IngredientsChitin-glucan complex (CGC) is a copolymer (polysaccharide) that makes up fungal cell walls, consisting of covalently-bonded chitin and branched 1,3/1,6-β-D-glucan. It is also referred to in the scientific literature as chitin-glucan (CG), chitin–β-glucan complex, or fungal chitin-glucan. Under its leading commercial formulation it has been designated KiOnutrime-CG™ (KitoZyme, Belgium) and branded in North America as ARTINIA™.
The chitin–glucan complex (CGC) is a naturally occurring copolymer composed of chitin, a linear polysaccharide of N-acetyl-D-glucosamine, covalently linked to β-(1,3)- and β-(1,6)-glucans, which are glucose homopolymers.
Chitin-glucan is composed of the polysaccharides chitin (repeat units N-acetyl-D-glucosamine) and 1,3-β-glucan (repeat unit D-glucose). The two polymers are covalently connected and form a three-dimensional network. The chitin/glucan ratio ranges from 25:75 to 60:40 (m/m).
Chitin and chitosan are closely related molecules: greater than 40% of the polymer chain of chitin is made of acetylated glucosamine units, whereas greater than 60% of chitosan is made of deacetylated glucosamine units. The distinction matters in the context of CGC because the degree of acetylation partially determines the biophysical behavior of the complex; it should not be confused with chitosan-glucan complexes, which are structurally related but chemically distinct.
Chitin-glucan complex (CGC) is a polysaccharide found in the cell wall of most fungi and yeasts, including Komagataella pastoris, Aspergillus niger, Schizophyllum commune, Gongronella butleri, Armillariella mellea, and Saccharomyces cerevisiae.
The primary commercial source for dietary supplement applications is the food-grade mold Aspergillus niger. It is of fungal origin and is a natural polymer, the main component of the cellular walls of Aspergillus niger. It is initially extracted and purified from the mycelium of Aspergillus niger. This fungal resource is a by-product of the citric acid produced for the food and pharmaceutical markets.
In mushrooms, chitin occurs as a copolymer of chitin and β-glucan, namely, a chitin-glucan complex (CGC) that is found in the cell walls. The relatively lower chitin content in mushrooms compared to that in crustaceans is ascribable to its association with β-glucan, which has numerous health benefits, including anti-inflammatory, antioxidant, and anti-tumor effects; the CGC structure is more pliable than that of chitin.
While Saccharomyces cerevisiae (baker's yeast) offers a safe, non-animal source of chitin-glucan (CG), its potential as a functional cosmetic ingredient has been overshadowed by industrial sources like Aspergillus niger.
As important natural biopolymers, chitin and chitosan are usually prepared from crustacean shells that may contain potential allergens. Recent studies have shifted the focus to mushrooms as a desirable source for chitin and chitosan because of the innate absence of allergenic proteins and inclusion of minerals at significantly lower levels compared to crustacean shells.
CGCs are alkaline-insoluble. Different species of fungi have different structural compositions of chitin and β-glucan making up the CGCs in their cell walls. Soil composition and other environmental factors can also affect the ratio of chitin to β-glucan found in the CGC.
Chitin, as the most abundant non-wood biopolymer on earth, exists widely in the shells of crustaceans, the cell walls of fungi, and the cuticles of insects. It consists of N-acetyl-D-glucosamine and D-glucosamine units with various molar ratios linked by β-(1→4)-glycoside bonds.
For almost all fungi, the central core of the cell wall is a branched β-1,3/1,6 glucan that is linked to chitin via a β-1,4 linkage.
Fungal chitin, generally present in the α-polymorph, is embedded in a chitin–glucan–protein matrix that ensures high crystallinity, mechanical stability, and compatibility for biomedical applications.
The Novel Food ingredient called "KiOnutrime-CG™" has a content of more than 90% chitin-glucan, which is the main component in the cell walls of the mycelium of Aspergillus niger derived from a fermentation process.
ARTINIA (listed as KiOnutrime-CG in the EFSA's scientific opinion) is a high-purity, natural, fungal ingredient that features the benefits of both soluble and insoluble fibers. The novel food ingredient is intended to be marketed as a food supplement, in the form of a powder in different formats such as gelatin capsules or tablets, to increase the daily intake of fibre.
