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THERE’S a hole in your leg, a nasty, suppurating flesh wound that’s been
there for a week and just isn’t getting any better. Now it’s infected. Forget
any misgivings you may have about a trip to the doctor’s—this is serious.
Down at the surgery, things turn a little weird. Your physician takes a look at
the hole and offers you a poultice of spit and sugar solution. “Quack,” you
think. “The guy’s a charlatan.” As if reading your thoughts, he assures you that
the combination of bee’s saliva and nectar—honey—has been used to
treat wounds for millennia. You point out that we now live in an age of
antibiotics, so you’d rather not resort to alternative therapies. But the doctor
tells you that in tests honey has outperformed conventional antibiotics in
treating infected Caesarean sections and burns.

Still not convinced? Well, neither is most of the medical profession. But a
small band of researchers is hoping to change that, and several of them spoke
last month in Melbourne at the First World Wound Healing Congress. They have
found that the sweet stuff fights an impressive line-up of microbes, including
E. coli, Salmonella and Helicobacter. What’s more, it
is equally effective against antibiotic-resistant bacteria—including the
infamous hospital superbug MRSA. And unlike most other antibiotics, honey
actively promotes wound healing.

But you have to chose your honey carefully. It turns out that the most
effective brews are two relative newcomers: honeys from New Zealand and
Australia that have only been made since the 19th century, when Europeans
introduced honeybees to the Antipodes. Both manuka and jelly bush honey are made
with nectar from native tea trees, which seems to account for their unusual
potency. How they work is still something of a mystery, but the researchers
believe that their talents for healing wounds and fighting antibiotic-resistant
microbes may catapult these honeys from the realms of alternative therapy into
mainstream medicine.

The secret of any honey’s success starts with the ingenious way honeybees
protect their hard-earned hoard to sustain them over the winter. Worker bees
gather nectar from flowers during spring and summer, and regurgitate it into the
mouths of waiting hive-mates. They spit it out into the honeycomb and fan it
with their wings until most of the water in the nectar has evaporated. At the
same time, their enzyme-rich saliva turns the sucrose into glucose and fructose,
which bind to the remaining water leaving a desert in which bacteria cannot
survive. While the honey is ripening, though, there’s ample opportunity for
pathogens to invade. Protection comes in the form of the bees’ prize enzyme,
glucose oxidase, which makes the brew acidic and hostile to most bacteria by
converting glucose into gluconic acid.

Sugar concentration and acidity were widely believed to be honey’s only
weapons against bacteria, although the plasma that oozes from wounds soon
dilutes them away. But it turns out that almost all honey has a secret weapon
that makes it deadly to microbes even in diluted form: hydrogen peroxide. This
chemical was once used to disinfect wounds in hospitals. As it breaks down,
hydroxyl radicals are formed that damage bacteria. Because this reaction happens
quickly, hydrogen peroxide had to be applied to wounds at concentrations so high
that it damaged healthy tissue.

In honey, where hydrogen peroxide is created from glucose, again with the
help of the enzyme glucose oxidase, levels of the chemical are around 1000 times
lower than those traditionally applied to wounds. As a result, there is no
tissue damage. What’s more, as the hydrogen peroxide breaks down, the enzyme
constantly replaces it by catalysing its formation from glucose. The diluting
action of fluids produced by a wound actually kick-starts the enzyme, which for
unknown reasons is inactive in full-strength honey. Honey can still prevent the
growth of bacteria such as MRSA after being diluted seven to 14 times beyond the
point where the sugar content is effective.

Not all honeys possess equal levels of this secret antibacterial weapon,
though. Some are indeed little better than sugary acid. “Most research has
entirely ignored the huge variation in the antibacterial potency of different
honeys,” says biochemist Peter Molan, who heads the Honey Research Unit at the
University of Waikato, New Zealand. Some honeys are so potent that they’ll stop
bacteria growing on agar at a concentration of just 0.4 per cent, while others
fail below a strength of 50 per cent.

