Folate administration increases n-3 polyunsaturated fatty acids in rat plasma and tissue lipids.

It has been shown that folic acid deficiency can modify polyunsaturated fatty acid (PUFA) metabolism and thus could contribute to the development of cardiovascular diseases. We have studied the effect of folate administration on fatty acid composition of plasma, platelet, erythrocyte, intestinal and liver lipids. Two groups of rats were daily injected with either saline solution (control group) or 5-methyl-tetrahydrofolate (MTHF) solution (MTHF group) for 15 days. Changes induced by folate treatment on n-6 PUFA were not very significant. Linoleic acid only decreased in liver and intestinal phospholipids of MTHF rats whereas arachidonic acid was unaffected by folate administration. However, n-3 PUFA significantly increased in plasma lipid fractions and in platelet, erythrocyte and intestinal phospholipids. It is well known that n-3 PUFA show antithrombotic properties. Thus, the increase of n-3 PUFA observed after MTHF administration might contribute to the prevention of vascular disorders.

Chronic alcoholism decreases polyunsaturated fatty acid levels in human plasma, erythrocytes, and platelets--influence of chronic liver disease.

The effect of chronic ethanol ingestion on fatty acid composition of plasma, erythrocyte and platelet phospholipids and on plasma 6-keto-PGF1alpha was studied. Two groups of alcoholic subjects, one of them with chronic liver disease, were studied and compared to a control group of healthy subjects. Linoleic acid was not affected by alcoholism but its larger metabolites arachidonic acid (20:4n6) and docosatetraenoic acid (22:4n6) tended to be lower in erythrocytes and platelets of both groups of alcoholic patients; the decrease was more marked in the presence of chronic liver disease. Docosahexaenoic acid (22:6n3) was markedly decreased in plasma, erythrocytes and platelets obtained from alcoholic patients with chronic liver disease. Plasma levels of 6-keto-PGF1alpha, a metabolite of prostacyclin (PGI2), remained unchanged. We conclude that chronic ethanol ingestion induces important changes in long-chain polyunsaturated fatty acids, mainly in platelets, and that these changes are exacerbated when patients suffer from chronic liver disease.

Changes in the fatty acid profile of plasma and adipose tissue in rats after long-term ethanol feeding.

The effect of chronic ethanol feeding on the fatty acid composition of plasma and abdominal adipose tissue in rats was studied. Animals were maintained on a 30% ethanol solution in drinking water for 3 and 5 months. Control rats were given water. Caloric intake was similar in control and ethanol-fed rats at the end of the experimental period. However, a decrease in body weight was observed in rats that had consumed ethanol. Palmitoleic (16:1n7) and oleic (18:1n9) acids increased markedly, and linoleic acid (18:2n6) decreased in the plasma and in the adipose tissue of ethanol-fed rats with respect to control rats. After 3 months of ethanol ingestion, long-chain polyunsaturated fatty acids were reduced both in plasma and adipose tissue. When ethanol was administered for 5 months, only plasma long-chain polyunsaturated fatty acids of the n-3 series were decreased. This suggest that changes induced by ethanol ingestion in essential fatty acid metabolism is less pronounced when ethanol feeding is maintained for a long period of time.

The n-3 polyunsaturated fatty acid levels in rat tissue lipids increase in response to dietary olive oil relative to sunflower oil.

In the present study, changes in phospholipid compositions of liver microsomes, erythrocyte membranes, platelets, aorta, cardiac muscle and brain of rats fed olive oil were compared with those of rats fed sunflower oil. Four groups of rats starting at weaning were fed for four weeks a basal diet containing 5 or 25% olive oil or sunflower oil. We found that oleic acid was higher and linoleic acid was lower in membrane phospholipids of olive oil fed rats compared to sunflower oil fed rats. Polyunsaturated fatty acids of the n-3 series were markedly elevated in all tissues of rats on the olive oil diets relative to those on the sunflower oil diets. The results are consistent with a lower linoleic/linolenic acid ratio induced by the olive oil diets, suggesting a positive correlation between olive oil ingestion and n-3 polyunsaturated fatty acid levels in cell and tissue lipids. The study suggests that an adequate intake of olive oil may enhance the conversion of n-3 fatty acids.

