Fatty Acid Supplementation Improves Respiratory,Inflammatory and Nutritional Parameters in Adults with Cystic Fibrosis

Introduction and aimsChronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study the changes seen after a oneyear course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters.Patients and methodSeventeen adult subjects with CF received 324mg of eicosapentaenoic, 216mg of docosahexaenoic, 480mg of linoleic and 258mg of gammalinolenic acid daily. We assessed inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life (St George's QoL), anthropometric parameters and serum phospholipid fatty acid composition.ResultsAt the end of the treatment period TNF alpha levels fell significantly and its soluble receptors (60 and 80) rose significantly. Levels of IgG and IgM anti-oxidised LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic ratio. The fat-free mass and hand grip dynamometry improved significantly.ConclusionsLow-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF.     

Omega‐3 Fatty Acid Supplementation in Advanced Kidney Disease

Long‐chain polyunsaturated omega‐3 fatty acids (n‐3 PUFA), which are obtained primarily from dietary sources such as coldwater fish, have diverse and potent mediating effects on the immune, inflammatory, and metabolic pathways, signal transduction, and cell membrane physiology. N‐3 PUFA are increasingly being studied for their clinical benefits in a variety of medical conditions, some of which are relevant to individuals with advanced chronic kidney disease (CKD). These include, among others, renoprotection in IgA nephropathy, cardioprotective effects via a variety of mechanisms including blood pressure and triglyceride reduction, maintenance of dialysis access patency, sparing of inflammation‐associated muscle loss, and even mortality. However, further confirmatory work needs to be performed before establishing formal intake recommendations and dosing goals for advanced CKD patients. In the meantime, the current American Heart Association n‐3 PUFA intake guidelines can be applied to CKD patients, especially given n‐3 PUFA’s potential benefits and negligible risk profile. Over time, it will be incumbent upon the nephrology community to more clearly define the utility and optimal dosing of n‐3 PUFA in CKD patients with advanced disease via randomized clinical trials.     

Plasma Fatty Acid Composition in Continuous Ambulatory Peritoneal Dialysis Patients: An Increased Omega-6/Omega-3 Ratio and Deficiency of Essential Fatty Acids

Abstract

Patients with end-stage renal disease, including those treated with peritoneal dialysis, have a high risk for death, particularly from cardiovascular causes. Plasma fatty acid (FA) composition is used as an indicator of disease risk, because its alteration has been related to metabolic disease and cardiovascular disease. For this purpose, we have measured plasma FA composition in continuous ambulatory peritoneal dialysis (CAPD) patients and compared them with those of healthy subjects. This study was performed on 51 (21 M, 30 F) CAPD patients at least 6 months under dialysis, aged 20–75 years (mean 47.81 ± 11.8 years) and 45 (25 M, 20 F) healthy control subjects aged 20–60 years (mean 38.62 ± 12.9 years). Plasma 10-cis-pentadecanoic acid, 10-cis-heptadecanoic acid, heneicosanoic acid, tricosanoic acid, nervonic acid, saturated fatty acid, and monounsaturated FA levels and delta 9 desaturase activity were significantly higher whereas linoleic acid, linolenic acid, 11,14-eicosedienoic acid, arachidonic acid, docosahexaenoic acid, and omega-3 FA levels were significantly lower in the CAPD group than those in the healthy group. Our results show that there are FA abnormalities and especially a depletion in essential FA levels and a high level of omega-6/omega-3 ratio in CAPD patients, the underlying mechanism of which is not known and needs to be investigated. Therefore, we believe that essential FA supplementation should be encouraged for CAPD patients.     

Marine n-3 Polyunsaturated Fatty Acid Supplementation and Quality of Life After Kidney Transplant

Marine n-3 polyunsaturated fatty acids (PUFAs) may improve cardiovascular, renal, and mental health. No previous trial has investigated the effects of marine n-3 PUFA supplementation on quality of life (QoL) indices after renal transplant.

Preoperative 4-Week Supplementation with Omega-3 Polyunsaturated Fatty Acids Reduces Liver Volume and Facilitates Bariatric Surgery in Morbidly Obese Patients

Background

Non-alcoholic fatty liver disease (NAFLD) is a very common condition among obese patients that may lead to the enlargement of the liver, that in turn impairs the access to the gastro-esophageal junction during laparoscopic bariatric surgery. Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) supplementation has been shown to reduce nutritional hepatic steatosis. The aim of this study was to assess the effects of a 4-week course of oral Ω-3 PUFAs supplementation on the volume of the liver.

