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Site Map Nutrition Aspects References

Bourre, J.M., Dumont, O., Piciotti,M., et al.

Essentiality of W-3 Fatty acids for brain structure and function.

Brain function is influenced by brain structure, which is genetically programmed. Nutrient deficits can influence brain function, as demonstrated by our data from rats reared through several generations on diets with differing lipid sources. Rats reared on peanut or sunflower diets showed significant shortages of omega-3 polyunsaturates in brain cells and organelles. They also demonstrated altered brain enzyme activity, reduced retinal sensitivity to light, deficits in learning ability, and enhanced sensitivity to the toxic effects of triethylin.

In Health Effects of w-3 Polyunsaturated Fatty Acids in Seafoods, eds Simopoloulos, A., Kifer,R., Martin,R., & Barlow,S. 66:103-117.

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Adams, P.B., Lawson, S., Sanigorski, A., Sinclair,A.J.

Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, we investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P <0.05) and the LRS for depression (P < 0.01). There was also a significant negative correlation between erythrocyte EPA and the LRS (P < 0.05). The AA/EPA ratio in plasma PL and the ratio of erythrocyte long-chain (C-20 and C-22 carbon) n-6 to long-chain n-3 PUFA were also significantly correlated with the LRS (P< 0.05). These findings do not appear to be simply explained by differences in dietary intake of EPA. We cannot determine whether the high ratios of AA/EPA in both plasma and erythrocyte PL are the result of depression or whether tissue PUFA change predate the depressive symptoms. We suggest, however, that our findings provide a basis for studying the effect of the nutritional supplementation of depressed subjects, aimed at reducing the AA/EPA ratio in tissues and severity of depression.

Lipids, 1996,31, Suppl.,S157-S161.

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Crawford,M.A, Cunnane,S., Harbige,L.S.

A New Theory of Evolution: Quantum Theory.

It is generally thought that Darwin was the originator of the idea that evolution progressed through random, genetic mutation with the survival of the fittest product by a process of natural selection. In the first edition of Darwin's book on the origin of species, he does not use the word "evolution" but writes about "modification". The modern view of the evolution of the large human brain suggests that our brain capacity simply enlarged from a 450 mL chimpanzee sized brain to the contemporary 1,500 mL capacity. It is not a question of linear growth from 450 mL to 1,500 mL, but of a much wider development involving not linear but cubic increments in dimensions and in sophistication. The most reasonable conclusion is that when the land/water interface was vacated after the last migration of the marine mammals, it was occupied by a primate that made use of the best of both worlds. That primate had a rich supply of both AA and DHA preformed as well as an abundance of trace elements and other nutrients. With such a rich source of the nutrients needed to support brain development, there would have been no need for such a species to lose its relative brain capacity, as happened to all other land-based species as body size developed and the ability to accumulate LCPUFA diminished.

in Essential Fatty Acids and Eicosanoids, eds, Sinclair,A., & Gibson,R., AOCS, Champaign, Illinois,USA, 1992, p87-95.

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Biochemical and Functional Effects of Prenatal and Postnatal w-3 Fatty Acid Deficiency on Retina and Brain in Rhesus Monkeys.

The author fed a group of Rhesus monkeys( Macaca mulatta) on a diet containing no w-3 fatty acids, and another, control group, on a diet providing ample w-3. In near-term fetuses and new born infants of the deprived group, brain level of DHA was a quarter of the control group, and retinal levels were half. By 22 months of age the levels of DHA in these tissues in the control group doubled, but those in the deficient group did not change. The low w-3 levels were accompanied by increased levels of the long chain w-6 polyunsaturates, especially 22:5w-6. Functionally the deficient animals had subnormal visual acuity at 4-12 weeks of age, and prolonged recovery time of dark adapted retinogram after a saturating flash.


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Reisbick, S.,Neuringer, M., Hasnain, R., Connor, W.E., 1994.

Home Cage Behaviour of Rhesus Monkeys with Long-Term Deficiency of Omega-3 Fatty Acids.In an observational study with a blind observer, rhesus monkeys deficient in omega-3 (omega-3 or n-3) fatty acids initiated more bouts of stereotyped behavior in their home cages than monkeys fed a matched control diet abundant in omega-3 fatty acids. Locomotion bouts were also more frequent in deficient monkeys, but nonstereotyped locomotion did not differ. Both stereotyped behavior and the sum of all behavioral bouts were more frequent in 4-5-year-old than in 2-3-year-old monkeys, and stereotypy decreased after meals in males but not females. The stereo typed behaviors associated with a deficit in omega-3 fatty acids were those typical of rhesus monkeys raised as partial social isolates or those whose surroundings have been disrupted.

Physiology & Behavior 1994,55,2,231-239.

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Farquharson,J., Jamieson,E., Abbasi, K., Patrick,W., Logan, R., & Cockburn, F.,1995.

