Search Results (34)

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Background: n-3 Docosapentaenoic acid (DPA; 22:5 n-3) is increasingly viewed as a distinct long-chain omega-3 fatty acid with biological activities that are not fully captured by eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). However, progress remains limited by restricted access to high-purity DPA: most commercial sources contain DPA as a minor component, and published isolation strategies often yield only enriched mixtures or require multi-step workflows that are difficult to scale in standard laboratories. Objectives: We aimed to establish a robust, laboratory-accessible purification workflow to obtain DPA ethyl ester at high purity while preserving oxidative quality. Methods: Candidate lipid sources were screened to select an optimal DPA-containing feedstock. Oils were stabilized with antioxidants and pre-fractionated by cold crystallization (−20 °C) to reduce saturated lipids and oxidation by-products. Preparative separation used a stacked C18 flash system (15 μm + 45 μm in series) operated isocratically (methanol/water 92:8, v/v) at 120 mL/min. Fractions were analyzed by GC and iteratively reinjected to progressively enrich the DPA window. Solvent was recovered by distillation and reused. Results: Omegavie^® 4020EE (5.4% n-3 DPA) was identified as the best starting material. Pretreatment eliminated detectable TBARS-derived malondialdehyde. The isocratic purification-loop strategy produced tens of grams of DPA ethyl ester at >98% purity (GC–FID) defined as n-3 DPA area% of total identified fatty acid methyl esters by GC–FID, with per-cycle DPA recovery of 91–95%, overall recovery of 76% from the starting DPA content, and >90% solvent recycling. The workflow is scalable at the gram-to-tens-of-grams level for research laboratories, although solvent burden and column maintenance remain practical constraints for larger-scale implementation. Identity and purity were confirmed by GC–MS and ^1H NMR, and oxidation indices remained low (peroxide value < 0.2 meq/kg; p-anisidine < 3). Conclusions: This scalable, solvent-conscious protocol enables reliable access to high-purity DPA and should be adaptable to other low-abundance polyunsaturated fatty acids. Full article

Tenbrio molitor (T. molitor) is a widely utilized feed ingredient, though it is deficient in long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this, dietary supplements containing EPA and DHA in ethyl ester and triglyceride forms were administered to investigate the lipid metabolism and bioenhancement potential of T. molitor. The larvae exhibited normal growth across all treatment groups. EPA/DHA levels were significantly elevated in T. molitor-enriched diets, with newly identified phospholipid species including phosphatidylcholine 18:1_20:5 (PC 18:1_20:5) and phosphatidylethanolamine 18:0_20:5 (PE 18:0_20:5). KEGG pathway analysis revealed that glycerol phospholipid metabolism (ko00564), endogenous cannabinoid signaling (ko04723), and cell division (ko04148) were the core pathways that promoted phospholipid synthesis and oxidative lipid conversion (such as peroxide value-phosphatidylcholine, POV-PC). T. molitor activates glycerophospholipid metabolism, converting EPA/DHA into more bioavailable medium- and short-chain phospholipids, thereby enhancing its nutritional value and providing a new strategy for the development of functional foods/feeds. Full article

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article

A traditional dairy product from northern Colombia is suero costeño (SC), typically handmade through artisanal processes involving the natural fermentation of raw cow’s milk (RM); it is characterized by a creamy texture and a distinctive sensory profile, with a sour/salty taste and rancid odor. This study aimed to determine the chemical identity (using GC-FID/MSD) of SC and RM samples (from eight locations in the department of Córdoba-Colombia) by analyzing volatile components (trapped by HS-SPME and SDE) and fatty acid content. Consequently, the most notable results were as follows: (a) myristic (7–12%), stearic (12–17%), oleic (13–23%), and palmitic (21–29%) acids were the most abundant constituents [without significant differences among them (p > 0.05)] in both RM and SC fats; these were also expressed as polyunsaturated (2–5%), monounsaturated (26–36%), saturated (59–69%), omega-9 (19–30%), omega-6 (0.5–1.6%), and omega-3 (0.2–1.2%) fatty acids; (b) differences in the composition (p < 0.05) of the volatile fractions were distinguished between RM and SC samples; likewise, the SC samples differed (from each other) in their volatile composition due to the preparation processes applied (processes with raw milk and natural fermentation had less variability); nonetheless, it was possible to determine the volatilome for the artisanal product; and (c) the major components responsible for the chemical identity of SC were ethyl esters (of linear saturated and unsaturated acids, short/medium chains), aliphatic alcohols (linear/branched, short/long chains), aliphatic aldehydes (long chains, >C₁₄), alkyl methyl ketones (long chains, >C₁₁), sesquiterpenes (caryophyllane/humulane types), monoterpenes (mono/bi-cyclics), short-chain fatty acids, and aromatic alcohol/acid, among others. Full article

