CONSTIPATION

Overview

Constipation is the most common gastrointestinal complaint in the United States affecting approximately 4.4 million people.1 Constipation, defined as decreased or difficult evacuation of the feces, has both functional and organic causes. Constipation is a symptom, not a disease. It is frequently caused by a disturbance in the operation of the colon. Constipation is a health problem related to diminished quality of life. There is conventional and alternative treatments that can provide immediate relief. The goal of treatment is to reestablish normal bowel habits without the use of laxatives or enemas.

EPIDEMIOLOGY AND GENETICS

• Prevalence
• Genetics
• Diagnosis

Prevalence

Chronic constipation is a relatively frequent symptom. Among its subtypes, colonic inertia represents a disease condition often considered for surgery.2 This disorder is the number one gastrointestinal complaint in the United States, particularly among the elderly. Constipation accounts for more than 2.5 million physician visits a year and is among the most frequent reasons for patient self-medication. Prevalence estimates of constipation range from 1.9% to 27.2%, with most estimates between 12% and 19%. Prevalence estimates by sex indicate a female-to-male ratio of 2.2:1. The prevalence of constipation appears to increase with age, particularly after age 65.3

Children

Constipation occurs in at least 5% of children, usually due to a functional disorder 4,5 In some cases, constipation is a result of stool-withholding behavior. The child who is being toilet-trained may intentionally refuse to defecate as a method to obtain some control over his/her behavior or environment.6,7 Children have been observed holding their fists clenched tightly, holding their breath, and virtually turning red with the effort to keep the rectal sphincter closed.6,7 Constipation that is present from birth or that begins in the neonatal period is most likely of congenital origin. Acute constipation usually has an organic cause, while chronic constipation has a functional cause.8-10

Older Adults

Constipation is common in older adults for several reasons. The elderly exercise less than those who are younger, drink less fluids, have a higher incidence of constipation-inducing diseases, and are more likely to be taking medications that slow bowel motility or harden stools.11,12 In the elderly, additional risk factors include inactivity, depression, confusion, medication, cultural influences, and neuromuscular changes. Although colonic transit time does not change during aging, anal sphincter pressures decline.12-15

Pregnancy

Constipation is common in pregnancy. Though it may be a result of bowel compression by the gravid uterus, it may be due to hormonal changes during pregnancy. Contributing factors include reduced mobility and higher intake of calcium and iron, which harden stools.16-18

The average defecation frequency is once per day and is similar in males and females. Higher frequencies of straining, feelings of incomplete emptying, difficult evacuations, and manual maneuvers to facilitate defecation are reported more frequently by females.19

Three main causes of constipation are known: Chagas' disease,20 congenital megacolon, (Hirschsprung's disease),21 and continent obstipation (severe constipation or obstruction). These diseases are rare and are treated with drugs, surgery, or psychotherapy.22 More common is idiopathic chronic constipation, observed mainly in females. Contributory factors include behavioral, endocrine, neurogenic, and drug-related processes.23-25 Insufficient dietary fiber is a major precipitating factor in developed countries where the diet contains a high proportion of industrially refined and processed foods.23,26,27 Changes in colonic motility can occur as a result of neurological factors such as damage to the pelvic floor during childbirth,28 pelvic surgery, exposure to environmental toxins, or exposure to an infectious agent, and these may cause constipation.29 Constipation is a frequent complication in patients treated for advanced cancer as a result of reduced food intake, general debility, and medication with opioid analgesics.30

Genetics

A history of abdominal pain or constipation in first-degree relatives is associated with irritable bowel syndrome and dyspepsia. Whether the familial associations represent similar exposures in a shared environment, heightened familial awareness of GI symptoms (reporting bias), or genetic factors remains to be determined.31,32

Hirschsprung's disease (HD) is a common cause of intestinal obstruction in the newborn, characterized by the absence of autonomic ganglion cells in the terminal bowel. Existence of familial cases indicates genetic factors are involved in the etiology of some cases of HD.33 Several genes were identified in the development and differentiation of the enteric nervous system (ENS). Hirschsprung's disease is linked to mutations in these genes. Glial cell-derived neurotrophin factor (GCNF) and its co-receptor RET are the genes with the most mitogene potency on precursor cells of the ENS. The endothelin system (EDNRB/EDN3) plays a key role in the development of the ENS.34-36

Diagnosis

Adequate therapy of obstructed defecation (pelvic outlet obstruction) is often challenging, as the etiology and clinical symptoms include many disorders. Standardized diagnostic assessment differentiates between obstructed defecation caused by pelvic outlet obstruction or slow transit constipation. Morphologic changes of colon, rectum, or the pelvic floor must be separated from functional disorders. With defecography or dynamic magnetic resonance (MR) of the pelvic floor, common causes of outlet obstruction such as sigmoidoceles, for which surgery is indicated, and rectal prolapse can be diagnosed with high accuracy.37

Functional constipation is diagnosed by the presence of symptoms of constipation in the absence of known causes.25,28,38 The Rome Diagnostic Criteria define the symptoms of functional constipation as the presence of two or more of the following; occurring for at least 12 weeks in the preceding 12 months (Nos. 1-5 must happen at least 25% of the time when defecating):

1. Straining,
2. Lumpy or hard stools,
3. Sensation of incomplete evacuation,
4. Sensation of anorectal obstruction or blockage,
5. Manual maneuvers to facilitate defecation
6. Infrequent (fewer than 3) bowel movements per week5,8,39

Measurement of colonic transit time (CTT) is sometimes used in the evaluation of chronic constipation.8,40,41 The upper limit of normal for segmental transit time is as follows: 14 hours for the ascending, 33 hours for the transverse, 21 hours for the descending, and 41 hours for the rectosigmoid colon.8,42

ETIOLOGY AND MECHANISMS OF ACTION

• General Causes
• Contributing Causes

General Causes

Understanding constipation is complicated by the varied definitions of patients and doctors.2,8,25,43 Generally constipation refers to a lack of satisfactory defecation due to unpleasant sensation or abnormal bowel function. For this reason a cluster of different symptoms could constitute constipation. Use of over-the-counter laxatives can complicate diagnostic assessment as the patient my report constipation but show no symptoms at the time of treatment. The stool formation scale provides an objective stool assessment and is used in clinical trials.5,38,44

Some believe normal bowel movement is three or four times per day, while others regard normal to be once a week. Though the human body may function well at either extreme, most people probably have a bowel movement every day or every couple of days.40,44 Normal evacuation should occur at least once daily. The movement should be formed, but not hard. Movements that are hard or small and occur only every other day signify constipation. Any sudden change in a person's ability to move their bowels should be treated with suspicion, particularly in the elderly (constipation can be a first sign of colon cancer due to obstruction).15,25,45 Constipation associated with fatigue can indicate hypothyroidism.46,47 Often, constipation is a functional problem unrelated to an underlying disease. Most individuals with uncontrolled constipation develop a variety of symptoms, ranging from large bowel pain, rectal discomfort, abdominal fullness and bloating, nausea, and anorexia, or a general feeling of malaise. These individuals feel they never completely evacuate their bowels. Severe chronic constipation may include fecal impaction.38,45,48 Anal blockage, straining, and hard stools show the greatest accuracy for the diagnosis of constipation.49

In patients with chronic constipation, identifying subtypes based on underlying physiology guides therapy. Chronic constipation subtypes include slow-transit constipation, pelvic floor dyssynergia, functional constipation, and irritable bowel syndrome with constipation. Chronic constipation subtypes are defined by the result of colonic transit, pelvic floor function, and the presence or absence of significant abdominal pain.38,50

Contributing Causes

Common causes of constipation include:

• Insufficient fiber in diet. When there is inadequate fiber in the diet or the fiber with is unable to soak up available liquid, this prevents the stool from attaining healthy size, shape and moisture, and makes it difficult for the colon to move it along easily.8,51,52
• Not enough liquids. Insufficient liquids results in dry and compacted stools.8,53
• Lack of exercise. Constipation is related to inactivity.54 Abdominal and intestinal muscles work together to move the bowel. After only a few days without exercise, these muscles can lose tone. Intestinal motility is slowed with loss of muscle tone.
• Medications. Some pain medications, especially narcotics, cause constipation, as can antidepressants, iron, and calcium supplements.55
• Laxative abuse. Excessive laxative use causes the bowels to become over-relaxed. This weakens the musculature of the gut, and causes the bowels to become incapable of moving bulky stools.22,56