CG and the control had the same galenic form and visual aspect but mainly differed by their fiber content. Both were presented as a 3 g sachet powder to be diluted in water. In clinical research settings, loose powder formulations dissolved in water have been the most widely used delivery form.
Artinia is a chitin-glucan fiber, derived from the mycelium of non-genetically-modified strains of Aspergillus niger and contains 80% dietary fiber, primarily insoluble.
Approximately 200 years ago, in 1811, French chemist Henri Braconnot was the first to extract a highly insoluble substance from fungi, naming it fongine. Later renamed chitin by Auguste Odier in 1823, this highly crystalline polymer composed of β-1,4 linked N-acetyl-D-glucosamine (GlcNAc) units has since been extensively studied for its structural role in fungi, insects, crustaceans and mollusks.
Historically, chitin was first isolated from mushrooms in the early 19th century, and progressive advances in purification and functionalization have enabled downstream production of chitosan and nanoscale derivatives tailored for biomedical use.
Two hundred years ago, Henri Braconnot described a polysaccharide containing a substantial percent of nitrogen, later to be called chitin: that discovery stemmed from investigations on the composition of edible mushrooms and their nutritional value.
The specific chitin-glucan complex as an isolated and purified ingredient is a modern, late-20th/early-21st-century development. However, CGC as an integral structural component of fungi and yeasts has been consumed as part of whole fungi in traditional diets across many cultures for centuries. Folk medicine, especially in the Far East, used medicinal mushrooms based on previous experience. At the end of the 19th century, but mainly since the middle of the 20th century, progressively more scientific information has been published.
Carbohydrates, including polysaccharide macromolecules, are the main constituents of the fungal cell wall. Among these, the homo- or heteropolymeric glucan molecules are decisive, as they not only protect fungal cells but also have broad, positive biological effects on the animal and human bodies. In addition to the beneficial nutritional properties of mushrooms (mineral elements, favorable proteins, low fat and energy content, pleasant aroma, and flavor), they have a high glucan content.
The importance of chitin content in nutritional physiology also has another aspect: it forms an important part of the dietary fiber fraction and thus plays a role in ensuring the fiber requirements of normal digestive processes.
The isolation and commercial development of purified CGC as a distinct dietary supplement ingredient is associated primarily with the work of the Belgian company KitoZyme, whose manufacturing process uses Aspergillus niger mycelium—itself a well-established food-industry microorganism—as a co-product of industrial citric acid production. The scientific study of CGC as a discrete ingredient began in earnest in the early 2000s.
CGC has properties of both chitin and β-glucan and can be hydrolyzed to produce chitin, chitosan, and β-glucan. Its bioactivity is therefore understood to reflect the combined properties of its two covalently linked components.
CGC exhibited higher oil-holding capacity, water-holding capacity and nitrite ion adsorption capacity than commercial chitin, and showed potential prebiotic effects.
For almost all fungi, the central core of the cell wall is a branched β-1,3/1,6 glucan that is linked to chitin via a β-1,4 linkage. Given CG insolubility, it is expected to be hardly fermented by the resident microbiota. Despite this expectation, fermentation in the colon has been experimentally demonstrated.
Using an in vitro approach with a Simulator of the Human Intestinal Microbial Ecosystem (SHIME), Marzorati et al. discovered that CG was fermented in all colon segments. This was shown by an increased distal colonic acidification, an enhanced SCFA production (mainly propionate and butyrate) and low levels of gas production.
Evaluation of the potential prebiotic features of chitin-glucan toward bifidobacteria under in vitro conditions highlighted the ability of 100 bifidobacterial strains to use this substrate as its sole carbon source. Chitin-glucan (CG) represents a natural carbohydrate source for certain microbial inhabitants of the human gut and may act as a prebiotic for a number of bacterial taxa.
Overall, CG and CGB (CG plus Bifidobacterium breve) promote health-beneficial short-chain fatty acid production and shift human gut microbiota composition, with a consistent effect increasing Roseburia spp. and butyrate-producing bacteria.