Effect of dietary olive and sunflower oils on the lipid composition of the aorta and platelets and on blood eicosanoids in rats.

The effects on aortic and platelet fatty acid compositions and on blood levels of prostacyclin and thromboxane A2 of low- and high-fat diets containing olive oil or sunflower oil were studied. For 4 weeks, four groups of weanling rats were fed a basal diet containing 5% or 25% olive oil or sunflower oil. Rats fed olive oil diets showed higher levels of 18:1(n-9) and polyunsaturated fatty acids of the n-3 series and lower percentages of 18:0 and 18:2(n-6) in aortic and platelet phosphatidylcholine and phosphatidylethanolamine than those fed the sunflower oil diets. Arachidonic acid increased in platelet phosphatidylethanolamine and aortic phosphatidylcholine of rats fed the diet containing 5% sunflower oil compared with those fed 5% olive oil. Plasma 6-ketoprostaglandin F1 alpha increased in both groups of animals fed olive oil while these rats also showed the lowest levels of serum thromboxane B2 and plasma cholesterol. Olive oil feeding leads to changes in lipid metabolism of the vascular compartment that could be favorable in the prevention of thrombosis and atherosclerosis.

Effect of dietary nucleotides and orotate on the blood levels of prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat.

Dietary nucleotides affect the maintenance of immune responses, tissue repair and polyunsaturated fatty acid metabolism. Orotate, a pyrimidine nucleotide precursor, induces fatty livers by impairing VLDL hepatic secretion. The aim of this study was to evaluate the changes in the blood levels of fatty acids and prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat caused by the dietary intake of nucleotides and orotate. Three groups of rats at weaning were fed a control diet, an orotate supplemented diet (O-50) and a nucleotide supplemented diet (N-50) during 4 weeks, respectively. Absolute values of plasma polyunsaturated fatty acids greater than 18 carbon atoms of the n-6 and n-3 series were increased in the N-50 group and decreased in O-50 with regard to the control. However, the relative fatty acid composition of plasma lipid fractions was mostly unaffected. Plasma 6-keto-PGF1 alpha showed a trend to be increased in N-50 and serum TXB2 was significantly increased in that group. Both eicosanoids were unchanged by dietary orotate intake. These results may be explained because of the increased plasma 20:4n-6 found in rats fed a supplemented nucleotide diet. Thus, nucleotides present in foods appear to modulate PUFA conversion and eicosanoids synthesis in early life.

Effect of dietary olive oil, corn oil and medium-chain triglycerides on the lipid composition of rat red blood cell membranes.

The effects of dietary olive oil, corn oil and medium-chain triglycerides (MCT) on factors that characterized erythrocyte membrane lipid fluidity were studied. Weanling rats were fed for 3 or 5 wk high fat diets (10%) containing olive oil, corn oil or a mixture of MCT with olive oil or corn oil. Total phospholipids and phosphatidylcholine of erythrocyte ghosts obtained from olive oil-fed animals, as compared to those fed corn oil, showed an increase in long-chain polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) series and a decrease in saturated fatty acids. The addition of MCT to the olive oil diet induced an increase in palmitic, palmitoleic and delta-5,8,11-eicosatrienoic acids and a decrease in long-chain PUFA of the (n-6) series in erythrocyte membrane phospholipids. Conversely, rats fed a mixture of MCT and corn oil, as compared to those fed exclusively corn oil, showed increase in long-chain PUFA of the (n-6) and (n-3) series, with no changes in saturated fatty acid levels. The cholesterol/phosphorus molar ratio showed only a slight increase with MCT supplementation. Olive oil feeding induced important changes in fatty acid composition of erythrocyte membrane phospholipids as compared to corn oil feeding without modifying the cholesterol/phosphorus ratio and MCT feeding slightly affected red blood cell membrane lipid composition.

