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Omega 3 / DHA Fish Oil

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Please note that the following studies relate primarily to the potential health benefits of 'normal' Omega 3 supplements. We believe that the Xtend-Life line of Omega-3 / DHA Fish Oil formulas are far superior.


Allergies

Studies about the health benefits of fish oil supplements and omega 3 fatty acids are frequent and wide ranging. Clinical studies have shown that fish oil may protect against symptoms of hay fever, sinus infections, asthma, food allergies and allergic skin conditions such as hives and eczema. Studies have also shown improved control in asthmatics that eat fish that is rich in Omega-3 essential fatty acids on a weekly basis. Apparently, fish oil lowers the level of airway narrowing (which causes restriction of breathing during an asthma attack) and calms inflammation.

Also, studies show that omega-3 intake by mothers during pregnancy may protect babies against the development of allergies.

Published Clinical Studies

Allergies Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial.

Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL.

BACKGROUND: There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic disease. OBJECTIVE: We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants. METHODS: In a randomized, controlled trial 98 atopic, pregnant women received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation until delivery. Neonatal PUFA levels and immunologic response to allergens were measured at birth. RESULTS: Eighty-three women completed the study. Fish oil supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes (mean +/- SD, 17.75% +/- 1.85% as a percentage of total fatty acids) compared with the control group (n = 43, 13.69% +/- 1.22%, P <.001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-gamma) responses (to all allergens) tended to be lower in the fish oil group (statistically significant only for IL-10 in response to cat). Although this study was not designed to examine clinical effects, we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; P =.055). Although there was no difference in the frequency of atopic dermatitis at 1 year of age, infants in the fish oil group also had significantly less severe disease (odds ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P =.045). CONCLUSIONS: These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation. More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children.

PMID: 14657879 [PubMed - in process]

Dietary components with demonstrated effectiveness in decreasing the severity of exercise-induced asthma.

Mickleborough T, Gotshall R.

Department of Kinesiology, Indiana University, 1025 E. 7th Street, HPER 112, Bloomington, IN 47401, USA. tmickleb@indiana.edu

Exercise-induced asthma (EIA) occurs in up to 90% of individuals with asthma and approximately 10% of the general population without asthma. EIA describes a condition in which vigorous physical activity triggers acute airway narrowing with heightened airway reactivity resulting in reductions in forced expiratory volume in 1 second of greater than 10% compared with pre-exercise values. Treatment of EIA almost exclusively involves the use of pharmacological medications. However, there is accumulating evidence that a dietary excess of salt and omega-6 fatty acids, and a dietary deficiency of antioxidant vitamins and omega-3 fatty acids, can modify the severity of EIA. The modification of these dietary factors has the potential to reduce the incidence and prevalence of this disease. The dietary component most studied to date is dietary salt. Recent studies have supported a role for dietary salt as a modifier of the severity of EIA, suggesting that salt-restrictive diets can reduce the severity of EIA. Since EIA is part of the asthmatic diathesis, it is possible that EIA may serve as a useful model for investigation of potential dietary interventions for reducing airway hyperresponsiveness.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 12846590 [PubMed - indexed for MEDLINE]

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Arthritis & Gout

What else does fish oil do for the body? Fish oil supplements have been shown to be of benefit to persons with rheumatoid arthritis (RA), and other inflammatory forms of arthritis, such as occurs in some persons with psoriasis and gout. EPA and DHA in fish oil supplements may reduce the amount of compounds causing inflammation.

Published Clinical Studies

A biomarker of n-3 compliance in patients taking fish oil for rheumatoid arthritis.

Cleland LG, Proudman SM, Hall C, Stamp LK, McWilliams L, Wylie N, Neumann M, Gibson RA, James MJ.

Rheumatology Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. Lcleland@mail.rah.sa.gov.au

Dietary fish oil supplements have been shown to have benefits in rheumatoid arthritis (RA), other inflammatory diseases, and in cardiovascular disease. As with any medical advice, variability will exist with regard to adherence and consequent biochemical or pharmacophysiologic effects. The aim was to explore the utility of plasma phospholipid EPA as a measure of n-3 PUFA intake and response to standardized therapeutic advice given in an outpatient or office practice setting, to increase dietary n-3 PUFA, including a fish oil supplement. Patients with early RA were given verbal and written advice to alter their dietary n-3 PUFA intake, including ingestion of 20 mL of bottled fish oil on juice daily. The advice included instructions to increase n-3 PUFA and to avoid foods rich in n-6 PUFA. Every 3 mon, blood samples were obtained for analysis of plasma phospholipid FA. Plasma phospholipid EPA was used as the primary index of n-3 PUFA intake. A diverse response was seen, with about one-third of patients achieving a substantial elevation of plasma phospholipid EPA over the 12-mon study period. A third had little change, with the remainder achieving intermediate levels. Data obtained longitudinally from individual patients indicated that substantial elevations of EPA (> 5% total plasma phospholipid FA) could be maintained for more than 3 yr. Plasma phospholipid EPA is a convenient measure of adherence to advice to take a dietary n-3 PUFA-rich fish oil supplement This measure may prove a useful adjunct to intention to treat analyses in determining the effect of dietary fish oil supplements on long-term outcomes in arthritis and other chronic inflammatory diseases. It may also provide a guide to the effectiveness of therapeutic and preventive messages designed to increase n-3 PUFA intake.

