Weeks Of Fish Oil Supplementation Research Articles

Omega-3 supplementation changes the physical properties of leukocytes but not erythrocytes in healthy individuals: An exploratory trial

n3-PUFA impact health in several ways, including cardiovascular protection and anti-inflammatory effects, but the underlying mechanisms are not fully understood. In this exploratory study involving 31 healthy subjects, we aimed to investigate the effects of 12 weeks of fish-oil supplementation (1500 mg EPA+DHA/day) on the physical properties of multiple blood cell types. We used deformability cytometry (DC) for all cell types and Laser-assisted Optical Rotational Red Cell Analysis (Lorrca) to assess red blood cell (RBC) deformability. We also investigated the correlation between changes in the physical properties of blood cells and changes in the Omega-3 Index (O3I), defined as the relative content of EPA+DHA in RBCs. Following supplementation, the mean±SD O3I increased from 5.3 %±1.5 % to 8.3 %±1.4 % (p < 0.001). No significant changes in RBC properties were found by both techniques. However, by DC we observed a consistent pattern of physical changes in lymphocytes, neutrophils and monocytes. Among these were significant increases in metrics correlated with the cells’ deformability resulting in less stiff cells. The results suggest that leukocytes become softer and have an increased ability to deform under induced short-term physical stress such as hydrodynamic force in the circulation. These changes could impact immune function since softer leukocytes can potentially circulate more easily and could facilitate a more rapid response to systemic inflammation or infection. In conclusion, fish-oil supplementation modulates some physical properties of leukocyte-subfractions, potentially enhancing their biological function. Further studies are warranted to explore the impact of n3-PUFA on blood cell biology, particularly in disease states associated with leukocyte dysregulation.

The effect of fish oil supplementation on fatigue perception following submaximal exercise during the COVID-19 pandemic

The pandemic of COVID-19 has created the "New Normal" lifestyle and limited people to performing their daily activities from home. These changes in turn affect the level of physical activities, including the intention to engage in regular exercise, in most people, subsequently putting them at risk of having negative effects due to being physically inactive. This condition may down regulate the human immune system, making it more vulnerable to various diseases. Oral supplementation of fish oil has been proposed to have benefits for decreasing pro-inflammatory markers induced by exercise. This study aimed to analyze the effect of fish oil supplementation on the degree of fatigue perception following submaximal exercise. Forty-four male college students participated in this non-equivalent pre-posttest experimental research. The participants were supplemented with 2 soft capsules of 1.5 grams of fish oil for 8 weeks. The effect of submaximal exercise was carried out by the sit-up and bleep tests, which were measured before and after 8 weeks of fish oil supplementation. The research procedure was approved by the ethics committee of the Makassar State University research institute. The results showed that there was a strong relationship between the administration of fish oil supplements and the level of fatigue perception following sit-ups and bleep tests (p values of -0.529 and -0.658, respectively) performed during the COVID-19 pandemic. This study concludes that the administration of fish oil supplementation affects the degree of fatigue perception after doing submaximal exercise, especially during the COVID-19 pandemic.

Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice.

Obesity significantly elevates the odds of developing mood disorders. Chronic consumption of a saturated high-fat diet (HFD) elicits anxiodepressive behavior in a manner linked to metabolic dysfunction and neuroinflammation in mice. Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) can improve both metabolic and mood impairments by relieving inflammation. Despite these findings, the effects of n-3 PUFA supplementation on energy homeostasis, anxiodepressive behavior, brain lipid composition, and gliosis in the diet-induced obese state are unclear. Male C57Bl/6J mice were fed a saturated high-fat diet (HFD) or chow for 20 weeks. During the last 5 weeks mice received daily gavage ("supplementation") of fish oil (FO) enriched with equal amounts of docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) or control corn oil. Food intake and body weight were measured throughout while additional metabolic parameters and anxiety- and despair-like behavior (elevated-plus maze, light-dark box, and forced swim tasks) were evaluated during the final week of supplementation. Forebrain lipid composition and markers of microglia activation and astrogliosis were assessed by gas chromatography-mass spectrometry and real-time PCR, respectively. Five weeks of FO supplementation corrected glucose intolerance and attenuated hyperphagia in HFD-induced obese mice without affecting adipose mass. FO supplementation also defended against the anxiogenic and depressive-like effects of HFD. Brain lipids, particularly anti-inflammatory PUFA, were diminished by HFD, whereas FO restored levels beyond control values. Gene expression markers of brain reactive gliosis were supressed by FO. Supplementing a saturated HFD with FO rich in EPA and DHA corrects glucose intolerance, inhibits food intake, suppresses anxiodepressive behaviors, enhances anti-inflammatory brain lipids, and dampens indices of brain gliosis in obese mice. Together, these findings support increasing dietary n-3 PUFA for the treatment of metabolic and mood disturbances associated with excess fat intake and obesity.

