It’s Alimentary

Nutritional Support is Vital to Digestive Health

References

Americans struggle with the specifics of digestion and are undereducated on how their own digestive systems work. While alarming, this lack of digestive awareness is no surprise, considering the complexity involved in the digestion process. “On the one hand we have an abundance of inexpensive food and the opportunity for most North Americans to eat quite healthy,” explained Dan Murray, associate director at Lonza. “On the other hand we have the digestive aids for heartburn as one of the largest categories by sales in the Food, Drug and Mass Market channel. We seem to demand an instant solution to heartburn and digestive problems rather than addressing and fixing the underlying issue.”

If the industry is to make ground against the digestive ailments that increasingly trouble Americans, education will lead the way. Retailers’ grasp of digestion, along with their ability to pass this knowledge on to consumers, is a crucial part of this educational effort.

Along its journey down the alimentary canal, or digestive tract, food makes many important stops. The mouth is an important first stop for incoming food, as chewing helps mechanically break down food into more moveable masses and prompts salivation. Amylase enzymes in saliva begin to break down starches and sugars. When food is swallowed, it heads down the esophagus and enters the J-shaped stomach through an important valve, the lower esophageal sphincter. When this valve malfunctions, it allows scorching stomach acid to flow back into the esophagus, a condition known as acid reflux or heartburn.

The stomach churns and mixes the food with acids and enzymes, further reducing it into smaller, more digestible pieces. Water, sugar, salt and alcohol can be absorbed through the stomach wall to some degree, but most of the food will need to be digested further down the digestive tract. Before it leaves the stomach, food is turned into chyme; when chyme, a thick liquid, has achieved the right consistency, the pylorus, a walnut-shaped muscular tube, allows the mixture into the small intestine.

Although not officially part of the alimentary canal, the liver, gallbladder and pancreas are three vital digestion organs, as they produce and store key digestive agents. The liver produces bile, which can be stored in the gallbladder and used to help digest fats. The pancreas produces a range of digestive enzymes, each with a specific receptor site for a specific substance. While amylase enzymes break down carbohydrates, proteases handle proteins, and lipases take care of fats. These enzymes reduce the food substances to molecules small enough to pass or almost pass through the intestinal wall, which has further digestive capability to handle the bigger molecules. All told, most nutrients and some water are absorbed in the small intestine’s three sections—the duodenum, jejunum and ileum.

After the small intestine, all remaining undigested food and some water moves on to the large intestine, where remaining water content is removed, which hardens the stool, and electrolytes (salt and chloride) get one final chance at absorption. The large intestine, also called the large gut, is home to a bacterial empire, which produces enzymes that can break down otherwise indigestible food particles, such as cellulose and other carbohydrates. This results in fatty acids, lactic acid, methane, hydrogen and carbon dioxide. Microflora can also synthesize vitamin K, which helps make clinical vitamin K deficiency rare, as well as vitamin B. At this point, the vitamin B is too far into the digestive tract to be absorbed.

Based on the timeline of digestion, food spends most of its digestive journey in the intestines, which are teeming with enzymes and bacteria. This is the focus of most dietary supplements designed to improve digestive health.

The body produces more than 20 enzymes for digestive use in the saliva, stomach and small intestines; although plant and animal foods often contain enzymes necessary for their own digestion. However, various environmental and health factors can decrease bodily enzyme production, and over-processing can leave foods devoid of their enzyme content. Depleted foods put even more pressure on the body’s enzyme reserves. Even in healthy people, enzyme production tends to decline as a consequence of aging. For all these reasons, enzyme supplementation has become important.

There is some debate about the effectiveness of digestive enzymes, as critics claim that as proteins, enzymes are digested before they can work. However, plantderived enzymes have different amino acid sequences and generally survive longer than animal-derived enzymes. And research has upheld the benefit of dietary enzymes. University of Manitoba, Winnepeg, researchers tested multi-enzyme combinations on pigs, finding the supplements improved digestibility and utilization of nutrients.¹ Chinese researchers achieved similar results, concluding enzymes boost overall growth in pigs with suppressed endogenous enzymes.² Other animal studies have confirmed enzyme supplementation can improve nutrient bioavailability and weight gain.^3,4

Studies on humans have also demonstrated positive digestive benefits from enzyme supplementation. A study conducted at the American Institute for Biosocial and Medical Research (AIBMR), Tacoma, Wash., showed a patented amylase enzyme (as Carbogen® from Triarco Industries) improved carbohydrate metabolism and increased resulting glucose assimilation in male cyclists.⁵ In another study, supplemental lipase reduced bloating and gassiness in subjects fed high-fat cookies.⁶

Forsyth, Mo.-based National Enzyme Co. (NEC) and TNO Nutrition and Food Research, based in Zeist, Netherlands, collaborated on a study to define the benefits of enzyme supplementation on digestion and nutrient absorption.⁷ They tested a fungal enzyme formula—containing amylase, protease and lipase enzymes—on both a perfect human digestion model and one of impaired human digestion. After sampling nutrients at various times and locations in the digestive tract, researchers found the NEC formula significantly increased carbohydrate digestion in the jejunum and ileum in both models, while slightly improving protein digestion in the ileum without any change in the jejunum. They noted the results were more pronounced in the impaired digestion model.

