Kidney Diseases e . 1982. Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney International 22:112-26. Polinsky, M.S., and Gruskin, A.B. 1984. Aluminum toxicity in children with chronic renal failure. Journal of Pediatrics 105:758-61. Pullman, T.N.; Alving, A.S.; Dern, R.J.; and Landowne, M. 1954. The influence of dietary protein intake on specific renal functions in normal man. Journal of Laboratory and Clinical Medicine 44:320-32. Purkerson, M.L.; Joist, J.H.; Greenberg, J.M.; Kay, D.; Hoffsten, P.E.: and Kiahr, 8. 1982. Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats. Thrombosis Research 26:227-40. Purkerson, M.L.; Joist, J.H.; Yates, J.; Valdes, A.; Morrison, A., and Klahr, S. 1985. Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation. Proceedings of the National Academy of Science. Medical Sciences 82:193-97. Rodriguez-Iturbe, B.; Garcia, R.; Rubio, L.; Cuenca, L.; Treser, G.; and Lange. K. 1976. Epidemic glomerulonephritis in Maracaibo: evidence for progression to chronicity. Clinical Nephrology 5:198-206. Rosman, J.B.; Meijer, S.; Sluiter, W.J.; Terwee, P.M.; Piercbec, T.P.; and Donker, A.J. 1984. Prospective randomized trial of early dietary protein restriction in chronic renal failure. Lancet 8(December):1291-95. Rowe, J.W.; Andres, R.; Tobin, J.D.; Norris, A.H.; and Shock, N.W. 1976. Age-adjusted standards for creatinine clearance. Annals of Internal Medicine 84:567-69. Rutherford, W.E.; Blondin, J.; Miller, J.P.; and Greenwalas, V. 1977. Chronic progressive renal disease: rate of change of serum creatinine concentration. Kidney International 11:62-70. Salusky, I.B.; Fine, R.N.; Nelson, P.; Blumenkrantz, M.J.; and Kopple, J.D. 1983. Nutritional status of children undergoing continuous ambulatory peritoneal dialysis. American Journal of Clinical Nutrition 38:599-611. Schmidt, R.W.; Blumenkrantz, M.; and Wiegmann, T.B. 1983. The dilemmas of patient treatment for end-stage renal disease. American Journal of Kidney Diseases 3:37-47. Senekjian, H.O.; Stinebaugh, B.J.; Mattioli, C.A.; and Suki, W.N. 1979. Irreversible renal ret following vesicoureteral reflux. Journal of the American Medical Association 41:160-62. Sherrard, D.J. 1983. Metabolic causes of nephrolithiasis. Western Journal of Medicine 138:541-45, Smith, L.H.; Van den Berg, C.J.; and Wilson, D.M. 1978. Current concepts in nutrition: nutrition and urolithiasis. New England Journal of Medicine 298:87-89. Striker, G.E.; Nagle, R.B.; Kohnen, P.W.; and Smuckler, E.A. 1969. Response to unilateral nephrectomy in old rats. Archives of Pathology 87:439-42. Suzuki, S.; Shapiro, R.; Mulrow, P.J.; and Tan, S.Y. 1980. Urinary prostaglandin E> excretion in chronic renal disease. Prostaglandins Medicine 4:377-82. Tisher, C.C., and Madsen, K.M. 1986. Anatomy of the kidney. In The Kidney. 3d ed.,ed. B.M. Brenner and F.C. Rector, Jr., pp. 3-60. Philadelphia, PA: Saunders. Toback, FG. 1977. Amino acid enhancement of renal regeneration after acute tubular necro- sis. Kidney International 12:193-98. 401 @) Nutrition and Health Torres, V.E.; Velosa, J.A.; Holley, K.E.; Kelalis, PP.; Stickler, G.B.; and Kurtz, S.B. 1980. The progression of vesicoureteral reflux nephropathy. Annals of Internal Medicine 92:776-84, Walser, M. 1975. Ketoacids in the treatment of uremia. Clinical Nephrology 3:180-86. Wilmore, D.W., and Dudrick, S.J. 1969. Treatment of acute renal failure with intravenous essential L-amino acids. Archives of Surgery 99:669-73. Wiseman, M.J.; Hunt, R.; Goodwin, A.; Gross, J.L.; Keen, H.; and Viberti, G.C. 1987. Dietary composition and renal function in healthy subjects. Nephron 46:37— 42. Wolfson, M.; Strong, C.J.; Minturn, D.; Gray, D.K.; and Kopple, J.D. 1984. Nutritional status and lymphocyte function in maintenance hemodialysis patients. American Journal of Clinical Nutrition 37:547-55. Zager, R.A., and Venkatachalam, M.A. 1983. Potentiation of ischemic renal injury by amino acid infusion. Kidney International 24:620-25. Zager, R.A.; Johannes, G.; Tuttle, S.E.; and Sharma, H.M. 1983. Acute amino acid nephrotoxicity. Journal of Laboratory Clinical Medicine 101:130-40. Zucchelli, P.; Cagnoli, L.; Casanova, S.; Donini, U.; and Pasquali, S$. 1983. Focal glomerulosclerosis in patients with unilateral nephrectomy. Kidney International 24:649-55. Zurier, R.B.; Damjanov, I.; Sayadoff, D.M.; and Rothfield, N.F. 1977. Prostaglandin E, treatment of NZB/NZW F, hybrid mice. II. Prevention of glomerulonephritis. Arthritis and Rheumatology 20:1449-56. 402 a Chapter 10 Gastrointestinal Diseases Now good digestions wait on appetite, and health on both. William Shakespeare Macbeth, IIIL.iv. (1605-1606) introduction The gastrointestinal system extracts nutrient- and energy-yielding mole- cules from plant and animal foods and digests them to smaller subunits that can be absorbed. Here also, indigestible food wastes are prepared for excretion. The full complement of essential nutrients is required for normal gastrointestinal function, as for any other bodily system, and malnutrition can adversely affect nutrient digestion and absorption. Similarly, infectious and other diseases that impair gastrointestinal function can impair nutri- tional status. These interrelationships are important in infant malnutrition as well as in the adult conditions reviewed in this chapter. Historical Perspective The history of digestive physiology is remarkable both for the early under- standing of its importance to nutrition and health and for the imaginative research experiments that elucidated its function. This early history was reviewed by McCollum (1957). Hippocrates (460-370 B.C.) believed that although there were many differ- ent kinds of foods, there was only one aliment. As early as the second century A.D., Galen (130-200) studied digestion in swine and concluded that the function of the stomach was to convert food into particles small enough to be absorbed. Inthe 18th century, de Reaumer (1683-1757) investigated digestion in birds. He inserted food into metal tubes closed at the ends by screens and placed 403 ie Nutrition and Health the tubes in the stomach of a predatory bird. When the bird regurgitated the tubes, he was able to observe the dissolution of bones and the partial dissolution of meat in a fluid that tasted salty and bitter. Later, he performed similar experiments in dogs. Similar studies were conducted by Stevens in 1777 using as a subject a man who had earned his living for the past 20 years by swallowing stones. Stevens placed foods in perforated silver containers, and the man swallowed them. By the time the containers were recovered in stool, all foods except seeds were observed to be completely dissolved. Perhaps the best known human digestive experiments were conducted by Beaumont (1785-1853) on a patient, Alexis St. Martin, who had a perma- nent opening from his stomach to the outside of his body (a fistula) as a result of a gunshot wound. Beaumont had easy access to and from St. Martin’s stomach through the fistula and was able to observe gastric action on many types of foods. Modern digestive physiology began in the 20th-century with the identifica- tion