Natural Digestifs

Its a universal truth that healthy, regular digestion is essential to overall health. Digestion doesnt stop or start in the gut; it affects the entire body. According to SPINS, sales of digestive aids and enzymes in the natural channel are up by 7.8 percent (52 week period ending March 19, 2011) from 2010 in all three categoriesfiber products and laxatives, miscellaneous enzyme products and digestive formulas, and prebiotics and probiotics. Total U.S. sales in the natural channel (excluding Whole Foods) topped out at $99,348,404, with the largest sales happening in the prebiotics/probiotics sector at $57,300,606. Its evident consumers are concerned with digestionfrom ulcerative colitis and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS), heartburn and everyday indigestionand theyre turning to the natural products industry for help.

Saving the Masses

So, how do we do it? How do we save the masses from their digestive woes? Well, we start with a little help from our bacterial friends, probiotics. They are one the hottest categories in the nutraceutical industry, with an estimated compound annual growth rate (CAGR) of 13 percent; but, there is no need to talk probiotics up. Their popularity and science speak for themselves. The fermented dairy beverage kefir has delivered gut goodness for centuries, and a recent Turkish study found a probiotic-containing product can help boost the effectiveness of triple therapy used to treat a Helicobacter pylori (H. pylori) infection.¹ The randomized, double blind study involved 82 consecutive patients with symptoms of dyspepsia and H. pylori infection. Twice daily for 14 days patients were given triple therapylansoprazole (30mg), amoxicillin (1,000mg) and clarithromycin (500mg)with either 250mL of kefir twice daily (n=46) or 250mL of milk containing a placebo (n=36). Eradication of H. pylori bacteria was significantly higher in patients taking both triple therapyandkefir (78.2 percent), compared to those taking triple therapy and placebo (50.0 percent). Those in the kefir group also experienced significantly less severe and less frequent side effects than did those in the placebo group.

Getting more specific, the probiotic strain, Bacillus coagulans GBI-30, PTA-6086 (as GanedenBC30, from Ganeden Biotech) was significantly more effective than placebo in providing relief to subjects suffering from intestinal gas in a randomized, double blind, placebo-controlled study.² Subjects taking Digestive Advantage Gas Defense Formula, an over-the-counter (OTC) product marketed by Ganeden Biotech that contains the Bacillus coagulans probiotic strain, experienced statistically significant improvement versus placebo in the Gastrointestinal Symptom Rating Scale (GSRS) total score during the four weeks of product use. In addition to its benefits on intestinal health, GanedenBC30 effectively relieved abdominal pain and bloating in patients with IBS in a 2009 eight-week study.³

Another probiotic supplementProbioplus DDS (from UAS Laboratories Inc.)was found effective on IBS, too. In an unpublished study, physicians from UND School of Medicine and Mayo found a probiotic combo containing Lactobacillus acidophilus (as DDS®-1 strain, from UAS Laboratories), Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium lactis improved IBS symptoms in 72 percent to 92 percent of the studied patients. For 60 days, researchers evaluated 25 patients with IBS who were treated with the multispecies probiotic product. Symptom severity was evaluated on a scale of one to 10. Improvement was classified with at least 50-percent reduction in severity. The most significant improvements occurred after 60 days of treatment showing a reduction of abdominal pain (84 percent of the patients), bloating (73.9 percent), belching (92 percent), flatulence (88 percent), diarrhea (90.9 percent ) and  constipation (86.9 percent). Two additional studies published in 2000 and 2009 also confirmed probiotics role in diarrhea via prevention of antibiotic-associated diarrhea and improving Clostridium difficile diarrhea symptoms, respectively.^4,5

