This common food additive may fuel weight gain, diabetes

Additives in bread

By Yella Hewings-Martin

Fact checked by Gianna D’Emilio

Food 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.
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
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
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
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
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

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.”
Dr. Amir Tirosh

Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.