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ood additives are a mainstay of
Western diets. New research shows how a commonly used anti-mold agent alters
sugar metabolism and drives insulin resistance in mice and men.
Does
a common preservative in bread alter our metabolism?
Obesity and type 2 diabetes have reached epidemic
levels, with nearly 40 percent of adults in the United States classed as
obese and, as of 2015, 9.4 percent living with diabetes.
Eating
a Western diet, high in processed foods, sugar, and fat, is a known risk factor
for obesity and type 2 diabetes.
Avoiding processed foods is actually not that easy.
Preservatives, which keep our food fresh for longer, lurk in many places.
One
such chemical is the anti-mold agent propionate, a short-chain fatty acid that
the bacteria in our gut produce naturally. As a preservative, its other name is
E282, and it features as a common food additive in bread and other baked goods.
According
to the Codex Alimentarius, the international food standards guide by
the World Health Organization (WHO) and the Food and Agriculture Organization
of the United Nations, propionate may be added to a host of other things, including breakfast
cereals, dairy- and egg-based deserts, sausage casings, processed cheese, and
sports drinks.
Researchers
from Harvard T.H. Chan School of Public Health, in Boston, MA, along with
colleagues at the Sheba Medical Center, in Ramat Gan, Israel, and others, made
a surprising discovery when they studied the effects of propionate in mice and
humans.
The
team recently published their findings in the journal Science
Translational Medicine.
Propionate leads to high blood sugar in mice
Dr.
Amir Tirosh, an associate professor of medicine at Tel-Aviv University's
Sackler Faculty of Medicine and director of the Institute of Endocrinology at
Sheba Medical Center, told Medical
News Today that he had initially set out to study the actions
of fatty acid-binding protein 4 (FABP4), which researchers
think plays a role in sugar and fat metabolism.
"We
incidentally came across an old scientific paper from 1912 demonstrating that administration
of propionate to dogs resulted in increased glucose production," he
explained.
To
study the connection between propionate and FABP4, Dr. Tirosh and the team gave
healthy, nonobese mice a dose of the preservative. As in the dogs, the team found
that blood sugar levels rose.
The
question is: How does propionate work to achieve this?
The researchers found that propionate activated the
sympathetic nervous system, as measured by levels of norepinephrine, and
increased the levels of the hormones glucagon and FABP4. This caused the liver
to produce high levels of glucose, which in turn led to high levels of insulin
in the blood.
"Normally,
these hormones act during fasting to protect against a dangerous drop in blood
glucose," Dr. Tirosh explained. "In this case, they are engaging
without such a threat and increasing blood glucose."
The
mice were then fed a low dose of between 0.15 and 0.3 percent propionate in
their diet over several weeks. This is equivalent to how much a person eating a
Western diet would consume.
As
a result, the mice developed higher levels of glucagon and FABP4, high levels
of blood insulin, and insulin resistance —
a hallmark of type 2 diabetes. They also put on more weight, with a significant
increase in fat mass, compared with the mice receiving a standard diet.
Propionate disrupts metabolism in humans
Next,
Dr. Tirosh and his colleagues recruited 14 healthy, nonobese volunteers.
The
study participants ate a meal containing 500 calories supplemented
with propionate in the form of 1 gram (g) of calcium propionate
or placebo.
"This
propionate dose of 1 g is equivalent to the most commonly used amount of 0.3%
[...] to which humans are exposed when consuming a single processed food–based
meal," the study authors explain.
After
2 weeks, the same participants returned, and the groups were switched, meaning
that the volunteers who were in the placebo group during the first visit ate
the propionate-containing meal during the second visit.
As
with the mice, the study participants experienced spikes of norepinephrine, glucagon,
and FABP4, increased blood insulin levels, and reduced insulin sensitivity.
"We were very surprised to see that even when
[a] small amount of propionate was given to humans, [it] had significant
effects on the systemic level of key hormones such as FABP4," Dr. Tirosh
commented.
Finally,
the research team analyzed data from 160 participants of the Dietary
Intervention Randomized Controlled Trial, known as DIRECT, to see if propionate
levels and weight loss were connected.
At
the start of the study, the team found a link between levels of propionate and
insulin resistance. After 6 months, lower levels of propionate showed an
association with more significant improvements in insulin sensitivity.
Study 'one piece of the puzzle'
Dr.
Tirosh acknowledges that the study's limitations include that fact that he was
unable to show cause and effect of propionate consumption on global obesity and
type 2 diabetes. The team also did not study the long-term effects of chronic,
low-level propionate exposure in humans.
MNT asked
Dr. Tirosh if he would recommend that people avoid propionate in their diet.
"It will be premature to do so based on a
single study. Therefore, we are not making such recommendations," he
explained. "Our research should serve as a proof-of-principle for the
potential interference of propionate in normal metabolism, but most of the data
was obtained in mice, and we need to be careful when translating these findings
to humans."
"We
see our findings as one piece of the puzzle," Dr. Tirosh explained.
Meanwhile,
the team's research efforts continue, with a focus on how preservatives,
artificial sweeteners, and other natural ingredients might affect our
metabolism.
"Given the epidemic proportion
of obesity and diabetes, there is a need, in our view, to extensively assess
the potential long-term metabolic effects of many environmental factors that
have changed over the past few decades, both for their potential harmful and
useful effects."
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