Changes in the fatty acid profiles of red blood cell membrane phospholipids in human neonates during the first month of life.

We have studied the changes in the fatty acid profiles of red blood cell membrane phospholipids in 47 infants who were exclusively fed human milk from birth to 1 month of life. Twenty blood samples were obtained from cord, 15 at 7 days and 12 at 30 days after birth. Membrane phospholipids were obtained from erythrocyte ghosts by thin-layer chromatography and fatty acid composition was determined by gas liquid chromatography. Phosphatidylcholine showed the most important changes during early life; stearic, w6 eicosatrienoic and arachidonic acids decreased whereas oleic and linoleic acids increased. In phosphatidylethanolamine, palmitic and stearic acid declined and oleic, linoleic and docosahexenoic acids increased with advancing age. Small changes were noted for individual fatty acids in phosphatidylserine. In sphingomyelin stearic acid increased from birth to 1 month and linoleic, arachidonic and nervonic acids decreased. Total polyunsaturated fatty acids of the w6 series greater than 18 carbon atoms increased with advancing age in phosphatidylethanolamine and decreased in choline and serine phosphoglycerides and in sphingomyelin. Long chain fatty acids derived from linoleic acid decreased in phosphatidylcholine but increased in ethanolamine and serine phosphoglycerides. The different behavior in the changes observed in fatty acid patterns for each erythrocyte membrane phospholipid may be a consequence of its different location in the cell membrane bilayer and specific exchange with plasma lipid fractions.

Changes in lipid composition of liver microsomes and fatty acyl-CoA desaturase activities induced by medium chain triglyceride feeding.

Changes in fatty acid composition, microsomal delta 9- and delta 6-desaturase activities and liver contents of cholesterol and phospholipids were studied in rats fed medium chain triglyceride-supplemented diets. Weanling rats were divided into four groups and fed for three weeks a basal diet with different 10%-fat supplements: corn oil, medium chain triglyceride-corn oil, olive oil and medium chain triglyceride-olive oil. The highest relative content of saturated fatty acids corresponded to corn oil-fed animals. Both monounsaturated fatty acid content and delta 9-desaturase activity were higher in the animals fed olive oil diets than in corn oil-fed rats. The long chain polyunsaturated fatty acids of the n-3 series were increased in the olive oil and medium chain triglyceride-olive oil-fed groups probably due to the lower linoleic/alpha-linolenic ratios found in these two diets. The cholesterol/phospholipid molar ratio was unaffected by diet and the unsaturation index was only slightly changed in the four groups. Thus, some mechanism may be operative under these conditions to maintain the homeostasis of the membrane.

Effects of postnatal age and diet on the fatty acid composition of plasma lipid fractions in preterm infants.

Diet and postnatal age effect the fatty acid composition of plasma and tissue lipids. This work was designed as a transversal study to evaluate the changes in the fatty acid composition of plasma phospholipids, cholesteryl esters, triglycerides and free fatty acids in preterm infants (28-35 weeks gestational age), fed human milk (HM) and milk formula (MF) from birth to 1 month of life. Sixteen blood samples were obtained from cord, and 19 at 6-8 h after birth, 14 at 1 week and 9 at 4 weeks from HM-fed infants and 18 at 1 week and 14 at 4 weeks from MF-fed ones. Groups had similar mean birth weight, gestational age and sex ratio. The MF provided 69 kcal/dl and contained 16% of linoleic acid and 1.3% of alpha-linolenic acid on the total fat. Plasma lipid fractions were extracted and separated by thin-layer chromatography and fatty acid methyl esters were quantitated by gas liquid chromatography. In plasma phospholipids, linoleic acid (18:2 omega 6) continuously increased from birth to 1 month of age, but no changes were seen as related to type of diet; polyunsaturated fatty acids greater than 18 carbon atoms of both the omega 6 and omega 3 series (PUFA omega 6 greater than 18 C and omega 3 greater than 18 C) dropped from birth to 1 week and continued to decrease in MF-fed infants until 1 month; eicosatrienoic (20:3 omega 6), arachidonic (20:4 omega 6) and docosahexaenoic (22:6 omega 3) were the fatty acids implicated. In cholesteryl esters palmitoleic (16:1 omega 7) and oleic (18:1 omega 9) acids decreased from birth to 1 month and linoleic acid increased and arachidonic acid dropped, especially in MF fed infants. In triglycerides, palmitic, palmitoleic and stearic acid (18:0) decreased during the first month of life; oleic acid remained constant and linoleic acid increased in all infants, but arachidonic acid decreased only in those fed formula. Free fatty acids showed a similar behavior in fatty acids and in plasma triglycerides. Preterm neonates seem to have special requirements of long-chain PUFA and adapted MF should contain these fatty acids in similar amounts to those of HM to allow the maintenance of an adequate tissue structure and physiology.

Lipid composition of liver microsomes in rats fed a high monounsaturated fatty acid diet.

The fatty acid and cholesterol contents of tissue membranes are the determinants of membrane stability and functionality. This study was designed to evaluate the influence of a high monounsaturated fatty acid diet on the fatty acid composition of rat liver microsomes and on their cholesterol and lipid phosphorus content. Weanling animals were fed for 5 weeks with high fat diets containing olive oil or corn oil. Saturated fatty acids were increased and oleic acid decreased in microsomal total phospholipids and in the three major phosphoglycerides, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), of rats fed corn oil as compared to the olive oil group. The percentage of linoleic acid was higher in the corn oil group, but only for total phospholipids and PC. Linoleic and alpha-linolenic metabolites were significantly increased in total phospholipids of olive oil-fed animals with respect to those fed corn oil. These changes were responsible for the low unsaturation index found in microsomal phospholipids of the corn oil group. The diet did not affect the microsome cholesterol or the lipid phosphorus content. These results show that, in olive oil-fed rats, the cholesterol content and the degree of unsaturation of liver microsomes was similar to that observed in weanling animals; this probably suggests an adequate maintenance of functionality of membranes in olive oil-fed animals.

Changes in the fatty acids pattern of red blood cell phospholipids induced by type of milk, dietary nucleotide supplementation, and postnatal age in preterm infants.

The fatty acid profile of red blood cell phospholipids and the total phospholipid and cholesterol contents of erythrocyte membrane in preterm infants in the first month of life were studied. Influences of human milk and adapted formula and dietary nucleotides supplementation at a level similar to that found in human milk were evaluated. Nineteen preterm newborn infants with adequate weight for gestational age were fed their own mother's preterm human milk, 18 with a standard milk formula and 18 with the same formula supplemented with nucleotides. Blood samples were obtained at birth from cord blood, and at 30 days of age. At 1 month of life, linoleic acid rose in formula fed infants compared to those fed human milk (p less than 0.05) and relative amounts of 20:3w6, 20:4w6, 22:4w6, 22:5w6, and total polyunsaturates of the w6 series greater than 18 carbon atoms were significantly decreased in standard milk formula fed infants (p less than 0.05-0.01). No significant differences for these fatty acids were found between human milk and nucleotide milk formula infants. Docosahexaenoic acid (22:6w3) decreased from birth to 1 month of age in formula fed infants (p less than 0.01) but not in human milk fed infants. Infants fed nucleotide milk formula showed intermediate values for 20:3w6 and 20:4w6 (p less than 0.1) between infants fed human milk and those fed standard milk formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Influences of diet and postnatal age on the lipid composition of red blood cell membrane in newborn infants.

