Short-term administration of omega-3 fatty acids in hemodialysis patients with balanced lipid metabolism.

BACKGROUND: At present, it is discussed whether omega-3 fatty acids show anti-inflammatory, antithrombogenic, and antiatherosclerotic effects, also in patients with chronic renal failure. METHODS: In this prospective study, 11 hemodialysis (HD) patients, ages 59 +/- 17 years, who had balanced lipid metabolism and had been on HD for 53 +/- 47 months, were treated with a moderate dose of omega-3 fatty acids (1.2 g/day combined with 11.2 g/day pectin) for 12 weeks. Serum concentrations of c-reactive protein, homocysteine (Hcy), lipids, complement factors, blood gas analyses, 24-hour blood pressure, heart rate variability, electrocardiography, shunt blood flow, and recirculation, as well as peripheral oxygen saturation at the hand and foot, were measured at the start (t0w), and after 12 weeks (t12w) of therapy. Results Several assessed cardiovascular risk factors were significantly influenced. Levels of very-low-density lipoproteins (t0w, 77 +/- 26; t12w, 63 +/- 32 mg/dL; P <.05) and triglycerides (t0w, 261 +/- 157; t12w, 228 +/- 131 mg/dL; P =.068) were decreased. However, Hcy concentrations increased from 35.5 +/- 32.5 to 43.5 +/- 36.7 micromol/L ( P <.01) after 12 weeks. Anti-inflammatory and investigated clinical parameters did not significantly change during the study period. CONCLUSION: Limited positive effects on metabolic parameters were evaluated by short-term administration of omega-3 fatty acids in HD patients. Based on previous studies and on suspicion of atherosclerotic disorder in examined HD patients, we suppose that only high doses of omega-3 fatty acids given for a longer time influence inflammation and atherosclerosis.     

The effect of n-3 fatty acids on C-reactive protein levels in patients with chronic renal failure.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic renal failure (CRF). C-reactive protein (CRP), a strong independent risk marker of CVD, is elevated in a large proportion of patients with CRF. The long-chain n-3 polyunsaturated fatty acids (PUFA) have cardioprotective effects, which may be partly attributed to their anti-inflammatory properties. OBJECTIVE: The study objective was to investigate the effect of n-3 PUFA on serum levels of CRP in patients with CRF. DESIGN: We performed a randomized, double-blind, placebo-controlled study. SETTING: The study took place at an outpatients clinic at the Department of Nephrology, Aalborg Hospital, Denmark. PATIENTS: The study comprised 46 patients (30 men and 16 women; mean age 59 +/- 11 years) with a serum creatinine level in the range of 150 to 400 micromol/L. INTERVENTION: The patients were randomly assigned to daily supplementation with 2.4 g n-3 PUFA or identical capsules containing 2.4 g of olive oil (control) for 8 weeks. MAIN OUTCOME MEASURE: CRP was measured with a high-sensitivity C-reactive protein (hs-CRP) assay and the content of n-3 PUFA in granulocyte membranes before and after supplementation. RESULTS: The n-3 PUFA concentration increased in granulocytes after the n-3 PUFA supplements but was unaltered by the control oil. A nonsignificant reduction in hs-CRP was observed in the n-3 PUFA group after supplementation (2.46 vs. 1.47 mg/L; P = .06), and hs-CRP was unaltered by the control oil (3.27 vs. 3.14 mg/L; P = .12). There was no difference in median hs-CRP change in the two groups. CONCLUSION: A trend was seen toward a reduction in hs-CRP in the n-3 PUFA group, but there was no significant difference in hs-CRP levels when both groups were compared.     

Comparison of C-reactive protein and high-sensitivity C-reactive protein levels in patients on hemodialysis

Chronic inflammation is highly prevalent in patients on hemodialysis (HD), as evidenced by increased levels of C-reactive protein (CRP). We compared CRP to high-sensitivity C-reactive protein (hs-CRP) to determine whether it has any clinical implications and prognostic significance in terms of mortality. CRP was measured using a standard immunoturbidometric assay on the COBAS? INTEGRA system and hs-CRP was measured using the Dade Behring on the Konelab Nephelometer in 50 patients on HD. CRP (≥6 mg/L) and hs-CRP (≥3 mg/L) levels were elevated in 30% and 54% of the patients, respectively. A significant correlation was noted between hs-CRP and CRP levels (r = 0.98, P <0.001). Deming regression analysis showed that the slope was near one (r = 0.90; 0.83-0.94) and that the intercept was small. Multivariate regression confirmed that age above 40 years (RR = 3.69, P = 0.027) and duration on HD greater than five years (RR = 3.71, P = 0.028) remained significant independent predictors of serum hs-CRP. Thirteen patients died during follow-up (26%). Multivariate Cox regression demonstrated that hs-CRP (RR = 1.062, P = 0.03) and CRP levels (RR = 1.057, P = 0.009) and age (RR = 1.078, P = 0.001) were the most powerful predictors of mortality. The CRP standard assay presents a reasonable alternative to the hs-CRP assay in patients on HD. The advantages of the CRP standard assay are its online and real-time availability as well as lower costs, particularly in developing countries.     