Researchers in California examined the effects of seven days of treatment with a mixture of three probiotic bacteria(as Kyo-Dophlus [K-D], from Wakunaga) consisting of Lactobacili acidophilus, Bifidobacterium bifidum and Bifidobacterium longumon plasma and splenic levels of inflammatory cytokines following an endotoxin challenge.⁶ In the first study, adult male rats were administered one billion bacteria/d or vehicle (potato starch) by gavage. Rats were then inject with 10 g of LPS or saline. There were no significant effects of K-D treatment on plasma levels of cytokines in response to LPS; however, there were significant treatment effects on splenic levels of cytokines. In the absence of LPS stimulation, the K-D-fed rats showed an elevation in splenic IL-6 levels, relative to the vehicle controls; however, LPS-induced splenic IL-6 levels observed in the control group were attenuated in the K-D-fed group. While LPS treatment produced a modest increase in splenic levels of INF-gamma in the controls, splenic levels of INF-gamma were increased further in the K-D fed group. There was a tendency for K-D treatment to reduce plasma corticosterone levels. In a second study researchers tested the effects of seven days of treatment with 2 billion bacteria/d or vehicle on cytokine production two hours following an injection of 25g LPS. Researchers found K-D treatment produced a significant decrease in both plasma and splenic levels of LPS-induced IL-6 and IFN-gamma, relative to vehicle treated controls. Plasma and spleen levels of TNF-alpha were lower in the K-D treated rat, but the effect was not significant. There was a tendency for plasma corticosterone levels to be lower in the K-D treatment group. These preliminary data from both studies indicated depending upon the route of endotoxin administration, both immunostimulatory and anti-inflammatory effects of K-D probiotics can be demonstrated.

On a different probiotic note, a link between stress and gastrointestinal (GI) disruptions has been made, resulting in a correlation between the gut and the brain. In fact, two studies with Probio'Stick®a combination of Lactobacillus Rosell-52 and Bifidobacterium Rosell-175(from Institut Rosell-Lallemand) revealed its effectiveness in reducing the GI symptoms experienced by individuals suffering from stress⁷ and its ability to significantly alleviate psychological distress in volunteers.⁸

And as probiotics fuel digestive health, prebiotics fuel probiotics. The two synergistically tackle GI health. Dietary fructooligosaccharide (FOS) supplementation demonstrated the link between the gut and immune health, as it changed the intestinal environment of microflora and lead to upregulation of IgA secretion in CD4+ PP cells in intestinal mucosa, and to suppression of the systemic immune response to type 2 helper T dominant.⁹ Lactobacillus helveticus M92 and inulin also worked together to confirm the immune and GI link via a synbiotic effect on intestinal and faecal microflora and immune system of mice.¹⁰

Psyllium husk functions as a prebiotic fiber and has proven its right in the digestive tract. In a 2010 study, psyllium husk showed a gut-stimulatory effect, confirming its role in both constipation and diarrhea.¹¹ An earlier study found psyllium was superior to docusate sodiuma medication commonly used for constipationfor softening stools by increasing stool water content, and had greater overall laxative efficacy in subjects with chronic idiopathic constipation.¹² The multi-site, randomized, double blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a two-week baseline (placebo) phase followed by two weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Compared to baseline, psyllium increased stool water content versus docusate; and it also increased stool water weight, total stool output and O'Brien rank-type score combining objective measures of constipation. Bowel movement frequency was significantly greater for psyllium versus docusate in treatment week two, with no significant difference between treatment groups in treatment week one. Additionally, a separate four-week study also found psyllium increased stool frequency and weight, and improved stool consistency in idiopathic constipation.¹³

Spanish researchers fed HLA-B27 transgenic rats (8 to 10 weeks old) a fiber-supplemented diet with a different soluble fiber5 percent Plantago ovata seeds.¹⁴ After 13 weeks, dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of short-chain fatty acids (SCFAs), butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production. They concluded dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats.

