NSAIDS plus DHA better than NSAIDS in melanoma
 

More straws in the wind.

Melanoma this time.

Another wild thought on the edge - As a short term measure? - Boost threes, NSAIDS to block six and force body to use up six reserves and at the same time cut down omega six intake ???

All significant changes to diet should be discussed with your medical advisor.

RB


Department of Biology, The Chinese University of Hong Kong, Shatin, China. chimingchiu@graduate.hku.hk

Recent studies have suggested the inhibition of cyclooxygenase-2 (COX-2) as strategy to prevent colorectal cancer. In this study, the cytostatic and cytotoxic effects of different non-steroidal anti-inflammatory drugs (NSAIDs), all of them are reported COX inhibitors, were investigated in human skin melanoma A-375 cells. Using BrdU-cell proliferation assay, we showed that 50 and 100 microM of celecoxib (CEL) reduced proliferation of the melanoma cells at 72-h incubations by 34.0% and 82.7%, respectively. As determined by Toxilight-cytotoxicity assay, the drug was only toxic to the cancer cells at 100 microM. Indomethacin (IND) also inhibited the cell proliferation by about 40% at 240 and 480 pM and was only slightly toxic to the melanoma. Neither aspirin (ASP) nor piroxicam (PIR) exhibited cytostatic or cytotoxic effect on the cancer cells. Combinatory effects of the above NSAIDs with dietary docosahexaenoic acid (DHA) on inhibiting growth of the melanoma cells were further elucidated. Each of the NSAIDs, at doses 10-480 pM, was incubated simultaneously with the melanoma cells and 160 pM of DHA for 72 h. Results from MTT assay showed that both CEL and IND, starting from 20 microM. exhibited additive effects on the DHA-induced growth inhibition. ASP also enhanced the DHA-induced growth inhibition by 42.8% at 480 microM. To our surprise, although PRX did not suppress the melanoma growth, the drug at 40-240 microM enhanced the DHA-induced growth inhibition by 15.9-66.4%, respectively. Results from these studies suggest that the anticancer effects of NSAIDs may not be explained solely by their COX-inhibitory activities. Further studies are therefore required to understand their modes of action, before they could be used alone or in combinations with other agents for cancer chemoprevention.

PMID: 16507396 [PubMed - indexed for MEDLINE]

NSAIDS DHA and PROSTATE CANCER
 

The same principle DHA plus NSAID shows possibility in Prostate Cancer.

RB


http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15703837

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. nnarayan@env.med.nyu.edu

Epidemiological studies have provided evidence that high intake of saturated fat and/or animal fat increases the risk of prostate cancer, but on the other hand, diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), present in fish oils were found to reduce the risk. There are indications of an increased expression of immunoreactive PPARgamma in prostatic intraepithelial neoplasia (PIN) and prostate cancer, suggesting that PPARgamma ligands may exert their own potent anti-proliferative effect against prostate cancer. The experimental evidence for the role of cyclooxygenase-2 (COX-2) in prostate carcinogenesis is well established through several investigations. It clearly suggests the need for development of strategies to inhibit COX-2 mediated prostate carcinogenesis. However, administration of high doses of COX-2 inhibitors, such as celecoxib, over longer periods may not be devoid of side effects. We assessed the efficacy of DHA and celecoxib individually and in combination at low doses in three prostate cancer cell lines (LNCaP, DU145 and PC-3) measuring cell growth inhibition and apoptosis, and on the levels of expression of COX-2, nuclear factor-kappaB (NF-kappaBp65), and nuclear receptors, such as PPARgamma and retinoid X receptors (RXR), all of which presumably participate in prostate carcinogenesis. A 48-h incubation of prostate cancer cells with 5 microM each of DHA or celecoxib induced cell growth inhibition and apoptosis, and altered the expression of the above molecular parameters. Interestingly, the modulation of these cellular and molecular parameters was more pronounced in cells treated with low doses of DHA and celecoxib (2.5 microM each) in combination than in cells treated with the higher doses of individual agents. In conclusion, the present study demonstrates for the first time that a combination of lower doses of the n-3 PUFA, and DHA with the selective COX-2 inhibitor celecoxib effectively modulates the above cellular and molecular parameters that are relevant to prostate cancer. This raises the intriguing prospect that the use of low doses of a COX-2 inhibitor in combination with an n-3 PUFA could be a highly promising strategy for prostate cancer chemoprevention while minimizing undesired side effects.

PMID: 15703837 [PubMed - indexed for MEDLINE]

NSAIDS OMEGA 3's and COLON CANCER
 

And Colon Cancer...

A subject for for your oncs?

RB


Chemoprevention and Nutritional Carcinogenesis Program, Institute for Cancer Prevention, American Health Foundation-Cancer Center, Valhalla, NY, USA.

To develop efficient synergistic or additive combinations of chemopreventive and nutritional agents to reduce the risk of colon cancer, experiments were designed to test the application of a selective cyclooxygenase-2 (COX-2) inhibitor together with dietary omega-3 polyunsaturated fatty acids (PUFAs), such as decosahexaenoic acid (DHA). Thus, individual application of celecoxib, a COX-2 inhibitor, DHA, a omega-3 PUFA, and combinations of both were tested for their effectiveness using cell proliferation, apoptosis, and COX-2 expression as markers in the human colon cancer HCA-7 cell line. HCA-7 cells exposed to various subtoxic doses of celecoxib, DHA, or combinations of both were analyzed for inhibition of cell proliferation by trypan blue exclusion and proliferating cell nuclear antigen methods, induction of apoptosis by 4',6-diamidino-2-phenylindole method, and COX-2 by reverse transcription-PCR and Western blot analysis. In addition, we examined the inhibitory potential of celecoxib and DHA on (14)C-arachidonic acid metabolism mediated by COX-2 in the HCA-7 cell line. We found that treatment with celecoxib (50-150 micro M) or DHA (150-225 micro M) individually induces apoptosis and inhibits cell proliferation only at high concentrations in HCA-7 cell lines. A synergistic effect was observed on induction of apoptosis and inhibition of proliferation when cells were exposed to low doses of celecoxib (50-100 micro M) together with DHA (75 micro M). At high concentrations, celecoxib and DHA blocked the increase in COX-2 protein and mRNA expression in HCA-7 cells. Importantly, the inhibition of COX-2 expression was more pronounced in cells treated with low-dose combinations than with individual agents at high concentrations. In addition, celecoxib and DHA at low-dose levels inhibited (14)C-arachidonic acid metabolism (50-85%, P < 0.0001) leading to very low levels of type 2 series prostaglandin formation. These findings provide the basis for the development of combinations of low-dose regimens of a COX-2 inhibitor and omega-3 PUFAs such as DHA for the prevention and treatment of colon cancer. We are currently testing this concept in preclinical models.

PMID: 14985462 [PubMed - indexed for MEDLINE]

omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.
 

Combined with the above I think this might even merit a smiley.


Would omega three plus low dose COX blocker yield even better result.


Maybe deliver as intravenous lipid feed plus cox blocker ?


As ever changes to diet should be discussed with your medical advisor.

RB


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. ydenkins@vetmed.lsu.edu

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

PMID: 15772428 [PubMed - indexed for MEDLINE]

n-3 Polyunsaturated fatty acids (PUFAs) inhibit microvessels in mammary tumours
 

Busy little things these n-3s ?

RB




http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15358633

Institute of General Pathology, Catholic University, L.go F. Vito, 1, 00168 Rome, Italy. g.calviello@rm.unicatt.it

n-3 Polyunsaturated fatty acids (PUFAs) inhibit the development of microvessels in mammary tumors growing in mice. Human colorectal tumors produce vascular endothelial growth factor (VEGF) whose expression is up-regulated in tumor cells by both cyclooxygenase-2 (COX-2) and PGE(2) and directly correlated to neoangiogenesis and clinical outcome. The goal of this study was to examine the capability of n-3 PUFAs to regulate VEGF expression in HT-29 human colorectal cells in vitro and in vivo. Constitutive VEGF expression was augmented in cultured HT-29 cells by serum starvation and the effects of eicosapentaenoic (EPA) or docosahexaenoic acid (DHA) on VEGF, COX-2, phosphorylated extracellular signal-regulated kinase (ERK)-1 and -2 and hypoxia-inducible-factor 1-alpha (HIF-1alpha) expression and PGE(2) levels were assessed. Tumor growth, VEGF, COX and PGE(2) analysis were carried out in tumors derived from HT-29 cells transplanted in nude mice fed with either EPA or DHA. Both EPA and DHA reduced VEGF and COX-2 expression and PGE(2) levels in HT-29 cells cultured in vitro. Moreover, they inhibited ERK-1 and -2 phosphorylation and HIF-1alpha protein over-expression, critical steps in the PGE(2)-induced signaling pathway leading to the augmented expression of VEGF in colon cancer cells. EPA always showed higher efficacy than DHA in vitro. Both fatty acids decreased the growth of the tumors obtained by inoculating HT-29 cells in nude mice, microvessel formation and the levels of VEGF, COX-2 and PGE(2) in tumors. The data provide evidence that these n-3 PUFAs are able to inhibit VEGF expression in colon cancer cells and suggest that one possible mechanism involved may be the negative regulation of the COX-2/PGE(2) pathway. Their potential clinical application as anti-angiogenic compounds in colon cancer therapy is proposed.

