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Sections : Digestion
Apr 10th, 2006 - 12:14:17

Heather Granato - Natural Products Industry Insider
Aug 11, 2004

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The foods that prolong life and increase purity, vigor, health, cheerfulness and happiness are those that are delicious, soothing, substantial and agreeable. ...Foods that are bitter, sour, salt, overhot, pungent, dry and burning produce unhappiness, repentance and disease.

- Henry Wadsworth Longfellow

If it were only possible that good health was as simple as consuming soothing, delicious foods. However, individual biological differences, taste perceptions and learned impulses (Mom always said to clean your plate) affect both food choices and how that food is utilized by the body. The process of digestion is essentially taking food from point A to point B while extracting out the nutrients necessary to sustain life. In practice, it's a little more complex.

Digestion starts even before food is introduced to the body. Tactile sensation, visual appeal and olfactory experience combine to kick off the process. Think of Paviov's dogs, which were trained to salivate to only the sound of a bell. Looking at a slice of chocolate cake, smelling the cocoa, running a finger across the thick frosting even just thinking about that chocolate cake starts the salivary glands. In addition to contributing moisture to lubricate the food, human saliva contains amylase, which begins to break down starch into smaller glucose molecules.

From the mouth, this food heads down the esophagus, through the esophageal sphincter into the stomach. Within the stomach, powerful enzymes and hydrochloric acid interact with the food to form a liquid substance called chyme. In the stomach, proteins are broken down into amino acids, and the food is macerated into a liquid state that can be absorbed by the body. The process can take up to four hours before the consistency is right to head into the small intestine, composed of the duodenum, jejunum and ileum. The small intestine contains the majority of the body's digestive enzymes, which are secreted by the pancreas, which further break down the food into usable particles that can be absorbed through the microvilli into the circulatory system for dissemination throughout the body.

After the nutrients are absorbed, the remainder moves into the large intestine, which is the primary home to the body's bacteria There are between 400 and 500 bacterial types that exist in the human digestive system. The most common types are bacteroides, bifidobacteria, eubacteria, fusobacteria, lactobacilli, peptococcaceae, rheumanoccoccae and streptococcae. These bacteria support immune function and nutrient production. The large intestine absorbs any excess water and forms the leftover material into stools.

With so many actions happening, it is not surprising that so many Americans suffer from digestive disorders. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) estimates between 60 million and 70 million people are affected by digestive diseases, with these conditions representing 13 percent of all hospitalizations.

Consumers show great willingness to turn to natural products to support their digestive health and treat related maladies. Among the top selections are digestive enzymes, probiotics and fibers. For example, market research data from ACNielserr'SPINScan for the 52 weeks ended July 12, 2003, shows sales of digestive enzymes were up 2.5 percent to $63 million, probiotic sales increased 14 percent to top $47 million, and psyllium/flber sales reached $20 million an increase of almost 20 percent over the previous reporting period. Usage was significantly greater by Empty Nesters and older singles compared to maturing families and younger singles, though usage by race was relatively even.

The increasing number of older Americans, therefore, bodes wall for sales of nutritional compounds to support digestive health. In addition, scientific research supports the use of ingredients such as probiotics, prebiolics, fiber, enzymes and more to keep digestion strong and avoid maladies such as indigestion and constipation. One review from Massachusetts General Hospital, Boston, noted many studies are supporting a strong role for nutrients such as vitamin A, zinc, probiotics and glutamine, and encouraged further research in this area.'

