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1.
Food Funct ; 12(14): 6588-6602, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34100498

RESUMO

The natural structure of whole food plays an important role in the physiological impact of bioactive compounds present within the food, also known as the "matrix effect". Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) are one example of a food-derived nutrient, mostly found in fish, that is believed to be influenced by the food matrix. However, most previous studies have compared only the long-term bioavailability of fish versus fish oil and have used commercial sources of fish oil. The present study aimed to investigate whether fish (salmon) matrix influences the transit of LCn-3PUFAs during in vitro digestion and affects bioavailability in healthy females. Meals containing intact salmon (intact structure), minced salmon (some structure) and defatted salmon + oil (no structure) with identical macronutrient compositions were developed. Healthy female participants (n = 13) consumed the meals in a postprandial crossover study and blood was collected at regular time points for 6 h post meal consumption. In parallel, in vitro digestion of the meals was performed using a human gastric simulator (HGS) and digesta samples were collected at regular time points for 6 h. Results: showed that plasma concentration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were significantly higher after participants consumed intact salmon compared to the other meals (covariate analysis p < 0.001). The in vitro digestion results showed defatted salmon + oil meal had a faster decrease in pH and faster fat emptying from the HGS than the other two meals. The defatted salmon + oil meal more closely followed fat emptying of a homogeneous unstructured meal, whereas the other meals exhibited phase separation with a delay in fat emptying. Conclusion: The fish matrix (salmon) plays an important role in the bioaccessibility and bioavailability of EPA and DHA. The differences are partly explained by fat digestion and emptying from the stomach. This study suggests that the natural structure of fish has a functional effect on the absorption and bioavailability of fish oil.


Assuntos
Digestão , Ácidos Graxos Ômega-3/farmacocinética , Refeições , Salmão , Adulto , Animais , Disponibilidade Biológica , Estudos Cross-Over , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacocinética , Feminino , Óleos de Peixe/farmacocinética , Humanos , Período Pós-Prandial , Alimentos Marinhos , Adulto Jovem
2.
Nutrients ; 13(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445698

RESUMO

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS-lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1ß increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.


Assuntos
Ácidos Graxos/sangue , Óleos de Peixe/farmacologia , Interleucina-1beta/sangue , Lipopolissacarídeos/toxicidade , Oxilipinas/sangue , Animais , Animais Recém-Nascidos , Emulsões , Óleos de Peixe/farmacocinética , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Infusões Parenterais , Suínos
3.
J Neurosci Res ; 99(2): 561-572, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32964457

RESUMO

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke-associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA-mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood-brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf-1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO-1 system) and anti-inflammatory effects (via promoting JNK/AP-1 signaling) of DHA.


Assuntos
Dano Encefálico Crônico/prevenção & controle , Ácidos Docosa-Hexaenoicos/uso terapêutico , AVC Isquêmico/dietoterapia , Degeneração Neural/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Transporte Biológico , Barreira Hematoencefálica , Dano Encefálico Crônico/etiologia , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacocinética , Gorduras na Dieta/uso terapêutico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácidos Docosa-Hexaenoicos/farmacologia , Proteínas de Ligação a Ácido Graxo/fisiologia , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacocinética , Humanos , Incidência , AVC Isquêmico/complicações , AVC Isquêmico/epidemiologia , Lipídeos de Membrana/metabolismo , Camundongos , Proteínas de Neoplasias/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacocinética , Transdução de Sinais/efeitos dos fármacos , Simportadores/deficiência , Simportadores/fisiologia , Ácido alfa-Linolênico/farmacocinética
4.
Clin Nutr ; 40(3): 987-996, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32753350

RESUMO

BACKGROUND & AIMS: Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. DESIGN: Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg-1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). RESULTS: MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min. CONCLUSION: A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.


