IngredientsAlpha-glucans are a class of polysaccharides composed of glucose units linked primarily by alpha-glycosidic bonds. In the scientific literature they are rendered interchangeably as alpha-glucans, alpha-glycans, α-D-glucans, or — for the oligomeric forms — alpha-glucan oligosaccharides. Structurally, based on the anomeric configuration, glucans have been categorized as α-D-glucans, β-D-glucans, and mixed α,β-D-glucans.
The α-D-glucans exhibit great structural and functional diversity, as the type of linkage and percentage of branching dictate the functional properties of glucans. Among the different linkages, bioactivities are greatly confined to the α-D-(1→3) linkages, whereas starch and other polymers consisting of α-D-(1→4) and (1→6) linkages are specific for food and pharmaceutical applications.
The most clinically discussed sub-types include:
A wide variety of bioresources including bacteria, fungi, lichens, algae, plants, and animals produce α-D-glucans either as an exopolysaccharide (EPS) or a cell wall component or an energy storage polymer.
Mostly α-D-(1→4) glucans function as an energy source in plants (starch), animals (glycogen), bacteria (glycogen), and fungi (glycogen, amylose). The following are the principal natural sources relevant to dietary supplementation:
Alpha-glucan oligosaccharide is an oligomer composed of glucose monomers with a pH stability range of 4.0–8.0; it is soluble in water, propylene glycol, and glycerol, and insoluble in oil and ethanol.
Alpha-glucans are commonly used in the pharmaceutical, food, and cosmetic industries and show high levels of safety and tolerability. They are mainly obtained from plants and therefore do not have to go through exhaustive purification processes. Their abundance in nature, their higher solubility, the presence of groups for their functionalization, and in some cases their natural particulate form (as in the case of starch) are advantages that position α-glucans as better candidates for various applications than other polysaccharides.
Supplemental and commercial forms of alpha-glucans include:
Alpha-glucans, a group of polysaccharides primarily composed of glucose units linked by alpha-glycosidic bonds, have a rich history in traditional medicine and nutritional health. Historically, alpha-glucans such as dextrins and maltodextrins were derived from the enzymatic breakdown of starches in grains and tubers. 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.
Fungi have traditionally been used for the prevention and also treatment of a multitude of disorders, and they have been increasingly consumed by cancer patients during their treatments as dietary supplements. Researchers have considered these fungi as healthy food because they are good sources of vitamins, minerals, proteins, and carbohydrates, apart from a low level of lipids and low caloric content.
The shiitake mushroom (Lentinula edodes), now recognized as the botanical source of AHCC®'s alpha-1,4-glucans, has deep roots in East Asian traditional medicine. Similarly, maitake (Grifola frondosa) has been widely eaten in Japan for centuries: maitake is an edible mushroom consumed widely in Asia as food and used in traditional medicine to treat diabetes and hypertension.
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.
Glucans are the most abundant natural polysaccharides across the living kingdom with tremendous biological activities. Nowadays, α-D-glucans are gaining importance as prebiotics, nutraceuticals, immunostimulants, antiproliferative agents, and biodegradable polymers in pharmaceutical and cosmetic sectors.
Within the alpha-glucan family, distinct linkage types govern distinct functions:
Starch and glycogen are synthesized by sets of specific enzyme activities that directly determine their molecular structures and physical properties. The extent of crystallinity, aggregation, and hydration is of fundamental importance for starch and its human analogue glycogen.
AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through the liquid culture process of shiitake mycelia. The most abundant component of AHCC® is oligosaccharides, which comprise about 74% of the dry weight of AHCC®.
AHCC is a standardized, cultured extract of an edible mushroom Lentinula edodes of the Basidiomycete family of fungi that is enriched in acylated α-1,4-glucans. The main component of AHCC is α-1,4-glucans, and the glucan fractions have been associated with the biological activities of AHCC.
The alpha-glucans and acetylated alpha-glucans in AHCC are thought to be responsible for some of its potential health benefits.
The novel bioactive polysaccharide YM-2A was isolated from the maitake mushroom and characterized as a glycogen-like polysaccharide consisting of linear 4-linked α-D-Glcp residues substituted at position 6 with α-D-Glcp branches. Although oral administration of YM-2A has a preventive effect against influenza infection in mice, YM-2A does not directly inhibit growth of the virus in vitro. YM-2A protects immunocompromised mice from influenza infection and increases the titer of anti-virus antibody to the same extent as that seen in normal mice, suggesting that YM-2A could modulate the immune system in mice.
Resistant starches (RS) are a broad categorization of many classes of starches formed under a variety of conditions, but all escape digestion in the upper GI tract. RS is a type of dietary fiber that bypasses digestion in the small intestine due to its resistance to amylase, reaching the large intestine where it is fermented by gut microbiota. Upon fermentation, RS produces high amounts of short-chain fatty acids (SCFAs), contributing to its benefits on the gut microbiome.
Studies reported the activation of natural killer (NK) and T cells by alpha-glucans extracted from edible mushrooms like Tricholoma matsutake and maitake (Grifola frondosa), supporting the implication of α-glucans in regulating the immune system.
Such immunological effects could be executed by directly modulating the numbers and functions of these cells as well as by affecting the function of monocytes, macrophages, and dendritic cells (DCs) with the capacity to promote T cell function.
The effects of AHCC® on T cells could be mediated by affecting innate immune cells, since oligosaccharides including α-glucans and β-glucans are known to stimulate innate immune cells such as monocytes, macrophages, and dendritic cells that can modulate the activation and differentiation of T cells.
AHCC® is classified as a Biological Response Modifier (BRM): AHCC showed anti-inflammatory and anticancer effects, enhanced resistance to microbial infections, and may protect against oxidative stress-induced disorders. In healthy adults, AHCC improved T-cell immune responses, and increased dendritic cell number.
Resistant starch (RS), a prebiotic, promotes proliferation of gut bacteria such as Bifidobacteria and Lactobacilli and increases the production of metabolites including short-chain fatty acids, which confer a number of health-promoting benefits.
RS acts as a prebiotic, selectively stimulating the growth of beneficial gut bacteria such as Bifidobacterium, Faecalibacterium prausnitzii, and Akkermansia muciniphila. This microbial modulation enhances SCFA production, particularly butyrate, which has been linked to anti-inflammatory effects, improved gut barrier function, and even modulation of systemic immune responses.
Cosmetic-grade alpha-glucan oligosaccharide works by a related prebiotic mechanism: Alpha-glucan oligosaccharide is a prebiotic sugar that provides energy to nourish the skin's "good" bacteria. It is claimed to be a bio-selective substrate that selectively protects and stimulates the growth of beneficial microorganisms that help maintain the skin in good condition, at the expense of pathogenic and/or undesirable flora. It also stimulates the release of anti-microbial peptides by keratinocytes.
Dietary carbohydrates that are digested and release glucose in a slow manner are recognized as providing health benefits. Slow digestion of glycemic carbohydrates can be caused by several factors, including a food matrix effect which impedes α-amylase access to substrate, or partial inhibition by plant secondary metabolites such as phenolic compounds. Differences in digestion rate of these carbohydrates may also be due to their specific structures such as variations in degree of branching and/or glycosidic linkages present.
Preclinical studies suggest antidiabetic effects of maitake alpha-glucan via increased insulin sensitivity on insulin receptors and decreased insulin resistance in peripheral target tissues.
More recently, it was demonstrated that glucan polysaccharides also have strong antioxidant properties related to the frequent exposition of these polysaccharides to oxidative bursts in nature and their capability to buffer against attack by radicals.
Since excessive inflammation can lead to diseases such as colitis, arthritis, and asthma, exopolysaccharides isolated from various sources including bacteria, fungi, and algae have been demonstrated to possess a wide range of bioactivities. Natural polysaccharides exert important roles in the treatment of inflammatory disorders, and anti-inflammatory activity has emerged as one of the most important bioactivities of exopolysaccharides.
The recognition of immunostimulant and immunomodulatory effects has encouraged scientists to isolate and characterize these compounds and to examine their efficacy and safety, particularly because these investigations represent an important opportunity in the search for next-generation vaccine adjuvants. Although the adjuvant compounds derived from plants and natural products have broad structural diversity, polysaccharides are of special interest due to their known effect on the immune system and their important advantages such as biodegradability, tolerability, and low side effects. Among polysaccharides, α-glucans are of particular interest.
Among these glucans, dextran and starch have been evaluated as mucosal vaccine adjuvants. They share a basic molecular structure and have been chemically modified to be used as delivery particulate systems with adjuvant properties.
