Liver Docosahexaenoic Acid Research Articles

Poly‐γ‐glutamate isolated from fermented soy products changes omega‐3 fatty acid contents of liver and brain in diet‐induced obese rats

The study was carried out to evaluate the effects of poly‐gamma‐glutamate (γ‐PGA) on the omega‐fatty acids of liver and brain in diet‐induced obese rats. The gamma‐PGA isolated from a Korean fermented soybean product, Cheongkukjang is an anionic biopolymer. Ten‐weeks‐old Sprague‐Dawley male rats (n=64) were divided into two groups and induced obesity by providing the low 10% fat control and high 45% fat diets for 4 weeks. Then, they were randomly blocked into four groups in each fat diet and provided four different diets containing no PGA control, PGA, PGA‐Ca, and PGA‐Mg. The gamma‐PGA content of the diets was 0.1% that was determined as appropriate by previous studies. After 4 week feeding, rats were decapitated and the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents of liver and brain were analyzed by gas chromatography. The low fat groups fed with three different types of PGA showed higher liver DHA content than the control and the high fat groups with PGA showed higher liver EPA content (p<0.05). In the brain, the high fat groups fed with PGA showed significantly higher EPA contents in cerebellum except in cerebrum and brain stem, and showed higher DHA contents in all three brain regions. The results suggest that gamma‐PGA accumulates EPA and DHA in liver and brain. The binding forms of PGA may not influence the omega‐fatty acid accumulation. (This study was supported by 2007 Seoul R& D Program).

Fish oil substitution by vegetable oils in commercial diets for gilthead sea bream ( Sparus aurata L.); effects on growth performance, flesh quality and fillet fatty acid profile : Recovery of fatty acid profiles by a fish oil finishing diet under fluctuating water temperatures

The effects of long term feeding (6 months) of commercial diets with low fish meal content and high levels of vegetable oils (69% fish oil substitution level) were determined in gilthead sea bream (110 g). A control diet containing South American fish oil (FO) was evaluated against feeds with either soybean oil (SO), palm oil (PO) or rapeseed oil (RO). Afterwards, all fish were fed a fish oil finishing diet to determine the progressive recovery of the fillet fatty acid profiles. The results showed that growth and feed utilization in gilthead sea bream are not affected by fish oil substitution with soybean and rapeseed oil, contrary to palm oil inclusion. Flesh and liver docosahexaenoic acid (DHA) and arachidonic acid (ArA) contents were reduced to a lower degree than their reduction in the diet, whereas eicosapentaenoic (EPA) reduction was more pronounced in both tissues. Sensory analysis revealed no difference in the organoleptic characteristics of the dietary groups. However, low acceptance scores were calculated for all treated groups. No histological alterations were seen in gut tissue but liver of the PO group showed intense lipid accumulation. Re-feeding with a fish oil finishing diet for 120 days was not adequate for restoration of DHA, ArA and EPA. Linoleic (LA) and oleic acid (OA) were retained even after 120 days re-feeding with the fish oil diet.

Heavy metal exposure in large game from a lead mining area: Effects on oxidative stress and fatty acid composition in liver

The Pb mining area of the valley of Alcudia and the Sierra Madrona mountains (S. Spain) has been exploited intermittently for over 2100 years, since Roman occupation and up until the late 1900s. Red deer ( n = 168) and wild boar ( n = 58) liver and bone (metacarpus) were analyzed for Pb, Zn, Cu, Cd, As and Se. Lipid peroxidation, total and oxidized glutathione (GSH), superoxide dismutase (SOD), GSH peroxidase (GPX) and fatty acid composition were studied in liver of red deer. The concentrations of Pb in liver and bone of red deer and wild boar were higher in the mining area than in the control area, and higher in the wild boar than red deer, but well below the level associated with clinical signs of Pb poisoning. Liver levels of Cu, Cd and Se were also higher in red deer from the mining area. Red deer from the mining area had 39% less total GSH than in the control area. The percentage of docosahexaenoic acid in liver of red deer from the mining area was 16% lower than in the control area.

Dietary fish oil replacement with lard and soybean oil affects triacylglycerol and phospholipid muscle and liver docosahexaenoic acid content but not in the brain and eyes of surubim juveniles Pseudoplatystoma sp.

