Omega-3 polyunsaturated fatty acids supplementation in patients with diabetes and cardiovascular disease risk: does dose really matter?

There is a vast disagreement in relation to the possible beneficial effects of omega-3 polyunsaturated fatty acids (omega-3 PUFA) supplementation in patients with diabetes and cardiovascular disease. The conflicting results between the various original studies and meta-analyses could be partially explained as a result of variable supplementation dosage and duration, either of which may modify the effects of omega-3 PUFA on cardio-metabolic biomarkers. Meta-analyses are limited usually by the inability to draw inferences regarding dosage, duration and the interaction of dosage and duration of omega-3 PUFA intake. Even so, almost all endpoints in the so-called "negative" meta-analyses leaned toward a trend for benefit with a near 10% reduction in cardiovascular outcomes and a borderline statistical significance. Many trials included in these meta-analyses tested an insufficient daily dose of omega-3 PUFA of less than 1000 mg. Probably, the consistent cardiovascular effects of omega-3 PUFA supplements could be expected only with daily doses above 2000 mg.

The Role of Omega-3 Fatty Acids in Diets.

The article is a summary of Dra. Carmen Gómez Candela's presentation at the Science in Nutrition 3rd International Congress in Milan, March 2014. The article covers omega-3 fatty acids use in different medical areas and several institutions' opinions in relation to the topic. Omega-3 acids are essential fatty acids. A certain amount of omega-3 is needed in our daily diet; however, the usual consumption is generally less than the recommended amount. Changes in dietary patterns in the course of history have led to deficit levels of omega-3 in the human body. Currently, there is increasing evidence of the benefits of omega-3 in different medical specialities. There are still some gaps regarding its role in illnesses such as dementia, psychiatric disorders, and inflammatory diseases. Nevertheless, stronger evidence is being proved in cardiovascular diseases and cancer. This article provides a reflection on possible ways to increase omega-3 daily consumption and the constraints associated with food with high contents of heavy metals, which, in turn, are also rich in omega-3s.

Determination of Microplastics in Omega-3 Oil Supplements.

Microplastics (MPs) are ubiquitous in the environment, posing a threat to ecosystems and causing increasing concerns regarding their impacts on the human body through exposure. However, there has been limited research on the presence of MPs in functional foods, despite them being consumed for health improvement. This study aimed to investigate MP occurrence in various omega-3 oils and oil products in the Korean market and its relation to the source of raw material or manufacture. MPs were investigated in omega-3 capsules and raw oil, sourced from both plant-based (PB) and animal-based (AB) sources. We developed a method of direct filtration with acetone washing for collecting and characterizing MPs larger than 5 µm using micro-Raman spectroscopy. The average number of MPs by mass was found to be 1.2 ± 1.7 MPs/g for PB raw oil, 2.2 ± 1.7 MPs/g for AB raw oil, 3.5 ± 3.9 MPs/g for PB capsule oil, and 10.6 ± 8.9 MPs/g for AB capsule oil. Polypropylene and polyethylene terephthalate were the major MP species (83-95%) found in omega-3 oil. The proportions based on size range remained consistent across all groups, with a trend of being detected at higher rates as the size decreased. The results reveal that the main reason for the MP contamination of omega-3 oil is not the source of raw material but the manufacturing and packaging process.

HPLC/HRMS and GC/MS for Triacylglycerols Characterization of Tuna Fish Oils Obtained from Green Extraction.

BACKGROUND: Fish oil is one of the most common lipidic substances that is consumed as a dietary supplement. The high omega-3 fatty acid content in fish oil is responsible for its numerous health benefits. Fish species such as mackerel, herring, tuna, and salmon are particularly rich in these lipids, which contain two essential omega-3 fatty acids, known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). OBJECTIVES: Due to the scarcity of information in the literature, this study aimed to conduct a qualitative and quantitative characterization of triglycerides (TAGs) in crude tuna fish oil using HPLC/HRMS. Fatty acid (FA) determination was also performed using GC/MS. The tuna fish oils analyzed were produced using a green, low-temperature process from the remnants of fish production, avoiding the use of any extraction solvents. RESULTS: The analyses led to the tentative identification and semi-quantitation of 81 TAGs. In silico saponification and comparison with fatty acid methyl ester results helped to confirm the identified TAGs and their quantities. The study found that the produced oil is rich in EPA, DHA, and erucic acid, while the negligible isomerization of fatty acids to trans-derivatives was observed.

Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels?