Effect of diet on the fatty acid composition of the major phospholipids of infant cerebral cortex.

The fatty acid compositions of the major cerebral cortex phospholipids,phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine were measured in 16 term and one preterm "cot death" infants fed exclusively either breast milk or one of two formulas. Docosahexaenoic acid (DHA; C22:6, n-3) content in cerebral cortex phosphatidylethanolamine and phosphatidylserine of breast fed infants was greater than in both formula groups with significances varying between p<0 01 and p<001. Compensation for this deficiency in DHA in the formula fed infants was largely achieved by increased incorporation of docosapentaenoic acid } (C22:5, n-6) } in the cerebral cortex of term infants and Mead (C20:3,n-9) and dihomo Mead acids (C22:3, n-9) in the preterm infant. As the phospholipids most affected are known to perform an important role in membrane function and are possibly integral to neurotransmission it is recommended that breast milk substitute infant formulas should contain n-3 and n-6 series polyunsaturated fatty acids in similar to those of human milk.


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Hibbeln , J.R. & Salem, N . 1995.

Dietary polyunsaturated fatty acids and depression: When cholesterol does not satisfy.

Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and postpartum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.

American Journal of Clinical Nutrition, 1995,62;1:1-9.

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Stevens, L.J., Zentall, S.S., Deck, J.L., Abate, M.L., Watkins, B.A., & Lipp, S.R.

Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial. Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism. The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6; 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptoms. The data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.

American Journal of Clinical Nutrition 1995,62;4:761-768.

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Laugharne, J.D.E., Mellor, J.E., & Peet, M.

Fatty acids and schizophrenia.

In a controlled study of red cell membrane fatty acids in patients with schizophrenia, substantial depletions of fatty acids from both the n-6 and n-3 series were demonstrated. Arachidonic acid and docosahexaenoic acid were particularly depleted. In a separate study, dietary analysis revealed no deficiency of fatty acid intake in this patient group, but greater intake of n-3 fatty acids was associated with less severe symptomatology. Dietary supplementation for six weeks with 10 g per day of concentrated fish oil (MaxEPA) led to significant improvement in schizophrenic symptoms. This clinical improvement was related to the increased level of n-3 fatty acids in red cell membranes. These findings form part of a growing body of research data suggestive of an abnormality in cell membrane fatty acid composition on in schizophrenia. The preliminary evidence for clinically effective dietary manipulation to correct such an abnormality opens up novel and exciting therapeutic possibilities.

Lipids 1996,31; Suppl.,S163-S165.

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Hamazaki, T., Sawazaki, S., Itomura, M., Asaoka, E, et al.

The effect of docosahexaenoic acid on aggression in young adults - A placebo-controlled double-blind study.

41 students took either docosahexaenoic acid (DHA)-rich oil capsules containing 1.5-1.8 grams DHA/day (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 months in a double-blind fashion. They took a psychological test (P-F Study) and Stroop and dementia-detecting tests at the start and end of the study. The present study started at the end of summer vacation and ended in the middle of mental stress such as final exams. In the control group extraggression (aggression against others) in P-F Study was significantly increased at the end of the study as compared with that measured at the start (diff = + 8.9%, P = 0.0022), whereas it was not significantly changed in the DHA group (diff= -1.0%). The 95% CI of differences between the DHA and control groups were -16.8 to -3.0%. DHA supplementation did not affect the Stroop and dementia-detecting tests. Thus, DHA intake prevented extraggression from increasing at times of mental stress. This finding might help understand how fish oils prevent disease like coronary heart disease.

Journal of Clinical Investigation 1996,97;4:1129-1133.

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Stevens, L.J., Zenta ll, S.S., Abate, M.L., Kuczek, T., & Burgess, J.R.

Omega-3 fatty acids in boys with behaviour, learning, and health problems.

The purpose of the study reported here was to compare behavior, learning, and health problems in boys ages 6 to 12 with lower plasma phospholipid total omega-3 or total omega-6 fatty acid levels with those boys with higher levels of these fatty acids. A greater frequency of symptoms indicative of essential fatty acid deficiency was reported by the parents of subjects with lower plasma omega-3 or omega-6 fatty acid concentrations than those with higher levels. A greater number of behavior problems, assessed by the Conners' Rating Scale, temper tantrums, and sleep problems were reported in subjects with lower total omega-3 fatty acid concentrations. Additionally, more learning and health problems were found in subjects with lower total omega-3 fatty acid concentrations. (Only more colds and more antibiotic use were reported by those subjects with lower total omega-6 fatty acids.) These findings are discussed in relation to recent findings for omega-3 experimentally deprived animals.

Physiology & Behavior 1996,59;4-5:915-920.

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Maes, M., Smith, R., Christophe, A., Cosyns, P., Desnyder, R., & Meltzer, H.

