Hemicellulose – A Natural Immune Enhancer?

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Plant and Mushroom Blend Provides Gut and Immune Support

Hemicellulose isn’t a new thing. In fact, it is as timeless as the plants and fungi that cover the face of our planet.

Within plants, much like cellulose, hemicellulose is structural in function. It differs from cellulose in that it is a polysaccharide comprised of various sugars (including glucose, mannose, galactose, xylose, and arabinose), whereas cellulose is comprised exclusively of glucose.^[1] Structurally, hemicellulose may be branched and contains 500 to 3,000 sugar units, while cellulose is unbranched and typically has 7,000 to 15,000 glucose molecules. The specific types and quantities of the different hemicellulose compounds differ by plant and features (leaf, stem, branch, etc.) of the plant.

Well-known hemicelluloses are arabinoxylan, glucomannan, and xylan, the base molecule from which xylitol and xylooligosaccharides (XOS), are formed.

Although hemicellulose compounds, for humans, offer very little to no caloric nourishment,^[2],[3] this does not mean they are unimportant. In fact, many of them have numerous important biological properties. Well-known hemicelluloses are xylan, the base molecule from which xylitol and xylooligosaccharides (XOS), a prebiotic fiber that promotes healthy bifidobacteria in the gut,^[4] are formed; arabinoxylan, which contains both soluble and insoluble fiber and also delivers a high level of antioxidant activity;^[5],[6] and glucomannan, a hemicellulose commonly used in constipation and weight loss formulas due to its high water affinity.^[7] Because of these and other medicinal properties, as well as their relative abundance and non-toxicity, hemicellulose products have gained substantial interest in both the pharmaceutical and dietary supplement industry.^[8]

One property of great interest is the ability of certain hemicellulose compounds to stimulate immune function. Herein, we look at the immune effects of the hemicellulose compound arabinoxylan and the closely related arabinogalactan, as well as the clinical and preclinical research surrounding a particular combination of plant and mushroom-sourced compounds, containing these and other active moieties.

Arabinoxylans

Arabinoxylans are food for the gut bacteria, which degrade them into short chain fatty acids (SCFAs); thus, they are considered a prebiotic.

Arabinoxylans are hemicellulose compounds found at high levels in the cell walls of numerous cereal grains including rice, wheat, rye, barley, millet, and maize.^[9] Because they are often a by-product of the processing of these grains for various food industry purposes, many have looked at processes to extract them, adding value and reducing waste.

Arabinoxylans are food for the gut bacteria, which degrade them into short chain fatty acids (SCFAs); thus, they are considered a prebiotic.^[10],[11] Studies have shown arabinoxylans are a food source for Bifidobacterium spp. and increase levels of butyrate-producing bacteria, although the bacteria that are stimulated depends in part on the specific arabinoxylan structure.^[12] In humans, supplementation with arabinoxylans was shown in a randomized crossover study to increase levels of bifidobacteria, total SCFAs, the SCFAs butyrate and acetate, and to reduce levels of potential pathogens.^[13] Positive effects on the distressing symptoms of irritable bowel syndrome (IBS) were also seen in a small clinical study, with rice bran-sourced arabinoxylans being found to significantly decrease scores of diarrhea and constipation compared to placebo, in addition to reducing levels of C-reactive protein (CRP), an inflammatory marker.^[14]

Arabinoxylans, due to their structure, are highly bonded to ferulic and other phenolic acids.^[15],[16] Rice-sourced arabinoxylans are highly ferulated (containing bound ferulic acid molecules) which contributes to their potent antioxidant activity.^[17],[18] Ferulic acid has affinity for biological membranes and prevents lipid peroxidation.^[19] The antioxidant activity and bowel-directed action of ferulated arabinoxylans has also led to their consideration for intestinal conditions associated with inflammation and oxidative stress such as inflammatory bowel disease and colon cancer.^[20]

Research suggests rice bran-sourced arabinoxylans enhance macrophage migration, attachment, and phagocytosis;^[21] increase natural killer (NK) cell and dendritic cell activity;^[22],[23] and induce CD4+ T cell proliferation and cytokine production.^[24] However, in lipopolysaccharide (LPS)-stimulated animals, they also have been shown to have anti-inflammatory activity, reducing levels of tumor necrosis factor (TNF)-α and inflammatory cytokines.^[25] Numerous additional sources of arabinoxylans have been shown to have immunomodulatory effects as well.^[26],[27]

Arabinogalactans

In humans, studies have shown arabinogalactans enhance normal immune function while in animal models they also have been shown to have anti-allergic and anti-asthmatic effects.