PMID: 12848288 [PubMed - in process]

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Brain Function

Depression: Persons with mood disorders such as depression benefit from fish oil supplementation. Lack of omega-3 fatty acids and in particular DHA has been linked by researchers to depression. The health benefits of omega 3 fatty acids on depressed patients has been proven via a range of studies.

Fatty acids are essential in the healthy formation of the brain's nerve cell membranes and membrane fluidity. The brain is the richest source of fatty acids in the body, and because nerve cell function depends on proper membrane functioning and membrane fluidity, changes in membrane fluidity have a negative effect on behavior, mood and mental function.

Aggression: A new study of teenagers has found that fish oil and DHA consumption relates to lower hostility rates in teenagers. Hostility has been shown to predict the development and manifestation of heart disease.

Attention Deficit-Hyperactivity Disorder (ADHD), dyslexia and dyspraxia: Like depression and other mood disorders, persons who suffer from ADHD, dyslexia and dyspraxia (absence of ability to perform coordinated skilled movements or clumsiness) all benefit from taking fish oil supplements.

ADHD has been linked by research to lack of omega 3 fatty acids, necessary for formation and repair of brain cell membranes, especially in the developing central nervous system of children. Fish oil may improve the efficiency of nerve impulses and neurotransmitters involved in brain function.

Memory, learning and Alzheimer's Disease: Studies have proven that omega-3 fatty acids improve brain function and that intake of fish oil and DHA is linked to a lowered risk of developing Alzheimer's disease. Studies suggest that the health benefits of fish oil and DHA may also include protecting the nervous system from degeneration.

DHA and fish oil have been proven to stimulate memory and learning abilities. Recent research learns that mothers who take DHA as a supplement during pregnancy and lactation may increase the IQ of their babies.

Published Clinical Studies

Recovery of brain docosahexaenoate leads to recovery of spatial task performance.

Moriguchi T, Salem N Jr.

Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA.

Infants fed vegetable oil-based formulas may have poorer visual function, lower cognitive scores and acquire learning tasks more slowly in comparison with those breast fed or those fed formulas supplemented with docosahexaenoate. The aim of the present study was to determine the reversibility of losses in brain function associated with the loss of brain DHA. Rats were fed very low or adequate levels of n-3 fatty acids through three generations. The n-3 fatty acid deficient animals of the F3 generation were then given an n-3 adequate diet containing alpha-linolenic and docosahexaenoic acids (DHA) at birth, weaning (3 weeks) or young adulthood (7 weeks). The spatial task performance of these animals returned to the n-3 adequate diet was then compared using the Morris water at two different ages, at 9 or 13 weeks. Our results indicate that animals repleted since birth or at weaning were able to achieve nearly the same level of brain DHA and spatial task performance as animals maintained for three generations on an n-3 adequate diet. In the case of young adult animals, the degree of DHA and behavioral performance recovery depended upon the duration of dietary repletion with substantial recovery in animals after 6 weeks but little recovery of function after two weeks. The significance of these findings is that they indicate that at least some of the adverse effects of DHA deficiency during neurodevelopment may be reversible with an n-3 fatty acid supplemented diet.

PMID: 14511107 [PubMed - indexed for MEDLINE]

Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.

Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J.

Rush Institute for Healthy Aging, Department of Internal Medicine, Rush Alzheimer's Disease Center, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA. Marth_C_Morris@rush.edu

BACKGROUND: Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease. OBJECTIVE: To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease. DESIGN: Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease. PATIENTS: A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. MAIN OUTCOME MEASURES: Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria. RESULTS: A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions. CONCLUSION: Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

PMID: 12873849 [PubMed - indexed for MEDLINE]

Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures.

Wang X, Zhao X, Mao ZY, Wang XM, Liu ZL.

School of Life Science, Nanjing University, Nanjing 210093.

SUMMARY: The neuroprotective effect of docosahexaenoic acid (DHA) on the glutamate-induced cytotoxicity in rat hippocampal cultures was investigated in the present study. DHA at 5-50 microg/ml successfully protected neurons against the cytotoxicity, markedly increased the cell viability, inhibited both nitric oxide (NO) production and calcium influx, and increased the activities of antioxidant enzymes of glutathione peroxidase (GSH-Px) and glutathione reductase (GR). However, it did not alter the levels of glutathione (GSH) as compared to the control. These results suggest that DHA might be a potent neuroprotector. In addition, they may help to improve our understanding of the effect of DHA on neurodegeneration.

PMID: 14663210 [PubMed - in process]

Omega-3 fatty acids in mood disorders: an overview.

Young C, Martin A.

Child Study Center. Yale University School of Medicine. New Haven, Connecticut 06520-7900, USA. christopher.young@yale.edu

This review addresses the potential role of omega-3 fatty acids in mood disorders, from the biochemical rationale for their use to the growing body of data supporting their clinical effectiveness.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 12975694 [PubMed - indexed for MEDLINE]

Dietary intake of n-3, n-6 fatty acids and fish: Relationship with hostility in young adults-the CARDIA study.

Iribarren C, Markovitz JH, Jacobs DR, Schreiner PJ, Daviglus M, Hibbeln JR.

1Division of Research, Kaiser Permanente, Oakland, CA, USA.

