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Larch

Scientific Name(s): Larix dahurica L., Larix decidua Mill., Larix eurolepis Gord., Larix europaea., Larix gmelinii., Larix kaempferi., Larix laricina Koch., Larix leptolepis (Sieb. et Zucc.) Gord., Larix occidentalis Nutt., Larix sibirica ledeb.
Common Name(s): Larch, Larch gum, Larix, Mongolian Larchwood (L. dahurica)

Clinical Overview

Use

Arabinogalactan, which is present in some larch species, has been reported to stimulate the immune system and boost antibody response to vaccines. It may be useful in treating upper respiratory infections and dyslipidemia. However, very limited clinical trials, primarily conducted in healthy individuals, support these uses. Larch arabinogalactan is approved by the US Food and Drug Administration (FDA) as a source of dietary fiber and for use in food products.

Dosing

The typical adult dose is 1 to 3 tablespoons/day of larch arabinogalactan powder in divided doses. In children, the typical dose is 1 to 3 teaspoons/day of the powder in divided doses. The powder can be mixed with water or juice, or added to food. Arabinogalactan extract (ResistAid) 1.5 to 4.5 g/day for 60 to 72 days, beginning 30 days prior to vaccine administration, has also been used.

Contraindications

Larch should not be used in patients with autoimmune disorders such as systemic lupus erythematous, Crohn disease, or rheumatoid arthritis due to its stimulating effects on the immune system. Larch is not recommended in patients with tuberculosis because arabinogalactans are structural components of cell walls of mycobacterium.

Pregnancy/Lactation

Avoid use. Clinical information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Because of its immunostimulating effects, larch should not be used with immunosuppressant drugs.

Adverse Reactions

Most individuals do not experience adverse reactions with larch. However, because larch is a source of dietary fiber, bloating, flatulence, and other mild GI adverse effects may occur.

Toxicology

Larch arabinogalactan is generally recognized as safe (GRAS) and is approved by the FDA as a source of dietary fiber and for use in food products.

Botany

Larch trees are deciduous conifers that lose their needles in the fall. One species, L. decidua, grows up to 50 m in height and has needle-like leaves and small, light-brown cones.1 It is indigenous to the Pacific Northwest United States and British Columbia.2 The Dahurian larch tree (L. gmelinii/L. dahurica) is found in central Siberia and as far east as Kamchatka, Russia.3, 4 Siberian larch (L. sibirica) is also found in Siberia. European larch (L. decidua) is cultivated in central Europe. Japanese larch (L. leptolepis/L. kaempferi) is found in Japan. Eastern larch (L. laricina) and Western larch (L. occidentalis) grow in North America.4

History

Larch trees were reportedly introduced in Great Britain in 1639 and have been cultivated there since the early 19th century. The tree is grown mainly for its timber, but the inner bark and resin are also used.1 Arabinogalactan constituents from certain Larix spp. have gained popularity because of their ability to enhance the immune system.5 Dietary sources of arabinogalactans include carrots, tomatoes, pears, radishes, and red wine.4, 6

Chemistry

Arabinogalactans are present in the species L. dahurica and L. occidentalis.7, 8, 9 Arabinogalactans belong to a group of carbohydrates known as hemicelluloses, which are long, densely-branched polysaccharides of varying weights widely found throughout the plant kingdom and in some microbial systems, especially acid-fast mycobacterium.4, 10 Anti-inflammatory, anti-allergenic, and anticomplement effects are generally associated with lower-weight polysaccharides. Higher-weight polysaccharides simulate natural killer cell cytotoxicity.2 Arabinogalactans are abundant in the genus Larix and are most often covalently linked to pectin and protein.5, 7 For example, the powdered extract from the pine bark of the western larch tree (L. occidentalis) is 98% arabinogalactan. The extract has a pine odor, a sweet taste, and is nonviscous and easily soluble in water.5 It also possesses stability over various concentrations, pH levels, and temperatures.10 Western larch arabinogalactan is made of galactose and arabinose molecules in a 6:1 ratio.2, 4, 10 All arabinogalactans isolated thus far from Larix are of the 3,6-beta-D-galactan type.7 The extract is harvested from already fallen trees, or from waste larch product from the lumber industry. A benefit of this natural polymer is that it possesses great uniformity. Batch variation is not a problem among larch trees, as it is with other natural products.5 According to one report, arabinogalactans from L. occidentalis have been isolated, characterized, and purified.9 The properties of arabinogalactans from L. dahurica have also been documented, and were found to comprise a homogeneous product with very narrow molecular weight distribution.7

