Effects of Marine n-3 Polyunsaturated Fatty Acids on Heart Rate Variability and Heart Rate in Patients on Chronic Dialysis: A Randomized Controlled Trial.

Marine n-3 polyunsaturated fatty acids (PUFA) may improve autonomic dysfunction, as indicated by an increase in heart rate variability (HRV) and reduce the risk of sudden cardiac death. Hence, the aim of this study was to investigate the effects of marine n-3 PUFA on 24-h HRV in patients on chronic dialysis, who have a high risk of sudden cardiac death. Between June 2014 and March 2016, 112 patients on chronic dialysis from Denmark were allocated to a daily supplement of 2 g marine n-3 PUFA or control for three months in a randomized, double-blinded, controlled trial. A 48-h Holter monitoring was performed and mean 24-h HRV indices for the two days were available in 85 patients. The mean age was 62.3 years (SD: 14.3) and median dialysis vintage was 1.7 years (IQR: 0.5, 6.4). Within-group and between-group changes in outcome were evaluated by a paired and two sample t-test, respectively. Marine n-3 PUFA did not change the primary endpoint SDNN (SD of all RR-intervals) reflecting overall HRV, but other HRV indices increased and the mean RR-interval increased significantly, corresponding to a decrease in heart rate by 2.5 beats per minute (p = 0.04). In conclusion, marine n-3 PUFA did not change SDNN, but the mean heart rate was significantly reduced and changes in other HRV-indices were also observed, indicating an increase in vagal modulation that might be protective against malignant ventricular arrhythmias.

Development of Kidney Transplant Fibrosis Is Inversely Associated With Plasma Marine Fatty Acid Level.

OBJECTIVE(S): We assessed associations between plasma levels of polyunsaturated fatty acids (PUFAs) and degree of inflammation and interstitial fibrosis in transplanted kidneys. DESIGN: The design of the study was single center cohort study. SUBJECTS: A study population of 156 patients who received a kidney transplant at Oslo University Hospital during 2010. MAIN OUTCOME MEASURE: Kidney transplant biopsies were obtained at 2 months and 1 year after transplantation. Degree of inflammation and interstitial fibrosis in the cortex of transplanted kidneys were estimated semi-quantitatively. Plasma phospholipid fatty acids levels were measured in a stable phase 2 months posttransplant. We used multivariate linear regression to assess associations between plasma levels of PUFAs and degree of inflammation and interstitial fibrosis at 2 months and 1 year postoperatively and change in degree of interstitial fibrosis during the first year after transplantation, adjusting for inflammation and fibrosis risk factors. RESULTS: Higher plasma marine n-3 PUFA levels were associated with less development of interstitial fibrosis in the kidney transplant (unstandardized ß-coefficient -1.12, standardized ß-coefficient -0.18, P = .03) during the first year after transplantation. Plasma levels of alpha linoleic acid, linoleic acid, and arachidonic acid were not associated with development of interstitial fibrosis. No associations were found between plasma levels of PUFAs and inflammation inside fibrotic areas or outside fibrotic areas in the kidney transplant at neither 2 months nor 1 year postoperatively. Linolenic acid levels in plasma were positively associated with change in renal function during the first year after transplantation. CONCLUSION: The inverse association between plasma marine n-3 PUFA levels and development of interstitial fibrosis during the first year after kidney transplantation suggests that marine fatty acid consumption might halt progression of fibrosis.

Marine n-3 polyunsaturated fatty acids affect the blood pressure control in patients with newly diagnosed hypertension - a 1-year follow-up study.

Marine long-chained n-3 polyunsaturated fatty acids (PUFA) are recognized for their cardio-protective effects, including potential lowering of blood pressure. We hypothesized that higher habitual fish intake and n-3 PUFA plasma levels were associated with lower blood pressure and being less likely to receive antihypertensive medication after one-year follow-up. In this prospective study of 115 patients, we assessed 24 h ambulatory and central blood pressure, plasma phospholipid fatty acid composition using gas chromatography and participants completed a food frequency questionnaire, including fish-eating habits. All measurements were repeated at one-year follow-up. At baseline, patients consuming fish ≥2 times per month for dinner had significantly higher plasma levels of total marine n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as significantly lower central blood pressure and a trend towards lower peripheral blood pressure. At follow-up, 21 patients (18%) without antihypertensive medication had significantly higher plasma levels of n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as a higher, but still acceptable 24 h ambulatory blood pressure (137/85 mmHg) compared to subjects receiving antihypertensive medication. The untreated group was more prone to take fish oil capsules and increased their plasma levels of n-3 PUFA compared to baseline. In patients with newly diagnosed, untreated hypertension, regular fish consumption was accompanied by lower blood pressure. After one year, patients without antihypertensive medication were characterized by a significant increase and higher plasma levels of n-3 PUFA. This supports a blood pressure-lowering effect and suggests an increase in marine n-3 PUFA intake as part of non-pharmacological treatment of hypertension.

