Docosahexaenoic acid is an independent predictor of all-cause mortality in hemodialysis patients.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid have been shown to reduce cardiovascular mortality. Patients on hemodialysis (HD) have a very high mortality from cardiovascular disease. Fish consumption reduces all-cause mortality in patients on HD. Moreover, n-3 PUFAs, especially DHA levels in red blood cells (RBCs), are associated with arteriosclerosis in patients on HD. The aim of this study was to determine whether DHA levels in RBCs predict the mortality of patients on HD in a prospective cohort study. METHODS: A cohort of 176 patients (64.1 ± 12.0 (mean ± SD) years of age, 96 men and 80 women) under HD treatment was studied. The fatty acid composition of their RBCs was analyzed by gas chromatography. RESULTS: During the study period of 5 years, 54 deaths occurred. After adjustment for 10 confounding factors, the Cox hazard ratio of all-cause mortality of the patients on HD in the highest DHA tertile (>8.1%, 15 deaths) was 0.43 (95% CI 0.21-0.88) compared with those patients in the lowest DHA tertile (<7.2%, 21 deaths). CONCLUSION: The findings suggest that the level of DHA in RBCs could be an independent predictor of all-cause mortality in patients on HD.

The effects of docosahexaenoic acid-rich fish oil on behavior, school attendance rate and malaria infection in school children--a double-blind, randomized, placebo-controlled trial in Lampung, Indonesia.

BACKGROUND: There are only a very limited number of reports of intervention studies on the effects of fish oil on behavior in normal school children. OBJECTIVE: To observe the effects of fish oil on behavior and school attendance rates in school children. DESIGN: Fourth to sixth graders (mostly 9-12 years of age) of an elementary school in Lampung Province, Indonesia, were randomly divided into either a docosahexaenoic acid (DHA) group (n=116) or a control group (n=117) in a double-blind manner. The subjects in the DHA group took 6 fish oil capsules per day (0.65 g DHA and 0.10 g eicosapentaenoic acid (EPA)/day) for 3 months. Controls took soybean oil capsules. Two questionnaires were administered and blood was taken at the start and end of the study. Two questionnaires were administered at the start and end of the study: Hostility-Aggression Questionnaire for Children (HAQ-C) and Barratt Impulsiveness Scale, version 11 (BIS-11), for measurement of aggression and impulsivity, respectively. Attendance was recorded during the study period. OUTCOMES: The concentrations of DHA and EPA in the phospholipid fraction in red blood cells were significantly increased in the DHA group. Behavior checked with HAQ-C or BIS-11 did not show any differences between groups. However, the odds ratio of inability to attend school regularly during the study period was 0.40 (95%CI: 0.23-0.71) in the DHA group compared with controls (p=0.002). CONCLUSIONS: DHA-rich fish oil may improve the school attendance rate of children in Lampung, Indonesia.

Factors influencing EPA+DHA levels in red blood cells in Japan.

The blood eicosapentaenoic and docosahexaenoic acid (EPA+DHA) concentration is an important inverse risk factor for sudden cardiac death. However, it is not known what kinds of factors influence the EPA+DHA levels in the total phospholipid fraction in red blood cells (RBC EPA+DHA) in Japan, who regularly eat more fish with increasing age. Four hundred and fifty-six healthy individuals (320 men and 136 women, 18 to 70 years old) were recruited between 2002 and 2005. RBC EPA+DHA were measured by gas chromatography and questionnaires were administered. Multivariate analysis indicated that there were significant correlations between RBC EPA+DHA and (i) dietary EPA+DHA (beta=0.31), (ii) age (beta=0.33), (iii) gender (beta=-0.15) and (iv) physical activity (beta=-0.11) but not with body mass index or smoking.

The effects of eicosapentaenoic acid-fortified food on inflammatory markers in healthy subjects--A randomized, placebo-controlled, double-blind study.