ANATOMY AND PHYSIOLOGY (STRUCTURE AND FUNCTION)

The colon at the end of the intestinal tract is 8 to 12 feet in length. It begins at the junction of the small bowel called the ileocecal valve, goes up along the right side of the abdomen, across the top and down the left side of the abdomen. These are respectively termed the ascending, transverse, and descending sections of the colon.57 The lower part of the colon is called the sigmoid, and the sigmoid joins the rectum about 15 centimeters (6 inches) from the anus. There is no difference between the colon and rectum and these terms designate an area of the large intestine. The rectum is 15 centimeters in length and is just above the anus. The anus is the muscle which closes the colon. When this muscle functions adequately it allows us to void at a socially convenient time. The anus is controlled by the voluntary skeletal sphincter muscles which act as a plug while the rectum acts as a storage area.57

The colon's primary function is to absorb water. When the stool enters the right side of the colon at the junction of the small bowel, the contents are semi-liquid. As the stool passes through the colon, most of the water is absorbed until it reaches the end of the left side where the stool becomes mostly solid. There is almost no nutritional absorption involved with the colon.57

The rectum is the sensing organ that initiates the process of defecation. As stool moves from the sigmoid colon into the rectum, pressure is exerted on the walls of the rectum and rectal valves. This pressure initiates a nervous impulse that triggers relaxation of the internal anal sphincter, which is sensed as urgency and the need to defecate. If it is convenient, defecation occurs. If it is not, the urge to defecate is consciously repressed by voluntary contractions of the external anal sphincter.57

There are two types of bacterial action on food in the large bowel – fermentation and putrefaction. Fermentation is the action of bacteria on starches or carbohydrates. Here the gases methane, hydrogen, and carbon dioxide are produced, as are organic acids, such as butyric, acetic and lactic acids. Colonization with diverse intestinal microbes is necessary for the development of important gut defenses.58,59 The second type of bacterial breakdown is putrefaction, the bacterial digestion of proteins forms the gases hydrogen sulfide, ammonia, and aromatic substances skatole, indole, phenol and creosol.60

Some degree of bacterial action in the lower bowel is beneficial since the bacteria split foods into products created by digestive enzymes.61 Bacteria breakdown of cellulose prepares food for digestion; transforms complex proteins into simpler compounds; triglycerides into fatty acids and glycerol; and disaccharides to monosaccharides.62-64

PATHOPHYSIOLOGY

• Common Constipation or Occasional Constipation
• Complications of Constipation

Normal defecation is a combination of autonomic and voluntary functions. Distention of the rectum is the stimulus that initiates reflex defecation. When the stool distends the rectum’s sensory receptors are stimulated; leading to perception of distention and involuntary relaxation of the internal sphincter. In the absence of voluntary contraction of the external anal sphincter, stool is expelled.65

The time is takes for the feces to pass through the colon is influenced by the fiber and liquids in the diet. Fiber-rich diets promote retention of water and increase stool weight and volume; leading to shorter transit times and frequent defecation. Normal stools that have an abnormally low water content produces constipation.41

Constipation is generally broken down into several categories:

Common Constipation or Occasional Constipation

While occasional constipation is not dangerous, recurrent bouts signal disease, allergic reaction, and other conditions. Extreme changes in the frequency or volume of stool produced warrants a trip to your family doctor. The presence of blood in the stool, pus, mucus, or fatty materials may indicate disease.

Chronic Constipation

Chronic constipation is the most common condition seen in primary care offices and is among the most common reasons for gastroenterology referral in the United States. Because of the overlap in symptoms reported by patients with irritable bowel syndrome and a predominant bowel complaint of constipation, it is difficult to differentiate between these disorders.

Travel-Related Constipation

A number of travel-related factors lead to constipation, from simply suppressing the natural urge while in transit, to avoiding unwelcoming lavatory conditions, to changes in diet and water. Remaining seated and inactive for a long time can upset natural rhythms of the bowel.

Age-Related Constipation

Most problems of the digestive system are not specific to older people; nor usually caused by aging. However, they may occur more frequently and complications may change as the body ages.

Childhood Constipation

Constipation that begins prior to toilet training indicates possible organic etiology such as Hirschsprung’s disease or pseudo-obstruction. Pseudo-obstruction may present in older children with a history of abdominal distention, pain, and intestinal paresis. The onset of constipation around toilet training when elimination was normal in the past, suggests functional constipation. Constipation may develop in some children with use of medications, chemotherapeutic agents, heavy metals, and anti-cholinergic agents.

Functional Constipation

Functional constipation occurs in both children and adults and is most common in women. Colonic inertia and delayed transit are two types of functional constipation caused by decreased muscle activity in the colon. These syndromes may affect the entire colon or may be confined to the lower or sigmoid colon. Functional constipation that stems from abnormalities in the structure of the anus and rectum is known as anorectal dysfunction, or anismus. These abnormalities result in an inability to relax the rectal and anal muscles that allow stool to exit.

Pregnancy-Related Constipation

Constipation is a common problem during pregnancy, though the actual causes are not known. Increased levels of the hormone progesterone, resulting in diminished smooth muscle contractility and inhibited gastrointestinal transit, are implicated.

Chronic Idiopathic Constipation

Chronic constipation means constipation lasting over 6 months. Idiopathic constipation means constipation of unknown cause. Patients with chronic idiopathic constipation show reduced intestinal motility in the condition.

Chemotherapy-Related Constipation

Although rare, chemotherapy treatment and medications involved cause constipation.

Complications of Constipation

Sometimes constipation causes complications; including hemorrhoids due to straining or anal fissures (tears in the skin around the anus) caused when hard, dry stool stretches the sphincter muscle. Rectal bleeding may appear as red streaks on the stool.65-68

Constipation means stool is in contact with the surface of the large bowel for a longer time. This increased contact increases exposure to toxins and carcinogens.25

Sometimes straining causes a small amount of intestinal lining to push out from the anal opening. This condition is rectal prolapse and leads to secretion of mucus from the anus. Eliminating the cause of prolapse (straining or coughing) is the only treatment necessary. Severe or chronic prolapse requires surgery to strengthen and tighten the anal sphincter muscle or repair the prolapsed lining.65,69,70

Constipation can contribute to a loss of bladder control by weakening the pelvic floor muscles due to straining. A full bowel pressing on the bladder, causing it to empty prematurely or blocking urine outflow is common. People with bladder control problems do not drink fluids for fear of incontinence, which results in constipation, further discomfort, and anxiety.71

Constipation causes hard stools to pack the intestine and rectum so tightly that the normal pushing action of the colon is not enough to expel the stool. This fecal impaction occurs in children and older adults.65,72

ENDOCRINOLOGY & BIOCHEMISTRY (REGULATION AND METABOLISM)

• Biochemical Function

The enteric nervous system (ENS) regulates the normal activity of the digestive system. It is a complex system comprising a population of approximately 100 million nerves. It has sensory and motor neurons, information processing circuits, and glial cells (that support nerve cells). Manipulating the ENS pharmacologically offers the opportunity to reprogram this key control system to improve bowel function.24,73 Interneurons of the ENS display 5-HT4 receptors, activation of which enhances the peristaltic reflex.74 This means that serotonin receptor type-4 agonists can be used for the treatment of constipation.

