PUFA, genotypes and risk for cardiovascular disease.

Polyunsaturated fatty acids (PUFAs) are long chain fatty acids that are characterized by the presence of more than one double bond. These include fatty acids such as ꞷ-3-α-linolenic acid (ALA) and ꞷ-6 -linoleic acid (LA) which can only be obtained from dietary sources and are therefore termed essential fatty acids. They contain the building blocks for dihomo-γ-linolenic acid and arachidonic acid in the ꞷ-6 family as well as eicosapentaenoic acid and docosahexaenoic acid in the ꞷ-3 family. Both ALA and LA are important constituents of animal and plant cell membranes and are important components of anti-inflammatory and pro-inflammatory hormones and therefore, often modulate cellular immunity under chronic inflammatory states. The variation in physiological PUFA levels is under significant genetic influence, the fatty acid desaturase (FADS) genes being key regulators of PUFA metabolism. These genetic variants have been shown to alter fatty acid metabolism and influence the onset and progression of various metabolic conditions. This detailed review discusses the role of PUFAs, diet and genotypes in risk for cardiovascular diseases.

Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies.

OBJECTIVE: To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer. DESIGN: Systematic review and meta-analysis of prospective cohort studies. DATA SOURCES: PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021. STUDY SELECTION: Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer. DATA SYNTHESIS: Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality. RESULTS: 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I2=37.1%, n=14). CONCLUSIONS: The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021229487.

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.

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.

Complex patterns of circulating fatty acid levels in gestational diabetes mellitus subclasses across pregnancy.

BACKGROUND & AIMS: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. METHODS: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). CONCLUSIONS: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

Time Course and Sex Effects of α-Linolenic Acid-Rich and DHA-Rich Supplements on Human Plasma Oxylipins: A Randomized Double-Blind Crossover Trial.

BACKGROUND: Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins. OBJECTIVES: Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined. METHODS: Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed. RESULTS: ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA. CONCLUSIONS: DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588.

Metabolomics Study of Whole-body Vibration on Lipid Metabolism of Skeletal Muscle in Aging Mice.

Ageing increases the occurrence and development of many diseases. Exercise is believed to be an effective way to improve ageing and skeletal muscle atrophy. However, many elderly people are unable to engage in active exercise. Whole-body vibration is a passive way of moving that is especially suitable for the elderly and people who find it inconvenient to exercise. Metabolomics is the systematic study of metabolic changes in small molecules. In this study, metabolomics studies were performed to investigate the regulatory effect of whole-body vibration on the skeletal muscles of ageing mice. After 12 weeks, we found that whole-body vibration had the most obvious effect on lipid metabolism pathways (such as linoleic acid, α-linolenic acid metabolism, glycerophospholipid metabolism pathways) in skeletal muscle of ageing mice. Through further research we found that whole-body vibration decreased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein in blood; decreased the lipid deposition in skeletal muscle; decreased the protein expression of monocyte chemoattractant protein-1 and interleukin-6; improved the protein levels of phosphorylated insulin receptor substrate-1, phosphate phosphoinositide 3-kinase and p-AKT; improved the protein levels of klotho; and decreased the protein expression of p53. These findings reveal that whole-body vibration might postpone senility by attenuating lipid deposition and reducing chronic inflammation and the insulin resistance of skeletal muscle.

Dietary and plasma blood α-linolenic acid as modulators of fat oxidation and predictors of aerobic performance.

BACKGROUND: Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain n-3 PUFAs, and it has pleiotropic effects, such as functioning as an energy substrate during long-term training when carbohydrate reserves are depleted. The purpose of this investigation was to study the link between the essential dietary and plasma ALA and aerobic performance, which is estimated via maximal fat oxidation (MFO), among skiers. METHODS: Twenty-four highly trained male athletes from the Russian cross-country skiing team participated in the study. ALA intake was determined by an original program used to assess the actual amount and frequency of fat consumption. The plasma level of ALA was determined using gas-liquid chromatography. The skiers' aerobic performance was estimated via MFO and determined by indirect calorimetry using the system "Oxycon Pro". RESULTS: The consumption of ALA in the diet in half of the skiers was below the recommended level at 0.5 ± 0.2 g/day. The deficiency of plasma ALA levels was on average 0.2 ± 0.1 Mol% for almost all participants. The consumption of ALA in the diet and its level in plasma were associated with MFO (rs = 0.507, p = 0.011; rs = 0.460, p = 0.023). Levels of ALA in plasma (p = 0.0523) and the consumption of ALA in the diet (p = 0.0039) were associated with high aerobic performance. CONCLUSIONS: ALA in the diet of the athletes may be used as nutritional support to increase MFO and aerobic performance.

