Polyunsaturated Fatty Acids In Adipose Tissue Research Articles

P0945STUDY PROTOCOL: ADIPOSE TISSUE CONTENT OF N-3 POLYUNSATURATED FATTY ACIDS AND THE RISK OF CHRONIC KIDNEY DISEASE

Abstract Background Chronic kidney disease (CKD) is associated with life style diseases such as hypertension and type 2 diabetes. However the role of diet is not yet clearly defined for development of CKD. Recent studies have shown that n-3 polyunsaturated fatty acids (PUFAs) may exert favourable effects on several processes that may inhibit the development and progression of CKD. A gold standard biomarker for long-term intake and metabolism of n-3 PUFAs, is their content in adipose tissue; because these fatty acids are essential and not endogenously produced. Aims The primary aim of this study is to investigate the association of adipose tissue content of marine and plant-based n-3 PUFAs to the risk of incident CKD. This study will also examine associations between the content of n-3 PUFAs in adipose tissue and the risk of main subtypes of CKD: Proteinuria with unknown cause, Hypertensive nephropathy, Glomerular diseases, Diabetic nephropathy and Chronic renal failure of unknown cause. Method In this case-cohort study based on data from the prospective Danish Diet, Cancer and Health cohort (DCH), information concerning diet and other lifestyle factors was obtained from 57,053 Danish men and women aged 50 to 65 years, using questionnaires and interviews. Anthropometric measurements were undertaken, and adipose tissue biopsies were taken from the buttocks of all participants at baseline. The follow-up period was from December 1993 to September 2017. The outcome CKD is defined as having a diagnosis of one of the CKDs causes in the Danish National Patient Registry (DNPR). Cases of CKD will be identified and included together with a randomly drawn subcohort, representative for all participants of the cohort. Adipose tissue samples will be analyzed by gas chromatography in all incident CKD cases and in 5,000 randomly drawn participants from the whole cohort. The outcome will be adjusted for age, sex, body mass index, physical activity, energy intake, alcohol consumption, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity. The study is approved by the Danish National Committee on Health Research Ethics (N-20180074) and the Danish Data Protection Agency (2018-139). Results No results are available yet. Conclusion Our hypothesis is that the content of total n-3 PUFAs, as well as both marine and plant-based n-3 PUFAs, in adipose tissue is inversely associated with the risk of CKD and its subtypes.

Adipose Tissue Modification through Feeding Strategies and Their Implication on Adipogenesis and Adipose Tissue Metabolism in Ruminants.

Dietary recommendations by health authorities have been advising of the importance of diminishing saturated fatty acids (SFA) consumption and replacing them by polyunsaturated fatty acids (PUFA), particularly omega-3. Therefore, there have been efforts to enhance food fatty acid profiles, helping them to meet human nutritional recommendations. Ruminant meat is the major dietary conjugated linoleic acid (CLA) source, but it also contains SFA at relatively high proportions, deriving from ruminal biohydrogenation of PUFA. Additionally, lipid metabolism in ruminants may differ from other species. Recent research has aimed to modify the fatty acid profile of meat, and other animal products. This review summarizes dietary strategies based on the n-3 PUFA supplementation of ruminant diets and their effects on meat fatty acid composition. Additionally, the role of n-3 PUFA in adipose tissue (AT) development and in the expression of key genes involved in adipogenesis and lipid metabolism is discussed. It has been demonstrated that linseed supplementation leads to an increase in α-linolenic acid (ALA) and eicosapentaenoic acid (EPA), but not in docosahexaenoic acid (DHA), whilst fish oil and algae increase DHA content. Dietary PUFA can alter AT adiposity and modulate lipid metabolism genes expression, although further research is required to clarify the underlying mechanism.

