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EPA and DHA are required for normal cell function and can also induce health benefits. Oily fish are the main source of EPA and DHA for human consumption. However, food choices and concerns about the sustainability of marine fish stocks limit the effectiveness of dietary recommendations for EPA + DHA intakes. Seed oils from transgenic plants that contain EPA + DHA are a potential alternative source of EPA and DHA. The present study investigated whether dietary supplementation with transgenic Camelina sativa seed oil (CSO) that contained EPA and DHA was as effective as fish oil (FO) in increasing EPA and DHA concentrations when consumed as a dietary supplement in a blinded crossover study. Healthy men and women (n 31; age 53 (range 20–74) years) were randomised to consume 450 mg/d EPA + DHA provided either as either CSO or FO for 8 weeks, followed by 6 weeks washout and then switched to consuming the other test oil. Fasting venous blood samples were collected at the start and end of each supplementation period. Consuming the test oils significantly (P < 0·05) increased EPA and DHA concentrations in plasma TAG, phosphatidylcholine and cholesteryl esters. There were no significant differences between test oils in the increments of EPA and DHA. There was no significant difference between test oils in the increase in the proportion of erythrocyte EPA + DHA (CSO, 12 %; P < 0·0001 and FO, 8 %; P = 0·02). Together, these findings show that consuming CSO is as effective as FO for increasing EPA and DHA concentrations in humans.
EPA and DHA are important components of cell membranes. Since humans have limited ability for EPA and DHA synthesis, these must be obtained from the diet, primarily from oily fish. Dietary EPA and DHA intakes are constrained by the size of fish stocks and by food choice. Seed oil from transgenic plants that synthesise EPA and DHA represents a potential alternative source of these fatty acids, but this has not been tested in humans. We hypothesised that incorporation of EPA and DHA into blood lipids from transgenic Camelina sativa seed oil (CSO) is equivalent to that from fish oil. Healthy men and women (18–30 years or 50–65 years) consumed 450 mg EPA + DHA from either CSO or commercial blended fish oil (BFO) in test meals in a double-blind, postprandial cross-over trial. There were no significant differences between test oils or sexes in EPA and DHA incorporation into plasma TAG, phosphatidylcholine or NEFA over 8 h. There were no significant differences between test oils, age groups or sexes in postprandial VLDL, LDL or HDL sizes or concentrations. There were no significant differences between test oils in postprandial plasma TNFα, IL 6 or 10, or soluble intercellular cell adhesion molecule-1 concentrations in younger participants. These findings show that incorporation into blood lipids of EPA and DHA consumed as CSO was equivalent to BFO and that such transgenic plant oils are a suitable dietary source of EPA and DHA in humans.
Humans can obtain pre-formed long-chain PUFA from the diet and are also able to convert essential fatty acids (EFA) to longer-chain PUFA. The metabolic pathway responsible for EFA interconversion involves alternating desaturation and carbon chain elongation reactions, and carbon chain shortening by peroxisomal β-oxidation. Studies using stable isotope tracers or diets supplemented with EFA show that capacity for PUFA synthesis is limited in humans, such that DHA (22 : 6n-3) synthesis in men is negligible. PUFA synthesis is higher in women of reproductive age compared with men. However, the magnitude of the contribution of hepatic PUFA synthesis to whole-body PUFA status remains unclear. A number of extra-hepatic tissues have been shown to synthesise PUFA or to express genes for enzymes involved in this pathway. The precise function of extra-hepatic PUFA synthesis is largely unknown, although in T lymphocytes PUFA synthesis is involved in the regulation of cell activation and proliferation. Local PUFA synthesis may also be important for spermatogenesis and fertility. One possible role of extra-hepatic PUFA synthesis is that it may provide PUFA in a timely manner to facilitate specific cell functions. If so, this may suggest novel insights into the effect of dietary PUFA and/or polymorphisms in genes involved in PUFA synthesis on health and tissue function.
Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.
Vegetarian diets have been associated with health benefits, but paradoxically are low in EPA and DHA which are important for development, particularly of the central nervous system, and for health. Humans have limited capacity for synthesis of EPA and DHA from α-linolenic acid, although this is greater in women than men. Oily fish and, to a lesser extent, dairy foods and meat are the primary sources of EPA and DHA in the diet. Exclusion of these foods from the diet by vegetarians is associated consistently with lower EPA and DHA status in vegetarian women compared with omnivores. The purpose of the present review was to assess the impact of low EPA and DHA status in vegetarian pregnancies on the development and health of children. EPA and DHA status was lower in breast milk and in infants of vegetarian mothers than those born to omnivore mothers, which suggests that in the absence of pre-formed dietary EPA and DHA, synthesis from α-linolenic acid is an important process in determining maternal EPA and DHA status in pregnancy. However, there have been no studies that have investigated the effect of low maternal DHA status in vegetarians on cognitive function in children. It is important to address this gap in knowledge in order to be confident that vegetarian and vegan diets during pregnancy are safe in the context of child development.
