The traditional diet of Greece and cancer.

[karen z]

Amy,
Thanks so much for your summary of main points for me. I know this wasn't easy to do and that you are busy. I greatly appreciate your help.
Grazie ! !
Karen Z

[R.B.]

Hi Karen and thanks for your help Mtngrl,

Whilst I have been nerding for several years on the subject of Omega 3 and 6 and wider diet, and have completed a not well written but general scientifically sound and hopefully thought provoking book on Omega 3 and 6, and their impact on western disease, I am not an expert in the traditional sense of the word in that I have no formal qualifications. I have been working for several years on a follow up that puts Omega 3 and 6 into a wider dietary context through the common thread of oxidative stress and its role in western disease.

Whilst the thread was titled the Greek Diet, the traditional Mediterranean diet lifestyle is in a sense a ghost, so it is not adequate just to refer to a particular diet plan, because even unprocessed food it not what it was a generation or two ago. Traditional Island foods were locally grown on highly mineralized often volcanic based soils. Goats and chicken got to wander and select their own foods. Islanders got sun and exercise etc.

The Mediterranean diet is not the only protective one. Reports by doctors working with a mix of European and native populations in locations around the world in the 1920s to 1940s clearly showed tribes on a wide variety of native diets rarely got western conditions - so it is as much about food quality and mix as type of diet.

Today in contrast western diseases are common in the same population groups that have moved to the west.

Our diets are not what they were. Most of us are deficient in one or more minerals (RDA) because the crops we and animals feed on no longer contain the mineral content they did. We abstract minerals in crops and do not replace them. A British paper records drops over the last 50 years of the amounts of various minerals in a basket of foods foods of between 20-70%. This is partly due to soil depletion and partly to breeding for carbohydrate quantity / size rather than mineral density etc. These mineral deficits obviously work up the food chain to us, and are a factor in all sorts of ailments, in both humans and animals (e.g. sheep often need to be routinely given minerals because the farmers know otherwise they are not sufficiently healthy to reproduce - but ironically we often do not ensure women with fertility issue are mineral sufficient)

Most of us are vitamin D deficient because we no longer go in the sun / wear sun cream / wash with soap before or after going in the sun.

Many of us are iodine deficient.

A good proportion of us are deficient in one or more B vitamins

Many of us are vitamin K deficient.

We eat way to much Omega 6 and not enough Omega 3

To add to these woes we refine food, and try to increase its shelf life. We treat crops / foods with all sorts of things like ammonia and bleach to prevent bacteria formation. As well as killing the bacteria these processes arguably can damage important sensitive nutrients. Many of the processes used in refining, damage the food (oxidation in various forms), as well as removing minerals.

Precooked stored meals etc probably add to the problem.

Vegetable water, the juices from meat etc and the nutrients they contain go down the sink. . .

Digestive disturbances can impair digestion - eg H Pylori affects absorption, of iron, vitamin c, and folate. Many of us have impaired digestion for a variety of reasons.

Grains contain anti nutrients, including phytate. Fermentation reduces phytate, but under the commercial imperative we have found ways of making bread rise quickly without fermenting it so saving several hours, and ironically sometimes even add phytate to bread, leading to blocking of mineral uptake. Most traditional cultures fermented their grains prior to eating them.

The lists just go on . . .

Trying to mimic a long gone Mediterranean diet of one sort or another is a hugely positive step compared to eating high levels of processed foods, but there is no ideal modern equivalent diet based on historic diets, because we have so badly distorted the quality and variety of food, and depleted it of nutrients. Even if you notionally ate the same food as your grandparents it will not contain as many nutrients, and will have been damaged by some of the industrial processes used in its storage and preparation.


Sunshine, a wide range of home grown foods on mineral rich volcanic soils, marine foods, chickens and goats that wandered round the mountains, and exercise, kept Mediterranean people healthy until they started working indoors and eating processed foods . . . better start saving for your own Island if you want a true Greek Island diet

So even with a whole (unprocessed) food diet most of us urban dwellers will be nutrient deficient. Appropriate supplementation, however imperfect and difficult to optimise, has to be a better option than deficiencies in essential very basic nutrients, particularly iodine, Vit D, minerals, K, etc. In very general terms at sensible recommended supplementation levels, for most healthy people but not necessarily those with specialist conditions, the negatives from deficiency far outweigh the risks of toxicity. Just to be clear I am not a fan of supplementation in general terms for iodine, Vit D, minerals, K, etc. as they are much better obtained in food (sunshine is the primary source in the case of Vit D) - the problem is they are not in general in foods in sufficient quantities any more. How much we get is a lottery as different soils contain different mixes and amounts.

