Effects of 12 Wk of Omega-3 Fatty Acid Supplementation in Long-Distance Runners.

PURPOSE: This study aimed to investigate the effects of 12 wk of omega-3 fatty acid supplementation during endurance training on omega-3 index (O3I) and indicators of running performance in amateur long-distance runners. METHODS: Twenty-six amateur male long-distance runners ≥29 yr old supplemented omega-3 fatty acid capsules (OMEGA group, n = 14; 2234 mg of eicosapentaenoic acid and 916 mg of docosahexaenoic acid daily) or medium-chain triglycerides capsules as placebo (medium-chain triglyceride [MCT] group, n = 12; 4000 mg of MCT daily) during 12 wk of endurance training. Before and after intervention, blood samples were collected for O3I assessment, and an incremental test to exhaustion and a 1500-m run trial were performed. RESULTS: O3I was significantly increased in the OMEGA group (from 5.8% to 11.6%, P < 0.0001). A significant increase in V̇O 2peak was observed in the OMEGA group (from 53.6 ± 4.4 to 56.0 ± 3.7 mL·kg -1 ⋅min -1 , P = 0.0219) without such change in MCT group (from 54.7 ± 6.8 to 56.4 ± 5.9 mL·kg -1 ⋅min -1 , P = 0.1308). A positive correlation between the change in O3I and the change in running economy was observed when data of participants from both groups were combined (-0.1808 ± 1.917, P = 0.0020), without such an effect in OMEGA group alone ( P = 0.1741). No effect of omega-3 supplementation on 1500-m run results was observed. CONCLUSIONS: Twelve weeks of omega-3 fatty acid supplementation at a dose of 2234 mg of eicosapentaenoic acid and 916 mg of docosahexaenoic acid daily during endurance training resulted in the improvement of O3I and running economy and increased V̇O 2peak without improvement in the 1500-m run trial time in amateur runners.

Systemic Elevation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Is Associated with Protection against Visual, Motor, and Emotional Deficits in Mice following Closed-Head Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor and sensory (visual) deficits, cognitive impairment, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas the sphingolipid, ceramide (Cer), is an inducer of neuroinflammation and degeneration. Using Fat1+-transgenic mice that contain elevated levels of systemic n-3 PUFA, we tested whether they are resistant to mild TBI-mediated sensory-motor and emotional deficits by subjecting Fat1-transgenic mice and their WT littermates to focal cranial air blast (50 psi) or sham blast (0 psi, control). We observed that visual function in WT mice was reduced significantly following TBI but not in Fat1+-blast animals. We also found Fat1+-blast mice were resistant to the decline in motor functions, depression, and fear-producing effects of blast, as well as the reduction in the area of oculomotor nucleus and increase in activated microglia in the optic tract in brain sections seen following blast in WT mice. Lipid and gene expression analyses confirmed an elevated level of the n-3 PUFA eicosapentaenoic acid (EPA) in the plasma and brain, blocking of TBI-mediated increase of Cer in the brain, and decrease in TBI-mediated induction of Cer biosynthetic and inflammatory gene expression in the brain of the Fat1+ mice. Our results demonstrate that suppression of ceramide biosynthesis and inflammatory factors in Fat1+-transgenic mice is associated with significant protection against the visual, motor, and emotional deficits caused by mild TBI. This study suggests that n-3 PUFA (especially, EPA) has a promising therapeutic role in preventing neurodegeneration after TBI.

[Pharmacological Interaction between Diets and Commensal Bacteria for the Creation of Lipid Environment in the Control of Health and Diseases].

The intestine is exposed to a variety of exogenous materials that are harmful, harmless, or useful, such as pathogenic viruses and bacteria, intestinal bacteria, or food components. As such, the intestinal immune system is important for the regulation of immunological homeostasis and biological defense. Accumulating evidence indicates that gut environmental factors, such as dietary components and intestinal bacteria are critical for controlling intestinal immunity, and thereby, health and disease. Among the important dietary components are fatty acids, which are metabolized to lipid mediators that act as signaling molecules and regulate immune responses. In previous work, we identified lipid mediators derived from ω3 fatty acids, such as 17,18-epoxyeicosatetraenoic acid, 15-hydroxyeicosapentaenoic acid, and 14-hydroxydocosapentaenoic acid, which show potent anti-allergic and anti-inflammatory activities. In addition, we revealed that lipid mediators play key roles in the enhancement of intestinal Immunoglobulin A responses, which provide the first line of defense against viral and bacterial infectious diseases. Here, we review the anti-allergic, anti-inflammatory, and host-protective effects of lipid mediators mainly derived from dietary lipids.

