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.     

Prostate tissue and leukocyte levels of n-3 polyunsaturated fatty acids in men with benign prostate hyperplasia or prostate cancer

OBJECTIVE: To compare the levels of n-3 polyunsaturated fatty acids (PUFAs) in leukocytes and prostate tissue in men with prostate cancer or benign prostatic hyperplasia (BPH), as dietary intake of n-3 PUFAs has been linked to the risk of prostate cancer; the prostate-specific antigen (PSA) level was also compared to prostate tissue levels of n-3 PUFAs. PATIENTS AND METHODS: Prostate tissue was obtained and leukocytes isolated from 20 men with prostate cancer and 35 with BPH. The n-3 PUFAs alpha-linolenic acid (ALA), eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) were measured in prostate tissue and in peripheral blood leukocytes using gas chromatography. PSA levels were measured in all of the men. RESULTS: There was a strong positive correlation between EPA and DHA in leukocytes and in prostate tissue (EPA: r = 0.80, DHA: r = 0.53, both P < 0.001) in all the men, whereas there was no association between the content of ALA in leukocytes and in prostate tissue (r = -0.15). Men with BPH had similar levels of ALA in leukocytes and in prostate tissue, but men with prostate cancer had more ALA in prostate tissue than in leukocytes. The PSA level was significantly positively correlated with ALA level in prostate tissue (r = 0.42, P < 0.01) but there was no significant correlation between PSA level and EPA and DHA levels. There were no significant correlations between PSA level and n-3 PUFA levels in leukocytes. CONCLUSION: Dietary intake of the marine n-3 PUFAs reflected in EPA and DHA levels in leukocytes are also reflected in EPA and DHA levels in prostate tissue in men with and without prostate cancer. However, there is a discrepancy between the levels of ALA in leukocytes and in prostate tissue, with higher levels in men with prostate cancer. This is in accordance with the strong positive association between PSA and ALA levels in prostate tissue. This study therefore does not support the hypothesis that intake of marine n-3 PUFAs might protect against prostate cancer, but lends support to the deleterious role of ALA in the development of prostate cancer.     

Continual supplementation with n-3 fatty acids does not modify plasma lipid profile in spinal cord injury patients

STUDY DESIGN: A prospective study during a diet modification. OBJECTIVE: To observe the evolution of the plasma lipid profile in a group of spinal cord injury (SCI) patients given a supplement of a mixture of docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA). SETTING: Department of Physiological Sciences II, Medical School of the University of Barcelona and Guttmann Institut of Badalona, Barcelona, Spain. METHODS: A total of 19 adult males with SCI, 17 with paraplegia and two with tetraplegia, were given a daily supplement of 1.5 g of DHA and 0.75 g of EPA for 6 months. Determination of plasma values of DHA, EPA, total cholesterol, HDL-c, LDL-c, VLDL-c, triglycerides, and glucose was performed before supplementation and at 3 and 6 months of supplementation. RESULTS: A statistically significant increase in the plasma concentration of EPA (F=30.556, P<0.05) and DHA (F=106.6, P<0.05) was observed after 3 and 6 months of supplementation. However, there were no observable differences in the plasma concentration of total-cholesterol, HDL-c, LDL-c, VLDL-c, and triglycerides during the study. CONCLUSION: DHA-EPA supplementation for 6 months does not modify the glycemic and lipid plasmatic levels in SCI patients. Despite its absence of effect on the serum lipid profile, n-3 fatty acids may induce beneficial cardiovascular effects in this population.     

Specific Effects of γ-Linolenic,Eicosapentaenoic, and Docosahexaenoic Ethyl Esters on Bone Post-ovariectomy in Rats

Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of γ-linolenic (GLA), eicosapentaenoic (EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area, and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism, and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly as a result of PTH-induced bone catabolism.     

Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients--a pilot study.