PMID: 15358633 [PubMed - indexed for MEDLINE]

65% of pregnant canadian women below minimum omega three recommendation
 

Thought provoking.

Particularly when considered in light of Canadian trial on trans fats in breast milk etc above - implications for wider community - etc.

RB

Directly Quantitated Dietary (n-3) Fatty Acid Intakes of Pregnant Canadian Women Are Lower than Current Dietary Recommendations1

http://jn.nutrition.org/cgi/content/full/135/2/206

Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian
 

This is interesting in that it gives an idea as to dietary fat profiles, and underlines the low levels of DHA EPA.

From the previous post some of this will be trans.

There are suggestions that the preference given to the omega three pathway drops after the 3 6 ratio gets lower than 1:7.

IF women are getting insufficient DHA EPA to provide for their infants, and the pathway for fabrication are restricted by trans fats, poor three six ratios, cox blockers in some instances aspirin, any inherent deficiency etc they can only provide by drawing on their own reserves.

Trials suggests sources include the brain. (A factor in post natal depression?).

Other trials suggest that in the absence of replenishment this reduction in the mothers stores becomes a trend.

The table below is helpful in that it gives an indication of the long chain three six balance in meat eggs fish etc.

RB


Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women1,2,3

http://www.ajcn.org/cgi/content/full/77/2/473

http://www.ajcn.org/cgi/content/full/77/2/473/T3

AA EPA DHA
mg/d
Fatty fish 3.5 ± 0.6 (0.0–16.0) 9.1 ± 3.3 (0.0–88.1) 83.5 ± 14.4 (0.0–384.4)
Lean fish 3.1 ± 0.3 (0.0–10.7) 14.9 ± 1.6 (0.0–51.6) 27.4 ± 3.0 (0.09–5.3)
Shellfish and crustaceans 7.6 ± 1.2 (0.0–38.8) 16.9 ± 2.7 (0.0–86.2) 14.7 ± 2.4 (0.0–75.0)
Total fish and seafood 14.2 ± 1.8 (0.0–50.8) 50.4 ± 6.1 (0.0–58.7) 125.7 ± 17.0 (0.0–426.5)
Chicken 34.6 ± 3.8 (0.0–120.1) 3.8 ± 0.4 (0.0–13.3) 6.7 ± 0.7 (0.0–23.2)
Turkey 24.3 ± 5.7 (0.0–188.9) 1.1 ± 0.2 (0.0–8.2) 3.8 ± 0.9 (0.0–29.1)
Total poultry 58.8 ± 6.5 (0.0–202.9) 4.9 ± 0.5 (0.0–13.3) 10.4 ± 1.1 (0.0–31.8)
Beef and beef products 20.5 ± 0.2 (0.0–63.1) 15.7 ± 1.6 (0.0–4.8) 2.7 ± 0.3 (0.0–8.5)
Pork and pork products 14.4 ± 1.8 (0.0–49.1) 1.4 ± 0.1 (0.0–4.9) 1.4 ± 0.1 (0.0–4.9)
Lamb and lamb products 1.5 ± 0.3 (0.0–8.7) 1.2 ± 0.3 (0.0–6.7) 0.4 ± 0.1 (0.0–2.2)
Total meat 36.4 ± 3.3 (0.0–97.4) 18.4 ± 1.8 (0.0–43.5) 4.6 ± 0.4 (0.0–11.9)
Eggs 32.7 ± 3.6 (0.0–82.7) 0.31 ± 0.04 (0.0–0.9) 14.6 ± 1.6 (0.0–37.0)
Total 112.0 ± 7.8 (0.5–275.8) 73.5 ± 6.3 (0.4–186.8) 153.6 ± 17.9 (17.7–518.6)

I don't mean to be a bad girl here, but I hope to provoke thought on this issue of diet. Diet plagues me... I have had a very good diet for a long time, and still managed to get breast cancer at age 28 because of my genetics. Is it possible that people in other countries have better genetics because they are in a different gene pool - per say? Over time, I have heard that if you take a chinese woman to the US and feed her american foods, that she will develop the same risk for breast cancer, so I feel compelled that there may be genetic factors that supercede dietary factors. Meaning, if you have bad genetics, no matter what you do, you will get cancer. If you have good genetics, you may be able to sway your risk if you eat better. But do you have any way of knowing what your risk are if you could potentially get a bad genetic combination at conception? I think it's always a good idea to eat right, but I wouldn't hold out my hopes on it preventing cancer or curing our cancer.

From the little I have read on genetics there are clearly those who carry higher risks of particular diseases.

Dietary change is not going to eliminate disease but can be a significant modifier of risk. For example I have previously posted this tale but I have read that vascular / heart disease was so rare at the turn of the 1900s that students would rush to see a case as they did not want to miss the opportunity.

Around 70 % is the figure most generally quoted for the increase of western diseases over those with more culturally traditional diets, and lack of access to refined western food.

Diet can and does manipulate expression of genes by significant amounts. ("Expression" Our gene pool is largely similar but we use or expression different amounts according to environmental factors - Most have the same basic ingredients in the kitchen cupboard but they "express" it in their cooking in different quantities according to cultural factors. )

I have previously tried to formulate a scenario where those who considered themselves on a very healthy diet high in polyunsaturates low in fat etc in fact had high omega six compared to omega three. As I keep reiterating it is not about absolute quantities it is about balance.

All of the evidence is that diet does pay a large part in the overall risk factor when looking at issues on a population wide basis.

BC is a dreadful disease. I cannot begin to understand how you feel having contracted it so young. If you have been healthy it must feel like a double whammy.

I too have read lots of health books etc, juiced, etc for many years and it was only about a year ago that I realised that my avid pursuit of polyunsaturates was actually very bad news as it was pushing my omega three six balance way out from the ideal of somewhere around one to one ( or may be even 2:1). I suspect I was not the only one falling into this trap.


My limited field of knowledge relates to what I have read on fats. I would urge all to look VERY closely at their dietary intake in terms of balancing the omega threes and sixes. This can only be done by knowing or looking up the approximate fat contents of the foods you eat until you get to have an reasonable idea of what you are likely to be consuming. For most on a western diet omega three supplementation will be needed. Sources are limited so this is likely to include flax seed and oily fish or fish oil, or algae based products for vegetarians.


RB

Here is a link where change expression of genes in the brain for rate fed high fish oil or high perilla diets is shown by reference to a standard diet.

The trials are looking at the impact of fats on the brain ageing alzheimer's etc. This is one of many in the general subject area.

I have no idea as to the significance of various genes.

I just post the chart to try and illustrate the point that changes in diet and particularly fats can alter the ways our bodies work even in the way we use the genetic ingredients available to us.

Significantly

In numerous subtle ways

At very fundamental levels

Different recipe for different cakes some of which will work and some which will not. I suspect nature is no different from cookery - go beyond certain parameters and your cake mix will not work.


http://www.pnas.org/cgi/content/full/99/5/2619/T5


and the link to the trial


http://www.pnas.org/cgi/content/full...7faf8fdb716645

I guess my point was that I watched my mother "juice" herself to her grave - thinking it would extend her life. She got 4 months, and the doctors thought she would have had 6. She was a healthy 33 year old woman with a good BMI and on a healthy food kick like you wouldn't believe... Then her son died at age 12 from Stage 4 Rhabdomyosarcoma, that was originally Stage 2 when he was 5. Then I got cancer at 28, early stage 2a and I was healthy... Then my daughter got cancer at age 5, stage 2 Adrenal Cortical Carcinoma... then she had a local recurrance. She was our healthiest eater, and of course at a normal BMI. Then I had a recurrance, and BOOM stage 4 for me. Then we found out that we had Li-Fraumeni syndrome. Back in 1991, they told us our p53 gene was normal. Now they told us our p53 gene was mutated. The far end of the gene was where the mutation was, which they didn't know about in 1991. So I just hesitate to hear so many hold out hope that diets were the cause of their cancers. For years I tried to "do the right thing" to prevent cancer. I asked the doctor in tears, why I couldn't have prevented it when I was doing so many things to prevent it. He said "Your risk was 80% of developing cancer before the age of 50. In your family, I would guess that it would be more like 80% before the age of 30. With odds like that, diet wouldn't prevent your cancer. I've seen hundreds people try to prevent cancer with diet, knowing they had the 'cancer gene', and failure was almost 100%." His field of study was Brazilian children with adrenal cortical carcinoma with a p53 mutation called Arg337Cys. He also studies genetic retinal cancer that almost 100% get before the age of 5 with the gene. You can probably see now why I am on the other side of the fence. It failed for me, my mother, my brother, my daughter, and probably will fail for my other 2 children, and hundreds of patients of my daughter's doctor. We have all tried to eat the "right diet" and it has failed us all. I think the only case I know of is an author with stage 4 breast cancer, named Jane Plant, who has been cancer free for a while now after practically eliminating cow and dairy products. And then I guess I know about Lance Armstrong, but he ate like 5 apple fritters every day...

Who Knows???
 

My husband has made vast improvements in his "heart health" after a heart attack 10 years ago. I have watched him exercise, eat "amazing things", and take a handful of supplements.

