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Abstract Background: It was shown that a traditional Chinese medicine, Hochu - ekki - to (HET), had adjuvant effects in influenze vaccination in an animal experiment. This, however, could not [...]

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. [ABSTRACT FROM AUTHOR]

High calcium intake may increase hip fracture (HF) incidence. This phenomenon, known as the calcium paradox, might be explained by vaccenic acid (18:1t n-7, VA), the highly specific trans fatty acid (TFA) present in dairy products. First, we ecologically investigated the relationship between 18:1 TFA intake and HF incidence using data from 12 to 13 European countries collected before 2000; then we measured the effects of VA and elaidic acid (18:1t n-9, EA) on osteoblasts from goldfish scales (tissues very similar to mammalian bone), with alkaline phosphatase as a marker; and finally we measured the effect of VA on mRNA expression in the scales for the major bone proteins type I collagen and osteocalcin. HF incidence was significantly correlated with 18:1 TFA intake in men (r=0.57) and women (r=0.65). Incubation with 1μmol/L VA and EA for 48h significantly decreased alkaline phosphatase activity by 25% and 21%, respectively. Incubation of scales with 10μmol/L VA for 48h significantly decreased mRNA expression for type I collagen and osteocalcin (by about 50%). In conclusion, VA may be causatively related to HF and could explain the calcium paradox. It may be prudent to reduce 18:1 TFA intake, irrespective of trans positions, to prevent HF., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A diet rich in omega-3 polyunsaturated fatty acids (PUFAs) may decrease risk of cardiovascular disease by improving the blood lipid profile. The purpose of this review was to (1) determine if fish oil (omega-3) consumption increased the risk of hemorrhaging after a military injury and (2) whether an improvement in the omega-3 PUFA profile had an impact on survivability from military wounds. The authors found no evidence to contradict the existing U.S. Food and Drug Administration safety ruling that 3 g of omega-3 PUFA per day is generally regarded as safe. However, there is insufficient data with regard to the safety of consuming more than 3 g of omega-3 PUFA per day. More research is needed to safely recommend use of higher doses omega-3 PUFA., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

We have previously conducted a cohort study to investigate n-3 polyunsaturated fatty acids (PUFAs) in red blood cells (RBCs) and risk of all-cause mortality in hemodialysis (HD) patients over 5 years and found that n-3 PUFAs, especially docosahexaenoic acid (DHA), might be an independent predictor of all-cause mortality. In the present study, we extended the study for another 5 years to determine whether DHA levels in RBCs still predict the mortality of HD patients during a 10-year study period. The study cohort consisted of 176 patients (64.1 ± 12.0 [mean ± standard deviation] years of age, 96 men and 80 women) under HD treatment. The fatty acid composition of patients' RBCs was analyzed by gas chromatography. During the study period of 10 years, 97 deaths occurred. After adjustment for 10 confounding factors, the hazard ratio of all-cause mortality of the HD patients in the highest DHA tertile (>8.1%) was 0.52 (95% confidence interval 0.30-0.91) compared with those in the lowest DHA tertile (<7.2%). However, other n-3 PUFAs such as eicosapentaenoic acid and docosapentaenoic acid (n-3) did not reveal any significant correlations. The level of DHA in RBCs could be an independent predictor of all-cause mortality in HD patients even during a long period of follow-up., (© 2014 International Society for Hemodialysis.)

Aim: In previous animal studies, we confirmed that linoleic acid (LNA) enhanced colon carcinogenesis, whereas eicosapentaenoic acid (EPA) had protective effects in azoxymethane-induced colon tumorigenesis. In regard to the protective effects of marine n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer however, evidence from epidemiological studies is inconsistent., Materials and Methods: In the present study we investigated the fatty acid composition in plasma, red blood cells (RBCs) and adipose tissue from Japanese patients with colorectal cancer, or benign disease., Results: Sixty-one patients with histologically-confirmed colorectal cancer and 42 patients with non-malignant disease were recruited for this study. The fatty acid composition of the total phospholipid (PL) fraction of plasma and washed RBCs was determined by gas chromatography. The fatty acid composition of the triacylglycerol (TAG) fraction of subcutaneous adipose tissue was determined in a similar manner. The EPA proportion in the plasma and RBC PL fractions was significantly lower in patients with cancer than in the controls (p<0.05). Similarly, the LNA proportion in the RBC PL fraction was lower in patients with cancer, but no changes were found in the plasma PL fraction. Arachidonic acid was the only PUFA in the adipose TAG fraction that exhibited significant differences, with higher levels in the patients with cancer than in the controls., Conclusion: Our findings suggest that patients with cancer have abnormalities in PUFAs in the plasma PL, erythrocyte PL, and adipose TAG fractions. Further investigation is needed to clarify the differences in the results between the various fractions.