Long chain n-3 polyunsaturated fatty acids and vascular function in patients with chronic kidney disease and healthy subjects: a cross-sectional and comparative study.

BACKGROUND: Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake. METHODS: Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids. RESULTS: Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake. CONCLUSIONS: The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n-3 polyunsaturated fatty acids.

Marine n-3 polyunsaturated fatty acids lower plasma proprotein convertase subtilisin kexin type 9 levels in pre- and postmenopausal women: A randomised study.

OBJECTIVE: To investigate whether a supplement of 2.2g of marine n-3 polyunsaturated fatty acids (PUFA) influences plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in pre- and postmenopausal women. METHODS: Ninety-two healthy women were randomly assigned to consume 2.2g marine n-3 PUFA or a control oil (thistle oil) daily for 12 weeks. Adipose tissue, a long-term marker of dietary intake of seafood was collected at baseline and blood samples were drawn at baseline and after 12 weeks of supplement intake. RESULTS: Plasma PCSK9 levels were significantly reduced by 11.4% for premenopausal women and 9.8% for postmenopausal women after the supplement of 2.2g of marine n-3 PUFA compared with control oil. The mean change of plasma PCSK9 levels between participants receiving marine n-3 PUFA and control oil was 16.1% for premenopausal women and 13.1% for postmenopausal women. There was, however, no correlation between baseline levels of plasma PCSK9 and the fatty acid content of marine n-3 PUFA in adipose tissue. CONCLUSION: This study showed that 2.2g marine n-3 PUFA reduce plasma PCSK9 levels in both pre- and postmenopausal women.

Plasma levels of marine n-3 polyunsaturated fatty acids and renal allograft survival.

BACKGROUND: Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss. METHODS: In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft loss were assessed by multivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation. RESULTS: During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97). CONCLUSION: High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival.

n-3 polyunsaturated fatty acids and adiponectin in patients with end-stage renal disease.

BACKGROUND AND AIM: In subjects without kidney disease, adiponectin appears to have anti-inflammatory, anti-diabetic, and anti-atherogenic effects. n-3 polyunsaturated fatty acids (PUFA) from seafood have several beneficial effects in patients with endstage renal disease (ESRD) and the aim of the present study was to assess the effect of n-3 PUFA supplementation on plasma adiponectin levels in ESRD patients. METHODS: In a double blinded intervention trial, 162 ESRD patients (mean age 67 years  ± 13, 56 women and 106 men) undergoing chronic hemodialysis were randomized to 1.7 g n-3 PUFA daily or placebo for 3 months. Adiponectin, plasma lipids and lipoproteins were measured at baseline and after the intervention period. RESULTS: At baseline, adiponectin was positively correlated to HDL-cholesterol (r = 0.55, p < 0.001) and inversely correlated to plasma triglycerides, body mass index (BMI) and high sensitive C-reactive protein (Hs-CRP) (r = -0.32, p < 0.01, r = -0.43, p < 0.01, and r = -0.21, p < 0.01, respectively). Furthermore, adiponectin was inversely correlated to the plasma levels of the two major n-3 PUFA docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (r = -0.19, p < 0.001, and r = -0.30, p < 0.001, respectively). Baseline plasma adiponectin levels were high in both groups but after 3 months of supplementation no significant change was observed in the groups. Thus, n-3 PUFA supplementation did not change adiponectin levels. CONCLUSION: We found an elevated plasma adiponectin level, which was inversely associated with plasma levels of DHA and EPA at baseline. Supplementation with n-3 PUFAs for 3 months did not change adiponectin levels. The negative result in this study may be related to a relatively low dose and future studies with higher dose and longer duration are needed to explore this mechanism.

