Serum Omega-3 Research Articles

Relationships among the serum omega fatty acid levels, serum C-reactive protein levels and arterial stiffness/wave reflection in Japanese men

Objective We examined the relationship among the serum omega-3 and omega-6 fatty acid (O3FA and O6FA) levels, serum C-reactive protein (CRP) levels, and arterial stiffness/wave reflection (AS/WR) in healthy Japanese men. Methods In 2206 Japanese healthy men, parameters related to the AS/WR (i.e., brachial–ankle pulse wave velocity and radial arterial pulse wave analysis) were measured. Results No significant inverse relationships were observed between the serum O3FA levels and the AS/WR-related parameters. Adjusted values of the AS/WR-related parameters and serum CRP levels were higher in the subjects with serum O6FA levels in the highest tertile than in those with serum O6FA levels in the lowest tertile. Conclusions In healthy Japanese men with known high dietary intakes of O3FAs, the serum O3FA levels may not reflect the pathophysiological abnormalities related to AS/WR. Increased serum O6FA levels appeared to be independently associated with the unfavorable conditions related to AS/WR and inflammation.

Serum Omega-3 and Omega-6 Fatty Acids and Cutaneous p53 Expression in an Australian Population

There is some evidence from experimental studies that long-chain n-3 and n-6 fatty acids may be able to modify early skin carcinogenesis, but whether this applies in the general population is not known. We investigated associations between serum polyunsaturated fatty acid concentrations and p53 expression in normal skin, as a biomarker of early UV-induced carcinogenesis, in an unselected sample of Australian adults. Participants in the Nambour Skin Cancer Prevention Trial provided a dorsal hand punch biopsy which was used for immunohistochemical assessment of p53 immunoreactivity. Cross-sectional associations with serum fatty acid concentrations were analyzed in 139 participants, adjusting for confounding variables including skin phenotype, past sun exposure, and smoking status. There was an inverse association, showing a dose-response relationship, between total n-3 fatty acid serum concentrations and p53 immunoreactivity in the whole epidermis and the basal layer. This was particularly due to eicosapentanoic acid and docosahexanoic acid concentrations. There was no evidence for increased p53 immunoreactivity in participants with relatively high serum n-6 fatty acid concentrations. The ratio of n-3 to n-6 fatty acid concentrations was not associated with p53 immunoreactivity. These results add to growing evidence that long-chain fatty acids may be able to modify early skin carcinogenesis. The prospect that increased intake of n-3 fatty acids could help prevent skin cancer is attractive.

Highlights of This Issue

In breast cancer patients, studies have shown that obesity is associated with both an increased risk of dying from breast cancer and increased risk of distant metastasis. In this pilot study, Pilie and colleagues focused on the potential differences in protein expression patterns of mammary epithelial cells obtained from obese versus nonobese women. They found that vimentin protein expression was significantly different between obese and nonobese women. Differential protein expression analysis may enhance the understanding of breast cancer initiation and progression in obese women.Epidemiologic studies have established an inverse association between isoflavone intake and breast and prostate cancer risks and an inverse association with lung cancer risk has also been suggested. To help clarify the association of isoflavone intake and lung cancer risk, Shimazu and colleagues examined plasma isoflavone concentrations and lung cancer risks in a population of Japanese women. An inverse association was indeed found between plasma levels of the isoflavone genistein and lung cancer risk, supporting the previously observed association between isoflavone intake and lung cancer risk.The evidence linking the acute phase inflammatory response marker C-reactive Protein (CRP) and cancer remains inconclusive. To address this, Van Hemelrijck and collleagues performed a prospective cohort study using repeated measurements of CRP and leukocyte levels to evaluate their association with cancer risk. They report a positive trend between CRP and cancer and found that the associations between leukocytes and cancer were slightly stronger than CRP. These encouraging results are evidence that the use of CRP for early cancer detection may have merit.Experimental evidence suggests that long-chain omega-3 and omega-6 fatty acids may modify early skin carcinogenesis, but it is not known if this effect exists in the general population. To explore this, van der Pols and colleagues used p53 expression as a biomarker of early UV-induced carcinogenesis and monitored serum omega-3 and omega-6 fatty acids as well as p53 immunoreactivity in dorsal hand punch biopsies. They report an inverse association between total serum omega-3 (but not omega-6) fatty acid and p53 immunoreactivity in the whole epidermis as well as basal layer. These results add to the growing evidence that long-chain fatty acids may modify early skin carcinogenesis.

