Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid-Eicosapentaenoic Acid Response During an ω-3 Fatty Acid Supplementation: A Secondary Analysis.

BACKGROUND: The brain is concentrated with omega (ω)-3 (n-3) fatty acids (FAs), and these FAs must come from the plasma pool. The 2 main ω-3 FAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), must be in the form of nonesterified fatty acid (NEFA) or esterified within phospholipids (PLs) to reach the brain. We hypothesized that the plasma concentrations of these ω-3 FAs can be modulated by sex, body mass index (BMI, kg/m2), age, and the presence of the apolipoprotein (APO) E-ε4 allele in response to the supplementation. OBJECTIVES: This secondary analysis aimed to determine the concentration of EPA and DHA within plasma PL and in the NEFA form after an ω-3 FA or a placebo supplementation and to investigate whether the factors change the response to the supplement. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Participants were randomly assigned to either an ω-3 FA supplement (DHA 0.8 g and EPA 1.7 g daily) or to a placebo for 6 mo. FAs from fasting plasma samples were extracted and subsequently separated into PLs with esterified FAs and NEFAs using solid-phase extraction. DHA and EPA concentrations in plasma PLs and as NEFAs were quantified using gas chromatography. RESULTS: EPA and DHA concentrations in the NEFA pool significantly increased by 31%-71% and 42%-82%, respectively, after 1 and 6 mo of ω-3 FA supplementation. No factors influenced plasma DHA and EPA responses in the NEFA pool. In the plasma PL pool, DHA increased by 83%-109% and EPA by 387%-463% after 1 and 6 mo of ω-3 FA supplementation. APOE4 carriers, females, and individuals with a BMI of ≤25 had higher EPA concentrations than noncarriers, males, and those with a BMI of >25, respectively. CONCLUSIONS: The concentration of EPA in plasma PLs are modulated by APOE4, sex, and BMI. These factors should be considered when designing clinical trials involving ω-3 FA supplementation. This trial was registered at clinicaltrials.gov as NCT01625195.

Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets.

During aging, changes in gene expression are associated with a decline in physical and cognitive abilities. Here, we investigate the connection between changes in mRNA and protein expression in the brain by comparing the transcriptome and proteome of the mouse cortex during aging. Our transcriptomic analysis revealed that aging mainly triggers gene activation in the cortex. We showed that an increase in mRNA expression correlates with protein expression, specifically in the anterior cingulate cortex, where we also observed an increase in cortical thickness during aging. Genes exhibiting an aging-dependent increase of mRNA and protein levels are involved in sensory perception and immune functions. Our proteomic analysis also identified changes in protein abundance in the aging cortex and highlighted a subset of proteins that were differentially enriched but exhibited stable mRNA levels during aging, implying the contribution of aging-related post- transcriptional and post-translational mechanisms. These specific genes were associated with general biological processes such as translation, ribosome assembly and protein degradation, and also important brain functions related to neuroplasticity. By decoupling mRNA and protein expression, we have thus characterized distinct subsets of genes that differentially adjust to cellular aging in the cerebral cortex.

Investigating the plasma-liver-brain axis of omega-3 fatty acid metabolism in mouse knock-in for the human apolipoprotein E epsilon 4 allele.

The metabolism of docosahexaenoic acid (DHA), an omega-3 fatty acid, is different in carriers of APOE4, the main genetic risk factor for late-onset Alzheimer's disease. The brain relies on the plasma DHA pool for its need, but the plasma-liver-brain axis in relation to cognition remains obscure. We hypothesized that this relationship is compromised in APOE4 mice considering the differences in fatty acid metabolism between APOE3 and APOE4 mice. Male and female APOE3 and APOE4 mice were fed either a diet enriched with DHA (0.7 g DHA/100 g diet) or a control diet for 8 months. There was a significant genotype × diet interaction for DHA concentration in the liver and adipose tissue. In the cortex, a genotype effect was found where APOE4 mice had a higher concentration of DHA than APOE3 mice fed the control diet. There was a significant genotype × diet interaction for the liver and hippocampal arachidonic acid (AA). APOE4 mice had 20-30% lower plasma DHA and AA concentrations than APOE3 mice, independent of diet. Plasma and liver DHA levels were significantly correlated in APOE3 and APOE4 mice. In APOE4 mice, there was a significant correlation between plasma, adipose tissues, cortex DHA and the Barnes maze and/or with a better recognition index. Moreover, higher AA levels in the liver and the hippocampus of APOE4 mice were correlated with lower cognitive performance. Our results suggest that there is a plasma-liver-brain axis of DHA that is modified in APOE4 mice. Moreover, our data support that APOE4 mice rely more on plasma DHA than APOE3 mice, especially in cognitive performance. Any disturbance in plasma DHA metabolism might have a greater impact on cognition in APOE4 carriers.

