Larch Arabinogalactan
Introduction
Larch Arabinogalactans are derived from the Western Larch tree. It has been well documented to have a very positive effect on the immune system. It has been shown to be effective in destroying both bacterial and viral infections in the human body.
The unusual immunological properties of Larch Arabinogalactans (wood gum, wood sugar, larch gum, etc.) suggest it may be used in numerous, exciting future applications. Evidence of this can be seen in the medicinal, pharmaceutical and bio-technical fields where current research and development has resulted in the creation of arabinoglactan-based products with unique characteristics.
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 found in a variety of plants but are more abundant in the Larix genus, primarily Larix occidentalis (Western Larch). The Western Larch is unique among pines in that it loses its needles in the fall. Western Larch is also known as Mountain Larch or Western Tamarack and is native to the Pacific and Inland Northwest United States as well as parts of British Columbia, Canada. Larch arabinogalactan is approved by the U.S. Food and Drug Administration (FDA) as a source of dietary fiber, but also has potential therapeutic 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 therefore easy 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 polysaccharides of varying molecular weights (10,000-120,000). Lower molecular weight polysaccharides typically exhibit an anti-inflammatory, anti-complement, antiallergy effect, while those of higher weights stimulate 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 wide range of therapeutic properties.
Pharmacokinetics
Human studies on the pharmacokinetics of larch arabinogalactan are few and the amount absorbed following an oral dose remains unclear. Animal studies indicate that intravenous injection of purified larch arabinogalactan results in 52.5 percent of the dose being present in the liver and 30 percent in the urine 90 minutes after dosing. Hepatic clearance occurred with a half-life of 3.42 days. Non-absorbed larch arabinogalactan is actively fermented by intestinal microflora and is particularly effective at increasing beneficial anaerobes such as Bifidobacteria and Lactobacillus.
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. It is well documented that butyrate is essential for proper colon health as it is the preferred substrate for energy generation by colonic epithelial cells. Butyrate also acts as a protectant for the intestinal mucosa against disease and cancer-promoting agents. Arabinogalactan added to human fecal
homogenates has also been shown to decrease ammonia generation, and therefore may be of clinical value in the treatment of portal-systemic encephalopathy, a disease characterized by ammonia build-up in the liver. Larch arabinogalactan given to human subjects increased levels of beneficial intestinal anaerobes, particularly Bifidobacterium longum, via their fermentation specificity for arabinogalactan compared to other complex carbohydrates.
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. Tumor metastasis to the liver is more common than to other organ sites, probably due to tumor cell specificity for lectin-like receptor sites found in liver parenchyma. Animal studies have demonstrated arabinogalactan’s ability to inhibit or block lectin receptor sites, thereby reducing tumor cell colonization of the liver and also increasing survival time of the subjects. Pretreatment with larch arabinogalactan was found to stimulate NK cell cytotoxicity via potentiation of the cytokine network, primarily via an increase in the release of gamma interferon.
Pediatric Otitis Media
Recurrent otitis media is common in pediatric populations and it appears that improving immune 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 immune response to bacterial infection via stimulation of phagocytosis, competitive binding of bacterial fimbriae, or bacterial opsonization. This was found to be particularly true for infection by gram-negative organisms such as Escherichia coli and Klebsiella species. In addition, D’Adamo reports a decrease in occurrence and severity of otitis media in pediatric patients supplemented prophylactically with larch arabinogalactan. Larch arabinogalactan’s mild taste and excellent solubility in water and juice make 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, viral hepatitis, HIV/AIDS, and autoimmune diseases such as multiple sclerosis. Stimulation of NK cell activity by larch arabinogalactan has been associated with recovery in certain cases of chronic fatigue syndrome. Viral hepatitis (hepatitis B and C) is also characterized by a decrease in NK cell cytotoxicity and therefore these patients may benefit from its stimulation by larch arabinogalactan. In the case of multiple sclerosis, a small 2-year study of patients with the relapsing/remitting type concluded that disease severity was correlated with NK cell functional activity, supporting the hypothesis that NK cells play a role in the immunopathogenesis of this disease. Consequently, stimulation of NK cell cytotoxicity might be of clinical benefit to these patients. Patients with HIV/AIDS develop low CD4 cell counts and often are plagued by opportunistic infections. By virtue of its immune- stimulating properties, larch arabinogalactan has been shown to effect a slight increase in CD4 cell counts, in addition to decreasing susceptibility to opportunistic pathogens.
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 permeability, larch arabinogalactan has been suggested as a vehicle for administering diagnostic or therapeutic agents to the liver.
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 be used in transfusions, bioassays, and research. Platelets washed with larch arabinogalactan solution were free of plasma proteins and retained both normal morphology and function.
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 studies in rats and mice reveal no evidence of toxicity. Human consumption is usually without side-effects; however, a small percentage of people (<3%) experienced bloating and flatulence, possibly due to the vigorous fermentation of the arabinogalactan by intestinal microflora. Because of its excellent safety profile and solubility in water and juice, larch arabinogalactan is considered a safe, effective immunestimulating agent for pediatric use. Larch Arabinogalactans possess minimal toxicity and are approved for food use.
Dosage
Larch arabinogalactan in powder form is typically dosed in teaspoons or tablespoons at a concentration of approximately 4-5 grams per tablespoon. The typical adult dosage is one to three tablespoons per day in divided doses; the pediatric dose is one to three teaspoons per day. The powder is usually mixed with water or juice but can be added to food if desired.
Alternative Medicine Review Vol.5, No.5, 2000; P-463-466.
Altern Med Rev 1999 Apr;4(2):96-103
Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide.
Kelly GS
Larch arabinogalactan is composed of greater than 98-percent arabinogalactan, a highly branched polysaccharide consisting of a galactan backbone with side-chains of galactose and arabinose sugars. Larch arabinogalactan is an excellent source of dietary fiber, and has been approved as such by the FDA. It has been shown to increase the production of short-chain fatty acids, principally butyrate and propionate, and has been shown to decrease the generation and absorption of ammonia. Evidence also indicates human consumption of larch arabinogalactan has a significant effect on enhancing beneficial gut microflora, specifically increasing anaerobes such as Bifidobacteria and Lactobacillus. Larch arabinogalactan has several interesting properties which appear to make it an ideal adjunctive supplement to consider in cancer protocols. Experimental studies have indicated larch arabinogalactan can stimulate natural killer (NK) cell cytotoxicity, enhance other functional aspects of the immune system, and inhibit the metastasis of tumor cells to the liver. The immune-enhancing properties also suggest an array of clinical uses, both in preventive medicine, due to its ability to build a more responsive immune system, and in clinical medicine, as a therapeutic agent in conditions associated with lowered immune function, decreased NK activity, or chronic viral infection.
Townsend Letter for Doctors and Patients 1996 July; 156:42-46
Larch Arabinogalactan is Novel Immune Modulator
D’Adamo P
Abstract
This paper discusses some of the applications and characteristics of naturally occurring arabinogalactans, with a special emphasis on those arabinogalactans derived from Western Larch. The unusual immunological properties of larch arabinogalactan (wood gum, wood sugar, larch gum, “Stractan,” “Ara-6”) suggest it may be used in numerous, exciting future applications. Evidence of this can be seen in the medicinal chemical, pharmaceutical, and bio-technical fields where current research and development has resulted in the creation of arabinogalactan-based products with unique characteristics. Larch arabinogalactan possesses minimal toxicity and is approved for food use.
Physical Character000)cs
Arabinogalactans are a class of long, densely branched high-molecular polysaccharides MW: 10,000-120,000. In nature, arabinogalactans are found in several microbial systems, especially acid-fast Mycobacteria where it is complexed between peptidoglycans and mycolic acids as a component of the cell wall and influences monocyte-macrophage immunoreactivity of Tubercular antigen. Many edible and inedible plants are rich sources of arabinogalactans, mostly in glycoprotein form, bound to a protein spine of threonine, proline or serine (“arabinogalactan protein”). These include leek seeds, carrots, radish, black gram beans, pear, maize, wheat, red wine, Italian ryegrass, tomatoes, ragweed, sorghum and bamboo grass, coconut meat and milk. Several of the major naturopathic immune “enhancer” herbs contain significant amounts of arabinogalactans, such as Echinacea purpurea, Baptisia tinctoria, Thuja occidentalis, Angelica acutiloba and Curcuma longa.
The major commercial source of arabinogalactan is the Larch tree. Two sources are Western Larch (Larix occidentalis) and Mongolian Larch (Larix dahurica). Most commercial arabinogalactan is produced from Western Larch, a renewable resource, through a countercurrent extraction process. The resultant liquor is refined into a light cream-colored powder having an indefinite shelf life. High-grade larch arabinogalactan is composed of greater than 98% arabinogalactan. Arabinogalactan gum is 100% water-soluble and produces low viscosity solutions. As produced, larch arabinogalactan is a dry, free-flowing powder, with a very slight pine-like odor and sweetish taste. As compared with other natural polysaccharides, the unique properties of larch arabinogalactan are: ease of solution complete solubility; good body properties without viscosity buildup; excellent dispersant and surfactant properties; and stability over a wide range of concentrations, pH and temperature.
Chemical Nature
Larch arabinogalactan is composed of galactose and arabinose units in a 6:1 ratio, with a trace of uronic acid. The molecular weights of the major fractions of arabinogalactan in larch are 16,000 and 100,000.
Effect on Immunologic Systems
Natural Killer cell (NK) and Macrophage activation. The receptor specificity of arabinogalactan is not well characterized. Cultures of human peripheral blood mononuclear cells as well as cultures of preseparated peripheral non-adherent cells and monocytes showed enhancement of natural killer cytotoxicity against K562 tumor cells when pretreated with larch arabinogalactan for 48-72 h. Moreover, preseparated peripheral non-adherent cells and monocytes of individual donors could exhibit various responses to arabinogalactan when cultures derived from bleedings after intervals of several months were assayed. Arabinogalactan-mediated enhancement of NK cytotoxicity was not initiated directly but was found to be governed by the cytokine network. Generally, larch arabinogalactan pretreatment induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta) and IL-6 but only IFN gamma was involved in enhancement of NK cytotoxicity.
A similar response has been noted for arabinogalactans, isolated from Echinacea purpurea. This polysaccharide induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), and interferon-beta.
Acidic arabinogalactan, a highly purified polysaccharide from plant cell cultures of Echinacea purpurea, with a molecular weight of 75,000, was effective in activating macrophages to cytotoxicity against tumor cells and microorganisms (Leishmania enriettii). This arabinogalactan did not activate B cells and did not induce T cells to produce interleukin-2, interferon-betaValeC or interferon-gamma, but it did induce a slight increase in T-cell proliferation. When injected intraperitoneally, arabinogalactan stimulated macrophages.
Antiviral effects
Arabinogalactans enhance the effectiveness of viral nucleotide analogs. Daily injections of a conjugate consisting of adenine arabinoside 5-monophosphate (araAMP, vidarabine monophosphate) and arabinogalactan (7.9 residues araAMP per molecule arabinogalactan), at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/ kg, 14 days) produced a slight drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP alone, WHV DNA rapidly returned to original levels.
Effects in Metastatic Disease
Blocking of organ-specific experimental metastasis:
Metastatic disease most commonly spreads to the liver, in preference to other organ sites. This has been theorized to be the result of a reaction between the galactose-based glycocongates on the metastatic cells and a hepatic-specific lectin (e.g., the D-galactose-specific hepatic binding protein) found in liver parenchyma. Several studies have compellingly shown that arabinogalactan inhibits this reaction, thus acting as a reverse lectin.” NOTE: LECTINS are certain types of proteins that bind to specific sugar molecules on cancer cells.
In one study, the effects of arabinogalactan were investigated in a syngeneic tumor-host system using a new tumor which primarily colonizes the liver upon intravenous injection. The study included systemic treatment with D-galactose and arabinogalactan as well as cell pretreatment with arabinogalactan and two other glycoconjugates. Treatment with arabinogalactan reduced the amount of liver metastases and prolonged the survival times of the animals in both studies. Host treatment was more effective than tumor cell pretreatment. This was shown to be an effect of arabinogalactan blockade of potential liver receptors by covering of galactosespecific binding sites. This was also verified in a repeat study.
In a third study, the rapid clearance and uptake by the liver of tritiated alpha 1-acid (asialo) glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of D-galactose or arabinogalactan. The preinjection (1 h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents D-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented.
Arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/ c mice and greatly reduced the colonization process of highly metastatic Esb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems.
Safety and Toxicity
Preliminary acute toxicity tests performed on albino rats have indicated that larch arabinogalactan is significantly less toxic than methylcellulose. Other studies have shown that laboratory diets comprising of up to 50% larch arabinogalactan had no apparent ill effects on animal subjects after 6 months.
Discussion
It is possible that the multiplicity of biologic actions in those medicinaatieants known to contain polysaccharides result from a series of “ranges” in which certain size polysaccharides produce either immune augmentation or inhibition.
In general, it may be said that “low” molecular weight polysaccharides (5,00015,000) tend to produce more of an anti-inflammatory, anti-complementary, antiallergy effect; whereas “high” molecular weight polysaccharides (75,000-125,000) produce more reticuloendothelial stimulation and monocyte-enhanced natural killer cytotoxicity. The “mid” weight polysaccharides (15,000-50,000) seem to act in an altogether different way, enhancing carbon and other types of toxin clearance by macrophages. The molecular weights of the major fractions of larch arabinogalactan are 16,000 (low/ mid) and .100,000 (high) which perhaps explain its peculiarly diverse actions.
Use in conjunction with other agents
In general, oxidative agents inhibit the activity of most polysaccharides whilst reduction can notably enhance them,” typically by “reducing” side chains into more antigenic forms. Thus, concurrent administration of arabinogalactans with antioxidants such as ascorbate may enhance their efficacy. The use of halide donors, such as potassium iodide, in conjunction with arabinogalactan and ascorbate can produce quite prodigious increases in cellular myeloperoxidase activity, as measured by a candicidal index. Myeloperoxidase, levels are typically depressed in chronic candidasis and increased in breast cancer.
The reticuloendothelial-activating effects of arabinogalactan would certainly dovetail well in such a therapeutic scenario. Larch arabinogalactan has been studied for use in experimental models of metastatic disease spread to the liver, including its use in conjunction with modified citrus pectin. Both polysaccharides work in essentially the same way, that is, by inhibiting the attachment of metastatic cells to liver parenchyma by competitive binding to a liver lectin, the hepatic galactose receptor.
Use in pediatric otitis media
Prophylactic use of larch arabinogalactan can decrease the frequency and severity of pediatric otitis media, especially in circumstances where the predominant organisms are gram negative rods. This may be the result of phagocytosis enhancement, improvement in opsonization, competitive binding of bacterial fimbrae, or all three.
Use in HIV
Although shown to produce only slight increases in CD4 cells, treatment of HIV disease with larch arabinogalactan can result in significant improvement in susceptibility of HIV-related opportunistic infections. This may result from activation or enhancement of macrophage/monocyte/NK cell activity, typically the role of CD4 cells.
Use as a delivery adjunct
Because of its effects on vascularity and rate of hepatic uptake, concurrent administration of larch arabinogalactan with other therapeutic agents can be considered rational. This may apply to anti-hepatitis agents in addition to hepatoprotective drugs. The immunoaugmentive effects, antiradiation effects and drug facilitative effects of larch arabinogalactan indicate promise as a concurrent therapy in patients undergoing conventional cancer treatment.
Use as a fiber supplement
Because of its ability to increase colonic butyrate and decrease colonic ammonia concentrations, arabinogalactan may be THE preferable form of fiber therapy, as the major commercial source, methylcellulose, does not do this to any significant degree (in addition to having a lower LD50!)