Systematic review of marine-derived omega-3 fatty acid supplementation effects on leptin, adiponectin, and the leptin-to-adiponectin ratio

Increasing evidence suggests that adipokines, leptin and adiponectin, produced and secreted by adipocytes, are involved in regulating systemic inflammation and may be important targets for interventions to reduce the chronic systemic inflammation linked to some conditions common in aging (e.g., atherosclerosis). Lower leptin levels and higher adiponectin levels in peripheral circulation have been associated with less systemic inflammation. While some studies have shown that marine-derived omega-3 fatty acids (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) have effects on leptin and adiponectin in the context of inflammation, the extent of their effects remain unclear. The purpose of this systematic review was to summarize findings from randomized, controlled trials that measured effects of EPA+DHA supplementation on circulating levels of leptin and adiponectin to determine the state of the science. PubMed, CINAHL, Web of Science, Scopus, and Cochrane Trials were searched up to June 2018 for studies meeting inclusion criteria. Thirty-one studies included in this review were conducted in 16 countries. Eighteen studies reported lower leptin and/or higher adiponectin levels with EPA+DHA supplementation versus placebo at study end point (9 reported statistically significant differences), but doses, supplementation duration, and population characteristics varied across studies. In 9 studies reporting significantly lower leptin and/or higher adiponectin levels the EPA+DHA dose was 0.52 to 4.2 g/day for 4 to 24 weeks. Additional studies are warranted which assess dose parameters and patient populations similar to studies reporting significant effects of EPA+DHA on leptin or adiponectin in order to evaluate the extent of reproducibility before recommending EPA+DHA as a therapy to target these adipokines

Sizes of walleye pollock (Theragra chalcogramma) and Atka mackerel (Pleurogrammus monopterygius) consumed by the western stock of Steller sea lions (Eumetopias jubatus) in Alaska from 1999 to 2000

Prey-size selectivity by Steller sea lions (Eumetopias jubatus) is relevant for understanding the foraging behavior of this declining predator, but studies have been problematic because of the absence and erosion of otoliths usually used to estimate fish length. Therefore, we developed regression formulae to estimate fish length from seven diagnostic cranial structures of walleye pollock (Theragra chalcogramma) and Atka mackerel (Pleurogrammus monopterygius). For both species, all structure measurements were related with fork length of prey (r2 range: 0.78−0.99). Fork length (FL) of walleye pollock and Atka mackerel consumed by Steller sea lions was estimated by applying these regression models to cranial structures recovered from scats (feces) collected between 1998 and 2000 across the range of the Alaskan western stock of Steller sea lions. Experimentally derived digestion correction factors were applied to take into account loss of size due to digestion. Fork lengths of walleye pollock consumed by Steller sea lions ranged from 3.7 to 70.8 cm (mean=39.3 cm, SD=14.3 cm, n=666) and Atka mackerel ranged from 15.3 to 49.6 cm (mean=32.3 cm, SD=5.9 cm, n=1685). Although sample sizes were limited, a greater proportion of juvenile (≤20 cm) walleye pollock were found in samples collected during the summer (June−September) on haul-out sites (64% juveniles, n=11 scats) than on summer rookeries (9% juveniles, n=132 scats) or winter (February−March) haul-out sites (3% juveniles, n=69 scats). Annual changes in the size of Atka mackerel consumed by Steller sea lions corresponded to changes in the length distribution of Atka mackerel resulting from exceptionally strong year classes. Considerable overlap (>51%) in the size of walleye pollock and Atka mackerel taken by Steller sea lions and the sizes of these species caught by the commercial trawl fishery were demonstrated

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Dietary Patterns and Fractures in Postmenopausal Women: Results From the Women\u27s Health Initiative

IMPORTANCE: Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. OBJECTIVE: To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women\u27s Health Initiative (WHI) observational study. Participants in the prospective cohort included 93676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. MAIN OUTCOMES AND MEASURES: Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. RESULTS: Of the 93676 participants, 90014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. CONCLUSIONS AND RELEVANCE: Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women

