REFERENCES:

Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women.
Eur J Clin Nutr. 2005 Nov 9
Vegetarians are generally deficient in long-chain n-3 fatty acids. Long-chain n-3 fatty acids have a beneficial effect on plasma lipid levels, and some studies showed that they had breast cancer suppression effect. To investigate the effect of docosahexaenoic acid (DHA, 22:6n-3) supplementation on blood lipids, estrogen metabolism and oxidative stress in vegetarians. Design: Single-blind, randomized, placebo-controlled trial. Twenty-seven postmenopausal vegetarian women were recruited. After a 2-week run-in period with 6 g placebo corn oil, the subjects were subsequently randomized to receive either 6 g corn oil (n=13) or 6 g DHA-rich algae oil (2.14 g of DHA /day) (n=14) for 6 weeks. Two subjects in corn oil group withdrew before completion. Conclusion: DHA supplementation at a dose of 2.14 g/day for 42 days decreases plasma cholesterol but neither does it show beneficial effects on estrogen metabolism, nor does it induce deleterious effects on the observed in vivo antioxidant or oxidative stress marker in postmenopausal vegetarian women.

Consuming a diet rich in the omega-3 fatty acid docosahexanoic acid (DHA) may help prevent or treat Alzheimer's disease. In the study, which is reported in The Journal of Neuroscience, mice that ate DHA-enriched chow showed less beta-amyloid build-up in the brain than mice fed regular chow. Beta-amyloid is a protein that forms the characteristic brain plaques seen in patients with Alzheimer's disease." These results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity," senior author Dr. Greg M. Cole, from the University of California at Los Angeles, and colleagues note. Research has linked high levels of DHA in the diet with a reduced risk of Alzheimer's disease. Still, the studies have shown an association, but don't prove that eating a diet high in DHA actually reduces amyloid levels and prevents Alzheimer's disease. To show this, animal studies are often needed. Cole's team used a mouse model of Alzheimer's disease and fed the animals low- or high-DHA chow or regular chow. The animals were fed the assigned diet until 22.5 months of age, at which point brain tissue was obtained and tested for amyloid build-up. The high-DHA diet reduced total amyloid level by 70 percent compared with the other diets, the investigators report. Moreover, brain plaques were reduced by 40.3 percent.

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects1,2,3
American Journal of Clinical Nutrition, Vol. 80, No. 5, 1167-1174, November 2004
During pregnancy there is a high demand for docosahexaenoic acid ( DHA ), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. We studied sex differences in DHA status and the role of sex hormones. First, DHA status was compared between 72 male and 103 female healthy volunteers who ate the same rigidly controlled diets. Second, the effects of sex hormones were studied in 56 male-to-female transsexual subjects, who were treated with cyproterone acetate alone or randomly assigned to receive oral ethinyl estradiol or transdermal 17ß-estradiol combined with cyproterone acetate, and in 61 female-to-male transsexual subjects, who were treated with testosterone esters or randomly assigned for treatment with the aromatase inhibitor anastrozole or placebo in addition to the testosterone regimen. Results: The proportion of DHA was 15 ± 4% ( ± SEM) higher in the women than in the men. Among the women, those taking oral contraceptives had 10 ± 4% higher DHA concentrations than did those not taking oral contraceptives. Administration of oral ethinyl estradiol, but not transdermal 17ß-estradiol, increased DHA by 42, whereas the antiandrogen cyproterone acetate did not affect DHA. Parenteral testosterone decreased DHA by 22 in female-to-male transsexual subjects. Anastrozole decreased estradiol concentrations significantly and DHA concentrations nonsignificantly. Conclusion: Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.

Omega-3 fatty acids from fish oils and cardiovascular disease.
Mol Cell Biochem. 2004 Aug;263(1-2):217-25.
Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid ( DHA ). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA / DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA / DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA / DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA / DHA from fish oils in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease.