Methods

20 morbidly obese patients were administered oral Ω-3 PUFAs (1,500 mg daily) for 4 weeks before undergoing the laparoscopic Roux-en-Y gastric bypass (LRYGBP) without any dietary restriction. The volume of the left hepatic lobe was estimated by liver ultrasonography at baseline and at the end of treatment. The degree of difficulty to access the gastro-esophageal junction was appreciated subjectively by the operating surgeon.

Results

All patients completed the study and no side effect was reported. The mean volume of the left hepatic lobe decreased by 20 % from 598?±?97 to 484?±?118 cm³ after the treatment (p?=?0.002). The access to the gastro-esophageal junction was reported as simple, with easy retraction of the left hepatic lobe by the operating surgeon in all cases.

Conclusions

This study demonstrates that a 4-week course of oral Ω-3 PUFAs supplementation results in a significant reduction in liver size that facilitates the LRYGBP.     

Systemic Inflammation in Morbidly Obese Subjects: Response to Oral Supplementation with Alpha-Linolenic Acid

Background Morbidly obese patients frequently display asymptomatic chronic activation of acute phase response, with potentially adverse metabolic and cardiovascular consequences. Nutritional preparations to improve this phenomenon have rarely been administered. Aiming to investigate the supplementation of flaxseed flour, a source of omega-3 fatty acids, a prospective randomized double-blind cross-over study was designed. Methods Outpatient obese subjects (n = 41) were clinically and biochemically screened, and results for 24 randomized subjects are shown. Age was 40.8 ± 11.6 years (83.3% females) and body mass index (BMI) was 47.1 ± 7.2 kg/m². Flaxseed flour (Farinha de Linhaca Dourada LinoLive, Cisbra, Brazil) in the amount of 30 g/day (5 g of alpha-linolenic acid – omega-3) and an equal mass of placebo (manioc flour) were administered for 2 weeks each. Variables included general biochemical investigation, white blood cell count (WBC), C-reactive protein (CRP), serum amyloid A (SAA) and fibronectin. Results No intolerance was registered. Body weight and general biochemical indices remained stable. Initial CRP and SAA were elevated (13.7 ± 9.9 and 17.4 ± 8.0). WBC (8100 ± 2100/mm³) and fibronectin (463.2 ± 61.3 mg/dL) were acceptable but in the upper normal range. Corresponding findings after supplementation of flaxseed were 10.6 ± 6.2 mg/L, 14.3 ± 9.2 mg/L, 7300 ± 1800/mm³ and 412.8 ± 38.6 respectively (P < 0.05 ). No change during the control period regarding baseline occurred when placebo was randomized to be given first; however, when it followed omega-3 supplementation, CRP and SAA recovered, whereas WBC and fibronection remained depressed during those 2 weeks (7500 ± 2100/mm³ and 393.2 ± 75.8 mg/dL, P < 0.05). Conclusions 1) Various inflammatory markers were elevated in the studied population, although not necessarily exceeding the normal range; 2) Significant reduction could be demonstrated; 3) Some persistent effects of flaxseed supplement 2 weeks after discontinuation were observed.     

The Calciotropic Hormone Response to Omega-3 Supple-Mentation During Long-Term Weight-Bearing Exercise Training in Post Menopausal Women

The purpose of this study was to examine the effects of ingestion of omega-3 (n-3) and aerobic exercise intervention on the calcium regulating hormones in healthy postmenopausal women. To this end, 56 healthy sedentary postmenopausal women with mean age 57.7 ± 3.5 yrs participated in this study. Participants were randomly divided into exercise plus supple-ment (E+S; n = 14), exercise (E; n = 14), supplement (S; n = 14) and control (Con, n = 14) groups. The subjects in E+S and E groups performed aerobic exercise training (walking and jog-ging) up to 65% of exercise HRmax, three times a week for 16 weeks. Subjects in E+S and S groups were asked to consume 1000 mg/d omega-3 for 16 weeks. The blood ionized Calcium (Ca⁺²), Parathyroid hormone (PTH), estrogen and Calcitonin (CT) were measured before and after 16 weeks of exercise training. Results indicated that consuming 1000 mg·day^-1 omega-3 during 16 weeks and or the aerobic exercise, significantly increased CT (p = 0.001) in E+S, E and S groups and significantly decreased PTH (p = 0.001) levels in E+S and E groups, also significantly increased estrogen (p = 0.024) levels in E+S and E groups, but had no significant effects on blood Ca⁺² (p = 0.619) levels. The results of present study demonstrate that omega-3 in combination with regular aerobic exercise training have significant effects on serum CT, estrogen and PTH in non-athletic post-menopausal women, suggesting that participating in moderate intensity weight-bearing exercise and incorporating sources of omega-3 in the diet a possible intervention to help slow the loss of bone that occurs following menopause.