COVID-19 and nutritional deficiency: a review of existing knowledge.

COVID-19 has resulted in an ongoing global pandemic, which spread largely among people who have had close contact with the infected person. The immunopathology of the SARS-CoV-2 virus includes the production of an excess amount of pro-inflammatory cytokines "a cytokine-storm". The respiratory system (main), cardiovascular system and the gastrointestinal tract are the most affected body systems during viral infection. It has been found that most of the patients who require admission to hospital are elderly or have chronic underlying diseases. Higher cases of malnutrition and co-morbidities like diabetes mellitus and cardiovascular diseases are reported in elderly patients due to which, the immune system weakens and hence, the response to the virus is diminished in magnitude. A deficiency of micronutrients results in impaired immune responses leading to improper secretion of cytokines, alterations in secretory antibody response and antibody affinity which increases susceptibility to viral infection. The deficiency of various micronutrients in COVID-19 patient can be treated by appropriate nutritional supplements, prescribed after evaluating the patients' nutritional status. Here we aim to highlight the role of a few particular nutrients namely Vitamin D, Vitamin C, Omega-3 fatty acids, Zinc and Magnesium along with the synergistic roles they play in enhancing immunity and thus, maintaining homeostasis.

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review.

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications.

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome-gut-brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.

Nutritional Lipids and Mucosal Inflammation.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation in the intestine. Given their role in regulation of inflammation, long-chain n-3 polyunsaturated fatty acids (PUFAs) represent a potential supplementary therapeutic approach to current drug regimens used for IBD. Mechanistically, there is ample evidence for an anti-inflammatory and pro-resolution effect of long-chain n-3 PUFAs after they incorporate into cell membrane phospholipids. They disrupt membrane rafts and when released from the membrane suppress inflammatory signaling by activating PPAR-γ and free fatty acid receptor 4; furthermore, they shift the lipid mediator profile from pro-inflammatory eicosanoids to specialized pro-resolving mediators. The allocation of long-chain n-3 PUFAs also leads to a higher microbiome diversity in the gut, increases short-chain fatty acid-producing bacteria, and improves intestinal barrier function by sealing epithelial tight junctions. In line with these mechanistic studies, most epidemiological studies support a beneficial effect of long-chain n-3 PUFAs intake on reducing the incidence of IBD. However, the results from intervention trials on the prevention of relapse in IBD patients show no or only a marginal effect of long-chain n-3 PUFAs supplementation. In light of the current literature, international recommendations are supported that adequate diet-derived n-3 PUFAs might be beneficial in maintaining remission in IBD patients.

The Role of Sphingolipids and Specialized Pro-Resolving Mediators in Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide giving rise to devastating forms of cognitive decline, which impacts patients' lives and that of their proxies. Pathologically, AD is characterized by extracellular amyloid deposition, neurofibrillary tangles and chronic neuroinflammation. To date, there is no cure that prevents progression of AD. In this review, we elaborate on how bioactive lipids, including sphingolipids (SL) and specialized pro-resolving lipid mediators (SPM), affect ongoing neuroinflammatory processes during AD and how we may exploit them for the development of new biomarker panels and/or therapies. In particular, we here describe how SPM and SL metabolism, ranging from ω-3/6 polyunsaturated fatty acids and their metabolites to ceramides and sphingosine-1-phosphate, initiates pro- and anti-inflammatory signaling cascades in the central nervous system (CNS) and what changes occur therein during AD pathology. Finally, we discuss novel therapeutic approaches to resolve chronic neuroinflammation in AD by modulating the SPM and SL pathways.

Omega-3 fatty acids as regulators of brown/beige adipose tissue: from mechanisms to therapeutic potential.