Serum polyunsaturated fatty acids in infancy are associated with body composition in adolescence.

BACKGROUND: Polyunsaturated fatty acids (PUFA) have been related to the development of adiposity. N-3 PUFA appears to be protective against obesity risk, while n-6 PUFA may be associated with greater adiposity. However, most studies have been conducted among adults. The role of PUFA in infancy is unknown. OBJECTIVE: To examine associations of serum PUFA at age 1 year with age- and sex-adjusted body mass index Z score (BMIZ) change through age 16 years and body composition at 16 years. METHODS: We quantified serum PUFA in 636 Chilean infants aged 1 year. We measured BMIZ at ages 1, 5, 10 and 16 years, and body composition by dual energy X-ray absorptiometry at 16 years. We estimated differences in 1- to 16-years BMIZ change between PUFA quartiles from multivariable linear mixed models with restricted cubic splines. At 16 years, we estimated differences in total fat mass (ToFM), truncal fat mass (TrFM), total lean mass (TLM), percent total fat mass (%ToFM) and percent truncal fat mass (%TrFM) between PUFA quartiles using linear regression. RESULTS: PUFA were not associated with BMIZ change. Alpha-linolenic acid (ALA) was positively associated with TrFM (P = .03) and %TrFM (P < .0001) at 16 years while eicosapentaenoic acid (EPA) was inversely associated with %TrFM (P = .001). Docosapentaenoic acid (DPA) was positively associated with ToFM (P = .01), TrFM (P = .009), %ToFM (P = .02) and %TrFM (P = .02). Gamma-linolenic acid (GLA) and the Δ6-desaturase (D6D) activity index were each positively, linearly associated with ToFM, TrFM and %ToFM. The Δ5-desaturase (D5D) activity index was inversely associated with %TrFM (P = .04). CONCLUSIONS: ALA, DPA, GLA and the D6D index at 1 year of age were positively associated with adiposity at age 16 years, while EPA and the D5D index were inversely associated with central adiposity. Our results related to EPA and desaturase indices are in agreement with limited prior studies.

Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study.

Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes ?5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.

Maternal polymorphisms in the FADS1 and FADS2 genes modify the association between PUFA ingestion and plasma concentrations of omega-3 polyunsaturated fatty acids.

There is a lack of studies about polymorphisms in FADS genes in pregnant women. We aimed to verify the interaction between three FADS gene polymorphisms (rs174561; rs174575; rs3834458) and dietary α-linolenic acid (ALA) or linoleic/α-linolenic acid ratio (LA/ALA) and plasma concentrations of omega-3 (n-3) PUFAs in pregnant women. Of the 250 women evaluated, the homozygous for the rs174561 and rs3834458 minor allele had high plasma ALA concentrations at the highest ALA and LA/ALA ratio tertile (p < 0.05). Plasma concentrations of EPA and DHA were not influenced by diet. For the rs174575 SNP, pregnant women who carried the minor allele presented lower proportions of plasma EPA in the second LA/ALA ratio tertile (p < 0.05). Increased dietary intake of ALA and LA/ALA ratio promoted plasma ALA accumulation in homozygotes for the minor allele rs174561 and rs3834458. Moderate intake of LA/ALA ratio may reduce plasma concentration of EPA in pregnants carrying the rs174575 minor allele.

Single-Dose SDA-Rich Echium Oil Increases Plasma EPA, DPAn3, and DHA Concentrations.