Other constituents from Larix have been identified. Larix flavonoids from various species have been analyzed, including flavanones (naringenin, hesperitin, hesperidin), flavones (apigenin, vitexin), and flavonols (kaempferols, quercetins, isorhamnetins, myricetins, syringetins).11 L. decidua contains lignans, resins, and volatile oil (mainly alpha- and beta-pinene and limonene).1 18-nor-abietatrienes and diterpenes, including abietane-type diterpenes (eg, 7alpha,15-dihydroxyabieta-8,11,13-trien-18-al), have been isolated from the species L. kaempferi.12, 13 Phenolics (flavonoids) from L. leptolepis have been reported.14 The resin constituent diterpene has been documented in L. europaea.15

Uses and Pharmacology

Stimulation of immune system/Upper respiratory infections

Arabinogalactans are often used for their immunostimulating effects; they stimulate phagocytosis to enhance the immune response.16 Arabinogalactans have been reported to increase the release of interferons, tumor necrosis factors (TNFs), and interleukins, all of which are known to enhance immune function. It has been suggested that larch arabinogalactan acts indirectly through microbiota-dependent mechanisms (eg, production of short-chain fatty acids) that impact the immune response and/or acts directly after passage to the immune cells through the intestinal barrier.4 Arabinogalactans have also been studied as a means to boost antibody response to vaccines. Results from clinical studies suggest that arabinogalactan may exert its immunostimulant effects by reducing infections and enhancing antibody response to immunizations.

Animal and in vitro data

Liver metastases in animals have been inhibited by arabinogalactans.5 When pretreated with arabinogalactans extracted from L. occidentalis, human peripheral blood mononuclear cells and other cell lines have shown enhancement of natural killer cytotoxicity against certain tumor cells.17

Clinical data

In a randomized, double-blind, placebo-controlled trial of 48 healthy females, the combination of larch arabinogalactan (1.5 g/day) with Echinacea purpurea (464 mg/day) and Echinacea angustifolia (36 mg/day) for 4 weeks resulted in an 18% increase in complement properdin, as well as improved overall physical and emotional health as measured by Short-Form 36 Health Survey. A reduction in TNF-alpha levels was noted in this treatment group as well as in the larch arabinogalactan only group. GI function, sleep, mood, and emotional health item scores (measured using the Symptoms Specific Assessment tool) decreased, indicating an improvement in the larch arabinogalactan plus E. purpurea plus E. angustifolia group.18

In another study, 199 healthy volunteers who had experienced at least 3 common colds within a 6-month period were randomized to receive arabinogalactan 4.5 g or placebo for 12 weeks. Treatment with arabinogalactan reduced the mean number of common cold occurrences (0.83; confidence interval [CI], 0.67 to 0.99) compared with placebo (1.06; CI, 0.89 to 1.23; P=0.055). The intensity and duration of symptoms were not significantly different between the 2 groups. However, the percentage of days without cold symptoms was higher in the treatment group (91.2%) compared with placebo (88.5%; P<0.001).19