Adipose tissue dysfunction represents the hallmark of obesity. Brown/beige adipose tissues play a crucial role in maintaining energy homeostasis through non-shivering thermogenesis. Brown adipose tissue (BAT) activity has been inversely related to body fatness, suggesting that BAT activation is protective against obesity. BAT plays also a key role in the control of triglyceride clearance, glucose homeostasis, and insulin sensitivity. Therefore, BAT/beige activation has been proposed as a strategy to prevent or ameliorate obesity development and associated commorbidities. In the last few years, a variety of preclinical studies have proposed n-3 polyunsaturated fatty acids (n-3 PUFAs) as novel inducers of BAT activity and white adipose tissue browning. Here, we review the in vitro and in vivo available evidences of the thermogenic properties of n-3 PUFAs, especially focusing on the molecular and cellular physiological mechanisms involved. Finally, we also discuss the challenges and future perspectives to better characterize the therapeutic potential of n-3 PUFAs as browning agents, especially in humans.

Shark liver oil consumption decreases contractility in EDL muscle of trained rats / O consumo de óleo de fígado de tubarão reduz a contratilidade do músculo EDL em ratos treinados / El consumo de aceite de hígado de tiburón reduce la contractilidad del músculo EDL en ratones entrenados

Abstract Introduction: Professional and recreational athletes make daily use of nutritional supplements to improve physical performance. Polyunsaturated fatty acids (PUFAs) have been used in this sense. N-3 PUFA, particularly eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are involved in important physiological functions and the benefits of supplementation are demonstrated in several types of users. Shark liver oil (SLO) is a natural source of n-3 PUFA. Objective: To evaluate the effect of supplementation with SLO on contractility of skeletal muscles with different metabolic characteristics, soleus and extensor digitorum longus (EDL) from rats submitted to eight weeks of interval training of progressive intensity on a motorized treadmill. In the supplemented group, animals were supplemented with SLO (1 g/kg) five times a week for eight weeks. Method: Contractile parameters as maximum isometric twitch force (Tmax), maximum speed of force development (+dF/dt), maximum speed of force decrease (-dF/dt), maximum tetanic force (Fmax) and resistance to fatigue were analyzed in isolated muscle. Results: Compared to the control group, EDL muscles from the supplemented group reduced Tmax at the first (10.82 ± 0.89 vs 14.30 ± 0.67 mN/mm2. p < 0.01) and second minutes of experimentation (9.85 ± 0.63 vs 13.12 ± 0.70 mN/mm2. p < 0.01). However, it increased resistance to fatigue (22.80 ± 0.97 vs 18.60 ± 0.51 seconds. p = 0.005). Conclusion: No difference was observed in the soleus muscle.

Resumo Introdução: Atletas profissionais e recreativos utilizam suplementos nutricionais diariamente para melhorar a performance física. Os ácidos graxos poliinsaturados (PUFA) têm sido usados nesse sentido. Os n-3 PUFA, particularmente os ácidos eicosapentaenoicos (EPA) e docosaexaenoico (DHA), são relacionados com importantes funções fisiológicas e os benefícios da suplementação são demonstrados em diversas populações. O óleo de fígado de tubarão (OFT) é fonte natural de n-3 PUFA. Objetivo: Avaliar o efeito da suplementação com OFT na contratilidade de músculos esqueléticos com diferentes características metabólicas, sóleo e extensor longo de dedos (EDL) de ratos submetidos a oito semanas de treinamento intervalado de intensidade progressiva em esteira motorizada. No grupo suplementado, os animais foram suplementados com OFT (1 g/kg) cinco vezes por semana por oito semanas. Método: Parâmetros contráteis como produção de força isométrica máxima (Tmax), velocidade máxima de contração (+dF/dt), velocidade máxima de relaxamento (-dF/dt), força tetânica máxima (Fmax) e resistência à fadiga foram analisados em músculos isolados. Resultados: Comparados ao grupo controle, os músculos EDL dos animais do grupo suplementado reduziram Tmax no primeiro (10.82 ± 0.89 vs 14.30 ± 0.67 mN/mm2. p < 0.01) e no segundo minutos de experimentação (9.85 ± 0.63 vs 13.12 ± 0.70 mN/mm2. p < 0.01), entretanto, aumentaram a resistência à fadiga (22.80 ± 0.97 vs 18.60 ± 0.51 segundos. p = 0.005). Conclusão: Nenhuma diferença foi observada no músculo sóleo.