This study investigated the fatty acids (FA) profile of 54 actinomycete strains isolated from marine sediments collected off the Portugal continental coast, specifically from the Estremadura Spur pockmarks field, by GC/MS. Fatty acid methyl esters (FAMEs) were prepared from the ethyl acetate lipidic extracts of these strains and analyzed by gas chromatography–mass spectrometry (GC/MS), with FA identification performed using the NIST library. The identified FAs varied from C12:0 to C20:0, where 32 distinct FAs were identified, including 7 branched-chain fatty acids (BCFAs), 9 odd-chain fatty acids (OCFAs), 8 monounsaturated fatty acids (MUFAs), 6 saturated fatty acids (SFAs), 1 polyunsaturated fatty acid (PUFA), and 1 cyclic chain fatty acid (CCFA). The average expressed content was BCFA (47.54%), MUFA (28.49%), OCFA (26.93%), and SFA (22.16%), of which i-C16:0, C18:1ω9, and C16:0 were predominant, while PUFA (3.58%) and CCFA (0.41%) were identified as minor components. The identified BCFA were i-C16:0, a-C15:0, i-C15:0, i-C15:1ω6, a-C16:0, a-C14:0, and i-C17:0, which include combined branching and unsaturation and branching and odd. SFAs were present in all species, with C16:0 and C18:0 being the most representative. Rare OCFAs C19:1ω9, C17:1ω7, C15:0, and C17:0 were expressed. PUFA C18:1ω9 was detected; within this class, omega families ω9, ω7, ω6, and ω5 were identified, and no ω3 was detected. The only CCFA was benzene-butanoic acid (benzene-C4:0). These findings highlight the metabolic versatility of actinomycetes, providing valuable insights into microbial chemotaxonomy and offering promising biochemical leads for the development of biofuel, nutraceutical, and antifungal agents. Furthermore, these results underline the diversity and biotechnological potential of FAs in actinomycetes, uncovering their potential to be used as microbial cell factories, and paving the way for innovations in biofuels, pharmaceuticals, and eco-friendly industrial products. Full article

Omega-3 fatty acids are an important factor contributing to the prevention and cure of numerous diseases, and therefore their supplementation with diet is a significant issue. There are numerous supplements on the market containing omega-3 acids, of both plant and animal origin. In our study, we compared an effect of linseed oil, ethyl esters of linseed oil and fish oil supplementation to rats’ diet on their blood serum and erythrocyte fatty acid profile. The animals were divided into nine groups, three groups did not receive supplements and differed in dietary fat content, three were fed a high-fat diet for the whole experiment and supplemented, three were fed a high-fat diet and then the control one together with supplements. The experiment lasted 12 weeks. Significant changes in the profile of omega-3 fatty acids, as well as the ration of omega-6 to omega-3, were found in supplemented groups compared to the controls, the changes were more beneficial in groups supplemented with ethyl esters of linseed oil. The results were also more beneficial in groups where in addition to supplementation, there was also a dietary change from high fat to control during the supplementation period. In the case of the erythrocytes, the alpha-linolenic acid (ALA) content in ethyl ester-supplemented groups increased (p < 0.05) by about 60–120%, eicosapentaenoic acid (EPA) by 80%, and docosahexaenoic acid (DHA) by 41–60% compared to the control. In turn, in the blood serum, this increase (p < 0.05) was about 70–125%, 26–40%, and 38–54%, respectively. In the case of ethyl esters, except for an increase in EPA and DHA acids, higher values of ALA were found, which can be further used in the process of conversion to longer-chain omega-3. Full article

