July 6, 2010
From mothers playing airplane with their toddlers food to assisted-care facilities where the meals look quite similar to toddler fare, the human body requires fuel. Through the teeth and past the gums goes whatever is seen as fit to ingest, starting the journey of digestion. First, chewing begins the mechanical breakdown as the enzyme amylase starts the chemical process. Swallowing triggers peristalsis, an involuntary muscular movement that propels food through the esophagus into the stomach. Here, it will be broken down both mechanically and chemically by the digestive juices of hydrochloric acid and enzymes into chyme. This mixture is doled out slowly into the small intestine for further enzymatic breakdown and nutrient absorption. Finally, anything left undigested passes into the large intestine, where the majority of the bodys beneficial bacteriabetween 400 and 500 bacterial types on averagereside. The large intestine absorbs any excess water before the waste is expelled from the colon.
This, of course, is an ideal scenario. It is a rare individual who has never felt the pain of indigestion or heartburn associated with reflux of gastric acid; possibly less common would be one who hasnt experienced gripes in the guts. However, the most recent estimates from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) state between 60 million and 70 million Americans are afflicted by digestive diseaseeverything from inflammatory bowel disease (IBD) to cancers of the digestive tract. The cumulative effect includes 50 million physician visits and 10 million hospitalizations annually, with a direct and indirect cost on the economy of more than $107 billion.
Some gastric conditions are amenable to the use of nutritional ingredients. IBD is a catch-all category that includes Crohns disease, a chronic disorder associated with inflammation of the entire gastrointestinal (GI) tract, and ulcerative colitis, which affects only the colon. The Crohns and Colitis Foundation of America (CCFA) estimates as many as one million Americans have IBD. Two other common digestive dysfunctions include gastroesophageal reflux disease (GERD), also known as acid reflux, and irritable bowel syndrome (IBS), which is characterized by abdominal bloating, irregular bowels and pain in the abdominal area.
The Pros of GI Health
As noted earlier, hundreds of bacteria species reside in the human GI tract; some are potentially pathogenic or putrefactive, and others are friendly. Probiotics can be defined as live microorganisms in a supplement or food form that, when administered in adequate amounts, exert health effects on the host when consistently ingested. These health effects include bolstering immune function, enhancing skin health and delivering digestive support.
Both the sales and study of probiotics continue to increase. According to a technical research report from BBC Research, the global market for probiotic ingredients is expected to reach $19.6 billion in 2013. Those ingredients are expected to contribute to the continued growth of functional foods and beverages for digestive health, which Packaged Facts expects to top $22 billion in sales in 2013.
Studies have sought to identify the various health effects of probiotics, as well as which strains exert specific effects. Researchers from the University of Southampton, England, noted some probiotic bacteria have the ability to improve components of immune response; reduce the incidence and duration of diarrhea in children and the risk of travelers diarrhea in adults; and provide possible benefit in cases of IBS, ulcerative colitis and Crohns.1 They noted the effects are mixed and appear to be affected not only by strain and species, but by duration of treatment. In early 2010, the British Nutrition Foundation released a review on probiotics and health, which found good evidence that probiotics are effective in preventing antibiotic-associated diarrhea, with promising results in the areas of constipation and IBS.2 Similarly, another review out of England focused on the potential of probiotics to address symptoms of IBS, concluding the beneficial microorganisms may have a role to play, although further evidence is needed to determine the optimal type and dosing.3
One such trial, from the University of Cork, Ireland, evaluated the efficacy of three different probiotics in reducing abdominal pain in rats.4 Following 14 days oral gavage of Lactobacillus salivarius UCC118, Bifidobacterium infantis 35624 or B. breve UCC2003, rats were exposed to novel stress, and effects on visceral pain were evaluated. Animals treated with B. infantis 35624 had significantly reduced pain levels, although there were no effects by the other strains. Another trial investigating B. infantis 35624 involved 362 primary care IBS patients who received placebo or active intervention for four weeks; the probiotic at a dose of 1 x 108 cfu was significantly superior to placebo for reducing abdominal pain and other symptoms of IBS including bloating, bowel dysfunction and gas.5