Assuntos
Emulsões Gordurosas Intravenosas/farmacocinética , Óleos de Peixe/farmacocinética , Lipídeos/sangue , Triglicerídeos/farmacocinética , Animais , Disponibilidade Biológica , Feminino , Cinética , Fígado/metabolismo , Macaca fascicularis , Masculino , Taxa de Depuração Metabólica , Camundongos , Modelos Animais , Azeite de Oliva/farmacocinética , Nutrição Parenteral , Ratos , Triglicerídeos/química
5.
Lipids ; 56(2): 189-200, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33047832

RESUMO

A finishing diet strategy is effective at increasing fillet long-chain n-3 fatty acid content in fish consuming sustainable plant oil-based diets. This study investigates the outcomes of a fish oil finishing diet upon the hepatic fatty acid and transcriptome profile in rainbow trout (Oncorhynchus mykiss). Fish were placed on one of three feeding treatments: (1) FO: a fish oil (FO) diet for 20 weeks, (2) VO/FO: a vegetable oil (VO) diet during weeks 1-12 then the FO diet for 8 weeks, or (3) VO/fd/FO: the VO diet between weeks 1-12, 2 weeks of feed deprivation, then the FO diet for 6 weeks. Hepatic fatty acid and transcriptome profiles were analyzed at week 12, 14, and 20. Hepatic fatty acid profiles at week 12 were similar to dietary profiles; transcriptomic analyses indicated 131 differentially regulated genes (DEG) between VO- and FO-fed fish, characterized by VO-induced up-regulation of cholesterol and long-chain fatty acyl-CoA synthesis and oxidation-reduction processes. At week 14, the hepatic fatty acid profile was similar between VO/FO and FO, although concentrations of 18:3n-3 remained higher in the VO/FO group. Thirty-three DEG were detected at week 14 with enrichment of genes associated with extracellular matrix assembly, supporting liver remodeling during the early finishing diet period. Only five DEG were detected at week 20 between VO/FO and FO. Collectively, these findings suggest that it takes several weeks for liver to reach a homeostatic state, even after the hepatic fatty acid equilibration following a finishing diet.


Assuntos
Ácidos Graxos/análise , Óleos de Peixe/farmacocinética , Fígado/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Dieta , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Óleos de Peixe/administração & dosagem , Fígado/química , Fígado/metabolismo , Oncorhynchus mykiss , Óleos de Plantas/administração & dosagem , Transcriptoma
6.
Food Funct ; 11(10): 8637-8647, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32936172

RESUMO

Fish oil-loaded hollow solid lipid micro- and nanoparticles were prepared by atomization of the CO2-expanded lipid mixture. The obtained particles were spherical and free-flowing with an average particle size of 6.9 µm. Fish oil loading efficiency was achieved at 92.3% (w/w). The in vitro digestive stability, lipid digestibility and EPA and DHA bioaccessibility of the fish oil-loaded particles were examined using an in vitro sequential digestion model. The mean particle diameter increased markedly after oral (15.2 µm) and gastric (32.4 µm) digestion and then decreased after the small intestinal stage (24.0 µm). Fish oil-loaded particles remained spherical and intact but mainly agglomerated on the top phase throughout the oral and gastric digestion. However, a mixed digesta was formed after the small intestinal digestion, which contained digested broken particle pieces, undigested fish oil-loaded particles, free fatty acids, monoacylglycerols and micelles. The extent of lipolysis was significantly increased for the 30% fish oil-loaded particles as compared to physical mixtures of empty hollow solid lipid particles or bulk FHSO and fish oil (p < 0.05). Moreover, EPA and DHA bioaccessibility was significantly improved from 9.7 to 18.2% with the 30% fish oil-loaded particles (p < 0.05).


Assuntos
Digestão , Óleos de Peixe , Nanopartículas , Disponibilidade Biológica , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/farmacocinética , Óleos de Peixe/química , Óleos de Peixe/farmacocinética , Técnicas In Vitro , Lipólise , Tamanho da Partícula
7.
Food Chem ; 326: 126963, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32413754

RESUMO

Neat epigallocatechin gallate (EGCG) has low bioavailability and tuna oil (TO) is prone to oxidation. Broccoli byproducts (BBP) were used for preparing TO-BBP (25% oil, dry basis) and TO-EGCG-BBP (20% oil and 20% EGCG, dry basis) powders. The gross composition and surface fat of powders and morphology of reconstituted emulsions were characterized. Oxipres® data (80 °C, 5 bar oxygen pressure) showed that the TO-EGCG-BBP formulation was more oxidatively stable [Induction period (IP) > 100 h] than TO-BBP (IP ~ 20 h). During in vitro digestion, 90% of EGCG was recovered in the whole intestinal digesta of the TO-EGCG-BBP formulation compared to 76% for the EGCG-BBP formulation and 66% for the neat EGCG. The use of BBP for co-delivering EGCG and TO increases oxidative stability of TO and improves EGCG stability during in vitro digestion. This study highlights the potential for formulating functional ingredient with BBP and contribute to food waste reduction.