Proteolytic enzymes, which target proteins, have other digestive talents besides nutrient absorption. Bromelain, from pineapple, can break down collagen and muscle fibers, and it also has anti-inflammatory properties that have shown potential benefit to individuals with diarrhea. University of Maryland, Baltimore, researchers concluded bromelain helps prevent diarrhea by inhibiting secretion of various toxins and pro-inflammatory mechanisms.⁸ Papain, from papaya, is another anti-inflammatory proteolytic enzyme used in digestion supplements.

Most people pay attention to digestion only when the system becomes dysfunctional. Diarrhea can result from many health issues, but its effect is felt in the digestive tract, with runny stool, too frequent bowel movements and dehydration. Persistent or severe diarrhea can be especially devastating to a person’s health. A pair of research reviews found probiotics can complement rehydration therapy used to treat infectious diarrhea in adults and children.^11,12 Chronic diarrhea associated with antibiotic use can also benefit from probiotic supplementation, according to a University of Ottawa study¹³ and confirmed by a British study.¹⁴

As diarrhea can be more pronounced and debilitating in children, research has focused more on this population. Israeli researchers discovered a lower resulting incidence of diarrhea in infants taking formula supplemented with Bifidobacterium lactis and Lactobacillus reuteri.¹⁵ Similarly, French researchers in a multi-center trial reported formula containing Bifidobacterium lactis reduced incidence and severity of diarrhea.¹⁶ However, another trial produced mixed results, as probiotic-fortified infant formula failed to decrease incidence of diarrhea but managed to decrease the severity of diarrhea episodes.¹⁷ Mixed results were also found in a recent study conducted in Bangladesh, which concluded Lactobacillus casei strain ST11 had an inhibitory effect on non-rotoviral diarrhea in children, but did not impact rotoviral diarrhea.¹⁸

Probiotics also benefit those suffering from constipation. A probiotic beverage containing L. casei helped improve severity of constipation and stool consistency in German patients with chronic constipation.¹⁹ In contrast, other studies have questioned or negated the benefit of various lactobacilli on constipation.²⁰

Constipation and diarrhea are two of the many symptoms associated with IBS, which affects up to 20 percent of Americans and is the most commonly diagnosed disorder by gastroenterologists. It is considered a functional disease or disorder, because it is attributed to a disturbance in interaction between the gut, brain and nervous system, instead of to a structural or biochemical cause. IBS is characterized by a set of symptoms in conjunction with abdominal pain.

Probiotic supplementation has been associated with decreased IBS symptoms.²¹ In a recent study, Japanese adults with IBS experienced numerous symptom improvements, including reduced pain and bloating, as well as normal bowel movement, after supplementing with a combination probiotic product for 12 weeks.²² An Italian study involving 70 IBS patients and a combination probiotic produced similar results.²³ Mayo Clinic researchers also reported bloating and pain relief in IBS patients after probiotic supplementation, noting the benefits may be unrelated to changes in intestinal transit time.²⁴ A recent French study showed a combination of L. acidophilus and L. rhamnosus (as Lactofil®, from Lallemand) inhibited symptoms of IBS. However, a recent trial conducted by the Sourasky Medical Center, Tel-Aviv, Israel, failed to find improvement to IBS symptoms by probiotic supplementation with L. reuteri.²⁵ They conceded lack of uniformity of the IBS patient population, along with a strong placebo effect, might have hindered the study’s results.

Probiotics have even gone head-to-head with IBS pharmaceuticals. Irish researchers gave 77 IBS patients either Bifidobacterium infantis, Lactobacillus salivarius or a placebo for eight weeks.²⁶ Based on their daily assessments, B. infantis outperformed the other treatments in alleviating symptoms of IBS, including abdominal pain, bloating and bowel movement difficulty. The scientists concluded the effectiveness of B. infantis was comparable to IBS drugs Zelnorm and Lotronex.

Healthy microflora is also useful against IBDs, including ulcerative colitis (UC) and Crohn’s disease. Some form of IBD affects as many as 500,000 Americans by attacking their intestinal lining, causing inflammatory pain and ulcers. UC affects the large intestine, while Crohn’s is active in the small intestine and adds malnutrition to its list of negative effects.

Scientists suggest probiotics have a significant impact on UC development and progression.²⁷ According to scientific theory, probiotics prevent pathogenic bacteria from colonizing in the gut, protection that extends to the gut barrier.²⁸ Italian researchers noted probiotics can also influence the extent of mucosal barrier injury.²⁹ A recent trial conducted in Spain confirmed all these gut and mucosal barrier protections.³⁰ Additional theory suggests beneficial bacteria also defuses inflammation in the gut, by way of inhibited pro-inflammatory cytokine expression.³¹

While probiotics, in general, can improve UC and promote remission,³² specific probiotic strains have made an impact on UC and its symptoms. L. farciminis given before induction of UC helped maintain intestinal integrity and dispel inflammation in a French animal study,³³ while L. reuteri and L. paracasei achieved similar results in a comparable study that monitored inflammatory cytokines and mucosal inflammation.³⁴ Bifido bacteria given to Japanese UC patients in a Tokyo University trial reduced disease activity scores, as well as scores of both endoscopy acticity and histology.³⁵

Both lactobacilli and bifido probiotics have benefited pouchitis, an inflammatory disease similar to and associated with UC. Norwegian patients given milk fermented with both lactobacilli and bifido bacteria prior to pouchitis surgery experienced reduced symptoms and post-surgical endoscopic activity.³⁶ Individually, Lactobacillus GG given to Dutch UC patients prior to surgery delayed the development of postoperative pouchitis;³⁷ while bifido probitics given to Chinese UC patients helped reduce flare-ups, compared to standard drug treatment with sulphasalazine and glucocorticoids.³⁸

Researchers from University of Dundee, England, gave bifido probiotic combined with prebiotic (as Synergy 1 inulin-igliofructose, from Orafti) to active UC patients for one month and monitored gut bacteria levels and inflammation.³⁹ Patients on the combination treatment displayed decreased inflammation and related cytokines, and exhibited gut epithelial tissue regeneration.

According to Japanese researchers, FOS can be converted into short chain fatty acids in the colon to improve immune function and the absorption of nutrients, particularly minerals.⁴⁰ Prebiotics, including FOS and inulin, were also found to influence the function of the Peyer’s patches in the gut,⁴¹ as well as increase levels of bifidobacteria and other endogenous beneficial bacteria in the gut.⁴²

On specific digestive malady, a combination product, FOS and L. sporogenes, significantly reduced duration of antibiotic-induced diarrhea in children in an Italian study.⁴³ Individually, inulin reduced diarrhea in an Ohio State University, Columbus, study,⁴⁴ and FOS (as NutraFlora®, from GTC Nutrition) reduced intestinal inflammation by increasing intestinal lactic acid bacteria in a French study.⁴⁵ Further, Belgium scientists investigated chicory inulin (as Oliggo-Fiber®, from Cargill) via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), monitoring microbial community from the colon, metabolic activity and community structure.⁴⁶ They concluded inulin exerts prebiotic effects in the colon and stimulates intestinal microbes, including bifido bacteria.

Germinated barley foodstuff (GBF) also contains prebiotic chains and has shown promise in modulating UC. An early Japanese study involved mild to moderate UC patients given GBF for four weeks, which resulted in clinical and endoscopic symptom improvements.⁴⁷ A subsequent study involving similar UC patients involved GBF supplementation for 24 weeks and resulted in a significant decrease in clinical UC activity scores, without side effects.⁴⁸

Prebiotics are a form of dietary fiber, one of the most essential dietary nutrients for digestive health. Soluble fiber can improve stool bulk and constipation, as evidenced by a Swedish trial that found a fiber-rich meal effectively addressed constipation and reduced the need for laxatives.⁴⁹ Flax fiber from psyllium (as FibrOmega, from Bioriginal Food and Science Corp.) has been shown to be an effective laxative, increasing fecal weight and promoting high satiety in one recent study.⁵⁰ In other fiber research, gum arabic fiber partially inhibited nitro oxide synthase (NOS), modulated nutrient absorption and improved small intestinal function.⁵¹ Gum arabic fiber also enhanced water absorption and limited potassium loss in a diarrhea model.⁵² Confirming these findings, University of Minnesota, Minneapolis, researchers gave gum arabic or psyllium to patients with fecal incontinence, concluding both fiber supplements were completely fermented in the colon and reduced incontinent stool.⁵³

Soluble fiber combined with probiotics and glutamine reduced incidence of diarrhea in HIV-positive patients in a study conducted by researchers from the Advocate Illinois Masonic Center, Chicago.⁵⁴ Glutamine, an amino acid, fuels intestinal cells and has shown various digestive health benefits. Turkish research has shown glutamine can reduce duration of diarrhea in children by promoting intestinal mucosal health.⁵⁵ Another study revealed the amino acid supplement increases water and electrolyte absorption in the jejunum of healthy adults.⁵⁶ The scientists concluded it could be a useful treatment in for diarrhea patients on rehydration therapy.

Research has also linked zinc levels with diarrhea and reported supplementation with the mineral could help treat and prevent the illness. Scientists from All India Institute of Medical Sciences, New Delhi, reported zinc deficiency is common in children from developing countries, where diarrhea is also widespread.⁵⁷ Other New Delhi research found zinc supplementation as a part of rehydration therapy reduced stool output and illness duration in children with acute diarrhea.⁵⁸ A University of Bergen, Norway, trial also concluded zinc should be among standard treatments for childhood diarrhea in developing countries. Combined supplementation with zinc and ferrous sulfate increased hemoglobin response and reduced incidence of diarrhea in a Peruvian trial.⁵⁹

Mineral supplementation goes beyond diarrhea inhibition. Low zinc levels were linked to zinc absorption in Crohn’s patients.⁶⁰ Despite the absorption issue, supplementation with zinc sulfate appears to improve intestinal barrier function and lower the risk of relapse in Crohn’s patients, according to an Italian study.⁶¹ Low zinc intake was revealed in a study conducted by scientists at the University of Valladolid, Spain, which also found low intakes of calcium, magnesium and fiber in IBS patients.⁶² Overall, they concluded patients with IBS displayed a deviation from normal dietary vitamin and mineral intake, and correlated low fiber intake with general symptoms.

A chelate complex of zinc and Lcarnosine (as PepZin GI™, from Lonza Inc.) has been touted for its effects on oxidation and mucosal health. “Most digestive products bring relief of discomfort by neutralizing or suppressing stomach acid, a short term solution,” Murray said. “Zinccarnosine works by supporting the stomach lining so the acid we need to digest our food is present, but kept from irritating the walls of our stomach.”

A research review concluded this chelate complex directly suppressed the growth of H. pylori, which can cause ulcers, and inhibited the activity of urease produced by H. pylori infection.⁶³ PepZin GI has also inhibited H. pylori-associated intestinal inflammation and leukocyte activation,⁶⁴ and promoted lesion healing by enhancing mucosal growth factor expression.⁶⁵ Researchers have also reported this mineralamino chelate can protect the stomach against NSAID-induced mucosal injury, most likely due to antioxidant and anti-inflammatory properties.⁶⁶

While known for its topical benefits, aloe has demonstrated antioxidant benefits to patients with IBDs. In a British in vitro study, aloe vera gel inhibited both ROS production and proliferation of inflammatory cytokines associated with IBDs.⁷⁰ The scientists then studied oral aloe supplementation in UC patients, who experienced a clinical response more often from aloe than from a placebo.⁷¹ In a Russian study, combined aloe and coenzyme Q10 (CoQ10) supplementation reduced inflammation and oxidative stress in an animal UC model.⁷²

Although not an antioxidant, folate has shown some promise in IBDs, as Crohn’s patients exhibit low levels of the B vitamin accompanied by high levels of homocysteine, which might also promote thrombotic complications.⁷³

Herbal supplements can help support digestive health and improve digestive problems; and, a few herbs and herbal formulas have been studied for constipation, diarrhea and IBD. Chlorella is a single-celled, green micro-algae that contains many digestive health nutrients, including nondigestible fiber, selenium, antioxidant vitamins and digestive enzymes. A research review conducted at the Medical College of Virginia, Richmond, discovered chlorella can reduce inflammation and improve quality of life patients with colitis.⁷⁴

The herbal formula LaxaCare® from Himalaya USA contains licorice, ginger, chicory (for bile secretion), Indian Jalip (a mild laxative) and Harataki (to promote regularity). In one study, LaxaCare given to 45 patients with chronic constipation improved symptoms in some patients after only three days, without side effects.⁷⁵ Two other studies found the company’s DiarCare® formula improved symptoms of IBS⁷⁶ and chronic diarrhea.⁷⁷ DiarCare contains bael tree, conessi tree, nut grass and guduchi.

Digestive dysfunction is also responsive to specialty supplementation. Hydrolyzed white fish concentrate can improve intestinal barrier function and strengthen intestinal integrity in IBDs. In one study, this fish concentrate supplement (as Seacure, from Proper Nutrition) improved intestinal permeability and symptoms in IBD patients.⁷⁸ In vitro study of this supplement revealed an ability to promote cell proliferation and migration, as well as gastric injury reduction.⁷⁹

Known for its effect on sleep, melatonin may also decrease pain in IBS patients who also report sleep problems, according to a study from the National University Hospital, Singapore.⁸⁰ Study results showed melatonin supplementation decreased abdominal pain and increased rectal pain threshold; however, it did not appear to impact bloating, stool type and frequency, anxiety and depression also associated with IBS.

IBS sufferers have hypersensitive dietary concerns, as certain common foods act as antigens to people with IBS issues such as constipation and diarrhea.⁸¹ Those with diarrhea may benefit from whey protein concentrate, which may reduce rotoviral disease by decreasing prevalence of diarrhea and promoting faster fecal viral shedding.⁸²

The infiltration by IBS, along with continuously poor dietary choices, has increased Americans’ awareness of digestive aids, but their overall knowledge of the digestion process is lacking. While countless advertisements for IBS, diarrhea and constipation drugs have littered the airwaves, these ads fail to educate and only serve to sell product.

“IBS and acid reflux are simple indicators of a digestive system in disarray,” explained Patrick Buehl, president and founder of Generation Plus. “Most people don’t know aging and a diverse array of ecotoxins— combined with consuming cooked, processed, nutrient-depleted foods, and inadequate chewing—negatively affects the life-sustaining processes, leading to a variety of potential disorders.”

In contrast, natural digestive product manufacturers help retailers educate themselves and their customers. “We feel education should be a priority,” said Maday Labrador, M.S., technical director with Enzymedica. “We have several educators who give consumer lectures and train retail store employees; we are in the process of updating this program to include a series of five consecutive trainings and a certification program for retailers.”

Education is particularly important when it comes to the two most popular digestion product categories—probiotics and enzymes. Enzyme products are often formulas combining a variety of enzymes, each of which targets a different nutrient. Therefore, it is important to know which specific enzymes in a formula are amylases, proteases or lipases. Once the enzyme type is determined, potency is the next issue.

Enzymes are listed in terms of active units, which represents how much of its target nutrient the enzyme will potentially breakdown in a specific pH and over a specific time frame. “The pH range of enzymes is important, since it determines how long it will work in the body,” said Labrador, who recommended retailers look for a formulation that will work in varying pH environments. She further suggested retailers take note of the number of strains of each single enzyme type in the formula. “For example, a product with four proteases will be more widely potent than a product with only one protease,” she noted.

Labrador reported a popular choice of enzyme formulas is one based on fungal enzymes, which are plant-derived. Enzymedica’s Digest Gold contains amylase, protease, maltase, glucoamylase, alpha- Galactosidase, lipase, cellulose, lactase, beta-glucanase, xylanase, pectinase/phytase, hemicellulase, invertase and L. acidophilus. Other enzyme products with similarly robust enzyme types include DigestMORE from RenewLife, Omega-Zyme from Garden of Life, and Digesticol™ from Generation Plus, which also contains flavonoids, amino acids and antioxidants.

Retailers have even more to consider when choosing probiotic products. “Probiotics, unlike most dietary supplements, may be rendered ineffective if manufactured inexpertly, or handled and stored improperly,” explained Tim Gamble, vice president of sales and marketing for Nutraceutix. “The form that the probiotic supplement takes (tablets/caplets, capsules, powders, liquids) and how they are packaged and stored are critical to determining the shelf life.”

Among probiotic products there is a range of delivery systems, including microencapsulation and enteric coating, each of which has its own set of advantages and disadvantages. “A probiotic delivery technology should ensure the delivery of greater numbers of viable organisms past stomach acids and, if it is particularly capable, release organisms to target optimal sites in the intestinal tract,” Gamble said. Nutraceutix developed its own patented controlled-delivery technology, BIO-tract™, which is designed to deliver probiotic payloads to a specific location. A protective gel layer forms over the tablet as it passes through he stomach; once in the intestines, it releases product at controlled intervals. Products such as FloraMORE from RenewLife utilize the BIOtract technology.

Shelf-life is another concern for retailers, as probiotics can lose viability under certain conditions, such as air, heat and moisture. Gamble reported while retailers cannot make up what has been done to the probiotic before it reaches their stores, they can request assurances from the manufacturer about the shelf-life of products. He noted such quality assurance is delivered by via Live-Bac tableting process, which has proven to maintain viability for at least 2.5 years. “Additionally, quality conscious retailers may want to consider refrigeration for probiotic products, particularly those that come in less than ideal forms,” he added.

The most commonly formulated probiotics are bifido and lactobacilli, both resident and transient. Resident bacteria, such as L. acidophilus, attach to the intestinal wall, whereas transient bacteria, such as L. casei, deliver benefits while passing through the intestines. Thus, formulas incorporating both resident and transient bacteria are often preferred. For example, FloraMORE contains acidophilus, rhamnosus, casei and salivarius lactobacilli, as well as bifidum and longum bifidobacteria. Likewise, Floracol™ from Generation Plus contains a blend of 29 different probiotic strains, including lactobacilli, bifido, Pseudomonas, Arthrobacter and Brevibacterium strains.

There are numerous products comprising multiple combinations of digestive health ingredients, designed to support general digestive health and relieve symptoms of digestive dysfunction, including heartburn, gas, diarrhea, constipation and indigestion. Research has outlined specific benefits achieved by specific ingredients. This knowledge in conjunction with an education on digestive system function and malfunction, as well as an awareness of formulation advantages, can help retailers find the best natural digestion supplements for their customers.

November 2005 Health Supplement Retailer
"It’s Alimentary - Digestive Health" References

1.Omogbenigum FO, Nyachoti CM, Slominski BA. "Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs." J Anim Sci. 82, 4:1053-61, 2004. http://jas.fass.org

2. Li WF et al. "Effects of non-starch polysaccharides enzymes on pancreatic and small intestinal digestive enzyme activities in piglet fed diets containing high amounts of barley." World J Gastroenterol. 10, 6:856-9, 2004. www.wjgnet.com

3. Cowieson AJ et al. "Supplementation of diets containing pea meal with exogenous enzymes: effects on weight gain, feed conversion, nutrient digestibility and gross morphology of the gastrointestinal tract of growing broiler chicks." Br Poult Sci. 44, 3:427-37, 2003.

