Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans.

Animal and human studies have shown that greatly increasing the amounts of flax seed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55-75 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.     

Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function

BACKGROUND: Greatly increasing dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA)] or fish oil [rich in the long-chain n-3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. OBJECTIVE: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. DESIGN: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to 1 of 5 interventions: placebo (no additional n-3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. RESULTS: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. CONCLUSION: An intake of 相似文献   

Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid

BACKGROUND: An increase in plasma n-3 fatty acid content, particularly eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), is observed after consumption of fish oil-enriched supplements. Because alpha-linolenic acid (18:3n-3; ALA) is the direct precursor of EPA and DHA, ALA-enriched supplements such as flax may have a similar effect, although this hypothesis has been challenged because of reported low conversion of ALA into DHA. OBJECTIVE: To address this question, we designed a clinical trial in which flax oil, fish-oil, and sunflower oil (placebo group) capsules were given to firefighters (n = 62), a group traditionally exposed to cardiovascular disease risk factors. DESIGN: Firefighters were randomly divided into 6 experimental groups receiving 1.2, 2.4, or 3.6 g flax oil/d; 0.6 or 1.2 g fish oil/d; or 1 g sunflower oil/d for 12 wk. Blood was drawn every 2 wk, and the total phospholipid fatty acid composition of red blood cells was determined. RESULTS: As expected, fish oil produced a rapid increase in erythrocyte DHA and total n-3 fatty acids. The consumption of either 2.4 or 3.6 g flax oil/d (in capsules) was sufficient to significantly increase erythrocyte total phospholipid ALA, EPA, and docosapentaenoic acid (22:5n-3) fatty acid content. There were no differences among groups in plasma inflammatory markers or lipid profile. CONCLUSIONS: The consumption of ALA-enriched supplements for 12 wk was sufficient to elevate erythrocyte EPA and docosapentaenoic acid content, which shows the effectiveness of ALA conversion and accretion into erythrocytes. The amounts of ALA required to obtain these effects are amounts that are easily achieved in the general population by dietary modification.     

Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans

Alpha-linolenic acid (ALA) is a major dietary (n-3) fatty acid. ALA is converted to longer-chain (n-3) PUFA, such as eicosapentaenoic acid (EPA) and possibly docosahexaenoic acid (DHA). EPA and DHA are fish-based (n-3) fatty acids that have proven cardioprotective properties. We studied the effect of daily supplementation with 3 g of ALA on the plasma concentration of long-chain (n-3) fatty acids in a predominantly African-American population with chronic illness. In a randomized, double-blind trial, 56 participants were given 3 g ALA/d from flaxseed oil capsules (n = 31) or olive oil placebo capsules (n = 25). Plasma EPA levels at 12 wk in the flaxseed oil group increased by 60%, from 24.09 +/- 16.71 to 38.56 +/- 28.92 micromol/L (P = 0.004), whereas no change occurred in the olive oil group. Plasma docosapentaenoic acid (DPA) levels in the flaxseed oil group increased by 25% from 19.94 +/- 9.22 to 27.03 +/- 17.17 micromol/L (P = 0.03) with no change in the olive oil group. Plasma DHA levels did not change in either group. This study demonstrates the efficacy of the conversion of ALA to EPA and DPA in a minority population with chronic disease. ALA may be an alternative to fish oil; however, additional clinical trials with ALA are warranted.     

Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids

BACKGROUND: For many persons who wish to obtain the health benefits provided by dietary n-3 fatty acids, daily ingestion of fish or fish oil is not a sustainable long-term approach. To increase the number of sustainable dietary options, a land-based source of n-3 fatty acids that is effective in increasing tissue concentrations of the long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is required. OBJECTIVE: The objective of the study was to examine the ability of dietary stearidonic acid (SDA) to increase tissue concentrations of EPA and DHA in healthy human subjects and to compare the effectiveness of SDA with that of the n-3 fatty acids alpha-linolenic acid (ALA) and EPA. DESIGN: Encapsulated SDA, ALA, or EPA was ingested daily in doses of 0.75 g and then 1.5 g for periods of 3 wk each by healthy male and postmenopausal female subjects (n = 15/group) in a double-blind, parallel-group design. RESULTS: Dietary SDA increased EPA and docosapentaenoic acid concentrations but not DHA concentrations in erythrocyte and in plasma phospholipids. The relative effectiveness of the tested dietary fatty acids in increasing tissue EPA was 1:0.3:0.07 for EPA:SDA:ALA. CONCLUSIONS: Vegetable oils containing SDA could be a dietary source of n-3 fatty acids that would be more effective in increasing tissue EPA concentrations than are current ALA-containing vegetable oils. The use of SDA-containing oils in food manufacture could provide a wide range of dietary alternatives for increasing tissue EPA concentrations.     