Little is known about nonpathological facial skin problems at present. The aim of the present study was to investigate the relationships among facial skin conditions, mood, and the fatty acid composition of red blood cells (RBCs) in women. One hundred and thirty-two apparently healthy Japanese women aged between 20 and 60 years were recruited. Facial skin conditions were analyzed using a Robo Skin Analyzer, and the RBC fatty acid composition was also determined. Questionnaires concerning mood were administered. Forehead pigmentation was more mood-dependent (in 20s group) and less arachidonic acid (AA)-dependent (in all participants) than that in other areas of the face. Actually there was no correlation in pigmentation between the forehead and other areas of the face when adjusted for age, smoking, and drinking. Skin conditions were adversely correlated with a negative mood. α-Linolenic acid concentrations were negatively correlated with negative mood scores. Pigmentation characteristics in the forehead were independent from other areas of the face. Negative mood and AA were adversely correlated with skin conditions.

The effects of polyunsaturated fatty acids on human cerebral blood oxygenation have yet to be extensively investigated. In this study, healthy participants (14 men, 40 women) aged between 20 and 49 years were recruited. All female participants entered the trial at the start of their menstrual cycle. Blood was sampled before measuring cerebral blood oxygenation in the prefrontal cortex (PFC) and prior to administering two kinds of questionnaires, the Profile of Mood States (POMS) and a questionnaire regarding participants' arousal level. Blood oxygenation in the PFC was continuously monitored immediately before and during the Uchida-Kraepelin Performance (UKP) test as a mental arithmetic task. Changes in the tissue oxygenation index (the ratio of oxyhemoglobin to oxyhemoglobin+deoxyhemoglobin; TOI, a simplified index for cerebral blood circulation) were measured by near-infrared spectroscopy. Multiple regression analysis was performed with sex, age, smoking and drinking as confounding factors. Eicosapentaenoic acid (EPA) was positively associated with TOI, which was positively associated with arousal level and inversely associated with negative mood (POMS). EPA and docosahexaenoic acid were inversely associated with depression-dejection (POMS) and positively associated with arousal level and overall performance in the UKP test. We suggest that EPA might increase the oxygenation level in the PFC, in turn improving various psychological parameters and performance., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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., (Copyright © 2010 S. Karger AG, Basel.)

Aim: To study the effects of eicosapentaenoic acid (EPA) on prostate-specific antigen (PSA) failure in prostate cancer patients who underwent prostatectomy., Patients and Methods: Sixty-two prostate cancer patients whose PSA levels were less than 0.2 ng/ml 3 months after surgery were randomized to either an EPA group (n=32) or a control group (n=30). EPA (2.4 g/day) was administered in the EPA group for 2 years. PSA was measured every two months., Results: The EPA concentration increased but the docosahexaenoic acid concentration decreased significantly (P<0.001) in erythrocytes. The PSA recurrence rates during a mean follow-up of 53.8 months were not different between the two groups (p=0.16)., Conclusion: A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence.

The composition of fatty acids in abdominal subcutaneous adipose tissue and the correlation of fatty acid values of plasma and erythrocytes had not been reported in Japan. The aim of the present study was to investigate the fatty acid composition and correlation of plasma and erythrocyte phospholipids (PL) and adipose triacylglycerols (TG) in 75 adult patients admitted for non-malignant diseases. We also examined the relationship of n-3 and n-6 polyunsaturated fatty acid (PUFA) with patients' characteristics. The total n-3 PUFA were 11.2, 11.8 and 1.9%, and the ratios of n-6/n-3 were 2.41, 1.87 and 8.20 in plasma and erythrocyte PL and adipose TG, respectively. There were the highest correlations for total n-3 PUFA and the n-6/n-3 ratio between plasma and erythrocyte PL and adipose TG. There was a positive correlation between n-3 PUFAs and age, but a negative correlation was found between n-6 PUFAs and age. There was no significant difference in the values of PUFAs in plasma and erythrocyte PL and adipose TG between men and women. The patients with cholesterol cholecystolithiasis showed a significantly lower proportion of eicosapentaenoic acid in plasma and erythrocyte PL than those of the other patients. Our findings suggest that PUFA in plasma and erythrocyte PL may be good biomarkers and more acceptable for studying participants than adipose TG.

