High Doses Of Fish Oil Research Articles

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring.

During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding. The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation. Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels. Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.

Fish oil supplements for treatment of psoriasis: An overview of systematic reviews

Abstract Background: Fish oil, known for its anti-inflammatory and immunomodulatory properties, has been reported to alleviate psoriasis symptoms. However, systematic reviews (SRs) on this topic have yielded inconsistent conclusions. Objectives: The objective was to compile the existing evidence concerning the efficacy of fish oil supplements for psoriasis, explore the possible reasons behind contradictory findings, and examine potential limitations. Methods: We searched CENTRAL, MEDLINE, and Embase databases, covering the period from their respective inception to January 25, 2023. Two reviewers independently performed study selection, data extraction, and methodological quality assessment using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) tool. The effects of fish oil supplements were evaluated using the psoriasis area and severity index (PASI) score, total body surface area (TBSA), erythema, scaling, infiltrations, pruritus, and any major or minor adverse events. Results: Eight SRs were included, with four demonstrating favorable improvements in psoriasis and the remaining four showing no similar benefits. Specifically, three SRs reported significant reductions in PASI score, one reported lower TBSA, two indicated improvements in either erythema, scaling, or infiltrations, and one supported a high dose of fish oil for alleviating pruritus. Three SRs highlighted the potential benefits of fish oil supplements as a combined therapy with conventional treatments. No serious adverse events were reported. Notably, none of the SRs achieved a high methodological quality rating based on AMSTAR-2. Conclusion: There is a lack of consistent evidence supporting the effectiveness of fish oil supplements for treating psoriasis. Further research is warranted to better understand the potential benefits of fish oil in managing psoriasis.

Fish oil supplementation of rats fed a high fat diet during pregnancy improves offspring insulin sensitivity.

IntroductionIn rats, a maternal high-fat diet (HFD) leads to adverse metabolic changes in the adult offspring, similar to the children of mothers with obesity during pregnancy. Supplementation with a high dose of fish oil (FO) to pregnant rats fed a HFD has been shown to prevent the development of insulin resistance in adult offspring. However, the effects of supplementation at a translationally relevant dose remain unknown.AimTo determine whether supplementation with a human-relevant dose of FO to pregnant rats can prevent the long-term adverse metabolic and cardiovascular effects of a maternal HFD on adult offspring.MethodsFemale rats (N = 100, 90 days of age) were assigned to HFD (45% kcal from fat) or control diet (CD) for 14 days prior to mating and throughout pregnancy and lactation. Following mating, dams received a gel containing 0.05 ml of FO (human equivalent 2–3 ml) or a control gel on each day of pregnancy. This produced 4 groups, CD with control gel, CD with FO gel, HFD with control gel and HFD with FO gel. Plasma and tissue samples were collected at day 20 of pregnancy and postnatal day 2, 21, and 100. Adult offspring were assessed for insulin sensitivity, blood pressure, DXA scan, and 2D echocardiography.ResultsThere was an interaction between maternal diet and FO supplementation on insulin sensitivity (p = 0.005) and cardiac function (p < 0.01). A maternal HFD resulted in impaired insulin sensitivity in the adult offspring (p = 0.005 males, p = 0.001 females). FO supplementation in the context of a maternal HFD prevented the reduction in insulin sensitivity in offspring (p = 0.05 males, p = 0.0001 females). However, in dams consuming CD, FO supplementation led to impaired insulin sensitivity (p = 0.02 males, p = 0.001 females), greater body weight and reduced cardiac ejection fraction.ConclusionThe effects of a human-relevant dose of maternal FO on offspring outcomes were dependent on the maternal diet, so that FO was beneficial to the offspring if the mother consumed a HFD, but deleterious if the mother consumed a control diet. This study suggests that supplementation with FO should be targeted to women expected to have abnormalities of metabolism such as those with overweight and obesity.