The fatty acid and cholesterol contents of tissue membranes are determinants of their stability and functionality. This study was designed to evaluate the influences of diet and postnatal age on the polyunsaturated fatty acid (PUFA) composition of erythrocyte membrane phospholipid fractions and on the red blood cell membrane cholesterol and phosphorus contents in newborn infants during the 1st month of life. A group of infants was fed on human milk and another group on adapted milk formula. Blood samples were obtained at birth, from cord blood, and at 7 and 30 days of age. Long-chain w6 PUFA declined with advancing age in all membrane phosphoglycerides and sphingomyelin (SM) in those infants fed formula. w6 PUFA also decreased in phosphatidylcholine (PC) and phosphatidylserine (PS) in infants fed human milk and were maintained constant in phosphatidylethanolamine (PE) and SM. w3 PUFA were less affected by postnatal age. PE and SM showed significantly higher percentages of w6 and w3 long-chain PUFA in infants fed human milk than in those fed formula. Membrane cholesterol content increased in all infants from birth to 1 month of life but phosphorus levels were unaffected by diet and postnatal age. These results suggest that diets with a low content of long-chain PUFA, such as adapted cow's milk formulas, may induce changes in membrane functionality and that incorporation of PUFA to the diet in amounts similar to those found in human milk should be considered at least in early life.

Effects of dietary nucleotides on the fatty acid composition of erythrocyte membrane lipids in term infants.

Human milk contains relatively high amounts of acid-soluble nucleotides, mainly CMP, AMP, UMP, IMP, and UDP sugars, and lacks orotate. On the contrary, cow's milk and adapted formulas contain high amounts of orotate and very low amounts of CMP and AMP. Nucleotides may be modulators of metabolic functions in gut and liver. To evaluate the possible role of dietary nucleotides in newborn fatty acid metabolism, we studied the polyunsaturated fatty acid (PUFA) composition of erythrocyte membrane phospholipids in 58 term infants at 30 days of age. Twenty of them were fed human milk (HM), 19 an adapted formula (MF), and 19 with the same formula supplemented with nucleotides (NMF) in an amount similar to that present in HM. Relative content of omega 6 and 3 PUFA greater than 18 carbon atoms was significantly reduced especially in phosphatidylethanolamine and phosphatidylserine for infants fed regular MF compared with those fed HM or NMF. Unsaturation index of red blood cell phospholipids showed a similar effect. These results suggest that dietary nucleotides play a role in the in vivo desaturation and elongation of essential fatty acids to long chain PUFA during early life for the human newborn.

Changes in the fatty acid composition of plasma and red blood cell membrane during the first hours of life in human neonates.

The objective of this work was to examine the changes in the fatty acid profiles of plasma lipid fractions and red blood cell membrane phospholipids in newborn infants during the first 6-8 h of life. Methyl esters of fatty acids from plasma free fatty acids and phospholipids and from membrane phosphatidylethanolamine, phosphatidylcholine and sphingomyelin for cord blood (n = 20) and venous blood (n = 19) were analyzed by GLC. Important changes were observed in plasma fatty acids. Palmitic and palmitoleic acid increased from birth to 6-8 h of age for both free fatty acids and phospholipids. Palmitic acid also increased in membrane phosphatidylcholine and phosphatidylethanolamine. In the former, stearic acid declined whereas oleic and docosatetraenoic acids increased. Phosphatidylethanolamine and sphingomyelin were less affected than phosphatidylcholine probably because the internal location of the two first fractions in erythrocyte membrane. Polyunsaturated fatty acids dropped slightly during the first hours of life in most lipid fractions. This may be a consequence of the interruption of placental fatty acid supply and the limited capacity of the newborn to desaturate their essential fatty acid tissue stores.

Changes in the protein fractions of human milk during lactation.