Eight weeks of fish oil supplementation does not prevent sitting-induced leg endothelial dysfunction.

Prolonged sitting impairs leg endothelial function and this impairment is thought to be mediated by a sustained reduction in blood flow-induced shear stress. However, whether nutritional strategies can be used to prevent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that 8 weeks of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation would prevent endothelial dysfunction associated with sitting. Nineteen healthy men were randomly assigned to a placebo group or EPA+DHA group in a double-blind fashion. The EPA+DHA group was administered EPA-rich fish oil, containing 600 mg EPA and 260 mg DHA per day for 8 weeks. The placebo group received matching capsules for the same duration of time. Popliteal artery flow-mediated dilation (FMD) was measured at baseline and before and after a 3-h sitting period. During sitting, blood pressure, popliteal artery diameter, and blood velocity were measured every hour. Throughout the sitting period, popliteal artery blood flow and shear rate were markedly and similarly reduced in both groups (P < 0.05). However, counter to the hypothesis, 3 h of sitting impaired popliteal artery FMD to the same extent in both groups (P < 0.05). In conclusion, daily EPA and DHA supplementation is not effective at preventing the detrimental effects of prolonged sitting on leg endothelial function. Novelty We provide evidence that sitting-induced leg endothelial dysfunction in young healthy subjects cannot be remediated by a nutritional strategy known to produce cardiovascular benefits. This could be partially due to the low total dose of EPA and DHA administered.

Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation.

Fish oil (FO) supplementation in humans results in the incorporation of omega-3 fatty acids (FAs) eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C20:6) into skeletal muscle membranes. However, despite the importance of membrane composition in structure–function relationships, a paucity of information exists regarding how different muscle membranes/organelles respond to FO supplementation. Therefore, the purpose of the present study was to determine the effects 12 weeks of FO supplementation (3g EPA/2g DHA daily) on the phospholipid composition of sarcolemmal and mitochondrial fractions, as well as whole muscle responses, in healthy young males. FO supplementation increased the total phospholipid content in whole muscle (57%; p < 0.05) and the sarcolemma (38%; p = 0.05), but did not alter the content in mitochondria. The content of omega-3 FAs, EPA and DHA, were increased (+3-fold) in whole muscle, and mitochondrial membranes, and as a result the omega-6/omega-3 ratios were dramatically decreased (-3-fold), while conversely the unsaturation indexes were increased. Intriguingly, before supplementation the unsaturation index (UI) of sarcolemmal membranes was ∼3 times lower (p < 0.001) than either whole muscle or mitochondrial membranes. While supplementation also increased DHA within sarcolemmal membranes, EPA was not altered, and as a result the omega-6/omega-3 ratio and UI of these membranes were not altered. All together, these data revealed that mitochondrial and sarcolemmal membranes display unique phospholipid compositions and responses to FO supplementation.

Inflammation and intestinal leakiness in older HIV+ individuals with fish oil treatment

Fish oil is a natural product that has shown efficacy for managing inflammatory conditions with few side effects. There is emerging evidence that crosstalks between gut epithelial cells and immune cells contribute to chronic infectious diseases. HIV-infected (HIV+) older adults show age-related co-morbidities at a younger age than their uninfected counterparts. Persistent inflammation related to the chronic viral infection and its sequelae is thought to contribute to this disparity. However, little is known about whether fish oil reduces intestinal inflammation in HIV + patients. We measure inflammation and gut barrier function in HIV + older adults (median age = 52, N = 33), following 12 weeks of fish oil supplementation (a total daily dose of 1.6 g of omega-3 fatty acids). We showed a reduction in inflammation and gut permeability as measured by CD14, inflammatory cytokines, lipopolysaccharide, and lipopolysaccharide binding protein. The results indicate that older HIV + adults may benefit from a diet supplemented with the omega-3 fatty acids found in fish oil.

Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study

Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=−0.43, p=0.097). Five patients showed a decrease of >50% on the 17-item Hamilton Depression Rating Scale and a final score <7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.

Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men.

Fish oil (FO) supplementation potentiates muscle protein synthesis (MPS) in response to a hyperaminoacidemic–hyperinsulinemic infusion. Whether FO supplementation potentiates MPS in response to protein ingestion or when protein ingestion is combined with resistance exercise (RE) remains unknown. In a randomized, parallel group design, 20 healthy males were randomized to receive 5 g/day of either FO or coconut oil control (CO) for 8 weeks. After supplementation, participants performed a bout of unilateral RE followed by ingestion of 30 g of whey protein. Skeletal muscle biopsies were obtained before and after supplementation for assessment of muscle lipid composition and relevant protein kinase activities. Infusion of l‐[ring‐13C6] phenylalanine was used to measure basal myofibrillar MPS at rest (REST), in a nonexercised leg following protein ingestion (FED) and following RE and protein ingestion (FEDEX). MPS was significantly elevated above REST during FEDEX in both the FO and CO groups, but there was no effect of supplementation. There was a significant increase in MPS in both groups above REST during FED but no effect of supplementation. Supplementation significantly decreased panPKB activity at REST in the FO group but not the CO group. There was a significant increase from REST at post‐RE for PKB and AMPK α2 activity in the CO group but not in the FO group. In FEDEX, there was a significant increase in p70S6K1 activity from REST at 3 h in the CO group only. These data highlight that 8 weeks of FO supplementation alters kinase signaling activity in response to RE plus protein ingestion without influencing MPS.

Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression

White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = −1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice

We have considered a novel gene targeting approach for treating pathologies and conditions whose genetic bases are defined using diet and nutrition. One such condition is Down syndrome, which is linked to overexpression of RCAN1 on human chromosome 21 for some phenotypes. We hypothesize that a decrease in RCAN1 expression with dietary supplements in individuals with Down syndrome represents a potential treatment. Toward this, we used in vivo studies and bioinformatic analysis to identify potential healthy dietary RCAN1 expression modulators. We observed Rcan1 isoform 1 (Rcan1-1) protein reduction in mice pup hippocampus after a 4-week curcumin and fish oil supplementation, with only fish oil reduction being statistically significant. Focusing on fish oil, we observed a 17% Rcan1-1 messenger RNA (mRNA) and 19% Rcan1-1 protein reduction in BALB/c mice after 5 weeks of fish oil supplementation. Fish oil supplementation starting at conception and in a different mouse strain (C57BL) led to a 27% reduction in hippocampal Rcan1-1 mRNA and a 34% reduction in spleen Rcan1-1 mRNA at 6 weeks of age. Hippocampal protein results revealed a modest 11% reduction in RCAN1-1, suggesting translational compensation. Bioinformatic mining of human fish oil studies also revealed reduced RCAN1 mRNA expression, consistent with the above studies. These results suggest the potential use of fish oil in treating Down syndrome and support our strategy of using select healthy dietary agents to treat genetically defined pathologies, an approach that we believe is simple, healthy, and cost-effective.

Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation

Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption.

Effect of Fish Oil-Derived Omega-3 Polyunsaturated Fatty Acid Supplementation on Exercise-Induced Bronchoconstriction and Immune Function in Athletes

