Archive for November, 2013

prostate cancer and Omega3 EPA

Saturday, November 16th, 2013

EPA, COQ10 Reduced Serum PSA Levels
Safarinejad MR, Shafiei N, Safarinejad S. Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial. Br J Nutr. 2012 Nov 30:1-8.
The main objective of the present study was to determine the potential of n-3 and n-6 fatty acids or coenzyme Q10 (CoQ10) to alter serum prostate-specific antigen (PSA) levels in normal healthy men.

A total of 504 healthy men with serum PSA level ≤ 2·5 ng/ml were recruited into the study. Serum PSA values were not segregated by decade of age. Participants were randomly assigned to a daily dietary supplement containing n-3 fatty acids (1·12 g of EPA and 0·72 g of DHA per capsule) (group 1, n 126), n-6 fatty acid (600 mg γ-linolenic acid (GLA) each capsule) (group 2, n 126), CoQ10 (100 mg per capsule) (group 3, n 126) or a similar regimen of placebo (group 4, n 126) for 12 weeks.

Study medication was administered as two capsules to be taken twice daily. Serum levels of PSA, EPA, DHA, GLA, lipid profile and reproductive hormones were also measured.

EPA treatment significantly reduced serum PSA level by 30·0 (95 % CI 25, 36) % (P = 0·004) from baseline. In contrast, GLA therapy significantly increased serum PSA concentration by 15·0 (95 % CI 11, 20) % (P = 0·02). CoQ10 therapy also significantly reduced serum PSA level by 33·0 (95 % CI 27, 40) % (P = 0·002). In multivariable analysis, serum values of PSA were strongly correlated with duration of EPA (r – 0·62; 95 % CI – 0·42, – 0·77; P = 0·003), n-6 (r 0·42; 95 % CI 0·31, 0·58; P = 0·02) and CoQ10 use (r – 0·77; 95 % CI – 0·56, – 0·87; P = 0·001).

There were also significant correlations between serum values of DHA, EPA, GLA and CoQ10 and serum PSA levels. The present study demonstrates that dietary supplements containing EPA, GLA or CoQ10 may significantly affect serum PSA levels.

Omega-3 PUFA Inhibit Human Breast Cancer Cell Growth

Saturday, November 16th, 2013

Omega-3 PUFA Inhibit Human Breast Cancer Cell Growth
Cao W, Ma Z, Rasenick MM, et al. N-3 poly-unsaturated Fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS One. 2012;7(12):e52838.
Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling.

The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 β-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ERα agonist failed to elicit, and ERα knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity.

These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.

Omega-3 Directly Inhibit Breast Cancer Growth

Saturday, November 16th, 2013

Omega-3 Directly Inhibit Breast Cancer Growth
MacLennan MB, Clarke SE, Perez K, et al. Mammary tumor development is directly inhibited by lifelong n-3 polyunsaturated fatty acids. J Nutr Biochem. 2013 Jan;24(1):388-95.
INTRODUCTION:
Despite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis.

METHODS:
fat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)-neu(ndl)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet.

RESULTS:
Mice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (~30%) and multiplicity (~33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndl)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice.

CONCLUSION:
Using complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention.

Carcinogenesis – Chemopreventative Potential Of Omega3 EPA

Saturday, November 16th, 2013

Carcinogenesis – Chemopreventative Potential Of EPA
Nikolakopoulou Z, Nteliopoulos G, Michael-Titus AT, et al. Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2. Carcinogenesis. 2013 Jul 26.
The long chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA), inhibit cancer formation in vivo but their mechanism of action is unclear. ERK1/2 activation and inhibition have both been associated with the induction of tumor cell apoptosis by n-3 PUFAs.

We show here that low doses of EPA, in particular, inhibited the growth of pre-malignant and malignant keratinocytes more than their normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478, or an EGFR blocking antibody, inhibited ERK1/2 phosphorylation and the blocking antibody partially antagonized growth inhibition by EPA, but not by DHA. DHA generated more reactive oxygen species and activated more JNK than EPA, potentially explaining its increased toxicity to normal keratinocytes.

Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signaling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supra-optimal level, supporting the chemopreventative potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA

Omega-3 FAs Decrease Plasma VLDL-TG Concentration

Saturday, November 16th, 2013

Omega-3 FAs Decrease Plasma VLDL-TG Concentration
Wong AT, Chan DC, Ooi EM, et al. Omega-3 fatty acid ethyl ester supplementation decreases very-low density lipoprotein triacylglycerol secretion in obese men. Clin Sci (Lond). 2013 Jan 28.
Dysregulated very-low density lipoprotein (VLDL)-triacylglycerol (TG) metabolism in obesity may account for hypertriacylglycerolaemia and increased cardiovascular disease.
Omega-3 fatty acid ethyl esters (ω-3 FAEEs) decrease plasma TG and VLDL concentrations, but the mechanisms are not fully understood.

In this study, we carried out a 6-week randomized, placebo-controlled study to examine the effect of high dose ω-3 FAEE supplementation (3.2g/day) on the metabolism of VLDL-TG in obese men using intravenous administration of d5-glycerol. We also explored the relationships of VLDL-TG kinetics with the metabolism of VLDL-apolipoprotein (apo) B-100 and high density lipoprotein (HDL)-apoA-I. VLDL-TG isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model.

Compared with placebo, ω-3 FAEE supplementation significantly lowered plasma concentrations of total (-14%, P<0.05) and VLDL-TG (-32%, P <0.05), as well as hepatic secretion of VLDL-TG (-32%, P<0.03). The fractional catabolic rate (FCR) of VLDL-TG was not altered by ω-3 FAEEs. There was a significant association between the change in secretion rates of VLDL-TG and VLDL-apoB-100 (r=0.706, P<0.05).

However, the change in VLDL-TG secretion rate was not associated with change in HDL-apoA-I FCR (r=0.139, P<0.05).

Our results suggest that the TG-lowering effect of ω-3 FAEEs is associated with decreased VLDL-TG secretion rate and hence lower plasma VLDL-TG concentration in obesity. The changes in VLDL-TG and apoB-100 kinetics are closely coupled

High Concentration Omega3 EPA improves vascular function

Saturday, November 16th, 2013

Highly Purified EPA Improves Vascular Function
Sasaki J, Miwa T, Odawara M. Administration of highly purified eicosapentaenoic acid to statin-treated diabetic patients further improves vascular function. Endocr J. 2012;59(4):297-304.
We prospectively examined the additional effects of highly purified eicosapentaenoic acid (EPA) particularly on the vascular function of diabetic patients with hypercholesterolemia receiving statin therapy.

We enrolled 28 patients with type 2 diabetes complicated by dyslipidemia who had been treated with statins for at least one year. The patients were randomly assigned to 2 groups: administration of statin alone (group S: n = 13) and addition of EPA to the current statin therapy (group SE: n = 15). The highly purified EPA was administered at a dose of 1,800 mg/day for 6 months. To evaluate vascular function, the duration of reactive hyperemia (DRH), which is the time required for forearm blood flow to return to the basal level after inducing reactive hyperemia, was measured using strain gauge plethysmography.

There were no significant differences in the clinical background factors between the 2 groups. Low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol levels significantly decreased after 6 months only in group SE. Compared with the baseline data, no significant change in DRH was observed after 6 months in group S.

By contrast, DRH was significantly prolonged after 6 months in group SE, indicating that the addition of highly purified EPA improved vascular function.

Our results showed that in patients with type 2 diabetes and receiving statin therapy whose LDL-C level was less than 100

Reduction in brain abnormalities in older adults associated with higher consumption of omega3 fatty acids from oily fish

Saturday, November 16th, 2013

Virtanen JK, Siscovick DS, Lemaitre RN, et al. Circulating Omega-3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study. J Am Heart Assoc. 2013 Oct 10;2(5):e000305.
BACKGROUND:
Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega-3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI.

METHODS AND RESULTS:
In the community-based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992-1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992-1993 and related to cross-sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long-chain omega-3 PUFA quartile. Higher long-chain omega-3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate-chain omega-3 PUFA alpha-linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha-linolenic acid intake.

CONCLUSIONS:
Among older adults, higher phospholipid long-chain omega-3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long-chain omega-3 PUFAs, on brain health in later life. The role of plant-derived alpha-linolenic acid in brain health requires further investigation.

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