There is a great deal we do not understand as to how the body absorbs minerals etc, but cows lick iron gateposts to get at the iron they contain, wild animals seek out mineral licks, and farmers give them mineral supplements so they reproduce, and they do. So clearly supplementation may not be optimal but has a place, and particularly so if you do not want to go to work with a gatepost for lunch - they are quite heavy and do not fit well into pockets.

However as stated. pragmatically supplementation however imperfect is a much better option than deficiency. For many of us, what we have done to the food chain / modern lifestyle, leaves us with little option but to supplement. Welcome to the nutritional lottery / risk reward guesstimate game.

Supplementation is of course an add on to doing the best we can do to pick the most nutritious foods available to us and should be undertaken only in consultation with your medical advisors.

I hope this helps. The above is a hint of what I have been nerding away at, and am currently preparing what I hope is a final restructure of the new book I have occasionally mentioned over the years, which has taken rather longer than expected, there is always just one more thing to check . . . In the meanwhile there is a book I would recommend with which I share much common ground albeit from a different perspective, which I will link to hopefully at the weekend (sorry for the delay), along with some blogs links that may be of interest

[karen z]

Hi R.B.,
Thanks again. This is very enlightening and, I can see, quite complex. I have had problems with D for some time (seems to be good now) and just found out from a holistic/integrative center I started going to that I am very low in B and have some definite digestive problems- so being supplemented with both with the help of a compounding pharmacy (also, again taking the correct omegas hopefully). Also, starting to take melatonin and magnesium at night for sleep. Will look forward to links and,hey, my first acupuncture treatment went very well (thought I'd throw that into the mix).
Best,
Karen

[SoCalGal]

Hi RB. Just wanted to say hello and thanks for all the awesome info. Been a bit lax in my vitamin taking and this thread has encouraged me to be more diligent. All the best! Flori

[R.B.]

I meant to do this at the weekend and got distracted, mostly usefully (-: but not always )-:

I have hesitated to post information that does not come directly out of trials, but I would recommend this book by impassioned scientists written from the knowledge gained in trying to sort out their own health issues. There are lots of good health books, but for me this flags some core health issues, some of which I have already raised on this site. I suspect the book is probably more accessible because it is written by people with a passion born of their own experience coming fresh to the subject. My totally revised and expanded book which I am trying to complete at the moment covers a lot of common ground with theirs, albeit from a different perspective. Trying to answer Karen z's post made me think I should highlight the book

http://perfecthealthdiet.com/?page_id=781
http://www.amazon.com/Perfect-Health...9178399&sr=8-1

I have had no contact with them but I do get a 'hat tip' in the notes - I suspect for my posts on this site.

This is their blog -http://perfecthealthdiet.com/

I do not agree with everything in it, but do agree with much of the general direction. I have found their book very useful, and though provoking.

I very much agree with the general direction of travel. The issue of what is the ideal mix of fats v carbs is more complex than they portray, which they acknowledge post book on their blog. They try to work out an ideal ratio and give their reasons for that, but nature throws exceptions, which exceptions beg questions.

For example Eskimos on a high marine (largely), often raw, meat / fish diet did not have western conditions, and neither did Indonesians who lived on a 97% carb diet eating mainly varieties of sweet potatoes. They each had their issues as a result of their diets - late development and small stature in the Indonesians - higher risk of cerebral hemorrhage in Eskimos - but both and all other tribes on traditional diets - no matter what the diet - had very low western diseases including BC - so the problem is not whole food but what we have done with it.

The Hunza who had very long lives ate grain -reportedly they lived well into their 100s - which suggests that grains are not inherently bad - but we have depleted soils, altered varieties, treat grains in storage, industrially process the result, . . . and now increasing numbers of people seem to have problems with grains . . .

I do think that wheat/ grains generally should be avoided unless fresh ground from organic sources, as industrial processing treatment in storage may (and based on small studies certain processes probably do) be leading to oxidative damage of the fats and proteins they contain. Grains also contain anti-nutrients which fermenting removes to a degree - our ancestors used to ferment grains - perversely we have worked out way of proving bread artificially in much shorter times because of economics. I think their argument that there are 'safer' carbs may have some basis, but in the negative some of these carbs may not be very nutrient rich.

I agree their arguments for keeping glucose levels under control, on the basis excess glucose leads to oxidation products, and glucose is arguably is a good fuel for cancer cells.