Resumen Introducción: Los atletas profesionales y recreativos utilizan suplementos nutricionales diariamente para mejorar el rendimiento físico. Los ácidos grasos poliinsaturados (PUFA) se han utilizado en este sentido. Los n-3 PUFA, particularmente los ácidos eicosapentaenoicos (EPA) y el docosaexáenoico (DHA), se relacionan con importantes funciones fisiológicas y los beneficios de la suplementación se demuestran en diversas poblaciones. El aceite de hígado de tiburón (AHT) es fuente natural de n-3 PUFA. Objetivo: Evaluar el efecto de la suplementación con AHT en la contractilidad de músculos esqueléticos con diferentes características metabólicas, sololeo y extensor largo de dedos (EDL) de ratas sometidas a ocho semanas de entrenamiento intervalado de intensidad progresiva en estera motorizada. En el grupo suplementario, los animales fueron suplementados con AHT (1 g/kg) cinco veces por semana durante ocho semanas. Método: Parámetros contráctiles como producción de fuerza isométrica máxima (Tmax), velocidad máxima de contracción (+dF/dt), velocidad máxima de relajación (-dF/dt), fuerza tetánica máxima (Fmax) y resistencia a la fatiga se analizaron en músculos aislados. Resultados: En comparación con el grupo control, los músculos EDL de los animales del grupo suplementado redujeron Tmax en el primer (10.82 ± 0.89 vs 14.30 ± 0.67 mN/mm2. p < 0.01) y en el segundo minuto de experimentación (9.85 ± 0.63 vs 13.12 ± 0.70 mN/mm2. p < 0.01), sin embargo, aumentaron la resistencia a la fatiga (22.80 ± 0.97 vs 18.60 ± 0.51 segundos. p = 0.005). Conclusión: No se observó ninguna diferencia en el músculo sóleo.

Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease.

The mechanisms of action of the dietary components of the Mediterranean diet are reviewed in prevention of cardiovascular disease, stroke, age-associated cognitive decline and Alzheimer disease. A companion article provides a comprehensive review of extra-virgin olive oil. The benefits of consumption of long-chain ω-3 fatty acids are described. Fresh fish provides eicosapentaenoic acid while α-linolenic acid is found in canola and soybean oils, purslane and nuts. These ω-3 fatty acids interact metabolically with ω-6 fatty acids mainly linoleic acid from corn oil, sunflower oil and peanut oil. Diets rich in ω-6 fatty acids inhibit the formation of healthier ω-3 fatty acids. The deleterious effects on lipid metabolism of excessive intake of carbohydrates, in particular high-fructose corn syrup and artificial sweeteners, are explained. The critical role of the ω-3 fatty acid docosahexaenoic acid in the developing and aging brain and in Alzheimer disease is addressed. Nutritional epidemiology studies, prospective population-based surveys, and clinical trials confirm the salutary effects of fish consumption on prevention of coronary artery disease, stroke and dementia. Recent recommendations on fish consumption by pregnant women and potential mercury toxicity are reviewed. The polyphenols and flavonoids of plant origin play a critical role in the Mediterranean diet, because of their antioxidant and anti-inflammatory properties of benefit in type-2 diabetes mellitus, cardiovascular disease, stroke and cancer prevention. Polyphenols from fruits and vegetables modulate tau hyperphosphorylation and beta amyloid aggregation in animal models of Alzheimer disease. From the public health viewpoint worldwide the daily consumption of fruits and vegetables has become the main tool for prevention of cardiovascular disease and stroke. We review the important dietary role of cereal grains in prevention of coronary disease and stroke. Polyphenols from grapes, wine and alcoholic beverages are discussed, in particular their effects on coagulation. The mechanisms of action of probiotics and vitamins are also included.

Exploring correlations between neuropsychological measures and domain-specific consistency in associations with n-3 LCPUFA status in 8-9 year-old boys and girls.