Studies show a physiological significance of cholinergic, adrenergic, non-adrenergic non-cholinergic inhibitory nerves in colons with slow transit constipation. A decrease of cholinergic nerve activity and an increase of non-adrenergic, non-cholinergic inhibitory nerve activity impairs motility in patients with this type of constipation.75 An increase of nitric oxide mediates non-adrenergic non-cholinergic inhibitory nerves and plays an important role in the dysmotility observed in the colons with slow-transit constipation.76

Dysfunctions of the gastrointestinal (GI) system, including dysphagia, constipation, diarrhea, and irritable bowel syndrome are common complaints of the elderly,12 yet knowledge of the aging GI tract and understanding of age-related changes in the enteric nervous system is poor.77-79 Significant risk factors in older women are failure of the anorectal angle to open or excessive perineal descent, which represent disturbances of pelvic floor function and rectal evacuation.80 Geriatric residents in nursing homes show that independent factors in the development of constipation are, in order of magnitude, decreased fluid intake, pneumonia, Parkinson's disease, and allergies.81

Biochemical Function

Poor diet, digestion and elimination contributes through accumulating toxins in tissues and blockade of elimination. Toxins depress the functions of tissue absorption and bowel motility. Chronic diseases are caused when toxins accumulate and disrupt tissue biochemistry. Toxins block circulation and elimination within affected areas. Blockages prevent nutrition from reaching tissues and block normal processes to cleanse these impurities.

Constipation leads to poor elimination, inadequate metabolism, mental, and physical stress. Recommended nutritional therapies address toxin accumulation by:

• Loosening toxins or harmful microflora embedded in colonic tissues and rehydrating them for easy movement and elimination.
• Softening and opening the tissue lining the bowels so feces can be eliminated.
• Enhancing the digestive system’s balance of beneficial microflora.

PHARMACOLOGY

• Drug Therapies

Drug Therapies

The latest advances in drug therapies for constipation are based on the enteric nervous system (ENS). Prokinetic agents that stimulate 5-HT4 receptors, tegaserod and prucalopride, are effective as investigational agents for chronic constipation.74

Prucalopride is a novel, selective, and specific serotonin (5-HT4) receptor agonist from a new medication class of benzofurancarboxamides. Prucalopride increases the frequency of bowel movements and improves colonic transit, key factors in treating constipation.82-84 Tegaserod is a 5-HT4 receptor partial agonist for chronic constipation. Tegaserod treatment improves chronic constipation and is safe and well-tolerated.85-87

NUTRITIONAL THERAPY

• Laxatives
• Laxative Addiction
• Dietary Modifications
• Supplements
• Herbal Supplements
• Alternative Therapy
• Lifestyle Changes

Laxatives

Laxatives speed passage of intestinal contents through the GI tract. Laxatives can be bulk, stimulants, or lubricants. Bulk laxatives, such as psyllium, are natural or semi-synthetic polysaccharides and cellulose, which hold water, soften the stool, and increase passage of stool by increasing fecal bulk. Fiber and laxatives decrease abdominal pain and improve stool consistency. Fiber and laxatives improve bowel movement frequency in adults with chronic constipation. There is no evidence to establish whether fiber is superior to laxatives or whether one laxative class is superior to another.88,89 Laxative use was reduced in a long-term care facility with increased fluid, fiber intake, timely toileting habits, regular activity, and led to a 50% reduction in patients receiving laxatives.90

Modern laxatives are safe to use, even with chronic use, with severe reactions rarely reported, although annoying side effects may occur.91 The long-term abuse of laxatives causes serious medical consequences, masks disease, delays diagnosis and appropriate treatment.92

Saline Laxatives

Magnesium Citrate and Magnesium Oxide. Magnesium citrate and magnesium oxide are saline laxatives in the hyperosmotic family. They attract water into the lumen of the intestines.93 The fluid buildup alters stool consistency, expands the bowel, and encourages peristaltic movement. Although the laxative action of magnesium is thought to be due to a local effect in the intestinal tract, it is possible that hormones such as cholecystokinin or activation of constitutive nitric oxide synthase might contribute to this pharmacological effect.94 Magnesium citrate and magnesium oxide are used to clear the bowels for rectal or bowel examinations and are not recommended for long-term use.46,95

Magnesium Sulfate. Magnesium sulfate is a potent laxative, and may be used when evacuation of the GI tract in needed rapidly. Results occur within 0.5-3 hours.

Stimulant Laxatives

Stimulant laxatives, such as sennosides, increase motor activity of the bowels by directly stimulating the nerve plexus in the intestinal wall, causing increased movement and stimulation of local reflexes.68,74,88,96 They are used to evacuate the bowel for rectal or bowel examinations. Most of these laxatives act on the colon; however, castor oil acts on the small intestine. Results occur in 6-10 hours.

Lubricant Laxatives

Lubricant laxatives, such as mineral oil, lubricate intestinal mucosa and soften stools to help the intestinal contents move more smoothly and make defecation easier without stimulating movement of the GI tract. They are used prophylactically to prevent straining in patients for endangered by straining68,74,88,96 Mineral oil is recommended at 5-30 mL at bedtime and results vary. Chronic mineral oil ingestion results in malabsorption of fat-soluble vitamins, minerals, and is not for continuous treatment.93

Emollients

Fecal softeners or emollients (docusate) promote water retention to soften stool. They prevent straining and are most beneficial when the stool is hard. It may require 3 days before results are experienced. Stool softeners and emollient laxatives have limited use because of their resorption of water from the forming stool. Fecal softeners should not be used exclusively but may be useful when given in combination with stimulant laxatives.74,96-98

Lactulose. A prescription drug used to treat constipation, lactulose is an indigestible synthetic sugar that is broken down into lactic acid, formic acid, acetic acid, and carbon dioxide in the colon. Lactulose produces minimal water and sodium loss or gain. These products increase water in stool to soften stool and increase frequency.93 Results occur in 24-48 hours. The metabolism of lactulose requires “friendly bacteria”; Lactobacillus acidophilus.99 Consumption of Lactobacillus acidophilus together with lactulose normalizes intestinal friendly bacteria content and eliminates pathogenic bacteria such as Clostridium.

Golytely. Golytely (Colyte®) is a prescription electrolyte solution used to clear the bowel with minimal water and sodium loss or gain.100 It is prescribed before colonoscopy.

Bulk-forming laxatives

Bulk-forming laxatives are the most commonly recommended initial treatments for constipation that work within 12 hours to three days. Some-bulk-forming laxatives are derived from natural sources of agar, psyllium, kelp (alginates), and plant gum. Others are synthetic cellulose compounds such as methylcellulose and carboxymethylcellulose. Natural and synthetic bulk-forming laxatives act similarly. They dissolve or swell in the intestines, lubricate and soften the stool, and make the passage of stools easy and frequent. Bulk-forming laxatives are not absorbed into the body and are safe for long-term use. They are safe for elderly patients.88,89,101,102

Laxative Addiction

The nature of laxative addiction is controversial. It can result from degeneration of intestinal nerves; dulling natural responses that stimulate peristalsis; or cause a psychological dependence. The link between use of stimulant laxatives and nerve damage or other structural changes is established.103 Potassium imbalance due to long-term use of (excessive) laxatives has been blamed for deaths of healthy women.104 Laxatives are always a factor in drug interactions because they exacerbate potassium losses that may be only a minor side effect of drug therapies.105

The use of stimulating laxatives should be limited in dosage and duration to avoid adverse health consequences related to melanosis coli (blackened colon). Damaged colon submucosal nerves is related to dosage and duration of laxative use.106

Pseudomelanosis coli occurs after a minimum of 9-12 months of regular stimulant laxative use. Discontinued use of laxatives for several weeks will normalize the colon and laxative therapy can be safely repeated if necessary. When discontinuing anthraquinone-containing preparations, use lactulose or polyethylene glycol preparations (the latest therapies to show good results) instead. These bulking agents act quickly; normal stools occur within one to four weeks.

Dietary Modifications

Dietary modifications help most people with constipation. Some cases are caused by insufficient peristalsis; there is not enough contractile activity of the colon to completely evacuate the bowel. There are specific nutrients that induce healthy colon peristaltic action without producing side effects.74,96,107,108

Fiber

Very few people in Africa suffer from constipation. Epidemiological studies establish the well-known fact that dietary fiber in North American diets is lacking. Low dietary fiber is connected to many illnesses, such as hemorrhoids, diabetes, varicose veins, heart disease, and appendicitis.109,110

The average American eats only 10-15 grams of fiber daily. Most agencies recommend a doubling or tripling of dietary fiber intake. Typical recommendations are 25 to 50 grams of dietary fiber daily.111 Fiber is excellent for overall intestinal health and alleviating chronic constipation. Humans can not digest fiber, but the 5 lbs of “friendly” intestinal bacteria ferment fiber and produce short-chain fatty acids that intestinal tract cells use for energy.

