Ultimate Guide to AHCC: Health Benefits & Uses

For over three decades, AHCC (Active Hexose Correlated Compound) has been quietly making waves in the world of integrative medicine. AHCC is not a traditional herbal remedy—but a product of precision fermentation, created to harness the immune-enhancing potential of alpha-glucans and other bioactive compounds. Originally researched to support patients undergoing cancer treatment, it has since become one of the most studied functional mushroom derivatives in clinical settings.

Over 30 human and animal studies have explored AHCC’s role in immune regulation, liver protection, inflammation control, infection resilience, and even stress modulation—making it a multifaceted ally for both acute and long-term health.

In this guide, we’ll examine the origins of AHCC, explore the unique process behind its creation, unpack the science behind its key compounds, and spotlight the most compelling areas of research. Whether you're aiming to strengthen your immune defences, recover more effectively, or build long-term resilience, this guide will give you the clarity you need to understand AHCC—and how to select a supplement that truly delivers on quality.

Index

1. What are Functional Mushrooms?
2. What Is Active Hexose Correlated Compound (AHCC)?
3. The Science Behind The Benefits Of AHCC
4. Health Benefits of AHCC
5. AHCC and Pets
6. How To Buy A Good Quality AHCC Supplement?
7. Dose, Safety, Side Effects
8. How To Take AHCC For Health Support
9. Frequently Asked Questions
10. Resources

What are Functional Mushrooms?

Referred to as 'functional mushrooms', these edible mushrooms boast a diverse range of bioactive compounds. Each type of functional mushroom possesses a unique bioactive profile, contributing to its ability to support specific bodily systems. AHCC, in particular, stands out for its remarkable capacity to help clear viral infections and to provide cancer and chemotherapy support.

What Is Active Hexose Correlated Compound (AHCC)?

Active hexose correlated compound is a blend of polysaccharides, amino acids, fats, and minerals obtained from the mycelial culture of the Lentinula edodes (Shiitake) mushroom [1].

This extract was first developed in Japan in 1989.

AHCC consists of a blend of polysaccharides, amino acids, and minerals [16]. Approximately 74% of its composition is made up of oligosaccharides, and around 20% of these are α-1,4-glucans (partially acetylated alpha-glucans). These particular glucans are thought to play a key role in contributing to AHCC’s biological activity and are also the key feature that sets AHCC apart from other mushroom-derived supplements [16].

While AHCC contains a higher concentration of α-1,4-glucans compared to other mushrooms, it also features compounds commonly found in various mushroom species, such as beta-glucans [17].

AHCC is produced through a specialized process called submerged fermentation that begins with with liquid culturing of shiitake mycelium in a nutrient-rich medium under sterile, controlled conditions—this is known as submerged fermentation. During this stage, the mycelium grows and begins to produce key bioactive compounds.

Next, the cultured material undergoes enzymatic decomposition using cellulase and hemicellulase enzymes. These enzymes break down the rigid cell walls of the fungus, allowing immune-supportive components such as alpha-glucans and oligosaccharides to be released.

Following enzymatic treatment, the mixture is heat-treated to deactivate the enzymes and stabilize the extract. It is then passed through a filtration system to remove insoluble materials, concentrating the liquid fraction that contains the active constituents.

Finally, the solution is concentrated and spray-dried, resulting in the finished AHCC powder used in supplements.

This multi-step refinement is what gives AHCC its distinct characteristics—low molecular weight, enhanced bioavailability, and consistent immune-modulating efficacy.

The Science Behind The Benefits Of AHCC

AHCC has gained widespread interest for its ability to modulate the immune system, support liver health, and enhance resilience during times of stress or infection. While many of its health benefits are well-documented in clinical and preclinical studies, fewer studies have identified which specific compounds are directly responsible for each of its actions. What we do know is that AHCC contains a unique combination of bioactive compounds, with partially acylated alpha-glucans believed to be the primary drivers of its immune-modulating effects.

In addition to these alpha-glucans, AHCC also contains oligosaccharides, amino acids, peptides, and nucleosides such as adenosine—each of which may contribute to its broad biological activity. Research continues to explore how these compounds work in concert to produce AHCC’s well-tolerated, multi-faceted benefits. Below, we explore the key constituents found in AHCC and the growing body of scientific evidence supporting their role in immune health, inflammation control, and metabolic balance.

Alpha-Glucans (Particularly α-1,4 Glucans)

Unlike the more common beta-glucans found in other medicinal mushrooms, AHCC is rich in alpha-glucans, primarily α-1,4-glucans with a low molecular weight. These unique polysaccharides are more easily absorbed and may play a key role in AHCC’s ability to modulate immune responses and other reported health benefits [16]. 
Research suggests that alpha-glucans stimulate dendritic cells and enhance the activity of natural killer (NK) cells and T lymphocytes, which are essential for antiviral and antitumor immunity [6, 8]. This makes AHCC particularly useful for reinforcing the immune system during infections or cancer therapy.

Oligosaccharides

Oligosaccharides are carbohydrate chains composed of three to ten monosaccharides, or simple sugars [57]. These compounds are found naturally in a variety of fruits and vegetables, meaning many people consume them as part of their regular diet.

Most oligosaccharides are resistant to digestion in the human gastrointestinal tract. Instead of being broken down, they pass into the colon intact, where they serve as fuel for beneficial gut bacteria [58, 59].

Because of this function, oligosaccharides are classified as prebiotics— feeding beneficial gut bacteria such as Lactobacillus and Bifidobacterium species and helping to lower inflammation and protect the gut lining, according to studies [3, 4, 60].

Polysaccharides vs. Oligosaccharides

Polysaccharides are long chains of monosaccharides, often made up of hundreds of sugar units, whereas oligosaccharides are shorter, typically consisting of three to twelve. While both are composed of simple sugars linked together, the key difference lies in the length and complexity of their chains.

Amino Acids and Peptides

The fermentation process also generates free amino acids and small peptides. These building blocks contribute to protein synthesis and cellular repair, but also influence immune modulation. For example, certain amino acids like glutamine are critical for maintaining gut lining integrity and fueling lymphocyte proliferation [61].

Although direct studies on the amino acid content of AHCC are scarce, the presence of these compounds aligns with its observed health benefits.

Adenosine

One of the more recently identified bioactive components in AHCC is adenosine, a nucleoside with potent regulatory effects on inflammation.

In a study investigating liver-protective properties, adenosine was shown to inhibit nitric oxide (NO) production by downregulating inducible nitric oxide synthase (iNOS) in hepatocytes [22]. Excess NO is a marker of inflammation and liver stress. Adenosine blocked NF-κB activation and reduced the expression of the interleukin-1 receptor (IL-1RI), both key drivers of inflammatory gene transcription. These effects translated into improved liver cell resilience and reduced inflammatory signaling—highlighting adenosine’s role in protecting organs under oxidative or immune-related stress.

Health Benefits of AHCC

AHCC has been extensively studied for its immune-modulating, anti-inflammatory, and organ-protective effects, making it one of the most researched functional mushroom extracts on the market.

Across clinical and preclinical studies, AHCC has demonstrated benefits ranging from enhanced immune cell function and faster viral clearance, to reduced inflammation, improved gut integrity, and support for liver health. What makes AHCC unique is its ability to enhance immune responsiveness without overstimulating the system—making it especially valuable for those with chronic infections, undergoing chemotherapy, or experiencing immune fatigue.

The following section highlights the key health benefits of AHCC, supported by peer-reviewed research and real-world clinical applications.

Health Benefits at a Glance:

• AHCC May Support Inflammation Relief
• AHCC May Enhance Gut Health
• AHCC May Strengthen the Immune System
• AHCC May Offer Stress Relief
• AHCC’s Potential Antioxidant Activities
• AHCC May Provide Liver Protection
• AHCC May Support Viral, Fungal and Bacterial Defense with Particular Focus On Human Papillomavirus (HPV)
• AHCC and Cancer
• AHCC May Help Regulate Blood Sugar & Manage Diabetes

AHCC May Support Inflammation Relief 

AHCC has shown promising anti-inflammatory effects in multiple scientific studies [2,3,4].

In a chronic gut inflammation model closely resembling human inflammatory bowel disease, AHCC reduced inflammation by lowering two key markers: colonic myeloperoxidase and alkaline phosphatase [2]. These markers are signs of immune overactivity and tissue damage in the colon. Lowering them is beneficial because it indicates reduced irritation, improved healing of the gut lining, and better immune regulation—key for anyone struggling with bloating, cramps, or autoimmune flare-ups.

AHCC also downregulated inflammatory messengers like TNF-α and IL-1β, which are often overproduced in chronic inflammation, contributing to persistent discomfort and fatigue.

Further, AHCC helped normalize immune responses by reducing levels of IL-6 and IL-17 and calming two inflammation-driving proteins: STAT4 and IκB-α [2]. These proteins act like switches for inflammatory genes, and turning them down may help the body respond more calmly to stress and immune triggers.

Another study looked at how AHCC affects inflammation triggered by bacterial toxins—specifically lipopolysaccharides (LPS), which mimic sepsis-like immune dysfunction [3]. In this study, rats were given AHCC in their drinking water before being exposed to LPS.

The group pre-treated with AHCC showed significantly lower levels of inflammation, including reduced cytokines (inflammatory messengers), nitric oxide, and tissue swelling (edema) [3]. Notably, AHCC also restored gut tissue integrity by reducing immune cell infiltration and preserving the structure of the intestinal lining.

A third study using another well-known model of colitis (TNBS-induced inflammation) found that AHCC significantly reduced gut inflammation even when given at different doses [4].

AHCC-treated rats had:

• Less tissue damage and necrosis
• Lower inflammation scores
• Reduced colonic swelling and oxidative stress
• Decreased expression of multiple inflammatory markers including TNF-α, IL-1β, monocyte chemoattractant protein-1, and IL-1 receptor antagonist

Notably, the anti-inflammatory effect of AHCC was comparable to sulfasalazine, a drug commonly used to treat inflammatory bowel disease [4]. This reinforces the potential of AHCC to support gut health and immune balance naturally—without the side effects often seen with pharmaceutical options.

AHCC May Enhance Gut Health

AHCC has also shown exciting potential to support gut health on multiple levels—by calming inflammation, protecting gut lining, and even helping to reshape the gut microbiome [3,4].

In one study using a model of LPS-induced gut inflammation (a condition that mimics bacterial infection and immune dysfunction), rats were given AHCC for five days before being exposed to LPS—a potent toxin that can cause gut injury and dangerous immune overreaction [3]. The results were striking.

AHCC:

• Reduced harmful inflammatory signals, including cytokines and nitric oxide, both of which are known to damage gut tissue
• Decreased swelling (edema) and prevented immune cells from attacking the intestinal lining
• Restored gut architecture, helping to preserve the structure and function of the gut barrier
• Even stabilized blood pressure, a sign of broader anti-inflammatory and protective effects beyond the gut

When the gut lining is damaged, it can lead to issues like bloating, cramping, poor nutrient absorption, and systemic inflammation. AHCC’s ability to prevent and protect against this kind of immune-driven injury suggests it may help maintain a strong, healthy gut barrier.

A second study looked at AHCC in a model of chronic colitis, which closely resembles inflammatory bowel diseases like Crohn’s and ulcerative colitis [4]. AHCC-treated rats experienced major improvements, including:

Healthier weight and food intake, suggesting reduced discomfort
Less tissue damage, less necrosis, and reduced colon swelling
Lowered levels of pro-inflammatory compounds like TNF-α, IL-1β, and MCP-1
Higher antioxidant levels (like glutathione), which are vital for tissue repair and gut lining protection

Here’s where it gets even more interesting: AHCC also influenced the gut microbiome—the community of bacteria living in the digestive tract. Rats given AHCC had:

More beneficial bacteria like aerobic, lactic acid bacteria, and bifidobacteria
Fewer potentially harmful bacteria, like clostridia

A healthy gut microbiome plays a vital role in digestion, immunity, and even mood regulation. By increasing good bacteria and reducing harmful ones, AHCC may help rebalance the gut ecosystem—supporting not just digestive health but your overall wellbeing.

Most notably, the overall anti-inflammatory and gut-protective effects of AHCC in this study were found to be on par with sulfasalazine, a standard pharmaceutical used to manage IBD symptoms [4]—highlighting AHCC’s potential as a natural and well-tolerated option for those seeking long-term gut support.

AHCC May Strengthen the Immune System

AHCC is best known for its ability to support and refine immune system function. Unlike many supplements that indiscriminately “boost” immunity, AHCC appears to work more intelligently—enhancing key immune responses while helping the body stay balanced and avoid overactivation. Research over the past two decades has explored AHCC’s effects in a wide range of contexts, including infections, vaccination, and even cancer recovery.

What stands out is the consistency across these studies: AHCC improves the performance and responsiveness of various immune cells—such as dendritic cells, natural killer (NK) cells, and T cells—without triggering excessive inflammation. Whether it’s helping the body respond faster to viruses, improving vaccine efficacy in older adults, or restoring balance to immune signaling in the gut, AHCC has shown immune-modulating potential across multiple systems.

The following studies offer a closer look at how AHCC works within the immune system—demonstrating not just increased immune activity, but more precise, efficient, and adaptive immune responses [5–11, 18].

One of the earlier studies examining this effect was conducted in 2008 and explored how AHCC influences dendritic cells (DCs)—critical components of the immune system responsible for detecting pathogens and activating other immune cells [8]. In healthy adults, researchers wanted to see if taking AHCC would increase both the number and function of these important immune messengers [8].

For four weeks, participants took either a placebo or 3 grams of AHCC per day [8]. The group that received AHCC saw a significant increase in dendritic cells, particularly two types: DC1s, which help activate T cells (crucial for fighting off infections and viruses), and DC2s, which are involved in regulating immune tolerance and modulating inflammation.

Not only were these immune cells more numerous, but their function also improved [8].

The AHCC group had a stronger mixed leukocyte reaction (MLR)—a lab test that measures how well immune cells respond to foreign substances. This means the participants’ immune systems became more responsive and better prepared to launch a targeted defense.

Interestingly, AHCC didn’t cause a broad, inflammatory response [8]. There were no significant changes in cytokine levels or overall NK cell activity, which suggests that AHCC helped fine-tune specific immune functions without overstimulating the entire system [8]. AHCC thus helped the immune system stay sharp by increasing the cells responsible for recognizing and alerting the body to pathogens, without pushing it into overdrive.

That same year, another study explored how AHCC helps the body fight bacterial infections in a surgical context, when the risk of infection is high and complications can be severe [10]. Using a mouse model of intramuscular infection, researchers examined how AHCC could influence immune mechanisms linked to survival.

Mice were either given AHCC or a placebo, then infected with bacteria. The AHCC-treated group cleared the infection much faster. By day 5, they had significantly lower bacterial load, and by day 6, the infection was completely gone—while the control group still struggled.

This faster recovery was attributed to earlier activation of the immune system. In the AHCC group, important immune messengers—IL-12, TNF-α, and IL-6—peaked at day 3, compared to day 5 in the placebo group. These cytokines help coordinate the immune attack against bacterial invaders.

AHCC also shifted the immune response: treated mice had more lymphocytes and monocytes (linked to long-term, targeted immunity) and fewer polymorphonuclear cells (associated with short-term inflammation), suggesting AHCC enhanced more effective immune defense [10].

Building on these foundational insights, a 2009 study explored how AHCC supports the immune system during a viral infection—specifically influenza—and whether the benefits depend on the dose [6]. Mice were given different daily doses of AHCC and then exposed to the influenza A (H1N1) virus to see how well their bodies could respond to the infection.

The results showed a clear dose-dependent effect, meaning the higher the dose of AHCC, the better the outcomes. Mice that received AHCC had higher survival rates and lost less body weight during the infection—a strong sign that their bodies were better equipped to handle the virus [6].

To understand what was happening behind the scenes, researchers looked more closely at a group that received a relatively low dose of AHCC. Even at this low level, the supplemented mice were able to clear the virus from their bodies more effectively and recovered faster than mice that did not receive AHCC.

One of the most interesting findings was that while AHCC didn’t increase the number of natural killer (NK) cells—the immune cells that help destroy virus-infected cells—it did make each NK cell more effective. This is known as improved "lytic efficiency," meaning that the NK cells in AHCC-supplemented mice were better at killing infected cells, even though the overall number of NK cells didn’t change [6].

This demonstrated that AHCC doesn’t flood the body with immune activity but instead improves the precision and performance of existing immune cells [6], reinforcing the findings from the earlier dendritic cell and bacterial infection studies [8,10].

In 2010, researchers investigated how AHCC could support immune response after flu vaccination, particularly in older adults whose immune systems typically respond less effectively to vaccines [9].The researchers wanted to know whether taking AHCC around the time of vaccination could strengthen the body’s defense system—especially since immune response to vaccines can weaken with age.

Participants took either 3,000 mg of AHCC daily or a placebo starting on the day they received the 2009–2010 seasonal flu vaccine and continued for two weeks afterward.

Blood tests taken before and after vaccination showed that those who took AHCC experienced a greater increase in key immune cells compared to the placebo group [9].

More specifically, AHCC-supplemented individuals had a higher increase in T cells, including CD8+ T cells (also known as cytotoxic T cells), which play a central role in identifying and destroying virus-infected cells. They also had more CD56+ natural killer (NK) cells, particularly the CD56^bright subset, which are especially important for releasing immune-signaling molecules and coordinating immune responses [9].

While AHCC didn’t raise the overall number of NK cells, it enhanced the presence of the most active, immune-supportive subtype [9]. These changes were even more pronounced in adults over 60, a group that typically has a weaker response to vaccines due to age-related immune decline. These results aligned with earlier animal findings on AHCC’s ability to enhance immune efficiency without broad overstimulation [6].

Shortly after, another 2010 study further confirmed AHCC’s immune-supporting potential in adults aged 50 and older [11]. Researchers focused on CD4+ and CD8+ T cells, which are key players in the body’s defense against viruses and infections. They found that AHCC increased the number of T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α)—both essential for coordinating effective immune responses.

