Ingredientsα-Glucans (alpha-glucans) are polysaccharides of D-glucose monomers linked with glycosidic bonds of the alpha form. Glucans are D-glucose polymers joined by glycosidic bonds between the anomeric carbon of one monosaccharide and the hydroxyl group of another, rendering alpha (α), beta (β), or mixed (α,β) patterns. Depending on the source, glucans exhibit a wide diversity related not only to the position and sequence of glycosidic bonds but also to the chain conformation, which can be linear or branched at different positions (1,3; 1,4; and 1,6) and degrees.
The term alpha-glucans refers to polysaccharides consisting of glucose units connected by α-1,4-glucosidic linkages and which can contain α-1,6-branch points. The common glycosidic bonds that are digestible by humans include (α1→4) and (α1→6) glucose-glucose that make up (iso)maltose, (iso)maltooligosaccharides, and starch.
Alpha (α)-D-glucans are linked together by α-glycosidic bonds aligned in the axial position. Alpha (α)-D-glucans are polysaccharide polymers found in plants, animals, and microbes.
Alpha-glucans encompass a chemically diverse family of molecules, which can be categorized by their primary structural characteristics:
Glucose-based polymers are the most abundant biomaterials on earth, but differ greatly in structure and function depending on whether they are β (1–4) linked as in cellulose, or α (1–4) linked as in starch and glycogen.
Alpha-glucan is commonly found in bacteria, yeasts, plants, and insects. Key natural sources include:
Alpha-glucans are available in multiple commercial and research forms:
Ancient cultures, particularly in Asia and Europe, utilized starchy plant extracts in remedies for digestive health and as a source of sustained energy. These preparations were commonly used to soothe gastrointestinal discomfort, replenish energy after illness, and support general vitality.
Alpha glucans have also played a significant role in the formulation of herbal combinations. When blended with medicinal herbs, they serve as effective carriers and stabilizers, enhancing the bioavailability and absorption of active compounds.
In East Asian traditional medicine, mushrooms rich in polysaccharides — including alpha-glucan-containing species such as maitake (Grifola frondosa) and shiitake (Lentinula edodes) — have been used for centuries. The maitake mushroom (Grifola frondosa) is a popular, edible mushroom in Japan, especially because its fruiting body can be artificially produced. Traditional Chinese and Japanese folk medicine used both maitake and shiitake mushrooms as tonics, believed to improve immunity and vitality. Mushrooms are popular folk medicines that have attracted considerable attention because of their efficient antitumor activities.
AHCC, one of the best-characterized alpha-glucan preparations, was originally developed in Japan. Active hexose correlated compound (AHCC) is an alpha-glucan-rich nutraceutical ingredient prepared by culturing shiitake and other Basidiomycetes mushrooms. AHCC was originally developed for lowering blood pressure, but significant immunostimulating effects were found later.
The use of starchy grain preparations in traditional medicine extended broadly across European and Asian cultures, where gruel-like preparations from oats, barley, and rice were historically prescribed for convalescence, fever, and digestive ailments — all of which would have delivered alpha-glucan polysaccharides as a primary bioactive component. Pharmacologically, glucans have important biological activities, and one of the most important is the immunostimulatory activity.
The biological activity of alpha-glucans is closely tied to their primary and higher-order structure. α-Glucans are polysaccharides of D-glucose monomers linked with glycosidic bonds of the alpha form. α-Glucans use cofactors in a cofactor site in order to activate a glucan phosphorylase enzyme. This enzyme causes a reaction that transfers a glucosyl portion between orthophosphate and α-1,4-glucan.
Whereas the main pathway of α-glucan synthesis is via glycosidic bonds of glucose monomers, α-glucan can be comparably synthesized via the maltosyl transferase GlgE and branching enzyme GlgB.
For AHCC specifically, AHCC is a proprietary extract derived from the mycelia of shiitake (Lentinus edodes) mushrooms. It is rich in alpha-1,4-glucan oligosaccharides that are thought to enhance its biological effects. The maitake-derived alpha-glucan YM-2A has been characterized in detail: NMR and methylation analysis revealed that YM-2A is a glycogen-like polysaccharide consisting of linear 4-linked α-D-Glcp residues substituted at position 6 with -α-D-Glcp branches.