The omega-3 (n3) polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits. The primary dietary source of EPA and DHA is seafood. Alpha-linoleic acid (ALA) has not been shown to be a good source for EPA and DHA; however, stearidonic acid (SDA)-which is naturally contained in echium oil (EO)-may be a more promising alternative. This study was aimed at investigating the short-term n3 PUFA metabolism after the ingestion of a single dose of EO. Healthy young male subjects (n = 12) ingested a single dose of 26 g of EO after overnight fasting. Plasma fatty acid concentrations and relative amounts were determined at baseline and 2, 4, 6, 8, 24, 48, and 72 h after the ingestion of EO. During the whole examination period, the participants received standardized nutrition. Plasma ALA and SDA concentrations increased rapidly after the single dose of EO. Additionally, EPA and DPAn3 concentrations both increased significantly by 47% after 72 h compared to baseline; DHA concentrations also significantly increased by 21% after 72 h. To conclude, EO increases plasma ALA, SDA, EPA, DPAn3, and DHA concentrations and may be an alternative source for these n3 PUFAs.

Alpha-Linolenic and Linoleic Fatty Acids in the Vegan Diet: Do They Require Dietary Reference Intake/Adequate Intake Special Consideration?

Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.

Effects of the rs3834458 Single Nucleotide Polymorphism in FADS2 on Levels of n-3 Long-chain Polyunsaturated Fatty Acids: A Meta-analysis.

OBJECTIVES: Evaluate the effects of the single nucleotide polymorphism (SNP) rs3834458 in the fatty acid desaturase 2 gene (FADS2) on n-3 long-chain polyunsaturated fatty acid (LC-PUFA) levels using statistical meta-analysis. METHODS: Literatures pertaining to the relationship between the SNP rs3834458 and LC-PUFA were retrieved from three electronic databases. Original information was analyzed using RevMan 5.3, including single statistics, test for heterogeneity, summary statistics and evaluation of publication bias. RESULTS: In total, five pieces of literature were retrieved and divided into seven trials. We observed that the minor allele (Tdel+deldel) carriers of rs3834458 had higher linolenic acid levels (P < 0.00001) and lower eicosapentaenoic acid (P < 0.00001), docosapentenoic acid (P = 0.005) and docosahexaenoic acid (P < 0.00001) levels compared to those of carrying major allele homozygote (TT). CONCLUSION: This meta-analysis indicates that minor allele of rs3834458 in FADS2 may result in lower activity of delta-6 desaturase leading to higher ALA and lower EPA, DPA and DHA in blood.

Sulfadiazine Sodium Ameliorates the Metabolomic Perturbation in Mice Infected with Toxoplasma gondii.

In this study, we analyzed the global metabolomic changes associated with Toxoplasma gondii infection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected with T. gondii GT1 strain and treated orally with SDZ (250 µg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection. We used ultraperformance liquid chromatography-mass spectrometry to profile the serum metabolomes in control (untreated and uninfected) mice, acutely infected mice, and SDZ-treated and infected mice. Infection induced significant perturbations in the metabolism of α-linolenic acid, purine, pyrimidine, arginine, tryptophan, valine, glycerophospholipids, and fatty acyls. However, treatment with SDZ seemed to alleviate the serum metabolic alterations caused by infection. The restoration of the serum metabolite levels in the treated mice was associated with better clinical outcomes. These data indicate that untargeted metabolomics can reveal biochemical pathways associated with restoration of the metabolic status of T. gondii-infected mice following SDZ treatment and could be used to monitor responses to SDZ treatment. This study provides a new systems approach to elucidate the metabolic and therapeutic effects of SDZ in the context of murine toxoplasmosis.

Associations of medium and long chain omega-3 polyunsaturated fatty acids with blood pressure in Hispanic and non-Hispanic smokers and nonsmokers.

