Chain Omega-3 Polyunsaturated Fatty Acids Research Articles

A Low Omega-3 Index and High AA/EPA Ratio in American College Football Players are Both Improved Following 5 Weeks of DHA-Rich Algae Oil Supplementation

Abstract Purpose Many athletes are deficient in long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA). A consequent low Omega-3 Index (O3I) and high arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio increase cardiovascular disease risk and inflammation. Algae oil is a plant-based, sustainable source of LC n-3 PUFA, suitable for vegans and vegetarians. Effects of algae oil supplementation on whole blood fatty acids among athletes has not been previously reported. This study evaluated the effects of 5 weeks of DHA-rich algae oil supplementation on the whole blood fatty acid profile, O3I and AA/EPA ratio of omnivorous Division I American College Football (ACF) players. Methods: Data, including a spot blood sample, were collected at baseline for all participants (n = 47), then for a subset of players (n = 22) following a 5-week control period (usual diet) and 5 weeks of algae oil supplementation (usual diet + 1575 mg docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) 5 days/week; average 1125 mg/day). Results: Baseline O3I was 4.3% ± 0.1% and AA/EPA ratio was 45.6 ± 23.8. After 5 weeks of algae oil supplementation, the O3I was 6.1% ± 1.0% and the AA/EPA ratio was 25.1 ± 11.6. The O3I was significantly higher and the AA/EPA ratio was significantly lower (P < 0.0001 for both) compared with both baseline and the end of the control period. The increase in O3I from baseline was correlated with calculated DHA + EPA dose per unit body mass (R = 0.641, P = 0.001). Conclusions: Algae oil supplementation for 5 weeks improved both the low baseline O3I and high AA/EPA ratio among ACF players, with body mass specific dose effects.

Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function.

Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention.

Effect of Tyrosol Acyl Esters on the Antioxidant Status of Mussel (Mytilus edulis) Oil During Accelerated Oxidative Storage

ABSTRACT The effect of tyrosol (Tyr) and tyrosol acyl ester (TYr-Es) on thiobarbituric acid reactive substance, peroxide value, acid value, aldehyde content, fatty acid composition, and tyrosol content of mussel (Mytilus edulis) oil (MO) during accelerated storage at 60°C was evaluated. The results indicated that TYr-Es and TYr showed effective protection of MO against lipid oxidation. However, the poor solubility of TYr may lead to the formation of a suspension in oils. Therefore, TYr-Es with good lipid solubility and oxidation resistance may serve as potential antioxidant in marine oils highly enriched in long chain omega-3 polyunsaturated fatty acids in phospholipid form.

New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: A scoping review.

Long chain polyunsaturated omega-3 fatty acids (n-3 FA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to be important components in a healthy diet and contribute to healthy functioning of the heart and the brain, among other organs. Although there are epidemiological studies on the strong relationship between fish or n-3 FA consumption and lower risk of cognitive decline, results from randomized controlled trials (RCTs) are less consistent. Here, we performed a scoping review on RCTs with n-3 FA supplementation where cognition was evaluated. Seventy-eight RCTs published before April 2022 were included in this review. Among these RCTs, 43.6% reported a positive cognitive outcome after the consumption of n-3 FA compared to the placebo. However, there was a large diversity of populations studied (age ranges and health status), wide range of doses of EPA +DHA supplemented (79mg/day - 5200mg/day) and a multitude of tests evaluating cognition, mainly diagnostic tests, that were used to assess cognitive scores and overall cognitive status. RCTs were thereafter categorized into non-cognitively impaired middle-aged adults (n=24), non-cognitively impaired older adults (n=24), adults with subjective memory complaints (n=14), adults with mild cognitive impairments (MCI, n=9) and people with diagnosed dementia or other cognitive changes (n=7). Among these categories, 66.7% of RCTs conducted with MCI adults reported a positive cognitive outcome when supplemented with n-3 FA vs. the placebo. Therefore, this scoping review provides rationale and questions to a) strengthen the design of future RCTs with n-3 FA for cognitive outcomes, and b) generate more informative data to support clinicians in their practice in assessing cognition before and after a nutritional intervention.

Comparison of Fish, Krill and Flaxseed as Omega-3 Sources to Increase the Omega-3 Index in Dogs

(1) Background: it is only the longer chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (20:5n-3, EPA), and docosahexaenoic acid (22:6n-3, DHA) and not the shorter chain α-linolenic acid (ALA, 18:3n-3) that have been linked to health benefits. (2) Methods: 45 dogs divided into three groups were first given premium dry food for 38 days (baseline). The O3I was then used as a diagnostic tool to provide a measure of the sum of EPA + DHA in red blood cell membranes given as a percentage of all fatty acids. The dogs were subsequently fed with either krill meal (krill), fishmeal/oil (fish) or flaxseed cake (flax) included in raw food providing daily 416 mg EPA + DHA (971 mg ALA), 513 mg EPA + DHA (1027 mg ALA) and 1465 mg ALA (122 mg EPA + DHA), respectively. (3) Results: the average baseline O3I level of all dogs was low (1.36%), warranting n-3 supplementation. After four weeks, O3I levels were significantly increased in the krill (from 1.36 ± 0.44 to 2.36 ± 0.39%) and fish (from 1.35 ± 0.22 to 1.9 ± 0.35%) groups (p < 0.001). No significant modification of the O3I was detected in the flax animals. (4) Conclusions: only marine n-3 PUFAs resulted in a significantly increased O3I, with dietary krill meal providing the highest increase.

Single cell analysis of docosahexaenoic acid suppression of sequential LPS-induced proinflammatory and interferon-regulated gene expression in the macrophage.

Preclinical and clinical studies suggest that consumption of long chain omega-3 polyunsaturated fatty acids (PUFAs) reduces severity of chronic inflammatory and autoimmune diseases. While these ameliorative effects are conventionally associated with downregulated expression of proinflammatory cytokine and chemokine genes, our laboratory has recently identified Type 1 interferon (IFN1)-regulated gene expression to be another key target of omega-3 PUFAs. Here we used single cell RNA sequencing (scRNAseq) to gain new mechanistic perspectives on how the omega-3 PUFA docosahexaenoic acid (DHA) influences TLR4-driven proinflammatory and IFN1-regulated gene expression in a novel self-renewing murine fetal liver-derived macrophage (FLM) model. FLMs were cultured with 25 µM DHA or vehicle for 24h, treated with modest concentration of LPS (20 ng/ml) for 1 and 4h, and then subjected to scRNAseq using the 10X Chromium System. At 0h (i.e., in the absence of LPS), DHA increased expression of genes associated with the NRF2 antioxidant response (e.g. Sqstm1, Hmox1, Chchd10) and metal homeostasis (e.g.Mt1, Mt2, Ftl1, Fth1), both of which are consistent with DHA-induced polarization of FLMs to a more anti-inflammatory phenotype. At 1h post-LPS treatment, DHA inhibited LPS-induced cholesterol synthesis genes (e.g. Scd1, Scd2, Pmvk, Cyp51, Hmgcs1, and Fdps) which potentially could contribute to interference with TLR4-mediated inflammatory signaling. At 4h post-LPS treatment, LPS-treated FLMs reflected a more robust inflammatory response including upregulation of proinflammatory cytokine (e.g. Il1a, Il1b, Tnf) and chemokine (e.g.Ccl2, Ccl3, Ccl4, Ccl7) genes as well as IFN1-regulated genes (e.g. Irf7, Mx1, Oasl1, Ifit1), many of which were suppressed by DHA. Using single-cell regulatory network inference and clustering (SCENIC) to identify gene expression networks, we found DHA modestly downregulated LPS-induced expression of NF-κB-target genes. Importantly, LPS induced a subset of FLMs simultaneously expressing NF-κB- and IRF7/STAT1/STAT2-target genes that were conspicuously absent in DHA-pretreated FLMs. Thus, DHA potently targeted both the NF-κB and the IFN1 responses. Altogether, scRNAseq generated a valuable dataset that provides new insights into multiple overlapping mechanisms by which DHA may transcriptionally or post-transcriptionally regulate LPS-induced proinflammatory and IFN1-driven responses in macrophages.

Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids - A Double Blind, Randomised Clinical Trial.

BackgroundObesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation.MethodsTo evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration.ResultsObesity was associated with scWAT hypertrophy (P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (P <0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals.ConclusionOur data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis.Clinical Trial Registration www.isrctn.com, identifier ISRCTN96712688.