Assuntos
Brassica , Catequina/análogos & derivados , Emulsões/química , Óleos de Peixe/administração & dosagem , Atum , Animais , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/química , Catequina/farmacocinética , Suplementos Nutricionais , Digestão , Óleos de Peixe/química , Óleos de Peixe/farmacocinética , Alimentos , Oxirredução , Pós , Eliminação de Resíduos , Resíduos
8.
Mol Nutr Food Res ; 64(12): e2000059, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32304625

RESUMO

SCOPE: Currently available omega-3 fatty acid supplements do not enrich the docosahexaenoic acid (DHA) of the adult brain because they are absorbed as triacylglycerol, whereas the transporter at the blood brain barrier requires lysophosphatidylcholine (LPC)-DHA. The hypothesis that treatment of krill oil (KO), which contains DHA/eicosapentaenoic acid (EPA) at the SN2 position of phosphatidylcholine, with SN1-specific lipase will generate LPC-DHA/EPA and which can be absorbed intact and transported into the brain, is tested. METHODS: KO and fish oil (FO) are treated with Mucor meihei lipase, incorporated into AIN 93G diet, and fed to 2-month-old mice for 30 days. Fatty acid composition is analyzed by gas chromatography/mass spectroscopy. Brain derived neurotrophic factor (BDNF) is measured by ELISA. RESULTS: Lipase-treated (LT) KO increases brain DHA and EPA, respectively, 5-and 70-fold better than untreated (UT) KO. FO, whether lipase-treated or not, has no effect on brain DHA/EPA. LTKO is also more efficient in enriching liver DHA/EPA, but less efficient than UTKO and FO in enriching adipose tissue and heart. Brain BDNF is significantly increased by LTKO, but only marginally by other preparations. CONCLUSIONS: Pretreatment of dietary KO with lipase enables it to efficiently increase brain DHA/EPA because of the generation of LPC-DHA/EPA.


Assuntos
Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/farmacocinética , Euphausiacea/química , Óleos/farmacocinética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/química , Óleos de Peixe/farmacocinética , Coração/efeitos dos fármacos , Lipase/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Óleos/química , Distribuição Tecidual
9.
Drug Deliv Transl Res ; 10(4): 1136-1146, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32219727

RESUMO

The present study investigates the role of fish oil (FO)- and butter oil (BO)-enriched microemulsion-based system of galantamine hydrobromide (GH), an anti-Alzheimer drug, for its potential role in brain permeation enhancement and neuroprotection against oxidative stress. Microemulsion (ME)-based system of GH was prepared using water phase titration. The prepared ME was characterized by several physicochemical parameters like particle size, polydispersity index, and ex vivo drug permeation. Cell-based oxidative stress assays and pharmacokinetic studies were performed using C6 glial cell lines, and Sprague Dawley rats, respectively. The optimized ME comprised 5.3% v/v of Capmul MCM EP (as oil),15.8% v/v of Tween-80 (as surfactant), 5.3% v/v of Transcutol P (as co-surfactant), and 73.6% v/v of water (as aqueous phase). The addition of FO and BO resulted in a slight increase in the droplet size and decrease in transparency of ME. Cell-based anti-oxidative stress assays (glutathione assay, nitrite assay, and lipid peroxidation assay) showed the efficacy of formulation in the order of ME, BO ME, and FO ME, respectively. A similar trend was also observed in in vivo animal studies, wherein GH FO ME showed a comparatively higher percentage of drug reaching the brain when administered by intranasal route than by IV route. The study concluded the potential benefits of co-administering FO- and BO-enriched microemulsion is not only enhancing the permeation of drugs across BBB but also improving efficacy against lipopolysaccharide-induced oxidative stress. Graphical abstract.