Omega-3 fatty acids are in high demand due to their efficacy in treating hypertriglyceridemia and preventing cardiovascular diseases. However, the growth of the industry is hampered by low purity and insufficient productivity. This study aims to develop an efficient RP-MPLC purification method for omega-3 fatty acid ethyl esters with high purity and capacity. The results indicate that the AQ-C18 featuring polar end-capped silanol groups outperformed C18 and others in retention time and impurity separation. By injecting pure fish oil esters with a volume equivalent to a 1.25% bed volume on an AQ-C18 MPLC column using a binary isocratic methanol–water (90:10, v:v) mobile phase at 30 mL/min, optimal omega-3 fatty acid ethyl esters were obtained, with the notable purity of 90.34% and a recovery rate of 74.30%. The total content of EPA and DHA produced increased from 67.91% to 85.27%, meeting the acceptance criteria of no less than 84% set by the 2020 edition of the Pharmacopoeia of the People’s Republic of China. In contrast, RP-MPLC significantly enhanced the production efficiency per unit output compared to RP-HPLC. This study demonstrates a pioneering approach to producing omega-3 fatty acid ethyl esters with high purity and of greater quantity using AQ-C18 RP-MPLC, showing this method’s significant potential for use in industrial-scale manufacturing. Full article

Marine microalgae Schizochytrium sp. have a high content of docosahexaenoic acid (DHA), an omega-3 fatty acid that is attracting interest since it prevents certain neurodegenerative diseases. The obtention of a bioactive and purified DHA fatty acid ester using a whole-integrated process in which renewable sources and alternative methodologies are employed is the aim of this study. For this reason, lyophilized Schizochytrium biomass was used as an alternative to fish oil, and advanced extraction techniques as well as enzymatic modification were studied. Microalgal oil extraction was optimized via a surface-response method using pressurized liquid extraction (PLE) obtaining high oil yields (29.06 ± 0.12%) with a high concentration of DHA (51.15 ± 0.72%). Then, the enzymatic modification of Schizochytrium oil was developed by ethanolysis using immobilized Candida antarctica B lipase (Novozym^® 435) at two reaction temperatures and different enzymatic loads. The best condition (40 °C and 200 mg of lipase) produced the highest yield of fatty acid ethyl ester (FAEE) (100%) after 8 h of a reaction attaining a cost-effective and alternative process. Finally, an enriched and purified fraction containing DHA-FAEE was obtained using open-column chromatography with a remarkably high concentration of 93.2 ± 1.3% DHA. The purified and bioactive molecules obtained in this study can be used as nutraceutical and active pharmaceutical intermediates of marine origin. Full article

The move towards environmentally friendly processing has been a driving force for research into green methods for the extraction of bioactive compounds from plant materials. In this study, a green and efficient process for the extraction of β-carotene from sea buckthorn berries through the simultaneous use of ultrasound and microwave, using a novel green solvent, fatty acid ethyl esters (FAEE), is described. For the same extraction time (45 min), the β-carotene content in the extract was significantly increased (according to ANOVA analysis—p < 0.05) by the simultaneous use of ultrasound and microwave, compared with the separate use of these technologies—an increase of 15 and 89% compared with ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE), respectively. The resulting extract can be used directly, without further purification, as a food supplement because the solvent itself is safe for consumption. Furthermore, FAEE contains omega-3 and omega-6 fatty acids which add to the health benefits of the extract. When β-carotene is extracted from the plant matrix, it is subjected to degradation due to oxidation, but the addition of the antioxidant vitamin E (13 mg/mL of extract) to the extract extends its stability to more than 90 days at room temperature even when exposed to light. The addition of vitamin E also enhances the health benefits of the extract. Full article

Dyslipidemia is a serious condition affecting an increasing number of people, and thus, preventive measures, including supplementation, are being developed. We aimed to compare the effect of linseed oil, its ethyl esters and fish oil supplementation on the serum lipid profiles of rats fed a high-fat diet. Wistar rats were divided into nine groups. Four of them were fed a high-fat diet for the whole experiment, four groups were fed a high-fat diet before the supplementation period and then the control one with supplements, and one was fed a control diet without supplements. The whole experiment lasted 12 weeks. A significant reduction in blood triglycerides, total cholesterol and the LDL fraction was noted in supplemented groups compared to the controls, especially in groups supplemented with ethyl esters of linseed oil and linseed oil compared to fish oil groups. The results were also more beneficial in groups where, in addition to supplementation, there was also a diet change from a high-fat diet to a control diet during the supplementation period. We may conclude that supplementation with omega-3 fatty acids, combined with a healthy diet, may be a good way of preventing or alleviating dyslipidemia. Full article