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.

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.

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.

The "Study of EPA Effects on Prostate Cancer" (SEEPC) Group has been conducting a clinical trial with patients who underwent radical prostatectomy. The main purpose of the SEEPC is to evaluate whether eicosapentaenoic acid (EPA) prevents prostate cancer (PC) recurrence. As the surrogate marker of recurrence, the prostate-specific antigen (PSA) level was measured. However, if EPA affects the PSA values independently of PC, PSA may not be a good marker of recurrence in the event of EPA treatment. Thus, in the present study, whether EPA affected the PSA values was investigated using non-PC volunteers. Twenty men, of at least 50 years of age, were recruited, mostly from hospital staff The volunteers were randomly allocated either to the EPA group or the control. The subjects in the EPA group were administered EPA-ethyl ester a dose of 2400 mg/day for 12 weeks, whereas the controls were administered none. Fasting blood samples were obtained before the start of EPA administration and 4 and 12 weeks later. The EPA concentrations in erythrocytes increased in all the subjects in the EPA group (174+/-96%) with no significant changes in the control group (8.5+/-14.0%). There were no significant differences between the two groups in the serum PSA levels, allowing the conclusion that the PSA is an appropriate surrogate marker of recurrence in prostate cancer.

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.

Background: Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels., Methods: We recruited 100 suicide-attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography., Results: Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001). When the highest and lowest quartiles of EPA in RBC were compared, the odds ratios of suicide attempt was.12 in the highest quartile (95% confidence interval:.04-.36, p for trend =.0001) after adjustment for possible confounding factors, Conclusions: Our findings suggest that low n-3 fatty acid levels in tissues were a risk factor of suicide attempt. Further studies including intervention with fish oil are warranted.

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.

DHA is abundant in the brain. Deficiency of DHA changes behavior in animals. The purpose of the present studies was to clarify the effect of DHA intake on hostility and plasma catecholamines. In study 1, forty-one students took either DHA-rich oil capsules containing 1.5-1.8 g DHA/d (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mon in a double blind fashion. They took a psychological test (P-F Study) at the start and end of the study. Study I started at the end of summer vacation and ended in the middle of mental stress of final exams. In the control group, hostility measured by P-F Study was significantly increased at the end of the study as compared with that measured at the start (+58%), whereas it was not significantly changed in the DHA group (-14%). In a similar double blind two-mon study (study 2), we measured plasma catecholamines and cortisol of students (3 females and 4 males for the DHA group and the same numbers for the control) at the start and end of the study. In study 2 the students were under a continuous stress of final exams that lasted for two mon throughout the whole study period. The plasma cortisol did not change in either group, but the norepinephrine concentration was significantly decreased in the DHA group (-31%), whereas it stayed at the same level in the control group. These effects of DHA intake may be applied to people under psychological stress.

Fish oils, purified eicosapentaenoic acid and docosahexaenoic acid (DHA) have been reported to improve blood lipid concentrations, especially those of triglycerides in humans. However, to our knowledge there have been no double-blind studies investigating the effects of DHA-rich fish oil on blood lipid concentrations. Therefore, we conducted a placebo-controlled double-blind study. Twenty-four healthy, normolipidemic young adults took either DHA-rich fish oil capsules containing 1.5-1.8 g of DHA or control oil capsules containing 97% soybean oil and 3% fish oil for 13 wk. Blood samples were taken at the start and end of the study, and serum lipids concentrations were compared. There were no significant changes over time in the DHA group in the following serum lipids: total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), and apolipoproteins A1 and B. In contrast, apolipoprotein A1 concentrations slightly (10%) but significantly increased over time in the control group. Docosahexaenoic acid at a dose of less than 2 g/d did not change serum lipid concentrations of normolipidemic subjects. The effects of DHA in hyperlipidemic patients remain to be investigated in a double-blind study.