We have a lot of choices to make about our diet.
Add to that, doing the right thing
when it comes to preventing
and treating a chronic disease,
fighting a virus, or losing weight,
and suddenly our nutrition choices
can seem almost overwhelming.
Well, I’m here to help.
Welcome to the Nutrition Facts Podcast.
I’m your host, Dr. Michael Greger.
Today we begin a two-part series on the effects of fasting on cancer.
Do we feed cancer?
Do we starve it?
What do randomized trials tell us?
Here’s our first story.
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 until you put it to the test,
which we'll explore next.
For the past 50 years, chemotherapy has been a major medical treatment
for a wide range of cancers.
Its main strategy has been largely based on targeting cancer cells,
by means of DNA damage caused in part by the
production of free radicals.
Although these drugs were first believed to be
quite selective for tumor cells,
we now know that normal cells also experience severe
chemotherapy-dependent damage, leading to dose-limiting side effects
including bone marrow and immune system suppression,
fatigue, vomiting, diarrhea, and in some cases even death.
And if you do survive, the DNA damage to normal cells
can even lead to new cancers down the road.
There are cell-protecting drugs that have been tried
to reduce the side effects,
so you can pump in higher chemo doses,
but these drugs have not been shown to increase survival,
in part because they may also be protecting the cancer cells.
What about instead using fasting
for cellular protection during cancer treatment?
Fasting may have an unrecognized role
in cancer prevention and treatment.
Short-term fasting before and immediately after chemotherapy
may minimize side effects, while at the same time
may actually make cancer cells more sensitive to treatment.
That's exciting.
During nutrient deprivation, healthy cells switch from growth
to maintenance and repair, but tumor cells are unable
to slow down their unbridled growth due to growth-promoting mutations
that led them to become cancer cells in the first place.
This inability to adapt to starvation may represent an important
Achilles' heel for many types of cancer cells.
As a consequence of these differential responses
of healthy versus cancer cells to short-term fasting,
chemotherapy causes more DNA damage and cell suicide
in tumor cells, while potentially leaving healthy cells unharmed.
Thus, short-term fasting may protect healthy cells
against the toxic properties of chemotherapy
and render tumor cells more sensitive,
or at least that's the theory.
Let's test it out.
Tyrosine kinase inhibitors are a group of chemo drugs
that are now the mainstay of treatment in many types of cancer.
Let's see them in action.
These are petri dishes filled with cancer cells that
have been dyed pink.
Two types of lung cancer cells and one type of colorectal cancer.
This is the before, and this the after, exposed to the chemo drugs
erlotinib, gefitinib, crizotinib, and regorafenib.
See how there's less pink?
That shows how many cancer cells the chemo killed off.
Starve the cells for 24 hours first, though,
and the drugs work even better.
Even the starvation alone without the drugs killed off a bunch of them.
The researchers conclude that these TKI drugs that are
commonly administrated for treating solid tumors become
potentiated in their activity by 24 hours of starvation,
but that's in a petri dish.
Similar results were found for breast cancer and
a chemo drug called doxorubicin.
Here's five days of unhindered growth of breast cancer in a petri dish,
from 150,000 cancer cells to 800,000 in under a week.
Dripping on a little chemo can knock it down to around 600,000,
but starve those cells for 48 hours first,
and the chemo can completely keep them in check.
Even the short-term starvation alone can restrain growth.
Short-term fasting raises the possibility that you could get
twice the effect for half the dose, which may be particularly important
for a drug as toxic as doxorubicin, which causes heart failure
in as many as 1 in 3 at higher doses.
Again, though, these are just in vitro studies in a petri dish
Then researchers moved to mice and found the same dual benefit:
less toxic chemo, yet at the same time
more effective, and not just by a little.
A high enough chemo dose to kill 100% in less than a week.
But after being starved for 60 hours, after the same dose, 100% survived.
Ok, that's the toxicity.
What about efficacy?
Here's tumor growth without chemo, growth with chemo,
and with chemo after short-term fasting,
and this translated into improved survival.
Interestingly, fasting alone appeared to work
as well as the chemo, and the same with radiation.
Unbridled tumor growth knocked down by radiation therapy,
and even more so after the combination of radiation
and alternate-day fasting,
but alternate-day fasting alone seemed to do as well as the radiation.
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There you’ll find all the detailed information you need –
plus, links to all of the sources we cite for each of these topics.
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