Comparative Pharmacokinetic of Curcuminoids Formulations with an Omega-3 Fatty Acids Monoglyceride Carrier: A Randomized Cross-Over Triple-Blind Study.

There is a growing interest for curcuminoids in the general population and the scientific research community. Curcuminoids, derived from turmeric spice, are lipophiles and therefore have a low solubility in water which hence have a low bioavailability in the human plasma. To circumvent this issue, a natural product developed by Biodroga Nutraceuticals combined curcuminoids with omega-3 fatty acids (OM3) esterified in monoglycerides (MAG). The objective was to perform a 24 h pharmacokinetics in humans receiving a single dose of curcuminoid formulated by three different means, and to compare their plasma curcuminoids concentration. Sixteen males and fifteen females tested three formulations: 400 mg of curcuminoids powder extract, 400 mg of curcuminoids in rice oil and 400 mg of curcuminoids with 1 g MAG-OM3. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 h post dose intake. Plasma samples were analyzed by ultra high-performance liquid chromatography with a triple quadrupole mass spectrometer (UPLC-MS/MS). Twenty-four hours after a single dose intake, the total plasma curcuminoids area under the curve (AUC) reached 166.8 ± 17.8 ng/mL*h, 134.0 ± 12.7 ng/mL*h and 163.1 ± 15.3 ng/mL*h when curcuminoids were provided with MAG-OM3, with rice oil or in powder, respectively. The Cmax of total curcuminoids reached between 11.9-17.7 ng/mL at around 4 h (Tmax). One-hour post-dose, the curcuminoids plasma concentration was 40% higher in participants consuming the MAG-OM3 compared to the other formulations. Thus, in a young population, plasma curcuminoids 24 h pharmacokinetics and its increase shortly after the single dose intake were higher when provided with MAG-OM3 than rice oil.

The Influence of Family History of Type 2 Diabetes on Metabolism during Submaximal Aerobic Exercise and in the Recovery Period in Postmenopausal Women.

Aging and family history of type 2 diabetes (T2D) are known risk factors of T2D. Younger first-degree relatives (FDR) of T2D patients have shown early metabolic alterations, which could limit exercise's ability to prevent T2D. Thus, the objective was to determine whether exercise metabolism was altered during submaximal exercise in FDR postmenopausal women. Nineteen inactive postmenopausal women (control: 10, FDR: 9) aged 60 to 75 years old underwent an incremental test on a cycle ergometer with intensity ranging from 40 to 70% of peak power output. Participants consumed 50 mg of 13C-palmitate 2 h before the test. At the end of each stage, glucose, lactate, glycerol, non-esterified fatty acids and 13C-palmitate were measured in plasma, and 13CO2 was measured in breath samples. Gas exchanges and heart rate were both monitored continuously. There were no between-group differences in substrate oxidation, plasma substrate concentrations or 13C recovered in plasma or breath. Interestingly, despite exercising at a similar relative intensity to control, FDR were consistently at a lower percentage of heart rate reserve. Overall, substrate plasma concentration and oxidation are not affected by family history of T2D in postmenopausal women and therefore not a participating mechanism in the altered response to exercise previously reported. More studies are required to better understand the mechanisms involved in this response.

Alteration of Fatty Acid Profile in Fragile X Syndrome.

