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Larch Arabinogalactan
Monograph
Larch Arabinogalactan
Introduction
Larch arabinogalactan is a polysaccharide powder derived from the wood of the larch tree (Larix species) and comprised of approximately 98 percent arabinogalactan. Arabinogalactans are foundin a variety of plants but are more abundant in the Larix genus, primarily Larix occidentalis (WesternLarch). The Western Larch is unique among pines in that it loses its needles in the fall. Western Larchis also known as Mountain Larch or Western Tamarack and is native to the Pacific and Inland North-west United States as well as parts of British Columbia, Canada.1 Larch arabinogalactan is approved bythe U.S. Food and Drug Administration (FDA) as a source of dietary fiber, but also has potential thera-peutic benefits as an immune stimulating agent and cancer protocol adjunct.
Description and Biochemistry
Pharmaceutical-grade larch arabinogalactan is a fine, dry, off-white powder with a slightly sweet taste and mild pine-like odor. It dissolves completely in water or juice, is low in viscosity and thereforeeasy to administer, even to children. It is composed of galactose and arabinose molecules in a 6:1 ratio,with a small amount of glucuronic acid. Arabinogalactans are long, densely branched polysaccharidesof varying molecular weights (10,000-120,000). Lower molecular weight polysaccharides typicallyexhibit an anti-inflammatory, anti-complement, antiallergy effect, while those of higher weights stimu-late natural killer (NK) cell cytotoxicity and reticuloendothelial cells. In the case of larch arabinogalactan,molecular weights of the two major fractions are 16,000 and 100,000, perhaps accounting for its widerange of therapeutic properties.2 Pharmacokinetics
Human studies on the pharmacokinetics of larch arabinogalactan are few and the amount ab- sorbed following an oral dose remains unclear. Animal studies indicate that intravenous injection ofpurified larch arabinogalactan results in 52.5 percent of the dose being present in the liver and 30percent in the urine 90 minutes after dosing. Hepatic clearance occurred with a half-life of 3.42 days.3Non-absorbed larch arabinogalactan is actively fermented by intestinal microflora and is particularlyeffective at increasing beneficial anaerobes such as Bifidobacteria and Lactobacillus.4 Alternative Medicine Review ◆ Volume 5, Number 5 ◆ 2000 Page 463
Copyright2000 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Clinical Indications
Dietary Fiber
Larch arabinogalactan is an excellent source of dietary fiber that is able to increase short-chain fatty acid production (primarily butyrate) via its vigorous fermentation by intestinal microflora.2 It iswell documented that butyrate is essential for proper colon health as it is the preferred substrate forenergy generation by colonic epithelial cells.5 Butyrate also acts as a protectant for the intestinal mu-cosa against disease and cancer-promoting agents.6 Arabinogalactan added to human fecal homogenateshas also been shown to decrease ammonia generation, and therefore may be of clinical value in thetreatment of portal-systemic encephalopathy, a disease characterized by ammonia build-up in the liver.4Larch arabinogalactan given to human subjects increased levels of beneficial intestinal anaerobes, par-ticularly Bifidobacterium longum, via their fermentation specificity for arabinogalactan compared toother complex carbohydrates.7,8 Cancer Protocols
Larch arabinogalactan may be an effective adjunct to cancer therapies due to its ability to stimulate NK cell cytotoxicity, stimulate the immune system, and block metastasis of tumor cells to the liver.2Tumor metastasis to the liver is more common than to other organ sites, probably due to tumor cellspecificity for lectin-like receptor sites found in liver parenchyma. Animal studies have demonstratedarabinogalactan’s ability to inhibit or block lectin receptor sites, thereby reducing tumor cell coloniza-tion of the liver and also increasing survival time of the subjects.9-11 Pretreatment with larcharabinogalactan was found to stimulate NK cell cytotoxicity via potentiation of the cytokine network,primarily via an increase in the release of gamma interferon.12 Pediatric Otitis Media
Recurrent otitis media is common in pediatric populations and it appears that improving im- mune system function might lead to a decrease in both frequency and severity of this condition. Re-search has demonstrated larch and other arabinogalactans to be capable of enhancing the immuneresponse to bacterial infection via stimulation of phagocytosis, competitive binding of bacterial fim-briae, or bacterial opsonization. This was found to be particularly true for infection by gram negativeorganisms such as Escherichia coli and Klebsiella species.2,13 In addition, D’Adamo reports a decreasein occurrence and severity of otitis media in pediatric patients supplemented prophylactically withlarch arabinogalactan.2 Larch arabinogalactan’s mild taste and excellent solubility in water and juicemake it a relatively easy therapeutic tool to employ in pediatric populations.
Chronic Disease
A number of chronic diseases are characterized by decreased NK cell activity, including chronic fatigue syndrome,14 viral hepatitis,15,16 HIV/AIDS,2 and autoimmune diseases such as multiple sclero-sis.17 Stimulation of NK cell activity by larch arabinogalactan has been associated with recovery incertain cases of chronic fatigue syndrome.18 Viral hepatitis (hepatitis B and C) is also characterized bya decrease in NK cell cytotoxicity15,16 and therefore these patients may benefit from its stimulation bylarch arabinogalactan. In the case of multiple sclerosis, a small 2-year study of patients with the relaps-ing/remitting type concluded that disease severity was correlated with NK cell functional activity, sup-porting the hypothesis that NK cells play a role in the immunopathogenesis of this disease.17 Conse-quently, stimulation of NK cell cytotoxicity might be of clinical benefit to these patients. Patients withHIV/AIDS develop low CD4 cell counts and often are plagued by opportunistic infections. By virtue of Page 464 Alternative Medicine Review ◆ Volume 5, Number 5 ◆ 2000
Copyright2000 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission its immune-stimulating properties, larch arabinogalactan has been shown to effect a slight increase inCD4 cell counts, in addition to decreasing susceptibility to opportunistic pathogens.2 Hepatic Drug Delivery
Hepatic uptake of an injected dose of larch arabinogalactan resulted in 52.5 percent of the dose arriving in the liver. Due to its high hepatic concentration and its ability to increase vascular permeabil-ity,19 larch arabinogalactan has been suggested as a vehicle for administering diagnostic or therapeuticagents to the liver.3 Platelet Washing Medium
Larch arabinogalactan solution has been studied as a medium for use in platelet washing; a technique employed to separate platelets from platelet-rich plasma. The washed platelets can then beused in transfusions, bioassays, and research. Platelets washed with larch arabinogalactan solutionwere free of plasma proteins and retained both normal morphology and function.20 Side-Effects and Toxicity
Larch arabinogalactan is a safe and effective immune-stimulating phytochemical. It is FDA- approved for use as a dietary fiber and in food applications. Both acute and long-term toxicity studiesin rats and mice reveal no evidence of toxicity.21 Human consumption is usually without side-effects;however, a small percentage of people (<3%) experienced bloating and flatulence, possibly due to thevigorous fermentation of the arabinogalactan by intestinal microflora.2 Because of its excellent safetyprofile and solubility in water and juice, larch arabinogalactan is considered a safe, effective immune-stimulating agent for pediatric use.
Larch arabinogalactan in powder form is typically dosed in teaspoons or tablespoons at a con- centration of approximately 4-5 grams per tablespoon. The typical adult dosage is one to three table-spoons per day in divided doses; the pediatric dose is one to three teaspoons per day. The powder isusually mixed with water or juice but can be added to food if desired.
References
1.
Odonmazig P, Ebringerova A, Machova E, Alfoldi J. Structural and molecular properties of the arabinogalactanisolated from Mongolian larchwood (Larix dahurica L.). Carbohydr Res 1994;252:317-324.
D’Adamo P. Larch arabinogalactan. J Naturopath Med 1996;6:33-37.
Groman EV, Enriquez PM, Jung C, Josephson L. Arabinogalactan for hepatic drug delivery. Bioconjug Chem1994;5:547-556.
Vince AJ, McNeil NI, Wager JD, Wrong OM. The effect of lactulose, pectin, arabinogalactan, and cellulose on theproduction of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system. Br JNutr 1990;63:17-26.
Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 1989;83:424-429.
Tsao D, Shi Z, Wong A, Kim YS. Effect of sodium butyrate on carcinoembryonic antigen production by humancolonic adenocarcinoma cells in culture. Cancer Res 1983;43:1217-1222.
Crociani F, Alessandrini A, Mucci MM, Biavati B. Degradation of complex carbohydrates by Bifidobacterium spp.
Int J Food Microbiol 1994;24:199-210.
Alternative Medicine Review ◆ Volume 5, Number 5 ◆ 2000 Page 465
Copyright2000 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Slavin J, Feirtag J, Robinson R, Causey J. Physiological effects of arabinogalactan (AG) in human subjects.
Unpublished research.
Hagmar B, Ryd W, Skomedal H. Arabinogalactan blockade of experimental metastases to liver by murinehepatoma. Invasion Metastasis 1991;11:348-355.
Beuth J, Ko HL, Oette K, et al. Inhibition of liver metastasis in mice by blocking hepatocyte lectins witharabinogalactan infusions and D-galactose. J Cancer Res Clin Oncol 1987;113:51-55.
Beuth J, Ko HL, Schirrmacher V, et al. Inhibition of liver tumor cell colonization in two animal tumor models bylectin blocking with D-galactose or arabinogalactan. Clin Exp Metastasis 1988;6:115-120.
Hauer J, Anderer FA. Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan fromLarix occidentalis. Cancer Immunol Immunother 1993;36:237-244.
Reith FJ. Pharmaceuticals containing lactic acid derivatives and Echinacea. Bundesrepublik Deutsches Patentamt27 21 014 11/16/78. [German Patent] Levine PH, Whiteside TL, Friberg D, et al. Dysfunction of natural killer activity in a family with chronic fatiguesyndrome. Clin Immunol Immunopathol 1998;88:96-104.
Corado J, Toro F, Rivera H, et al. Impairment of natural killer (NK) cytotoxicity activity in hepatitis C virus(HCV) infection. Clin Exp Immunol 1997;109:451-457.
Machado IV, Deibis L, Risquez E, et al. Immunoclinical, molecular and immunopathologic approach to chronicviral hepatitis. Therapeutic considerations. GEN 1994;48:124-132. [Article in Spanish] Kastrukoff LF, Morgan NG, Zecchini D, et al. A role for natural killer cells in the immunopathogenesis ofmultiple sclerosis. J Neuroimmunol 1998;86:123-133.
Uchida A. Therapy of chronic fatigue syndrome. Nippon Rinsho 1992;50:2679-2683.
Kind LS, Macedo-Sobrinho B, Ako D. Enhanced vascular permeability induced in mice by larch arabinogalactan.
Immunology 1970;19:799-807.
Hill RJ, Stenberg PE, Sullam PM, Levin J. Use of arabinogalactan to obtain washed murine platelets free ofcontaminating plasma proteins and appropriate for studies of function, morphology, and thrombopoiesis. J LabClin Med 1988;111:73-83.
Wagner H. Low molecular weight polysaccharides from composite plants containing arabinogalactan,arabinoglucan, and arabinoxylan. Bundesrepublik Deutsches Patentamt DE 3042491 7/15/82. [German Patent] Page 466 Alternative Medicine Review ◆ Volume 5, Number 5 ◆ 2000
Copyright2000 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

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