Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y

BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans. OBJECTIVE: Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 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 and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.     

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.     

The effect of dietary trans alpha-linolenic acid on plasma lipids and platelet fatty acid composition: the TransLinE study

OBJECTIVE: To collect (i) baseline data and (ii) execute a large multicentre study examining the effect of trans alpha-linolenic acid on its incorporation into plasma lipids and on risk factors for coronary heart disease. DESIGN: Male volunteers were recruited and the habitual diet assessed by a 4-d weighed record. Fatty acid composition of plasma and platelet lipids were determined by gas chromatography at baseline. After a 6 week run-in period on a trans 'free' diet, male volunteers were randomised to consume 0.6 % of energy trans alpha-linolenic acid or to continue with a diet 'low' in trans alpha-linolenic acid for 6 weeks. SETTING: Three European university research departments supported by the research and development departments of the food industry. Subjects: Male volunteers (88) recruited by local advertisement. METHODS: Replacement of 30 % of the fat of the habitual diet by margarine, oil and foods. Rapeseed oil was deodorised especially to produce the trans 'free' and 'high' trans foods for this study. The incorporation and conversion of trans alpha-linolenic acid into plasma lipids and platelets was assessed by gas chromatography and dietary compliance was verified by 4-d weighed record. Results: Less trans alpha-linolenic acid isomers are incorporated into human plasma lipids in French volunteers than in Dutch or Scottish volunteers consuming their habitual diets. Trans 'free' alpha-linolenic acid-rich oil can be produced by careful deodorization during refining. The 'high' trans diet provided 1410+/-42 mg/d trans isomers of alpha-linolenic acid, whilst the 'low' trans group consumed 60+/-75 mg/d. The change in plasma lipid and platelet fatty acid composition documented that trans linolenic isomers are incorporated and converted to a trans isomer of eicosapentaenoic acid. Only the 15-trans alpha-linolenic acid is incorporated into plasma cholesteryl esters. The group consuming low trans diet had a slightly higher intake of fat, especially saturated and monounsaturated fat. CONCLUSIONS: Trans 'free' rapeseed oil, rich in alpha-linolenic acid, can be produced by careful deodorization. Dietary records show good compliance. Dietary trans isomers of alpha-linolenic acid are incorporated in plasma lipids and converted to long-chain polyunsaturated fatty acids. Their effects on risk factors for coronary heart disease and their metabolism will be reported elsewhere. Sponsorship: European Commission (FAIR 95-0594 grant). European Journal of Clinical Nutrition (2000) 54, 104-113     

Modulation of human immune and inflammatory responses by dietary fatty acids.

I review the effects of the amount and composition of dietary fat on indices of human immune and inflammatory responses. A reduction in the amount of fat intake enhanced several indices of immune response, including lymphocyte proliferation, natural-killer-cell activity, cytokine production, and delayed-type hypersensitivity. When total fat intake was held constant, an increase in the intake of linoleic acid (18:2 omega-6) or arachidonic acid (20:4 omega-6) by healthy human volunteers did not inhibit many indices of immune response tested but did increase the production of inflammatory eicosanoids (prostaglandin E2 and leukotriene B4). Supplementation of human diets with omega-3 fatty acids reduced several aspects of neutrophil, monocyte, and lymphocyte functions, including the production of inflammatory mediators. Most of the studies have indicated reductions in these functions, with a minimum of 1.2 g/d of supplementation with eicosapentaenoic acid and docosahexaenoic acid for 6 wk. However, other studies concomitantly supplementing with 205 mg/d of vitamin E did not find inhibition of immune-cell functions, even with larger amounts and longer durations of supplementation with these fatty acids. One study reported that supplementation with docosahexaenoic acid selectively inhibits inflammatory responses without inhibiting T- and B-cell functions. Despite some discrepancies, fish oils have been used successfully in the management of several inflammatory and autoimmune diseases. The potential for the use of fish oils in the management of these diseases is tremendous, even though further studies are needed to establish safe and adequate intake levels of omega-3 fatty acids.     

Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women

BACKGROUND: Fetal growth requires n-3 docosahexaenoic acid (DHA), which is derived from the essential n-3 fatty acids in the maternal diet. DHA is accumulated in the developing brain and is critical for normal neural and visual function. Available estimates suggest that 67 mg DHA/d is accumulated by the fetus during the third trimester of gestation. Little is known about n-3 fatty acid intakes in pregnant women, although human milk concentrations of DHA have decreased in recent years. OBJECTIVE: We prospectively determined the n-3 and n-6 fatty acid intakes of 55 pregnant Canadian women. DESIGN: A food-frequency questionnaire was completed at 28 and 35 wk, and plasma n-3 and n-6 fatty acids were measured at 35 wk gestation. The fatty acid composition of approximately 500 foods was analyzed to allow analysis of dietary intakes from specific foods. RESULTS: Intakes, as a percentage of energy, were (macro x +/- SEM) total fat, 28.0 +/- 3.6%; saturated fat, 9.8 +/- 0.3%; monounsaturated fat, 11.2 +/- 0.4%; polyunsaturated fat, 4.7 +/- 0.2%; linoleic acid, 3.9 +/- 0.2%; and alpha-linolenic acid, 0.54 +/- 0.05%. The daily intakes (range) were 160 +/- 20 (24-524) mg DHA/d, 121 +/- 8 (15-301) mg arachidonic acid/d, and 78 +/- 2 (4-125) mg eicosapentaenoic acid/d. The plasma phospholipids had (mg/100 g fatty acid) 5.0 +/- 0.18 DHA, 8.7 +/- 0.18 arachidonic acid, and 0.52 +/- 0.32 eicosapentaenoic acid. CONCLUSION: The low intake of DHA among some pregnant women highlights the need for studies to address the functional significance of maternal fat intakes during pregnancy on fetal development.     

The effect of dietary energy percentage of fat and its P/S ratio on incorporation of n-3 PUFA and leukotriene production during fish oil supplementation in healthy volunteers.

The effect of low (25 per cent of energy) and high (35 per cent of energy) fat diets with either low (less than 0.4) or high (greater than 1.0) polyunsaturated/saturated fatty acid (P/S) ratios on fatty acid compositions of plasma cholesterol esters and neutrophil phospholipids, and leukotriene production was studied in four groups of healthy volunteers supplemented with 6 g fish oil daily for four weeks. Except for three subjects, eicosapentaenoic acid (20:5n-3) content markedly increased from baseline in the plasma cholesterol ester fraction and to a lesser extent in the neutrophil phospholipid fraction. The increase in the plasma cholesterol ester fraction was inversely, though weakly related to the dietary intake of linoleic acid (18:2n-6). At supplementation endpoints, the 20:5n-3/20:4n-6 ratio in both plasma cholesterol esters and neutrophil phospholipids was highest in the groups consuming diets with low P/S ratio. In vitro leukotriene B5 production by neutrophils, did not differ between groups and there was no consistent suppression of LTB4 production in this four-week study. It is suggested that factors other than the actual dietary 18:2n-6 intake additionally influence the accumulation of 20:5n-3 in tissue during dietary fish oil supplementation.     

Site-specific differences in the fatty acid composition of abdominal adipose tissue in an obese population from a Mediterranean area: relation with dietary fatty acids, plasma lipid profile, serum insulin, and central obesity.

BACKGROUND: Abdominal obesity is associated with coronary risk, although causality is not well established. OBJECTIVE: In an obese Mediterranean population, we measured the fatty acid composition of adipose tissue, its relation with dietary fatty acids and central fat deposition, and its influence on plasma lipids and insulin. DESIGN: Adipose tissue samples were obtained from 84 obese patients (29 men, 55 women) aged 30-70 y (body mass index, in kg/m(2): 27-35). We measured concentrations of insulin and lipids in plasma and fatty acids in subcutaneous, omental, and perivisceral fat. Dietary fatty acid intake was assessed with a 7-d diet record. RESULTS: The population studied was normolipidemic and normoinsulinemic. There were important differences in fatty acid composition between tissue sites: saturated fatty acids were higher and monounsaturated fatty acids were lower in perivisceral than in subcutaneous fat (P < 0.05). Significant correlations were found for oleic, linoleic, alpha-linolenic, and total n-6 polyunsaturated fatty acids between the subject's habitual diet and adipose tissue composition. Oleic and n-3 fatty acids from adipose regions were negatively correlated with apolipoprotein B and triacylglycerols; adipose tissue 22:1n-9, 20:2n-6, stearic acid, and eicosapentaenoic acid were positively correlated with HDL and apolipoprotein A; and adipose tissue myristic acid was negatively correlated with apolipoprotein A (P < 0.05). Central obesity was positively associated with n-6 polyunsaturated fatty acids and inversely associated with monounsaturated fatty acids and n-3 polyunsaturated fatty acids in adipose tissue (P < 0.05). CONCLUSION: The differences found in the composition and metabolism of perivisceral, omental, and subcutaneous fats may indicate that their atherogenic capacities also differ.     

Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial

BACKGROUND AND AIMS: Various anti-inflammatory therapies, including dietary omega-3 polyunsaturated fatty acids (PUFA) supplementation, have been investigated in cystic fibrosis (CF) patients. To further explore this nutritional approach, biological effects of an omega-3 PUFA oral liquid supplementation were measured in 17 CF patients in a double-blind, randomized, crossover without a washout period and placebo-controlled study. METHODS: CF patients (age: 18+/-9 year; weight: 43+/-13 kg) received a liquid dietary supplementation either enriched or not in omega-3 PUFA (390-1170 mg/day according to patient weight) during two 6-month periods. RESULTS: Increase in eicosapentaenoic acid was observed in neutrophil membrane following omega-3 PUFA dietary supplementation (from 0.7+/-0.6 to 1.6+/-0.6 micromol%, P<0.01). The leukotriene B(4) (LTB(4))/leukotriene B(5) (LTB(5)) ratio was decreased (from 72+/-27 to 24+/-7, P<0.001) in CF patients taking omega-3 PUFA supplements. In contrast, omega-3 PUFA supplementation affected neither internalization of IL-8 receptors following IL-8 exposure, nor IL-8-induced neutrophil chemotaxis. CONCLUSION: Our results show that omega-3 PUFA are incorporated in neutrophil membranes. The subsequent decrease in LTB(4)/LTB(5) ratio suggests that, in such conditions, neutrophils may produce less pro-inflammatory mediators from the acid arachidonic pathway. These data indicate that omega-3 PUFA intake may have anti-inflammatory effect that still need to be assessed by long-term studies following large groups of patients.     

Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomized pilot study

OBJECTIVE: The effect of fish oil (FO), melatonin (MLT), or their combination and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer. METHODS: Twenty-four patients not amenable to standard anticancer treatment and with documented weight loss and/or decreased serum albumin were included. They were randomized to 30 mL/d of FO, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid, or 18 mg/d of MLT for 4 wk. During the next 4 wk, all patients had FO and MLT. Serum or plasma was analyzed for tumor necrosis factor-alpha, interleukin-1beta, soluble interleukin-2 receptor, interleukin-6, and interleukin-8 and the fatty acids eicosapentaenoic acid, docosahexanoic acid, arachidonic acid, and linoleic acid. RESULTS: Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with FO. No major changes in biochemical variables and cytokines were observed with any intervention. In the FO group, 5 of 13 patients (38%) showed weight stabilization or gain compared with 3 of 11 patients (27%) in the MLT group. After combining interventions, approximately 63% of patients showed such responses. CONCLUSIONS: FO, MLT, or their combination did not induce major biochemical changes indicative of a strong anticachectic effect. Nonetheless, the interventions used may have produced a weight-stabilizing effect.     

Pathophysiology of metabolic syndrome X and its links to the perinatal period

It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Delta-6 and Delta-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-alpha and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-alpha and interleukin-6 enhance expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.     

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.     

Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women.

Fifteen young (22-35 y) and 10 older (51-71 y) women received six capsules of fish oil (Pro-Mega)/d, providing a total of 1,680 mg eicosapentaenoic (EPA), 720 mg docosahexaenoic (DHA), 600 mg other fatty acids, and 6 IU vitamin E. Blood was collected before and after 1, 2 and 3 mo of supplementation. Compliance was confirmed by the significant increase in plasma EPA and DHA in all women. Older women had a significantly higher increase in EPA and DHA than did young women (10-fold increases in EPA and 2.5-fold increases in DHA vs. 8-fold in EPA and 2-fold in DHA for older and young women, respectively). The decrease in the arachidonic acid:EPA ratio was more dramatic in the older women. Plasma total triglycerides (TG) decreased significantly, and the ratio of polyunsaturated fatty acids to saturated fatty acids was significantly (P less than 0.01) increased. Plasma vitamin E levels did not change significantly after supplementation; however, after 3 mo of supplementation by young women, plasma vitamin E was significantly lower than after 1 mo. The vitamin E: TG ratio was significantly increased and vitamin E:(EPA + DHA) significantly decreased. All women showed a significant increase in plasma lipid peroxide through mo 2 of supplementation. After 2 mo, older women had significantly higher lipid peroxide levels than young women. The lipid peroxide:TG ratio, which declined by mo 3, was still significantly higher than baseline. These data indicate that although long-term fish oil supplementation may be beneficial in reducing plasma total TG, susceptibility of plasma lipids to free radical attack is potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Dietary supplementation of obese children with 1000 mg alpha-linolenic acid per day: a placebo-controlled double blind study

