Sunday 12 August 2012

Εκκολπωμάτωση και Φυτικές Ίνες

 THE RELATIONSHIP OF HIGH FIBER DIET AND COLONIC DIVERTICULAR DISEASE
By
C- A. B. Sakellariou  and  B. K. Sakellariou
  
 Athens 2007


‘’Once every ten years or so a new idea emerges about the cause of disease….. To these we may now add a deficiency of dietary fiber…..
Personally, however, I have little doubt that the fibre hypothesis will be found to have established for itself a permanent place in the structure of medical knowledge.’’

Sir Richard Doll FRS from the Preface of ‘Refined Carbohydrates Foods and Disease’, eds. D.P. Burkitt and H.C. Trowel, New York, Academic Press, 1975.


TABLE OF CONTENTS


ABSTRACT

INTRODUCTION


FIBER (CRUDE FIBER AND DIETARY FIBER)


          SOURCES AND TYPES OF DIETARY FIBER


                              -    SOLUBLE FIBER

                              -    INSOLUBLE FIBER

          PHYSIOLOGIC AND METABOLIC EFFECTS OF DIETARY FIBER

EPIDEMIOLOGIC RELATIONSHIP OF DIVERTICULAR DISEASE AND HIGH FIBER DIET

CONCLUSION


APPENDIX


REFERENCES



ABSTRACT

A low-residue fiber-deficient diet has been postulated as one of the main causes of  diverticular disease (DD), the commonest affliction of the colon in western societies. Epidemiological evidence suggests that a decrease in dietary fiber, as well as increasing age, lead to formation of DD.
This essay reviews the epidemiology of fiber in relation to the development of DD. Dietary fiber, soluble and insoluble, and its effects are also reviewed as the principal component which has been deficient in western diets and is the culprit which leads to the establishment of the disease.
However there are still certain unexplained or unanswered questionings as to the high frequency of right-sided DD in Asian countries in divergence from what is seen in the West countries i.e. left-sided DD.
We believe that sufficient circumstantial and epidemiological data exist confirming the ‘’fibre hypothesis’’ as central to the etiology of DD which warrant modification of eating habits in order to prevent the increasing prevalence of the disease and its deleterious consequences.

 

INTRODUCTION

The health benefits of eating cereal fiber and high-fiber plant foods in general were promoted in the 19th century by the well- known health advocates Graham and Kellogg in America and Allinson in Britain. However, much of the interest generated thirty five years ago from the work of D. Burkitt and N. Painter, who suggested  the “fiber hypothesis”, in which it was postulated that there was a link between the consumption of a diet rich in fibre and non-processed carbohydrates and the level of protection against certain colonic (constipation, irritable bowel syndrome, appendicitis, haemorrhoids, diverticular disease, large bowel cancer), metabolic (diabetes mellitus, obesity, gallstones) and vascular (ischaemic heart disease, thromboembolism, varicose veins) disorders or diseases.(1,2)
Since that time numerous studies have been done presenting and analyzing results of international comparisons and correlation and case-control studies in an effort to demonstrate the relationship between fibre and disorders of the gastro-intestinal tract and other processes with severe health implications. 

Diverticular disease (D.D.), although a rarity before the 20th century, is the most frequent structural abnormality of the colon (large bowel) nowadays. It is a multifuctorial disease, meaning that many factors affect it, in its pathogenesis, due mostly to lifestyle changes, particularly in westernized societies, with reduced fiber diet are supposed to be one of the main causes for its high prevalence.


The pathophysiology of colonic diverticular disease has not yet been completely understood. The main factors considered to be involved in the development of D.D. are dietary factors, colonic motility and structural changes affecting the colonic wall.
During the last decades these factors have been extensively studied from the epidemiological point of view to the basic research study. The first of these factors i.e. dietary factors will be reviewed extensively here, because the results from the studies done despite some discrepancies have provided a rationale for the currently accepted way of managing of diverticular disease.