Another study looked at the role of soluble fiber and the production of SCFAs and their ability to attenuate inflammation associated with ulcerative colitis.¹⁵ Researches assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C and selenium on disease activity and medication use in adults with mild to moderate ulcerative colitis. A total of 121 patients with ulcerative colitis and a disease activity index (DAI) from three to nine on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for six months. A total of 86 patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (n=36) compared with the placebo group (n=50) (P<0.05). Both groups showed significant and similar degree of improvement at six months in DAI and histologic index. Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over six months as compared with the placebo group (P<0.001).Therefore, researchers said, The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with ulcerative colitis. Galactooligosaccharides (GOS) are another type of prebiotic. In a Japanese study, volunteers who received GOS in a drink experienced an increase in bowel movements.¹⁶ A total of 128 healthy volunteers who struggled with constipation drank 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 g/d of GOS for one week. In the 5.0 g/d and 10 g/d groups, defecation frequency increased significantly, and subjects in all the groups had significant increases in number of days per week when defecation occurred. Moreover, 9 g/d of GOS via yogurt (supplied by FrieslandCampina Domo) helped 14 elderly women relieve constipation symptoms by increasing the frequency of their bowel movements and with more ease.¹⁷ And again in 2007, GOS relieved constipation in elderly subjects (n=43) in a test yogurt containing GOS (12 g/d), prunes (12 g/d) and linseed (6 g/d).¹⁸

Going Green

The hot, new trendgoing green in the world of sustainability is also a hot trend in digestion, i.e., aloe vera, among its other applications. Aloe vera is a popular commodity in the digestive sector of health. In 2009, SPINS listed aloe vera first in its five top-selling herbal supplements, and SPINS 2010 data showed aloe experienced a 6.7-percent increase from 2009, selling $11,695,785 in the natural channel, excluding Whole Foods Market. Aloe ferox is the part of the plant best known for its laxative effect. Results from a 2010 study using an extract of aloe ferox Mill compared favorably to a standard laxative on various aspects of constipation.¹⁹ The best results were seen with 200mg/kg of aloe ferox Mill, which improved intestinal motility, increased fecal volume and normalized body weight in constipated rats.

English researchers discovered aloe veras anti-inflammatory effect in vitro, making it a potential therapy in combating inflammatory bowel disease (IBD).²⁰ The antioxidant activity of aloe vera was assessed in two cell-free, radical-generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. The gel had a dose-dependent inhibitory effect on reactive oxygen metabolite production; 50-percent inhibition occurred at one in 1,000 dilution in the phycoerythrin assay and at one in 10-50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30 percent at one in 50 dilution (P=0.03), but had no effect on thromboxane B2 production. The release of interleukin-8 by CaCo2 cells fell by 20 percent (P<0.05) with aloe vera diluted at one in 100, but not at one in 10 or one in 1,000 dilutions.

Thai researchers also investigated aloe veras anti-inflammatory effects on leukocyte-endothelium in the gastric microcirculation of H. pylori-infected rats.²¹ Thirty-six male Sprague-Dawley rats were divided into three groups: control, H. pylori-infected and aloe vera-treated group (200 mg/kg/bw twice daily). In the H. pylori-infected group on day eight, the leukocyte adhesion was 13.40+/-1.00 cells/100 microm vessel length and the tumor necrosis factor-alpha (TNF-alpha) was 76.76+/-23.18 pg/ml, which increased significantly (P<0.05), compared with the control group. Treatment with aloe vera reduced the leukocyte adhesion and TNF-alpha significantly (P<0.05). Researchers concluded the H. pylori enhanced leukocyte-endothelium interaction in the posterior stomach area markedly and could be improved by the treatment of aloe vera, associated with reduction in TNF-alpha level.

Other plant-derived ingredients known to help tame the tummy are digestive enzymes. Although not all are derived from plants, enzymes are essential in the break down of foods. The human body produces more than 20 digestive enzymes; more specifically, the stomach glands produce gastric enzymespeptidase (for proteins), gelatinase (for gelatin/collagen from meats) and gastric lipase (for tributyrin, a butter fat)and the pancreas secretes numerous proteases and amylasestrypsin (a peptidase), pancreatic amylase (for starch and glycogen) and several elastases (for protein elastin). Others are also created in the in the small intestines. Many fruits and plants are popular for their enzyme content such as pineapple, which contains bromelain in its stem and juice. Papaya is also another dessert-like fruit that contains the enzyme papain. Pectinase is derived from the cell walls of plants and used physiologically to break down pectin. However, even though these enzymes are available via diet, multiple variables deplete their availability, and many consumers struggle with producing enough enzymes due to age and other health factors, so supplementation is often necessary.