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial electrophysiology

Omega-3 polyunsaturated fatty acids in fish oils may have antifibrillatory effects. Their mechanism of action in humans is poorly understood. The purpose of this study was to investigate the effects of chronic fish oil supplementation on human atrial electrophysiology (EP). Two groups of patients without clinical AF or structural heart disease and fish intake ≤1/week were prospectively recruited into a control group (n = 30) and a fish oil group (n = 31). The latter were prescribed 6 g/day of fish oil for ≥1 month before an EP study. The following were compared at time of EP study: serum omega-3 levels; right atrial and coronary sinus effective refractory periods (ERPs); interatrial, intra-atrial, left atrial, and coronary sinus conduction at baseline and the maximal conduction delay with the shortest propagated extrastimulus; and inducibility of AF (10 inductions/patient). The following significant differences were noted favoring the fish oil group at time of EP: (1) twofold higher total omega-3 levels (P < .001); (2) lengthening of ERPs by 8%-14% at all measured sites and pacing cycle lengths (P < .05); (3) no effect on baseline interatrial, intra-atrial, left atrial, and coronary sinus conduction but a significant attenuation of maximal conduction delay (P < .05); (4) less inducible AF (AF ≥30 seconds: 24.2% vs. 7.9%; P < .001); (5) shorter mean duration of induced AF (P = .003); and (6) prolongation of induced AF cycle length (P < .001). Chronic fish oil supplementation in humans prolongs atrial refractoriness and reduces vulnerability to inducible AF. These EP changes may explain the antifibrillatory effect of chronic fish oil ingestion.

The relationship of hair mercury levels with early in vitro fertilization (IVF) outcomes

OBJECTIVE: Environmental mercury (Hg) contamination has led to increased human exposure through the primary route of seafood consumption. Despite widespread exposure, data is limited on the impact of Hg on reproduction. We conducted a preliminary study of the potential impact of Hg on early human reproduction. DESIGN: Prospective cohort study on the association of hair Hg in women and early IVF outcomes. MATERIALS AND METHODS: Total Hg in parts per million (ppm) was measured in the proximal 3-cm of hair in women prior to their IVF cycle. Outcomes included number of oocytes, fertilization rate, blastocyst development and implantation failure. Covariates included age, stimulation protocol, day 3 FSH, peak serum estradiol and Omega-3 fatty acid (FA) consumption through self-reporting in a food survey. Generalized estimating equations were used to explore the associations between outcomes and hair Hg levels, accounting for within-woman correlations of outcomes across repeated treatment cycle attempts. We applied the Poisson log link function for the early embryo and oocyte level outcomes. RESULTS: There were a total of 170 cycles from 120 women. The mean hair Hg level was 1.07 ppm (range 0.03 to 5.66 ppm), 33% of the women exceeded the EPA reference dose of 1 ppm. Number of oocytes (p for trend=0.23) and fertilization rate (p for trend=0.29) did not differ by Hg level quartiles. A one log unit increase in Hg was associated with a 25% increased incidence rate of blastocysts (p=0.002) and a 44% decreased odds of implantation failure (p=0.021). CONCLUSION: Unexpectedly there was a positive association of hair Hg levels with indicators of successful early IVF outcomes. Since fish consumption may be beneficial for reproductive success and it is the primary source of Hg exposure, it may confound the association of Hg with IVF outcomes.

Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents

Objective Compared to normal weight adolescents, obese adolescents have lower serum omega-3 (n-3) polyunsaturated fatty acid (PUFA) concentrations, augmented inflammatory activity and endothelial dysfunction. We wanted to assess whether n-3 supplementation increases the serum n-3 PUFA concentration, improves vascular function and morphology, and lowers inflammation in obese adolescents. Methods Twenty-five obese adolescents (14 females, 11 males, age 15.7 ± 1.0 years, BMI 33.8 ± 3.9) were randomized to receive capsules containing either 1.2 g/day n-3 or placebo for 3 months. The study was performed using a double-blind, cross-over design with a 6-week washout period. Anthropometry, blood pressure measurements and fasting blood samples were obtained before and after each treatment period. The vascular structure and function was measured after each treatment period. Results The serum n-3 PUFA concentration increased with n-3 treatment. The reactive hyperemia response improved with n-3 treatment compared to placebo ( p < 0.01). N-3 supplementation also decreased the lymphocyte, monocyte, TNF-α, IL-6 and IL-1β levels. No difference was found in the total cholesterol, triacylglycerol, HDL cholesterol, anthropometry, blood pressure, pulse wave velocity or vascular structure between the two treatment groups. Conclusion Daily supplementation with n-3 capsules increases the serum n-3 PUFA concentration, improves vascular function, and lowers the degree of inflammation in obese adolescents.

Serum n−6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP Study

The associations of serum omega-6 (n-6) fatty acids with lipoprotein subclasses at the population level are uncertain. We aimed to examine associations between major n-6 fatty acids [ie, linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6)] and the lipoprotein subclasses VLDL, LDL, and HDL. We conducted a cross-sectional study in 1098 participants using population-based data from US white, Japanese American, Japanese, and Korean men aged 40-49 y. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Multiple linear regression models as a function of each fatty acid were used after adjustment for age, population, body mass index, pack-years of smoking, alcohol consumption, diabetes, hypertension, and omega-3 (n-3) and trans fatty acids. Serum LA was inversely associated with large VLDL (beta = -0.62, P < 0.001), total LDL (beta = -22.08, P < 0.001), and small LDL (beta = -31.89, P < 0.001) particle concentrations and VLDL size (beta = -0.72, P < 0.001). Serum LA was positively associated with large HDL particle concentration (beta = 0.21, P < 0.001) and HDL size (beta = 0.03, P < 0.001). The patterns of association of AA with large VLDL and large HDL particle concentrations were comparable with those of LA. At the population level, higher serum concentrations of LA were significantly associated with lower concentrations of total LDL particles. Higher serum concentrations of LA and AA were significantly associated with a lower concentration of large VLDL particles and a higher concentration of large HDL particles. These associations were consistent across the population groups. This trial was registered at clinicaltrials.gov as NCT00069797.

Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder.

This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder. Children and adolescents aged 6-17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses. There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %alpha-LNA (r = -0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = -0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms. Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.

Fish consumption and polyunsaturated fatty acids in relation to psychological distress

It has been suggested that high fish consumption improves mental well-being. The aim of this study was to assess whether high fish consumption or omega-3 polyunsaturated fatty acid (PUFA) intake was associated with reduced self-reported psychological distress. We used three cross-sectional data sets, the nationwide Health 2000 Survey (n = 5840), the Fishermen Study on Finnish fishermen and their family members (n = 1282) and the Finntwin16 Study on young adults (n = 4986). Data were based on self-administered questionnaires, interviews, health examinations and blood samples. Psychological distress was measured using the 12-item and 21-item General Health Questionnaires (GHQs). Fish consumption was measured by a food frequency questionnaire (FFQ, g/day) and independent frequency questions (times/month). Dietary intake (g/day) and serum concentrations (% from fatty acids) of PUFAs were determined. Relationships were analysed using regression analysis. Regardless of the measure, fish consumption and omega-3 PUFA dietary intake were not associated with distress in any of the data sets. In contrast to the hypothesis, high serum docosahexaenoic acid was associated with high distress in the Fisherman Study men. Some non-linear associations were detected between serum omega-3 PUFAs or fish consumption (times/month) and distress. In the Fishermen Study, the associations were modified by alcohol consumption, smoking and physical activity. Our results do not support the hypothesis that fish consumption or omega-3 PUFA intake are associated with reduced psychological distress in the general population or in a population with high fish consumption.

Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption

To assess biomarkers and frequency questions as measures of fish consumption. Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.

Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: A comparison between fertile and infertile men

Fatty acid (FA) composition of the spermatozoa may be an important determinant of fertility. The aim was to evaluate polyunsaturated fatty acid (PUFA) composition of the blood plasma and spermatozoa in infertile men with idiopathic oligoasthenoteratozoospermia (OAT). Eighty-two infertile men with idiopathic OAT and seventy-eight fertile men defined according to semen concentration and proven fertility were enrolled in the study. The semen parameters were assessed according to World Health Organization criteria; three omega-3 fatty acids--alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and two omega-6 fatty acids--linoleic acid (LA) and arachidonic acid (AA) concentrations were measured in blood plasma and spermatozoa; and the seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were also assessed. Proven fertile men had higher blood and spermatozoa levels of omega-3 FAs compared with the infertile patients. The ratio of serum omega-6/omega-3 fatty acids was significantly higher in infertile (14.8+/-4.3) patients compared to fertile controls (6.3+/-2.2) (P=0.001). Additionally, levels of AA were higher and the omega-3 index (EPA+DHA) was lower in infertile subjects than in fertile controls (all P values<0.05). Infertile men had higher mean AA:DHA ratio and AA:EPA (6.4+/-2.9 and 12.0+/-4.9, respectively) than fertile men (3.3+/-1.8 and 6.7+/-2.6, respectively) (both P=0.001). A strong negative correlation was found between the AA:DHA and AA:EPA ratios and total sperm count (r=-0.62, P=0.001 and r=-0.64, P=0.001, respectively), sperm motility (r=-0.63, P=0.001 and r=-0.61, P=0.001, respectively), and sperm morphology (r=-0.61, P=0.001, and r=-0.59, P=0.002, respectively). Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.

Serum omega-3 fatty acids are associated with ultimatum bargaining behavior

In the ultimatum game (UG), two players are involved to bargain over a division of a given sum of money. The proposer makes an ultimatum offer of a fraction of money, while the responder can either accept or reject the proposer's decision. In case of rejection of the proposed splitting by the responder, neither player gets anything. Adverse psychological reactions are deemed to play a role in the rejection of unfair offers. Low serum levels of omega-3 polyunsaturated fatty acids have been linked to impulse control and hostility. This study examined the serum omega-3 and omega-6 fractions in relation to the ultimatum bargaining behavior. Participants were sixty economy students (31 males and 29 females, mean age: 24.4 ± 2.3 years) who played a €10 ultimatum game. Ultimatum offers were constrained to be €5 (proposer keeps €5) or €1 (proposer keeps €9) to generate a roughly even split between fair (5:5) and unfair (1:9) offers. Fasting serum alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) and arachidonic acid (AA) were assayed with gas chromatography. In participants who rejected unfair offers there was a significant depletion of ALA, EPA and DHA. Moreover, the ratio of serum omega-3/omega-6 fatty acids was significantly lower in patients who rejected unfair offers as compared to those who did not. The results of this study suggest that a depletion of the serum omega-3 fatty acids is associated with rejections of unfair ultimatum offers in an experimental neuroeconomic setting.