Epidemiology studies and clinical trials have shown that omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with blood pressure. We sought to determine the influence of cigarette smoking and Hispanic ethnicity on this association. Age- and sex-matched smokers and nonsmokers (n = 98) 19-50 years old lacking cardiovascular disease were recruited. Systolic and diastolic blood pressure (SBP, DBP), heart rate, HbA1c, lipids, BMI, and RBC fatty acids were measured. The omega-3 index (percent eicosapentaenoic and docosahexaenoic acid, EPA+DHA, in RBCs) was significantly lower in smokers (Smokers: 3.19 ± 0.86%; Nonsmokers, 3.88 ± 1.05%, p = 0.001) and Hispanics (Hispanic 3.32 ± 0.93%; Non-Hispanic, 3.82 ± 1.03%, p = 0.006). DHA exhibited a significant inverse association with BP in both smokers and nonsmokers, while alpha-linolenic acid (ALA) exhibited a significant positive association with BP only in smokers. Multiple regression analyses showed that BMI, DHA, smoking status, and smoking status*ALA interaction significantly predicted SBP (p < 0.0001, R2 = 0.44) and DBP (p < 0.0001, R2 = 0.33), while ethnicity had no effect. The observed lower BP when DHA levels are high suggests a possible protective role of DHA on BP in normotensive smokers and nonsmokers. Additionally, the observed higher BP when ALA levels are high only in smokers suggests that ALA may influence the BP-lowering effects of chronic smoking.

Comparisons of Estimated Intakes and Plasma Concentrations of Selected Fatty Acids in Pregnancy.

The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) within the Danish National Birth Cohort (DNBC), by comparing 345 women's reported intake with concentration of plasma biomarkers. The applied questionnaire- and biomarker data reflect dietary intake from around the same time point in mid-pregnancy and relationships were investigated by use of Pearson and Spearman correlation and linear regression statistics. We demonstrated moderate but consistent adjusted correlations between dietary intake estimates and the corresponding plasma biomarker concentrations (differences in plasma concentration per 100 mg/day greater intake of 0.05 (95% CI: 0.02; 0.08)) and 0.05 (95% CI: 0.01; 0.08) percentage of total plasma fatty acids for EPA and DHA, respectively). The associations strengthened when restricting the analyses to women with ALA intake below the median intake. We found a weak correlation between the dietary intake of ALA and its plasma biomarker with a difference in plasma concentration of 0.07 (95% CI: 0.03; 0.10) percent of total plasma fatty acids per 1 g/day greater intake, while the dietary intake of LA and AA did not correlate with their corresponding biomarkers.

Fear of cancer recurrence among breast cancer survivors could be controlled by prudent dietary modification with polyunsaturated fatty acids.

BACKGROUND: The pathophysiology of fear of cancer recurrence (FCR), the leading unmet psychological need of cancer survivors, may involve the dysfunctional processing of fear memory. n-3 polyunsaturated fatty acids (PUFAs) have beneficial effects on psychiatric disorders, including depressive disorder and anxiety disorders, and are involved in fear memory processing. We hypothesized that n-3 PUFA composition is associated with FCR in cancer survivors. METHODS: We conducted a cross-sectional study to examine the relationship between n-3 PUFAs and FCR among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer and were not undergoing chemotherapy were asked to participate. Blood PUFA composition was evaluated by using capillary blood. We directly administered the Concerns About Recurrence Scale (CARS) to assess the grade of FCR. RESULTS: Among 126 participants used for the analysis, the mean age (SD) was 58 (11) years and 47% had stage I cancer. Multiple regression analysis controlling for possible confounders, depressive symptoms, and post-traumatic stress disorder (PTSD) symptoms revealed that the alpha-linolenic acid (ALA) level was significantly inversely associated with the average score on the CARS overall fear index (beta = -0.165, p = 0.04). No significant associations were found for other PUFAs. LIMITATIONS: Our findings were obtained from a cross-sectional study in a single institute. CONCLUSION: These findings provide the first evidence of a beneficial effect of ALA on FCR and indicate the need for prospective study of this association. FCR among breast cancer survivors might be controllable by prudent selection of ALA-containing cooking oil.

α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients.

BACKGROUND: The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity. OBJECTIVE: To investigate the association between ALA levels and disease activity. METHODS: We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a. RESULTS: In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37-0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48-1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34-1.16) and new relapses (OR: 0.49, 95% CI: 0.22-1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results. CONCLUSION: We found that higher levels of ALA were associated with lower disease activity in MS-patients.

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

RATIONALE: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. OBJECTIVE: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. METHODS: Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs. RESULTS: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; ßSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; ßSNP×DHA interaction = 36.2 ml). CONCLUSIONS: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.