Exercise-induced bronchoconstriction (EIB) is a condition in which vigorous physical activity triggers acute airway obstruction in asthmatic and nonasthmatic individuals with hyperresponsive airways. Studies have shown that inflammatory mediators and contraction of airway smooth muscle are central components in the pathogenesis of EIB, and it has long been recognized that leukotrienes and prostaglandins play an important role in the EIB response. Clinical responses to current therapy, such as leukotriene modifiers and corticosteroids are heterogeneous, and even with optimal treatment there is a substantial burden of unaddressed disease. While daily medications such as leukotriene modifiers provide only modest protection against symptoms, prolonged use of several medications can result in reduced effectiveness or tachyphylaxis. Although the treatment of EIB almost exclusively involves pharmacotherapy, there is now convincing evidence that dietary modification has the potential to reduce the severity of this condition. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oils, compete with arachidonic acid as substrates for the formation of proinflammatory mediators, such as leukotrienes, prostaglandins, and cytokines. Studies have shown that 3 weeks of fish oil supplementation, rich in EPA and DHA, reduces exercise-induced airway narrowing, airway inflammation, and bronchodilator use in elite athletes and asthmatic individuals with EIB. Based on the evidence to date, fish oil supplementation may represent a potentially beneficial treatment intervention for athletes and asthmatic individuals with EIB. From this, it follows that physicians should pay more attention to what their asthma/EIB patients eat, and incorporate dietary assessment and nutritional counseling in their everyday practice.

Incorporation and Clearance of Omega-3 Fatty Acids in Erythrocyte Membranes and Plasma Phospholipids

The sum of eicosapentaenoic acid (EPA, 20:5 omega3) and docosahexaenoic acid (DHA, 22:6 omega3) in erythrocyte membranes, termed the omega-3 index, can indicate suboptimal intake of omega-3 fatty acids, a risk factor for cardiovascular disease (CVD). To study the effects of fatty acid supplementation, we investigated the rate of incorporation and clearance of these fatty acids in erythrocyte membranes and plasma after intake of supplements. Twenty study participants received supplementation with either fish oil (1296 mg EPA + 864 mg DHA/day) or flaxseed oil (3510 mg alpha-linolenic acid + 900 mg linoleic acid/day) for 8 weeks. We obtained erythrocyte membrane and plasma samples at weeks 0, 4, 8, 10, 12, 14, 16, and 24 and extracted and analyzed fatty acids by gas chromatography. After 8 weeks of fish oil supplementation, erythrocyte membrane EPA and DHA increased 300% (P < 0.001) and 42% (P < 0.001), respectively. The mean erythrocyte omega-3 index reached a near optimal value of 7.8%, and remained relatively high until week 12. EPA and DHA showed greater increases and more rapid washout period decreases in plasma phospholipids than in erythrocyte membranes. Flaxseed oil supplementation increased erythrocyte membrane EPA to 133% (P < 0.05) and docosapentaenoic acid (DPA, 22:5 omega3) to 120% (P < 0.01) of baseline, but DHA was unchanged. In plasma phospholipids, EPA, DPA, and DHA showed a slight but statistically insignificant increase. Erythrocyte membrane EPA+DHA increases during relatively short intervals in response to supplementation at rates related to amount of supplementation. These results may be useful to establish appropriate dosage for omega-3 fatty acid supplementation.

Effects of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males.

To evaluate the effects of four weeks of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males. Very low density lipoprotein (VLDL) apolipoprotein B100 (apoB100) kinetics in ten healthy, white males, aged 22-43 y (mean 32 y) were investigated using 13C-leucine technique and gas chromatography-mass spectrometry before and after fish oil supplementation. All subjects received 10 g (1.8 g EPA, 1.2 g DHA)/d of fish oil concentrate for four weeks. Fish oil supplementation resulted in a decrease of total plasma VLDL (mean +/- s.d. 1.11 +/- 0.41 vs 0.87 +/- 0.28 mmol/l, P < 0.05) and triacylglycerol concentrations (0.74 +/- 0.27) vs 0.48 +/- 0.21 mmol/l, P < 0.01). VLDL apoB100 pool size was decreased without alteration of the fractional synthetic rate but a significant decrease of apoB100 production (2.23 +/- 0.90 vs 1.54 +/- 0.52 mg/dl/h, P < 0.02). Following fish oil supplementation plasma concentrations of glucose and insulin as well as lipoprotein and hepatic lipase activities were unchanged. Fasting plasma concentrations of non-esterified fatty acid (NEFA) were decreased (0.45 +/- 0.12 vs 0.33 +/- 0.10 mmol/l, P < 0.05). Dietary supplementation with fish oil in healthy males results in decreased VLDL-triacylglycerol concentrations through a decrease in VLDL particle synthesis. The decrease in NEFA substrate supply also contributes.

