Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Puerarin improves OVX-induced osteoporosis by regulating phospholipid metabolism and biosynthesis of unsaturated fatty acids based on serum metabolomics.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a serious problem for the women over 50 years old. Natural product puerarin (PUE) has been proven to improve PMOP with high safety. PMOP is a metabolic disorder affecting bone metabolism, indicating that endogenous metabolites amelioration may be a novel strategy for PMOP therapy. However, what the metabolic profile of POMP will be after PUE treatment is still obscure. PURPOSE: We purpose to figure out the metabolic characteristics of PMOP and to explore the intrinsic mechanism on the anti-osteoporosis efficacy after PUE treatment based on the serum metabolomics. METHODS: We established OVX rats as osteoporosis model, and the animals were distributed into Sham, OVX, and OVX+PUE (100 mg/kg/d) group. The femurs were analyzed by µ-CT and three-point bending test. Serum metabolomics was performed by UPLC/Q-TOF-MS. We also determined the body weight, liver weight, and the levels of serum TC, TG, LDL-C, and HDL-C. The key proteins of the PPARγ pathway and Wnt pathway were analyzed by Western blot and qPCR experiments. RESULTS: PUE treatment for 14 weeks both improved the bone structure and ameliorated lipid metabolism in ovariectomized rats. By determination and further analysis of serum metabolomics, we revealed that the endogenous metabolites was significantly changed in ovariectomized rats, and PUE treatment adjusted 23 differential metabolites, which were involved in phospholipid metabolism metabolism and PUFAs metabolic pathways. Close correlationships were futher found between the indexes of bone metabolism, lipid metabolism and the differential metabolites, particularly LysoPA, S1P and n-3/n-6 PUFAs. Further, we discovered that PUE regulated differentiation of BMSCs to elicit anti-osteoporosis efficacy, attributing to Wnt/ß-catenin signaling activation and PPARγ pathway inhibition initiated by metabolomics. CONCLUSION: PUE improves OVX-induced osteoporosis and lipid metabolism by regulating phospholipid metabolism and biosynthesis of PUFAs, resulting in reducing the adipogenic differentiation and promoting osteogenic differentiation of BMSCs via Wnt pathway activation and PPARγ pathway inhibition in ovariectomized rats. The study provides us a novel mechanism to explain the improvement of osteoporosis by PUE, depicts a metabolic profile of PMOP, and gives us another point cut for further exploring the pathogenesis of PMOP and looking for biomarkers of osteoporosis.

Specialized Proresolving Mediators in Symptomatic Women With Coronary Microvascular Dysfunction (from the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD [WARRIOR] Trial).

Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients.

Trimester-Specific Reference Ranges for Saturated, Monounsaturated and Polyunsaturated Fatty Acids in Serum of Pregnant Women: A Cohort Study from the ECLIPSES Group.

In the course of pregnancy, increasing importance is being placed on maintaining optimal fatty acid (FA) levels and particularly n-3 PUFAs to ensure correct fetal development. However, reference ranges for FA have been reported in only a few studies. Our objective is to provide quantitative reference intervals for SFAs, MUFAs, and PUFAs (n-6 and n-3) in a large population of healthy pregnant women from a developed country. A prospective study of pregnant women (n = 479) was conducted from the first trimester (T1) to the third trimester (T3). A total of 11 fatty acids were analyzed in serum by gas chromatography mass spectrometry and were expressed as absolute (µmol/L) and relative (percentage of total FA) concentration units. Serum concentrations of SFAs, MUFAs, n-6 PUFAs, n-3 PUFAs, various FA ratios, and the EFA index were determined. The reference intervals (2.5/97.5 percentiles) in absolute values from T1 ranged from 1884.32 to 8802.81 µmol/L for SFAs, from 959.91 to 2979.46 µmol/L for MUFAs, from 2325.77 to 7735.74 µmol/L for n-6 PUFAs, and from 129.01 to 495.58 µmol/L for n-3 PUFAs. These intervals mainly include the values of other studies from European populations. However, reference ranges vary according to some maternal factors. The FA levels proposed, obtained from a large sample of pregnant women, will be a useful tool for assessing the degree of adequacy of FAs in pregnant women and will help to carry out dietary interventions based on certain maternal factors.

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (-50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.

The associations of circulating common and uncommon polyunsaturated fatty acids and modification effects on dietary quality with all-cause and disease-specific mortality in NHANES 2003-2004 and 2011-2012.