Triplicate groups of juvenile suribim were fed for 183 days one of four different isonitrogenous (47.6% crude protein) and isolipidic (18.7% lipid) diets formulated using three different lipid sources: 100% fish oil (FO, diet 1); 100% pig lard (L, diet 2); 100% soybean oil (SO, diet 3), and FO/L/SO (1:1:1, w/w/w; diet 4). The tissue levels of fatty acids 18:2n-6 and 18:3n-3 decreased relative to corresponding dietary fatty acid values. The 20:5n-3 and 22:6n-3 composition of muscle and liver neutral lipids were linearly correlated with corresponding dietary fatty acid composition. In contrast, the 22:6n-3 composition of the brain and eye were similar among treatments. The 22:6n-3 level was enriched in all tissues, particularly in the neural tissues. Similar results were observed for tissue polar lipids: fatty acids content reflected dietary composition, with the exception of the 22:6n-3 level, which showed enrichment and no differences between groups. Given these results, the importance of the biochemical functions (transport and/or metabolism) of 22:6n-3 in the development of the neural system of surubim warrants further investigation.

Differential Tissue Dose Responses of (n-3) and (n-6) PUFA in Neonatal Piglets Fed Docosahexaenoate and Arachidonoate 3

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are commonly added to infant formula worldwide; however, dietary concentrations needed to obtain optimal tissue levels have not been established. Hence, we studied tissue responses in piglets fed various doses of DHA and ARA. Doses were 0, 1, 2, and 5 times those used in U.S. infant formulas and DHA/ARA in Diet 0, Diet 1, Diet 2, and Diet 5 were 0, 4.1/8.1, 8.1/16.2, and 20.3/40.6 mg/100 kJ formula, respectively. Supplementation of dietary DHA and ARA increased DHA in brain, retina, liver, adipose tissue, plasma, and erythrocyte by 1.1- to 25.8-fold of Diet 0 (P-trend < 0.01). Tissue ARA (1.1- to 6.0-fold of Diet 0) responded to dietary ARA in liver, adipose tissue, plasma, and erythrocytes (P-trend < 0.05); brain and retina ARA was, however, unresponsive to dietary DHA and ARA. Plasma and erythrocyte DHA were positively associated with DHA in neural (brain and retina) and visceral (liver and adipose) tissues (r2 = 0.11–0.56; P < 0.001–P = 0.042). Plasma and erythrocyte ARA did not correlate with neural ARA. Only plasma ARA was associated with liver ARA (r2 = 0.222; P = 0.02) and adipose ARA (r2 = 0.867; P < 0.001) and erythrocyte ARA correlated with adipose ARA (r2 = 0.470; P < 0.001). We conclude that dietary DHA supplementation affords an effective strategy for enhancing tissue DHA, ARA in visceral but not neural tissues is sensitive to dietary ARA, and erythrocyte and plasma DHA can be used as proxies for tissue DHA, although blood-borne ARA is not an indicator of neural ARA.

Polyunsaturated Fatty Acid Pattern in Liver and Erythrocyte Phospholipids from Obese Patients

Our aim was to study the fatty acid (FA) composition of liver phospholipids and its relation to that in erythrocyte membranes from patients with obese nonalcoholic fatty liver disease (NAFLD), as an indication of lipid metabolism alterations leading to steatosis. Eight control subjects who underwent antireflux surgery and 12 obese patients with NAFLD who underwent subtotal gastrectomy with a gastro-jejunal anastomosis in Roux-en-Y were studied. The oxidative stress status of patients was assessed by serum F2-isoprostanes levels (gas chromatography/negative ion chemical ionization tandem mass spectrometry). Analysis of FA composition of liver and erythrocyte phospholipids was carried out by gas-liquid chromatography. Patients with NAFLD showed serum F2-isoprostanes levels 84% higher than controls. Compared with controls, liver phospholipids from obese patients exhibited significantly 1) lower levels of 20:4n-6, 22:5n-3, 22:6n-3 [docosahexaenoic acid (DHA)], total long-chain polyunsaturated FA (LCPUFA), and total n-3 LCPUFA, 2) higher 22:5n-6 [docosapentaenoic acid (DPAn-6)] levels and n-6/n-3 LCPUFA ratios, and 3) comparable levels of n-6 LCPUFA. Levels of DHA and DPAn-6 in liver were positively correlated with those in erythrocytes (r = 0.77 and r = 0.90, respectively; p < 0.0001), whereas DHA and DPAn-6 showed a negative association in both tissues (r = -0.79, p < 0.0001 and r = -0.58, p < 0.01, respectively), associated with lower DHA/DPAn-6 ratios. Obese patients with NAFLD showed marked alterations in the polyunsaturated fatty acid pattern of the liver. These changes are significantly correlated with those found in erythrocytes, thus suggesting that erythrocyte FA composition could be a reliable indicator of derangements in liver lipid metabolism in obese patients.

