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)

Medically reviewed by Drugs.com. Last updated on Dec 19, 2022.

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. 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 the cell walls of mycobacterium.

Pregnancy/Lactation

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

Interactions

Because of its immunostimulant 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.

Scientific Family

• Pinaceae

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.(Chevallier 1996) It is indigenous to the Pacific Northwest United States and British Columbia.(Larch 2000) The Dahurian larch tree (L. gmelinii/L. dahurica) is found in central Siberia and as far east as Kamchatka, Russia.(Dion 2016, Schauss 2015) 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) both grow in North America.(Dion 2016)

History

Larch trees were reportedly introduced to 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.(Chevallier 1996) Arabinogalactan constituents from certain Larix spp. have gained popularity because of their ability to enhance the immune system.(Benedikt 1999) Other dietary sources of arabinogalactans include carrots, tomatoes, pears, radishes, and red wine.(Dion 2016, Robinson 2001)

Chemistry

Arabinogalactans are present in the species L. dahurica and L. occidentalis.(Groman 1994, Odonmazig 1994, Prescott 1995) Arabinogalactans belong to a group of carbohydrates known as hemicelluloses, which are long, densely-branched polysaccharides of varying weights. They are widely found throughout the plant kingdom and in some microbial systems, especially acid-fast mycobacterium.(Dion 2016, D'Adamo 1996) Anti-inflammatory, anti-allergenic, and anticomplement effects are generally associated with lower-weight polysaccharides. Higher-weight polysaccharides generally simulate natural killer cell cytotoxicity.(Larch 2000) Arabinogalactans are abundant in the genus Larix and are most often covalently linked to pectin and protein.(Benedikt 1999, Odonmazig 1994) 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 it is non-viscous and easily soluble in water.(Benedikt 1999) It also possesses stability over various concentrations, pH levels, and temperatures.(D'Adamo 1996) Western larch arabinogalactan is made of galactose and arabinose molecules in a 6:1 ratio.(D'Adamo 1996, Dion 2016, Larch 2000) All arabinogalactans isolated thus far from Larix are of the 3,6-beta-D-galactan type.(Odonmazig 1994) 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.(Benedikt 1999) According to one report, arabinogalactans from L. occidentalis have been isolated, characterized, and purified.(Prescott 1995) The properties of arabinogalactans from L. dahurica have also been well documented, and were found to comprise a homogeneous product with a very narrow molecular weight distribution.(Odonmazig 1994)

Other constituents from Larix species have also 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).(Niemann 1977) L. decidua contains lignans, resins, and volatile oil (mainly alpha- and beta-pinene and limonene).(Chevallier 1996) More recently, flavonoids, spiro-polyphenols, and procyanidins have also been identified in L. decidua.(Baldan 2017) 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.(Ohtsu 1998, Ohtsu 1998) Phenolics (flavonoids) from L. leptolepis have been reported.(Niemann 1974) The resin constituent diterpene has been documented in L. europaea.(Bruns 1969)

Uses and Pharmacology

Stimulation of the immune system (upper respiratory tract infections)

Arabinogalactans are often used for their immunostimulating effects; they stimulate phagocytosis to enhance the immune response.(Roxas 2007) 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.(Dion 2016) 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.(Benedikt 1999) When pretreated with arabinogalactans extracted from L. occidentalis, mononuclear cells from human peripheral blood as well as other cell lines have shown enhancement of natural killer cytotoxicity against certain tumor cells.(Hauer 1993) The construction of arabinogalactans/selenium nanoparticle composites for the enhancement of the antitumor activity is also being successfully explored.(Tang 2019)

Clinical data

In one study, 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 (N=199). 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 the 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 the placebo group (88.5%; P<0.001).(Riede 2013)