FIBER (CRUDE FIBER AND DIETARY FIBER)

Fiber is a group of structural substances present in plant cell walls. The common term crude fiber (CF) used until the early 1970s refers to the heterogeneous residue remaining after plant material has been treated successively with dilute acids and alkalis. This procedure was useful to farmers in the past enabling them to measure the indigestible material present in foodstuffs. Although in use today in more food tables, it underestimates by 80% to 90% the amount of material in foods that is indigestible by human intestinal enzymes (2).
The term dietary fiber (DF) is a generic term and refers to a heterogeneous mixture of plant-based carbohydrates that are resistant to ingestion by human intestinal enzymes. In western-type diets DF is about 3-5 times the estimated CF. No food tables report DF constituent because of disagreement concerning methods of analysis between USA and British analysts (2).
 

The definition of DF has always been controversial. Some considering the term obsolete favor other terms such as plant cell wall non-starch polysaccharides (NSP) (3), but the most widely accepted definition of DF is that of Trowel et al (4) ‘’Fiber is composed of the plant polysaccharides and lignin which are resistant to digestion by the digestive enzymes of man’’. This is a physiologic rather than a chemical definition.
According to their chemical structure fibers are grouped into two distinct categories.

Polysaccharides and non-carbohydrate components
. The first category consists of polysaccharides constituting the structural-matrix components of plant cell wall and polysaccharides not associated with cell wall. The former includes cellulose (β 1-4 glucose), hemicellulose (pentose-hexose branched polymers), pectins (mixed colloidal polysaccharides), starches resistant to enzyme action (amylase) entering the colon as compact unbranched structure and fructo-oligosaccharides (mixed β-D-fructose monomers linked by β 2-1 linkages) which are not hydrolyzed by digestive enzymes but fermented and metabolized in the colon producing a change in the microflora (bifidobacteria increase and bacteroids-anaerobes decrease). The latter includes mucilages and gums which are branched polymers containing uronic acid that has the properties of holding water and forming gell. The second category of non-carbohydrate components include polyphenols particularly flavonoids. Such a compound is lignin, a group of phenylpropane polymers that reinforces the cellulose support structure and inhibits microbial cell wall digestion (resistant to anaerobic digestion systems).


SOURCES AND TYPES OF DIETARY FIBERS

High-fiber foods include whole grains, vegetables, fruits, beans, nuts and seeds. Components of DF in plants vary with species, part of plant and stage of maturity. High levels of cellulose and hemicellulose are contained in grains, roots, green vegetables, legumes and some fruits. High levels of lignin are contained in the wall of matured plant cells and most fruits (5).
The heterogeneity of DF has induced numerous classifications based on source, structure, chemistry, physicochemical properties and physiological effects. Many physicochemical properties of DF are physiologically important such as hydratability (water and detergent solubility, viscosity), ion binding-exchange (Ca+2; Fe+3, Mg+2,Zn+2, Ph-3) and absorptive capacity (bile salts, proteins and bacterial cells) (6). 

Basically, DFs are classified into two distinct categories: Those that are water soluble and those that are water insoluble, although it has been proposed that these terms should be abandoned because most foods contain both components in varying ratios, with an average in western diets being 1:3 soluble: insoluble fibers.


SOLUBLE FIBER

Soluble fibers attract water and form a viscous or gummy gel during digestion. Food sources of SF include fruits, oats, barley and legumes. SFs are fermentable and metabolized by a variety of colonic bacteria into gases and short-chain fatty acids (S-CFA) (7). Therefore the soluble fibers have little fecal bulking effect. A notable exception to this is psyllium husk, which has a high viscosity, but is not well fermented by colonic microflora and thus has a fecal bulking effect (3). However it has been suggested that fermentable fiber can increase fecal output by stimulating microbial growth (bifidobacteria) which generates the S-CFAs (and other products) which has important physiologic effects locally in the colon and finally in the host (8). 

It is noteworthy that S-CFAs are the preferred fuel of colonocytes and are also the providers of an additional source of caloric uptake, enabling the colon to function as a nutritional organ. In remote history with a fiber uptake far greater than today the amount of calories absorbed through the colon was far greater than today. For example the western lowland gorilla, whose diet is similar to Paleolithic man diet, takes nearly 60% of its calories through the colon. Today the typical western diet may have 2% to 9% of total calories absorbed through this pathway (9).