Another probiotic studied for its efficacy in GI health is Lactobacillus rhamnosus GG (LGG). Polish researchers investigated the efficacy of LGG in treating abdominal pain in children (n=104) with functional dyspepsia (FD), IBS or functional abdominal pain (FAP).6 The children received LGG or a placebo in the four-week, double blind, randomized controlled trial. Overall, 25 percent of subjects receiving LGG reported no pain, compared to 9.6 percent in the placebo group; among children with IBS, 33 percent of those in the LGG group had more treatment success. LGG has also been shown to exert antioxidant effects against hydroxyl radicals in the gut,7 but has the ability to induce radical oxygen species generation to reduce inflammatory signaling.8
Saccharomyces boulardii is another probiotic studied for its efficacy in addressing gut health. A May 2010 systematic review included 31 randomized, placebo-controlled treatment arms in 27 trials, finding S. boulardii was significantly efficacious and safe in 84 percent of those treatment arms.9 It found significant efficacy in preventing antibiotic-associated diarrhea and travelers diarrhea, as well as reducing Helicobacter pylori (H. pylori) treatment-related symptoms. There was some support for its use in addressing IBS, Crohns and other diarrhea-related issues, however, more evidence is recommended. These findings were echoed in another review, out of the University of California, Los Angeles (UCLA), which concluded S. boulardii exerts multiple anti-inflammatory effects, including inhibiting production of pro-inflammatory cytokines and interfering with the global mediator of inflammation nuclear factor kappaB.10
Several trials have focused on Bacillus coagulans GBI-30, 6086 (marketed as GanedenBC(30), from Ganeden Biotech). In one recent randomized, double blind, placebo-controlled, parallel clinical trial, 44 subjects received either placebo or B. coagulans daily for eight weeks.11 Improvements from baseline abdominal pain and bloating scores in the intervention group were statistically significant each week. Similarly, in a study of adults (n=61) with post-prandial intestinal gas-related symptoms, administration of B. coagulans (as GanedenBC(30)) for four weeks significantly improved GI symptoms, such as pain and distension.12 The Ganeden patented formula was also shown in a randomized, double-blind, placebo-controlled clinical trial to significantly reduce the number of bowel movements per day in patients with diarrhea-predominant IBS.13
In vitro trials have explored the safety and metabolic activity of the GandenBC(30) strain. One such study looked at the anti-inflammatory and immune modulating properties of the strain, with the spores first heat-activated and grown, and the culture supernatant harvested as a source of metabolites (MTB) with the bacteria used to isolate cell wall fragments (CW).14 While the anti-inflammatory activity was strongest for CW, the metabolites also impacted cytokine production, resulting in immune modulation and anti-inflammatory effects. GanedenBC(30) was also found in an in vitro model of the stomach and small intestine (TIM-1) that survival was high, and the probiotic also had the ability to aid in lactose and fructose digestion.15 Toxicological safety assessments have also indicated the strain does not show any mutagenic or genotoxic effects, and has a safety factor of many thousand times of suggested human dose.16
There is also interest in combinations of probiotics. One of the best known is VSL#3® (from Sigma-Tau Pharmaceuticals), a combination of eight probiotic strains. Studies have demonstrated its efficacy in addressing a number of digestive conditions. Italian researchers recently reported eight weeks of treatment with VSL#3 (dose 3,600 billion CFU/d) significantly decreased the ulcerative colitis activity index, with subjects showing greater rate of remission than comparable subjects taking a placebo.17 Similar findings were reported in an Indian trial of adults with mild-to-moderate UC, with subjects taking VSL#3 showing a significantly greater rate of remission and reduction in symptom scores.18 Additional studies have shown VSL#3 is effective in reducing symptoms of IBS in children,19 and reducing intestinal inflammation related to the use of non-steroidal anti-inflammatory drugs (NSAIDs).20
Another multi-strain product containing L. acidophilus (DDS-1 strain), B. longum, B. bifidum and B. lactis (as Multi-Flora Plus/Probioplus DDS®, from UAS Laboratories) was used in a clinical case study (pending publication) to determine whether the probiotic could minimize symptoms of IBS. Researchers evaluated 25 patients with IBS for 60 days as they received the combination probiotic product. Patients symptom severity was evaluated on a scale of 1 to 10, with at least 50-percent reduction in severity classified as improvement. The most significant improvements occurred after 60 days of treatment with 84 percent of patients showing improvement in abdominal pain, 73.9 percent in bloating, 92 percent in belching, 88 percent in flatulence, 90.9 percent in diarrhea and 86.9 percent in constipation.
