CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Oct. 19, 1999
UI study adds evidence linking homocysteine, high-protein
diet to heart attack, stroke risk
IOWA CITY, Iowa -- Studies have shown homocysteine
plays a role in blood clots and hardening of the arteries, conditions that
can lead to heart attack or stroke. A recent University of Iowa Health Care
study indicates that elevated homocysteine can rapidly affect small blood
vessels, which likely contributes to high blood pressure. In addition, the
UI study adds evidence that vitamin C may prevent homocysteine from damaging
both small and large blood vessels.
British researchers previously showed that homocysteine
damages large blood vessels, thus contributing to atherosclerosis, and that
a weeklong vitamin C treatment reverses the effect. The UI study suggests
that homocysteine also damages the small blood vessels that control blood
pressure, and that vitamin C can reverse the impact within hours, said William
G. Haynes, M.D, UI assistant professor of internal medicine and lead investigator
of the study.
Methionine, an amino acid derived from animal protein,
performs essential functions that produce a homocysteine byproduct. If not
removed, the homocysteine damages blood vessel linings by increasing the number
of oxygen free radicals. High cholesterol can cause risk factors for heart
attacks through the same mechanism. Antioxidants such as vitamin C seem to
"quench" or neutralize the free radicals.
"An additional implication of our research is
that the methionine found in diets high in animal protein needs more consideration
as a contributing factor to elevated homocysteine levels," Haynes said.
"Most previous research has focused on how genetics and vitamin B deficiencies
cause high homocysteine levels."
A genetic deficiency in a small number of people prevents
them from producing enough of the enzyme that normally disposes of homocysteine.
Vitamin B supplements (folic acid, B6 and B12) usually help lower homocysteine,
but not in some individuals.
The UI team studied how methionine and vitamin C affected
homocysteine levels in 40 healthy adults (31 males and 9 females) without
risk factors or clinical evidence of atherosclerosis. Some participants drank
cranberry juice containing about 8 grams of dissolved methionine -- two to
three times the amount many people consume daily through protein-rich foods.
Other participants drank a plain juice placebo.
Homocysteine levels in people who consumed the methionine
rose to about 25 micromoles per liter of plasma within a few hours. The participants
homocysteine levels returned to normal later that day; however, people who
regularly eat protein-rich food may repeatedly raise their homocysteine above
the healthy norm of 10 micromoles per liter. An 8-oz lean chicken breast contains
about 2 grams of methionine. Other methionine-rich foods include beef, tuna,
shrimp and cheese. A homocysteine level above 10 micromoles per liter is increasingly
considered a risk factor for coronary artery disease.
"We need to further investigate whether high
dietary protein can increase homocysteine levels and cause harm, but the findings
suggest that a lot of protein in the diet over time is not a good idea,"
Haynes said his teams study also builds on a
previous UI study using animal models that showed a high methionine and low
folic acid diet lasting one month elevates homocysteine to a level that causes
blood vessel dysfunction. That investigation was led by Donald D. Heistad,
M.D., UI professor of internal medicine and pharmacology, and head of the
cardiovascular disease division; and Steven R. Lentz, M.D., Ph.D., UI associate
professor of internal medicine.
When individuals in the study led by Haynes ingested
methionine and then took a megadose (2 grams) of vitamin C, their large and
small blood vessel function rapidly improved. Haynes emphasized that clinically
applying the findings to manage a patients care or prescribe vitamin
C treatments is down the road.
"At this time we do not suggest using megadoses
of vitamin C to reverse the risk of high homocysteine levels," he said.
"However, the findings indicate that if vitamin B treatments do not lower
homocysteine levels, then antioxidants might work to help protect blood vessels
and prevent heart attack and stroke."
In addition to investigating whether lower levels
of homocysteine may cause blood vessel damage, the UI team will study whether
the antioxidant vitamin E might also offer protection.
The findings were published in the Sept. 14 issue
of Circulation. The lead author was
Prapti M. Kanani, M.D., a former UI fellow in pediatric cardiology who is
now an assistant professor of pediatric cardiology at the University of Pittsburgh.
In addition to Kanani and Haynes, the UI research team included Christine
A. Sinkey, assistant nurse manager in internal medicine; Roger L. Browning,
ultrasound technician; Margaret Allaman, assistant researcher; and Howard
R. Knapp, M.D., Ph.D., UI professor of pharmacology and internal medicine.
The study was supported by grants from the National
Institutes of Health, the Iowa Affiliate of the American Heart Association,
and the federal Department of Veterans Affairs. In addition, Kanani received
a training grant in pediatric cardiology from the National Institutes of Health,
and Haynes was supported by a faculty development grant from the Pharamceutical
Research Manufacturers of America Foundation.
University of Iowa Health Care describes the partnership
between the UI College of Medicine and the UI Hospitals and Clinics and the
patient care, medical education and research programs and services they provide.