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Supplementation of n-3 fatty acids during pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants.

OBJECTIVE: Docosahexaenoic acid (DHA, 22:6 n-3) is considered an essential fatty acid for the fetus and newborn infant, but the optimal level of supply is not known. We studied the effect of supplementing pregnant and lactating women with marine n-3 polyunsaturated fatty acids (PUFAs) as compared to n-6 PUFAs related to maternal and infant lipid levels. STUDY DESIGN: Five hundred and ninety pregnant women in weeks 17-19 of pregnancy were recruited. They were given either 10 mL cod liver oil (n-3 PUFAs) or corn oil (n-6 PUFAs) daily until three months after delivery, and 341 women took part in the study until giving birth. RESULTS: Maternal supplementation with cod liver oil increased the concentration of DHA in maternal as well as infant plasma and umbilical tissue phospholipids, as compared to corn oil. The maternal plasma triacylglycerol increase during pregnancy was less pronounced in women supplemented with cod liver oil as compared to corn oil. The concentration of high-density lipoprotein (HDL)-cholesterol was unchanged during pregnancy in the cod liver oil group, whereas it decreased in the corn oil group, promoting a greater increase in the ratio of total cholesterol/HDL-cholesterol in the corn oil group. CONCLUSION: Maternal supplementation with n-3 fatty acids during pregnancy and lactation provides more DHA to the infant and reduces maternal plasma lipid levels compared to supplementation with n-6 fatty acids.

Adult↗

Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women.

OBJECTIVE: There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids (PUFAs) during pregnancy may increase birth weight and gestational length. In addition, n-3 long-chain PUFAs may be important for the neurobiological development of the infants. High levels of docosahexaenoic acid (DHA, 22:6 n-3) are found in the gray matter of the cerebral cortex and in the retina, and it seems as if the availability of long-chain PUFAs may be limiting cerebral development. The fetus and the newborn are dependent on a high supply from their mothers, either via the placenta or via breast milk. We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight, gestational length, and infant development. DESIGN: We performed a double-blind, randomized study recruiting 590 pregnant, healthy, nulli- or primiparous women (19-35 years old) in weeks 17 to 19 of pregnancy. The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery. MAIN OUTCOME MEASURES: Primary outcomes were gestational length and birth weight. Electroencephalography (EEG) was done on the second day of life and at 3 months of age. Novelty preference (Fagan test) was used as an indicator of cognitive function at 6 and 9 months of age. The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured, and dietary assessments were performed, both on the mothers during pregnancy and on the infants at 3 months of age. The growth of the infants was followed up to 1 year of age. RESULTS: Three hundred forty-one mothers took part in the study until delivery. There were no significant differences in maternal body mass index before pregnancy and at birth, or parity between the 2 groups. Smoking habits and parental education were also similar in the 2 groups. The mean age of the mothers receiving cod liver oil was, by chance, 1 year higher than the age of the mothers receiving corn oil (28.6 [3.4] vs 27.6 [3.2] years). The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar, except for the supplementation. There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group (279.6 [9.2] vs 279.2 [9.3] days; 3609 [493] vs 3618 [527] g, respectively). Birth length, head circumference, and placental weight were also similar in the 2 groups. The concentrations of the n-3 fatty acids eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3), and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group (10.8 [7.6] vs 2.5 [1.8] microg/mL, 5.0 [2.6] vs 2.9 [1.3] microg/mL, 55.8 [20.6] vs 45.3 [12.8] microg/mL, respectively). Neonates with high concentration of DHA in umbilical plasma phospholipids (upper quartile) had longer gestational length than neonates with low concentration (lower quartile; 282.5 [8.5] vs 275.4 [9.3] days). No differences in EEG scores or Fagan scores were found, but neonates with mature EEG (N = 70) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG (N = 51) on the second day of life. Dietary information from 251 infants at 3 months of age was collected and 85% of these infants were exclusively breastfed, in addition to 12% who were partly breastfed. The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil. There were no significant differences in infant growth during the first year of life between the 2 groups. CONCLUSIONS: This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome, cognitive development, or growth, as compared with supplementation with n-6 fatty acids. However, it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn.

Abnormalities, Multiple↗

Effects of peroxidative stress and age on the concentration of a deoxyguanosine-malondialdehyde adduct in rat DNA.