BACKGROUND: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy). OBJECTIVES: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout the 3-years of treatment with an additional 2 years of observational follow-up. DESIGN: Experimental study. PARTICIPANTS: From the 1680 participants that were randomized in the four groups of the MAPT study (two of which received n-3 PUFA, the other two without n-3 PUFA), 782 were selected because they had baseline data on both Hcy and n-3 PUFA. MEASUREMENTS: Cognitive performance was measured with a broad set of cognitive tests including free and total recall of the cued selective reminding test, digit symbol substitution test, category naming test and Trail-making tests (TMT-A and B) and Clinical dementia rating scale. RESULTS: We found a significant association between TMT-A and red blood cell n-3 PUFA levels in participants with Hcy values ≤16.8 µMol/L after adjustments at baseline (Estimate: -1.3, 95% CI: -2.3; -0.3, p=0.01). Additionally, participants with high Hcy values had a significant worsening after adjustments in TMT-B after a 5-year n-3 PUFA supplementation, compared to low levels of Hcy (Mean difference: 34.8, 95% CI: 7.8;61.7). CONCLUSION: This study shows that Hcy levels could modify the association between red blood cell n-3 PUFA and executive function. People with high Hcy may benefit less from a n-3 PUFA supplementation to prevent cognitive decline.

Dietary Interventions with or without Omega-3 Supplementation for the Management of Rheumatoid Arthritis: A Systematic Review.

Rheumatoid Arthritis (RA) is a chronic autoimmune condition characterized by symptoms of inflammation and pain in the joints. RA is estimated to have a worldwide prevalence of 0.5-1%, with a predominance in females. Diet may play an important role in the symptoms of RA; however, little is known about the effects of various diets. The aim of this systematic review is to explore the effect of dietary interventions, with or without omega-3 supplementation for the management of RA. The electronic databases MEDLINE, EMBASE, CINAHL, and the Cochrane Library were systematically searched for clinical trials investigating dietary interventions, with or without omega-3 supplementation to retrieve papers from inception to April 2021. Randomized and non-randomized controlled trials of dietary interventions in adults with RA were eligible for inclusion. Twenty studies with a total of 1063 participants were included. The most frequently reported outcomes were pain, duration of morning stiffness, joint tenderness, grip strength and inflammatory markers. Dietary interventions with an anti-inflammatory basis may be an effective way for adults with RA seeking complementary treatments, potentially leading to improvements in certain parameters. However, there is a need for longer duration studies that are well-designed and sufficiently powered to investigate the influence of diet on RA.

Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and FADS Genetic Variation.

Human diets in developed countries such as the US have changed dramatically over the past 75 years, leading to increased obesity, inflammation, and cardiometabolic dysfunction. Evidence over the past decade indicates that the interaction of genetic variation with changes in the intake of 18-carbon essential dietary omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), respectively, has impacted numerous molecular and clinical phenotypes. Interactions are particularly relevant with the FADS1 and FADS2 genes, which encode key fatty acid desaturases in the pathway that converts LA and ALA to their long chain (≥20 carbons), highly unsaturated fatty acid (HUFA) counterparts. These gene by nutrient interactions affect the levels and balance of n-6 and n-3 HUFA that in turn are converted to a wide array of lipids with signaling roles, including eicosanoids, docosanoids, other oxylipins and endocannabinoids. With few exceptions, n-6 HUFA are precursors of pro-inflammatory/pro-thrombotic signaling lipids, and n-3 HUFA are generally anti-inflammatory/anti-thrombotic. We and others have demonstrated that African ancestry populations have much higher frequencies (vs. European-, Asian- or indigenous Americas-ancestry populations) of a FADS "derived" haplotype that is associated with the efficient conversion of high levels of dietary n-6 PUFA to pro-inflammatory n-6 HUFA. By contrast, an "ancestral" haplotype, carrying alleles associated with a limited capacity to synthesize HUFA, which can lead to n-3 HUFA deficiency, is found at high frequency in certain Hispanic populations and is nearly fixed in several indigenous populations from the Americas. Based on these observations, a focused secondary subgroup analysis of the VITAL n-3 HUFA supplementation trial stratifying the data based on self-reported ancestry revealed that African Americans may benefit from n-3 HUFA supplementation, and both ancestry and FADS variability should be factored into future clinical trials design.

Evaluation of the composition and oxidative status of omega-3 fatty acid supplements on the Finnish market using NMR and SPME-GC-MS in comparison with conventional methods.

Previous studies disagree on the oxidative status of omega-3 supplements. The great deviation raises concerns about quality and the methods used to monitor it. This study investigated 49 omega-3 products for their fatty acid content, lipid class and oxidative status using official methods, gas and liquid chromatography with mass spectrometry and nuclear magnetic resonance spectroscopy. With minor deviations, omega-3 fatty acid content and lipid class of all products were as declared. 24% of studied products exceeded thresholds set by The Global Organization for EPA and DHA Omega-3s for peroxide and/or p-anisidine value suggesting a compromised oxidative status. However, peroxide and/or p-anisidine value were only suitable for detection of lipid oxidation in 90% or 73%, respectively, of the products. Analysis of volatile oxidation compounds can be an alternative method for p-anisidine value. Nuclear magnetic resonance spectroscopy was shown to be a rapid method for determination of oil type and lipid class.