Influence of n-3 polyunsaturated fatty acids (PUFA) on the antigen-presenting function of human monocytes.

N-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of cell mediated immune responses and there is growing interest in the potential use of dietary fish oil [rich in the n3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid @HA)] supplementation in the treatment of disorders involving an overreactive immune response, such as rheumatoid arthritis [see 1 for review]. Specific immune responses are initiated by the presentation of antigen to helper T-lymphocytes on the surface of an antigen-presenting cell (APC). A pre-requisite for this function of APCs is the cell surface expression of major histocompatibility complex (MHC) class I1 molecules (HLA-DR, -DP and D Q , aided by the presence of adhesion molecules. It has been shown that the percentage of MHC class 11-positive monocytes and the density of these molecules on the cell surface can alter the degree of immune responsiveness of an individual [2]. We have previously shown in vitro that EPA can inhibit the expression of the MHC class I1 molecule HLA-DR and of the adhesion molecule ICAM-1 on both unstimulated monocytes and on interferon-gamma (IFN-g) activated human monocytes [3]. In conaast, DHA increased the expression of these surface molecules on unstimulated monocytes, although it inhibited their expression on IFN-g stimulated cells in a similar manner to EPA [3]. In a dietary study, we observed a reduction in the relative number of HLA-DR and ICAM-1 molecules expressed on human peripheral blood monocytes following 3 weeks of fish oil supplementation [4]. Since most commercially available fish oil supplements contain a mixture of EPA and DHA, we undertook further in virro experiments to determine the combined effect of these n-3 PUFA on the cell surface expression of surface molecules involved in the process of antigen-presentation. In addition, the antigen-presenting function of monocytes, following incubation with or without n-3 PUFA, was assessed using tetanus toxoid as a challenge antigen. Purified monocytes, obtained from healthy volunteers, were incubated with or without a mixture of EPA and DHA (final total concentration 20 pg/ml, combined at the same ratio as is commonly found in fish oil supplement capsules, ie. 2:l) in RPMI culture medium supplemented with 5% fetal calf serum for 48 h at 37'C. In addition, parallel cultures were performed in the presence of IFN-g (400 U/ml) to stimulate upregulation of MHC class I1 molecule expression by the monocytes.

Fish oil and cyclosporin A-induced renal hypoperfusion in kidney-transplanted patients

Dietary supplementation with fish oil has been said to improve renal function in cyclosporin A (CsA)-treated subjects. Renal function and the acute renal haemodynamic and tubular response to an oral CsA-dose (3 mg/kg) were investigated before and after 12 weeks of fish oil supplementation (6 g/day) in 12 low-dose CsA-treated kidney-transplanted patients (s-creatinine, 124 +/- 24 mumol/l, mean +/- SD). After an overnight fast, ten l-h renal clearance periods were performed, two periods before and eight after CsA-ingestion. An additional control clearance study without CsA intake was performed in six subjects. Fish oil did not change baseline values of the effective renal plasma flow (ERPF) or the glomerular filtration rate (GFR). Compared to the control study, CsA decreased GFR and ERPF significantly on average 20 +/- 3% (P < 0.01) and 23 +/- 3% (P < 0.01) respectively, 4-6 h after peak CsA blood concentration with no additional effect of fish oil. CsA also significantly decreased the renal clearance of lithium, used as an index of proximal tubular outflow, with no impact of dietary fish oil. Fish oil supplementation had no effect on baseline renal function or CsA-induced hypoperfusion in stable renal transplant recipients treated with a low maintenance dose of CsA.

