The traditional diet of Greece and cancer.

[Andrea Barnett Budin]

Ok, Denise (and all interested in zucchini pancakes)...!

First -- you go to Costco.

Buy GABELIA'S ZUCCHINI PANCAKES from freezer section.

I am laughing. But this is the recipe.

Keep in freezer till ready to cook. Put extra virgin olive oil (of course) in pan. Saute 2 minutes on each side. Serve. Eat.

My family like raspberry jam w/these. But they are excellent with nothing. They are 120 calories each. I had 1 last night -- without spreading any omega 3 on it. LOL... My husband had 1 and 1/2 (which he split w/my son-in-law who'd already eaten his 1). My dghtr ate 1. I could have eaten 2 for sure.

Really yummy delicious!! **** 4 stars!!!!

(Aside: I swallowed my Omega 3 and alllllllll my other supplements with a gallon of filtered water an hour before and ate a banana.)

This is how I "cook"...

Much love,
Andi

[NEDenise]

Yay Costco! I love that place!
This recipe is VERY do-able!
You got me! Now we're even!

Don't know how I've never been there on a day these were 'sampled'...but your recommendation is good enough for me! Now what will they be topped with? chopped tomatoes? butter? cheese? krill oil?

Denise

[R.B.]

Hi Karen Z

I will respond to your question re products brands etc in the next day or so.

This is a great interview by Martie Whittekin a passionate health radio show host of many years standing, of one of the leading research lights in the Omega 3:6 field Artemis Simopolous, whose name you will see on some of the papers cited.

Martie is a charming knowledgeable passionate and very active proponent of the importance of diet to health, who also promotes health conferences and events.

The interview is about Omega 3 and 6 generally.


http://www.radiomartie.com/archives/2013.shtml

3rd item down in Martie's archive (-:

http://www.hbnarchive.com/2013/052513.mp3

[karen z]

R.B.
Thanks. I look forward to receiving the information.
Best wishes,
Karen z

[R.B.]

AndiBB emailed me about the report that Omega 3 increases prostate cancer risk and particularly high grade cancer, which seems to have caused considerable concern.

Karen z sorry about the delay - I have started but not yet finished a response - things have been a bit hectic.

This was the paper, http://jnci.oxfordjournals.org/conte...jt174.abstract
which I consider in more depth below. The title of the press release of the nested Select trial was:

“Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk ”

This was the press release
http://www.fhcrc.org/en/news/release...te-cancer.html

Sadly publicity is often important to research organisations; the media respond to ‘results’ that people will talk about and are clear cut or appear as such; human nature dictates in consequence media departments; self evidently non-specialists, are at risk of over egging results, and the result is public ends up getting very confused by potentially misleading messages.

Apart form a few basic truths about the need for essential nutrients for life, the reality is things in cell biology are very rarely simple.

There is a lot of work that suggests that Omega 3 intake is associated with lower rates of prostate cancer. There are a number of biological mechanisms that would explain why Omega 3 may reduce prostate http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676993/ and some other cancer risks, and a number of observations suggest this is the case. In contrast some papers do not support this generality as is the case in this paper and its predecessor, but closer reading of the Select paper raises a host of questions as to the conclusion, some of which I raise below.

My first thought based on wider reading of reports from the mid 1900s, was that cancers were low in historic populations on non-western diets, which prompted the thought do people like Inuit who eat loads of Omega 3s have higher prostate cancer rates; the answer is no; they actually appear to have very low rates of prostate cancer. http://cebp.aacrjournals.org/content/12/9/926.long In the summary this paper includes the following statement “the prevalence of latent carcinoma is extremely low among Inuits compared with other populations”. The introduction includes the following comment "In Greenland, the age-standardized incidence rate for the 1969–1988 period was 1.7/100 000, and only four cases were diagnosed." Intriguingly the one prostate cancer case they found in the study was in a man with an unusually (for Inuit) poor Omega 3:6 ratio.

Historically population groups on non-western diets who ate significant amounts of fish also had relatively low rates of prostate cancer, and this paper, although having limitations, looking at 6272 Swedish men over 30 years found men that ate no fish had a two to three times greater risk of prostate cancer . http://www.sciencedirect.com/science...40673600048893 http://ajcn.nutrition.org/content/77/3/532.full

There is also a genetically created mouse called fat1, that unlike normal mammals can convert Omega 6 to Omega 3, and even if fed Omega 6 tends to make enough Omega 3 to balance the Omega 6 in it's diet. Prostate cancer invasion and proliferation was significantly inhibited in fat1 mice. https://www.google.co.uk/search?q=fa...fflb&gws_rd=cr Ok this is in rather special mice but the generality of the result goes against the suggestion that Omega 3s increase prostate cancer risk.

The fact traditional fish eaters appear to have very low or low incidence of prostate cancer suggests that whatever the Select trial was picking up, it is not as simple as dietary Omega 3s increases the risk of prostate cancer.

What might the above Select paper and its predecessor actually have detected? Unfortunately that is a pretty big question; the studies did not look at participants diet they just assumed that changed levels of long chain Omega 3 EPA and DHA in the blood must be the result of dietary intake of fish or fish oil, but these two fats are also made in the body from the plant based Omega 3 linolenic acid. As discussed below men do this pretty poorly but a host of things could alter conversion rates including hormonal changes. So the results could be down to a host of reasons excluding dietary intake, or may be due to dietary intake, as we have no idea what these people ate we simply do not know. Let us look at things in a bit more detail.

The latest Select trial was a subset of the original Select Trial which looked at the question did a particular form and dosage of Vitamin E (synthetic all rac-α-tocopheryl acetate), and or a particular form of selenium reduce prostate cancer http://jama.jamanetwork.com/article....ticleid=183163 . The result was that no real change was seen for the type of selenium selected, and those that took the form of vitamin E chosen had higher rates of aggressive prostate cancer.

The particular form is important because different forms may be differently absorbed and act in different ways in the cells. Other papers have shown other forms of Vitamin E and Selenium to reduce the risk of prostate cancer. http://jnci.oxfordjournals.org/content/92/24/2018.short The dosage may also be an important factor as positive results have been seen with lower doses of some forms of vitamin E.

In the Select trial they selected those with high grade prostate cancer from all participants, including those taking selenium and vitamin E. They did not breakdown those with high Omega 3 in the blood high and high grade prostate cancer by treatment group, so we do not know if most or conversely few of the them were taking vitamin E, but we do know from the main trial that vitamin E was found to increase the risk of high grade prostate cancer, and the majority of the participants were taking vitamin E. We also know that there were more people with high BMIs in the high grade cancer group, and a greater number were taking asprin. We also know that vitamin E can block http://cancerres.aacrjournals.org/content/57/12/2410 http://www.sciencedirect.com/science...71531799001554 or sometimes increase the process of apoptosis (cell death) depending on what type it is and what the dosage is.

Some forms of vitamin E at high dosages may reduce cell death because they protect polyunsaturated fats from oxidation; the oxidation of polyunsaturated fats have important roles in process of cell death, so reducing oxidation may reduce cell death, which may be great in some circumstances, but not so good if you are wanting to kill damaged or cancerous cells.

The conclusion to the Select paper should maybe have been vitamin E in the synthetic all rac-α-tocopheryl acetate form at the dosage selected, increases high grade prostate cancer, and the increase in high grade cancer was also linked with high levels of Omega 3 in the blood, but the groups were not separated out to determine if the effect of high Omega 3 was dependent on the presence of either Vitamin E or selenium in the forms selected – which would not have grabbed much media attention ! The trial is telling us something but exactly what is not clear. It is clear the press release headline should not have been the bald simplistic press statement that dietary Omega 3 increases the risk of high grade prostate cancer.

The predecessor trial looking at Omega 3s http://en.wikipedia.org/wiki/Finasteride and its original primary purpose was to look at the use of a product called finasteride http://en.wikipedia.org/wiki/Finasteride to reduce prostate cancer. The result was that finasteride may reduce prostate cancer but also may ? increase the risk of high grade cancers. Again the researchers used the same study population group including those who took the finasteride and looked at their Omega 3 status; again they found a link between Omega 3s and high grade cancers, but consideration of the effect of Omega 3 on prostate cancer risk is tainted by the fact at least part of the selected group was taking finasteride which may? increase the risk of high grade prostate cancer; did Omega 3 add to the finasteride risk; maybe, but we do not know from the information available; we cannot separate out and quantify from the information the effects of finasteride and long chain Omega 3s (be that from the diet or improved conversion) so the observed result cannot justify a conclusion that Omega 3 on its own increases the risk of high grade prostate cancer, or even that or that higher amounts of long chain Omega 3s in the plasma originated in the diet rather than by increased conversion.