Dietary α‐linolenic acid increases brain but not heart and liver docosahexaenoic acid levels

Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation.

Where Does the Developing Brain Obtain Its Docosahexaenoic Acid? Relative Contributions of Dietary α-Linolenic Acid, Docosahexaenoic Acid, and Body Stores in the Developing Rat

Docosahexaenoic acid (DHA), a 22-carbon, highly unsaturated, n-3 fatty acid, is important for optimal nervous system function. In this study, designed to quantify how preformed dietary DHA regulates metabolic pathways in vivo, 8-d-old rat pups were divided into four groups and fed artificial rat milk diets. One group was fed formula with deuterium-labeled LNA (d5-LNA) as the only source of n-3 fatty acids, and a second group was fed formula that contained d5-LNA and unlabeled DHA. Two additional groups were dam-reared to permit analysis of fatty acyl pool sizes at postnatal days 8 and 28. The dams were fed a diet that contained 3% unlabeled LNA. DHA in brain and liver was analyzed. Our study demonstrated that preformed DHA in the diet markedly decreased the amount of biosynthesized DHA that accumulated in the brain and the liver. Surprisingly, 40% of the DHA that was newly acquired during this period in the "LNA" group was unlabeled. Because there were no unlabeled n-3 fatty acids in this diet, this DHA must have been derived from body stores of n-3 fatty acids. Thus, body stores can be a significant source of brain DHA in animals that are fed LNA as the only source of n-3 fatty acids.

Effects of an n-3-deficient diet on brain, retina, and liver fatty acyl composition in artificially reared rats

Rat pups born to dams fed a diet with 3.1% of total fatty acids as alpha-linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model.

Supplementation of Female Rats with α-Linolenic Acid or Docosahexaenoic Acid Leads to the Same Omega-6/Omega-3 LC-PUFA Accretion in Mother Tissues and in Fetal and Newborn Brains

Background: Maternal omega-3 fatty acid supplementation has been suggested to provide docosahexaenoic acid (DHA) for the normal brain development during gestation. DHA can be given as such (preformed) or through the omega-3 precursor alpha-linolenic acid (LNA) which is transformed into DHA by elongation and desaturation reactions. Western diet provides low amounts of LNA and DHA; therefore, supplementation with these omega-3 fatty acids has been suggested for pregnant women. However, the bioequivalence of LNA ingestion to DHA supplementation has not been established. Methods: Recently weaning female Wistar rats were fed a diet containing a small amount of LNA and no DHA. The animals were daily supplemented 40 days before mating, during pregnancy, and until delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty acids were given as ethyl ester derivatives. Controls received coconut oil. The fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and 21-day-old rats were also analyzed for fatty acid composition. Results: Supplementation with LNA and DHA induced a similar accretion of DHA in plasma, erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn rats was similar when the mothers were supplemented with LNA and DHA. Our results show that under our experimental conditions a similar accretion of DHA in the different tissues of the mothers and in the brain segments of fetuses and newborn rats is obtained after LNA and DHA supplementation. Conclusion: LNA and DHA, at the amounts given in this study, show a similar bioequivalence for DHA accretion in different tissues of the mother and in brain segments of fetuses and newborn rats.