In a randomized, double-blind, placebo-controlled, parallel-group study evaluating antibody response to the pneumococcal vaccine in 45 healthy volunteers, arabinogalactan 4.5 g/day (provided as the proprietary product ResistAid) or placebo was given for 72 days. After 30 days of administration, the participants were given the 23-valent pneumococcal vaccination. Patients receiving arabinogalactan had significantly higher immunoglobulin G (IgG) antibody response in the 18C and 23F subtypes compared with placebo at day 51 (P=0.006 and P=0.002, respectively) as well as at day 72 (P=0.008 and P=0.042, respectively). No differences in total white blood cell count, cytokines, or complement levels occurred between the 2 groups.20 In a similar study, the effects of ResistAid on antibody response to tetanus and influenza vaccines were evaluated. Seventy-five healthy volunteers were randomized to receive ResistAid 1.5 g or 4.5 g daily, or placebo daily for 60 days, with administration of the tetanus and influenza immunizations on day 30. At the end of the treatment period, there was a significantly higher tetanus IgG level in patients receiving ResistAid 1.5 g/day compared with placebo (P=0.008); however, no other significant differences in tetanus or influenza antibody response were noted between any of the groups at any other time point.21

GI effects

Arabinogalactan is a source of dietary fiber and is found in foods such as carrots, tomatoes, pears, radishes, and red wine. It resists hydrolysis by enzymes in the gut and is slowly fermented by microflora in the large bowel.4, 6

Animal data

A study conducted in ileally cannulated dogs assessed the fecal concentrations of microbes following administration of arabinogalactan. Dogs that received a low dose (ie, 0.55 g/day) and those who received a high dose (ie, 1.65 g/day) of arabinogalactan had higher concentrations of fecal Lactobacillus compared with control (P=0.04). However, total anaerobic fecal bacterial concentrations were not impacted. Fecal scores were increased in dogs supplemented with low-dose arabinogalactan compared with control, meaning there was more fecal moisture; however, diarrhea was not noted in the treatment group.22

Clinical data

In a small crossover study of healthy volunteers, supplementation of arabinogalactan 15 g and 30 g per day for a total of 6 weeks increased levels of anaerobes and Lactobacillus spp.6

Dyslipidemia

Because larch is a source of dietary fiber, it theoretically may be useful in improving lipid levels.

Animal and in vitro data

No animal or in vitro data exist regarding the effects of larch or arabinogalactan on lipid levels.

Clinical data

In a small crossover study of healthy volunteers, supplementation of arabinogalactan 15 g and 30 g per day for 6 weeks had no impact on lipid levels.6 In another study of healthy volunteers, administration of larch arabinogalactan 8.4 g/day for 6 months was not associated with reductions in lipid levels from baseline. No clinically significant reduction was noted after 2 months of administration.23

Dosage delivery

As both a natural and functional food ingredient, arabinogalactan exhibits moisture retention, flavor encapsulation, film-forming capabilities, and desirable viscosities for a pleasant feeling in the mouth.5 Larch arabinogalactan has GRAS status and is permitted to be used as a stabilizer, binder, and emulsifier, among other uses.24 Additionally, complexes containing arabinogalactan have been used as a method of drug delivery.

Animal and in vitro data

Arabinogalactan has properties that make it an ideal carrier to deliver agents to hepatocytes via the asialoglycoprotein receptors. Of radiolabeled arabinogalactans, 52.5% (4 mg/kg) were identified in the livers of rats receiving an intravenous (IV) injection.8 Arabinogalactan was highly bound to this receptor in both in vitro and in vivo experimentation. One study reported that arabinogalactans with a lower molecular weight may be more desirable than others for hepatic drug delivery.9 In another study, arabinogalactan conjugated with the antiviral vidarabine was effective in suppressing serum viral DNA titers in woodchucks infected with the hepatitis virus.25 The complexation of ibuprofen with arabinogalactan in animal models increased the bioavailability of ibuprofen, thereby reducing the required effective dose and ultimately the potential for adverse effects.26 In sheep with various parasitic infections, a complex of arabinogalactan and albendazole demonstrated anthelmintic activity at 10-fold lower doses than did albendazole alone. In addition, the complex demonstrated less acute toxicity and hepatotoxicity.27 Conjugation of amphotericin B to arabinogalactan has also been studied.28

Clinical data

No clinical data exist regarding dosage delivery using arabinogalactans.