In vitro, using human intestinal HT-29 epithelial cells, chitin-glucan used at clinically and biologically relevant concentrations was able to increase the expression of IL-10 mRNA, which is an important player in the regulation of intestinal inflammation. Furthermore, the anti-inflammatory activity of chitin-glucan was investigated in LPS-stimulated HT-29 epithelial cells, showing potent inhibition of major inflammatory cytokine genes, such as IL-1β and IL-8.
CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.
In hamsters fed an atherogenic diet, chitin-glucan mixed with food lowered plasma triglycerides and markedly reduced the diet-induced formation of aortic fatty streak lesions. It also reduced aortic cholesterol, cardiac superoxide anion production and hepatic malondialdehyde, and increased hepatic antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase). These effects were observed in animal models and are not directly translatable to humans without supporting clinical data.
Although several findings by these studies are apparently controversial, β-glucans may effectively lower LDLc by binding bile acids and reducing their reabsorption. This bile acid sequestration mechanism—well-established for soluble β-glucans—is proposed as a contributing mechanism for lipid modulation by CGC.
A 4-week administration of CG significantly improved metabolic parameters in mice on a high fat (HF) diet (body weight gain, glucose tolerance, hepatic steatosis). In parallel to the metabolic outcomes, an increase of Roseburia spp., a butyrate-producing bacterium, was also detected in mice supplemented with CG. These findings are from preclinical animal studies.
On the basis of studies in animals and humans, it has been proposed that fermentable-prebiotic dietary fiber might increase satiety, improve metabolic disorders, and modulate gut-related immunity through mechanisms related to SCFA influencing endocrine and metabolic functions and intestinal epithelial integrity.
In vitro and animal evidence: Evaluation of the potential prebiotic features of chitin-glucan toward bifidobacteria under in vitro conditions highlighted the ability of 100 bifidobacterial strains to use this substrate as its sole carbon source. Chitin-glucan represents a natural carbohydrate source for certain microbial inhabitants of the human gut and may act as a prebiotic for a number of bacterial taxa.
Human evidence: A 3-week intervention exploring the effect of CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites was conducted. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). A 3-week supplementation with CG was well tolerated in healthy humans. CG induced specific changes in the gut microbiota composition, with Eubacterium, Dorea, and Roseburia genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal bile acid profile following CG intervention.
A shift in the gut microbiota composition after 3 weeks—including in particular an increase of Roseburia and Eubacterium genera—could clearly be attributed to CG treatment, and was not due to intra-individual variations of microbiome with time.
Overall, CG and CGB promote health-beneficial short-chain fatty acid production and shift human gut microbiota composition, with a consistent effect increasing Roseburia spp.
Evidence strength: Prebiotic activity is one of the most well-documented areas of CGC research. In vitro and animal data are consistent, and multiple human studies using validated methods (16S rRNA sequencing, SCFA profiling) have demonstrated microbiota modulation. However, these human studies are small (n=13–15) and of short duration (3 weeks). Clinical outcomes linked to these microbiota changes in humans remain to be established through larger, longer-term trials.
Human evidence: In a double-blind, randomized, cross-over, twice 3-week exploratory study, the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions were investigated in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control.
Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge.
This study showed that CG was fermented in the colon and induced the production of gut-derived metabolites such as short chain fatty acids (SCFA).
Evidence strength: These results are from a small, exploratory, cross-over study (n=15). The improvements in postprandial glycemia and triglyceridemia are preliminary and require replication in larger, longer-duration randomized controlled trials before clinical conclusions can be drawn.
Preclinical evidence: Results from well-controlled clinical trials support the view that consumption of soluble β-glucans reduces total cholesterol (TC) and LDL-C, typically without affecting high-density lipoprotein cholesterol (HDL-C) or triglycerides (TGs). Whether the same holds for insoluble CGC is a separate question that has been directly tested in humans.
Human RCT evidence: The primary objective of a key study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels. This 6-week, randomized, double-blind, placebo-controlled study evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37–4.92 mmol/l and glucose ≤ 6.94 mmol/l. Participants were randomly assigned to receive CG (4.5 g/day; n=33), CG (1.5 g/day; n=32), CG (1.5 g/day) plus OO extract (135 mg/day; n=30), or matching placebo (n=35).
Administration of 4.5 g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5 g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels.