Dietary effects of eicosapentaenoic acid and docosahexaenoic acid on lipid metabolism in black sea bream

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were fortified at a level of 1.5% in a composed diet. The effects were confirmed in 0-year black sea bream Acanthopagrus schlegeli in terms of lipid metabolism and physiological activity. The EPA group was high in EPA in muscle, liver, intraperitoneal fat body (IPF), eye and brain. The levels of DHA in liver, eye, brain and heart were also high in the EPA group, suggesting that conversion of EPA to DHA occurred in those organs. Fortification of DHA increased the levels of DHA in organs except the eye, but did not affect EPA levels. Both the EPA and DHA groups showed smaller adipocytes or lower levels of lipid content than the control group. The starvation followed by feeding experiment caused marked body weight loss in the control group by consumption of muscle protein and lipids in IPF. Fortifications of EPA and DHA induced less mobilization of muscle protein and IPF lipids as energy. Liver function and resistance to air-dipping were improved by both EPA and DHA fortifications. The present results implied conversion of EPA to DHA in the fish with regard to parameters, such as lipid metabolism and physiological vitality.

Sows’ Milk Attenuates Dexamethasone-Induced Reductions in Liver Docosahexaenoic Acid

The objective was to determine the effects of dexamethasone (Dex) on growth and arachidonic (AA) and docosahexaenoic (DHA) acid status. Piglets were randomized to suckling or formula feeding plus Dex or placebo treatment for 15 days. Weight and length at the beginning and end of study was used to assess growth. After 15 days, AA and DHA in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were measured in liver and plasma and total AA and DHA in forebrain and brainstem. Dex treatment significantly reduced weight and length. Dex reduced liver PC and PE DHA in the formula group, but the reduction in the suckled group was not significant. PC AA and DHA were positively related in liver and plasma. A main effect of Dex to reduce AA and DHA was observed in forebrain but not in brainstem. Sows’ milk attenuated the Dex-induced reduction in liver DHA but not forebrain AA and DHA or somatic growth.

The effects of dietary EPA and DHA fortification on lipolysis activity and physiological function in juvenile black sea breamAcanthopagrus schlegeli(Bleeker)

Hatchery-reared juvenile black sea bream Acanthopagrus schlegeli (Bleeker) are characterized by high lipid storage and low levels of highly unsaturated fatty acids in their bodies. In the present study, we assessed the effects of dietary fortification of the diet with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the improvement of physiological activity. Black sea bream 50 days old with an average weight of 0.02 g were reared for 50 days on either a control diet (commercial diet) or a commercial diet fortified with 3% EPA and DHA. The fortification with EPA and DHA reduced lipid storage in adipocytes in the intraperitoneal cavity, but decreased muscle lipid level. Consequently, the total lipid level decreased in the bodies of the fish. The proportions of EPA and DHA in muscle, liver and adipocytes were markedly increased by diet fortification, and the EPA and DHA proportions did not differ from those of wild fish. The cell diameter of adipocytes was reduced by EPA and DHA fortification. Liver function and resistance to air-dipping were improved by fortification. The results of a starvation test revealed the efficient mobilization of lipid reserves in response to energy demands prior to protein exhaustion in the EPA/DHA-enriched group. The results implied that increasing the incorporation of dietary EPA and/or DHA should be considered in the larval stage of black sea bream culture.

Linolenic Acid Provides a Source of Docosahexaenoic Acid for Artificially Reared Rat Pups

The goal of the present study was to determine the effectiveness of linolenic acid for enriching docosahexaenoic acid (DHA) in infant rats. Seven-day-old rat pups were artificially reared and fed intragastrically for 8 d a milk substitute containing either 1) corn oil, high in linoleic acid (35.6 g/100 g fatty acids, 775 kJ/L); 2) menhaden oil, high in DHA (3 g/100 g, 67 kJ/L) and eicosapentaenoic acid (EPA, 6 g/100 g, 132 kJ/L); or 3) linseed oil, rich in linolenic acid (34 g/100 g, 750 kJ/L). Growth rates were comparable among the artificially fed pups and those raised by lactating dams. Feeding the DHA precursor linolenic acid enriched EPA in plasma, erythrocytes and liver, but enriched DHA only in the liver, compared with feeding corn oil. The proportion of liver DHA in the pups fed the linolenic acid-rich substitute was twice that detected in the corn oil-fed pups and 60% of the level found in the pups fed the preformed DHA. The significant elevation of hepatic DHA indicates active desaturation and elongation in the developing rat liver. The failure to enrich erythrocyte DHA suggests the need for caution in the use of erythrocytes as an index of DHA status in tissues capable of in situ synthesis. The artificial rearing of rat pups was proven suitable for studying the interaction of dietary manipulation and tissue accretion of essential fatty acids during the postnatal development.