Digestive Support
Probiotics are possibly the best known of the proactive nutraceutical treatments. Mainstream magazines advise readers to consume probiotic rich yogurts or take a supplement after finishing a course of antibiotics to re enrich the gastrointestinal (GI) tract with beneficial bacteria. The importance of the gut flora has been well researched. Among its major functions are metabolic activities to salvage nutrients, support immune health and protect the body against pathogenic microbes.2

Consumers can take in probiotics and prebiotics (non digestible fibers that serve as "food" for the good bacteria) in a variety of ways. Food items such as yogurt, sauerkraut and cheese often contain live lactic acid bacteria, and may deliver the prebiotics inulin.(3) Taking in such products can help alter both nutrient absorption and immune function, as the digestive system operates as an integral part of the systemic immune system.4 This is of particular interest in the clinical setting, where critically ill and postoperative patients rely on their innate immunity and the power of the bugs to prevent opportunistic infection. A research review from London Medical School noted probiotics help patients to reduce or eliminate potentially pathogenic organisms, eliminate toxins, modulate immune responses, promote apoptosis, and release nutrient and growth factors necessary for recovery.(5)

This role in immune health is critical. One French study noted probiofics enhance gut associated lymphoid tissue (GALl) responses through enhanced growth of lactic bacteria and production of short chain fatty acids.5 Another study, conducted at the University of Regensburg, Germany, investigated the immunomodulating effects of Lactobacillus rhamnosus GG in 10 healthy volunteers.7 After oral administration of the probiotic and a challenge with pathogenic bacteria, researchers found the probiotic treatment activated CD4 T lymphocytes and interleukin 10 (IL b) and IL 4. And in a mouse study hang encapsulated Bifidobactetium bifidum, researchers found the probiotics stimulated immunoglobulin synthesis by the Peyer's patch cells (the immune secreting bodies in the digestive system).(8)

Probiotics also have been studied for their ability to treat diarrhea. One meta analysis out of the Children's Hospital of Boston reviewed 18 eligible studies that used coadministration of probiotics with standard rehydration therapy.(9) The researchers noted the addition of probiotic therapy shortened the duration of diarrheal illness in children by approximately one day. In addition, such therapy may also help manage the disease state. In a randomized, controlled clinical study at the Airlangga University School of Medicine, Surabaya, Indonesia, researchers examined the effects of probiotic therapy on acute diarrhea, and found infants who received probiotic containing formula had significantly less frequency of stools,(10) The benefits are not limited to children; a metaanalysis from the University of Wales, England, included 23 studies with a total of 1,917 participants and found probiotics were a useful adjunct to rehydration therapy in treating diarrhea in children and aduits.(11) Additional research has shown probiotics reduce the overall risk of antibioticassociated diarrhea,(12) and enhance recovery afterfasting or malnutrition.(13)

These 'good bugs" are also beneficial in treating the opposite condition constipation. Researchers at the German Institute of Human Nutrition, Bergholz Rehbrucke, conducted a four week, double blind, placebo controlled study in 70 patients with chronic constipation.14 The patients received 65 mL/d of a probiotic beverage with Lactobacillus casei Shirota or an identical placebo. The treatment group reported a significant improvement in severity of constipation and stool consistency, starting in the second week of intervention.

It is not only probiotics that have beneficial effects on 01 and immune heath. A review from the University of Alberta, Edmonton, noted there is increasing evidence that fermentable dietary fiber and prebiotics can modulate immune function by influencing the GALT.1 The researchers speculate prebiotics work by directly stimulating intestinal immune cells, by changing mucin production or by producing short chain fatty acids (SOFA). Another review suggested part of the GI benefit of whole grain ingestion is their concentrated delivery of dietary fiber, resistant starch and other carbohydrates that are fermented to produce SCFA16

The primary categories of prebiotics are fructooligosaccharides (FOS) and inulin, with the differences primarily seen in the length of the fructose terminated chain. Inulin is primarily a long chain, glucoseterminated polysaccharide mixture; its partially hydrolyzed form is known as oligofructose. FOS, while used generically in many cases, primarily refers to a mixture of glucose terminated fructose chains with a maximum length of five units. In a critical review from the Universite Catholique de Louvaln, Belgium, researchers compared the differences in fermentation time between short chain FOS and inulin.(17) In vitro fermentation showed prebiotics with a chain length longer than 10 were fermented on average half as quickly, though ad were classified as beneficial for bacterial growth.