Long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) have in some studies been associated with cognitive and socioemotional outcomes in children, but results are inconsistent possibly due to the use of different tests and potential gender-specific effects. The objective of this cross-sectional study was to explore overall patterns in neuropsychological scores as well as correlations between scores within specific domains, and to examine potential gender differences and consistency in associations with n-3 LCPUFA status. In 199 Danish 8-9 year-old children, we performed a large battery of tests and questionnaires on attention, processing speed, executive functions, memory, and socioemotional traits, and measured erythrocyte fatty acid composition. Principal component analyses (PCA) showed that most of the variation in both cognitive performance and socioemotional traits was explained by overall performance, followed by speed-accuracy trade off and externalizing vs. internalizing problems, respectively. Boys had higher speed, lower attention and higher externalizing problem scores than girls. Measures of performance within both processing speed and attention domains correlated moderately, whereas no correlations were found for measures of executive functions apart from some weak correlations for impulsivity. Parent-rated scores for both externalizing and internalizing problems correlated strongly, whereas correlations with child-rated scores were weak. Scores within specific domains did not consistently associate with n-3 LCPUFA, except for processing speed measures which all pointed to faster processing with increased n-3 LCPUFA status. Gender differences in the associations were observed for attention and impulsivity. Child- but not parent-rated internalizing and social problems tended to associate directly with n-3 LCPUFA, supported by increased internalizing problems measured by the PCA component. In conclusion, measures of speed and attention seem to represent these domains in general, whereas single measures of more complex cognitive functions should be interpreted with caution. One approach could be to use multiple tests and create multivariate scores to guide interpretations. Furthermore, the results indicate a need to consider both parent- and child-rated socioemotional scores and gender differences in neuropsychological functions e.g. in investigations of n-3 LCPUFA effects.

Omega-3 fatty acids protects against chronic sleep-deprivation induced memory impairment.

AIMS: The current study aims to evaluate the possible protective effect of omega-3 fatty acids on memory impairment induced by sleep-deprivation in rats. MATERIALS AND METHODS: Animals were chronically sleep deprived using the modified multiple platform model (8 h/day for 8 weeks). Omega-3 fatty acids were administered as fish oil via oral gavage at a daily dose of 100 mg omega-3 PUFA/100 g BWT. The spatial learning and memory were evaluated using the radial arm water maze (RAWM). Additionally, the following oxidative stress biomarkers were measured in the hippocampus: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD), and thiobarbituric acid reactive substance (TBARS). KEY FINDINGS: Animals in the SD group committed significantly more errors in both short- and long- term memory tests of the RAWM compared to other groups. On the other hand, animals that were sleep deprived and treated with omega-3 fatty acids committed similar number of errors compared to the control group. This indicates that SD impaired both short- and long- term memories, and that chronic omega-3 fatty acids administration prevented these effects. Omega-3 fatty acids also prevented the decreases in hippocampal GPx, catalase and GSH/GSSG ratio and normalized the increases in GSSG levels, which were impaired by SD model. No changes were observed on hippocampal TBARS levels, or activity of SOD among experimental groups. SIGNIFICANCE: In conclusion, a protective effect of omega-3 fatty acids administration has been observed against chronic SD-induced memory impairment probably via improving hippocampus antioxidant effects.

Association of blood n-3 fatty acid with bone mass and bone marrow TRAP-5b in the elderly with and without hip fracture.

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

Effects of dietary fatty acid content on humeral cartilage and bone structure in a mouse model of diet-induced obesity.

Obesity is a primary risk factor for osteoarthritis (OA), and previous studies have shown that dietary content may play an important role in the pathogenesis of cartilage and bone in knee OA. Several previous studies have shown that the ratio of ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, and saturated fatty acids can significantly influence bone structure and OA progression. However, the influence of obesity or dietary fatty acid content on shoulder OA is not well understood. The goal of this study was to investigate the role of dietary fatty acid content on bone and cartilage structure in the mouse shoulder in a model of diet-induced obesity. For 24 weeks, mice were fed control or high-fat diets supplemented with ω-3 PUFAs, ω-6 PUFAs, or saturated fatty acids. The humeral heads were analyzed for bone morphometry and mineral density by microCT. Cartilage structure and joint synovitis were determined by histological grading, and microscale mechanical properties of the cartilage extracellular and pericellular matrices were quantified using atomic force microscopy. Diet-induced obesity significantly altered bone morphology and mineral density in a manner that was dependent on dietary free fatty acid content. In general, high-fat diet groups showed decreased bone quality, with the ω-3 diet being partially protective. Cartilage mechanical properties and OA scores showed no changes with obesity or diet. These findings are consistent with clinical literature showing little if any relationship between obesity and shoulder OA (unlike knee OA), but suggest that diet-induced obesity may influence other joint tissues. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain.