Now, I am working hard to eat right, exercise everyday, and take some vitamins and fish oil.

But I must confess that I don't have a clue whether it will help with my cancer. I just know when I eat those veggies and fruit and drink my tons of water, I feel better to fight the next fight!

I'm so glad that I have access to so many who are learning so much and are willing to share. Thanks a million!
ma

Thank you for your post.

Life has certainly dealt you all a desperately difficult hand, and you appear to be dealing with it very bravely.

I very clearly understand your point and position.

I have never claimed diet will cure cancer. I have just suggested that on a population wide basis it will reduce risks for some, and that specifically that there are a significant number of trials implicating fat intake in cancer risk and inflammatory pathways etc.

I have also always said there that the commonly quoted figure of differential in "western" disease from non "western" populations is about 70%. This leaves a very large 30% for whom it would be reasonable to assume that diet if that is the factor has no effect.

I still hold to a position that there is evidence that balancing the omega threes and sixes will moderate the inflammatory pathways, and assist in maintaining the immune system, general health, and moderate risks based on the trials I have read.

Based on the trials being conducted research organisations are sufficiently interested to explore the impacts of lipids on health, and some products developed in consequence, some products being legislated against in some countries eg trans fats etc.

Again I understand your position, and can only begin to imagine your frustration. Please do not associate me with those that are holding diet as the only way to go, or who does not appreciate the huge advances in medicine.

There is room for both and it is important we do not lose sight that the body is immensely complex and has developed this complexity in relation to its environment and the limiting factors in that environment, and so much is simply not understood.

I wish I had the knowledge and expertise to relate what I have read over the last year to your very specific circumstances but I don't.

I have not begun to walk in your shoes and experience the see-saw of hurt and anguish that you must have been through and continue to face.

Thank you for your post. It is important for all of us to know and try and understand if that is ever possible the impossible difficulties in life that many have to face.

RB


PS please find below the results of a search on the ncbi site for "p53 gene and fats" which might suggest fats have a bearing on P53 activity which may or may not be relevant in your circumstances just in case of any interest to you or your doctor.


http://www.ncbi.nlm.nih.gov/entrez/q...arch&DB=pubmed

1: Wu B, Iwakiri R, Ootani A, Tsunada S, Fujise T, Sakata Y, Sakata H, Toda S, Fujimoto K. Related Articles, Links
Free Full Text Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.
Exp Biol Med (Maywood). 2004 Nov;229(10):1017-25.
PMID: 15522837 [PubMed - indexed for MEDLINE]

2: Chi TY, Chen GG, Lai PB. Related Articles, Links
Abstract Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells.
Cancer J. 2004 May-Jun;10(3):190-200.
PMID: 15285929 [PubMed - indexed for MEDLINE]

3: Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS. Related Articles, Links
Abstract Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.
Mutat Res. 2003 Oct 29;531(1-2):25-36. Review.
PMID: 14637245 [PubMed - indexed for MEDLINE]

4: Hanibuchi M, Sone S. Related Articles, Links
No abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2002 May;60 Suppl 5:63-6. Review. Japanese. No abstract available.
PMID: 12101751 [PubMed - indexed for MEDLINE]

5: Shabany K, Chiu PC, Raghian A, Chang KW, Solt DB. Related Articles, Links
Abstract Rapid in vivo assay for topical oral cancer chemopreventive agents.
Int J Oncol. 2002 Jul;21(1):159-64.
PMID: 12063563 [PubMed - indexed for MEDLINE]

6: Perjesi P, Pinter Z, Gyongyi Z, Ember I. Related Articles, Links
Abstract Effect of rancid corn oil on some onco/suppressor gene expressions in vivo. A short-term study.
Anticancer Res. 2002 Jan-Feb;22(1A):225-30.
PMID: 12017293 [PubMed - indexed for MEDLINE]

7: Diggle CP, Pitt E, Roberts P, Trejdosiewicz LK, Southgate J. Related Articles, Links
Free Full Text N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function.
J Lipid Res. 2000 Sep;41(9):1509-15.
PMID: 10974058 [PubMed - indexed for MEDLINE]

8: Yano S, Sone S. Related Articles, Links
Abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2000 May;58(5):1017-22. Review. Japanese.
PMID: 10824542 [PubMed - indexed for MEDLINE]

9: Taylor DD, Gercel-Taylor C, Weese JL. Related Articles, Links
Abstract Modulation of colon tumor oncogene expression by cancer patient-derived lipids.
J Surg Oncol. 1996 Sep;63(1):46-51.
PMID: 8841466 [PubMed - indexed for MEDLINE]

Thanks Rhonda, great nutritional links!
 

A bit late Rhonda, but thank you for your nutritional links...teamed up with RB's data, it was extremely helpful. My sis in law has scleroderma and this information will be helpful to her as well. You and RB are sharing a real wealth of information and "food" for thought!
Love Kim from CT

Julierene.

Re P53 gene mutation and fats.

The technicalities are beyond me but the generality seems to be that oxidised fats and particularly omega 6 (AA archidonic acid is a product of omega six.) can induce gene mutation, AND it seems to suggest the body may have some ability to repair them...? (thanks I had not seen anything about this subject before)

"HNE-dG adducts were detected exclusively in incubations with AA."

"It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers,"

"Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation."





One for your doctor if of interest?


RB







http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Biochemistry. 2003 Jul 1;42(25):7848-54. Related Articles, Links
Click here to read
Mutational spectrum and genotoxicity of the major lipid peroxidation product, trans-4-hydroxy-2-nonenal, induced DNA adducts in nucleotide excision repair-proficient and -deficient human cells.

Feng Z, Hu W, Amin S, Tang MS.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.

trans-4-Hydroxy-2-nonenal (4-HNE), a major product of lipid peroxidation, is able to interact with DNA to form 6-(1-hydroxyhexanyl)-8-hydroxy-1,N(2)-propano-2'-deoxyguanosine (4-HNE-dG) adducts, but its genotoxicity and mutagenicity remain elusive. It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers, particularly in hepatocellular carcinoma. This G.C to T.A transversion at codon 249, however, has been thought to be caused by etheno-DNA adducts induced by the endogenous metabolite of 4-HNE, 2,3-epoxy-4-hydroxynonanal. We have recently found that 4-HNE preferentially forms 4-HNE-dG adducts at the GAGG*C/A sequence in the p53 gene including codon 249 (GAGG*C). Our finding supports the possibility that G.C to T.A mutations at codon 249 may be induced by 4-HNE-dG adducts. To investigate this possibility, we determined the mutational spectrum induced by 4-HNE-dG adducts in the supF gene of shuttle vector pSP189 replicated in human cells. We have found that 4-HNE-dG adducts are mutagenic and genotoxic in human cells, and that G.C to T.A transversions are the most prevalent mutations induced by 4-HNE-dG adducts. Furthermore, 4-HNE-dG adducts induce a significantly higher level of genotoxicity and mutagenicity in nucleotide excision repair (NER)-deficient human and Escherichia coli cells than in NER-proficient cells, indicating that NER is a major pathway for repairing 4-HNE-dG adducts in both human and E. coli cells. Together, these results suggest that 4-HNE-dG adducts may contribute greatly to the G.C to T.A mutation at codon 249 of the p53 gene, and may play an important role in carcinogenesis.

PMID: 12820894 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Chem Res Toxicol. 2002 Mar;15(3):367-72. Related Articles, Links
Click here to read
Formation of cyclic deoxyguanosine adducts from omega-3 and omega-6 polyunsaturated fatty acids under oxidative conditions.

Pan J, Chung FL.

Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, Valhalla, New York 10595, USA.

The discovery of the cyclic 1,N(2)-propanodeoxyguanosine adducts of acrolein (Acr), crotonaldehyde (Cro), and t-4-hydroxy-2-nonenal (HNE) as endogenous DNA lesions from lipid peroxidation has raised questions regarding the role of different types of fatty acids as sources for their formation. In this study, we carried out reactions at pH 7 and 37 degrees C with deoxyguanosine 5'-monophosphate and omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA), linolenic acid (LNA), and eicosapentaenoic acid (EPA); or omega-6 PUFAs, including linoleic acid (LA) and arachidonic acid (AA), each in the presence of ferrous sulfate. The formation of Acr, Cro, and HNE-derived 1,N(2)-propanodeoxyguanosine adducts (Acr-, Cro-, and HNE-dG) in the incubation mixture was determined by reversed-phase HPLC analysis. The results showed that Acr and Cro adducts are primarily derived from omega-3 PUFAs, although Acr adducts are also formed, to a lesser extent, from oxidized AA and LA. HNE-dG adducts were detected exclusively in incubations with AA. The kinetics of the formation of these adducts was determined during incubations for 2 weeks and 5 days. The rate of Acr adduct formation was about 5-10-fold that of Cro adducts, depending on the type of PUFAs, and the rate of formation of HNE adducts from AA was also considerably slower than that of Acr adducts. Unlike other cyclic adducts, the formation of Acr adducts was independent of types of PUFAs, but its yield was proportional to the number of double bonds in the fatty acid. Only one of the isomeric Acr adducts was detected, and its stereoselective formation is consistent with that observed previously in vivo. Two previously unknown cyclic adducts, one derived from pentenal and the other from heptenal, were also detected as products from omega-3 and omega-6 fatty acids, respectively. This study demonstrated the specificity for the formation of the cyclic adducts of Acr, Cro, and HNE and other related enals by oxidation of omega-3 and omega-6 PUFAs. These results may be important for the understanding of the specific roles of different types of fatty acids in tumorigenesis.


