Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. METHODS: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. RESULTS: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001). CONCLUSIONS: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Effect of minocycline on changes in affective behaviors, cognitive function, and inflammation in breast cancer survivors undergoing chemotherapy: a pilot randomized controlled trial.

PURPOSE: Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy. METHODS: This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated. RESULTS: Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01). CONCLUSION: Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.

Dietary EPA and DHA enrichment of a high fat diet during doxorubicin-based chemotherapy attenuated neuroinflammatory gene expression in the brain of C57bl/6 ovariectomized mice.

Chemotherapy agents in breast cancer are associated with chemotherapy-related cognitive impairments (CRCI). Mechanisms are not fully clear, but alterations of glucose and lipid metabolism, neuroinflammation and neurodegeneration may contribute to CRCI. The aim of this study was to investigate the combined effects of a high fat (HF) diet combined with doxorubicin-based chemotherapy on glucose and lipid metabolism, neuroinflammation, and neurodegeneration in mice. Additionally, we examined the therapeutic potential of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to attenuate these effects. Female C57Bl/6 mice (n = 42) were fed HF, HFn-3 (2 % kcals as EPA + DHA) or Low Fat (LF) diets for seven weeks, with and without chemotherapy. In this study, two chemotherapy injections led to weight and body fat loss associated with a decrease in insulin resistance measured by HOMA-IR. HOMA-IR was significantly greater in HF versus LF groups; but HOMA-IR in HFn-3 group did not significantly differ from either HF or LF groups. Chemotherapy resulted in higher brain concentrations of the inflammatory chemokine KC/GRO. Compared to LF diet plus chemotherapy, HF diet plus chemotherapy upregulated multiple genes involved in neuroinflammation and neurodegeneration pathways. HFn-3 diet plus chemotherapy attenuated gene expression by downregulating multiple genes involved in neuroinflammation and blood brain barrier regulation, including Mapkapk2, Aqp4, and s100b, and upregulating Kcnb1 and Atxn3, genes involved in reduction of oxidative stress and anxiety, respectively. Overall, a HF diet combined with chemotherapy is associated with neuroinflammatory and neurodegenerative gene expression changes in this mouse model; dietary enrichment of EPA and DHA attenuated these effects. Further studies are needed to understand how diet impacts behavioral outcomes of CRCI.

Mental health in society's margins: poor n-3 PUFA intake and psychological well-being of homeless youth.

Dietary intake of long-chain n-3 PUFA (n-3 PUFA), particularly EPA and DHA, has been associated with psychological well-being, but little is known about the n-3 PUFA intake of homeless youth. The current study determined the association between depression and anxiety symptoms and n-3 PUFA intake and erythrocytes status in homeless youth. Totally, 114 homeless youth aged 18-24 years were recruited from a drop-in centre. n-3 PUFA dietary intake was assessed using an FFQ, and erythrocytes status was determined by gas chromatography (GC). Linear regression models were used to determine the relationship between psychological well-being and n-3 PUFA intake and status. The mean intakes of EPA and DHA for all participants (0·06 ± 0·13 g/d and 0·11 ± 0·24 g/d) were well below recommended levels, and mean erythrocytes EPA + DHA (n-3 index) in the cohort (2·42 %) was lower than reported for healthy, housed adolescents and those with clinical depression. There was no association of n-3 PUFA intake and erythrocytes status with either depression or anxiety. However, the relationships of depression with dietary EPA (P = 0·017) and DHA (P = 0·008), as well as erythrocytes DHA (P = 0·007) and n 3-index (P = 0·009), were significantly moderated by sex even after adjusting for confounders. Specifically, among females, as the intake and status of these n-3 PUFA decreased, depression increased. Our findings show poor dietary intake and low erythrocytes status of n-3 PUFA among homeless youth, which is associated with depressive symptoms among females.

A remote Whole Food Dietary Intervention to Reduce Fatigue and Improve Diet Quality in Lymphoma Survivors: Results of a Feasibility Pilot Study.