4.Garcia MI et al. "Alpha-amylase supplementation of broiler diets based on corn." Poult Sci. 82, 3:436-42, 2003.

5. Frank LL et al. "The effects of a pre-exercise feeding with or without fungal carbohydrates (Carbogen™) on blood parameters and exercise performance in elite cyclists: a preliminary study." Int J Sport Nutr Exercise Metab. 12:310-7, 2002.

6. Suarez F et al. "Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal." Dig Dis Sci. 44, 7:1317-21, 1999. www.kluweronline.com/issn/0163-2116/current

7. “First Quantitative evidence Proving the efficacy of supplemental enzymes.” TNO Nutrition and Food Research Institute, Zeist, Netherlands, 2004. www.tno.nl

8. Mynott TL et al. “Bromelain prevents secretion caused by Vibrio cholerae and Escherichia coli enterotoxins in rabbit ileum in vitro.” Gastroenterol. 113, 1:175-84,1997.

9. Fedorak RN, Madsen KL. "Probiotics and prebiotics in gastrointestinal disorders." Curr Opin Gastroenterol. 20, 2:146-55, 2004. www.co-gastroenterology.com

10. Gill HS, Guarner F. "Probiotics and human health: a clinical perspective." Postgrad Med J. 80, 947-516-26, 2004. http://pmj.bmjjournals.com

11. Allen SJ et al. "Probiotics for treating infectious diarrhea." Cochrane Database Syst Rev. 2:CD003048, 2004. www.cochrane.org

12. Huang JS et al. “Efficacy of probiotic use in acute diarrhea in children: a meta-analysis.” Dig Dis Sci. 47, 11:2625-34, 2002. www.kluweronline.com/issn/0163-2116/current

13. Benchimol EI, Mack DR. "Probiotics in relapsing and chronic diarrhea." J Pediatr Hematol Oncol. 26, 8:515-7, 2004.

14. Plummer S et al. "Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea." Int Microbiol. 7, 1:59-62, 2004.

15. Weizman Z, Asli G, Alsheikh A. "Effect of a probiotic infant formula on infections in child care centers: a comparison of two probiotic agents." Pediatrics. 115, 1:5-9, 2005. www.pediatrics.org

16. Chouraqui JP, Van Egroo LD, Fichot MC. "Acidified milk formula supplemented with bifidobacterium lactis: impact on infant diarrhea in residential care settings." J Pediatr Gastroenterol Nutr. 38, 3:288-92, 2004. www.jpgn.org

17. Thibault H et al. "Effects of long-term consumption of a fermented infant formula (with Bifidobacterium breve c50 and Streptococcus thermophilus 065) on acute diarrhea in healthy infants." J Pediatr Gastroenterol Nutr. 39, 2:147-52, 2004. www.jpgn.org

18. Sarker SA et al. “Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh.” Pediatrics. 116, 2:e221-8, 2005. www.pediattrics.org

19. Wagner I et al. “Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation.” Can J Gastroenterol. 17, 11:655-9, 2003.

20. Banaszkiewicz A and Szajewska H. “Ineffectiveness of Lactobacillus GG as an adjunct to lactulose for the treatment of constipation in children: a double-blind, placebo-controlled randomized trial.” J Pediatr. 146, 3:364-9, 2005.

21. Floch MH. "Use of diet and probiotic therapy in the irritable bowel syndrome: analysis of the literature." J Clin Gastroenterol. 39, 5 Suppl:S243-6, 2005.

22. Tsuchiya J et al. "Single blind follow-up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome." Chin J Dig Dis. 5, 4:169-74, 2004.

23. Saggioro A. "Probiotics in the treatment of irritable bowel syndrome." J Clin Gastrenterol. 38, 6 Suppl:S104-6, 2004.

24. Kim HJ et al. "A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome." Aliment Pharmacol Ther. 17, 7:895-904, 2003.

25. Niv E et al. “The efficacy of Lactobacillus reuteri ATCC 55730 in the treatment of patients with irritable bowel syndrome-a double blind, placebo-controlled, randomized study. Clin Nutr. Epub ahead of print: Jul7 26, 2005. www.ajcn.org

26. O’Mahony L et al. “Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.” Gastroenterol. 128, 3:541-51, 2005. http://www2.gastrojournal.org

27. Gill HS, Guarner F. "Probiotics and human health: a clinical perspective." Postgrad Med J. 80, 947-516-26, 2004. http://pmj.bmjjournals.com

28. Fedorak RN, Madsen KL. "Probiotics and the management of inflammatory bowel disease." Inflamm Bowel Dis. 10, 3:286-99, 2004. www.ccfa.org/physician/table7.htm

29. Gionchetti P et al. “Probiotics and barrier function in colitis.” Gut. 54, 7:898-900, 2005. http://gut.bmjjournals.com