They also 'broadly' encapsulate the Omega 3:6 argument although they are not aware that plant based Omega 3 has important roles, as does plant based Omega 6, which is why an imbalance is so damaging, etc.

There is also lots of useful information on commonly deficient essential nutrients; Iodine, Vitamin D, minerals, vitamin K, some B vitamins etc.

They also raise the issue of the effect of different diets and fasting on the immune function, which lead me to start reading more on this very complex and fascinating issue.

This is a highly thought provoking and useful book that tries to explain why rather than just telling you to take things. So I return the compliment and hats off to Paul and Shou-Ching Jaminet. http://perfecthealthdiet.com/?page_id=2

Tests that accurately disclose the status of many nutrients are simply not available. Even where they are available they are often only looking at one area eg blood. For example mineral levels in the blood will not tell you much about your bone mineral status.

As posted above, trying to get the dietary nutrients that meet our basic needs by using supplements to try and address the damage we have done to our foods is a bit of a guessing game. Even whole organic foods may well not contain the same levels of minerals as those eaten 50 years ago - which by then were already often depleted compared with foods from earlier in the century. . .

As ever it is important not to lose sight that the body is enormously complex, much is not know, we are all subtly different, so please discuss dietary changes etc with you medical and or dietary advisors.

[R.B.]

http://www.ncbi.nlm.nih.gov/pubmed/22412148

J Clin Oncol. 2012 Mar 12. [Epub ahead of print]
Fatigue, Inflammation, and ω-3 and ω-6 Fatty Acid Intake Among Breast Cancer Survivors.
Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Wilder Smith A, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, Ballard-Barbash R.
Source

Catherine M. Alfano, Ashley Wilder Smith, and Rachel Ballard-Barbash, National Cancer Institute, National Institutes of Health, Bethesda, MD; Ikuyo Imayama, Marian L. Neuhouser, Anne McTiernan, and Cornelia M. Ulrich, Fred Hutchinson Cancer Research Center; Anne McTiernan, University of Washington, Seattle, WA; Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine, Columbus, OH; Kathleen Meeske, University of Southern California, Los Angeles; Leslie Bernstein, City of Hope National Medical Center, Duarte, CA; Kathy B. Baumgartner, University of Louisville, Louisville, KY; and Cornelia M. Ulrich, German Cancer Research Center, Heidelberg, Germany.
Abstract

PURPOSEEvidence suggests that inflammation may drive fatigue in cancer survivors. Research in healthy populations has shown reduced inflammation with higher dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), which could potentially reduce fatigue. This study investigated fatigue, inflammation, and intake of ω-3 and ω-6 PUFAs among breast cancer survivors. METHODSSix hundred thirty-three survivors (mean age, 56 years; stage I to IIIA) participating in the Health, Eating, Activity, and Lifestyle Study completed a food frequency/dietary supplement questionnaire and provided a blood sample assayed for C-reactive protein (CRP) and serum amyloid A (30 months after diagnosis) and completed the Piper Fatigue Scale and Short Form-36 (SF-36) vitality scale (39 months after diagnosis). Analysis of covariance and logistic regression models tested relationships between inflammation and fatigue, inflammation and ω-3 and ω-6 PUFA intake, and PUFA intake and fatigue, controlling for three incremental levels of confounders. Fatigue was analyzed continuously (Piper scales) and dichotomously (SF-36 vitality ≤ 50).ResultsBehavioral (P = .003) and sensory (P = .001) fatigue scale scores were higher by increasing CRP tertile; relationships were attenuated after adjustment for medication use and comorbidity. Survivors with high CRP had 1.8 times greater odds of fatigue after full adjustment (P < .05). Higher intake of ω-6 relative to ω-3 PUFAs was associated with greater CRP (P = .01 after full adjustment) and greater odds of fatigue (odds ratio, 2.6 for the highest v lowest intake; P < .05). CONCLUSION Results link higher intake of ω-3 PUFAs, decreased inflammation, and decreased physical aspects of fatigue. Future studies should test whether ω-3 supplementation may reduce fatigue among significantly fatigued breast cancer survivors.

[R.B.]

Low vitamin D is a huge issue for lots of reasons. This information comes from this thread
http://her2support.org/vbulletin/showthread.php?t=43711
in case you have not seen it.



