University of North Carolina Health Care
The findings, reported today in the British Medical Journal,
suggest that using vegetable oils high in linoleic acid might be worse than
using butter when it comes to preventing heart disease, though more research
needs to be done on that front.
This latest evidence comes from an analysis of
previously unpublished data of a large controlled trial conducted in Minnesota
nearly 50 years ago, as well as a broader analysis of published data from all
similar trials of this dietary intervention.
The analyses show that interventions using linoleic
acid-rich oils failed to reduce heart disease and overall mortality even though
the intervention reduced cholesterol levels.
"Altogether, this research leads us to conclude that
incomplete publication of important data has contributed to the overestimation
of benefits -- and the underestimation of potential risks -- of replacing
saturated fat with vegetable oils rich in linoleic acid," said co-first
author Daisy Zamora, PhD, a researcher in the Department of Psychiatry at the
UNC School of Medicine.
Along with corn oil, linoleic acid-rich oils include
safflower oil, soybean oil, sunflower oil, and cottonseed oil.
The belief that replacing saturated fats with vegetable oils
improves heart health dates back to the 1960s, when studies began to show that
this dietary switch lowered blood cholesterol levels.
Since then, some studies,
including epidemiological and animal studies, have suggested that this intervention
also reduces heart attack risk and related mortality.
In 2009, the American
Heart Association reaffirmed its view that a diet low in saturated fat and
moderately high (5-10 percent of daily calories) amounts of linoleic acid and
other omega-6 unsaturated fatty acids probably benefits the heart.
However, randomized controlled trials -- considered the gold
standard for medical research -- have never shown that linoleic acid-based
dietary interventions reduce the risk of heart attacks or deaths.
The largest of these trials, the Minnesota Coronary
Experiment (MCE), was conducted by researchers at the University of Minnesota
between1968 and 1973. It enrolled 9,423 patients in six state mental hospitals
and one state-run nursing home.
Its results did not appear in a medical journal
until 1989. The investigators reported then that a switch to corn oil from
butter and other saturated fats did lower cholesterol levels but made no
difference in terms of heart attacks, deaths due to heart attacks, or overall deaths.
In the course of investigating the health effects of
linoleic acid-rich oils, the team of investigators led by Chris Ramsden, a
medical investigator at the National Institutes of Health, came across the MCE
study and the 1989 paper.
"Looking closely, we realized that some of the
important analyses that the MCE investigators had planned to do were missing
from the paper," Zamora said.
With the help of Robert Frantz, the son of the deceased MCE
principal investigator, the team was able to recover much of the raw data from
the study, which had been stored away for decades in files and on magnetic
tapes.
The team also found some trial data and analyses in a University of
Minnesota master's degree thesis written by written by Steven K. Broste, a
student of one of the original investigators.
Using the recovered data to perform analyses that had been
pre-specified by the MCE investigators but never published, the team confirmed
the cholesterol-lowering effect of the dietary intervention.
But they also
found that in the recovered autopsy records, the corn oil group had almost
twice the number of heart attacks as the control group.
Perhaps most strikingly, graphed summaries contained in
Broste's thesis indicated that in the intervention group, women and patients
older than 65 experienced roughly 15 percent more deaths during the trial,
compared to their control group counterparts.
"We did not recover the individual patient data
underlying those graphs and so we couldn't determine whether those differences
were statistically significant," said Zamora.
She also cautioned that the other analyses were based on
only partial recovery of patient data from the MCE files, so it would be
premature to conclude from them that replacing saturated fats with corn oil is
actually harmful to heart health.
In a much-cited study published in 2013, however, Ramsden,
Zamora and colleagues were able to recover unpublished data from a smaller
trial, the Sydney Diet Heart Study, and there they also found more cases of
heart disease and death among patients who received a linoleic acid
intervention (safflower oil), compared to controls.
Following their recovery of data from the MCE study, the
researchers added new data to their existing datasets from the Sydney study and
the other three published randomized clinical trials of linoleic acid-based
dietary interventions.
In a meta-analysis of the combined data, they again
found no evidence that these interventions reduced deaths from heart disease or
deaths from all causes.
"There were some differences among these studies, but
on the whole they didn't really disagree," said Zamora.
Why linoleic acid-containing oils would lower cholesterol
but worsen or at least fail to reduce heart attack risk is a subject of ongoing
research and lively debate. Some studies suggest that these oils can -- under
certain circumstances -- cause inflammation, a known risk factor for heart
disease.
There is also some evidence they can promote atherosclerosis when the
oils are chemically modified in a process called oxidation.