Soluble vs Insoluble Beta-Glucans in Medicinal Mushrooms: What Every Supplement Brand Needs to Know

Not all beta-glucans are created equal. The difference between soluble and insoluble fractions determines how your mushroom extract interacts with the immune system — and whether the beta-glucan percentage on your Certificate of Analysis actually reflects bioactive content.

Beta-glucans have become the defining quality marker for medicinal mushroom supplements. Brands cite beta-glucan percentages on product pages, retailers use them to justify price points, and consumers have learned to look for them on labels. Yet the single number printed on a Certificate of Analysis conceals a critical distinction that most brands — and many manufacturers — overlook: not all beta-glucans are the same, and the difference between soluble and insoluble fractions has profound consequences for bioavailability, immune activity, and the real-world efficacy of your product.

The Architecture of the Mushroom Cell Wall

To understand why solubility matters, it helps to understand where beta-glucans come from. In medicinal mushrooms, beta-glucans are structural polysaccharides — long-chain glucose polymers — that form the scaffold of the fungal cell wall. They are not freely floating molecules inside the mushroom tissue; they are locked into a dense, cross-linked matrix alongside chitin (a tough nitrogen-containing polysaccharide), proteins, and other structural components. This matrix is what gives the mushroom its physical rigidity and protects its cellular contents.

Chemically, mushroom beta-glucans are defined by their glycosidic linkages: a backbone of glucose units connected by β-1,3 bonds, with branching side chains attached via β-1,6 bonds. The ratio of 1,3 to 1,6 linkages, the length of the side chains, and the overall degree of branching vary between species — Reishi (Ganoderma lucidum) produces highly branched, high-molecular-weight polysaccharides, while Turkey Tail (Trametes versicolor) is known for its linear PSK and PSP fractions. These structural differences directly influence which immune receptors the beta-glucan binds to, how strongly, and for how long.

Soluble vs Insoluble: The Core Distinction

Within the cell wall matrix, beta-glucans exist in two fundamentally different physical states. Insoluble beta-glucans are tightly bound within the chitin-protein scaffold and cannot dissolve in water under normal conditions. Soluble beta-glucans, by contrast, have been liberated from this matrix — either through the natural biochemistry of the mushroom or, more commonly, through deliberate extraction — and can disperse in aqueous solution.

The biological significance of this distinction is substantial. Research published in Nutrients (Cerletti et al., 2021) confirms that beta-glucans ingested as food or supplement reach the small intestine without gastric digestion. From there, soluble beta-glucan fractions are internalized by intestinal epithelial cells and macrophages, and presented to immune cells within the Peyer's patches — the lymphoid tissue embedded in the gut wall. Insoluble whole glucan particles, by contrast, must be physically transported by macrophages across the intestinal barrier before they can interact with the immune system. This is a slower, less efficient, and less predictable pathway.

The key immune receptor involved in beta-glucan recognition is Dectin-1, a C-type lectin expressed on the surface of monocytes, macrophages, neutrophils, dendritic cells, and natural killer (NK) cells. Dectin-1 binds specifically to the β-1,3 backbone of beta-glucans and triggers an intracellular signalling cascade that activates NF-κB, stimulates cytokine production, and primes both innate and adaptive immune responses. Soluble beta-glucans — particularly those with a well-defined triple-helix conformation — are recognised by Dectin-1 with high affinity. Insoluble particles are recognised too, but the interaction is less consistent and depends heavily on particle size, surface area, and the physical state of the gut environment at the time of ingestion.

How Mushroom Beta-Glucans Become Soluble: The Extraction Process

Raw mushroom powder — whether from the fruiting body or the mycelium — contains beta-glucans predominantly in their insoluble, cell-wall-bound form. The chitin matrix that surrounds them is highly resistant to digestion by human enzymes; humans lack the chitinase activity needed to break it down efficiently. This means that consuming raw or lightly processed mushroom powder delivers far less bioavailable beta-glucan than the total beta-glucan content would suggest. The percentage on the label may be accurate as a chemical measurement, but it does not reflect what the body can actually access.

