The existence of a dietary requirement for fatty acids of the omega-3 or Alpha-linolenic acid family has been an unresolved issue in human nutrition. Like the omega-6 or linoleic acid family, omega-3 fatty acids cannot be synthesized by animals. The high content of these fatty acids, particularly docosahexaenoic acid (22:6 omega-3 or DHA), in the phospholipids of the retina and cerebral cortex suggests an important role in the function of neuronal and photoreceptor membranes. We have now produced omega-3 fatty acid deficiency in rhesus monkeys by dietary deprivation throughout gestation and infancy. The deficiency state is characterized by both biochemical and functional changes. The plasma and tissues exhibit reduced levels of omega-3 fatty acids from birth to two years of age. Levels of DHA are greatly reduced in brain and retina. Visual defects and abnormal electroretinograms occur in deficient animals. We now propose to continue studies of existing omega-3 fatty acid deficient monkeys to investigate these questions: 1. Does the deficient state produce increasing manifestations of visual loss with increased age? 2. Do juvenile deficient animals show impairments in tests of complex learning? 3. Will the correction of the omega-3 fatty acid deficient diet with DHA or linolenic acid correct both the functional and biochemical abnormalities of deficient monkeys? In addition, we propose to begin breeding a new group of deficient adult females in order to investigate the following questions: 4. How rapidly will infants deficient at birth regain normal levels of DHA after dietary repletion with dietary omega-3 fatty acids (DHA or linolenic acid)? Will visual loss then be avoided? These studies will help determine the nutritional needs of primates for omega-3 fatty acids during different stages of development. This work has implications for the optimum diet of pregnant and lactating women, human infants, and perhaps of older humans. Finally, these studies will provide information about the biochemistry of the developing primate brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK029930-09
Application #
3229133
Study Section
(SSS)
Project Start
1981-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
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Connor, William E; Lin, Don S; Pappu, Anuradha S et al. (2005) Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues. Lipids 40:919-23
Anderson, Gregory J; Neuringer, Martha; Lin, Don S et al. (2005) Can prenatal N-3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys. Pediatr Res 58:865-72
Leung, Ivan Y-F; Sandstrom, Marita M; Zucker, Charles L et al. (2005) Nutritional manipulation of primate retinas. IV. Effects of n--3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region. Exp Eye Res 81:513-29

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