132 DOI: 10.1089/act.2008.14305 • MARY ANN LIEBERT, INC. • VOL. 14 NO. 3 JUNE 2008 Digestive disorders are increasingly common and affect millions of Americans. ere were 41.3 million office visits to physicians and 15.1 visits to the emergency rooms for digestive- system symptoms in 2004, according to the Centers for Disease Control and Prevention’s (CDC’s) most recent data. 1 Condi- tions include irritable bowel syndrome (IBS); inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn’s disease; celiac disease; gastroesophageal reflux disease (GERD); gastrointestinal (GI) cancers; and other conditions such as diar- rhea, constipation, indigestion, nausea, and flatulence. Approximately 60–70 million people are affected by overt diagnosable digestive diseases, 2 yet tens of millions of other patients suffer from subclinical GI health conditions that alter their ability to absorb nutrients from their diets and supple- ments. is has a dramatic impact on quality of life with 1.9 million people disabled due to GI disease. 3 Annually, an as- tounding 234,000 people die from GI diseases including GI cancer. 4 e GI tract is the absolute barrier between the burdensome outside world that enters the human body as foods and con- taminants (herbicides, pesticides, heavy metals, and an array of other health saboteurs) and the well-ordered 75 trillion cells that work in harmony to sustain human existence. erefore, regardless of whether an individual has any overt signs of GI dysfunction, fortifying the GI tract enhances the ability for nutrients from food and supplements to be most optimally absorbed. Intestinal Permeability and Overall Health Intestinal permeability, which refers to the potential for nutrients and bacteria to pass through a weakened intestinal wall—as well as, to some degree, through healthy tissues—is an important factor for optimal GI health. When intestinal permeability is increased, food and nutrient absorption is im- paired. Dysfunctions in intestinal permeability can result in leaky gut syndrome, in which larger molecules in the intes- tines pass through them into the blood. is syndrome can trigger immediate damage and immune-system reactions be- cause these large molecules are perceived as foreign. Progres- sive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the bloodstream. Dysfunctions in intestinal permeability are associated not only with intestinal diseases, such as ulcerative colitis, IBS, and Crohn’s disease, but also with chronic fatigue syndrome, psoriasis, food allergies, autoimmune diseases, and arthritis. Impaired intestinal permeability can also occur in patients un- dergoing chemotherapy and patients with heart disease, such as those with chronic heart failure. A dysfunction in intestinal permeability may be present when an individual is consuming a less-than-optimal diet or as the result of other factors such as psychologic stress. 5 Intestinal permeability is associated with food sensitivity. One group of researchers evaluated the intestinal permeability of subjects with adverse reactions to food. 6 Twenty-one sub- jects with food allergy and 20 with food hypersensitivity who were on allergen-free diets were enrolled in the study and di- vided into 4 groups according to the seriousness of their clini- cal symptoms. e researchers found statistically significant differences in intestinal permeability in subjects with food al- lergy or hypersensitivity compared with control patients. e results showed that the worse the intestinal permeability was, the more serious were the clinical symptoms in patients with food allergy and hypersensitivity. 6 Impaired intestinal permeability is often linked with GI dis- eases such as ulcerative colitis and Crohn’s disease. However, Supporting Gastrointestinal Health with Nutritional Therapy Chris D. Meletis, N.D., and Nieske Zabriskie, N.D.
Transcript
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
132 DOI: 10.1089/act.2008.14305 • MARY ANN LIEBERT, INC. • VOL. 14 NO. 3JUNE 2008
Digestive disorders are increasingly common and affect millions of Americans. There were 41.3 million office visits to physicians and 15.1 visits to the emergency rooms for digestive-system symptoms in 2004, according to the Centers for Disease Control and Prevention’s (CDC’s) most recent data.1 Condi-tions include irritable bowel syndrome (IBS); inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn’s disease; celiac disease; gastroesophageal reflux disease (GERD); gastrointestinal (GI) cancers; and other conditions such as diar-rhea, constipation, indigestion, nausea, and flatulence.
Approximately 60–70 million people are affected by overt diagnosable digestive diseases,2 yet tens of millions of other patients suffer from subclinical GI health conditions that alter their ability to absorb nutrients from their diets and supple-ments. This has a dramatic impact on quality of life with 1.9 million people disabled due to GI disease.3 Annually, an as-tounding 234,000 people die from GI diseases including GI cancer.4
The GI tract is the absolute barrier between the burdensome outside world that enters the human body as foods and con-taminants (herbicides, pesticides, heavy metals, and an array of other health saboteurs) and the well-ordered 75 trillion cells that work in harmony to sustain human existence. Therefore, regardless of whether an individual has any overt signs of GI dysfunction, fortifying the GI tract enhances the ability for nutrients from food and supplements to be most optimally absorbed.
Intestinal Permeability and Overall Health
Intestinal permeability, which refers to the potential for nutrients and bacteria to pass through a weakened intestinal wall—as well as, to some degree, through healthy tissues—is
an important factor for optimal GI health. When intestinal permeability is increased, food and nutrient absorption is im-paired. Dysfunctions in intestinal permeability can result in leaky gut syndrome, in which larger molecules in the intes-tines pass through them into the blood. This syndrome can trigger immediate damage and immune-system reactions be-cause these large molecules are perceived as foreign. Progres-sive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the bloodstream.
Dysfunctions in intestinal permeability are associated not only with intestinal diseases, such as ulcerative colitis, IBS, and Crohn’s disease, but also with chronic fatigue syndrome, psoriasis, food allergies, autoimmune diseases, and arthritis. Impaired intestinal permeability can also occur in patients un-dergoing chemotherapy and patients with heart disease, such as those with chronic heart failure. A dysfunction in intestinal permeability may be present when an individual is consuming a less-than-optimal diet or as the result of other factors such as psychologic stress.5
Intestinal permeability is associated with food sensitivity. One group of researchers evaluated the intestinal permeability of subjects with adverse reactions to food.6 Twenty-one sub-jects with food allergy and 20 with food hypersensitivity who were on allergen-free diets were enrolled in the study and di-vided into 4 groups according to the seriousness of their clini-cal symptoms. The researchers found statistically significant differences in intestinal permeability in subjects with food al-lergy or hypersensitivity compared with control patients. The results showed that the worse the intestinal permeability was, the more serious were the clinical symptoms in patients with food allergy and hypersensitivity.6
Impaired intestinal permeability is often linked with GI dis-eases such as ulcerative colitis and Crohn’s disease. However,
Supporting Gastrointestinal Health with Nutritional Therapy
Chris D. Meletis, N.D., and Nieske Zabriskie, N.D.
14_3ACT_B.indd 132 6/24/08 3:09:14 PM
creo
133
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
cell line in studies.15 In particular, butyrate has been investi-gated for its inhibition of proinflammatory markers and the role this plays in prevention of IBD and colon cancer.16 Bu-tyrate has also been studied in the prevention of colon cancer, by promoting cell differentiation, cell-cycle arrest, and apopto-
sis of transformed colon cells. Butyrate has also been shown to decrease experimentally induced DNA damage in human co-lon cells and colon-cancer cell lines by approximately 50%.17
Butyrate may also play a role in preventing certain types of colitis. A deficiency of SCFAs could lead, in the short-term, to incomplete development of the mucosal lining and, in the long-term, to colitis.18 Some researchers believe that a diet low in resistant starch and fiber and the resulting low production of SCFAs in the colon, may explain the high occurrence of colon disorders seen in Western societies.19 Decreased produc-tion of SCFAs appears to be involved in antibiotic-associated diarrhea, diversion colitis,* and possibly in pouchitis.†20 SCFA deficiency also may play a role in the development of ulcer-ative colitis and other intestinal disorders.21 Thus, SCFAs may reduce the risk of developing cancer, GI disorders, and cardio-vascular disease.22
new research is finding a surprising link between malfunctions in the colonic barrier and a number of non-GI conditions such as heart disease. In a recent study, scientists evaluated the func-tion of the gut in 22 patients with chronic heart failure (CHF) and 22 control subjects. Patients with CHF, compared with control patients, had a 35% increase of small-intestinal per-meability and a 210% increase of large-intestinal permeability. In addition, higher concentrations of adherent bacteria were found within the mucus of patients who had CHF compared with control subjects. The researchers suggested that CHF is a disorder in which intestinal morphology, permeability, and absorption are altered and may contribute to the origin of both chronic inflammation and malnutrition in this condition.7
The Role of Short-Chain Fatty Acids
Short-chain fatty acids (SCFAs), primarily acetate, propi-onate, and butyrate, are produced in the colon by fermentation of dietary carbohydrates, particularly from degradation-resis-tant starches and dietary fiber. These fatty acids play an impor-tant role in intestinal health. The amount and rate of SCFA production depends on several factors. These include the spe-cies and amounts of microflora in the colon, the fermentation substrate source, and the transit time of fecal matter through the gut. SCFA concentrations in the intestines vary markedly with diet.8
SCFAs have numerous functions in the intestines. SCFAs are readily absorbed by the intestinal mucosa and have been shown to stimulate intestinal mucosal growth. In particular, butyrate is the major energy source for the cells that line the colon. Butyrate has been shown to induce enzymes promoting mucosal-cell restoration.
SCFAs also stimulate sodium and water absorption in the colon.9 In addition, SCFAs enhance the motility of the in-testinal tract by stimulating contractions and shortening of ileum emptying, which may protect ileal mucosa against the potentially harmful effects of reflux of colonic contents.10 In addition, mucus secretion, an important part of the intestinal mucosal barrier, has been shown to be stimulated by SCFAs, especially butyrate, in the colon.11
SCFAs have been shown to play a role in many disease condi-tions, including cancer, cardiovascular disease, and digestive dis-orders.12 Propionate has been shown to inhibit cholesterol syn-thesis, making it an important factor in cardiovascular disease.13
Butyrate, acetate, and propionate have been shown to be ef-fective anti-inflammatory and immune-modulating agents in human colon-cancer cell lines and mouse models.14 Butyrate, propionate, and acetate inhibited the proliferation and migra-tion and increased the differentiation of a human colon-cancer
*This inflammation develops in a lower part of the large intestine after the passage of stool above this intestine has been surgically diverted.†This inflammation of a surgically made pouch from the ileum can occur in patients who undergo restorative proctocolectomy.
Nutritional Support for Optimal Colon Health
Glutamine Glycyrrhiza glabra (licorice)
Berberine Hydrastis canadensis ([goldenseal] and Mahonia aquifolium [Oregon grape])
Brassica oleracea (cabbage)
Ulmus fulva (slippery elm)
Althaea officinalis (marshmallow)
Aloe vera (aloe)
N-acetyl-glucosamine
Phosphatidylcholine
Gamma-oryzanol
Fiber
Larch arabinogalactan
Probiotics
Vitamin D3
Short-chain fatty acids
SCFAs may reduce the risk of developing cancer, GI disorders, and
cardiovascular disease.
14_3ACT_B.indd 133 6/26/08 7:13:18 PM
creo
134
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
Glutamine is one of the most powerful tools for reducing intestinal permeability, thereby protecting the body against the negative consequences of a leaky gut. In a recent review, researchers studied the medical literature to determine if glu-tamine was effective in reducing intestinal permeability in critically ill patients.29 In this patient population, intestinal permeability can have particularly lethal consequences, causing bacteremia, sepsis, and multiple organ failure syndrome. The scientists concluded that glutamine has a protective effect that prevents or reduces increases in intestinal permeability. Glu-tamine also reduces the frequency of systemic infections.29
Another group of researchers drew a similar conclusion after studying patients with GI cancer who received che-motherapy. In these subjects, oral glutamine decreased in-testinal permeability and maintained the intestinal barrier.30 Studies using animal models also suggest that, in addition to improving intestinal permeability and decreasing bacterial translocation, glutamine supplementation may also decrease systemic inflammation and increase killing of bacteria by the immune system.31
LicoriceGlycyrrhiza glabra (licorice) has historically been used for its
anti-inflammatory, soothing, laxative, and antispasmodic activi-ties. Most of the research on deglycyrrhizinated licorice (DGL) has been focused on upper GI health, including ulcer healing and dyspepsia. DGL seems to have similar properties as car-benoxolone, a semisynthetic derivative of glycyrrhetic acid used outside the United States for treating gastric and duodenal ulcer disease.32,33 DGL utility is not limited to upper GI health, as in the clinical setting DGL has also demonstrated great utility in lessening intestinal irritation and related symptoms.34
BerberineBerberine is a constituent found in multiple herbs such as
Hydrastis canadensis (goldenseal) and Mahonia aquafolium (Oregon grape). Berberine may benefit colon health by main-taining healthy GI flora and inhibiting pathogenic microbes in the colon. Berberine has antimicrobial effects, including antibacterial, antifungal, antimycobacterial, and antiproto-zoal activity.
Berberine has demonstrated activity against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Shigella boydii, Vibrio cholerae, Mycobacterium tuberculosis, Candida albicans, Candida tropicalis, Trichophyton mentagrophytes, Microsporum gypseum, Cryptococcus neoformans, Sporotrichum schenkii, Enta-moeba histolytica, and Giardia lamblia.35–39 In addition, ber-berine helps control inflammation in the GI tract by selectively inhibiting cyclo-oxygenase (COX)–2 expression and blocking proinflammatory cytokines.40
Based on animal models, berberine may reduce intestinal perme-ability.41 Research has also shown that berberine induces apoptosis in human colon-cancer cells.42 In addition, berberine has decreased inflammation in experimentally induced colitis in rats by decreas-ing the cytokine interleukin (IL)–8, which is commonly elevated in individuals with ulcerative colitis and Crohn’s disease.43
Adverse Effects of Ammonia in the Colon
Ammonia is produced in the colon as a byproduct of bac-terial fermentation of protein and other nitrogen-containing substances. Levels of ammonia in the colon increase as protein intake increases. Elevated levels of colonic ammonia may have adverse health effects. Research indicates that ammonia levels as low as 5 mmol/L can have detrimental effects on the epithe-lial cells that line the colon. The toxicity of ammonia in colonic epithelial cells can lead to cell destruction and increased turn-over of these cells.23
In addition, increased production of ammonia from eating a high-protein diet was shown to increase the incidence of colon cancer in animal models.24 Levels of ammonia found in the colons of individuals consuming a typical Western diet were associated with increased viral infections, promotion of growth of cancer cells, cell toxicity and altered nucleic-acid synthesis, and increased mass of intestinal mucosal cells.25
Dietary and Herbal Support for the Colon
Specific supplements, taken together, can provide critical building blocks for daily repair of the GI tract and also help soothe irritation that arises from innate colonic function.
GlutamineGlutamine is the most-abundant free amino acid in the
body.26 Though this substance is classified as a nonessential amino acid, it is a conditionally essential amino acid during times of increased stress.27 Glutamine serves as metabolic fuel for the enterocytes that line the colon and the small intestine and that may play a role in cell proliferation and differentia-tion. The GI tract has the largest demand for glutamine in the body.28 Insufficient glutamine can cause atrophy, ulceration, and necrosis of the colon lining.
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
damaging effects of digestive enzymes. Studies indicate that, in individuals with IBD, N-acetylation of glucosamine is rela-tively deficient in the intestinal mucosa, possibly reducing the synthesis of the gastric and intestinal mucosa’s protective gly-coprotein cover.55
PhosphatidylcholinePhosphatidylcholine is an important lipid component of the
protective intestinal mucosal layer. A defective phosphatidyl-choline layer may contribute to increased inflammation and ulceration. Animal models suggest that treatment with lipids, including phosphatidylcholine, increases surface hydropho-bicity in the colon and reduces colonic permeability.56 This surface hydrophobicity is an important defense mechanism against macromolecules and toxins.
Low levels of phosphatidylcholine in colonic mucus are a likely contributory factor in the development of ulcerative coli-tis. In a recent, randomized, double-blind placebo-controlled study, patients with ulcerative colitis were given 2 g per day of phosphatidylcholine. Phosphatidylcholine supplementation reduced corticosteroid dependence in patients with chronic steroid-refractory ulcerative colitis.57
In a similar study, 6 g per day of phosphatidylcholine (using delayed- or “retarded-” release phosphatidylcholine) was ad-ministered to patients with ulcerative colitis over 3 months.58 At the end of the study, 53% of patients had clinical remission, while 90% had improvement. In addition, 55% of the patients treated with phosphatidylcholine reported improvements in quality of life, 63% had reductions in length of affected ar-eas, and 52% had improvement in histology scores as noted by evaluation.58
Research also suggests that phosphatidylcholine can en-hance butyrate’s ability to inhibit colon-cancer cells, and, therefore works well with fiber to strengthen the intestinal environment.59
tection to the GI tract. Cabbage contains several important nutrients, such as vitamins A, B (such as folic acid), C, E, and K1; calcium; and amino acids including glutamine. Evidence suggests that individuals who consume large amounts of cab-bage and other Brassica vegetables have a lower risk of develop-ing stomach and colorectal cancer.44
In a study, 100 patients who had peptic ulcers drank 4 glasses of fresh, raw cabbage juice daily. The patients reported having dramatically reduced pain, while X-rays showed sig-nificantly reduced healing time. Eighty-one percent of the patients were symptom-free within 1 week, and more than two thirds were better within 4 days.45 Cabbage also pro-duces antioxidant activity.46
lage constituents that are demulcent and emollient. Slippery-elm preparations trigger gentle stimulation of nerve endings in the GI tract, leading to mucus secretion that coats and protects the delicate lining of the intestines from ulcers, excess acidity, ingested irritants, and toxins.47 In addition, a study evaluated damaging oxygen free-radical release from mucosal biopsies from patients with active ulcerative colitis. Incubation with slippery elm reduced oxygen free radicals showing antioxidant activity in the colon.48
MarshmallowAlthaea officinalis (marshmallow) leaf and root contain mu-
cilage polysaccharides that soothe and protect mucous mem-branes by creating a protective layer against local irritants.49,50 These mucilage constituents can also have antimicrobial, spas-molytic, and wound-healing effects.49,51
Aloe Aloe vera (aloe) is commonly used for digestive problems,
such as constipation, IBD, and ulcers. Research has demon-strated that aloe gel has antioxidant and anti-inflammatory activity in the colon, and decreases levels of colorectal prosta-glandin E2 and IL-8, which have been shown to play a role in inflammatory bowel disease.52
In a double-blind, randomized, placebo-controlled study, aloe gel was administered at a dose of 100 mL, twice daily, for 4 weeks to patients with mild-to-moderate active ulcerative colitis. At the end of the study, 30% of patients had clinical remissions, improvement was seen in 37%, and 47% responded to treatment. Simple Clinical Colitis Activity Index and histo-logic scores decreased significantly during treatment as well.53 Aloe gel also has antibacterial and antifungal activity.54
N-Acetyl-GlucosamineN-acetyl-glucosamine (NAG) is the acetylated derivative
of the amino sugar glucosamine. NAG, a precursor to proteo-glycans, is a major constituent of the mucosal barrier cover-ing absorptive enterocytes and protects these cells from the
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
by the Food and Drug Administration as a dietary fiber source, is a nondigestible, soluble dietary fiber that resists breakdown by enzymes and enters the large bowel intact, where this fiber is fermented by colonic bacteria. Larch AG is used medicinally for the effects of these polysaccharides on the intestines and immune system.
Larch AG has been shown to increase the production of short-chain fatty acids, particularly butyrate and propionate. This fiber has decreased the generation and absorption of am-monia in the colon. In addition, research has demonstrated that ingestion of Larch AG has a significant effect on enhanc-ing beneficial gut microflora, specifically increasing anaerobes such as Lactobacillus.
To assess the effects of Larch AG on healthy individuals, participants in a study were given either 15 or 30 g of Larch AG daily for 6 weeks. Ingestion of Larch AG increased levels of the total anaerobic bacteria in the colon and significantly increased Lactobacillus levels. Fecal ammonia levels also de-creased significantly, which may have been the result of the in-crease in anaerobic bacteria, because some strains use ammonia as a preferred nitrogen source.23
Larch AG also has immune-modulating activity, which is important for several intestinal disorders. This substance has stimulated natural-killer (NK) cell cytotoxicity, which can be abnormal in conditions such as IBS and IBD. Larch AG also can inhibit metastasis of tumor cells to the liver, making this substance an important adjunct to cancer protocols.64
ProbioticsThere are more than 400 different strains of bacteria in the
intestines. Proper intestinal microflora are necessary for optimal health and are critical for normal immune system functioning. For example, in many studies, probiotics, such as Lactobacillus and Bifidobacteria, have provided health benefits. Probiotics can improve the barrier function of the intestines, compete with and suppress pathogenic bacteria, and modulate or stimulate the im-mune response.65
A recent study showed that giving probiotics and prebiotics to patients with colon cancer decreased cell proliferation and other cancer markers while stimulating the immune response. In addition, taking supplements with these beneficial bacte-ria decreased the levels of pathogenic bacteria in the colon.66 Taking Lactobacillus to increase colonic levels of this organism has shown benefit for patients with several intestinal disorders including diarrhea, chronic IBD, ulcerative colitis, IBS, and pouchitis.67,68
Vitamin DVitamin D has been shown to play an important role in GI
health. Evidence suggests that, in patients with IBD, vitamin D deficiency (a serum 25OHD3 concentration of less than 15 ng/mL) is present in 22–70% in patients with Crohn’s disease and in 45% of those with ulcerative colitis.69
Animal models suggest that the vitamin D receptor is in-volved in mucosal-barrier homeostasis by preserving the in-tegrity of tight-junction complexes and the healing capacity
Gamma-OryzanolGamma-oryzanol extracted from bran (such as rice-bran
oil) contains ferulic esters that have antioxidant properties. Gamma-oryzanol is highly regarded in Japan for the ability to promote a healthy GI environment. Numerous studies have been performed in Japan with gamma-oryzanol, which have shown efficacy for treating GI problems, such as IBS, gastritis, and peptic and duodenal ulcers.60
Animal models indicate that gamma-oryzanol modulates pituitary secretion, inhibits excess gastric-acid secretion, and inhibits platelet aggregation.61 There is also evidence of cho-lesterol-lowering properties that work by decreasing choles-terol absorption from the gut.62
FiberIncreasing fiber intake is one of the easiest ways to increase bu-
tyrate levels in the body. Fiber is well-known for its ability to pro-tect the body against colon cancer and the ability to raise butyrate levels, which is thought to be one of the main ways in which fiber protects the colon. The benefits of dietary fiber in IBD may also be related to the production of butyrate that occurs when fiber is fermented in the colon, which decreases the inflammatory re-sponse.63 (See section on short-chain fatty acids.)
Larch Arabinogalactan Larch arabinogalactan (AG) is a highly-branched polysac-
charide derived from the bark of the Larix spp. (larch) tree, pri-marily L. occidentalis (Western larch). AG, which is approved
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
12. Hijova E, Chmelarova A. Short chain fatty acids and colonic health. Bratisl Lek Listy 2007;108:354–358.13. Berggren AM, Nyman EM, Lundquist I, Björck IM. Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats. Br J Nutr 1996 Aug;76:287–294.14. Tedelind S, Westberg F, Kjerrulf M, et al. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: A study with relevance to inflammatory bowel disease. World J Gastroenterol 2007;13:2826–2832.15. Fu H, Shi YQ, Mo SJ. Effect of short-chain fatty acids on the proliferation and differentiation of the human colonic adenocarcinoma cell line Caco-2. Chin J Dig Dis 2004;5:115–117.16. Andoh A, Tsujikawa T, Fujiyama Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharm Des 2003;9:347–358.17. Rosignoli P, Fabiani R, De Bartolomeo A, et al. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells. Carcinogenesis 2001;22:1675–1680.18. Scheppach W, Christl SU, Bartram HP, et al. Effects of short-chain fatty acids on the inflamed colonic mucosa. Scand J Gastroenterol Suppl 1997;222:53–57.19. Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut 1994;35(suppl):S35–S38.20. Mortensen PB, Clausen MR. Short-chain fatty acids in the human colon: Relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl 1996;216:132–148.21. Rabassa AA, Rogers AI. The role of short-chain fatty acid metabolism in colonic disorders. Am J Gastroenterol 1992;87:419–423.22. Wong JM, de Souza R, Kendall CW, et al. Colonic health: Fermentation and short chain fatty acids. J Clin Gastroenterol 2006;40:235–243.23. Robinson RR, Feirtag J, Slavin JL. Effects of dietary arabinogalactan on gastrointestinal and blood parameters in healthy human subjects. J Am Coll Nutr 2001;20:279–285.24. Bartram HP, Scheppach W, Schmid H, et al. Proliferation of human colon-ic mucosa as an intermediate biomarker of carcinogenesis: Effects of butyrate, deoxycholate, calcium, ammonia, and pH. Cancer Res 1993;53:3283–3288.25. Visek WJ. Diet and cell growth modulation by ammonia. Am J Clin Nutr 1978;31(suppl):S216–S220.26. Medina MA. Glutamine and cancer. J Nutr 2001;131(suppl):2539S–2542S.27. Sacks GS. Glutamine supplementation in catabolic patients. Ann Pharma-cother 1999;33:348–354.28. Miller AL. Therapeutic considerations of l-glutamine: A review of the literature. Altern Med Rev 1999;4:239–248.29. De-Souza DA, Greene LJ. Intestinal permeability and systemic infec-tions in critically ill patients: Effect of glutamine. Crit Care Med 2005;33: 1125–1135.30. Jiang HP, Liu CA. Protective effect of glutamine on intestinal barrier func-tion in patients receiving chemotherapy. Zhonghua Wei Chang Wai Ke Za Zhi 2006;9:59–61.31. White JS, Hoper M, Parks RW, et al. Glutamine improves intestinal barrier function in experimental biliary obstruction. Eur Surg Res 2005;37:342–347.32. van Marle J, Aarsen PN, Lind A, et al. Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium. Eur J Pharmacol 1981;72:219–225.33. Tewari SN, Wilson AK. Deglycyrrhizinated liquorice in duodenal ulcer. Practitioner 1973;210:820–823.34. Kwon HS, Oh SM, Kim JK. Glabridin, a functional compound of liquorice, attenuates colonic inflammation in mice with dextran sulphate sodium-in-duced colitis. Clin Exp Immunol 2008;151:165–173.35. Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate: Antimi-crobial activity, bioassay, and mode of action. Can J Microbiol 1969;15: 1067–1076.
of the colon epithelium. Tight junctions are intercellular junc-tions that provide a functional barrier and regulate paracellular permeability across the epithelium. This evidence suggests that vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and in-creased risk of IBD.70
Vitamin D deficiency has also been shown to play a role in cancer development. Studies indicate an inverse relationship between vitamin D intake and sunlight exposure and the risk for colon cancer. There appears to be a dose–response relation-ship between vitamin D intake or serum 25OHD3 and risk for colon cancer. Observational studies have shown that individu-als with a >1000 international units (IU) per day oral vitamin D intake had 50% lower risk for developing colon cancer.71 In addition, vitamin D3 metabolites have recently been shown to play an important role in the regulation of cellular prolifera-tion, differentiation, and apoptosis.72
Conclusion
Digestive disorders are increasingly common. Optimal co-lon health is paramount in effectively managing patients with these conditions. Several nutritional supplements, herbs, and foods may help provide substantial improvement in GI func-tion and GI-related symptoms.
References
1. Centers for Disease Control and Prevention. Fast StatsAtoZ: Digestive Dis-orders. Online document at: www.cdc.gov/nchs/fastats/digestiv.htm Accessed on November 8, 2007.2. Adams PF, Hendershot GE, Marano M; National Center for Health Statistics; Centers for Disease Control and Prevention. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat 1999; 200:1–203.3. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected diges-tive diseases in the United States. Gastroenterology 2002;122:1500–1511.4. National Center for Health Statistics. Technical Appendix from Vital Sta-tistics of the United States: Mortality. 2002. Hyattsville, MD, 2004.5. Zareie M, Johnson-Henry K, Jury J, et al. Probiotics prevent bacterial trans-location and improve intestinal barrier function in rats following chronic psy-chological stress. Gut 2006;55:1553–1560.6. Ventura MT, Polimeno L, Amoruso AC, et al. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis 2006;38:732–736.7. Sandek A, Bauditz J, Swidsinski A, et al. Altered intestinal function in pa-tients with chronic heart failure. J Am Coll Cardiol 2007;50:1561–1569.8. Sanderson IR. Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium. J Nutr 2004;134(suppl):2450S–2454S.9. D’Argenio G, Mazzacca G. Short-chain fatty acid in the human colon: Rela-tion to inflammatory bowel diseases and colon cancer. Adv Exp Med Biol 1999; 472:149–158.10. Cherbut C, Aubé AC, Blottière HM, et al. Effects of short-chain fatty ac-ids on gastrointestinal motility. Scand J Gastroenterol Suppl 1997;222:58–61.11. Shimotoyodome A, Meguro S, Hase T, et al. Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon. Comp Biochem Physiol A Mol Integr Physiol 2000;125:525–531.
14_3ACT_B.indd 137 6/24/08 3:09:18 PM
creo
138
ALTERNATIVE AND COMPLEMENTARY THERAPIES • JUNE 2008
MARY ANN LIEBERT, INC. • VOL. 14 NO. 3
58. Stremmel W, Merle U, Zahn A, et al. Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis. Gut 2005;54:966–971.
59. Hossain Z, Konishi M, Hosokawa M, et al. Effect of polyunsaturated fatty acid–enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem Funct 2006;24:159–165.
60. Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing, 1996:332–335.
61. Cicero AF, Gaddi A. Rice bran oil and gamma-oryzanol in the treat-ment of hyperlipoproteinemias and other conditions. Phytotherapy Res 2001; 15:277–289.
62. Seetharamaiah GS, Chandrasekhara N. Effect of oryzanol on choles-terol absorption and biliary and fecal bile acids in rats. Indian J Med Res 1990;92:471–475.
63. Rose DJ, DeMeo MT, Keshavarzian A, et al. Influence of dietary fiber on inflammatory bowel disease and colon cancer: Importance of fermentation pattern. Nutr Rev 2007;65:51–62.
64. Kelly GS. Larch arabinogalactan: Clinical relevance of a novel immune-enhancing polysaccharide. Altern Med Rev 1999;4:96–103.
65. Fedorak RN, Madsen KL. Probiotics and the management of inflamma-tory bowel disease. Inflamm Bowel Dis 2004;10:286–299.
66. Rafter J, Bennett M, Caderni G, et al. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr 2007;85:488–496.
67. Schultz M, Sartor RB. Probiotics and inflammatory bowel diseases. Am J Gastroenterol 2000;95(suppl):S19–S21.
68. Nobaek S, Johansson ML, Molin G, et al. Alteration of intestinal micro-flora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol 2000;95:1231–1238.
69. Pappa HM, Grand RJ, Gordon CM. Report on the vitamin D status of adult and pediatric patients with inflammatory bowel disease and its signifi-cance for bone health and disease. Inflamm Bowel Dis 2006;12:1162–1174.
70. Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008;294:G208–G216.
71. Murillo G, Matusiak D, Benya RV, et al. Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer. J Steroid Biochem Mol Biol 2007;103:763–767.
72. Kim KE, Brasitus TA. The role of vitamin D in normal and pathologic processes in the colon. Curr Opin Gastroenterol 2001;17:72–77.
Chris D. Meletis, N.D., is executive director of the Institute for Healthy Ag-ing, a non-profit educational group, in Carson City, Nevada, and an associate professor of natural pharmacology at the National College of Natural Medi-cine, in Portland, Oregon. Nieske Zabriskie, N.D., is a naturopathic doctor in Grand Rapids, Michigan.
To order reprints of this article, e-mail Karen Ballen at: [email protected] or call at (914) 740-2100.
36. Scazzocchio F, Corneta MF, Tomassini L, et al. Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids. Planta Med 2001;67:561–564.37. Rehman J, Dillow JM, Carter SM, et al. Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the me-dicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunol Lett 1999;68:391–395.38. Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimi-crob Agents Chemother 1988;32:1370–1374.39. Kaneda Y, Torii M, Tanaka T, et al. In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Ann Trop Med Parasitol 1991;85:417–425.40. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxy-genase-2 transcriptional activity in human colon cancer cells. J Ethnopharma-col 1999;66:227–233.41. Taylor CT, Winter DC, Skelly MM, et al. Berberine inhibits ion transport in human colonic epithelia. Eur J Pharmacol 1999;368:111–118.42. Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch Toxicol 2007;81:719–728.43. Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J Pharmacol Exp Ther 2000;294:822–829.44. van Poppel G, Verhoeven DT, Verhagen H, et al. Brassica vegetables and cancer prevention: Epidemiology and mechanisms. Adv Exp Med Biol 1999;472:159–168.45. Cheney G. Vitamin U Therapy of Peptic Ulcer. California Med 1952;77: 248–252.46. Isbir T, Yaylim I, Aydin M, et al. The effects of Brassica oleraceae var capi-tata on epidermal glutathione and lipid peroxides in DMBA-initiated-TPA-promoted mice. Anticancer Res 2000;20:219–224.47. The Review of Natural Products by Facts and Comparisons. St. Louis: Wolters Kluwer, 1999.48. Langmead L, Dawson C, Hawkins C, et al. Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: An in vitro study. Aliment Pharmacol Ther 2002;16:197–205.49. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: Pharmaceutical Press, 1996.50. Martindale W. The Extra Pharmacopoeia. London, UK: Pharmaceutical Press, 1999.51. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines, 1st ed. Montvale, NJ: Medical Economics, 1998.52. Langmead L, Makins RJ, Rampton DS. Anti-inflammatory effects of Aloe vera gel in human colorectal mucosa in vitro. Aliment Pharmacol Ther 2004;19:521–527.53. Langmead L, Feakins RM, Goldthorpe S, et al. Randomized, double-blind, placebo-controlled trial of oral Aloe vera gel for active ulcerative colitis. Aliment Pharmacol Ther 2004;19:739–747.54. Klein AD, Penneys NS. Aloe vera. J Am Acad Dermatol 1988;18:714–720.55. Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol 1983;78:19–22.56. Lugea A, Salas A, Casalot J, et al. Surface hydrophobicity of the rat co-lonic mucosa is a defensive barrier against macromolecules and toxins. Gut 2000;46:515–521.57. Stremmel W, Ehehalt R, Autschbach F, et al. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: A randomized trial. Ann Intern Med 2007;147:603–610.