of digestive enzymes. Although the basic principles of digestive phys- iology have been known for decades, the complex neuroendocrine interac- tions between the brain, digestive tract, and other tissues that control and regulate gastrointestinal function are as yet incompletely understood and are the subject of much current investigation (Nicholl, Polak, and Bloom 1985). Significance for Public Health Data from several national surveys provide evidence that these gastroin- testinal conditions are extremely prevalent and cause considerable impair- ment of health and functional ability in the American population. In 1984, the incidence of digestive diseases and conditions that required medical attention or restricted normal activities was 7.6 per 100 persons per year. The incidence rate was highest for infants, children, and young adults (10.3 to 11.9 per 100) and lowest for adults ages 45 to 64 (4.7 per 100). Gastroin- testinal conditions were responsible for an average of 32 days per 100 persons per year of limited activity among people of all ages, but among adults over age 65, the rate of restricted activity was 63 days per 100 persons per year (NCHS 1986). Also in 1984, diseases of the digestive system accounted for a total of over 4 million hospitalizations at an average length of stay of 6.3 days. For patients under age 15, the leading gastrointestinal causes of hospitalization were Gastrointestinal Diseases C) appendicitis, noninfectious gastroenteritis, and colitis. For patients ages 15 to 44, gastroenteritis and colitis were the leading causes. For adults ages 45 to 64, ulcers and gallstones predominated, and for adults over age 65, cancer, diverticula, and gallstones were the most important causes (NCHS 1987b). The total direct medical cost for gastrointestinal diseases in the United States is estimated at $17 billion per year (Klurfeld 1987). Mouth, pancreas, colon, and rectal cancers were responsible for about 20 percent of all cancer deaths in 1986. There were 245,000 new cases of cancers of the mouth and digestive tract, and these diseases caused 125,000 deaths that year. Cancers of the colon and rectum are the second leading cause of new cancer cases in men and the third leading cause in women (see chapter on cancer). In 1986, 60,000 Americans died of colon and rectal cancers (Silverberg and Lubera 1987). The interaction between infectious diarrheal diseases and malnutrition is the primary cause of infant and child mortality and morbidity worldwide (see chapter on infections and immunity), accounting for about 1.5 billion diarrheal episodes annually (Chen and Scrimshaw 1983). In the United States, these conditions are relatively rare but still were estimated to be responsible for about 5 percent of all infant deaths in 1985 (Wegman 1986). Because most persons with diverticular disease are asymptomatic, the true prevalence of this condition is unknown. Diverticular disease is common in industrialized countries but extremely rare among rural populations in developing countries. Its frequency ranges from about 5 to 40 percent of subjects in Westernized nations (Painter 1985). Among Americans sur- veyed, 8.4 out of every 1,000 persons reported having diverticula (NCHS 1986). Frequency increases with age, and up to 70 percent of people from age 40 to 70 may be affected (Taylor and Duthie 1976). In 1980, diver- ticulosis caused 200,000 hospitalizations, incurring health care costs that exceeded $300 million dollars (Almy and Howell 1980). For hospitaliza- tions recorded in 1984, the average hospital stay for such disorders was 8 days (NCHS 1987b). Data from the National Hospital Discharge Survey, conducted by the National Center for Health Statistics, indicate that gallstones were respon- sible for 488,000 operations annually in the United States; the average hospital stay for this condition was 7.6 days in 1984 (NCHS 1987b). Nearly 3,000 Americans died of complications of gallbladder disease in 1986 (NCHS 1987a). 405 C Nutrition and Health The estimated incidence of inflammatory bowel diseases increased from 1.9 cases per 100,000 population in the period 1935 to 1954 to 6.6 cases per 100,000 in 1965 to 1975. Projections based on incidence rates suggested that 20,000 to 25,000 new cases of this condition were admitted to hospitals in the United States in 1980 (Kirsner and Shorter 1982). The National Center for Health Statistics reported that 9.6 of every 1,000 Americans surveyed stated that they had enteritis or colitis (NCHS 1986). Chronic liver disease and cirrhosis are the ninth leading cause of total deaths and the seventh cause of disease in the United States. They caused the death of more than 26,000 Americans in 1986 (NCHS 1987a). These conditions are discussed in more detail in the chapter on alcohol. Scientific Background: The Digestive System The primary functions of the digestive system are to ingest, digest, absorb, transport, and excrete food components. It accomplishes these tasks by means of the various digestive organs of the body and the enzymes listed in Table 10-1, as well as by response to the numerous regulatory neu- rochemical and hormonal substances produced by the brain, organs of the digestive system, and other tissues that are summarized in Table 10-2. This complex system extracts essential vitamins and minerals from diverse plant and animal foods and breaks down the carbohydrate, protein, and fat molecules in these foods to common subunits that can be absorbed. Once absorbed, these subunits are used as building blocks for the molecules that make up body tissues or for energy production. The structure and function of the digestive system, its response to disease, and the relationship between gastrointestinal function and nutritional status have been re- viewed extensively (Floch 1981; Green and Greene 1984; LSRO 1987; Martin, Mayes, and Rodwell 1985; Trowell, Burkitt, and Heaton 1985). The cellular lining of the digestive tract has a very large surface area and is readily exposed to potential mechanical, thermal, and microbial damage. Its anatomic location, gastric acidity, and elements of the immune system protect it from damage (Cole and Kagnoff 1985; Kagnoff 1983). This topic is reviewed in the chapter on infections and immunity. Mouth The physical and chemical breakdown of food begins in the mouth with the physical action of chewing and the enzymatic action of saliva. The parotid and submaxillary salivary glands produce fluids and enzymes that convert smaller carbohydrates and proteins to sugars and amino acids. Fats, how- ever, are not generally altered in the mouth. Secretion of salivary fluid 406 LOb Summary of Digestive Processes Table 10-1 Source of Secretion and Stimulus for Secretion Enzyme Method of Activation and Optimal Conditions for Activity Substrate End Products or Action Salivary glands: Secrete sali- va in reflex response to presence of food in oral cavity. Salivary amylase Chloride ion necessary. pH 6.6-6.8. Starch Glycogen Maltose plus 1:6 glucosides (oligosac- charides) plus malto- triose. Lingual glands Lingual lipase pH range 2.0-7.5; optimal, 