INSOLUBLE FIBER

IF is the major dietary fiber fraction, which passes through the gastrointestinal tract unaltered by digestive processes or bacteria. It is found primarily in wheat, most grain products, fruits and vegetables. Overall fruits and vegetables tend to be higher in cellulose than cereals. Cellulose comprises approximately 30% of the total fiber in most foods, except for legumes, in which it is about half. In fruits and vegetables cellulose amount to an average of 30% and 50% of the insoluble fraction respectively (7).
In general IFs are insoluble in water but hold more water than do the water soluble fibers (e.g. vegetable fiber, pectins, gums) (6). 

As regards fermentation it has been suggested that IFs are not fermentable or at least less fermentable than SFs. Indeed fermentation is not exclusiveness to SFs, because some 60% of ingested cellulose appears in human feces. This indicates that IF is fermented to some degree and S-CFA are not abolished when the diet contains exclusively IF such as cellulose or wheat bran. Also in an animal study it was observed that IF may modify the production of S-CFA (8).


PHYSIOLOGIC AND METABOLIC EFFECTS OF DIETARY FIBERS

Dietary fiber has numerous effects on metabolism and digestive processes.
1/ Insoluble fibers are considered to be those with the greatest effect on fecal bulk (e.g. cereal brans from wheat, rye and rice). Increased fiber intake increases fecal bulk and usually increases frequency of bowel movements (3, 7). 

2/ Fiber can increase or decrease mouth to anus transit time depending on fiber type, particle size and bulking forming capacity. Intestinal transit time and stool bulk are inversely related. Large particle size such as coarse wheat bran produces a greater increase in stool bulk and a greater decrease in intestinal transit time than does a small particle size such as finely ground bran. The mechanism by which fiber decreases colonic transit time is unknown but may be due to increased colonic peristalsis secondary to increased fecal mass (6). 


3/  Dietary fibers of the viscous type such as gums and pectins delay gastric emptying and slow small intestinal uptake of sugars, amino acids and drugs  (3). The fiber content of foods affects the rate of intestinal absorption of carbohydrates by several mechanisms: One mechanism is to slow gastric emptying based on the viscosity of gastric contents. Another is to impede digestion in the intestinal lumen by decreasing the accessibility of starch to enzymes (10). 


4/ unabsorbed fiber reaching the colon serves as a fuel for colonic bacteria (microflora). The bacterial products of fiber metabolism include S-CFAs, hydrogen and methane. S-CFAs serve as a fuel to colonocytes (10). 


5/ the viscosity of the fiber appear to determine its metabolic effects. Soluble fiber (e.g. pectins from fruit and vegetables, β-glean from oats and barley, gums from legumes, roots from the outer surface of plants such as sea weeds) tend to flatten blood glucose and insulin levels postprandially, reduce serum cholesterol and increase bile acid losses in stools. They also reduce low- density lipoprotein (L-DL) levels by about 10%, but it has no effect on the levels of high-density lipoproteins (H-DL) and triglycerides. Soluble fibers have little fecal bulking effect since they are rapidly fermented to gases and S-CFAs by the colonic bacteria (3,10). 


Dietary fiber may have a beneficial effect on a number of disease processes including metabolic, vascular and colonic disorders.
Viscous fiber preparations have been used in the management of diabetes (increased insulin sensitivity, better control of blood glucose level) and in reduction of serum cholesterol levels in hyperlipidemia (lower atherogenic serum lipids). These preparations also improve symptoms following certain gastric operations (dumping syndrome) by delaying gastric emptying (3). 

Epidemiologic observations, as has been mentioned at the introduction, led to the hypothesis that dietary fiber and increased stool output can decrease the risk for western gastrointestinal diseases such as diverticulosis and others (irritable bowel syndrome, constipation, haemorrhoids, anal fissure, appendicitis). Dietary fiber may prevent colonic diverticulosis by increasing intracolonic fecal bulk, which decreases intralumenal pressures by maintaining a large diameter lumen of the colon and eliminating closed segmental colonic wall contractions which result in the appearance of diverticular disease.


Based also on the results of epidemiologic studies it has been concluded that an inverse relationship exists between the amount of ingested fiber and the incidence of  large bowel (colorectal) cancer. Although the mechanism of the effect of fiber on the incidence of colorectal cancer is unknown it is possible that colonic metabolites of fiber, particularly of S-CFAs (e.g. butyrate) are involved in cancer growth regulation (10).


EPIDEMIOLOGIC RELATIONSHIP OF COLONIC DIVERTICULAR DISEASE  AND HIGH FIBER DIET

Diverticulosis is considered to be the commonest disorder among the elderly in most of the developed countries of the world, including USA, Britain and Greece although the absolute prevalence of the disease in Greece is considerably lower (11,12).

The disease was first described in the mid-19th century as a curiosity than a significant disease entity. However, in the early 20thcentury, an increasing prevalence of the disease has been recognized in industrialized countries. The incidence increases with age and the adaption of a diet high in red meat, refined sugars, and milled flour but low in wholemeal breads, cereals, and vegetables.

The initial hypothesis of a fiber deficiency as central to the aetiology of DD was first proposed by Dennis Burkitt and N.S. Painter in 1971 (13). While in Uganda, D.Burkitt found that DD was virtually non existent in rural Africa. He investigated fiber intake, stool weight ,and transit time by comparing a rural Ugandan population to an English population, and he found that the Ugandan had an average transit time of 30 to 40 hours and a stool volume of more than 300g/d as compared with the English population, which has an average time of 70 to 80 hours and an average stool weight of  110g/d, this difference obviously being due to a diet higher in refined sugar and lower in dietary fiber (14).The observation that the stools of the native inhabitants were larger and softer than those of individuals in the west led him to write in 1973 ‘’Particular attention should be paid to that portion of the diet which is not absorbed in the small bowel and consequently reaches the colon little unchanged, that is, the fiber content’’ (15).


The fiber deficiency hypothesis is also supported in epidemiologic studies by the inverse relationship between dietary fiber  and the presence of colonic diverticula. In a prospective cohort study of 47.888 health professionals, it was found that total dietary fiber intake was inversely associated with the risk of DD, with a relative risk of 0.58 for men in the highest quintile of dietary fiber (16). In another study on the same cohort, insoluble fiber intake, especially cellulose, was significantly associated with a decreased risk of DD (8). Vegetarians living in Oxford, England have a 12% incidence of DD as compared with a 33% incidence among non vegetarians who ingest  one half (21,4g/d) of the mean daily vegetarian intake (41,5g/d) of dietary fiber (17,18).Moreover, animal studies have shown an increased risk for developing diverticulosis in rats fed with a fiber-deficient diet compared to a high-fiber diet {42% vs 0%,respectively}. (19) 


The exact incidence of DD is unknown or at least not well documented because it is difficult to asses accurately the frequency with which DD occurs in the community as it often remains symptomless and many individuals with the disorder do not seek medical advise or present for investigation at hospital.

Medical reports of DD were uncommon until the 20th century, but since then a substantial body of epidemiologic, autopsy and clinical studies have shown that the incidence has increased drammatically with age over the past 75 years, from around 5% near the turn of the century to 50% or more by 1975. It is now estimated that the risk of developing DD in USA approximates 5% at the age of 40 years with a trend to increase to more than 80% at the age of 80 years (20).

Autopsy studies in the early 20th century found a prevalence of 2% to 10% of DD. In contrast, in late 1960s DD was found to be present in 10% of individuals below the age of 40 years, 30% over 50 years, 50% over 70 years, and up to 66% of those over 85 years (9). Autopsy studies in the UK and Australia have shown that the prevalence of colonic diverticula increases with age. It is rare in those under 30 years of age but occurs in more than 50% of those over 70 years (21).

From  medical studies in 1930, the prevalence among North American population estimated from  barium enema (X-ray) studies, was 5-8%, whereas a recent endoscopic study (colonoscopy) found extensive distal diverticulosis in 23% of subjects with a mean age of 58,5 years (13,22). In Endiborough, 23% of all barium enemas of the colon demonstrated diverticula. The annual incidence increased from 0.17/1.000 in those under 45 years to 5.7/1.000 in those over 75 years of age (21).  No sex differences have been clearly established although Hospital admissions for diverticulitis are more frequent in men aged >65 years, whereas in older patients female gender is more frequent (23).

The prevalence of DD varies considerably in different parts of the world. Geographic location has been an important predictor of this disease. As economic development and the adoption of a western diet increases the prevalence of DD rises. This disorder is common in western countries, less common in Latin America and exceedingly rare in Africa and certain areas of Asia. It is worth mentioning that this condition is virtually unknown in rural African blacks (0.2%), who live south of Sahara, and who have not changed their traditional residue diet. Urbanization and adaptation of a diet, that in almost all aspects is similar to that consumed by western population, has been accompanied by the emergence of DD, a condition virtually non existent before (24). The prevalence rate in Singapore, a developed eastern country, as estimated by autopsy and barium enema studies, is comparable to that in western countries (19% and 20% respectively) (9,25). Studies from Japan provide valuable information about the increased prevalence rate of DD today, as this country has changed its traditional diet for a more western-type diet (low fiber).The prevalence rate of DD has risen from 3,3% in rural-urban inhabitans to 12,3% in inhabitans coming from Tokyo. Hawaians of Japanese ancestry, in autopsy study, have found to have DD in 53% of subjects. This increase in DD mirrors a decrease in dietary fiber intake. Indeed, the introduction of polished rice in Japan in the late 20th century, initiated a reduction in fiber intake from 1952 with a mean daily intake of 20g to a decline more than 70% by 1998. Similar findings have also been observed in Hong Kong (9). However, the geographical distribution of DD is not due to race, as west Indians and Asians living in Britain, American blacks and Japanese who have moved to Hawaii or the mainland United States are just as prone to disease as Caucasians. It is now clear that the incidence of DD rises within a society as it reduces the intake of dietary fiber.

Geographic differences have also been recognized in anatomic distribution of diverticula. In general, industrialized countries with a western diet, including North America, Europe , and Australia, have predominantly left-sided colon diverticula ,particularly the sigmoid colon either alone or in combination with more proximal regions, in approximately 95% of patients (26,27). In contrast, in Asia the predominant site of colon diverticula is the right side in approximately 83% of patients, whereas only 17% had lesions located exclusively  in the left colon (28). Singapore and Hong Kong have found similar results. The reasons for this divergence are unexplained, but these variations in anatomic distribution  among  ethnic groups support the concept of a multifactorial basis for this disease,i.e. although the cause for diverticular disease may be acquired-racial and congenital factors may control the site of development (25).

CONCLUSION

From the above it becomes obvious that considerable epidemiologic evidence supports the hypothesis of Burkitt and Painter that diverticular disease emerged as a significant intestinal disorder in the past century due to a decrease intake in dietary fiber. Certain differences are noteworthy and unexplained, in particular the increased frequency of right-sided diverticular disease in Asian countries compared with the west.

Fiber increases stool bulk in three ways: By holding water, by bacterial proliferation, and from the by-products of bacterial fermentation. The effects of increased dietary fiber include more frequent stools, more voluminous stools, alteration in the fecal flora and possibly a reduction of the intracolonic pressures in the  colon, particularly the sigmoid colon. In other words the effects of decreased insoluble fiber intake are decreased transit time and increased intracolonic pressures. The effects of decreased soluble fiber fraction are alterations in gut flora. Consequently the decrease in fiber intake has pathologic consequences not only due to the mechanical results of a low non-soluble fiber intake and the increased colonic pressures but also due to other changes in the colonic environment, particularly in the altered colonic flora due to a decrease in soluble fiber intake.