BACKGROUND:: Hostility has been shown to predict both the development and manifestation of coronary disease. Examining the inter-relation of dietary intake of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility may provide additional insights into the cardioprotective effect of dietary fish and polyunsaturated fatty acids. OBJECTIVE:: To examine the association of dietary n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban white and black young adults. DESIGN:: Cross-sectional observational study as part of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of hostility and other covariates in 1990-1991 were used in the analysis. RESULTS:: The multivariate odds ratios of scoring in the upper quartile of hostility (adjusting for age, sex, race, field center, educational attainment, marital status, body mass index, smoking, alcohol consumption and physical activity) associated with one standard deviation increase in docosahexaenoic acid (DHA, 22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in n-3 fatty acids, compared to no consumption, was also independently associated with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02). CONCLUSIONS:: These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 fatty acids and hostile personality merits further research.European Journal of Clinical Nutrition (2004) 58, 24-31. doi:10.1038/sj.ejcn.1601739

PMID: 14679363 [PubMed - in process]

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Cardiovascular Benefits

General heart benefits: Heart disease is a widespread health problem in modern society. Fish oil, rich in omega-3 fatty acids (DHA and EPA) has been proven in many clinical studies to benefit heart health, also supported by the American Heart Association guidelines (http://www.americanheart.org/presenter.jhtml?identifier=4632) which recommend the benefits of consumption of fish and fish oil. They recommend two servings for healthy persons and a daily serving of fish or fish oil supplement containing at least 900mg of fish oil for persons with heart disease.

Lowers Triglycerides: The effectiveness of Fish oil in lowering blood triglycerides (fats) known to be a risk factor for cardiovascular disease has been well established in multiple clinical studies. Additionally, research has proven that DHA present in fish oil lowers the level of small, dense particles of LDL cholesterol, which are associated with heart disease. The level of large buoyant particles of LDL cholesterol (which pose no health problem) is increased. Total HDL cholesterol remains unchanged by DHA supplementation, while large, buoyant HDL particles are increased. HDL cholesterol benefits cardiovascular health.

Benefits Hypertension (High blood pressure): Fish oil has been shown to lower mild hypertension when it is due to cardiovascular disease, specifically high cholesterol and atherosclerosis (hardening of the artery walls).

Anti-clotting: Fish oil helps avoid thrombosis (blood clots) as it prevents platelets (smallest cells in the blood) sticking together and forming blood clots.

Reduces Heart Irregularities: Fish oil... especially the DHA content of it has been shown to lower heart rates and also prevent arrhythmias (disturbances of the normal rhythm in the heart's beating), thus decreasing the chance of sudden death by a heart attack.

Circulatory problems: Circulatory problems such as varicose veins and Raynaud's disease benefit from fish oil. Fish oil stimulates blood circulation and increases the breakdown of fibrin, a compound involved in clot and scar formation.

Published Clinical Studies

Non-drug therapy in prevention and control of hypertension.

Sainani GS.

Grant Medical College, Mumbai.

Non-drug therapy is a very vital aspect in prevention and treatment of hypertension. The successive reports of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension, WHO scientific report on primary prevention of essential hypertension and national High Blood Pressure Education Program's working groups report on primary prevention of hypertension have stressed on the non-drug therapy. Today a busy family physician does not spend enough time to explain to the patient various dietary and lifestyle modifications but straightaway prescribes the drugs. Every patient of hypertension from the stage of pre-hypertension to grade 2 hypertension should follow non-drug therapy. If non-drug therapy is strictly adhered, one can prevent cases of pre-hypertension from progressing to hypertension stage and one can reduce or stop the medications in Grade I (mild) hypertension. We have discussed the role of low salt, high potassium diet, role of caffeine intake, calcium and magnesium supplements, fish oil intake, cigarette smoking, alcohol consumption, role of physical exercise, stress reduction and bio-feedback, yoga, meditation and acupuncture. These recommendations regarding diet and lifestyle modifications should be targeted to population at large through public health authorities, non-government organisations and news media.

PMID: 14719592 [PubMed - in process]

Heart Antiarrhythmic effects of omega-3 fatty acids: from epidemiology to bedside.

De Caterina R, Madonna R, Zucchi R, La Rovere MT.

University Cardiology Division, G. d'Annunzio University, Chieti, Italy. rdecater@unich.it

Omega-3 polyunsaturated fatty acids are emerging as a safe and effective means to reduce sudden death after acute myocardial infarction. This review summarizes the epidemiological background for the use of omega-3 fatty acids with this indication, clinical trials performed so far, and experimental data supporting their antiarrhythmic effectiveness.

Publication Types:

Review

Review Literature

PMID: 12947358 [PubMed - indexed for MEDLINE]

Fish consumption is associated with lower heart rates.

Dallongeville J, Yarnell J, Ducimetiere P, Arveiler D, Ferrieres J, Montaye M, Luc G, Evans A, Bingham A, Hass B, Ruidavets JB, Amouyel P.

INSERM U 508, Institut Pasteur de Lille, 1 rue du Pr Calmette, 59019 Lille Cedex, France. jean.dallongeville@pasteur-lille.fr