Long-chain n-3 polyunsaturated fatty acid dietary recommendations are moderately efficient in optimizing their status in healthy middle-aged subjects with low fish consumption: a cross-over study

Several dietary recommendations have been made for marine n-3 polyunsaturated fatty acid (PUFA) intake; however, the effectiveness of these fatty acids has not been thoroughly examined. The aim of this study was to investigate whether public-aimed dietary recommendations for long-chain n-3 PUFA from oily fish or fish oil supplements are efficient in optimizing their status in red blood cells (RBCs) and platelets of healthy middle-aged subjects with low customary fish consumption. In a randomized, cross-over trial conducted over an 8-week period and separated by a 6-month washout period, 33 participants received an oily fish (salmon), providing 274 mg eicosapentaenoic acid (EPA) + 671 mg docosahexaenoic acid (DHA) per day, or a commercial fish oil supplement, providing 396 mg EPA + 250 mg DHA per day. Blood samples were collected before and after each intervention period, and RBCs and platelets were used for analysis of fatty acids. After 8 weeks, there were significant increases in EPA and DHA content in RBCs and platelets with both salmon and fish oil capsules. The increase in EPA in both RBCs and platelets was higher with capsules, whereas the increase in DHA in both RBCs and platelets was higher with salmon. In spite of the quantitative and qualitative differences between n-3 fatty acid profiles in salmon and the fish oil supplement, the overall incorporation of these fatty acids into RBCs and platelets did not differ in our short-term study (P > .05). The sum of EPA + DHA significantly increased in both compartments following dietary recommendations for oily fish and fish oil supplements intake in middle-aged healthy subjects with low baseline long-chain n-3 PUFA status, although targeted values with optimal cardioprotective effect of more than 8% were not achieved.     

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.     

Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.     

Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturated fatty acids in subjects with and without major depressive disorder

The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a topic of public health importance. This report describes development and biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ) intended for use in psychiatric research to assess intake of α-linolenic acid (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to September 2008, sixty-one ethnically diverse adult participants with (n=34) and without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's ρ, FFQ-estimated intake correlated with plasma levels of DHA (r=0.50; P<0.0001) and EPA (r=0.38; P=0.002), but not with ALA levels (r=0.22; P=0.086). Participants were classified into quartiles by FFQ-estimated intake and plasma PUFA concentrations. Efficacy of the FFQ to rank individuals into same or adjacent plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA; misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2% for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide researchers and clinicians with valuable information concerning dietary intake of DHA and EPA.     

When balanced for precursor fatty acid supply echium oil is not superior to linseed oil in enriching lamb tissues with long-chain n-3 PUFA

Vegetable oils containing stearidonic acid (SDA, 18 : 4n-3) are considered better precursors of long-chain n-3 PUFA (LC n-3 PUFA) than those with only α-linolenic acid (ALA, 18 : 3n-3). The present study re-examined this premise using treatments where added ALA from linseed oil was matched with ALA plus SDA from echium oil. Lambs (n 6) were abomasally infused with saline (control (C), 25 ml), echium oil low (EL, 25 ml), echium oil high (EH, 50 ml), linseed oil low (LL, 25 ml) or linseed oil high (LH, 50 ml) for 4 weeks. The basal ration used was identical across all treatments. EPA (20 : 5n-3) in meat increased from 6·5 mg in the C lambs to 16·8, 17·7, 13·5 and 11·7 (SEM 0·86) mg/100 g muscle in the EL, EH, LL and LH lambs, respectively. For muscle DPA (docosapentaenoic acid; 22 : 5n-3), the corresponding values were 14·3, 22·2, 18·6 18·2 and 19·4 (SEM 0·57) mg/100 g muscle. The DHA (22 : 6n-3) content of meat was 5·8 mg/100 g in the C lambs and ranged from 4·53 to 5·46 (SEM 0·27) mg/100 g muscle in the oil-infused groups. Total n-3 PUFA content of meat (including ALA and SDA) increased from 39 mg to 119, 129, 121 and 150 (SEM 12·3) mg/100 g muscle. We conclude that both oil types were effective in enhancing the EPA and DPA, but not DHA, content of meat. Furthermore, we conclude that, when balanced for precursor n-3 fatty acid supply, differences between linseed oil and echium oil in enriching meat with LC n-3 PUFA were of little, if any, nutritional significance.     