Innovative food ingredients based on the milk protein–chitosan complex particles for the fortification of food with essential lipids

The aim of this work was to elucidate the influence of both the structural features of milk proteins [whey proteins (WPI) and sodium caseinate (SC)] and the character of their electrostatic associative interactions with chitosan (CHIT) on the structure, thermodynamic parameters and functionality of their complexes with essential lipids. These lipids included soybean phosphatidylcholine liposomes (PC), rich in omega-6 linoleic (LA) polyunsaturated fatty acid (PUFA), and long chain omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) from fish oil (FO) to their equal weight ratio with LA. A laser light scattering method was used in static, dynamic and electrophoretic modes to characterise the structure and thermodynamic parameters of the supramolecular complexes in an aqueous medium. The functionality of the supramolecular complexes (WPI−CHIT−PC−FO and SC−CHIT−PC−FO) was considered from the point of view of their solubility in an aqueous medium and protective abilities against oxidation of the essential lipids encapsulated in them.

Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial.

SummaryBackgroundObesity is associated with enhanced inflammation. However, investigation in human subcutaneous white adipose tissue (scWAT) is limited and the mechanisms by which inflammation occurs have not been well elucidated. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and may reduce scWAT inflammation.MethodsSubcutaneous white adipose tissue (scWAT) biopsies were collected from individuals living with obesity (n=45) and normal weight individuals (n=39) prior to and following a 12-week intervention with either 3 g/day of a fish oil concentrate (providing 1.1 g eicosapentaenoic acid (EPA) + 0.8 g docosahexaenoic acid (DHA)) or 3 g/day of corn oil. ScWAT fatty acid, oxylipin, and transcriptome profiles were assessed by gas chromatography, ultra-pure liquid chromatography tandem mass spectrometry, RNA sequencing and qRT-PCR, respectively.FindingsObesity was associated with greater scWAT inflammation demonstrated by lower concentrations of specialised pro-resolving mediators (SPMs) and hydroxy-DHA metabolites and an altered transcriptome with differential expression of genes involved in LC n-3 PUFA activation, oxylipin synthesis, inflammation, and immune response. Intervention with LC n-3 PUFAs increased their respective metabolites including the SPM precursor 14-hydroxy-DHA in normal weight individuals and decreased arachidonic acid derived metabolites and expression of genes involved in immune and inflammatory response with a greater effect in normal weight individuals.InterpretationDownregulated expression of genes responsible for fatty acid activation and metabolism may contribute to an inflammatory oxylipin profile and limit the effects of LC n-3 PUFAs in obesity. There may be a need for personalised LC n-3 PUFA supplementation based on obesity status.FundingEuropean Commission Seventh Framework Programme (Grant Number 244995) and Czech Academy of Sciences (Lumina quaeruntur LQ200111901).

Isolation of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid - EPA and docosahexaenoic acid - DHA) from diatom biomass using different extraction methods

The long chain omega-3 polyunsaturated fatty acids are essential for the proper functioning of human body. With an increasing demand for such products, an evaluation on the use of alternative sustainable sources of omega-3 fatty acids becomes extremely relevant. The present study concerned the isolation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from diatom biomass by different extraction methods. The first step concerned the optimization of the analysis method based on high-performance liquid chromatography - diode array detector (HPLC-DAD), and the evaluation of corresponding validation parameters. The developed method provided adequate limits of detection and quantitation, as well as appropriate criterion for reproducibility and linearity. Biomass samples harvested from cultures of Pseudostaurosira trainorii were pre-treated and submitted to Soxhlet extraction using methanol-chloroform, reflux extraction with acetone and supercritical fluid extraction (SFE) using 96% ethanol as co-solvent. Prior analysis, the extracts were subjected to derivatization process utilizing 2,4′-dibromoacetophenone in acetone andtriethylamine. The yielded derivatives were analyzed by HPLC-DAD and concentrations of EPA and DHA recovered from dry biomass were determined. The greatest content of omega-3 fatty acids was obtained for reflux extraction (EPA – 63.746 mg g−1, DHA – 1.379 mg g−1), followed by Soxhlet method (EPA – 39.729 mg g−1, DHA – 1.059 mg g−1) and SFE extraction (EPA – 33.701 mg g−1, DHA – 0.455 mg g−1). Although a lower fraction of fatty acids was recovered by using SFE, the obtained extracts present lower toxicity and may be directly applied to the development of daily products.