The Effect of n-3 Fatty Acids on Small Dense Low-Density Lipoproteins in Patients With End-Stage Renal Disease: A Randomized Placebo-Controlled Intervention Study.

OBJECTIVE: Patients with end-stage renal disease (ESRD) have a high risk of cardiovascular disease. Small dense low-density lipoprotein (sdLDL) particles are particularly atherogenic. Marine n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on numbers of sdLDL particles, and the aim of this study was to investigate the effect of n-3 PUFA on plasma levels of sdLDL in patients with ESRD. METHODS: ESRD patients with cardiovascular disease (n = 161) on chronic hemodialysis were randomized to treatment with 1.7 g of n-3 PUFA (n = 81) or 2 g of placebo (olive oil; n = 80) for 3 months. The study was double-blinded. Densities of LDL and percentages of sdLDL (sdLDL%) of total LDL were measured before and after intervention. On the basis of sdLDL%, patients were classified as having lipid pattern A, I (intermediate), or B defined by a successive increase in sdLDL concentration and decrease in lipid particle size. RESULTS: n-3 PUFAs significantly reduced triglycerides. However, LDL cholesterol remained unchanged. In the n-3 group, the LDL density did not change significantly during follow-up. Similarly, the LDL density remained unchanged in the placebo group. In the n-3 group, the sdLDL% was 34% at baseline and unchanged at follow-up. At baseline 71% had LDL pattern A, 9% had pattern I, and 20% had pattern B, and none of these patterns were significantly changed by n-3 PUFA supplementation. CONCLUSION: Dietary supplementation with 1.7 g of n-3 PUFA had no effect on LDL density or sdLDL levels in patients with ESRD.

No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring.

The intake of marine n-3 PUFA has been shown to decrease the risk of CVD in a number of studies. Since the development of CVD is often a lifelong process, marine n-3 PUFA intake early in life may also affect the development of later CVD. The aim of the present study was to investigate the association between maternal intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. The study was based on the follow-up of the offspring of a Danish pregnancy cohort who participated in a study conducted from 1988 to 1989. A total of 965 pregnant women were originally included in the cohort and detailed information about the intake of marine n-3 PUFA during the second trimester was collected. In 2008-9, the offspring were invited to participate in a clinical examination including anthropometric, blood pressure (BP) and short-term heart rate variability measurements. Also, a fasting venous blood sample was drawn from them. Multiple linear regression modelling, using the lowest quintile of marine n-3 PUFA intake as the reference, was used to estimate the association with all outcomes. A total of 443 offspring participated in the clinical examination. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and offspring adiposity, glucose metabolism, BP or lipid profile was found. In conclusion, no association between the intake of marine n-3 PUFA during the second trimester of pregnancy and the factors associated with cardiometabolic risk in the 20-year-old offspring could be detected.

Omega-3 fatty acids and cardiac arrhythmias.

PURPOSE OF REVIEW: There are suggestions of effects of marine omega-3 polyunsaturated fatty acids (PUFAs) in relation to ventricular arrhythmia and sudden cardiac death and, more recently, also of possible effects related to atrial fibrillation. RECENT FINDINGS: On the basis of the recently published human studies, this article not only focusses primarily on recent developments and current knowledge on the effect of marine omega-3 PUFAs on atrial fibrillation, but also provides a status for their effects on ventricular arrhythmias. SUMMARY: Marine omega-3 PUFAs may protect against ventricular arrhythmias, and there is growing evidence for an effect of marine omega-3 PUFAs in the prevention and treatment of atrial fibrillation. Further studies are needed to establish which patients are more likely to benefit from omega-3 PUFAs, the timing of treatment, and the dosages.

The effect of maternal fish oil supplementation during the last trimester of pregnancy on blood pressure, heart rate and heart rate variability in the 19-year-old offspring.

Studies in experimental animals and human subjects have suggested that intake of n-3 fatty acids in early life can affect cardiovascular risk factors in adult life. Therefore, the aim of the present study was to investigate the effect of fish oil (FO) supplementation during the third trimester of pregnancy on blood pressure (BP), heart rate (HR) and HR variability (HRV) in the 19-year-old offspring. The study was based on follow-up of a randomised, controlled trial from 1990, in which 533 pregnant women were randomised to FO, olive oil (OO) or no oil (NO) during the last trimester of pregnancy. The offspring was invited to a physical examination including BP, HR and HRV measurements. A subgroup consisting of the offspring of mothers with a low baseline fish intake also had 24 h HRV determined. The OO group was used as reference and multiple linear regression modelling was used to compare the FO and OO groups. A total of 180 of the offspring from the FO and OO groups agreed to participate in the study (45%). The adjusted difference between the FO and OO groups was 2 (95% CI -1, 4) mmHg in systolic and 1 (95% CI 0, 3) mmHg in diastolic BP. The difference in HR was 1 (95% CI -2, 4). Also, HRV indices did not differ significantly between groups. Hence, FO supplementation during late pregnancy was not associated with offspring BP, HR and HRV during adolescence.

Fish oil supplementation during late pregnancy does not influence plasma lipids or lipoprotein levels in young adult offspring.

Nutritional influences on cardiovascular disease operate throughout life. Studies in both experimental animals and humans have suggested that changes in the peri- and early post-natal nutrition can affect the development of the various components of the metabolic syndrome in adult life. This has lead to the hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial effect on lipid profile in the offspring. The aim of the present study was to investigate the effect of supplementation with n-3 fatty acids during the third trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring. The study was based on the follow-up of a randomized controlled trial from 1990 where 533 pregnant women were randomized to fish oil (n = 266), olive oil (n = 136) or no oil (n = 131). In 2009, the offspring were invited to a physical examination including blood sampling. A total of 243 of the offspring participated. Lipid values did not differ between the fish oil and olive oil groups. The relative adjusted difference (95% confidence intervals) in lipid concentrations was -3% (-11; 7) for LDL cholesterol, 3% (-3; 10) for HDL cholesterol, -1% (-6; 5) for total cholesterol,-4% (-16; 10) for TAG concentrations, 2%(-2; 7) for apolipoprotein A1, -1% (-9; 7) for apolipoprotein B and 3% (-7; 15) in relative abundance of small dense LDL. In conclusion, there was no effect of fish oil supplementation during the third trimester of pregnancy on offspring plasma lipids and lipoproteins in adolescence.

Intake of fish oil during pregnancy and adiposity in 19-y-old offspring: follow-up on a randomized controlled trial.

BACKGROUND: It is well established that obesity tends to track from early childhood into adult life. Studies in experimental animals have suggested that changes in the peri- and early postnatal intake of n-3 (omega-3) polyunsaturated acids can affect the development of obesity in adult life. OBJECTIVE: The aim of the current study was to investigate the effect of daily supplementation with 2.7 g long-chain n-3 fatty acids during the third trimester of pregnancy on adiposity in 19-y-old offspring. DESIGN: The study was based on follow-up of a randomized controlled trial from 1990, in which 533 pregnant women were randomly assigned to receive fish oil, olive oil, or no oil. At ≈19 y of age, the offspring of subjects from the randomized controlled trial were invited to undergo a physical examination, including anthropometric measurements and fasting blood sampling. The blood sample was analyzed for insulin, glucose, glycated hemoglobin, leptin, adiponectin, insulin-like growth factor I, and high-sensitivity C-reactive protein. Multiple linear regression modeling, adjusted for sex, smoking, and parental overweight, was used to estimate the effect of fish oil relative to that of olive oil on BMI (in kg/m(2)), waist circumference, and biochemical measures. RESULTS: A total of 243 of the offspring were followed up. We found no difference between the fish-oil and olive oil groups in BMI (0.13; -0.92, 1.17) or waist circumference (0.7 cm; -2.1, 3.4 cm). Overall, results of the biochemical analyses supported the finding of no difference between the groups. CONCLUSION: We detected no effect of fish-oil supplementation during pregnancy on offspring adiposity in adolescence.

Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

OBJECTIVE: Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. RESEARCH DESIGN: A comparative study was carried out. SETTING: This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. PARTICIPANTS: This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. INTERVENTION: The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. MAIN OUTCOME MEASURE: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. RESULTS: EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. CONCLUSION: HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease.