BACKGROUND: Associations of dietary or supplementary intake of several unsaturated fatty acids and mortality have been widely studied but the results were still hitherto inconsistent or limited. It is still need to explore the effects of these fatty acids by using the objective biomarkers. OBJECTIVE: We aimed to investigate the relevancy of several serum n-3 and n-6 fatty acids with all-cause and disease-specific mortality to confirm their health effects and effects on the associations between dietary quality and all-cause mortality. METHODS: A total of 4132 people from NHANES 2003-2004 and 2011-2012 and the mortality information was confirmed from the NDI. CPH models adjusted for known risk factors were conducted to explore the associations between circulating n-3 and n-6 fatty acids and all-cause or CVD or cancer mortality under complex sampling. We further evaluated their effects on association between dietary quality and all-cause mortality. RESULTS: A total of 437 deaths occurred during the mean follow-up of 83.34 months, including 157 CVD death and 100 cancer death. Serum LA, ALA, EPA and DHA were associated with all-cause mortality (HR in quintile5: LA:0.584, 95%CI: 0.387-0.882, Ptrend = 0.011; ALA:0.626, 95%CI: 0.432-0.907, Ptrend = 0.008; EPA:0.535, 95%CI: 0.375-0.764, Ptrend = 0.001; DHA:0.669, 95%CI: 0.468-0.955, Ptrend = 0.031). Additionally, serum EPA and ALA were respectively related to CVD and cancer mortality (Q5 HR: EPA:0.450, 95%CI: 0.23-0.854, Ptrend = 0.009; ALA:0.387, 95%CI: 0.167-0.900, Ptrend = 0.022). Serum AA, GLA, DGLA and SDA were not associated with any risk of mortality. The effect on all-cause mortality of the lower AHEI scores can be improved by adherence to a higher serum LA, EPA and DHA (in the lowest AHEI strata, LA in tertile3 compared to tertile1 HR:0.596, 95%CI: 0.366-0.970; EPA:0.660, 95%CI: 0.454-0.959; DHA:0.666, 95%CI; 0.444-1.000). CONCLUSIONS: Our results support the recent dietary recommendations to increase the intake of plant-derived and marine-derived n-6 and n-3 to improve the ability of primary and secondary prevention.

Blood fatty acid analysis reveals similar n-3 fatty acid composition in non-pregnant and pregnant women and their neonates in an Israeli pilot study.

Maternal docosahexaenoic acid (DHA) is required during pregnancy to supply for normal fetal growth and development. This pilot study aimed to assess the unknown fatty acid (FA) composition in a cohort of non-pregnant and pregnant Israeli women at term and their offspring on a normal diet without n-3 FA supplementation. The fatty acid profile, analyzed using gas chromatography, showed significantly higher plasma monounsaturated (MUFA) and lower n-6 FA percent distribution with similar n-3 index, in pregnant compared to non-pregnant women. RBC exhibited significantly higher MUFA with similar n-3 index, in pregnant compared to non-pregnant women. N-3 FA significantly correlated between neonates' plasma, with higher n-3 index, and pregnant women's DHA. Conclusion: DHA levels in non-pregnant and pregnant Israeli women at term were comparable and the DHA in pregnant women's plasma positively correlated with their neonate's level, suggesting an efficient mother-fetus FA transfer and/or fetal fatty acid metabolism to longer FA products.

The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study.

BACKGROUND: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season. METHODS: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p< .05. RESULTS: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 - .005, drange = 0.59-0.85]). CONCLUSIONS: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes. TRIAL REGISTRATION: This trial was registered with the ISRCTN registry ( ISRCTN90306741 ).

Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.

BACKGROUND: Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS: We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS: We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P  <  0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P  <  0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P  <  0.05). CONCLUSIONS: GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis.

BACKGROUND: Keratinocyte cancer is the commonest cancer, imposing a high economic burden on the health care system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFA) and keratinocyte cancer, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We explored whether genetically predicted PUFA levels are associated with BCC and SCC risks. METHODS: We conducted a two-sample Mendelian randomization study using PUFA level genome-wide association studies (GWAS) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC (n = 651,138) and SCC (n = 635,331) risk. RESULTS: One SD increase in genetically predicted levels of linoleic acid [OR = 0.94, 95% confidence interval (CI) = 0.91-0.97, P = 1.4 × 10-4] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10-4) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10-4) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, P = 1.5 × 10-3) were associated with an increased BCC risk. CONCLUSIONS: Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk. IMPACT: PUFA-related diet and supplementation could influence BCC etiology.

Association of circulating omega 3, 6 and 9 fatty acids with gestational diabetes mellitus: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM. METHODS: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies. RESULTS: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles. CONCLUSIONS: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO ( www.crd.york.ac.uk/PROSPERO ) as CRD42020196122.

Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study.

BACKGROUND: The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. METHODS: RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. RESULTS: Having RBC EPA+DHA in the second quintile (4.2-4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. CONCLUSIONS: There is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed.

Associations Between Macronutrients From Different Dietary Sources and Serum Lipids in 24 639 UK Biobank Study Participants.

[Figure: see text].

Omega-3 polyunsaturated fatty acid intake and plasma fatty acids of school going Indian children - a cross-sectional study.