Key points

• Long-term weight-bearing exercise was shown to prove positive effects on bone metabolism.
• Serum calciotropic hormone levels and Ca⁺² can be affected by exercise intensity as well as dura-tion.
• There is a good relationship between dietary omega-3 (n-3) and bone metabolism in post-menopausal women.
• Omega-3 in combination with long-term weight-bearing exercise training has significant effects on serum calciotropic hormone levels in non-athlete post-menopausal women.

Key words: Postmenopausal women, physical activity, parathyroid hormone, calcitonin, omega-3 fatty acids, bone mineral density     

Inhibition of Proliferation by Omega-3 Fatty Acids in Chemoresistant Pancreatic Cancer Cells

Background Pancreatic cancer-gemcitabine (GEM) chemoresistance has been demonstrated to be associated with enhanced NF-kB activation and antiapoptotic protein synthesis. The well-known capacity of omega-3 fatty acids (n-3 FAs) to inhibit NF-kB activation and promote cellular apoptosis has the potential to restore or facilitate gemcitabine chemosensitivity. Methods Four pancreatic cancer cell lines (MIA PaCa-2, BxPC-3, PANC-1, and L3.6), each with distinct basal NF-kB and differing GEM sensitivity profiles, were administered: 100 uM of (1) n-3FA, (2) n-6FA, (3) GEM, (4) n-3FA + GEM, or (5) n-6FA + GEM for 24 and 48 hours. Proliferation was assessed using the WST-1 assay. To define the mechanism(s) of altered proliferation, electron mobility shift assay for NF-kB activity, western blots of phoshoStat3, phosphoIκB, and poly(ADP-ribose) polymerase (PARP) cleavage were performed in the MIA PaCa-2 cell line. Results All cell lines demonstrated a time/dose-dependent inhibition of proliferation in response to n-3FA. For MIA PaCa-2 cells, n-3FA and n-3FA + GEM treatment resulted in reduction of I-kB phosphorylation and NF-kB activation when compared with n-6FA control. n-3FA and combination treatment also significantly decreased Stat3 phosphorylation, whereas GEM alone had no effect. n-3FAs and n-3FA + GEM groups demonstrated increased PARP cleavage, mirroring NF-kB activity and Stat3 phosphorylation. Conclusions n-3 FA treatment is specifically associated with inhibition of proliferation in these four pancreatic cell lines irrespective of varied gemcitabine resistance. An experimental paradigm to screen for potential contributory mechanism(s) in altered pancreatic cancer cellular proliferation was defined, and using this approach the co-administration of n-3 FA with GEM inhibited GEM-induced NF-kB activation and restored apoptosis in the MIA PaCa-2 cell-line. Supported by: NIDDK K08 DK DK60778 (Espat)     

The effect of eccentric strength training at various speeds on concentric strength of the quadriceps and hamstring muscles

This study investigated the effect of eccentric training on concentric strength of the quadriceps and hamstring muscles. The dominant legs of 43 college-age males were pretested concentrically using the KIN-COM(R) at speeds of 60 and 180 degrees /sec. Twenty-eight treatment subjects trained eccentrically at one of the testing speeds for a period of eight weeks; the remainder served as the control group. Prior to each training session, the subjects gave a subjective evaluation of muscle soreness. Delayed muscle soreness did not affect the subjects' ability to train eccentrically. A concentric posttest was taken to determine any treatment effects. The quadriceps muscle did not show any significant change after eccentric training. Eccentric training at 60 and 180 degrees /sec significantly increased the concentric strength of the hamstrings. Eccentric training does appear to be effective in developing concentric strength in the hamstrings. The speed of eccentric training was not a factor in concentric conditioning. J Orthop Sports Phys Ther 1991;13(5):226-230.     

Effects of N-3 PUFAs Supplementation on Insulin Resistance and Inflammatory Biomarkers in Hemodialysis Patients

Aims/Hypothesis. It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. Methods. This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 ± 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. Results. Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. Conclusion. It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.     