Most foods contain soluble and insoluble fiber112 important in treating constipation.113 Soluble fiber contained in oats, apples, lentils, barley, breads and cereals mixes evenly with water, forming a soft gel. Insoluble fiber in raw wheat bran, other whole grains, and fruits and vegetables mixes unevenly with water, forming a soft pulp. Your body does not absorb soluble or insoluble fiber during digestion. Fiber contribute volume to the stool mass; making it easier for the colon to push and propel larger and softer stools to improve constipation. Insoluble fiber encourages contraction of the colon.

The following table lists food sources of fiber:114

Chitosan. Fiber supplements frequently fail to correct chronic constipation. One fiber that may work when others fail is chitosan; a fiber composed of chitin, from shellfish shells that reduces cholesterol.115 Chitosan uniquely binds fats in the stomach and intestines. Increasing fat content in the bowel makes the feces soft and smooth.116 Six 500-mg capsules of chitosan and 1000 mg of vitamin C taken before each meal may alleviate constipation. Ascorbic acid (vitamin C) activates chitosan in the stomach and intestine into a fat-absorbing gel. Ascorbic acid given with chitosan to rats trapped and excreted far more fat in the feces than chitosan without ascorbic acid.117

Ispaghula Husk (Psyllium). Psyllium is a bulk-forming laxative high in fiber and mucilage. Psyllium seeds contain 10-30% mucilage. The laxative properties of psyllium are due to swelling of the husk when it contacts water; forming a gelatinous mass that keeps feces hydrated and soft. The resulting bulk stimulates a reflex contraction that empties the bowel.118

Psyllium fiber is more effective than other laxatives because bowel movements are more frequent, of greater bulk, and without side effects.88,118 Ispaghula husk increases the probability of benign tumor development in those with a history tumors known as adenomas.119,120

Glucomannan. Glucomannan is a water-soluble dietary fiber derived from konjac root (Amorphophallus konjac). It is a hydrocolloidal polysaccharide of D-glucose and D-mannose. Glucomannan is a “bulk-forming laxative that promotes larger, bulkier stools allowing easier passage through the colon.121,122 Glucomannan produces a bowel movement within 12 to 24 hours.123

Constipation is frequently encountered during pregnancy. A preparation of lactulose and glucomannan are effective and well-tolerated in pregnant women.99,124,125 Pregnant females with constipation treated with a preparation of glucomannan (3-6 grams) and lactulose (8-16 grams) twice a day for 1-3 months showed a return of normal frequency of evacuations and control of weight gain.121,126-128

Supplements

Ascorbic acid

Ascorbic Acid is a water-soluble vitamin found in peppers, citrus fruits, tomatoes, melons, broccoli, and green leafy vegetables. Vitamin C assists in production of collagen, is a strong antioxidant, a cancer fighter, and detoxifies foreign substances.129,130 Ascorbic acid may reduce colorectal cancer.131

Vitamin B5

Vitamin B5 (pantothenic acid) in a dose of 2000-3000 mg, on an empty stomach, produces rapid evacuation of bowel contents.132 Natural sources of pantothenic acid include sesame seeds, peanuts, walnuts, pecan nuts, avocado pears, dried fruit, such as apricots and figs, and calf’s liver.

One way of comsuming vitamin B5 and other peristalsis-inducing nutrients is through a multi-nutrient formula, such as Powermaker II. This pleasant-tasting powder contains vitamins B5, C, choline, and L-arginine, which induce peristaltic action.

Digest RC

Digest RC is a natural digestive supplement in Europe. It stimulates peristalsis, speeds digestion of fats, and prevents stagnation of food in the digestive tract. It may reduce acid reflux, alleviate fullness and bloating, decreases digestive tract tension, alkalinizes the gastric contents, causing relief from constipation and normalizes elimination. Digest RC is an immune system stimulant containing six active ingredients; black radish, charcoal, cholic acid, calcium phosphate, peppermint, and artichoke, all of which offer beneficial effects. The suggested dosage is 2-3 tablets with every heavy meal for 2-3 weeks. As symptoms of discomfort are alleviated, the dosage may be reduced.

Note: see Appendix C for Cautions and Contraindications.

Black radish. Black radish juice extract (the active ingredient in Digest RC) stimulates liver production of fat-digesting bile and lowers tension in bile ducts.133 Its high fiber content increases peristaltic movements.134 Radish contains large amounts of water, which combined with its fiber improves GI transit.135 Other radish compounds increase bile flow important in digestion.133 Radish maintains a healthy gallbladder,133 has antibacterial effects on digestive flora,136 and assists the immune system through antimicrobial actions.137 Regular consumption of radishes may improve resistance against microbial infections such as colds, sore throats, ear infections, and the flu.138 Liquid radish extract administered prophylactically to mice protected against influenza infection. There is a decrease in mortality rate and a pronounced increase in survival.138

Charcoal. The charcoal in Digest RC absorbs toxins. Charcoal is commonly used for gastrointestinal decontamination by most North American poison control centers.139 It calms a stressed digestive system, allowing digestive enzymes to be released.140 The charcoal in Digest RC is a special herbal preparation of linden tree bark, traditionally used in Europe as a digestive aid133 and has antibacterial properties which balances the digestive tract and supports creation of the proper intestinal flora. It creates an inhospitable environment for parasitic infestation.

Cholic acid. Digest RC contains liver enzymes for digestion. Through ion exchange, insoluble fibers combine with cholic acid in the intestines.141,142 The amount of cholesterol used to synthesize bile acid increases, dropping cholesterol level in the blood.143 The small fatty acids produced from glycolysis of soluble fibers decreases acidity in the intestines; inhibiting formation of carcinogens and facilitating their discharge.144

Peppermint. Peppermint’s active ingredient, menthol, is a natural antispasmodic that relaxes smooth muscles that line the intestines.145,146 The menthol in peppermint increases the beneficial flow of all digestive juices, including bile133 and calms digestive spasms.133

Artichoke. Artichoke relieves gastrointestinal problems due to inadequately processed fats resulting from poor bile secretion.133 Because the liver is stimulated to produce gastric "juices," artichoke eases upset stomach symptoms such as nausea, bloating, abdominal pain, and vomiting.133 Artichoke leaf may relieve flatulence.65,147

Probiotics

Probiotics are beneficial for digestive health. Components of bowel flora such as Lactobacillus acidophilus and Bifidobacterium are therapeutic agents for GI disorders.148 More complex combinations of probiotics for bacteriotherapy are available, however, the most elaborate mix of human-derived probiotic bacteria is, by definition, the entire fecal flora. Fecal bacteriotherapy uses human flora as a probiotic mixture of living organisms. This type of bacteriotherapy has a long history in animal health and is used occasionally against chronic infections of the bowel.63,149-151

Herbal Supplements

Herbal supplements may alleviate symptoms of constipation and include alfalfa, flaxseed, ginger,152 licorice, dandelion, and rhubarb root.153 They offer a gentle solution to constipation that is not habit-forming.

Primal Defense

Primal Defense contains alfalfa to eliminate toxins and aid digestion of fats, carbohydrates, and protein.

Flaxseed

Flaxseed offers a combination of fiber and omega-3 essential fatty acids (EFAs). EFAs soften stool and promote bowel movements. Flaxseed cleanses the colon and continued use may reduce colon cancer.154 Overall, essential fatty acids promote bowel movements.155

Ginger Root

Ginger root stimulates the intestines and promotes production of saliva, digestive juices, bile, and boosts the pumping action of the heart.152

Licorice

Licorice is a gentle laxative that soothes inflamed mucous membranes and protects against inflammation. Its components tone, strengthen, and invigorate organs.152

Note: see Appendix C for Cautions and Contraindications.