Protective Effects of Eicosapentaenoic Acid on Adiposity and Amyloidogenic Features in the APPswePS1dE9 Alzheimer’s Mouse Model

ObjectivesAlzheimer’s disease (AD) is a degenerative brain disease characterized by atypical development of amyloid-beta (Aβ) plaques. We previously showed that eicosapentaenoic acid (EPA), found in fish oil exerted anti-obesity and anti-inflammatory effects in diet-induced obese (DIO) mice. Here we hypothesize that EPA will reduce both adiposity and neuroinflammation in an amyloidogenic Alzheimer’s DIO mouse model. MethodsTwo-month-old male and female APPswePS1E9 transgenic (TG) and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or HF supplemented with EPA (36 g/kg EPA) diets for eight months. Body weights were recorded weekly, blood and tissues were harvested at termination. Serum amyloid Aβ-40 (AD marker), leptin, adiponectin, and resistin (adiposity markers) levels were quantified by Multiplex assays (n = 6–7/group). Outcomes were analyzed in three-way ANOVA, modeling genotype interactions, sex, and diet, using GraphPad (Version 9.0.1). ResultsOn average, TG mice had higher Aβ-40 in serum (p < 0.05) compared to non-TG mice in both males and females; Aβ-40 concentration did not differ by sex. However, serum leptin and resistin were higher in males vs. females (p < 0.001). Adiponectin did not differ by sex (P = 0.1897) and no adipokine differed by genotype. Interestingly, in TG males, compared to HF, EPA decreased serum Aβ-40, leptin, and resistin (P = 0.0182, P = 0.0086, P = 0.0051 respectively). Moreover, in non-TG male mice, EPA increased serum adiponectin compared to HF (P = 0.0342) and no other interactions were significant. ConclusionsEPA reduced adiposity, resistin, and serum Aβ-40 in HF-fed TG male mice. Additional analyses in the brain and adipose tissues from these mice are ongoing. These findings warrant future studies in humans to determine whether consumption of high doses of fish oil, known to reduce hypertriglyceridemia, may benefit patients with AD and whether there are sex differences in response to fish oil. Funding SourcesNIH (NCCIH and NIA) grant #R15AT008879–01A1.

Pharmacokinetics of omega-3 fatty acids in patients with severe sepsis compared with healthy volunteers: A prospective cohort study

Pharmacokinetics (PK) of pharmaceuticals and pharmaconutrients are poorly understood in critically ill patients, and dosing is often based on healthy subject data. This might be particularly problematic with enteral medications due to metabolic abnormalities and impaired gastrointestinal tract absorption common in critically ill patients. Utilizing enteral fish oil, this study was undertaken to better understand and define PK of enteral omega-3 fatty acids (eicospentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in critically ill patients with severe sepsis. Healthy volunteers (n=15) and mechanically ventilated (MV) adults with severe sepsis (n=10) were recruited and received 9.75g EPA and 6.75g DHA daily in two divided enteral doses of fish oil for 7 days. Volunteers continued their normal diet without other sources of fish oil, and sepsis patients received standard enteral feeding. Blood was collected at frequent intervals during the 14-day study period. Peripheral blood mononuclear cells (PMBCs) and neutrophils were isolated and analyzed for membrane fatty acid (FA) content. Mixed linear models and t-tests were used to analyze changes in FA levels over time and FA levels at individual time points, respectively. PK parameters were obtained based on single compartment models of EPA and DHA kinetics. Healthy volunteers were 41.1±10.3 years; 67% were women. In patients with severe sepsis (55.6±13.4 years, 50% women), acute physiologic and chronic health evaluation (APACHE) II score was 27.2±8.8at ICU admission and median MV duration was 10.5 days. Serum EPA and DHA were significantly lower in sepsis vs. healthy subjects over time. PBMC EPA concentrations were generally not different between groups over time, while PBMC DHA was higher in sepsis patients. Neutrophil EPA and DHA concentrations were similar between groups. The half-life of EPA in serum and neutrophils was significantly shorter in sepsis patients, whereas other half-life parameters did not vary significantly between healthy volunteers and sepsis patients. While incorporation of n-3 FAs into PBMC and neutrophil membranes was relatively similar between healthy volunteers and sepsis patients receiving identical high doses of fish oil for one week, serum EPA and DHA were significantly lower in sepsis patients. These findings imply that serum concentrations and EPA and DHA may not be the dominant driver of leukocyte membrane incorporation of EPA and DHA. Furthermore, lower serum EPA and DHA concentrations suggest that either these n-3 FAs were being metabolized rapidly in sepsis patients or that absorption of enteral medications and pharmaconutrients, including fish oil, may be impaired in sepsis patients. If enteral absorption is impaired, doses of enteral medications administered to critically ill patients may be suboptimal.

