Influence of clinical characteristics on maternal DHA and other polyunsaturated fatty acid status in pregnancy: A systematic review.

INTRODUCTION: Omega-3 DHA is important for the prevention of preterm birth, however there is limited knowledge of the determinants of omega-3 status during pregnancy. The primary objective of this systematic review was to synthesise data from existing studies assessing relationships between clinical factors and maternal DHA status. MATERIALS AND METHODS: The Medline, Embase, Amed, and CINAHL databases were searched for studies reporting measures of maternal omega-3 status and one or more clinical characteristics. RESULTS: Eighteen studies were included in the final analyses. Factors associated with a higher BMI (overweight, higher gestational weight gain, gestational diabetes), or lower parity were each associated with higher omega-3 status in the majority of studies, with mixed findings for other comparisons. DISCUSSION: Inconsistent findings between studies make it difficult to draw clear conclusions about the relationship between clinical factors and maternal omega-3 DHA status. However, maternal overweight and associated metabolic conditions may increase lipid metabolism.

Influence of sociodemographic, lifestyle and genetic characteristics on maternal DHA and other polyunsaturated fatty acid status in pregnancy: A systematic review.

INTRODUCTION: Omega-3 DHA is important for the prevention of preterm birth, however there is limited knowledge of the determinants of omega-3 status during pregnancy. The primary objective of this systematic review was to synthesise data from existing studies assessing relationships between sociodemographic, diet, lifestyle and genetic factors and maternal DHA status. MATERIALS AND METHODS: The Medline, Embase, Amed, and CINAHL databases were searched for studies reporting measures of maternal omega-3 status and a sociodemographic/lifestyle/genetic characteristic. RESULTS: Twenty-two studies were included in the final analyses. Higher dietary fish consumption/PUFA intake, higher education level and an older maternal age were associated with higher maternal omega-3 status. Higher alcohol intake, smoking and FADS genotype were each associated with lower maternal omega-3 status. DISCUSSION: Differences in findings between studies make it difficult to draw clear conclusions about the relationship between these factors and maternal omega-3 DHA status, although socioeconomic status may play a role.

The effect of maternal DHA supplementation on body fat mass in children at 7 years: follow-up of the DOMInO randomized controlled trial.

BACKGROUND: Animal studies have suggested that an increased supply of omega-3 long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic acid (DHA), during the perinatal period can prevent later excess body fat mass. However, previous human studies have produced inconsistent findings, and few have assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the effect of supplementing women in the second half of pregnancy with omega-3 LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age, as assessed by two methods: air displacement plethysmography (BOD POD) and bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise Maternal Infant Outcome) randomized controlled trial, in which women took either high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to delivery, at Adelaide-based centers. Primary outcomes were the percentage body fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height, waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252 DOMInO children (n=135 males, n=117 females) completed the follow up study. There were no differences between the DHA and placebo groups in percentage body fat as assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16; P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI z-scores were also similar between groups [adjusted mean difference: 0.18, 95% CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or waist and hip circumference between the DHA and placebo groups at 7 years of age. CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on childhood growth or fat mass at 7 years of age, supporting findings from follow ups of the DOMInO children at 3 and 5 years.

The effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.

This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid (ALA) and omega-6 polyunsaturated fatty acid (n-6 PUFA) linoleic acid (LA) intakes on n-3 long-chain polyunsaturated fatty acid (LCPUFA) status in adult humans. The results suggest that it is possible to increase n-3 LCPUFA status by reducing LA and/or increasing ALA intake in humans, although decreasing LA intake to below 2.5%E may be required to specifically increase levels of the n-3 LCPUFA docosahexaenoic acid (DHA). The majority of studies in this area to date have been relatively poor in quality, which limits the ability to draw robust conclusions, and we present a series of recommendations to improve the quality of future studies in fatty acid nutrition in humans.

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats.

OBJECTIVES: To assess the effects of providing a wide range of foodstuffs containing n-3 polyunsaturated fatty acids (PUFA), occurring naturally or from fortification, on intake and blood and tissue proportions of n-3 PUFA. DESIGN: Before/after dietary intervention study. SETTING: Adelaide, Australia. SUBJECTS: 16 healthy males recruited from the community. INTERVENTIONS: Subjects were provided with a range of foodstuffs naturally containing n-3 PUFA (fresh fish, canned fish, flaxseed meal, canola oil) and items fortified with fish oil (margarine spread, milk, sausages, luncheon meat, french onion dip). Food choices were left to the discretion of each subject. Intake was estimated by diet diary. Blood was collected at-2, 0, 2, and 4 weeks for fatty acid analysis. MAIN OUTCOME MEASURES: Dietary intakes; plasma, platelet, and mononuclear cell phospholipid fatty acids. RESULTS: Consumption of n-3 PUFA increased significantly: alpha-linolenic acid (ALA) from 1.4 to 4.1 g/day (P<0.001), eicosapentaenoic acid (EPA) from 0.03 to 0.51 g/day (P<0.001), and docosahexaenoic acid (DHA) from 0.09 to 1.01 g/day (P<0.001). Linoleic acid (LA) intake decreased from 13.1 to 9.2 g/day (P<0.001). The proportions of EPA and DHA increased significantly in all phospholipid pools examined; plasma EPA from 1.13% of total fatty acids to 3.38% (P<0.001) and DHA from 3.76 to 7.23% (P<0.001); mononuclear cell EPA from 0.40 to 1.25% (P<0.001) and DHA from 2.33 to 4.08% (P<0.001); platelet EPA from 0.41 to 1.2% (P<0.001) and DHA from 1.64 to 3.07% (P<0.001). CONCLUSION: Incorporating fish oil into a range of novel commercial foods provides the opportunity for wider public consumption of n-3 PUFA with their associated health benefits. SPONSORSHIP: Dawes Scholarship, Royal Adelaide Hospital.