Two telling excepts from scientific papers


"More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population."
http://jcem.endojournals.org/cgi/con...ract/90/6/3215

"These findings show that free-living elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter and that dietary enrichment or supplementation with vitamin D should be seriously considered during this season."
http://grande.nal.usda.gov/ibids/ind...&therow=110910




(-: Some Must Watch University of California TV videos (-:

Pass them on please (-:

This is a passionate understandable very punchy slightly acerbic lecture to doctors by Dr Holick, a man ahead of his time, an expert in the vitamin D field, and someone who bravely stuck to his science through the dark days despite wide opposition and ridicule, and now thanks to his grit and the determined work of others Vitamin D is on the agenda.


Dr Holick - D-Lightful Vitamin D: Bone & Muscle Health and Prevention of Autoimmune and Chronic Diseases
http://www.uctv.tv/search-details.aspx?showID=15773




Other fascinating UCLA lectures

Vitamin D Prevents Cancer: Is It True?
http://www.uctv.tv/search-details.aspx?showID=16940

Skin Cancer/Sunscreen - the Dilemma
http://www.uctv.tv/search-details.aspx?showID=15770

Dose-Response of Vitamin D and a Mechanism for Cancer Prevention
http://www.uctv.tv/search-details.aspx?showID=15767

Vitamin D & Cardiovascular Disease- New Frontiers for Prevention
http://www.uctv.tv/search-details.aspx?showID=15772

[R.B.]

Iodine is another potential major dietary issue.

It is hard to believe in a modern world with so many resources and so much technology that many people are iodine deficient, but that is exactly what the evidence and science points to.

Iodine is truly fundamental to the function of the body. Only 20% of the stored iodine in the body is in the thyroid, the other 80% is used in other cells all over the body, in a variety of very important ways. Iodine has very particular chemical properties and may well have been fundamental in the development of life as outlined by Professor Venturi, a leading and arguably under-recognised researcher in the field.

"Environmental iodine deficiency: A challenge to the evolution of terrestrial life?

Venturi S, Donati FM, Venturi A, Venturi M.
Thyroid. 2000 Aug;10(8):727-9.

http://iodine4health.com/special/evo..._evolution.htm

“In conclusion, we believe that environmental iodine deficiency might be an important evolutionary factor of terrestrial life of vertebrates. ”"

Many people are arguably iodine insufficient due to a combination of low intake, iodine blocking foods, higher iodine utilisation, iodine blocking chemicals, and the inclusion in the diet of 'large' amounts of bromine and fluorine products which compete with iodine.

Western recommended intakes are much lower than recorded Japanese intakes. Current Japanese intake was reported to be about 1mg a day, and their parents ate more. Historically the Japanese had lower levels of many western conditions.

Iodine in the soil is deficient in many parts of the world, so you cannot count on getting it in your diet. Some Governments have recognised falling iodine intake is a serious health issue, for example in Australia they have restarted to iodise bread.

Iodine intakes have fallen significantly over the last 30 years, for a number of reasons. For example the intake / iodination of foods has fallen and iodine is no longer used to disinfect cattle milking systems / teats.

There are many factors in the modern lifestyle and diet that increase the requirement for iodine. Things that block iodine uptake and usage by the body are everywhere, for example fire retardants, and form an increasing part of our lives. Many of the healthy green vegetables such as brassica are goitregenic (iodine blocking). Industrial production and some rock based fertilizers introduce perchlorate into the food chain. Perchlorate is a strong iodine blocker.

Other chemicals of the same family as iodine, the halides, such as fluoride and bromide compete with iodine and block iodine usage and uptake. Our intakes of bromine and fluorine have significantly increased.

For example bromide is added to flour in some countries, and included in drinks. It is also used a a flame retardant. Bromide is found in sea food but with iodine.

Fluoride is added to water and toothpaste, and there is evidence it may protect young teeth, but does not seem to have much effect on adult teeth - but possibly at the cost of reducing the structural 'hardness' of the bone in teeth - does that include other bones I have no idea, but logically it might.

Most foods contain very little iodine. The primary source of iodine is marine foods. Seaweeds often contain from significant to very large amounts of iodine.

Iodine is concentrated by the breast and dairy foods are an important dietary iodine source, but many now avoid dairy products. The amount of iodine in the milk will reflect the amount in the pasture / and or feed - so cattle fed on deficient pastures will produce milk low in iodine.

Some fresh water plants provide a source of iodine and some cultures would burn them and eat the ash.

We are probably able to survive on relatively low iodine intakes on a 'natural' diet in an unpolluted world, and many peoples who had relatively limited access to iodine lived long health lives. These people may have relied on particular food sources to provide the minimum of iodine needed. People of the Andes carried and traded fish eggs far inland. Mountain people like the Georgians and Hunza ate dairy products. People in Africa are reported to have collected burnt and ate fresh water plants. In contrast some populations are seriously iodine deficient with very serious health and developmental consequences.