The content of docosahexaenoic acid in serum phospholipid is inversely correlated with plasma homocysteine levels in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) have a high morbidity and mortality from cardiovascular disease. An elevated homocysteine level is an independent predictor of cardiovascular events in patients with ESRD. Interestingly, some studies have found an inverse relationship between the content of marine n-3 polyunsaturated fatty acids (PUFAs) and homocysteine levels, but data are ambiguous. In patients with ESRD, we hypothesized that serum phospholipid n-3 PUFA content would inversely correlate with homocysteine levels in plasma and that supplementation with n-3 PUFA would reduce plasma homocysteine levels. In a double-blind, randomized, controlled design, 206 patients with documented cardiovascular disease and treated with hemodialysis for a minimum of 6 months were randomized to treatment with daily supplement of 1.7 g n-3 PUFA or placebo (olive oil) for 3 months. The content of n-3 PUFA in serum phospholipids and homocysteine levels in plasma were measured at baseline and after 3 months of intervention. A dietary questionnaire was filled out at baseline, and study participants were divided into groups of low, intermediate, and high fish intake. Docosahexaenoic acid was inversely correlated with homocysteine at baseline (coefficient = -0.161; P = .03). Homocysteine was not related to self-reported fish intake. Supplementation with n-3 PUFA did not reduce homocysteine levels compared with placebo (mean ± SD difference, -0.3 ± 7.8 versus 0.3 ± 7.1; P = .58). The content of docosahexaenoic acid in serum phospholipids is inversely correlated with plasma homocysteine levels, and supplementation with n-3 PUFA does not reduce homocysteine levels in patients with ESRD.

The effect of n-3 fatty acids on levels of methylarginines in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a very high mortality mainly caused by cardiovascular disease (CVD). It has been suggested that plasma concentrations of asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor, are markedly elevated in patients with ESRD. Elevation of ADMA is linked to CVD and an adverse prognosis. Supplementation with n-3 fatty acids has previously been shown to prevent CVD, but there is very little data regarding the effect of n-3 fatty acids on levels of ADMA. METHODS: Patients with ESRD and documented CVD were randomized to treatment with 1.7 g of n-3 fatty acids (n=103, 34% women) or olive oil (n=103, 38% women) for three months. ADMA, symmetric dimethyl arginine (SDMA), L-arginine, and the relative content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in serum phospholipids were measured before and after treatment. RESULTS: ADMA was normally distributed with a mean value of 0.56+/-0.13 micromol/L (range 0.21-1.01) and only 14/206 (6.8 %) had elevated levels of ADMA. SDMA was generally elevated with a mean value of 1.88+/-0.64 micromol/L (range 0.67-4.56). Supplementation with n-3 fatty acids for three months did not change plasma levels of ADMA, SDMA or L-arginine. CONCLUSIONS: The present data do not support a beneficial effect of n-3 fatty acids on methylarginines in patients with ESRD.

The incorporation of marine n-3 PUFA into platelets and adipose tissue in pre- and postmenopausal women: a randomised, double-blind, placebo-controlled trial.

The primary aim of the trial was to investigate the influence of menopause on the incorporation of marine n-3 PUFA into platelets and adipose tissue. A secondary aim was to evaluate whether marine n-3 PUFA may change levels of circulating oestrogens in women. Ninety-two pre- and postmenopausal women were randomly assigned to consume 2.2 g of marine n-3 PUFA or control oil daily for 12 weeks. Adipose tissue biopsies and blood samples were collected at baseline and after intervention. Eighty-nine women completed the study. Baseline contents of total marine n-3 PUFA and each of the major long-chained n-3 PUFA, EPA, docosapentaenoic acid and DHA were all significantly lower (P < 0.05) in the premenopausal group both in platelets and adipose tissue, except for EPA in platelets (P = 0.05). After supplementation with fish oil, the content of all marine n-3 PUFA increased significantly in platelets and adipose tissue in both pre- and postmenopausal women. The increase in platelets and adipose tissue was, however, the same in both groups. There was no effect of fish oil on oestrogen levels in postmenopausal women. We found a significant difference in premenopausal women, in whom oestradiol (P < 0.04) and oestrone (P < 0.02) serum concentrations increased after the fish oil supplement. This trial did not reveal any difference in the ability of pre- and postmenopausal women to incorporate marine n-3 PUFA into platelets or adipose tissue. However, supplementation with fish oil increased oestrogen levels in premenopausal women.