Adverse events did not substantively differ between treatments and placebo. In this 6-week study, CG (4.5 g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.
A separate prospective study investigated a related compound. This study aimed to evaluate the effects of a polysaccharide-rich compound containing β-glucan/chitin–chitosan (βGluCnCs) on lipid profiles and lipoprotein function. In a prospective, two-arm clinical trial, 58 overweight and obese individuals were randomized to receive either 3 g/day of βGluCnCs or a placebo (microcrystalline cellulose) for 12 weeks. Serum lipids and lipoprotein functions were assessed at baseline and at 4-week intervals throughout the study. The administration of βGluCnCs led to a significant increase in HDL cholesterol (HDLc) levels and improved HDLc/non-HDLc and HDLc/total cholesterol (TC) ratios, while reducing apolipoprotein B (ApoB) levels (p < 0.05). However, the intervention did not affect HDL particle diameter, particle number, or lipoprotein functionality. Note that this study used a β-glucan/chitin-chitosan compound, which is related but not identical to pure chitin-glucan complex.
Women demonstrated greater sensitivity to changes in HDLc during βGluCnCs supplementation, whereas men exhibited a significant reduction in ApoB levels.
Evidence strength: The 6-week RCT (n=130) provides the most rigorous evidence in this area. The finding that 4.5 g/day significantly reduced OxLDL is notable and methodologically sound. The LDL-C reduction at 1.5 g/day but not at the higher dose reflects a complex dose-response that is not fully explained. Overall, evidence is promising but limited to a single well-conducted RCT; independent replication is needed before firm conclusions can be drawn.
Animal and in vitro evidence: In vitro, using human intestinal HT-29 epithelial cells, chitin-glucan used at clinically and biologically relevant concentrations was able to increase the expression of IL-10 mRNA. Furthermore, the anti-inflammatory activity of chitin-glucan was investigated in LPS-stimulated HT-29 epithelial cells, showing potent inhibition of major inflammatory cytokine genes, such as IL-1β and IL-8.
Increased intestinal permeability is a pathophysiological observation in IBS, observed mostly in the diarrhea-predominant patient subgroup.
Human evidence: GASTRAP® DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action. To evaluate the efficacy, tolerability, and safety of 4-week GASTRAP® DIRECT treatment in patients with IBS, 120 patients with IBS received three sticks of GASTRAP® DIRECT (1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone) per day for 4 weeks in a prospective, multicenter, open-label trial.
CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.
Evidence strength: The human IBS data are preliminary. The prospective open-label multicenter trial (n=120) lacks a placebo control group, which substantially limits interpretation of efficacy. The animal and in vitro mechanistic data are internally consistent and provide a biological rationale, but controlled human evidence specific to IBS endpoints remains limited as of the available literature.
Human evidence: Two clinical studies were conducted to evaluate the tolerance and effects of a copolymer of chitin and beta-glucan, forming the exoskeleton of fungal cell walls. A 6-week randomized, double-blind, placebo-controlled study was conducted on 13 volunteers with sensitive skin to compare 0.5–2% formulations of chitin–glucan applied twice daily. Biometrological evaluations showed that erythema did not develop, the water retention capacity of the stratum corneum increased and the transepidermal water loss moderately decreased.
Another 16-week randomized, double-blind, placebo-controlled study was conducted on 20 men showing signs of ageing skin. A 1.5% chitin–glucan formulation was applied twice daily. Objective biometrological assessments showed a progressive increase in skin firmness and stratum corneum hydration when desquamation and skin roughness decreased.
In conclusion, the chitin–glucan formulations appear safe. They significantly mitigate some signs of skin ageing and improve both stratum corneum hydration and skin barrier function.
Chitin-glucan is a copolymer found in the cell wall of several mushrooms with good moisturizing properties and has potential for use in skin moisturizing and anti-aging formulations.
Evidence strength: The cosmetic application evidence is limited to two small, short-term, placebo-controlled RCTs (n=13 and n=20) using topical formulations. While results are consistent and statistically supported within their small sample sizes, the studies are underpowered. No long-term safety or efficacy data for topical CGC are available in these published sources.