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Mutat Res. 2003 Oct 29;531(1-2):25-36. Related Articles, Links
Click here to read
Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.

Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS.

Division of Carcinogenesis and Molecular Epidemiology, Institute for Cancer Prevention, American Health Foundation Cancer Center, Valhalla, NY 10595, USA. fchung@ifcp.us

The cyclic 1,N(2)-propanodeoxyguanosine adducts, derived from alpha,beta-unsaturated aldehydes or enals, including acrolein (Acr), crotonaldehyde (Cro), and trans-4-hydroxy-2-nonenal (HNE), have been detected as endogenous DNA lesions in rodent and human tissues. Collective evidence has indicated that the oxidative metabolism of polyunsaturated fatty acids (PUFAs) is an important pathway for endogenous formation of these adducts. In a recent study, we examined the specific role of different types of fatty acids, omega-3 and omega-6 PUFAs, in the formation of cyclic adducts of Acr, Cro, and HNE. Our studies showed that the incubation of deoxyguanosine 5'-monophosphate with omega-3 or omega-6 fatty acids under oxidative conditions in the presence of ferrous sulfate yielded different amounts of Acr, Cro, and HNE adducts, depending on the types of fatty acids. We observed that Acr- and Cro-dG adducts are primarily formed from omega-3, and the adducts derived from longer chain enals, such as HNE, were detected exclusively from omega-6 fatty acids. Acr adducts are also formed from omega-6 fatty acids, but to a lesser extent; the yields of Acr adducts are proportional to the number of double bonds present in the PUFAs. Two previously unknown cyclic adducts, one from pentenal and the other from heptenal, were detected as products from omega-3 and omega-6 fatty acids, respectively. Because omega-6 PUFAs are known to be involved in the promotion of tumorigenesis, we investigated the role of HNE adducts in p53 gene mutation by mapping the HNE binding to the human p53 gene with UvrABC nuclease and determined the formation of HNE-dG adducts in the gene. The results showed that HNE-dG adducts are preferentially formed in a sequence-specific manner at the third base of codon 249 in the p53 gene, a mutational hotspot in human cancers. The DNA repair study using plasmid DNA containing HNE-dG adducts as a substrate in HeLa cell extracts showed that HNE adducts are readily repaired, and that nucleotide excision repair appears to be a major pathway involved. Together, results of these studies provide a better understanding of the involvement of different PUFAs in DNA damage and their possible roles in tumorigenesis.

Publication Types:

* Review


PMID: 14637245 [PubMed - indexed for MEDLINE]

Simple explanation of 6 to 3!
 

http://en.wikipedia.org/wiki/Omega-6_fatty_acid

This made it simple to me. I followed the other links on the page and found more good information to help me understand (at least these people's opinion) the importance of 6 to3. I'm still reading and I'm beginning to understand. I'm getting why my husband's health changed and the doctors thought he'd been on statins when he had just eaten and supplemented right. If he can do it, I can too. Thanks to all who keep making me learn!
ma

The Blame Game
 

I just received my copy of "Cure" magazine, Summer issue Volume 5, Number 2 2006.

On page 14 there is an article entitled "The Blame Game, Moving past myriad rationales for cancer guilt"

Here is an excerpt from the article:

"Labels lead to guilt, which can be a huge burden for newly diagnosed patients because it lurks around almost every turn. We feel guilt about causing our cancer, about having our families go through it, about not being able to do what we did before, if only for a short time. Then there are the financial burdens, and the list goes on. Particular guilt comes with behaviors linked to cancer: smoking, sun overexposure, a common sexually transmitted disease and obesity.

It's not unusual to try and find an answer to why cancer occurs, says Kymberley Bennett, PhD, assistant professor of psychology at Indiana State University in Terre Haute. "With any stressor, and cancer is a big stressor, we try to figure out why it happened to us," she says. "Ultimately, we want to try to identify something that we can, in turn, control."

And stressing about the cause of cancer can lead to additional stress, says Dr. Bennett, who recently led a study of 115 women newly diagnosed with breast cancer that showed that those who blamed themselves for their cancer showed higher levels of distress than those who didn't. The findings also suggested that self-blame negatively affected a patient's ability to psychologically adjust throughout the year following diagnosis."

I think the danger here is that of blaming the victim. The unpalatable truth is, no one knows what causes cancer. Period.

R.B. may be correct in his(?) assertions that Omega 3's and 6's play some sort of a role in cancer development/treatment. The fact is, however, that despite all of our very best efforts many of us here on this forum will die untimely deaths and that is not our fault. I can't help but bristle whenever I catch a nasty whif of blame.

Yes, R.B., I am taking Fish Oil supplements. I will probably die from breast cancer anyway.

I admire your dedication to research, however, perhaps on your wife's behalf? Unless I am mistaken, and you a a female. Clearly you are a warrior, and every country needs its warriors, whatever your sex may be.

Mary

I don't see WHAT difference it makes as to RB's sex...
 

a wealth of information comes from this source and I for one am PISSED off as to the negativity that comes out on the board (we have lost a lot of good members...Gina, ALMOST lost AL and many others...due to people not just voicing their opinion and offering constructive criticism, but adding unnecessary comments) not to mention that there ARE male breast cancer survivors on the board. I belive that cancer has MANY causes (ie, smoking, poor diet, genetics, environment, lack of exercise, etc.) and while some of us may have gotten it because of 1 cause, others may have gotten it for another (or MANY causes). I choose to do EVERYTHING I can to not get it again (surgery, drugs, diet, exercise, yoga, prayer) and do offer myself 1 cheat day a week so as to not feel deprived. Mary, you go ahead and die of cancer (since that's what you choose to believe), but I and all the OTHER survivors choose to LIVE, some WITH cancer and others WITHOUT. Understand that there are SEVERAL people on the board who offer helpful information that have not had breast cancer, BUT they provide valuable information for those that do. I'm done.

Rhonda

Thank you for your response.

Blame.

I apologise if my posts allow interpretation as blame. This is not in any way my intention. In life we are where we are - changing the past is not an option.


Control.

It is widely accepted that diet can influence health.

IF improved diet gives people something they have some small sense of control over it seems to me providing it is not obsessive that any sense of control must be good news.

If it achieve really positive benefit so much the better.


Implication of fats in cancer.

I am certain fats are implicated in the risk of some cancers and a wide number of other inflammatory based diseases, a number of issues of the nervous system including depression, as well as the immune system and general health. This is based on extensive reading of trials and the works of others. I would challenge anybody with the time to read what I have seen to come to a different conclusion

Gender.

Thanks for the compliment but definatively male, and always so.


Reasons for posting

Various including previous contact with BC sufferer, time on my hands, a need to be kept mentally occupied, a sense that the issue of fats is one that needs airing and the answers found, the implications are too enormous to ignore, and once you have glimpsed them they are not easily put back in the box. Answering questions make one check things, prompts new directions of thought, and gives one a sense of being of a little use.


Causes of cancer.

Human nature and the human dynamic. There is no "profit" (in the widest sense job opportunities, praise, conferences, funding etc.) in finding cancer causes, except where so obvious that they may involve the companies in a law suit. There have been suggestions that trans fats may be problematic for human consumption and yet the level of research on trans fats is moderate. For example a search on PubMed for trans fats and herceptin produces about 1700 for both but trans fats are consumed by probably billions and if as suggested they have negative health impacts the health / life cost will be truly huge huge in global terms. But there is not "profit" in researching / restricting trans fats and the situation will not change except by government intervention, public outcry, or sufficient potential medical downsides to justify the rsik of lawyers involving themselves in a group action. It is suggested they have no nutritional advantage so why are we conducting an experiment on global health?

I am not complaining about the amount of research on herceptin which is clearly making a huge difference to many women. I merely making the point that research and new products is "sexier" than prevention at very many levels - and the reality is we to give equal attention to both side of the problem cause and treatment. How that is to be achieved is another issue.


RB

Of course, Rhonda, none of us on this board have chosen or ever would have chosen breast cancer. My friend Katie, who died two weeks back, never chose to have this horrible disease. I am not trying to be negative, but I did find the article in Cure magazine to be thought provoking.

Personally speaking, from the day I was diagnosed I asked myself "Why has this disease happened to me?". Further I wondered "and why did I get the worst variety (Her2Neu) of the worst?" I think it's probably the number one question we all ask ourselves. There's even a group called "Why Me?".

Like so many other sufferers, I would try just about anything to get a survival advantage. I am currently taking Herceptin, A/I's, have had radiation of my body and my brain. I even sought the help of a faith healer. Much to my husband's chagrin I am eating broccoli and salads like a rabbit and do take fish oil. But I can't believe that this is my fault. Or your fault. Or Katie's fault. Faults, I think, are character defects and not diseases.