Fragile X Syndrome (FXS) is the most prevalent monogenic cause of Autism Spectrum Disorders (ASDs). Despite a common genetic etiology, the affected individuals display heterogenous metabolic abnormalities including hypocholesterolemia. Although changes in the metabolism of fatty acids (FAs) have been reported in various neuropsychiatric disorders, it has not been explored in humans with FXS. In this study, we investigated the FA profiles of two different groups: (1) an Argentinian group, including FXS individuals and age- and sex-matched controls, and (2) a French-Canadian group, including FXS individuals and their age- and sex-matched controls. Since phospholipid FAs are an indicator of medium-term diet and endogenous metabolism, we quantified the FA profile in plasma phospholipids using gas chromatography. Our results showed significantly lower levels in various plasma FAs including saturated, monosaturated, ω-6 polyunsaturated, and ω-3 polyunsaturated FAs in FXS individuals compared to the controls. A decrease in the EPA/ALA (eicosapentaenoic acid/alpha linoleic acid) ratio and an increase in the DPA/EPA (docosapentaenoic acid/eicosapentaenoic acid) ratio suggest an alteration associated with desaturase and elongase activity, respectively. We conclude that FXS individuals present an abnormal profile of FAs, specifically FAs belonging to the ω-3 family, that might open new avenues of treatment to improve core symptoms of the disorder.

Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex.

BACKGROUND: Omega-3 (n-3) PUFAs are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodologic issues, including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier. OBJECTIVES: This study evaluated the association between serum n-3 PUFAs and performance across 4 cognitive domains, overall and by sex, while controlling for other LCFAs. METHODS: In total, 386 healthy older adults (aged 77.4 ± 3.8 y; 53% females) from the Quebec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and nonverbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs. RESULTS: Higher n-3 PUFA concentrations were associated with better nonverbal memory and processing speed in fully adjusted models not including other LCFAs (ßs of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (ßs of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (ßs of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of EPA, whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and nonverbal episodic memory in females and with better executive functioning and processing speed in males. CONCLUSIONS: These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.

Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer's disease mouse model.

The defining features of Alzheimer's disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment.

Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial.

OBJECTIVE: To investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation improve cognitive performance and if apolipoprotein E (APOE) genotype or age were effect modifiers. METHODS: Healthy adults of 20 to 80 years old (n = 193) were completed a 6-month double-blind randomized controlled trial with two groups: 2.5 g/day of n-3 PUFA or a placebo. Primary outcomes were visuospatial ability and working memory and secondary outcomes were episodic memory and executive function, measured at baseline and 6 months. RESULTS: Cognitive performances did not significantly differ between groups on primary or secondary outcomes after 6 months of treatment. APOE carriers and age were not effect modifiers for any outcomes. Those with low episodic memory scores and taking the n-3 PUFA supplement, significantly improved their scores (p = 0.043). CONCLUSIONS: A 6-month n-3 PUFA supplementation did not improve cognitive performance in cognitively healthy adults and APOE status or age were not effect modifiers.

Women have higher levels of CoQ10 than men when supplemented with a single dose of CoQ10 with monoglycerides omega-3 or rice oil and followed for 48 h: a crossover randomised triple blind controlled study.

Coenzyme Q10 (CoQ10), a lipid involved in ATP synthesis, exhibits very limited oral absorption, and its endogenous production decreases with ageing and with the occurrence of oxidative stress. Our group previously showed that monoglycerides omega-3 (MAG-OM3) increase OM3 plasma concentrations. Since CoQ10 is liposoluble, we hypothesised that its 48 h pharmacokinetics is higher when provided with MAG-OM3 compared to CoQ10 alone (in powder form) or added to rice oil (a neutral triacylglycerol oil). A randomised triple-blind crossover study was performed with fifteen men and fifteen women consuming the three supplements providing 200 mg of CoQ10 in a random order. Blood samples were collected before (t = 0) and 1, 3, 5, 6, 7, 8, 10, 11, 24 and 48 h after the supplement intake. Plasma total CoQ10 concentrations were analysed on ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometer (UPLC-MS/MS). Participants were 26⋅1 ± 4⋅8 years old. When CoQ10 was provided with rice or MAG-OM3 oils, the 48 h area under the curve (AUC 0-48 h) was approximately two times higher compared to when provided without an oil. The delta max concentration (ΔCmax) of plasma CoQ10 was, respectively, 2 (MAG-OM3) and 2⋅5 (rice oil) times higher compared to CoQ10 alone. There was a significant sex by treatment interaction (P = 0⋅0250) for the AUC 0-6 h supporting that in postprandial, men and women do not respond the same way to the different supplement. Women had a higher CoQ10 concentration 48 h after the single-dose intake compared to men. We conclude that CoQ10 supplements must be provided with lipids, and their kinetics is different between men and women.