Assuntos
Óleos de Peixe/administração & dosagem , Galantamina/administração & dosagem , Ghee , Fármacos Neuroprotetores/administração & dosagem , Administração Intranasal , Administração Intravenosa , Animais , Encéfalo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Emulsões , Óleos de Peixe/química , Óleos de Peixe/farmacocinética , Galantamina/sangue , Galantamina/química , Galantamina/farmacocinética , Glutationa/metabolismo , Cabras , Lipopolissacarídeos , Malondialdeído/metabolismo , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
10.
JAMA Netw Open ; 3(1): e1919462, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31951274

RESUMO

Importance: Many young men have poor semen quality, and the causes are often unknown. Supplement intake of ω-3 polyunsaturated fatty acid has been found to improve semen quality among men with infertility, but the association with semen quality among healthy men is unknown. Objective: To determine if intake of ω-3 fatty acid supplements is associated with testicular function as measured by semen quality and reproductive hormone levels among healthy men. Design, Setting, and Participants: This cross-sectional study included young Danish men from the general population recruited between January 1, 2012, and December 31, 2017, at compulsory examinations to determine their fitness for military service. Young unselected men were approached after the examination and invited to participate in a study of reproductive function, regardless of their fitness for military service. Data analysis was conducted from September 1, 2018, to June 30, 2019. Exposures: Intake of supplements, including fish oil, during the past 3 months. Main Outcomes and Measures: Semen quality, measured as volume, concentration, total sperm count, percentage of morphologically normal spermatozoa, and motility, and serum reproductive hormone levels, measured as follicle-stimulating hormone, luteinizing hormone, testosterone, free testosterone, and inhibin B levels. Results: Among 1679 young Danish men (median [interquartile range] age, 18.9 [18.7-19.4] years) recruited to participate, 98 men (5.8%) reported use of fish oil supplements during the past 3 months, of whom 53 (54.1%) reported intake on 60 or more days. After adjustment and compared with men with no supplement intake, men with fish oil supplement intake on fewer than 60 days had semen volume that was 0.38 (95% CI, -0.03 to 0.80) mL higher, and men with fish oil supplement intake on 60 or more days had semen volume that was 0.64 (95% CI, 0.15 to 1.12) mL higher (P for trend < .001). Similarly, testicular size in men with supplement intake on fewer than 60 days was 0.8 (95% CI, -0.2 to 1.9) mL larger and in men with fish oil supplement intake on 60 or more days was 1.5 (95% CI, 0.2 to 2.8) mL larger compared with men with no supplement intake (P for trend = .007). After adjustment, men with fish oil supplement intake had a 20% (95% CI, 9%-31%) lower follicle-stimulating hormone level and 16% (95% CI, 8%-24%) lower luteinizing hormone level compared with men with no supplement intake. There were no associations of intake of other supplements with measures of testicular function. Conclusions and Relevance: These findings suggest that intake of fish oil supplements was associated with better testicular function, which is less likely to be due to confounding by indication, as no associations of intake of other supplements with testicular function were found. This cross-sectional study did not examine the actual content of ω-3 fatty acids in the supplements; therefore, these findings need confirmation in well-designed randomized clinical trials among unselected men.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacocinética , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/farmacocinética , Infertilidade Masculina/tratamento farmacológico , Comportamento Sexual/efeitos dos fármacos , Contagem de Espermatozoides , Adolescente , Estudos Transversais , Dinamarca , Hormônio Foliculoestimulante/sangue , Humanos , Inibinas , Hormônio Luteinizante/sangue , Masculino , Motilidade dos Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Adulto Jovem
11.
ACS Appl Mater Interfaces ; 12(5): 6536-6545, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31940164

RESUMO

Contrasting to the traditional centimeter-sized soft capsules that are difficult to swallow or micro/nanometer-sized soft capsules that suffer from limited loading capacity for fish oil/nutrients and lowered stability, the millimeter-sized soft capsules with good enough stability could be a potential solution in solving these problems. Herein, we report millimeter-sized soft core-shell capsules of 0.42-1.85 mm with an inner diameter of 0.36-1.75 mm, for fish oil/nutrients, obtained through an electrospray approach upon optimization of different fabrication parameters such as applied voltage, sodium alginate concentration, shell/core feeding rate ratio, times of feeding rate, and types of coaxial needles. Further in vitro and in vivo studies reveal that the resulting soft capsules were apparently weakened and became mechanically destructive in the simulated small intestine solution and were totally destroyed in the simulated small intestine solution if they were first treated in the simulated stomach solution but not in the simulated stomach solution, which makes the millimeter-sized capsules useful as containers for specific delivery of fish oils and lipophilic nutrients to the stomach and intestines with excellent in vivo bioavailability (>90%). The whole fabrication approach is very facile with no complicated polymer modification and formulations involved, which endows the resulting soft capsules with broad application prospect in food and drug industries.