The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: A scoping systematic review and meta-analysis.

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and function, which reduces mobility and quality of life. Risk factors for sarcopenia include advanced age, physical inactivity, obesity, and chronic diseases such as cancer or rheumatoid arthritis. Omega-3 long chain polyunsaturated fatty acids (LC PUFAs) might be associated with a reduction in risk of sarcopenia due to their anti-inflammatory effects. We conducted a systematic review and meta-analysis to quantify the effects of omega-3 LC PUFAs on muscle mass, volume and function parameters. The National Library of Medicine's MEDLINE/PubMed database was searched on 9th October 2020 for randomized controlled trials that used omega-3 LC PUFAs as an intervention with muscle-related endpoints. A snowballing search to identify additional studies was completed on 23rd April 2021. The meta-analysis was conducted using meta-essentials worksheet 3. Bias was assessed using the Jadad scale. 123 studies were identified with the systematic searches. Most studies were performed in disease populations, such as cancer or chronic obstructive pulmonary disease (COPD), or in healthy individuals after a fatiguing exercise bout. The endpoints lean body mass, skeletal muscle mass, mid-arm muscle circumference, handgrip strength, quadriceps maximal voluntary capacity (MVC), and 1-repetition maximum chest press were selected for meta-analysis based on the number of available studies; thus 66 studies were included in the quantitative synthesis. Using a random effects model and 2-tailed p-value, there was a significant relationship in favor of omega-3 LC PUFA supplementation for lean body mass (effect size 0.27, 95%CI 0.04 to 0.51), skeletal muscle mass (effect size 0.31, 95%CI 0.01 to 0.60) and quadriceps MVC (effect size 0.47, 95%CI 0.02 to 0.93). The results indicate that there is a positive effect of omega-3 LC PUFA supplementation on overall body muscle mass and strength. Small study size and heterogeneity limit the applicability of these findings for sarcopenia prevention. Larger trials in populations at risk of sarcopenia would strengthen the evidence base.

APOE ε4 alters docosahexaenoic acid's influence on preclinical markers of Alzheimer disease

Docosahexaenoic acid (DHA) is the main long chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30% to 40% of fatty acids in the grey matter of the human cortex. Although the influence of circulating DHA levels on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic AD, and that spatial navigation crucially relies on hippocampal and the entorhinal cortex integrity. Thus, we investigated the relationship between DHA levels and the major structural and cognitive markers of preclinical AD, namely hippocampal volume, entorhinal volume, and spatial navigation ability, across two independent non-demented populations. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum DHA (including serum lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. After testing interactions between DHA and APOE ε4 on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for AD in an independent population of APOE genotyped adults (n = 46). We hypothesized that higher DHA levels would be associated with preserved brain volume and better spatial navigation performance in APOE ε4 non-carriers but not in APOE ε4 carriers. APOE genotype modulated serum free DHA associations with entorhinal cortex volume and hippocampal volume, both key nodes of the human spatial navigation network. Linear models showed that greater circulating DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in APOΕ ε4 non-carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. Crucially, the APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. Interventions aiming to increase DHA status to protect against cognitive decline must consider APOE ε4 carrier status.

Non-polar lipid from greenshell mussel (Perna canaliculus) inhibits osteoclast differentiation

The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 μg/mL, p < 0.001). Moreover, actin ring formation was significantly diminished by non-polar lipids at 10–20 μg/mL. The bone digestive enzymes released by osteoclasts into the pit formation were also compromised by downregulating gene expression of cathepsin K, carbonic anhydrase II (CA II), matrix metalloproteinase 9 (MMP-9), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). This study revealed that the non-polar lipid fraction of GSM oil contains bioactive substances which possess potent anti-osteoclastogenic activity.

Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation-associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α-linolenic acid, the precursor of long chain omega-3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti-inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF-κB. However, few studies have examined the anti-neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD-like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation-mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down-regulation of proinflammatory mediators, such as inducible NOS, COX-2, IL-1β, and TNF-α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF-κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.