4.0-4.5. Short-chain primary ester link at sn-3 Fatty acids plus 1,2- diacylglycerols. Stomach glands: Chief cells and parietal cells secrete gastric juice in response to - reflex stimulation and Pepsin A (fundus) Pepsin B (pylorus) Pepsinogen converted to active pepsin by HCl. pH 1.0-2.0. Protein Peptides. action of gastrin. Rennin a nao for Casein of milk Coagulates milk. Pancreas: Presence of acid Trypsin Trypsinogen converted to Protein Polypeptides. chyme from the stomach active trypsin by enteroki- Peptides Dipeptides. activates duodenum to nase of intestine at pH produce (1) secretin, which 5.2-6.0. Autocatalytic at pH hormonally stimulates flow 7.9. OS ecevaiakt Ee oh Chymotrypsin Secreted as chymotrypsino- _ Protein Same as trypsin. lolecy inin, wae’ gen and converted to active —_ Peptides More coagulating stimulates the production form by t in. 0H 8.0 f tk of enzymes. y trypsin. pH 8.0. power for milk. Elastase Secreted as proelastase and —_— Protein Polypeptides. converted to active form by _— Peptides Dipeptides. trypsin. nN Saseasiq, [BUTISa}U 1oIseL) 80¥ Table 10-1 (continued) Source of Secretion and Stimulus for Secretion Pancreas (continued) Enzyme Carboxypeptidase Pancreatic amylase Lipase Ribonuclease Method of Activation and Optimal Conditions for Activity Secreted as procarboxypepti- dase, activated by trypsin. pH 7.1. Activated by bile salts, phospholipids, colipase. pH 8.0. Deoxyribonuclease Cholesteryl ester hydrolase Phospholipase A, Activated by bile salts. Secreted as proenzyme, activated by trypsin and Ca2+, Substrate Polypeptides at the free carboxyl end of the chain Starch Glycogen Primary ester linkages of triacyl- glycerol Ribonucleic acid Deoxyribonucleic acids Cholesteryl esters Phospholipids End Products or Action Lower peptides. Free amino acids. Maltose plus 1:6 glucosides (oligosac- charides) plus maltotriose. Fatty acids, mono- acylglycerols, di- acylglycerols, glycerol. Nucleotides. Nucleotides. Free cholesterol plus fatty acids. Fatty acids, lyso- phospholipids. yyeay, pue uonwiny n Liver and galibladder: Cho- Fats—also lecystokinin, a hormone neutralize acid from the intestinal chyme mucosa—and possibly also gastrin and secretin— stimulate the gallbladder and secretion of bile by the liver. (Bile salts and alkali) Fatty acid-bile salt conjugates and finely emulsified neutral fat-bile salt micelles and liposomes. Small intestine: Secretions of _Aminopeptidase Brunner’s glands of the Polypeptides at the Lower peptides. free amino end of Free amino acids. duodenum and glands of the chain Lieberkfihn. Dipeptidases Dipeptides Amino acids. Sucrase pH 5.0-7.0. Sucrose Fructose, glucose. Maltase pH 5.8-6.2. Maltose Glucose. Lactase pH 5.4-6.0. Lactose Glucose, galactose. Trehalase Trehalose Glucose. Phosphatase pH 8.6. Organic phosphates Free phosphate. Isomaltase or 1:6 1:6 glucosides Glucose. glucosidase Polynucleotidase Nucleic acid Nucleotides. Nucleosidases Purine or pyrimidine Purine or pyrimidine (nucleoside nucleosides bases, pentose phosphorylases) phosphate. Source: Murray, R.K.; Granner, D.K.; Mayes, P.A.; and Rodwell, V.W. 1988. Harper's Biochemistry, pp. 584-85. 21st ed. San Mateo, CA: Appleton & Lange. Copyright Appleton & Lange 1988, reprinted with permission. Qn sasvasiq] [euUNsa}UIONSELD O Nutrition and Health Table 10-2 Gastrointestinal Hormones Hormone Localization Major Action Gastrin Gastrin antrum, Gastric acid and pepsin secretion duodenum Cholecystokinin (CCK) Duodenum, Pancreatic amylase secretion jejunum Secretin Duodenum, Pancreatic bicarbonate secretion jejunum Gastric inhibitory Small bowel Enhances glucose-mediated peptide insulin release. Inhibits gastric acid secretion Vasoactive intestinal Pancreas Smooth muscle relaxation; polypeptide stimulates pancreatic bicarbonate secretion Motilin Small bowel Initiates interdigestive intestinal motility Somatostatin Stomach, Numerous inhibitory effects duodenum, pancreas Pancreatic polypeptide Pancreas Inhibits pancreatic bicarbonate and protein secretion Enkephalins Stomach, Opiate-like actions duodenum, gallbladder Substance P Entire gastroin- Uncertain testinal tract Bombesin-like Stomach, Stimulates release of gastrin and immunoreactivity duodenum CCK Enteroglucagon Pancreas, small Unknown intestine Source: Adapted from Martin, Mayes, and Rodwell 1985. depends on neuroendocrine regulation and is affected by the sight, smell, taste, and thought of food. The role of salivary secretions is discussed further in the chapter on dental diseases. Esophagus Swallowed food enters the esophagus and travels through it to the stomach. At the esophagogastric junction, the lower esophageal sphincter muscle 410 Gastrointestinal Diseases le normally prevents gastric fluids from flowing into the body of the esophagus. Neurohormonal mechanisms control the pressure of this sphincter and, as discussed below, may be affected by digestion of certain foods in the small intestine (Pope 1983). Stomach In the stomach, food is broken down into increasingly smaller particles and compounds by mechanical, chemical, and enzymatic means. The acidic gastric secretions contain the enzyme pepsin, which converts proteins into short chains of amino acids, and gastric lipases, which, along with lingual lipase, initiate triglyceride digestion. The movement of the stomach emp- ties liquids into the duodenum continuously while food solids are reduced to the consistency of paste. The selective rates of discharge of substances into the duodenum may be related to their caloric density (Brener, Hendrix, and McHugh 1983), to effects of neuropeptides (Morley 1982), or other hormones that control gastrointestinal function. Small Intestine Most digestion and absorption take place in the small intestine, as do modulation of fluid balance, orderly advancement of food residues into the colon, reabsorption of bile salts, and absorption of vitamin B,,. The spe- cialized absorbing cells, enterocytes, are distinguished by numerous mi- crovilli that greatly increase the absorptive surface area. This surface epithelium contains enzymes that split carbohydrates and small peptides. These cells also convey nutrients to the circulatory and lymphatic systems, which distribute them to the rest of the body. Digestion is primarily accom- plished by enzymes secreted by the pancreas and delivered to the small intestine: amylase, which converts starch to sugar; lipase, which splits triglycerides into fatty acids and monoglycerides; and trypsin and chymo- trypsin, which split proteins into amino acids and small peptides. Other substances such as secretin, which is produced by the cells of the duo- denum, and pancreatic polypeptide help to control the level of intestinal acidity. The absorption of sugars, peptides, amino acids, and fatty acids proceeds in the upper part of the small intestine (jejunum), whereas bile salts and vitamin B,, are absorbed in the distal portion or the ileum. By the time food residues pass the ileum, most usable food molecules have been digested and absorbed, so that only small amounts of carbohydrates (Levine and Levitt 1981), other macronutrients, and fiber are delivered to the colon. 