Feasibility of a portable, low-cost near-infrared spectrophotometer for the quality screening of omega-3 dietary supplements.

The quality of omega-3 supplements, commercialized at substantial high prices and supplied by several manufacturers, must be assessed. The existing reference methods to attest the quality of omega-3 supplements are based on chromatography, which requires expensive equipment, a cumbersome analytical protocol to determine the contents of the active components, and operates ex-situ. This work evaluates, comprehensively, the feasibility of a low-cost near-infrared spectrophotometer and simple chemometrics to achieve fast and robust characterization of omega-3 supplements. The necessary attention, very often neglected, to the performance of the low-cost portable equipment is highlighted, and an appropriate sample measurement protocol is established. A non-conventional way to construct multivariate regression models based on partial least square regression to evaluated the omega-3 content in the supplements was proposed using few references values and completing the data set with the label values selected using the X-Y relation outliers plots. The results showed that the simple, fast and inexpensive approach proposed could deliver in situ relevant information related to the quality of the supplements such as identification several raw materials employed in its fabrication, screening for the content of the active components, identify frauds/non-conformities, and report on unscrupulous marketing practices.

Oxidation levels of North American over-the-counter n-3 (omega-3) supplements and the influence of supplement formulation and delivery form on evaluating oxidative safety.

The aim of the present study was to evaluate the oxidation status of North American n-3 (omega-3) PUFA nutritional supplements commercially available in Canada and evaluate the influence of product formulation and delivery form on oxidative safety. A total of 171 North American over-the-counter n-3 PUFA nutritional supplements were analysed for oxidation safety. Primary and secondary oxidation and total oxidation (TOTOX) were determined using the American Oil Chemists' Society (AOCS) procedures. Comparisons between supplements' final forms, oil source and n-3 PUFA concentration quartiles, as measures of product formulations and delivery forms, were compared using ANOVA. Of the products successfully tested, 50 % exceeded the voluntary recommended levels for markers of oxidation. Another 18 % of products were approaching the limits with 1-3 years before expiration. Encapsulated products without flavour additives had significantly lower secondary and TOTOX levels than bulk oils and flavoured products (P < 0·05). Children's products had significantly higher primary, secondary and TOTOX levels compared with all other products (P < 0·05). Markers of oxidation did not differ between oil sources (P > 0·05), with the exception of krill oil products having higher secondary oxidation levels than plant-based products (P > 0·05). Markers of oxidation did not differ between n-3 PUFA supplement concentration quartiles. Consumers may be at risk of exposure to higher levels of oxidative products. New regulatory mandates need to be introduced to ensure that all n-3 PUFA products, used as nutritional supplements, regardless of their formulation or delivery form, can be tested for oxidative safety and compliance.

Determination of lipid oxidation products in vegetable oils and marine omega-3 supplements.

BACKGROUND: There is convincing evidence that replacing dietary saturated fats with polyunsaturated fats (PUFA) decreases risk of cardiovascular diseases. Therefore, PUFA rich foods such as vegetable oils, fatty fish, and marine omega-3 supplements are recommended. However, PUFA are easily oxidizable and there is concern about possible negative health effects from intake of oxidized lipids. Little is known about the degree of lipid oxidation in such products. OBJECTIVE: To assess the content of lipid oxidation products in a large selection of vegetable oils and marine omega-3 supplements available in Norway. Both fresh and heated vegetable oils were studied. DESIGN: A large selection of commercially available vegetable oils and marine omega-3 supplements was purchased from grocery stores, pharmacies, and health food stores in Norway. The content of lipid oxidation products were measured as peroxide value and alkenal concentration. Twelve different vegetable oils were heated for a temperature (225°C) and time (25 minutes) resembling conditions typically used during cooking. RESULTS: The peroxide values were in the range 1.04-10.38 meq/kg for omega-3 supplements and in the range 0.60-5.33 meq/kg for fresh vegetable oils. The concentration range of alkenals was 158.23-932.19 nmol/mL for omega-3 supplements and 33.24-119.04 nmol/mL for vegetable oils. After heating, a 2.9-11.2 fold increase in alkenal concentration was observed for vegetable oils. CONCLUSIONS: The contents of hydroperoxides and alkenals in omega-3 supplements are higher than in vegetable oils. After heating vegetable oils, a large increase in alkenal concentration was observed.