Ketone Body Therapy Protects From Lipotoxicity and Acute Liver Failure Upon Pparα Deficiency.

Acute liver failure (ALF) is a severe and rapid liver injury, often occurring without any preexisting liver disease, which may precipitate multiorgan failure and death. ALF is often associated with impaired β-oxidation and increased oxidative stress (OS), characterized by elevated levels of hepatic reactive oxygen species (ROS) and lipid peroxidation (LPO) products. Peroxisome proliferator-activated receptor (PPAR)α has been shown to confer hepatoprotection in acute and chronic liver injury, at least in part, related to its ability to control peroxisomal and mitochondrial β-oxidation. To study the pathophysiological role of PPARα in hepatic response to high OS, we induced a pronounced LPO by treating wild-type and Pparα-deficient mice with high doses of fish oil (FO), containing n-3 polyunsaturated fatty acids. FO feeding of Pparα-deficient mice, in contrast to control sunflower oil, surprisingly induced coma and death due to ALF as indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, ammonia, and a liver-specific increase of ROS and LPO-derived malondialdehyde. Reconstitution of PPARα specifically in the liver using adeno-associated serotype 8 virus-PPARα in Pparα-deficient mice restored β-oxidation and ketogenesis and protected mice from FO-induced lipotoxicity and death. Interestingly, administration of the ketone body β-hydroxybutyrate prevented FO-induced ALF in Pparα-deficient mice, and normalized liver ROS and malondialdehyde levels. Therefore, PPARα protects the liver from FO-induced OS through its regulatory actions on ketone body levels. β-Hydroxybutyrate treatment could thus be an option to prevent LPO-induced liver damage.

Interaction between fish oil and plant oils or starchy concentrates in the diet: Effects on dairy performance and milk fatty acid composition in goats

Two experiments were performed to investigate the effects of supplementing a diet with fish oil either alone or with plant oils on dairy goat performance and milk fatty acid (FA) profile (Experiment 1), and the interaction between fish oil with the type and level of starch concentrate (Experiment 2). In Experiment 1, 84 goats were allocated to 7 experimental diets without a lipid supplement or with a low or high dose of fish oil (20 or 40g/d, respectively) either alone or with linseed or sunflower-seed oils (the combinations included 130g/d of oil supplements). In Experiment 2, 72 goats were allocated to 6 experimental diets without a lipid supplement and with a concentrate rich in corn and barley grain starch or with the high dose of fish oil (40g/d) and concentrates rich in starch from barley grain, corn grain or both; or that were low in starch from barley grain or corn grain. In contrast to cows, in goats, fish oil supplements modulated milk FA composition without decreasing the milk fat content; this result may have been related to specific milk FA responses, such as a lack of or a small reduction in 18:0 and c9-18:1 (Experiment 1) or a moderate reduction compensated through increases in short-chain FA (Experiment 2) and limited increases in t10-18:1. The combinations of fish oil with sunflower-seed oil were more efficient than either fish oil plus linseed oil or fish oil alone at increasing (P<0.05) milk c9,t11-18:2 and t11-18:1 concentrations (up to 24- and 35-fold increases, respectively), simultaneously decreasing (P<0.05) medium-chain saturated FA (on average, 40% decrease). Based on the milk FA changes (e.g., 18:2n-6, 18:3n-3, t11-18:1 and 18:0) in Experiment 2, diets rich in barley grain starch with fish oil would induce less extensive ruminal dietary FA biohydrogenation and better inhibit the trans 18:1 reduction than diets that are supplemented with the same level of fish oil but are low in barley grain starch or rich in corn grain starch. The apparent transfer rates of 20:5n-3 and 22:6n-3 from fish oil to milk were low (on average, 2.8% and 2.4%, respectively; Experiment 1) but were slightly higher in barley-grain treatments (on average, 5.1% and 7.6%, respectively) compared with corn-grain-only treatments (on average, 2.5% and 3.7%, respectively; Experiment 2). The milk t10-18:1 concentration remained low (≤1.1% total FA) and the t10-18:1/t11-18:1 ratio was much lower than in cows fed fish oil with plant oils.