BACKGROUND: Fish consumption decreases risk of sudden death. The goal of the present study was to assess the relationship between fish consumption and heart rate. METHODS AND RESULTS: A cross-sectional analysis was conducted of 9758 men, age 50 to 59 years, without coronary heart disease (CHD) who were recruited in France and Belfast, Ireland, from 1991 to 1993. Heart rate and CHD risk factors were compared among 4 categories of fish consumption, as follows: (1) less than once per week (n=2662), (2) once per week (n=4576), (3) twice per week (n=1964), and (4) more than twice per week (n=556). Fatty acid profiles of erythrocyte phospholipids were determined in a random subsample of 407 subjects. In erythrocyte phospholipids, eicosapentaenoic acid (P<0.0005), docosahexaenoic acid (P<0.0001), and total n-3 fatty acid (P<0.0008) increased across the categories of fish intake. Triglycerides (P<0.0001), systolic blood pressure (P<0.006), and diastolic blood pressure (P<0.0001) were lower and HDL cholesterol levels (P<0.004) were higher in fish consumers than in nonconsumers. Similarly, heart rate decreased across the categories of fish intake (P<0.0001). After adjustment for age, center, education level, physical activity, smoking habit, alcohol consumption, body mass index, and antiarrhythmic medications, heart rate remained statistically lower among fish consumers than among nonconsumers (P for trend <0.0001). Docosahexaenoic acid content of erythrocyte phospholipids was inversely correlated with heart rate (P<0.03). CONCLUSIONS: Fish consumption is associated with decreased heart rate in men. Because heart rate is positively associated with risk of sudden death, this association may explain, at least in part, the lower risk of sudden death among fish consumers. Publication Types: " Multicenter Study

PMID: 12912821 [PubMed - indexed for MEDLINE]

Fish oil prevents the adrenal activation elicited by mental stress in healthy men.

Delarue J, Matzinger O, Binnert C, Schneiter P, Chiolero R, Tappy L.

Laboratoire regional de nutrition humaine, Hopital de la Cavale Blanche, Brest, France.

OBJECTIVES: A diet rich in n-3 fatty acids (fish oils) is associated with reduced risks of cardiovascular and metabolic diseases, but the mechanisms remain incompletely understood. Sympathoadrenal activation is postulated to be involved in the pathogenesis of these diseases, and may be inhibited by n-3 fatty acids. We therefore evaluated the effects of a diet supplemented with n-3 fatty acids on the stimulation of the sympathetic nervous system and of stress hormones elicited by a mental stress. METHODS: Seven human volunteers were studied on two occasions, before and after 3 weeks of supplementation with 7.2 g/day fish oil. On each occasion, the concentrations of plasma cortisol, and catecholamines, energy expenditure (indirect calorimetry), and adipose tissue lipolysis (plasma non esterified fatty acid concentrations) were monitored in basal conditions followed by a 30 min mental stress (mental arithmetics and Stroop's test) and a 30 min recovery period. RESULTS: In control conditions, mental stress significantly increased heart rate, mean blood pressure, and energy expenditure. It increased plasma epinephrine from 60.9 +/- 6.2 to 89.3 +/- 16.1 pg/ml (p<0.05), plasma cortisol from 291 +/- 32 to 372 +/- 37 micromol/l (p<0.05) and plasma non esterified fatty acids from 409 +/- 113 to 544 +/- 89 micromol/l (p<0.05). After 3 weeks of a diet supplemented with n-3 fatty acids, the stimulation by mental stress of plasma epinephrine, cortisol, energy expenditure, and plasma non esterified fatty acids concentrations, were all significantly blunted. CONCLUSION: Supplementation with n-3 fatty acids inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system.

PMID: 12909818 [PubMed - indexed for MEDLINE]

The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease.

Lee KW, Lip GY.

Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.

It has long been recognized from epidemiological studies that Greenland Eskimos have substantially reduced rates of acute myocardial infarction (MI) compared with Western controls. From these epidemiological observations, the benefits of fatty fish consumption have been explored in cell culture and animal studies, as well as randomized controlled trials investigating the cardioprotective effects of omega-3 fatty acids. Dietary omega-3 fatty acids seem to stabilize the myocardium electrically, resulting in reduced susceptibility to ventricular arrhythmias, thereby reducing the risk of sudden death. These fatty acids also have potent anti-inflammatory effects, and may also be antithrombotic and anti-atherogenic. Furthermore, the recent GISSI-Prevention study of 11 324 patients showed a marked decrease in risk of sudden cardiac death as well as a reduction in all-cause mortality in the group taking a highly purified form of omega-3 fatty acids, despite the use of other secondary prevention drugs, including beta-blockers and lipid-lowering therapy. The use of omega-3 fatty acids should be considered as part of a comprehensive secondary prevention strategy post-myocardial infarction.

Publication Types:

  • Review
  • Review Literature

PMID: 12881589 [PubMed - indexed for MEDLINE]

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Diabetes

Diabetics suffering from non-insulin dependent diabetes or type II diabetes benefit from fish oil supplementation. Research shows that person’s who consume 5-10 percent of their dietary energy consumption in the form of fish or fish oil, have less insulin resistance.

Diabetics suffering from non-insulin dependent diabetes or type II diabetes benefit from fish oil supplementation. Research show that persons who consume 5-10 percent of their dietary energy consumption in the form of fish or fish oil, have less insulin resistance, which causes diminished glucose uptake and glucose metabolism in non-insulin dependent diabetics. Fish oil enhances insulin secretion from beta-cells in the pancreas, regulating blood sugar levels. DHA plays a protective role in diabetic neuropathy in all forms of diabetes.

Published Clinical Studies

Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects.

Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin LJ.

