Many of us, particularly those who
prefer to eat our cake and look like we
have not done so, have a love-hate
relationship with artificial sweeteners.
These seemingly magical molecules
deliver a dulcet taste without its
customary caloric punch. We guzzle
enormous quantities of these chemicals,
mostly in the form of aspartame,
sucralose and saccharin, which are used
to enliven the flavor of everything from
Diet Coke to toothpaste. Yet there are
worries. Many suspect that all this
sweetness comes at some hidden cost to
our health, although science has only
pointed at vague links to problems.
Last year, though, a team of Israeli
scientists put together a stronger case.
The researchers concluded from studies
of mice that ingesting artificial
sweeteners might lead to—of all things—
obesity and related ailments such as
diabetes. This study was not the first to
note this link in animals, but it was the
first to find evidence of a plausible
cause: the sweeteners appear to change
the population of intestinal bacteria that
direct metabolism, the conversion of
food to energy or stored fuel. And this
result suggests the connection might also
exist in humans.
In humans, as well as mice, the ability to
digest and extract energy from our food
is determined not only by our genes but
also by the activity of the trillions of
microbes that dwell within our digestive
tract; collectively, these bacteria are
known as the gut microbiome. The
Israeli study suggests that artificial
sweeteners enhance the populations of
gut bacteria that are more efficient at
pulling energy from our food and
turning that energy into fat. In other
words, artificial sweeteners may favor
the growth of bacteria that make more
calories available to us, calories that can
then find their way to our hips, thighs
and midriffs, says Peter Turnbaugh of
the University of California, San
Francisco, an expert on the interplay of
bacteria and metabolism.
Bacterial gluttons
In the Israeli experiment, 10-week-old
mice were fed a daily dose of aspartame,
sucralose or saccharin. Another cluster
of mice were given water laced with one
of two natural sugars, glucose or sucrose.
After 11 weeks, the mice receiving sugar
were doing fine, whereas the mice fed
artificial sweeteners had abnormally
high blood sugar (glucose) levels, an
indication that their tissues were having
difficulty absorbing glucose from the
blood. Left unchecked, this “glucose
intolerance” can lead to a host of health
problems, including diabetes and a
heightened risk of liver and heart
disease. But it is reversible: after the
mice were treated with broad-spectrum
antibiotics to kill all their gut bacteria,
the microbial population eventually
returned to its original makeup and
balance, as did blood glucose control.
“These bacteria are not agnostic to
artificial sweeteners,” says
computational biologist Eran Segal of the
Weizmann Institute of Science in
Rehovot, Israel, one of the two scientists
leading the study. The investigators also
found that the microbial populations that
thrived on artificial sweeteners were the
very same ones shown—by other
researchers—to be particularly
abundant in the guts of genetically obese
mice.
Jeffrey Gordon, a physician and biologist
at Washington University in St. Louis,
has done research showing that this
relation between bacteria and obesity is
more than a coincidence. Gordon notes
that more than 90 percent of the
bacterial species in the gut come from
just two subgroups—Bacteroidetes and
Firmicutes. Gordon and his team found
several years ago that genetically obese
mice (the animals lacked the ability to
make leptin, a hormone that limits
appetite) had 50 percent fewer
Bacteroidetes bacteria and 50 percent
more Firmicutes bacteria than normal
mice did. When they transferred a
sample of the Firmicutes bacterial
population from the obese mice into
normal-weight ones, the normal mice
became fatter. The reason for this
response, Gordon says, was twofold:
Firmicutes bacteria transplanted from
the fat mice produced more of the
enzymes that helped the animals extract
more energy from their food, and the
bacteria also manipulated the genes of
the normal mice in ways that triggered
the storage of fat rather than its
breakdown for energy.
Gordon believes something similar
occurs in obese humans. He found that
the proportion of Bacteroidetes to
Firmicutes bacteria increases as fat
people lose weight through either a low-
fat or low-carbohydrate diet. Stanford
University microbiologist David Relman
says this finding suggests that the
bacteria in the human gut may not only
influence our ability to extract calories
and store energy from our diet but also
have an impact on the balance of
hormones, such as leptin, that shape our
very eating behavior, leading some of us
to eat more than others in any given
situation.