Several preclinical findings provide a mechanistic backdrop for the human cardiometabolic studies. A 4-week administration of CG significantly improved metabolic parameters in mice on a high fat (HF) diet (body weight gain, glucose tolerance, hepatic steatosis). In parallel to the metabolic outcomes, an increase of Roseburia spp., a butyrate-producing bacterium, was also detected in mice supplemented with CG.
Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice.
Evidence strength: These are animal (rodent) data only. They establish biological plausibility but cannot be directly extrapolated to human outcomes.
Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5–3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.
The ingredient is intended to be marketed as a food supplement to increase the daily intake of fibre. The intended intake of chitin-glucan is 2 to 5 g/day.
The following specific dosages have been documented in clinical studies:
The EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) issued a Scientific Opinion on the safety of "Chitin-Glucan" as a Novel Food ingredient (EFSA Journal 2010;8(7):1687).
EFSA noted that the A. niger strain is non-toxic and non-pathogenic and has a history of safe use in production of food ingredients. An examination of the compositional data and the manufacturing process did not give rise to concerns.
After an extensive scientific review, the European Food Safety Authority (EFSA) panel on Dietetic Products, Nutrition and Allergies determined that the chitin-glucan novel food ingredient is considered safe as a food ingredient at the proposed conditions of use and intake levels.
The product (KiOnutrime-CG™) assessed by EFSA was composed of >90% chitin-glucan (a structure that combines chitin and beta (1,3) glucan) and ≤ 6% protein, and was intended to provide a daily intake of 2–5 grams of chitin-glucan. The Panel reviewed a report showing no observed adverse effects at the highest dose administered (about 6.6 g/kg bw) in a 13-week rat study (TNO, 2009).
Because this dose is approximately 80-fold higher than the maximum intended level of intake for humans on a g/kg bw basis, the Panel concluded that KiOnutrime-CG™ was safe as a food ingredient at the proposed conditions of use and at the proposed intake levels.
A 3-week supplementation with CG is well tolerated in healthy humans.
Adverse events did not substantively differ between treatments and placebo in the 6-week lipid RCT (n=130).
A clinically important safety consideration relates to the potential cross-reactivity of fungal CGC with shellfish allergens. In 2010, the EFSA panel on NDA assessed the safety of chitin-glucan as a novel food ingredient. This chitin-glucan was derived from A. niger through a fermentation process, and therefore did not contain shellfish protein.
The major allergen in shellfish responsible for anaphylaxis is the protein tropomyosin, which is absent in fungal-derived CGC. Because the commercially developed CGC (from Aspergillus niger) is a protein-free polysaccharide complex (protein content ≤6% per the EFSA assessment), it structurally differs from crustacean-derived chitin and does not carry the shellfish protein allergens. Individuals with documented shellfish protein allergy should nonetheless review the source material of any specific CGC supplement, as product quality and protein residue levels may vary across manufacturers.
The commercial CGC ingredient is derived from Aspergillus niger, which is used broadly in the food and pharmaceutical industries. EFSA noted that the A. niger strain is non-toxic and non-pathogenic and has a history of safe use in production of food ingredients. Individuals with documented Aspergillus mold allergies or hypersensitivities may wish to consider this source, though the purification process removes intact mycelial proteins and does not retain whole-organism allergens in the finished ingredient.
As an insoluble dietary fiber, CGC may theoretically affect the absorption of fat-soluble nutrients and certain medications when taken simultaneously, consistent with general fiber pharmacokinetics. CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels at the doses studied, suggesting a favorable metabolic safety profile in healthy individuals with borderline-to-high LDL-C over a 6-week period. No formal drug interaction studies specific to CGC have been identified in the peer-reviewed literature accessible for this review.
CG was fermented in all colon segments with increased distal colonic acidification, enhanced SCFA production (mainly propionate and butyrate) and low levels of gas production, suggesting that unlike some soluble fermentable fibers, CGC produces relatively low amounts of intestinal gas—a property consistent with its classification as a predominantly insoluble, slowly fermented fiber.
The overall evidence base for chitin-glucan complex as a dietary supplement ingredient can be characterized as preliminary to moderate across all health domains. The following observations apply:
Health conditions that Chitin-glucan complex may help support.
Body systems that Chitin-glucan complex may help support.
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