Baylor. US: Adding vitamin E (α-tocopherol) to lipid emulsions used to feed
premature pigs intravenously (parenteral nutrition) prevents liver
damage, said researchers at the USDA/ARS Children Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital. Many of the more than 500,000 infants born prematurely in the United
States each year rely on intravenous nutrition support.
Different causes
include prematurity, lung disease requiring certain forms of mechanical
ventilation, infections and inadequate absorption of nutrients in the
gastrointestinal tract.
In order to survive and grow, infants rely on the technique called
total parenteral nutrition where they are fed intravenously with an
emulsion of fluid, electrolytes, amino acids, glucose, fats, vitamins
and minerals. The lipid component is especially important since it has
been linked to parenteral nutrition-assisted liver disease, which can be
life threatening if babies remain on it for a long period. Only one
lipid emulsion composed of soybean oil, Intralipid®,is approved in the
United States, but other emulsions that are approved in Europe may
reduce the risk of liver disease.
“There is emerging evidence that new generation emulsions are
healthier for premature infants than the pure soybean oil emulsions,”
said Dr. Douglas G. Burrin, professor of pediatrics – nutrition at Baylor College of Medicine and physiologist at Children’s Nutrition Research Center.
In a previous study, he and colleagues tested lipid emulsions in
three groups of piglets. One group received the soybean-oil based
emulsion, while the others got new-generation emulsions containing
either pure-fish oil or a third a mixture that contained soybean oil,
medium chain triglycerides and olive and fish oils. The piglets on the
two new-generation emulsions were less likely to develop the liver
disease. These findings prompted Burrin’s group to explore the mechanism
explaining the protective effects of new generation emulsions.
“The prevailing theory is that phytosterols present in lipid emulsion
trigger liver disease,” said Burrin. Phytosterols are compounds similar
to cholesterol that are enriched in plant seed oils, especially the
soybean lipid emulsion Intralipid®. In the latest study that appears in the Journal of Parenteral and Enteral Nutrition,
Burrin and his colleagues set out to test the phytosterol theory in
piglets, which closely simulate human premature infants. They fed one
group of piglets the soybean-based, Intralipid® emulsion. A second
group received one of the protective new generation emulsions,
Omegaven, which contains 100 percent fish oil and no phytosterols. A
third group was given Omegaven plus phytosterols. A fourth group was
given Intralipid® with vitamin E added since new generation emulsions
are enriched with a potent vitamin E form (α-tocopherol). Burrin said,
“We wanted to test the adverse effect of phytosterols, but also the
possible protective role of nutrients that are enriched in new
generation emulsions, especially vitamin E.
They found that adding the vitamin E (α-tocopherol) to the Intralipid
and Omegaven prevented the liver damage, but, surprisingly, adding
phytosterols to Omegaven did not result in liver damage.
“This paper is important for two reasons,” said Burrin. “First, our
results challenge the phytosterol theory since we found that that adding
the phytosterols to Omegaven did not cause liver disease. Secondly, we
showed that the biologically active vitamin E form, α-tocopherol, is
protective and may explain why new generation emulsions prevent liver
disease.”
“The enrichment of lipid emulsion with vitamin E may not only delay
the development of parenteral nutrition associated liver disease, but
also potentially reverse it. The findings from this paper will hopefully
serve as the foundation for future clinical studies,” said Dr. Kenneth
Ng.
“This paper is clinically relevant because it adds to our
understanding of why lipid emulsions cause liver disease infants,” he
said. “The FDA (U.S. Food and Drug Administration) is currently
considering whether new generation lipid emulsions are safer than
Intralipid for pediatric use. They are concerned that the phytosterols
are not healthy for pediatric patients.”
So far in the United States, Omegaven is only available for use under
an investigational new drug application for compassionate use in the
treatment of pediatric cholestasis.
Others to who took part in this work include Drs. Kenneth Ng, Barbara
Stoll, Shaji Chacko, Juan Marini, Irving J. Zamora, MD and Oluyinka O.
Olutoye, all of BCM; Dr. Miguel Saenz de Pipaon of La Paz University
Hospital in Madrid, Spain; Dr. Charlotte Lauridsen of Aarhus University
in Tjele, Denmark; and Drs. Matthew Gray and E. James Squires of the
University of Guelph, Guelph, Ontario.
Funding for this work came from the U.S. Department of Agriculture,
Agricultural Research Service under Cooperative Agreement Number
58-6250-6-001, the American Society for Parenteral and Enteral
Nutrition, NIH Grant DK-094616 and the Texas Medical Center Digestive
Diseases Center (NIH Grant P30 DK-56338), the American Liver Foundation
and the Instituto de Salud Carlos III, (Grant BA12/00086).