Archive for the ‘Uncategorized’ Category

Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Peet M1, Brind J, Ramchand CN, Shah S, Vankar GK.

Wednesday, September 9th, 2015

Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Peet M1, Brind J, Ramchand CN, Shah S, Vankar GK.
Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, S5 7JT, Sheffield, UK. m.peet@sheffield.ac.uk
Abstract
Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.

Omega 3 and cancer the facts

Saturday, March 15th, 2014

Omega-3 supplements linked to prostate cancer” (Fox News) “Omega-3 supplements could raise prostate risk” (Telegraph)

“Fish oil supplements linked to prostate cancer” (Health News) “Men who take omega-3 supplements at 71 percent higher risk of prostate cancer” (NY Daily News) “Omega-3 supplements may trigger prostate cancer” (Nursing Times) “Hold the salmon: Omega-3 fatty acids linked to higher risk of cancer” (CNN)

The headlines that appeared are familar to everyone , they would be funny due to the idiocy of them if the subject matter and consequences were not so serious.

We all know the way scientific studies are carried out so the assumption would be that researchers gave one group omega3 fish oil supplements, another group placebos.The group that were given the omega3 fish oil supplements were the ones to develop prostate cancer.

That was not the case in fact it couldnt be further from the truth

It is astounding bearing in mind the reporting by the worlds media however the plain and simple fact is no fish oil supplements — or any other kind of supplements, for that matter — were given in this study. This study looked at blood levels of long-chain fatty acids such as those found in fish (EPA and DHA). And even there, the association between higher blood levels and prostate cancer was only found for DHA. No association was found between EPA and prostate cancer, nor between prostate cancer and ALA (the omega-3 found in flax and chia).

The study was as many these days an observational one (based on nested data from participants in the Prostate Cancer Prevention Trial from 1994-2003). There was no experiment, just an observation about what things were found together in this particular population

When you look at the whole picture it does appear that DHA and NOT EPA is responsible – on looking at the individual fatty acids EPA and DHA are very diiferent yet the media chose to lump them together. TakeOmega3 / TO3 is unique amongst omega3 products in that it has high levels of EPA and very low levels DHA .Recent capsule analysis showed each capsule contained 810mg EPA and 120mgDHA . So even taking multiple capsules of T03 it means minimum levels of DHA. Other brands available tend to be high in DHA with minimum levels EPA.

The study however came up with even more contraversial data which the worlds media chose to ignore – the study participents who had the highest levels of trans fats in their blood had the lowest risk of prostate cancer.

We all know that people are recommended to eat fish and avoid foods that are high in trans fats – yet based on the study data ….

Is there an explanation for high levels of DHA in the blood amongst the group at most risk of prostate cancer ?

DHA levels in the blood do not necessarily co relate with dietary intake. The men with the higher levels of DHA weren’t necessarily eating more fish, they werent taking omega 3 supplements (because the researchers said as much). Though DHA levels in the blood go up when you you take omega3 , they can also go up for other reasons, ie a low fat diet

The “highest levels of serum DHA” were based on percentage values, not absolute values. percentage-based measurements can be at times misleading. A higher percentage of DHA might mean a lower percentage of something that the researchers didn’t investigate. (They only looked at eight fatty acids.) Dr Ching Kuang Chow wtote in American Journal of Nutrition “Expressing plasma phospholipid fatty acid composition as a percentage of the total is meaningful only when the total fatty acid content is identical for all subjects,”

A really really important point is thar correlation is not causation – this was an observational study and was not randomized or controlled. What also wasnt highlighted was the following

1. 53 percent of the subjects with prostate cancer were smokers.

2. 64 percent of the cancer subjects regularly consumed alcohol.

3. 30 percent of the cancer subjects had at least one first-degree relative with prostate cancer.

4. 80 percent of the cancer subjects were overweight or obese.

Interestingly, the findings of this study are extremely similar to a previously published article by the same authors in 2011.[2] Reporting their findings from the Prostate Cancer Prevention Trial, the group published data showing DHA to be significantly and positively associated with the risk of high-grade prostate cancer whilst EPA was not.Brasky et al., Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial Am J Epidemiol. 2011 173:1429-39
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Research on the function of EPA and DHA, both together and as individual fatty acids, has progressed significantly in the last couple of decades. Indeed,to just refer to them as omega3 is seriously flawed and is no longer viable. Because DHA is the most unstable of the long-chain omega-3s, the products of lipid peroxidation derived from DHA supplementation may actually counteract the benefits normally attributed to omega-3. Conversley with specific regards to EPA , which T03 is uniquely high in there are a number of ongoing studies which show the chemo protective properties of EPA and its viability in both cancer prevention and treatment .

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.

High Dose EPA / DHA up to 5g / day DO NOT increase risk of bleeding -European Food Safety Authority

Wednesday, January 16th, 2013

European Food Safety Authority state
Long-term supplemental intakes of EPA and DHA combined up to about 5 g/day do not increase the risk of spontaneous bleeding episodes or bleeding complications even in subjects at high risk of bleeding (e.g. taking acetylsalicylic acid or anti-coagulants).or affect glucose homeostasis immune function or lipid peroxidation,

DHA at doses of 2 4 g/day, induce an increase in LDL-cholesterol concentrations of about 3 % which may not have an adverse effect on cardiovascular disease risk, whereas EPA at doses up to 4 g/day has no significant effect on LDL cholesterol.

Supplemental intakes of EPA and DHA combined at doses up to 5 g/day, and supplemental intakes of EPA alone up to 1.8 g/day, do not raise safety concerns for adults.

he Panel concludes that the available data are not sufficient to establish a tolerable upper intake level for n-3 LCPUFA (DHA, EPA, and DPA, individually or combined) for any population group.

At observed intake levels, consumption of n-3 LCPUFA has not been associated with adverse effects in healthy children or adults.

The Panel considers that supplemental intakes of EPA and DHA combined at doses up to 5 g/day, and supplemental intakes of EPA alone up to 1.8 g/day, do not raise safety concerns for the adult population. Limited data are available on the effects of long-term supplementation with these n-3 LCPUFAs at higher doses. The Panel also notes that observed intakes of EPA and DHA from food and food supplements in European populations are generally below these amounts.

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