Probiotics work synergistically with fiber in the gut. One recent trial, for example, examined the impact of a symbiotic combination that found positive effects in patients with IBS.21 There are two different kinds of fiber, soluble and insoluble, both with a role to play in digestive health. Insoluble fiber, found in whole-grain products and vegetables, helps promote laxation and balances the pH in the intestines. Soluble fiber, found in beans, fruit, oats and barley, dissolves in water to form a gel that can help prolong stomach emptying time, regulate blood sugar and lower cholesterol levels.
One common source of supplemental fiber is psyllium (Plantago ovata Forsk) seeds, which contain the bioactive mucilage polysaccharide. Psyllium is a soluble gel-forming fiber that has been shown to bind to the bile acids in the gut and prevent their normal reabsorption, helping to lower cholesterol levels.22 Studies have also found psyllium seeds may be as effective as the drug mesalamine in maintaining remission in ulcerative colitis.23 Guar gum is a non-gelling fiber that has been shown to help decrease symptoms of both constipation-predominant and diarrhea-predominant forms of IBS.24 And a comparative trial of fibers derived from maize (including promitor Resistant Starch and promitor Soluble Corn Fiber, from Tate & Lyle) found when healthy adults consumed 12 g/d of fiber, there were positive impacts on colon health due to fermentation as seen in fecal pH and individual short-chain fatty acids (SCFAs).25
Resistant starches also exert other positive effects in the digestive tract. Researchers at Provident Clinical Research, Bloomington, IN, provided healthy adults with 25 g/d resistant starch (as promitor) or wheat bran fiber for 14 days, finding the added fiber increased daily fecal output in the test subjects.26 Studies on another resistant starch (as Hi-Maize, from National Starch Food Innovation) have found it has a number of physiological effects in the colon due to the fermentation of the resistant starch, including enhancing the apoptotic response to DNA damage, preventing the development of abnormal cells in the colon.27 It has also been found quite effective in combination with B. lactis to increase production of SCFAs to significantly increase the apoptotic response in the colon.28
This highlights the role of resistant starch as a prebiotic, food for beneficial intestinal bacteria. A review by Greg Kelly, N.D., in Alternative Medicine Review explored inulin-type prebiotics, which include inulin, fructooligosaccharides (FOS) and oligofructose.29 In the area of GI health, he found existing evidence supports an effect by inulin-type prebiotics on bowel transit and stool consistency in infants, while such products also appear to have a clinical role in alleviating existing constipation in adults. He added human studies on IBD and inulin-type prebiotics have been small, but have found positive functional change in inflammation levels.