Department of Medicine, The University of Western Australia, The West Australian Heart Research Institute and The Western Australian Institute for Medical Research, Perth, Western Australia 6000, Australia. tmori@cyllene.uwa.edu

au n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms. Despite this, there has been concern that these fatty acids may increase lipid peroxidation. The data in vivo are inconclusive, due in part to limitations in the methodologies. In this regard, the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress. This study aimed to assess the effects of supplementation with purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), the two major n-3 fatty acids, on urinary F2-isoprostanes and markers of inflammation, in type 2 diabetic patients. In a double-blind, placebo controlled trial of parallel design, 59 nonsmoking, treated-hypertensive, type 2 diabetic subjects, were randomized to 4 g daily of purified EPA, DHA, or olive oil for 6 weeks, while maintaining their usual diet. F2-isoprostanes, measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were measured before and after intervention. Thirty-nine men and 12 women aged 61.2 +/- 1.2 years, with body mass index (BMI), 29.5 +/- 0.5 kg/m2; 24 h blood pressure, 138/73 mmHg; HbA1c, 7.3 +/- 0.1% and fasting glucose, 7.9 +/- 0.2 mmol/l completed the intervention. Baseline urinary F2-isoprostanes were positively associated with HbA1c (p=.011) and fasting glucose (p=.032). Relative to the olive oil group, postintervention urinary F2-isoprostanes were decreased 19% by EPA (p=.017) and 20% by DHA (p=.014). There were no significant changes in CRP, IL-6, and TNF-alpha following EPA or DHA supplementation. In regression analysis, Delta F2-isoprostanes were positively associated with Delta HbA1c (p=.007) independent of treatment group; and with Delta TNF-alpha (p=.034) independent of age, gender, BMI, and treatment group. There were no associations with Delta CRP or Delta IL-6. This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation, in treated hypertensive, type 2 diabetic subjects.

PMID: 14583341 [PubMed - in process]

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

Coste TC, Gerbi A, Vague P, Pieroni G, Raccah D.

UPRES EA 2193, Faculte de Medecine Timone, Marseille, France. Thierry.Coste@medecine.univ-mrs.fr

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.

PMID: 14514643 [PubMed - indexed for MEDLINE]

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Immune System & Cancer

The intake of fish oil may be beneficial for the body's immune function. Research has even linked intake of fish oil to a lowered risk of breast cancer and prostate cancer.

Published Clinical Studies

Inuit are protected against prostate cancer.

Dewailly E, Mulvad G, Sloth Pedersen H, Hansen JC, Behrendt N, Hart Hansen JP.

Public Health Research Unit, CHUQ-Laval University, Sainte-Foy, Quebec, G1V 5B3 Canada. eric.dewailly@crchul.ulaval.ca

Incidence and mortality rates for prostate cancer are reported to be low among Inuit, but this finding must be additionally supported given the difficulty of obtaining a precise medical diagnosis in the Arctic. We conducted an autopsy study in 1990-1994 among 61 deceased males representative of all deaths occurring in Greenland and found only one invasive prostate cancer. Histological data were available for 27 autopsies and revealed no latent carcinoma. Our results suggest that in situ carcinoma is rare among Inuit and that their traditional diet, which is rich in omega-3 polyunsaturated fatty acids and selenium, may be an important protective factor.

PMID: 14504206 [PubMed - indexed for MEDLINE]

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study.

Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC.

USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089-9181, USA. mgago@usc.edu

We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively). Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01). To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.

PMID: 14583770 [PubMed - indexed for MEDLINE]

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Inflammatory Bowel Disease

Fish oil has been proven to be beneficial in intestinal health. Fish oil has an anti-inflammatory effect in inflammatory bowel disease (Ulcerative colitis and Crohn's disease).

Published Clinical Studies

Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids.

Barbosa DS, Cecchini R, El Kadri MZ, Rodriguez MA, Burini RC, Dichi I.

Laboratory of Biochemistry, Londrina State University, Londrina, Parana, Brazil.

OBJECTIVE: The potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress. METHODS: Nine patients (seven female and two male; mean age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation, both induced by tert butyl hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant status was assayed by total plasma antioxidant capacity (TRAP) and microsomal lipid peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase erythrocyte enzymatic activities were also determined. RESULTS: No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores, with the exception of erythrocyte sedimentation rate, which decreased with both treatments. Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels, increased chemiluminescence induced by t-BuOOH, and higher SOD activity in patients with UC. Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid peroxidation, and catalase were not different from those in the control group. CONCLUSIONS: The results indicated that plasma oxidative stress occurs in patients with UC, and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids. However, there was no improvement in most laboratory indicators, sigmoidoscopy, and histology scores. The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress.

PMID: 14559317 [PubMed - in process]

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Skin Disorders & Skin Health

Skin disorders such as psoriasis have been shown to improve with the intake of fish oils. In the skin of persons with psoriasis the amount of compounds causing inflammation is many times greater than normal. Fish oil inhibits the production of these inflammatory compounds. Fish oil intake may also improve the health of skin, nails and hair.

Published Clinical Studies

n-3 fatty acids in psoriasis.

Mayser P, Grimm H, Grimminger F.

Department of Dermatology and Andrology, Justus Liebig University, Giessen, Germany. Peter.Mayser@derma.med.uni-giessen.de Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the effectiveness and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 11895157 [PubMed - indexed for MEDLINE]

Effects of micronutrient supplements on u.v.-induced skin damage.

Jackson MJ, Jackson MJ, McArdle F, Storey A, Jones SA, McArdle A, Rhodes LE.

Department of Medicine, University of Liverpool, Liverpool L69 3GA, UK. mjj@liv.ac.uk

Development of an orally-administered systemic agent that could reduce the effects of u.v. exposure on skin could potentially have a major effect on the incidence of skin cancers and photo-ageing. A number of micronutrients have been suggested to have metabolic properties that could induce this protection, and our data indicate that n-3 polyunsaturated fatty acids are particularly effective in this role. The mechanisms of action of n-3 polyunsaturated fatty acids appear to depend on their anti-inflammatory properties, acting to reduce the u.v.-induced release of cytokines and other mediators from a variety of skin cell types.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 12133200 [PubMed - indexed for MEDLINE]

The significance of polyunsaturated fatty acids in cutaneous biology.