This is a wonderful site and I have gained much support and inspiration here. For me the struggle and the challenge of breast cancer is not just physical, although it certainly is that. Today I am struggling with pain and this is a brand new thing for me. The bigger struggle is psychological, feeling like I have any control at all in a situation where there is none. Trying to move past anger that this has happened to me at all. Trying to feel like cancer is not my fault, that it is not something I have mistakenly brought on myself by some unknown means. Struggling to feel valuable to my family, my friends and society, that I still have value even though my body may be under assault. That I am inherently valuable, not only for the services that I provide but just by being me. I imagine that these struggles are not isolated to me alone, but are common to everyone who comes to the board. They are the tie that binds.

Mary

Mary mary

A powerful comment. We are all "frail" flawed and human it is part of our condition.

At the risk of being repetitive I note that many posts say I take threes or fish oil etc as part of their personal program, but few make reference to balancing the sixes.

Please excuse the "shout" but I wonder if I am managing to convey the other half of the omega 3/EPA DHA message which is

PLEASE BALANCE THE SIXES AND THREES.

Please do excuse me if you have already more than got that part of the message too.

Fish oil together with flaxseed or oil (personal preference see flax seed debate) according to reports is really beneficial at lots of levels, BUT the one that is at the root of the INFLAMMATORY PATHWAYS, and IN VAST excess in the average diet is OMEGA SIX family which includes the key player AA Arachidonic acid. Omega three six ratios in the US are reported as in some cases up to 1:50. The often suggested best average is 1:1. The pathways to make the longer chain omega threes are reported to go astray around one 1:7.

So for most it is necessary to look at your omega six intake, cut right down or out on vegetable, nut and seed oils except those exceptions that are high in three, moderate nut intake, and beware of processed food. (Me too - this is where this quest started when I realised how skewed my own intake was)

Thanks for your post. It sounds like you have been through a great deal.

RB

"There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs."


By the same author as the initial posts.

RB





http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: J Am Coll Nutr. 2002 Dec;21(6):495-505. Related Articles, Links
Click here to read
Omega-3 fatty acids in inflammation and autoimmune diseases.

Simopoulos AP.

The Center for Genetics, Nutrition and Health, Washington, DC 20009, USA. cgnh@bellatlantic.net

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

Publication Types:

* Review


PMID: 12480795 [PubMed - indexed for MEDLINE]

Omega three - improved immune markers - significantly decreased IL6
 

This fits in with other trials but good to see it in writing.

No mention of looking at omega six intake and effect of reductions which could possibly going to produce significant effect as well.

Some trials please


RB





http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum


1: Br J Nutr. 2003 May;89(5):679-89.Click here to read Links
Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects.

* Wallace FA,
* Miles EA,
* Calder PC.

Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.

Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) oil (rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)) or fish oil (FO; rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in the diet can decrease a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18-39 years were randomised to receive placebo or 3.5 g ALNA/d or 0.44, 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks. The EPA:DHA ratio in the FO used was 1.0:2.5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-10 or interferon-gamma by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d.

PMID: 12720588 [PubMed - indexed for MEDLINE]

Men 6g DHA a day reduced PGE2 LTB4 response to lipopolysacceride by 60-75%
 

"DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding."

PGE2 is a percusor of aromatase which is a percusor of oestrogens.

So as a preventative in terms of oestrogen restriction DHA at higher doses may be a useful dietary additive. See previous post as to DHA fish oil dosages. Low dosages were reported as not showing the same effects.

Again omega six intake / reduction not examined to determine impact.

Please see posts on balancing omega threes and sixes.

Please do talk to youe medical advisor about significant dietary changes.

You can always think about printing the trials to take i to save you trying to explain. Any feed back positive or negative is most welcome.

RB

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract


1: Lipids. 1999 Apr;34(4):317-24. Related Articles, Links

Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men.

Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Ferretti A, Erickson KL, Yu R, Chandra RK, Mackey BE.

USDA, ARS, Western Human Nutrition Research Center, Presidio of San Francisco, California 94129, USA. Dkelley@whnrc.usda.gov

The purpose of this study was to examine the effects of feeding docosahexaenoic acid (DHA) as triacylglycerol on the fatty acid composition, eicosanoid production, and select activities of human peripheral blood mononuclear cells (PBMNC). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of Western Human Nutrition Reach Center. Four subjects (control group) were fed the stabilization diet throughout the study; the remaining seven subjects were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg D alpha-tocopherol acetate per day. PBMNC fatty acid composition and eicosanoid production were examined on day 30 and 113; immune cell functions were tested on day 22, 30, 78, 85, 106, and 113. DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding. These parameters remained unchanged in the subjects fed the control diet. B-cell functions as reported here and T-cell functions that we reported previously were not altered by DHA feeding. Our results show that inhibitory effects of DHA on immune cell functions varied with the cell type, and that the inhibitory effects are not mediated through increased production of PGE2 and LTB4.

Publication Types:

* Clinical Trial


PMID: 10443964 [PubMed - indexed for MEDLINE]

This is a link which sort of explains what a lippolysacceride is in this complex.
Something to get the prostaglandin out of bed (the membrane) and off to work (immune defence). If somebody can could confirm this it would be helpful.

http://en.wikipedia.org/wiki/Lipopolysaccharide

Mice were fed a high omega six diet 43 % energy from corn oil (high omega six source).

Estrogen receptors up SIX fold.

And equally mind boggoling the potential fro offspring to carry a greater risk level. I have seen this suggested elsewhere.

(ER is not the same as HER which relates to growth factors - it took me a while to work that one out - please tell me if I am wrong!)




"In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice."


RB




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9485017

1: Cancer Res. 1998 Feb 15;58(4):654-60. Links
Consumption of a high-fat diet alters estrogen receptor content, protein kinase C activity, and mammary gland morphology in virgin and pregnant mice and female offspring.

* Hilakivi-Clarke L,
* Stoica A,
* Raygada M,
* Martin MB.

Lombardi Cancer Center, Department of Psychiatry, Georgetown University, Washington, DC 20007, USA.

Previous studies have shown that a diet high in polyunsaturated fatty acids increases mammary tumor incidence in adult and pregnant mice and rats and in the female offspring. The present study investigated whether a high-fat diet alters the number of estrogen receptor (ER) binding sites and protein kinase C (PKC) activity in the mammary gland of these animals. In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epithelial tree were studied also. BALB/c mice were kept on a diet containing either 43% (high-fat) or 16% (low-fat) calories from corn oil, which consists mostly of n-6 polyunsaturated fatty acids, for 1 month. In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice. In pregnant mice, a high-fat diet increased ER binding sites by 61% and PKC activity by 51%. In contrast to adult and pregnant mice, females exposed to a high-fat diet only in utero through their pregnant mother exhibited a significantly reduced number of mammary ER binding sites by age 45 days (78% decrease) and a reduction in PKC activity by ages 30 and 100 days (44 and 20% decrease, respectively). The mammary epithelial tree of the high-fat offspring contained more terminal end buds and was less differentiated than that of the low-fat offspring. These findings show that consumption of a high-fat diet increases ER and PKC in the adult and pregnant mouse mammary gland, perhaps contributing to the fat-induced promotion of mammary tumorigenesis. In contrast, reduced ER and PKC following a high-fat exposure in utero may be associated with increased susceptibility to carcinogenesis, possibly due to an increased number of terminal end buds that are the sites of neoplastic transformation in the mammary gland.

PMID: 9485017 [PubMed - indexed for MEDLINE]

greek diet and cancer
 

i live in greece. unfortunately the hospitals here in greece are full of cancer patients, especially in crete.
my mother has metastatic breast cancer, since she was a child she followed a very healthy nutrition but unfortunately this did'nt helped to prevent the disease.
The truth is that -at the moment- she never had symptoms of the disease. she feels very good, full of energy, she does a lot of things every day.
from this point of view, maybe this could be a sign that greek diet helps cancer patients to have a good qol and live with dignity.
take care
lorenzo

Thank you for your post.

I am glad your mother has a good qol.

I was sorry to hear of the suggestion of high numbers of cases in Crete. I would be positive to know of corners that had managed to avoid the increase that are being seen in numbers.

The articles do refer to the pre 1960 diet, and I guess was based on then (1960) statistics.

The introduction in dietary changes, vegetable oils, vegetable oils in processed foods etc may have changed the comparative cancer ratio bringin them more in line with other western countries since then.

It is not something I have specifically looked at.

Also sadly there are always going to be those for whom diet may offer better qol but have some sort of predisposition, exposure to other environmental factors etc.

Thank you agin for your post.

I hope your mother continues to enjoy a good qol. grape vines, Tavernas feta, juicy fresh peaches, local honey, feta basil and tomatoes come to mind but that was some years ago.

RB

RB thanks so much for the omega three balancing dietary posts which are prudent for overall healthy living and to help prevent many disease conditions. I think it has made me more conscious of what I, my kids and husband eats which is a good thing. Afterall, we are what we eat to a certain degree, and also as the above abstracts suggests we are what mother ate while we were in utero as well. Of course, I agree that genetics and environment also plays into the equation and defines our weakness, strengths and our suspectibility to disease.