Extraction is the process by which beta-glucans are liberated from the cell wall and converted into their soluble, bioavailable form. There are four primary extraction methods used in commercial mushroom supplement manufacturing, each suited to different species and target compounds.

<strong>Hot water extraction</strong> is the most widely used and best-validated method. Mushroom material is immersed in water at 80–100 °C for an extended period — typically several hours. The heat disrupts the hydrogen bonds holding the chitin-glucan matrix together, breaking down the cell wall and releasing water-soluble polysaccharides, including beta-glucans, into solution. The resulting liquid is filtered, concentrated, and spray-dried to produce a soluble extract powder. Hot water extraction is particularly effective for species with high water-soluble polysaccharide content, such as Turkey Tail, Shiitake, and Maitake. The resulting beta-glucan fractions retain their triple-helix conformation and Dectin-1 binding capacity.

<strong>Alcohol (ethanol) extraction</strong> targets a different class of bioactive compounds — specifically the triterpenes, sterols, and other lipophilic molecules that are not water-soluble. For species like Reishi (Ganoderma lucidum) and Chaga (Inonotus obliquus), whose therapeutic profiles depend on both polysaccharides and triterpenes, alcohol extraction is essential. However, alcohol extraction alone does not efficiently liberate beta-glucans from the cell wall. This is why the most rigorous manufacturers use <strong>dual extraction</strong> — a sequential process combining hot water and alcohol extraction to capture the full spectrum of bioactive compounds. Dual extraction is the gold standard for Reishi, Chaga, and Cordyceps.

<strong>Alkaline extraction</strong> uses sodium hydroxide (NaOH) or potassium hydroxide (KOH) solutions to solubilise beta-glucans that are resistant to hot water alone. This method is particularly relevant for insoluble beta-glucan fractions such as pleuran from Oyster mushroom (Pleurotus ostreatus) and schizophyllan from Schizophyllum commune. Alkaline-extracted beta-glucans are highly soluble and have demonstrated strong immunomodulatory activity in research settings, but the process requires careful neutralisation and purification to ensure product safety. Alkaline extraction is less common in commercial supplement manufacturing but is used in pharmaceutical-grade applications.

<strong>Enzymatic extraction</strong> uses cellulases, chitinases, and other carbohydrate-active enzymes to degrade the cell wall matrix and release beta-glucans without the need for high temperatures or harsh chemicals. Enzymatic methods can preserve the native conformation of beta-glucan chains more effectively than thermal methods, potentially yielding fractions with enhanced biological activity. However, enzymatic extraction is more expensive and technically demanding, and is currently used primarily in research and high-value nutraceutical applications rather than mainstream supplement manufacturing.

Measuring What Matters: The Beta-Glucan Assay Problem

The measurement of beta-glucan content in mushroom extracts is more complex than most product labels suggest. The most widely used analytical method — the Megazyme enzymatic assay — measures total beta-glucan content by enzymatically hydrolyzing the sample and quantifying the released glucose. This method is accurate for total beta-glucan, but it does not distinguish between soluble and insoluble fractions, nor does it assess the triple-helix conformation that is critical for Dectin-1 binding.

A product with 40% total beta-glucans could theoretically contain predominantly insoluble, cell-wall-bound fractions with limited bioavailability — particularly if the raw material was not properly extracted. Conversely, a well-extracted product with 25% soluble beta-glucans may deliver significantly greater immune activity than a poorly extracted product with 40% total beta-glucans. This is why the extraction method, not just the percentage, is the most important quality indicator for a mushroom supplement.

For B2B brands building products that genuinely perform, the relevant questions to ask a manufacturer are: What extraction method was used? What fraction of the reported beta-glucan content is water-soluble? Is the extract standardised to soluble beta-glucans specifically, or to total beta-glucans? And is the beta-glucan content verified by an independent third-party laboratory using the enzymatic assay method?