Epidemiological studies showed that habitual fish intakes were associated with lower blood inflammatory markers. In the present study the effects of a fish oil-containing food on inflammatory markers were investigated in healthy, mostly middle-aged subjects (59 men and 82 women) with normal to mildly elevated triglyceride levels. Study subjects were randomly allocated to two groups in a double-blind manner; one group ingested an eicosapentaenoic acid (EPA)-rich fish oil-fortified drink (0.60 g EPA+0.26 g docosahexaenoic acid/d. EPA group, n=68) for 12 wk. The rest of the subjects took a placebo (control group, n=73). Plasma levels of high sensitivity C-reactive protein (hs-CRP) and soluble tumor necrosis factor-receptors 1 and 2 (sTNF-Rs 1 and 2) were measured at the start and end of intervention. EPA concentrations in the total RBC phospholipid fraction significantly increased by 79% in the EPA group at the end of the study, and they changed very little in the control group (+0.68%). The inflammatory markers did not change in either group. It is likely that fish oil does not change hs-CRP or sTNF-Rs 1 or 2 in subjects without active inflammation.

Fish oil reduces tooth loss mainly through its anti-inflammatory effects?

Competing at several steps of arachidonic acid metabolism, n-3 fatty acids reduce production of highly active prostaglandins and leukotrienes and exert anti-inflammatory effects. They are also experimentally shown to be anti-osteoporotic. Periodontitis is responsible for most tooth loss in adult populations. If enough n-3 fatty acids are provided, periodontitis with alveolar bone resorption may be controlled, and tooth loss may be prevented. In fact, n-3 fatty acid administration lowered prostaglandin E(2) production, tooth movement and alveolar bone resorption in animal experiments. Aggression, which may be related with tooth loss, was also controlled with fish oil. Our cross-sectional data supported our hypothesis. We recruited 256 men (22-59 y of age) and 95 women (22-66 y), counted the numbers of their remaining teeth, and analyzed the fatty acid composition of the total phospholipid fraction of RBCs. The beta-coefficient of the numbers of remaining teeth and EPA concentrations in the fraction was 0.89 (per 1% EPA, p=0.007) after adjustment for 9 possible confounding factors. Long-term intervention studies with fish oil planned in the future should be able to test our hypothesis by just adding another very simple endpoint in those studies: tooth loss during the intervention period. This hypothesis may explain the linkage between periodontitis/tooth loss and coronary heart disease.

The relationship between tissue RBC n-3 fatty acids and pulse wave velocity.

Consumption of n-3 fatty acids is well-known to prevent deaths from coronary heart disease. However, not many studies have investigated the effects of n-3 fatty acids on arteriosclerosis in free living subjects. The pulse wave velocity between the brachia and ankles (baPWV) of 161 healthy male subjects was measured and the fatty acid composition of the total phospholipid fraction of their red blood cells (RBC) analyzed. There was a significant inverse correlation between the eicosapentaenoic acid concentrations in the RBC phospholipid fraction and baPWV of the subjects after adjustment for age, pulse rate and diastolic pressure, or further for body mass index, smoking status, diabetes and the ratio of low-density cholesterol to high-density cholesterol. Although baPWV values may not directly indicate arteriosclerosis, the present study suggests that long-term n-3 fatty acid intake is beneficial for the vascular system.

Effects of cooking plant oils on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: One-third of the total population seems to develop minor recurrent aphthous stomatitis (RAS) during their lifetime. However, well-controlled dietary intervention studies to prevent minor RAS are very rare. The objective of the present study was to investigate whether the prevalence of RAS decreased with perilla oil (rich in alpha-linolenic acid). METHODS: Thirty subjects (8 men and 22 women) who had minor RAS at least once a month were randomly allocated to a soybean oil group or a perilla oil group in a double-blind manner (experimental phase) after a run-in phase of 4 mo during which subjects used a reference oil, the most popular cooking oil in Japan, or a 50/50 mixture of soybean oil and rapeseed oil. During the experimental phase, subjects were asked to use soybean oil or perilla oil as the sole cooking oil for 8 mo. Blood samples were collected at the start and end of the experimental phase for fatty acid analysis of total plasma phospholipid fraction. Occurrence and needed days for healing of minor RAS were recorded during the two phases and compared. RESULTS: alpha-Linolenic acid concentrations in the plasma phospholipid fraction increased significantly in both groups during the experimental phase to a similar extent. The prevalence of minor RAS in the experimental phase decreased significantly in both groups compared with the run-in phase to a similar extent, without intergroup differences. CONCLUSION: Perilla oil, which is rich in alpha-linolenic acid, was not superior to soybean oil in preventing minor RAS. There was a possibility that avoiding rapeseed oil might be beneficial for prevention of minor RAS.

Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: We previously reported that administration of fish oil rich in docosahexaenoic acid (DHA) increased the plasma ratio of epinephrine to norepinephrine (NE) at rest in young adults who were under chronic stress and that this effect was achieved mainly through depression of NE. However, not many reports have documented the effects of eicosapentaenoic acid (EPA) and DHA on blood catecholamine levels in healthy humans. Therefore, we performed another intervention study to test their effect on catecholamines with healthy subjects under no chronic stress. METHODS: Twenty-one healthy young adults (15 men and 6 women) were randomly assigned to an omega-3 group (n = 9) or a control group (n = 12) in a double-blind manner. Twenty capsules of shellfish-derived lipids containing 762 mg of EPA plus DHA per day were administered to the omega-3 group for 2 mo. The controls took the same amount of placebo capsules. Fasting blood samples after a 30-min rest with a catheter in a forearm vein were obtained at the start and the end of the study for catecholamine measurements. RESULTS: EPA but not DHA concentrations in red blood cells significantly increased in the omega-3 group compared with the control group (P < 0.001). Plasma NE concentrations were significantly decreased in the omega-3 group (from 1.49 +/- 0.39 nmol/L to 1.05 +/- 0.14 nmol/L) compared with the control group (from 1.12 +/- 0.24 nmol/L to 1.39 +/- 0.32 nmol/L) with analysis of covariance (P < 0.001). The differences remained significant (P = 0.01) even after deletion of three subjects in the omega-3 group who had the highest baseline NE values and one in the control group who had the lowest baseline NE value to nullify a significant baseline differences in NE between groups. CONCLUSION: This study demonstrated that EPA plus DHA supplementation lowered plasma NE concentrations in normal volunteers even at the small dose of 762 mg of EPA plus DHA per day. This effect of EPA plus DHA to lower plasma NE concentrations may be important to understand some of the effects of fish oils on diseases.

The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The aim of the study was to investigate whether fish oil supplementation affected Japanese schoolchildren's behavior, with changes in aggression over time as the primary endpoint. DESIGN AND SUBJECTS: A placebo-controlled double-blind study with 166 schoolchildren 9-12 years of age was performed. The subjects of the fish oil group (n=83) took fish oil-fortified foods (bread, sausage and spaghetti). These foods were provided in amounts such that each subject in the fish oil group had an intake of 3600 mg of docosahexaenoic acid+840 mg of eicosapentaenoic acid (EPA)/week for 3 months. The rest (the controls, n=83) took control supplements. At the start and end of the study, psychological tests were performed to assess their aggression. RESULTS: Physical aggression assessed by Hostility-Aggression Questionnaire for Children in girls increased significantly (median: 13 to 15, n=42) in the control group and did not change (13 to 13, n=43) in the fish oil group with a significant intergroup difference (P=.008) with baseline as covariate. The changes in physical aggression scores over time and those of the ratio of EPA/arachidonic acid in RBC (DeltaEPA/AA) were significantly correlated in girls who agreed to blood collection (r=-.53, P=.01, n=23). On the contrary, there were no significant changes in physical aggression in boys. Aggression against others (extraggression) assessed by Picture Frustration Study did not change in the control group (median: 5 to 5) but increased significantly in the fish oil group (4 to 5) with a significant intergroup difference (P=.02) with baseline as covariate. These changes in extraggression might be explained partly by significantly lower baseline values of extraggression in the fish oil group (P=.02) than in the control group. There were no significant correlations between Deltaextraggression and DeltaEPA/AA in blood-sampled children (n=49). Impulsivity of girls assessed by parents/guardians using the diagnostic criteria for attention deficit/hyperactivity disorder of DSM-IV was reduced in the fish oil group (1 to 0) with a significant (P=.008) intergroup difference from the control group (1 to 1). There were no significant correlations between Deltaimpulsivity and DeltaEPA/AA in blood-sampled girls. In males, impulsivity reduced in both groups without any intergroup differences. CONCLUSION: There is a possibility that changes in fatty acid nutrition might affect physical aggression especially in girls.

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans.

A large number of papers have reported that administration of n-3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n-3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n = 41) whose serum TG concentrations were 100-300 mg/dL were recruited and randomly assigned to either an n-3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n-3 FA group were administered 125 mL of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8, and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n-3 FA group, with no significant changes in the control group. TG levels decreased more in the n-3 FA group than in the control group at weeks 4 (P < 0.05), 8 (P < 0.01), and 12 (P < 0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n-3 FA group than in the control at weeks 8 (P < 0.01) and 12 (P < 0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n-3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.