INTRODUCTION: Enhanced dietary intake of omega-3 fatty acids may benefit persons with increased cardiovascular risk, among them obese subjects. Incorporation of omega-3 fatty acids into the plasma lipids is a prerequisite to achieve the favorable effects; however, only very few data are available on the dose of omega-3 fatty acid supplementation in children. The aim of our study was to examine the effects of the consumption of a diet supplemented with 1000 mg alpha-linolenic acid daily on plasma lipids in obese children. METHODS: In this two times six-week-long, placebo-controlled, crossover study, 9 obese children (age: 13.1 [2.5] years, body mass index: 31.2 [6.2] kg/m 2 ), median [IQR]) incorporated into their diet one egg and one meatball (50 g) per day from hens fed diets containing flaxseed oil, i.e. supplementary dietary intake of 1000 mg alpha-linolenic acid per day was provided. The fatty acid composition of plasma lipids was determined by high-resolution gas-liquid chromatography. RESULTS: Tendencies of increase were observed in the alpha-linolenic acid content of plasma lipids in the phospholipid, triacyl-glycerine and sterol-ester fractions after the supplementation with alpha-linolenic acid. In the non-esterified fatty acid fraction, the values of alpha-linolenic acid were significantly higher after the supplementation (0.11 [0.08] versus 0.14 [0.20], % weight/weight, p < 0.05), indicating the beginning of the accumulation of alpha-linolenic acid in plasma lipids. CONCLUSION: In obese children a six-week-long supplementation of the diet with 1000 mg alpha-linolenic acid per day increased significantly the contribution of omega-3 fatty acids only to the non-esterified fatty acids of plasma lipids, but had no significant effect on the esterified fractions. Increase of the dose of supplementation may be needed to influence omega-3 fatty acid status in obese children.     

Short-term carnitine supplementation does not augment LCPomega3 status of vegans and lacto-ovo-vegetarians

OBJECTIVE: Long-chain polyunsaturated omega-3 fatty acids (LCPomega3) synthesis, notably that of docosahexaenoic acid (DHA), from the precursor alpha-linolenic acid (ALA) proceeds with difficulty. We investigated whether carnitine supplementation augments the LCPomega3 status of apparently healthy vegans and lacto-ovo-vegetarians, who are expected to have low carnitine status. METHODS: Group A (n = 11) took 990 mg/day l-carnitine from weeks 1-4, and 990 mg/day l-carnitine + 4 mL/day linseed oil from weeks 5-8. Group B (n = 9) took 4 mL/day linseed oil from weeks 1-4, and 4 mL/day linseed oil + 990 mg/day l-carnitine from weeks 5-8. Fatty acid compositions of red blood cells, platelets, plasma cholesterol esters and plasma triglycerides were measured in the fasting state at baseline, and after 4 and 8 weeks. RESULTS: Carnitine supplementation increased plasma free and total carnitine concentrations with 30 and 25%, respectively, but did not affect eicosapentaenoic acid (EPA) and DHA contents of any of the investigated compartments. EPA and DHA changes were negatively related to initial carnitine status. CONCLUSIONS: Our results suggest that carnitine is not an important limiting factor, if any, for LCPomega3 synthesis in vegans and lacto-ovo-vegetarians. This conclusion is also likely to apply to omnivores. The most efficient means to augment EPA and particularly DHA status remains consumption of LCPomega3 from e.g. fish or supplements.     

Effect of n-3 polyunsaturated fatty acids on Barrett's epithelium in the human lower esophagus

BACKGROUND: Epidemiologic studies suggest a reduced risk of esophageal adenocarcinoma in populations with a high consumption of fish, and n-3 fatty acids inhibit experimental carcinogenesis. One possible explanation is the suppression of eicosanoid production through inhibition of cyclooxygenase 2 (COX-2). OBJECTIVE: The objective was to determine the effects of dietary supplementation with the n-3 fatty acid eicosapentaenoic acid (EPA) on a number of biological endpoints in Barrett's esophagus. DESIGN: Fifty-two participants with known Barrett's esophagus underwent endoscopy. Biopsy samples were obtained from a recorded level within the area of Barrett's esophagus, and then 27 patients were randomly assigned to consume EPA capsules (1.5 g/d) for 6 mo or no supplement (controls). At the end of this period, patients again underwent endoscopy, and biopsy samples were collected at the same level. Tissue samples were analyzed for mucosal lipid, prostaglandin E2, leukotriene B4, COX-2 protein, and RNA concentrations. Cellular proliferation was also measured, by Ki-67 immunohistochemistry. RESULTS: The EPA content of esophageal mucosa increased over the study period in the n-3-supplemented subjects and was significantly different from the content in the controls (P < 0.01). There was also a significant decline in COX-2 protein concentrations (measured by immunoblotting) in the n-3 group, and the difference was significant from that in the controls (P < 0.05); no difference in COX-2 RNA concentrations was observed between groups. This change in COX-2 protein was inversely related to the change in EPA content (P < 0.05). There was no significant difference in the change in prostaglandin E2, leukotriene B4, or cellular proliferation between the 2 groups. CONCLUSION: Supplementation with EPA significantly changed n-3 fatty acid concentrations and reduced COX-2 concentrations in Barrett's tissue.     

