Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys.

Neuringer, Martha; Connor, William E.; Lin, Don S.; Barstad, L; Luck, Steven J.

doi:10.1073/pnas.83.11.4021

Cited by 788 publications

(438 citation statements)

References 15 publications

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“…It is not possible to determine whether genotype or dietary management played the more critical role in lowering plasma acylcarnitines in this data set, because subjects who had β-subunit mutations also had among the lowest dietary LCFA intakes and the highest MCT intakes for all the participants. DHA (C22:6n−3) supplementation has been shown to elevate previously reduced plasma DHA levels to the normal range and improve visual acuity as measured behaviorally or by VEP in both rhesus monkeys and human infants [31][32][33][34]. Increased levels of n−3 fatty acid were also correlated with improved ERG parameters including an increased R max and a decreased log K in preterm infants [35], whereas n−3 deficiency produces ERG abnormalities in several animal models [36,37].…”

Section: Discussionmentioning

confidence: 99%

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency

Gillingham

Weleber

Neuringer

et al. 2005

Molecular Genetics and Metabolism

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The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6ω-3) supplementation prevents the progression of the severe chorioretinopathy that develops in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Physical, biochemical, and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and annually following the initiation of 65-130 mg/day DHA supplementation and continued treatment with a low-fat diet. Fourteen children with LCHAD or TFP deficiency, 1-12 years of age at enrollment, were followed for 2-5 years. Three subjects with TFP β-subunit mutations had normal appearance of the posterior pole of the ocular fundi at enrollment and no changes over the course of the study. Eleven subjects who were homozygote and heterozygote for the common mutation, c.1528G > C, had no change to severe progression of atrophy of the choroid and retina with time. Of these, four subjects had marked to severe chorioretinopathy associated with high levels of plasma hydroxyacylcarnitines and decreased color, night and/or central vision during the study. The plasma level of long-chain 3-hydroxyacylcarnitines, metabolites that accumulate as a result of LCHAD and TFP deficiency, was found to be negatively correlated with maximum ERG amplitude (R max ) (p=0.0038, R 2 =0.62). In addition, subjects with sustained low plasma long-chain NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines. Visual acuity, as determined with the VEP, appeared to increase with time on DHA supplementation (p=0.051) and there was a trend for a positive correlation with plasma DHA concentrations (p=0.075, R 2 =0.31). Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency.

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Section: Discussionmentioning

confidence: 99%

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency

Gillingham

Weleber

Neuringer

et al. 2005

Molecular Genetics and Metabolism

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“…Thus, the fetus appears to be largely protected against substantial shifts in maternal dietary fatty acid intake. Nevertheless, the reduced n-3 LCPUFA transfer to the fetuses of cafeteria-fed dams may still have significant implications for fetal development given the critical role of the n-3 LCPUFA in the neurodevelopment and immune function in the perinatal period [27,28].…”

Section: Maternal Cafeteria Feeding and Offspring Fatty Acid Statusmentioning

confidence: 99%

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells

Vithayathil

Gugusheff

Gibson

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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In all cases accepted manuscripts should:  link to the formal publication via its DOI  bear a CC-BY-NC-ND license -this is easy to do, click here to find out how  if aggregated with other manuscripts, for example in a repository or other site, be shared in alignment with our hosting policy  not be added to or enhanced in any way to appear more like, or to substitute for, the published journal article ABSTRACTPrevious studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further explanation.

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“…However, for the sake of clarity, only 9 separate fatty acids and 11 fatty acid combinations are reported (see Table 2a). The following indexes were calculated: EFA-index ( (n-3 n-6)a (n-9 n-7) (Hornstra et al, 1992), EFA-de®ciency index (20 : 3n-9a20 : 4n-6) (Holman, 1960), DHADI (docosahexaenoic acid de®ciency index : 22 : 5n-6a22 : 4n-6) (Holman, 1986;Neuringer et al, 1986) and DHASI (docosahexaenoic acid suf®ciency index : 22 : 6n-3a22 : 5n-6) .…”

Section: Discussionmentioning

confidence: 99%

“…They found no differences in retinal DHA between breastfed and formula-fed infants, in spite of differences in DHA levels in RBC PL. However, there are animal studies in which dietary manipulation showed to have large effects on DHA content of retinal phospholipids of rhesus monkeys (Neuringer et al, 1986), guinea pigs (Weisinger et al, 1995), rats (Suh et al, 1996) and felines (Pawlosky et al, 1997). Unfortunately, in these studies, the fatty acid values in plasma and RBC were not measured and no breastfeeding group was included to compare with.…”

Section: Discussionmentioning

confidence: 99%

Early nutrition, essential fatty acid status and visual acuity of term infants at 7 months of age

1999

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Objective: In term infants the relationship between visual acuity and dietary fatty acid composition is not consistent, possibly due to confounders, which were mostly neglected in the studies concerned. In the current study, therefore, the in¯uence of the essential fatty acid status and potential confounders on the visual acuity was investigated. Design: The essential fatty acid status was determined at 7 months of age in red blood cell and plasma phospholipids of breastfed and formula-fed infants, born at term. Visual acuity was measured with Teller Acuity Cards. Information about potential confounding factors was obtained during an interview and with a retrospective questionnaire.Results: This study, like others, showed that the concentrations of docosahexaenoic acid (DHA, 22 : 6n-3) are lower in plasma and red blood cell phospolipids of formula-fed infants compared to that of breastfed infants. However, no differences in visual acuity could be found between the two groups. Moreover, no signi®cant relationship was found between the amounts of docosahexaenoic acid in plasma and red blood cell phospholipids and the visual acuity. Although dummy (paci®er) use showed a signi®cant positive correlation with visual acuity, it did not in¯uence the relationship between the essential fatty acids in the infant diet and visual acuity. There was also no confounding in¯uence of smoking habits and alcohol use during pregnancy, socioeconomic background and other potential confounders. Conclusions: At 7 months of age no in¯uence of fatty acid status, infant diet or potential confounders on visual acuity was found.

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Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys.

Cited by 788 publications

References 15 publications

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells

Early nutrition, essential fatty acid status and visual acuity of term infants at 7 months of age

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