The effect of age and peroxidative stress on the concentration of a deoxyguanosine malondialdehyde adduct (dG-MDA) in rat tissues was investigated. Vitamin E deficiency had no effect on the dG-MDA content of liver DNA in rats fed a diet containing 10% corn oil. When 2% cod liver oil was added to this diet, the dG-MDA content of liver DNA doubled in the positive controls fed a high level of vitamin E (100 ppm dl-alpha-tocopherol), and there was a further increase when vitamin E was deleted. Neither iron nitrilotriacetate administration nor choline deficiency had any effect on the dG-MDA content of liver DNA. Carbon tetrachloride had a lowering effect. The failure of iron or carbon tetrachloride administration and of vitamin E deficiency to increase liver dG-MDA is consistent with their failure in previous experiments to affect the urinary excretion of dG-MDA. In contrast, these forms of peroxidative stress produce large increments in the urinary excretion of MDA adducts with lysine, reflecting increased formation and degradation of MDA-modified proteins. DNA appears to be protected from modification by MDA produced at extranuclear sites. The frequency of dG-MDA in different tissues of 4-month-old rats varied markedly: brain >> liver > kidneys and testes. Higher concentrations of dG-MDA were found in the liver and kidneys, but not the testes, of 25-month-old rats. The determinants of the concentration of dG-MDA in DNA merit further investigation.

Aging↗

Inanition may reduce alkaline phosphatase activity in liver and intestine of zinc-deficient mice.

Zinc-deficiency was induced in mice by feeding a Zn-deficient basal diet (ZD dietary group) containing 9% lipid (6% corn oil, 3% cod liver oil) for 8 wk. Thereafter, the corn oil was withdrawn from the basal diet and a subset of Zn-deficient animals (ZDLR group) was fed this modified low fat diet for another 8 wk. Alkaline phosphatase activity in intestine and liver was compared in these mice and in those allowed ad libitum access to the lipid-adequate Zn-supplemented diet (ZS group), in those pair-fed the Zn-supplemented diet (PF group) and in those fed the lipid-adequate, Zn-deficient diet ad libitum (ZD group). The enzyme activity in both intestine and liver of the ZDLR group was greater than in those of the ZD group and greater than or equal to those of the ZS and PF diet groups. The results of this study suggest that the reduction in alkaline phosphatase in Zn-deficient animals is a response secondary to associated inanition.

Alkaline Phosphatase↗

High dietary fish oil alters the brain polyunsaturated fatty acid composition.

Feeding adult rats a 17% corn-oil diet for 8 weeks did not change brain polyunsaturated fatty acids (PUFA) compared to rats fed 2.2% corn oil (with 2.2% lard added). When the corn-oil diet was supplemented with 14.5% cod liver oil or 12.5% salmon oil, the fatty acid composition of brain PUFA was significantly altered, even if alpha-tocopherol was added to the salmon-oil diet. Comparing salmon-oil- and cod-liver-oil-fed animals with corn-oil-fed animals, arachidonic acid 22:4(n-6) and 22:5(n-6) were reduced, and 20:5(n-3), 22:5(n-3) and 22:6(n-3) were increased. Liver fatty acids were also significantly altered. Thus, the brain is not protected against a large excess of very-long-chain n-3 PUFA, which increase n-3/n-6 ratio and could lead to abnormal function, and which might be difficult to reverse.

Animals↗

[Seasonal changes in the makeup of cod oil].

The vitamin A activity and the quantitative correlation of individual fatty acids in the liver oil of Barenz Sca cod were investigated. Seasonal changes of its composition and nutritional value were educed. The vitamin A activity varies according to seasons by more than twice each way and the content of dominant acids undergoes material changes. The greatest nutritional value has been found to display the medicinal cod liver oil of the fish caught during the autumn and winter months and the least - of that caught in spring and summer.

Animals↗

Interactive effects of dietary (n-3) polyunsaturated fatty acids and chronic ethanol intoxication on synaptic membrane lipid composition and fluidity in rats.

