The women's hospital at the University of Würzburg used to be the
biggest of its kind in Germany. Its former size is part of the
historical burden it carries — countless women were involuntarily
sterilized here when it stood in the geographical center of Nazi
Germany.
Today, the capacity of the historical building overlooking the
college town, where the baroque and mid-20th-century concrete stand in a
jarring mix, has been downsized considerably. And the experiments
within its walls are of a very different nature.
Since early 2007, Dr. Melanie Schmidt and biologist Ulrike Kämmerer,
both at the Würzburg hospital, have been enrolling cancer patients in a
Phase I clinical study of a most unexpected medication: fat. Their trial
puts patients on a so-called ketogenic diet, which eliminates almost
all carbohydrates, including sugar, and provides energy only from
high-quality plant oils, such as hempseed and linseed oil, and protein
from soy and animal products.
What sounds like yet another version of the Atkins craze is actually
based on scientific evidence that dates back more than 80 years. In
1924, the German Nobel laureate Otto Warburg first published his
observations of a common feature he saw in fast-growing tumors: unlike
healthy cells, which generate energy by metabolizing sugar in their
mitochondria, cancer cells appeared to fuel themselves exclusively
through glycolysis, a less-efficient means of creating energy through
the fermentation of sugar in the cytoplasm. Warburg believed that this
metabolic switch was the primary cause of cancer, a theory that he
strove, unsuccessfully, to establish until his death in 1970.
To the two researchers in Würzburg, the theoretical debate about what
is now known as the Warburg effect — whether it is the primary cause of
cancer or a mere metabolic side effect — is irrelevant. What they
believe is that it can be therapeutically exploited. The theory is
simple: If most aggressive cancers rely on the fermentation of sugar for
growing and dividing, then take away the sugar and they should stop
spreading. Meanwhile, normal body and brain cells should be able to
handle the sugar starvation; they can switch to generating energy from
fatty molecules called ketone bodies — the body's main source of energy
on a fat-rich diet — an ability that some or most fast-growing and
invasive cancers seem to lack.
The Würzburg trial, funded by the Otzberg, Germany–based diet food
company Tavartis, which supplies the researchers with food packages, is
still in its early, difficult stages. "One big problem we have," says
Schmidt, sitting uncomfortably on a small, wooden chair in the crammed
tea kitchen of Kämmerer's lab, "is that we are only allowed to enroll
patients who have completely run out of all other therapeutic options."
That means that most people in the study are faring very badly to begin
with. All have exhausted traditional treatments, such as surgery,
radiation and chemo, and even some alternative ones like hyperthermia
and autohemotherapy. Patients in the study have pancreatic tumors and
aggressive brain tumors called glioblastomas, among other cancers;
participants are recruited primarily because their tumors show high
glucose metabolism in PET scans.
Four of the patients were so ill, they died within the first week of
the study. Others, says Schmidt, dropped out because they found it hard
to stick to the no-sweets diet: "We didn't expect this to be such a big
problem, but a considerable number of patients left the study because
they were unable or unwilling to renounce soft drinks, chocolate and so
on."
The good news is that for five patients who were able to endure three
months of carb-free eating, the results were positive: the patients
stayed alive, their physical condition stabilized or improved and their
tumors slowed or stopped growing, or shrunk. These early findings have
elicited "very positive reactions and an increased interest from
colleagues," Kämmerer says, while cautioning that the results are
preliminary and that the study was not designed to test efficacy, but to
identify side effects and determine the safety of the diet-based
approach. So far, it's impossible to predict whether it will really
work. It is already evident that it doesn't always: two patients
recently left the study because their tumors kept growing, even though
they stuck to the diet.
Past studies, however, offer some hope. The first human experiments
with the ketogenic diet were conducted in two children with brain cancer
by Case Western Reserve oncologist Linda Nebeling, now with the
National Cancer Institute. Both children responded well to the high-fat
diet. When Nebeling last got in contact with the patients' parents in
2005, a decade after her study, one of the subjects was still alive and
still on a high-fat diet. It would be scientifically unsound to draw
general conclusions from her study, says Nebeling, but some experts,
such as Boston College's Thomas Seyfried, say it's still a remarkable
achievement. Seyfried has long called for clinical trials of low-carb,
high-fat diets against cancer, and has been trying to push research in
the field with animal studies: His results suggest that mice survive
cancers, including brain cancer, much longer when put on high-fat diets,
even longer when the diets are also calorie-restricted. "Clinical
studies are highly warranted," he says, attributing the lack of human
studies to the medical establishment, which he feels is single-minded in
its approach to treatment, and opposition from the pharmaceutical
industry, which doesn't stand to profit much from a dietetic treatment
for cancer.
The tide appears to be shifting. A study similar to the trial in
Würzburg is now under way in Amsterdam, and another, slated to begin in
mid-October, is currently awaiting final approval by the ethics
committee at the University Hospital in Tübingen, Germany. There, in the
renowned old research institution in the German southwest,
neuro-oncologist Dr. Johannes Rieger wants to enroll patients with
glioblastoma and astrocytoma, aggressive brain cancers for which there
are hardly any sustainable therapies. Cell culture and animal
experiments suggest that these tumors should respond particularly well
to low-carb, high-fat diets. And, usually, these patients are physically
sound, since the cancer affects only the brain. "We hope, and we have
reason to believe, that it will work," says Rieger.
Still, none of the researchers currently studying ketogenic diets,
including Rieger, expects it to deliver anything close to a universal
treatment for cancer. And none of them wants to create exaggerated hopes
for a miracle cure in seriously ill patients, who may never benefit
from the approach. But the recent findings are difficult to ignore.
Robert Weinberg, a biology professor at MIT's Whitehead Institute who
discovered the first human oncogene, has long been critical of
therapeutic approaches based on the Warburg effect, and has certainly
dismissed it as a primary cause of cancer. Nevertheless, he conceded, in
an email, for tumors that have been affected by the ketogenic diet in
animal models, "there might be some reason to go ahead with a Phase I
clinical trial, especially for patients who have no other realistic
therapeutic options."
Source: Time.com
Lead author Debra Barton, from the Mayo Clinic in Rochester, Minnesota
said that nearly all patients with cancer can suffer from fatigue at
some point; either at diagnosis, during treatment and even after
treatment, and (fatigue) can linger for several years. 