When multiple monosaccharides are linked together, they form polysaccharides, which are used for energy storage and structure. For example, glycogen is a storage polysaccharide within the human body, consisting of (α1→4)-linked glucose molecules that are relatively highly branched through (α1→6) linkages. Starch, which is the glucose storage form in plants and the most common dietary polysaccharide, consists of two types of polymers: amylose and amylopectin.
Blood sugar levels rise after a meal. As the α-glucans of the invention display reduced digestibility compared to materials such as starch, meals prepared containing them will cause a reduced blood glucose response compared to the equivalent meal with starch, and will provoke a lower insulin response.
Alpha-glucans exert biological effects through several established and proposed mechanisms:
Evidence strength: Moderate (human RCTs available, but results are mixed and size-limited)
The role of resistant starch (RS) in glucose, insulin, insulin resistance or sensitivity, and lipid parameters has been reported in several studies and remained controversial.
A systematic review and meta-analysis published in Nutrition & Diabetes (2019) identified 13 case-control studies including 428 subjects with BMI ≥25. RS supplementation reduced fasting insulin in overall and stratified (diabetics and nondiabetics trials) analysis (SMD = –0.72; 95% CI: –1.13 to –0.31), and reduced fasting glucose in overall and stratified analysis for diabetic trials. However, although an association between RS supplementation and insulin concentrations, insulin sensitivity, and lipid parameters is biologically credible, the results of epidemiological studies on this relationship are inconsistent.
A randomized, controlled crossover study in 17 individuals with well-controlled type 2 diabetes tested 40 g/day of high-amylose maize resistant starch type 2 (HAM-RS2) over 12 weeks. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c.
A further randomized controlled clinical trial in 56 women with type 2 diabetes mellitus used 10 g/day RS2 or placebo for 8 weeks. After 8 weeks, RS2 caused a significant decrease in the levels of MDA (–34.10%), glycosylated hemoglobin (–9.40%), insulin (–29.36%), homeostasis model of insulin resistance (–32.85%) and endotoxin (–25.00%), and a significant increase in total antioxidant capacity (18.10%) and glutathione peroxidase (11.60%) as compared with control. No significant changes were observed in fasting plasma glucose or high-sensitivity CRP.
A study in normoglycemic adults (n=13) compared a nutrition bar containing cross-linked RS type 4 to standard wheat starch. The RS4 peak glucose and insulin concentrations were lower than the glucose and puffed wheat control (P < .05). The incremental area under the curve for glucose and insulin were lower following ingestion of RS4 compared with the glucose and puffed wheat control trials.
Evidence strength: Preliminary to moderate (mostly in vitro and animal; some human pilot data)
A mixture of α-(1→3)-GOS, notably with a degree of polymerization of 2 to 9, was obtained from the hydrolysis of fungal glucan. The hydrolysate was utilized for growth by most of the Lactobacillus strains tested and showed a strong bifidogenic effect, but did not promote the growth of Escherichia coli and Enterococcus faecalis. α-(1→3)-GOS proved to be effective in the selective stimulation of beneficial bacteria and can be further tested to determine their prebiotic functionality.
The findings of in vitro fermentation studies support the potential for alpha-GOS, XOS, and oat beta-glucan to serve as novel prebiotics, due to their association with positive shifts in microbiome composition and short-chain fatty acid production that point to potential health benefits.
Regarding the fermentation behavior of resistant alpha-glucans in the colon: Due to its highly branched structure, the α-glucan will resist enzymatic degradation in the upper gastrointestinal tract and end up in the large intestine where it can be fully fermented by the colonic microflora. In addition, such dietary fibres enhance satiety in humans or animals.