FOS occur naturally in a wide variety of plant foods, including onion, chicory, banana and artichoke. A review from the University of Murcia, Spain, noted dietary FOS are not hydrolyzed in the small intestine, traveling into the cecum where they are metabolized by intestinal microflora to form SCFAs, hydrogen, L-lactate and other metabolites.30 The reviewers added FOS can improve mineral absorption and help decrease cholesterol levels, and exert a prebiotic effect, positively affecting bowel health. In fact, in a recent study of home-living, tube-feeding-dependent adult patients, adding FOS to the feeding increased levels of fecal Bifidobacteria and enhanced quality of life scores.31 Similarly, adding FOS to infant weaning foods increased the fecal proportion of Bifidobacteria and levels in intestinal microflora of fully formula-fed infants.32
Studies have also looked at galactooligosaccharides (GOS), a type of prebiotic consisting of linked galactose units in an oligo- or polysaccharide chain. A study out of Japan involved 128 healthy volunteers with constipation tendencies who received a beverage with 2.5 g/d or 5.0 g/d of GOS (supplied by FrieslandCampina Domo) for one week or a beverage with 10.0 g/d of GOS for one week.33 Defecation frequency increased significantly in the 5.0 g/d and 10.0 g/d groups, while subjects in all groups had significant increases in number of days per week when defecation occurred. Similar results were reported in a Finnish trial, in which 14 elderly women who suffered from constipation received 9 g/d GOS (supplied by FrieslandCampina Domo) in yogurt, or yogurt without GOS.34 During GOS ingestion, subjects had increased defecation frequency, and there was a tendency toward easier defecation. A more recent trial involved 43 elderly subjects with self-reported constipation who received 260 g/d control yogurt or test yogurt with GOS (12 g/d), prunes (12 g/d) and linseed (6 g/d).35 Daily intake of the yogurt with FrieslandCampina Domos GOS, prunes and linseed reduced constipation severity.
Another soluble fiber option is larch arabinogalactan (LA), which is a long, densely-branched non-starch polysaccharide. Lonza supplies the ingredient as FiberAid®. Studies have shown LA can decrease the generation and absorption of ammonia in the gut.36,37,38 Due to its highly branched structure, LA is slowly fermented.39 FiberAid was shown to have a high-digestive tolerance at dosages up to 15 g/d, while effective dosages are achieved at only 4.5 g/d.40
Beyond the Bugs
Starting in the mouth and continuing through the GI tract, enzymes help in the chemical breakdown of food. The human body produces more than 20 digestive enzymes in various organs and glands. The stomach glands produce gastric enzymes, including peptidase (for proteins), gelatinase (for gelatin/collagen from meats) and gastric lipase (for tributyrin, a butter fat). Meanwhile, the pancreas is responsible for secreting numerous proteases and amylases, including trypsin (a peptidase), pancreatic amylase (for starch and glycogen) and several elastases (for protein elastin). Then, the epithelium in the small intestines creates many peptidases and the more well-known amlyases that break disaccharides into monosaccharidessucrase for sucrose and glucose, lactase for lactose and maltase for maltose.
Vegetables and fruits also offers vital enzymes needed to digest foods. For instance, pectinase from the cell walls of plants helps degrade pectin, while bromelain is a mixture of proteolytic enzymes found in the stems and juice of pineapples. Enzymes from bacteria are also beneficial for digesting foodphytase helps denature phytic acid found in grains and seeds; and cellulose breaks down the indigestible fibers found in plant cell walls. Most commercial enzymes are not microbial-derived from fungal sources, such as lipase from Aspergillus oryzae.
An article in Alternative Medicine Review noted solid evidence supports the role of enzyme supplementation in digestive disorders including exocrine pancreatic insufficiency and lactose intolerance.41 The author also noted studies have seen synergistic effects in using combinations of animal-based and microbe-derived enzymes. Another review agreed acid- and protease-stable bacterial and fungal lipases may offer positive therapeutic alternatives for enzyme replacement.42
As the research behind supplemental enzymes for digestive health is developing, there is also interest in ensuring optimal delivery of enzymes into the gut. CTC International produces Innova Shield Digestive Enzyme, which protects digestive enzymes from acidic gastric fluids in the stomach, enabling enzymes to reach the small intestine tract, according to an in-house, unpublished study. It uses two shields, known as Duo Zyma Shield technology. This coating delivery system (CDS) allows the enzymes to be mixed with wider recipients, including probiotics, protein powder, etc.