411 C Nutrition and Health Liver and Biliary Tract The liver, the largest body organ, synthesizes proteins, oxidizes fat, regu- lates the release of glucose from glycogen, and detoxifies drugs, hormones, and other potentially deleterious substances. It also converts cholesterol into bile acids and secretes hepatic bile, which is concentrated in the gallbladder before delivery into the duodenum. Pancreas The pancreas has both exocrine and endocrine functions that influence digestion and nutrient metabolism. It secretes hormones such as glucagon and insulin into the blood, and digestive enzymes, principally amylase, lipase, and proteases, into the digestive tract. Colon The principal functions of the large intestine are to concentrate, store, and excrete food wastes. The colon contains large numbers of bacteria, which produce enzymes that act on the remaining food residues, fiber, and cells and mucus sloughed from the upper intestinal tract. The products of this bacterial digestion and fermentation include short-chain fatty acids (e.g., propionic, butyric); gases such as carbon dioxide, methane, and hydrogen; and other volatile substances (Cummings 1983). The ascending colon has a thinner muscle wall, a greater luminal volume, and a much larger popula- tion of bacteria than does the more muscular descending colon, which slows the movement of feces until they are partially dehydrated, concen- trated, and ready to be expelled through the anus. Key Scientific Issues e Effects of Dietary Factors on Gastrointestinal Function ® Role of Dietary Factors in Intestinal Disorders @ Role of Dietary Factors in Gallbladder Disease ® Role of Dietary Factors in Other Digestive Disorders Effects of Dietary Factors on Gastrointestinal Function The diet must provide sufficient nutrients and energy to synthesize the rapidly renewing cells that line the gastrointestinal tract, the enzymes that digest and transport nutrients across the intestinal wall, and the regulatory neuropeptides and other hormones that control these processes. Digestive function can be seriously disrupted by inadequate nutrition as well as by 412 Gastrointestinal Diseases CO) infections, toxic substances, and chronic disease. The composition of the diet can influence the rate of reproduction of bacteria in the intestine and, thus, can affect nutrient absorption. Dietary components affect the mor- phology and synthesis of the cells that line the digestive tract as well as fecal composition and elimination. Malnutrition Nutritional inadequacies can cause abnormalities of the mucous mem- branes of the mouth, tongue, and digestive tract. Frequent consequences of starvation and protein-energy malnutrition are an inability to absorb or digest food molecules and decreased pancreatic function (Kerndt et al. 1982). As discussed in the chapter on infections and immunity, cellular immune functions are depressed in malnutrition and starvation. Because the cells that line the digestive tract are renewed every few days, nutrient deficiencies can be reflected in ulceration, hemorrhage, or loss of resis- tance to micro-organisms that are usually not pathogenic. Atrophy of the gastric and intestinal mucosa is an especially serious consequence of malnutrition. The microvilli flatten and lose much of their absorptive surface and no longer produce adequate digestive or absorptive enzymes. Food passes undigested and unabsorbed into the colon, where bacterial action induces gas production and the influx of water, inducing diarrhea and further damage to the digestive tract. These effects are most severe in young children and cause a characteristic cycle of malnutrition, infectious disease, malabsorption, and diarrhea that is common throughout the developing world (Chandra 1983; Hamilton 1985; see chapter on infec- tions and immunity). They also occur among patients with chronic diseases that interfere with adequate nutrition, anorexia nervosa, impaired immuno- logic responses to certain food substances (Floch 1981), or severe micro- bial infections of the gastrointestinal tract (DuPont 1984). Once the microvilli are reduced, recovery of gastrointestinal function occurs only slowly, if at all. Because food intake induces diarrhea, enteral and parenteral feeding methods that bypass the digestive tract must be employed along with immediate efforts to prevent dehydration, edema, vitamin and mineral deficiencies, and excessive accumulation of body fat (Roediger 1986). In various conditions in which the bowel mucosa are compromised by disease, macromolecules that are normally excluded may be absorbed. These, especially protein molecules, may alter systemic immune functions (see chapter on infections and immunity). 413 le Nutrition and Health Effects of Fiber Most studies of the relationship of diet to gastrointestinal function have focused on the role of dietary fiber. Physiologic responses to dietary fiber occur within the entire length of the gastrointestinal tract. Dietary fibers from different plant sources have diverse chemical constituents; some are soluble and some are insoluble. The major constituents of dietary fiber are cellulose, hemicelluloses, pectins, mucilages, gums, algal polysaccha- rides, and lignin. Fibers from different foods have different effects on water-holding capacity, viscosity, ion-exchange capacity, binding of miner- als and organic compounds, bacterial fermentation, and transit time. Food processing can alter these effects. In general, dietary fibers from many sources increase the flow of saliva, improve feelings of satiety, delay digestion and absorption, bind intestinal bile acids, increase the mass of intestinal bacteria, decrease the time stools take to pass through the bowel, and increase stool weights and frequency of elimination (Trowell, Burkitt, and Heaton 1985). Although animal studies demonstrate that fiber intake increases the length of the intestine and causes greater proliferation of mucosal cells, these effects cannot be readily distinguished from those of other dietary factors, and their applicability to humans is uncertain (LSRO 1987). Some potential adverse effects have also been observed very infrequently with diets high in fiber, including intestinal obstruction (primarily due to gel-forming fiber); interference with absorption of calcium, magnesium, zinc, manganese, and iron; inflammation of the bowel mucosa (with certain gums); and colonic volvulus (Klurfeld 1987). Role of Dietary Factors in Intestinal Disorders Diseases of the gastrointestinal tract affect food consumption, digestion, absorption, and excretion. Although one might expect dietary factors to be important in preventing and treating such conditions, research in this area has not been extensive, and present understanding is limited. The dietary factors most frequently associated with gastrointestinal illnesses are alco- hol (liver disease and cancer); inadequate fiber (constipation, hemor- rhoids, diverticular disease, and possibly some types of cancer); fat (gall- bladder disease and possibly some types of cancer); and substances suchas gluten in wheat (celiac disease in genetically predisposed individuals). Cancer The effects of dietary risk factors such as alcohol, fat, and food mutagens and carcinogens on the causation of cancers of the gastrointestinal tract, 414 Gastrointestinal Diseases @| and the effects of substances such as fiber or vitamin A in their prevention, are reviewed in the chapter on cancer. Celiac Disease This genetic-immunologic disorder, also known as nontropical sprue or gluten-induced enteropathy, results from an immunologic reaction to the gluten fraction of proteins from wheat, rye. or oats (Chandra and Sahni 1981). Its symptoms may be silent and its prevalence is uncertain, but it is thought to affect about | in 2,500 persons in the United States (Gluten Intolerance Group 1982). When patients with this disorder ingest gluten. the cells that line the small intestine undergo atrophy. causing malnutrition, stunting of growth, and anemia. Although strict removal of gluten from the diet alleviates symptoms and restores the integrity of the intestinal mucosa, some immunologic abnormalities may persist. Neither the fundamental defect nor the genetic basis of celiac disease is understood (Cole and Kagnoff 1985). Constipation The National Center for Health Statistics has reported that more than 20 of every 1,000 persons surveyed state that they suffer from frequent constipa- tion (NCHS 1986). Although constipation, defined as three or fewer bowel movements per week, can be caused by diabetes, hypothyroidism, uremia, neurogenic bowel disorders, abnormalities in the structure of the colon, rectum, or anus, and by various medications, most constipation cannot be attributed to an underlying disease. Instead, dietary intake patterns are widely presumed to cause this condition, in particular, inadequate con- sumption of fiber and, especially in the older person, insufficient fluid intake. The effect may vary with coarseness of bran or degree of cooking (Klurfeld 1987), but numerous studies have demonstrated that increased intake of wheat bran and other sources of insoluble fiber prevents constipa- tion and relieves its symptoms (LSRO 1987). Diverticular Disease Diverticulosis occurs when diverticula, abnormal outpocketings of the intestinal wall, form in the colon and cause pain in the left lower abdomen without fever. Although diverticula may occur over extensive areas of the colon, they do not usually produce demonstrable muscle thickening, changes in intraluminal pressures, or other noticeable symptoms (Fleischner, Ming, and Henken 1964; Weinreich and Andersen 1976). A closely related disease, diverticulitis, which occurs when the outpocket- ings become infected, causes constipation and diarrhea, flatulence, ab- sominal pain, fever, and mucus and blood in the stools (Almy and Howell 0). 415 ie Nutrition and Health Some experts believe that diverticula occur as a result of increased colonic intraluminal pressure needed to eliminate small, hard stools that form as a result of low-fiber diets (Burkitt, Walker, and Painter 1974). The idea that diverticular disease might result from inadequate intake of dietary fiber is supported by animal studies (Cello 1981); by measurements in humans of intestinal transit times, bowel motility, stool weights, and intraluminal pressures (Burkitt, Walker, and Painter 1974; Painter 1985); and by interna- tional comparisons of fiber intake and disease prevalence rates (Mendeloff 1986). Numerous dietary intervention trials have reported beneficial ef- fects of bran and other fiber sources on pain, constipation, and other symptoms as well as on intraluminal pressures (Painter 1985; LSRO 1987). Despite concerns that these studies have not always employed adequate control groups, and despite the needs for further research to define the role of other nutrients such as fat (Manousos et al. 1985) and to identify the most effective sources and types of fiber, fiber supplements are now often used successfully in clinical management of uncomplicated diverticular disease (LSRO 1987). Inflammatory Bowel Disease Nonspecific inflammatory bowel disease includes two diseases of the di- gestive tract: (1) ulcerative colitis, characterized by rectal bleeding, diar- rhea, abdominal cramping and pain, loss of appetite, and weight loss, and (2) Crohn’s disease, a chronic inflammation anywhere throughout the length of the digestive tract that may induce similar symptoms along with fistulas and narrowing of the bowel (Kirsner and Shorter 1982). Their etiology and pathogenesis is unknown. Patients with these conditions can become severely malnourished. Active cases are usually treated with low- residue diets and caloric supplements (Harries et al. 1983), elemental enteral formulas (Neidich, Schussel, and Sharp 1985), or total parenteral nutrition with complete bowel rest (Ostro, Greenberg, and Jeejeebhoy 1985). Potential food allergens, such as carrageenan thickeners and cow milk, and low-fiber diets have been suggested as possible dietary factors aggravating these diseases, but evidence to support such inferences is limited (Kirsner and Shorter 1982). Studies of the relationship of low-fiber diets to etiology or treatment of Crohn’s disease (Jones et al. 1985) have yielded equivocal results, and the role of diet in inflammatory bowel disease is uncertain at this time (LSRO 1987). 416 Gastrointestinal Diseases ) Irritable Bowel Syndrome This condition of pain, abdominal distension, and alteration in bowel habits is thought to be due to an inappropriate reaction of the intestinal wall to stress (Eastwood and Passmore 1983), motility disturbances, diet (Harvey 1985), or food hypersensitivity reactions (Bentley, Pearson, and Rix 1983). Dietary fiber has been used to treat irritable bowel syndrome with demon- strable improvements in constipation (Fielding 1985; Harvey 1985), but its effects on other symptoms have been equivocal (LSRO 1987). Lactose Intolerance An insufficiency of lactase, the enzyme responsible for breakdown of lactose (milk sugar) in the small intestine, can cause lactose intolerance, characterized by abdominal discomfort, pain, and diarrhea as a result of bacterial action on undigested lactose in the colon (Newcomer and McGill 1984), Lactose intolerance is not an inevitable consequence of lactase deficiency. Many lactase-deficient individuals can consume modest amounts of lactose-containing foods with little difficulty. Modification of milk and milk products by addition of lactase, or the use of fermented products such as cheese or yogurt, permits consumption of milk products by such individuals with minimal symptoms (Kolars et al. 1984; Barillas and Solomons 1987). Genetic absence of lactase beyond the age of 5 or 6 occurs among remark- ably high proportions of Asians (85 to 95 percent), Africans (50 to 99 percent), American Indians (85 to 95 percent), and American blacks (70 to 75 percent), as well as among a significant percentage of healthy Caucasians (Gray 1983). Acquired deficiencies can occur as a result of malnutrition (Kerndt et al. 1982) or disease. Reports that lactase activity is lost with aging have not been confirmed (Rosenberg and Bowman 1984). Role of Dietary Factors in Gallbladder Disease Cholesterol, precipitated from supersaturated bile, is the principal compo- nent of most gallstones in patients from industrialized countries. Dietary and diet-related risk factors for this condition include diabetes, obesity (Diehl et al. 1987), and excess intake of calories and dietary fat (Heaton 1985). Many of these are also risk factors for coronary heart disease. Low-fiber diets are associated with gallstone formation. In primates, the action of fiber and other substances that bind cholesterol in the intestine is 4i7 ie Nutrition and Health thought to stimulate the liver to increase production of bile acids, thereby increasing cholesterol solubility (Strasberg, Petrunka,.and Ilson 1976). Although cellulose, hemicellulose, lignin, and other insoluble fiber compo- nents have little effect on blood cholesterol levels, soluble components such as pectin and guar appear to reduce cholesterol levels by 10 to 15 percent (LSRO 1987). Dietary fiber has also been shown to increase the pool of bile acids in laboratory animals (Usuga et al. 1976). In humans, large doses of wheat bran have been reported to increase bile cholesterol solubility (Pomare et al. 1976). One study has indicated that a fiber-rich diet decreases the cholesterol saturation index of bile signifi- cantly (Thornton et al. 1983). Human epidemiologic investigations, how- ever, have not been able to distinguish associations of gallstone formation with varying levels of fiber from associations with other dietary factors such as sugar, alcohol, or other macronutrients (Smith and Gee 1979; Scragg, McMichael, and Baghurst 1984). Role of Dietary Factors in Other Disorders of the Digestive System Cirrhosis The only digestive system disorder besides cancers in the 10 leading causes of death for Americans is cirrhosis (with other chronic liver diseases), and its most powerful dietary correlate is alcohol consumption. This issue is addressed in the chapter on alcohol. Appendicitis Studies based on epidemiologic comparisons between industrialized na- tions and less developed regions have associated low-fiber diets with in- creased prevalence of appendicitis (Segal 1985; Walker and Burkitt 1985). However, Western trends in fiber intake are not consistent with the decline in appendicitis rates during the past few decades, and not all studies have shown that patients with appendicitis consume less fiber than control subjects (Cove-Smith and Langman 1975). Nondietary factors may be more important (Barker et al. 1986). Nevertheless, reports that children 7 to 18 years of age whose fiber intake is in the upper 50th percentile have a 50 percent lower risk of appendicitis (Brender et al. 1985) warrant further investigation. Reflux Esophagitis This disorder, an inflammation of the lower esophagus (heartburn) caused by the backflow of stomach acids, can occur when the lower esophageal sphincter does not contract properly. Alcohol, dietary fat, and both regular 418 Gastrointestinal Diseases @) and decaffeinated coffee (Cohen 1980; Feldman et al. 1981) have been demonstrated to reduce sphincter pressure and to increase reflux. Spices and tomato and orange juices also may affect some persons. Ulcers Gastric and duodenal ulcers are local erosions of the mucosa that result from excessive production of gastric acid and pepsin or from decreased mucosal resistance to these substances. They may result from defects in control of secretion and motility or in synthesis of prostaglandins that either inhibit gastric acid secretion or promote secretion of bicarbonate (Johannson and Bergstrom 1982). The role of nutritional factors in the etiology of ulcers is uncertain. Speculation that refined foods reduce the buffering capacity of stomach secretions (Cleave 1975) has not been con- firmed, nor is evidence sufficient to define a causal relationship for linoleic acid, prostaglandins, or peppers in peptic ulcers. The geographic distribu- tion of duodenal ulcers is not consistently associated with fiber consump- tion (Tovey 1985), nor have clinical studies reported consistent effects of fiber on treatment (LSRO 1987). The observation that increased dietary fiber intake reduces rates of recurrence (Rydning et al. 1982) requires further confirmation. The bland milk-and-cream-based Sippy diet, used in former years, is no longer recommended as treatment; it has not been demonstrated to im- prove symptoms better than any other method, is atherogenic, and is deficient in essential vitamins and minerals (Zucker and Clayman 1983). Today, ulcer patients typically are encouraged to consume a varied and balanced diet, taken slowly in four or five small meals a day, but limited in alcohol, coffee, and other substances that lead to discomfort and pain. Patients should avoid late evening snacking that stimulates nocturnal acid secretion (Floch 1981). Patients are also advised to avoid cigarette smok- ing, which accentuates symptoms and retards healing, and aspirin, which irritates the gastrointestinal mucosa and can cause mucosal hemorrhages. It should be noted that there are many current, very effective phar- macologic therapies for the management of ulcer disease. Implications for Public Health Policy Dietary Guidance General Public Dietary fat, fiber, and alcohol are significant factors associated with gas- trointestinal diseases, although the great variety of these conditions makes 419 C Nutrition and Health generalizations difficult. Because diets that contain a large proportion of calories from fat may be low in fiber, it is often difficult to separate the effects of these substances on gastrointestinal disease. Thus, current evj- dence on whether dietary fiber helps prevent diverticulosis is not con- clusive. Similarly, whether dietary fiber helps prevent inflammatory or irritable bowel disease is uncertain. Nevertheless, evidence that dietary fiber helps treat and prevent constipation and manage chronic diverticular disease suggests the prudence of consuming diets higher in fiber and lower in fat. The strong cause-and-effect association between excessive alcohol con- sumption and the development of chronic liver disease and cirrhosis (as reviewed in the chapter on alcohol) emphasizes that persons who consume alcoholic beverages should do so in moderation. Epidemiologic associa- tions between diet and some types of gastrointestinal cancer (as reviewed in the chapter on cancer) suggest—but do not yet prove—that consuming less fat and alcohol and more fiber would help reduce the risk for these cancers. Evidence on the role of dietary factors in the development of gastric or duodenal ulcers or reflux esophagitis is insufficient to make recommenda- tions at this time. Special Populations Higher intakes of dietary fiber can prevent or relieve symptoms of constipa- tion and chronic diverticular disease. Qualified health professionals should inform persons with these conditions about foods with relatively high fiber contents. Individuals with celiac disease should be provided with informa- tion on foods free of wheat gluten. Those with inflammatory bowel disease, irritable bowel syndrome, lactose intolerance, gallbladder disease, heart- burn, and ulcers should be provided with guidance on diets appropriate to their conditions. Nutrition Programs and Services Food Labels Evidence related to the role of dietary factors in gastrointestinal disease suggests that food manufacturers should include on package labels infor- mation about nutritional content of the food, especially for fat and carbohy- drate components (and including fiber components to the extent permitted by analytical methods). 