"Fasting for Cancer: What About Cachexia?"
In 1974, an influential paper was published decrying
physician-induced malnutrition as the skeleton in the hospital closet ---
the fact that many patients in hospitals were malnourished,
which the editorial board of the journal of the AMA
described as shocking.
"Even a single case is one too many,"
yet still to this day the issue persists.
If anything, people with serious illness would seem to need
even more nutrition, not less, yet underfeeding
persists, involving as many as 50% of hospitalized patients.
The ethical principle of justice requires that every patient
be fed enough, given that hospital malnutrition
has been associated with increased
risk of disease and death, but is it cause and effect?
Does eating less make you sicker,
or does being sicker just make you eat less?
You don't know until you put it to the test.
But would it be ethical to randomize patients to remain starved?
I mean wouldn't nutritional support obviously help?
It turns out, no. Not one, but 22 randomized controlled
trials involving thousands of malnourished patients
found that, sure, you can plump them up;
however, there seemed to be little effect on clinical outcomes.
In fact, sometimes it can actually make things worse.
Maybe your body is losing your appetite on purpose.
Ever since Hippocrates, fasting has been offered as a treatment
for acute and chronic diseases, based on the observation
that when people get sick, they frequently lose their appetite,
so maybe that's part of our body's wisdom and we shouldn't force it?
OK, but that was 2400 years ago. What have we learned since?
Along with fever, decreased food consumption is indeed
one of the most common signs of infection, often regarded
as an undesirable manifestation of sickness,
but it's actually an active, beneficial defense mechanism.
Now obviously, chronic under-nutrition can impair
our defenses, but data suggest that in the short-term,
immune function can be enhanced by lowering food intake.
Some of the data are crazy, like 95% alive versus 95% dead
after the same infection,
but that was in mice starved for 48 hours.
Obviously, you can't randomize people to a fatal infection,
but what they showed is that the blood from starved mice was
nearly 8 times better at killing off the invading bacteria
in a petri dish. It dramatically boosted
the capacity of their white blood cells to kill off the pathogens.
Why can't we just test people like that? Indeed, we can.
Researchers fasted people for two weeks
on an 80 calorie a day diet,
and their white blood cells showed the same kind of boost
in bacteria-killing activity, a boost in antibody production,
and natural killer cell activity increased by an average of 24%.
Now that's especially interesting because our natural killer cells
don't just help clear infections, but also kill cancer cells.
In fact, that's how they measured natural killer cell activity by pitting
them against K562 cells --- those are tumor cells, human leukemia cells.
So two weeks of fasting boosted their bloodstream's ability
to kill off cancer cells by 24%.
So fasting is said to improve anticancer immunosurveillance,
or more poetically
"stimulate the appetite of the immune system for cancer. "
So why isn't fasting used more to treat cancer? Until recently,
fasting therapy was not considered to be a treatment option
in cancer, related to the fact that a common therapeutic goal
in palliative cancer treatment is to avoid weight loss
and to counteract the wasting syndrome known as cachexia,
which is the ultimate cause of death in many cancer cases.
Tumors are voracious, rapidly expanding,
and needing lots of energy and protein,
and so metabolically reprograms our body
to start breaking down to feed it.
It does this by triggering inflammation throughout the body.
It's not just that people lose their appetite.
The fundamental difference between weight loss
observed in cancer cachexia and that seen in simple starvation
is the lack of reversibility with feeding alone.
For example, here's the weight of a cancer patient that started to drop.
No wonder: they were only taking in a few hundred calories a day.
So in addition to giving them about 100 grams of protein a day,
they stuck a tube into a vein and infused up to 4,000 calories a day.
But it didn't matter. They continued to lose weight.
Therapeutic nutritional interventions to correct or reverse
cachexia have met with little success.
The best treatment for cancer cachexia therefore
is to treat the cause and cure the cancer.
In fact, maybe forcing extra nutrition on cancer patients
could be playing right into the tumor's hands.
Like in pregnancy when the fetus gets first dibs on nutrients
even at the mother's expense,
the tumor may be first in the feeding line.
Maybe our loss of appetite when we get cancer
is even a protective response.
But in the 1960s, TPN was born --- total parenteral nutrition ---
where people no longer had to eat;
and you could infuse all the nutrition people needed straight
into their veins, and the modern era of nutrition support was born.
It became widely accepted and implemented,
growing into a multibillion-dollar industry.
So should it be routinely given to malnourished cancer patients?
The answer is not as obvious as one might think.
When it was put to the test in dozens of randomized trials,
the results were both disappointing and surprising.
Parenteral nutrition didn't just fail to provide any benefit
to these patients; it caused harm.
Not only did it appear to provide zero survival benefit,
there was an increase in complications and infections,
and a decrease in tumor response to chemotherapy,
presumed to be due to all those extra nutrients
stimulating tumor growth. Similarly, oral nutritional
interventions in malnourished patients with cancer,
like giving them bottles of Ensure, found no survival advantage.
Despite the lack of demonstrated benefit, the knee jerk reaction
of many oncologists to the idea of cancer patients fasting
is the concern they're not eating enough already.
But you don't know until you put it to the test,
which we'll explore next.