Ziboh VA.

Department of Dermatology, University of California, Davis, USA.

The skin epidermis displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA) and 18-carbon (n-6) PUFA results in characteristic scaly skin disorder and excessive epidermal water loss. Arachidonic acid, a 20-carbon (n-6) PUFA is metabolized via the cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) PGF2 alpha, and PGD2 and via the lipoxygenase pathway into predominantly 15-hydroxyeicosatetraenoic acid (15-HETE). The prostaglandins modulate normal skin physiological processes at low concentrations and inflammatory reactions at high concentrations. Similarly, the very active epidermal 15-lipoxygenase transforms dihomogammalinolenic acid (DGLA) into 15-hydroxy eicosatrienoic acid (15-HETrE), eicosapentaenoic acid (EPA) into 15-hydroxyeicosapentaenoic acid (15-HEPE) and docosahexaenoic acid (DHA) into 17-hydroxydocosahexaenoic acid (17-HDoHE), respectively. These monohydroxy acids exhibit anti-inflammatory properties. In contrast, the 18-carbon (n-6) PUFA is transformed into 13-hydroxy-9,11-octadecadienoic acid (13-HODE), which exerts antiproliferative properties in the tissue. Thus, the supplementation of diets with appropriate purified vegetable oils and/or fish oil may generate local cutaneous anti-inflammatory metabolites which could serve as a less toxic in vivo monotherapy or as adjuncts to standard therapeutic regimens for the management of skin inflammatory disorders.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 8729128 [PubMed - indexed for MEDLINE]

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Visual Function

Research has shown that consumption of fish oil is linked to lowered risk of age related macular degeneration, an eye condition which is the leading cause of severe visual loss in people over age 50.

The macula is the central area in the retina of the eye used for fine focus such as reading. Omega-3 fatty acids form an important part of the building blocks of the retina and studies show that fish oil intake may well improve focus, color, perception and clarity of vision.

Published Clinical Studies

Scotopic electroretinogram in term infants born of mothers supplemented with docosahexaenoic acid during pregnancy.

Malcolm CA, Hamilton R, McCulloch DL, Montgomery C, Weaver LT.

Department of Vision Sciences, Glasgow Caledonian University, Glasgow, United Kingdom. gcl305@clinmed.gla.ac.uk

PURPOSE: To test the hypothesis that the supplementation of the diets of pregnant women with a fish oil rich in docosahexaenoic acid (DHA) enhances retinal development in their healthy term infants, as measured during the early postnatal period by the electroretinogram (ERG). METHODS: One hundred pregnant women were randomized to receive either a fish oil (n = 50) or a placebo oleic acid dietary supplement (n = 50) from 15 weeks of pregnancy until delivery. Total fatty acids in red blood cells (RBCs) and plasma were measured in mothers at 15 and 28 weeks of pregnancy and at delivery and in their infants in umbilical cord blood. Infant retinal development was assessed within the first week of life with full-field ERGs that included a scotopic blue intensity series (n = 41) and a bright white flash (2.0 log cd-s/m(2); n = 44). RESULTS: Infants born of mothers who received supplements did not differ at birth in weight, gestational age, or any other standard variable. Infant DHA status at birth, as measured from umbilical cord blood, did not differ significantly between maternal supplementation groups. ERG implicit times, amplitudes, and parameters of the stimulus-response function did not differ significantly between infants in the maternal supplemented and placebo groups. There was, however, a relationship between infant DHA status and maturity of the retina at birth, regardless of maternal supplementation group. A measure of retinal sensitivity (log sigma) correlated significantly (P < 0.005) with DHA status (as a percentage of total fatty acid; TFA) in infant cord blood. Infants in the highest quartile for cord blood DHA had higher retinal sensitivity compared with infants in the lowest quartile. Infants in the highest quartile for plasma DHA, both as a percentage of TFA and concentration, were born at a significantly later gestational age than were infants in the lower quartiles. CONCLUSIONS: These findings demonstrate an association between the DHA status of term infants and retinal sensitivity, suggesting an essential role of this long-chain polyunsaturated fatty acid (LCPUFA) in the development and function of the retina. However, maternal DHA status was not significantly associated with infant retinal sensitivity and no direct effect of maternal supplementation was observed.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial

PMID: 12882824 [PubMed - indexed for MEDLINE]

Docosahexaenoic and arachidonic acid influence on preterm baboon retinal composition and function.

Diau GY, Loew ER, Wijendran V, Sarkadi-Nagy E, Nathanielsz PW, Brenna JT.

Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.