Other uses

In a study of plant remedies used for gout, L. laricina inhibited xanthine oxidase, thereby reducing uric acid formation. This was the greatest inhibition observed among the evaluated 26 species from 18 families.29

Dihydroquercitin from L. sibirica was noted to inhibit coxsackievirus B4.30

In a study of rabbits, an arabinogalactan formulation improved dry eyes. The 5% w/w formulation of arabinogalactan protected against the appearance of corneal dry spots. Additionally, the formulation reduced the healing time of corneal lesions at 27, 29, 31, 34, and 41 hours after the initial treatment.31

Dosing

Larch arabinogalactan powder is typically dosed in teaspoons or tablespoons at a concentration of approximately 4 to 5 g per tablespoon. The typical adult dose is 1 to 3 tablespoons of powder per day in divided doses. In children, the typical dose is 1 to 3 teaspoons of powder per day in divided doses. The powder can be mixed with water or juice, or added to food.2 Arabinogalactan extract (ResistAid) 1.5 to 4.5 g/day for 60 to 72 days, beginning 30 days prior to vaccine administration, has also been used.20, 21

Pregnancy / Lactation

Avoid use. In a murine model, Lavitol, an extract containing dihydroquercetin from the Dahurian larch tree, did not increase spontaneous abortions, cause skeletal abnormalities, or negatively impact postnatal development at doses of 75 and 1,500 mg/kg.3 However, clinical information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Because of its immunostimulating effects, larch should not be used with immunosuppressant drugs.

Adverse Reactions

Most individuals do not experience adverse reactions with larch. However, because larch is a source of dietary fiber, bloating, flatulence, and other mild GI adverse effects may occur.2

Toxicology

Larch arabinogalactan has GRAS status and is FDA approved as a dietary source of fiber and for use in food products.2 Arabinogalactan produced no adverse reactions when administered as single IV doses of 5,000 mg/kg in mice, or as repeat doses of 500 mg/kg/day for 90 days in rats.8 Lavitol did not cause DNA damage in bone marrow, liver, or peripheral blood cells at a single dose of 2,000 mg/kg or at repeat doses of 15 mg/kg. In another animal study, single doses of Lavitol 10,000 and 15,000 mg/kg were not lethal.3