Further in vitro work has supported this finding, noting that probiotics tended to grow more quicly on short chain energy sources, while inulintype fructans are metabolized more slowly.(18) However, delivering inudin with probiotics was shown in a German animal study to specifically enhance immune function.(19) The combined supplement increased secretion of immunoglobulin A and IL 10 to a greater degree than in the animals only given probiotics.

Shorter chain FOS has also been investigated for its immunomodulatory effects. In an Austrian animal study, mice given a diet enriched in FOS increased Payer's Patch lymphocyte numbers under both healthy and toxemic conditions.(20) This may increase the body's resistance to microbial infection, as a study in piglets found those which received FOS prior to infection with Salmonella showed higher resistance and enhanced recovery from the infectbn.(21) This finding is supported in human studies that have shown children who take FOS had greater recovery from diarrhea associated with bacterial infection22 and with antibiotic use.(23)

Researchers are also looking for ways to enhance the function of prebiotics and probiotics in the gut. One animal study conducted in the Slovak Republic investigated the effects of omega 3 polyunsaturated fatty acids on Lactobacillus paracasel colonization and cellular immunity.24 The experimental group showed a significant increase in both probiotic adhesion to the jejunal mucosa and an increase in the phagocytic activity of neutrophils. Further, omega 3 essential fatty acids (EFAs) have been shown to increase the integrity of gut tissue. Two rat studies conducted by Australian researchers investigated the ability of omega 3 EFA5 to affect the contractility of gut tissue.(25,26) Both studies showed an increase in gut tissue PUFA content, increased contractility in the small intestine, and enhanced gut integrity.

In addition, gut function can be influenced by the presence or absence of appropriate digestive enzymes. The hydrolase class of enzymes exists specifically to break down foods, and is divided into proteases (to digest protein), lipases (to digest fats) and amylases (to digest carbohydrates). While many foods in their raw state contain enzymes for digestion, heating and processing break down those enzymes, forcing the gut to use more of its endogenous supply to digest food. Therefore, many consumers are turning to supplemental enzymes to ease the body's burden of enzyme production.

To determine whether supplemental enzymes do, in fact, assist in nutrient digestion and absorption, National Enzyme Co. conducted a collaborative research project with TNO Nutrition & Food Research in Zeist, Netherlands. TNO used a computer controlled dynamic gastrointestinal model (TIM) to simulate the digestive conditions in the human stomach and intestines in both a healthy and an impaired digestive model. The results showed the broad spectrum fungal enzyme blend improved the digestibility and bioaccessibility of proteins and carbohydrates in the small intestine.

Specific studies support these findings. For example, a study conducted at the American Institute for Biosocial and Medical Research (AIBMR) in Tacoma, Wash., investigated the effects of a patented fungal carbohydrase (CarbogenTM, from Wayne, N.J based Triarco Industries) on glucose metabolism in male cyclists.(27) Those athletes taking the enzyme product showed an increase in blood glucose concentrations, indicating faster and more complete assimilation of the carbohydrate product. In another study of supplemental enzymes, healthy subjects were given 185 g of cookies (1196 calories and 72 g fat) with lipase or placebo.(28) Those in the treatment group experienced significantly less bloating, gas and fullness throughout the day compared to placebo.

Digestive Disorders
Nutritional support can do more than just enhance normal digestive function. Studies increasingly show the ability of products such as dietary fiber and probiotics to treat the symptoms associated with (31 disorders, such as inttable bowel syndrome (IBS) and inflammatory bowel disorders (IBO) including Crohn's disease and ulcerative colitis.

IBS is not a life threatening condition, but is one of the most common (31 complaints, affecting 20 percent of Americans, according to NIDDK. IBS causes symptoms such as abdominal cramping and pain, bloating, constipation and diarrhea. lBDs, meanwhile, cause abdominal pain and frequent diarrhea, and impact quality of life. Crohn's causes inflammation in the small intestines, while ulcerative colitis causes inflammation and ulcers in the lining of the large intestine.