Results of a long-term administration of omega-3 fatty acids in haemodialysis patients with dyslipoproteinaemia

In this study we evaluated the effect of a daily administration of 1 g salmon-oil concentrate containing 0.2 g eicosapentaenoic acid (EPA) on the blood pressure, serum cholesterol, HDL and LDL cholesterol, triglycerides and magnesium of ten patients on chronic haemodialysis. Systolic and diastolic blood pressure values decreased significantly from 156 +/- 27.7/84 +/- 14.3 to 140 +/- 22.8/75.6 +/- 8.21 mmHg. Concordantly, mean arterial pressure (MAP) decreased significantly from 108 to 96 mmHg. Total serum cholesterol decreased significantly by 64%, HDL cholesterol increased by 47% (P less than 0.001). Serum triglyceride values decreased significantly to 48%. There was a distinct decline of magnesium from 1.42 +/- 0.27 to 1.28 +/- 0.13 mg/dl (P less than 0.001). According to these results, the administration of omega-3 fatty acids may be considered as a reasonable approach in the treatment of dyslipoproteinaemia in patients on continuous haemodialysis.     

Effect of a sardine supplement on C-reactive protein in patients receiving hemodialysis.

OBJECTIVE: The study evaluated the effect of a canned sardine supplement in C-reactive protein (CRP) in patients on hemodialysis (HD) and the compliance and adherence to this supplement. DESIGN: This was a quasi-experimental study: Participants with a serum CRP of 5 mg/dL or less volunteered to consume a sardine supplement or were maintained on the usual cheese/ham sandwich supplement. SETTING: The study took place in two outpatient dialysis units in Lisbon, Portugal. PATIENTS: The study comprised 63 patients receiving maintenance HD three times per week for at least 6 months and an initial CRP concentration of 5 mg/dL or less. Exclusion criteria included the presence of graft vascular access or history of cancer. INTERVENTION: After a 4-week washout period, the nutritional intervention included a canned sardine sandwich for the case group (n = 31) and a cheese or ham sandwich for the control group (n = 32), to be ingested during each routine HD session, 3 times per week, for 8 weeks. MAIN OUTCOME MEASURE: Serum levels of high-sensitivity CRP were the outcome measure. RESULTS: Only 65 patients from the invited 186 patients met the inclusion criteria and agreed to eat the sardine sandwich supplement three times per week and were involved in the study. A significant proportion of 48% (n = 31, case group) consumed the sardine sandwich supplement three times per week for 8 weeks, fulfilling the requirements and completing the study. The present investigation showed that a sardine sandwich supplement had no effect on CRP levels among patients on HD. However, when participants were stratified according to tertiles of CRP distribution values at baseline, a reduction in CRP levels was found for those in the higher tertile, being higher for the case group (P = .047). Although diabetic patients were excluded from the analysis (eight in the sardine supplementation group and seven in the control group) a significant CRP reduction was found (P = .034). CONCLUSION: Although a supplement of low-dose n-3 long-chain polyunsaturated fatty acids had no effect on the plasma high-sensitivity CRP of the supplemented group, a reduction in CRP levels was found when patients were stratified for tertiles of CRP (for the upper tertile) and diabetic status (for nondiabetic patients). These findings need to be further confirmed. This canned sardine supplement was accepted by an important proportion of patients, enhancing diet variety and contributing for a greater n-3 long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid intake.     

Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats

The aim of this study was to investigate the influence of omega-3 fatty acids (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increases in mortality rate, intestinal permeability, bacterial infection in pancreas and extrapancreatic organs, and serum activity of urea and amylase, alanine transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and a considerable decrease of concentrations of calcium, protein and albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha values. Serum triglyceride increased only in the omega3FA groups. Serum amylase, ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no difference between the pancreatitis groups. Increased intestinal permeability and cytokine levels, and free radical damage play an important role during the course of acute pancreatitis. The treatment with omega3FA improves these effects. omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be beneficial in patients with pancreatitis.     

阿托伐他汀钙对急性脑梗死患者血清C反应蛋白和肿瘤坏死因子-α的影响

目的观察阿托伐他汀钙对急性脑梗死患者血清C反应蛋白（CRP）和肿瘤坏死因子（TNF）-α水平的影响,探讨阿托伐他汀钙抑制急性脑缺血后炎性损伤的机制。方法选择发病24h内住院的急性脑梗死患者84例,随机分为阿托伐他汀钙治疗组（A组）和常规治疗组（B组）,每组各42例。两组均应用抗血小板和改善脑血液循环药物等常规治疗,A组在此基础上口服阿托伐他汀钙20mg／d,连续治疗28d。于治疗前及治疗后3、7d检测两组患者血清CRP和TNF-α水平,并比较两组患者欧洲卒中量表（ESS）评分的差异。另选择同期健康体检者16例作为健康对照组（C组）。结果84例急性脑梗死患者发病后血清TNF—Ot和CRP水平显著升高（P＜0．01或＜0．05）,其中CRP在治疗后3d达高峰,TNF—α在治疗后7d达高峰。A组峰值均低于B组[（13．00±2．45）mg/L比（19．21±3．67）mg／L,（19．79±11．01）ng／L比（30．69±18．47）．g／L,P＜0．05]。治疗后7dA组ESS评分高于B组[（79．19±30．59）分比（63．91±27．87）分],差异有统计学意义（P＜0．05）。结论阿托伐他汀钙可通过降低血清CRP和TNF—α水平而抑制急性脑缺血后炎性损伤,具有降脂以外的神经保护作用。     

Plasma fatty acid composition in continuous ambulatory peritoneal dialysis patients: an increased omega-6/omega-3 ratio and deficiency of essential fatty acids

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.     

Elevated serum levels of C-reactive protein in hemodialysis patients

Serum C-reactive protein (CRP) levels were measured by nephelometry in 30 healthy subjects (controls) and in 99 patients with uncomplicated terminal uremia on conservative therapy (group 1, n = 30) or chronic hemodialysis (group 2, n = 69). Whereas there was no difference between controls and group 1, both the mean concentration of CRP and the incidence of elevated levels were significantly higher in group 2 in comparison with both controls and group 1. Moreover, the degree of increase in these patients was directly correlated with the duration of hemodialysis. The abnormality, therefore, is somehow related to chronic hemodialysis per se. From a practical standpoint, we concluded that this test cannot be recommended as an acute-phase reactant in this clinical setting.     

The role of fish oil/omega-3 fatty acids in the treatment of IgA nephropathy

Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported in recent epidemiologic studies and randomized clinical trials in a variety of cardiovascular and autoimmune diseases. Fish and marine oils are the most abundant and convenient sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major n-3 fatty acids that serve as substrates for cyclooxygenase and lipoxygenase pathways leading to less potent inflammatory mediators than those produced through the n-6 PUFA substrate, arachidonic acid. N-3 PUFA can also suppress inflammatory and/or immunologic responses through eicosanoid-independent mechanisms. Although the pathophysiology of IgA nephropathy is incompletely understood, it is likely that n-3 PUFA prevents renal disease progression by interfering with a number of effector pathways triggered by mesangial immune-complex deposition. In addition, potential targets of n-3 PUFA relevant to renal disease progression could be similar to those involved in preventing the development and progression of cardiovascular disease by lowering blood pressure, reducing serum lipid levels, decreasing vascular resistance, or preventing thrombosis. In IgA nephropathy, efficacy of n-3 PUFA contained in fish oil supplements has been tested with varying results. The largest randomized clinical trial performed by our collaborative group provided strong evidence that treatment for 2 years with a daily dose of 1.8 g of EPA and 1.2 g of DHA slowed the progression of renal disease in high-risk patients. These benefits persisted after 6.4 years of follow up. With safety, composition, and dosing convenience in mind, we can recommend two products that are available as pharmaceutical-grade fish-oil concentrates, Omacor (Pronova Biocare, Oslo, Norway) and Coromega (European Reference Botanical Laboratories, Carlsbad, CA).     

Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients.

BACKGROUND: Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo. METHODS: The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography. RESULTS: In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04). CONCLUSION: Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.     

Effect of omega-3 fatty acids in diet of type I diabetic subjects on lipid values and hemorheological parameters

Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (omega 6FAs) were isocalorically exchanged with omega 3FAs (2.7 g/day provided by fish oil concentrates) for 10 wk. Subject selection was based on the fact that the atherogenic index (total cholesterol/high-density lipoprotein cholesterol [HDL-chol]) remained greater than 5. Total cholesterol did not change, but HDL-chol (P less than .05) increased significantly, and the mean +/- SD atherogenic index decreased from 5.9 +/- 1.1 to 5.1 +/- 1.3. Plasma triglyceride levels also decreased (P less than .05). There was a small (approximately 2%) but significant (P less than .05) decrease of whole-blood viscosity at low shear rate because of a similarly small (approximately 2% decrease (P less than .05) of plasma viscosity. Erythrocyte viscosity values and the erythrocyte transit time, measured with the St. George's filtrometer, remained unchanged during fish oil intake. Four weeks after stopping the omega 3FA administration, the triglyceride level was again increased (P less than .05) and was even higher than the starting value (P less than .05). Plasma and whole-blood viscosity also increased to the starting levels, demonstrating that lipid alterations are accompanied with blood viscosity changes in the presence of a stable metabolic control.     