As neither trial actually asked people what they were eating let alone if their Omega 3 came from fish or fish oil, we cannot even begin to differentiate the effects of fish intake or supplementation in the form of fish or krill oil on prostate cancer risk, or indeed determine if the higher levels of long chain Omega 3 in the blood was due to dietary intake, or some metabolic differences in the rate of conversion of plant based Omega 3 to long chain Omega 3. Interestingly one of the factors that affect the rates of conversion of the plant based to the longer chain Omega 3s and 6s is hormonal status; women convert much better than men, with oestrogen primarily with help from progesterone arguably increasing, and conversely testosterone arguably decreasing, conversion rates. So we do not actually know why these men had higher long chain Omega 3 in the blood; higher EPA and DHA could even for example be a marker of hormonal changes such as falling testosterone or rising oestrogen due to treatment protocols or changes in metabolism with onset of prostate cancer, or it might be what they ate, or a combination of both.

In conclusion there is no doubt the Select and Finasteride papers are telling us something; maybe long chain Omega 3 plus vitamin E, higher BMI, and aspirin use together, increase the risk of prostate cancer, or finasteride and Omega 3 further increase the risk of prostate cancer in those taking finasteride, or hormone levels change in aggressive cancers, or treatments affect hormones, so impacting on Omega 3 and 6 plant based fat conversion to long chain fats; but I suggest the basis of the trial and consequent results simply do not justify the bald title of the press release namely “Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk” which in the circumstances is not a conclusion which can in anyway be definitely drawn from the study.

It is important not to forget that Omega 3 and 6 along with many other nutrients are fundamental to cell function, and in nature are more of less in balance in the diet. Many men are very poor converters, and some population groups are genetically less efficient converters. If you are not very good at making long chain Omega 3 from plant based Omega3 you have to get it from food or supplements.

Our massive intake of Omega 6 fats increases the requirements for Omega 3s; reducing Omega 6 intake is a better strategy that taking lots of Omega 3 to compensate. Taking higher amounts of Omega 3s in the short term may be a good way to initially try and help rebalance the bodies Omega 3 / 6 status, so reducing inflammatory, replenishing tissue, displacing Omega 6s etc, but as ever the body is complex and ultimately there are down as well as upsides to all supplementation, and particularly so large amounts in the longer term.

In summary looking at the biology of the body you cannot escape the fact Omega 3 is essential to cellular function, nervous system and brain function, vision, and indeed arguably life; on which basis there is no question that in the absence of adequate dietary supply, supplementation will be of benefit. Based on a raft of reasons I recommend marine whole food sources over fish oil; but many do not eat fish, and pressure on fish populations is a fast increasing issue. Ultimately there is no question that marine oil supplementation has a place; taking fish oil is better than being Omega 3 deficient due to dietary deficiencies, and or genetic or other common dietary factors leading to poor conversion of plant based to long chain fats. Many do not get adequate dietary plant based Omega 3, even if they could efficiently convert it, and I repeat men are generally very poor converters.

In conclusion long chain Omega supplementation definitely for some has a place, because it is a healthier option than being deficient; but not as good as getting adequate long chain Omega 3s from whole foods ( and this really means quite a lot of marine foods as the way we grow our animals means they too are often low in Omega 3s eg eggs, and we no longer eat the Omega 3 rich parts like brain)


PS Martie Whittekin, impassioned health journalist, and talk show host, includes some excellent links on the Omega 3 prostate issue in the second section of her weekly diary

http://www.radiomartie.com/newsletter/2013/072513.htm

(One of the papers suggests an increased risk of prostate cancer with fried fish, which on the balance of probabilities may actually contain little Omega 3 and a lot of Omega 6 if fried in vegetable oil, and more if in batter. Fried foods absorbs considerable amounts of frying oils)

[Andrea Barnett Budin]

RB, You're the best! Important info ladies -- for the man in your life.

The CNN report caught many of us offguard. It was alarming news. So I went to the source on Omegas.

I suppose many studies are flawed, unfortunately. And we need to investigate further.

Remember when they warned us about carcinogens in our lipstick? I have really dry lips. Chapsticks don't quite do it for me. That was decades ago. And, I'm still here...

Thanks, RB.

[NEDenise]

Oh! How I cherish the man in my life!
Fortunately, I already have him on Omega 3s and CoQ10 for heart health.