The influence of dietary polyunsaturated fatty acids on fatty acid composition, cholesterol and phospholipid content as well as 'fluidity' (assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) probes) of brain synaptic plasma membranes (SPM) and their interactions with chronic ethanol effects were studied in rats fed for two generations with diets either devoid of (n-3) fatty acids (sunflower oil diet), rich in alpha-linolenic acid (soya oil diet) or in long chain (n-3) fatty acids (sunflower + cod liver oil diet). Results were compared with rats fed standard lab chow. Sunflower oil led to an increase in the (n-6)/(n-3) ratio in the membranes with an increase of the 'fluidity' at membrane apolar level; sunflower + cod liver oil decreased the (n-6)/(n-3) ratio without affecting membrane 'fluidity' while no difference was seen between the SPM of rats fed soya oil and standard diet. After 3 weeks alcohol intoxication in rat fed the standard diet: oleic alpha-linoleic acids and cholesterol levels were increased, arachidonic acid and the double bond index/saturated fatty acids were decreased and there was a decrease of 'fluidity' in the lipid core of the SPM. Soya oil almost totally abolished these usually observed changes in the SPM fatty acids composition but increased oleic acid and cholesterol without any change in fluidity. Sunflower oil led to the same general alterations of fatty acid as seen with standard diet but to a greater extent, with decrease of the 'fluidity" at the apolar level and in the region probed by TMA-DPH. When sunflower oil was supplemented with cod liver oil, oleic and alpha-linoleic acids were increased while the 'fluidity' of the apolar core of SPM was decreased. So, the small changes in fatty acid pattern seem able to modulate neural properties i.e. the responses to a neurotoxic like ethanol. A structurally specific role of PUFA is demonstrated by the pernicious effects of the alpha-linolenic acid deficient diet which are not totally prevented by the supply of long chain (n-3) PUFA.

Alcoholic Intoxication↗

Effect of dietary n-3 fatty acids on weight gain and liver polar lipid fatty acid composition of fingerling channel catfish.

A 10-wk experiment was conducted to determine the effect of supplementing a 5% tristearin basal diet with linoleic acid [18:2(n-6)], linolenic acid [18:3(n-3)], an n-3 highly unsaturated fatty acid (n-3 HUFA) mixture, cod liver oil, corn oil or linseed oil on growth and fatty acid composition of the liver polar lipid fraction of fingerling channel catfish (Ictalurus punctatus). The lowest weight gain was observed in fish fed the basal diet. Weight gain was improved by certain levels of supplemental n-3 fatty acids. Fish fed a diet containing 2% 18:3(n-3) grew at the same rate as fish fed a diet containing 2.5% cod liver oil plus 2.5% corn oil. The best growth rate was observed in fish fed diets containing either 5% cod liver oil or 5% linseed oil. Growth rate was depressed by supplementation with 4% 18:3(n-3) or 1.25% n-3 HUFA mix. No improvement in growth rate was observed with dietary 18:2(n-6). Dietary linolenate was converted to docosahexaenoic acid [22:6(n-3)]. The ratio of 20:3(n-9) to 22:6(n-3) of the fish showing good growth was less than 0.4. The data obtained in this experiment indicate that n-3 fatty acids are essential for channel catfish and that the 18:3(n-3) or n-3 HUFA dietary requirement is 1.0-2.0% or 0.5-0.75%, respectively.

Animals↗

Calories, fat, fibers, and cellular proliferation in Swiss Webster mice.

Increased cellular proliferation has been associated with the enhanced expression of several key stages in carcinogenesis. A standard protocol was used to investigate the effect of specific dietary regimens on cellular proliferation. Young adult Swiss Webster mice were fed for 30 days with modified AIN-76A semi-purified diets designed to illustrate the effects of the levels of dietary or calorie restriction, different fibers and bulking agents, and different fats on cellular proliferation. Female mice were used for the restriction and fat studies, males for the fiber and bulking agent studies. Vaginal smears were taken from females from treatment day 15, and the mice killed 2 days following the first estrus following 30 days feeding; males were killed on the 30th day. One hour before death, mice were injected ip with 0.25 micro Ci/g 3[H]-thymidine. Slides were prepared for radioautography and histopathology. Both dietary and calorie restriction led to reduced 3[H]-thymidine labeling indices in each of the seven tissues studied, the mammary gland being the most severely affected. Different fibers and bulking agents, in specific cases, reduced labeling in the duodenum but not to a consistent statistically significant extent in the colon or colo-rectal region. In the duodenum, oat bran and oat gum were the most effective while wood cellulose (alphacel) had no effect. Investigations on the effects of different fats is continuing. High levels of lard, menhaden oil, or cod liver oil as the fat component of the AIN-76A diet, led to much higher levels of labeled cells in the mammary gland or colo-rectal region than did fat components rich in vegetable oils. The labeling indices appeared to be inversely correlated with the level of linoleic acid in the diet, a presumption that has been confirmed by investigating a series of diets containing different levels of this acid. Anti-oxidants were not used in any of these fat-modified diets. The overall results obtained in these studies clearly indicate the utility of cellular proliferation studies in investigating the effects of dietary modifications.