Based on data from 4,521 healthy participants enrolled in 20 randomized controlled trials (including 1 study with larch arabinogalactan), meta-analyses demonstrated that flavonoid-containing supplements were safe and effective in preventing acute respiratory tract infections (ARTIs) compared to controls with a relative risk (RR) of 0.81 (95% CI, 0.74 to 0.89; P<0.001) and low heterogeneity. A reduction in mean ARTI sick days was also observed with the supplements; however, heterogeneity was significant (weighted mean difference [WMD], −0.56; 95% CI, −1.04 to −0.08; P=0.021). In subgroup analysis, significance in mean ARTI sick days was retained with flavonoid mixtures (as seen with larch arabinogalactan) but not with use of single flavonoids (ie, quercetin, catechin). Pooled results from 16 of the trials indicated that adverse reactions were not increased in the flavonoid supplement groups compared to controls.(Yao 2022)

In a randomized, double-blind, placebo-controlled, parallel-group study evaluating antibody response to the pneumococcal vaccine in healthy volunteers, arabinogalactan 4.5 g/day (provided as the proprietary product ResistAid) or placebo was given for 72 days (N=45). 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.(Udani 2010) In a similar study, the effects of ResistAid on antibody response to tetanus and influenza vaccines were also 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.(Udani 2013)

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 the microflora found in the large bowel.(Dion 2016, Robinson 2001)

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 the control group (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 the control group, meaning there was more fecal moisture; however, diarrhea was not noted in the treatment group.(Grieshop 2002)

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.(Robinson 2001)

Dyslipidemia

Because larch is a source of dietary fiber, it theoretically may be useful in improving 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.(Robinson 2001) 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.(Marett 2004)

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.(Benedikt 1999) Larch arabinogalactan has GRAS status and is permitted to be used as a stabilizer, binder, and emulsifier, among other uses.(FDA 2002) 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.(Groman 1994) 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.(Prescott 1995) In another study, arabinogalactan conjugated with the antiviral vidarabine was effective in suppressing serum viral DNA titers in woodchucks infected with the hepatitis virus.(Enriquez 1995) 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.(Khvostov 2016) 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.(Chistyachenko 2015) Conjugation of amphotericin B to arabinogalactan has also been studied.(Elgart 2010)

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 evaluated species from 18 families.(Owen 1999)

Dihydroquercitin from L. sibirica was noted to inhibit coxsackievirus B4.(Galochkina 2016)

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.(Burgalassi 2007)

Taxifolin-rich extracts from Dahurian Larch (L. gmelinii) are a novel food ingredient in non-alcoholic beverages, yogurts, chocolate confectionery and food supplements. They are reported to be safe.(EFSA 2017)

Taxifolin, extracted from waste L. olgensis roots, is able to attenuate CCl₄-induced liver fibrosis by regulating the PI3K/AKT/mTOR and TGF-beta1/ smads signaling pathways. This was demonstrated in vivo with mice and suggested that taxifolin might be an efficient hepatoprotective agent.(Liu 2021)

The in vitro anti-inflammatory and anti-lipid accumulation properties of taxifolin-rich extracts from the Japanese larch, L. kaempferi, have been reported.(Muramatsu 2020)

In vitro studies have shown that larch bark procyanidins have very strong inhibitory effects on Staphylococcus aureus and can kill S. aureus by destroying the integrity and permeability of the cell wall and cell membrane, affecting protein synthesis, and binding to DNA.(Li 2017) Polyphenol-rich L. decidua bark extract demonstrated in vitro antimicrobial activity against respiratory-tract pathogens and has potential pharmaceutical and nutraceutical applications.(Faggian 2021)

Protection of the brain through supplementation with larch arabinogalactan in a rat model of vascular dementia has been successfully demonstrated. Cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. This study showed that larch arabinogalactan has potential for development as a functional food to prevent vascular dementia.(Lim 2017)

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. The powder can be mixed with water or juice, or added to food.(Larch 2000) 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.(Udani 2010, Udani 2013)

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.(Schauss 2015) 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.(Larch 2000)

Toxicology

Larch arabinogalactan has GRAS status and is FDA approved as a dietary source of fiber and for use in food products.(Larch 2000) 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.(Groman 1994) 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.(Schauss 2015)

References

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