Paul was recently Chair of the Forum on Food and
Health at the Royal Society of Medicine and a former Senior Scientific
Advisor to the UK government's Committee on the Safety of Medicines.
Dr Clayton is Research Director of Medical Nutrition Matters, a
post-graduate course in Oxford registered with, and approved by the
BMA. Its function is to teach nutrition to GPs and other health care
"The next global flu pandemic is on our
doorstep. Klaus Stohr of the WHO Global Influenza
Programme recently stated ‘There will be another pandemic. In the best
case we expect billions to fall ill, with 2 to 7 million deaths – but
it could be far worse'. In the UK, for example, the Department of
Health predicts there could be as many as 750,000 deaths. Why are the
experts so pessimistic?
History shows that flu pandemics occur every 30
years or so. After this time the genetic makeup of a flu virus has
changed so much that immunity built up from previous strains becomes
irrelevant; so that herd immunity, our main defence against
pandemics, has become negligible.
There were three pandemics in the 20th
century, and all spread worldwide within a year of being detected.
The Spanish flu in 1918-19 killed up to 50 million people. In the
50’s the Asian flu pandemic killed a mere million, and in ’68 Hong
Kong flu killed another million or so. That was 41 years ago – so
we’re due for the next one. Prime candidate is the swine flu now
gathering momentum around the world, and which has already shown
Antibiotics are no use in treating viral
infections, and the right vaccines to protect us against the new
strain of swine flu won’t be ready until at least 6 months after the
epidemic has started, which will be too late for many. Various EU
member state governments have decided to purchase anti-viral
treatments for, in some cases, as many as 1 in 4 of the population.
Those decisions were based on two assumptions: firstly, that the
emergency could be managed, and secondly that the anti-viral drugs
will be reasonably effective. Both of these assumptions are very
questionable. Our ability to deal with the fall-out of a contagious
and highly lethal viral epidemic is, realistically, inadequate. And
the efficacy of the anti-virals (which was never very high) is being
seriously under-mined by the emergence of drug resistance.
Let us assume, however, that the anti-viral
drugs are still at least partially effective when the time comes,
and the emergency plans will actually work. One in four people
deemed sufficiently important (army, police, medical personnel and
the political classes) will be protected. What should the rest of us
The best defence against viral infection is to
prep your innate immune system, which is the body’s first line of
defence against invasion by bacteria and viruses. Unlike the
acquired (or adaptive) immune system, the innate immune system does
not recognise every possible antigen. Instead, it is geared up to
recognise and react to a small number of highly conserved molecules
which are present in the cell walls of many pathogens; including LPS
(gram negative bacteria), lipotechoic acids (gram positive
bacteria), and 1-3, 1-6 beta glucans (bacteria and fungi).
Once stimulated, the innate immune response
mounts both cellular and humoral responses. These involve:
- Phagocytic cells. These include
macrophages and related cell species such as Langerhans cells in
the epidermis, Kupffer cells in the liver, microglia in the
brain and osteoclasts in bone.
- Cells that produce inflammatory mediators
(mast cells, eosinophils and basophils)
- Natural Killer cells
- Mediator molecules such as complement
proteins, acute phase proteins and cytokines. These include
tumor necrosis factor (TNF), interleukins 1 and 6, hydrogen
peroxide, and gamma interferon, all of which fight against
Of all the natural compounds known to stimulate
the innate immune system, the best documented and most effective are
the 1-3, 1-6 beta glucans, generally derived from brewer’s yeast (Kernodle
et al ’98, Wakshull et al ‘99). These molecules activate the innate
immune system very strongly indeed; in humans and other mammals, and
in birds, fish and even crustacea (Mansell et al ’75, Hahn &
Albersheim ’78, Robertsen et al ’94, Song & Hsieh ‘94).
Macrophages have receptors which specifically recognise 1-3, 1-6
beta glucans (Czop & Austen ’85), because they occur in the cell
walls of many bacteria and fungi. This means that when you ingest
beta glucans your innate immune system thinks, not unreasonably,
that an enemy has arrived and it rises to the challenge. This
important first line of defence is now fully activated, and several
well-conducted research papers have shown that resistance to
infection is greatly enhanced (Onderdonk et al ’92, Kernodle et al
’98, Vetvicka et al ‘02).
The beta glucans’ ability to activate
macrophages has been extensively tested (Rasmussen et al ’85, ’87,
’89, ’90, ’91, ‘92); and has been shown to protect animals such as
mice against otherwise fatal infections (Williams & Deluzio ’78,
’79, ’80, ’83, Leibovich & Danon ’80, Lahnborg et al ’82, Deluzio &
Williams ’83, Browder et al ’83, Rasmussen & Seljelid ’91, Tzianabos
& Cisneros ’96). Trials have shown the same substantial protective
effects in human infections also (de Felipe ’93, Babineau & Hackford
‘94, Barbineau & Marcello ‘94, Dellinger et al ’99).