The Effect of Anti-L-Selectin (Aselizumab) on the Posttraumatic Inflammatory Response in Multiply Traumatized Patients

Abstract Purpose: This prospective phase II parallel-group, double- blind, randomized, placebo-controlled clinical trial was meant to evaluate the effect of a humanized monoclonal anti-L-selectin antibody (aselizumab) on the posttraumatic inflammatory response in severely injured patients. Patients and Methods: To be eligible for the study, patients had to have sustained a trauma due to a blunt or penetrating injury, which involved at least two organ systems according to the Abbreviated Injury Scale (AIS) resulting in a total Injury Severity Score (ISS) of ≥ 25. Included patients (n = 84) received either placebo or 0.5 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of aselizumab within 6 h of the traumatic event. Parameters representing the posttraumatic inflammatory response were monitored for 10 days, patients’ general records were monitored for 14 days and discontinuously until day 42. Results: The incidence of multiple organ failure (MOF) defined as a median value of the total Goris MOF score of ≥ 5 on ≥ 2 consecutive days within the first 14 days was not significantly different for the placebo and the 0.5-mg/kg, 1.0-mg/kg, and 2.0-mg/kg groups. The cytokine interleukin-(IL-)6 and IL-10 serum levels as well as neutrophil elastase serum concentrations revealed the well-described posttraumatic acute response which resolved from day 3 after trauma in all four study groups. Also complement factor C3a and procalcitonin followed the same pattern. There were no statistically significant differences between placebo and patients having received anti-L-selectin at different dosages. Conclusion: For all of the measured variables, IL-6, IL-10, elastase, C3a and procalcitonin, there were only a few trends but no significant differences between all study groups indicating that the effect of the administered anti-L-selectin antibody on the posttraumatic inflammatory response was similar to that of placebo.     

Attenuation of the Systemic Inflammatory Response and Infectious Complications After Gastrectomy with Preoperative Oral Arginine and ω-3 Fatty Acids Supplemented Immunonutrition

Background  Past trials have shown perioperative immunonutrition to improve the outcome for patients with gastric cancer. The present study was designed to evaluate the effect of preoperative oral immunonutrition on cellular immunity, the duration of the systemic inflammatory response syndrome (SIRS), and detailed postoperative complications in patients with gastric cancer. Methods  Sixty patients with gastric cancer were randomly assigned to two groups: one group received immune-enhanced formulas supplemented with arginine and ω-3 fatty acids (immune-enhancing diet (ID) group, n = 30); the other received standard formulas (conventional diet (CD) group, n = 30) for 7 days before the operation. These groups were well matched in terms of age, sex, operations, cancer stages, and intraoperative variables. The postoperative outcome was evaluated based on clinical variables, including postoperative infectious complications, noninfectious complications, and SIRS duration. In addition, the perioperative state of cellular immunity was evaluated and compared between the two groups. Results  The incidence of postoperative infectious complications in the ID group (6%) was significantly (p < 0.05) lower than that of the CD group (28%). The duration of SIRS in the ID group (0.77 ± 0.9 days) was significantly (p < 0.05) shorter than that in the CD group (1.34 ± 1.45 days). The postoperative lymphocyte and CD4⁺T-cell counts significantly decreased (p < 0.05) in both groups. However, the number of CD4⁺T-cells on preoperative day 1 and postoperative day 7 was significantly (p < 0.05) higher in the ID group than in the CD group. Conclusions  Preoperative oral immune-enhanced formulas supplemented with arginine and ω-3 fatty acids enhanced the immune status of the patients, reduced the duration of SIRS, and decreased the incidence of postoperative infectious complications. CD4⁺T-cell immunity likely played an important role in the modulation of the postoperative immune and inflammatory response after gastrectomy.     

体外循环术中小剂量抑肽酶对急性炎性反应的作用

目的 探讨体外循环（ECC）术中小剂量抑肽酶是否能减轻ECC所致的急性炎性反应。方法 将28例首次心瓣膜置换术患者随机分为抑肽酶组和对照组,各14例。于麻醉诱导前、ECC前、ECC后1小时和24小时测定血浆中白细胞介素－10（IL－10）、肿瘤坏死因子－α（TNF-α）和白细胞计数。结果 两组IL－10ECC后1小时比麻醉诱导前明显升高（P＜0．01）,且抑肽酶组明显高于对照组（P＜0．01）;对照组TNF－α和白细胞计数在ECC后1小时和24小时较麻醉诱导前明显升高,且高于抑肽酶组（P＜0．05）。结论 小剂量抑肽酶可抑制ECC所致的炎性反应。