Echium oil is better than rapeseed oil in enriching poultry meat with n-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosapentaenoic acid

alpha-Linolenic acid (ALA; 18 : 3n-3) and stearidonic acid (SDA; 18 : 4n-3) are on the biosynthetic pathway of EPA (20 : 5n-3) and DHA (22 : 6n-3). The n-3 fatty acid in rapeseed oil is ALA while Echium oil contains both ALA and SDA. To determine the comparative efficacy of ALA- and SDA-rich oils in enriching broiler meat with n-3 PUFA, we offered diets supplemented with rapeseed oil (rapeseed group) or Echium oil (Echium group) for 35 d to two groups of chicks (age 21 d). There were no differences in carcass weight (2.20 (sem 0.06) v. 2.23 (sem 0.05) kg), boned, skinless thigh muscle (494 (sem 20.5) v. 507 (sem 16.7) g), boned, skinless breast muscle (553 (sem 13.4) v. 546 (sem 11.6) g) or organ weights (heart, liver and gizzard) between the two groups. The total intramuscular fat (IMF) percentage of thigh (8.0 (sem 0.64) v. 8.1 (sem 0.62) %) and breast muscles (2.3 (sem 0.24) v. 2.0 (sem 0.19) %) were also similar between the groups. In contrast, the concentrations of most of the individual n-3 fatty acids (ALA, SDA, EPA and docosapentaenoic acid) were all higher in the Echium than the rapeseed group (P < 0.05). However, differences in DHA concentrations were significant in breast but not thigh muscle IMF. The total n-3 yields/100 g serve thigh muscle were 265 and 676 mg for the rapeseed and Echium groups, respectively (P < 0.0001). The corresponding values for equivalent breast muscles were 70 and 137 mg, respectively (P < 0.01). We conclude that Echium oil is a better lipid supplement than rapeseed oil in changing the concentration and yield of n-3 fatty acids, except DHA, in broiler meat.     

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition

OBJECTIVE: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition. DESIGN: A double-blind, randomised, placebo-controlled study. SETTING:: Subiaco, Western Australia. SUBJECTS: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study. INTERVENTION: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery. MAIN OUTCOME MEASURES: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth. RESULTS: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group. CONCLUSION: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made. SPONSORSHIP: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.     

Maternal Factors Associated with Levels of Fatty Acids,Specifically n-3 PUFA during Pregnancy: ECLIPSES Study

An optimal fatty acid (FA) profile during pregnancy, especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is essential for the health of the mother and child. Our aim was to identify the socioeconomic and maternal lifestyle factors associated with serum FA concentration in pregnant women. A longitudinal study was conducted on 479 pregnant women, who were assessed during the first (T1) and third (T3) trimesters of pregnancy. Data on maternal characteristics, food consumption, and lifestyle were collected. Serum FA concentrations were analysed by a gas chromatography–mass spectrometry combination. The multiple linear regression showed that high educational level and older age were significantly associated with higher EPA and DHA concentrations and lower values of n-6/n-3 and arachidonic acid (AA)/EPA in T1 and/or T3. Regarding diet—fish and seafood consumption increased EPA concentration and reduced n-6/n-3 and AA/EPA values in both trimesters, whereas its consumption increased DHA concentration only in T1. Smoking was associated with lower DHA concentration in T1 and higher values of n-6/n-3 ratio in both trimester. Overweight and obesity were associated with higher values of n-6/n-3 ratio and AA/EPA ratio in T1. A statistically non-significant association was observed with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA). In conclusion, high educational levels, older age, fish, seafood consumption, and/or non-smoking, are factors that influence better omega-3 polyunsaturated fatty acid (n-3 PUFA) profile in both trimesters of pregnancy. Further research is needed to go in-depth into these findings and their health consequences.     