A glance at the references above shows that
most of the key studies had already been completed by the mid –
90’s, but the work was not thought to be commercial, and was not
developed for clinical use. Antibiotics still ruled the roost, and
were highly profitable for the drug companies, while brewer’s yeast
extracts were cheap and belonged to everybody. This meant that none
of the drug companies was interested in investing in them.
National authorities, however, was taking
careful note. Starting in the late ‘80’s, they ran an exhaustive
test programme to measure the immuno-protective effects of beta
glucans and over 100 other immuno-stimulants, and as recently as
2004 reported that the beta glucans were the most effective of them
all. Not only did they protect against infection with bacteria,
viruses and fungi, they also conferred protection against radiation
injury (Patchen et al ’87, Patchen & McVittie ’85).
Given that soldiers may at any time face an
unpredictable range of biological weapons and even, in the worst
case, radiation, the US army began to stock-pile beta glucans. To
this day Washington keeps significant amounts of beta glucans in
readiness, to be issued as and when circumstances dictate. (To put
this in context, all cases of ‘bacterial warfare’ reported in the US
to date - such as the notorious ‘anthrax by post’ episode – were
identified as being internal affairs!)
I personally think that these valuable
compounds are too good to be left to the armed forces. I have put up
a couple of kilos of purified beta glucans on the top kitchen shelf.
When the time comes I will give them to my children, at a dose of
500 mg of beta glucans per day; armed with the knowledge that they
are safe (Williams et al ‘88) and effective prophylactic agents. In
trials with pigs, beta glucans reduce the harm done to the lungs
after infection with swine flu virus, and reduce replication of the
virus itself (Jung et al ‘04). As pigs and people have a good deal
in common (metabolically and physiologically speaking), the pig
model is very relevant to our own situation. When one looks at our
governments’ flu management strategies, George Orwell’s porcine
metaphors seem more appropriate than ever.
WHICH BETA GLUCAN?
It is no easy to ascertain which beta glucan
preparation is most effective. Surprisingly, the actual amount of
beta glucan per capsule is not critical; particle size is as or more
important, with particles of around 100 k.daltons found to be the
most effective immuno-stimulants. Another criterion is purity,
generally expressed as a low protein and ash content. This will
minimise the risk of an allergic reaction, a potential hazard in
those rare individuals who have a genuine allergy to baker’s yeast –
as opposed to the much larger numbers who claim to be allergic! At
this time, however, as none of the physical parameters has yet been
validated as an appropriate proxy marker, it is probably best to
rely on biological assays to measure quality. And as there are some
very shoddy materials on the market, you may prefer to work with
beta glucans from companies with a strong research background and an
established track record.
here for an independent comparative review of commercial beta-glucan
Two of the best are Glucasan made by a German
company working in association with the University of Berlin who
have done large scale studies using beta glucans to replace
antibiotics as growth promoters; and Biothera, a US company who have
also invested in research and quality control."
Details of Glucasan, distributed in the UK by
Vitalize, can be found here:
or by phoning 0870 042 8423
Dr Paul Clayton
- the expert view
Gerhard Gerber, Prof. Dr. sc.
Alumnus, Medical Faculty (Charité),
Humboldt University of Berlin, Germany
Bird/Swine Flu - an alternative approach
adult has had more than a few colds and several bouts of flu over the
years, but many people
were very apprehensive about
the last swine influenza pandemic even
though the virus was relatively mild with mostly moderate
worry was what might happen if the virus mutated or combined with
another virus making it very much more virulent and
turning it into the
killer flu that everyone has been worrying about, the one that could
kill millions. In 1918 Spanish flu killed 50 million people.
year, seasonal flu causes an estimated fifty thousand deaths in the
European Union; most people die from bacterial infections and
secondary illnesses. The highly variable type A is the most virulent
one among the influenza viruses. Based on the antibody response these
pathogens can be subdivided into different sterotypes, e.g. H5N1 that
causes avian flu, or H1N1 that caused Spanish flu in 1918, and the
swine flu 2009. Owing to frequent variations in their genetic pattern,
every year different strains prevail and, therefore, specially
designed vaccines have to be manufactured.