A number of other ingredients also may support digestive health. A review from the UCLA Medical Center examined complementary and alternative medicine (CAM) modalities of interest to gastroenterologists.43 In addition to mention of probiotics, the researchers called out peppermint for its use in patients with IBS or dyspepsia, and ginger to relieve nausea and vomiting. Another review noted peppermint leaf and oil have a long history of use for digestive disorders, with more recent studies focusing on its use in addressing IBS and dyspepsia.44 One such study, conducted at G d'Annunzio University, Chieti-Pescara, Italy, involved 57 patients with IBS, who received peppermint oil (two enteric-coated capsules twice daily) or placebo for four weeks.45 At the end of four weeks, 75 percent of patients in the peppermint oil group had a significant reduction in IBS symptoms, compared with 38 percent in the placebo group; symptoms were still statistically reduced four weeks after cessation of therapy. In the area of dyspepsia, a combination of peppermint, chamomile and Iberis (from Iberogast) has shown statistically significant efficacy in reducing the digestive ailment in placebo-controlled studies.46
As mentioned in the CAM review, ginger (Zingiber officinale) has also been historically used for gastric disorders, particularly dyspepsia. In vitro work suggests ginger extract has a prokinetic action, while also exerting a spasmolytic effect, helping to calm hyperactivity in the gut.47 The finding was echoed in a study in isolated rat ileum, in which ginger inhibited induced contractions, with both prejunctional and postjunctional inhibitory effects on ileal contractility.48 Researchers have also reported gingerols, polyphenolic compounds extracted from ginger, can inhibit the growth of H. pylori strains in vitro, possibly contributing chemopreventive effects.49
Another well-studied plant in this arena is licorice (Glycyrrhiza glabra), which was used traditionally for addressing peptic ulcer and skin conditions; it also appears to be an anti-inflammatory and antioxidant compound.50 Researchers from Al-Isra University, Amman, Jordan, investigated the anti-inflammatory activities of licorice extract and glycerrhitinic acid (GA) in two animal models, comparing the extracts to traditional drug therapies.51 In both areas, the licorice extracts performed as well as drug therapy, exerting significant anti-inflammatory effects and anti-ulcer activity. Korean researchers also found oral administration of glabridin, extracted from licorice, could attenuate mortality, loss of body weight, shortening of the colon and severe clinical symptoms in mice with induced colitis.52 And, researchers from the University of Munster, Germany, found in an in vitro trial, licorice extract significantly inhibited the adhesion of H. pylori to human stomach tissue, an effect related to licorices polysaccharides.53
Aloe vera, the common name for the species Aloe vera (L.) Burm. f., has been studied for its usefulness in wound healing, taken internally or applied topically.54 Considering peptic ulcer as a type of internal wound, researchers have examined the efficacy of aloe vera in this area. In a recent in vitro trial, researchers found Aloe vera dose dependently inhibited gastric acid secretion, and was active at a fairly low concentration against mucosal injury induced by HCl.55 Thai researchers also conducted an animal trial to compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing.56 Animals treated with Aloe vera plus sucralfate had reduced leukocyte adherence, reduced levels of inflammatory cytokines and reduced ulcer size after eight days.
Curcumin (Curcuma longa), the active compound in the Indian botanical turmeric, is a powerful antioxidant, but has also been studied in the area of GI wellness and specifically for its ability to fight gastritis. In vitro research has shown curcumin scavenges reactive oxygen species and regulates the activity of matrix metalloproteinases (MMP), which play a critical role in inflammation and wound healing, while also working to block H2 histamine receptors to inhibit gastric acid secretion.57,58 Thai researchers working with a gastric ulcer model system examined the effects of bisdemethoxycurcumin, a yellow pigment found in C. longa, versus curcumin and found curcumin significantly suppressed inducible nitric oxide synthase (iNOS) production and tumor necrosis factor-alpha protein production, while bisdemethoxycurcumin had a greater inhibitory effect on gastric acid secretion.59 Oral administration of both compounds to rats accelerated the healing of induced gastric ulcer, and promoted mucosal regeneration.
