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Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review.
Rees, G, Brough, L, Orsatti, GM, Lodge, A, Walker, S
Nutrients. 2022;(2)
Abstract
Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.
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Omega-3 Supplementation and Heart Disease: A Population-Based Diet by Gene Analysis of Clinical Trial Outcomes.
Fernandez, ML, Blomquist, SA, Hallmark, B, Chilton, FH
Nutrients. 2021;(7)
Abstract
Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and their metabolites have long been recognized to protect against inflammation-related diseases including heart disease. Recent reports present conflicting evidence on the effects of n-3 PUFAs on major cardiovascular events including death. While some studies document that n-3 PUFA supplementation reduces the risk for heart disease, others report no beneficial effects on heart disease composite primary outcomes. Much of this heterogeneity may be related to the genetic variation in different individuals/populations that alters their capacity to synthesize biologically active n-3 and omega 6 (n-6) PUFAs and metabolites from their 18 carbon dietary precursors, linoleic acid (LA, 18:2 n-6) and alpha-linolenic (ALA, 18:3, n-3). Here, we discuss the role of a FADS gene-by-dietary PUFA interaction model that takes into consideration dietary exposure, including the intake of LA and ALA, n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in determining the efficacy of n-3 PUFA supplementation. We also review recent clinical trials with n-3 PUFA supplementation and coronary heart disease in the context of what is known about fatty acid desaturase (FADS) gene-by-dietary PUFA interactions. Given the dramatic differences in the frequencies of FADS variants that impact the efficiency of n-3 and n-6 PUFA biosynthesis, and their downstream signaling products among global and admixture populations, we conclude that large clinical trials utilizing "one size fits all" n-3 PUFA supplementation approaches are unlikely to show effectiveness. However, evidence discussed in this review suggests that n-3 PUFA supplementation may represent an important opportunity where precision interventions can be focused on those populations that will benefit the most from n-3 PUFA supplementation.
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3.
PUFA Supplementation and Heart Failure: Effects on Fibrosis and Cardiac Remodeling.
Oppedisano, F, Mollace, R, Tavernese, A, Gliozzi, M, Musolino, V, Macrì, R, Carresi, C, Maiuolo, J, Serra, M, Cardamone, A, et al
Nutrients. 2021;(9)
Abstract
Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1-2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021.
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Meta-Analysis Comparing the Effect of Combined Omega-3 + Statin Therapy Versus Statin Therapy Alone on Coronary Artery Plaques.
Fan, H, Zhou, J, Yuan, Z
The American journal of cardiology. 2021;:15-24
Abstract
Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 μm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.
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5.
Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021.
Djuricic, I, Calder, PC
Nutrients. 2021;(7)
Abstract
Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose-response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.
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6.
Perinatal Dietary Polyunsaturated Fatty Acids in Brain Development, Role in Neurodevelopmental Disorders.
Martinat, M, Rossitto, M, Di Miceli, M, Layé, S
Nutrients. 2021;(4)
Abstract
n-3 and n-6 polyunsaturated fatty acids (PUFAs) are essential fatty acids that are provided by dietary intake. Growing evidence suggests that n-3 and n-6 PUFAs are paramount for brain functions. They constitute crucial elements of cellular membranes, especially in the brain. They are the precursors of several metabolites with different effects on inflammation and neuron outgrowth. Overall, long-chain PUFAs accumulate in the offspring brain during the embryonic and post-natal periods. In this review, we discuss how they accumulate in the developing brain, considering the maternal dietary supply, the polymorphisms of genes involved in their metabolism, and the differences linked to gender. We also report the mechanisms linking their bioavailability in the developing brain, their transfer from the mother to the embryo through the placenta, and their role in brain development. In addition, data on the potential role of altered bioavailability of long-chain n-3 PUFAs in the etiologies of neurodevelopmental diseases, such as autism, attention deficit and hyperactivity disorder, and schizophrenia, are reviewed.
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7.
Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention.
Kapoor, K, Alfaddagh, A, Stone, NJ, Blumenthal, RS
Journal of clinical lipidology. 2021;(4):545-555
Abstract
Residual risk mediated by hypertriglyceridemia among statin-treated individuals is an important clinical and public health challenge. Niacin, fibrates and omega-3 FA are three classes of non-statin agents with demonstrated TG-lowering effects. Randomized controlled trials of niacin and fibrates have been consistently negative, but the trial landscape for two key sources of omega-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is more complex. Clinical trials evaluating omega-3 FA can be differentiated into those that studied mixed formulations (EPA + DHA) and those that studied EPA alone. Those assessing the impact of mixed formulations have not consistently demonstrated CVD risk reduction, whereas trials of EPA alone have been successful. Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm.
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Zinc, ω-3 polyunsaturated fatty acids and vitamin D: An essential combination for prevention and treatment of cancers.
Story, MJ
Biochimie. 2021;:100-122
Abstract
Zinc, ω-3 polyunsaturated fatty acids (PUFAs) and vitamin D are essential nutrients for health, maturation and general wellbeing. Extensive literature searches have revealed the widespread similarity in molecular biological properties of zinc, ω-3 PUFAs and vitamin D, and their similar anti-cancer properties, even though they have different modes of action. These three nutrients are separately essential for good health, especially in the aged. Zinc, ω-3 PUFAs and vitamin D are inexpensive and safe as they are fundamentally natural and have the properties of correcting and inhibiting undesirable actions without disturbing the normal functions of cells or their extracellular environment. This review of the anticancer properties of zinc, ω-3 PUFAs and vitamin D is made in the context of the hallmarks of cancer. The anticancer properties of zinc, ω-3 PUFAs and vitamin D can therefore be used beneficially through combined treatment or supplementation. It is proposed that sufficiency of zinc, ω-3 PUFAs and vitamin D is a necessary requirement during chemotherapy treatment and that clinical trials can have questionable integrity if this sufficiency is not checked and maintained during efficacy trials.
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Inflammatory Depression-Mechanisms and Non-Pharmacological Interventions.
Suneson, K, Lindahl, J, Chamli Hårsmar, S, Söderberg, G, Lindqvist, D
International journal of molecular sciences. 2021;(4)
Abstract
Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.
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10.
Nutrition-Based Approaches in Clinical Trials Targeting Cognitive Function: Highlights of the CTAD 2020.
Giudici, KV
The journal of prevention of Alzheimer's disease. 2021;(2):118-122
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Abstract
The Clinical Trials on Alzheimer's Disease (CTAD) 2020 conference was the stage for researchers from all over the world to present their recent and ongoing research focused on potential Alzheimer's disease (AD) treatments and prevention of cognitive decline. Among a varied range of topics, nutritional aspects arose as possibilities of treatments towards the promotion of a healthy aging. Among the discussed themes, supplementation of omega-3 polyunsaturated fatty acids and multi-nutrient approaches were presented, suggesting that long-term supplementation (i.e., over 3 years) might be needed for observing positive effects on cognitive performance. Trials testing ketogenic agents and carbohydrate-restricted diet were also presented and showed promising effects on improving cognitive function of mild-cognitive impaired (MCI) and pre-diabetic individuals, respectively, in a short-term way (i.e. after 3 to 6 months). The combination of some of the nutritional approaches with physical activity interventions raises the question on whether they would individually perform in a similar way. Promising therapies involving nutrition appear to be safe and well tolerated by volunteers. Failures on achieving positive findings raise questions on whether they were driven by specific characteristics of the studied populations, insufficient doses or duration of treatment. Notwithstanding, current evidence on the applicability of nutrition-based approaches as AD treatments are encouraging but demand further research on the topic.