vaccination may help to avoid influenza. Antiviral medicines lessen
flu symptoms, but they are usually only for individuals who could
become seriously ill from flu. Side effects of antiviral drugs include
nausea, vomiting, dizziness, and insomnia. In children much has
recently been made of the fact they also cause nightmares. Although
the H1N1 type causing the current influenza outbreak is of lower
virulence, authorities nevertheless do fear the mortality rate could
increase this winter and assess the pandemic as a potentially huge
challenge for the health authorities. It has been announced that a
vaccine against the swine flu virus should be available in the last
quarter of this year. But virus researchers worry about one thing
above all; the formation of a new subtype combining two different
strains of virus initiating a sudden antigenic shift. Such a rare but
not unrealistic incident could thwart all efforts to contain the
Sober-minded contemporaries may wonder about alternative approaches to
prevent flu carefully considering issues such as why so many
individuals are not becoming ill in spite of contact with
infected persons? The main reason might be that their immune defence
copes effectively with the virus challenge. Until recently, immunity
was seen as the process whereby extremely specific antibodies targeted
the invading pathogen. However, it takes quite a long time before the
acquired immune system produces the explicit antibody; though
vaccination with innocent viruses may bridge that gap. One should
nevertheless bear in mind that the overwhelming part of the
antimicrobial defence still has to be done by the innate immune
system. This arm of immunity was the poor cousin of biomedical
research for a long time but recently many advances have been made in
understanding host innate responses to microorganisms.
It is now
generally accepted that macrophages and other white blood cells
constitute the backbone of our innate immune system. Just like gate
keepers they accumulate in the epithelia of nasopharynx (nasal
cavities), mouth, intestine and other mucous surfaces – the main entry
ports of viruses, bacteria, fungi, and parasites. These cells are
armed with germ-line encoded proteins to recognize a set of surface
structures on pathogens, engulf, kill and destroy the invader. In that
way the overwhelming majority of potential infections are arrested in
epithelial and superficial connective tissues long before antibodies
and antigen specific killer cells have had time enough to come to the
Occasionally, the immune system may become unbalanced, overwhelmed
and/or respond incorrectly. Allergy, asthma, arthritis pain, chronic
fatigue, diabetes, cancer, and frequently recurring infections are
related to impaired immunity or inappropriate reactivity. A wide range
of factors may restrict immune defence: old age, poor diet, exhaustive
life style, mental or physical stress, sudden change in personal life,
grief, exposure to UV irradiation, and possible insufficient exposure
to microbial products that exercise the innate immune system in a
natural manner. Furthermore the immune system of infants and school
children may have not be fully developed.
many laboratories have begun to elucidate the network of surface
receptors on immune cells and signalling mediator molecules. On this
basis it has become possible to design ways using ummuno-modulators to
up-regulate or down-regulate specific facets of the host response to
infectious agents. This approach allows the host to better cope itself
with invading microorganisms. Viruses and other pathogens are not
able to develop any resistance to such immuno-modulators.
reports document the ability of certain sugar polymers to
non-specifically activate cellular and humoral components of the host
immune system. During evolution, the immune system has “learned” to
recognize surface beta-glucans as alien to the members of the animal
kingdom and to allot a microbial as a potential pathogen that is
implemented with such a molecular assembly. Beta-glucan – or
exactly beta (1,3),(1,6)-D-glucan
- primes the host immune system through a mechanism similar to that of
an infection by a pathogen.
occurs as a primary constituent in the cell wall of fungi and
bacteria. Beta-glucan molecules apparently have a structural function
in forming a fibrous scaffold of the cell wall of bakers yeast and are
responsible for its rigidity and cell shape. Disintegration of yeast
cells by autolysis and skilful fractional purification of the cell
wall have been shown to be a sufficiently gentle procedure to create
products that have a very high immuno-modulatory effect. Detailed
studies elucidated a pattern recognition mechanism for the beta-glucan
interaction with the receptor complex on macrophages. Harsh procedures
to yield highly purified beta-glucan may disorganize the
supramolecular assemblage of the polyglucoside-glycoprotein-network.
In experimental assays on neutrophils highly purified samples have
proven lower biological activity.
has virtually disappeared from today’s diet since it has been replaced
with chemical surrogates in the baking of bread and cakes and beer
brewing, a daily intake of about ½ a gram of beta-glucan can help
prevent flu virus infection and puts our innate immune system on
highest alert to cope with any subsequent infection such as
pneumonia. As soon as a vaccine against flu is available
continuous regular administration of beta-glucan is recommended.
Veterinarians investigating the antibody titre (using special testing
dilutions) against the swine flu virus in vaccinated pigs confirmed
much better results when the animals were fed beta-glucan brands
derived from yeast.
If used in combination with anti-viral drugs, where the mode of action
is very different, each component amplifies the efficacy of the other.
Furthermore, no adverse effects, reactions or toxicities were reported
by any healthy or ill individuals involved in studies. Both in the US
and Germany beta-glucan 1-3, 1-6 has been consumed as a food
supplement in large quantities for years.
Gerhard Gerber, Prof. Dr. sc.
Alumnus, Medical Faculty (Charité),
Humboldt University of Berlin, Germany
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