Dietary supplementation is an effective means to improve EPA and DHA status. However, it is unclear whether lipid structure affects EPA+DHA bioavailability. We determined the effect of consuming different EPA and DHA lipid structures on their concentrations in blood during the postprandial period and during dietary supplementation compared with unmodified fish oil TAG (uTAG). In a postprandial cross-over study, healthy men (n 9) consumed in random order test meals containing 1·1 g EPA+0·37 g DHA as either uTAG, re-esterified TAG, free fatty acids (FFA) or ethyl esters (EE). In a parallel design supplementation study, healthy men and women (n 10/sex per supplement) consumed one supplement type for 12 weeks. Fatty acid composition was determined by GC. EPA incorporation over 6 h into TAG or phosphatidylcholine (PC) did not differ between lipid structures. EPA enrichment in NEFA was lower from EE than from uTAG (P=0·01). Plasma TAG, PC or NEFA DHA incorporation did not differ between lipid structures. Lipid structure did not affect TAG or NEFA EPA incorporation and PC or NEFA DHA incorporation following dietary supplementation. Plasma TAG peak DHA incorporation was greater (P=0·02) and time to peak shorter (P=0·02) from FFA than from uTAG in men. In both studies, the order of EPA and DHA incorporation was PC>TAG>NEFA. In conclusion, EPA and DHA lipid structure may not be an important consideration in dietary interventions.
The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was: MCF10A, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen up-regulated); and Hs578T, 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion that differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.
Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.
Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI −1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI −122, −20) % and 93 (95 % CI −116, −70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.
It is well established that genotype plays an important role in the ageing process. However, recent studies have suggested that epigenetic mechanisms may also influence the onset of ageing-associated diseases and longevity. Epigenetics is defined as processes that induce heritable changes in gene expression without a change in the DNA nucleotide sequence. The major epigenetic mechanisms are DNA methylation, histone modification and non-coding RNA. Such processes are involved in the regulation of tissue-specific gene expression, cell differentiation and genomic imprinting. However, epigenetic dysregulation is frequently seen with ageing. Relatively little is known about the factors that initiate such changes. However, there is emerging evidence that the early life environment, in particular nutrition, in early life can induce long-term changes in DNA methylation resulting in an altered susceptibility to a range of ageing-associated diseases. In this review, we will focus on the changes in DNA methylation that occur during ageing; their role in the ageing process and how early life nutrition can modulate DNA methylation and influence longevity. Understanding the mechanisms by which diet in early life can influence the epigenome will be crucial for the development of preventative and intervention strategies to increase well-being in later life.
Maternal folic acid (FA) supplementation is well recognised to protect against neural tube defects. Folate is a critical cofactor in one-carbon metabolism involved in the epigenetic regulation of transcription that underpins development. Thus, it is possible that maternal FA supplementation may have additional, unforeseen persistent effects in the offspring. This is supported by the modification by maternal supplementation with one-carbon donors and FA of the epigenetic regulation of offspring phenotype in mutant mice. The present article reviews studies in human subjects and experimental animals of the effect of maternal FA intake and phenotypic outcomes in the offspring. Maternal FA intake was associated with a short-term increased incidence of allergy-related respiratory impairment in children and multigenerational respiratory impairment in rats. Higher maternal folate status during pregnancy was associated positively with insulin resistance in 6-year-olds. In rats, maternal FA supplementation modified hepatic metabolism and vascular function through altered transcription, in some cases underpinned by epigenetic changes. FA supplementation in pregnant rats increased mammary tumorigenesis, but decreased colorectal cancer in the offspring. Maternal FA supplementation decreased a range of congenital cardiac defects in children. These findings support the view that maternal FA supplementation induces persistent changes in a number of phenotypic outcomes in the offspring. However, the number of studies is limited and insufficient to indicate a need to change current recommendations for FA intake in pregnancy. Nevertheless, such effects should be investigated thoroughly in order to support firm conclusions about the risk of unanticipated long-term negative effects of maternal FA supplementation in humans.
Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile–pubertal period in rats on the epigenetic regulation of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1 mg/kg feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P < 0·05) in females, but not in males. Post-weaning FS diet decreased glucose concentration significantly in females, but increased glucose concentration in males. There were no effects of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in males, while the pattern of expression was related to plasma glucose concentration in females. The FS diet induced specific changes in the methylation of individual CpG in females, but not in males, which were related to the time of exposure. Methylation of CpG − 248 increased the binding of CCAAT-enhancer-binding protein β to the PEPCK promoter. Together, these findings show that both the period during the life course and sex influence the effect of increased exposure to folic acid on the epigenetic regulation of PEPCK and glucose homeostasis.
The developing fetus requires an adequate supply of fatty acids, in particular PUFA, for optimal growth and development. Little is known about the transfer of fatty acids by the placenta into the fetal circulation. However, the molecular form in which fatty acids are transferred into the fetal circulation may influence their metabolism and hence their availability to specific tissues. The aim of the present study was to determine which lipid pools in the fetal circulation become enriched in fatty acids from the placenta by comparing the fatty acid compositions of individual lipid pools between umbilical venous (UV) and umbilical arterial (UA) plasma. Plasma from the UV and UA was collected after delivery from ten uncomplicated pregnancies, and the fatty acid composition of each lipid class was determined by GC. Total NEFA concentration in the UV was twofold higher than in the UA (P < 0·05) due to enrichment in 16 : 0, 16 : 1n-7, 18 : 1n-9, 18 : 1n-7, 18 : 2n-6, 20 : 3n-6, 20 : 4n-6, 24 : 0 and 22 : 6n-3. Total cholesteryl ester concentration was twofold higher in the UV than in the UA (P < 0·05) due to enrichment in 16 : 0, 16 : 1n-7, 18 : 0, 18 : 1n-9, 18 : 1n-7, 18 : 2n-6 and 20 : 4n-6. There were no significant UV–UA differences in the total concentration or composition of TAG or phosphatidylcholine. The present study demonstrates differential enrichment across the placenta of fatty acids into specific lipid pools in the fetal circulation. Such partitioning may facilitate supply of individual fatty acids to specific fetal tissues.