Effects of fish oil on serum lipids and lipoprotein(a) levels in heterozygous familial hypercholesterolemia

Ten patients (mean age, 49 ± 14 years) with heterozygous familial hypercholesterolemia who had high levels of lipoprotein (Lp)(a) (>30 mg/dl) and were receiving chronic treatment with simvastatin were treated with six capsules a day of fish oil for 4 weeks. Each 1-gm fish oil capsule contained almost 850 mg of omega-3 fatty acids with a ratio of eicosapentaenoic acid:docosahexaenoic acid of 1:1; the total daily dosage of omega-3 fatty acid was 5.1 gm/day. After 2 and 4 weeks of fish oil supplementation, mean serum Lp(a) levels did not change significantly (baseline, 67 ± 29 mg/dl; week 2, 68.3 ± 35 mg/dl; week 4, 60.6 ± 26 mg/dl). Triglyceride levels decreased by 23% after 2 weeks (from 1.355 ± 0.38 mmol/L to 1.05 ± 0.35 mmol/L) and by 33% after 4 weeks (to 0.91 ± 0.18 mmol/L) ( P < 0.001). Total cholesterol and low-density lipoprotein (LDL) cholesterol showed a less pronounced but still statistically significant reduction of 8% (from 7.33 ± 2.55 mmol/L to 6.76 ± 1.31 mmol/L) and 9% (from 5.52 ± 1.98 mmol/L to 5.00 ± 1.67 mmol/L), respectively, after 2 weeks. A 14% decrease in total cholesterol (to 6.30 ± 1.36 mmol/L) and LDL cholesterol (to 4.75 ± 1.49 mmol/L) ( P < 0.05) was seen after 4 weeks. High-density lipoprotein cholesterol did not change significantly. Our results on the effect of fish oil on Lp(a) levels must be confirmed by double-blind, placebo-controlled studies before any definite conclusion can be drawn.

Effects of fish oil supplementation in rheumatoid arthritis.

Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids. A randomised, double blind, placebo controlled crossover design with 12 week treatment periods was used. Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study. Placebo consisted of fractionated coconut oil. The following results favoured fish oil rather than placebo: joint swelling index and duration of early morning stiffness. Other clinical indices improved but did not reach statistical significance. During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased, mainly at the expense of the omega-6 fatty acids. The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation. Leucotriene B5 production, which could not be detected either in the control or in the placebo period, rose to substantial quantities during fish oil treatment. This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis.

The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man

Both fish oils and aspirin are readily available to the consumer as over-the-counter preparations. Since both of these products have been shown to prolong bleeding times, it is possible that hemostasis might be adversely affected in subjects taking them in combination. This study was undertaken to examine the effects of n-3 fatty acids and aspirin on platelet function. Eight healthy men took a total of 485 mg of aspirin over 3 days before beginning two weeks of fish oil supplementation (4.5 g of n-3 fatty acids/day). Subjects continued with fish oil while resuming aspirin treatment for 3 days. Aspirin alone prolonged bleeding times by 34% (p < 0.05). Fish oil alone raised bleeding times only slightly (9%; N.S.), but aspirin plus fish oil raised them by 78% (p<0.01). The increase in bleeding times with the combination (78%) was not significantly different than the sum of the individual increases (43%). The effects of fish oil and aspirin on platelet aggregation were investigated using single and dual agonists. Although fish oil alone did not significantly raise aggregation thresholds for collagen, arachidonic acid, or PAF, it did reduce the extent of aggregation with collagen. When challenged by single or dual agonists, the combination of fish oil and aspirin did not make platelets less sensitive than did aspirin alone. Since fish oil and aspirin had synergistic effects on bleeding times, but not on platelet aggregation, these two substances appear to affect hemostasis by different mechanisms.

Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients.

The effect of the daily administration of Max EPA fish oil (equivalent to 2.7 g per day of eicosapentaenoic acid) on serum lipid levels was examined in insulin-dependent male diabetic patients with cholesterol levels of less than 6.5 mmol/L. After three weeks of fish-oil supplementation there was a significant rise in total cholesterol levels, which was due largely to increases in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels. The increase in HDL-cholesterol levels was accounted for by its HDL2 subclass. There was a decrease in serum triglyceride levels, but this was also observed in a control group of diabetic patients who did not receive fish oil and is probably explained by weight loss in this group. Similar changes in lipid levels were found in a subgroup of diabetic patients with retinopathy. The possible detrimental effect of the increase in total cholesterol and LDL-cholesterol levels after Max EPA fish oil at this dose may be offset by the selective rise in the protective HDL2 subclass.