Assuntos
Óleos de Peixe , Mucosa Gástrica/metabolismo , Intestino Delgado/metabolismo , Alginatos/química , Animais , Cápsulas , Técnicas Eletroquímicas , Óleos de Peixe/química , Óleos de Peixe/metabolismo , Óleos de Peixe/farmacocinética , Tamanho da Partícula , Coelhos
12.
Clin Nutr ; 39(3): 958-965, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31005335

RESUMO

BACKGROUND: Pharmacokinetics (PK) of pharmaceuticals and pharmaconutrients are poorly understood in critically ill patients, and dosing is often based on healthy subject data. This might be particularly problematic with enteral medications due to metabolic abnormalities and impaired gastrointestinal tract absorption common in critically ill patients. Utilizing enteral fish oil, this study was undertaken to better understand and define PK of enteral omega-3 fatty acids (eicospentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in critically ill patients with severe sepsis. MATERIALS AND METHODS: Healthy volunteers (n = 15) and mechanically ventilated (MV) adults with severe sepsis (n = 10) were recruited and received 9.75 g EPA and 6.75 g DHA daily in two divided enteral doses of fish oil for 7 days. Volunteers continued their normal diet without other sources of fish oil, and sepsis patients received standard enteral feeding. Blood was collected at frequent intervals during the 14-day study period. Peripheral blood mononuclear cells (PMBCs) and neutrophils were isolated and analyzed for membrane fatty acid (FA) content. Mixed linear models and t-tests were used to analyze changes in FA levels over time and FA levels at individual time points, respectively. PK parameters were obtained based on single compartment models of EPA and DHA kinetics. RESULTS: Healthy volunteers were 41.1 ± 10.3 years; 67% were women. In patients with severe sepsis (55.6 ± 13.4 years, 50% women), acute physiologic and chronic health evaluation (APACHE) II score was 27.2 ± 8.8 at ICU admission and median MV duration was 10.5 days. Serum EPA and DHA were significantly lower in sepsis vs. healthy subjects over time. PBMC EPA concentrations were generally not different between groups over time, while PBMC DHA was higher in sepsis patients. Neutrophil EPA and DHA concentrations were similar between groups. The half-life of EPA in serum and neutrophils was significantly shorter in sepsis patients, whereas other half-life parameters did not vary significantly between healthy volunteers and sepsis patients. CONCLUSIONS: While incorporation of n-3 FAs into PBMC and neutrophil membranes was relatively similar between healthy volunteers and sepsis patients receiving identical high doses of fish oil for one week, serum EPA and DHA were significantly lower in sepsis patients. These findings imply that serum concentrations and EPA and DHA may not be the dominant driver of leukocyte membrane incorporation of EPA and DHA. Furthermore, lower serum EPA and DHA concentrations suggest that either these n-3 FAs were being metabolized rapidly in sepsis patients or that absorption of enteral medications and pharmaconutrients, including fish oil, may be impaired in sepsis patients. If enteral absorption is impaired, doses of enteral medications administered to critically ill patients may be suboptimal.


Assuntos
Nutrição Enteral/métodos , Ácidos Graxos Ômega-3/farmacocinética , Óleos de Peixe/farmacocinética , Sepse/metabolismo , Adulto , Estudos de Coortes , Estado Terminal , Ácidos Graxos Ômega-3/metabolismo , Feminino , Óleos de Peixe/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Mol Nutr Food Res ; 64(4): e1900824, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31797565