Dandelion

Dandelion is a mild stimulant for the bowels and benefits many liver functions. By removing poisons, it is a stimulating tonic helpful for many GI conditions.156,157

Rhubarb Root

Rhubarb root is a gentle laxative and mild tonic that cleanses and tones the bowels and the liver. It stimulates the gall bladder to empty.158,159

Alternative Therapies

Biofeedback Therapy

Biofeedback therapy is a neuromuscular re-education tool that ascertains if certain bodily functions are working. This painless process uses a computer monitor to display bodily functions. Special sensors measure and display these functions as audible sounds or as graphs on a computer screen. Patients use the displayed information to modify or change abnormal responses into normal patterns. Biofeedback therapy uses special equipment to relax the pelvic floor and anal sphincter muscles. Biofeedback techniques assist constipated patients with spasms of the pelvic musculature during defecation.160 In some conditions, such as nonrelaxing puborectalis syndrome, 90% of patients respond to biofeedback therapy.160-163

Lifestyle Changes

• Add more fruits and vegetables to your diet — take an extra helping at dinner, or replace processed food with fruit.
• Substitute whole grain foods for refined products. Try whole wheat bread and brown rice instead of the "white" varieties.
• Add wheat bran or oat bran to cereal or homemade muffins or breads.
• Add legumes to daily meals, either as side dishes or as a casserole; they are foods offering the most fiber per serving, encouraging growth of “friendly” bacteria in the colon, and adding to stool bulk.
• Cut back on low-fiber foods: meats, cheese, and processed foods.
• Drink plenty of water. As you increase fiber, step up your fluid intake. Some liquids are better for preventing constipation. Water is best. Vegetable and fruit juices, which are high in calories, lack the fiber found in whole vegetables and fruit. Milk causes intestinal upset in many people, and broth can be high in salt. Caffeine-containing drinks such as coffee, tea, and colas mildly dehydrate the body, but do promote bowel contractions that can sometimes facilitate bowel movements.
• Eat on a regular schedule to help regulate elimination.
• Respond to your body’s signals (defecation reflexes) to pass stool and keep bowel movements regular.
• Exercise can manage constipation. Regular exercise, especially for the abdominal muscles, or brisk walking is recommended if physically okay for the individual.

SUMMARY

• Scientific Summary
• Functional Summary

Scientific Summary

Constipation is a decrease in the frequency of bowel movements. For some people, it may mean difficulty in passing stools. A constipated stool is hard because it contains less water. Constipation is a symptom, not a disease. One common misconception about constipation is that wastes stored in your body are absorbed, are dangerous to your health, and may shorten your life-span. Some people fear they will be poisoned by their intestinal wastes (feces) if they retain waste in their bodies to long. Those who do not eliminate regularly, accumulate hardened feces that cling to the colon walls and inhibit its normal function. This increases harmful bacteria and reduces motility of stools.

Functional Summary

Constipation is a universal affliction of Western civilization. There are alternative therapies that are safer and more effective than conventional laxatives and work better for more people than fiber supplements. Chronic constipation is amenable to changes in lifestyle, such as increased exercise or activity that can be as little as 20 minutes of brisk, regular walking. Removal of processed foods from your diet and replacement with fiber-rich foods such as fruits, vegetables, and whole-grain cereals is effective. Addition of 1 tbsp of wheat bran, ground flaxseed, or oat bran to your diet will speed up the process. In most cases changes occur over days or perhaps weeks until your bowels begin to move more frequently and easily. If these changes do not produce desired effects, and you have ruled out the possibility of underlying disease with your healthcare provider, then the suggestions below may be helpful.

LIFE EXTENSION’S INTEGRATED PROTOCOL

• Acute Constipation
• Chronic Constipation

Acute Constipation

• Ascorbic Acid: 4000-8000 mg of ascorbic acid powder with 1500 mg of magnesium oxide powder taken with the juice of a freshly squeezed grapefruit or orange (best taken on an empty stomach)
• Buffered Vitamin C: Up to 15 grams daily may be taken under physician supervision
• Vitamin B5: Take 2000-3000 mg of pantothenic acid (vitamin B5) powder on an empty stomach
• Power Maker II Sugar-Free Powder: Mix one tablespoon in 4 to 8 ounces of cold water or fruit juice, stir briskly, and drink

Chronic Constipation

• Chitosan: one to three capsules with 8 ounces of water, 3 times daily, preferably with meals. Start with one capsule with each meal to allow the body to adjust to a higher level of fiber
• Fiber Food: Take six capsules up to three times daily. Always take Fiber Food with at least ten ounces of water. Consume it immediately and follow it with another glass of water
• Digest RC: For 3 weeks, take 2-3 tablets with every meal that contains fat or protein. After symptomatic relief occurs, the dosage may be reduced
• Flaxseed can be sprinkled on cereal at breakfast time. The flaxseed should be purchased fresh and should be ground in a coffee grinder daily
• Primal Defense: Adults may take 1 caplet three times per day with eight ounces of water. For advanced usage take 6-12 caplets per day for 90 days followed by a maintenance level of three per day for life. This product should be taken on an empty stomach
• Ginger: Two capsules in the morning and two capsules in the evening with food
• Licorice: Chew two tablets 20 minutes before each meal. For support of the lining of the stomach and intestine, chew two 380-mg tablets three to four times daily between meals
• Acidophilus: One capsule with meals three times daily for 4 or 5 days, then once daily

Refer to the various Protocols describing other Digestive Disorders for additional information.

For more information Contact the Consumer Nutrition Hotline of the National Center for Nutrition and Dietetics, (800) 366-1655.

PRODUCT AVAILABILITY

Ascorbic acid powder, magnesium oxide powder, buffered vitamin C, vitamin B5 powder, Power Maker II Sugar-Free Powder, chitosan capsules, Digest RC, Fiber Food, ginger, DGL Deglycyrrhizinated Licorice, acidophilus, flaxseeds, and Primal Defense are available by calling (800) 544-4440 or by ordering online.

Disclaimer

This protocol was written and edited by Corinna Underwood, M.A. Corinna has studied the sociology of health and nutrition and published articles in a broad range of health magazines in Canada, USA, and the UK. For several years she has been particularly interested in nutritional and complimentary therapies, in relation to disease, theories, and cultural understanding of embodiment.

Sections were written and edited by Randall Lee Kohl, Ph.D., R.Ph.,F.C.P., Senior Editor for LE Publications, Inc. Please direct your comments to rkohl@lef.org. and your questions to the Life Extension Health Advisory staff at 1 800 544-4440

CONSTIPATION

REFERENCES

1. NDDIC. Digestive statistics National Digestive Diseases Information Clearinghouse page. Available at: http://digestive.niddk.nih.gov/statistics/statistics.htm Accessed 5 A.D. Jan 24

2. Bassotti G, Roberto GD et al. Toward a definition of colonic inertia. World J Gastroenterol. 2004 Sep 1;10(17):2465-7.

3. Anonymous. [Chronic constipations in elderly people]. Eksp Klin Gastroenterol. 2004;(4):48-54, 109.

4. McDonald LA, Rennie AC et al. Constipation and soiling--outcome of treatment at one year. Scott Med J. 2004 Aug;49(3):98-100.

5. Voskuijl WP, Heijmans J et al. Use of Rome II criteria in childhood defecation disorders: applicability in clinical and research practice. J Pediatr. 2004 Aug;145(2):213-7.

6. Blum NJ, Taubman B et al. Why is toilet training occurring at older ages? A study of factors associated with later training. J Pediatr. 2004 Jul;145(1):107-11.

7. Blum NJ, Taubman B et al. During toilet training, constipation occurs before stool toileting refusal. Pediatrics. 2004 Jun;113(6):e520-e522.

8. Corazziari E. Definition and epidemiology of functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):613-31.

9. Sutcliffe JR, King SK et al. Paediatric constipation for adult surgeons--article 1: targeting the cause. ANZ J Surg. 2004 Sep;74(9):777-80.

10. Torres M, McGregor T et al. What is the most effective way for relieving constipation in children aged >1 year? J Fam Pract. 2004 Sep;53(9):744-6.

11. Bliss MR. The rationale for sitting elderly patients in hospital out of bed for long periods is medically unsubstantiated and detrimental to their recovery. Med Hypotheses. 2004;62(4):471-8.

12. Wilson JA. Constipation in the elderly. Clin Geriatr Med. 1999 Aug;15(3):499-510.

13. Johanson JF, Irizarry F et al. Risk factors for fecal incontinence in a nursing home population. J Clin Gastroenterol. 1997 Apr;24(3):156-60.