Notably, this increase in immune activity didn’t occur immediately. It took at least 30 days of daily supplementation for the effect to become noticeable, and the heightened immune function persisted for another 30 days after stopping supplementation. This suggests that AHCC not only strengthens immune performance but also provides long-lasting benefits, even after use is discontinued [11].

In 2012, a study provided further insight into AHCC’s immune-modulating mechanisms by examining its effect on the interaction between innate and adaptive immune cells [18]. AHCC was shown to stimulate monocytes—cells involved in early immune defense—to produce interleukin-1 beta (IL-1β), a key signaling molecule that influences T helper (Th) cell development.

When CD4+ T cells (the precursor to T helper cells) were co-cultured with AHCC-treated monocytes, there was a significant increase in IL-17 and IFN-γ production—cytokines critical for fighting bacterial and viral infections. This response was blocked by an IL-1 receptor antagonist, confirming that AHCC’s effects were mediated through IL-1β signaling. These findings demonstrate that AHCC strengthens the adaptive immune response by supporting the Th1 and Th17 pathways, which play vital roles in protecting the body from pathogens [18].

In 2013, a separate clinical trial focused on whether AHCC could improve the immune system’s response to the seasonal influenza vaccine in healthy adults [7]. In this clinical trial, 30 healthy adults were randomly divided into two groups. Everyone received the 2009–2010 flu vaccine, but only one group started taking 3 grams of AHCC daily immediately afterward. Three weeks later, their blood was analyzed to see how their immune systems responded.

The results were encouraging. People who took AHCC showed an increase in important immune cells, specifically CD8 T cells, which play a key role in killing virus-infected cells, and NKT cells, which help bridge innate and adaptive immunity [7]. These are both essential for a strong and well-coordinated response to infection.

Even more notable was the improvement in antibody production [7]. Those who took AHCC produced significantly more protective antibodies against influenza B, which means their immune systems were better prepared to recognize and fight off that strain of the virus. In contrast, the control group did not show a significant increase in these protective antibodies [7].

The study concluded that taking AHCC right after a flu shot helped the body build stronger and more effective immunity, both by boosting virus-fighting immune cells and by improving the production of flu-specific antibodies. These findings further supported earlier research on AHCC’s ability to improve virus-fighting cell function and immune regulation [6, 8, 10, 11, 18].

Finally, in 2016, a study took a closer look at how AHCC interacts with the immune system in the gut, where much of the body's immune activity is concentrated [5]. What they found was that AHCC doesn’t push the immune system into overdrive—it helps orchestrate a more balanced, effective response.

When AHCC was given to mice, it increased the number of IgA-producing immune cells in the gut and raised levels of secretory IgA (sIgA) in the intestinal fluid [5]. This is important because sIgA is one of the body’s first lines of defense, acting like a shield in the gut lining to trap viruses, harmful bacteria, and toxins before they can do damage.

In addition to this frontline protection, AHCC also increased two key immune messengers—IL-10 and IFN-γ. IL-10 helps calm excessive inflammation, which is useful in preventing immune overreactions, while IFN-γ plays a crucial role in helping the body fight off infections, especially viruses.

Interestingly, AHCC also interacted with toll-like receptors (TLR-2 and TLR-4) on intestinal epithelial cells—the gut’s built-in immune sensors [5]. These receptors usually react to danger signals like bacterial infections. When AHCC made contact with them, it gently activated a small increase in IL-6, an immune signal that helps rally other immune cells. However, unlike harmful triggers like LPS or E. coli, AHCC didn’t cause a pro-inflammatory response. This shows that AHCC helps "train" the immune system to stay responsive and alert, without tipping it into harmful inflammation.

Taken together, these studies across nearly a decade show a consistent theme: AHCC doesn't overstimulate the immune system but rather enhances specific functions, improves immune cell efficiency, supports targeted responses to vaccines and viruses, accelerates bacterial clearance, stimulates Th1/Th17 pathways, sustains T cell immunity, and helps maintain immune balance.

AHCC May Offer Stress Relief

Emerging research suggests that AHCC may support stress relief through a combination of nervous system modulation, immune system support, hormonal balance, and psychological resilience. Rather than acting as a sedative or stimulant,

AHCC appears to help the body respond to stress more intelligently—enhancing alertness when needed, supporting recovery in times of rest, and promoting overall homeostasis.

Based on the extensive findings from a clinical study, AHCC may support stress relief through multiple interconnected mechanisms involving the autonomic nervous system (ANS), immune modulation, and improved psychological resilience [12].

First, under physical stress, AHCC was shown to enhance sympathetic nervous activity, which is crucial for rapid adaptation to sudden physical demands, such as standing up quickly (Study 1). This enhancement may help stabilize blood pressure and reduce symptoms like dizziness or fatigue in stressful physical scenarios, indicating better physiological resilience [12].

In contrast, when subjects were at rest, AHCC increased parasympathetic nervous activity (Study 2). The parasympathetic system is associated with calmness, digestion, and recovery. This suggests that AHCC helps the body return to a restorative, balanced state when not under stress, rather than leaving the nervous system in a heightened, sympathetic state. These effects were accompanied by improvements in mood and reduced anger/hostility, as well as self-reported trends toward better sleep and less fatigue [12].

During mental stress, AHCC again increased sympathetic nervous system activity, allowing the body to remain alert and responsive (Study 3). Importantly, this activation was context-dependent—seen during stress exposure, but not at rest—indicating that AHCC supports adaptive stress responses rather than chronic overstimulation of stress pathways [12].

The most impactful findings came from individuals with chronic mental stress and mild depression (Study 4). In these individuals, AHCC improved sleep quality, task performance (measured by cognitive testing), and significantly increased NK cell activity, a known marker of both immune competence and psychological stress resilience. Since chronic stress and depression are often linked to immune suppression, the increase in NK cell activity points to a restorative effect on both mood and immune health [12].

Additionally, AHCC is known to possess antioxidant properties, which may contribute to its anti-stress effects. Oxidative stress is often elevated in individuals with depression and stress-related disorders. By potentially reducing oxidative damage, AHCC may further support neuroendocrine balance and mental wellbeing [12].

Separately, a study investigating AHCC in a mouse model of sepsis-induced physiological stress revealed that AHCC may also offer stress relief by regulating key stress hormones, particularly cortisol and norepinephrine (NE)—both of which are commonly elevated in response to physical or psychological stress [13]. Mice pretreated with AHCC for 10 days showed significantly lower cortisol levels 24 hours after stress exposure compared to untreated mice, suggesting AHCC may help the body return to baseline more efficiently after acute stress [13].

Similarly, norepinephrine levels—a hormone associated with the fight-or-flight response—were also lower in the AHCC group at 24 hours post-stress [13]. This reduction in NE points to a calmer, more regulated sympathetic nervous system response, helping to avoid prolonged stimulation that can lead to burnout, insomnia, or anxiety.

Although both groups in the study initially experienced an expected spike in stress hormones following the stressful event, AHCC-treated mice showed a faster normalization, implying that AHCC may buffer the body’s hormonal reaction to stress and support quicker recovery [13].

Together, these findings suggest AHCC may be a valuable natural support for managing daily stress, improving resilience, and protecting both mental and immune health—especially for individuals under persistent stress or showing early signs of burnout.

AHCC’s Potential Antioxidant Activity

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize them with antioxidants. While ROS play essential roles in cell signaling and immune responses, excessive amounts can damage DNA, proteins, and lipids, leading to various diseases such as cancer, cardiovascular disorders, and neurodegenerative conditions [14].

Environmental factors like pollution, radiation, and certain medications can increase ROS levels, exacerbating oxidative stress. The body employs antioxidant enzymes like superoxide dismutase, catalase, and glutathione peroxidase to combat ROS. However, when ROS production overwhelms these defenses, oxidative stress ensues [14].

A study conducted in 2017 highlighted the antioxidant potential of AHCC by demonstrating its ability to protect the body from damage caused by oxidative stress, particularly in the liver and kidneys [15].

Researchers used ferric nitrilotriacetate (Fe-NTA) to induce oxidative stress in rats. Fe-NTA generates hydroxyl radicals, which are highly reactive molecules that damage cells and tissues through a process called lipid peroxidation, as well as by altering DNA and proteins [15].

After administering Fe-NTA, the researchers observed:

• Increased levels of serum lipid peroxidation, indicating damage to fats in cell membranes.
• Elevated aminotransferase enzymes, markers of liver injury.
• A rise in urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a well-known marker of DNA oxidative damage.
• Upregulated ornithine decarboxylase (ODC) activity in both the liver and kidney, which is associated with inflammation and tissue proliferation following oxidative injury [15].

However, in animals pretreated with AHCC, these oxidative markers were significantly reduced or returned to normal levels. AHCC not only suppressed the increase in ODC activity, but it also restored the antioxidant defense system, including:

Glutathione peroxidase and glutathione reductase, two crucial enzymes that protect cells from oxidative damage.

Oxidized glutathione (GSSG) levels, which are part of the body’s mechanism to neutralize free radicals [15].

These results suggest that AHCC:

• Neutralizes free radicals before they cause harm.
• Protects vital organs like the liver and kidney from oxidative injury.
  
• Reduces markers of cellular and DNA damage.
• Maintains antioxidant enzyme function, enhancing the body’s natural defense system.

In summary, AHCC demonstrates antioxidant activity, helping to buffer the body against harmful oxidative stress [15]. These findings suggest AHCC may help with protecting against oxidative damage linked to inflammation, toxicity, and chronic disease.

AHCC May Provide Liver Protection

AHCC may offer liver-protective effects through a range of mechanisms, from enhancing immune response and reducing inflammation to improving recovery following surgery or injury. Across both clinical and preclinical studies, AHCC has shown a consistent pattern of supporting liver health in the face of cancer, fibrosis, surgical stress, and alcohol-related damage [19-25].

A 2002 clinical study suggests that AHCC may offer protective benefits for the liver, particularly in patients recovering from liver cancer surgery [19].

Researchers conducted a prospective cohort study involving 269 patients with hepatocellular carcinoma (HCC)—the most common type of primary liver cancer. All patients had undergone curative surgery to remove their tumors. Of these, 113 patients received AHCC orally after surgery, while the remaining served as a control group [19].

The study found that patients in the AHCC group experienced a significantly longer period without cancer recurrence. This means that AHCC may help reduce the likelihood of the cancer returning, which is a major concern in HCC patients following surgery [19]. The overall survival rate was also significantly higher in the AHCC group. Statistically, the hazard ratio for recurrence was 0.639 and for death was 0.421, both showing a substantial reduction in risk compared to those who did not take AHCC [19].

AHCC appears to provide liver-protective benefits in individuals with liver cancer by improving post-surgical outcomes, extending survival, and reducing recurrence rates. This highlights its potential role as a supportive therapy for liver health, especially in patients at risk of liver dysfunction or tumor relapse.

Supporting this finding in a non-surgical context, a 2006 study explored the potential of AHCC to support patients with advanced liver cancer, particularly those not eligible for surgery—a group typically limited to palliative care options and poor long-term survival [20].

A prospective cohort study was conducted with 44 patients who had histologically confirmed liver cancer and were receiving supportive (non-curative) care. Of these, 34 patients received AHCC orally, and 10 served as a control group taking a placebo.

Researchers evaluated multiple factors, including survival time, quality of life, liver function markers, and immune function indicators such as lymphocyte levels, IL-12, and neopterin [20].

Patients in the AHCC group lived significantly longer than those in the placebo group (p = 0.000), suggesting that AHCC may meaningfully extend life expectancy even in late-stage liver cancer [20]. After just three months of AHCC supplementation, patients also reported notable improvements in mental stability, general physical health, and their ability to perform normal daily activities. These improvements were statistically significant (p = 0.028, 0.037, and 0.040), highlighting AHCC’s potential to enhance not only longevity but also day-to-day well-being [20].

In terms of liver function, AHCC-treated patients had significantly higher albumin levels (p = 0.000), indicating better liver health and nutritional status. They also maintained higher lymphocyte percentages (p = 0.026), reflecting stronger immune function.

Moreover, AHCC patients experienced slower increases in liver enzymes (AST and ALT), which typically rise as liver function worsens—suggesting slower disease progression [20].

There was also mild immune activation, with slight increases in interleukin-12 (IL-12) and neopterin—both of which are involved in immune regulation and defense—pointing to a gentle immune-boosting effect that could help the body better respond to disease [20]. These results closely mirror the improved survival and immune stabilization seen in the surgical cohort from the 2002 study [19], indicating that AHCC may consistently support liver function and immune resilience regardless of surgical eligibility.

This protective trend prompted further investigation into the molecular mechanisms behind AHCC’s effects. A 2007 study examined how AHCC might reduce inflammation-induced liver damage at the cellular level, particularly in the context of nitric oxide (NO) overproduction [21].

In liver diseases—especially those marked by inflammation—a major driver of cellular injury is nitric oxide (NO), a reactive molecule produced in excess by the enzyme inducible nitric oxide synthase (iNOS). When overproduced, NO contributes to oxidative stress, inflammation, and damage to hepatocytes (liver cells) [21]. The researchers aimed to understand how AHCC might interact with this pathway to support liver health.

Using primary cultured rat hepatocytes, the cells were treated with interleukin-1β (IL-1β)—a pro-inflammatory cytokine known to induce iNOS—and then exposed to AHCC. The researchers assessed NO production, iNOS protein and mRNA levels, and the molecular signaling events that regulate iNOS activation.

AHCC significantly reduced NO production. When liver cells were stimulated with IL-1β, they produced large amounts of nitric oxide. AHCC treatment cut this production by over 80% at a concentration of 8 mg/mL, indicating a powerful inhibitory effect on this inflammatory process [21].

AHCC also lowered both iNOS protein and mRNA levels, suggesting that its effects occur upstream—likely at the level of gene expression or mRNA regulation [21]. 

Interestingly, AHCC did not block the NF-κB pathway, which is commonly activated by IL-1β to induce iNOS expression. AHCC had no effect on the degradation of IκB (an inhibitor of NF-κB) or the activation of NF-κB itself, meaning it does not interfere with the initial signaling cascade triggered by inflammation [21].

Instead, AHCC reduced the stability of iNOS mRNA, particularly by targeting AU-rich elements in the 3’ untranslated region (UTR) of the gene—regions that influence how long mRNA remains intact within the cell. This destabilization leads to faster degradation of iNOS mRNA, and thus less production of the harmful nitric oxide enzyme [21].

In conclusion, this study suggests that AHCC helps protect liver cells by reducing nitric oxide production, a central mediator of liver inflammation and oxidative damage. Rather than blocking the entire inflammatory response, AHCC acts more subtly—destabilizing the mRNA of iNOS to reduce the enzyme’s harmful impact. In simpler terms, AHCC functions as a post-transcriptional “off switch” for liver inflammation, offering a unique anti-inflammatory and antioxidant mechanism that may contribute to its liver-protective properties.

To build upon this mechanistic insight, researchers aimed to identify the specific compound within AHCC that is responsible for its liver-protective and anti-inflammatory effects, particularly its ability to reduce nitric oxide (NO) production, which is a major inflammatory marker linked to liver damage [22]. Excessive production of NO, driven by inducible nitric oxide synthase (iNOS), is a known contributor to liver inflammation and injury. While prior research had demonstrated that AHCC can suppress iNOS activity, as mentioned in the previous study [21], the precise compound within AHCC responsible for this effect remained unclear [22].

To pinpoint the active compound, researchers used advanced purification techniques including cation exchange chromatography, size exclusion chromatography, and both normal- and reversed-phase high-performance liquid chromatography (HPLC). Each fraction of the AHCC extract was then tested on primary cultured rat hepatocytes stimulated with interleukin-1β (IL-1β), a cytokine that triggers iNOS expression and NO production [22].

Adenosine was identified as the key bioactive compound using activity-guided fractionation combined with mass spectrometry [22]. Adenosine significantly inhibited NO production and reduced iNOS mRNA and protein levels, confirming its central role in downregulating the iNOS pathway and thereby limiting inflammation in liver cells [22].

The mechanisms by which adenosine exerts these effects were multifaceted. First, it inhibited NF-κB activation, a transcription factor critical for switching on the iNOS gene—an action that distinguishes adenosine from whole AHCC, which did not affect NF-κB directly in previous studies [22]. Second, adenosine suppressed IL-1 receptor type I (IL-1RI) expression, dampening the cellular response to inflammatory IL-1β signals [22].

In addition, adenosine reduced the stability of iNOS mRNA, meaning it caused the mRNA to degrade more quickly, limiting how much iNOS protein could be produced.

This was demonstrated using a luciferase reporter system, which showed reduced promoter activity and mRNA lifespan in the presence of adenosine [22]. The compound also inhibited iNOS antisense transcripts, which normally work to stabilize iNOS mRNA—adding another layer to its inhibitory action [22].

In conclusion, this study demonstrated that adenosine is a key functional compound in AHCC responsible for its anti-inflammatory and liver-protective actions. It blocks multiple stages of the NO production pathway, including:

• Inhibiting NF-κB activation,
• Suppressing IL-1β receptor signaling,
• Reducing iNOS gene expression and mRNA stability,
• And inhibiting stabilizing antisense transcripts.

These findings align with the 2007 study [21], providing direct confirmation of AHCC’s molecular target and clarifying how adenosine mediates both transcriptional and post-transcriptional suppression of liver inflammation, supporting its potential as a natural therapeutic agent for managing liver inflammation and protecting against liver injury. 

This anti-inflammatory potential was supported in a 2014 clinical trial on individuals with mildly elevated liver enzymes due to alcohol use—a population at risk of progressive liver damage [23].

Participants were randomly assigned to take either a placebo, 1 gram of AHCC, or 3 grams of AHCC daily for 12 weeks. Throughout the study, liver function and inflammation were assessed through blood tests for liver enzymes like ALT, measurements of inflammatory cytokines such as TNF-α and IL-1β, and levels of adiponectin, a hormone known for its anti-inflammatory and liver-protective effects.