The pathogenesis of diverticular disease still remains unclear. However, it is believed that it is the result of complex interactions between colonic wall structure, intestinal motility, diet, and genetic factors. Diet regulation is the only weapon at present to combat the disease which is a significant cause of morbidity and mortality in the western world. Its frequency has increased throughout the whole of the 20th century. It is now clear that not only the asymptomatic form but also the symptomatic form of the disease and its relating complications are increasing. This is exemplified by increasing costs in the treatment of DD which accounts for nearly 450.000 hospital admissions, 2 milion office visits, 112.000 disability cases, and 3.000 fatalities each year in the USA (20). It is estimated that costs will continue to increase as the population continues to age in the next several years.

 

APPENDIX

A diverticulum (plural:diverticula) is a sac-like protrusion of the peptic tube wall. Divertivula can be found throughout the gastrointestinal tract (esophagus, stomach, duodenum, small intestine and large intestine), but are most commonly seen in the large intestine particularly in the sigmoid and descending portions of the colon.

For reference purposes the large intestine consists, in descending anatomical order, of the colon (cecum, ascending-transverse-descending-sigmoid colon), the rectum and the anus. The colon is divided into right and left-sided colon by an imaginary vertical line drawn in the middle of the transverse colon.

Diverticula are classified as acquired or congenital diverticula, true diverticula containing all bowel wall layers or false diverticula containing some of the bowel wall layers (mucosa and submucosa) that have herniated through the outer-lying muscular layer of the bowel wall. Diverticula are also distinguished into traction and pulsion diverticula, the latter due to increased intralumenal pressure.

Diverticula are more common in the colon than in any other part of gastrointestinal part. Acquired, false and pulsion diverticula are the most prevalent type of diverticula in the colon. The presence of a solitary congenital diverticulum and the occurrence of multiple diverticula limited to the right colon are distinct entities often seen in Asian people but seldom encountered in other populations, as mentioned in the main text.

Diverticular disease of the colon refers to acquired small outpouchings (herniations) of the inner layers (mucosa-submucosa) of the colonic wall through sites of low resistance which are the points of greatest muscular weakness, where nutrient blood vessels (vasa recta) penetrate the muscular layer to the submucosa (25). Diverticula vary from a few millimeters to several centimeters in diameter. The neck of the diverticula may be narrow or wide and some contain inspissated fecal matter (Pict. 1).


Picture 1: Cross-sectional drawing of the colon showing the points of penetration of the vasa recta around the bowel cercumference and mucosal diverticular formation
Diverticular disease of the colon includes a constellation of symptoms that range from wild irregularities in defecatory functions to bleeding and the consequences of severe intraabdominal inflammation.

The term “Diverticulosis” was proposed independently in 1914 by Case and de Quervain to describe the condition characterized by the presence of uncomplicated and non inflamed colonic mucosal pouches (pict 2). 


Picture 2: Left-sided colon diverticulosis with most diverticula located in sigmoid and descending segments of the colon.

The terms “Diverticulitis” and “Peridiverticulitis” indicate inflammation in and around diverticula (pict 3). The distinction between diverticulosis and diverticulitis is not always clear and so it is helpful to adopt the nomenclature ”Diverticular Disease” to encompass the complicated as well as the uncomplicated state (29).


Picture 3: Diverticulitis and Peridiverticulitis with some of its consequent complications (peri-colic abscess, communication ‘’fistula” of the colon with urinary bladder, small intestine and skin)

As stated in the main text diverticular disease is a disease due to multiple factors: The anatomy intrinsic to the colon, structural colonic wall changes with age, motility dysfunction and lack of dietary fiber all contribute to the development of diverticulosis (25).

The dietary fiber factor has been extensively examined in the main text.  Among the other factors it is worth refering colonic motility changes in diverticular disease. It has been shown (30,31) that contraction of the circular muscle of the colon  produce colonic segmentation, a motility process in which proximal and distal segmental muscular ring-type contractions separate the lumen of the colon into isolated closed high pressure chambers. The strong occlusive contractions at both ends of the chambers lead to marked segmental increases in intraluminal pressure which may predispose to herniation of the mucosal diverticula at the sites where the blood vessels penetrate the circular muscular layers of the colon. As the sigmoid colon is the segment of the colon with the smallest diameter elevation of intraluminal pressure will result in even greater increases of wall tension compared to other segments of the colon (32).

Application of the principles of the law of Laplace may explain in part the development of colonic diverticula. According to the law the pressure (P) is proportional to the wall tension (T) and inversely proportional to the radius (R) of the colon-that is P=k*T/R (where k is conversion factor) (25,32) (pict. 4) . 


Picture 4: Painter’s conception of formation of ‘’little bladders’’ in sigmoid colon. Intraluminal pressure rises higher when contractions occlude the lumen and form isolated segments which results in pulsion diverticula formation.
Normally, intraluminal pressure is the same throughout the colon. However, segmentation of the colon is believed to be exaggerated in diverticulosis.

In general, The mechanism of genesis (pathogenesis) of diverticular disease remains unclear as yet. However, it is the result of complex interactions between colonic structure, intestinal motility, diet and genetic factors.



REFERENCES


1/   Trowell H.C. Dietary Fibre and Colonic Diseases. Monograph. The Present                   State of Knowledge No 6, Norgine Ltd, London,1975
 2/   Trowell H.C. Dietary Fibre: Metabolic and Vascular Diseases. Monograph. The Present State of Knowledge No 7, Norgine Ltd, London,1975
 3/   Jenkins D.J.A., Wolever T.M.S., Jenkins A.L. Fiber and Other Dietary Factors Affecting Nutrient Absorption and Metabolism. In: Modern Nutrition in Health and Disease. Shils M.E., Olson J.A., Shike M., Ross C. A.(Eds),9th ed., Lippincott,William & Wilkins (Publ.), 1999, pp.1108-1136*
 4/   Trowel H.C., Southgate D.A.T., Wolever T.M.S. et al. Lancet 1976; i,967
 5/   Greenwald P. Dietary Fibers. In: De Vita V.T.Jr., Helman S., Rosenberg S.A. (Eds), Lippincott,William & Wilkins (Publ.),Philadelphia-N.Y., 2001, pp.1127-1140*
 6/   Alpers D.H. and Kleins S. General Nutritional Principles. In:Yamada’s Textbook of Gastroenterology. Yamada T., Alpers D.H., Laine L., Kaplowitz N., Owyang C., Powell D.W.(Eds),4th Ed., Lippincott,William & Wilkins (Publ.),Philadelphia-N.Y., 2003,  pp 935-977*
 7/   Anderson J.W. Nutritional Management of Diabetes Mellitus. In: Modern Nutrition in Health and Disease. Shils M.E., Olson J.A., Shike M., Ross C. A.(Eds),9th ed., Lippincott,William & Wilkins (Publ.), 1999, pp.2147-2198*
 8/   Aldoori W.H., Giovannucci E.L., Rochett H.R. et al. A Prospective Study of Dietary Fiber Types and Symptomatic Diverticular Disease in Men. J. Nutr., 1998; 128: 714-719
 9/   Korzenik J.R. Case Closed? Diverticulitis: Epidemiology and Fiber. J. Clin. Gastroenterol., 2006; 40 (7 supp.3): S112- S116.
10/   Traber P.G. Carbohydrate Assimilation. In:Yamada’s Textbook of Gastroenterology. Yamada T., Alpers D.H., Laine L., Kaplowitz N., Owyang C., Powell D.W.(Eds),4th Ed., Lippincott,William & Wilkins (Publ.),Philadelphia-N.Y., 2003,  pp 753-791*
11/   Manousos O.N., Vrachliotis G., Papaevangelou G. et al. Relation of        Diverticulosis  of the Colon to Enviromental Factors in Greece. Am. J. Dig. Dis., 1973; 18: 174-176
12/   Manousos O.N., Day N.E., Tzonou A. et al. Diet and Other Factors in the Aetiology of Diverticulosis: An Epidemiological Study in Greece. Gut, 1985; 26: 544-549
13/   Painter N.S. and Burkitt D.P. Diverticular Disease of the Colon: A Deficiency Disease of Western Civilazation. BMJ, 1971; 2:450-454