A diet rich in docosahexaenoic acid enhances reactive astrogliosis and ramified microglia morphology in apolipoprotein E epsilon 4-targeted replacement mice.

Docosahexaenoic acid (DHA) consumption reduces spatial memory impairment in mice carrying the human apolipoprotein E ε4 (APOE4) allele. The current study evaluated whether astrocyte and microglia morphology contribute to the mechanism of this result. APOE3 and APOE4 mice were fed either a DHA-enriched diet or a control diet from 4 to 12 months of age. Coronal brain sections were immunostained for GFAP, Iba1, and NeuN. Astrocytes from APOE4 mice exhibited signs of reactive astrogliosis compared to APOE3 mice. Consumption of DHA exacerbated reactive astrocyte morphology in APOE4 carriers. Microglia from APOE4-control mice exhibited characteristics of amoeboid morphology and other characteristics of ramified morphology (more processes, greater process complexity, and greater distance between neighboring microglia). DHA enhanced ramified microglia morphology in APOE4 mice. In addition, APOE4 mice fed the DHA diet had lower hippocampal concentrations of interleukin-7, lipopolysaccharide-induced CXC chemokine and monocyte chemoattractant protein 1, and higher concentration of interferon-gamma compared to APOE4-control mice. Our results indicate that a diet rich in DHA enhances reactive astrogliosis and ramified microglia morphology in APOE4 mice.

Diet enriched in omega-3 fatty acids alleviates olfactory system deficits in APOE4 transgenic mice.

Olfactory dysfunction is observed in several neurological disorders including Mild Cognitive Impairment (MCI) and Alzheimer disease (AD). These deficits occur early and correlate with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite extensive human studies, there has been little characterization of the olfactory system in models of AD. In order to determine if olfactory structural and/or molecular phenotypes are observed in a model expressing a genetic risk factor for AD, we assessed the olfactory bulb (OB) in APOE4 transgenic mice. A significant decrease in OB weight was observed at 12 months of age in APOE4 mice concurrent with inflammation and decreased NeuN expression. In order to determine if a diet rich in omega-3s may alleviate the olfactory system phenotypes observed, we assessed WT and APOE4 mice on a docosahexaenoic acid (DHA) diet. APOE4 mice on a DHA diet did not present with atrophy of the OB, and the alterations in NeuN and IBA-1 expression were alleviated. Furthermore, alterations in caspase mRNA and protein expression in the APOE4 OB were not observed with a DHA diet. Similar to the human AD condition, OB atrophy is an early phenotype in the APOE4 mice and concurrent with inflammation. These data support a link between the structural olfactory brain region atrophy and the olfactory dysfunction observed in AD and suggest that inflammation and cell death pathways may contribute to the olfactory deficits observed. Furthermore, the results suggest that diets enriched in DHA may provide benefit to APOE4 allele carriers.

Peptides Derived from Growth Factors to Treat Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood-brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease.

