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Nutritional Food Active Hexose Correlated Compound (AHCC) Enhances Resistance against Bird Flu
Abstract
AHCC is a nutritional food that has been broadly adopted in Japan as well as other countries. Several laboratories have demonstrated that AHCC has immune modulating effect. Increasing immunity against bird flu virus, H5N1, may help to prevent the next pandemic. We hypothesize that uptaking AHCC improve immunity against infection with this virus. Administration of AHCC for 7 days effectively improved survival rate by 30%, and this effect can last for 3 to 4 weeks. Our results indicate a potential role of AHCC in helping to build up immunity for preventing the pandemic of bird flu.
... Active hexose correlated compound (AHCC) is a dietary supplement prepared from Basidiomycetes mushrooms, largely comprised of α-1,4-glucans [3]. Animal studies have demonstrated that AHCC increases survival during acute infections such as influenza virus [4][5][6], avian flu [5], West Nile virus [7], and opportunistic infections [8][9][10][11]. Our laboratory has shown that AHCC supplementation, even in small doses, increases survival of young mice against influenza infection [4,6]. ...
... Active hexose correlated compound (AHCC) is a dietary supplement prepared from Basidiomycetes mushrooms, largely comprised of α-1,4-glucans [3]. Animal studies have demonstrated that AHCC increases survival during acute infections such as influenza virus [4][5][6], avian flu [5], West Nile virus [7], and opportunistic infections [8][9][10][11]. Our laboratory has shown that AHCC supplementation, even in small doses, increases survival of young mice against influenza infection [4,6]. ...
... Many animal studies support the idea that AHCC enhances survival from several primary infections [4][5][6][7][8][9][10][11], a protective effect attributed to AHCC's actions on DCs, CD8 T cells and NK cells. The bioactive compound of AHCC is acetylated α-glucans but the exact mechanism of action is not known. ...
... Of the oligosaccharides in AHCC®, about 20% are α-1,4-glucans, of which a proportion is partially acylated, with a mean molecular weight around 5000 Daltons [6,7]. The effects of AHCC® on immune cells of humans and animals were reported in in vitro and in vivo studies, suggesting the possible help of its supplementation in defending the host against infections and malignancies via modulating the immune system [6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This review focuses on the reported effects of AHCC® on natural killer (NK) and T cells given their roles in host defense and inflammation [29][30][31][32][33][34], providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC® and possibly other medical mushrooms in health and disease. ...
... The effect of AHCC® can be beyond H1NI influenza. The survival benefit by AHCC® supplementation was observed in mice infected with avian (bird) influenza virus H5N1 which could infect humans and poultry although its mechanism is yet to be demonstrated [15]. In fact, the mortality rate of H5N1 avian influenza is much higher than that of past influenza pandemics, reaching up to 60% [42]. ...
Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.
... These glucans are thought to provide a carbohydrate that stimulates immune responses [8,9]. It has been previously reported that AHCC influences both natural immunity and acquisition immunity and is also effective against viral infection, Eumycota and other bacteria [10][11][12]. It has been reported that AHCC attenuated infection caused by Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) in a neutrophil depleted murine model by cyclophosphamide [13]. ...
... AHCC was provided from Amino Up Chemical (Sapporo, Japan). Detail of AHCC was described previously [8][9][10][11][12][13][14][15][16][17]. Infected mice were supplied with 1,000 mg/kg/day of AHCC by oral administration until euthanasia. ...
Introduction: Pulmonary Mycobacterium avium disease is a chronic and progressive disease that is known to be difficult to treat. Active hexose correlated compound (AHCC) is an extract obtained by culturing mycelia of Basidiomycota. AHCC is reported to attenuate several experimental animal infection models. We hypothesized that AHCC could attenuate pulmonary M. avium disease in mice. Methods: Mycobacterium avium (108 cfu/head) was administered intratracheally into mice (C57/BL6). Infected mice were supplied with 1,000 mg/kg/day of AHCC by oral administration until euthanasia. The mice were sacrificed at seven days later or 21 days later after M. avium infection. The lung homogenates were cultured on Middlebrook 7H10 agar plates for bacterial colony counts. Additionally, the number of inflammatory cells in the lungs was analyzed by FACS. Tissue sections of the lungs were stained by hematoxylin and eosin or Ziehl-Neelsen methods. In addition, the number of bacterial colonies in the macrophages was counted in vitro. Approximately 1x106 macrophages were incubated with M. avium at an MOI of 10 with or without 1 mg/ml of AHCC. Results: The administration of AHCC improved lung inflammation caused by M. avium according to the histology results and decreased number of M. avium in the lungs. In the analysis of lung inflammatory cells, the number of TNFR1 cells and NK cells remained unchanged by AHCC administration, however, the number of TNFR2 cells slightly increased. There was no difference in the number of M. avium in macrophages treated with or without AHCC in the in vitro study. Conclusion: AHCC plays a protective role in a murine model of pulmonary M. avium disease.
... Functional food, active hexose correlated compound (AHCC), is an extract prepared from cultured mycelium of a Basidiomycetes mushroom. Recent reports have shown that supplementation with AHCC exerts a general positive effect on the immune system, as well as anti-inflammatory and anti-oxidant effects8910111213. AHCC is a mixture of poly-and oligo-saccharides, amino acids, lipids, minerals, etc., in which oligosaccharides are the major components , comprising approximately 74% of the mixture. ...
... Supplementation studies with AHCC have demonstrated positive effects on immune function in humans and animal models, including decreased tumor formation [1][2][3] ; increased resistance to viral and bacterial infection [4][5][6][7][8][9] ; enhanced natural killer (NK) cell activity 6,10,11 ; increased dendritic cell function 12 ; increased T-cell proliferation, including altered T-cell activity 3,13 ; altered cytokine production 3,5,13,14 ; suppressed dexamethasone-induced thymic apoptosis in rats 15 ; increased nitric oxide release by peritoneal cells 13 ; and antioxidant [16][17][18] and antiinflammatory effects. 19 Clinical effects and safety have been demonstrated in humans with malignancy, 11,[20][21][22][23][24][25][26] as well as in healthy subjects, 12,27,28 most recently in a report investigating the potential application of AHCC as an immune adjuvant in influenza vaccination. ...
Active hexose correlated compound (AHCC) is a fermented mushroom extract that is commercially available and promoted for immune support. This review focuses on safety and efficacy results from human clinical trials that have included subjects with a variety of cancers, as well as healthy populations. Animal data are also briefly discussed in the context of recent human data, with an emphasis on the possible applications of AHCC in promoting resistance to influenza virus infection. Available data suggest that AHCC supplementation clearly affects immune outcomes and immune cell populations— especially natural killer cell activity. Additional human studies are needed, as well as studies to explore the mechanistic rationale for these reported effects.
... Functional food, active hexose correlated compound (AHCC), is an extract prepared from cultured mycelium of a Basidiomycetes mushroom. Recent reports have shown that supplementation with AHCC exerts a general positive effect on the immune system, as well as anti-inflammatory and anti-oxidant effects8910111213. AHCC is a mixture of poly-and oligo-saccharides, amino acids, lipids, minerals, etc., in which oligosaccharides are the major components , comprising approximately 74% of the mixture. ...
Supplementation of active hexose correlated compound (AHCC) improved the prognosis of postoperative hepatocellular carcinoma patients. Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that AHCC has a potential liver-protective effect. However, the active component in AHCC responsible for NO suppressive activities has not been identified. The objective of this study was to identify this NO suppressive component and to investigate its mechanisms of action. AHCC was subjected to fractionation by cation exchanger, size exclusion chromatography, and normal- and reversed-phase HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes stimulated with interleukin (IL)-1β, and NO production was assayed. By activity-guided fractionation and electron spray ionization mass spectrometry analysis, adenosine was identified as one of the NO suppressive components in AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS protein and mRNA. It had no effects on IκB degradation, but it inhibited NF-κB activation. Adenosine also inhibited the upregulation of type I IL-1 receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed that adenosine decreased the levels of iNOS mRNA at the promoter transactivation and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC suppressed iNOS induction by blocking NF-κB activation and the upregulation of the IL-1RI pathways, resulting in the inhibition of NO production.
... 30 The potential effects of AHCC supplementation against infection with H5N1 avian influenza virus were evaluated in young (6-8-week-old) female BALB/c mice. 16 Mice received AHCC at a dose of 0.5 g/kg body weight/d or an equal volume of phosphate buffer solution (PBS) by gavage for 7 days. At 21 or 28 days posttreatment, mice were infected i.n. with 100 times the 50% lethal dose (LD50) of H5N1 avian influenza virus. ...
Active hexose correlated compound (AHCC) is a fermented mushroom extract that is promoted for immune support. This review focuses on results from in vivo studies evaluating the effects of AHCC supplementation on survival and the immune response to a variety of infectious agents, including influenza virus, avian influenza virus, Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Supplementation with AHCC appears to modulate immunity and increase survival in response to acute infection and warrants further investigation.
The aim of this study was to investigate the leucopoetic and testosterone levels of rats administered sub-chronic methanolic leave extract of Dracenea arborea. Acute toxicity study of the extract was performed using male rats. A total of 120 male rats weighing 140±14.14 g were used for the sub-chronic study divided into four groups. Groups B, C, and D were given 50, 100, and 500 mg/kg body weight, bw of the extract, respectively, while group A which served as the con-trol was given normal saline at the dosage of 10 ml/kg bw. Both the extract and the normal saline were given daily for 91 days using the oral route. The parameters assessed in the sub-chronic study were—testosterone levels (TesL), total leu-cocyte counts (TLC), differential leucocyte counts, and his-tology of the testes. The mean TesL of the treated groups showed significant increase (p<0.05) in a dose-dependent fashion from each other as from day 35 post administration of the extract to the end of the experimental period. The groups treated with the extract equally showed significant increase (p<0.05) in the mean TesL when compared to the control group. The mean TLC of rats in group D and C were significantly higher (p<0.05) than that of groups B and A between day 77 and 91 post administration of the extract. The mean neutrophil counts of groups D and C showed significant increase (p<0.05) when compared to groups B and A between day 35 and the end of the experimental period. Histological evaluation of the testes revealed increased spermatogenesis in group D when compared to groups B and C. The extract-treated groups showed increase spermatogenesis when com-pared to the control group. It was concluded that sub-chronic administration of the extract led to enhancement of progester-one levels, spermatogenic effects, and leucopoetic potentials in rats.
An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
AHCC (Active Hexose Correlated Compound) is an extract from mycelia of Lentinula edodes, a mushroom of the basidiomycetes family, which is cultivated in liquid media in a large tank. It is one of the most frequently used products in complementary and alternative medicine among cancer patients in Japan. Also in recent studies, it has been reported as efficacious in treatment of infectious and inflammatory diseases. AHCC has been proved as safe food by various safety evaluations and drug interaction studies have been conducted. The result of a Phase I trial in healthy volunteers concluded that AHCC is safe as a supplement in clinical practice. The present paper reviews the effects of AHCC in ameliorating the side effects of anti-cancer drugs, in modulating the immune system, in reducing inflammation and in infection prophylaxis.
Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver-protective effect.
Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured hepatocytes were treated with interleukin-1β in the presence or absence of AHCC-sugar fraction (AHCC-SF).
AHCC-SF inhibited the production of NO and reduced expressions of iNOS mRNA and its protein. AHCC-SF had no effects on either IκB degradation or nuclear factor-κB (NF-κB) activation. In contrast, AHCC-SF inhibited the upregulation of type I interleukin-1 receptor (IL-1RI) through the inhibition of Akt phosphorylation. Transfection experiments with iNOS promoter-luciferase constructs revealed that AHCC-SF reduced the levels of iNOS mRNA at both promoter transactivation and mRNA stabilization steps. AHCC-SF inhibited the expression of iNOS gene antisense transcript, which is involved in iNOS mRNA stabilization. These findings demonstrate that AHCC-SF suppresses iNOS gene expression through a IκB/NF-κB-independent but Akt/IL-1RI-dependent pathway, resulting in the reduction of NO production. AHCC-SF may have therapeutic potential for various liver injuries.
Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.
The outbreak of highly pathogenic avian influenza of the H5N1 subtype in Asia, which has subsequently spread to Russia, the Middle East, Europe, and Africa, has put increased focus on the role of wild birds in the persistence of influenza viruses. The ecology, epidemiology, genetics, and evolution of pathogens cannot be fully understood without taking into account the ecology of their hosts. Here, we review our current knowledge on global patterns of influenza virus infections in wild birds, discuss these patterns in the context of host ecology and in particular birds' behavior, and identify some important gaps in our current knowledge.
Previous studies have demonstrated that resistance to infection is decreased in Swiss Webster female mice maintained in the hindlimb-unloading model (Aviles H, Belay T, Fountain K, Vance M, and Sonnenfeld G. J Appl Physiol 95: 73-80, 2003; Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 110: 262-268, 2002). This is a model of some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. Active hexose correlated compound (AHCC), extracted from Basidiomycete mushrooms, has been shown to induce enhancement of immune responses, including enhanced natural killer activity. In the present study, AHCC was orally administered to mice to determine whether the treatment could decrease immunosuppression and mortality of mice maintained in the hindlimb-unloaded model and infected with Klebsiella pneumoniae. The results of the present study showed that administration of AHCC by gavage for 1 wk (1 g/kg body wt) before suspension and throughout the 10-day suspension period yielded significant beneficial effects for the hindlimb-unloaded group, including 1). decreased mortality, 2). increased time to death, and 3). increased ability to clear bacteria. The results suggest that AHCC can decrease the deleterious effects of the hindlimb-unloading model on immunity and resistance to infection.
Hindlimb unloading is a ground-based model that simulates some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. It has been shown that treatment with active hexose correlated compound (AHCC) restores resistance to infection in mice maintained under hindlimb-unloading conditions. The present study was designed to clarify the mechanisms by which AHCC enhances resistance to infection in this model. We hypothesized that oral administration of AHCC will enhance the function of the immune system, which could lead to the increased resistance to infection observed in this model. AHCC or the excipient was orally administered to mice, and the function of the immune system was assessed in spleen and peritoneal cells isolated from those groups. The results of the present study showed that administration of AHCC for 1 wk before and throughout the second day of the hindlimb-unloading period enhanced the function of the immune system assessed by spleen cell proliferation and cytokine production in spleens and nitric oxide and cytokine production in peritoneal cells. These findings suggest that AHCC can be used as a potent immunoenhancer, especially in cases in which the immune system is suppressed by any condition, including diseases such as human immunodeficiency virus infection and cancer.
In the last few years, the genomic sequence data for thousands of influenza A virus strains, including the 1918 pandemic strain,
and hundreds of isolates of the avian influenza virus H5N1, which is causing an increasing number of human fatalities, have
become publicly available. This large quantity of sequence data allows us to do comparative genomics with the human and avian
versions of the virus. We find that the nucleotide compositions of influenza A viruses infecting the two hosts are sufficiently
different that we can determine the host at almost 100% accuracy. This assignment works at the segment level, which allows
us to construct the reassortment history of individual segments within each strain. We suggest that the different nucleotide
compositions can be explained by a host-dependent mutation bias. To support this idea, we estimate the fixation rates for
the different polymerase segments and the ratios of synonymous to nonsynonymous changes. Additionally, we provide evidence
supporting the hypothesis that the H1N1 influenza virus entered the human population just prior to the 1918 outbreak, with
an earliest bound of 1910.
The respiratory tract-mucosa is the site of either contact with influenza virus or defense against the virus. Such a defense is mediated by immune competent cells. The precursors of IgA-producing B cells and immune T cells are first induced in the mucosal inductive sites such as nasal-associated lymphoid tissues (NALT) or bronchus-associated lymphoid tissues (BALT). They are disseminated to mucosal effector sites for the development of immune responses, where IgA-producing cells in the lamina propria produce polymeric IgA, which are secreted through the epithelial cell into the external. The secretory IgA and serum IgG are mainly involved in protection against influenza in the upper respiratory tract and pneumonia in the lower respiratory tract, respectively. CD8+ cytotoxic T cells and Th1 cells are involved in recovery from influenza.
Active hexose correlated compound (AHCC), an extract derived from fungi of Basidiomycetes family, has been found to be a potent antioxidant. Since the secretion of some hormones can be affected by reactive oxygen species, the objective of this study was to examine how ferric nitrilotriacetate (FeNTA), which generates hydroxyl radicals in vivo, modulates the hormone secretion and the effects of AHCC.
AHCC at 3 % in drinking water was given to male rats for one week, and the animals were decapitated at different time intervals after the treatment with FeNTA intraperitoneally. Serum levels of hormones (corticosterone, testosterone, thyroxine and triiodothyronine), adrenal ascorbic acid as well as changes in hepatic oxidative status were evaluated by immunoassay and spectrometry.
Serum corticosterone levels increased significantly following FeNTA treatment, while AHCC reduced the increased levels to normal. Adrenal ascorbic acid levels that reflect ACTH secretion, were decreased by FeNTA and restored to normal by AHCC. Serum levels of testosterone and thyroxine (T4) decreased rapidly after FeNTA treatment, while AHCC pretreatment prevented this fall. Serum triiodothyroxine (T3) levels remained unchanged either by FeNTA or AHCC treatment. The hepatic oxidized glutathione, glutathione-related enzymes and also serum lipid peroxide were greatly enhanced after FeNTA treatment. All of these changes were restored to normal by AHCC pretreatment.
FeNTA induces various endocrine disorders and AHCC ameliorates these effects by acting as an antioxidant.
Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.
Avian influenza A (H5N1) first emerged as a global public health threat in 1997 when it caused a major human outbreak in Hong Kong. Endemic in waterfowl and highly virulent in poultry, H5N1 is capable of incidentally infecting humans and other mammals. Although H5N1 is not yet capable of efficient human-to-human transmission, the protean nature of its genome could transform it into the source of the next human influenza pandemic. In the spring of 2006, migrating birds spread the virus from Asia to Europe and Africa. Preparing for a new influenza pandemic involves increasing global influenza surveillance and developing practical strategies for containing outbreaks at the source. Prompt case recognition, isolation, and treatment will be crucial for disease control. Pharmacologic interventions will focus on streamlining the production of vaccine, extending vaccine supplies, stockpiling antiviral drugs such as oseltamivir, and distributing these agents in a timely manner to persons who have the most need. Nonpharmacologic measures will include the use of masks, social distancing, quarantine, travel restrictions, and increasing the emergency capacity of health care systems.
During recent years, a conceptual shift took place with respect to the genetic dynamics of influenza A viruses. In difference of the widely accepted approach that avian viral strains have the capacity to infect man only after undergoing genetic reassortment within pigs, it is now contended that direct transfection of man by intact avian-harbored viral genotypes is an actual, recurrent move, which may bring bout the generation of a new pandemic strain. This cardinal conceptual shift has been propelled by the appearance in 1997 of the zoonotic avian influenza H5N1 virus--a virulent, not yet contagious strain for humans--and ostensibly followed a genuine, unprecedented path within the evolutionary paradigm of Influenza A virus. This paper suggests that direct avian-human genetic interface is a pristine fundamental within the natural history of this protean pathogen, points at earlier as well as corroborative findings leading to such postulation, and regards the course of the H5N1 virus (and alike), as a readily detectable and traceable one, presently, rather then a novel development It further examines the general feasibility of various components of that interface at large, such that give rise--whether gradually or abruptly--to pandemic genotypes, in terms of infectivity, pathogenicity and contagiousness. Within that context, the anticipated involvement of certain human-adapted antigenic subtypes is referred to, extrapolatively. Connectedly, the significance of natural ice as plausible regenerator of influenza A viruses, and its possible contribution to the emergence and reemergence of pandemic strains are accentuated.
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