Just one high-fat meal
sets the perfect stage for heart disease
Medical College of
Georgia at Augusta University
A single high-fat
milkshake, with a fat and calorie content similar to some enticing restaurant
fare, can quickly transform our healthy red blood cells into small, spiky cells
that wreak havoc inside our blood vessels and help set the perfect stage for cardiovascular
disease, scientists report.
Just four hours after
consuming a milkshake made with whole milk, heavy whipping cream and ice cream,
healthy young men also had blood vessels less able to relax and an immune
response similar to one provoked by an infection, the team of Medical College
of Georgia scientists report in the journal Laboratory Investigation.
While the dramatic,
unhealthy shift was likely temporary in these healthy individuals, the
scientists say there is a definite cumulative toll from this type of eating,
and that their study could help explain isolated reports of death and/or heart
attack right after eating a super-high fat meal.
"We see this hopefully as a public service to get people to think twice about eating this way," says Dr. Neal L. Weintraub, cardiologist, Georgia Research Alliance Herbert S. Kupperman Eminent Scholar in Cardiovascular Medicine and associate director of MCG's Vascular Biology Center.
"The take-home
message is that your body can usually handle this if you don't do it again at
the next meal and the next and the next," says Dr. Julia E. Brittain,
vascular biologist at the MCG Vascular Biology Center and a corresponding
author of the study.
As a practicing
cardiologist, Weintraub, also a corresponding author, has patients with
cardiovascular disease who continue to eat a high-fat diet and he definitely
asks them to think twice: "Is this food worth your life?"
While none of the
scientists recommend going overboard on calories and sugar either, the healthy
males in the study who instead consumed a meal with the same number of calories
but no fat -- three big bowls of sugar-coated flakes with no-fat milk -- did
not experience the same harmful changes to their blood, red blood cells and
blood vessels.
"You are looking
at what one, high-fat meal does to blood-vessel health," says Dr. Ryan A.
Harris, clinical exercise and vascular physiologist at MCG's Georgia Prevention
Institute and study co-author.
Their study in 10
young men was the first to look specifically at red blood cells, the most
abundant cell in our blood. Red cells are best known for carrying oxygen and
are incredibly flexible so they flow through blood vessels essentially
unnoticed, Brittain says. But with a single high-fat meal, they essentially
grow spikes and spew poison.
"They changed
size, they changed shape, they got smaller," Harris says of the rapid
changes to the form and function of red blood cells.
In both the cells and
blood, there was evidence of myeloperoxidase, or MPO, an enzyme expressed by a
type of white blood cell which, at high levels in the blood, has been linked to
stiff blood vessels, oxidative stress and heart attack in humans.
MPO is associated with
impaired ability of blood vessels to dilate, even oxidation of HDL cholesterol,
which converts this usually cardioprotective cholesterol into a contributor to
cardiovascular disease. When taken up by a diseased artery, it can even help
destabilize plaque buildup, which can result in a stroke or heart attack.
"Myeloperoxidase
levels in the blood are directly implicated in heart attack," Weintraub
notes. "This is a really powerful finding."
When they used flow
cytometry to examine the red blood cells, they found an increase in reactive
oxygen species, a natural byproduct of oxygen use that is destructive at high
levels. One effect of their elevated level is permanently changing the function
of proteins, including the one that helps red blood cells maintain their normal
negative charge.
MPO also impacts the
cytoskeleton, the physical infrastructure of the usually plump red cells so
they can't function and flex as well, says Tyler W. Benson, a doctoral student
in The Graduate School at Augusta University and the paper's first author.
"Again, your red
blood cells are normally nice and smooth and beautiful and the cells, after
consumption of a high-fat meal, get these spikes on them," says Brittain.
Much like huge ice chunks do to a river, these physical changes affect how
blood flows, she says.
Bad changes occur
quickly in these cells, which are "exquisitely sensitive" to their
environment, Brittain says.
There were changes in
white blood cells, called monocytes, which got fat themselves trying to take up
the excessive fat. Their earlier studies have shown these so-called foamy
monocytes promote inflammation and show up in atherosclerotic plaque. Monocytes
more typically travel the circulation looking for red blood cells that need
elimination, because they are old and/or diseased.
The fluid portion of
the blood, called the plasma, also looked different. When they spin and
separate different components of the blood to get to the red blood cells, they
typically get a clear yellowish plasma on top, Benson says. But after a single,
high-fat load, the fluid portion of the blood was already thick, off-color and
filled with lipids.
Their blood also
contained the expected high fat and cholesterol levels.
At least in mice
studies and in some of Brittain's other human studies, the unhealthy changes
also resolve quickly, at about eight hours, unless the high-fat feasts
continue. The investigators note they only tested their participants after four
hours, which is about how long it takes food to digest.
Studies to measure
longer-term impact on humans would be problematic primarily because you would
not want to subject healthy young individuals to the risk, Weintraub notes.
However, the MCG team
also has shown that mice continuously fed a high-fat diet experience permanent
changes to their red blood cells and blood similar to those experienced
transiently by the young men. Changes include triggering a significant immune
response that can contribute to vascular disease.
More studies are
needed to see if changes in the red blood cell shape impact vascular health,
the scientists write. But they conjecture that the remodeled red blood cells
themselves could be targeted for elimination by monocytes. In mice chronically
fed a high-fat diet, they have seen red blood cells actively consumed by
macrophages, immune cells that eat cellular debris, and resulting inflammation.
Weintraub says primary
prevention is the most prudent course for a healthy cardiovascular system
including eating healthy, exercising regularly, and keeping tabs on vitals like
cholesterol and blood pressure levels. Even patients with a high genetic risk of
cardiovascular disease can dramatically reduce that risk with these positive
changes, he says.
Harris' research team
has done studies that indicate a single aerobic exercise session by young
healthy individuals like these can counteract the unhealthy slump at four hours
and related reduction in the blood vessels ability to dilate.
Participants in the
new study included 10 physically active men with a good medical history, taking
no prescription medicines and with good cholesterol and lipid levels.
The investigators did
two thorough assessments of cardiovascular disease risk at least seven days
apart. Participants were told to avoid caffeine and strenuous physical activity
for 24 hours before each test and vitamin supplements for 72 hours. Like going
to the doctor for bloodwork, they also were asked to fast overnight.
Half the men got the
milkshakes containing about 80 grams of fat and 1,000 calories. The cereal meal
also contained about 1,000 calories but very little fat. Meals were
individually tweaked to ensure everyone got the same amount of fat relative to
their body weight, Harris says.
Since estrogen is
considered cardioprotective in non-obese premenopausal females, investigators
opted to limit the study to males.
Red blood cells,
probably best known for carrying oxygen, are the most abundant cell type
circulating in our blood. "You have 25 trillion red blood cells and they
affect every other cell in your body," says Brittain. They also carry and
release the energy molecule ATP and nitric oxide, which helps blood vessels
relax, as well as cholesterol.
A healthy red blood
cell has a negative charge that keeps them away from other cells and traveling
more toward the outer edge of blood vessels. In the arterial system, they
travel fast, Brittain says.
The cells last about
120 days, but like many of us, they become less efficient with age as they use
up their energy, or ATP stores, says Benson.
The American Heart
Association recommends that healthy adults limit fat intake to 20-35 percent of
their daily calories. The research was funded by the National Institutes of
Health.