Marine n-3 polyunsaturated fatty acids in adipose tissue and breast cancer risk: a case-cohort study from Denmark.

OBJECTIVE: The aim of this study was to investigate the association between the content of marine n-3 polyunsaturated fatty acids (PUFA) in adipose tissue, a biomarker for the long-term intake of seafood, and the subsequent development of breast cancer (BC). DESIGN: We designed a case-cohort study based on a cohort of healthy Danish women, who in the 1990 s donated adipose tissue biopsies to a biobank in order to investigate the role of diet for the development of cancer and chronic disease. During follow-up, incident cases of BC were identified through national registries, and the content of n-3 PUFA in adipose tissue was compared between cases and the cohort sample. RESULTS: During follow-up, 463 new cases of BC were identified. After adjusting for potential confounders, no significant association between the content of marine n-3 PUFA and BC was found. When comparing the highest with the lowest quintile, the hazard ratio (HR) was 0.96 (95% CI 0.64-1.43) for total marine n-3 PUFA, 0.84 (95% CI 0.58-1.23) for eicosapentaenoic acid (EPA), and 1.08 (95% CI 0.73-1.58) for docosahexaenoic acid (DHA). CONCLUSION: This study does not indicate any association between the content of total or individual marine n-3 PUFA in adipose tissue and development of BC.

The effect of fish oil supplementation on heart rate in healthy Danish infants.

Polyunsaturated n-3 fatty acids (n-3PUFA) may improve brain development and prevent cardiovascular disease. Heart rhythm is autonomically controlled and among the affected cardiovascular risk markers in adults. The aim of the study was to examine whether fish oil supplementation in late infancy could modify heart rate (HR) and heart rate variability (HRV). In a 2 x 2-intervention, 83 healthy Danish infants were randomized to +/- fish oil (3.4 +/- 1.1 mL/d) and cow's milk or infant formula from 9 to 12 mo of age. In 57 infants, 0.5-h ECG recordings were successfully obtained before and after the intervention and erythrocyte fatty acid composition was determined in 30 of these. Fish oil supplementation raised erythrocyte n-3PUFA content (p < 0.001). No significant group differences were seen in HR or HRV. However, a fish-oil x gender interaction was observed on mean RR interval (p = 0.001) with a 6% longer mean RR interval in fish-oil-supplemented boys (p = 0.007). Irrespective of gender, there was a positive association between the 9- and 12-mo changes in RR interval and erythrocyte n-3PUFA (p < 0.001). In infants with confirmed changes in erythrocyte n-3PUFA, mean RR interval was found to be longer (p = 0.011) in the fish-oil-supplemented groups. The study suggests that fish oil may affect heart rhythm in infants similar to that observed in adults. This may imply low n-3PUFA-status in late infancy and n-3PUFA influence on CNS function.

The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: a randomized placebo-controlled intervention study.

BACKGROUND: Patients with end-stage renal disease (ESRD) have an increased mortality, mainly due to cardiovascular disease (CVD). ESRD is accompanied by several lipid abnormalities, which may be responsible for part of the increased risk of CVD in this population. n-3 polyunsaturated fatty acids (PUFA) lower plasma triglycerides in patients with normal renal function. The aim of the present study was to examine the effect of n-3 PUFA on serum lipid and lipoproteins in patients treated with chronic haemodialysis (HD). METHODS: In a double-blind randomized placebo-controlled design, patients with documented CVD, treated with HD for a minimum of 6 months, were randomized to treatment with n-3 PUFA or a control treatment (olive oil). A dietary intake of n-3 PUFA was assessed with a dietary questionnaire. Plasma lipids and lipoproteins and the content of n-3 PUFA in serum phospholipids were measured at baseline and after 3 months. RESULTS: Two hundred and six patients were included. Serum phospholipid levels of n-3 PUFA were significantly higher in patients reporting a high fish intake compared to patients reporting a low fish intake. After 3 months, a significant decrease was seen in serum triglycerides in the n-3 PUFA group compared to the control group (P = 0.01). No significant effect was seen on total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, Lp(a) or apoB. CONCLUSION: In patients treated with HD, consumption of fish increases levels of n-3 PUFA. Additional supplementation with n-3 PUFA for 3 months further increases levels of n-3 PUFA and lowers serum triglycerides, but does not significantly affect other plasma lipids or lipoproteins.