14. Meiring PJ, Joubert G. Constipation in elderly patients attending a polyclinic. S Afr Med J. 1998 Jul;88(7):888-90.

15. Talley NJ, Fleming KC et al. Constipation in an elderly community: a study of prevalence and potential risk factors. Am J Gastroenterol. 1996 Jan;91(1):19-25.

16. Broussard BS. The constipation assessment scale for pregnancy. J Obstet Gynecol Neonatal Nurs. 1998 May;27(3):297-301.

17. Lilienfeld MC. The treatment of constipation in pregnant women. Am Pract Dig Treat. 1952 Aug;3(8):638-9.

18. Tytgat GN, Heading RC et al. Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting. Aliment Pharmacol Ther. 2003 Aug 1;18(3):291-301.

19. Bassotti G, Bellini M et al. An extended assessment of bowel habits in a general population. World J Gastroenterol. 2004 Mar 1;10(5):713-6.

20. Hagger R, Finlayson C et al. A deficiency of interstitial cells of Cajal in Chagasic megacolon. J Auton Nerv Syst. 2000 Apr 12;80(1-2):108-11.

21. Fiori MG. Domenico Battini and his description of congenital megacolon: a detailed case report one century before Hirschsprung. J Peripher Nerv Syst. 1998;3(3):197-206.

22. Stelzner F, Hansen H. [Pathophysiology of chronic constipation and new therapy recommendation]. Zentralbl Chir. 1999;124(9):804-11.

23. Eberhardie C. Constipation: identifying the problem. Nurs Older People. 2003 Dec;15(9):22-6.

24. Hansen MB. The enteric nervous system II: gastrointestinal functions. Pharmacol Toxicol. 2003 Jun;92(6):249-57.

25. Talley NJ. Definitions, epidemiology, and impact of chronic constipation. Rev Gastroenterol Disord. 2004;4 Suppl 2:S3-S10.

26. Dukas L, Willett WC et al. Association between physical activity, fiber intake, and other lifestyle variables and constipation in a study of women. Am J Gastroenterol. 2003 Aug;98(8):1790-6.

27. Guimaraes EV, Goulart EM et al. Dietary fiber intake, stool frequency and colonic transit time in chronic functional constipation in children. Braz J Med Biol Res. 2001 Sep;34(9):1147-53.

28. West L, Warren J et al. Diagnosis and management of irritable bowel syndrome, constipation, and diarrhea in pregnancy. Gastroenterol Clin North Am. 1992 Dec;21(4):793-802.

29. Johanson JF, Sonnenberg A et al. Clinical epidemiology of chronic constipation. J Clin Gastroenterol. 1989 Oct;11(5):525-36.

30. Tsuji Y, Sagawa T et al. [Management of cancer treatment-related diarrhea and constipation]. Nippon Rinsho. 2003 Jun;61(6):966-72.

31. Knowles CH, Gayther SA et al. Idiopathic slow-transit constipation is not associated with mutations of the RET proto-oncogene or GDNF. Dis Colon Rectum. 2000 Jun;43(6):851-7.

32. Locke GR, III, Zinsmeister AR et al. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000 Sep;75(9):907-12.

33. Kusafuka T, Puri P. Genetic aspects of Hirschsprung's disease. Semin Pediatr Surg. 1998 Aug;7(3):148-55.

34. Amiel J, Salomon R et al. [Molecular genetics of Hirschsprung disease: a model of multigenic neurocristopathy]. J Soc Biol. 2000;194(3-4):125-8.

35. Holland-Cunz S, Krammer HJ et al. Molecular genetics of colorectal motility disorders. Eur J Pediatr Surg. 2003 Jun;13(3):146-51.

36. Puri P, Ohshiro K et al. Hirschsprung's disease: a search for etiology. Semin Pediatr Surg. 1998 Aug;7(3):140-7.

37. Bruch HP, Fischer F et al. [Obstructed defecation]. Chirurg. 2004 Sep;75(9):861-70.

38. Rao SS. Constipation: evaluation and treatment. Gastroenterol Clin North Am. 2003 Jun;32(2):659-83.

39. Whitehead WE, Bassotti G et al. Factor analysis of bowel symptoms in US and Italian populations. Dig Liver Dis. 2003 Nov;35(11):774-83.

40. de Lorijn F, van Wijk MP et al. Prognosis of constipation: clinical factors and colonic transit time. Arch Dis Child. 2004 Aug;89(8):723-7.

41. Sakakibara R, Odaka T et al. Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy. Mov Disord. 2004 Aug;19(8):924-9.

42. Wagener S, Shankar KR et al. Colonic transit time--what is normal? J Pediatr Surg. 2004 Feb;39(2):166-9.

43. Christer R, Robinson L et al. Constipation: causes and cures. Nurs Times. 2003 Jun 24;99(25):26-7.

44. Heaton KW, Radvan J et al. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. 1992 Jun;33(6):818-24.

45. Le Marchand L. Constipation and colon cancer. Epidemiology. 1998 Jul;9(4):371-2.

46. Bharucha AE, Philips SF. Slow-transit Constipation. 2001 Aug;4(4):309-15.

47. Unachak K, Dejkhamron P. Primary congenital hypothyroidism: clinical characteristics and etiological study. J Med Assoc Thai. 2004 Jun;87(6):612-7.

48. Arce DA, Ermocilla CA et al. Evaluation of constipation. Am Fam Physician. 2002 Jun 1;65(11):2283-90.

49. Garrigues V, Galvez C et al. Prevalence of constipation: agreement among several criteria and evaluation of the diagnostic accuracy of qualifying symptoms and self-reported definition in a population-based survey in Spain. Am J Epidemiol. 2004 Mar 1;159(5):520-6.

50. Prather CM. Subtypes of constipation: sorting out the confusion. Rev Gastroenterol Disord. 2004;4 Suppl 2:S11-S16.

51. Gomes RC, Maranhao HS et al. [Fiber and nutrients intake in children with chronic constipation]. Arq Gastroenterol. 2003 Jul;40(3):181-7.

52. Speridiao PG, Tahan S et al. Dietary fiber, energy intake and nutritional status during the treatment of children with chronic constipation. Braz J Med Biol Res. 2003 Jun;36(6):753-9.

53. Whitehead WE, Drinkwater D et al. Constipation in the elderly living at home. Definition, prevalence, and relationship to lifestyle and health status. J Am Geriatr Soc. 1989 May;37(5):423-9.

54. Simren M. Physical activity and the gastrointestinal tract. Eur J Gastroenterol Hepatol. 2002 Oct;14(10):1053-6.

55. Muller-Lissner S. General geriatrics and gastroenterology: constipation and faecal incontinence. Best Pract Res Clin Gastroenterol. 2002 Feb;16(1):115-33.

56. Siegers CP, Hertzberg-Lottin E et al. Anthranoid laxative abuse--a risk for colorectal cancer? Gut. 1993 Aug;34(8):1099-101.

57. Guyton AC HJ. Textbook of Medical Physiology. 10th ed. Anonymous. New York: Elsevier Science;2000.

58. Chin J. Intestinal microflora: negotiating health outcomes with the warring community within us. Asia Pac J Clin Nutr. 2004;13(Suppl):S24-S25.

59. Shi HN, Walker A. Bacterial colonization and the development of intestinal defences. Can J Gastroenterol. 2004 Aug;18(8):493-500.

60. Kontula P, Jaskari J et al. The colonization of a simulator of the human intestinal microbial ecosystem by a probiotic strain fed on a fermented oat bran product: effects on the gastrointestinal microbiota. Appl Microbiol Biotechnol. 1998 Aug;50(2):246-52.

61. Rothman S, Liebow C et al. Conservation of digestive enzymes. Physiol Rev. 2002 Jan;82(1):1-18.

62. Acheson DW, Luccioli S. Microbial-gut interactions in health and disease. Mucosal immune responses. Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):387-404.

63. Goossens D, Jonkers D et al. Probiotics in gastroenterology: indications and future perspectives. Scand J Gastroenterol Suppl. 2003;(239):15-23.

64. Turner NJ, Thomson BM et al. Bioactive isoflavones in functional foods: the importance of gut microflora on bioavailability. Nutr Rev. 2003 Jun;61(6 Pt 1):204-13.