RESUMO

Omega-3 fatty acid consumption has been suggested to be beneficial for the prevention of type 2 diabetes mellitus (T2DM). Its effects have been attributed to anti-inflammatory activity, with the inhibition of arachidonic acid metabolism playing a central role. However, a more recent view is that omega-3 fatty acids play an active role as the precursors of potent, specialized pro-resolving mediators (SPMs), such as resolvins, protectins, and maresins. Docosahexaenoic acid (DHA)- and eicosapentaenoic-acid-derived SPMs are identified in the adipose tissue but the levels of certain SPMs (e.g., protectin D1) are markedly reduced with obesity, suggesting adipose SPM deficiency, potentially resulting in unresolved inflammation. Supplementation of the biosynthetic intermediates of SPM (e.g., 17-hydroxy-DHA) or omega-3 fatty acids increases the level of adipose SPMs, reduces adipose inflammation (decrease in macrophage accumulation and change to less inflammatory macrophages), and enhances insulin sensitivity. The findings from studies using rodent obesity models must be translated to humans. It will be important to further elucidate the underlying mechanisms by which obesity reduces the levels of and the sensitivity to SPM in adipose tissues. This will enable the development of nutrition therapy to enhance the effects of omega-3 fatty acids in the prevention and/or treatment of T2DM.


Assuntos
Antígenos CD59/imunologia , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácidos Graxos Ômega-3/farmacocinética , Síndrome Metabólica/imunologia , Animais , Antígenos CD59/metabolismo , Antígenos CD59/farmacocinética , Diabetes Mellitus Tipo 2/prevenção & controle , Ácidos Docosa-Hexaenoicos/imunologia , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/imunologia , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacocinética , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/química , Óleos de Peixe/farmacocinética , Humanos , Inflamação/dietoterapia , Inflamação/prevenção & controle , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Obesidade/complicações , Obesidade/dietoterapia
14.
Environ Sci Pollut Res Int ; 27(4): 3950-3961, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31823254

RESUMO

Krill oil (KO) is a recent supplement which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are found in both krill oil and fish oil. In krill oil, they esterified to phospholipids, but in fish oil, they are esterified to triacylglycerols. The target of this study was to investigate whether KO could help against iron overload-induced toxicity in liver and spleen. Rats were randomly assigned into 3 categories: control rats, rats received iron in a drinking water for 8 weeks followed by either vehicle or KO (40 mg/kg) treatment for an extra 8 weeks. Extent of hepatic and splenic injury was assessed via biochemical, histopathological and immunohistochemical evaluations. KO effectively improved the microscopic features of liver and spleen. Moreover, it decreased the increased levels of serum transaminases, ALP, LDH, iron, and ferritin and increased albumin serum level as well. In addition, it restored the balance between oxidants and antioxidants in the hepatic and splenic tissues. Furthermore, it decreased HO-1 levels, upregulated the production of Nrf2, and limited the expression of MMP9. These findings altogether suggest that KO might be a new candidate for treatment of iron overload-induced toxicity. Graphical abstract Graphical abstract.


Assuntos
Euphausiacea , Óleos de Peixe/química , Sobrecarga de Ferro , Fígado/fisiopatologia , Animais , Euphausiacea/química , Fibrose , Óleos de Peixe/farmacocinética , Ferro , Estresse Oxidativo , Ratos , Baço
15.
Nutrition ; 70: 110417, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30867119

RESUMO

OBJECTIVES: Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55-enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats. METHODS: Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1ß and IL-10, blood-brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery. RESULTS: FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1ß levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment. CONCLUSIONS: FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.


Assuntos
Anti-Inflamatórios/farmacologia , Disfunção Cognitiva/prevenção & controle , Óleos de Peixe/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Sepse/psicologia , Animais , Biomarcadores/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Doenças do Ceco/complicações , Doenças do Ceco/microbiologia , Ceco/irrigação sanguínea , Ceco/microbiologia , Disfunção Cognitiva/microbiologia , Modelos Animais de Doenças , Emulsões , Lobo Frontal/efeitos dos fármacos , Interleucina-1beta/metabolismo , Perfuração Intestinal/complicações , Perfuração Intestinal/microbiologia , Ligadura/efeitos adversos , Masculino , Permeabilidade , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/etiologia , Sepse/microbiologia
16.
Nutrients ; 11(10)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652561