Immune Response of Postpartum Dairy Cows Fed Flaxseed

Thirty Holstein cows were allotted at calving to 10 groups of three cows blocked for similar calving dates to determine the effects of dietary fatty acids on functional properties of immunocompetent cells in early lactation and at breeding. Cows were assigned at calving to one of three isonitrogenous, isoenergetic, and isolipidic supplements based on either calcium salts of palm oil, Megalac, micronized soybeans, or whole flaxseed. On the day of AI and 20 d later, cows were injected with ovalbumin to measure the antibody response. Blood samples were taken at different times after calving (d 5, 21, 42, and 105) and after AI (d 0, 10, 20, and 40) for quantification of serum progesterone, fatty acids, and prostaglandin E2 concentrations. Isolated peripheral blood mononuclear cells were cultured to evaluate the proliferative response to concanavalin A and in vitro productions of interferon-γ and prostaglandin E2. In general, feeding flaxseed increased serum omega-3 fatty acids concentration compared with feeding Megalac or soybeans, which decreased the omega-6 to omega-3 fatty acids ratio. There was a significant diet×day interaction for the proliferative response of mononuclear cells after calving and AI, indicating that cell responses from cows fed flaxseed were transiently reduced compared with those fed Megalac and soybeans. Moreover, during the breeding period, serum progesterone concentration was significantly greater in cows fed flaxseed compared with those fed Megalac, whereas serum concentration of prostaglandin E2 was significantly lower in cows fed flaxseed than in those fed Megalac or soybeans. Dietary treatments had no effect on the antibody response to ovalbumin and on in vitro productions of interferon-γ and prostaglandin E2. However, interferon-γ and prostaglandin E2 were impaired in the first 3 wk after parturition regardless of dietary treatment. These results suggest that changes in fatty acids, progesterone, and prostaglandins E2 concentrations in serum due to dietary treatment and physiological status influenced systemic immunity as shown by reduced proliferative response. However, other mechanisms must be considered and are discussed to explain dietary effect on lymphocyte proliferative response to mitogenic stimulation and other immune functions.

Changes in Coronary Heart Disease Risk Among Japanese Exchange Students

The purpose of this study was to examine the effects of environmental changes (diet and exercise) on coronary heart disease (CHD) risk factors in Japanese exchange students when visiting the United States for six months and two months after their return to Japan. Thirteen subjects completed the study. While visiting the US, the subjects increased their consumption of calories and % calories derived from fat while they decreased their % calories derived from carbohydrates and dietary polyunsaturated to saturated fat ratio (P:S) The subjects’ serum fatty acid profiles showed an increased in the saturated fatty acids 15:0 and 24:0 while there was a trend of decreasing omega - 3 fatty acids. While in the US, subjects significantly increased their fitness level as estimated using a sub-maximal cycle ergometer test. Subjects significantly increased body weight and body mass index and showed an increased trend of percent body fat. Blood pressure and blood Hpid concentrations (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides) remained unchanged. Following their return to Japan, subjects significantly decreased caloric intake and % calories from fat compared to their US diets. Serum concentrations of the saturated fatty acids 15:0 and 24:0 significantly decreased while the omega-3 polyunsaturated fatty acid 22:6 increased. In addition, the ratio of eicosapentaenoic acid to arachadonic acid and total serum omega-3 fatty acids showed trends of increasing. Finally, body weight body fat, and body mass index significantly decreased.

Food intake, serum lipids and amino acids of school children in agricultural communities in Japan.

To investigate the correlation among serum lipids, amino acids and diet of children in Japan where the mortality of ischemic heart disease is still very low. Cross-sectional study. Two towns in Shimane prefecture, typical mountainous agricultural communities in the western part of the mainland of Japan. 514 children (10-15 y) in the communities were recruited. The mean cholesterol levels ranged from 3.9 to 4.4 mmol/l for boys and from 4.3 to 4.5 mmol/l for girls, and serum cholesterol level fell with age in boys. Serum cholesterol level of girls rose once between 11 and 13 y and fell gradually. Fish intake was positively correlated with serum omega-3 series fatty acids. Milk intake was negatively and soybean intake was positively correlated with omega-3/omega-6 series fatty acids ratio. Serum branched-chain amino acids were correlated negatively with serum polyunsaturated/saturated fatty acids ratio. Serum cholesterol level of children in agricultural communities in Japan has risen, and is probably affected by the change of food intake. Promoting the intake of soybean and fish, which are traditional Japanese foods, will be important in preventing atherosclerosis and ischemic heart disease. Attention should be paid to the relationship between branched-chain amino acids level in blood and fatty acids metabolism to verify the mechanism of the progress of atherosclerosis.