Long-term, persistent cancer-related fatigue (CRF) is the most common side effect reported by lymphoma survivors. CRF reduces quality of life, and treatments are limited. This pilot study aimed to determine feasibility of recruiting and retaining diffuse large B-cell lymphoma (DLBCL) survivors in a 12-week remote Fatigue Reduction Diet (FRD) intervention and evaluate preliminary efficacy of the intervention. Participants met remotely with a registered dietitian nutritionist for eight individual sessions. FRD goals included consuming specific fruits, vegetables, whole grains, and omega-3 fatty acid rich foods. Acceptability was assessed by session attendance, FRD goal attainment, and exit surveys. Self-reported dietary intake and fatigue were measured using the Healthy Eating Index-2015 and PROMIS Fatigue Short Form, respectively, at baseline and post-intervention. Ten DLBCL survivors enrolled; nine attended all sessions and completed the intervention. Weekly adherence to targeted food intake goals improved significantly throughout the study (all p < 0.05), with participants meeting goals over 4 day per week by week 11. Mean[SD] diet quality improved significantly from baseline (65.9[6.3]) to post-intervention (82.2[5.0], p < 0.001). Mean[SD] fatigue reduced significantly from baseline (50.41[9.18]) to post-intervention (45.79[6.97], p < 0.05). The 12-week remote FRD intervention was feasible, acceptable, and holds promise to improve diet quality and fatigue in DLBCL survivors.

Fruit and vegetable intake is inversely associated with severity of inattention in a pediatric population with ADHD symptoms: the MADDY Study.

OBJECTIVES: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a U.S. pediatric prevalence of 8-10%. It presents with inattention and hyperactivity/impulsivity; frequently associated with emotional dysregulation (ED) symptoms common in Oppositional Defiant Disorder and Disruptive Mood Dysregulation Disorder. The etiology of ADHD is multi-factorial; symptom severity is associated with diet. This study examines the association of diet quality with ADHD and ED symptoms within a pediatric research cohort. METHODS: Baseline data were analyzed for 134 children aged 6-12 years with symptoms of ADHD and ED enrolled in an RCT of multinutrient supplementation. Diet quality was based on Healthy Eating Index-2015 (HEI-2015). ADHD and ED symptoms were assessed using Child and Adolescent Symptom Inventory-5 and Strengths and Difficulties Questionnaire. Linear regression models, adjusting for covariates when necessary, determined association. RESULTS: The mean HEI Total Score of 63.4 (SD = 8.8) was not significantly associated with any outcome symptoms. However, after adjusting for covariates, HEI component scores for total fruit intake (ß = -0.158, p = .037) and total vegetable intake (ß = -0.118, p = .004) were negatively associated with inattention. CONCLUSIONS: The lack of association with total diet quality could be explained by the relatively good baseline diet quality and mild symptom severity in this sample, along with measurement error from dietary intake estimates and relatively small sample size. These findings suggest that dietary intake may impact inattention in children with ADHD and ED: those eating less fruits and vegetables were likely to have more severe symptoms of inattention. Causality is not established by this cross-sectional analysis.

Effects of plant-based versus marine-based omega-3 fatty acids and sucrose on brain and liver fatty acids in a mouse model of chemotherapy.

Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

Sugars measured enzymatically in a fasting overnight urine sample are not sensitive biomarkers of dietary added sugar intake in postmenopausal women.

BACKGROUND: Restricting dietary sugar is a leading recommendation, but limited biomarkers assessing intake exist. Although 24-h urinary sucrose (U-Suc) and urinary fructose (U-Fruc) excretion has been used with mixed success, collection is burdensome. AIM: This study aimed to test the sensitivity of an enzymatic assay of U-Suc and U-Fruc to detect changing added sugar intake using low-burden overnight urine samples in 30 postmenopausal women. METHODS: Women consumed usual dietary intake during day 1 and usual intake plus a sugar sweetened beverage during day 2. Weighed, photographed food records assessed intake. Enzymatic assay measured U-Suc and U-Fruc from fasting overnight samples; liquid chromatography mass spectrometry (LC-MS) validated U-Suc findings. RESULTS: Dietary added sugars increased significantly during day 2 (p < 0.001), but urinary sugars were not significantly increased. Enzymatic assay detected urinary sugars in 75% (U-Suc) and 35% (U-Fruc) of samples. Dietary sucrose was not associated with U-Suc, however dietary fructose was significantly associated with U-Fruc [ß = 0.031; p < 0.05] among women with detectable urinary sugars. Participants with detectable U-Fruc consumed more energy from added sugars [12.6% kcal day 1; 21.5% kcal day 2] than participants with undetectable U-Fruc [9.3% kcal day 1; 17.4% kcal day 2], p < 0.05. Using LC-MS, U-Suc predicted sucrose and added sugar intake [ß = 0.017, ß = 0.013 respectively; both p < 0.05]. CONCLUSIONS: Urinary sugars measured enzymatically from overnight urine samples were not sensitive biomarkers of changing added sugar intake in postmenopausal women. However, urinary fructose measured by enzymatic assay or LC-MS may differentiate low versus high added sugar consumers.

Psychoneurological symptom cluster in breast cancer: the role of inflammation and diet.

Patients with breast cancer experience treatment-related symptoms which are unlike side effects associated with therapy such as surgery, chemotherapy or radiation. These symptoms are collectively referred to as symptoms cluster and include concurrent physical and/or psychosocial symptoms. Psychoneurological symptom cluster has been used to describe fatigue, mood changes, cognitive and sleep disturbances and pain seen in patients diagnosed with cancer. The etiology of psychoneurological symptom cluster is unclear; however, inflammation has been shown to play a role. High quality diets defined as diets rich in fruits, vegetables, whole grains and polyunsaturated fatty acids and low in added sugar have been shown to decrease inflammation in patients. This article reviews the role of inflammation and high quality diet on the prevalence of psychoneurological symptoms clusters.

Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.

PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.

Activity, energy intake, obesity, and the risk of incident kidney stones in postmenopausal women: a report from the Women's Health Initiative.

Obesity is a strong risk factor for nephrolithiasis, but the role of physical activity and caloric intake remains poorly understood. We evaluated this relationship in 84,225 women with no history of stones as part of the Women's Health Initiative Observational Study, a longitudinal, prospective cohort of postmenopausal women enrolled from 1993 to 1998 with 8 years' median follow-up. The independent association of physical activity (metabolic equivalents [METs]/wk), calibrated dietary energy intake, and body mass index (BMI) with incident kidney stone development was evaluated after adjustment for nephrolithiasis risk factors. Activity intensity was evaluated in stratified analyses. Compared with the risk in inactive women, the risk of incident stones decreased by 16% in women with the lowest physical activity level (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [95% CI], 0.74 to 0.97). As activity increased, the risk of incident stones continued to decline until plateauing at a decrease of approximately 31% for activity levels ≥10 METs/wk (aHR, 0.69; 95% CI, 0.60 to 0.79). Intensity of activity was not associated with stone formation. As dietary energy intake increased, the risk of incident stones increased by up to 42% (aHR, 1.42; 95% CI, 1.02 to 1.98). However, intake <1800 kcal/d did not protect against stone formation. Higher BMI category was associated with increased risk of incident stones. In summary, physical activity may reduce the risk of incident kidney stones in postmenopausal women independent of caloric intake and BMI, primarily because of the amount of activity rather than exercise intensity. Higher caloric intake further increases the risk of incident stones.

Fatty Acid Intake and Polyunsaturated Fatty Acid Biomarkers and Risk of Total Knee or Hip Arthroplasty Among Older Women in the Women's Health Initiative.

OBJECTIVE: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. METHODS: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. RESULTS: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. CONCLUSION: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

Low sucrose diets protect long-term memory and EPA & DHA enriched diets alter insulin resistance in a mouse model of chemotherapy.

Chemotherapy-related cognitive impairment (CRCI) and affective symptoms negatively impact quality of life in breast cancer survivors. The aim of this study was to determine the efficacy of high eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) and low sucrose diets to alleviate these symptoms in a mouse model of chemotherapy. Potential mechanisms involving insulin resistance were explored. We hypothesized that diets enriched in EPA+DHA and low amounts of sucrose would protect against the impact of chemotherapy on measures of CRCI. Female C57Bl/6 mice were randomized to 1 of 4 diets (2% kcal eicosapentaenoic acid + docosahexaenoic acid [EPA+DHA]/high or low sucrose, low omega-3/high or low sucrose) for 6 weeks and treated with two injections of doxorubicin-based chemotherapy or vehicle during week 2 and 4. Behavioral tests were performed 7 days after second injection. Chemotherapy increased serum insulin and decreased body weight, locomotion and exploratory behavior (all p < .05). Low sucrose consumption resulted in better long-term memory regardless of chemotherapy or vehicle injection (p < .05). 2% EPA+DHA consumption lessened insulin resistance (p < .05); however, controlling for body weight attenuated this effect (p = .08). There were no significant differences by diet or injection on liver lipid content; however, liver lipid content was positively correlated with insulin resistance scores (p < .05). Low sucrose diets may protect long-term memory during chemotherapy. The effect of EPA+DHA on insulin resistance and affective side effects during chemotherapy requires further investigation.

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.

Genome-wide association study of Red Blood Cell fatty acids in the Women's Health Initiative Memory Study.

Despite their widespread associations with a wide variety of disease phenotypes, the genetics of red blood cell fatty acids remains understudied. We present one of the first genome-wide association studies of red blood cell fatty acid levels, using the Women's Health Initiative Memory study - a prospective cohort of N = 7,479 women aged 65-79. Approximately 9 million SNPs were measured directly or imputed and, in separate linear models adjusted for age and genetic principal components of ethnicity, SNPs were used to predict 28 different fatty acids. SNPs were considered genome-wide significant using a standard genome-wide significance level of p < 1 × 10-8. Twelve separate loci were identified, seven of which replicated results of a prior RBC-FA GWAS. Of the five novel loci, two have functional annotations directly related to fatty acids (ELOVL6 and ACSL6). While overall explained variation is low, the twelve loci identified provide strong evidence of direct relationships between these genes and fatty acid levels. Further studies are needed to establish and confirm the biological mechanisms by which these genes may directly contribute to fatty acid levels.

A systematic review of omega-3 fatty acids and osteoporosis.

Some epidemiological evidence suggests that diets high in omega 3 fatty acids (n-3 FAs) may be beneficial for skeletal health. The aim of this systematic review was to determine if randomized controlled trials (RCTs) support a positive effect of n-3 FAs on osteoporosis. A systematic search was performed in PubMed and EMBASE databases. We included RCTs with skeletal outcomes conducted in adults or children (> = 1 year old) using n-3 FA fortified foods, diets or supplements alone or in combination with other vitamins/minerals, versus placebo. Primary outcomes were incident fracture at any site and bone mineral density (BMD) in g/cm2. Secondary outcomes included bone formation or resorption markers and bone turnover regulators. A total of 10 RCTs met inclusion criteria. Effect sizes with 95 % confidence intervals were estimated to compare studies across various treatments and outcome measures. No pooled analysis was completed due to heterogeneity of studies and small sample sizes. No RCTs included fracture as an outcome. Four studies reported significant favorable effects of n-3 FA on BMD or bone turnover markers. Of these, three delivered n-3 FA in combination with high calcium foods or supplements. Five studies reported no differences in outcomes between n-3 FA intervention and control groups; one study included insufficient data for effect size estimation. Strong conclusions regarding n-3 FAs and bone disease are limited due to the small number and modest sample sizes of RCTs, however, it appears that any potential benefit of n-3 FA on skeletal health may be enhanced by concurrent administration of calcium.

Potential Cardioprotective Effects and Lipid Mediator Differences in Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplemented Mice Given Chemotherapy.

Many commonly used chemotherapies induce mitochondrial dysfunction in cardiac muscle, which leads to cardiotoxicity and heart failure later in life. Dietary long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) have demonstrated cardioprotective function in non-chemotherapy models of heart failure, potentially through the formation of LC n-3 PUFA-derived bioactive lipid metabolites. However, it is unknown whether dietary supplementation with LC n-3 PUFA can protect against chemotherapy-induced cardiotoxicity. To test this, 36 female ovariectomized C57BL/6J mice were randomized in a two-by-two factorial design to either a low (0 g/kg EPA + DHA) or high (12.2 g/kg EPA + DHA) LC n-3 PUFA diet, and received either two vehicle or two chemotherapy (9 mg/kg anthracycline + 90 mg/kg cyclophosphamide) tail vein injections separated by two weeks. Body weight and food intake were measured as well as heart gene expression and fatty acid composition. Heart mitochondria were isolated using differential centrifugation. Mitochondrial isolate oxylipin and N-acylethanolamide levels were measured by mass spectrometry after alkaline hydrolysis. LC n-3 PUFA supplementation attenuated some chemotherapy-induced differences (Myh7, Col3a1) in heart gene expression, and significantly altered various lipid species in cardiac mitochondrial preparations including several epoxy fatty acids [17(18)-EpETE] and N-acylethanolamines (arachidonoylethanolamine, AEA), suggesting a possible functional link between heart lipids and cardiotoxicity.