Association of left ventricular hypertrophy with high-sensitive C-reactive protein in hemodialysis patients

Background

Micro inflammation and cardiovascular disease such as left ventricular hypertrophy (LVH) are common in hemodialysis (HD) patients. Hence, we have evaluated the relationship between high-sensitive C-reactive protein (hs-CRP), as an inflammation marker, and left ventricular mass index (LVMi) and left ventricular mass (LVM) in HD patients.

Methods

An analytical cross-sectional study was performed in 104 HD patients. Serum hs-CRP, LVMi, LVM, and blood pressure were evaluated; demographic data and duration of HD were also recorded. Finally, results were analyzed by using Student’s t test, Pearson’s correlation coefficient, one-way ANOVA and multiple regression to determine the relationship between LVMi and other variables.

Results

A total of 66 male patients (63.46 %) and 38 female patients, with a mean age of 51.75 ± 15.98 years-old, participated in this study. Hypertension was the most common underlying disease (65.4 %). The mean LVMi was 366.98 ± 120.89 g/m² and the mean hs-CRP was 8.55 mg/l. Eighty-nine percent of patients had LVH. The hs-CRP level was significantly associated with age and with LVM (P = 0.0001, P = 0.039, respectively). On multivariate analysis, hs-CRP and systolic blood pressure were found to be independent predictors of LVM and LVMi.

Conclusions

This study shows that hs-CRP and systolic BP are independent predictors of LVH in HD patients.     

The effect of n-3 fatty acids on heart rate variability in patients treated with chronic hemodialysis.

OBJECTIVE: The aim of the present study was to address the effect of n-3 polyunsaturated fatty acids (PUFAs) on heart rate variability (HRV) in patients treated with chronic hemodialysis. DESIGN: We performed a randomized, placebo-controlled intervention trial. SETTING: The study took place at two hospital-based dialysis centers. PATIENTS: Thirty patients with documented cardiovascular disease who were treated with hemodialysis for at least 6 months were included. INTERVENTION: Treatment consisted of 1.7 g of n-3 PUFA or a control treatment (olive oil). MAIN OUTCOME MEASURE: The outcome measure was 24-hour Holter recordings with time domain HRV measurements at baseline and after 3 months of treatment. Blood samples were obtained to assess the content of n-3 PUFA in serum phospholipids before and after treatment. RESULTS: n-3 PUFA did not significantly affect time domain parameters of HRV, compared with a control group. CONCLUSION: We conclude that treatment with n-3 PUFA does not increase HRV in patients treated with chronic hemodialysis, a result that may have been compromised by a small sample size.     

Dietary omega-3 fatty acids may be associated with increased neuropathic pain in nerve-injured rats

Certain dietary proteins and oils are capable of decreasing chronic neuropathic pain levels in rats after partial sciatic nerve ligation injury. We tested, for the first time, the role of dietary polyunsaturated fatty acids in suppressing pain in partial sciatic nerve ligation-injured rats. Six groups of male Wistar rats were fed an identical casein-based, fat-free diet for 1 wk preceding partial sciatic nerve ligation injury and for 1 wk thereafter. In addition, rats received, via gavage, 1 mL/day of pure canola, corn, hemp, soy, or sunflower oil, differing significantly in their omega-3 and omega-6 polyunsaturated fatty acid content, or 1 mL of plain water. Responses to tactile and noxious heat stimuli were recorded before and after surgery and a difference score was calculated for each group by subtracting the preoperative from the post-partial sciatic nerve ligation values. Heat hyperalgesia, but not tactile allodynia, was significantly different among the dietary groups (P = 0.005). Heat hyperalgesia of rats fed hemp oil, developing the most robust response, was significantly larger compared with rats fed corn oil, developing the least pain model (difference score: 24.3 +/- 4.1 s versus 6.1 +/- 3.1 s, respectively; P < 0.001). These oils contain similar levels of omega-6 polyunsaturated fatty acids (hemp, 60%; corn, 58%) but their omega-3 levels are 28-fold different (20% versus 0.7%, respectively). A significant correlation was found among dietary levels of omega-3, but not omega-6 or the omega-3/omega-6 ratio, of the six dietary groups and heat hyperalgesia (P = 0.006). We conclude that dietary oil might predict levels of neuropathic pain in rats and that this effect may be associated with dietary omega-3 levels. IMPLICATIONS: We found that certain commonly used oils can have a significant analgesic effect in rats with persistent pain after partial nerve injury. This effect may be associated with the amounts of omega-3 fatty acids consumed by rats.