Disorders of Serum Polyunsaturated Fatty Acids in Renal Transplant Patients

BackgroundDisturbances in polyunsaturated fatty acids (PUFA) could predispose renal transplant (RTx) patients to cardiovascular risk. The purpose of this study was to evaluate serum content of ω-3 and ω-6 PUFA in RTx subjects, in comparison to nontransplanted chronic kidney disease (CKD) patients in predialysis stages and to healthy controls. In the second part of the study, PUFA were analyzed in subcutaneous adipose tissue of CKD subjects at the time of kidney transplantation. MethodsThe first part of the study was conducted in a cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (control group, n = 43). The fatty acids (FA) assessed by gas chromatography-mass spectrometry (GC-MS) were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). Diet was assessed by food frequency questionnaire FFQ-6. In the second part of the study, the same FA were evaluated in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controls from the adipose tissue collected during hernia surgeries. ResultsThe first part of the study showed that RTx patients presented significantly lower serum content of all the examined PUFA, in comparison to the CKD-ND group and controls. For instance, EPA in RTx equaled 0.65 ± 0.32%, in CKD-ND 0.82 ± 0.43%, and in controls 1.06 ± 0.68% (P = .005). No significant correlations were found between serum PUFA and diet in RTx patients. The second part of the study revealed no significant difference in the adipose tissue PUFA between CKD patients at the time of kidney transplantation and controls. ConclusionsRTx patients present with low serum content of potentially beneficial PUFA. This finding does not seem to be solely due to an altered diet. Observed disorders might result from immunosuppressive drugs or other, yet undetermined, causes.

Marine n-3 Fatty Acids and the Risk of Peripheral Arterial Disease

BackgroundThe content of marine n-3 polyunsaturated fatty acids (PUFAs) in adipose tissue is considered a long-term biomarker for the body’s endogenous exposure to seafood. ObjectivesThis study sought to examine associations between the content of marine n-3 PUFAs in adipose tissue and the risk of incident peripheral arterial disease (PAD). MethodsIn this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, adipose tissue biopsies were taken from the buttocks of all participants at baseline. After a median follow-up of 13.5 years, 870 validated cases of PAD were identified and included together with a randomly drawn subcohort of 3,204 participants using weighted Cox regression. Adipose tissue samples were analyzed by gas chromatography. ResultsIn multivariable analyses using the lowest quintile as the reference and adjusting for established risk factors for PAD, we found a statistically significant lower rate of PAD in the highest quintile of eicosapentaenoic acid (EPA) (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.41 to 0.74) and a nonsignificant lower rate for docosahexaenoic acid (HR: 0.79; 95% CI: 0.59 to 1.06). We observed a lower rate of PAD, when comparing the highest quintile of the combined EPA and docosahexaenoic acid with the reference (HR: 0.71; 95% CI: 0.53 to 0.96). In contrast, docosapentaenoic acid had an HR of 1.31 (95% CI: 0.97 to 1.77) in the highest quintile. ConclusionsA high content of marine n-3 PUFAs in adipose tissue, in particular EPA, was associated with a lower risk of incident PAD.

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children

Background and aimsPolyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica. Method and resultsWe conducted a cross-sectional study among 468 parents and 201 children aged 7–12 y from the capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, and Tuxtla Gutiérrez in Mexico. We measured PUFA biomarkers in gluteal adipose tissue by gas chromatography. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. In children, we created an age- and sex-standardized metabolic risk score using abdominal circumference, the homeostasis model of insulin resistance, blood pressure, serum HDL cholesterol, and triglycerides. We estimated prevalence ratios of MetS and mean differences in metabolic score across quartiles of PUFA using multivariable-adjusted Poisson and linear regression models, respectively. Among adults, MetS was associated with low alpha-linolenic acid (ALA), high eicosapentaenoic acid (EPA), and low gamma-linolenic acid (GLA). It was linearly, positively associated with dihomo-gamma-linolenic acid (DGLA) and estimated Δ6-desaturase (D6D) activity. Among children, the metabolic score was positively associated with docosapentaenoic acid (DPA), DGLA, and D6D activity. ConclusionsAmong Mesoamerican adults, MetS prevalence is inversely associated with adipose tissue ALA and GLA, and positively associated with EPA, DGLA, and the D6D index. Among children, metabolic risk score is positively associated with DPA, DGLA, and the D6D index.

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

ObjectiveTo 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. MethodsNinety-two healthy women were randomly assigned to consume 2.2g marine n-3 PUFA or a control oil (thistle oil) daily for 12weeks. 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. ResultsPlasma 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. ConclusionThis study showed that 2.2g marine n-3 PUFA reduce plasma PCSK9 levels in both pre- and postmenopausal women.

Polyunsaturated fatty acid regulation of adipocyte FADS1 and FADS2 expression and function.