Hair mercury levels, dietary intake of omega-3 fatty acids and ovarian reserve among women attending a fertility center

BACKGROUND AND AIM: We investigated the association of hair mercury (Hg) levels with antral follicle count (AFC), as a marker of ovarian reserve, and evaluate whether this relationship differed among women with high vs. low intake of long chain omega-3 polyunsaturated fatty acids (n3PUFA). METHODS: We included 295 women attending an academic fertility center (2007-2016) who had data on hair Hg levels (assessed using a Direct Mercury Analyser), n3PUFA intake (estimated using a validated food frequency questionnaire) and AFC (assessed by transvaginal ultrasonography and abstracted from electronic medical records). Poisson regression models adjusted for potential confounders were used to evaluate the association of hair Hg levels (divided into tertiles, and as above vs below EPA reference (1ppm)) with AFC. Associations were also evaluated after stratification by n3PUFA intake (≤0.124 vs. 0.125 %calories/week). RESULTS:Women’s median hair Hg level was 0.55 ppm (range=0.01-8.51 ppm), with more than 30% 1 ppm. Hair Hg was positively related to AFC after adjusting for age, BMI, smoking status, infertility diagnosis, and alcohol intake. However, associations became attenuated after further adjustment for intake of calories and n3PUFA. The positive associations of hair Hg and AFC were observed only among women with high n3PUFA intake. Specifically, women who consumed 0.125 %calories/week of n3PUFA had a mean AFC of 11.9, 13.2 and 14.5, respectively, across increasing tertiles of hair Hg (p=0.002). Similar results were found when hair Hg was divided as above vs below EPA reference (mean AFC=12.7 vs. 14.6, p=0.002). CONCLUSIONS:In women from a fertility clinic, positive associations of hair Hg with AFC may be reflective of beneficial effects of n3PUFA on ovarian reserve rather than a beneficial effect of Hg per se. Our findings highlight the importance of considering diet when exploring Hg effects on women’s reproductive health. KEYWORDS: Heavy metals, food/nutrition, female reproductive outcomes.

Hair mercury levels, intake of omega-3 fatty acids and ovarian reserve among women attending a fertility center

To investigate the association of hair mercury (Hg) levels with antral follicle count (AFC), as a marker of ovarian reserve, and evaluate whether this relationship differed among women with high vs. low total intake of long chain omega-3 polyunsaturated fatty acids (n3PUFA) from foods and supplements. We included 353 women attending an academic fertility center (2007-2019) who had data on hair Hg levels, total n3PUFA intake, and AFC. Hair Hg levels were assessed using a Direct Mercury Analyser, total n3PUFA intake was estimated using an extensively validated food frequency questionnaire, and AFC was assessed by transvaginal ultrasonography. Poisson regression models adjusted for potential confounders were used to evaluate the association of hair Hg levels (divided into tertiles, and as above vs below EPA reference (1ppm)) with AFC. Associations were also evaluated after stratification by median n3PUFA intake (≤0.124% vs. >0.125% calories/week). Women's median hair Hg level was 0.60ppm (range=0.001-8.60ppm), with more than 30%>1ppm (EPA reference level). Hair Hg was positively related to AFC after adjusting for age, BMI, smoking status, infertility diagnosis, and alcohol intake. However, associations became attenuated after adjustment for intake of total n3PUFA. The positive associations of hair Hg and AFC were observed only among women above the median total n3PUFA intake. Specifically, women who consumed >0.125% calories/week of total n3PUFA had mean AFCs of 11.9, 13.2 and 14.1, respectively, across increasing tertiles of hair Hg (p,trend=0.004). Similar results were found when hair Hg was divided above vs below EPA reference (mean AFC=12.7 vs. 14.1, p=0.008). In these women, positive associations of hair Hg with AFC may be reflective of beneficial effects of n3PUFA on ovarian reserve rather than a beneficial effect of Hg per se. Our findings highlight the importance of considering diet when exploring Hg effects on women's reproductive health in urban settings.

The Sources, Synthesis and Biological Actions of Omega-3 and Omega-6 Fatty Acids in Red Meat: An Overview.

The maximisation of available resources for animal production, food security and maintenance of human–animal wellbeing is important for an economically viable, resilient and sustainable future. Pasture and forage diets are common sources of short chain omega-3 (n-3) polyunsaturated fatty acids (PUFA), while grain-based and feedlot diets are common sources of short chain omega-6 (n-6) PUFA. Animals deposit n-3 and n-6 PUFA as a result of their direct consumption, as feeds or by synthesis of longer chain PUFA from short chain FA precursors in the body via desaturation and elongation processes. Research conducted over the last three decades has determined that the consumption of n-3 PUFA can improve the health and wellbeing of humans through its biological, biochemical, pathological and pharmacological effects. n-6 PUFA also play an important role in human health, but when consumed at high levels, are potentially harmful. Research shows that current consumption of n-6 PUFA by the human population is high due to their meal choices and the supplied food types. If consumption of n-3 PUFA from land- and marine-based foods improves human health, it is likely that these same food types can improve the health and wellbeing of livestock (farm animals) by likewise enhancing the levels of the n-3 PUFA in their circulatory and tissue systems. Modern agricultural systems and advanced technologies have fostered large scale animal and crop production systems. These allow for the utilisation of plant concentrate-based diets to increase the rate of animal growth, often based on economics, and these diets are believed to contribute to unfavourable FA intakes. Knowledge of the risks associated with consuming foods that have greater concentration of n-6 PUFA may lead to health-conscious consumers avoiding or minimising their intake of animal- and plant-based foods. For this reason, there is scope to produce food from plant and animal origins that contain lesser amounts of n-6 PUFA and greater amounts of n-3 PUFA, the outcome of which could improve both animal and human health, wellbeing and resilience to disease.

Fish oil replacement prevents, while docosahexaenoic acid-derived protectin DX mitigates end-stage-renal-disease in atherosclerotic diabetic mice.

Diabetic nephropathy (DN) remains the major cause of end-stage renal disease (ESRD). We used high-fat/high-sucrose (HFHS)-fed LDLr-/- /ApoB100/100 mice with transgenic overexpression of IGFII in pancreatic β-cells (LRKOB100/IGFII) as a model of ESRD to test whether dietary long chain omega-3 polyunsaturated fatty acids LCω3FA-rich fish oil (FO) could prevent ESRD development. We further evaluated the potential of docosahexaenoic acid (DHA)-derived pro-resolving lipid mediators, 17-hydroxy-DHA (17-HDHA) and Protectin DX (PDX), to reverse established ESRD damage. HFHS-fed vehicle-treated LRKOB100/IGFII mice developed severe kidney dysfunction leading to ESRD, as revealed by advanced glomerular fibrosis and mesangial expansion along with reduced percent survival. The kidney failure outcome was associated with cardiac dysfunction, revealed by reduced heart rate and prolonged diastolic and systolic time. Dietary FO prevented kidney damage, lean mass loss, cardiac dysfunction, and death. 17-HDHA reduced podocyte foot process effacement while PDX treatment alleviated kidney fibrosis and mesangial expansion as compared to vehicle treatment. Only PDX therapy was effective at preserving the heart function and survival rate. These results show that dietary LCω3FA intake can prevent ESRD and cardiac dysfunction in LRKOB100/IGFII diabetic mice. Our data further reveals that PDX can protect against renal failure and cardiac dysfunction, offering a potential new therapeutic strategy against ESRD.

Raman and Infrared Spectroscopic Data Fusion Strategies for Rapid, Multicomponent Quantitation of Krill Oil Compositions

Krill oil contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), long chain omega-3 polyunsaturated fatty acids with essential roles in human health, and astaxanthin, a naturally occu...

\u03c9-3PUFA supplementation ameliorates adipose tissue inflammation and insulin-stimulated glucose disposal in subjects with obesity: a potential role for apolipoprotein E

BackgroundLong chain omega-3 polyunsaturated fatty acids (ω-3PUFA) supplementation in animal models of diet-induced obesity has consistently shown to improve insulin sensitivity. The same is not always reported in human studies with insulin resistant (IR) subjects with obesity.ObjectiveWe studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in IR subjects with obesity.MethodsThirteen subjects (BMI = 39.3 ± 1.6 kg/m2) underwent 80 mU/m2·min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after 3 months of ω-3PUFA (DHA and EPA, 4 g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program.ResultsPalmitic and stearic acid plasma levels were significantly reduced (P < 0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P < 0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P < 0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.7 ± 0.6 mg/kg ffm•min vs. 5.9 ± 0.9 mg/kg ffm•min) despite no change in body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with Apolipoprotein E (APOE) being one of the most upregulated genes.ConclusionHigh dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT, and systemic inflammation. These findings are associated with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as among the most differentially regulated gene after ω-3PUFA supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.