Docosahexaenoic acid promotes neurite growth in hippocampal neurons.
J Neurochem. 2004 Aug;90(4):979-88.
Docosahexanoic acid (22:6n-3; DHA) deficiency during development is associated with impairment in learning and memory, suggesting an important role of DHA in neuronal development. Here we provide evidence that DHA promotes neuronal differentiation in rat embryonic hippocampal primary cultures. DHA deficiency in vitro was spontaneously induced by culturing hippocampal cells in chemically defined medium. DHA supplementation improved DHA levels to values observed in freshly isolated hippocampus. We found that DHA supplementation in culture increased the population of neurons with longer neurite length per neuron and with higher number of branches. However, supplementation with arachidonic, oleic or docosapentaenoic acid did not have any effect, indicating specificity of the DHA action on neurite growth. Furthermore, hippocampal cultures obtained from n-3 fatty acid deficient animals contained a lower DHA level and a neuronal population with shorter neurite length per neuron in comparison to those obtained from animals with adequate n-3 fatty acids. DHA supplementation to the deficient group recovered the neurite length to the level similar to n-3 fatty acid adequate cultures. Our data demonstrates that DHA uniquely promotes neurite growth in hippocampal neurons. Inadequate neurite development due to DHA deficiency may contribute to the cognitive impairment associated with n-3 fatty acid deficiency.

Effect of fish and fish oil-derived omega-3 fatty acids on lipid oxidation.
Redox Rep. 2004;9(4):193-7.
There is evidence that omega-3 (omega3) fatty acids derived from fish and fish oils reduce the risk of cardiovascular disease via mechanisms underlying atherosclerosis, thrombosis and inflammation. Despite these benefits, there has been concern that these fatty acids may increase lipid peroxidation. However, the in vivo data to date are inconclusive, due in part to limitations in the methodologies. In this regard, our findings using the measurement of F(2)-isoprostanes, a reliable measure of in vivo lipid peroxidation and oxidant stress, do not support adverse effects of omega3 fatty acids on lipid peroxidation.

Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model.
Neuron. 2004 Sep 2;43(5):633-45.
Learning and memory depend on dendritic spine actin assembly and docosahexaenoic acid (DHA), an essential n-3 (omega-3) polyunsaturated fatty acid (PFA). High DHA consumption is associated with reduced Alzheimer's disease risk, yet mechanisms and therapeutic potential remain elusive. Here, we report that reduction of dietary n-3 PFA in an Alzheimer's disease mouse model resulted in 80%-90% losses of the p85alpha subunit of phosphatidylinositol 3-kinase and the postsynaptic actin-regulating protein drebrin, as in Alzheimer's disease brain. The loss of postsynaptic proteins was associated with increased oxidation, without concomitant neuron or presynaptic protein loss. n-3 PFA depletion increased caspase-cleaved actin, which was localized in dendrites ultrastructurally. Treatment of n-3 PFA-restricted mice with DHA protected against these effects and behavioral deficits and increased antiapoptotic BAD phosphorylation. Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially Alzheimer's disease.

Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk.
J Nutr. 2004 Sep;134(9):2307-13.
Between 6 and 12 mo of age, blood levels of the (n-3) long-chain PUFA, docosahexaenoic acid (DHA), in breast-fed infants typically decrease due to diminished maternal DHA stores and the introduction of DHA-poor solid foods displacing human milk as the primary source of nutrition. Thus, we utilized a randomized, clinical trial format to evaluate the effect of supplemental DHA in solid foods on visual development of breast-fed infants with the primary outcome, sweep visual-evoked potential (VEP) acuity, as an index for maturation of the retina and visual cortex. At 6 mo of age, breast-fed infants were randomly assigned to receive 1 jar (113 g)/d of baby food containing egg yolk enriched with DHA (115 mg DHA/100 g food; n = 25) or control baby food (0 mg DHA; n = 26). Gravimetric measures were used to estimate the supplemental DHA intake which was 83 mg DHA/d in the supplemented group and 0 mg/d in controls. Although many infants in both groups continued to breast-feed for a mean of 9 mo, RBC DHA levels decreased significantly between 6 and 12 mo (from 3.8 to 3.0 g/100 g total fatty acids) in control infants, whereas RBC DHA levels increased by 34% from 4.1 to 5.5 g/100 g by 12 mo in supplemented infants. VEP acuity at 6 mo was 0.49 logMAR (minimum angle of resolution) and improved to 0.29 logMAR by 12 mo in controls. In DHA-supplemented infants, VEP acuity was 0.48 logMAR at 6 mo and matured to 0.14 logMAR at 12 mo (1.5 lines on the eye chart better than controls). At 12 mo, the difference corresponded to 1.5 lines on the eye chart. RBC DHA levels and VEP acuity at 12 mo were correlated, supporting the need of an adequate dietary supply of DHA throughout 1 y of life for neural development.

The fatty acids found in fish may slightly lower a man's risk of prostate cancer, but another type of fatty acid found in a range of foods may raise the risk, a large study suggests. Researchers found that among nearly 48,000 U.S. men followed for 14 years, those with the highest intakes of two fatty acids found in oily fish were 26 percent less likely than men with the lowest intakes to develop advanced prostate cancer. The opposite was true, however, when it came to alpha-linolenic acid, or ALA. Like the two fish-oil fats, ALA is an omega-3 unsaturated fatty acid that is thought to promote heart health; it is found in vegetable sources such as soybeans, canola oil, walnuts and flaxseed, and to a lesser extent in meat and dairy products. In this study, men with the highest intake of ALA were about twice as likely as those with the lowest intakes to develop advanced prostate cancer. And the risk was increased regardless of whether the ALA came from vegetable or animal sources, according to findings published in the American Journal of Clinical Nutrition.

The July/August 2004 edition of the journal Child Development reports a study found that infants whose mothers' had higher blood levels of docosahexaenoic acid (DHA) at birth showed more mature forms of attention during their first two years of development. These findings add to the evidence that DHA is an important factor in early development and that women who are pregnant, or intend to become pregnant, should consider supplementing their diets with DHA or fish oils. DHA supports an infant's brain and eye development. Reported studies have consistently shown that women's diets in the U.S. have one of the lowest levels of DHA in the world. Clinical studies have demonstrated that women who supplement their diets with DHA during pregnancy experience elevated DHA levels in their blood.

People who ate an average of 180 mg or more a day of DHA had about 40% less Alzheimer's disease and other dementia, compared with people who consumed less DHA, according to epidemiologic data collected in the Framingham Heart Study.

Fish oil interaction with warfarin.
Buckley MS, Goff AD,Shawnee Mission, KS of Arizona, Tucson, AZ 85724
Ann Pharmacother. 2004 Jan;38(1):50-2.
OBJECTIVE: To report a case of elevated international normalized ratio (INR) in a patient taking fish oil and warfarin. CASE SUMMARY: A 67-year-old white woman had been taking warfarin for 1(1/2) years due to recurrent transient ischemic attacks. Her medical history included hypothyroidism, hyperlipidemia, osteopenia, hypertension, and coronary artery disease. She also experienced an inferior myocardial infarction in 1995 requiring angioplasty, surgical repair of her femoral artery in 1995, and hernia repair in 1996. This patient has her INR checked in the anticoagulation clinic and is followed monthly by the clinical pharmacist. Prior to the interaction, her INR was therapeutic for 5 months while she was taking warfarin 1.5 mg/d. The patient admitted to doubling her fish oil dose from 1000 to 2000 mg/d. Without dietary, lifestyle, or medication changes, the INR increased from 2.8 to 4.3 within 1 month. The INR decreased to 1.6 one week after subsequent fish oil reduction, necessitating a return to the original warfarin dosing regimen. DISCUSSION: Fish oil supplementation could have provided additional anticoagulation with warfarin therapy. Fish oil, an omega-3 polyunsaturated fatty acid, consists of eicosapentaenoic acid and docosahexaenoic acid. This fatty acid may affect platelet aggregation and/or vitamin K-dependent coagulation factors. Omega-3 fatty acids may lower thromboxane A(2) supplies within the platelet as well as decrease factor VII levels. Although controversial, this case report illustrates that fish oil can provide additive anticoagulant effects when given with warfarin. CONCLUSIONS: This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled. Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.

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