Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice.

INTRODUCTION: Alzheimer's disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes? METHODS: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor. RESULTS: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males. CONCLUSION: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.

Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-ß (Aß) plaques. Systemic inflammation and obesity may exacerbate AD pathogenesis. We previously reported anti-inflammatory and anti-obesity effects of EPA in mice. OBJECTIVES: We aimed to determine whether EPA reduces obesity-associated metabolic dysfunctions and Aß accumulation in AD amyloidogenic mice. METHODS: Two-mo-old APPswe/PS1dE9 transgenic (TG) mice and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or EPA (36 g/kg)-supplemented HF diets. Body composition, glucose tolerance, and energy expenditure were measured, and serum and brain metabolic markers were tested 38 wk postintervention. Outcomes were statistically analyzed via 3-factor ANOVA, modeling genotype, sex, and diet interactions. RESULTS: HF-fed males gained more weight than females (Δ = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Δ = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Δ = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Δ = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Δ = -2.51 g/mL and Δ = -0.694 ng/mL, respectively compared with HF, P ≤ 0.05) and increasing adiponectin (Δ = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Aß than WT mice (Δ = 0.131 ng/mL; P < 0.001 and Δ = 0.56%; P < 0.01, respectively), and EPA reduced serum Aß1-40 in TG males compared with HF (Δ = 0.053 ng/mL; P ≤ 0.05). CONCLUSIONS: To our knowledge, this is the first report that EPA reduces serum Aß1-40 in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD.

The effects of omega-3 fatty acid supplementation on inflammatory factors in HIV-infected patients: A systematic review and meta-analysis of randomized clinical trials.

High concentrations of C-reactive protein (CRP) and inflammatory markers are common in human immunodeficiency virus (HIV)-infected patients and are associated with non-HIV related comorbidity and mortality. Data on the benefits of omega-3 fatty acid (omega-3 FA) supplementation for improving inflammation status in HIV-infected patients are controversial. Thus, we conducted a systematic review and meta-analysis on the beneficial effects of omega-3 FAs on controlling inflammation in HIV-infected patients. We conducted a comprehensive search of the major biomedical databases, including PubMed, EMBASE, Scopus, Web of Science and Cochrane library, for all potentially relevant studies published without restriction from the beginning of time to June 2020. Overall, nine RCTs were included comprising a total of 427 participants. A random-effects model was used to calculate 95% confidence intervals (CI) and the effect was measured as standardized mean difference (SMD). Supplementation of omega-3 FAs showed a significant reduction of CRP (SMD: -0.27, 95% CI: -0.48 to -0.07, P = 0.007). There was no significant difference in levels of TNF-α (SMD: 0.03, 95% CI: -0.79 to 0.85, P = 0.94, I2 = 87%) and IL-6 (SMD: -0.13, 95% CI: -0.59 to 0.32, P = 0.57, I2 = 73%, Fig. 3). The results indicate that the supplementation of omega-3 FAs in HIV-infected patients significantly decreases serum CRP levels when compared to the control group, however has no significant effect on IL-6 and TNF-α levels.

Omega-3 fatty acids supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

Omega-3 fatty acids (omega-3 FAs) supplementation effects on oxidants and antioxidants are always controversial. Oxidative stress (OS) is one of the major mechanisms that contribute to the pathogenesis of several chronic diseases. The present systematic review and meta-analysis aimed to summarize the finding of randomized clinical trials (RCTs) examining the effects of omega-3 FAs on OS markers. Five databases including PubMed, Embase, Scopus, Web of science, and Cochrane were searched up to May 5th, 2019 with no language restriction. RCTs included if they compared OS indices among subjects who received omega-3 FAs supplements and subjects who supplemented with placebo. To estimate the effects of omega-3 FAs supplementation, standardized mean difference (SMD) with 95% confidence intervals (95% CI) were pooled using random effects model. Of 5,887 publications, 39 trials involving 2,875 participants were included for the meta-analysis. The pooled analysis of data indicated that omega-3 FAs significantly increased serum total antioxidant capacity (TAC) (SMD: 0.48, 95% CI: 0.23, 0.72, P< 0.001; I2= 60%), glutathione peroxidase (GPx) (SMD: 0.73, 95% CI: 0.30, 1.16, P= 0.001; I2= 83%) activity and decreased malondialdehyde (MDA) (SMD= -0.42, 95% CI: -0.62, -0.21; P < 0.001; I2= 74%) compared to the placebo group. However, the effects of omega-3 FAs on nitric oxide (NO) (SMD: -0.17 , 95% CI: -0.77, 0.43, P = 0.57; I2= 91%), reduced glutathione (GSH) (SMD= 0.23, 95% CI= -0.17, 0.64, P= 0.25; I2= 75%), superoxide dismutase (SOD) (0.12 , 95% CI: -0.40, 0.65, P= 0.64; I2= 89%) and catalase (CAT) (0.16, 95% CI: -0.33, 0.65, P= 0.52; I2= 75%,) activities was not significant. Supplementation with omega-3 FAs significantly improves MDA, TAC levels, and GPx activity. Thus, omega-3 FAs can be mentioned as enhancer factors in antioxidant defense against reactive oxygen species (ROS).