Inhibition Activities of Fish Oil in iNOs, COX-2, and β-Catenin Expressions in Colorectal Preneoplasia of Mice Induced by Azoxymetane and Dextran Sodium Sulfate

Epidemiological studies of the relationship between dietary fish oil and risk of colorectal cancer have been inconsistent. The present study was conducted in order to determine the inhibitory effect of fish oil on inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and β-catenin expressions in the colorectal preneoplasia development of mice induced by azoxymetane (AOM) and dextran sodium sulfate (DSS). In this study, balb/c mice was injected intraperitoneally by a single dose of 10 mg/kg of body weight AOM followed by administered of 1% DSS during a week in drinking water. Fish oil was administered orally in three different doses (1.5 mg/ low dose, 3 mg/ medium dose and 6 mg/high dose) in each group of mice per day until the mice were terminated. The expression of iNOs, COX-2, and β-catenin were observed in the epithelial cells of colon mucosa crypts. In the second month, the iNOs expression was decreased in the medium and high groups of fish oil. In the third and fourth month, decreasing of the iNOs expression were observed in all groups (p&lt;0.05). The COX-2 expression was decreased in the medium and high groups on the second month. The expression of β-catenin was also decreased in the medium group on the fourth month. The inhibition effect of high dose of fish oil on β-catenin was observed on the third month. In conclusion, administration of medium dose of fish oil in mice induced by AOM/DSS was the most effective dose to decreased the expression of iNOs, COX-2, and β-catenin in the second month.

Effect of soy product kinako and fish oil on serum lipids and glucose metabolism in women with metabolic syndrome

ObjectivesAt the doses typically used to treat hypertriacylglycerolemia, fish oil may increase low-density lipoprotein (LDL) cholesterol and blood glucose levels. The aim of the present study was to verify whether soy could attenuate the effects of fish oil on blood lipids and carbohydrate metabolism in patients with metabolic syndrome. MethodsSixty-five women (47.9 ± 9.98 y) were studied with the use of a parallel, randomized design. The control group maintained the usual diet; the second group received 29.14 g/d of soy (kinako); the third group received 3 g/d of fish oil n-3 fatty acids; and the fourth group received fish oil (3 g/d) and kinako (29.14 g/d). Assessments were performed at baseline and after 45 and 90 d. ResultsIn relation to baseline values, fish oil increased (P < 0.05) total and LDL cholesterol, glucose, insulin, and homeostasis model assessment of insulin resistance levels after 90 d. Comparisons among groups demonstrated a decrease (P < 0.05) in total cholesterol in the fish oil and kinako group after 90 d as compared with the fish oil group. LDL cholesterol decreased (P < 0.01) in the kinako group as compared with the fish oil group. Blood glucose and homeostasis model assessment of insulin resistance levels decreased after 90 d (P < 0.01 and P < 0.05, respectively) and insulin levels decreased (P < 0.05) after 45 d when the kinako group was compared with the fish oil group. ConclusionsThe present study showed that kinako moderates the adverse effects of high doses of fish oil on LDL cholesterol, total cholesterol, and glucose metabolism levels.

Effects of High Dose Fish Oil Supplementation on Delayed Onset Muscle Soreness and Inflammatory Markers

Delayed muscle soreness (DOMS) is caused, in part, by muscle damage associated with the eccentric component of exercise and this muscle damage can result in an inflammatory response by the body. Fish oil rich in eicosapaetonic acid (EPA) and docosahexeoric acid (DHA) have been shown to have anti-inflammatory properties. However, studies have not investigated the impact of consuming a high dose offish oil for a prolonged period of time on DOMS. The purpose of this study was to determine the effects of high dose fish oil supplementation on DOMS and the associated muscle inflammatory response. The control group (CON; n=10) consumed 3.45 grams of wheat germ and the experimental group (FO; n=10) received 3.0 grams fish oil per day for 65 days. On Day 60, participants performed eccentric muscle contractions at an angular velocity of 60°-sec -1 through 20° to 90° of knee flexion until exhaustion. Perceived muscular soreness, isometric strength, and muscle inflammatory markers were measured before exercise and at 8, 24,48, 72, 96 and 120 hours post-exercise. We found no significant differences between the CON and FO groups for all variables. The data suggests the fish oil had no effect on inflammatory markers and the signs and symptoms of DOMS when compared to a placebo.

EFFECT OF n‐3 POLYUNSATURATED FATTY ACIDS ON OXIDATIVE STRESS IN RATS SUPPLEMENTED WITH DIFFERENT DOSES OF FISH OIL

ABSTRACT The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n‐3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY‐FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and α‐linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY‐FISH and FISH diets reducing the n‐6/n‐3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY‐FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P &lt; 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY‐FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n‐3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY‐FISH, and FISH groups, respectively. Thus, n‐3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration.PRACTICAL APPLICATIONSBecause fish oil intake is associated with risk reduction for cardiovascular disease, individuals are taking supplements containing a high dose of fish oil. However, there is no scientific consensus if the intake of a high dose of fish oil could increase the oxidative stress. Thus, more studies are necessary to assure the safety of this kind of supplementation.

Effect of Supplementation with Calcium Salts of Fish Oil on n-3 Fatty Acids in Milk Fat

Enrichment of milk fat with n-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be advantageous because of their beneficial effects on human health. In addition, these fatty acids play an important role in reproductive processes in dairy cows. Our objective was to evaluate the protection of EPA and DHA against rumen biohydrogenation provided by Ca salts of fish oil. Four Holstein cows were assigned in a Latin square design to the following treatments: 1) ruminal infusion of Ca salts of fish oil and palm fatty acid distillate low dose (CaFO-1), 2) ruminal infusion of Ca salts of fish oil and palm fatty acid distillate high dose (CaFO-2), 3) ruminal infusion of fish oil high dose (RFO), and 4) abomasal infusion of fish oil high dose (AFO). The high dose of fish oil provided ∼16 and ∼21g/d of EPA and DHA, respectively, whereas the low dose (CaFO-1) provided 50% of these amounts. A 10-d pretreatment period was used as a baseline, followed by 9-d treatment periods with interceding intervals of 10 d. Supplements were infused every 6h, milk samples were taken the last 3 d, and plasma samples were collected the last day of baseline and treatment periods. Milk fat content of EPA and DHA were 5 to 6 times greater with AFO, but did not differ among other treatments. Milk and milk protein yield were unaffected by treatment, but milk fat yield and DM intake were reduced by 20 and 15%, respectively, by RFO. Overall, results indicate rumen biohydrogenation of long chain n-3 fatty acids was extensive, averaging >85% for EPA and >75% for DHA for the Ca salts and unprotected fish oil supplements. Thus, Ca salts of fish oil offered no protection against the biohydrogenation of EPA and DHA beyond that observed with unprotected fish oil; however, the Ca salts did provide rumen inertness by preventing the negative effects on DM intake and milk fat yield observed with unprotected fish oil.

Effect of Fish Oil on Appetite and Other Symptoms in Patients with Advanced Cancer and Anorexia/Cachexia: A Double‐Blind, Placebo‐Controlled Study

Background: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. Methods: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well‐being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. Results: The baseline weight loss was 16 ± 11 and 16 ± 8kginthe fish oil (n = 30) and placebo (n = 30) group, respectively, whereas the baseline appetite (0 mm = best and 100 mm = worst) was 58 ± 24 mm and 67 ± 19 mm, respectively (p = not significant). The mean daily dose was 10 ± 4 (fish oil group) and 9 ± 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (p &lt; .05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow &gt;10 fish oil capsules per day, mainly because of burping and aftertaste. Conclusion: Fish oil did not significantly influence appetite, tiredness, nausea, well‐being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.

Impaired nitric oxide production, brachial artery reactivity and fish oil in offspring of ischaemic heart disease patients

The offspring of coronary heart disease (CHD) patients are at particularly high risk for developing CHD. Endothelial dysfunction is present in the majority of CHD and atherosclerosis patients. Fish oil, rich in n-3 fatty acids has been shown to augment endothelium-dependent vasodilatation in human peripheral and coronary arteries. The aims of this study are to investigate presence of endothelial dysfunction determined by the brachial flow-mediated diameter, nitric oxide, plasma lipids and fibrinogen, and the effect of high doses of fish oil on these parameters. Twenty-four healthy offspring of CHD patients (study group) were supplemented with 9 g/day Alsepa fish oil (each gram containing 180mg EPA and 120mg DHA), for a period of two weeks. Plasma nitric oxide, urine nitric oxide, fibrinogens and flow-mediated vasodilatation (FMD) were determined prior to fish oil therapy, two weeks into therapy and four weeks after the end of therapy with fish oil. Twelve healthy subjects (control group) with no family history of heart disease were studied as controls (day one only). The offspring had a lower increase in FMD and lower nitric oxide production, compared with the control group. No other parameters varied between the two groups. The administration of fish oil did not result in any changes in the studied parameters. In healthy offspring of CHD patients, early endothelial dysfunction was documented before evidence of atherosclerosis. Ingestion of fish oil over a 13-day period did not improve endothelial dysfunction.

Nonpharmacologic treatment of hypertriglyceridemia: focus on fish oils.

Early studies in Greenland Eskimos stimulated interest in evaluating the effect of Omega-3 fatty acids on coronary artery disease. Subsequent studies showed a significant decrease in triglyceride levels in patients receiving high doses of fish oil containing DHA and EPA. Slight increases in LDL were also observed in patients receiving fish oil supplements. These studies have also shown a dose-response effect which persists as long as supplementation continues. Later trials, specifically the Diet and Reinfarction Trial and the Indian Experiment of Infarct Survival, have demonstrated a reduction in cardiac death rates and in the incidence of cardiac symptoms in patients receiving fish oil.

Effects of long-term consumption of high doses of fish oil concentrates on clinical parameters in male and female rats.

Many studies suggest that a diet supplemented with fish oil concentrates (FOCs) may provide protection against cardiovascular and other diseases. The possible harmful effects of long-term consumption of high doses of FOCs, however, have not been adequately investigated. Corn oil, fish oil (MaxEPA) and various mixtures of the oils were administered by gavage to 120 male and 120 female rats, 5 d/wk for 13 wk at the rate of 5 mL/kg/d. Although MaxEPA had no effect on prothrombin time or activated partial thromboplastin time, it caused a statistically significant diminution of the total serum cholesterol level. Correlations between relative liver and spleen weights and dose levels were positive but a negative correlation was found between dose levels and serum vitamin E concentration. In female rats, the negative correlations between dose levels and serum iron and triglyceride levels were highly significant. The pathology data showed no remarkable lesions in any of the tissues examined. Results of this study suggest that long-term consumption of high levels of FOCs in rats may reduce serum cholesterol and triglycerides and adversely affect serum iron level and relative liver weight in female rats and relative spleen weights in both sexes.

Modulation of the endogenous leukotriene production by fish oil and vitamin E

We investigated the effects of fish oil and vitamin E on the endogenous leukotriene production. 10 healthy volunteers were supplemented for 1 week with fish oil (containing 40 mg/kg body weight per day of eicosapentaenoic and docosahexaenoic acid), vitamin E (540 mg, i.e., 800 IU of D-α-tocopherol per day), or with both agents. Treatment resulted in a significant increase in the eicosapentaenoate concentration in red blood cell membranes and/or in the vitamin E concentration in serum. In addition, nine obese patients were investigated who were on a hypocaloric diet including 10 mg vitamin E/day for 8 weeks. This diet was associated with a significant decrease in serum vitamin E concentration. The urinary concentration of leukotriene E 4 plus N-acetylleukotriene E 4 served as a measure for the endogenous leukotriene production. Fish oil reduced leukotriene production in eight of the 10 healthy individuals. After vitamin E supplementation, urinary leukotrienes were significantly reduced in all of the healthy volunteers. The combination of vitamin E plus fish oil had no synergistic effect on leukotriene production in the individuals tested. The decrease in serum vitamin E concentration during the hypocaloric, 10 mg vitamin E/day diet was associated with an increase in urinary leukotrienes in 8 of the 9 obese patients. Urinary prostaglandin metabolites, determined as tetranorprostanedioic acid, increased or decreased in parallel with urinary leukotrienes in most individuals; however, changes were less pronounced than those observed with leukotrienes. We conclude that the endogenous leukotriene production can be reduced effectively by high doses of fish oil or vitamin E, whereas vitamin E depletion is associated with an increase in leukotriene generation.

Fish oil, essential fatty acids, and hypertension.

A proper balance between the n-3 and n-6 series of essential fatty acids (EFAs) is essential for homeostasis and normal growth in humans. Dietary supplement with fish oil and related n-3 EFAs has been used to study their antihypertensive property in animals and humans with borderline and essential hypertension. In the animal models, chronic treatment of young animals generally only attenuated the development of hypertension. In animals with hypercholesterolemia, n-3 EFA supplement increased the incidence of atherosclerosis. In humans, chronic treatment with fish oil only produced a small reduction in blood pressure. The concerns are that the high dose of fish oil may interfere with the control of blood glucose in diabetic patients, and may cause prolonged bleeding in surgical patients. Studies on the animal models of hypertension showed that n-6 EFAs are more effective than n-3 EFAs in lowering and normalizing the blood pressure of these animals, probably through the production of tissue prostaglandins, which favour vasodilation. The antihypertensive effect of the n-6 EFAs in humans is not well known, because there are only a few studies, usually involving a very small number of patients. A possible side effects of n-6 EFAs for concern is that they might stimulate tumour development. A careful examination of these risk factors is needed before any recommendation can be made concerning the use of EFAs for the control of hypertension for humans.

Increased susceptibility of cellular membranes to the induction of oxidative stress after ingestion of high doses of fish oil: effect of aging and protective action of dl-α tocopherol supplementation

Feeding young and aged rats (2 and 18 months old, respectively) with sardine oil (10 g/kg body weight) for 14 days increases the content of eicosapentaenoic acid and docosahexaenoic acid in erythrocyte membranes. These changes are associated with an increased membrane susceptibility to the induction of oxidative stress. Supplementation of the dietary oil with dl-α tocopherol (1 g/kg oil) protects the membranes from young rats against this increased susceptibility, while membranes from aged animals appear equally susceptible to oxidation when compared with membranes obtained from rats fed nonsupplemented oil. Following fish oil ingestion, plasma and membrane dl-α tocopherol levels are reduced to undetectable levels. Supplementation of the oil with the antioxidant, restores dl-α tocopherol pool but to a different level in young and aged animals. The differential response of membranes from young and aged rats to the induction of oxidative stress can be ascribed to a different membrane availability of dl-α tocopherol and therefore to a different free radical scavenging capacity.

Ingestion of high doses of fish oil increases the susceptibility of cellular membranes to the induction of oxidative stress

Feeding rats with 4 g/kg body weight of sardine oil during 7 or 14 days increases the content of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte and hepatic microsomal membranes by 2 to 6%. These membranes show increased susceptibility to the induction of oxidative stress, expressed as lipid peroxidation, when they are exposed to Fe2+-ascorbate and to NADPH-FE3+-ADP, respectively. The results indicate that in order to prevent the increased susceptibility to lipid peroxidation, supplementation with larger amounts of antioxidants may be needed than those required to stabilize the oil.