BACKGROUND: We previously reported that haemodialysis patients have suboptimal blood levels of the cardioprotective omega-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. In the present pilot study, we tested the hypothesis that supplementing haemodialysis patients for 12 weeks with the American Heart Association (AHA)-recommended fish oil dose would be well tolerated and efficacious in boosting blood n-3 PUFA levels and improving cardiovascular risk biomarkers. METHODS: Twenty-seven subjects were randomized in a 2 : 1 ratio to either 1.3 g of EPA + DHA daily or placebo. RESULTS: At baseline, 83% of subjects consumed inadequate dietary fish and had the following erythrocyte n-3 PUFA levels (mean +/- SD,% weight)-EPA: 0.3 +/- 0.2, DHA: 2.9 +/- 2.0, and ratio of n-6/n-3 PUFA: 4.2 +/- 1.3. Supplementation induced large increases in mean blood EPA and DHA levels (% increase, P-value vs placebo group): erythrocyte-EPA: +400%, P = 0.0018, DHA: +205%, P < 0.0001; plasma-EPA: +275%, P = 0.0003, DHA: +69%, P = 0.0352. Levels in the placebo group remained relatively unchanged. The omega-3 index, a value correlating with the level of cardioprotection, increased significantly in the fish oil group. A reduction in mean C-reactive protein levels (-3.3 +/- 8.1 mg/l, P = 0.0282) and a trend towards lower triglyceride levels (-24 +/- 74 mg/dl, P = 0.0783) were also observed in the active vs placebo group. Minimal side effects were noted. CONCLUSIONS: Our preliminary observations that the AHA-recommended fish oil dose is well tolerated, efficacious and may improve surrogate markers of cardiovascular disease in haemodialysis patients paves the way for larger clinical trials to confirm a clinical benefit.     

Plasma and erythrocyte phospholipid fatty acids composition in Serbian hemodialyzed patients

Dyslipidemia is one of the possible risk factors for advanced atherosclerosis in patients with chronic renal failure. Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in patients with renal failure. The aim of this study was to determine specific characteristics of plasma and erythrocyte phospholipid content and fatty acid composition in 37 patients with chronic renal failure on hemodialysis (HD). The results were compared with the characteristics of healthy subjects. Briefly, plasma triglyceride (p < 0.001), total cholesterol (p < 0.05), and total phospholipids (p < 0.01) levels were significantly higher and HDL-cholesterol level significantly lower (p < 0.01) in HD patients. Plasma phosphatidylcholine and phosphatidylethanolamine concentration were significantly higher (p < 0.001) in HD patients. The plasma phospholipid fatty acids composition indicated significantly (p < 0.01) higher level of oleic (18:1 n-9) and lower levels of eicopentaenoic (20:5 n-3 EPA) and docosahexaenoic (22:6 n-3 DHA) acids (p < 0.05). However, in HD patients, the relative concentration of plasma phospholipid n-6 polyunsaturated fatty acid (PUFA) was significantly lower (p < 0.05). The fatty acid composition of erythrocyte phospholipid in HD patients was modified with EPA and DHA levels significantly lowered (p < 0.05). Our results demonstrate an abnormal phospholipid metabolism and deficiency of n-3 PUFA in plasma and erythrocyte phospholipids in hemodialyzed patients.     

Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy

A deficiency in essential fatty acid metabolism has been widely reported in both human and animal diabetes. Fish oil supplementations (n-3 fatty acids), containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were less effective on diabetic neuropathy than (n-6) fatty acids. This partial effect of (n-3) fatty acids might be attributed to the presence of EPA, a competitor of arachidonic acid, which enhanced the diabetes-induced decrease of this fatty acid in serum and tissues. For determining whether a supplementation with DHA alone could prevent neuropathy in streptozotocin-induced diabetes, diabetic rats were given daily, by gavage, liposomes containing DHA phospholipids, at a dose of 60 mg/kg. Eight weeks of diabetes induced significant decreases in nerve conduction velocity (NCV), nerve blood flow (NBF), and sciatic nerve and erythrocyte (red blood cells [RBCs]) Na,K-ATPase activities. DHA phospholipids totally prevented the decrease in NCV and NBF observed during diabetes when compared with the nonsupplemented diabetic group. DHA phospholipids also prevented the Na,K-ATPase activity decrease in RBC but not in sciatic nerve. Moreover, DHA level in sciatic nerve membranes was correlated with NCV. These results demonstrate a protective effect of daily doses of DHA on experimental diabetic neuropathy. Thus, treatment with DHA phospholipids could be suitable for evaluation in clinical trials.     

Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women

The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m^-2) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might facilitate better training adaptations and exercise adherence.

Key points

• Seven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise.
• This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and women
• The benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oil
• The findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive option
• These findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients).

Key words: Delayed-onset muscle soreness, omega-3 fatty acids, fish oil     

ω-3多不饱和脂肪酸诱导人胃癌细胞凋亡的实验研究

目的观察ω-3多不饱和脂肪酸(ω-3PUFAs)对SGC-7901人胃癌细胞系凋亡的影响并探究其机制。方法采用四甲基偶氮唑蓝(MTT)法、细胞形态学、DNA电泳和流式细胞技术对细胞生长与凋亡进行观察和分析,利用荧光探针rhodamine123检测线粒体跨膜电位,酶联免疫吸附法分析线粒体和胞质中细胞色素C的分布,气相色谱分析线粒体膜磷脂构成。结果二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)能显著抑制胃癌细胞的生长,诱发细胞凋亡,并呈现时间和剂量依赖性关系。40μg/mlEPA和DHA作用细胞24h后,线粒体跨膜电位显著降低(P<0.001),线粒体膜间细胞色素C大量释入胞质,EPA和DHA在线粒体膜磷脂构成中的比例迅速升高(P<0.001),而花生四烯酸(20:4ω-6,AA)占总磷脂的比例明显降低,由对照组的30.8%分别下降为20.9%和18.6%。结论ω-3PUFAs通过诱导细胞凋亡抑制胃癌细胞的生长,线粒体膜构成和功能的改变可能是ω-3PUFAs诱导凋亡的重要机制。     

Effect of n-3 fatty acids on nutritional status and inflammatory markers in haemodialysis patients

AIMS: Nutrition as an aetiological factor participates a great deal in premature atherosclerosis in haemodialysis (HD) patients. The basic mechanisms of end-stage renal disease and premature atherosclerosis are connected with changes in cell functions at the membrane level. We investigated the red cell membrane fatty acids and the effects of fish oil supplements on nutritional status and inflammatory markers in HD patients. METHODS: We examined 42 HD patients (mean age 55 +/- 8 years). The control group consisted of 16 healthy subjects of similar age and sex to the tested group. HD patients were administered supplements with 2.4 g of n-3 polyunsaturated fatty acids per day for 2 months. Before and after supplementation, we examined plasma lipids, cell membrane erythrocyte phospholipids content, serum albumin, haemoglobin, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). RESULTS: Baseline values in the tested group confirmed the presence of essential fatty acids deficiency. A statistically significant negative correlation between TNF-alpha and eicosapentaenoic acid (EPA) (r = -0.497; P < 0.05) and IL-6 and EPA (r = -468; P = 0.03) was found in HD patients before supplementation. There was a significant increase in docosahexaenoic acids, high density lipoprotein cholesterol, plasma albumin, haemoglobin levels in HD patients after supplementation (P = 0.0001). There was a significant increase in EPA (P = 0.01) after treatment, and there was a significant decrease in inflammatory markers (IL-6 and TNF-alpha, P = 0.0001) after supplementation in the tested group. CONCLUSION: A dietary regime with fish oil could be used in dialysis patients to slow down the development of atherosclerosis and improve nutritional parameters.     

Association of inflammatory biomarkers with metabolic syndrome in hemodialysis patients

The relative importance of inflammatory markers in relation with metabolic syndrome (MeS) in hemodialysis (HD) patients is uncertain. This study investigated the association between MeS and high-sensitive C-reactive protein (hsCRP), hallmark of inflammation, and other inflammatory-related biomarkers. The study included 153 patients who were dialyzed at least for the last 3?months. The serum level of hsCRP was assessed by high-sensitive Enzyme-linked immunosorbent assay (ELISA). MeS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III (ATP-III). Ninety-one HD patients (59.5%) were diagnosed as having MeS. Lower level of high-density lipoprotein-cholesterol (HDL-C) was the most prevalent MeS component (85.6%). The serum level of hsCRP in these patients was significantly higher than that in HD patients without MeS (2.3?±?1.7 vs. 1.7?±?1.6?mg/dL, p?=?0.03). A significant linear increase in the hsCRP levels was found according to the number of MeS components (β?=?0.09, p?=?0.022). The study concluded that increasing inflammatory biomarkers, especially hsCRP, is associated with MeS in HD patients.     

Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.     

