Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil.

Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial ß-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.

Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children.

N - 3 fatty acids during chemotherapy: toward a higher level of evidence for clinical application.

PURPOSE OF REVIEW: Recommendations for intakes of n - 3 fatty acids (FAs) in patients who are receiving chemotherapy for cancer are based on weak evidence. This review highlights themes within the emergent literature to suggest improvements in the design of studies that provide n - 3 FA supplements concurrent with cytotoxic agents. RECENT FINDINGS: Following earlier research in animal models and human pilot studies, recent human studies have evaluated the effect of providing n - 3 FAs during delivery of single agent and multiagent chemotherapy regimens for breast and gastro-intestinal cancers. Regimens were based on platinum compounds, fluoropyrimidines or both, and a variety of additional agents. Tumor location and stage, supplement dose and duration, and endpoints were dissimilar across studies. Overall, the recent research continues to support the safety and tolerability of n - 3 FA supplementation with chemotherapy and provides additional evidence, albeit weak, for enhanced tumor response, maintenance of weight and muscle, and reduction in inflammation and toxicities in the host across multiple cancer sites and chemotherapy regimens. SUMMARY: The barriers to implementation in practice remain small study sizes, variations in supplement dosage and methodology, and differences in primary endpoints. Randomized, blinded trials with a justifiable sample size, adequate doses, monitored compliance and measures of clinically important endpoints are required to move these findings to a higher level of evidence for implementation into clinical practice.

Fish oil supplementation and maintaining muscle mass in chronic disease: state of the evidence.

PURPOSE OF REVIEW: Providing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the form of fish oils, to benefit muscle is an emerging area of interest. The aim of this work was to evaluate the current literature that has assessed muscle mass as an outcome during a fish oil intervention in any chronic disease. RECENT FINDINGS: The vast majority of studies published in the last 3 years (12 of 15) have been conducted in the oncological setting, in patients undergoing treatment for cancers of the gastrointestinal tract, breast, head and neck, lung, cervix, and hematological cancers. Three studies were conducted in patients with chronic obstructive pulmonary disease (COPD). Fish oil was provided as part of nutrient mixtures in 12 studies and as capsules in three studies. SUMMARY: Overall, the evidence for an effect of fish oil supplementation on muscle mass in patients with cancer undergoing treatment and in COPD remains unequivocal and reveals limited new knowledge in the area of fish oil supplementation in the cancer setting. Recent literature continues to provide mixed evidence on the efficacy of fish oil on muscle mass and function. The present review highlights challenges in comparing and interpreting current studies aimed at testing fish oil supplementation for muscle health.

Sarcopenia in Chronic Liver Disease: Impact on Outcomes.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

Visceral adiposity increases risk for hepatocellular carcinoma in male patients with cirrhosis and recurrence after liver transplant.

Visceral adipose tissue (VAT) is a metabolically active organ, associated with higher risk of malignancies. We evaluated whether VAT is associated with the risk of hepatocellular carcinoma (HCC) in patients presenting with cirrhosis as well as HCC recurrence after liver transplantation (LT). Patients with cirrhosis (n = 678; 457 male) who were assessed for LT (289 with HCC) were evaluated for body composition analysis. Patients who underwent LT (n = 247, 168 male) were subsequently evaluated for body composition, and 96 of these patients (78 male) had HCC. VAT, subcutaneous adipose tissues, and total adipose tissues were quantified by computed tomography at the level of the third lumbar vertebra and reported as indexes (cross-sectional area normalized for height [square centimeters per square meter]). At the time of LT assessment, the VAT index (VATI) was higher in male patients with HCC compared to non-HCC patients (75 ± 3 versus 60 ± 3 cm2 /m2 , P = 0.001). The VATI, subcutaneous adipose tissue index, and total adipose tissue index were higher in male patients with HCC compared to non-HCC patients. By multivariate analysis, male patients with VATI ≥65 cm2 /m2 had a higher risk of HCC (hazard ratio, 1.90; 95% confidence interval, 1.31-2.76; P = 0.001). In male patients with HCC who underwent LT, a VATI ≥65 cm2 /m2 adjusted for Milan criteria was independently associated with higher risk of HCC recurrence (hazard ratio, 5.34; 95% confidence interval, 1.19-23.97; P = 0.03). CONCLUSION: High VATI is an independent risk factor for HCC in male patients with cirrhosis and for recurrence of HCC after LT. (Hepatology 2018;67:914-923).

Mixed Lipid, Fish Oil, and Soybean Oil Parenteral Lipids Impact Cholestasis, Hepatic Phytosterol, and Lipid Composition.

OBJECTIVES: In parenteral nutrition-dependent infants and children, intestinal failure (IF)-associated liver disease (IFALD) remains an important problem. A comparative study was undertaken of parenteral mixed lipid (ML), ω-3 predominant fish oil (FO), and ω-6 predominant soybean oil (SO) emulsions in regards to hepatic phytosterol, neutral lipid, fatty acid (FA) content, and the relationship to cholestasis in piglets. METHODS: Neonatal piglets received parenteral nutrition, varying in lipid dose (5 or 10 g·â€Škg ·â€Šday) and formulation: SO5 (n = 5), SO10 (n = 5), FO5 (n = 5), and ML10 (n = 5). On day 14, liver chemistry, bile flow, histology and neutral lipid staining were assessed. Hepatic triglyceride FA content was determined using thin layer and gas chromatography, and phytosterol content was assessed using gas chromatography-mass spectrometry. RESULTS: SO groups had higher prevalence of biochemical cholestasis (P < 0.04) and lower bile flow (P < 0.0001). Hepatic campesterol, stigmasterol, and ß-sitosterol were highest in SO10 (P < 0.0001). Hepatic FA (P < 0.03) and ω-6/ω-3 FA ratio (P < 0.0001) were higher in the SO groups. Neutral lipid accumulation (P = 0.3) and liver histology (P = 0.16) were not different between groups. Univariate predictors of bile flow were: campesterol (r = -0.77, P = 0.001), ß-sitosterol (r = -0.74, P = 0.002), stigmasterol (r = -0.74, P = 0.002), ω-6 FA (r = -0.72, P = 0.002), and ω-3 FA (r = 0.59, P = 0.02). Only campesterol independently predicted bile flow. CONCLUSIONS: ML and FO lipid emulsions reduce cholestasis in association with lowered hepatic phytosterol and lipid content. Lower hepatic phytosterol and ω-6 FA content, and higher ω-3 FA content are hepatoprotective. Multivariate analysis suggests reduced phytosterol accumulation may best explain the hepatoprotective effect of fish oil-containing lipids.

Sensory preferences of supplemented food products among cancer patients: a systematic review.

PURPOSE: Oral nutritional supplements and fortified foods, here considered supplemented food products (SFP), are recommended as part of nutrition therapy guidelines to treat malnutrition among cancer patients. However, their successful use is limited by patients' failure to meet recommended intakes. This systematic review aimed to identify sensory preferences for SFP among cancer patients and evaluate the methodologies employed in sensory preference assessment. METHODS: A systematic search was conducted in several relevant databases yielding 1056 papers of which 19 met the inclusion criteria. Two authors independently selected papers and extracted findings. The included papers were categorized according to the focus of the preference assessment. RESULTS: Studies comparing sensory preferences for SFP of cancer patients with those of a control group suggested that the liking for SFP by cancer patients differs from healthy participants. Patient heterogeneity in site and stage of tumor, variation in study methodologies, and type of treatment complicated a conclusion regarding the effects of cancer treatment and taste changes on taste preferences. However, some general results were observed among the studies, such as the preference for fresh milk-based supplements when compared with other supplement types. CONCLUSION: This review highlighted the need for consistent reporting and control of variables that influence the sensory characteristics of SFP when sensory preferences are assessed in the clinical setting. Attention to these methodological details will enhance the reliability and accuracy of sensory preference assessment among cancer patients for realistic evaluation of SFP targeted to their nutritional needs.

Barriers to Oral Food Intake for Children Admitted to Hospital.

Children are at risk for malnutrition in hospital, and a contributing factor may be poor oral intake. Barriers to intake have been studied in adults, but there is a lack of research in children. The purpose of this study was to identify the potential barriers to oral intake for children in hospital. Patients and families (n = 58) admitted to surgery and medicine units at the Stollery Children's Hospital completed a survey on barriers to oral food intake. Barriers were classified into 6 domains and major barriers were those identified by at least 30% of the population. On average each patient was affected by 22% of the barriers. Within each domain, the proportion of patients identifying at least 1 barrier was as follows: organization (74%), hunger (67%), quality (60%), effects of illness (53%), choice (38%), and physical limitations (29%). Having food brought in from home due to hunger, not wanting what was ordered once it arrives, food quality, decreased appetite, sickness, fatigue, and pain were identified as major barriers. Children have unique barriers to oral food intake in hospital which have not been previously identified. Food service models should consider these barriers to better meet the needs of this population.

Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes.

Cancer cachexia (i.e., skeletal muscle wasting with or without fat loss) relates to several adverse outcomes. Computed tomography (CT) cross-sectional images serve as an efficient biomarker for assessment of cachexia in cancer patients. We systematically reviewed literature reporting quantitative evaluation of the cross sectional area of the main tissues implicated in cancer cachexia, muscle and visceral, subcutaneous and inter-muscular fat in CT scans at the 3rd lumbar vertebra. Our main goal was to summarize CT-defined variation of muscle and fat and the relationship between these features and cancer outcomes such as chemotherapy toxicity, post-surgery complications and survival.

Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis.

BACKGROUND & AIMS: Two major body compartments, skeletal muscle and adipose tissue, exhibit independent functions. We aimed to explore the prognostic significance of skeletal muscle, visceral and subcutaneous adipose tissue, according to sex, in patients with cirrhosis assessed for liver transplantation (LT). METHODS: CT images taken at the 3rd lumbar vertebra from 677 patients were quantified for three body composition indexes (cm2/m2), visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI). Cox proportional and competing-risk analysis hazard models were conducted to assess associations between mortality and body composition. RESULTS: The majority of patients were male (67%) with a mean age of 57 ±â€¯7 years, model for end-stage liver disease (MELD) score of 14 ±â€¯8 and mean body mass index of 27 ±â€¯6 kg/m2. Despite similar body mass index between the sexes, male patients had greater SMI (53 ±â€¯12 vs. 45 ±â€¯9 cm2/m2), whereas SATI (67 ±â€¯52 vs. 48 ±â€¯37 cm2/m2) was higher in females (p <0.001 for each). In sex stratified multivariate analyses after adjustment for MELD score and other confounding variables, SATI in females (hazard ratio [HR] 0.99; 95% CI 0.98-1.00; p = 0.01) and SMI in males (HR 0.98; 95% CI 0.96-1.00; p = 0.02) were significant predictors of mortality. Female patients with low SATI (<60 cm2/m2) had a higher risk of mortality (HR 2.06; 95% CI 1.08-3.91; p = 0.03). Using competitive risk analysis in female patients listed for LT, low SATI was also an independent predictor of mortality (subdistribution HR 2.80; 95% CI 1.28-6.12; p = 0.01) after adjusting for MELD, and other confounding factors. CONCLUSIONS: A lower SATI is associated with higher mortality in female patients with cirrhosis. Subcutaneous adipose tissue has a favorable metabolic profile - low SATI may reflect depletion of this major energy reservoir, leading to poor clinical outcomes. LAY SUMMARY: We looked at the importance of two of the main body compartments, skeletal muscle and adipose tissue (fat) on the prognosis of males and females with end-stage liver disease. Lower amounts of subcutaneous fat but not visceral fat (around internal organs), are associated with higher mortality in female patients with end-stage liver disease. However, low skeletal muscle predicts mortality in male patients with end-stage liver disease.

A quantitative multimodal metabolomic assay for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

Head and Neck Cancer Patients Do Not Meet Recommended Intakes of Micronutrients without Consuming Fortified Products.

This study assessed dietary and micronutrient intakes of head and neck cancer (HNC) patients at key points in the disease trajectory and evaluated the contribution of oral nutritional supplements (ONS) to micronutrient intake. HNC patients (n = 114) completed a three-day dietary record and a tool to assess Nutrition Impact Scores (NIS) at baseline, post-treatment, and follow-up. Foods were classified into food categories. Micronutrient, protein, and energy intakes were compared to European Society for Parenteral and Enteral Nutrition guidelines for cancer patients. The majority of patients did not meet recommended dietary intakes for vitamins D, E, C, folate, and magnesium at any study time point. Relative to baseline, the proportion of calories from milk, soup, and ONS significantly increased at post-treatment, while grain, meat, potato, baked dessert, and oil and sugar decreased (P < 0.03). At all study time points, patients categorized as high ONS consumers (>15% of total daily calories from ONS) had higher intakes of micronutrients (P < 0.003). They also had a higher NIS (P = 0.006) and experienced greater weight loss (P < 0.04) during the study, despite having similar energy intake to patients consuming <15% kcal from ONS. Fortification of usually consumed foods to improve micronutrient intake among cancer patients should be evaluated.

Subcutaneous adiposity is an independent predictor of mortality in cancer patients.

BACKGROUND: Prognostic significance of adiposity, at the time of cancer diagnosis, on survival is not clear. Body mass index (kg m-2) does not provide an appropriate assessment of body composition; therefore, the concept of the 'obesity paradox' needs to be investigated based on the prognostic significance of fat and muscle. Independent prognostic significance of adipose tissue in predicting mortality, importance of visceral and subcutaneous adiposity in the presence and absence of sarcopenia on survival, was investigated. METHODS: Adiposity markers including total adipose index (TATI), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI) were estimated for 1473 gastrointestinal and respiratory cancer patients and 273 metastatic renal cell carcinoma patients using computed tomography. Univariate and multivariate analysis to determine mortality hazard ratios (HR) were conducted using cox proportional hazard models. RESULTS: Low SATI (SATI <50.0 cm2 m-2 in males and <42.0 cm2 m-2 in females) independently associated with increased mortality (HR: 1.26; 95% CI: 1.11-1.43; P<0.001) and shorter survival (13.1 months; 95% CI, 11.4-14.7) compared to patients with high SATI (19.3 months; 95% CI, 17.6-21.0; P<0.001). In the presence of sarcopenia, the longest survival was observed in patients with high subcutaneous adiposity. CONCLUSIONS: Subcutaneous adipose tissues appear to associate with reduction in mortality risk demonstrating the prognostic importance of fat distribution. The effect of sarcopenia on survival was more pronounced in patients with low subcutaneous adiposity.

Nutrition and the transplant candidate.

Cirrhosis is the most common indication for liver transplantation (LT) worldwide. Malnutrition is present in at least two-thirds of patients with cirrhosis awaiting LT. It negatively impacts survival, quality of life, and the ability to respond to stressors, such as infection and surgery. Muscle wasting or sarcopenia is the most objective feature of chronic protein malnutrition in cirrhosis, and this condition is associated with increased morbidity and mortality before and after LT. In addition to its objectivity, muscularity assessment with cross-sectional imaging studies is a useful marker of nutritional status in LT candidates, as sarcopenia reflects a chronic decline in the general physical condition, rather than acute severity of the liver disease. Despite the high prevalence and important prognostic role, malnutrition and sarcopenia are frequently overlooked because standards for nutritional assessment are lacking and challenges such as fluid retention and obesity are prevalent. In this review, current diagnostic methods to evaluate malnutrition, including muscle abnormalities in cirrhosis, are discussed and current knowledge regarding the incidence and clinical impact of malnutrition in cirrhosis and its impact after LT are presented. Existing and potential novel therapeutic strategies for malnutrition in cirrhosis are also discussed, emphasizing the treatment of muscle wasting in the LT candidate in an effort to improve survival while waiting for LT and to reduce morbidity and mortality after LT.Liver Transplantation 23 1451-1464 2017 AASLD.

Modification of Ganglioside Content of Human Gastric Epithelial Cell Membrane Decreases Helicobacter pylori Adhesion.

BACKGROUND: In polarized cells, ganglioside location determines ganglioside function. Diet alters ganglioside content and composition in cell membranes. Ganglioside acts as a receptor for Helicobacter pylori. H pylori infects the stomach epithelium and may cause peptic ulcer disease and gastric cancer. The present study used purified gangliosides to modify the ganglioside composition of human gastric epithelial cells in vitro to reduce H pylori adhesion. METHODS: A human gastric epithelial cell line (NCI-N87) was cultured with a ganglioside mix or with pure ganglioside (GM3 or GD3) at different concentrations (0-30 µg/mL) and ganglioside membrane content of gastric cells was determined after 48 hours. LC/triple quadrupole MS was used to analyse ganglioside concentration. H pylori was inoculated into the culture media of gastric cells previously treated with gangliosides GM3 or GD3 or a combination of GM3 and GD3. RESULTS: GD3 and GM3 content increased in the plasma membrane in a dose-dependent manner. Gastric cells treated with GD3 showed more GM3 content than GD3 (P < 0.01). Ganglioside content was modified in the apical membrane, but GM3 and GD3 were also found in the basolateral membrane after treatments. Gastric cells treated with GM3, GD3 or the combination of GM3:GD3 decreased H pylori adhesion to gastric cells at all ganglioside concentrations tested by 80% compared with untreated gastric cells (P < 0.05). CONCLUSIONS: These observations suggest that GD3 and GM3 present in the stomach lumen may be taken up into the apical gastric membrane and decrease H pylori adhesion to the epithelium.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

Chemotherapy diminishes lipid storage capacity of adipose tissue in a preclinical model of colon cancer.

BACKGROUND: Accelerated loss of adipose tissue in cancer is associated with shorter survival, and reduced quality of life. Evidence is emerging suggesting tumour association with alterations in adipose tissue, but much less is known about drug-related mechanisms contributing to adipose atrophy. Identification of mechanisms by which tumour and cancer treatments, such as chemotherapy, affect adipose tissue are required to develop appropriate therapeutic interventions to prevent fat depletion in cancer. This pre-clinical study aimed to assess alterations in adipose tissue during the clinical course of cancer. METHODS: Fischer 344 rats bearing the Ward colorectal tumour were euthanized before chemotherapy, after 1- cycle, or 2-cycles of a combination chemotherapy consisting of Irinotecan (CPT-11) combined with 5-fluorouracil (5-FU), which recapitulates first line treatment for human colorectal cancer. Periuterine adipose tissue was isolated. Healthy rats served as a reference group. Histological analysis (hematoxylin and eosin), Real-time PCR (TaqMan) and proteomic analysis (LC-MS/MS) were performed. RESULTS: Larger adipocytes (3993.7 ± 52.6 µm2) in tumour-bearing animals compared to the reference group (3227.7 ± 36.7 µm2; p < 0.001) was associated with reduced expression of proteins involved in mitochondrial fatty acid oxidation. The presence of a tumour has a significant effect on phospholipid but not triglyceride fatty acid composition. There were greater proportions of saturated fatty acids concurrent with lower monounsaturated fatty acids within the PL fraction of adipocytes in tumour-bearing animals. Chemotherapy treatment decreased the size of adipocytes (2243.9 ± 30.4 µm2; p < 0.001) and led to depletion of n-3 polyunsaturated fatty acids in adipose tissue triglyceride. Evaluation of the proteome profile revealed decreased expression of proteins involved in ATP generation, ß-oxidation, and lipogenesis. Overall, adipose tissue may not be able to efficiently oxidize fatty acids to provide energy to maintain energy demanding pathways like lipogenesis inside the tissue. CONCLUSIONS: In conclusion, metabolic adaptations to mitochondrial impairment may contribute to diminished lipid storage capacity of adipose tissue following chemotherapy delivery.

Determination of the Relative Efficacy of Eicosapentaenoic Acid and Docosahexaenoic Acid for Anti-Cancer Effects in Human Breast Cancer Models.

Epidemiological studies have associated high fish oil consumption with decreased risk of breast cancer (BC). n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish and fish oils exert anti-cancer effects. However, few studies have examined the relative efficacy of EPA and DHA alone and in mixtures on BC subtypes. This was the objective of the present review, as this research is a necessity for the translation of findings to human health and disease. The literature suggests that DHA has a greater anti-cancer effect in triple negative BC (TNBC). In estrogen positive (ER+) BC, DHA has a greater effect on cell viability, while both fatty acids have similar effects on apoptosis and proliferation. These effects are associated with preferential uptake of DHA into TNBC lipid rafts and EPA in ER+ BC. EPA:DHA mixtures have anti-cancer activity; however, the ratio of EPA:DHA does not predict the relative incorporation of these two fatty acids into membrane lipids as EPA appears to be preferentially incorporated. In summary, DHA and EPA should be considered separately in the context of BC prevention. The elucidation of optimal EPA:DHA ratios will be important for designing targeted n-3 LCPUFA treatments.

Clinical Implications of Sarcopenic Obesity in Cancer.

Sarcopenia has been associated with several negative clinical outcomes in cancer. However, the consequences of sarcopenic obesity, a condition of combined sarcopenia and obesity burden, have been less extensively investigated. The aim of this paper was to review the current evidence on the prevalence and clinical implications of sarcopenic obesity in cancer. A total of 14 studies linking sarcopenic obesity to a clinical outcome in cancer were included. There is considerable inconsistency in methods used to evaluate body composition as well as in the criteria used to define sarcopenic obesity, which limits comparison among studies. Therefore, the prevalence of sarcopenic obesity varied substantially: between 1 and 29 % in studies including individuals from all body mass index categories and between 15 and 36 % for those including obese individuals only. Negative clinical outcomes reported to be associated with sarcopenic obesity included higher risk of dose-limiting toxicity, surgical complications, physical disability, and shorter survival.