While some researchers have suggested dietary modification is of value in IRS patients,(29) others have not found diet therapies such as bulking agents or supplements of value.(30) In fact, one review from Utrech University Medical Center, Netherlands, examined the effects of different types of fiber in treating IBS.(31) The meta analysis of 17 studies suggested soluble and insoluble fibers have different impacts on IBS, with soluble fibers such as ps4Iium and isphaghula showing significant improvement in relief of constipation, whereas insoluble fiber (i.e., wheat bran) in many cases worsened the clinical outcome.

Instead, IBS patients may be turning to probiotics to naturally enhance (31 function. A study conducted at the Mayo Clinic, Rochester, Minn., examined the impact of VSL#3 (from VSL Pharmaceuticals, Fort Lauderdale, Fla.) on IBS patients with predominant diarrhea.(32) Twenty live patients received VSL#3 powder or placebo dally for eight weeks; while there were no significant differences in GI transit measurements or bowel function, there was benefit in abdominal bloating. A review of studies on VSL#3 noted there have been "encouraging results" in patients with IRS, as well as those with lBDs.(33) For exame, two European studies investigated the impact of VSL#3 on patients with chronic pouchitis.(34,35) The first study followed 20 patients treated with VSL#3 for a year, and found a significant improvement in prevention of acute pouchitis compared to the 20 patients receiving placebo. Similarly, the second study found a once daily dose of VSL#3 was effective in maintaining antibiotic induced remission in patients with recurrent or refractory pouchitis.

More general reviews have also touted the role probiotics may play in 180 control. A review from Hopital Huriez in UIIe, France, noted, 'intestinal bacteria play a key role in inflammatory bowel disease. ...[and] some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis."(36) However, the researchers added studies have been focused on particular 180 subgroups, and more clinical studies are required to elucidate the role of probiotics in IBD treatment. Similarly, a review from Imperial College, London, stated there is some suggestion that probiotics can prevent and treat intestinal inflammation, and that clinical studies have demonstrated efficacy of probiotics in treating certain aspects of lBDs.(37) They, too, called for large controlled trials to determine the dose, duration, frequency of treatment, mechanism of action and use of single or multiple strains.

Studies have investigated the action of probiotics in specific types of IBD. German researchers noted probiotics may both impact the intestinal flora and the immune response, thus impacting the progression of ulcerative colitis and pouchitis.(38) A recent study from Lund University in Malmo, Sweden, investigated the effect of probiotic administration in rats prior to induction of colitis.(39) Researchers noted administration of certain strains of Lactobacillus and Bifidobacterium significantly improved the disease progression and reduced the translocation of pathogenic bacteria. In another study in which rats were induced with colitis, pretreatment with Clostridium butyncum prevented bloody diarrhea and mucosal damage in the GI tract.(40)

Studies on colitis have also considered using a combination of probiotics and prebiotics to positivaly impact the condition. In one study at the University of Regensburg, Germany, researchers investigated the impact of a probiotic formula that included inulin on the severity of coFrtls and the gut bacterial profile in rats.(41) Administration of the combination formula increased the diversity of gut microflora, particularly supporting Bifidobacterium growth; however, there was no increase of probiotic bacteria in the cecal content, suggesting the inulin was the more effective compound in the mix. Another study compared the effects of germinated barley (as a prebiotic fiber) with probiotic and antibiotic treatment in a rat colitis model.42 Researchers found the prebiotic treatment significantly reduced colonic inflammation, whereas probiotic treatment had no effect. Finafly, a study of FOS in a rat colitis model found ingestion of FOS significantly reduced intestinal inflammation, primarily by increasing the growth of lactic acid bacteria.(43)

Researchers have also looked beyond just probiotics and prebiotics in treatment of colitis. One study at the University of Aberdeen, Scotland, investigated the effects of EFA supplementation in patients with ulcerative colitis.(44) The six month, double blind study assessed disease activity and immune function; researchers reported omega 3 supplementation suppressed immune reactivity and reduced disease activity. Another study looked at how a natural antioxidant preparation combining aloe vera and ubiquniol affected intestinal inflammation and disease progression in a rat colitis model.(45) Inflammation, gut impairment and oxidative stress were reduced by pre treatment with the antioxidant preparation, but had no significant effects if delivered after disease induction.