Low dose supplementation with two different marine oils does not reduce pro-inflammatory eicosanoids and cytokines in vivo

In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.     

Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men.

In 1986-1987, the authors assessed the fatty acid intake of 118 Boston-area men, aged 40-75 years, by a semiquantitative food frequency questionnaire administered twice, by two 7-day diet records, and by capillary gas chromatography of subcutaneous fat samples obtained by needle aspirate from the lateral buttock. Spearman correlation coefficients between diet record estimates of fatty acid intake (as a percentage of total fat) and fat aspirate measures (as a percentage of total peak area) were as follows: saturated fat, r = 0.16 (p = 0.09); monounsaturated fat, r = 0.22 (p = 0.01); and polyunsaturated fat, r = 0.49 (p = 0.0001). Spearman correlation coefficients between estimates derived from the food frequency questionnaire were as follows: saturated fat, r = 0.18 ( p = 0.05); monounsaturated fat, r = 0.14 (p = 0.14); polyunsaturated fat, r = 0.50 (p = 0.0001); and eicosapentaenoic acid, r = 0.47 (p = 0.0001). These data confirm that the polyunsaturated and eicosapentaenoic fatty acid content of subcutaneous fat is a measure of dietary intake of these fats. Although diet records are commonly thought to be the "gold standard" method of dietary assessment, the similar correlations observed between the fatty acid composition of adipose tissue and estimates of intake from the food frequency questionnaire and from diet records suggest that these two dietary assessment methods have similar validity in the measurement of polyunsaturated fatty acid intake.     

Effect of short-term use of omega-3-type polyunsaturated fatty acids in subjects with hypertriglyceridemia]

OBJECTIVE. To study the effect of omega-3 polyunsaturated fatty acid supplementation on lipid profile in hypertriglyceridaemic patients. SETTING. General practice. DESIGN. Prospective, double blind study of 12 weeks' duration. PATIENTS AND METHODS. Eight patients received fish oil (1800 mg C20: 5 omega-3 eicosapentaenoic acid (EPA) and 1200 mg C22:6 omega-3 docosahexaenoic acid (DHA). Nine patients received corn oil (3000 mg C18: 2 omega-6 linoleic acid daily). RESULTS. Lipid profile analysis showed a decrease in triglyceride levels after fish oil supplementation. An unexpected and unexplained finding was the rise in total cholesterol and LDH cholesterol with corn oil supplementation. CONCLUSION. Fish oil causes a decrease in triglyceride levels in hypertriglyceridaemic patients.     

Fatty acid composition of skeletal muscle reflects dietary fat composition in humans

BACKGROUND: It is still unknown whether the fatty acid composition of human skeletal muscle lipids is directly influenced by the fat composition of the diet. OBJECTIVE: We investigated whether the fatty acid composition of the diet is reflected in the fatty acid profile of skeletal muscle phospholipids and triacylglycerols. DESIGN: Thirty-two healthy adults (25 men and 7 women) included in a larger controlled, multicenter dietary study were randomly assigned to diets containing a high proportion of either saturated fatty acids (SFAs) [total fat, 36% of energy; SFAs, 18% of energy; monounsaturated fatty acids (MUFAs), 10% of energy] or MUFAs (total fat, 35% of energy; SFAs, 9% of energy; MUFAs, 19% of energy) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish oil capsules [containing 3.6 g n-3 fatty acids/d; 2.4 g eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)] or placebo. A muscle biopsy sample was taken from the vastus lateralis muscle after the diet period. Parallel analyses of diet and supplementation effects were performed. RESULTS: The proportions of myristic (14:0), pentadecanoic (15:0), heptadecanoic (17:0), and palmitoleic (16:1n-7) acids in the skeletal muscle phospholipids were higher and the proportion of oleic acid (18:1n-9) was lower in the SFA group than in the MUFA group. The proportion of total n-3 fatty acids in the muscle phospholipids was approximately 2.5 times higher, with a 5 times higher proportion of eicosapentaenoic acid (20:5n-3), in subjects supplemented with n-3 fatty acids than in those given placebo. Similar differences were observed in the skeletal muscle triacylglycerols. CONCLUSION: The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.