Enzymes are beneficial for several digestive aliments, and help thwart symptoms related to lactose intolerance²² and celiac disease.^23,24 In 2011, Japanese researchers tested the ability of glycopolypeptides (GPP) prepared from buttermilk with trypsin, papain, pancreatin, bromelain or pepsin to exfoliate H. pylori bound to gastric mucin.²⁵ H. pylori adhered more strongly to all of the GPP tested than to whole buttermilk, the soluble fraction of buttermilk, gastric mucin prepared from mouse stomach or commercial pig gastric mucin. The GPP digested with trypsin, papain or pancreatin were significantly more adherent. When the GPP concentration was 10 mg/mL, bound H. pylori and five clinical isolates were exfoliated markedly from immobilized porcine gastric mucin following treatment with GPP digested with trypsin or pancreatin.

Since bromelain has been shown to decreased the severity of colonic inflammation in C57BL/6 Il10(-/-) mice with chronic colitis, researchers at Duke University aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with chronic colitis as compared with bromelain derived from stem.²⁶ Colitis was triggered in mice by exposure to the non-steroidal anti-inflammatory drug (NSAID) piroxicam. Mice with colitis were supplemented with fresh versus boiled pineapple juice or bromelain purified from stem for up to six months. Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 14 mg of bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (P=0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35 percent versus 66 percent; (P<0.02), with fewer neoplastic lesions/colon (P=0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Researchers concluded long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes decreased inflammation severity, and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of IBD. 

Molecular Motivation

A molecular approach to digestion is zinc-carnosine, a combination of L-carnosine and zinc. It supports the mucosal lining of the GI tract by stabilizing the gut mucosa.²⁷ Several studies have confirmed zinc-carnosines role in gastric ulcers. In a human study of 299 subjects, zinc-carnosine (as PepZin GI, supplied in the United States by Xsto Solutions) improved 81 percent of objective and subjective symptoms after four weeks and 91.7 percent after eight weeks.²⁸ After four weeks of treatment with zinc-carnosine, 26.3 percent were healed of gastric ulcers (as assessed by endoscopy) and 60.4 percent after eight weeks. A second human study of 229 subjects, designed as a multicenter, double blind comparative study, administered three doses of 50 mg, 75 mg or 100 mg twice daily zinc-carnosine (as PepZin GI).²⁹ Final markedly improved rates of objective and subjective symptoms of gastric ulcers were 75.4 percent in the 100-mg group, 71.6 percent in the 150-mg group and 78.5 percent in the 200-mg group. Final cure rates as endoscopic rating were 55 percent in the 100-mg group, 58 percent in the 150-mg group and 54.4 percent in the 200-mg group. In a 2006 study, researchers found polaprezinc, containing zinc, to be a therapeutic agent for treatment of colitis.³⁰

Tying up Loose Ends

A few odds and ends are ginger and fenugreek. Taiwanese researcher found taking ginger capsules may provide some relief to people with functional dyspepsia by improving the delayed gastric emptying often experienced in such patients.³¹ The randomized, double blind trial involved 11 patients with functional dyspepsia, who were studied twice. An eight-hour fast was followed by ingestion of three capsules of ginger (1.2 g total) or placebo; one hour later, they each consumed a 500-mL, low-nutrient soup. Gastric emptying was increased in those taking ginger, compared to placebo; median half-emptying time was 12.3 minutes following ginger intervention, and 16.1 min. after placebo (P0.05). There was a trend for more antral contractions (P=0.06) in the ginger group, but there was no observed effect on fundus dimensions, GI symptoms, serum concentrations of GLP-1, motilin and ghrelin.