Similar to the studies in colitis, researchers investigating Crohn's disease have turned to dietary factors to modulate inflammation. In particular, low fat diets have been shown useful, even with additional medium chain triglycerides added, while probiotic/prebiotic treatment may help as well.(45) As dietary fat may exacerbate intestinal inflammation, one Japanese study looked at how chitosan could increase fat excretion; the researchers found patients given chitosan for 8 weeks showed a significant increase in fecal fat concentration.(47) Fat metabolism may also be impaired in patients with Crohn's, as it appears EFA profiles are altered in children with Crohn's. Researchers investigating blood lipids in 30 adolescents with Crohn's found the patients had particularly high levels of arachidonic acid (a pro inflammatory fatty acid) and low levels of inoleic and alpha linoleic acid.48 In a human study at the University of Maastrich, Netherlands, patients given antioxk:lants plus omega 3 EFAs demonstrated attenuated proinfiammatory activity.(49)

Similar to many omega 3 ingredients, hydrolyzed white fish protein concentrate is derived from marine sources and may have application in improving and maintaining intestinal health. Intestinal permeability testing and symptom assessment indicated 3 g/d of a hydrolyzed white fish protein concentrate (as Seacure® from Wilmington, Del. based Proper Nutrition Inc.) strengthened intestinal integrity in 20 IBD patents after six weeks.(50) Further, a study of 15 IBD patients given 3 g/d of Seacure showed improvements in intestinal perrneabitty and symptom assessment.(51)

At the far end of the digestive tract is the colon. Depending on the health of digestion, the colon can be exposed to toxins for several days. Fortunately, the colonic mucal layer is a defensive barrier. Researchers have suggested both soluble and insoluble fiber are needed to support the mucosal layer and colon health.(52) The prebiotic fiber inulin was reviewed by researchers from Friedrich Schiller University Jena, Germany, and found to act chemopreventivaly by stimulating probiotic growth and through fermentation into short chain fatty acids.(53) Similarly, researchers from Universite Catholique de Louvaln in Brussels, Belgium, suggested manipulating colonic flora through ingestion of prebiotics could prevent or treat colonic carcinogenesis.(54)

Peptic Ulcers & Gastric Cancer
The stomach is not immune to digestive distress, as anyone familiar with commercials for acid reducing products can attest. Enzymes and hydrochloric acid in the stomach are responsible for breaking down food before it goes to the intestine. While the stomach is lined with mucous to protect it from the corrosive contents, the mucous can thin out and the hydrochloric acid damage the stomach lining.

One in 10 Americans will suffer a peptic ulcer a sore on the lining of the stomach or start of the small intestine during his lifetime, according to NIDDK. Ulcers are not caused by spicy foods or stress; rather, they can develop from long term use of nonsteroidal anti inflammatory drugs (NSAIDs) or as a result of bacterial infection most often by Helicobacter pylori (H. pylori).

H. pylon infection is also linked to development of gastric cancer. A review from Hacettep University in Ankara, Turkey, noted chronic H. pylon infection produces DNA damaging free radicals which can lead to carcinogenic gene modification.(55) The review added many types of antioxidants including vitamin C and astaxanthin both scavenge the free radials and show antimicrobial activity against H. pylon. Another review indicated H. pylon infection impacts absorption of iron and vitamin B12, leading to anemia.(56) Finally, it also appears dietary intake of compounds such as salt and ascorbic acid can impact the rate of H. pylori infection and subsequent gastric cancer development.(57)