The burning question, of course, is
whether artificial sweeteners can truly
make humans sick and fat. Segal thinks
they probably do, at least in some cases.
He and his team analyzed a database of
381 men and women and found that
those who used artificial sweeteners
were more likely than others to be
overweight. They were also more likely
to have impaired glucose tolerance.
Obesity is, in fact, well known as a risk
factor for the development of glucose
intolerance as well as more severe
glucose-related ailments, such as
diabetes.
These patterns do not prove that the
sweeteners caused the problems. Indeed,
it is quite possible that overweight people
are simply more likely than others to
consume artificial sweeteners. But
Segal's team went further, testing the
association directly in a small group of
lean and healthy human volunteers who
normally eschewed artificial sweeteners.
After consuming the U.S. Food and Drug
Administration's maximum dose of
saccharin over a period of five days,
four of the seven subjects showed a
reduced glucose response in addition to
an abrupt change in their gut microbes.
The three volunteers whose glucose
tolerance did not dip showed no change
in their gut microbes.
Although not everyone seems susceptible
to this effect, the findings do warrant
more research, the scientists say. The
Israeli group concluded in its paper that
artificial sweeteners “may have directly
contributed to enhancing the exact
epidemic that they themselves were
intended to fight”—that is, the
sweeteners may be making at least some
of us heavier and more ill.
A cause-and-effect chain from
sweeteners to microbes to obesity could
explain some puzzles about obese people,
says New York University
gastroenterologist Ilseung Cho, who
researches the role of gut bacteria in
human disorders. He points out that in
studies, most people who switch from
sugar to low-calorie sweeteners in an
effort to lose weight fail to do so at the
expected rate. “We've suspected for
years that changes in gut bacteria may
play some role in obesity,” he says,
although it has been hard to pinpoint
this effect. But Cho adds that it is clear
that “whatever your normal diet is can
have a huge impact on the bacterial
population of your gut, an impact that is
hard to overestimate. We know that we
don't see the weight-loss benefit one
would expect from these nonnutritive
sweeteners, and a shift in the balance of
gut bacteria may well be the reason,
especially a shift that results in a change
in hormonal balances. A hormone is like
a force multiplier—and if a change in
our gut microbes has an impact on
hormones that control eating, well, that
would explain a lot.”
Microbes vs. genes
Naturally there are many questions left
to answer. Cathryn Nagler, a pathologist
at the University of Chicago and an
expert on gut bacteria and food allergies,
says that the enormous genetic
variations in humans make
extrapolations from mice suspect. “Still, I
found the data very compelling,” she
says of the Israeli artificial sweetener
study. Relman agrees that rodent studies
are not always reflective of what
happens in humans. “Animal studies can
point to a general phenomenon, but
animals in these studies tend to be
genetically identical, while in humans,
lifestyle histories and genetic differences
can play a very powerful role,” he says.
The constellation of microbes in a
human body is a reflection of that body's
particular history—both genetic and
environmental.
“The microbiome is a component
intertwined in a complex puzzle,”
Relman continues. “And sometimes the
genetics is so strong that it will override
and drive back the microbiota.” Genetic
variations might explain why only four
of the seven saccharin-fed humans had a
change in their gut bacteria, for
instance, although genetics is only one of
a number of possible factors. And if
someone is genetically predisposed to
obesity and consumes a diet that
promotes that obesity, the microbes
might change to take advantage of that
diet, thereby amplifying the effect.
The Israeli researchers agree that it is far
too soon to conclude that artificial
sweeteners cause metabolic disorders,
but they and other scientists are
convinced that at least one—saccharin—
has a significant effect on the balance of
microbes in the human gut. “The
evidence is very compelling,” Turnbaugh
says. “Something is definitely going on.”
Segal, for one, is taking no chances: he
says that he has switched from using
artificial to natural sweetener in his
morning coffee.
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