PURPOSE. Dietary n-3 polyunsaturated fatty acid deficiency and prematurity are both associated with suboptimal visual function in nonhuman primates and in humans. This study reports measurements of retinal long chain polyunsaturate (LCP) concentrations and electroretinogram (ERG) parameters for term and preterm neonatal baboons consuming clinically relevant diets. METHODS. ERGs and retinal fatty acid compositions were obtained from baboon neonates in four groups: term-delivered/breast-fed (B), term/formula-fed (T-), preterm/formula-fed (P-), and preterm/formula (P+) supplemented with long chain polyunsaturates. Initial a-wave slope change (a), a-wave amplitude (a(amp)) and implicit time (a(i)), and b-wave amplitude (b(amp)) and implicit time (b(i)) were determined and correlations to retinal fatty acid concentrations were evaluated. RESULTS. The P+ group a and b(amp) significantly improved between 0 and 4 weeks' adjusted age, whereas no P- group parameter improved with age. At four weeks, both a(amp) and b(amp) were significantly greater in group B than in all other groups, and a and a(i) were greater for P+ than for P-. Concentrations of 22:6n-3, 22:5n-3, and Sigman-3 and the 22:5n-6/22:6n-3 ratio correlated positively with improved retinal response parameters, whereas 22:5n-6, 22:4n-6, 20:4n-6, 20:3n-6, 20:2n-9, 20:1n-9, and 18:1n-9 all correlated negatively (P < 0.05); saturates were uncorrelated. The parameters most linearly related to retinal 22:6n-3 were a, a(i), and a(amp). Retinal 20:4n-6 concentrations were not influenced by prematurity or supplementation. CONCLUSIONS. Breast-feeding optimizes retinal response in 4-week-old baboons. Formula supplemented with 22:6n-3 prevents a decrease in retinal 22:6n-3 and improves preterm ERG parameters compared with unsupplemented formula. Retinal 22:6n-3 status is most closely associated with a-wave parameters.

PMID: 14507905 [PubMed - indexed for MEDLINE]

Dietary docosahexaenoic acid protects against N-methyl-N-nitrosourea-induced retinal degeneration in rats.

Moriguchi K, Yuri T, Yoshizawa K, Kiuchi K, Takada H, Inoue Y, Hada T, Matsumura M, Tsubura A.

Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.

The effect of dietary intake of specific types of fatty acids on retinal degeneration due to N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis was evaluated. Fifty-day-old female Sprague-Dawley rats were given a single intraperitoneal injection of 50 mg kg(-1) body weight of MNU, and were then switched to one of five different diets containing the following fatty acids at the following weight percentages: 10% linoleic acid (LA); 9.5% palmitic acid (PA) and 0.5% LA; 9.5% eicosapentaenoic acid (EPA) and 0.5% LA; 4.75% EPA, 4.75% docosahexaenoic acid (DHA) and 0.5% LA; or 9.5% DHA and 0.5% LA. When rats developed MNU-induced mammary tumors with a diameter of > or =1 cm, or at the termination of the experiment (20 weeks after MNU injection), retinal tissue samples were obtained and examined. Incidence and severity of retinal damage were compared by histologic examination. MNU-induced retinal degeneration was prevented in rats fed the diet containing 9.5% DHA (4.75% DHA was less effective), whereas it was accelerated in rats fed the 10% LA diet. Over the course of the 20-week experimental period, the fatty acid composition of serum reflected differences in dietary fatty acids. The present results indicate that a diet containing 9.5% DHA can counteract MNU retinotoxicity in the rat retina. DHA may play a role in protection against MNU-induced photoreceptor cell apoptosis in the rat retina.

PMID: 12873446 [PubMed - indexed for MEDLINE]

Protective effect of docosahexaenoic acid on oxidative stress-induced apoptosis of retina photoreceptors.

Rotstein NP, Politi LE, German OL, Girotti R.

Institute of Biochemical Research and Universidad Nacional del Sur, Bahia Blanca, Buenos Aires, Argentina. inrotste@criba.edu.ar

PURPOSE: In a recent study, it was demonstrated that docosahexaenoic acid (DHA) promotes the survival of retinal photoreceptors in vitro, delaying apoptosis. However, lipid enrichment in DHA is known to contribute to retina vulnerability to oxidative stress. In this study, the effect of oxidative damage on rat retina neurons in vitro and whether DHA enhances or diminishes this damage were investigated. METHODS: Rat retina neurons in 3-day cultures, with or without DHA, were treated with the oxidant paraquat. After 24 hours, apoptosis, mitochondrial membrane integrity, and Bcl-2 and Bax expression were immunocytochemically determined. RESULTS: Paraquat induced apoptosis in amacrine and photoreceptor neurons, major neuronal types in the culture. Neuronal apoptosis was accompanied by mitochondrial membrane depolarization, an increase in the amount of photoreceptors expressing Bax, and a decrease in those expressing Bcl-2. Addition of DHA reduced photoreceptor apoptosis by almost half, simultaneously preserving their mitochondrial membrane integrity. DHA blocked the paraquat-induced increase in Bax expression and remarkably upregulated Bcl-2 expression. Glia-derived neurotrophic factor, a photoreceptor trophic factor, only slightly increased Bcl-2 expression and did not protect photoreceptors from oxidative damage. Similarly, other fatty acids tested did not prevent photoreceptor apoptosis. CONCLUSIONS: These results show that oxidative damage induces apoptosis in retinal neurons during their early development in culture and suggest that the loss of mitochondrial membrane integrity is crucial in the apoptotic death of these cells. DHA activates intracellular mechanisms that prevent this loss and by modulating the levels of pro- and antiapoptotic proteins of the Bcl-2 family selectively protect photoreceptors from oxidative stress.

PMID: 12714668 [PubMed - indexed for MEDLINE]

Cell cycle regulation in retinal progenitors by glia-derived neurotrophic factor and docosahexaenoic acid.

Insua MF, Garelli A, Rotstein NP, German OL, Arias A, Politi LE.

Institute of Biochemical Research (INIBIBB) and Universidad Nacional del Sur, Bahia Blanca, Buenos Aires, Argentina.