By some classifications, arabinogalactans are considered hemicellulose compounds, as simply put, they are plant wall polysaccharides that are not cellulose components;^[28],[29] however, by more stringent definitions of hemicellulose that include specifics concerning their molecular structure, they are not.^[30] Either way, these non-starch polysaccharides serve a similar structural function in plants, and even have similar effects in the human body.

Arabinogalactans are found at high levels in plants such as the larch tree, which we often associate with this compound due to it commonly being the source. Similar to arabinoxylan, other sources of arabinogalactans include cereal grains such as wheat, rye, barley, and spelt.^[31]

Arabinogalactans also have been shown to serve as prebiotics for the gut bacteria, increasing levels of healthy bacteria such as Faecalibacterium prausnitzii and Bifidobacterium spp., decreasing levels of pathogenic Clostridium perfringens,^[32] and enhancing levels of the SCFAs butyrate and propionate.^[33] In an intestinal simulator, arabinogalactans were also shown to improve parameters related to intestinal permeability (leaky gut) and inflammation.^[34]

There is considerable research on arabinogalactans as immune-supportive agents. Studies specifically looking larch-sourced arabinogalactans have shown they enhance NK cell amount, activity, and cytotoxicity,^[35],[36] and increase macrophage activity and their production of hydrogen peroxide and nitric oxide – substances that are important in their response against microbial invaders.^[37] Animal models have shown arabinogalactans from various botanical sources also have anti-allergic and anti-asthmatic effects, in part by enhancing the Th1 response.^{[38],[39],[40]}

In healthy humans, modest doses (4 to 4.5 g/d) of arabinogalactans have been shown to enhance immune activity,^[41] while in adults with recurrent respiratory tract infections, they were shown to significantly decrease the incidence of the common cold, with a trend towards decreased cold duration as well.^[42] Supplementation at 1.5 g/d and 4.5 g/d for a prolonged period before vaccination was also shown to significantly increase the antibody response to vaccination with tetanoid toxin and Streptococcus pneumoniae, respectively, when compared to placebo.^[43],[44]

Blended hemicellulose compound (BHCC)

A hemicellulose blend from a combination of Asian rice, barley, Chinese and purple yam, European olive, reishi, shiitake, hen-of-the-woods, and split gill mushrooms has been shown to have immune-supportive effects.

A particular blended hemicellulose complex (BHCC) has been the topic of multiple research studies. Comprised of the hemicellulose fraction of Oryza sativa (commonly known as Asian rice), Hordeum vulgare (barley), Dioscorea spp. (Chinese and purple yam), Olea europaea (European olive), Ganoderma lucidum (reishi mushroom), Lentinula edodes (shiitake mushroom), Grifola frondosa (hen-of-the-woods mushroom), and Schizophyllum commune (split gills mushroom), it is perhaps not surprising that this proprietary blend, containing a high level of mushroom-derived compounds, has been demonstrated to have immune activities. Containing polysaccharides, polyphenols, and fatty acids, BHCC delivers both arabinoxylans and arabinogalactans. During the extraction of these compounds, naturally occurring plant and fungal enzymes also partially break down, or “pre-digest”, the larger polysaccharides and other compounds, making them smaller, more water soluble, and digestible.

Initial cellular studies with BHCC showed that this specific combination has immune-enhancing effects. Specifically, the combination stimulated murine macrophage phagocytosis, nitric oxide production, and proliferation by 65%, 517%, and 155% respectively.^[45] In regards to protecting against excess inflammation, a contributor to many disease processes, on a cellular level BHCC was shown to inhibit α5β1 integrin-mediated T-cell binding to fibronectin (a structural component of our extracellular matrix) in the presence of bifenthrin (a pyrethroid insecticide).^[46] α5β1 integrin signaling plays a role in the damaging inflammatory response to pollutants and infectious respiratory disease,^[47] and is a contributor to conditions like atherosclerosis.^[48]

In the first human study, a small pilot study of healthy individuals, supplementation of BHCC at a dose of 3 g/d for two weeks significantly increased NK cell cytotoxicity, with no adverse effects being seen.^[49] A larger human study, in which BHCC was taken at a dose of only 250 mg twice daily for eight weeks, showed a significant increase in circulating total lymphocyte levels.⁴⁵ While there were increases in T-cell, B-cell and NK cell subsets as well, the increases were not statistically significant. As approximately 15% of individuals in this study were immunosuppressed (having HIV, hepatitis C, or cancer), this lends further weight to these findings.

Although these were small clinical studies, their positive findings, the cellular studies, and the research backing other compounds found in BHCC collectively point towards these hemicellulose compounds as agents that support and enhance a normal, healthy immune response. Once again, we are reminded of the fact that mother earth may provide everything we need to remain healthy, physically wealthy, and wise.

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