Fatty acid composition in major depression: Decreased omega 3 fractions in cholesteryl esters and increased C20:4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids.

Recently, there were some reports that major depression   may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20:4 omega 6/C20:5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2; C20:4) fatty acids in phospholipid  and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depress e d subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

Journal of Affective Disorders 1996,38;1:35-46.

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Hamazaki, T., Sawazaki, S.,Nagao, Y., Kuwamori, T., Yazawa, al.

Docosahexaenoic acid does not affect aggression of normal volunteers under nonstressful conditions.

A randomized, placebo-controlled, double-blind study. We previously found that docosahexaenoic acid (DHA) intake prevents aggression enhancement at times of mental stress. In the present study we investigated changes in aggression under nonstressful conditions. Forty-six students of two universities took either DHA-rich fish oil capsules containing 1.5 g DHA (DHA group: 13 males and 9 females) or control oil capsules containing 97% soybean oil plus 3% of another fish oil (control group: 11 males and 13 females) for 3 months in a double-blind fashion. At the start and end of the study they took an aggression-estimating test (P-F Study) without a stressor component. DHA (5.9 to 8.5%, P <0.001 ) and eicosapentaenoic acid (0.7 to 1.5%, P < 0.001) increased in red blood cell phospholipids in the DHA group, while linoleic acid increased slightly (8.3 to 9.1%, P < 0.002) in the soybean oil control group. In the control group, measured aggression levels decreased from 34.8 to 29.4% (P < 0.005), whereas they remained stable in the DHA group (33.5 to 33.8%). The intergroup differences(-5.4 vs. 0.3%) were marginally significant (P less than or equal to 0.05). Aggression levels were stable in the DHA group whether there was stressor (as previously shown) or not. This effect of DHA appears to be interesting, considering the reported association between a low intake of n-3 fatty acids and depression.


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Lamptey, M.S., & Walker, B.L..

A possible role for dietary linolenic acid in the development of the young rat.

Female rats were fed semi-purified diets containing 10% safflower oil or 10% soybean oil for six weeks prior to mating and throughout pregnancy and lactation. The progeny were weaned to the diet of the dam. Physical, neuromotor and reflex development was monitored in the progeny prior to weaning and learning ability of the mature progeny was assessed in a simple Y-maze test. Brain lipid analyses were conducted in the progeny at birth, 21 and 210 days of age. Inclusion of soybean oil in the diet resulted in higher levels of 22:6,w-3 and lower levels of 22:5,w-6 in the brain ethanolamine glycerophosphatides. The nature of the dietary fat exerted no effect on the physical development, onset of reflexologic responses or onset of neuromotor co-ordination in the pups. The soybean oil -fed animals spent more time in certain neuromotor activities possibly associated with explorative drive than did their safflower-oil fed counterparts. The performance of the mature soybean oil-fed group in the discrimination-learning test was superior to that of progeny fed safflower oil. The association of superior learning capacity with dietary soybean oil-induced incorporation of w3 fatty acids into the brain glycerophosphatides is offered as support for an essential role for dietary linolenic acid for the young rat.

J.Nutr. 1976,106; 86-93.

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Lanting,C.I., Fidler,V., Huisman,M., Touwen,B., & Boersma, E.

Neurological differences between 9 year old children fed breast-milk or formula-milk as babies. The presence of minor neurological dysfunction is associated with behaviour and cognitive development at school age. We have previously shown a relation between minor neurological dysfunction and perinatal disorders, especially abnormal neonatal neurological condition. We studied 135 breast-fed (for at least 3 weeks) and 391 formula-fed children born at term in the University Hospital Groningen between 1975 and 1979. A standard neonatal neurological examination was used to classify the infants as normal (247) slightly abnormal (213) or frankly abnormal (66). At 9 years of age the children were re-examined. In 1993 their mothers were asked to complete a questionnaire about how the children were fed as infants. After adjustment for obstetric, perinatal, neonatal neurological and social differences, a small advantageous effect of breastfeeding on neurological status at 9 years of age was found (odds ratio 0.54 {95% C.I.0.30-0.97}). Although a retrospective design cannot lead to definite conclusions, our data suggest a beneficial effect of breast-feeding on postnatal neurological development. Longer-chain polyunsaturated fatty acids, which are present in breast-milk but not in most formula-milks, may have a role since they are vital for brain development.

Lancet 1994,344;1319-22.

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Edwards, R., Peet, M., Shay, J., & Horrobin, D.

Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients.