Polyunsaturated fatty acids (PUFAs) regulate fatty acid desaturase (FADS1, FADS2) expression in the liver; however, it is unknown whether PUFAs regulate FADS in adipocytes. This is important to study considering reports that link altered desaturase activity with adipose tissue PUFA profiles, body weight, and whole-body glucose homeostasis. Therefore, the present study aimed to determine the direct effects of PUFAs on FADS expression in differentiated 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated with either α-linolenic (ALA), linoleic (LA), eicosapentaenoic (EPA), or arachidonic acid (AA). Gene expression, protein abundance, and cellular PUFA content were analyzed by real-time RT-PCR, Western blotting, and gas chromatography, respectively. Fads1 and Fads2 gene expression was reduced by EPA and AA, but not ALA or LA. Reductions in gene expression were reflected in FADS2 protein levels, but not FADS1. Treating cells with ALA and LA led to significant increases in the cellular content of downstream PUFAs. Neither ALA nor EPA changed docosahexaenoic acid content. Differentiated 3T3-L1 adipocytes have a functional FADS pathway that can be regulated by PUFA. Therefore, this common adipocyte model is suitable to study dietary regulation of the FADS pathway.

Impact of dietary fat sources and feeding level on adipose tissue fatty acids composition and lipid metabolism related gene expression in finisher pigs

The present study investigated the effects of dietary fat sources and feeding level on performance, adipose tissue fatty acid profile and lipid metabolism related genes expression in finisher pigs. A total of 128 finisher pigs [average initial body weight (BW), 81.2±0.322kg] were allotted to 4 treatments on the basis of BW. There were 4 replicates in each treatment with 8 pigs per replicate. Pigs were fed diets containing 50.0g/kg linseed oil or animal fat, either ad libitum or restricted (15.0% less) in 2×2 factorial arrangement for 28d. Dietary fat source did not affect (P>0.05) average daily gain (ADG), average daily feed intake (ADFI) and gain to feed ratio (G:F). The ADG and ADFI of pigs fed ad libitum were greater (P<0.05) than that of restricted fed pigs. The G:F of restricted fed pigs was greater (P<0.05) than that of ad libitum fed pigs. Pigs fed 50.0g/kg linseed oil diet had greater (P<0.05) concentrations of adipose tissue polyunsaturated fatty acids (PUFA) like linoleic acid and α-linolenic acid than that of pigs fed 50.0g/kg animal fat diet. Saturated fatty acids (SFA) like palmitic acid (P<0.05), palmetoleic acid and steric acid (P<0.10) concentrations of adipose tissue were greater in pigs fed animal fat than pigs fed linseed oil. However, adipose tissue fatty acids concentrations were not affected (P>0.05) by feeding level. Adipose tissue expression of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) were down-regulated, whereas expression of lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) were up-regulated in finishing pigs fed restricted diets. However, fat sources of diet had no effects (P>0.05) on expression of ACC, FAS, LPL and HSL genes. Results obtained in the present study indicates that dietary inclusion of 50.0g/kg linseed oil have potential to improve the adipose tissue PUFA contents, and 15.0% feed restriction resulted into down-regulation of ACC and FAS and up-regulation of LPS and HSL expression in adipose tissue.

The Effect of Low-Dose Marine n-3 Fatty Acids on Plasma Levels of sCD36 in Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

CD36 is a scavenger receptor involved in lipid uptake and inflammation. Recently, non-cell-bound CD36 (sCD36) was identified in plasma and suggested to be a marker of lipid accumulation in the vessel wall. Marine n-3 polyunsaturated fatty acids (PUFA) may have cardioprotective effects. This study evaluated the effect of marine n-3 PUFA on sCD36 levels in overweight subjects. Fifty overweight subjects were randomized to 1.1 g of n-3 PUFA or 2 g of olive oil daily for six weeks. Neutrophils were isolated at baseline and after six weeks of treatment while an adipose tissue biopsy was obtained at baseline. The content of n-3 PUFA in adipose tissue and neutrophils was analyzed by gas chromatography, while plasma levels of sCD36 were determined using an enzyme-linked immunosorbent assay (ELISA). After six weeks of supplement plasma sCD36 did not differ between supplements (P = 0.18). There was no significant correlation between plasma sCD36 levels and n-3 PUFA in neutrophils at baseline (r = −0.02, P = 0.88), after six weeks supplement (r = −0.03, P = 0.85) or in adipose tissue (r = 0.14, P = 0.34). This study therefore does not provide evidence for a cardioprotective effect of n-3 PUFA acting through a CD36-dependent mechanism.

Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study

ObjectiveConsumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to...