As such, nutrition researchers have sought for ways to eradicate H. pylori in the body. Antioxidants have been one primary focus. A study from Lund University, Sweden, investigated whether guinea pigs infected with H. pylori recovered with the use of antio'ddants.58 After six weeks, the animals supplemented with vitamins A, C and E plus selenium showed a significant recovery from infection. A follow up study found the combination also lowered the incidence of severe gastritis in the test animals. And an in vitro study using a combination antioddant formula of vitamin C (ascorbic acid) and palmftoyl ascorbate (PA) determined PA was an important addition in eradication of H. pylori.(59)

In fact, vitamin C has been the leading nutritional compound investigated in H. pylori infection and eradication. Data from 6,746 adults enrolled in the Third National Health and Nutrition Examination Study (NHANES Ill) was analyzed to determine the relationship between serum ascorbic acid and H. pylori expression.(60) The researchers found higher serum levels of ascorbic acid were associated with a decreased incidence of H. pylori infection, leading them to conclude ascorbic acid may impact infection rate and the risk for peptic ulcer and gastric cancer. Another study examining ascorbic acid levels and H. pylori infection involved 452 children in Korea who underwent gastrodenoscopy over a live year petiod.(61) Those children with higher levels of vitamin C in the blood, plasma and gastric juice had a significantly lower risk of severe H. pylori infection and histologic changes in the stomach. Similarly, a five year intervention study in Japan involved 244 subjects receiving bw dose (50 mg/d) or high dose (500 mg/d) of vitamin C to assess H. pylori infection and gastritis progression.62 Both vitamin C groups showed a significant protection against progression of gastric mucosal atrophy compared to placebo.

H. pylon infection has been shown to itself lower gastric concentrations of ascorbic acid, which may impact the pH of the gastric juice.(63) In vitro work has further found vitamin C can dose dependently inhibit the growth of gastric cell cancer lines, but that this effect is significantly reduced if the dose is similar to that seen in the gastric juice of H. pylori patients.(64) As such, supplemental doses of vitamin C may be necessary for subjects with H. p4ori to reach efficacious levels.

Probiotics may also prove effective in this area of GI wetness. A review from Royal Free and University College Medical School in London noted in vivo models have shown pretreatment with probiotics can prevent H. plod infections, and treatment after infection can reduce the infection rate.(65) One supporting animal trial found mice that were previously infected with H. p4ori and given Lactobacillus casei strain Shirota showed a significant reduction in the levels of H. plod colonization, associated with a decline in the associated gastric mucosal inflammation.(66)

These findings are supported by a clinical trial conducted at the University of Chile, Santiago, involving 326 asymptomatic children.(67) Children who were found to have H. pylori infection were treated with live or killed Lactobacillus Johnsonii La1 or L. paracaseiST11. Children receiving the live cultures showed a significant decrease in infection compared to the killed culture or placebo group.

Also in the field of gastric support, a chelate complex of L carnosine with zinc has been patented in Japan and extensively studied for its ability to support mucous secretion and exert antioxidant effects. Research studies have referenced it by several names, including Polaprezinc, Z 103, and Zinc L camosine; it is sold in the United States by Lonza Inc. as PepZin GI TM.

A review of drugs for gastrointestinal (GI) ulcers examined the action of Pelaprezinc, noting zinc directly suppresses the growth of H. pyloii and inhibits the activity of urease produced by H. pylon infection.(66) The researchers added Polaprezinc also potentiated the activity of antibiotics in eradicating H. pylon. Additional research found Polaprezinc inhibited H. pylori associated GI inflammation and leukocyte activation;(69) enhanced mucosal growth factor expression to heal lesions;(70) and further protected the stomach against NSAID induced mucosal injury, probably through its antioxidative and anti inflammatory properties.(71)

Whether consumers are looking to boost their digestive power, turning to supplements to overcome a health condition, or investigating complementary therapies to support medical treatments, natural ingredients offer great support. And at the end of the day, if all else fails, it helps to remember the words of Erma Bombeck: "Never order food in excess of your body weight."

For a full list of references for this story, visit

Natural Products Industry Insider 6/21/04
P30 39

By Heather Granato

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