The idea of him having to deal with cancer from the patient side of the fence is revolting! Horrifying! More than a just God would allow!

So...I hope the supplements do the trick!
Denise

[Andrea Barnett Budin]

A doctor friend of my my husband's said he thinks that omega study and prostate cancer was based on the same science as -- if you play basketball, you'll grow taller...

Paul is on omega, co-enzyme, carnitine, alpha lipoic acid, b12. let me see, did I leave something out?

ANDI

[Jackie07]

http://www.ncbi.nlm.nih.gov/pubmed/23872953

[R.B.]

Whilst this thread is primarily about Omega 3 and 6, many are also vitamin D deficient, iodine insufficient, and lacking in one or more minerals, and may have other deficiencies in other essential nutrients, and these deficiencies ultimately inevitably must impact on cell function and most likely in a negative way.

I would strongly recommend the videos on the vitamin D thread, and in particular those by Dr Holick and Dr JoEllen Welsh.

http://her2support.org/vbulletin/showthread.php?t=43711


There is also a fascinating talk by Dr Flechas on iodine on this thread

http://her2support.org/vbulletin/showthread.php?t=53928

[R.B.]

More evidence that Omega 3s - and Omega 6s (in excess - ) have a role in breast cancer risk reduction.

(Ooops just noted that Lani is quicker off the mark than me - thanks Lani - http://her2support.org/vbulletin/showthread.php?t=59076 )

FAT1 is a mouse with a gene from a worm inserted that allows them to convert Omega 6 to Omega 3; normally mammals including humans cannot convert Omega 6 to Omega 3, and we must get it from our diet, which is why getting Omega 3 in the diet is so important. Fat1 mice tend to change enough Omega 6 into Omega 3 to create an equal balance of the two in their body.

They compared how implanted HER2 cells grew in FAT1 and normal wild type (WT) mice.

Both mice were fed the same diet which contained lots of Omega 6 and very little Omega 3 (Safflower oil), but FAT1 mice (-: unlike the WT mice )-: could make their own Omega 3.

The implanted HER2 tumors initially grew in both normal (WT) and FAT1 mice, and continued to grow in the normal WT mice -, but in contrast shrunk and eventually disappeared - in the FAT1 mice.

The tumors in the FAT1 mice contained much more EPA and DHA and a much better Omega 3:6 ratio -.


Clearly we are not FAT1 mice, but nonetheless the results are intriguing.


(15-HEPE, 17-HDHA and PGE3 are downstream Omega 3 products produced in the body
https://www.caymanchem.com/app/templ.../catalog/14990

WT is the normal mouse (Wild Type)




http://www.ncbi.nlm.nih.gov/pubmed/24052576

J Lipid Res. 2013 Sep 19. [Epub ahead of print]
Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice.
Zou Z, Bellenger S, Massey KA, Nicolaou A, Geissler A, Bidu C, Bonnotte B, Pierre AS, Minville-Walz M, Rialland M, Seubert J, Kang JX, Lagrost L, Narce M, Bellenger J.
Source

Universite de Bourgogne, France;
Abstract

Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25% to 30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFA from n-6 PUFA, were protected against BC development and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in HER2 signaling pathway and lipidomic analyses were performed in tumor tissues and plasma. Our results showed that tumors totally disappeared by day 15 in fat-1 mice when they continued to grow up in the WT. This prevention can be related in part to significant repression of the HER2/beta-catenin signaling pathway and formation of significant levels of n-3 PUFAs derived bioactive mediators (particularly 15-HEPE, 17-HDHA and PGE3) in the tumor of fat-1 mice compared to WT. All together these data demonstrate an anti-BC effect of n-3 PUFAs through, at least in part, HER2 signaling pathway downregulation, and highlight the importance of gene-diet interactions in BC.

The full paper can be read free here (-: http://www.jlr.org/content/early/201...r.M042754.long and includes the comment below

"To test the hypothesis that balanced ratio of n-6/n-3 fatty acid is able to decrease the risk of
BC, we implanted E0771 mouse BC cells into the fat-1 and WT mice and examined the
tumorigenicity of inoculated tumor cells. As shown in Fig.1, there was a dramatic difference
in the tumor volume between fat-1 transgenic (n=10) and WT mice (n=6). Over an
observation period of 25 days, all mice initially developed a palpable tumor by day 7 but,
importantly, all the tumors in fat-1 mice never grew up more and all palpable tumors
disappeared at day 18. By contrast, all the tumors in wild-type mice continued to grow up
until host sacrifice. These findings clearly show that expression of fat-1 inhibits the growth of
BC cells in vivo and results in mammary tumor regression.
Inhibition"