Species-Specific Considerations

The soluble-to-insoluble ratio of beta-glucans varies significantly between mushroom species, and this has direct implications for formulation decisions. Turkey Tail (Trametes versicolor) is one of the most water-soluble species — its primary bioactive polysaccharides, PSK (Krestin) and PSP, are readily extracted with hot water and have been the subject of extensive clinical research, including as adjuvant therapy in oncology. A well-produced Turkey Tail extract should yield a high proportion of soluble beta-glucans with minimal insoluble residue.

Reishi (Ganoderma lucidum) presents a more complex picture. Its beta-glucan fraction is predominantly water-soluble following hot water extraction, but its full therapeutic profile — including the anti-inflammatory and adaptogenic effects attributed to ganoderic acids — requires the alcohol-extracted triterpene fraction as well. A Reishi extract standardised only to beta-glucans, without the triterpene fraction, is an incomplete product.

Chaga (Inonotus obliquus) is notable for its high content of beta-glucans in the form of beta-1,3/1,6-D-glucan, but also for its exceptionally high antioxidant content — betulinic acid, inotodiol, and melanin complexes. Like Reishi, dual extraction is recommended to capture both the polysaccharide and the non-polar bioactive fractions. Lion's Mane (Hericium erinaceus) is primarily valued for its hericenones and erinacines — compounds that stimulate nerve growth factor (NGF) synthesis — which are alcohol-soluble. Its beta-glucan content is modest relative to other species, and a quality Lion's Mane extract should be standardised to both polysaccharides and the NGF-stimulating compounds.

Why FUNGY Uses Soluble Beta-Glucan Extracts

At FUNGY, we made a deliberate decision from the outset to work exclusively with properly extracted mushroom materials that deliver soluble beta-glucans — not raw mushroom powder or mycelium-on-grain products that report high total beta-glucan percentages without the extraction step that makes those compounds bioavailable.

Every extract in our portfolio undergoes hot water extraction as a minimum standard, with dual extraction applied to species where the full bioactive profile requires it — Reishi, Chaga, and Cordyceps. The beta-glucan content reported on our Certificates of Analysis reflects soluble, extracted fractions verified by the Megazyme enzymatic assay at an independent third-party laboratory. We do not count insoluble cell wall material in our beta-glucan figures.

This matters for the brands we work with because it means the number on the label corresponds to what the consumer's body can actually use. When a FUNGY-manufactured product states 30% beta-glucans, that figure represents 30% soluble, bioavailable, Dectin-1-activating polysaccharides — not 30% total carbohydrate content that includes indigestible cell wall material. For brands building products in a market where consumer sophistication is increasing rapidly, this distinction is not a technical footnote. It is the foundation of a credible efficacy claim.

Formulation Implications for Supplement Brands

Understanding the soluble/insoluble distinction has several practical implications for brands formulating mushroom supplements. First, soluble beta-glucan extracts dissolve readily in water, making them ideal for beverage applications — mushroom coffees, functional drinks, and liquid shots — where insoluble particles would create sedimentation, poor mouthfeel, and inconsistent dosing. Second, soluble extracts are more amenable to standardisation: because the active fraction is well-defined and measurable, it is possible to set a precise target dose and verify it analytically, which is essential for any brand making structure/function claims.

Third, and perhaps most importantly for the growing category of premium supplements, soluble beta-glucan extracts allow brands to make meaningful comparisons between products. When both the extraction method and the analytical method are standardised, a 30% beta-glucan extract from one manufacturer can be meaningfully compared to a 30% extract from another. Without that standardisation, the number is almost meaningless — and sophisticated buyers and formulators are increasingly aware of this.

The insoluble fraction is not without value. Research has shown that insoluble whole glucan particles can be physically transported by intestinal macrophages into the gut-associated lymphoid tissue, where they trigger immune responses through a different pathway than soluble fractions. Some researchers argue that a product containing both soluble and insoluble fractions may offer a broader immunological stimulus than a purely soluble extract. However, for the vast majority of commercial supplement applications — capsules, powders, beverages, and shots — the soluble fraction is the primary driver of efficacy, and it is the fraction that should be measured, standardised, and communicated to consumers. If you are building a mushroom supplement brand and want to understand how our extraction standards translate into your finished product specifications, contact our formulation team for a technical consultation.

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