Background: There is a hypothesis that lack of n-3 polyunsaturated fatty acids (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial component of synaptic cell membranes. The aim of this study was to measure RBC membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. Method: Red blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10 depressed patients and 14 matched healthy control subjects. Results: There was a significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with RBC membrane levels and with dietary intake of n-3 PUFAs. Conclusion: Lower RBC membrane n-3 PUFAs are associated with the severity of depression. Limitations: Although patient numbers were small, confounding factors were well controlled for and the results were highly significant. Results of the dietary data would tend to be weakened due to the limitations associated with dietary assessment. Clinical Relevance: The findings raise the possibility that depressive symptoms may be alleviated by n-3 PUFA supplementation.

Journal of Affective Disorders,1998,48;2-3:149-155.

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Hibbeln, J.R., Umhau, J.C., Linnoila, M., George, D.T., Ragan, P.W ., et al.

A replication study of violent and nonviolent subjects: Cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids.

Background: Among an independent group of subjects selected for their history of violent, impulsive behaviours and nonviolent control subjects, we attempted to replicate the finding that plasma docosahexaenoic acid concentrations were negatively correlated with cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations. Methods: CSF 5-HIAA and homovanillic acid (HVA), fasting total cholesterol, and plasma fatty acid concentrations were examined in violent and nonviolent subjects matched for their severity of alcohol dependence. Results: Violent subjects had significantly higher lifetime violence and hostility ratings and lower concentrations of CSF 5-HIAA than nonviolent subjects. Plasma docosahexaenoic acid was negatively correlated with CSF 5-HIAA only among violent subjects. Conclusions: This observational study suggests that dietary essential fatty acids may change neurotransmitter concentrations. Prospective dietary intervention trials will be required to determine if increasing dietary intake of docosahexaenoic acid will increase or decrease either CSF 5-HIAA concentrations or impulsive and violent behaviours.

Biological Psychiatry,1998,44;4:243-249.

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Stoll, A.L., ,Severus,W.E., Freeman,M.P., Rueter,S., et al.     

Omega 3 fatty acids in bipolar disorder - A preliminary double-blind, placebo-controlled trial.

.Background: Omega 3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega 3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. 

Methods: A 4-month, double-blind, placebo-controlled study, comparing omega 3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. 

Results: Kaplan-Meier survival analysis of the cohort found that the omega 3 fatty acid patient group had a significantly longer period of remission than the placebo group (P=.002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega 3 fatty acid group performed better than the placebo group. 

Conclusion: Omega 3 fatty acids were well tolerated and improved the short- term course of illness in this preliminary study of patients with bipolar disorder.

Archives of General Psychiatry,1999:56(5);407-412.

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Willatts, P., Forsyth, J.S., DiModugno, M.K., Varma, S., & Colvin, M.

Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age.

Background: Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and brain development. Although present in human milk, LCPUFA have until recently been absent from artificial formulas, and infants may have limited ability to synthesise LCPUFA. To determine the clinical significance of this relative deficiency of LCPUFA, we undertook a randomised trial of the relation between LCPUFA supplementation and infant cognitive behaviour. Methods 44 term infants had been randomised to a formula supplemented with LCPUFA (21) or not supplemented with LCPUFA (23), which they had taken from birth to age 4 months. Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test -the intentional execution of a sequence of steps to achieve a goal. The problem required three intermediate steps to achieve the final goal, uncovering and retrieving a hidden toy. Findings: Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Intention scores (median 14.0 vs 11.5 [maximum 18]) were also increased in this group (p=0.035). Interpretation: These findings suggest that term infants may benefit from LCPUFA supplementation, and that the effects persist beyond the period of supplementation. Since higher problem-solving scores in infancy are related to higher childhood IQ scores, supplementation with LCPUFA may be important for the development of childhood intelligence.

Lancet,1998,352;9129 :688-691.

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Makrides,M, Neumann,M., Byard,R., Simmer,K., & Gibson,R.

Fatty acid composition of brain,retina, and erythrocytes in breast- and formula-fed infants.

Breast-fed infants score better on visual and developmental tests than do formula-fed infants and this has been related to higher concentrations of erythrocyte docosahexaenoic acid (DHA,22:6,w-3). This prompted an investigation into the relationship between brain,retina and erythrocyte fatty acids in infancy. Total lipids of erythrocytes, retina, and brain cortex from 35 term infants were analyzed by capillary gas-liquid chromatography. Breast-fed infants had a greater proportion of DHA in their erythrocytes and brain cortex relative to those fed formula (P<0.005) but differences were not observed in retina. Cortex DHA increased in breast-fed (but not formula-fed) infants with age (r2=0.72, P<0.01, n=15), largely an effect of length of feeding (r2= 0.62, P<0.01, n= 35). There was an association between age at death and erythrocyte DHA with cortex DHA (r2=0.50,P<0.01). In contrast, accretion of cortex arachidonic acid was dependant on age but not diet. The higher concentration of DHA in the brains of breast-fed infants may explain the improved neurodevelopment reported in breast-fed infants compared with formula-fed infants.


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