420 Gastrointestinal Diseases Q Food Services Evidence related to the role of dietary factors in gastrointestinal diseases suggests that food services should include provisions for adequate intake of high-fiber and low-fat foods. Food Products Evidence related to the role of dietary factors in gastrointestinal diseases suggests that the public would benefit from additional products that are low in fat and calories and higher in fiber. Special Populations Persons with gastrointestinal diseases should receive counseling and assis- tance in developing appropriate diets for their particular condition. Qualified health professionals should provide appropriate training and enteral or parenteral nutritional support to persons with conditions that prevent food ingestion, cause malabsorption, or impair bowel function. Research and Surveillance Research and surveillance issues of special priority related to dietary factors affecting gastrointestinal function and diseases of the gastroin- testinal tract should include investigations into: @ The prevalence of gastrointestinal diseases among the population. ® The influence of dietary factors such as specific dietary fibers, fat, and calories on development and function of the digestive tract. ® The influence of dietary factors on the development and release of enzymes and hormones that affect gastrointestinal function. © The role of intestinal flora on nutrient bioavailability. © The most effective nutrient-related interventions to improve the recov- ery of intestinal function following episodes of malnutrition or disease. ® The mechanisms by which dietary fiber may w: rk in the prevention and treatment of bowel cancer, appendicitis, diverticular disease, gall- bladder disease, and other gastrointestinal conditions. ® The identification of specific dietary factors that might influence the causation, prevention, and treatment of celiac disease, inflammatory and irritable bowel syndromes, ulcers, and other gastrointestinal disor- ders. ® The most effective means to achieve dietary counseling to help allevi- ate gastrointestinal disorders. 421 C) Nutrition and Health Literature Cited Almy, T.P., and Howell, D.A. 1980. Diverticular disease of the colon. New England Journal of Medicine 302:324-31. Almy, T.P., and Naitove, A. 1983. Diverticular disease of the colon. In Gastrointestinal disease, 3rd ed., ed. M.H. Sleisenger and }.S. Fordtran. Philadelphia, PA: Saunders. Barillas, C., and Solomons, N.W. 1987. Effective reduction of lactose maldigestion in pre- school children by direct addition of beta-galactosidases to milk at mealtime. Pediatrics 79:766-72. Barker, D.J.P.; Morris, J.; and Nelson, M. 1986. Vegetable consumption and acute appen- dicitis in 59 areas in England and Wales. British Medical Journal 292:927-30. Bentley, S.J.; Pearson, D.J.; and Rix, K.J.B. 1983. Food hypersensitivity in irritable bowel syndrome. Lancet ii:295-97. Brender, J.D.; Weiss, N.S.; Koepsell, T.D.; and Marcuse, E.K. 1985. Fiber intake and childhood appendicitis. American Journal of Public Health 75:399-400. Brener, W.; Hendrix, T.R.; and McHugh, P.R. 1983. Regulation of the gastric emptying of glucose. Gastroenterology 65:76-82. Burkitt, D.P.; Walker, A.R.P.; and Painter, N.S. 1974, Dietary fiber and disease. Journal of the American Medical Association 229:1068-74. Cello, J.P. 1981. Diverticular disease of the colon. Western Journal of Medicine 134:515-23. Chandra, R.K. 1983. Nutrition, immunity, and infection: present knowledge and future directions. Lancet i:688-91. Chandra, R.K., and Sahni, S. 1981. Immunological aspects of gluten intolerance. Nutrition Reviews 39:117-20. Chen, L.C., and Scrimshaw, N.S. 1983. Diarrhea and malnutrition: interactions, mecha- nisms, interventions. New York: Plenum. Cleave, T.L. 1975. Peptic ulcer. In The saccharine disease. New Canaan, CT: Keats Publish- ing. Cohen, S. 1980. Pathogenesis of coffee-induced gastrointestinal symptoms. New England Journal of Medicine 303:122-24. Cole, S.G., and Kagnoff, M.F. 1985, Celiac disease. In Annual review of nutrition, vol. 5, ed. R.E. Olson, E. Butler, and H.P. Broquist, pp. 241-46. Palo Alto, CA: Annu. Rev. Cove-Smith, J.R., and Langman, M.J.S. 1975. Appendicitis and dietary fibre. Gur 16:409. Cummings, J.H. 1983. Fermentation in the human large intestine: evidence and implications for health. Lancet i:1206-9. Diehl, A.K.; Haffner, S.M.; Hazuda, H.P.; and Stern, M.P. 1987. Coronary risk factors and clinical gallbladder disease: an approach to the prevention of gallstones? American Journal of Public Health 77:841-45. DuPont, H.L. 1984. Food-borne infections and poisonings leading to diarrhea. Clinical Nutrition 2(1):13-17. Eastwood, M.A., and Passmore, R. 1983. Dietary fibre. Lancet ii:202-6. 422 Gastrointestinal Diseases le Feldman. E.J.; Isenberg, J.1.; and Grossman, M.I, 1981. Gastric acid and gastric response to decaffeinated coffee and a peptone meal. Journal of the American Medical Association 246:248-50. Fielding. J.F. 1985. The irritable bowel controversy. Proceedings of the Nutrition Society 44; 139-40. Fleischner, F.G.; Ming, S.C.; and Henkin, E.M. 1964. Revised concepts on diverticular disease of the colon. I. Diverticulosis: emphasis on tissue derangements and its relation to the irritable colon syndrome. Radiology 83:859-71. Floch, M.H. 1981. Nutrition and diet therapy in gastrointestinal disease. New York: Plenum. Gluten Intolerance Group. 1982. Fact sheet on celiac sprue. Seattle, WA. Gray. G.M. 1983. Intestinal disaccharidease deficiencies and glucose-galactose malabsorp- tion. In The metabolic basis of inherited disease. 5th ed..ed. J.B. Stanbury. J.B. Wyngaarden, and D.S. Frederickson, pp. 1729-42. New York: McGraw-Hill. Green, M., and Greene, H.L.. eds. 1984. The role of the gastrointestinal tract in nutrient delivery. New York: Academic. Hamilton, J.R. 1985. Acute diarrhea. In Nutrition in pediatrics: basic science and clinical application, ed. W.A. Walker and J.B. Watkins, pp. 529-40. Boston, MA: Little Brown. Harries, A.D.; Jones, L.A.; Danis. V.; Fified, R.. Heatley, R.V.; Newcombe, R.G.: and Rhodes, J. 1983. Controlled trial of supplemented oral nutrition in Crohn's disease. Lancet 1:888-90. Harvey, R.F. 1985. Functional gastrointestinal disorders: irritable bowel and other syn- dromes. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt. and K. Heaton, pp. 217-28. New York: Academic. Heaton, K. 1985. Gallstones. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton, pp. 289-304. New York: Academic. Johansson, C., and Bergstrom, S. 1982. Prostaglandins and protection of the gastroduodenal mucosa. Scandinavian Journal of Gastroenterology (suppl. 77):21-46. Jones, V.A.; Dickinson, R.J.; Workman, E.; Wilson, A.J.; Freeman, A.H.; and Hunter. j.0. 1985. Crohn’s disease maintenance of remission by diet. Lancet ii:177-80. Kagnoff, M.F. 1983. Immunology and disease of the gastrointestinal tract. In Gastrointestinal ellen 3rd ed., ed. M.H. Sleisenger and J.S. Fordtran, pp. 20-43. Philadelphia, PA: Saun- ers. Kerndt, PR.; Naughton, J.L.; Driscoll, C.E.; and Loxterkamp, D.A. 1982. Fasting: the history, pathophysiology, and complications. Western Journal of Medicine 137:379-99. Kirsner, J.B., and Shorter, R.G. 1982. Recent developments in “nonspecific” inflammatory bowel disease. New England Journal of Medicine 306:775-85, 837-48. Klurfeld, D.M. 1987. The role of dietary fiber in gastrointestinal disease. Journal of the American Dietetic Association 87:4172-76. Kolars, J.C.; Levitt, M.D.; Aouji, M.; and Savaiano, D.A. 1984. Yogurt—an autodigesting source of lactose. New England Journal of Medicine 310:1-3. Levine, A.S., and Levitt, M.D. 1981. Malabsorption of the starch moiety of oats, corn, and potatoes. Gastroenterology 80:1029. 423 O Nutrition and Health Life Sciences Research Office. 1987. Physiological effects and health consequences of dietary fiber. Contract No. FDA 223-84-2059. Bethesda, MD: Federation of American Societies for Experimental Biology. LSRO. See Life Sciences Research Office. Manousos, O.; Day, N.E.; Tzonou, A.; Papadimitrious, C.; Kapetanakis, A.; Poly- chronopoulou-Trichopoulou A.; and Trichopoulos D. 1985. Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece. Gut 26:544~49. Martin, D.W.; Mayes, P.A.; and Rodwell, V.W., eds. 1985, Harper’s review of biochemistry. 20th ed. Palo Alto, CA: Appleton & Lange. McCollum, E.V. 1957. A history of nutrition, Boston, MA: Houghton Mifflin. Mendeloff, A.I. 1986. Thoughts on the epidemiology of diverticular disease. Clinical Gas- troenterology 15:855-77. Morley, J.E. 1982. Food peptides: a new class of hormones? Journal of the American Medical Association 247:2379-80. Murray, R.K.; Granner, D.K.; Mayes, P.A.; and Rodwell, V.W. 1988. Harper's biochemis- try, pp. 584-85. 21st ed. San Mateo, CA: Appleton & Lange. National Center for Health Statistics. 1985. 1985 Summary, National Hospital Survey. Advance Data from Vital and Health Statistics, No. 127. DHHS publication no. (PHS) 86-1250. Hyattsville, MD: National Center for Health Statistics. . 1986. Current estimates from the National Health Interview Survey, United States, 1984. DHHS publication no. (PHS) 86-1584. Hyattsville, MD: National Center for Health Statistics. - 1987a, Annual summary of births, marriages, divorces, and deaths: United States, 1986. Monthly Vital Statistics Report 35(13), August 24. Hyattsville, MD: National Center for Health Statistics. ———. 1987b. Inpatient utilization of short-stay hospitals by diagnosis, United States, 1984. DHHS publication no. (PHS) 87-1750. Hyattsville, MD: National Center for Health Statistics. NCHS. See National Center for Health Statistics. Neidich, G.; Schussel, K.; and Sharp, H.L. 1985. Noninvasive outpatient nutritional therapy in inflammatory bowel disease. Journal of Parenteral and Enteral Nutrition 9:350-52. Newcomer, A.D., and McGill, D.B. 1984. Clinical consequences of lactase deficiency. Clinical Nutrition 3(2):53-58. Nicholl, C.G.; Polak, J.M.; and Bloom, S.R. 1985. The hormonal regulation of food intake, digestion, and absorption. In Annual review of nutrition, vol. 5, ed. R.E. Olson, E. Beutler, and H.P. Broquist, pp. 213-39. Palo Alto, CA: Annu. Rev. Ostro, M.J.; Greenberg, G.R.; and Jeejeebhoy, K.N. 1985. Total parenteral nutrition and complete bowel rest in the management of Crohn’s disease. Journal of Parenteral and Enteral Nutrition 9:280-87. Painter, N. 1985. Diverticular disease of the colon. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton, pp. 145-60. New York: Academic. Pomare, E.W.; Heaton, K.W.: Low-Beer, T.S.; and Espiner, H.J. 1976. The effect of wheat bran upon bile salt metabolism and upon the lipid composition of bile in gallstone patients. American Journal of Digestive Diseases 21:521-26. 424 Gastrointestinal Diseases @) Pope, C.E.., II. 1983. Gastroesophageal reflux disease (reflux esophagitis). In Gastrointestinal Disease. 3rd ed., ed. M.H. Sleisenger and J.S. Fordtran. Philadelphia, PA: Saunders. Roediger, W.E.W. 1986. Metabolic basis of starvation diarrhoea: implications for treatment. Lancet i:1082-84. Rosenberg, I.H., and Bowman, B.B. 1984. Gastrointestinal function and aging. In The role of the gastrointestinal tract in nutrient delivery, ed. M. Green and H.L. Greene, pp. 260-74. New York: Academic. Rydning, A.; Berstad, A., Aadland, E.; and Odegaard, B. 1982. Prophylactic effect of dietary fibre in duodenal ulcer disease. Lancet 1i:736-39. Scragg, R.K.R.; McMichael, A.J.: and Baghurst, P.A. 1984. Diet. alcohol. and relative weight in gallstone disease: a case control study. British Medical Journal 288:1113-19. Segal, 1. 1985. Hiatal hernia and gastroesophageal reflux. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton. pp. 241-48. New York: Academic. Silverberg, E., and Lubera, J. 1987. Cancer statistics 1987. CA: A Cancer Journal for Clinicians 37:2-19. Smith, D.A., and Gee, M.I. 1979. A dietary survey to determine the relationship between diet and cholelithiasis. American Journal of Clinical Nutrition 32:1519-26. Strasberg, S.M.; Petrunka, C.N.; and Ison, R.G. 1976. Effect of bile acid synthesis rate on cholesterol secretion rate in the steady state. Gastroenterology 71:1067-70. Taylor, I., and Duthie, H.L. 1976. Bran tablets and diverticular disease. British Medical Journai 1:988-90. Thornton, J.R.; Emmett, P.M.;and Heaton, K.W. 1983. Diet and gallstones: effects of refined and unrefined carbohydrate diets on bile cholesterol saturation and bile acid metabolism. Gut 24:2-6. Tovey, F. 1985. Duodenal ulcer. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton, pp. 229-40. New York: Academic. Trowell, H.; Burkitt, D.; and Heaton, K. 1985. Definitions of dietary fibre and fibre-depleted foods. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton, pp. 21-30. New York: Academic. Usuga, T.; Portman, O.W.; Tanaka, N.; Alexander, M.; and Ochsner, A.J., Ill. 1976. The effect of diet on hepatic bile formation and bile acid metabolism in squirrel monkeys with and without cholesterol gallstones. Journal of Laboratory and Clinical Medicine 88:649-61. Walker, A., and Burkitt, D. 1985. Appendicitis. In Dietary fibre, fibre-depleted foods and disease, ed. H. Trowell, D. Burkitt, and K. Heaton, pp. 191-203. New York: Academic. Wegman, M.E. 1986. Annual summary of vital statistics—1985. Pediatrics 78:983-94. Weinreich, J., and Andersen, D. 1976. Intraluminal pressure in the sigmoid colon. II. Patients with sigmoid diverticula and related conditions. Scandinavian Journal of Gastroenterology 11:581-86. Zucker, G.M., and Clayman, C.B. 1983. Landmark perspective: Bertram W. Sippy and ulcer disease therapy. Journal of the American Medical Association 250:2198-202. 425