Further animal trials have also shown promise. Chinese researchers used a acetic acid-induced gastric ulcers model in rats to test the pharmacological action of curcumin solid dispersions, and reported the active treatment reduced ulcer indices and increased serum nitric oxide (NO) levels compared to control animals.60 Similar findings were reported in a study out of Egypt in which rats received different doses of curcumin or placebo orally before ulcer induction.61 Curcumin exerted an anti-ulcer activity, attenuating several measures including gastric acid hyper-secretion, total peroxides and IL-6 incidence.
Zinc is a key mineral for the health of the intestinal lining, and studies have shown zinc supplementation (up to 110 mg three times daily) may resolve intestinal permeability problems seen in leaky gut.62 A combination of zinc and L-carnosine (polaprezinc) has been approved in Japan as an anti-ulcer drug, as studies have shown the complex can adhere to lesions before releasing the L-carnosine and zinc to exert healing effects; it also inhibits H. pylori.63 It appears the zinc primarily works to inhibit H. pylori-induced inflammation, affecting cytokine expression by gastric epithelial cells.64 The zinc/L-carnosine complex also may induce heme oxygenase (HO)-1 in a dose dependent manner, increasing mucosal protective activities by the gut,65 and work to quench reactive oxygen species, functioning as a powerful antioxidant.66
Obviously, with so many natural ingredients exerting protective effects on the GI tract, the market is ripe with opportunity; all it takes is correct formulation and marketing to encourage consumers to take a bite.
References are on the next page...
References for Chew On This: Digestive Health
1. Lomax AR, Calder PC. Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr Pharm Des. 2009;15(13):1428-518.
2. Weichselbaum E. Potential benefits of probiotics--main findings of an in-depth review. Br J Community Nurs. 2010 Mar;15(3):110, 112, 114.
3. Hoveyda N et al. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol. 2009 Feb 16;9:15.
4. McKernan DP et al. The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat.: Neurogastroenterol Motil. 2010 Jun 1. [Epub ahead of print]
5. Whorwell PJ et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006 Jul;101(7):1581-90.
6. Gawroska A et al. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther. 2007 Jan 15;25(2):177-84.
7. Sun J et al. Lactobacilli prevent hydroxy radical production and inhibit Escherichia coli and Enterococcus growth in system mimicking colon fermentation. Lett Appl Microbiol. 2010 Mar;50(3):264-9. Epub 2009 Dec 10.
8. Lin PW et al. Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation. Free Radic Biol Med. 2009 Oct 15;47(8):1205-11. Epub 2009 Aug 3.
9. McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May 14;16(18):2202-22.
10. Pothoulakis C. Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment Pharmacol Ther. 2009 Oct 15;30(8):826-33. Epub 2008 Jul 23.
11. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009;121(2):119-24.
12. Kalman DS et al. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms. BMC Gastroenterol. 2009;9:85.
13. Dolin BJ. Effects of a proprietary Bacillus coagulans preparation on symptoms of diarrhea-prominent irritable bowel syndrome. Methods Find Exp Clin Pharmacol. 2009 Dec;31(10):655-9.
14. Jenson GS et al. GanedenBC(30) cell wall and metabolites: anti-inflammatory and immune modulating effects. BMC Immunol. 2010;11(1):15.
15. Maathius AJH et al. Survival and metabolic activity of the GanedenBC(30) strain of Bacillus coagulans in a dynamic in vitro model of the stomach and small intestine. Beneficial Microbes. 2010;1(1):31-36.
16. Endres JR et al. Safety assessment of a proprietary preparation of a novel probiotic, Bacillus coagulans, as a food ingredient. Food Chem Toxicol. 2009;47:1231-38.
17. Tursi A et al. Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study. Am J Gastroenterol. 2010 Jun 1. [Epub ahead of print]
18. Sood A et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009 Nov;7(11):1202-9, 1209.e1. Epub 2009 Jul 22.
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