The aim of this study was to determine the effect of supplementation with ethyl esters of linseed oil on the fatty acid profile in hair sebum, blood serum and erythrocyte membranes in healthy dogs. The material for the study included hair and blood samples of adult beagle dogs. The experiment was performed in two periods: summer and winter. Each time it lasted 16 weeks. During the first 8 weeks, the dogs received a supplement, the amount of which was determined individually so that the ratio of α-linolenic acid (ALA) to linoleic acid (LA) together in the feed and supplement was 1:1. Hair coat and blood samples were collected on days 0, 56 and 112; i.e., before the start of supplementation, after 8 weeks of supplementation and 8 weeks after supplementation was completed. The study included a determination of the fatty acid profile with a particular emphasis on polyunsaturated fatty acids (PUFAs) and the ratio of omega-6 to omega-3 in hair sebum, blood serum and erythrocyte membranes. As a result of supplementation, a significant decrease in saturated acids and an increase in unsaturated acids was observed in hair sebum both in summer and winter and especially in omega-3 fatty acids; i.e., α-linolenic (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The same relationships were observed in blood serum and in erythrocyte cell membranes in all the studied periods. Additionally, 8 weeks after the end of supplementation, the level of polyunsaturated fatty acids was still higher compared to the period before supplementation. Moreover, the supplementation resulted in a favorable decrease in the ratio of omega-6 to omega-3 acids in the tested samples, which persisted even after the withdrawal period. Full article

Numerous studies have shown that improvements in the sperm and semen quality of males of many species can be achieved with appropriate dietary supplements added to feed or fodder. Particularly promising seems to be the inclusion of omega polyunsaturated fatty acids in the diets of males. Among other things, it has been shown that linseed oil ethyl esters (EELO can be an excellent source of omega 3 polyunsaturated fatty acids in animal diets. These compounds are more durable and resistant to oxidation, epoxidation and resinification processes, and do not exhibit toxic properties in living organisms. At present, there is a lack of data in the literature on the enrichment of boar diets with EELO. The purpose of this study was to analyze the effects of the addition of EELO to boar diets on the properties of sperm in fresh semen. The study was conducted during the summer on semen collected from 12 boars of the line 990. Linseed oil ethyl esters were administered in each feeding at a rate of 3.0% (45 mL each) in basal diets for each boar on a daily basis for 16 weeks. Ejaculates were collected manually by the gloved-hand technique, at one-week intervals for eight-week periods, from the eighth week onwards after the start of feeding. Eight ejaculates were collected from each boar, totaling 96 samples. The addition of EELO to the diets of boars caused an increase in sperm viability (p < 0.001), semen volume (310 mL versus 216 mL, p < 0.001) and sperm concentration (331 versus 216 million per mL, p < 0.001). Furthermore, in the experimental animals, there was a decrease in the percentage of spermatozoa exhibiting DNA fragmentation. The experimental boars also showed an increase in the percentage of gametes without apoptosis and capacitation and an increase in the percentage of viable spermatozoa not showing lipid peroxidation membranes. Consequently, EELO nutritional supplementation resulted in the improved quality of the fresh semen of boars. Full article

Cardiovascular diseases (CVDs) are among the most impactful illnesses globally. Currently, the available therapeutic option has several side effects, including hypotension, bradycardia, arrhythmia, and alteration in different ion concentrations. Recently, bioactive compounds from natural sources, including plants, microorganisms, and marine creatures, have gained a lot of interest. Marine sources serve as reservoirs for new bioactive metabolites with various pharmacological activities. The marine-derived compound such as omega-3 acid ethyl esters, xyloketal B, asperlin, and saringosterol showed promising results in several CVDs. The present review focuses on marine-derived compounds’ cardioprotective potential for hypertension, ischemic heart disease, myocardial infarction, and atherosclerosis. In addition to therapeutic alternatives, the current use of marine-derived components, the future trajectory, and restrictions are also reviewed. Full article