30. Llopis M et al. “Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by exposure to trinitronbenzene sulphonic acid.” Gut. 54, 7:955-9, 2005. http://gut.bmjjournals.com

31. Petrof EO et al. "Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition." Gastroenterology. 127, 5:1474-87, 2004. www.gastrojournal.org

32. Sartor RB. "Probiotic therapy of intestinal inflammation and infections." Curr Opin Gastroenterol. 21, 1:44-50, 2005. www.co-gastroenterol.com

33. Lamine F et al. "Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats." Scand J Gastroenterol. 39, 12:1250-8, 2004. www.tandf.co.uk/journals/titles/00365521.html

34. Pena JA et al. "Probiotic Lactobacillus spp. diminish Helicobacter hepaticus-induced inflammatory bowel disease in interleukin-10-deficient mice." Infect Immun. 73, 2:912-20, 2005. http://iai.asm.org

35. Kato K et al. "Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis." Aliment Pharmacol Ther. 20, 10:1133-41, 2004.

36. Laake KO et al. "Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis." Scand J Gastroenterol. 40, 1:43-51, 2005. www.tandf.co.uk/journals/titles/00365521.html

37. Gosselink MP et al. "Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus GG." Dis Colon Rectum. 47, 6:876-84, 2004.

38. Cui HH et al. "Effects of probiotic on intestinal mucosa of patients with ulcerative colitis." World J Gastroenterol. 10, 10:1521-5, 2004. www.wjgnet.com

39. Furrie E et al. "Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomized controlled pilot trial." Gut. 54, 2:242-9, 2005. http://gut.bmjjournals.com

40. Tokunaga T. "Novel physiological function of fructooligosaccharides." Biofactors. 21, 1-4:89-94, 2004. www.iospress.nl/site/html/09516433.html

41. Manhart N et al. "Influence of fructooligosaccharides on Peyer's patch lymphocyte numbers in health and endotoxemic mice." Nutrition. 19, 7-8, 657-60, 2003. www.journals.elsevierhealth.com/periodicals/nut

42. Bouhnik Y et al. "The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double blind, randomized, placebo-controlled, parallel-group, dose-response relation study." Am J Clin Nutr. 80, 6:1658-64, 2004. www.ajcn.org

43. La Rosa M et al. "[Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructooligosaccharides in children. A multicentric double-blind vs placebo study.]" Minerva Pediatr. 55, 5:447-52, 2003.

44. Kien CL et al. “Effects of prefeeding a prebiotic on diarrhea and colonic cell proliferation in piglets fed lactulose.” J Parenter Enteral Nutr. 28, 1:22-6, 2004. http://jpen.aspenjournals.org

45. Cherbut C et al. “The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats.” J Nutr. 133, 1:21-7, 2003. www.nutrition.org

46. Jacobs H et al. “Prebiotic effects of chicory inulin in the stimulator of the human instestinal microbial ecosystem.” FEMS Microbiol Ecol. 51, 1:143-53, 2004. http://www.sciencedirect.com/science/journal/01686496

47. Bamba T et al. "A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis." J Gastroenterol Hepat. 17, 8:818-24, 2002.

48. Kanauchi O et al. "Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial." Int J Mol Med. 12, 5:701-4, 2003. http://virology.med.uoc.gr/IJMM/ijmm.htm

49. Wisten A and Messner T. “Fruit and fibre (Pajala porridge) in the prevention of constipation.” Scand J Caring Sci. 19, 1:71-6, 2005. http://www.blackwell-synergy.com/loi/scs

50. Presented at the Experimental Biology 2004 conference in Washington, April 2004. www.bioriginal.com.

51. Rehman KU, Codipilly CN, Wapnir RA. "Modulation of small intestinal nitric oxide synthase by gum arabic." Exp Biol Med (Maywood). 229, 9:895-901, 2004. www.ebmonline.org

52. Rehman KU et al. "Gum arabic (GA) modifies paracellular water and electrolye transport in the small intestine." Dig Dis Sci. 48, 4:755-60, 2003. www.kluweronline.com/issn/0163-2116/current

53. Bliss DZ et al. "Supplementation with dietary fiber improves fecal incontinence." Nurs Res. 50, 4:203-13, 2001.

54. Heiser CR et al. "Probiotics, soluble fiber, and L-glutamine (GLN) reduce nelfinavir (NFV)- or lopinavir/ritonavir (LPV/r)-related diarrhea." J Int Assoc Physicians AIDS Care (Chic Ill). 3, 4:121-9, 2004.