RESUMO

As an essential nutrient, the organic water-soluble compound choline is important for human health. Choline is required for numerous biological processes, including the synthesis of neurotransmitters, and it is an important prerequisite for structural integrity and the functioning of cells. A choline-rich diet provides crucial choline sources, yet additional choline dietary supplements might be needed to fully meet the body's requirements. Dependent on the structure of choline in different sources, absorption and metabolism may differ and strongly impact the bioavailability of circulating choline. This study in healthy volunteers aimed to compare the pharmacokinetics of free choline and of selected choline metabolites between the single dose intake of phosphatidylcholine, present in SuperbaBoostTM krill oil, and choline bitartrate salt. Results demonstrate that albeit free choline levels in plasma were comparable between both choline sources, peak choline concentration was reached significantly later upon intake of SuperbaBoostTM. Moreover, the occurrence of choline metabolites differed between the study products. Levels of the biologically important metabolites betaine and dimethylglycine (DMG) were higher, while levels of trimethylamine N-oxide (TMAO) were substantially lower upon intake of SuperbaBoostTM compared to choline bitartrate.


Assuntos
Colina/metabolismo , Colina/farmacocinética , Euphausiacea/química , Fosfatidilcolinas/metabolismo , Fosfatidilcolinas/farmacocinética , Adolescente , Adulto , Idoso , Animais , Produtos Biológicos , Colina/administração & dosagem , Colina/sangue , Estudos Cross-Over , Feminino , Óleos de Peixe/metabolismo , Óleos de Peixe/farmacocinética , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/sangue , Adulto Jovem
17.
Food Chem ; 275: 135-142, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724179

RESUMO

The physiological efficacy of nutraceuticals is dependent on their physicochemical nature and bioavailability across biological barriers. In the present work, effects of nano-sizing of emulsion-based delivery vehicle on the bioavailability of polyunsaturated fatty acids rich fish oil have been investigated via three-step experimental design; ex vivo rat everted intestinal sac model, cellular lipid uptake and the bioactivity in rat PBMCs. Nanoemulsion in comparison to the conventional emulsion has shown significant higher rate of uptake of polyunsaturated fatty acids in three segments of small intestine. The time-kinetics of such uptake was correlated with appearance of short-chain fatty acids in basal side of the everted sac. The bioavailability of the formulated fish oil and its inhibitory response against lipopolysaccharide-induced nitric oxide production in rat PBMCs were positively correlated. This formulation with nano-sized droplets can be utilized as smart delivery vehicles for designing oral therapies in future.


Assuntos
Emulsões/química , Óleos de Peixe/farmacocinética , Nanoestruturas/química , Animais , Disponibilidade Biológica , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacocinética , Emulsões/farmacocinética , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/farmacocinética , Óleos de Peixe/administração & dosagem , Intestino Delgado/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Veículos Farmacêuticos/química , Veículos Farmacêuticos/farmacocinética , Ratos Sprague-Dawley
18.
J Am Assoc Nurse Pract ; 29(12): 791-801, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29280361

RESUMO

BACKGROUND AND PURPOSE: Despite achievement of optimal low-density lipoprotein cholesterol (LDL-C) control with statin therapy, patients with elevated triglycerides (TGs) and residual cardiovascular risk are commonly encountered in clinical practice. METHODS: We present information from completed and ongoing clinical trials examining Rx omega-3s for TG-lowering and omega-3 dietary supplements to highlight important differences affecting patient management for nurse practitioners. CONCLUSIONS: Rx omega-3s demonstrate robust reductions in TGs and may have a role in reducing residual cardiovascular risk. Products containing docosahexaenoic acid (DHA) may raise LDL-C and should not be substituted for Rx eicosapentaenoic acid (EPA)-only icosapent ethyl, which does not raise LDL-C. Omega-3 dietary supplements (e.g., fish oils containing EPA and DHA) may be used for general health promotion; however, they are not regulated as medications and concerns regarding quality, purity, safety, and variability of content exist. It is important to advise patients that omega-3 dietary supplements are not medications and should not be substituted for Rx omega-3s. Large-scale cardiovascular outcomes studies are underway for Rx omega-3s in statin-treated patients. IMPLICATIONS FOR PRACTICE: Nurse practitioners can take an active role in reducing residual cardiovascular risk and educating patients about important differences between Rx omega-3s and fish oil supplements.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais/normas , Ácidos Graxos Ômega-3/farmacocinética , Medicamentos sob Prescrição/normas , Doenças Cardiovasculares/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacocinética , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/farmacocinética , Óleos de Peixe/uso terapêutico , Humanos , Hipertrigliceridemia/tratamento farmacológico , Fatores de Risco , Triglicerídeos/análise , Triglicerídeos/sangue
19.
Exp Biol Med (Maywood) ; 242(1): 80-87, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27510581

