In the past 2 decades, views about dietary n-3 fatty acids have moved from speculation about their functions to solid evidence that they are not only essential nutrients but also may favorably modulate many diseases. Docosahexaenoic acid (22:6n-3), which is a vital component of the phospholipids of cellular membranes, especially in the brain and retina, is necessary for their proper functioning. n-3 Fatty acids favorably affect atherosclerosis, coronary heart disease, inflammatory disease, and perhaps even behavioral disorders. The 38 articles in this supplement document the importance of n-3 fatty acids in both health and disease.

Docosahexaenoic acid [22:6w3;7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other w3 fatty acids, chiefly a-linolenic acid (18:3w3). We tested the effect of dietary w3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurifled diets very low in 18:3w3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3cw.3. In near-term fetuses and newborn infants of the deficient group, the 22:6w3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6w3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6w3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain w6 fatty acids, particularly 22:5w6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6&3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary w3 fatty acids are essential for normal prenatal and postnatal development of the retina and brain.Neither linoleic acid (18:2w6)t nor a-linolenic acid (18:3w3)

The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol Delta7-reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol Delta7-reductase. We cloned cDNA encoding a human sterol Delta7-reductase (DHCR7) on the basis of its homology with the sterol Delta7-reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta7-reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol Delta7-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS.

As bstract. Linolenic acid (18:3w3) is a dietary precursor of docosahexaenoic acid (22:6w3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary w-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets low in w-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from birth. A control group of mothers and infants received similar diets but supplying ample linolenic acid. In the plasma phospholipids ofdeficient infants, linolenic acid was generally undetectable and 22:6w3 levels became progressively depleted, falling from 42% of control values at birth to 21% at 4 wk. 9% at 8 wk, and 6% at 12 wk of age. In the other plasma lipid classes, 22:6w3 was undetectable by 12 wk. The visual acuity of the deprived infants, as measured by the preferential looking method, was reduced by one-fourth at 4 wk (P < 0.05) and by one-half at 8 and 12 wk (P < 0.0005) compared with control infants. These results suggest that w-3 fatty acids may be an essential nutrient, and that 22:6w3 may have a specific function in the photoreceptor membranes of the retina.A preliminary report of this work was presented at

These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.