55. Yalcin SS et al. "Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea." J Pediatr Gastroenterol Nutr. 38, 5:494-501, 2004. www.jpgn.org

56. Coeffier M et al. "Effect of glutamine on water and sodium absorption in human jejunum at baseline and during PGE1-induced secretion." J Appl Physiol. 98, 6:2163-8, 2005. http://jap.physiology.org

57. Bhatnagar S, Natchu UC. "Zinc in child health and disease." Indian J Pediatr. 71, 11:991-5, 2004.

58. Bhatnagar S et al. "Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial." J Pediatr Gastroenterol Nutr. 38, 1:34-40, 2004. www.jpgn.org

59. Alarcon K et al. "Effects of separate delivery of zinc or zinc and vitamin A on hemoglobin response, growth and diarrhea in young Peruvian children receiving iron therapy for anemia." Am J Clin Nutr. 80, 5:1276-82, 2004. www.ajcn.org

60. Griffin IJ et al. "Zinc metabolism in adolescents with Crohn's disease." Pediatr Res. 56, 2:235-9, 2004. www.pedresearch.org

61. Sturniolo GC et al. "Zinc supplementation tightens 'leaky gut' in Crohn's disease." Inflamm Bowel Dis. 7, 2:94-8, 2001. www.ccfa.org/physician/table7.htm

62. Aller R et al. “[Dietary intake of a group of patients with irritable bowel syndrome; relation between dietary fiber and symptoms.]” An Med Interna. 21, 12:577-80, 2004.

63. Kuwayama H et al. "Polaprezinc." Nippon Rinsho. 60 Suppl 2:717-20, 2002.

64.Suzuki H et al. " Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy." Aliment Pharmacol Ther. 15:715-25, 2001.

65. Korolkiewicz R et al. "Polaprezinc exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats." Dig Dis Sci. 45, 6:1200-9, 2000. www.kluweronline.com/issn/0163-2116/current

66. Naito Y et al. "Effects of polaprezinc on lipid peroxidation, neutrophil accumulation, and TNF-alpha expression in rats with aspirin-induced gastric mucosal injury." Dig Dis Sci. 46, 4:845-51, 2001. www.kluweronline.com/issn/0163-2116/current

67. Andoh A et al. “Serum selenoprotein-P levels in patients with inflammatory bowel disease.” Nutrition. 21, 5:574-9, 2005. http://www.sciencedirect.com/science/journal/08999007

68. Ademoglu E et al. "Do vitamin E and selenium have beneficial effects on trinitrobenzenesulfonic acid-induced experimental colitis." Dig Dis Sci. 49, 1:102-8, 2004. www.kluweronline.com/issn/0163-2116/current

69. Oz HS et al. "Antioxidants as novel therapy in a murine model of colitis." J Nutr Biochem. 16, 5:297-304, 2005. www.elsevier.com/locate/jnutbio

70. Langmead L, Makins RJ, Rampton DS. "Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro." Aliment Pharmacol Ther. 19, 5:521-7, 2004.

71. Langmead L et al. "Randomized, double blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis." Aliment Pharmacol Ther. 19, 7:739-47, 2004.

72. Korkina L et al. "The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats." Biofactors. 18, 1-4:255-64, 2003. www.iospress.nl/site/html/09516433.html

73. Chowers Y et al. "Increased levels of homocysteine in patients with Crohn's disease are related to folate levels." Am J Gastroenterol. 95, 12:3498-502, 2000. www.amjgastro.com

74. Merchant RE, Andre CA. "A review of recent clinical trials of the nutritional supplement Chlorella pyrenoidosa in the treatment of fibromyalgia, hypertension and ulcerative colitis." Altern Ther Health Med. 7, 3:79-91, 2001.

75. Reddy K. "A clinical trial of Herbolax in constipation during post-operative period." Antiseptic. 18, 7:252-3, 2001.

76. Tiwari S, Sharma NK. "Clinical study on the trial drug New Diarex in cases of irritable bowel syndrome." Ind J Clin Pract. 12, 7:52-6, 2001.

77. Tomar GS. "Clinical evaluation of New Diarex in patients with chronic diarrhea." The Ind Pract. 54, 2:119-23, 2001.

78. Nichols TW et al. "Preliminary reports: Improvement in mucosal integrity in IBD patients and reduction in GI symptoms in HIV patients with hydrolyzed white fish." Peptides. 108, 1:31, 2002. www.sciencedirect.com/science/journal/01969781

79. Fitzgerald AJ et al. "Reparative properties of a commercial fish protein hydrolysate preparation." Gut. 54, 6:775-81, 2005. http://gut.bmjjournals.com

80. Song GH et al. “Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study.” Gut. 54, 10:1402-7, 2005. http://gut.bmjjournals.com

81. Zar S et al. “Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome.” Am J Gastroenterol. 100, 7:1550-7, 2005. http://www.blackwell-synergy.com/loi/ajg

82. Wolber FM et al. “Supplemental dietary whey protein concentrate reduces rotavirus-induced disease symptoms in suckling mice.” J Nutr. 135, 6:1470-4, 2005 . www.nutrition.org

Share this article: Email, Slashdot, Digg, Del.icio.us, Yahoo!MyWeb, Windows Live Favorites, Furl
Add this article feed to: RSS, My Yahoo, Newsgator, Bloglines

Read Comments [0]