The researchers also monitored adherence, safety, and overall physical health. 

By the end of the 12-week supplementation period, the researchers observed that ALT levels, a key marker of liver inflammation, improved significantly in both AHCC groups compared to the placebo group [23]. While those in the placebo group showed only a slight increase of around 4%, individuals taking AHCC experienced over a 220% improvement, a statistically significant difference (p = 0.04) that points to AHCC’s strong potential to support liver enzyme normalization.

Further supporting its benefit to liver health, AHCC supplementation led to significantly lower levels of TNF-α (p < 0.05) and IL-1β (p < 0.01)—two inflammatory markers that are commonly elevated during liver injury [23]. These reductions suggest that AHCC helped calm inflammation in the liver, potentially slowing or reversing stress-induced damage.

Additionally, both AHCC groups exhibited elevated levels of adiponectin (p < 0.01), which is particularly encouraging because adiponectin not only fights inflammation but also promotes metabolic and liver function stability [23]. This increase suggests that AHCC may do more than reduce damage—it may also help create a more resilient internal environment in the liver.

Importantly, the study reported no adverse effects, and participant adherence was high, confirming that AHCC was safe and well-tolerated over the course of the trial [23]. 

These human results complement the anti-inflammatory mechanisms observed in studies [21, 22], further validating AHCC’s role in calming liver inflammation and supporting enzyme normalization in early-stage liver stress.

A 2024 preclinical study investigated the protective effects of AHCC—referred to in the study as ECLM, a standardized extract of cultured Lentinula edodes mycelia—on liver damage caused by ischemia-reperfusion injury combined with partial hepatectomy (HIRI+PH), a model that mimics the liver trauma and inflammation experienced during surgeries or transplants [24].

When the liver temporarily loses and then regains blood supply, known as ischemia followed by reperfusion, a strong inflammatory response is triggered. This process, particularly when paired with the surgical removal of 70% of the liver (partial hepatectomy), can cause severe tissue damage, cell death, compromised liver function or post-surgical complications. The body responds with an influx of inflammatory mediators that further amplify the injury [24].

In the study, rats were fed either a standard diet or a diet supplemented with 2% ECLM (AHCC) for 10 days prior to undergoing a combined surgical procedure known as HIRI+PH. This procedure involves two components: hepatic ischemia-reperfusion injury (HIRI), where blood flow to the liver is temporarily interrupted and then restored—mimicking the type of stress the liver experiences during surgeries or transplants—and partial hepatectomy (PH), which is the surgical removal of a portion of the liver.

Together, these procedures create a highly demanding environment for the liver, allowing researchers to evaluate how well it can recover from damage.

Following surgery, liver and blood samples were collected at 3, 6, and 24 hours, and survival outcomes were assessed using a more intense version of the model involving 30 minutes of ischemia. This design allowed researchers to investigate whether AHCC supplementation could support liver resilience, reduce injury, and improve recovery under severe physiological stress [24].

Rats that received AHCC showed less liver damage and significantly reduced hepatocyte cell death, demonstrating a protective effect on liver tissue under extreme surgical stress [24]. In parallel, AHCC significantly improved liver enzyme profiles by lowering serum aminotransferase activity, a key marker of liver injury, indicating better functional preservation after the procedure [24].

Further analysis revealed that AHCC downregulated two major inflammatory genes: iNOS, which promotes oxidative stress, and CXCL1, which recruits immune cells to inflamed tissue. At the same time, it upregulated IL-10, an anti-inflammatory cytokine, suggesting that AHCC not only reduces damaging inflammation but also promotes a more balanced immune response [24].

In addition to reducing injury, AHCC enhanced liver regeneration. Researchers observed increased expression of hepatocyte growth factor (HGF), which plays a central role in liver repair, and a higher number of Ki-67-positive nuclei, indicating accelerated cellular regeneration in the liver 24 hours after surgery [24].

Crucially, in a more severe surgical model involving prolonged ischemia, AHCC significantly reduced mortality, underscoring its potential as a protective intervention during high-risk liver procedures [24].

These results demonstrate that AHCC may prevent liver injury associated with surgery by reducing inflammation, minimizing liver cell death, and enhancing tissue repair. Its ability to improve survival rates and modulate both injury and regeneration pathways positions AHCC as a promising nutritional strategy to support liver health and recovery in surgical or transplant settings.This study also reinforces earlier findings [21–23] that AHCC modulates both inflammatory and regenerative pathways.

In a related 2024 investigation into fibrosis, researchers investigated how AHCC may help prevent the progression of liver fibrosis, a major contributor to cirrhosis—a serious, often life-threatening condition for which there is currently no effective cure [25]. Liver fibrosis is primarily driven by the activation of hepatic stellate cells, which are responsible for producing excessive collagen and other scar-forming substances. When these cells stay activated, they accelerate the deterioration of liver tissue, pushing early-stage liver disease toward irreversible cirrhosis.

To investigate whether AHCC could counteract this process, researchers used both animal and cellular models. In mice, liver fibrosis was chemically induced using carbon tetrachloride, and the animals were given 3% AHCC orally to assess its protective potential [25]. In human hepatic stellate cells, scientists examined how AHCC affected genes and proteins known to be involved in fibrotic activity [25].

Mice that received AHCC had significantly reduced levels of key fibrosis markers, including collagen1a, α-smooth muscle actin (αSMA), and heat shock protein 47 (HSP47)—all of which are strongly associated with tissue scarring in the liver [25]. At the same time, AHCC increased levels of cytoglobin, a protein tied to quiescent or inactive stellate cells, suggesting that AHCC may help revert these cells from an active, fibrogenic state back to a healthier resting mode [25].

The mechanisms behind this effect appear to involve modulation of key immune signaling pathways. AHCC activated the TLR2-SAPK/JNK pathway, which led to more cytoglobin and less αSMA, helping reduce the fibrotic behavior of the cells [25]. In parallel, AHCC suppressed the TLR4-NF-κB pathway, which resulted in decreased collagen1a production, thereby limiting the overall progression of fibrosis [25].

These findings suggest that AHCC may help suppress liver fibrosis by reducing the activation of hepatic stellate cells, decreasing collagen production, and promoting a return to a non-fibrotic state. By modulating important immune pathways, AHCC may offer a natural strategy to slow or even prevent the advancement of liver fibrosis, particularly when taken during early stages of liver disease such as MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), potentially preventing progression to more advanced stages like MASH or cirrhosis. 

These pathways also tie directly into the same immune cascades implicated in studies [21, 22, 24], reinforcing that AHCC may prevent liver fibrosis by modulating stellate cell activation and promoting anti-fibrotic signaling.

Together, these studies illustrate that AHCC offers multi-level protection for the liver, acting on molecular, cellular, and systemic levels. From enhancing post-surgical survival in liver cancer patients, to reducing inflammation and oxidative damage, supporting liver enzyme normalization, promoting cell regeneration, and slowing fibrosis progression, AHCC demonstrates an exceptionally broad therapeutic profile. The overlapping findings across human and animal models further affirm its role as a natural liver-supportive compound with both preventive and restorative applications.

AHCC May Support Viral, Fungal and Bacterial Defense with Particular Focus On Human Papillomavirus (HPV)

Over the last two decades, AHCC has emerged as one of the most studied natural compounds for immune support, with research spanning bacterial, viral, and fungal infections—both acute and chronic. From early investigations in immunocompromised models to recent clinical trials in viral persistence like HPV, AHCC has demonstrated a consistent and multi-layered ability to modulate the immune system.

Across diverse studies, certain immune mechanisms repeatedly appear. AHCC has been shown to enhance natural killer (NK) cell activity [6, 7, 27, 29, 30, 33]—crucial for the body’s rapid response to infected or abnormal cells—and to improve T cell responses, including CD8+ and γδ subsets, which orchestrate long-term and targeted immunity [6, 7, 29, 30, 33, 34, 35]. A recurrent theme is AHCC’s ability to shift the immune profile toward a Th1-dominant state, marked by increased IL-12 and IFN-γ production [6, 27, 29, 30, 33, 34, 35] and, in some cases, reduced IL-4 and IFN-β [30, 34, 35, 37], which may otherwise interfere with effective viral clearance.

This immune shift is not just theoretical—it has translated into practical outcomes like faster pathogen clearance [6, 10, 26, 29, 30], lower levels of inflammation [10, 27, 32, 33], stronger antibody responses [7, 29, 33], and improved survival rates in infection models [6, 10, 26, 27, 28, 29, 33]. Some studies even show that AHCC offers long-term immune memory and lasting protection [28, 35].

The following section explores this robust body of evidence in detail—highlighting both the individual findings and the common threads that make AHCC a compelling addition to integrative immune support strategies.

AHCC and Bacterial & Fungal Infection

A foundational 2000 study laid the groundwork by exploring how AHCC may help defend the body against serious bacterial and fungal infections—especially in cases where the immune system is severely weakened [26]. Researchers focused on mice whose immune systems had been deliberately suppressed using a chemotherapy drug called cyclophosphamide, mimicking the immune-compromised state of patients undergoing cancer treatment or suffering from other immunodeficiencies.

In this vulnerable state, the mice were exposed to Candida albicans [26], a common fungal infection, and various dangerous bacteria including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA)—pathogens known for causing serious infections when the immune system is down.

The mice were given AHCC either orally or via injection for four consecutive days before they were infected. The results were promising:

• AHCC significantly prolonged the survival time of the infected mice [26]. This means the supplement helped their bodies resist infection long enough to reduce damage or fight it off.
• In the case of Candida albicans, AHCC-treated mice had fewer fungal cells in their kidneys [26], indicating that AHCC helped the body reduce fungal load, which is crucial in preventing organ damage and sepsis.
• When tested against lethal bacterial infections, AHCC showed protective effects against Pseudomonas aeruginosa and MRSA [26], two highly dangerous and often drug-resistant bacteria.

By reducing the number of pathogens and increasing survival time, AHCC demonstrated that it may prime or support the immune system in advance—a quality referred to as prophylactic or preventive action. This suggests that AHCC could be especially helpful for individuals at high risk of infection, such as those undergoing chemotherapy or experiencing compromised immunity. This early evidence of immune priming would go on to be echoed and expanded in later studies.

Building on this, a 2008 study explored how AHCC could support the immune system in fighting off serious bacterial infections [10]—particularly those that can arise after surgery, where infection is one of the leading causes of late complications and death.

Researchers used a mouse model of intramuscular bacterial infection to test whether AHCC could help the body clear infection faster and improve survival [10].

The results were striking. Mice that received AHCC were able to completely clear the infection by day 6, while the control group still had lingering bacterial loads [10]. Not only did AHCC help the body eliminate the infection faster, but it also reduced the number of bacteria present at day 5, showing a clear advantage in early bacterial control [10].

The reason behind this improved response lies in how AHCC affected the immune system. The AHCC group experienced an earlier peak in key immune-signaling molecules, including

• Interleukin-12 (IL-12)
• Tumor necrosis factor-alpha (TNF-α)
• Interleukin-6 (IL-6)

These cytokines help coordinate the body's defense by activating immune cells and prompting them to attack pathogens. In the AHCC group, these important messengers peaked two days earlier (on day 3) compared to the control group (day 5) [10]. Earlier activation means the immune system responded faster, which likely explains the faster bacterial clearance and recovery.

On a cellular level, AHCC also shifted the makeup of immune cells in the bloodstream [10]. Treated mice had more lymphocytes and monocytes—immune cells that are involved in long-term, targeted defense—and fewer polymorphonuclear cells, which are linked to short-term inflammation. This shift suggests that AHCC helps promote a more effective and sustainable immune response, instead of relying on short-lived, inflammatory immune reactions. These findings support the 2000 study’s results and introduce a key insight: AHCC promotes faster, more coordinated immune mobilization, reducing infection severity and improving outcomes [10, 26].

AHCC’s benefits against bacterial pathogens were further confirmed in 2022 when AHCC inhibited the growth and biofilm formation of Pseudomonas aeruginosa.

The study explored how AHCC may help combat infections caused by Pseudomonas aeruginosa, a bacteria classified by the World Health Organization as a top-priority pathogen due to its resistance to many antibiotics and its role in severe hospital-acquired infections [32].

One of the most concerning traits of P. aeruginosa is its ability to form biofilms—sticky bacterial communities that protect it from antibiotics and the immune system. AHCC was found to inhibit the growth rate of P. aeruginosa and significantly reduce its ability to form biofilms [32]. Disrupting biofilm formation is a key therapeutic goal because biofilms are a major reason why chronic infections caused by this bacterium are so difficult to treat.

In terms of mobility, bacteria like P. aeruginosa use different forms of movement—swimming, swarming, and twitching—to spread and invade host tissues. While AHCC did not affect swarming, it significantly hampered both swimming and twitching motility, meaning the bacteria’s ability to move and spread was limited [32]. These changes reduce its ability to infect new cells and establish deeper infections.

On a genetic level, AHCC was shown to reduce the expression of genes involved in bacterial metabolism, growth, and biofilm development. By turning down these genes, the bacteria become less capable of thriving and spreading within the host [32].

Importantly, AHCC also reduced the levels of exotoxin A, one of P. aeruginosa’s most harmful toxins. This toxin can cause tissue damage and suppress immune responses, so lowering it reduces the severity of the infection [32]. In infected intestinal epithelial cells (IEC18), there were fewer bacteria present when treated with AHCC, suggesting reduced bacterial invasion and improved host cell defense [32]. 

In immune cells called macrophages, AHCC helped lower the secretion of inflammatory cytokines IL-6, IL-10, and TNF, which are typically elevated during infection and contribute to systemic inflammation. By calming this inflammatory storm, AHCC helps prevent tissue damage caused by an overreactive immune response [32]. 

Mechanistically, these benefits were linked to a reduction in MAPK phosphorylation, a key step in the activation of cellular signaling that leads to inflammation and cytokine production. By modulating these pathways, AHCC reduced the bacteria’s ability to trigger excessive immune responses and invade host tissues [32].

In summary, this study suggests that AHCC may serve as a novel, natural strategy to help prevent or reduce the severity of P. aeruginosa infections by limiting bacterial growth, suppressing biofilm formation, reducing toxin production, calming excessive inflammation, and strengthening host defense systems [32].

The findings of a 2021 study suggest that AHCC helps support the body’s resilience and recovery, even without directly killing the pathogen.

The study explored how AHCC may help improve the clinical status of patients with pulmonary tuberculosis (TB) who are also infected with HIV, a group that faces significant immune challenges. HIV weakens the immune system, making it harder for patients to fight TB, which is already difficult to treat on its own. AHCC, known for its immune-supportive properties, was tested to see if it could offer added support alongside standard treatment [31].

Participants received either 3 grams of AHCC daily or a placebo, and their progress was monitored over six months through clinical evaluations and chest X-rays. Both groups showed some improvement over time, but the AHCC group consistently demonstrated greater and faster recovery across several key symptoms.

Shortness of breath, a common and distressing symptom in TB, improved more effectively in the AHCC group. By the end of the six months, only 20% of placebo patients had improved breathing, while this symptom was completely resolved in the AHCC group [31].

Appetite returned to normal in 100% of patients who received AHCC, compared to only 32% of those taking placebo. Appetite loss in TB/HIV patients is a major cause of malnutrition and weakness, so full appetite recovery suggests significant improvement in overall wellbeing [31].

This was further supported by body weight gain, which is a reliable indicator of recovery in TB. 96% of patients in the AHCC group gained weight, compared to 72% in the placebo group, showing that AHCC helped restore strength and nutritional balance more effectively [31].

Other improvements were seen in digestive symptoms. After 6 months, no patients in the AHCC group reported nausea, whereas 8% of those taking placebo still did. Vomiting was also eliminated in the AHCC group, while it persisted in 16% of the placebo group [31]. These changes suggest improved tolerance to treatment and better gastrointestinal function with AHCC supplementation.

When it came to lung recovery, chest X-rays were normal in 92% of the AHCC group by month six, compared to 80% in the placebo group. This points to faster lung healing and resolution of TB-related lesions in patients receiving AHCC [31].

Interestingly, while many clinical parameters improved with AHCC, there was no difference in the conversion rate of acid-fast bacillus (AFB) tests between groups. This means that while AHCC did not directly speed up bacterial clearance, it helped the body recover more efficiently from the disease’s effects [31].

In summary, six months of daily AHCC supplementation led to significant improvements in respiratory symptoms, appetite, weight gain, digestive tolerance, and lung healing in HIV/TB co-infected patients. These results support AHCC’s role as a valuable adjunct in managing complex immune-compromised infections, helping patients regain strength and quality of life even when facing two major infections simultaneously [31].

AHCC and Viral Infections

Several studies have also explored AHCC’s antiviral activity, with influenza infection serving as a primary model.

In 2006, researchers investigated whether AHCC could help the body fight off viral infections, specifically influenza A (H1N1) [27]—the same strain responsible for seasonal flu and past pandemics. The researchers were especially interested in how AHCC might improve innate immunity, which is the body’s first line of defense against infections. 

To test this, young mice were given AHCC at a dose of 1 gram per kilogram of body weight per day starting one week before they were infected with influenza, and the supplementation continued throughout the infection [27].

The results showed clear immune-supporting benefits:

• AHCC increased the survival rate of the mice infected with the flu. Mice that received AHCC were more likely to live through the infection compared to those that didn’t [27].
• It also reduced the severity of the illness and helped the mice recover faster, which was measured by how quickly they regained their body weight and repaired the lining of their lungs [27]—an area flu viruses typically damage.
• One of the key mechanisms behind this protection was the increase in natural killer (NK) cell activity, an essential part of the immune system that helps destroy virus-infected cells. AHCC boosted NK activity in the lungs on day 1 and day 4 after infection, and in the spleen on day 2—showing it had a sustained effect across multiple immune organs [27].

AHCC also increased the number and percentage of NK cells (identified by NK1.1+ markers) in the lungs [27], which means there were more virus-fighting cells available right where the flu virus attacks.