A randomized placebo-controlled clinical trial examined digestion-resistant potato starch (MSPrebiotic®) — an alpha-glucan type RS — in elderly (>70 years) and mid-age (30–50 years) Canadian adults. ELD and MID adults were randomized to consume 30 g of either MSPrebiotic® or placebo per day for 12 weeks. In total, 42 ELD and 42 MID participants completed the study. Recent evidence suggests that prebiotics can modulate the gut microbiome, which then plays an important role in regulating lipid metabolism, blood glucose, and insulin sensitivity. As such, prebiotics are appealing potential therapeutic strategies for prediabetes and type 2 diabetes.
Evidence strength: Moderate for AHCC (multiple human RCTs); preliminary for other alpha-glucan sources (mainly animal and in vitro)
Alpha-glucan-containing substances have demonstrated an ability to enhance immune functions.
AHCC, derived from shiitake mycelia and primarily composed of alpha-glucans, has the most extensive human clinical data among alpha-glucan preparations. In healthy adults, AHCC improved T-cell immune responses, increased dendritic cell number and function, improved antibody response to influenza vaccine, and when used with Bifidobacterium longum, modulated T regulatory and dendritic cell phenotypes to favor anti-inflammatory responses after antibiotic use.
Regarding the alpha-glucan YM-2A from maitake (Grifola frondosa), animal research has shown immune activation through gastrointestinal lymphoid tissue: results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. This remains preclinical; direct human confirmatory trials are lacking for this specific compound.
Short-term oral application of natural immunomodulating glucans from maitake and shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. It should be noted that the mushroom preparations in these studies typically contain both alpha- and beta-glucan fractions, making attribution of effects to alpha-glucans alone difficult.
Evidence strength: Moderate (single Phase II RCT; small sample size)
A randomized, double-blind, placebo-controlled study (NCT02405533) enrolled 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N=25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 months followed by 6 months of placebo (N=25).
AHCC was found to be effective against persistent high-risk human papillomavirus (HPV) infections. The mechanistic basis proposed for this effect is: AHCC exhibits unique immune modulation to downregulate the hyper-stimulated IFN-β level resulting in negative feedback to kick-start the release of IFN-γ and T lymphocytes needed to clear chronic viral infections.
Earlier pilot data from the same research group had shown: an encouraging response in 4 of 8 (50%) patients with confirmed HR-HPV DNA eradication after at least 3 months and up to 6 months of daily 3-g AHCC supplementation.
Evidence strength: Preliminary (mostly preclinical; limited human data for AHCC as adjuvant)
Patients use AHCC to prevent and treat cancer. AHCC showed anti-inflammatory and anticancer effects, enhanced resistance to microbial infections, and may protect against oxidative stress-induced disorders.
Several animal and human studies have reported a variety of therapeutic effects, including antioxidant and anticancer activities and modulation of the immune system to prevent the infectious processes of both viral and bacterial infections.
For maitake-derived polysaccharides (containing both alpha- and beta-glucans): when maitake polysaccharides were used in conjunction with chemotherapy, they increased the response rates by 12–28%, improved immunological responses by 1.2–1.4 times, and reduced the negative effects of chemotherapy. However, these figures come from observational or uncontrolled clinical data and must be interpreted cautiously.
Because of their relatively low toxicities, natural products have been studied for the development of new immunomodulatory agents.
Evidence strength: Preliminary (mostly preclinical; limited and methodologically weak human data)
A systematic review and meta-analysis examined resistant starch (alpha-glucan-based) therapy in IBD. 21 preclinical (n=989 animals) and seven clinical (n=164 patients) studies met eligibility. Preclinically, resistant starch was associated with a significant reduction in bowel mucosal damage compared to placebo (standardized mean difference −1.83, 95% CI −2.45 to −1.20). Clinically, five studies reported data on clinical remission but clinical and methodological heterogeneity precluded pooling. In all five, a positive effect was seen in patients who consumed resistant starch supplemented diets. The majority of studies in both the preclinical and clinical settings were at a high or unclear risk of bias due to poor methodological reporting.
The review demonstrates that resistant starch is associated with reduced histology damage in animal studies, and improvements in clinical remission in IBD patients. These results need to be tempered by the risk of bias of included studies. Rigorously designed preclinical and clinical studies are warranted.
Evidence strength: Mechanistically well-established; direct clinical translation remains under active investigation
Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source, and gut transit time.
Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues.
In addition to supplying energy from dietary fibre via SCFA absorption, these acids have multiple effects on host gene expression and cellular development as inhibitors of histone deacetylation and through signaling via G-protein coupled receptors. The effects have been shown to include anti-inflammatory action via the maturation of regulatory T-cells, and the production of hormones that influence satiety.
Alpha-glucans — particularly resistant starch and alpha-glucan oligosaccharides — exert their most well-characterized effects in the gastrointestinal tract. Due to the highly branched structure of some alpha-glucans, they resist enzymatic degradation in the upper gastrointestinal tract and end up in the large intestine where they can be fully fermented by the colonic microflora. This fermentation supports colonocyte energy supply via butyrate and selectively enriches beneficial bacterial populations including Lactobacillus and Bifidobacterium species.
Pharmacologically, glucans have important biological activities, and one of the most important is the immunostimulatory activity. Alpha-glucan-rich preparations such as AHCC have been shown in human studies to influence T-cell function, dendritic cell activity, and cytokine profiles. Some α-glucans isolated from fungi also have potent immune stimulatory activity.
Resistant alpha-glucans influence postprandial glucose and insulin responses. RS has been well documented for its promising nutritional interventions in cardiovascular disease and in a variety of metabolic disorders. The proposed metabolic mechanism involves both slowing of carbohydrate absorption and stimulation of GLP-1 secretion from colonic enteroendocrine cells.
Alpha-glucan preparations, primarily AHCC and maitake-derived glucans, have been evaluated as adjuncts in oncology settings. The antitumor mechanisms of mushroom polysaccharides are mediated by stimulated T cells or other immune cells. These polysaccharides are able to trigger various cellular responses, such as the expression of cytokines and nitric oxide.
The following dosage information is drawn directly from clinical and research publications:
Alpha-glucans are commonly supplied as powders (for incorporation into foods or beverages), capsules, and functional food ingredients. The food composition may be a beverage, for example a powdered beverage mix or a beverage creamer; a breakfast cereal; a pet food product; a baked dough product; or a confectionery product.
Adverse effects after RS supplementation were reported in five studies, including flatulence, abdominal discomfort, diarrhea and swelling, fullness, nausea, and constipation. Most of which were mild and disappeared after few days of consumption.
These gastrointestinal effects are consistent with fermentation activity in the colon and are most frequently reported during the initial days to weeks of supplementation as the gut microbiota adapts.
While findings are encouraging, it is important to note that more research is needed to fully validate the diverse health benefits of alpha glucans, especially through large-scale, well-controlled human studies. Existing evidence suggests alpha glucans contribute positively to nutritional products, supporting energy metabolism, gut health, and potentially immune function. Their inclusion in supplements and functional foods continues to be justified by their safety profile and the growing interest in carbohydrate-based bioactives.
Differential clinical responses to prebiotics in adults can be more effective in some individuals, identified as responders, than in others, identified as non-responders. Responders are individuals with appropriate baseline commensal microbes for whom the prebiotic may confer a health benefit. The reports of responders and non-responders in intervention studies encourage the determination of individual characteristics to better apprehend the efficacy of dietary intervention.
Although it has been reported that α-glucans are recognized by several receptors such as TLRs and DC-SIGN, correlation between structure and activity has not been fully elucidated.
Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.
The ADA position on RS states "there are no published long-term studies in subjects with diabetes to prove benefits from the use of resistant starch."
The field is complicated by the structural heterogeneity of alpha-glucans across different sources, preparations, and manufacturers, making direct comparison across trials difficult. The standardization of clinical protocols could provide details on the subjects enrolled in studies, including sex, age, ethnicity, diet, and the compositional and functional features of their gut microbiota.
Health conditions that Alpha glucans may help support.
Body systems that Alpha glucans may help support.
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