14/  Burkitt D.P.,Walker A.R., Painter N.S. Effect of Dietary Fibre on Stools and the Transit-Times, and its Role in the Causation of Disease. Lancet, 1972, 2: 1408-1412
15/   Burkitt D.P. Diverticular Disease of the Epidemiological Evidence Relating it to Fibre-Depleted Diets. Trans. Med. Soc. Lond., 1973; 89:81-84   
16/    Aldoori W.H., Giovannucci E.L., Rimm E.B., et al. A prospective Study of Diet and the Risk of Symptomatic Diverticular Disease in Men. Am. J. Clin. Nutr., 1994; 60:757-764 
17/   Gear J.S., Ware A., Furdson P., et al. Symptomless Diverticular Disease and Intake of Dietary Fibre. Lancet. 1979; i:511-514
18/   Nair P. and Mayberry J.F. Vegetarianism, Dietary Fibre and Gastro-intestinal Disease. Dig. Dis., 1994; 12:177-185
19/   Wess L., Eastwood M.A., Edwards C.A. et al. Collagen Alteration in an Animal Model of Colonic Diverticulosis. Gut, 1996; 38:701-706
20/   Thorson G. and Goldberg M. Benign Colon: Diverticular Disease. In: The ASCRS Textbook of Colon and Rectal Surgery. Wolff B.G., Fleshman J.W., Beck D.E., Pemperton J.H., Wexner S.D. (Eds.), Springer Sci.(Publ.). 2007, pp. 269-285
21/   Mortensen N.J.Mc C. and Kettlewell M.G.W. Colonic Diverticular Disease. In: Oxford Textbook of Medicine. Warrell D.A., Cox T.M., Firth J.D., Edward J.,Jr., Benz M.D. (Eds.),4th Ed., Oxford Press, 2003, pp. 3894-3901*
22/   Kieff B.J., Eckert G.J., Imperiale T.F. Is Diverticulosis Associated with Colorectal Neoplasia? A Cross-sectional Colonoscopic Study. Am. J. Gastroenterol., 2004; 10:2007-2011
23/   Jun S. and Stolmlman N. Epidemiology of Diverticular Disease. Best Pract. Res. Clin. Gastroenterol., 2002, 16: 529-542
24/   Segal I., Solomon A., Hunt J.A. Emergence of Diverticular Disease in the Urban South African Black. Gastroenterology, 1979; 72:215-219
25/   Parra- Blanco A. Colonic Diverticular Disease: Pathophysiology and Clinical Picture. Digestion, 2006; ( 73 suppl.),1: 47-57
26/   Parks T.G. Natural History of Diverticular Disease of the Colon. Clin. Gastroenterol., 1975; 4: 53-69
27/   Rodkey G.V. and Welch C.E. Changing Patterns in the Surgical Treatment of Diverticular disease. Ann. Surg., 1984, 200:466
28/   Miura S., Kodaira S., Shatari T., et al. Recent Trends in Diverticulosis of the Right Colon in Japan: Retrospective Review in a Regional Hospital. Dis. Colon Rectum, 2000; 43:1383-1389
29/   Parks T.G. Diverticular Disease of the Colon. In: Maingot’s Abdominal Operations. Schwarts S.I.. Ellis H. (Eds.), Appleton-Century-Crofts (Publs.), Norwalk, Connecticut, 1985, pp. 1327-1350
30/   Painter N.S., Truelove S.C. The Intraluminal Pressure Patterns in Diverticulosis of the Colon. Gut, 1964;5:365-369
31/   Painter N.S., Truelove S.C., Ardran G.M., Tuckey M. Segmentation and the Localization of Intraluminal Pressures in the Human Colon, with Special Reference to the Pathogenesis of Colonic Diverticula. Gastroenterology, 1965; 49:169-177
32/   Young-Fadok T.M., Sarr M.G. Diverticular Disease of the Colon. In: Yamada’s Textbook of Gastroenterology. Yamada T., Alpers D.H., Laine L., Kaplowitz N., Owyang C., Powell D.W.(Eds),4th Ed., Lippincott,William & Wilkins (Publ.),Philadelphia-N.Y., 2003,  pp 3499-3530*  



* Comp. Print. Pag. Of pdb. doc