The changes in the absolute and relative contents of alpha- and kappa-caseins, lactoferrin, alpha-lactalbumin, serum albumin and lysozyme in human milk have been studied through the period of lactation. Protein fractions of 209 samples were analyzed by a discontinuous polyacrylamide gel electrophoresis method. beta- and kappa-caseins decreased from colostrum to mature milk although their relative percentages remained constant. They accounted for 12-15 and 9-13% of the total protein in human milk, respectively. Lactoferrin decreased in absolute and relative amounts with advancing lactation. This protein represented 32-19% of the human milk proteins. alpha-Lactalbumin slightly decreased from colostrum to transitional milk but there was an increase in mature milk by 16-30 days. The percentages of this protein in colostrum and mature milk were approximately 23 and 30%, respectively. Serum albumin also decreased with advancing lactation, but the differences between transitional and mature milk were not statistically significant. Lysozyme increased from colostrum to mature milk both in relative and absolute amounts. Colostrum contained about 262 micrograms/ml, and mature milk 1,246 micrograms/ml, representing 1.5 and 12.1% of total milk proteins.

Influence of the mother's weight and socioeconomic status on the fatty acid composition of human milk.

The influences of the maternal diet and of the mothers' nutritional and socioeconomic status on the fatty acid composition of human milk have not yet been fully elucidated. Fatty acids from capric (8:0) to docosahexaenoic (22:6w3) acids were determined in 209 samples of human milk obtained from voluntary donors. Samples were classified according to the time of lactation and in relation to the socioeconomic status and to the weight of the lactating women. Capric and lauric acid increased in mature milk while palmitic and stearic acids decreased. Polyunsaturated fatty acids (PUFA) of the w6 and w3 series with more than 18 carbon atoms also decreased from colostrum to mature milk. However, the ratio w3 PUFA/w6 PUFA remained unaltered. Oleic acid decreased in milk from mothers of a medium and low socioeconomic status who consumed almost exclusively seed vegetable oils. The mother's weight did not influence the fatty acid composition of her milk.

Urinary 3-methylhistidine derivative as indicator of nutrients intake in low-birth-weight infants.

Urinary excretion levels of N-methylhistidine derivatives and N-methylhistidine/creatinine ratios were studied in a group of 20 small for date newborns, 10 premature infants and 8 normal infants, at birth and at one week of life. All infants were fed with an adapted milk formula supplying 2.8 g protein/kg body weight. 1-methyl and 3-methylhistidine urinary excretion were increased in all groups of infants from birth to the 7th day of life. Creatinine and N-methyl derivatives/creatinine ratios were also significantly increased at one week of life. The two ratios showed a higher level in small for date and premature infants than in normal infants at birth which continued relatively increased at one week of life. 3-methyl-histidine/creatinine ratio appears as a useful indicator of the turnover rate of muscular proteins in low-birth-weight infants.

Serum and urine amino acid patterns during the first month of life in small-for-date infants.

Prenatal nutrition is impaired in small-for-gestational-age infants. Serum amino acids may show some biochemical features related to the nutritional state of these children. We have carried out a study on serum and urine amino acids in 12 small-for-date infants (SFD) and 14 healthy newborns from birth to 1 month of life. SFD infants showed a high serum level of alanine and decreased concentrations of branched chain amino acids, aspartate, cystine and tryptophan at birth. The results are compatible with a protein malnutrition state. Levels of serum amino acids in SFD infants showed no differences in relation to normal infants after 1 month of rehabilitation with a diet consisting of an adapted milk formula.

Changes in serum albumin, transferrin and amino acid indices during the first month of life in small-for-date infants.

Total serum proteins, albumin, albumin/globulin ratio, and plasma-free amino acids have been determined in 12 small-for-date infants and in 14 normal infants at birth, at 1 week and at 1 month after birth. All infants were fed ad libitum with an adapted infant formula providing 1.9 g protein and 74 kcal/100 ml. Total serum proteins and albumin but not transferrin were low at birth in small-for-date infants, reaching normal values after 1 week of feeding. Serum globulins were low from birth to 1 week in small-for-date infants but they were normal after 1 month. Values for classical amino acid malnutrition indices suggest a state of protein-energy malnutrition which disappeared after 1 week of feeding.