I have see trial that suggest negative impacts for trans fats including blocking the pathways to make long chain fats which could compromise immune function, exacerbate related conditions, and as previously posted potentially impact on risks of cancer etc.

Margerines come in different "shapes" and sizes with different levels of polyunsaturates contents and thrans fats etc.

But you may like to try this with your brand, and some butter as a contol.

The author has a way with words.

RB





http://www.healthy-communications.co...margerine.html

Subject Butter or Parkay?
Date Sat, 18 Mar 2006

Margarine was originally manufactured to fatten turkeys. When it killed the
turkeys, the people who had put all the money into the research wanted a
payback so they put their heads together to figure out what to do with this
product to get their money back. It was a white substance with no food
appeal so they added the yellow coloring and sold it to people to use in
place of butter. How do you like it? They have come out with some clever
new flavorings.

DO YOU KNOW... the difference between margarine and butter?

Read on to the end...gets very interesting!

Both have the same amount of calories.

Butter is slightly higher in saturated fats at 8 grams compared to 5 grams.

Eating margarine can increase heart disease in women by 53% over eating
the same amount of butter, according to a recent Harvard Medical Study.

Eating butter increases the absorption of many other nutrients in other
foods.

Butter has many nutritional benefits where margarine has a few only because
they are added!

Butter tastes much better than margarine and it can enhance the flavors of
other foods.

Butter has been around for centuries where margarine has been around for
less than 100 years.

And now, for Margarine. Very high in trans fatty acids.

Triple risk of coronary heart disease.

Increases total cholesterol and LDL (this is the bad cholesterol) and
lowers HDL cholesterol, (the good cholesterol)

Increases the risk of cancers up to five fold.

Lowers quality of breast milk.

Decreases immune response.

Decreases insulin response.

And here's the most disturbing fact.... HERE IS THE PART THAT IS VERY
INTERESTING!

Margarine is but ONE MOLECULE away from being PLASTIC..

This fact alone was enough to have me avoiding margarine for life and
anything else that is hydrogenated (this means hydrogen is added, changing
the molecular structure of the substance).

You can try this yourself

Purchase a tub of margarine and leave it in your garage or shaded area.
Within a couple of days you will note a couple of things

* no flies, not even those pesky fruit flies will go near it (that should
tell you something)

* it does not rot or smell differently because it has no nutritional value
nothing will grow on it. Even those teeny weeny microorganisms will not a
find a home to grow.

Why? Because it is nearly plastic. Would you melt your Tupperware and
spread that on your toast?


Share This With Your Friends.....(If you want to "butter them up")

RB...THIS is why I've come to the conclusion that
 

IF I "splurge" on my diet, I would rather use the REAL thing (i.e. butter, sugar) instead of the margarine, splenda, etc. as it seems that all the "stuff" they put in the food to lower the calories and/or fat, we have YET to know what it will do to our bodies and while YES, it may be helping us lose weight, do we REALLY know what it is doing to our bodies that's why everything is "real". It just seems like all the low fat, artificially sweetened food (with fewer) calories MAY be doing us more harm than good. Well, I have to go now as I'm off to the market to pick up my 40lbs of organic blueberries (sounds like a lot, BUT I use them as well as other berries...already froze 25lbs of strawberries...in Diana Dyers phytochemical shake that I have every day) AND I'm splurging and making a blueberry cobbler...mmm. Take care and God bless.

Rhonda

Omega three boost bone marrow - more resistant to chemo? useful adjuvant?
 

See also previous post re DHA reducing bone loss and here a 2006 trial as well



"Bone marrow from LF-CO animals appeared to be more resistant to araC treatment than either MF group. Thus, DHA, fed as DHASCO, has advantages over low or moderate n-6 diets and chow as it is has both hypolipidemic- and bone marrow-enhancing properties in weanling Fischer 344 rats. This suggests that DHA supplementation may be useful in adjuvant chemotherapy."




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9076666

1: Lipids. 1997 Mar;32(3):293-302. Links
Incorporation of long-chain n-3 fatty acids in tissues and enhanced bone marrow cellularity with docosahexaenoic acid feeding in post-weanling Fischer 344 rats.

* Atkinson TG,
* Barker HJ,
* Meckling-Gill KA.

Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.

We wanted to examine the effects of an oil rich in docosahexaenoic acid (DHA), without eicosapentaenoic acid, on the composition of membrane phospholipid in a variety of tissues. Our in vitro studies had previously shown that DHA could modify glucose and nucleoside transport in cells in culture and also increase selectivity of the nucleoside drug, arabinosylcytosine (araC) toward tumor cells. Here we wanted to examine what effect DHA supplementation would have in the whole animal in terms of the chemosensitivity of normal bone marrow, the dose-limiting tissue during chemotherapy, to araC. The purpose was to determine whether fatty acid supplementation might be useful as an adjuvant to chemotherapy. We fed diets containing 5% (w/w) low fat-corn oil (LF-CO group), 10% moderate fat-safflower oil (MF-SO group), or 10% DHASCO (MF-DHA group) to weanling Fischer 344 rats for 8-9 wk. Feed intake and growth were not different between the different diets. Similarly, treatment of animals with the chemotherapeutic drug araC did not differentially affect growth, feed intake, or tissue fatty acid composition for the different diet groups. Fatty acid compositions of bone marrow, liver, red blood cells, plasma phospholipid and triglyceride, as well as skeletal and cardiac muscle, were substantially different between the dietary groups. The DHASCO oil contained 46% DHA (22:6n-3) and resulted in profound incorporation of DHA in all tissues examined. The most dramatic response was seen in skeletal muscle of MF-DHA fed animals where DHA represented 46% of membrane phospholipid fatty acids. This is likely to have consequences to muscle function. Although DHASCO contains a similar level of saturated fatty acids (42%), few differences in saturates were noted between the various dietary groups for most of the tissues examined. Both LF-CO and MF-SO diets were hypercholesterolemic, and the LF-CO was also hypertriglyceridemic compared to the chow-fed animals. Animals fed the MF-DHA diet had the lowest triglyceride levels of any of the treatment groups and cholesterol levels comparable to chow-fed animals. MF-DHA had substantially higher numbers of colony-forming units-granulocyte macrophage (CFU-GM) as reflected in a twofold higher bone marrow cellularity than either chow or LF-CO animals, suggesting expansion of the bone marrow compartment with DHA feeding. Although higher than LF-SO, the number of CFU-GM in MF-SO animals was not significantly higher than animals fed chow. Bone marrow from LF-CO animals appeared to be more resistant to araC treatment than either MF group. Thus, DHA, fed as DHASCO, has advantages over low or moderate n-6 diets and chow as it is has both hypolipidemic- and bone marrow-enhancing properties in weanling Fischer 344 rats. This suggests that DHA supplementation may be useful in adjuvant chemotherapy.

PMID: 9076666 [PubMed - indexed for MEDLINE]



http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16102959


1: J Nutr Biochem. 2006 Apr;17(4):282-9. Epub 2005 Jun 21.Click here to read Links
Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats.

* Watkins BA,
* Li Y,
* Seifert MF.

Center for Enhancing Foods to Protect Health, Lipid Chemistry and Molecular Biology Laboratory, Purdue University, West Lafayette, IN 47907-2009, USA. baw@purdue.edu

Hypoestrogenic states escalate bone loss in animals and humans. This study evaluated the effects of the amount and ratio of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) on bone mineral in 3-month-old sexually mature ovariectomized (OVX) Sprague-Dawley rats. For 12 weeks, the rats were fed either a high-PUFA (HP) or a low-PUFA (LP) diet with a ratio of n-6/n-3 PUFAs of 5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided 110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended with n-3 PUFAs (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid analyses confirmed that the dietary ratio of 5:1 significantly elevated the amount of DHA in the periosteum, marrow and cortical and trabecular bones of the femur. Dual-energy X-ray absorptiometry measurements for femur and tibia bone mineral content (BMC) and bone mineral density showed that the DHA-rich diets (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at 12 weeks. Rats fed the LP diets displayed the lowest overall serum concentrations of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline, whereas the bone formation marker osteocalcin was lowest in the HP groups. Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5) preserved rat femur BMC in the absence of estrogen. This study indicates that the dietary ratio of n-6/n-3 PUFAs (LP5 and HP5) and bone tissue concentration of total long-chain n-3 PUFAs (DHA) minimize femur bone loss as evidenced by a higher BMC in OVX rats. These findings show that dietary DHA lowers the ratio of 18:2n-6 (linoleic acid)/n-3 in bone compartments and that this ratio in tissue correlates with reduced Pyd but higher bone alkaline phosphatase activity and BMC values that favor bone conservation in OVX rats.

PMID: 16102959 [PubMed - indexed for MEDLINE]

{omega}-3 PUFA regulate COX-2-mediated invasion in brain-melanoma
 

"Taken together, these results indicate that {omega}-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma."


http://www.jlr.org/cgi/content/abstract/46/6/1278


Role of {omega}-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma

Yvonne Denkins1, Doty Kempf, Melissa Ferniz, Shilpa Nileshwar and Dario Marchetti

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803

Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400474-JLR200

1 To whom correspondence should be addressed. e-mail: ydenkins@vetmed.lsu.edu

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that {omega}-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, {omega}-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of {omega}-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-{alpha} upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) {omega}-3 and {omega}-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in {omega}-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased MatrigelTM invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in MatrigelTM invasion.