ω-3 and ω-6 Polyunsaturated Fatty Acid Intakes and the Risk of Breast Cancer in Mexican Women: Impact of Obesity Status

ω-3 polyunsaturated fatty acids (PUFA) could play a protective role on the risk of breast cancer; however, little is known about this relation among Mexican women. We evaluated the association between ω-3 and ω-6 PUFA intake and breast cancer risk by obesity status in Mexican women. A population-based case-control study was conducted in Mexico, including 1,000 incident breast cancer cases and 1,074 controls matched to cases by age, health care system, and region. Women provided information on health and diet by in-person interview. Body mass index (BMI) measures were used to define overall obesity. Obesity status was categorized as normal weight (18.5 < BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30). A conditional logistic regression model was used to assess the association between PUFA and breast cancer risk. Overall, there was no significant association between ω-3 PUFA intake and breast cancer risk (P = 0.31). An increased risk of breast cancer was associated with increasing ω-6 PUFA intake in premenopausal women [OR = 1.92, 95% confidence interval (CI) = 1.13-3.26; P = 0.04]. A decreased risk of breast cancer was significantly associated with increasing ω-3 PUFA intake in obese women (OR = 0.58, 95% CI = 0.39-0.87; P = 0.008) but not in normal weight nor in overweight women (P(heterogeneity) = 0.017). Obesity status may affect the association between ω-3 PUFA intake and breast cancer risk. The underlying mechanisms may be related to decreased inflammation and improved adipokin and estrogen levels induced by ω-3 PUFA in adipose tissue in obese women. Increased intake of ω-3 PUFA should be recommended among Mexican women in particular in obese women.

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

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). 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. 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). 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.

Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete

Only one study has investigated the relationship of essential fatty acids in the adipose tissue with depression in adults and suggested an inverse relationship between docosahexaenoic acid (22:6 n-3) (DHA) and depression. To examine the relation between adipose tissue polyunsaturated fatty acids especially n-3 and n-6 fatty acids, an index of long-term or habitual fatty acid intake, and depression in adults. Cross-sectional study of healthy adults from the island of Crete. The Preventive Medicine and Nutrition Clinic, University of Crete, Greece. A total of 130 healthy adults (59 males, 71 females) aged 22-58 years. The sample was a sub-sample of the Greek ApoEurope study group. Fatty acids were determined by gas chromatography in adipose tissue. Information about depression was obtained through the Zung Self-rating Depression Scale. Adipose tissue DHA was inversely related with depression. Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index, smoking and educational level confirmed this association. The inverse relationship between adipose DHA and depression in adults, replicates findings of a previous study. This relationship indicates that a low long-term dietary intake of DHA is associated with an increased risk for depression in adults.

Adipose tissue triglyceride fatty acids and atherosclerosis in Alaska Natives and non-Natives

Essential polyunsaturated fatty acids (PUFA) of the ω-3 family are believed to protect against cardiovascular disease. A rich source of ω-3 PUFA is found in fish and marine mammals (seal, walrus, whale), which are a large part of the traditional diet of Alaska Natives (Eskimo, American Indians, Aleuts), a group that has been reported to have a lower mortality rate from cardiovascular disease than non-Natives. An autopsy study using standardized methods to evaluate the extent of atherosclerosis and its risk factors, and analyses of stored triglyceride fatty acids was conducted in a sample of Alaska Native subjects and non-Native subjects living in Alaska. Findings indicate that Alaska Natives had less advanced atherosclerosis in coronary arteries, along with higher proportions of ω-3 and lower proportions of ω-6 PUFA in adipose tissue, than did non-Natives. We conclude that high dietary intake of ω-3 PUFA may account for the lower extent of coronary artery atherosclerosis, contributing to the reported lower heart disease mortality among Alaska Natives.

Depression and adipose polyunsaturated fatty acids in an adolescent group

The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 90 adolescents from the island of Crete. There were 54 girls and 36 boys, aged 13–18. The mean age was 15.2 years. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies Depression Scale (CES-D). Unlike other studies, there were no significant relations between adipose tissue n-3 or n-6 polyunsaturated fatty acids and depression. BDI correlated positively with adipose tissue C20:3n-6/C18:3n-6 ratio, while CES-D correlated positively with adipose tissue (C20:3n-6+C22:5n-3)/(C18:3n-6+C20:5n-3) ratio. Depressed subjects (BDI>16, CES-D>16) had significantly elevated adipose tissue C20:3n-6/C18:3n-6 and (C20:3n-6+C22:5n-3)/(C18:3n-6+C20:5n-3) ratios, than non-depressed subjects. The observed positive relation between depression and the particular fatty acid ratios, in the present study, appears to indicate increasing activity of elongases, the enzymes responsible for elongating polyunsaturated fatty acids into their longer-chain derivatives, with increasing depression. This is the first literature report of a possible relation between elongases and depression. The observed relation may stem from a possible over-expression of the HELO1 (ELOVL5) gene, the gene encoding a protein responsible for elongating long-chain polyunsaturated fatty acids, in the adipose tissue of depressed adolescents.