Docosahexaenoic Acid Is Transferred through Maternal Diet to Milk and to Tissues of Natural Milk-Fed Piglets

Docosahexaenoic acid (DHA) is incorporated in large amounts in structural lipids of the developing central nervous system. Milk DHA varies with maternal dietary DHA, but the effect of different intakes of DHA from milk on infant tissue fatty acids is unknown. The effect of milk high or low in DHA on the fatty acid composition of piglet brain, synaptic plasma membranes, retina, liver, plasma and RBC was studied. Pregnant sows were fed diets with 2.5 g/100 g vegetable oil until 4 d pre-partum and were then fed diets with 2.5 g/100 g soybean and canola oils or 4 g/100 g soybean oil plus 1 g/100 g fish oil to 15 d postpartum. Fish oil increased the milk DHA and eicosapentanoic acid from 0.1 to 1.5% and from 0.2 to 0.4% of fatty acids, respectively, but did not alter milk arachidonic acid. The level of DHA was significantly higher in plasma, liver and RBC phospholipids, brain and synaptic plasma membrane of 15-d-old piglets fed milk with high DHA compared with low DHA. Liver, plasma and RBC, but not brain or retina arachidonic acid, was significantly lower in piglets fed the high DHA milk compared with low DHA milk. Thus, differences in plasma, RBC and liver arachidonic acid and DHA of 15-d-old nursing piglets due to the maternal dietary fat were not accompanied by similar differences in central nervous system fatty acids. These studies show maternal DHA intake determines in part the infant plasma, RBC and liver phospholipid DHA.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of endogenous and exogenous n-3 and n-6 fatty acids on microsomal synthesis of docosahexaenoic acid in vitro.

Effects of endogenous and exogenous polyunsaturated fatty acids (PUFA) on microsomal synthesis of docosahexaenoic acid (DHA) from eicosapentaenoic acid (EPA) in vitro were studied using rat livers. Liver microsomes prepared from three groups of rats which had been fed n-3/n-6 ratios of 0.01, 0.39, and 2.70, respectively, for 1 month, were incubated with [1-14C]EPA at 37 degrees C for 30 min. There were no significant differences between the formations of docosapentaenoic acid (DPA) or DHA in the groups. Liver microsomes from rats fed a diet with an n-3/n-6 ratio of 2.70 for 3 weeks were then incubated with [1-14C]EPA in the presence of unlabeled DHA or arachidonic acid (AA). The additional DHA did not have any effect. However, a significant inhibition of DHA synthesis was observed by addition of AA (EPA/AA = 5:2). These results suggest that the microsomal biosynthesis of DHA in rat liver is not susceptible to feedback inhibition.

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.

9 - Neurological Aspects of Folate and Vitamin B12 Metabolism

Vitamin B12 and omega-3 fatty acid deficiency is prevalent in the vegetarian population and is associated with adverse pregnancy outcomes and cardiometabolic risk. The present study investigates the long-term effects of vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids on cardiometabolic profile and long-chain polyunsaturated fatty acid levels (LCPUFA) in the F3 generation offspring.Three generations of rats were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient + omega-3 fatty acid supplemented; vitamin B12 + omega-3 fatty acid supplemented. Animals were sacrificed at 3 months of age.Vitamin B12 deficiency lowered (p <0.01 for both) plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), liver DHA (p <0.05), plasma/liver omega-3 fatty acids (p <0.05 for both), increased triglycerides (p <0.05) and systolic BP (p <0.01) and lowered cholesterol levels (p <0.05) as compared to control. Vitamin B12 deficiency in the presence of omega-3 fatty acids improved plasma/liver EPA, DHA and omega-3 fatty acid profile and maintained cholesterol, triglyceride and BP levels. Vitamin B12 supplementation lowered liver DHA (p <0.05) and cholesterol (p <0.01), whereas BP was similar to control. Combined supplementation of vitamin B12 and omega-3 fatty acids improved omega-3 fatty acid profile, lowered cholesterol/triglyceride levels and maintained the BP similar to that of control.Vitamin B12 deficiency across three generations adversely affects LCPUFA and cardiometabolic profile in the adult offspring. This study provides clues for a combined supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk for noncommunicable diseases.