Biochemical effects of a diet containing foods enriched with n-3 fatty acids.

BACKGROUND: Results of many studies indicate that consumption of n-3 fatty acids can benefit persons with cardiovascular disease and rheumatoid arthritis. However, encapsulated fish oil is unlikely to be suited to lifetime daily use and recommendations to increase fish intake have not been effective. OBJECTIVE: The objective was to examine the effectiveness of a diet that incorporates foods rich in n-3 fatty acids in elevating tissue concentrations of eicosapentaenoic acid and in suppressing the production of inflammatory mediators. DESIGN: Healthy male volunteers were provided with foods that were enriched in alpha-linolenic acid (cooking oil, margarine, salad dressing, and mayonnaise) and eicosapentaenoic and docosahexaenoic acids (sausages and savory dip) and with foods naturally rich in n-3 fatty acids, such as flaxseed meal and fish. Subjects incorporated these products into their food at home for 4 wk. Fatty acid intakes, cellular and plasma fatty acid concentrations, and monocyte-derived eicosanoid and cytokine production were measured. RESULTS: Analyses of dietary records indicated that intake of eicosapentaenoic acid plus docosahexaenoic acid averaged 1.8 g/d and intake of alpha-linolenic acid averaged 9. 0 g/d. These intakes led to an average 3-fold increase in eicosapentaenoic acid in plasma, platelet, and mononuclear cell phospholipids. Thromboxane B(2), prostaglandin E(2), and interleukin 1beta synthesis decreased by 36%, 26%, and 20% (P < 0.05), respectively. CONCLUSIONS: Foods that are strategically or naturally enriched in n-3 fatty acids can be used to achieve desired biochemical effects without the ingestion of supplements or a change in dietary habits. A wide range of n-3-enriched foods could be developed to support large-scale programs on the basis of the therapeutic and disease-preventive effects of n-3 fatty acids.

The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil.

The effect of a flaxseed oil-based diet on tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNF alpha and IL-1 beta production by approximately 30%. Fish-oil supplementation (9 g/d) continued for a further 4 wk; TNF alpha and IL-1 beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNF alpha or IL-1 beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n--3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha-linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to approximately 1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF alpha and IL-1 beta synthesis.

Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites.

Increased concentrations of cellular eicosapentaenoic acid (EPA) have been shown to be beneficial in coronary heart disease, hypertension, and inflammatory disorders. Successful long-term strategies for increasing cellular EPA concentrations require information on the relationships between cellular concentrations of EPA and dietary amounts of alpha-linolenic acid (alpha-LA), a precursor of EPA, and dietary amounts of linoleic acid (LA), an antagonist of alpha-LA conversion to EPA. A dietary intervention study with healthy human volunteers that incorporated alpha-LA-rich vegetable oil (flaxseed oil), against a background diet low in LA, allowed us to examine these relationships. Linear relationships were found between dietary alpha-LA and EPA in plasma fractions and in cellular phospholipids. By contrast there was no relationship observed between dietary LA and tissue concentrations of its metabolite, arachidonic acid (AA). There was an inverse relationship between dietary alpha-LA and docosahexaenoic acid concentrations in the phospholipids of plasma, neutrophils, mononuclear cells, and platelets. The results indicate that increasing dietary alpha-LA will elevate tissue EPA concentrations in a predictable manner. This insight will facilitate the rational planning of practical dietary strategies for the long-term elevation of EPA concentrations in tissues.

Ratios of linoleic acid to alpha-linolenic acid in formulas for term infants.

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues.

Thirty healthy male volunteers were randomly allocated into two dietary treatment groups. The flaxseed group (n = 15) maintained a diet high in alpha-linolenic acid (alpha-LA; 18:3n-3) and low in linoleic acid (LA; 18:2n-6) by using a flaxseed oil and spread that are high in alpha-LA. The control group (n = 15) maintained a diet high in LA and low in alpha-LA, typifying a Western diet. Both groups maintained their diets for 4 wk, followed by another 4-wk period in which they supplemented the diets with fish oil [1.62 g eicosapentaenoic acid (EPA, 20:5n-3) daily and 1.08 g docosahexaenoic acid (DHA, 22:6n-3) daily] in a triglyceride form. The flaxseed oil-containing diet resulted in significant increases in alpha-LA concentrations in the plasma phospholipid, cholesteryl ester, and triglyceride fractions (eightfold increase) and neutrophil phospholipids (50% increase). EPA concentrations increased by 2.5-fold in the plasma lipid fractions and neutrophil phospholipids. After fish-oil supplementation EPA concentrations increased in parallel in both dietary groups, remaining higher in the flaxseed group for both the plasma lipid fractions and neutrophil phospholipids. The results indicate that alpha-LA-rich vegetable oils can be used in a domestic setting (in conjunction with a background diet low in LA) to elevate EPA in tissues to concentrations comparable with those associated with fish-oil supplementation.