65. Kaur G, Gardiner A et al. Rectoanal reflex parameters in incontinence and constipation. Dis Colon Rectum. 2002 Jul;45(7):928-33.

66. Chiarelli P, Brown W et al. Constipation in Australian women: prevalence and associated factors. Int Urogynecol J Pelvic Floor Dysfunct. 2000;11(2):71-8.

67. Pfenninger JL, Zainea GG. Common anorectal conditions: Part I. Symptoms and complaints. Am Fam Physician. 2001 Jun 15;63(12):2391-8.

68. Wald A. Constipation, diarrhea, and symptomatic hemorrhoids during pregnancy. Gastroenterol Clin North Am. 2003 Mar;32(1):309-22, vii.

69. Heitland W. [Rectal prolapse in adults]. Chirurg. 2004 Sep;75(9):882-9.

70. Sobrado CW, Kiss DR et al. Surgical treatment of rectal prolapse: experience and late results with 51 patients. Rev Hosp Clin Fac Med Sao Paulo. 2004 Aug;59(4):168-71.

71. Chen GD, Hu SW et al. Prevalence and correlations of anal incontinence and constipation in Taiwanese women. Neurourol Urodyn. 2003;22(7):664-9.

72. Scarlett Y. Medical management of fecal incontinence. Gastroenterology. 2004 Jan;126(1 Suppl 1):S55-S63.

73. De Giorgio R, Guerrini S et al. New insights into human enteric neuropathies. Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:143-7.

74. Schiller LR. New and emerging treatment options for chronic constipation. Rev Gastroenterol Disord. 2004;4 Suppl 2:S43-S51.

75. Tomita R, Tanjoh K et al. Regulation of the enteric nervous system in the colon of patients with slow transit constipation. Hepatogastroenterology. 2002 Nov;49(48):1540-4.

76. Tomita R, Fujisaki S et al. Role of nitric oxide in the colon of patients with slow-transit constipation. Dis Colon Rectum. 2002 May;45(5):593-600.

77. Orr WC, Chen CL. Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging. Am J Physiol Gastrointest Liver Physiol. 2002 Dec;283(6):G1226-G1231.

78. Wade PR. Aging and neural control of the GI tract. I. Age-related changes in the enteric nervous system. Am J Physiol Gastrointest Liver Physiol. 2002 Sep;283(3):G489-G495.

79. Watson R. Assessing the gastrointestinal (GI) tract in older people: 2. The lower GI tract. Nurs Older People. 2001 Mar;13(1):27-8.

80. Camilleri M, Lee JS et al. Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people. J Am Geriatr Soc. 2000 Sep;48(9):1142-50.

81. Robson KM, Kiely DK et al. Development of constipation in nursing home residents. Dis Colon Rectum. 2000 Jul;43(7):940-3.

82. Coremans G, Kerstens R et al. Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trial. Digestion. 2003;67(1-2):82-9.

83. Emmanuel AV, Roy AJ et al. Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther. 2002 Jul;16(7):1347-56.

84. Sloots CE, Poen AC et al. Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation. Aliment Pharmacol Ther. 2002 Apr;16(4):759-67.

85. Farup PG, Bytzer P. Tegaserod--merely a laxative? Scand J Gastroenterol. 2004 Apr;39(4):404-5.

86. Fisher RS, Thistle J et al. Tegaserod does not alter fasting or meal-induced biliary tract motility. Am J Gastroenterol. 2004 Jul;99(7):1342-9.

87. Johanson JF, Wald A et al. Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial. Clin Gastroenterol Hepatol. 2004 Sep;2(9):796-805.

88. Klaschik E, Nauck F et al. Constipation--modern laxative therapy. Support Care Cancer. 2003 Nov;11(11):679-85.

89. Pietrusko RG. Use and abuse of laxatives. Am J Hosp Pharm. 1977 Mar;34(3):291-300.

90. Benton JM, O'Hara PA et al. Changing bowel hygiene practice successfully: a program to reduce laxative use in a chronic care hospital. Geriatr Nurs. 1997 Jan;18(1):12-7.

91. McClung HJ, Potter C. Rational use of laxatives in children. Adv Pediatr. 2004;51:231-62.

92. Motola G, Mazzeo F et al. Self-prescribed laxative use: a drug-utilization review. Adv Ther. 2002 Sep;19(5):203-8.

93. Schiller LR. Review article: the therapy of constipation. Aliment Pharmacol Ther. 2001 Jun;15(6):749-63.

94. Izzo AA, Gaginella TS et al. The osmotic and intrinsic mechanisms of the pharmacological laxative action of oral high doses of magnesium sulphate. Importance of the release of digestive polypeptides and nitric oxide. Magnes Res. 1996 Jun;9(2):133-8.

95. Pampati V, Fogel R. Treatment Options for Primary Constipation. Curr Treat Options Gastroenterol. 2004 Jun;7(3):225-33.

96. Doughty DB. When fiber is not enough: current thinking on constipation management. Ostomy Wound Manage. 2002 Dec;48(12):30-41.

97. Corazziari E, Badiali D et al. Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation. Dig Dis Sci. 1996 Aug;41(8):1636-42.

98. Sharif F, Crushell E et al. Liquid paraffin: a reappraisal of its role in the treatment of constipation. Arch Dis Child. 2001 Aug;85(2):121-4.

99. DiPalma JA. Current treatment options for chronic constipation. Rev Gastroenterol Disord. 2004;4 Suppl 2:S34-S42.

100. Cohan CF, Kadakia SC et al. Serum electrolyte, mineral, and blood pH changes after phosphate enema, water enema, and electrolyte lavage solution enema for flexible sigmoidoscopy. Gastrointest Endosc. 1992 Sep;38(5):575-8.

101. Rousseau P. Treatment of constipation in the elderly. Postgrad Med. 1988 Mar;83(4):339-5, 349.

102. Yakabowich M. Prescribe with care. The role of laxatives in the treatment of constipation. J Gerontol Nurs. 1990 Jul;16(7):4-11.

103. Riemann JF, Schmidt H et al. The fine structure of colonic submucosal nerves in patients with chronic laxative abuse. Scand J Gastroenterol. 1980;15(6):761-8.

104. Fireman Z, Kopelman Y et al. Effect of oral purgatives on gastric and small bowel transit time in capsule endoscopy. Isr Med Assoc J. 2004 Sep;6(9):521-3.

105. Lembo A. Irritable bowel syndrome medications side effects survey. J Clin Gastroenterol. 2004 Oct;38(9):776-81.

106. Ohlen K. [The effect of polyethylene glycol in chronic constipation is not sufficiently evaluated. A systematic literature review]. Lakartidningen. 2004 Aug 19;101(34):2568-72.

107. Browning SM. Constipation, diarrhea, and irritable bowel syndrome. Prim Care. 1999 Mar;26(1):113-39.

108. McIntyre PB, Pemberton JH. Pathophysiology of colonic motility disorders. Surg Clin North Am. 1993 Dec;73(6):1225-43.

109. Holmberg SB. [The man behind the syndrome. Denis Burkitt. He surveyed malignant lymphoma in African children--also a pioneer in dietary fiber research]. Lakartidningen. 1991 Dec 11;88(50):4333-4.

110. Lee TC. Seeing the wood for the trees--the early papers of Denis Burkitt. J Ir Coll Physicians Surg. 1996 Apr;25(2):126-30.

111. Slavin JL. Dietary fiber: classification, chemical analyses, and food sources. J Am Diet Assoc. 1987 Sep;87(9):1164-71.

112. Yin W, Huang C et al. [Determination of total, soluble and insoluble dietary fiber in foods]. Wei Sheng Yan Jiu. 2004 May;33(3):331-3.

113. Gray DS. The clinical uses of dietary fiber. Am Fam Physician. 1995 Feb 1;51(2):419-26.

114. Anonymous. Modern Nutrition in Health and Disease. 9th ed. Shils ME OJSMRA Ed. New York: Lippincott Williams & Wilkins;1999.
115. Han LK, Kimura Y et al. Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet. Int J Obes Relat Metab Disord. 1999 Feb;23(2):174-9.

116. Ylitalo R, Lehtinen S et al. Cholesterol-lowering properties and safety of chitosan. Arzneimittelforschung. 2002;52(1):1-7.

117. Kanauchi O, Deuchi K et al. Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. Biosci Biotechnol Biochem. 1995 May;59(5):786-90.

118. McRorie JW, Daggy BP et al. Psyllium is superior to docusate sodium for treatment of chronic constipation. Aliment Pharmacol Ther. 1998 May;12(5):491-7.

119. Bouchoucha M, Faye A et al. Effect of an oral bulking agent and a rectal laxative administered alone or in combination for the treatment of constipation. Gastroenterol Clin Biol. 2004 May;28(5):438-43.

120. Salwen WA, Basson MD. Effect of four-day psyllium supplementation on bowel preparation for colonoscopy:A prospective double blind randomized trial [ISRCTN76623768]. BMC Gastroenterol. 2004 Feb 2;4(1):2.

121. Marsicano LJ, Berrizbeitia ML et al. [Use of glucomannan dietary fiber in changes in intestinal habit]. G E N. 1995 Jan;49(1):7-14.

122. Passaretti S, Franzoni M et al. Action of glucomannans on complaints in patients affected with chronic constipation: a multicentric clinical evaluation. Ital J Gastroenterol. 1991 Sep;23(7):421-5.

123. Marzio L, Del Bianco R et al. Mouth-to-cecum transit time in patients affected by chronic constipation: effect of glucomannan. Am J Gastroenterol. 1989 Aug;84(8):888-91.

124. Gremse DA, Hixon J et al. Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children. Clin Pediatr (Phila). 2002 May;41(4):225-9.

125. van der SM, Vermeulen H et al. Effectiveness of lactulose syrup after cardiac surgery. Appl Nurs Res. 2004 Feb;17(1):48-54.

126. Loening-Baucke V, Miele E et al. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics. 2004 Mar;113(3 Pt 1):e259-e264.

127. Signorelli P, Croce P et al. [A clinical study of the use of a combination of glucomannan with lactulose in the constipation of pregnancy]. Minerva Ginecol. 1996 Dec;48(12):577-82.

128. Staiano A, Simeone D et al. Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children. J Pediatr. 2000 Jan;136(1):41-5.

129. Krone CA, Ely JT. Ascorbic acid, glycation, glycohemoglobin and aging. Med Hypotheses. 2004;62(2):275-9.

130. May JM, Qu ZC. Transport and intracellular accumulation of vitamin C in endothelial cells: relevance to collagen synthesis. Arch Biochem Biophys. 2005 Feb 1;434(1):178-86.

131. Nelson RL, Persky V et al. Determination of factors responsible for the declining incidence of colorectal cancer. Dis Colon Rectum. 1999 Jun;42(6):741-52.

132. Guillard O, Delmotte JS et al. [Treatment of constipation with vitamin B5 or dexpanthenol]. Med Chir Dig. 1979;8(7):671-4.

133. German Federal Institute for Drugs and Medical Devices. Complete German Commission E Monographs. ed. Therapeutic Guide to Herbal Medicines. Blumenthal M Ed. Boston: American Botanical Council;1998.
134. Schrader R. [Black radish in the treatment of liver and bile duct diseases.]. Hippokrates. 1956 Sep 15;27(17):561-3.

135. Rigo J. [Role of food fiber in nutrition]. Vopr Pitan. 1982 Jul;(4):26-30.

136. Gutierrez RM, Perez RL. Raphanus sativus (Radish): Their Chemistry and Biology. ScientificWorldJournal. 2004 Sep 13;4:811-37.

137. Safuanova GS, Nikulicheva VI et al. [Comprehensive evaluation of the immune system and various cytokines in patients with iron-deficient anemia]. Klin Lab Diagn. 2004 Jan;(1):24, 33-24, 35.

138. Esanu V, Prahoveanu E. The effect of an aqueous horse-radish extract, applied as such or in association with caffeine, on experimental influenza in mice. Virologie. 1985 Apr;36(2):95-8.

139. Burns MM. Activated charcoal as the sole intervention for treatment after childhood poisoning. Curr Opin Pediatr. 2000 Apr;12(2):166-71.

140. Hubner WD, Moser EH. Charcoal tablets in the treatment of patients with irritable bowel syndrome. Adv Ther. 2002 Sep;19(5):245-52.

141. Hepner GW, Hofmann AF. Cholic acid therapy for constipation. A controlled study. Mayo Clin Proc. 1973 May;48(5):56-8.

142. Veysey MJ, Thomas LA et al. Colonic transit influences deoxycholic acid kinetics. Gastroenterology. 2001 Oct;121(4):812-22.

143. Chanussot F, Domingo N et al. Influence of dehydrocholic and cholic acids on the biliary secretion of anionic polypeptide fraction, the major apoprotein of the biliary lipoprotein complex. Scand J Gastroenterol. 1992;27(3):238-42.

144. Fleming SE, Fitch MD et al. High-fiber diets: influence on characteristics of cecal digesta including short-chain fatty acid concentrations and pH. Am J Clin Nutr. 1989 Jul;50(1):93-9.

145. Friedman G. Treatment of the irritable bowel syndrome. Gastroenterol Clin North Am. 1991 Jun;20(2):325-33.

146. Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. Gastroenterology. 1991 Jul;101(1):55-65.

147. Bundy R, Walker AF et al. Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J Altern Complement Med. 2004 Aug;10(4):667-9.

148. Koebnick C, Wagner I et al. Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation. Can J Gastroenterol. 2003 Nov;17(11):655-9.

149. Borody TJ, Warren EF et al. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol. 2004 Jul;38(6):475-83.

150. Hamilton-Miller JM. Probiotics and prebiotics in the elderly. Postgrad Med J. 2004 Aug;80(946):447-51.

151. Wanitschke R, Goerg KJ et al. Differential therapy of constipation--a review. Int J Clin Pharmacol Ther. 2003 Jan;41(1):14-21.

152. Langmead L, Rampton DS. Review article: herbal treatment in gastrointestinal and liver disease--benefits and dangers. Aliment Pharmacol Ther. 2001 Sep;15(9):1239-52.

153. Kadake K, Fukumoto K et al. [Clinical effect of rhubarb and glycyrrhiza extract tablets on constipation]. Nippon Rinsho. 1973 Oct;31(10):3069-73.

154. Trepel F. [Dietary fibre: more than a matter of dietetics. II. Application in prevention and therapy]. Wien Klin Wochenschr. 2004 Aug 31;116(15-16):511-22.

155. Huang CT, Gopalakrishna GS et al. Fiber, intestinal sterols, and colon cancer. Am J Clin Nutr. 1978 Mar;31(3):516-26.

156. Hu C, Kitts DD. Antioxidant, prooxidant, and cytotoxic activities of solvent-fractionated dandelion (Taraxacum officinale) flower extracts in vitro. J Agric Food Chem. 2003 Jan 1;51(1):301-10.

157. Leu YL, Shi LS et al. Chemical constituents of Taraxacum formosanum. Chem Pharm Bull (Tokyo). 2003 May;51(5):599-601.

158. Dai C, Weng X. The theory of "expelling pathogens regardless of hard stool", a significant contribution of Wu Youke. Zhonghua Yi Shi Za Zhi. 1999 Apr;29(2):77-8.

159. Yan SQ. [Actions of rhubarb and other Chinese drugs and compound prescriptions in animal models]. Zhong Yao Tong Bao. 1988 Aug;13(8):43-5, 64.

160. Palsson OS, Heymen S et al. Biofeedback treatment for functional anorectal disorders: a comprehensive efficacy review. Appl Psychophysiol Biofeedback. 2004 Sep;29(3):153-74.

161. Bassotti G, Chistolini F et al. Biofeedback for pelvic floor dysfunction in constipation. BMJ. 2004 Feb 14;328(7436):393-6.

162. Heymen S, Jones KR et al. Biofeedback treatment of constipation: a critical review. Dis Colon Rectum. 2003 Sep;46(9):1208-17.

163. Stessman M. Biofeedback: its role in the treatment of chronic constipation. Gastroenterol Nurs. 2003 Nov;26(6):251-60.