Long-chain omega-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an essential role in cognitive and behavioural changes among school going children. This study delineates the dietary omega-3 PUFA [alpha-Linolenic acid (ALA), DHA, and EPA] intake and plasma fatty acids levels among school-going children. This is a cross-sectional study purely observational in nature, wherein 625 apparently healthy boys and girls aged between 7 and 13 years were selected from five different schools of Hyderabad. Dietary information on omega-3 PUFA (ALA, DHA, and EPA) intake was collected using a food frequency questionnaire. Plasma fatty acid concentrations were measured in 34% of sub-sample using standard gas chromatography. The study revealed that the average dietary intakes of omega-3 PUFA, ALA, DHA, and EPA were 55.46, 15.82, 35.59, 4.06 mg/day, respectively. There was a significant difference in mean DHA intake among gender and age group [girls (38.64±1.45 mg/day), boys (31.80±1.38 mg/day) p < 0.001] and [7-10 years (31.75±1.38 mg/day), 11-13 years (38.07±1.40 mg/day) p < 0.01]. The mean plasma DHA and DPA levels of overall subjects were 0.98 nmol% and 0.18nmol% respectively which was comparable among different gender, age and BMI-for age groups. There was a positive correlation between dietary DHA intake and plasma DHA level [ρ=0.376 (p < 0.001)]. The current study demonstrated that the omega-3 PUFA intake in school going children was less and reinforces the importance of increasing the omega-3 PUFA intake through diet and supplements.

4-week eicosapentaenoic acid-rich fish oil supplementation partially protects muscular damage following eccentric contractions.

BACKGROUND: We previously showed 8-week of fish oil supplementation attenuated muscle damage. However, the effect of a shorter period of fish oil supplementation is unclear. The present study investigated the effect of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for 4 weeks on muscular damage caused by eccentric contractions (ECCs) of the elbow flexors. METHODS: Twenty-two untrained men were recruited in this double-blind, placebo-controlled, parallel design study and the subjects were randomly assigned to the EPA and DHA group (EPA and DHA, n = 11) and placebo group (PL, n = 11). They consumed either EPA 600 mg and DHA 260 mg per day or placebo supplement for 4 weeks prior to exercise. Subjects performed 60 ECCs at 100 % maximal voluntary contraction (MVC) using a dumbbell. Changes in MVC torque, range of motion (ROM), upper arm circumference, muscle soreness, echo intensity, muscle thickness, serum creatine kinase (CK), and interleukin-6 (IL-6) were assessed before exercise; immediately after exercise; and 1, 2, 3, and 5 days after exercise. RESULTS: ROM was significantly higher in the EPA and DHA group than in the PL group immediately after performing ECCs (p < 0.05). No differences between groups were observed in terms of MVC torque, upper arm circumference, muscle soreness, echo intensity, and thickness. A significant difference was observed in serum CK 3 days after ECCs (p < 0.05). CONCLUSIONS: We concluded that shorter period EPA and DHA supplementation benefits joint flexibility and protection of muscle fiber following ECCs.

Association of plasma polyunsaturated fatty acids with arterial blood pressure: A Mendelian randomization study.

ABSTRACT: High polyunsaturated fatty acids (PUFAs) intake is recommended for primary and secondary prevention of cardiovascular disease (CVD). However, the association of PUFAs with blood pressure (BP) is still controversial. In the present study, two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship of PUFAs with BP, including systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP).Genetic instruments and summary statistics for two-sample MR analysis were obtained from 3 large-scale genome-wide association studies (GWASs). Eight single nucleotide polymorphisms (SNPs) significantly (P < 5 × 10-8) related to 6 PUFAs were used as instrumental variables. Conventional inverse-variance weighted method was adopted to evaluate the causality of PUFAs with BP; the Weighted Median, MR-egger, and Leave-one-out method were used for sensitivity analyses.As a result, there was no evidence of a causal association between all PUFAs and SBP. In addition, arachidonic acid (AA, ß = -0.04, P < .001) and eicosapentaenoic acid (EPA, ß = -0.47, P = .02) were negatively associated with DBP, while linoleic acid (LA, ß = 0.03, P = .005) and α-linolenic acid (ALA, ß = 3.83, P < .001) were positively associated with DBP. There was no evidence of a causal relationship between either docosapentaenoic acid (DPA) or docosahexaenoic acid (DHA) with DBP.In conclusion, a genetic predisposition to plasma polyunsaturated fatty acid (PUFA) had a divergent effect on DBP, independent of SBP. It suggested that it is helpful for lower DBP level to supplemental intake of AA and EPA or promote the conversion of LA and ALA to AA and EPA respectively, which need to be further validated with randomized controlled studies.

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood.

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5'-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20-59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (ß) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (ß = 0.138, b = 0.104, p = 0.0004), DHA (ß = 0.101, b = 0.058, p = 0.036), EPA + DHA (ß = 0.125, b = 0.073, p = 0.005), EPA/AA (ß = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (ß = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer's Dementia in the Oldest Old.

BACKGROUND: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties. METHODS: We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD. RESULTS: During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia. CONCLUSIONS: Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.

Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity.

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs-microbiome-immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.