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is often accompanied by metabolic abnormalities and inflammation that might play a role in the development of cognitive impairment. The use of ketogenic medium-chain triglycerides (kMCT) to improve cognition in this population has shown promising results but remains controversial because of the potentially detrimental effect of elevated intake of saturated fatty acids on cardiovascular (CV) health and perhaps inflammatory processes. The primary aim of this secondary data analysis report is to describe changes in cardiometabolic markers and peripheral inflammation during a 6-month kMCT intervention in MCI. METHODS: Thirty-nine participants with MCI completed the intervention of 30 g/day of either a kMCT drink or calorie-matched placebo (high-oleic acid) for 6 months. Plasma concentrations of cardiometabolic and inflammatory markers were collected before (fasting state) and after the intervention (2 h following the last drink). RESULTS: A mixed model ANOVA analysis revealed a time by group interaction for ketones (P < 0.001), plasma 8:0 and 10:0 acids (both P < 0.001) and IL-8 (P = 0.002) with follow up comparison revealing a significant increase in the kMCT group (+48%, P = 0.005), (+3,800 and +4,900%, both P < 0.001) and (+147%, P < 0.001) respectively. A main effect of time was observed for insulin (P = 0.004), triglycerides (P = 0.011) and non-esterified fatty acids (P = 0.036). CONCLUSION: Under these study conditions, 30 g/d of kMCT taken for six months and up to 2-hour before post-intervention testing had minimal effect on an extensive profile of circulating cardiometabolic and inflammatory markers as compared to a placebo calorie-matched drink. Our results support the safety kMCT supplementation in individuals with MCI. The clinical significance of the observed increase in circulating IL-8 levels is presently unknown and awaits future studies.

APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular amyloid ß (Aß) and intraneuronal tau protein aggregations. One risk factor for developing AD is the APOE gene coding for the apolipoprotein E protein (apoE). Humans have three versions of APOE gene: ε2, ε3, and ε4 allele. Carrying the ε4 allele is an AD risk factor while carrying the ε2 allele is protective. ApoE is a component of lipoprotein particles in the plasma at the periphery, as well as in the cerebrospinal fluid (CSF) and in the interstitial fluid (ISF) of brain parenchyma in the central nervous system (CNS). ApoE is a major lipid transporter that plays a pivotal role in the development, maintenance, and repair of the CNS, and that regulates multiple important signaling pathways. This review will focus on the critical role of apoE in AD pathogenesis and some of the currently apoE-based therapeutics developed in the treatment of AD.

Pharmacokinetics of Supplemental Omega-3 Fatty Acids Esterified in Monoglycerides, Ethyl Esters, or Triglycerides in Adults in a Randomized Crossover Trial.

BACKGROUND: Omega-3 (n-3) fatty acid (FA) supplements increase blood concentrations of EPA and DHA. Most of the supplements on the market are esterified in triglycerides (TGs) or ethyl esters (EEs), which limits their absorption and may cause gastrointestinal side effects. OBJECTIVE: The objective of this study was to compare the 24-h AUC of the plasma concentrations of EPA, DHA, and EPA+DHA when provided esterified in monoglycerides (MAGs), EEs, or TGs, (primary outcomes) and evaluate their side effects over 24 h (secondary outcome). METHODS: This was a randomized, triple-blind, crossover, controlled clinical trial. Eleven women and 11 men between 18 and 50 y of age ingested, in random order, a single oral dose of ∼1.2 g of EPA and DHA esterified in MAGs, EEs, and TGs with low-fat meals provided during the 24-h follow-up. Eleven blood samples over 24 h were collected from each participant, and the plasma n-3 FAs were quantified. Friedman's paired ANOVA statistical rank test was used for the pharmacokinetic parameters and a chi-square statistical test was used for the side effects. RESULTS: The 24-h AUC of plasma EPA was ∼2 times and ∼1 time higher after the MAG compared with the EE and TG forms of n-3 FAs, respectively (P ≤ 0.0027). Effects of the EE and TG treatments did not differ. The 3 supplements had similar eructation, dysgeusia, abdominal discomfort, nausea, and bloating side effects. CONCLUSIONS: The plasma n-3 FA concentration in adults is greater after acute supplementation with n-3 FAs esterified in MAGs rather than in EEs or TGs, suggesting that with a lower dose of MAG n-3 FAs, the plasma n-3 FA concentrations attained are similar to those after higher doses of n-3 FAs esterified in EEs or TGs. This trial is registered at www.clinicaltrials.gov as NCT03897660.

Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.