Effects of supplementation of vitamins D, C and E on Idiopathic Pulmonary Fibrosis (IPF): A clinical trial.

BACKGROUND & AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients. METHODS: Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant. RESULTS: Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFß, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged. CONCLUSIONS: It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans.

Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation's biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.

Effect of omega-3 fatty acid plus vitamin E Co-Supplementation on oxidative stress parameters: A systematic review and meta-analysis.

BACKGROUND & AIMS: The impact of combined omega-3 FAs and vitamin E supplementation on oxidative stress (OS) has been evaluated in several studies. However the results are inconsistent. Therefore, we performed a systematic review and meta-analysis to assess the role of omega-3 FAplus vitamin E on anti-oxidant and OS parameters. METHODS: We searched five databases (PubMed, Embase, Web of Sciences, Scopus and the Cochrane Central Register of Controlled Trials) from inception until March 15th 2018 for RCT covering OS parameters combined with omega-3 FAs and vitamin E. The effect of omega-3 FAs plus vitamin E combination on OS factors was determined as the standardized mean difference (SMD) calculated according to DerSimonian and Laird for the random effects model. RESULTS: Nine articles were included in our analyses, significant improvements were observed in trials supplementing with omega-3 FAs plus vitamin E vs placebo for total antioxidant capacity (TAC) (SMD=0.63, 95%CI: 0.31 to 0.95, P<0.001) and nitric oxide (NO) (SMD=0.55, 95%CI: 0.23 to 0.87, P<0.001). Significant reduction was observed for malondialdehyde (MDA) (SMD: -0.48, 95%CI: -0.68 to -0.28, P<0.001). However, the results of meta-analysis did not show a significant difference in levels of glutathione (GSH) (SMD=0.34, 95%CI: -0.07 to 0.75, P=0.10), superoxide dismutase (SOD) activity (SMD: 0.07, 95% CI: -0.58 to 0.73, P=0.82) and Catalase (CAT) activity (SMD: 0.74, 95% CI: -0.30 to 1.79, P=0.16). CONCLUSION: Co-supplementation with omega-3 FAs and vitamin E increases the levels of NO and TAC, while MDA levels decrease compared to placebo. However, the results showed no significant alterations on GSH concentrations, CAT, and SOD activities.

Impact of Dietary Calcium Supplement on Circulating Lipoprotein Concentrations and Atherogenic Indices in Overweight and Obese Individuals: A Systematic Review.

Dyslipidemia is the main risk factor for developing cardiovascular disease. There are discrepancies in the effects of calcium supplementation on modulation of lipid status. Therefore, we aimed to summarize the effects of dietary calcium supplement on circulating lipoprotein concentrations and atherogenic indices in overweight and obese individuals. We conducted a systematic literature search from 2000 until July 2016. PubMed, Scopus, Cochran Library, and ISI Web of Science databases were searched for clinical trials written in English. Placebo controlled clinical trials on calcium or calcium with vitamin D supplement in overweight and obese indiciduals were considered. Finally, 11 clinical trials met the criteria and were included. Most studies (n = 9) evaluated Ca/D co-supplementation. Positive effects of calcium supplementation alone or with vitamin D were as follows: serum levels of total cholesterol (TC; n = 1), triglyceride (TG) concentrations (n = 1), serum levels of low-density lipoprotein cholesterol (LDL-C; n = 5) and high-density lipoprotein cholesterol (HDL-C; n = 3). Seven clinical trials reported atherogenic indices and three of them demonstrated beneficial effects of calcium supplementation on at least one atherogenic index. Calcium supplementation may not be helpful to reduce serum levels of TC and TG in overweight and obese individuals. However, it may modulate LDL-C and HDL-C concentration. More studies are warranted to clarify the effects of calcium supplementation on each atherogenic index.