AHCC has been shown in laboratory studies to stimulate the activity of natural killer (NK) cells, a type of immune cell that targets tumor cells or cells infected with a virus. It also appears to boost T-cell immune response in healthy older adults, which might reduce infection risk. For this reason, AHCC has been investigated for its anticancer or antiviral effects.
The effects of AHCC® on immune cells of humans and animals were reported in in vitro and in vivo studies, suggesting the possible help of its supplementation in defending the host against infections and malignancies via modulating the immune system.
Evidence strength: Several studies have demonstrated immunological effects in humans (NK cell activity, T-cell counts, cytokine profiles), but many of the most favorable results come from uncontrolled or small studies. The evidence for a functional immune benefit in healthy adults is preliminary but consistent in direction.
In experiments, maitake activated various effector cells such as macrophages, NK cells, T cells, IL-1, and superoxide anions. In patients with myelodysplastic syndromes, maitake mushroom extract increased neutrophil and monocyte function.
Evidence strength: Primarily preclinical; limited human clinical data in specific disease populations (myelodysplastic syndromes). Large-scale controlled human trials are lacking.
The prevention and treatment of the recurrence of hepatocellular carcinoma following hepatic resection has been studied extensively. However, the prognosis for HCC remains unsatisfactory, with the 5-year survival rate after primary surgical treatment at approximately 40% in Japan. There have been many attempts to treat the cancer by stimulating with biological response modifiers (BRMs), but the clinical efficacy of these substances has not been clearly confirmed. AHCC® may be considered a potent BRM in the treatment of cancer patients. An observational study design was used: a prospective cohort study from February 1, 1992 to December 31, 2001 enrolled a total of 269 consecutive patients with histologically confirmed HCC. All of the patients underwent resection of a liver tumor. The enrolled patients were addressed to each arm of the study based on their choice of the therapeutic options and were trusted with self-administration of AHCC®.
Potential benefits with this compound in patients with cancer have been reported in a few uncontrolled or nonrandomized studies.
Evidence strength: Weak to moderate. The HCC cohort study is large (n=269) but non-randomized and observational. Selection bias and confounding cannot be excluded. No randomized controlled trial has confirmed a survival benefit in HCC.
Animal research has examined the specific alpha-glucan fraction YM-2A from maitake: In contrast to the traditional functions of glycogen, recent studies have reported that some glycogens have immunomodulatory activities. Researchers investigated whether oral administration of YM-2A exerts antitumor and immunomodulatory effects in a murine colon carcinoma model and an aggressive melanoma model.
Alpha-glucan from the fruiting body of maitake (Grifola frondosa) was assessed for its hypoglycemic and hypolipidemic effects using a streptozotocin and high-fat diet diabetic mouse model. Treatment with 300 or 100 mg/kg of MT-Glucan may lead to a significant decrease in fasting plasma glucose, triglycerides, cholesterol, and free fatty acids.
Evidence strength: These findings are animal/preclinical only. No direct translation to human doses or outcomes has been established.
The most developed human clinical evidence for AHCC® (alpha-1,4-glucan) concerns its effects on persistent high-risk human papillomavirus (HPV) infections.
Two pilot studies of 10 patients each were conducted in women with confirmed persistent high-risk HPV infections. The first study evaluated AHCC 3 g from 5 weeks up to 6 months, and the second study evaluated AHCC 1 g for less than 8 months. High-risk HPV DNA status and the immune panel were monitored at each visit.
Four of six (66.7%) patients had confirmed high-risk HPV clearance after 3–6 months of AHCC 3 g. Similarly, 4 of 9 (44%) patients had confirmed high-risk HPV clearance after 7 months of AHCC 1 g. Suppression of IFN-β to less than 25 pg/mL was observed in those clearing the HPV infection.
Smith JA and team conducted a Phase II randomized, double-blind, placebo-controlled study in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. This study investigated AHCC® as a prospective candidate for nutritional supplementation to support the host immune system in removing chronic infections. Participants were randomized into two groups: the control group (n=25) receiving placebo for 12 months and the intervention group (n=25) receiving 3 g of AHCC orally once in a fasting state for 6 months. Study completion: 41 participants completed the study out of 50 enrolled. For the AHCC arm, 14 of 22 patients (63.6%) achieved HPV RNA/DNA negativity after 6 months.
Results from this phase II study demonstrated that AHCC 3 g once daily was effective to support the host immune system to eliminate persistent HPV infections and was well tolerated with no significant adverse side effects reported. The duration of AHCC supplementation required beyond the first negative result needs more evaluation to optimize durable outcomes based on both HPV infection status and the target IFN-β level.
The suppression of IFN-β level to less than 20 pg/ml correlated with clearance of HPV infections and merits further evaluation as a clinical tool for monitoring patients with HPV infections.
Evidence strength: This Phase II RCT is among the strongest human clinical data for an alpha-glucan preparation. The trial was adequately blinded and placebo-controlled, though its sample size was small (50 enrolled, 41 completed). The results are promising but require confirmation in larger phase III trials.
Results demonstrated promising effects with a 12-week course of AHCC® supplementation for improving liver enzyme levels and circulating pro-inflammatory and anti-inflammatory cytokines in patients with alcohol-induced liver enzyme elevation. AHCC® supplementation for 12 weeks significantly improved ALT levels, decreased pro-inflammatory cytokines (TNF-α and IL-1β), and elevated anti-inflammatory cytokines (adiponectin) in both AHCC® groups without any adverse events. Hepatoprotective effects accompanied by striking anti-inflammatory effects were observed regardless of the dosage.
Hepatitis C virus (HCV) infection is a worldwide important issue, with over 170 million people throughout the world having been infected. Generally, 2–35% of people infected with HCV will finally develop cirrhosis and hepatocellular carcinoma. The treatment for chronic hepatitis C patients causes many side effects and is expensive. Previous research has shown that AHCC® can increase numbers and function of several kinds of immune cells, while reducing HCV and ALT, a liver enzyme involved in the progression of hepatitis C. A prospective, randomized, double-blind, placebo-controlled trial was conducted in which patients received AHCC® (n=19) or placebo (n=20) for 24 weeks. All patients received HCV RNA levels and liver function test monitoring.
Evidence strength: The liver enzyme study is encouraging and controlled, but small. The HCV trial is properly designed (RCT, double-blind), though the sample size is again small. Larger confirmatory studies are needed before drawing firm conclusions about clinical hepatoprotection.
A murine (animal model) study evaluated AHCC's effects on SARS-CoV-2: Researchers evaluated the effects of the oral administration of AHCC on the host response to SARS-CoV-2 infection in two murine models, K18-hACE2 transgenic mice and immunocompetent BALB/c mice. Oral administration of AHCC every other day for one week before and one day post SARS-CoV-2 infection in both strains of mice decreased the viral load and attenuated inflammation in the lungs. AHCC treatment also significantly reduced SARS-CoV-2-induced lethality in the K18-hACE2 mice.
Evidence strength: This is animal (murine) data only. No human clinical trial has evaluated AHCC® for COVID-19 prevention or treatment. These results cannot currently be extrapolated to human outcomes.
Attempts to leverage resistant starch as microbiome-modifying interventions in clinical studies have yielded remarkable inter-individual variation. Their utility as a potential therapy likely depends predominantly on the selected resistant starch and the subject's baseline microbiome.
A well-designed clinical trial using resistant potato starch found: A three-arm randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the effect of 3.5 g and 7 g daily doses of Solnul™ resistant potato starch (RPS) on beneficial populations of gut bacteria and stool consistency after a 4-week period. The relative abundance of Bifidobacterium and Akkermansia was determined by 16Sv4 sequencing of stool samples. To assess the effect of RPS on laxation and bowel movements, stools were scored using the Bristol Stool Form Scale. Participants consuming 3.5 g/day of RPS experienced significantly greater changes in Bifidobacterium and Akkermansia compared to placebo after 4 weeks. The number of diarrhea- and constipation-associated bowel movements were both significantly lower in the 3.5 g RPS arm compared to the placebo group. Participants consuming 7 g of RPS responded similarly to those in the 3.5 g arm.
A separate clinical trial (RESISTA-PD) using resistant starch in Parkinson's disease patients found: Resistant starch was well-tolerated. In the PD+RS group, fecal butyrate concentrations increased significantly, and fecal calprotectin concentrations dropped significantly after 8 weeks of RS intervention. Clinically, a reduction in non-motor symptom load was observed in the PD+RS group.
Several studies confirmed that intake of RS, particularly RS1 and RS2, improves glycemic control by lowering postprandial glucose and fasting insulin levels. This effect is highly relevant for the management and prevention of type 2 diabetes and related metabolic conditions.
Evidence strength: The prebiotic effects of resistant starch (an alpha-glucan) on gut microbiome composition are supported by multiple randomized controlled trials. Glycemic benefit is also credibly supported. Evidence in specific disease states (kidney disease, Parkinson's disease) is early-stage and requires replication.
Antilipidemic effects with maitake polysaccharides occurred by modulating gut microbial phylotypes and regulating genes involved in hepatic lipid and cholesterol metabolism.
Adequate dietary fiber consumption is associated with several health benefits, including reduced risk of obesity, metabolic syndrome, type 2 diabetes (T2D), CVD, colon cancer, and constipation.
Evidence strength: The antilipidemic associations for maitake alpha-glucan are currently based on preclinical (animal) research. The broader metabolic benefits of fiber-type alpha-glucans (resistant starches) are supported by epidemiological and intervention data, with multiple controlled trials showing glycemic and lipid-modulating effects.
The following dosages are reported as used in cited human studies or formulation standards, and should not be interpreted as recommendations.
The required dosage in cosmetic products is from 0.5% to 5%.
In a high-dose safety study, researchers concluded that "when used in high dose in healthy subjects, AHCC causes no significant abnormality in laboratory parameters." The adverse effects of 9 grams of liquid AHCC per day, a higher dose than used in routine clinical applications, are minimal and the dose was tolerated by 85% of the subjects. This trial supports the anecdotal evidence that AHCC is a safe supplement in clinical practice and that the side effects are generally mild and tolerable.
In the Phase II HPV study, AHCC 3 g once daily was well tolerated with no significant adverse side effects reported.
A phase 1 trial reported mild GI complaints, including nausea, diarrhea, and bloating. Some patients also reported headache, fatigue, and foot cramps with the liquid form of AHCC.
Consumption of AHCC (4.5 g/d for 6 months) resulted in itching and diarrhea in a study of patients with early-stage prostate cancer.
There is concern that AHCC may affect the blood levels of certain drugs, although these interactions have not been confirmed in humans. A laboratory study showed that AHCC increased the activity of cytochrome P450 2D6 (CYP2D6), an enzyme involved in the metabolism of drugs such as doxorubicin and ondansetron. By increasing the activity of CYP2D6, AHCC may decrease the levels of these drugs.
In a previous study evaluating phase I metabolism, AHCC was found to be a substrate as well as an inducer of the CYP450 2D6 pathway. Otherwise, the overall data suggested that AHCC would not interact with the other CYP450 pathways and would be generally safe to administer.
The clinical significance of these interactions has yet to be determined.
A laboratory study showed that AHCC may increase the activity of aromatase enzyme. Theoretically, by increasing aromatase activity, AHCC may decrease the effectiveness of drugs that are aromatase inhibitors, such as letrozole, anastrozole, and exemestane.
A case report suggests maitake can interact with warfarin, resulting in INR elevation.
Maitake may increase the effects of hypoglycemic medications.
AHCC seems to increase immune function and might make autoimmune diseases worse. People with autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or others should avoid or use AHCC cautiously.
Individuals hypersensitive to any of the components of AHCC or to basidiomycete mushrooms should avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.
Resistant starch was well-tolerated in the RESISTA-PD clinical trial. Attempts to leverage resistant starch as microbiome-modifying interventions in clinical studies have yielded remarkable inter-individual variation. Their utility as a potential therapy likely depends predominantly on the selected resistant starch and the subject's baseline microbiome.
More research is needed to fully validate the diverse health benefits of alpha-glucans, especially through large-scale, well-controlled human studies.
Clinical trials have generally not shown a clear benefit of AHCC in cancer treatment, reducing side effects of chemotherapy, preventing or treating the flu, or treating persistent human papillomavirus (HPV) infection — this assessment from ConsumerLab.com (a rigorous reference database) reflects the state of the evidence as of its publication date and stands in some contrast to the specific Phase II HPV findings discussed above, underscoring the importance of distinguishing between available evidence (small trials) and established efficacy.
Key research gaps include: the absence of large-scale Phase III RCTs for AHCC® in any indication; the need to separate the contribution of alpha-1,4-glucans specifically from other components in AHCC® (amino acids, minerals, other polysaccharides); a lack of standardized alpha-glucan preparations across studies making comparisons difficult; and insufficient long-term safety data in diverse populations.
Health conditions that Alpha-glycans may help support.
Body systems that Alpha-glycans may help support.
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