Mitigation of Particulate Matter-Induced Inflammation and Vasoactivity in Human Vascular Endothelial Cells by Omega-3 Polyunsaturated Fatty Acids

Airborne particulate matter (PM) exposure remains the leading environmental risk factor for disease globally. Interventions to mitigate the adverse effects of PM are required, since there is no discernible threshold for its effects, and exposure reduction approaches are limited. The mitigation of PM (specifically diesel exhaust particles (DEP))-induced release of pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) and vasoconstrictor endothelin-1 (ET-1) after 24 and 48 h of exposure by pre-treatment with individual pure, combined pure, and an oil formulation of two fish oil omega-3 polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were all tested at an equivalent concentration of 100 µM in vitro in human umbilical vein endothelial cells. The PUFAs and fish oil formulation completely mitigated or diminished the DEP-induced release of IL-6, IL-8, and ET-1 by 14–78%. DHA was more effective in reducing the levels of the DEP-induced release of the cytokines, especially IL-6 after 48 h of DEP exposure in comparison to EPA (p < 0.05), whereas EPA seemed to be more potent in reducing ET-1 levels. The potential of fish ω-3 PUFAs to mitigate PM-induced inflammation and vasoactivity was demonstrated by this study

Intolerance of Uncertainty and Cognition in Breast Cancer Survivors: The Mediating Role of Anxiety

Cancer-related cognitive impairment (CRCI) is one of the most prevalent symptoms that breast cancer survivors experience. While cancer treatments are established contributors to CRCI, inter-individual differences in CRCI are not well understood. Individual differences in sensitivity to uncertainty are potential contributors to CRCI; however, no prior studies have attempted to examine this link in the context of breast cancer. To address the gap, we used preliminary findings from an ongoing cross-sectional study. A total of 38 women with stage I–III breast cancer (1–4 years post-treatment) were included in this study. Intolerance of uncertainty (IU) was assessed using the Intolerance of Uncertainty Scale. Self-reported cognitive function was assessed with the Neuro-QoL questionnaire. Anxiety was assessed using the Patient-Reported Outcomes Measurement System Bank. From this study, we found that anxiety mediates the association between IU and cognitive function of survivors. In other words, among post-menopausal breast cancer survivors, those with higher IU showed higher anxiety and consequently had lower cognitive function. This finding suggests that assessing IU may help predict the risk of CRCI. This study expands the current knowledge that addresses the importance of IU as a factor associated with cognitive health

Dietary Impacts on Changes in Diversity and Abundance of the Murine Microbiome during Progression and Treatment of Cancer

The intestinal microbial population is recognized for its impact on cancer treatment outcomes. Little research has reported microbiome changes during cancer progression or the interplay of disease progression, dietary sugar/fat intake, and the microbiome through surgery and chemotherapy. In this study, the murine gut microbiome was used as a model system, and changes in microbiome diversity, richness, and evenness over the progression of the cancer and treatment were analyzed. Mice were categorized into four diet cohorts, combinations of either high or low sucrose and high or low omega-3 fatty acids, and two treatment cohorts, saline vehicle or chemotherapy, for a total of eight groups. Fecal samples were collected at specific timepoints to assess changes due to diet implementation, onset of cancer, lumpectomy, and chemotherapy. Akkermansia muciniphila abundance was very high in some samples and negatively correlated with overall Amplicon Sequence Variant (ASV) richness (r(64) = −0.55, p = 3 × 10−8). Throughout the disease progression, ASV richness significantly decreased and was impacted by diet and treatment. Alpha-diversity and differential microbial abundance were significantly affected by disease progression, diet, treatment, and their interactions. These findings help establish a baseline for understanding how cancer progression, dietary macronutrients, and specific treatments impact the murine microbiome, which may influence outcomes

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease)