The strongest case for the use of nutritional
supplements can be made, even to the typically
skeptical mainstream medical community,
when traditional pharmaceuticals have shown
to be of limited efficacy. In such cases, the
use of nutraceuticals as both preventive and
therapeutic agents becomes very compelling.
The need to consider and employ natural bioactive compounds
is particularly strong in the field of infectious diseases.
Infectious diseases remain a significant public health threat
in the U.S. and throughout the world. The Centers for Disease
Control and Prevention (CDC) reports that five to 20 percent of
U.S. residents get the flu, more than 200,000 are hospitalized
and about 36,000 die on average from flu complications
every year. This year the ineffectiveness of the flu vaccine was
associated with an even more severe flu season. Furthermore,
the pandemic threat from mutating influenza viruses such
as the H5N1 virus, better known as “avian flu” or “bird flu,” is
particularly worrisome given that the virus strain which caused
human illness and death in Asia was found to be resistant
to two antiviral medications most commonly used to treat
influenza infections. Likewise, there is currently no specific
treatment for the West Nile virus, although cases were reported
in 43 states last year. Another health risk relates to opportunistic
and often-drug-resistant infections. Such infections tend to
occur at health care facilities and among immunocomprised
patients but also occasionally affect healthy patients. (As was
the case with “community-associated MRSA” that made the
headlines in 2007.) So in this era of continued emergence of
new or increasingly common infectious agents, not to mention
the increasing threat of bio-terrorism in which infectious agents
could be used as weapons, natural compounds that have the
potential to modify the body’s response to acute infection must
be considered.
While there are plenty of nutritional supplements claiming
immune boosting properties, very few compounds have
undergone rigorous research and rarely are products studied
in response to actual infectious diseases. Furthermore, studies
on the most popular immune ingredients, such as vitamin
C, ginseng or echinacea for the prevention and treatment of
the common cold, have produced mixed results. Finally, the
mechanism of action of most of the ingredients is still unclear,
making it difficult to infer their efficacy for conditions more
serious than the common cold.
One exceptional ingredient in this respect is AHCC (an
acronym for Active Hexose Correlated Compound), a novel
bionutraceutical developed in Japan that has been extensively
studied and used as a countermeasure to infectious disease.
Studies on the effects of AHCC on influenza, avian flu, West
Nile virus, MRSA and opportunistic infections make it one of
the most researched natural compounds for stimulating the
immune response to viruses and infections. Manufactured
using a proprietary process that entails enzymatic fermentation
of hybridized subspecies of cultivated medicinal mushrooms,
AHCC is rich in oligosaccharides (74 percent by dry weight).
While most medicinal mushroom extracts tend to contain
mostly beta-glucans, AHCC is rich with alpha-glucans (a different
type of a complex sugar molecule) which have a low molecular
weight of under 5,000 Daltons (as compared to >200,000 for
most other well-known immune support ingredients).
The body of research supporting the immuno-modulating
properties of AHCC is vast and growing. Supported by over 80
studies, AHCC has been extensively studied by researchers at the
Harvard Medical School and the affiliated Faulkner Hospital, Yale
University School of Medicine, Drexel University Department
of Bioscience and Biotechnology, and SUNY Binghamton’s
Department of Biological Sciences, among many others.
In addition to drawing significant interest in the academic
community, AHCC has gained an impressive level of adoption
in the medical community. Over 700 hospitals and medical
clinics throughout Asia prescribe AHCC to patients as part of
an immune enhancement maintenance regimen. Hundreds
of doctors throughout the world have also used AHCC as an
adjunct alternative therapy for cancer, hepatitis C and other
chronic conditions. Consequently, AHCC has become the
number one selling specialty immune supplement in Japan and
has gained broad acceptance in the U.S., where it is available in
most health food stores nationwide.
Both human and animal studies have pointed to AHCC’s
ability to enhance the activity of natural killer cells (“NK cells”).
These cells provide a crucial first defense for the body, launching
a rapid attack while the other cells of the immune system are
still mobilizing. Researchers believe that although the ability of
NK cells to destroy tumors and virus-infected cells is present at
birth, NK cells have to be activated. Thus, agents that stimulate
NK cell activity might be expected to enhance the control of
tumors and virus replication.
Activated NK cells are believed to help the body through
two modes of action. First, they promptly secrete cytokines—
chemical messenger proteins that “awaken the artillery” of the
body’s immune system. Second, NK cells secrete substances
that directly induce the destruction of tumors and virus-infected
cells.
It has also been shown in numerous studies that NK cells
play a significant role in controlling virus infections, and the
correlation between NK cell activity and the frequency of the
common cold has been well established. So the clinical evidence
that AHCC increases NK cell activity and the fact that NK cell activity
helps the immune system fight viral infections suggests that
AHCC is a potential agent to boost the NK cell response to viral
infections. However, while this inference is compelling, direct
research on the effect of AHCC on viral infections is required.
And fortunately such research exists. AHCC has been the
subject of several studies, which investigated its potential as
a countermeasure to various infectious diseases, including the
H1N1 influenza (flu) virus, the H5N1 avian influenza (bird flu)
virus, West Nile virus, methicillin-resistant Staphylococcus aureus
(MRSA) and several other opportunistic infections (Klebsiella
pneumoniae, Candida albicans and Pseudomonas aeruginosa).
The challenge of researching infectious diseases is there are
no ethical, practical or reliable means of evaluating the human
response to infectious agents, forcing researchers to rely
on animal models. Therefore, the research strategy for AHCC
has been to show efficacy in infectious diseases using animal
models while conducting human clinical trials to demonstrate
its ability to stimulate NK cell activity in immune compromised
patients.
Two published peer-reviewed human clinical studies (on 269
and 40 subjects respectively) evaluating advanced liver cancer
showed extended survival, lower recurrence and improved
quality of life among patients taking AHCC. Several other studies
demonstrated the ability of AHCC to significantly increase NK
cell activity in immune compromised patients.
While these clinical studies support the efficacy of AHCC in
humans, animal studies have been used to examine whether
AHCC can be effective in fighting specific viruses and explore
the mechanism or mechanisms for the observed effects.
The most recent study published in the prestigious Journal
of Nutrition examined the effect of AHCC on the influenza
(flu) virus. The research found that mice supplemented with
AHCC showed increased survival and maintained body weight
during the infection compared to controls (indicative of a less
severe infection). Supplementation with AHCC also resulted
in enhanced NK cell activity in the lungs and spleen and rapid
virus clearance from lungs. So the data clearly suggested that
AHCC supplementation enhanced NK cell activity in response
to influenza infection, which was associated with a decrease in
lung virus titers, a less severe infection and increased survival.
Another study looked at the effect of AHCC supplementation
against infection with H5N1 avian influenza virus (bird flu).
Mice were infected with 100 times the 50 percent lethal dose
of the H5N1 influenza virus. The control mice that did not
receive AHCC demonstrated 100 percent mortality at 12 days
post-infection. In contrast, the group that was fed AHCC prior to
infection demonstrated a 30 percent survival through 28 days
post-infection. In a second study utilizing the same protocol, the
effects of AHCC supplementation alone were compared to H5N1
vaccination (the flu vaccine) alone as well as the combination
of AHCC supplementation and the flu vaccine administered
together. Vaccination alone resulted in approximately 80
percent survival, while AHCC supplementation combined with
vaccination resulted in 100 percent survival. This
data suggests while AHCC supplementation alone
offers some protection against mortality associated
with highly-virulent avian influenza virus infection in
mice, supplementation with AHCC may be even more
effective as an addition to the flu vaccine.
In another study, mice infected with a lethal dose
of West Nile virus showed that mice supplemented
with AHCC prior to the infection exhibited an increase
in survival and a decrease in virus load in the blood at
four days post-infection.
Looking at “opportunistic” or hospital-acquired
infections, the effects of AHCC supplementation on
the resistance to Klebsiella pneumoniae (principally
associated with bacterial pneumonia and urinary tract
infections) was studied in both infected and stressinduced
mice. Again, the AHCC-supplemented mice
demonstrated increased survival, increased mean
time until death, decreased susceptibility to infection
and increased bacterial clearance from the blood. Studies on
other types of opportunistic infections including methicillinresistant
Staphylococcus aureus (MRSA), Candida albicans
and Pseudomonas aeruginosa provided similar results: AHCC
overwhelmingly increased survival in immune compromised
mice in response to infectious challenge.
Given the abundance of preliminary positive results across
different infections, AHCC supplementation demonstrates valuable
and clinically-relevant potential as an immune-enhancing
compound. Furthermore, since AHCC supplementation was
shown in one study to be even more beneficial when used in
conjunction with the flu vaccine, studies are underway to further
evaluate the use of AHCC as a preventive during flu season. Finally,
AHCC boasts a strong safety profile supported by a Phase
I study conducted at Harvard, a 20-year history of use in Japan,
its adoption by over 700 clinics and use by an estimated 70,000
people worldwide (including 20,000 in the U.S.). Thus, there is
a strong case to be made for adding AHCC to a daily supplement
regimen to support the body’s immune system, not only during
the apparent times of increased infectious threat such as the flu
season, but also all year long.
Dr. Fred Pescatore, M.D., MPH, is the Medical Director of Partners in
Integrative Medicine and an author of several best-selling books on
health and nutrition.
Barry Ritz, Ph.D. is the Professor of Bioscience and Biotechnology at
Drexel University, whose paper on AHCC and influenza was recently
published in the Journal of Nutrition.