"Tumor n-3 fatty acid enrichment and formation of PUFA-derived mediators
As shown in Fig. 3A, fatty acid composition of tumor total lipids revealed higher levels of
10
EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in fat-1 transgenic mice compared
with WT animals, whereas AA (20:4n-6) was decreased by 70%. Interestingly, the n-6/n-3
PUFA ratio (Figure 3B) was significantly reduced in tumors from fat-1 mice (8.92±2.63)
compared to WT animals (30.51±6.99) despite the animals were fed the same diet. These
results indicate expression of fat-1 enriches the transgenic animals in n-3 PUFA at the
expense of n-6, giving a lower n-6/n-3 ratio."



The pictures of the dead mice and their tumors or lack of them are not pretty but exceptionally powerfully make the point of this important trial; and yes I do 'feel' for the mice. (page 27)

The graph of the relative tumor sizes is equally very powerful. (page 27)


All of which takes us back to a French paper in which it was noted that women with higher levels of DHA in breast tissue had a 70% lower risk of their excised breast tissue 'lumps' being cancerous

[R.B.]

This trial was mentioned in the paper above and is specifically relevant to HER2. I do not recall posting it before.

Essentially more of the same . . .

LA = linoleic acid the omega 6 found in quantity in most vegetable oils

Dietary fatty acids regulate the activation status of Her-2/neu (c-erbB-2) oncogene in breast cancer cells

http://annonc.oxfordjournals.org/con...5/11/1719.long

"This report shows, to the best of our knowledge for the first time, that dietary FAs previously characterized for either their breast cancer protective effect (ALA, EPA, DHA and OA) or its tumoricidal actions (GLA) significantly downregulate Her-2/neu ECD concentration and, consequently, the activation status of Her-2/neu in SK-Br3 and BT-474 human breast cancer cell lines, which contain Her-2/neu oncogene amplification. Remarkably, LA, a ω-6 FA with a strong tumorigenesis stimulating effect, significantly increased Her-2/neu ECD concentration. "

"Nonetheless, it is reasonable to suggest that some types of dietary FAs not only represent promising therapies for prevention and/or management of Her-2/neu-overexpressing breast carcinomas, but also may be even more beneficial when given in combination with novel therapies directed against Her-2/neu. We are currently investigating whether these findings will be helpful in the design of novel approaches to delay or prevent trastuzumab (Herceptin™) resistance. "

[R.B.]

Number of views 44,444

I just visited and saw this and it made me smile; I like patters in numbers, looking forward to 55,555

Thank you very much for your interest and support everybody

I have learned a lot in the process

[Andrea Barnett Budin]

Hi RB,

It's always good to feel appreciated for all your hard work and well-intentioned efforts! And that you are.

Plus, you're right, as we give we learn, and grow and that is the marvelous part of giving of yourself. It's a WIN WIN situation!!

Love,
Andi

[R.B.]

A bit complicated but yet more evidence of the involvement of Omega 6 in breast cancers.

D6D is one of the enzymes that convert plant based Omega 6 (LA) and plant based Omega 3 to the longer fats of the same respective families. The amount of Omega 3 or 6 stored in cell membranes ready for conversion by these enzymes is proportional to the dietary intake.

AA is a longer chain Omega 6.

PGE2 is an oxidized from of AA.

So it is possible to change the processes that take place in these pathways though the choice of dietary intakes of fats.

As often discussed in general on a population wide basis we eat far to much plant based Omega 6 (50% to 70% of many vegetable oils), and too little Omega 3 both plant based and long chain including EPA and DHA, which are not found in many food in quantity. etc etc.



Cancer Sci. 2013 Jun;104(6):760-4. doi: 10.1111/cas.12129. Epub 2013 Mar 19.
Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue.
Pender-Cudlip MC, Krag KJ, Martini D, Yu J, Guidi A, Skinner SS, Zhang Y, Qu X, He C, Xu Y, Qian SY, Kang JX.
Source

Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE(2)), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE(2) levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER-) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER- breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE(2) levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P < 0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P < 0.001), and was higher in ER- than in ER+ patients, indicating genotype-related trends. Similarly, PGE(2) levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE(2) levels are increased in breast tumors, particularly those of the ER- genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment.

OR eat much less Omega 6 and more Omega 3, a whole food diet that has not been de-mineralised and oxidised in storage and processing etc . . . but to give this advice would not be very helpful if your future career depended on securing future funding for drugs research. . . there has to be a better way of looking at health provision, a market that is more aware that we all share a very small precious planet, and will need to be at our best to have any hope of keeping it that way, that allows researchers to both secure research funding to expand important knowledge and give optimal health advice !

[R.B.]

Thing are rarely simple, and still much is unknown; the mysteries of estrogen !

N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth

http://www.plosone.org/article/info%...l.pone.0052838

WenQing Cao, ZhiFan Ma, Mark M. Rasenick, ShuYan Yeh, JiangZhou Yu

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


"Introduction

Fish oil dietary supplements have become increasingly popular. They are consumed for a variety of ailments as well as for promotion of general health. Population and preclinical studies have suggested that n-3 PUFAs inhibit BCa growth and improve treatment outcomes [1]. Accumulating evidence states that n-3 PUFAs may exert an antitumor action by altering lipid composition of the plasma membrane, which may affect the physical and chemical properties of lipid rafts, consequently, affecting localization of and interactions among signaling components in the microdomains of cell membrane [2]–[4]. Recent studies in breast cancer cells also found that, n-3 PUFA could incorporate different components of the cell membrane to remodel membrane architecture [5], [6]. These suggested a potential mechanism underlying n-3 PUFA anti-cancer effect. N-3 PUFA treatment decreases EGFR signaling [7], and down-regulates CXCR4 signaling in MDA-MB-231 cells [8], which might play the important roles in the anti-BCa effect of n-3 PUFAs. While E2 signaling is crucial for BCa tumorigenesis and progression, fewer studies have addressed how n-3 PUFAs affect E2 signaling and biologic function in BCa cells. It is noteworthy that in the animal studies on chemo-preventive properties of n-3 PUFAs, estrogen does not override the inhibitory effect of high n-3 PUFA diet on BCa growth [9], implying that n-3 PUFAs might abrogate/reduce/reverse the pro-proliferative effect of estrogen.

Estrogen, a mitogen, stimulates cell proliferation and prevents cell death in many different cell types, and is an important risk factor for BCa development [10]. Anti-estrogen therapies have been widely employed to treat hormone dependent BCa. However, laboratory studies have suggested that estrogen stimulates the apoptosis in long-term estrogen deprivation of MCF-7 BCa cells, and switches from being a mitogenic agent to inhibiting growth and inducing apoptosis [11]–[13]. Two potential mechanisms underlying this paradoxical effect of estrogen have been suggested in the studies that can be triggered either through the extrinsic death receptor pathway [12] or via the intrinsic pathway of mitochondrial disruption and release of cytochrome C [11]. Nevertheless, it is not clear how estrogen might promote BCa cell apoptosis.

Based on the above scientific findings, we propose that n-3 PUFAs alter estrogen signaling cascades in BCa cells, and initiate/augment the inhibitory effect of E2 (or compounds binding to membrane E2 receptors) on breast cancer. In this study, we first found that n-3 PUFA treatment initiated the inhibitory effect of E2 on MCF-7 and T47D BCa cell growth, and increased cell apoptosis. While these effects of estrogen were independent of the classical estrogen receptors, ERα or ERβ, they required the presence of the estrogen-sensitive G protein coupled receptor (GPCR), GPER1. Data from this study could lead to novel insights into the usefulness of n-3 PUFAs in the treatment of BCa."

[R.B.]

And just in case you missed this on the iodine thread on the nutrition page . . .

"And for all you reggae fans; something to listen to http://tonyvendryes.com/ whilst reading this thread (-:

(It takes a few seconds for the music to start once you the page opens, worth the wait )

Bear with the spoken intro (-:

Love the lyrics (-:

I have not looked at the site content, but love this Doctor's approach."

http://tonyvendryes.com/

"Prevention is better than cure you often have been told make wellness your number one goal for health is better than gold"

[Andrea Barnett Budin]

Love the music, the accent AND THE MESSAGE!

We are each a healer. We just have to awaken that part of ourselves.

Thanks, R.B.

[R.B.]

Both Omega 3 and calorie restriction have been suggested to have a role inhibiting cancers.

Here mice that over-express HER2 were allowed to eat as much as they wanted (AL), or calorie restricted. Some were fed with an omega 6 rich oil (soy oil which contains some plant based Omega 3 unlike many other vegetable oils) as their main fat and others with the Omega 3 EPA as their main fat.

The eat all you like high Omega 6 mice had an 87% tumor incidence, and the intermittently calorie restricted with a high Omega 3 EPA intake had a 15% tumor incidence, which is thought provoking as well as supporting the general contention of this thread.

It is interesting that intermittent calorie restriction was more effective than chronic restriction, which raises a lot of questions.

It would be interesting to know the original dietary content of the mice and their fat tissue compositions prior to the experiment; I have not seen the full paper.

As previously discussed on the separate but related topic of ketogenic diets for cancer, it is also likely that outcomes will depend on the type of fat consumed.

control (Con) ad libitum (AL),
intermittent calorie-restricted (ICR)
chronic calorie-restricted (CCR)




Cancer Prev Res (Phila). 2013 Jun;6(6):540-7. doi: 10.1158/1940-6207.CAPR-13-0033. Epub 2013 Apr 2.
Combination of intermittent calorie restriction and eicosapentaenoic acid for inhibition of mammary tumors.
Mizuno NK, Rogozina OP, Seppanen CM, Liao DJ, Cleary MP, Grossmann ME.
Author information
Abstract

There are a number of dietary interventions capable of inhibiting mammary tumorigenesis; however, the effectiveness of dietary combinations is largely unexplored. Here, we combined 2 interventions previously shown individually to inhibit mammary tumor development. The first was the use of the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the second was the implementation of calorie restriction. MMTV-Her2/neu mice were used as a model for human breast cancers, which overexpress Her2/neu. Six groups of mice were enrolled. Half were fed a control (Con) diet with 10.1% fat calories from soy oil, whereas the other half consumed a diet with 72% fat calories from EPA. Within each diet, mice were further divided into ad libitum (AL), chronic calorie-restricted (CCR), or intermittent calorie-restricted (ICR) groups. Mammary tumor incidence was lowest in ICR-EPA (15%) and highest in AL-Con mice (87%), whereas AL-EPA, CCR-Con, CCR-EPA, and ICR-Con groups had mammary tumor incidence rates of 63%, 47%, 40%, and 59%, respectively. Survival was effected similarly by the interventions. Consumption of EPA dramatically reduced serum leptin (P < 0.02) and increased serum adiponectin in the AL-EPA mice compared with AL-Con mice (P < 0.001). Both CCR and ICR decreased serum leptin and insulin-like growth factor I (IGF-I) compared with AL mice but not compared with each other. These results illustrate that mammary tumor inhibition is significantly increased when ICR and EPA are combined as compared with either intervention alone. This response may be related to alterations in the balance of serum growth factors and adipokines.

[R.B.]

Nutr Cancer. 2014 Jan;66(1):68-76. doi: 10.1080/01635581.2014.847964. Epub 2013 Nov 25.
High-dose eicosapentaenoic Acid and docosahexaenoic Acid supplementation reduces bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors: a pilot study.
Hutchins-Wiese HL, Picho K, Watkins BA, Li Y, Tannenbaum S, Claffey K, Kenny AM.
Author information
Abstract

Postmenopausal breast cancer survivors are living longer; however, a common class of drugs, aromatase inhibitors (AI), depletes estrogen levels, promotes bone loss, and heightens fracture risk. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may offset AI effects to bone because of the known effects on cellular processes of bone turnover. Therefore, we hypothesized that 4 g of EPA and DHA daily for 3 mo would decrease bone turnover in postmenopausal breast cancer survivors on AI therapy in a randomized, double-blind, placebo controlled pilot study that included 38 women. At baseline and 3 mo, serum fatty acids, bone turnover, and inflammatory markers were analyzed. Serum EPA and DHA, total and long-chain (LC) omega (n)-3 polyunsaturated fatty acids (PUFA) increased, whereas arachidonic acid, total and LC n-6 PUFA, and the LC n-6:n-3 PUFA ratio decreased compared to placebo (all P < .05). Bone resorption was inhibited in the fish oil responders compared to placebo (P < .05). Inflammatory markers were not altered. This short-term, high-dose fish oil supplementation study's findings demonstrate that fish oil can reduce bone resorption; however, longer-term studies are needed to assess bone density preservation and to explore mechanistic pathways in this population at high risk for bone loss.