References

1. Chevallier A. Larch. Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 1996:224.
2. Larch arabinogalactan. Altern Med Rev. 2000;5(5):463-466.11056416
3. Schauss AG, Tselyico SS, Kuznetsova VA, Yegorova I. Toxicological and genotoxicity assessment of a dihydroquercetin-rich Dahurian larch tree (Larix gmelinii Rupr) extract (Lavitol). Int J Toxicol. 2015;34(2):162-181.25850419
4. Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials. Nutr Metab (Lond). 2016;13:28.27073407
5. Benedikt H. Arabinogalactans: new immune boosting fiber. Natural Pharmacy. 1999;3:12.
6. 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(4):279-285.11506055
7. Odonmazig P, Ebringerová A, Machová E, Alföldi J. Structural and molecular properties of the arabinogalactan isolated from Mongolian larchwood (Larix dahurica L.). Carbohydr Res. 1994;252:317-324.8137369
8. Groman EV, Enriquez PM, Jung C, Josephson L. Arabinogalactan for hepatic drug delivery. Bioconjug Chem. 1994;5(6):547-556.7533005
9. Prescott JH, Enriquez P, Jung C, Menz E, Groman EV. Larch arabinogalactan for hepatic drug delivery: isolation and characterization of a 9 kDa arabinogalactan fragment. Carbohydr Res. 1995;278(1):113-128.8536264
10. D'Adamo PJ. Larch arabinogalactan is a novel immune modulator. J Naturopath Med. 1996;4:32-39.
11. Niemann GJ, Koerselman-Kooy JW. Phenolics from Larix needles. XΙΙΙ. Analysis of main Larix flavonoids by high-pressure liquid chromatography. Planta Med. 1977;31(3):297-301.866496
12. Ohtsu H, Tanaka R, Matsunaga S. 18-nor-Abietatrienes from the cones of Larix kaempferi. J Nat Prod. 1998;61(3):406-408.9548885
13. Ohtsu H, Tanaka R, Matsunaga S. Abietane diterpenoids from the cones of Larix kaempferi. J Nat Prod. 1998;61(10):1307-1309.9784178
14. Niemann GJ. Phenolics from Larix needles. 8. Flavonoids of L. leptolepis. Planta Med. 1974;26(2):101-103.4415046
15. Bruns K. Diterpene. VΙ. Neutral constituent of the resin from Larix europaea D.C. (Pinaceae). Tetrahedron. 1969;25(8):1771-1775.5796570
16. Roxas M, Jurenka J. Colds and influenza: A review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev. 2007;12(1):25-48.17397266
17. Hauer J, Anderer FA. Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from Larix occidentalis. Cancer Immunol Immunother. 1993;36(4):237-244.8439987
18. Kim LS, Waters RF, Burkholder PM. Immunological activity of larch arabinogalactan and Echinacea: a preliminary, randomized, double-blind, placebo-controlled trial. Altern Med Rev. 2002;7(2):138-149.11991793
19. Riede L, Grube B, Gruenwald J. Larch arabinogalactan effects on reducing incidence of upper respiratory infections. Curr Med Res Opin. 2013;29(3):251-258.23339578
20. Udani JK, Singh BB, Barrett ML, Singh VJ. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers. Nutr J. 2010;9:32.20796315
21. Udani JK. Immunomodulatory effects of ResistAid: a randomized, double-blind, placebo-controlled, multidose study. J Am Coll Nutr. 2013;32(5):331-338.24219376
22. Grieshop CM, Flickinger EA, Fahey GC Jr. Oral administration of arabinogalactan affects immune status and fecal microbial populations in dogs. J Nutr. 2002;132(3):478-482.11880574
23. Marett R, Slavin JL. No long-term benefits of supplementation with arabinogalactan on serum lipids and glucose. J Am Diet Assoc. 2004;104(4):636-639.15054349
24. Rulis AM. Agency Response Letter GRAS Notice No. GRN 000084. Food and Drug Administration website. http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm154598.htm. Published February 19, 2002. Accessed July 19, 2016.
25. Enriquez PM, Jung C, Josephson L, Tennant BC. Conjugation of adenine arabinoside 5′-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity. Bioconjug Chem. 1995;6(2):195-202.7541249
26. Khvostov MV, Borisov SA, Tolstikova TG, et al. Supramolecular complex of ibuprofen with larch polysaccharide arabinogalactan: studies on bioavailability and pharmacokinetics [published online ahead of print June 28, 2016]. Eur J Drug Metab Pharmacokinet. 2016.27351190
27. Chistyachenko YS, Meteleva ES, Pakharukova MY, et al. A physicochemical and pharmacological study of the newly synthesized complex of albendazole and the polysaccharide arabinogalactan from larch wood. Curr Drug Deliv. 2015;12(5):477-490.25981412
28. Elgart A, Farber S, Domb AJ, Polacheck I, Hoffman A. Polysaccharide pharmacokinetics: amphotericin B arabinogalactan conjugate – a drug delivery system or a new pharmaceutical entity? Biomacromolecules. 2010;11(8):1972-1977.20690709
29. Owen PL, Johns T. Xanthine oxidase inhibitory activity of northeastern North American plant remedies used for gout. J Ethnopharmacol. 1999;64(2):149-160.10197750
30. Galochkina AV, Anikin VB, Babkin VA, Ostrouhova LA, Zarubaev VV. Virus-inhibiting activity of dihydroquercitin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis. Arch Virol. 2016;161(4):929-938.26780775
31. Burgalassi S, Nicosia N, Monti D, Falcone G, Boldrini E, Chetoni P. Larch arabinogalactan for dry eye protection and treatment of corneal lesions: investigations in rabbits. J Ocul Pharmacol Ther. 2007;23(6):541-550.18001233

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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