Are the n-3 fatty acids from dietary fish oil deposited in the triglyceride stores of adipose tissue?

Adipose tissue is the chief reservoir of the essential fatty acids (n-3 and n-6). To study the incorporation of the dietary n-3 fatty acids eicosapentaenoic acid (EPA) (20:5) and docosahexaenoic acid (DHA) (22:6), and a unique monounsaturated fatty acid, cetoleic acid (22:1n-11), into adipose tissue, rabbits were fed two different processed fish oils: MaxEPA (high in EPA and DHA; Seven Sea Ltd, Hull, UK) and herring oil (high in cetoleic acid). EPA and DHA increased from 0% of total adipose tissue fatty acid, in the adipose tissue of control rabbits to 2.2% and 4.9%, respectively, in MaxEPA-fed rabbits. The DHA-to-EPA ratio in the adipose tissue was higher than that in the diet, indicating alternative metabolic pathways for EPA. In the adipose tissue of herring-oil-fed rabbits, cetoleic acid increased from 0% to 7.9% of total fatty acids. The deposition of EPA and DHA was 1.8% and 2.8%, respectively. Our data indicated that these unique long-chain unsaturated fatty acids from dietary fish oils were readily incorporated into the fat stores from whence they could be mobilized.     

Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications.

To examine the incorporation of n-3 polyunsaturated fatty acids (PUFAs) into erythrocyte membranes during and after moderate n-3 PUFA intake, 12 healthy men were fed three diets for 6-wk periods in a 3 x 3 crossover design, supplying different amounts of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3): a control diet, a fish diet (0.15 g EPA/d, 0.41 g DHA/d), and a fish + oil diet (5 g fish oil/d; 0.99 g EPA/d and 0.99 g DHA/d). A 6-wk washout period was allowed between diets. Between 6 and 12 wk after the fish + oil diet, erythrocyte EPA and DHA were still declining and it was only after 18 wk that erythrocyte EPA had returned to baseline whereas DHA had not. Investigators examining variables that are influenced by altered membrane fatty acid composition should be aware of these prolonged effects when designing studies. Protracted washout periods (greater than 18 wk) make the classic crossover design prohibitive and a parallel design becomes essential.     

Cardiovascular disease risk factors and n-3 fatty acid status in the adult population of James Bay Cree

BACKGROUND: Canadian native populations, which traditionally consume large amounts of fish, have lower rates of mortality from heart disease than do Canadian nonnative populations, which have low fish intakes. Fish oils rich in n-3 fatty acids may have a protective effect against cardiovascular disease (CVD) risk factors. OBJECTIVES: The purposes were to examine the profile of plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) among James Bay Cree and to verify the relation between these concentrations and CVD risk factors. DESIGN: The study population consisted of 917 subjects aged 18-74 y who participated in the 1991 Santé Québec Health Survey. Data were obtained through home interviews and clinic visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: The mean fish consumption on the day before the survey was 60 g among the adult Cree population. Expressed as a percentage of total fatty acids, relative concentrations of EPA and DHA were 0.65% and 2.80%, respectively. n-3 Fatty acids were higher among coastal residents than among inland residents. A positive association was observed between plasma HDL and n-3 fatty acids. EPA and EPA+DHA were inversely associated with triacylglycerols. Among subjects aged 50-74 y, an inverse association between EPA and EPA:AA and total:HDL cholesterol was observed. CONCLUSIONS: n-3 Fatty acids may favorably influence some CVD risk factors. The Cree population must be encouraged to maintain their traditional fish-based diet, which may be one of the factors protecting them against mortality from CVD.     

Short-term fish oil supplementation improved innate immunity, but increased ex vivo oxidation of LDL in man--a pilot study

Summary Background: Fish and fish oils are rich in the two long-chain polyunsaturated fatty acids (LCPUFAs) eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). The n-3 LCPUFAs have been reported to have beneficial effects on cardiovascular functions, but their role in relation to immune functions is still controversial. Aim of the study: The objectives of this study were to determine the effects of supplementation with fish oil on immune cell functions in human subjects. We have also assessed the effects on plasma lipids, antioxidant status and susceptibility of low-density lipoproteins (LDL) to oxidative stress. The antioxidant status was determined by measuring plasma vitamin C, tocopherols and carotenoids in plasma and LDL, and superoxide dismutase (SOD) in red blood cells. Design: For 30 days, 10 volunteers ingested 25 g/d of either fish oil, providing n-3 LCPUFAs (7.5 g), or high-oleic sunflower oil, providing monounsaturated fatty acids mainly as oleic acid (22 g). The oils contained similar profiles of tocopherols. At day 0 and day 30, blood samples were drawn by venipuncture for plasma lipid and antioxidant analyses and lipoprotein isolation, and for isolation and functional tests of mononuclear cells and granulocytes. Fatty acid profiles of immune cells and LDL were also determined. Results: Fish oil supplementation resulted in an accumulation of n-3 LCPUFAs (EPA, DHA) in LDL and immune cells. The phagocytic activity, a measure of immune cell activity, was increased in both groups. Whereas the plasma and LDL antioxidant status do not appear to be affected by fish oil supplementation, an increased susceptibility of LDL to oxidation was observed in these healthy volunteers. Conclusions: The optimal amounts of n-3 fatty acids required to modulate immune functions remain to be established. In addition, adequate levels of antioxidant protection need to be provided during fish oil supplementation. Received: 19 September 2000 / Accepted: 12 February 2001     

n-3 Polyunsaturated fatty acids,fatal ischemic heart disease,and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study

BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.     

Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers

OBJECTIVE: To compare the individual effects of dietary alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on low-density lipoprotein (LDL) fatty acid composition, ex vivo LDL oxidizability and tocopherol requirement. DESIGN, SETTING AND SUBJECTS: A randomized strictly controlled dietary study with three dietary groups and a parallel design, consisting of two consecutive periods. Sixty-one healthy young volunteers, students at a nearby college, were included. Forty-eight subjects (13 males, 35 females) completed the study. INTERVENTIONS: Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids (21% energy) followed by experimental diets enriched with about 1% of energy of ALA, EPA or DHA for 3 weeks. The omega-3 (n-3) fatty acids were provided with special rapeseed oils and margarines. The wash-in diet and the experimental diets were identical, apart from the n-3 fatty acid composition and the tocopherol content, which was adjusted to the content of dienoic acid equivalents. RESULTS: Ex vivo oxidative susceptibility of LDL was highest after the DHA diet, indicated by a decrease in lag time (-16%, P<0.001) and an increase in the maximum amount of conjugated dienes (+7%, P<0.001). The EPA diet decreased the lag time (-16%, P<0.001) and the propagation rate (-12%, P<0.01). Tocopherol concentrations in LDL decreased in the ALA group (-13.5%, P<0.05) and DHA group (-7.3%, P<0.05). Plasma contents of tocopherol equivalents significantly decreased in all three experimental groups (ALA group: -5.0%, EPA group: -5.7%, DHA group: -12.8%). The content of the three n-3 polyunsaturated fatty acid differently increased in the LDL: on the ALA diet, the ALA content increased by 89% (P<0.001), on the EPA diet the EPA content increased by 809% (P<0.001) and on the DHA diet, the DHA content increased by 200% (P<0.001). In addition, the EPA content also enhanced (without dietary intake) in the ALA group (+35%, P<0.01) and in the DHA group (+284%, P<0.001). CONCLUSIONS: Dietary intake of ALA, EPA or DHA led to a significant enrichment of the respective fatty acid in the LDL particles, with dietary EPA preferentially incorporated. In the context of a monounsaturated fatty acid-rich diet, ALA enrichment did not enhance LDL oxidizability, whereas the effects of EPA and DHA on ex vivo LDL oxidation were inconsistent, possibly in part due to further changes in LDL fatty acid composition.     

Dietary intakes of arachidonic acid and alpha-linolenic acid are associated with reduced risk of hip fracture in older adults

PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988-1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26-0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04-0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men.