Fenugreek (as FenuLife®, marketed by Frutarom Inc.) reduced heartburn symptoms when the fenugreek fiber extract was taken before two meals/d.³² The pilot study followed subjects, aged 32 to 62 years, who were non-smoking males (n=21 males) and non-pregnant females (n=24) that were experiencing heartburn after three to eight meals per week for at least a month, but were not taking prescription drugs intended to treat this condition. Subjects either took FenuLife 30minutes before two meals/d for two weeks (500 mg per capsule, four capsules per serving), the conventional over-the-counter (OTC) antacid ranitidine (75mg, twice/d) or a placebo. Subjects were allowed to use two to four tablets of chewable calcium carbonate (TUMS E-X®, 750mg CaCO3 per tablet), supplied free of charge, as a rescue for very severe heartburn. The researchers found FenuLife diminished heartburn severity based on symptom diary results and reduction of ranitidine use. The placebo produced some statistically significant effects, but the fiber product's effects differed significantly from the placebo. Most subjects in the fenugreek group showed two to three symptom-free days at the end of the second intervention week. The number of symptom-free days at the end differed significantly between the fenugreek and placebo groups. This was not the case for the placebo versus the positive control. Moreover, the researchers noted FenuLife effects were generally similar to the results produced by ranitidine.

As earlier research revealed, fatty acids play their role in digestion via serving as an anti-inflammatory; and a Norwegian study further confirmed their role in the gut. Patients with active colitis appear to experience reduced disease activity after regular consumption of salmon, which increases the patients anti-inflammatory fatty acid index.³³ Researchers from the Department of Internal Medicine at Stavanger University Hospital conducted a pilot study in patients with mild ulcerative colitis, comparing a salmon-rich diet; they noted salmon fillet contains not only omega-3 polyunsaturated fatty acids (PUFAs), which have an anti-inflammatory effect, but also contains bioactive peptides that may have improve the effects. A total of 12 patients with ulcerative colitis consumed 600 g of Atlantic salmon weekly; before and after intervention, researchers assessed simple clinical colitis activity index (SCCAI), the diet (using a dietary questionnaire), sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles. Biopsies taken after dietary intervention revealed C20:4n-6 arachidonic acid correlated with histology and endoscopy scores. The concentrations of omega-3 PUFAs, C20:5n-3 eicosapentaenoic acid (EPA), C22:6n-3 docosahexaenoic acid (DHA), and the omega-3/omega-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. The researchers concluded intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis, based on improved SCCAI and AIFAI scores along with the tendency of decreased levels of CRP and homocysteine in patients on the dietary intervention.

Other fatty acids that play a role in digestion are medium-chain triglycerides (MCTs), which carry nutrients and interact with enzymes to aid the digestive process. Since digestion plays a role in many aspects of health, including weight management and energy, MCTs work indirectly on digestion. In one study, 15 male Sprague-Dawley rats were divided into two groups: One group was fed a MCT diet, the other an isocaloric diet containing long-chain triglyceride (LCT) in excess (150 percent) of spontaneous calorie intake. Both diets, fed for six weeks, derived 50 percent of calories from fat.³⁴ MCT rats gained 15-percent less weight than LCT controls. Total dissectible fat was significantly lower in the MCT group, as was mean adipocyte size. Resting and maximal norepinephrine-stimulated 02 consumptions were 39.7 percent and 22.1 percent higher in MCT than in LCT group, respectively. Resting and norepinephrine-stimulated metabolic rates were 38.8 percent and 22.2 percent higher in MCT than LCT fed rats, respectively.

Digestion is a comprehensive process that can go wrong at any stage and cause a myriad of symptoms; fortunately for consumers, the natural products industry is hard at work researching and developing natural solutions to soothe their digestive hiccups.

References are on the next page...

References for "Natural Digestifs"

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