Doxazosin,but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective,randomized-controlled study

Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this randomized-controlled study, we aimed to compare the effect of doxazosin and amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female: 5/10, mean age: 46 +/- 13 years) and 9 controls (male/female: 3/6, mean age: 35 +/- 8 years) were included. Patients and controls had no family history of diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker of IR. Patients were grouped randomly to doxazosin (n = 8; 2-4 mg/day) and amlodipine (n = 7; 5-10 mg/day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C peptide, HOMA) were similar between amlodipine and doxazosin groups. There was no difference in age, gender and body mass index among study groups. The follow-up time was 12 weeks. Patients with CRF had higher HOMA (1.83 +/- 0.55 vs 1.00 +/- 0.36, p = 0.001), fasting insulin (8.06 +/- 1.98 vs 4.46 +/- 1.31 IU/l, p < 0.001) and serum triglyceride levels (197 +/- 136 vs 112 +/- 67 mg/dl, p = 0.04) as compared to controls. Serum HDL cholesterol levels were significantly lower in patients with CRF than controls (40 +/- 10 vs 57 +/- 14 mg/dl, p = 0.02). HOMA significantly decreased after doxazosin (1.91 +/- 0.45 vs 1.41 +/- 0.21, p = 0.02), however, no difference was found after amlodipine. Also, fasting insulin levels were decreased after a 12-week doxazosin therapy from 8.17 +/- 1.22 vs 6.58 +/- 0.84 IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did not significantly change during the study period in 2 groups. No adverse effect requiring drug discontinuation was observed during the 12-week period in the study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas amlodipine has no effect. This may be of advantage in the treatment of hypertension in this group of patients for preventing some long-term complication of IR.     

The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients

Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05). However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.     

Fatty acid composition of some South African fresh-water fish

Because of the antithrombotic and anti-inflammatory properties of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in large quantities in marine fish, the fatty acid composition of the flesh of 18 different species of fresh-water fish found in South Africa was analysed by capillary gas chromatography. In general all the fish studied had low percentages of EPA and DHA and fairly high percentages of arachidonic acid and linoleic acid when compared with some marine fish. The saturated fats constituted 33% of total fatty acids and the mono-enes averaged 35%. The fish studied are therefore not as good a source of n-3 fatty acids as marine fish.     

No effects of n-3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial

The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI) patients, who are at risk of testosterone deficiency. In a double-blind, placebo-controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850 male post-MI patients aged 60-80?years who participated in the Alpha Omega Trial. Patients were randomly allocated to margarines that provided 400?mg/day of EPA-DHA (n?=?453), 2?mg/day of ALA (n?=?467), EPA-DHA plus ALA (n?=?458), or placebo (n?=?472). Serum testosterone levels were assessed at baseline and after 41?months using whole day blood samples obtained at the subjects' home or at the hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had baseline mean serum total testosterone of 14.8 (SD 5.6)?nmol/L. The four randomized groups did not differ for baseline characteristics. ALA, EPA-DHA, and EPA-DHA plus ALA supplementation did not affect serum total testosterone compared to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of incident testosterone deficiency (n?=?76 with total testosterone <8.0?nmol/L). We conclude that n-3 fatty acids supplementation did not affect serum total testosterone in men who had had a MI.     

Fatty acids platelets and oxidative markers following intravenous n-3 fatty acids administration in cystic fibrosis: An open pilot observational study.

BACKGROUND: An imbalance in the ratio of arachidonic acid and docosahexaenoic acid (DHA) was found in cystic fibrosis (CF) affected tissues and was suggested to promote inflammation. Several studies have shown that the long chain n-3 fatty acids reduced inflammatory activity while others have highlighted prooxidant activity of DHA at high concentrations. The aim of our study was to evaluate the effects of an intravenous fish-oil emulsion enriched with n-3 FA in patients with CF on plasma and platelet FA composition and peroxidation markers. METHODS: 13 patients with CF received one IV emulsion per week of 2 mL/kg fish-oil n-3 emulsion for 12 weeks. RESULTS: There was a significant increase in 20:5 n-3 and 22:6 n-3 platelet FA composition, no variation in 20:4 n-6, a decrease in n-9. There was no variation in plasma FA composition. Specific urinary markers of lipid peroxidation derived from n-3 and n-6 showed a very high level before infusion compared with usual values in healthy subjects which was not affected by treatment. A significant weight loss and a decrease in reduced glutathione were observed in adult patients. CONCLUSIONS: The intravenous administration of n-3 FA in CF patients induced a significant modification in platelet FA composition but no modification of oxidative markers. However, the weight loss and the decreased level in reduced glutathione observed in adult patients may suggest a potential deleterious activity for some patients. Further studies are necessary to determine the optimal dose and route for long chain FA administration required to reach a potential beneficial effect.     

Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds

Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω‐3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study's purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either EPA+DHA supplementation (Active Group) or placebo. After 28 days, the Active Group had significantly higher plasma levels of EPA (p<0.001) and DHA (p<0.001) than the Placebo Group and significantly lower wound fluid levels of two 15‐lipoxygenase products of ω‐6 polyunsaturated fatty acids (9‐hydroxyoctadecadienoic acid [p=0.033] and 15‐hydroxyeicosatrienoic acid [p=0.006]), at 24 hours postwounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more reepithelialization on Day 5 postwounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing.     

Cellular Production of n-3 PUFAs and Reduction of n-6�Cto�Cn-3 Ratios in the Pancreatic ��-Cells and Islets Enhance Insulin Secretion and Confer Protection Against Cytokine-Induced Cell Death

OBJECTIVE

To evaluate the direct impact of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the functions and viability of pancreatic β-cells.

RESEARCH DESIGN AND METHODS

We developed an mfat-1 transgenic mouse model in which endogenous production of n-3 PUFAs was achieved through overexpressing a C. elegans n-3 fatty acid desaturase gene, mfat-1. The islets and INS-1 cells expressing mfat-1 were analyzed for insulin secretion and viability in response to cytokine treatment.

RESULTS

The transgenic islets contained much higher levels of n-3 PUFAs and lower levels of n-6 PUFAs than the wild type. Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets. When challenged with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and γ-interferon (IFN-γ), the transgenic islets completely resisted cytokine-induced cell death. Adenoviral transduction of mfat-1 gene in wild-type islets and in INS-1 cells led to acute changes in the cellular levels of n-3- and n-6 PUFAs and recapitulated the results in the transgenic islets. The expression of mfat-1 led to decreased production of prostaglandin E₂ (PGE₂), which in turn contributed to the elevation of insulin secretion. We further found that cytokine-induced activation of NF-κB and extracellular signal–related kinase 1/2 (ERK_1/2) was significantly attenuated and that the expression of pancreatic duodenal hemeobox-1 (PDX-1), glucokinase, and insulin-1 was increased as a result of n-3 PUFA production.

CONCLUSIONS

Stable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced β-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo.Polyunsaturated fatty acids (PUFAs) are synthesized from the modification of saturated fatty acid precursors by different desaturases and elongation enzymes. Mammals have neither the desaturase necessary to synthesize the precursors of other PUFAs, linoleic acid (LA, n-6), and α-linolenic acid (ALA, n-3), nor the n-3 fatty acid desaturase to convert n-6 PUFAs to n-3 PUFAs. Therefore, LA and ALA and their elongation products are essential fatty acids to mammals and must be taken from diets (1,2). Physiologically, n-3 PUFAs play critical roles in the development and functions of retina, spermatozoa, and the central nervous system (1,3).A series of epidemiological studies have established the health benefits of dietary intake of n-3 PUFAs in preventing cardiovascular diseases and type 2 diabetes (4,5). Two recent large-scale clinical studies also demonstrated that long-term dietary intake of fish oil starting at 1 year of age lowers the risk of type 1 diabetes and islet autoimmunity (6,7). Consistent with such epidemiological evidence, recent studies in rodents indicated that dietary gain or direct administration of n-3 PUFAs could restore palmitate acid– or linoleic acid–impaired insulin secretion (8,9). An issue central to this study is whether the effects of n-3 PUFAs on type 1 diabetes are related to the direct impact on the functions and viability of β-cells. To evaluate such effects as well as the underlying mechanisms, we developed a transgenic mouse model that expresses a C. elegans gene, fat-1, encoding a n-3 fatty acid desaturase (10). Since this enzyme can convert n-6 PUFAs into the corresponding n-3 forms, transgenic expression of fat-1 will render the host endogenous capability of producing n-3 PUFAs while concomitantly reducing the levels of n-6 PUFAs. Using such a unique animal model, we are able to evaluate the impact of stable cellular elevation of n-3 PUFAs on insulin secretion and viability of β-cells without the need of lengthy feeding of fish oil. The positive outcomes from our studies may reveal the potential utility of this type of gene to deter and mitigate type 1 diabetes.