RESUMO

Omega-3 fatty acids, especially long-chain omega-3 fatty acids, have been associated with potential health benefits for chronic disease prevention. Our previous studies found that dietary omega-3 fatty acids could accumulate in the meat and eggs in a duck model. This study was to reveal the effects of various dietary fats on fatty acid profile and conversion of omega-3 fatty acids in duck liver. Female Shan Partridge Ducks were randomly assigned to five dietary treatments, each consisting of 6 replicates of 30 birds. The experimental diets substituted the basal diet by 2% of flaxseed oil, rapeseed oil, beef tallow, or fish oil, respectively. In addition, a dose response study was further conducted for flaxseed and fish oil diets at 0.5%, 1%, and 2%, respectively. At the end of the five-week treatment, fatty acids were extracted from the liver samples and analyzed by GC-FID. As expected, the total omega-3 fatty acids and the ratio of total omega-3/omega-6 significantly increased in both flaxseed and fish oil groups when compared with the control diet. No significant change of total saturated fatty acids or omega-3 fatty acids was found in both rapeseed and beef tallow groups. The dose response study further indicated that 59-81% of the short-chain omega-3 ALA in flaxseed oil-fed group was efficiently converted to long-chain DHA in the duck liver, whereas 1% of dietary flaxseed oil could produce an equivalent level of DHA as 0.5% of dietary fish oil. The more omega-3 fatty acids, the less omega-6 fatty acids in the duck liver. Taken together, this study showed the fatty acid profiling in the duck liver after various dietary fat consumption, provided insight into a dose response change of omega-3 fatty acids, indicated an efficient conversion of short- to long-chain omega-3 fatty acid, and suggested alternative long-chain omega-3 fatty acid-enriched duck products for human health benefits.


Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos/análise , Fígado/efeitos dos fármacos , Animais , Gorduras na Dieta/farmacocinética , Relação Dose-Resposta a Droga , Patos , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-6/farmacocinética , Ácidos Graxos Ômega-6/farmacologia , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacocinética , Feminino , Óleos de Peixe/farmacocinética , Óleos de Peixe/farmacologia , Óleo de Semente do Linho/química , Óleo de Semente do Linho/farmacologia , Fígado/metabolismo , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Óleo de Brassica napus
20.
J Lipid Res ; 57(12): 2208-2216, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27707818

RESUMO

It was hypothesized that under induced lipid malabsorption/maldigestion conditions, an enriched sn-1(3)-monoacylglycerol (MAG) oil may be a better carrier for n-3 long-chain PUFAs (LC-PUFAs) compared with triacylglycerol (TAG) from fish oil. This monocentric double blinded clinical trial examined the accretion of EPA (500 mg/day) and DHA (300 mg/day) when consumed as TAG or MAG, into the erythrocytes, plasma, and chylomicrons of 45 obese (BMI ≥30 kg/m2 and ≤40 kg/m2) volunteers who were and were not administered Orlistat, an inhibitor of pancreatic lipases. Intake of MAG-enriched oil resulted in higher accretion of LC-PUFAs than with TAG, the concentrations of EPA and DHA in erythrocytes being, respectively, 72 and 24% higher at 21 days (P < 0.001). In addition, MAG increased the plasma concentration of EPA by 56% (P < 0.001) as compared with TAG. In chylomicrons, MAG intake yielded higher levels of EPA with the area under the curve (0-10 h) of EPA being 55% greater (P = 0.012). In conclusion, in obese human subjects with Orlistat-induced lipid maldigestion/malabsorption conditions, LC-PUFA MAG oil increased LC-PUFA levels in erythrocytes, plasma, and chylomicrons to a greater extent than TAG. These results indicate that MAG oil might require minimal enzymatic digestion prior to intestinal uptake and transfer across the epithelial barrier.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/farmacocinética , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Monoglicerídeos/administração & dosagem , Adulto , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Membrana Celular/metabolismo , Quilomícrons , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Eritrócitos/metabolismo , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacocinética , Humanos , Lactonas/efeitos adversos , Lactonas/uso terapêutico , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/tratamento farmacológico , Orlistate
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