Animals↗

Schistosoma mansoni: experimental chemoprophylaxis in mice using oral anti-penetration agents.

The ability to prevent schistosomiasis by using an oral chemoprophylactic agent, which acts by preventing cercarial penetration, has been unexplored. We initially examined the effect of praziquantel (PZQ) as such an agent and found that it was moderately effective in blocking cercarial penetration, but that this effect was dependent on the vehicle used to administer the drug. ICR mice were given a total of 200 mg/kg PZQ per os over an 8-hr period in a divided dose of 50 mg/kg/2 hr. At time periods ranging from 0 to 92 hr after the last dose, mice were exposed to approximately 75 75Se-labeled cercariae via the tail. Twenty-four hours later, mice were sacrificed, their tails were removed and subjected to autoradiography, and the percentage of penetration was calculated. Cremophor El, 50% PEG 200, 50% propylene glycol, vegetable oil, and cod liver oil were used as PZQ vehicles. When Cremophor El (ethoxylated castor oil) was used to administer PZQ, a 93% reduction in cercarial penetration was seen at 0 hr and a 98%+ reduction rate was seen from 4 to 24 hr postexposure. However, Cremophor El alone had an essentially equivalent effect on cercarial penetration from 8 to 92 hr after administration. These unexpected results led us to investigate both castor oil and ricinoleic acid (castor oil is 87% ricinoleate as triglyceride) as oral anti-penetration agents. Mice were given the lipids orally by gavage for 7 days. On Day 8, each group of 12 mice was exposed to approximately 75 75Se-radiolabeled cercariae. Castor oil gave protection rate ranging from 90 to almost 100% at an optimal concentration of 0.3 ml/day x 3 or 7 days (approximately 9.8 g/kg/day). These observations suggest that chemoprophylaxis may be possible by dietary supplementation with lipids having anti-penetration activity or by molecules that resemble these lipids.

Administration, Oral↗

Biological basis for the benefit of nutraceutical supplementation in arthritis.

Arthritis is a common disease in which the end-point results in joint replacement surgery. This article reviews the use of nutraceuticals as alternative treatments for pathological manifestations of arthritic disease. The efficacy of fish oils (e.g. cod liver oil) in the diet has been demonstrated in several clinical trials, animal feeding experiments and in vitro models that mimic cartilage destruction in arthritic disease. In addition, there is some evidence for beneficial effects of other nutraceuticals, such as green tea, herbal extracts, chondroitin sulphate and glucosamine. However, in most cases, there is little scientific evidence at the cellular and molecular levels to explain their mechanisms of action.

Adult↗

Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet.

The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets.

Animals↗

Fish oils lower rat plasma and hepatic, but not immune cell alpha-tocopherol concentration.

These studies were designed to measure the impact of different fish oil sources of dietary (n-3) polyunsaturated fatty acid on the alpha-tocopherol content of rat immune cells. In the first experiment, rats were fed diets containing either lard, corn oil, menhaden fish oil or cod liver oil. In the second study, sardine fish oil replaced corn oil. Dietary fat source did not significantly influence body weights or the yield of immune cells in either study. In both studies, plasma and liver alpha-tocopherol concentrations were significantly lower in (n-3) polyunsaturated fatty acid-fed rats than in rats fed lard. In the first study, immune cell alpha-tocopherol concentrations followed those observed in the plasma and liver. These concentrations closely paralleled the amount of RRR-alpha-tocopheryl acetate added to diets and not the total vitamin E present, which was the same for all treatment groups. However, in the second study, alpha-tocopherol concentration of immune cells was not significantly different among rats fed lard, menhaden fish oil, and sardine fish oil. In that study both the amount and form of vitamin E were carefully balanced across dietary treatment groups. In conclusion, despite having similar amounts of (n-3) polyunsaturated fatty acids, two out of three fish oils tested did not lower immune cell alpha-tocopherol concentration even in the face of significantly reduced plasma and liver alpha-tocopherol concentrations.

Animals↗

Bait bases for Mastomys natalensis Smith 1834: a murid of public health interest in Africa.