Depression and adipose polyunsaturated fatty acids in the survivors of the seven countries study population of Crete

The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 150 elderly males from the island of Crete. The subjects were survivors of the Greek Seven Countries Study group. The mean age was 84 years. The number of subjects with complete data on all variables studied was 63. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the short form of the Geriatric Depression Scale (GDS-15). Depression correlated negatively with adipose tissue alpha-linolenic acid (C18:3n-3). Depressed subjects had significantly reduced (−10.5%) adipose tissue C18:3n-3 levels than non-depressed subjects. The observed negative relation between adipose tissue C18:3n-3 and depression, in the present study, appears to indicate increasing long-term dietary C18:3n-3 intakes with decreasing depression. This agrees with findings of other studies indicating an inverse relation between depression and consumption of fish and n-3 polyunsaturated fatty acids. This is the first literature report of a relation between adipose tissue C18:3n-3 and depression. Furthermore, this is the first report of a relation between adipose PUFA and depression in an elderly sample. Depression has been reported to be associated with elevated cytokines, such as, IL-1, IL-2, IL-6, INF- γ and INF- α. Fish oil and omega-3 fatty acids, on the other hand, have been reported to inhibit cytokine production. The observed negative relation between adipose C18:3n-3 and depression, therefore, may stem from the inhibiting effect of C18:3n-3 or its long-chain metabolites on cytokine synthesis.

Depression and adipose essential polyunsaturated fatty acids

The objective of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake, and depression. The sample consisted of 247 healthy adults (146 males, 101 females) from the island of Crete. The number of subjects with complete data on all variables studied was 139. Subjects were examined at the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Zung Self-rating Depression Scale. Mildly depressed subjects had significantly reduced (−34.6%) adipose tissue docosahexaenoic acid (DHA) levels than non-depressed subjects. Multiple linear regression analysis indicated that depression related negatively to adipose tissue DHA levels. In line with the findings of other studies, the observed negative relation between adipose tissue DHA and depression, in the present study, appears to indicate increasing long-term dietary DHA intakes with decreasing depression. This is the first literature report of a relation between adipose tissue DHA and depression. Depression has been reported to be associated with increased cytokine production, such as IL-1, IL-2, IL-6, INF-γ and INF-α. On the other hand, fish oil and omega-3 fatty acids have been reported to inhibit cytokine synthesis. The observed negative relation between adipose DHA and depression, therefore, may stem from the inhibiting effect of DHA on cytokine synthesis.

Marine n-3 fatty acids, wine intake, and heart rate variability in patients referred for coronary angiography.

Dietary n-3 polyunsaturated fatty acids (PUFAs) derived from fish may reduce the incidence of sudden cardiac death (SCD). In addition, wine drinking is suggested to have a protective effect against cardiovascular death. We included 291 patients referred for coronary angiography in whom ischemic heart disease was suspected and all of whom completed a food questionnaire regarding fish and wine intake. The n-3 PUFA composition of granulocyte membranes and of adipose tissue was measured. In addition, 24-hour heart rate variability (HRV) was analyzed. Fish intake was positively associated with the level of n-3 PUFAs in adipose tissue. Significant positive correlation coefficients were found between HRV indices and the levels of n-3 PUFAs in granulocytes. Wine intake was also significantly positively related to HRV, but the patients with the highest wine intake also had the highest intake of fish, as documented by a high n-3 PUFA content in adipose tissue. Multiple linear regression analysis revealed that traditional factors such as treatment with ss-blockers, smoking, age, and previous myocardial infarction were independently related to HRV, and furthermore that n-3 PUFAs (but not wine intake) were significantly independently associated with HRV. The close positive association between n-3 PUFAs and HRV in patients suspected of having ischemic heart disease may indicate a protective effect of n-3 PUFAs against SCD. This may partly explain the reduction in SCD observed in humans with a modest intake of n-3 PUFA. Wine intake was also positively correlated with HRV, but this correlation was no longer significant after controlling for the cellular level of n-3 PUFA.