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AHCC: the story of a Japanese mushroom that stimulates the immune system's 'sentinels'

Long before the advent of medicines, humans treated their health problems using properties present in living organisms; certain mushrooms, for example, were used to boost the immune defences. Thousands of years later, science is validating our forebears’ methods and empirical knowledge: today’s studies show that mushrooms, particularly the shiitake variety, are indeed able to increase our immune capacity1-5. And researchers are well on their way to understanding the mechanisms involved. A new study on AHCC - a natural, Japanese mushroom-based supplement - has provided clarification of the immune-stimulant effects of these forest-dwelling flora …

Mushroom extract for boosting the immune system

AHCC (Active Hexose Correlated Compound) is an extract of the Basidiomycetes species of mushroom, of which 74% is comprised of oligosaccharides. It is a natural immune-stimulant – in other words, its constituents boost the body’s immune response helping it to fight external aggressors and cancer cells. When ingested, it theoretically enables the immune system to resist attacks more effectively. Faced with the ‘flu virus, for example, consuming AHCC may be enough to drive out the aggressor, prevent the infection or at least reduce its severity. In the case of more serious diseases such as cancer, improved long-term immunity can tip the outcome of a treatment in the right direction: a cure can sometimes come down to very little ... So how do the molecules in AHCC do it? Scientists have long struggled with this question but it now seems they are closer to finding the answer.

AHCC’s polysaccharides increase the efficacy of NK lymphocytes

Researchers have discovered that AHCC’s long chain carbohydrates increase the recruitment, activity and efficacy of specific cells called NK lymphocytes6 (or Natural Killer cells ). These cells remain the same throughout a person’s life: they do not adapt to the aggressors they encounter. Their principal mission is to kill any cells in their path. They are sometimes described as sentinels – the immune system’s first line of defence. Fortunately, specific membrane receptors enable these cells to recognise their own kind, and disengage from their killer mode. The destructive chemicals they contain (perforin, granzyme, serglycin) are thus preserved for other cells – either foreign ones, or cells so abnormal they appear to be foreign 7. This is particularly the case with tumour cells, where the cell membranes often present abnormal characteristics. If there are enough such abnormalities, NK lymphocytes will decide to attack. They are also able to recognise cells bound to antibodies - a sign they have been identified by other immune cells as posing a risk - and deliver a similarly fatal blow …. In this sense, they are thus the immune system’s first line of defence. However, to pursue the military analogy, they differ from the front line soldiers who charge ahead blindly, sacrificing themselves in the process. NK cells do much more than that. They are responsible for secreting chemical messengers (interferon-y, TNFα, TNFβ, GM-CSF, IL-10, and IL-13) which then coordinate, control or recruit all the other elements of the body’s defences8. In other words, they draw up the orders and make sure they’re implemented!
  • By secreting IFN-γ, they activate macrophages which produce molecules such as nitrogen monoxide, known for its ability to destroy pathogenic microorganisms.
  • By secreting TNF-β and Fas proteins, they induce the death of tumour cells.
  • They also promote the maturation and activation of other important immune cells such as dendritic cells, macrophages and T lymphocytes.
This therefore forms a kind of fundamental unit, where cohesion, quality and numbers can be crucial in determining the outcome of a battle or war.

AHCC’s specific effect in cancer

The benefits of AHCC observed by researchers in cancers of the stomach, colon, ovaries and liver, are not, however, entirely accounted for by its stimulation of the immune system and the increased anti-tumour action of NK lymphocytes. AHCC’s polysaccharide chains actually interfere directly with a mechanism involved in the development of cancer.
This mechanism starts with transcription factor STAT3, a protein complex which moves around freely in cells’ cytoplasm and is completely harmless. However, when certain chemical messengers attach themselves to it, STAT3 is able to enter the cell’s nucleus and activate hitherto-unexpressed genes. These genes have the ability to prevent cells from dying by deactivating the normal process of senescence as well as increasing their resistance to the NK lymphocytes trying to destroy them. It is thus no surprise to see overexpression of these genes in cancer: by making tumour cells invincible, they ensure the proliferation and survival of the tumour as a whole9.
To prevent this immortalisation and enhanced resistance of cancer cells, transcription factor STAT3 must be blocked from activating the genes responsible. This means either stopping it from translocating to the cell nucleus, or preventing the chemical messengers from becoming attached to it. This is precisely what AHCC’s α-1,4-glucan chains do10. As a result of their interaction with the SHP-1 group of proteins, they are able to inhibit STAT3 and thus prevent the development of cancer.

A difference that can tip the scales

In both increasing the number and deadliness of Natural Killer cells and other immune cells, and disrupting the mechanism that keeps cancer cells alive, AHCC should be seriously considered in cases of immune deficiency, as well as in the battle against diseases such as cancer.
In a difficult fight, the smallest advantage can make a crucial difference to the outcome. And the immune advantages offered by AHCC are by no means insignificant … Those who stand to gain from taking it to improve the quality of their immune response include people:
  • who are fighting cancer.
  • who have sleep problems.
  • whose diet contains insufficient micronutrients.
  • who are stressed.
  • who smoke or consume a lot of alcohol.
  • who are exposed to pollutants on a daily basis.
  • whose immune systems are compromised either through age or disease.
  • who wish to maximise their resistance to winter infections (gastroenteritis, colds, ‘flu, etc).

1. Burikhanov, R. B., Wakame, K., Igarashi, Y., Wang, S., and Matsuzaki, S. Suppressive effect of active hexose correlated compound (AHCC) on thymic apoptosis induced by dexamethasone in the rat. Endocr.Regul. 2000;34(4):181-188.
2. Gao, Y., Zhang, D., Sun, B., Fujii, H., Kosuna, K., and Yin, Z. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunol.Immunother. 2006;55(10):1258-1266.
3. Ritz, B. W., Nogusa, S., Ackerman, E. A., and Gardner, E. M. Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. J Nutr. 2006;136(11):2868-2873.
4. Aviles, H., O'Donnell, P., Sun, B., and Sonnenfeld, G. Active hexose correlated compound (AHCC) enhances resistance to infection in a mouse model of surgical wound infection. Surg.Infect.(Larchmt.) 2006;7(6):527-535.
5. Ritz, B. W. Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. Nutr.Rev. 2008;66(9):526-531.
6. Ye SF, Ichimura K, Wakame K, Ohe M. Suppressive effects of Active Hexose Correlated Compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress. Life Sci 2003;74:593-602.
7. Moretta, L., et al., Allorecognition by NK cells: nonself or no self? Immunol Today, 1992. 13(8): p. 300-6.
8. Vivier, E., et al., Functions of natural killer cells. Nat Immunol, 2008. 9(5): p. 503-10.
9. Cai L, Zhang G, Tong X, You Q, An Y, et al.: Growth inhibition of human ovarian cancer cells by blocking STAT3 activation with small interfering RNA. Eur J Obstet Gynecol Reprod Biol 148, 73–80, 2010.
10. Jin Young Choi, Seul Lee, Sun-Mi Yun, Dong Hoon Suh, Kidong Kim, Jae Hong No, Eun-Hwan Jeong & Yong Beom Kim (2017): 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, DOI: 10.1080/01635581.2018.1380203
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One of the most active components of colostrum (the first form of breast milk)

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