Mastomys natalensis is widely distributed in the whole of Africa and is a reservoir of important zoonoses including plague. In order to control this species efficiently using rodenticides, tests were carried out to find the most preferred cereal and bait additives to form a suitable bait base. Investigations were based on food choice tests in caged animals. Among the cereals tested, rice was significantly preferred (P=0.01) followed by wheat, sorghum and maize. Of the additives tested, both sexes of M. natalensis significantly preferred baits containing either 1,3 and 5% sucrose (p=0.05), or 3 and 5% glycerine, or 3% fish, or 1% sucrose. Also both sexes rejected bait containing 1 and 3% molasses. Additives such as 1% glycerine, 1 and 3% groundnut did not significantly influence bait intake. Sex preference differential was observed on baits containing 1 and 5% fish, 1 and 5% groundnut, 5% cotton oil, 5% cod liver oil and 0.5% salt. It was concluded that bait additives which scored 70% or more should be considered suitable for M. natalensis bait. However further studies are recommended on this subject.

Journal Article↗

Determination of iodine values using 1,3-dibromo-5,5-dimethylhydantoin (DBH) without the employment of chlorinated hydrocarbons. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 17.

Low and medium iodine values of fixed oils and fats can be determined in glacial acetic acid within reduced waiting times of only 5 min. Highly unsaturated compounds such as those of linseed oil, cod-liver oil, sunflower oil, soybean oil, wheat germ oil and the emulsifier sorbitan trioleate result too low values in comparison to PH. EUR. 2002 [2] and USP 2000 [3]. Cocoa butter with a low iodine number is insoluble in glacial acetic acid. The iodine values of nonionogenic emulsifiers such as ceteareth-30 (Macrogol cetostearyl ether PH. EUR. 2002), oleth-10 resp. 20 (Macrogol oleyl ether PH. EUR. 2002) and polysorbate-80 PH. EUR. 2002 are obtained in aqueous solutions. Oleth-2 (Macrogol oleyl ether PH. EUR. 2002), polyoxyl-40 castor oil (Macrolglycerol ricinoleate PH. EUR. 2002), polysorbate-60 PH. EUR. 2002 and sorbitan trioleate PH. EUR. 2002 need the addition of ethyl acetate. Fixed oils even with high iodine values can be determined in an o/w emulsion with a reaction time of 5 min in most cases, when nonionogenic emulsifiers such as ceteareth-30, polyoxyl-30 glycerol monolaurate or polyoxyl-60 hydrogenated castor oil (Macrolglycerol hydroxystearate PH. EUR. 2002) are used.

Acetates↗

[Polyunsaturated fatty acid preparations available on the Danish market. Composition and oxidative stability].

The emerging interest in essential polyunsaturated fatty acids has resulted in a number of products available in the Danish market. These products contain essential fatty acid oils rich in n-6 and n-3 fatty acids. The quality of these products plays a major role in planning prophylactic and clinical studies. This investigation therefore illustrates the quality and the contents of undesirable oxygenated compounds--peroxides and polymeric/oxidative components. Intake of these undesirable substances can theoretically contribute to the development of cancer. It is therefore of utmost importance to be aware of the quality of the product especially when relatively large doses are employed for a considerable period. Our results show that the oxidation values of the fish oil products are much higher than vegetable oils. Furthermore we observed higher amounts of polymerised/oxidised components in Pikasol although the peroxide value was relatively low. Okholm's fish oil and cod liver oil contain higher amounts of undesirable gadoleic and cetoleic acids. A quality control from the authorities is desirable as the consumer has only the producer's/importer's "assurances" to rely on and these are not always in accordance with the real facts.

Denmark↗

[Lipolytic activity of osmotolerant yeasts].

The ability to hydrolyse olive oil, cod-liver oil, caviar oil, and yeast oil was studied in osmotolerant yeasts Candida mogii 2, Debaryomyces hansenii 8, and Rhodotorula rubra 9, isolated from salted caviar. The lipolytic activity was manifested at 5, 15 and 26 degrees C and pH 4.0--9.2, even in the presence of high concentrations (0.5--3 M) of such chlorides as KCl, NaCl and CaCl2. The lipolytic activity of S variant of D. hansenii 8 was higher than the activity of its R variant.

Culture Media↗

[Changes in the alanine aminotransferase and alkaline phosphatase activity and the bilirubin content under the action of spermaceti oil, corn oil and fish oil].

Effect of spermaceti oil, cod-liver oil and corn oil on the content of total, direct and indirect bilirubin, on the activity of transaminase, alkaline phosphatase and colloid resistance was studied in three animal species (rabbits, guinea-pigs and albino rats) during 120 days (90 days of administration and 30 days of after-effect). Histological examination was performed on a selective basis with the use of hematoxylin eosin staining. Use was made of MacManus technique to reveal neutral polysaccharides, glycogen and lipids. It has been shown that the test oils exert largely consistent effects on renal function, the degree of these effects being dose-dependent.

Alanine Transaminase↗