The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that display immunomodulatory properties in the brain. At the periphery, the modulation of inflammation by LC-PUFAs occurs through lipid mediators called oxylipins which have anti-inflammatory and pro-resolving activities when derived from n-3 LC-PUFAs and pro-inflammatory activities when derived from n-6 LC-PUFAs. However, whether a diet rich in LC-PUFAs modulates oxylipins and neuroinflammation in the brain has been poorly investigated. In this study, the effect of a dietary n-3 LC-PUFA supplementation on oxylipin profile and neuroinflammation in the brain was analyzed. Mice were given diets deficient or supplemented in n-3 LC-PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS) at adulthood. We first showed that dietary n-3 LC-PUFA supplementation induced n-3 LC-PUFA enrichment in the hippocampus and subsequently an increase in n-3 PUFA-derived oxylipins and a decrease in n-6 PUFA-derived oxylipins. In response to LPS, n-3 LC-PUFA deficient mice presented a pro-inflammatory oxylipin profile whereas n-3 LC-PUFA supplemented mice displayed an anti-inflammatory oxylipin profile in the hippocampus. Accordingly, the expression of cyclooxygenase-2 and 5-lipoxygenase, the enzymes implicated in pro- and anti-inflammatory oxylipin synthesis, was induced by LPS in both diets. In addition, LPS-induced pro-inflammatory cytokine increase was reduced by dietary n-3 LC-PUFA supplementation. These results indicate that brain n-3 LC-PUFAs increase by dietary means and promote the synthesis of anti-inflammatory derived bioactive oxylipins. As neuroinflammation plays a key role in all brain injuries and many neurodegenerative disorders, the present data suggest that dietary habits may be an important regulator of brain cytokine production in these contexts.

Emergence of omega-3 fatty acids in biomedical research.

Shortly after the discovery that linoleic acid was an essential fatty acid in 1930, α-linolenic acid also was reported to prevent the fatty acid deficiency syndrome in animals. However, several prominent laboratories could not confirm the findings with α-linolenic acid, and as a result there was a loss of interest in omega-3 fatty acids in lipid research. Even the findings that a prostaglandin can be synthesized from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is necessary for optimum retinal function generated only limited interest in omega-3 fatty acids. The breakthrough came in the 1970s when Dyerberg and Bang reported that the low incidence of atherosclerotic coronary disease in Greenland Eskimos was due to the high marine lipid content of their diet. They subsequently found that EPA, which was increased in Eskimo plasma, inhibited platelet aggregation, and they concluded that the low incidence of coronary artery disease was due to the anti-thrombotic effect of EPA. This stimulated widespread interest and research in EPA and DHA, leading to the present view that, like their omega-6 counterparts, omega-3 fatty acids have important physiological functions and are essential fatty acids.

The Role of Omega-3 Fatty Acids in the Setting of Coronary Artery Disease and COPD: A Review.

Chronic obstructive pulmonary disease (COPD) is a growing healthcare concern and will represent the third leading cause of death worldwide within the next decade. COPD is the result of a complex interaction between environmental factors, especially cigarette smoking, air pollution, and genetic preconditions, which result in persistent inflammation of the airways. There is growing evidence that the chronic inflammatory state, measurable by increased levels of circulating cytokines, chemokines, and acute phase proteins, may not be confined to the lungs. Cardiovascular disease (CVD) and especially coronary artery disease (CAD) are common comorbidities of COPD, and low-grade systemic inflammation plays a decisive role in its pathogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert multiple functions in humans and are crucially involved in limiting and resolving inflammatory processes. n-3 PUFAs have been intensively studied for their ability to improve morbidity and mortality in patients with CVD and CAD. This review aims to summarize the current knowledge on the effects of n-3 PUFA on inflammation and its impact on CAD in COPD from a clinical perspective.

Phenotypic heterogeneity of obesity-related brain vulnerability: one-size interventions will not fit all.

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.

A new perspective on lipid research in age-related macular degeneration.

There is an urgency to find new treatment strategies that could prevent or delay the onset or progression of AMD. Different classes of lipids and lipoproteins metabolism genes have been associated with AMD in a multiple ways, but despite the ever-increasing knowledge base, we still do not understand fully how circulating lipids or local lipid metabolism contribute to AMD. It is essential to clarify whether dietary lipids, systemic or local lipoprotein metabolismtrafficking of lipids in the retina should be targeted in the disease. In this article, we critically evaluate what has been reported in the literature and identify new directions needed to bring about a significant advance in our understanding of the role for lipids in AMD. This may help to develop potential new treatment strategies through targeting the lipid homeostasis.