Interestingly, AHCC also reduced the number of infiltrating lymphocytes and macrophages [27], which are types of immune cells involved in inflammation. Too much of this infiltration can lead to lung damage, so reducing it helps protect the lungs from excessive inflammation.

In short, AHCC not only strengthened the immune system’s ability to respond to the flu virus—it did so in a way that balanced immunity: improving the body’s defense while reducing damaging inflammation. 

A 2007 study offered additional insight into the findings of the above-mentioned study [27]. Researchers examined whether AHCC could help the body build resistance against highly dangerous viruses, specifically the H5N1 bird flu [28], which has raised global concern due to its potential to cause pandemics. Researchers were focused on whether AHCC could strengthen the immune system enough to improve survival rates after exposure to such a deadly virus [28].

In this study, AHCC was administered for 7 consecutive days, and the results were promising:

• AHCC improved the survival rate by 30% in animals infected with the bird flu virus. This is a significant boost considering how deadly this virus can be [28].
• Even more encouraging, the protective effects of AHCC lasted for 3 to 4 weeks after supplementation ended [28]. This suggests that AHCC doesn’t just offer short-term immune support—it may help the immune system remain primed for a longer duration.

Taking AHCC helped prepare the immune system to fight off a serious viral threat, and that preparation lasted for several weeks. This means that AHCC may not only help during an active infection but may also act like a preemptive shield, keeping the immune system on alert for future threats. This lasting immune priming mirrors the long-term benefits seen in the 2008 bacterial infection study [10], reinforcing the idea that AHCC extends immune readiness beyond active infection.

The findings of studies [27] and [28] were further expanded by a 2009 study that investigated how AHCC supports immune defense against influenza by testing different daily doses of the supplement in mice infected with the H1N1 flu virus. The aim was to determine whether AHCC’s protective effects are dose-dependent, and to better understand how even low doses might improve immune performance in response to viral infection [6].

Researchers supplemented mice daily with 0.05, 0.1, 0.5, or 1 g/kg of AHCC and exposed them to a standard strain of influenza A (H1N1). The results showed a clear dose-dependent benefit: as the dose of AHCC increased, the mice experienced higher survival rates and less body weight loss, which is a key indicator of illness severity in this model [6]. In other words, AHCC helped the mice recover faster and survive better, with more pronounced effects at higher doses.

The researchers then focused on the lower 0.1 g/kg dose to explore whether even modest supplementation could still improve the immune response. They found that even this low dose enhanced viral clearance—meaning the body was able to get rid of the virus more quickly—and reduced weight loss, showing meaningful protection despite the smaller dose [6].

Interestingly, while low-dose AHCC did not increase the total number of natural killer (NK) cells—which are key immune defenders against viruses—it did improve their efficiency. The NK cells in AHCC-treated mice became better at killing virus-infected cells, even though the overall number of NK cells didn’t change [6]. This suggests that AHCC makes immune cells more effective, rather than just boosting their quantity. 

Together, these studies underscore AHCC’s ability to enhance both the speed and precision of antiviral immune responses [6, 10, 27, 28].

Another 2009 study explored how AHCC may strengthen immune defenses against West Nile Virus (WNV)—a virus that can be especially dangerous for the elderly and individuals with weakened immune systems. Since no vaccines or treatments for WNV are currently available for humans, the study looked at how AHCC could help reduce infection severity and improve survival outcomes [29].

In this research, mice were given AHCC at 600 mg/kg every other day, starting one week before being infected with WNV and continuing through days 1 and 3 after infection. The researchers then measured viremia levels (how much virus is in the blood), immune responses, and survival rates to assess how well the mice were able to fight off the virus [29].

Among young mice (6–8 weeks old), AHCC significantly lowered viremia, meaning there was less virus circulating in their bloodstream. Lower viremia levels indicate better viral control and a stronger immune response. AHCC-treated mice also had higher survival rates after infection compared to the untreated group, showing a clear protective benefit [29].

On an immune level, these mice produced more WNV-specific IgM and IgG antibodies, which are crucial for identifying and neutralizing the virus. There was also an increase in γδ T cells, a unique group of immune cells that play a frontline role in controlling viral infections. These results suggest that AHCC stimulates both the antibody response and cellular immunity, improving the body’s overall ability to eliminate the virus [29].

In aged mice (21–22 months old), who are typically more vulnerable to severe WNV infection, AHCC still had a notable effect. While these older mice didn’t survive at higher rates, they did show reduced viremia, indicating some level of viral suppression. AHCC also boosted WNV-specific IgG antibodies and enhanced Vγ1⁺ T cell activity, a protective immune subset that is often impaired with age [29].

In conclusion, this study showed that AHCC improves immune responses to WNV infection, particularly in young mice by increasing survival, reducing viral load, and enhancing key immune markers. While in older mice AHCC didn’t significantly improve survival, it still supported better immune function and reduced viral levels, suggesting potential as a supportive immune-enhancing supplement in viral defense [29].

Turning to humans, a 2013 clinical study investigated whether AHCC could help boost the immune system's response to seasonal influenza vaccination in healthy adults—a strategy increasingly explored to enhance vaccine efficacy [7]. Previous research had already shown that AHCC could protect mice from lethal influenza infections, especially when given before vaccination. Building on those findings, this study aimed to see if similar immune-enhancing effects occurred in humans.

Thirty healthy adults were recruited and randomly assigned to either an AHCC group or a control group. Everyone received the 2009–2010 seasonal flu vaccine. After vaccination, the AHCC group began daily supplementation of 3 grams of AHCC. Blood samples were taken before vaccination and again three weeks later to measure changes in immune cell populations and antibody levels [7].

By the end of the study, AHCC supplementation led to noticeable changes in immune cell activity. There was a significant increase in CD8+ T cells (P < .05)—which are crucial for killing virus-infected cells—and a trend toward higher natural killer T (NKT) cell levels (P < .1), known for bridging innate and adaptive immunity. These shifts suggest that AHCC helped strengthen the cellular arm of the immune system, which plays a vital role in controlling viral infections [7].

In addition to boosting T cell activity, AHCC also improved antibody production against influenza B. Participants who took AHCC showed significantly increased protective antibody titers three weeks after vaccination, whereas those in the control group did not experience a statistically significant improvement [7]. This is important because higher antibody titers translate to better protection against the flu virus, making the vaccine more effective.

In summary, AHCC supplementation shortly after vaccination enhanced both cellular immunity (via T cells and NKT cells) and antibody responses, particularly against influenza B [7]. This complements the murine influenza studies [6, 27, 28], indicating that AHCC’s antiviral benefits extend across species and immune challenges.

A 2023 study investigated how AHCC may support the body’s immune defense against SARS-CoV-2, the virus responsible for COVID-19, using two different mouse models to represent both healthy and highly vulnerable immune systems [33].

Mice that were given oral AHCC every other day for a week before and shortly after infection showed reduced viral load in their lungs—meaning they had fewer virus particles actively replicating in their bodies. Lowering viral load helps reduce the severity of illness and improves chances of recovery [33].

In the more severe infection model using K18-hACE2 transgenic mice (which are genetically modified to mimic human vulnerability to COVID-19), AHCC significantly reduced mortality, showing that it helped the body survive even high-risk viral infection [33].

One of the standout findings was that AHCC reduced lung inflammation, a major complication in COVID-19 that can lead to difficulty breathing and long-term lung damage. By calming excessive immune responses, AHCC helped protect lung tissue while still allowing the immune system to fight off the virus [33].

Immunologically, AHCC boosted both innate and adaptive immune responses. It increased γδ T cells in the spleen and lungs—immune cells that act quickly to detect and destroy infected cells before the virus can spread [33]. AHCC also promoted a T helper 1 (Th1)-prone response, which is particularly important for defending against viruses. Th1 responses help activate other immune cells and coordinate a targeted attack on the virus, while avoiding the overproduction of inflammatory signals that can lead to tissue damage [33].

In the BALB/c mouse model (representing a more balanced immune system), AHCC enhanced the production of virus-specific IgG antibodies—the type of antibodies that help neutralize the virus and provide longer-term immunity [33].

These mechanisms echo those found in earlier flu and WNV studies [6, 27, 29], highlighting a consistent pattern: AHCC strengthens both innate and adaptive arms of immunity, helping the body mount faster, more focused, and more durable responses.

Beyond influenza, AHCC also supported infection immunity in more specialized settings.

AHCC and Chlamydia

A 2021 study explored how AHCC may help reduce susceptibility to Chlamydia muridarum genital infection, particularly in cases where immune function is compromised by stress—a common factor known to weaken the body’s defenses [30].

Previous research had shown that cold-induced stress suppresses the immune system, leading to worse chlamydia infections in mice. However, when stressed mice were fed AHCC, they shed fewer bacteria from their genital tract, suggesting that AHCC played a role in restoring protective immunity. This study aimed to understand how AHCC helped modulate the immune system to produce this effect.

The researchers found that AHCC-fed stressed mice had significantly lower bacterial shedding, indicating a lower infection load [30]. At the same time, AHCC reduced plasma catecholamines—stress hormones like norepinephrine—which are known to impair immune responses when elevated. Lowering these hormones helped relieve stress-induced immune suppression, allowing the immune system to function more effectively.

One of the key mechanisms identified was that AHCC shifted the immune response toward a Th1 profile, which is the branch of the immune system that excels at clearing bacterial and viral infections—especially those that live inside cells, like chlamydia. This shift means the immune system becomes better at recognizing and destroying infected cells instead of overreacting with inflammation or focusing on less effective antibody-based responses. 

Specifically, there was increased expression of T-bet, a protein that acts like a switch, telling immune cells to activate the Th1 pathway. At the same time, levels of GATA-3 were reduced. GATA-3 pushes the immune system toward a Th2 response, which is more about producing antibodies and is less effective against bacteria that hide inside cells. By increasing T-bet and reducing GATA-3, AHCC helps steer the immune system into a more precise and infection-clearing mode [30]. This pattern of reinforcing a broader Th1 immune shift is also seen in the West Nile [29] and flu [6, 27] studies.

This Th1 shift also resulted in higher production of two critical immune signals: interleukin-12 (IL-12) and interferon gamma (IFN-γ). These are cytokines—messenger molecules the immune system uses to coordinate attacks. IL-12 helps activate natural killer cells and T cells, which directly destroy infected cells, while IFN-γ enhances the ability of immune cells to recognize and kill pathogens inside infected tissues. Together, they form a powerful one-two punch against intracellular infections like Chlamydia muridarum [30].

Meanwhile, levels of IL-4 were lowered. IL-4 is another cytokine, but it promotes a Th2 response, which can interfere with the immune system’s ability to clear certain types of infections. By reducing IL-4, AHCC helps remove a roadblock that would otherwise dampen the body's ability to eliminate bacteria hiding inside cells [30].

In addition to improving T cell responses, AHCC also boosted the activation of dendritic cells and natural killer (NK) cells, both of which are critical for identifying threats and launching immune responses. Dendritic cells act like scouts—detecting pathogens and informing the rest of the immune system—while NK cells are frontline defenders that can destroy infected or abnormal cells without needing prior exposure. AHCC improved their readiness and signaling power, which helped jump-start a faster and more effective immune response [30].

Finally, when bone marrow-derived dendritic cells (BMDCs)—a type of immune cell trained to communicate with T cells—were cultured with CD4+ T cells from AHCC-fed mice, the result was increased production of Th1 cytokines and decreased production of Th2 cytokines. This further confirmed that AHCC actively supports a shift toward the type of immune response that’s best at clearing stubborn infections like chlamydia. Altogether, this immune rebalancing created a stronger, more focused defense, improving the body’s ability to eliminate the infection efficiently [30].

AHCC and High Risk Human Papillomavirus (HR-HPV) Infections

Unlike acute infections, HPV is often persistent and difficult to clear, especially high-risk strains like HPV16 and HPV18 that can lead to cervical cancer. AHCC’s ability to modulate chronic immune activity—particularly by suppressing IFN-β and promoting IFN-γ—has shown promising effects in this context.

A 2019 study investigated whether AHCC could help clear persistent high-risk human papillomavirus (HR-HPV) infections, a major cause of cervical cancer, especially HPV16 and HPV18 strains [34]. Since there is currently no approved supplement or medicine specifically for HPV clearance, the research aimed to assess AHCC’s potential from lab to human trials.

In the lab (in vitro) phase, researchers treated cervical cancer cell lines that were HPV-positive (HPV16+, HPV18+, or both) and HPV-negative with AHCC at a daily dose of 0.42 mg/mL for 7 days, followed by a 7-day observation period. The result showed clearance of HR-HPV expression, meaning AHCC helped suppress the virus within infected cells [34].

The next step tested this in animal models using mice implanted with either HPV-positive or HPV-negative tumors. Mice were divided into three groups and received either AHCC (50 mg/kg/day), a vehicle (placebo), or no treatment at all for 90 days, with a 30-day follow-up period. Tumors were monitored, and blood samples were taken regularly to track immune system changes, particularly interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), and immunoglobulin G (IgG). The animals receiving AHCC showed suppression of HR-HPV in tumor tissue, confirming the in vitro results and suggesting that AHCC helped clear the virus at a systemic level [34].

Crucially, AHCC supplementation led to a reduction in interferon beta (IFN-β) to levels below 25 pg/mL. This was consistently observed in both animals and human participants who successfully cleared the virus. While IFN-β is an antiviral cytokine, its chronic elevation in persistent infections may actually prevent immune resolution. AHCC’s ability to reduce IFN-β appeared to help restore immune balance and promote virus clearance [34].

Finally, two pilot clinical trials involving women with confirmed persistent HR-HPV infections were conducted. In the first, 3 grams of AHCC daily for 5 weeks to 6 months resulted in HPV clearance in 4 out of 6 participants (66.7%). In the second study, a lower dose of 1 gram daily taken for up to 8 months resulted in HPV clearance in 4 out of 9 participants (44%) [34].

These results not only supported the lab and animal findings but also showed that AHCC may help the body’s immune system naturally clear persistent HR-HPV infections, which are notoriously difficult to resolve. The observed suppression of IFN-β in patients who cleared the virus suggests this might be a key immune mechanism triggered by AHCC.

In summary, AHCC supported HR-HPV clearance both in cell and animal studies and in early human trials, with its effects potentially tied to normalizing immune responses and reducing overactive interferon-beta levels [34].

A 2022 randomized controlled trial confirmed these effects [35].

The 2022 phase II randomized, double-blind, placebo-controlled study evaluated whether AHCC supplementation could help clear persistent high-risk human papillomavirus (HR-HPV) infections, especially in women over the age of 30 who had tested positive for HR-HPV for more than two years [35].

Fifty women were enrolled and randomly assigned to one of two groups. One group received a daily dose of 3 grams of AHCC for 6 months followed by 6 months of placebo, while the other group received placebo for the full 12 months [35]. Every three months, the researchers tested each participant’s HPV DNA and RNA status to confirm whether the virus was still active. They also monitored several key immune markers, including interferons (α, β, γ), immunoglobulin G1 (IgG1), T lymphocytes, and natural killer (NK) cells to assess how the immune system was responding throughout the study [35].

By the 6-month mark, 63.6% (14 out of 22) of the women in the AHCC group tested negative for both HPV RNA and DNA, meaning the virus was no longer detectable [35]. More importantly, of those who cleared the virus, 64.3% (9 out of 14) remained HPV-negative even after stopping AHCC supplementation for six additional months, suggesting a durable and lasting immune effect [35].

In contrast, only 10.5% (2 out of 19) in the placebo group cleared the virus after 12 months, showing that natural clearance without intervention was far less common [35].
Additionally, women in the placebo group who later opted to take AHCC in an unblinded extension of the study showed promising results as well—50% (6 out of 12) cleared the virus after 6 months of supplementation [35]. When combining both the original AHCC group and those who took it after the blinded trial, 58.8% of all AHCC-supplemented participants cleared their persistent HPV infections [35].

One of the most insightful findings was the role of interferon-beta (IFN-β)—a molecule that normally helps regulate immune responses. Women with persistent HPV infections had high baseline levels of IFN-β (around 60.5 pg/ml), but those who cleared the virus after taking AHCC had IFN-β levels drop below 20 pg/ml [35]. This suppression of IFN-β was linked to increases in both T lymphocytes and interferon-gamma (IFN-γ)—immune factors known to help destroy infected cells and viral particles. These changes were strongly associated with durable HPV clearance, and suggest that IFN-β may be a clinical marker worth monitoring in the future [35].

In conclusion, this study demonstrated that AHCC 3 g daily for 6 months was effective, safe, and well-tolerated for helping women clear persistent HR-HPV infections. With a response rate of nearly 59% and signs of long-term immune benefits, AHCC may offer a promising natural strategy to support immune system recovery and HPV clearance [35]. The correlation between IFN-β suppression and viral clearance adds a new layer of scientific understanding and may guide future therapeutic monitoring approaches.

A 2024 observational cohort study investigated the effects of Active Hexose Correlated Compound (AHCC) in combination with Lactobacillus crispatus M247 (a prebiotic) on women with chronic cervicitis or low-grade squamous intraepithelial lesions (L-SIL) caused by high-risk HPV (HR-HPV)—types like HPV 16 and 18 that are linked to cervical cancer [36]. While many cases of HR-HPV and L-SIL clear on their own, a portion of them can progress into high-grade lesions or even malignancy, making effective interventions essential.

The study enrolled 40 women and split them into two groups. Group A received AHCC and L. crispatus supplementation, while Group B underwent standard follow-up with no specific treatment [36]. The women were monitored over six months using molecular testing, biopsies, and colposcopy to track viral clearance and lesion progression. Researchers also tracked safety, adherence, and dropout rates.

The results were striking. By the 6-month mark, 73.3% of women in Group A had cleared their HR-HPV infection, while none in the control group (Group B) cleared the virus—a statistically significant difference (p < 0.001) [36]. This means the combination treatment demonstrated strong immune-enhancing effects that supported the body’s ability to eliminate the virus, which untreated women were unable to achieve over the same period.

In addition to viral clearance, 13% of women in Group A saw their cervical lesions (L-SIL) regress to chronic cervicitis, indicating tissue improvement. Meanwhile, 26.3% of women in the untreated group progressed to a more serious stage of disease—high-grade squamous intraepithelial lesions (H-SIL), which significantly differed from the treated group (p = 0.042) [36]. This shows that the AHCC and probiotic combination may not only help clear the virus but also prevent lesion progression and potentially lower the risk of developing cervical cancer.

Importantly, the treatment was well-tolerated with no side effects, and adherence was high. Although there was a 17.5% dropout rate, this was largely attributed to unrelated factors such as COVID-19 disruptions [36].

In conclusion, this study supports that AHCC combined with microbiome support is a promising, side-effect-free strategy for promoting HR-HPV clearance and regression of early cervical lesions, while also helping prevent their progression into more dangerous conditions [36]. 

A 2025 retrospective study assessed AHCC’s ability to prevent relapse of genital warts (condyloma acuminata) after cauterization. could help prevent recurrence in individuals who had undergone cauterization for condyloma acuminata—genital warts caused by human papillomavirus (HPV), one of the most common sexually transmitted infections globally [37]. Although cauterization removes visible warts, relapse is common, and no durable systemic treatment exists to reduce recurrence risk. The study aimed to explore whether AHCC could fill this therapeutic gap.

The researchers retrospectively reviewed the medical records of 133 patients who had been treated for condyloma acuminata between January 2019 and June 2022 and had undergone cauterization. Patients were divided into two groups—those who received AHCC supplementation and those who did not—and were followed up every three months for recurrence monitoring [37].

Interestingly, the AHCC group began with more severe disease, showing a higher number of condylomas and larger lesion diameters before treatment compared to the non-AHCC group (p = 0.006 and p = 0.004, respectively) [37]. Despite this, when researchers analyzed cases of recurrence, those who took AHCC had significantly fewer and smaller lesions than those who did not supplement (p = 0.019 and p = 0.042, respectively) [37].

This suggests that AHCC may help reduce the severity of relapse, even in those starting with a more advanced presentation. While AHCC did not prevent recurrence in all patients, its use was associated with milder recurrences, indicating a possible benefit in managing long-term disease burden [37].

No adverse effects were reported, and the authors noted AHCC’s potential as a safe, supportive, and non-pharmaceutical intervention for HPV-related conditions in the absence of approved systemic therapies. They also highlighted the need to explore IFN-β (interferon-beta) as a potential biomarker to tailor AHCC use more precisely—building on previous HPV studies that found lower IFN-β levels correlated with better HPV clearance outcomes [37].

In summary, this study reinforces the idea that AHCC may help control HPV-related symptoms and reduce the intensity of recurrence after standard treatments like cauterization, providing a promising nutritional support strategy in HPV care [37].

AHCC and Cancer

Cancer is not a single disease but a complex spectrum of conditions that require more than just tumor-targeting strategies—they demand support for the body’s own defense systems. 

Rather than acting through a single pathway, AHCC works on multiple fronts: it strengthens both innate immunity (via NK cells, dendritic cells, and γδ T cells) and adaptive immunity (enhancing CD4⁺ and CD8⁺ T cell responses), while also disrupting survival mechanisms used by cancer cells—such as the STAT3 and HSP27 pathways.

AHCC has also been shown to reduce inflammation, modulate antioxidant defenses, and restore immune balance during chemotherapy.

What makes AHCC especially promising in cancer care is its ability to work alongside conventional treatments, helping reduce toxicity, preserve quality of life, and enhance treatment effectiveness across a range of cancer types.

In the sections that follow, we explore how AHCC supports the body’s anti-cancer response through immune modulation, in synergy with chemotherapy, and across specific cancer types—revealing its potential as a powerful ally in integrative oncology.

AHCC’s Anti-Cancer Action

AHCC works against cancer through a multi-layered approach that both strengthens immune surveillance and directly disrupts cancer cell survival mechanisms. Its actions span across key branches of the immune system—innate and adaptive—as well as intracellular pathways that control tumor growth and resistance.

One of AHCC’s core strengths lies in its ability to enhance tumor immune surveillance, the body’s internal monitoring system that identifies and eliminates cancerous cells before they can establish or spread

In a 2005 study, mice that were orally administered AHCC showed a delayed onset of tumor development after being injected with melanoma and lymphoma cells, compared to control mice that received water [39]. This delay was linked to increased activation and proliferation of CD4+ helper T cells and CD8+ cytotoxic T cells, particularly those that were specific to tumor antigens. CD8+ T cells that produced interferon-gamma (IFN-γ)—a key immune signal for attacking cancer cells—were notably more abundant, indicating not just more T cells, but better-equipped ones with the molecular tools needed to recognize and destroy abnormal cells early [39].

Alongside this boost in adaptive immunity, AHCC also increased the number of natural killer (NK) cells and γδ T cells, which are part of the innate immune system and act as the body’s rapid responders against abnormal cells. These innate-like lymphocytes are crucial for catching early signs of cancer, especially when tumors attempt to evade standard immune detection, providing a fast-acting line of defense before the rest of the immune system is fully mobilized [39].

Diving deeper into the immune cascade, a 2008 human trial explored AHCC’s effect on dendritic cells—immune cells that serve as messengers between the innate and adaptive immune systems. Dendritic cells are responsible for recognizing abnormal or cancerous cells and presenting these “threats” to T cells to initiate a full immune response. In the AHCC group, researchers observed a significant increase in total dendritic cells, including both CD11c+ DC1 cells (which activate T cells to recognize and kill cancer) and CD11c− DC2 cells (which help regulate immune balance, preventing overactivation or misfiring) [6]. Not only did their numbers rise, but their function improved as well: the AHCC group showed a stronger mixed-leukocyte reaction, meaning the dendritic cells were more effective in stimulating immune activity and kickstarting the targeted T cell response [6]. 

These changes suggest that AHCC helps fortify the immune system’s frontline detection network, a key step in stopping cancer before it progresses.

Further up the immune chain, AHCC has also been shown to enhance the dialogue between monocytes (innate immune cells) and T helper (Th) cells. A 2012 study demonstrated that AHCC stimulated human monocytes to produce large amounts of IL-1β, a cytokine that drives the development of Th1 and Th17 cells [18]. These T helper subsets play critical roles in cancer defense: Th1 cells release IFN-γ to mobilize cellular attacks on tumors, while Th17 cells release IL-17 to fortify inflammation and tissue-based defenses [18]. The presence of IL-1β helped amplify this cascade, and when blocked, the effect disappeared—highlighting how AHCC stimulates a potent, cytokine-driven immune response that bridges early immune detection and sustained T cell action, creating an ongoing immune presence in areas where tumors may try to grow [18].

Beyond immune activation, AHCC directly targets tumor cells through intracellular signaling pathways. In a 2018 in vitro study, ovarian cancer cells treated with AHCC exhibited significantly reduced viability, pointing to an antiproliferative effect (i.e., AHCC helps stop cancer cells from multiplying) [50]. This was traced to AHCC’s ability to inhibit the phosphorylation of STAT3, a protein that—when constantly activated—helps cancer cells grow, avoid death, and form new blood vessels to feed themselves. AHCC increased SHP-1, a protein that deactivates STAT3, and this deactivation led to the downregulation of survival-promoting genes like cyclin D1, Bcl-2, Mcl-1, survivin, and VEGF [50]. By disrupting this cancer-promoting signaling network, AHCC not only halts cancer cell growth but makes them more vulnerable to apoptosis—a natural process of programmed cell death that the body uses to eliminate damaged or dangerous cells, essentially helping the body recognize and remove malfunctioning cells more efficiently.

This ability to interfere with cancer cell defenses was further supported in another 2018 study focusing on CDCP1, a protein linked with tumor invasiveness and metastasis. In gemcitabine-resistant pancreatic cancer cells, AHCC significantly reduced CDCP1 expression, which is often elevated in aggressive cancers. Importantly, this reduction was specific and did not affect unrelated proteins, suggesting that AHCC selectively weakens cancer’s metastatic machinery without harming healthy cells [51]. These effects build on AHCC’s previously documented ability to lower other tumor-associated proteins like HSP27, HSF1, and SOX2, marking it as a promising agent in drug-resistant cancer settings by dismantling the molecular infrastructure cancer cells rely on to spread and survive.

AHCC also contributes to a healthier internal environment that’s less favorable for tumor growth. In a 2015 study, when AHCC was combined with the synthetic immune stimulant KSK-CpG ODN in a melanoma model, the combination led to smaller tumor size, stronger antioxidant defenses, and a rebalanced immune signaling network [46]. Levels of harmful reactive oxygen species (ROS) dropped significantly, while antioxidant enzyme glutathione peroxidase (GPx) rose. This shift in redox balance helps reduce the oxidative stress that cancer cells often exploit for growth, since high oxidative stress can damage DNA and promote mutations that fuel cancer progression [46]. 

Immune signals also changed: nitric oxide levels increased (supporting immune activation and blood flow), IL-10 (an anti-inflammatory cytokine) rose, and pro-tumor cytokine IL-6 dropped significantly, signaling a more tumor-resistant immune profile and an environment less supportive of tumor development [46].

Perhaps most strikingly, a 2022 study revealed that AHCC can even amplify the effects of advanced cancer immunotherapy. When combined with dual immune checkpoint blockade (DICB)—a treatment that unleashes T cells by blocking PD-1 and CTLA-4—AHCC further reduced tumor size, boosted the function and proliferation of CD8+ T cells, and enhanced granzyme B production, a molecule used by T cells to kill cancer [52]. This means the immune system not only recognized the tumor but had more active and better-armed cells to eliminate it.

The synergy didn’t stop at the immune system: AHCC also altered the gut microbiome, increasing levels of Ruminococcaceae bacteria, which have been associated with better immunotherapy outcomes [52]. When antibiotics eliminated these bacteria, the benefits disappeared, suggesting AHCC works both by directly enhancing immune function and indirectly by supporting gut-driven immune modulation, making it a unique two-pronged approach.

Altogether, these findings show that AHCC operates on multiple fronts:

1. Strengthens the immune system’s early detection (dendritic cells)
2. Amplifies immune system response (T cells, NK cells, cytokines),
3. Disrupts key cancer growth pathways (STAT3, CDCP1), and
4. Supports the body’s internal balance through oxidative stress reduction and microbiome support.

This layered, synergistic approach may explain why AHCC has shown such promise across various cancer models—not by replacing standard treatments, but by helping the body mount a more robust, targeted, and sustained defense against cancer.

AHCC in Combination with Chemotherapy

When combined with chemotherapy, AHCC has demonstrated a unique ability to both support the body’s resilience and enhance the effects of anticancer treatments across various types of cancer. Its effects are twofold: reducing treatment-related side effects and amplifying immune and antitumor responses. Several studies show overlapping mechanisms that reinforce AHCC’s synergistic potential.

In a 2007 study examining cisplatin—a potent chemotherapy drug known for its efficacy but also its severe kidney and bone marrow toxicity—AHCC not only enhanced the tumor-reducing effects of cisplatin but also mitigated multiple side effects [40]. It improved food intake and body weight, reduced kidney damage as measured by blood urea nitrogen and creatinine levels (which are markers that rise when the kidneys are under strain), and improved hematopoietic recovery—meaning the bone marrow was better able to produce healthy blood cells after being suppressed by chemotherapy. This is vital because chemotherapy often limits the body’s ability to regenerate red and white blood cells, which are needed for oxygen transport, immunity, and healing. This effect was also observed in a later breast cancer study where AHCC reduced the need for granulocyte colony-stimulating factor (G-CSF), a drug used to treat chemotherapy-induced neutropenia—a dangerous drop in white blood cells that raises infection risk [42]. This indicates a recurring protective effect of AHCC on bone marrow function and blood cell counts across different cancer treatments.

Similarly, in a 2013 breast cancer trial, patients receiving anthracyclines and taxanes experienced significantly fewer neutrophil-related complications when supplemented with AHCC (odds ratio: 0.30; p=0.016) [42]. Neutrophils are a type of white blood cell critical for fighting infections, and when their levels drop too low—a common side effect of chemotherapy—patients become much more vulnerable to illness. Like in the cisplatin study, this suggests AHCC helps stabilize blood cell counts, reducing infection risk and improving chemotherapy tolerance. Though different in cancer type, both studies reflect AHCC’s consistent benefit in preserving hematologic health and reducing dose-limiting toxicity, a key barrier in oncology treatment [40, 42].

In gemcitabine-resistant pancreatic cancer, AHCC took on a different but equally important role. A 2014 in vitro study showed that AHCC downregulated HSP27, a heat-shock protein known to protect cancer cells and promote chemotherapy resistance.

Alone, AHCC reduced cancer cell viability. But in combination with gemcitabine, it triggered a synergistic cytotoxic effect, significantly amplifying cancer cell death beyond what either agent achieved alone [43]. This restoration of drug sensitivity—by suppressing resistance-promoting proteins—is a distinct mechanism from the bone marrow protection seen in other studies but highlights how AHCC can help overcome chemoresistance in stubborn cancers.

A similar dual-action was observed in a 2015 study pairing AHCC with low-dose 5-fluorouracil (5-FU) in a liver cancer mouse model [44]. AHCC reversed liver damage and bone marrow suppression, echoing the protective effects seen in the cisplatin and breast cancer studies [40, 42]. But it also enhanced 5-FU’s direct antitumor impact by increasing tumor cell apoptosis (a process of programmed cell death that helps eliminate cancerous or damaged cells) and shifting the immune system into a more activated state. Elevated levels of IL-2 and TNF-α—key immune signaling molecules—plus increases in CD3⁺, CD4⁺, and NK cells, mirrored mechanisms observed in earlier immune surveillance studies [39], showing repeated immune-enhancing pathways across contexts. Notably, the combination also altered gene expression within tumors—upregulating pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2, making cancer cells more vulnerable to elimination [44]. These intracellular effects support AHCC’s role in promoting cancer cell clearance when used alongside chemotherapy.

Beyond immune activation and toxicity protection, AHCC also appears to help preserve quality of life (QOL) in cancer patients. In a 2014 study where 24 patients received AHCC during a chemotherapy cycle, researchers tracked immune suppression using human herpesvirus-6 (HHV-6) DNA in saliva—a biomarker that rises when the immune system is under significant stress or suppression. When AHCC was introduced, HHV-6 levels dropped, while patient-reported QOL scores on the EORTC QLQ-C30 questionnaire improved, particularly in fatigue and general well-being [45]. This immune-supportive effect—reflected by reduced viral reactivation—aligns with AHCC’s ability to help maintain natural killer (NK), T cell, and dendritic cell function seen in other cancer-related studies [6, 39].

In patients with pancreatic ductal adenocarcinoma (PDAC), a 2016 clinical study showed that AHCC reduced inflammatory markers such as C-reactive protein (CRP)—a substance produced by the liver in response to inflammation and often elevated during chemotherapy-induced tissue stress. It also better preserved serum albumin—an important protein that helps maintain fluid balance and reflects overall nutritional and immune status [47]. A stable albumin level indicates that the body is better coping with treatment and maintaining essential functions. This anti-inflammatory effect, paired with a significant reduction in taste disorders (which can lead to appetite loss and poor nutrition) and improved prognostic scores (mGPS), demonstrates how AHCC may stabilize the body under chemotherapy stress, maintaining resilience and treatment adherence. Again, this aligns with earlier observations where AHCC prevented liver and bone marrow damage during chemotherapy [40, 44].

Finally, in a 2017 randomized trial on ovarian and peritoneal cancer patients undergoing six cycles of chemotherapy, AHCC supplementation resulted in significantly higher CD8+ T cell counts by the sixth cycle (median 392.5 vs. 259.5/μL, p = 0.03), which are key cytotoxic cells involved in targeting and killing cancer cells [16]. These immune cells help monitor and destroy abnormal or infected cells before they can spread. While overall CD4/CD8 changes weren't significantly different, this mid-treatment boost in CD8⁺ counts may support long-term antitumor immunity—mirroring findings from the melanoma surveillance model where AHCC elevated IFN-γ-producing CD8+ T cells [39].

The immune benefit was accompanied by a reduction in chemotherapy-induced nausea and vomiting, further supporting its role in improving tolerance and overall treatment experience [16].

In summary, AHCC’s combination with chemotherapy consistently shows a pattern of enhanced immune surveillance, reduced toxicity, improved treatment tolerance, and—when relevant—synergistic tumor suppression. Whether it's reducing chemotherapy resistance via HSP27 suppression [43], protecting organs and bone marrow [40, 44], boosting CD8+ T cells [16], or lowering inflammation and improving quality of life (QOL) [45, 47], AHCC supports the body through multiple mechanisms that reinforce rather than compete with standard cancer treatments. These repeated outcomes across cancers and chemotherapy types position AHCC as a uniquely supportive and potentially synergistic agent in modern oncology care.

AHCC and Studies on Specific Cancer Types

Liver Cancer (Hepatocellular Carcinoma)

A 2002 clinical study suggests that AHCC® (Active Hexose Correlated Compound) may offer protective benefits for the liver, particularly in patients recovering from liver cancer surgery [19].

Researchers conducted a prospective cohort study involving 269 patients with hepatocellular carcinoma (HCC)—the most common type of primary liver cancer. All patients had undergone curative surgery to remove their tumors. Of these, 113 patients received AHCC orally after surgery, while the remaining served as a control group [19].

The study found that patients in the AHCC group experienced a significantly longer period without cancer recurrence. This means that AHCC may help reduce the likelihood of the cancer returning, which is a major concern in HCC patients following surgery [19].

The overall survival rate was also significantly higher in the AHCC group. Statistically, the hazard ratio for recurrence was 0.639 and for death was 0.421, both showing a substantial reduction in risk compared to those who did not take AHCC [19].

AHCC appears to provide liver-protective benefits in individuals with liver cancer by improving post-surgical outcomes, extending survival, and reducing recurrence rates.

This highlights its potential role as a supportive therapy for liver health, especially in patients at risk of liver dysfunction or tumor relapse.

Additional support comes from a 2015 liver cancer model treated with low-dose 5-fluorouracil (5-FU). Researchers explored how AHCC could enhance the antitumor effects of low-dose 5-fluorouracil (5-FU)—a commonly used chemotherapy drug—by supporting the immune system. Using a mouse model of liver cancer (Hepatoma 22), the study compared the effects of 5-FU alone to 5-FU combined with AHCC, and evaluated a range of immune and tumor-related responses [44].

One of the standout findings was that AHCC had no apparent toxicity, as it did not negatively impact diet consumption or body weight during the study [44]. Even more importantly, AHCC helped reverse liver damage and bone marrow suppression caused by 5-FU, both of which are common side effects that limit the use of chemotherapy [44].

In terms of immune enhancement, AHCC significantly increased the proportions of CD3⁺ T cells, CD4⁺ helper T cells, and natural killer (NK) cells in the peripheral blood compared to 5-FU alone [44]. It also raised the CD4⁺/CD8⁺ T cell ratio, a marker often used to assess the strength and balance of the immune response. These immune cell boosts were accompanied by elevated levels of key cytokines, including interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α), both of which play crucial roles in activating and sustaining immune defenses against cancer [44].

The combination of AHCC and 5-FU didn’t just support immunity—it also amplified the tumor-killing effects of the chemotherapy. Mice that received AHCC alongside 5-FU showed greater tumor tissue apoptosis, or programmed cell death, as measured by TUNEL staining [44]. This enhanced antitumor response was further backed by molecular data showing that the combination therapy increased the expression of Bax, a protein that promotes apoptosis, while decreasing Bcl-2, a protein that protects cancer cells from dying [44].

Taken together, these results highlight several key benefits: AHCC not only reduced 5-FU toxicity and restored immune health, but also boosted the direct tumor-killing power of the chemotherapy itself. By shifting the balance toward immune activation and apoptosis, AHCC enhanced both the safety and the efficacy of 5-FU treatment in this cancer model [44]. These immune benefits parallel those seen in earlier immune surveillance studies [39].

Pancreatic Cancer

Pancreatic cancer is notoriously aggressive and often resistant to treatment. 

A 2014 study focused on addressing chemotherapy resistance in pancreatic cancer—specifically resistance to gemcitabine, a frontline chemotherapy drug often used in this aggressive cancer type. A major contributor to this resistance is heat-shock protein 27 (HSP27), a stress-related protein known to protect cancer cells from damage and make them less responsive to treatment.

The research investigated how AHCC might affect this resistance mechanism in a gemcitabine-resistant pancreatic cancer cell line called KLM1-R. When these resistant cancer cells were treated with AHCC, researchers observed a down-regulation of HSP27 [43]. This is an important finding because lowering HSP27 may remove one of the key shields that protects cancer cells from chemotherapy, potentially making them more vulnerable to treatment.

Moreover, AHCC alone showed a direct cytotoxic effect on the pancreatic cancer cells, indicating it can reduce cancer cell viability on its own. But even more promising was the result of combining AHCC with gemcitabine. The combination treatment didn’t just add to the effects—it produced a synergistic cytotoxic response, meaning the two agents worked better together than either could alone [43].

This synergistic interaction suggests that AHCC could restore or even enhance the effectiveness of gemcitabine in resistant cancer types. By suppressing HSP27 and boosting chemotherapy-induced cell death, AHCC may offer new hope in treating gemcitabine-resistant pancreatic cancers—a notoriously hard-to-treat form of the disease [43].

In summary, AHCC enhanced the sensitivity of pancreatic cancer cells to chemotherapy by reducing HSP27 expression, and when used alongside gemcitabine, it significantly amplified cancer cell death, supporting the potential for AHCC to be used in combination therapies for better treatment outcomes in resistant cancers [43].

In 2018, researchers followed up with another KLM1-R (pancreatic cancer cells) study.

This 2018 study focused on how AHCC influences the expression of a specific cancer-related protein, CUB domain-containing protein 1 (CDCP1), in gemcitabine-resistant pancreatic cancer cells (KLM1-R) [51]. CDCP1 is a transmembrane glycoprotein known to be upregulated in many types of cancers and has been strongly associated with tumor invasion and metastasis—the ability of cancer to spread to other tissues.

In this study, the pancreatic cancer cells were treated with AHCC at a concentration of 10 mg/mL for 48 hours. Researchers then used Western blot analysis to measure protein levels. The results showed that AHCC significantly reduced the expression of CDCP1, while actin—a housekeeping protein used for comparison—remained unchanged. This indicates that the effect was specific to CDCP1 and not due to general cell damage or protein degradation.

The CDCP1/actin ratio was significantly lower in AHCC-treated cells, meaning that AHCC specifically downregulated this protein (p < 0.05) [51]. Reducing CDCP1 expression is beneficial, as high levels of this protein are linked with increased cancer cell aggressiveness, invasiveness, and the likelihood of metastasis. Therefore, AHCC’s ability to suppress CDCP1 suggests it may help inhibit the malignant progression of resistant pancreatic cancer—particularly important in treatment-resistant cancers like KLM1-R cells that no longer respond to conventional chemotherapy like gemcitabine [51].

These findings builds on the previous study's mechanism of action, which showed that AHCC also downregulated other tumor-associated proteins like HSP27, HSF1, and SOX2, further highlighting its potential to weaken cancer cells at multiple levels of their growth and stress-response machinery. 

The clinical significance of these findings was reinforced in a 2016 human study of patients with unresectable pancreatic ductal adenocarcinoma (PDAC) receiving gemcitabine

In this 2016 study, researchers investigated whether AHCC could help reduce the adverse effects of chemotherapy in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) who were being treated with gemcitabine (GEM), a common chemotherapy drug. Patients were divided into two groups: one received 6.0 g of AHCC daily for two months, while the other did not. The study then compared various markers of treatment-related toxicity and inflammation between these groups.

The results showed that AHCC significantly suppressed the rise in C-reactive protein (CRP) (P = 0.0012), which is a key marker of inflammation often elevated during chemotherapy. Lower CRP levels suggest that AHCC helped reduce systemic inflammation, which is a frequent driver of fatigue, weakness, and tissue stress during cancer treatment [47].

Alongside this, the decline in serum albumin levels—a common sign of deteriorating nutritional status and inflammation—was significantly less severe in the AHCC group (P = 0.0007). Maintaining higher albumin levels reflects better overall health, immune status, and treatment resilience, all of which are critical for patients undergoing chemotherapy [47].

One of the most tangible quality-of-life benefits observed was that taste disorders, a common and frustrating side effect of gemcitabine, occurred much less frequently in the AHCC group (17%) compared to the control group (56%) (P = 0.0007). Taste alterations can contribute to appetite loss, malnutrition, and emotional distress, so this finding suggests AHCC may help patients maintain appetite and food enjoyment during treatment [47].

Another important finding was the difference in modified Glasgow Prognostic Score (mGPS), a marker combining CRP and albumin levels to predict prognosis and treatment tolerance. Only 14% of AHCC users reached grade 3 mGPS—a level indicating poor prognosis—compared to 53% in the control group (P = 0.0005) [47]. This result suggests that AHCC may help preserve treatment tolerance and potentially improve outcomes by stabilizing key prognostic indicators during chemotherapy.

In summary, AHCC significantly reduced inflammation, improved nutritional indicators, lowered chemotherapy-induced taste disorders, and preserved a better prognostic profile in patients with pancreatic cancer undergoing gemcitabine treatment [47]. These findings highlight AHCC’s potential to not only reduce treatment-related side effects but also help maintain quality of life and systemic stability during aggressive cancer therapies.

Ovarian and Peritoneal Cancer

In a 2017 randomized clinical study investigating patients undergoing chemotherapy for epithelial ovarian or peritoneal cancer, AHCC was evaluated for its ability to support immune function and reduce chemotherapy-related side effects [16]. Over the course of six cycles of chemotherapy, patients received either AHCC at a daily dose of 3 grams or a placebo. The primary focus was on immune modulation—specifically, changes in two critical types of immune cells: CD4+ and CD8+ T lymphocytes, which play essential roles in coordinating and executing immune responses.

Although there were no statistically significant differences between the AHCC and placebo groups in overall changes from baseline to post-treatment in CD4+ or CD8+ levels, an important observation was made at the sixth cycle of chemotherapy: CD8+ T cell levels were significantly higher in the AHCC group (median 392.5/μL) compared to the placebo group (259.5/μL), with a p-value of 0.03 [16]. This elevation in CD8+ cells is important because these cytotoxic T lymphocytes directly attack tumor cells and viral infections, and maintaining or enhancing their levels during chemotherapy may contribute to stronger antitumor surveillance and immune defense.

In terms of side effects, patients in the AHCC group experienced significantly less nausea and vomiting, which are among the most debilitating and common adverse effects of chemotherapy. However, there was a trade-off noted in the form of increased reports of muscle pain in the AHCC group, although the clinical impact of this was not deeply discussed [16].

There were no significant differences between groups in terms of bone marrow suppression or overall quality of life scores measured using the FACT-G questionnaire.

Still, the preserved immune function, particularly the enhanced CD8+ T cell count at later chemotherapy cycles, suggests that AHCC may help sustain immune resilience during intensive cancer treatment—a factor that could be vital for long-term recovery and recurrence prevention [16].

A 2018 in vitro study further examined AHCC’s role in ovarian cancer.

In this study, researchers investigated the direct effects of AHCC on ovarian cancer cells, with a focus on how it may inhibit their growth and survival [50]. The findings showed that AHCC significantly reduced ovarian cancer cell viability, meaning the treated cancer cells were less likely to survive compared to untreated controls. This highlights AHCC’s potential as an antiproliferative agent, capable of slowing or stopping the uncontrolled growth of cancer cells.

To understand how this occurred, the researchers explored the molecular pathways involved and found that AHCC inhibited the phosphorylation (activation) of STAT3, a signaling protein that plays a key role in cancer progression. When STAT3 is continuously activated (a common feature in many cancers), it promotes the expression of genes that help cancer cells grow, resist cell death, and form new blood vessels. By blocking STAT3 activation, AHCC was able to interfere with this cancer-promoting process [50].

Interestingly, the study also showed that AHCC increased the levels of SHP-1, a protein that deactivates STAT3 by removing its phosphate groups. When the cells were treated with pervanadate—a substance that prevents SHP-1 from working—the inhibitory effect of AHCC on STAT3 was reversed, confirming that SHP-1 is likely responsible for AHCC’s effect on STAT3.

Additionally, AHCC treatment led to suppressed expression of multiple genes controlled by STAT3, including cyclin D1 (which drives cell division), Bcl-2, Mcl-1, and survivin (which all help cancer cells avoid death), and VEGF (which supports tumor blood vessel formation). By downregulating these survival and growth-promoting genes, AHCC disrupted the cellular machinery that allows cancer to thrive [50].

Altogether, these findings demonstrate that AHCC exerts an antiproliferative effect on ovarian cancer cells by blocking a major cancer survival pathway (STAT3). This not only slows tumor cell growth but also promotes pathways that make the cells more susceptible to death. This is similar to the mechanism observed in pancreatic cancer studies where AHCC suppressed resistance proteins [43, 51].

Leukemias: Acute Myeloid Leukemia (AML) & Chronic Lymphocytic Leukemia (CLL)

Acute Myeloid Leukemia (AML) is a particularly aggressive and deadly blood cancer, especially in patients over 60 who often cannot tolerate intensive chemotherapy. 

In 2017, AHCC was tested in both lab and animal models of Acute Myeloid Leukemia (AML). 

AHCC was shown to trigger programmed cell death (apoptosis) in AML cells, specifically through Caspase-3 activation, a central enzyme involved in the execution phase of apoptosis. Additionally, AHCC activated Caspase-8 and increased the expression of Fas and TRAIL, two surface markers known to initiate the extrinsic apoptotic pathway—a process where cells are signaled from the outside to self-destruct. This suggests that AHCC doesn't just cause general cell damage but instead activates targeted pathways that tell leukemia cells to die [49].

Importantly, when AHCC was tested on healthy donor monocytes—a type of normal immune cell—it did not induce the same apoptotic response. In fact, Caspase-3 activation was suppressed in healthy monocytes, meaning that AHCC showed a selective effect against cancer cells while sparing healthy immune cells. This cancer-specific cytotoxicity is a highly desirable trait in any potential cancer therapy [49].

The findings were further validated in a murine AML engraftment model, where human leukemia cells were introduced into mice. In this model, AHCC significantly increased the survival time of the mice and reduced leukemia (blast) cell counts, showing that these cellular effects translated into real-world disease suppression and extended life expectancy [49].

In summary, AHCC induced targeted apoptosis (cell death) in AML cells via the extrinsic pathway, enhanced survival in AML-bearing mice, and spared healthy immune cells, making it a compelling candidate for adjuvant use in treating AML, particularly in elderly or chemo-intolerant patients [49].

Building on this, a 2023 study focused on Chronic Lymphocytic Leukemia (CLL). 

Researchers explored the effects of Active Hexose-Correlated Compound (AHCC) on chronic lymphocytic leukemia (CLL)—a slow-growing but currently incurable cancer that affects older adults and is characterized by the accumulation of abnormal CD19⁺CD5⁺CD23⁺ B cells in the blood and lymphoid tissues [53]. 

A major challenge in treating CLL is the supportive tumor microenvironment, particularly the role of nurse-like cells (NLCs). These myeloid-derived cells are manipulated by CLL cells to promote tumor survival, proliferation, and even drug resistance, acting similarly to tumor-associated macrophages. Since conventional therapies often overlook these tumor-supporting cells, NLCs represent a unique and valuable therapeutic target.

Building on previous work that showed AHCC selectively killed acute myeloid leukemia (AML) cells while sparing healthy monocytes [49], the researchers hypothesized that AHCC might also disrupt the NLC-mediated support system in CLL [53]. When CLL patient-derived peripheral blood mononuclear cells (PBMCs) were treated with AHCC, a direct cytotoxic effect against CLL cells was observed. Beyond directly targeting the leukemia cells, AHCC significantly reduced the number of NLCs and altered their tumor-supportive phenotype, weakening the microenvironment that typically shelters the cancer from treatment [53].

To confirm these effects in vivo, AHCC was tested in two different mouse models: Eµ-TCL1 for CLL and Mll^PTD/WT Flt3^ITD/WT for AML. In both models, AHCC treatment resulted in reduced tumor burden and extended survival—a particularly impressive outcome for CLL, which is notoriously difficult to eradicate [53]. Moreover, in the CLL mouse model, AHCC enhanced the efficacy of anti-tumor antibody therapy, suggesting a synergistic effect when used in combination with standard treatments [53].

These findings reveal that AHCC exerts both direct antileukemic activity and indirect immune-modulating effects by disrupting tumor-supportive cells, offering a dual mechanism: targeting both cancer cells and their supportive microenvironment [53]

By weakening the cancer’s defenses and enhancing immune-targeted therapies, AHCC may open up new opportunities in treating chronic and difficult-to-manage blood cancers like CLL [53].

Breast Cancer

A 2013 study evaluated whether AHCC could reduce the severity of side effects commonly experienced during breast cancer chemotherapy, particularly with drugs like anthracyclines and taxanes [42]. These chemotherapy agents are powerful but are often associated with neutropenia—a condition in which white blood cells (neutrophils) drop to dangerously low levels, increasing the risk of infection. Neutropenia is a dose-limiting toxicity, often requiring treatment delays or supportive care interventions like granulocyte colony-stimulating factor (G-CSF) injections.

Among 41 women undergoing adjuvant chemotherapy for breast cancer at Nagumo Clinic in Tokyo, some were given AHCC in addition to standard treatment, while others were not. The researchers tracked various chemotherapy-related adverse events, with a particular focus on blood cell counts and liver enzymes. The results revealed that the group taking AHCC experienced significantly fewer neutrophil-related complications compared to those not taking AHCC (odds ratio: 0.30; p=0.016), indicating a markedly reduced risk of severe neutropenia [42].

Additionally, the AHCC group required significantly less G-CSF support—a medication typically given to stimulate the production of neutrophils—highlighting AHCC’s potential to help maintain more stable white blood cell levels without relying as heavily on pharmaceutical interventions [42]. While there was a slightly higher rate of liver enzyme (γ-glutamyl transpeptidase) changes in the AHCC group, this was not statistically significant and did not indicate clinical harm.

In summary, AHCC supplementation during chemotherapy appeared to help reduce the frequency and severity of neutropenia, potentially improving treatment tolerance and reducing the need for supportive medications like G-CSF [42]. This mirrors the bone marrow support observed in cisplatin and 5-FU studies [40, 44], confirming AHCC’s role in hematopoietic recovery and immune stabilization.

The findings of this study support AHCC’s use as a complementary approach to mitigate one of the most challenging and treatment-limiting side effects in breast cancer care.

Altogether, these cancer-specific studies reveal that AHCC supports treatment from multiple angles—improving immune surveillance, lowering inflammation, enhancing chemotherapy sensitivity, and selectively targeting tumor-supportive cells. Whether it’s solid tumors like liver, pancreatic, and ovarian cancer or blood cancers like AML and CLL, AHCC consistently reinforces the body’s defense systems while working synergistically with conventional therapies to improve outcomes.

AHCC May Help Regulate Blood Sugar & Manage Diabetes

While AHCC is best known for its immune-modulating and anti-inflammatory effects, research also suggests it may help regulate blood sugar and support pancreatic health—two crucial factors in diabetes prevention and management.

In a preclinical study using a widely accepted model of diabetes, researchers tested AHCC’s ability to protect against diabetes onset in rats exposed to streptozotocin (STZ), a compound that selectively damages insulin-producing cells in the pancreas, leading to high blood sugar and symptoms that closely mimic type 1 diabetes [54]. To evaluate AHCC’s protective potential, rats were given 4% AHCC in their drinking water prior to and after receiving a single dose of STZ.

The results were striking. Rats that received STZ without AHCC developed hallmark signs of diabetes: elevated blood glucose levels, significantly lower insulin levels, poor weight gain, and increased markers of liver stress and oxidative damage—including elevated serum GOT and GPT (liver enzymes that rise when the liver is under strain) and lipid peroxides (a byproduct of oxidative stress) [54].

However, when rats were treated with AHCC, these negative effects were largely reversed. Blood glucose levels normalized, insulin levels were restored, and healthy weight gain resumed. AHCC also reduced the elevated GOT and GPT enzyme levels and brought down lipid peroxide levels, indicating both liver protection and reduced oxidative stress [54]. These findings suggest AHCC may help protect multiple organs affected by diabetes, including the pancreas and liver.

A closer look at pancreatic tissue revealed another important insight: STZ had drastically reduced the number of insulin-producing beta cells in the islets of Langerhans—clusters of cells in the pancreas responsible for maintaining blood sugar balance. But in rats treated with AHCC, these insulin-producing cells were preserved, and insulin staining within the islets returned to near-normal levels [54]. This implies that AHCC not only helps maintain blood sugar but also supports the survival and function of the very cells that produce insulin.

Altogether, these findings suggest AHCC may help regulate blood sugar by:

• Protecting pancreatic beta cells from damage,
• Preserving insulin production,
• Reducing oxidative stress and liver strain,
• And normalizing blood glucose levels even under diabetic challenge.

While these results are from animal studies and further research is needed in humans, they point to a promising potential role for AHCC in blood sugar regulation and diabetes prevention strategies [54].

AHCC and Pets

AHCC May Help Prevent Disease Progression in Dogs Infected with Leishmania

Leishmaniosis is a serious parasitic disease caused by Leishmania infantum, and it’s especially common in certain parts of Europe, South America, and the Mediterranean.

A recent randomized, double-blind, placebo-controlled study explored the preventive potential of AHCC when combined with dietary nucleotides in dogs infected with Leishmania infantum—a disease that can lie dormant in dogs while still posing a risk of transmission to other animals and humans. 

Dietary nucleotides are the building blocks of DNA and RNA that, when added to the diet, can support immune function, tissue repair, and overall cellular health—especially during stress or illness.

Many dogs in endemic areas remain clinically healthy despite infection, but they can progress to active disease over time. Although treatment is not recommended in dogs with subclinical infection (where the dog is infected but shows no clinical signs of disease) these animals should be managed to prevent disease progression and parasite transmission to human beings or to other dogs [55]. 

This study aimed to investigate whether long-term supplementation could delay or prevent that progression.

Forty-six clinically healthy, Leishmania-infected dogs were enrolled and divided into two groups: one received a placebo, while the other was given a daily supplement containing AHCC and nucleotides for 12 months. Throughout the year, clinical signs were monitored using a validated scoring system, and blood, urine, and bone marrow samples were assessed for markers of infection and immune response [55].

The findings were notable. Only 3 out of 20 dogs (15%) in the supplement group developed active disease, compared to 10 out of 22 (45.5%) in the placebo group—a statistically significant difference (P = 0.047), suggesting a strong protective effect of the supplement [55]. In addition to slowing disease progression, the supplement group showed a consistent and significant reduction in Leishmania-specific antibodies, as measured by ELISA, at all checkpoints (P < 0.01), indicating improved immune regulation over time [55]. This matters because high antibody levels in leishmaniosis are associated with immune system imbalance and worsening disease.

By day 180, dogs receiving AHCC and nucleotides also had significantly lower clinical severity scores (P = 0.014), meaning they exhibited fewer signs of illness as the infection progressed. This effect was not observed in the placebo group, highlighting the supplement’s potential to keep infected animals in a healthier state for longer [55].

Importantly, no significant adverse effects were reported, confirming the supplement’s safety for long-term use [55].

Overall, this study shows that daily supplementation with AHCC and nucleotides may help maintain immune balance in Leishmania-infected dogs, reducing their chances of developing clinical disease, and potentially decreasing the risk of parasite transmission to others [55].

How To Buy A Good Quality AHCC Supplement?

Choosing a good quality mushroom supplement can be a daunting task, as there are many options available in the market. However, there are a few key things to consider when selecting a high-quality mushroom supplement:

Safety Tests

Heavy metals and pesticides tests are safety tests which will indicate whether mushrooms are safe to consume.

At Antioxi, all our mushrooms are third-party tested and verified to ensure heavy metals, mycotoxins, pesticides, herbicides, microbial contaminants, ethylene oxide (ETO), and polycyclic aromatic hydrocarbons (PAHs) are all within safe limits.

How It's Made

Unlike many mushroom supplements that rely on hot water or alcohol extraction, AHCC is produced through a specialized method known as submerged fermentation—a process that transforms the natural compounds of shiitake mycelia into a highly bioavailable and immune-supportive form. If you’re considering AHCC, it’s essential to choose a product that follows this process, as the method directly affects its quality and effectiveness.

The process begins with liquid culturing of shiitake mycelium in a nutrient-rich medium under sterile, controlled conditions. This is the submerged fermentation stage, where the mycelia grow and begin producing valuable bioactive compounds.

Next comes enzymatic decomposition, where specific enzymes—cellulase and hemicellulase—are used to break down the tough fungal cell walls. This step is crucial, as it releases immune-modulating components like alpha-glucans and oligosaccharides that would otherwise remain trapped and unabsorbed.

After the enzymes have done their work, a heat treatment step is used to deactivate them and stabilize the extract. The mixture is then filtered to remove insoluble residues, keeping only the liquid fraction that contains the active compounds. 

Finally, the solution is concentrated and spray-dried, resulting in the finished AHCC powder used in supplements.

This method is what gives AHCC its signature profile—low molecular weight, high absorption, and reliable immune-supporting benefits. Products that do not follow this fermentation-based process may lack the bioactive compounds that make AHCC effective.

To guarantee the top-notch quality of your AHCC supplement, check whether the product has utilised a submerged fermentation method.

Click the link below to learn more about what to look for when choosing a high-quality mushroom supplement.

Learn More

Read the Supplement Label

To make an informed decision, it’s essential to understand how to read supplement labels correctly. Labels can often be misleading, and knowing what to look for, such as beta-glucan content, fruiting body vs. mycelium, and extraction method, can help you avoid low-quality products.

Please read our full guide on how to decode supplement labels here: How to Read Supplement Labels

Click the link above to learn more about what to look for when choosing a high-quality mushroom supplement.

Dose, Safety, Side Effects

Dose

Baseline Dose
Start with 2 capsules or 1 gram per day for general wellness. This helps you experience the foundational benefits of AHCC.

Enhanced Dose
For more pronounced effects, please get in touch with us. Our team can help you determine the best approach for your needs.

Flexible Dosage Regimen
Whether you prefer splitting the dose throughout the day or taking it all at once, the choice is yours. For optimal absorption, it is recommended to consume mushrooms on an empty stomach. However, if you have a sensitive constitution, consider splitting the dose and taking it after a meal.

Feeling unsure about where to begin? Schedule your free private online consultation with Marko, our Founder, and discover the perfect products to meet your wellness goals.

Click here to book a free consultation with Marko.

Safety

Individuals with diabetes are advised to seek guidance from their healthcare provider before incorporating AHCC into their diet, as it may impact blood sugar levels. 

Some studies suggest that AHCC may stimulate the immune system. Therefore, individuals with autoimmune diseases should seek medical guidance before considering the use of AHCC.

For individuals who are pregnant, breastfeeding, are using prescription medication or have an autoimmune disease, it is crucial to consult with a healthcare professional before considering the use of AHCC mushrooms.

Do not consume AHCC if you are allergic to mushrooms.

MEDICATION INTERACTIONS

While AHCC is generally well tolerated, it interacts with the liver enzyme CYP2D6, which is responsible for metabolizing a wide range of medications. AHCC is both a substrate and an inducer of this enzyme, meaning it is broken down by CYP2D6 and may also influence how the enzyme processes other substances [41].

This can impact how quickly your body clears certain medications—potentially lowering their effectiveness if they’re metabolized too fast. Additionally, one study found that AHCC might interfere with hormone-regulating enzymes in individuals with a specific genetic profile (COMT variant), which could reduce the efficacy of certain hormone therapies [48].

For this reason, we suggest speaking with your doctor if you’re using AHCC alongside medications typically processed by the liver, especially if they relate to pain, depression, heart function, or hormone therapy.

For an at-a-glance overview, see the table below, which summarizes how AHCC may interact with various liver enzymes and hormone regulation, and also lists examples of substances that could be affected [41, 48]. 

Individuals who are taking the following medications should also consult their healthcare provider before incorporating AHCC into their regimen:

• Medications for diabetes management
• Medication for liver disease / dysfunction
• Medications to suppress the immune system

If you have any concerns regarding the interaction between AHCC and your medications, it's a good idea to discuss it with your healthcare provider. They can offer you the most appropriate guidance.

Please bear in mind that the information we provide is for educational purposes and shouldn't be considered a replacement for professional medical advice. 

Your health and safety are important to us, and we want to ensure all our customers use our products to their benefit, not detriment.

Side Effects

Several human clinical trials and animal studies have assessed the safety of AHCC, and to date, no serious adverse effects have been reported. In fact, AHCC has consistently demonstrated strong tolerability even at higher doses and in medically vulnerable populations.

In a prospective clinical trial involving patients with unresectable pancreatic cancer undergoing chemotherapy, participants took 6 grams of AHCC daily for 2 months alongside gemcitabine treatment [47]. There were no reports of toxicity, and AHCC appeared to help preserve overall health and nutritional status during treatment [47].

Two randomised controlled studies further reinforce the safety of AHCC in healthy individuals. In both trials, participants took 3 grams of AHCC daily for 2–3 weeks following influenza vaccination [7,9]. Across both studies, no adverse events were reported [7,9].

Finally, a dose-dependent animal study explored the safety of AHCC at doses ranging from 0.05 to 1 g/kg per day in mice infected with influenza [6]. Even at the highest dose, there were no signs of toxicity. Instead, AHCC helped reduce weight loss and enhance viral clearance, confirming its immune-supportive effects without harmful side effects [6].

In summary, available data from both human and animal studies suggest that AHCC is well-tolerated at daily doses of up to 6 grams in adults, with no observed liver, kidney, or systemic toxicity. Whether used short-term or as ongoing support, AHCC appears to be a safe option for immune health and broader wellbeing.

How To Take AHCC For Health Support

Powders vs. Capsules

For those with a fast-paced lifestyle, intricate recipes might not be in the cards. That's precisely why Antioxi has crafted an our version of AHCC: Hexose Mycelium Extract available in convenient capsule form.

If you're a cooking enthusiast or favour the convenience of a powder, our Hexose Mycelium  Extract in powder form could be an ideal option for you. Our Hexose Mycelium Extract can be seamlessly incorporated into smoothies, stews, coffee and all your other favourite meals and drinks.

It's essential to note that there is no difference in potency between our powdered extracts and capsules. Our capsules contain the exact same powdered extract, guaranteeing uniform effectiveness throughout our product line.

Frequently Asked Questions

Is It Safe To Consume Medicinal Mushrooms During Pregnancy Or Whilst Breastfeeding?

While medicinal mushrooms can offer some great benefits during pregnancy such as strengthening immune health, improving digestion and of course the much needed energy boost, there is unfortunately not yet enough information regarding studies during pregnancy and whilst breastfeeding where we can confidently give advice.

The best would be to consult with your healthcare provider and/or midwife.

Can Children Use Medicinal Mushrooms?

Research regarding the use of medicinal mushrooms by children is still at its infancy. There is however an interesting study conducted in 2018 which investigated the effects of Reishi on immune system cells of 3-5 year olds. [56]

The study showed that Reishi increased immune system cell counts in the peripheral blood, which are crucial for defending against infections. The treatments were also well-tolerated and safe, with no abnormal increases in serum creatinine or hepatic aminotransferases. While the study shows promise in the safety and effectiveness of the use of medicinal mushrooms in children, we do always suggest consulting with your child's doctor prior to introducing anything new into their diet.

If you do get the go ahead we suggest reducing the diet to 1/4 of a dose for young children.

These findings suggest the need for more extended controlled clinical trials to evaluate the effectiveness of medicinal mushrooms in preventing infections in children.

What Is The Difference Between The Powder And Capsules?

There is no difference in terms of benefits. The only difference is preference of use.

What Is The Difference Between Using The 8 Mushroom Blend And Using An Individual Mushroom?

Our 8-blend mushroom product is like an all-in-one health elixir. It's perfect for those seeking overall well-being, boosting digestion, or just looking for a daily health lift.

However, if you're using mushrooms as targeted support for a specific health concern, say, Lion's Mane for cognitive clarity or Reishi for stress relief, the individual route is your best bet.

Are There Any Allergy Precautions/Medication Interactions?

Individuals with diabetes are advised to seek guidance from their healthcare provider before incorporating AHCC into their diet, as it may impact blood sugar levels. 

Some studies suggest that AHCC may stimulate the immune system. Therefore, individuals with autoimmune diseases should seek medical guidance before considering the use of AHCC.

For individuals who are pregnant, breastfeeding, are using prescription medication or have an autoimmune disease, it is crucial to consult with a healthcare professional before considering the use of AHCC mushrooms.

Do not consume AHCC if you are allergic to mushrooms.

MEDICATION INTERACTIONS

While AHCC is generally well tolerated, it interacts with the liver enzyme CYP2D6, which is responsible for metabolizing a wide range of medications. AHCC is both a substrate and an inducer of this enzyme, meaning it is broken down by CYP2D6 and may also influence how the enzyme processes other substances [41].

This can impact how quickly your body clears certain medications—potentially lowering their effectiveness if they’re metabolized too fast. Additionally, one study found that AHCC might interfere with hormone-regulating enzymes in individuals with a specific genetic profile (COMT variant), which could reduce the efficacy of certain hormone therapies [48].

For this reason, we suggest speaking with your doctor if you’re using AHCC alongside medications typically processed by the liver, especially if they relate to pain, depression, heart function, or hormone therapy.

For an at-a-glance overview, see the table below, which summarizes how AHCC may interact with various liver enzymes and hormone regulation, and also lists examples of substances that could be affected [41, 48]. 

Individuals who are taking the following medications should also consult their healthcare provider before incorporating AHCC into their regimen:

• Medications for diabetes management
• Medication for liver disease / dysfunction
• Medications to suppress the immune system

If you have any concerns regarding the interaction between AHCC and your medications, it's a good idea to discuss it with your healthcare provider. They can offer you the most appropriate guidance.

Please bear in mind that the information we provide is for educational purposes and shouldn't be considered a replacement for professional medical advice.

Your health and safety are important to us and we want to ensure all our customers use our products to their benefit, not detriment.

How is Your Hexose Mycelium Extract Made?

Our Hexose Mycelium Extracted is crafted by way of submerged fermentation.

The process begins with liquid culturing of shiitake mycelium in a nutrient-rich medium under sterile, controlled conditions. This is the submerged fermentation stage, where the mycelia grow and begin producing valuable bioactive compounds.

Next comes enzymatic decomposition, where specific enzymes—cellulase and hemicellulase—are used to break down the tough fungal cell walls. This step is crucial, as it releases immune-modulating components like alpha-glucans and oligosaccharides that would otherwise remain trapped and unabsorbed.

After the enzymes have done their work, a heat treatment step is used to deactivate them and stabilize the extract. The mixture is then filtered to remove insoluble residues, keeping only the liquid fraction that contains the active compounds.

Finally, the solution is concentrated and spray-dried, resulting in the finished AHCC powder used in supplements.

This method is what gives Hexose Mycelium Extract its signature profile—low molecular weight, high absorption, and reliable immune-supporting benefits.

Resources

1. Takanari, J., Hirayama, Y., Homma, K., Miura, T., Nishioka, H., & Maeda, T. (2014). Effects of active hexose correlated compound on the seasonal variations of immune competence in healthy subjects. Journal of Evidence-Based Complementary & Alternative Medicine, 20(1), 28–34. https://doi.org/10.1177/2156587214555573  
2. Mascaraque, C., Suárez, M. D., Zarzuelo, A., Sánchez de Medina, F., & Martínez-Augustin, O. (2014). Active hexose correlated compound exerts therapeutic effects in lymphocyte driven colitis. Molecular nutrition & food research, 58(12), 2379–2382. https://doi.org/10.1002/mnfr.201400364 
3. Doursout, M.-F., Liang, Y., Sundaresan, A., Wakame, K., Fujii, H., Takanari, J., Devakottai, S., & Kulkarni, A. (2016). Active hexose correlated compound modulates LPS-induced hypotension and gut injury in rats. International Immunopharmacology, 39, 280–286. https://doi.org/10.1016/j.intimp.2016.07.023
4. Daddaoua, A., Martínez-Plata, E., López-Posadas, R., Vieites, J. M., González, M., Requena, P., Zarzuelo, A., Suárez, M. D., Sánchez de Medina, F., & Martínez-Augustin, O. (2007). Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. The Journal of Nutrition, 137(5), 1222–1228. https://doi.org/10.1093/jn/137.5.1222
5. Mallet, J. F., Graham, É., Ritz, B. W., Homma, K., & Matar, C. (2016). Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4. European journal of nutrition, 55(1), 139–146. https://doi.org/10.1007/s00394-015-0832-2 
6. Nogusa, S., Gerbino, J., & Ritz, B. W. (2009). Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutrition research (New York, N.Y.), 29(2), 139–143. https://doi.org/10.1016/j.nutres.2009.01.005 
7. Roman, B. E., Beli, E., Duriancik, D. M., & Gardner, E. M. (2013). Short-term supplementation with active hexose correlated compound improves the antibody response to influenza B vaccine. Nutrition research (New York, N.Y.), 33(1), 12–17. https://doi.org/10.1016/j.nutres.2012.11.001 
8. Terakawa, N., Matsui, Y., Satoi, S., Yanagimoto, H., Takahashi, K., Yamamoto, T., Yamao, J., Takai, S., Kwon, A. H., & Kamiyama, Y. (2008). Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled trial. Nutrition and cancer, 60(5), 643–651. https://doi.org/10.1080/01635580801993280 
9. Gardner, E. M., Beli, E., Kempf, L. P., Lifton, D., & Fujii, H. (2010). Active hexose correlated compound (AHCC) improves immune cell populations after influenza vaccination of healthy subjects. The FASEB Journal, 24(S1), lb327–lb327. https://doi.org/10.1096/fasebj.24.1_supplement.lb327 
10. Aviles, H., O'Donnell, P., Orshal, J., Fujii, H., Sun, B., & Sonnenfeld, G. (2008). Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection. American journal of surgery, 195(4), 537–545. https://doi.org/10.1016/j.amjsurg.2007.05.045 
11. Yin, Z., Fujii, H., & Walshe, T. (2010). Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon-γ and/or tumor necrosis factor-α in healthy adults. Human immunology, 71(12), 1187–1190. https://doi.org/10.1016/j.humimm.2010.08.006 
12. Takanari, J., Sato, A., Waki, H., Miyazaki, S., Uebaba, K., & Hisajima, T. (2018). Effects of AHCC® on Immune and Stress Responses in Healthy Individuals. Journal of evidence-based integrative medicine, 23, 2156587218756511. https://doi.org/10.1177/2156587218756511 
13. Love, K. M., Barnett, R. E., Holbrook, I., Sonnenfeld, G., Fujii, H., Sun, B., Peyton, J. C., & Cheadle, W. G. (2013). A natural immune modulator attenuates stress hormone and catecholamine concentrations in polymicrobial peritonitis. The journal of trauma and acute care surgery, 74(6), 1411–1418. https://doi.org/10.1097/TA.0b013e31829215b1 
14. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., & Bitto, A. (2017). Oxidative Stress: Harms and Benefits for Human Health. Oxidative medicine and cellular longevity, 2017, 8416763. https://doi.org/10.1155/2017/8416763
15. Ye, S. F., Ichimura, K., Wakame, K., & Ohe, M. (2003). Suppressive effects of Active Hexose Correlated Compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress. Life sciences, 74(5), 593–602. https://doi.org/10.1016/j.lfs.2003.06.038 
16. Suknikhom, W., Lertkhachonsuk, R., & Manchana, T. (2017). The Effects of Active Hexose Correlated Compound (AHCC) on Levels of CD4+ and CD8+ in Patients with Epithelial Ovarian Cancer or Peritoneal Cancer Receiving Platinum Based Chemotherapy. Asian Pacific journal of cancer prevention : APJCP, 18(3), 633–638. https://doi.org/10.22034/APJCP.2017.18.3.633 
17. Hou, Y. N., Deng, G., & Mao, J. J. (2019). Practical Application of "About Herbs" Website: Herbs and Dietary Supplement Use in Oncology Settings. Cancer journal (Sudbury, Mass.), 25(5), 357–366. https://doi.org/10.1097/PPO.0000000000000403 
18. Lee, W. W., Lee, N., Fujii, H., & Kang, I. (2012). Active Hexose Correlated Compound promotes T helper (Th) 17 and 1 cell responses via inducing IL-1β production from monocytes in humans. Cellular immunology, 275(1-2), 19–23. https://doi.org/10.1016/j.cellimm.2012.04.001 
19. Matsui, Y., Uhara, J., Satoi, S., Kaibori, M., Yamada, H., Kitade, H., Imamura, A., Takai, S., Kawaguchi, Y., Kwon, A. H., & Kamiyama, Y. (2002). Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. Journal of hepatology, 37(1), 78–86. https://doi.org/10.1016/s0168-8278(02)00091-0
20. Cowawintaweewat, S., Manoromana, S., Sriplung, H., Khuhaprema, T., Tongtawe, P., Tapchaisri, P., & Chaicumpa, W. (2006). Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment. Asian Pacific journal of allergy and immunology, 24(1), 33–45. https://pubmed.ncbi.nlm.nih.gov/16913187/ 
21. Matsui, K., Kawaguchi, Y., Ozaki, T., Tokuhara, K., Tanaka, H., Kaibori, M., Matsui, Y., Kamiyama, Y., Wakame, K., Miura, T., Nishizawa, M., & Okumura, T. (2007). Effect of active hexose correlated compound on the production of nitric oxide in hepatocytes. JPEN. Journal of parenteral and enteral nutrition, 31(5), 373–381. https://doi.org/10.1177/0148607107031005373 
22. Tanaka, Y., Ohashi, S., Ohtsuki, A., Kiyono, T., Park, E. Y., Nakamura, Y., Sato, K., Oishi, M., Miki, H., Tokuhara, K., Matsui, K., Kaibori, M., Nishizawa, M., Okumura, T., & Kwon, A. H. (2014). Adenosine, a hepato-protective component in active hexose correlated compound: its identification and iNOS suppression mechanism. Nitric oxide : biology and chemistry, 40, 75–86. https://doi.org/10.1016/j.niox.2014.05.007 
23. Kim, H., Kim, J. H., & Im, J. A. (2014). Effect of Active Hexose Correlated Compound (AHCC) in alcohol-induced liver enzyme elevation. Journal of nutritional science and vitaminology, 60(5), 348–356. https://doi.org/10.3177/jnsv.60.348 
24. Nakatake, R., Okuyama, T., Ishizaki, M., Yanagida, H., Kitade, H., Yoshizawa, K., Nishizawa, M., & Sekimoto, M. (2024). Hepatoprotection of a Standardized Extract of Cultured Lentinula edodes Mycelia against Liver Injury Induced by Ischemia-Reperfusion and Partial Hepatectomy. Nutrients, 16(2), 256. https://doi.org/10.3390/nu16020256 
25. Urushima, H., Matsubara, T., Qiongya, G., Daikoku, A., Takayama, M., Kadono, C., Nakai, H., Ikeya, Y., Yuasa, H., & Ikeda, K. (2024). AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway. American journal of physiology. Gastrointestinal and liver physiology, 327(6), G741–G753. https://doi.org/10.1152/ajpgi.00134.2024 
26. Ishibashi, H., Ikeda, T., Tansho, S., Ono, Y., Yamazaki, M., Sato, A., Yamaoka, K., Yamaguchi, H., & Abe, S. (2000). Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 120(8), 715–719. https://doi.org/10.1248/yakushi1947.120.8_715 
27. Ritz, B. W., Nogusa, S., Ackerman, E. A., & Gardner, E. M. (2006). Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. The Journal of nutrition, 136(11), 2868–2873. https://doi.org/10.1093/jn/136.11.2868 
28. Fujii, H., Nishioka, H., Wakame, K., & Sun, B. (2007). Nutritional food Active Hexose Correlated Compound (AHCC) enhances resistance against bird flu. Japanese Journal of Complementary and Alternative Medicine, 4(1), 37–40. https://doi.org/10.1625/jcam.4.37 
29. Wang, S., Welte, T., Fang, H., Chang, G. J., Born, W. K., O'Brien, R. L., Sun, B., Fujii, H., Kosuna, K., & Wang, T. (2009). Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. The Journal of nutrition, 139(3), 598–602. https://doi.org/10.3945/jn.108.100297 
30. Belay, T., Sahu, R., Martin, E., Brown, K., Rolen, C., Hankins, S., Punturi, B., Patterson, M., Chambers, C., Kirby, B., & Butchar, J. (2021). Active hexose-correlated compound restores gene expression and protein secretion of protective cytokines of immune cells in a murine stress model during Chlamydia muridarum genital infection. Infection and Immunity, 89(4), e00786-20. https://doi.org/10.1128/IAI.00786-20 
31. Madolangan, J., Yusuf, I., Djaharuddin, I., Wahyudin, E., & Bukhari, A. (2021). The Active Hexose Correlated Compound (AHCC®) effect on clinical outcome of pulmonary tuberculosis in HIV-infected patients. Teikyo Medical Journal, 44(3), 827. https://www.teikyomedicaljournal.com/volume/TMJ/44/03/the-active-hexose-correlated-compound-ahcc-effect-on-clinical-outcome-of-pulmonary-tuberculosis-in-hiv-infected-patients-610e29bb4c305.pdf
32. Tena-Garitaonaindia, M., Ceacero-Heras, D., Montoro, M. D. M., Sánchez de Medina, F., Martínez-Augustin, O., & Daddaoua, A. (2022). A standardized extract of Lentinula edodes cultured mycelium inhibits Pseudomonas aeruginosa infectivity mechanisms. Frontiers in Microbiology, 13, 814448. https://doi.org/10.3389/fmicb.2022.814448 
33. Singh, A., Adam, A., Rodriguez, L., Peng, B.-H., Wang, B., Xie, X., Shi, P.-Y., Homma, K., & Wang, T. (2023). Oral Supplementation with AHCC®, a Standardized Extract of Cultured Lentinula edodes Mycelia, Enhances Host Resistance against SARS-CoV-2 Infection. Pathogens, 12(4), 554. https://doi.org/10.3390/pathogens12040554 
34. Smith, J. A., Mathew, L., Gaikwad, A., Rech, B., Burney, M. N., Faro, J. P., Lucci, J. A., 3rd, Bai, Y., Olsen, R. J., & Byrd, T. T. (2019). From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections. Frontiers in oncology, 9, 173. https://doi.org/10.3389/fonc.2019.00173 
35. Smith, J. A., Gaikwad, A. A., Mathew, L., Rech, B., Faro, J. P., Lucci, J. A., 3rd, Bai, Y., Olsen, R. J., & Byrd, T. T. (2022). AHCC® Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections. Frontiers in oncology, 12, 881902. https://doi.org/10.3389/fonc.2022.881902 
36. Salimbeni, V., Martinelli, C., Porto, L., Le Donne, M., Alibrandi, A., Di Pierro, F., Cau, F., Granese, R., Iannone, V., Marchetta, L., & Ercoli, A. (2024). A prospective observational study to evaluate impact of oral supplementation with AHCC and Lactobacillus crispatus M247 on HPV clearance and low-grade squamous intraepithelial lesion regression. Annals of Research in Oncology, 4(1), 3–18. https://www.annals-research-oncology.com/wp-content/uploads/2024/03/AnnResOnc_Martinelli.pdf
37. Atlihan, U., Yavuz, O., Ata, C., Avsar, H. A., Bildaci, T. B., Ozay, A. C., Ersak, B., Solmaz, U., & Erkilinc, S. (2025). Evaluation of the Efficacy of Active Hexose Correlated Compound as an Adjuvant in Reducing Recurrence After Condyloma Cauterization. Medicina, 61(4), 622. https://doi.org/10.3390/medicina61040622 
38. Yagita, A., Maruyama, S., Wakasugi, S., & Sukegawa, Y. (2002). H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts. In vivo (Athens, Greece), 16(1), 49–54. https://pubmed.ncbi.nlm.nih.gov/11980361/ 
39. Gao, Y., Zhang, D., Sun, B., Fujii, H., & Su, Z. (2006). Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunology, Immunotherapy, 55(10), 1258–1266. https://doi.org/10.1007/s00262-005-0111-9
40. Hirose, A., Sato, E., Fujii, H., Sun, B., Nishioka, H., & Aruoma, O. I. (2007). The influence of active hexose correlated compound (AHCC) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice. Toxicology and applied pharmacology, 222(2), 152–158. https://doi.org/10.1016/j.taap.2007.03.031 
41. Mach, C. M., Fugii, H., Wakame, K., & Smith, J. (2008). Evaluation of active hexose correlated compound hepatic metabolism and potential for drug interactions with chemotherapy agents. Journal of the Society for Integrative Oncology, 6(3), 105–109. https://pubmed.ncbi.nlm.nih.gov/19087767/ 
42. Hangai, S., Iwase, S., Kawaguchi, T., Kogure, Y., Miyaji, T., Matsunaga, T., Nagumo, Y., & Yamaguchi, T. (2013). Effect of active hexose-correlated compound in women receiving adjuvant chemotherapy for breast cancer: a retrospective study. Journal of alternative and complementary medicine (New York, N.Y.), 19(11), 905–910. https://doi.org/10.1089/acm.2012.0914 
43. Suenaga, S., Kuramitsu, Y., Kaino, S., Maehara, S., Maehara, Y., Sakaida, I., & Nakamura, K. (2014). Active hexose-correlated compound down-regulates HSP27 of pancreatic cancer cells, and helps the cytotoxic effect of gemcitabine. Anticancer research, 34(1), 141–146. https://pubmed.ncbi.nlm.nih.gov/24403454/  
44. Cao, Z., Chen, X., Lan, L., Zhang, Z., Du, J., & Liao, L. (2015). Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice. Nutrition Research and Practice, 9(2), 129–136. https://doi.org/10.4162/nrp.2015.9.2.129
45. Ito, T., Urushima, H., Sakaue, M., Yukawa, S., Honda, H., Hirai, K., Igura, T., Hayashi, N., Maeda, K., Kitagawa, T., & Kondo, K. (2014). Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy--the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy. Nutrition and cancer, 66(3), 377–382. https://doi.org/10.1080/01635581.2014.884232 
46. Ignacio, R. M., Kim, C.-S., Kim, Y.-D., Lee, H.-M., Qi, X.-F., & Kim, S.-K. (2015). Therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with CpG-ODN (oligodeoxynucleotide) in B16 melanoma murine model. Cytokine, 76(2), 131–137. https://doi.org/10.1016/j.cyto.2015.06.002 
47. Yanagimoto, H., Satoi, S., Yamamoto, T., Hirooka, S., Yamaki, S., Kotsuka, M., Ryota, H., Michiura, T., Inoue, K., Matsui, Y., Tsuta, K., & Kon, M. (2016). Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy-Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma. Nutrition and cancer, 68(2), 234–240. https://doi.org/10.1080/01635581.2016.1134597 
48. Mathew, L., Gaikwad, A., Gonzalez, A., Nugent, E. K., & Smith, J. A. (2017). Evaluation of Active Hexose Correlated Compound (AHCC) in combination with anticancer hormones in orthotopic breast cancer models. Integrative Cancer Therapies, 16(3), 300–307. https://doi.org/10.1177/1534735417704948 
49. Fatehchand, K., Santhanam, R., Shen, B., Erickson, E. L., Gautam, S., Elavazhagan, S., Mo, X., Belay, T., Tridandapani, S., & Butchar, J. P. (2017). Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells. PloS one, 12(7), e0181729. https://doi.org/10.1371/journal.pone.0181729 
50. Choi, J. Y., Lee, S., Yun, S. M., Suh, D. H., Kim, K., No, J. H., Jeong, E. H., & Kim, Y. B. (2018). Active Hexose Correlated Compound (AHCC) Inhibits the Proliferation of Ovarian Cancer Cells by Suppressing Signal Transducer and Activator of Transcription 3 (STAT3) Activation. Nutrition and cancer, 70(1), 109–115. https://doi.org/10.1080/01635581.2018.1380203 
51. Kuhara, K., Tokuda, K., Kitagawa, T., Baron, B., Tokunaga, M., Harada, K., Terasaki, M., Uehara, O., Ohta, T., Takai, R., Hamada, J. I., Kobayashi, M., Shimo, T., Nagayasu, H., & Kuramitsu, Y. (2018). CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells. Anticancer research, 38(11), 6107–6111. https://doi.org/10.21873/anticanres.12961 
52. Park, H. J., Boo, S., Park, I., Shin, M. S., Takahashi, T., Takanari, J., Homma, K., & Kang, I. (2022). AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Frontiers in immunology, 13, 875872. https://doi.org/10.3389/fimmu.2022.875872 
53. Merchand-Reyes, G., Santhanam, R., Valencia-Pena, M. L., Kumar, K., Mo, X., Belay, T., Woyach, J. A., Mundy-Bosse, B., Tridandapani, S., & Butchar, J. P. (2023). Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia. Nutrients, 15(24), 5138. https://doi.org/10.3390/nu15245138 
54. Wakamei, K. (1999). Protective effects of Active Hexose Correlated Compound (AHCC) on the onset of diabetes induced by streptozotocin in the rat. Biomedical Research, 20(3), 145–152. https://www.jstage.jst.go.jp/article/biomedres/20/3/20_145/_pdf 
55. Segarra, S., Miró, G., Montoya, A., Pardo-Marín, L., Boix, C., & Homedes, J. (2018). Prevention of disease progression in Leishmania infantum-infected dogs with dietary nucleotides and Active Hexose Correlated Compound. Parasites & Vectors, 11(1), 103. https://doi.org/10.1186/s13071-018-2705-z 
56. Henao SLD, Urrego SA, Cano AM, Higuita EA. Randomized Clinical Trial for the Evaluation of Immune Modulation by Yogurt Enriched with β-Glucans from Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), in Children from Medellin, Colombia. Int J Med Mushrooms. 2018;20(8):705-716. doi: 10.1615/IntJMedMushrooms.2018026986. PMID: 30317947. https://pubmed.ncbi.nlm.nih.gov/30317947/ 
57. Holesh, J. E., Aslam, S., & Martin, A. (2023). Physiology, carbohydrates. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459280/
58. Corona, L., Lussu, A., Bosco, A., Pintus, R., Cesare Marincola, F., Fanos, V., & Dessì, A. (2021). Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics. Children (Basel, Switzerland), 8(9), 804. https://doi.org/10.3390/children8090804 
59. Belorkar, S. A., & Gupta, A. K. (2016). Oligosaccharides: a boon from nature's desk. AMB Express, 6(1), 82. https://doi.org/10.1186/s13568-016-0253-5
60. Brosseau, C., Selle, A., Palmer, D. J., Prescott, S. L., Barbarot, S., & Bodinier, M. (2019). Prebiotics: Mechanisms and Preventive Effects in Allergy. Nutrients, 11(8), 1841. https://doi.org/10.3390/nu11081841
61. Moughan, P. J. (2009). Digestion and absorption of proteins and peptides. In D. J. McClements & E. A. Decker (Eds.), Designing functional foods (pp. 148–170). Woodhead Publishing. https://doi.org/10.1533/9781845696603.1.148