunters and

gatherers in our modern world.

As the cohort of those born before the World War II had few chances

to survive infancy, we nowadays have few adult cases and few long term

complications. Where the intolerance is still manifested mainly in the

classical way (infants and small children, malabsorption, diarrhea, often

switched on by an infection) we do not frequent encounter 'atypical'

presentations and adult cases or long term complications. In this case

the epidemiological calculations on observed cases made by

gastroenterologist may be in great contrast with those made by

pediatricians. On the contrary the rarity of 'classical' cases, which has

been used as the proof of the 'disappearance' of gluten intolerance, is

counterbalanced by the presence of atypical and late diagnosis, where

actively searched for.

Finally nutritional attitudes have played a major role with regard to

the chances for hunters to manifest themselves in different age groups:

the example of Sweden as compared to the nearest Denmark or Finland is

paradigmatic (14).

As shown by Maki et al, the ability to identify atypical cases may

completely change the observed epidemiological pattern in a given region.

Hence the reason for the 'iceberg': most cases still to be discovered

(15). Similarly, population-based screening programs uncover more

'silent' than overt cases (3).

Nevertheless, the 'cohort effect', regional differences and so on,

have up to now failed to overcome the limits of numbers: when local

incidence rates are compared with other regions' rates, the 95% Confidence

Intervals of the rates are very often so wide to contain the all lot of

observed rates. No clear-cut statistical difference has really been

shown in the incidence of gluten intolerance in Europe (16).

Wherever extensive studies on symptomatic cases have been run an

incidence of 1 case per each 1000 live births has been reached, but very

often the incidence has been much lower: up to 1 cases every 250 live

births. Population screening studies invariably come to an incidence rate

of 1 every 250. This is very close to the rate predicted by age-adjusted

incidence density studies (17). Recent reports indicate an incidence close

to 1 case per every 100 live births, but this finding needs confirmation.

_________________________________________________________________

Gluten Sensitive Versus Gluten Intolerant

But the epidemiology of gluten intolerance, which entails the tracing

of a group of our ancestors, may completely change once we consider the

increasing knowledge about the 'gluten-sensitive' individuals. 6 to 10%

of first degree relatives of known cases themselves are gluten intolerant

and have a flat intestinal mucosa (these are silent cases), but up to 30%

of sibs of cases, when challenged with a dose of gluten (or its digest)

activates a specific mucosal immune-response (with increase in

intraepithelial infiltration and activation of TCells), without having

any sign of mucosal damage (potential cases?) (18).

We may, in the near future, have a substantial group of individuals

who do not activate, in presence of gluten, a 'pathogenic' immune response

(auto-immunity), but who recognize gluten as a 'suspect' protein in the

same way as their peers really intolerant.

Finally gluten intolerance is indeed linked to a specific genetic

predisposition: most probably at least two genetic loci are involved in

running the risk of intolerance.

How many possess these specific genetic risk at a 'carrier' state?

Certainly more than 5% of the actual population. In conclusion we have a

wide population of 'gluten-reactants' in Europe (EC): at least 1 million

cases of total intolerance to gluten an estimated similar amount of

'gluten sensitive' people 10-15 times more 'carriers' of the risk of

becoming gluten intolerant.

So we have found our ancestral hunters and gatherers: they are a

substantial proportion of our actual community and do deserve a

'gluten-free' alternative not only as a therapeutic mean, but as an option

of our daily life.

References

1. Gobbi G, Bouquet F, Greco L, Lambertini A, Tassinari CA, Ventura A,

Zaniboni MG: "Coeliac Disease, epilepsy and cerebral calcifications"

Lancet, 340, Nx 8817, 439-443, 1992

2. Epilepsy and other neurological disorders in Coeliac Disease. Republic

of S. Marino Meeting, April 10-12 1995, G. Gobbi edt., Raven Press, in

preparation.

3. Catassi C, Ratsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F,

Coppa GV, Giorgi PL: Coeliac Disease in the year 2000: exploring the

iceberg. Lancet, 1994, 343: 200-203.

4. Furon R. Manuel de Prehistorie Generale., 1958, Payor, Paris.

5. Cambel H, Braidwood RJ. An old farmer's village in Turkey. Le Scienze,

1970, 22: 96-103.

6. Heichelheim F. An Ancient Economic History. A.W. Sijthoff edt., Leiden,

1970.

7. Cavalli-Sforza L. Chi Siamo (Who are we). 1993 Mondadori, Milano.

8. Raven PH, Evert RF, Eichorn S Biology of plants. 4th ed. Worth Publ.

Inc, New York, 1986.

9. Feldman M, Sears ER The wild gene resources of wheat. Scientific

American, 1981: 98-109.

10. Lucio Giunio Moderato Columella " Libri rei rusticae" Anni 60-65 dopo

Cristo. Ed. Einaudi,1977.

11. Simoons FJ: Coeliac Disease as a Geographic Problem. Food, Nutrition

and Evolution, 1982, 179-199.

12. Greco,L.: " Malnutrizione di classe a Napoli" Inchiesta, 24, 53-63,

1976.

13. Greco,L., Mayer,M., Grimaldi,M., Follo,D., De Ritis,G., Auric-

chio,S.: "The effect of Early Feeding on the onset of Sympthoms in Coeliac

Disease" J.Pediat. Gastroenterology Nutrition, 4:52-55, 1985.

14. Maki M, Holm K, Ascher H, Greco L.: Factors affecting clinical

presentation of coeliac disease: role of type and amount of gluten

containing cereals in the diet. In "Common Food Intolerances 1:

Epidemiology of Coeliac Disease", Auricchio S, Visakorpi JK, editors,

Karger, Basel, 1992, pp 76-83.

15. Maki M, Kallonen K, Landeaho ML, Visakorpi JK.:Changing pattern of

childhood coeliac disease in Finland. Acta Paediatr Scand 1988;

77:408-412.

16. Greco L, Maki M, Di Donato F, Visakorpi JK. Epidemiology of Coeliac

Disease in Europe and the Mediterranean area. A summary report on the

Multicentric study by the European Society of Paediatric Gas-

troenterology and Nutrition. In "Common Food Intolerances 1: Epidemiology

of Coeliac Disease", Auricchio S, Visakorpi JK, editors, Karger, Basel,

1992, pp 14-24.

17. Magazzu, Bottaro G, Cataldo F, Iacono G, Di Donato F, Patane R,

Cavataio F, Maltese I, Romano C, Arco A, Totolo N, Bragion E, Traverso G,

and Greco L: "Increasing Incidence of childhood celiac disease in Sicily:

results of a multicentric study" Acta Paediatr, 83:1065-1069, 1994.

18. Troncone R, Greco L, Mayer M, Mazzarella G, Maiuri L, Congia M, Frau

F, De Virgiliis S, Auricchio S.: "In half of Siblings of Coeliac Chil-

dren rectal gluten challenge reveals gluten sensitivity not restricted to

coeliac HLA."

:cool: TJ :cool: