Larch Larix occidentalis and Arabinogalactan:Anti-Metastatic and Immune Stimulant natural source.

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Toxicity of Arabinogalactan.

Western Larch Extract D-Arabinogalacatan Arabinogalactan Extract CAS 9036-66-2 Larix occidentalis Nutt L-arabinofuranose unit or 3-O-(beta-L-arabinopyranosyl)-alfa-L-arabinofuranosyl units photo picture image Neither arabinogalactan nor any of its colonic fermentation breakdown products are known to exert any toxicity either systemically or in the gastrointestinal tract following oral dosing. Toxicity of purified arabinogalactan was investigated in rodents,but only after single and repeat IV dosing(50 mg/ml in 0.9% saline).No overt signs of toxicity were seen,and no evidence of hepatic damage or alteration,in particular,abnormal vacuolisation in either the mouse or rat livers was found.

 No dedicated investigations of arabinogalactan toxicity after oral administration were found,except for limited findings in dogs,as summarised below.

 Three different forms of arabinogalactan given at 0.55 or 1.55 g/day for 10 days did not affect serum immunoglobulin G,M or A concentrations in dogs.Relatively minor increases (~10%) white blood cell (neutrophil and eosinophil) concentrations were noted,but the significance of this effect is unclear.furthermore,arabinogalactan supplementation did not affect feed intake,wet faecal weight or faecal dry matter in dogs.Increased faecal weight is a common outcome of dietary fibre supplementation and some faecal parameters,particularly moisture and levels of arabinose and galactose,were affected in dogs supplemented with the LD and HD of arabinogalactan. The likely outcome of the ingestion of arabinogalactan for prolonged periods as typically utilised in chronic toxicity studies is now known and any colonic carcinogenic potential or other long term effects in animals have not therefore been determined.Also,there were no arabinogalactan-specific data on genotoxic and reproductive,and developmental toxicity of arabinogalactan.Similarly,there was no data on the capacity of arabinogalactan to induce colonic or small intestinal cell proliferation as a prelude to carcinoma.While some experimental studies show reduced carcinogenesis with high fibre diets,an equivalent number show increased carcinogenesis,leading as it does to the somewhat contentious suggestion that caution is required in adding fermentable fibre supplements to foods.There is mixed opinion on the significance of finding obtained in vitro or with animal models for humans.

 Clinical Data

 Arabinogalactan at 15 or 30 g/day for 6 weeks in human volunteers with a 3 week crossover period,significantly increased the total anaerobes,but did not alter the numbers of lactobacillus spp.,Bifidobacterium spp.,Enterobacteriaceae or Clostridium spp after 3 weeks.At 6 weeks,there was a significant increase in total anaerobes and Lactobacillus spp.,The SCFAs load and SCFA ratios, faecal pH,mean faecal weight,transit time and frequency did not change after arabinogalactan administration at either dose.In contrast,the mean faecal ammonia levels decreased significantly.The occurrence of bloating and flatulence was significantly higher,but at the HD only.However,no discomfort or any other adverse reaction was noted among the subject at either dose level.

 Arabinogalactan given at 15 or 30 g/day for 3 weeks in human volunteers had no effect on blood lipids.However,rather surprisingly,the mean blood level of glucose increased significantly (~10%) after three weeks of supplementation at the HD only,although a similar trend was seen at the LD.The mean increase in insulin blood level after three weeks at the HD was not reported as statistically significant,but the insulin level was elevated almost 2 fold compared with the baseline value.The mechanism of the hyperglycaemic and hyperinsulinemic action of arabinogalactan has not been clarified,but authors suggested that it may be related to the metabolic conversion of propionic acid into glucose in the liver.Although this metabolic pathway is a possible contributor to blood glucose,it is metabolically virtually implausible that a relatively small increase in a daily dietary load of arabinogalactan(from 15 to 30 g) could produce a relatively large increase in gluconeogenesis and induce marked hyperinsulinemia.Propionate is clearly one of a number of SCFA derived from cell-wall polysaccharides,including arabinogalactan,in the human gut.Although results presented show that fecal propionate load did not differ significantly between the baseline and the two levels of supplementation,the total amount of propionate produced in the gut was not determined,and it is unclear how much propionate could be generated in the human gut from 30 g of arabinogalactan,but that amount is unlikely to be greater than few grams.And as mentioned above,there is likely to be a marked variations in dietary load of cell-wall polysaccharides,including arabinogalactan,depending on dietary preferences,and the net contribution of arabinogalactan to the overall load of propionate absorbed by the liver may not be significant.Therefore,it is possible that this apparent,possibly clinically serious,adverse effect may be an unexplained artefact,which must be verified in the independent clinical investigation,before it can be accepted as a valid safety concern.It is also possible that these changes were due to another factor,such as the reported reduction(~20%) in dietary fat intake.

 Arabinogalactan given at 8.4 g/day for 6 months in 54 healthy human volunteers produced no significant alterations in serum cholesterol, high-density lipoprotein cholesterol,triglycerides,apolipoprotein B,apolipoprotein A-I,glucose and insulin.

 Conclusion

 arabinogalactan has no history of therapeutic use,although it has been used apparently extensively as a food additive particularly in the USA.

 Regrettably,no dietary exposure data are available for arabinogalactan,even though it is likely to be present in the human diet at relatively high levels,as part of traditional daily food intake.arabinogalactan is also likely to be present in many processed food items such as sports/nutritional beverages and bars,as well as in baked confectionary because of its unique physical characteristics.

 There is a virtual absence of toxicological information on oral use of arabinogalactan as a therapeutic agent or food supplement,although limited pre-clinical and clinical data suggest no apparent safety concerns.This view is reinforced by the fact that arabinogalactan is virtually not absorbable from the human GIT,and its only metabolic contribution in the human body is in the form of SCFAs,to which it is converted by a redident bacterial flora in the human colon.The metabolic fate of SCFAs is well understood and there are unlikely to be any adverse consequences from the relatively small increase in one type of dietary cellwall polysaccharide,considering possible marked differences afforded by dietary preferences.

 Interestingly,there is still an intense scientific debate whether or not increasing the dietary load of fermentable fibre is likely to protect against or promote intestinal neoplasia.Nevertheless,there is no evidence to suggest that the use of arabinogalactan at doses generally specified for medicinal purposes(1.5 g/day) or as a dietary supplement (4.5g/day),presents any safety concerns.However,because daily supplementation with arabinogalactan at 30 g for a period of 3 weeks was apparently shown to induce hyperglycaemia and hypernsulinemia,the upper therapeutic daily intake level may need to be considered to assure its safety-in-use,until this finding is reviewed by further investigations.

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Reference:

citations1.Larch Larix occidentalis and Arabinogalactan:Anti-Metastatic and Immune Stimulant natural source.
citations2.Arabinogalactan evaluation report.

last edit date:20th,June.2009.