The potency of a honey depends on the bees—or, more specifically, the
type of flower they take a liking to. The nectar of some flowers contains high
levels of catalase, an enzyme that destroys hydrogen peroxide. Other nectars
somehow make glucose oxidase particularly susceptible to degradation by heat and
light, so these honeys require delicate treatment after harvesting. Whatever
flower the bees choose, though, you can be sure that a hot lemon and honey drink
will be bereft of the active enzyme because glucose oxidase cannot stand the
heat.

So Molan was surprised to discover that even boiling doesn’t destroy the
antibacterial activity of some honeys. He also found that honey from the flower
of a New Zealand tea tree called manuka retains a whopping half of its
antibacterial activity after being bombarded with catalase. Clearly, there is
something else at work other than glucose oxidase and hydrogen peroxide. Molan
has spent 18 years trying to identify this mystery manuka ingredient, which he
refers to as a phytochemical agent. “We still haven’t got it isolated in a pure
enough form to work out its chemical structure,” he says.

When it comes to fighting the most common bacteria that infect wounds, the
manuka phytochemical agent outperforms hydrogen peroxide on an agar plate. And
honey researchers suspect it might positively excel in the wounds of real
patients. Ironically, the factors that make the phytochemical impossible to
isolate also make it ideal for wounds. Water-loving and tiny, it can penetrate
flesh much more deeply than hydrogen peroxide. It can get through at least 1
centimetre of pork skin, fat and muscle overnight, Molan found. The
phytochemical also works at any pH, even in the acidity of
full-strength honey, because it lacks an ionic charge.

Its other beauty is that because it does not rely on an enzyme to catalyse
its production, it is sturdy. A jar of manuka honey can sit on a sunny window
sill for months and still remain active. Glucose oxidase needs oxygen, but the
phytochemical can withstand being smothered by a wound dressing. And the
catalase in human plasma, which degrades hydrogen peroxide, doesn’t faze the
phytochemical. Molan is concerned that this degradation could undermine most
honeys’ ability to kill off bacteria in wounds.

Ready and waiting

The phytochemical’s superiority in real wounds is purely theoretical so far,
but a clinical trial is being prepared in New Zealand to compare the
effectiveness of catalase-treated manuka honey, where all the hydrogen peroxide
has been broken down, with honey that owes most of its healing power to hydrogen
peroxide.

Lab tests have already shown that manuka honey is effective against
antibiotic-resistant strains of bacteria. Whether microbes will acquire
resistance to honey remains to be seen, but Molan is optimistic. Most
antibiotics are based on the defence products of soil fungi and bacteria, he
explains. These organisms have probably been involved in germ warfare with
infectious human bacteria for millennia. So when their defensive chemicals were
turned into medicines last century, bacterial genes that allowed human pathogens
to resist the onslaughts were already waiting in the wings. “There’s not likely
to have been much chance for germ warfare over manuka nectar, which only exists
for a few weeks each year, in a tiny area of the globe,” says Molan.

People probably began using manuka honey on wounds shortly after New
Zealand’s newly imported honeybees began churning it out in the 19th century,
making the mystery phytochemical agent a relative newcomer on the medical scene.
Elsewhere, although honey has been used on wounds since Egyptian times, bacteria
don’t seem to be able to defend themselves against its hydrogen peroxide. Some
species of bacteria, including Staphylococcus aureus (the resistant
strain is MRSA), do produce catalase. Yet not only is S. aureus one of
the species most sensitive to honey, no relationship has been found between the
catalase activity of its various strains and their sensitivity to hydrogen
peroxide, suggesting the bacteria can’t break it down.

Honey also has a huge advantage over conventional antibacterial drugs because
it promotes healing. Many other treatments actually damage human cells along
with the bacteria, and heal only by controlling the growth of microbes. In
contrast, most honey seems to heal directly. Honey creates an unusually moist
environment—which is perfect for tissue growth—while simultaneously
controlling bacteria that would otherwise fester in the damp. Moistness prevents
the pain and cell damage that occur when dried-out dressings are changed.

Hospital staff have also found that honey cleans away dead tissue
painlessly—an appealing alternative to the normally traumatic chemical or
surgical removal of necrotic tissue. “Anyone using it for the first time is rapt
with that effect,” says Molan. It works because hydrogen peroxide activates
protein-munching enzymes in the patient that dissolve only dead or dying tissue.
Maggots clean wounds in a similar way, he explains. But honey doesn’t
squirm.

Molan suspects that hydrogen peroxide is responsible for at least some of
honey’s healing powers. At the minuscule levels in honey, hydrogen peroxide
stimulates the growth of blood vessels, which deliver oxygen and nutrients, as
well as the cells known as fibroblasts, which create new connective tissue.

Honey’s healing ability has also impressed Ken Jones and Rose Cooper from the
University of Wales Institute Cardiff (UWIC). They grew human cells exposed to
honey and found signs of an “incredibly immunostimulatory compound”. Jones, an
immunologist, told the congress in Melbourne that weak dilutions of honey
activate a type of immune cell called monocytes. “Monocytes release growth
factors that stimulate epithelial cells to regenerate and close the wound,” he
explains. They also mature into another type of immune cell called a macrophage,
which guzzles microbes and dead cells.

But once again, not all honeys are equally effective. The researchers were
mainly impressed by Australian honey from the jelly bush which, like manuka, is
a tea tree. Jones believes that a phytochemical agent is at work again, because
another honey that relies solely on the healing powers of hydrogen peroxide did
not perform nearly as well as jelly bush honey in the monocyte test. He is now
hoping to identify the active phytochemical. “It may be something completely
unrelated to the components involved in its antimicrobial properties,” he
says.

So should we all adopt Pooh Bear-like habits and start to guzzle honey, or
does it only work externally? “There’s no evidence that eating honey helps
immunity,” according to Jones. That said, Molan has found that swallowing half a
teaspoon of manuka honey on an empty stomach will put a stop to the
Helicobacter that cause most gastric ulcers.

Cooper hopes that manuka honey inhalers might also be a possibility one day.
She has shown that the antibiotic resistant bacterium Burkholderia
cepacia, which plague the lungs of cystic fibrosis patients, succumbs to
honey on agar plates. Honey aerosols have already been used in Eastern Europe to
treat chronic bronchitis.

One therapy that nobody is advocating is home treatment from the kitchen
cupboard. “Wound infections should be managed only by medical professionals,”
says Cooper. Honey can contain the spores that cause botulism, and there is a
risk of introducing these into wounds. Fortunately, the spores are destroyed by
steam sterilisation or gamma-irradiation, but only the latter leaves hydrogen
peroxide and phytochemical activities intact. Many honeys processed for eating
have been pasteurised, which does not kill spores but does destroy glucose
oxidase.

Only a scattering of experts in wound care around the world have adopted
honey as a standard dressing for wounds. And Keith Harding, head of the
respected Wound Healing Research Unit at the University of Wales College of
Medicine, thinks there will be a huge battle in getting honey taken up by
mainstream medicine. “I personally was sceptical at first. It was only after the
laboratory research findings showed such impressive results that I was convinced
to try it on some of my patients,” he says. His results have been mixed, and
although he describes honey as “a very interesting therapy”, he advises caution.
“Further work is required, in my view, to identify much more accurately the
exact group of patients that may benefit from this intervention.”

In other words it’s a matter of wait and see. Physicians are waiting to be
convinced, and until the evidence is compelling, honey will hover on the
alternative medicine side of the fence. But the spectre of antibiotic resistance
makes the bees’ therapy worth pursuing. Because bacteria, like Winnie the Pooh
with his head stuck in a sticky pot, just can’t resist honey.