Larch Arabinogalactan and Intestinal Health

By Nieske Zabriskie, ND

Digestive disorders are a common complaint and affect many Americans. They can include Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD) (including Ulcerative Colitis and Crohn\'s Disease), Gastroesophageal Reflux (GERD), cancer, diarrhea, constipation, indigestion and flatulence. According to the American Gastroenterological Association, IBS alone affects 14-24 percent of women and 5-19 percent of men.¹ In fact, there were 41.3 million office visits to physicians and 15.1 visits to the Emergency Department for digestive system symptoms in 2004, according to the most recent data from the Centers for Disease Control and Prevention (CDC).² There are numerous studies showing a variety of physiological abnormalities found in many of these conditions. Short chain fatty acids, presence of ammonia, and number and type of microflora can impact the health of the intestinal tract.

Short-Chain Fatty Acids: Caretakers of the Colon

Short chain fatty acids (SCFA), primarily acetate, propionate and butyrate, are produced in the colon by fermentation of dietary carbohydrates, particularly from degradation-resistant starches and dietary fiber. These fatty acids play an important role in intestinal health and insufficient SCFA can contribute to a significantly less healthy colon.

The amount and rate of SCFA production depends on several factors. These include the species and amounts of microflora in the colon, the ingested items being fermented, and the transit time through the gut. SCFA concentrations in the intestines vary markedly with diet.³

The SCFAs have numerous functions in the intestines. SCFAs are readily absorbed by the intestinal mucosa, or the innermost lining of the colon, and have been shown to stimulate intestinal mucosal growth. Particularly, 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.⁴ In addition, SCFAs enhance the motility of the intestinal tract by stimulating contractions and shorten emptying of the ileum (the last section of the small intestine), which may protect ileal mucosa against the potentially harmful effects of the reflux of colonic contents.⁵ Also, the secretion of mucus, an important part of the intestinal mucosal barrier, has been shown to be stimulated by SCFAs, especially butyrate, in the colon.⁶

SCFAs have been shown to play a role in the inhibition of many disease conditions including cancer, cardiovascular disease and digestive disorders. Propionate has been shown to inhibit cholesterol synthesis, making it an important factor in cardiovascular health. Butyrate, acetate and propionate have been shown to be effective anti-inflammatory and immune-modulating agents in human colon cancer cell lines and mouse models.⁷ Butyrate, propionate and acetate inhibited the proliferation and migration and increased the differentiation of a human colon cancer cell line in studies.⁸ Particularly, butyrate has been investigated for its inhibition of pro-inflammatory markers and the role this plays in prevention of IBD and cancer.⁹ Butyrate has also been studied in the prevention of colon cancer, by promoting cell differentiation, cell-cycle arrest and apoptosis (programmed cell death) of transformed colon cells. In fact, butyrate has been shown to decrease experimentally induced DNA damage in human colon cells and colon cancer cell lines by approximately 50 percent.¹⁰ Butyrate may also have 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.¹¹ 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 civilizations.¹² Production of SCFAs appears to be involved in antibiotic-associated diarrhea, diversion colitis and possibly in pouchitis, an acute inflammation that occurs in the surgically produced pouch used after removal of the colon and rectum.¹³ A SCFA deficiency state also may play a role in ulcerative colitis and other intestinal disorders.¹⁴ Thus, SCFAs may reduce the risk of developing cancer, gastrointestinal disorders and cardiovascular disease.¹⁵

Ammonia\'s Destructive Effects

Ammonia is produced as a by-product in the colon by bacterial 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 epithelial cells that line the colon. The toxicity of ammonia toward colonic epithelial cells can lead to cell destruction and increased turnover of these cells.¹⁶ In addition, increased production of ammonia from eating a high-protein diet was shown to increase the incidence of colon cancer in animal models.¹⁷ Levels of ammonia found in the colon after consumption of the typical Western diet are associated with increased viral infections, promotion of growth of cancer cells, cell toxicity and altered nucleic acid synthesis, and increased mass of the intestinal mucosal cells.¹⁸

The Role of Intestinal Microflora

There are over 400 different strains of bacteria in the intestines. Proper intestinal microflora are necessary for optimal health and are critical for normal immune system functioning. Probiotics, such as Lactobacillis and Bifidobacteria, have been shown in many studies to provide health benefits. Probiotics can improve the barrier function of the intestines, compete and suppress pathogenic bacteria, and modulate or stimulate the immune response.¹⁹ A recent study showed that supplementation with probiotics and prebiotics in patients with colon cancer decreased cell proliferation and other cancer markers while stimulating the immune response. Additionally, supplementation of these beneficial bacteria decreased the levels of pathogenic bacteria in the colon.²⁰ Supplementation with Lactobacillus increasing colonic levels of this organism has shown benefit in several intestinal disorders including diarrhea, chronic IBD, ulcerative colitis, IBS and pouchitis.^21-22

Immune System and Intestinal Disorders

Individuals with intestinal conditions such as IBS and IBD have been shown to have abnormal immune system responses as well. Particularly, studies have shown that in these conditions, there is a significant decrease in the activity and/or number of natural killer (NK) cells, which are important for anti-viral and anti-tumor activity by the immune system.^23-24

Larch Arabinogalactan and Digestive Health

Larch arabinogalactan is a highly-branched polysaccharide (a large sugar molecule resistant to degradation) derived from the bark of the larch tree (Larix species), primarily Larix occidentalis (Western Larch). Larch is used medicinally for the effects of these polysaccharides on the intestines and immune system. Arabinogalactan (AG) is a non-digestible soluble dietary fiber that resists breakdown by enzymes and enters the large bowel intact where it is fermented by colonic bacteria. Arabinogalactan is approved by the FDA as a dietary fiber source.

Larch AG has been shown to increase the production of short-chain fatty acids, particularly butyrate and propionate. It has also been shown to decrease the generation and absorption of ammonia in the colon. Additionally, research has demonstrated that ingestion of Larch AG has a significant effect on enhancing beneficial gut microflora, specifically increasing anaerobes such as Lactobacillus. A study was performed with healthy individuals to assess the effects of Larch AG on this population. Participants were given either 15 or 30 grams of Larch AG daily for 6 weeks. The results showed that ingestion of Larch AG for 6 weeks increased levels of the total anaerobic bacteria in the colon and significantly increased levels of the beneficial bacteria Lactobacillus. Fecal ammonia levels were also shown to decrease significantly. Larch AG supplementation was well tolerated, with flatulence with the higher dose the only adverse complaint in some subjects.²⁵

Larch arabinogalactan also has immune modulating activity that is important for several intestinal disorders. Larch arabinogalactan has been shown to stimulate natural killer (NK) cell cytotoxicity, which has been shown to be abnormal in conditions such as IBS and IBD. There is evidence Larch also may inhibit the metastasis of tumor cells to the liver.²⁶

Conclusion

Digestive disorders are very common and affect a great number of the population. The typical American diet, which is low in fiber and high in protein and carbohydrates, is a factor in the prevalence of these digestive disorders. Low levels of short-chain fatty acids and elevated levels of ammonia are associated with this type of diet. Intake of fiber, particularly Larch AG, has been shown to combat the detrimental effects caused by the diet. Larch AG has been shown to increase short-chain fatty acids, decrease colonic ammonia levels, increase the numbers of beneficial bacteria in the colon, as well as improve the immune response. These favorable effects of Larch AG may positively modulate many of these too-common intestinal disorders.

References

1. American Gastroenterological Association Medical Position Statement: Irritable Bowel Syndrome. Available at: www3.us.elsevierhealth.com/gastro/policy/v112n6p2118.html. Accessed on: 11-08.07.

2. The Center for Disease Control and Prevention. Available at: www.cdc.gov/nchs/fastats/digestiv.htm. Accessed on 11-08-07.

3. Sanderson IR. Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium.

J Nutr. 2004 Sep;134(9):2450S-2454S.

4. D\'Argenio G, Mazzacca G. Short-chain fatty acid in the human colon. Relation to inflammatory bowel diseases and colon cancer. Adv Exp Med Biol. 1999;472:149-58.

5. Cherbut C, Aubé AC, Blottière HM, Galmiche JP. Effects of short-chain fatty acids on gastrointestinal motility. Scand J Gastroenterol Suppl. 1997;222:58-61.

6. Shimotoyodome A, Meguro S, Hase T, Tokimitsu I, Sakata T. Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon. Comp Biochem Physiol A Mol Integr Physiol. 2000 Apr;125(4):525-31.

7. Tedelind S, Westberg F, Kjerrulf M, Vidal A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J Gastroenterol. 2007 May 28;13(20):2826-32.

8. 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(3):115-7.

9. Andoh A, Tsujikawa T, Fujiyama Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharm Des. 2003;9(4):347-58.

10. Rosignoli P, Fabiani R, De Bartolomeo A, Spinozzi F, Agea E, Pelli MA, Morozzi G. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells. Carcinogenesis. 2001 Oct;22(10):1675-80.

11. Scheppach W, Christl SU, Bartram HP, Richter F, Kasper H. Effects of short-chain fatty acids on the inflamed colonic mucosa. Scand J Gastroenterol Suppl. 1997;222:53-7

12. Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut. 1994 Jan;35(1 Suppl):S35-8.

13. Mortensen PB, Clausen MR. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl 1996;216:132-48.

14. Rabassa AA, Rogers AI. The role of short-chain fatty acid metabolism in colonic disorders. Am J Gastroenterol. 1992 Apr;87(4):419-23.

15. Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol. 2006 Mar;40(3):235-43.

16. Robinson RR, Feirtag J, Slavin JL. Effects of dietary arabinogalactan on gastrointestinal and blood parameters in healthy human subjects. J Am Coll Nutr. 2001 Aug;20(4):279-85.

17. Bartram HP, Scheppach W, Schmid H, Hofmann A, Dusel G, Richter F, Richter A, Kasper H. Proliferation of human colonic mucosa as an intermediate biomarker of carcinogenesis: effects of butyrate, deoxycholate, calcium, ammonia, and pH. Cancer Res. 1993 Jul 15;53(14):3283-8.

18. Visek WJ. Diet and cell growth modulation by ammonia. Am J Clin Nutr. 1978 Oct;31(10 Suppl):S216-S220.

19. Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflamm Bowel Dis. 2004 May;10(3):286-99.

20. Rafter J, Bennett M, Caderni G, Clune Y, Hughes R, Karlsson PC, Klinder A, O\'Riordan M, O\'Sullivan GC, Pool-Zobel B, Rechkemmer G, Roller M, Rowland I, Salvadori M, Thijs H, Van Loo J, Watzl B, Collins JK. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr. 2007 Feb;85(2):488-96.

21. Schultz M, Sartor RB. Probiotics and inflammatory bowel diseases. Am J Gastroenterol. 2000 Jan;95(1 Suppl):S19-21.

22. Nobaek S, Johansson ML, Molin G, Ahrné S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000 May;95(5):1231-8.

23. Hirata I, Hayashi K, Asada S, Miyoshi H, Iwakoshi K, Ohshiba S. Alteration of natural killer cell subsets (two color analysis) and their activity in peripheral blood in inflammatory bowel disease. Bull Osaka Med Coll 1990 Nov;36(1-2):47-55.

24. Elsenbruch S, Holtmann G, Oezcan D, Lysson A, Janssen O, Goebel MU, Schedlowski M. Are there alterations of neuroendocrine and cellular immune responses to nutrients in women with irritable bowel syndrome? Am J Gastroenterol. 2004 Apr;99(4):703-10.

25. Robinson RR, Feirtag J, Slavin JL. Effects of dietary arabinogalactan on gastrointestinal and blood parameters in healthy human subjects. J Am Coll Nutr. 2001 Aug;20(4):279-85.

26. Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. Altern Med Rev. 1999 Apr;4(2):96-103.