Taken together, these results indicate that {omega}-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cance
 

For those of you who may have read the "very thought provoking" http://www.her2support.org/vbulletin...ight=provoking post on the man who claimed to have significantly impacted on lung cancer by balancing the omega threes and sixes here is some more evidence that would support such a possibility.

RB

http://carcin.oxfordjournals.org/cgi...tract/26/4/779

Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes
Shu-Hua Xia, Jingdong Wang and Jing X. Kang*

Departments of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

* To whom correspondence should be addressed. Tel: +1 617 726 8509; Fax: +1 617 726 6144; Email: kang.jing@mgh.harvard.edu

Recent studies have shown opposing effects of n-6 and n-3 fatty acids on the development of cancer and suggest a role for the ratio of n-6 to n-3 fatty acids in the control of cancer. However, whether an alteration in the n-6/n-3 fatty acid ratio of cancer cells affects their invasive potential has not been well investigated. We recently developed a genetic approach to modify the n-6/n-3 ratio by expression of the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase that converts n-6 to n-3 fatty acids in mammalian cells. The objective of this study was to examine the effect of alteration in the n-6/n-3 fatty acid ratio on the invasive potential of human lung cancer A549 cells. Adenovirus-mediated gene transfer of the n-3 desaturase resulted in a marked reduction of the n-6/n-3 fatty acid ratio, particularly the ratio of arachidonic acid to eicosapentaenic acid. Cell adhesion assay showed that the cells expressing fat-1 gene had a delayed adhesion and retarded colonization. Matrigel assay for invasion potential indicated a 2-fold reduction of cell migration in the fat-1 transgenic cells when compared with the control cells. An increased apoptosis was also observed in the fat-1 transgenic cells. Microarray and quantitative polymerase chain reaction revealed a downregulation of several adhesion/invasion-related genes (MMP-1, integrin-{alpha}2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that a decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably downregulating the cell adhesion/invasion-related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in the prevention and treatment of cancer.

Organic milk lower omega six higher omega three and Swiis alpine cows do well!
 

Fats in milk will obviously depend on feed as cows like us are what they eat.

So I suppose you need to know what your organics cows ate but a Uk trial suggests organic milk has a better fat profile.

High levels of vegetable seed in feed are likely to produce high six contents.

Interestingly swiss cows from alpine pastures seem to have high omega three content.

RB


http://www.dairy-science.org/cgi/con...ract/89/6/1938

Comparing the Fatty Acid Composition of Organic and Conventional Milk
K. A. Ellis*,1, G. Innocent*, D. Grove-White{dagger}, P. Cripps{dagger}, W. G. McLean{ddagger}, C. V. Howard§ and M. Mihm#

* Division of Animal Production and Public Health, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow, G61 1QH, UK
{dagger} Division of Livestock Health and Welfare, University of Liverpool, Faculty of Veterinary Medicine, Leahurst, Neston, CH64 7TE, UK
{ddagger} Department of Pharmacology & Therapeutics School of Biomedical Sciences, Sherrington Buildings, Ashton Street, Liverpool, Merseyside, L69 3GE, UK
§ Centre for Molecular Biosciences, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK
# Division of Cell Sciences, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow, G61 1QH, UK

1 Corresponding author: k.ellis@vet.gla.ac.uk

During a 12-mo longitudinal study, bulk-tank milk was collected each month from organic (n = 17) and conventional (n = 19) dairy farms in the United Kingdom. All milk samples were analyzed for fatty acid (FA) content, with the farming system type, herd production level, and nutritional factors affecting the FA composition investigated by use of mixed model analyses. Models were constructed for saturated fatty acids, the ratio of polyunsaturated fatty acids (PUFA) to monounsaturated fatty acids, total n-3 FA, total n-6 FA, conjugated linoleic acid, and vaccenic acid. The ratio of n-6:n-3 FA in both organic and conventional milk was also compared. Organic milk had a higher proportion of PUFA to monounsaturated fatty acids and of n-3 FA than conventional milk, and contained a consistently lower n-6:n-3 FA ratio (which is considered beneficial) compared with conventional milk. There was no difference between organic and conventional milk with respect to the proportion of conjugated linoleic acid or vaccenic acid. A number of factors other than farming system were identified which affected milk FA content including month of year, herd average milk yield, breed type, use of a total mixed ration, and access to fresh grazing. Thus, organic dairy farms in the United Kingdom produce milk with a higher PUFA content, particularly n-3 FA, throughout the year. However, knowledge of the effects of season, access to fresh grazing, or use of specific silage types could be used by producers to enhance the content of beneficial FA in milk.

Key Words: organic farming • fatty acid • n-3 fatty acid • conjugated linoleic acid



http://circ.ahajournals.org/cgi/cont...ract/109/1/103

Basic Science Reports
High {omega}-3 Fatty Acid Content in Alpine Cheese
The Basis for an Alpine Paradox
Christa B. Hauswirth, MD; Martin R.L. Scheeder, Dr sg agr; Jürg H. Beer, MD

From the Department of Medicine, Kantonsspital Baden, and the Federal Institute of Technology, Zürich, Switzerland.

Correspondence to J.H. Beer, MD, Department of Medicine, Kantonsspital Baden, 5404 Baden, Switzerland. E-mail hansjuerg.beer@ksb.ch

Received June 17, 2003; revision received August 21, 2003; accepted August 22, 2003.

Background— {alpha}-Linolenic acid (ALA) may protect from cardiovascular disease. Because fresh alpine grass contains high amounts of ALA, we hypothesized that the levels of {omega}-3 fatty acids would concentrate to nutritional relevance in the cheese of milk from cows with alpine grass feeding compared with cheese from silage and concentrate feeding; the newly available cheese produced from cows fed with linseed supplementation should contain even higher ALA concentrations.

Methods and Results— Forty different cheeses were analyzed by gas chromatography for their fatty acid profile: (1) 12 from well-defined alpine regions around Gstaad, Switzerland; (2) 7 commercially available English cheddar cheeses; (3) 6 cheeses from cows fed with linseed supplementation; (4) 7 industrial-type Emmentals; and (5) 8 alpine cheeses with partial silage feeding. The alpine cheese contained 4 times more linolenic acid (C18:3{omega}-3) compared with cheddar, more total {omega}-3 fatty acids, and showed a significantly lower n-6:{omega}-3 ratio. Conjugated linoleic acid (C18:2 c9/t11) was 3-fold higher, whereas the amount of palmitic acid was 20% lower. The Emmental reached 40% of the ALA content compared with alpine cheese, and surprisingly, cheese from linseed-supplemented cows contained only 49% of that of the alpine cheese (P<0.001 for each trait in the 5 cheese groups).

Conclusions— Cheese made of milk from cows grazed on alpine pastures had a more favorable fatty acid profile than all other cheese types. Alpine cheese may be a relevant source of ALA and other cardioprotective fatty acids.


Key Words: nutrition • fatty acids • coronary disease • diet • death, sudden

ABSTRACT

"The omega-3 fatty acids continue to accumulate research that suggests that they may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In the first part of this article, the potential for these compounds to prevent certain cardiovascular conditions are discussed. In the second part, the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurologic diseases, osteoporosis, and other medical disciplines are also briefly covered. "








http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Urol Oncol. 2005 Jan-Feb;23(1):36-48.Click here to read Links
An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part II.

* Moyad MA.

Phil F. Jenkins Director of Complementary & Alternative Medicine, Department of Urology, University of Michigan Medical Center, Ann Arbor, 48109-0330, USA. moyad@umich.edu

The correction of a subtle nutritional deficiency that may reduce the risk of a future chronic disease is indeed a challenge. However, some specific examples in the past, such as the addition of folic acid to prevent neural tube defects and calcium and vitamin D to prevent osteoporosis, should provide some encouragement that some conditions can be prevented with the appropriate addition of a deficient compound. One of the most intriguing current and future impacts on public health may come from a higher intake of omega-3 fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 fatty acids continue to accumulate research that suggests that they may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In the first part of this article, the potential for these compounds to prevent certain cardiovascular conditions are discussed. In the second part, the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurologic diseases, osteoporosis, and other medical disciplines are also briefly covered. The future appears bright for these agents, but specifically which conditions, who qualifies, testing, frequency, adequate sources, future trials, and numerous other questions need to be addressed and answered before the potential impact can catch up to the recent hype.

PMID: 15885582 [PubMed - indexed for MEDLINE]

curcumin and sesamin - inhibits AA but allows DHA and EPA ?
 

Blocking delta destaurase 5 will inhibit the formation of Archnidonic acid the omega six raw material for the eisosanoid pathways.

It may aslo push the omega six to DGLA conversion via the series one pathway which is reported as producing less inflamatory agents that the series two pathways.

This presumably acounts for its reported anti inflamatory properties.

But does it also block the 5 pathway for omegas threes long chain fabrication in the body (DHA and EPA)? (AMENDMENT I have just found a trial which suggests it does not which makes it a really interesting dietary adjunct) [Trial see below)

Also if excess omega six souces is a factor in inflamtion in a persons body the consequences in blocking the elongation pathways. The body has been supplied with the omega six and has to do something with it - burn it in exercise or for energy - store it in fat - and if there is too much of it in the circulation trials suggest things start going wrong with inapproriate oxidation leading heart conditions.