PURPOSE: A recent study has shown that glia-derived neurotrophic factor (GDNF) and docosahexaenoic acid (DHA) promote the survival and differentiation of retina photoreceptors. The current study was undertaken to investigate whether these molecules participate in cell cycle regulation in retinal progenitors in vitro. METHODS: Developmental changes in the expression of the stem cell marker nestin and of cell cycle and differentiated neuron markers were analyzed in neuroblasts obtained from 1-day-old rat retinas. The effects of GDNF and DHA on those changes were then determined. RESULTS: Expression of nestin, found in more than one third of neuroblasts at day 1, rapidly decreased during development, with most neuroblasts acquiring the photoreceptor phenotype. GDNF increased the percentage of photoreceptor progenitors expressing nestin, whereas DHA reduced it, simultaneously enhancing photoreceptor differentiation. Several markers of cell cycle progression indicated that photoreceptor progenitors maintained an active cell cycle during the first 2 days in vitro. GDNF stimulated the cell cycle, increasing the number of dividing cells and generating more photoreceptor progenitors, whereas DHA induced cell cycle exit and photoreceptor differentiation. Analysis of the expression of the cyclin-Cdk inhibitor p27(Kip1) confirmed these results. CONCLUSIONS: GDNF and DHA acted as molecular cues, counterbalancing the decision of photoreceptors to remain in or exit the cell cycle. The results strongly suggest that both factors participate in determining the number of photoreceptors in vitro, regulating the cell cycle and survival at early and late stages of development, respectively. Hence, GDNF and DHA may coordinately control the histogenesis of photoreceptors in the retina by modulating both neurogenesis and apoptosis.

PMID: 12714666 [PubMed - indexed for MEDLINE]

Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids.

Elner VM.

Department of Ophthalmology, University of Michigan, Ann Arbor, USA.

PURPOSE: To show that fish oil-derived omega-3 polyunsaturated fatty acids, delivered to the retinal pigment epithelium (RPE) by circulating low-density lipoproteins (LDL), enhance already considerable RPE lysosomal acid lipase activity, providing for more efficient hydrolysis of intralysosomal RPE lipids, an effect that may help prevent development of age-related macular degeneration (ARMD). METHODS: Colorimetric biochemical and histochemical techniques were used to demonstrate RPE acid lipase in situ, in vitro, and after challenge with phagocytic stimuli. Receptor-mediated RPE uptake of fluorescently labeled native, aceto-acetylated, and oxidized LDL was studied in vitro and in vivo. LDL effects on RPE lysosomal enzymes were assessed. Lysosomal enzyme activity was compared in RPE cells from monkeys fed diets rich in fish oil to those from control animals and in cultured RPE cells exposed to sera from these monkeys. RESULTS: RPE acid lipase activity was substantial and comparable to that of mononuclear phagocytes. Acid lipase activity increased significantly following phagocytic challenge with photoreceptor outer segment (POS) membranes. Receptor-mediated RPE uptake of labeled lipoproteins was determined in vitro. Distinctive uptake of labeled lipoproteins occurred in RPE cells and mononuclear phagocytes in vivo. Native LDL enhanced RPE lysosomal enzyme activity. RPE lysosomal enzymes increased significantly in RPE cells from monkeys fed fish oil-rich diets and in cultured RPE cells exposed to their sera. CONCLUSIONS: RPE cells contain substantial acid lipase for efficient metabolism of lipids imbibed by POS phagocytosis and LDL uptake. Diets rich in fish oil-derived omega-3 fatty acids, by enhancing acid lipase, may reduce RPE lipofuscin accumulation, RPE oxidative damage, and the development of ARMD.

PMID: 12545699 [PubMed - indexed for MEDLINE]

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Women's Benefits

The benefits of fish oil extend across all age groups. Consumption of fish oil may lower the risk for cardiovascular disease and osteoporosis in post-menopausal women. (Pre)Menstrual symptoms such as menstrual pain are often alleviated from the use of fish oil supplementation. Omega 3 fatty acids are converted into pain relieving substances (prostaglandins type-3) that control contractions of the uterus, which cause the cramping.

Published Clinical Studies

Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT.

Ciubotaru I, Lee YS, Wander RC.

Department of Nutrition, The University of North Carolina at Greensboro, Greensboro, NC 27402, USA.

BACKGROUND: Atherogenesis is a complex process involving both a low-grade inflammation and a disturbed lipid profile. Although dietary fish and fish oil improve the latter of these two risk factors, their impact on the former is less clear. OBJECTIVE: This study addressed the effect of supplementation with fish oil in doses achievable with diet on serum C-reactive protein (CRP), interleukin-6 (IL-6), and the lipid profile. METHODS AND RESULTS: Thirty healthy subjects taking HRT were randomly divided into three groups and supplemented for five weeks with 14 g/day safflower oil (SO), 7 g/day of both safflower oil and fish oil (LFO), or 14 g/day fish oil (HFO). Measurements included serum high-sensitivity CRP, IL-6 in plasma and in cell culture supernatant collected from 24-hr lipopolysaccharide (LPS)-stimulated whole blood, and lipid profile markers. CRP and IL-6 were adjusted for body mass index (BMI). Fish oil supplementation significantly decreased CRP and IL-6 compared to SO, with a greater effect in the LFO than HFO groups. Plasma triacylglycerol (TG) and the TG/HDL-C ratio were significantly lower in the HFO compared to the SO group. CONCLUSIONS: These results suggest that dietary fish oil may decrease the risk for cardiovascular disease through the modulation of both plasma lipids and inflammatory markers in healthy postmenopausal women.

PMID: 14505813 [PubMed - in process]

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