All of which might lead on to the conclusion that the easiest long term option is not getting to much in the first place.

RB




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=1291640

1: J Nutr Sci Vitaminol (Tokyo). 1992 Aug;38(4):353-63. Links
Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid metabolism in primary cultured rat hepatocytes.

* Fujiyama-Fujiwara Y,
* Umeda R,
* Igarashi O.

Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan.

Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.

PMID: 1291640 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9610840

1: Prostaglandins Leukot Essent Fatty Acids. 1998 Mar;58(3):185-91. Links
Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.

* Chavali SR,
* Zhong WW,
* Forse RA.

Department of Surgery, Harvard Institute of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

PMID: 9610840 [PubMed - indexed for MEDLINE]

Omega three and chronic fatigue
 

1: Neuro Endocrinol Lett. 2005 Dec;26(6):745-51. Links
In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.

* Maes M,
* Mihaylova I,
* Leunis JC.

M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Antwerp, Belgium.

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.

PMID: 16380690 [PubMed - indexed for MEDLINE]

Fish oil or farmed fish if that is the choice.....
 

If you are debating the best way to get your fish omega threes and sixes the articles below would provide arguments for fish oil or wild fish however humble, and thats without looking at other issues.

I must admit the figures made my draw drop.

The conversion rate from wild fish as food to farmed fish is apparently about 4 or 5 to 1.

A high price to fill our shelves with particular fish types?

I am not against farming fish to preserve wild stocks but where is the environmental "value" balance.

RB


Antarctic Krill: a case study on the ecosystem implications of fishing
http://72.14.221.104/search?q=cache:...ient=firefox-a


ABSTRACT

The fish farming industry already uses up
around 75% of the world’s fish oil and
around 40% of the world’s fish meal. By
2010, these figures might go up to 90% and
56% respectively, according to predictions
by the International Fish Meal and Fish Oil
Manufacturers Association (IFOMA). FAO
has indicated that by 2010, farmed salmon and trout alone could consume 620,000 tonnes
of fish oil (Staniford 2002). With demand exceeding supply and rising prices, fish oil has
been labelled “the new blue gold” (Staniford 2001).

http://72.14.221.104/search?q=cache:...ient=firefox-a


ABSTRACT

"Number 8
Winter 2001
Effects of Aquaculture on World Fish Supplies
SUMMARY
Global production of farmed fish, shrimp, clams, and oysters more than doubled in weight and value during the
1990s while landings of wild-caught fish remained level. Many people look to this growth in aquaculture to relieve
pressure on ocean fish stocks, most of which are now fished at or beyond capacity, and to allow wild populations to
recover. Production of farmed fish and shellfish does increase world fish supplies. Yet by using increasing amounts of wild-
caught fish to feed farmed shrimp and salmon, and even to fortify the feed of herbivorous fish such as carp, some sectors
of the aquaculture industry are actually increasing the pressure on ocean fish populations.
The available scientific evidence indicates that some types of aquaculture are on a destructive path that poses a
threat not only to wild fish stocks but also to the industry’s own long-term potential. One of the most disturbing trends is
the rapid expansion and intensification of shrimp and salmon farming and culture of other high-value carnivorous marine
fish such as cod, seabass, and tuna. Production of a single kilogram of these species typically uses two to five kilograms
of wild-caught fish processed into fish meal and fish oil for feed.
Besides this direct impact on wild fish stocks, some aquaculture as currently practiced degrades the marine
environment and diminishes the ecological life support services it provides to fish, marine mammals, and seabirds, as well
as humans. These impacts include
• Destruction of hundreds of thousands of hectares of mangrove forests and coastal wetlands for construction
of aquaculture facilities
• Use of wild-caught rather than hatchery-reared finfish or shellfish fry to stock captive operations, a practice
that often leads to a high rate of discarded bycatch of other species
• Heavy fishing pressure on small ocean fish such as anchovies for use as fish meal, which can deplete food for
wild fish such as cod, as well as seals and seabirds
• Transport of fish diseases into new waters and escapes of non-native fish that may hybridize or compete with
native wild fish
As aquaculture production continues to expand and intensify, both its reliance and its impact on ocean fisheries are
likely to increase. The balance between farmed and wild-caught fish, as well as the total supply of fish available for human
consumption, will depend on future trends in aquaculture practices. If the goal of aquaculture is to produce more fish for
consumers than can be produced naturally, then it will become increasingly counterproductive to farm carnivores that must
be fed large amounts of wild-caught fish that form the foundation of the ocean food chain. Indeed, non-carnivorous
species such as marine mollusks and carps account for most of the current net gain in world fish supplies from aquaculture.
Without clear recognition of its dependence on natural ecosystems, the aquaculture industry is unlikely to develop
to its full potential or continue to supplement ocean fisheries. We recommend the adoption of four priority goals for
aquaculture:
• Encourage farming of species lower on the food web – that is, fish with herbivorous or omnivorous diets or
filter feeders such as oysters
• Improve feed management and efficiency in industrial aquaculture systems and develop substitutes for fish-
derived feed ingredients
• Develop integrated fish farming systems that use multiple species to reduce costs and wastes while increasing
productivity
• Promote environmentally sound aquaculture practices and resource management
Governments have a key role to play in developing regulations to protect coastal ecosystems and in reexamining
subsidies to unsustainable marine fisheries. Development agencies are strategically placed to help in developing and
implementing sustainable production practices and in financing otherwise economically and socially unattainable reforms in
developing countries. If public and private interests act jointly to reduce the environmental costs generated by fish farm-
ing, present unsustainable trends can be reversed and aquaculture can make an increasingly positive contribution to global
fish supplies..............."
Cover (clockwise from top): shrimp ponds in Honduras (courtesy CODDEFFAGOLF); basket of milkfish (J. Primavera); harvesting catfish in
Mississippi (K. Hammond, courtesy USDA).

Re conversion rate of wild fish used in feed to farmed fish
 

Having done some more searches on the subject of fish farming there is contoversy about the "conversion" rate.

Here is another link to an article on conversion which contains three figues and one from the industry to balance things.



RB


http://www.davidsuzuki.org/Oceans/Fi...n/Net_Loss.asp

Net loss of wild fish to produce farmed salmon

A total of 2.7 to 3.5 tonnes of wild fish are used to make 1 tonne of farmed salmon

ABSTRACT



"Since a salmon farm in BC currently uses between 1.3 and 1.7 tonnes of dry feed (ie: FCR of 1.3 to 1.7) to make one tonne of farmed salmon, then the total amount of wild fish used to make one tonne salmon is between 2.7 and 3.5 tonnes (ie: the FCR multiplied by 2.08). It should be noted that in practice, BC salmon farms do not often reach the lower FCR of 1.3 which is achievable only when feed is used very efficiently on the farm. Rather than taking pressure off ocean resources then, salmon farming is currently adding greatly to that pressure..........................Much more research needs to be done and it is unclear when, or if the day will come when farmed salmon will be vegetarian. In the meantime, the stress on the ocean ecosystem will increase as salmon aquaculture expands globally. The consumption of 6.2 tonnes of wild fish for each tonne of salmon produced not only means less food for humans, but also for the many ocean species that rely on these fish as part of their food chain. Currently, the continued expansion of salmon farming is not sustainable.."



http://www.wfga.net/issues.asp?id=37

The Environmental Impact Of Salmon Farms

Low dosage celcoxib DHA and P53
 

Please also see prior posts on COX inhibitors and DHA.

This is prostate but there seems to be some communality of mechanisms in many cancers.

RB



1: Int J Cancer. 2006 Apr 27; [Epub ahead of print]Click here to read Links
Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells.

* Narayanan NK,
* Narayanan BA,
* Bosland M,
* Condon MS,
* Nargi D.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY.

The role of cyclooxygenase-2 (COX-2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX-2 inhibitors may be effective against prostate cancer via COX-2-independent mechanisms. But administration of high doses of COX-2 inhibitors over longer period of time may not be devoid of side effects. There is increasing interest in using COX-2 inhibitors in combination with other chemopreventive agents to overcome the issue of toxicity. However, the molecular mechanisms underlying their combined actions are not well understood. Therefore, the present study was designed to determine the effects of low doses of docosahexaenoic acid (DHA) in combination with celecoxib on the molecular targets at the proteins level in rat prostate cancer cells. Two-dimensional gel electrophoresis, in combination with mass spectrometry analysis, was used for protein identification. Western blot analysis confirmed the proteins identified. Paraffin-embedded tissue sections from the rat prostate tumor were used to detect base level expression of heat shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses (2.5 muM each). A total number of twelve proteins were differentially expressed by the combined action of DHA and celecoxib at low doses. It was interesting to note that these agents activated both HSP70 and p53 proteins. Activation of HSP70 by the combined actions of DHA and celecoxib in the presence of wild-type p53 reveals a unique COX-2 independent mode of action against prostate cancer. (c) 2006 Wiley-Liss, Inc.

PMID: 16646082 [PubMed - as supplied by publisher]