Many western populations are also seriously iodine deficient. The problem today is a combination of changing diets that increase iodine need, dietary goitregens, chemical goitregens, and declining intake.

Iodine has many roles in the body and deficiency results in a wide range of health issues.

Everything in the body interlinks, for example selenium has particular importance in the metabolism of iodine, and in considering iodine intakes it is important not to loose sight of the whole picture. Omega 3 and 6 which also interact with iodine, which is where my interest started, and lead to me reading round the subject.

This passionate excellent and highly thought provoking video by a respected Doctor who has been working with iodine for a number of years deals with some of the items mentioned above in more detail, as well as setting out his clinical experience in using iodine to treat his patients. The video is iodine centric, and needs to be considered in a wider dietary context.

You may wish to start the video at 1 hour 24 minutes 20 seconds where Dr Brownstein talks about iodine and breast cancer.

Sadly research into iodine is limited presumably because it cannot be patented - one of the flaws of a purely financially driven economic model.

I have started an iodine thread on the nutrition page which includes this post, included further information, and tries to bring together historic posts by others.
http://her2support.org/vbulletin/showthread.php?t=53928

As usual please discuss dietary change with your doctor.

Must watch video. You may want to start at the breast cancer / fibrosis section at just after 1 hour 24 minutes in.

Iodine The Misunderstood Nutrient David Brownstein

http://www.youtube.com/watch?v=Kd34EJ5E3bI

[Ellie F]

Thanks for the reminders!! Having recently been diagnosed with osteoporosis I am trying very hard to get the balance right so as to get as much calcium from diet but also to ensure I get enough vit d and magnesium.AS I hardly eat dairy it is much more of a struggle.
Ellie

[R.B.]

The ratios and amounts of the fats you eat ultimately alters the structure of the membranes of the cells. Changes in the the structure of the cell membrane alters their function. Polyunsaturated fats make cell membranes more flexible.

For example skin is made of cells, and cells are enclosed by membranes. Women make more long chain Omega 3 DHA than men and this may be part of the explanation for softer skin etc

Cell membranes have different composition in different parts, in a sense in the same way as our skin, our membrane with the outside world, differs in composition according to its functions. Lipid rafts are areas with a different composition within the main membrane.

The body also uses the cell membrane as a 'larder' for fats, and draws down on them when they are needed as ingredients to make chemical messengers.

The the type and amount of Omega 3 and 6 you eat really does matter, in that it has significant effect on the function of cells and so the body.






Cell Biochem Biophys. 2012 May 24. [Epub ahead of print]
Chemical-Physical Changes in Cell Membrane Microdomains of Breast Cancer Cells After Omega-3 PUFA Incorporation.
Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F, Arosio P, Rizzo AM.
Source

Dipartimento di Scienze Farmacologiche e Biomolecolari, UniversitÃ* degli Studi di Milano, Via D. Trentacoste 2, 20134, Milan, Italy, paola.corsetto@unimi.it.
Abstract

Epidemiologic and experimental studies suggest that dietary fatty acids influence the development and progression of breast cancer. However, no clear data are present in literature that could demonstrate how n - 3 PUFA can interfere with breast cancer growth. It is suggested that these fatty acids might change the structure of cell membrane, especially of lipid rafts. During this study we treated MCF-7 and MDA-MB-231 cells with AA, EPA, and DHA to assess if they are incorporated in lipid raft phospholipids and are able to change chemical and physical properties of these structures. Our data demonstrate that PUFA and their metabolites are inserted with different yield in cell membrane microdomains and are able to alter fatty acid composition without decreasing the total percentage of saturated fatty acids that characterize these structures. In particular in MDA-MB-231 cells, that displays the highest content of Chol and saturated fatty acids, we observed the lowest incorporation of DHA, probably for sterical reasons; nevertheless DHA was able to decrease Chol and SM content. Moreover, PUFA are incorporated in breast cancer lipid rafts with different specificity for the phospholipid moiety, in particular PUFA are incorporated in PI, PS, and PC phospholipids that may be relevant to the formation of PUFA metabolites (prostaglandins, prostacyclins, leukotrienes, resolvines, and protectines) of phospholipids deriving second messengers and signal transduction activation. The bio-physical changes after n - 3 PUFA incubation have also been highlighted by atomic force microscopy. In particular, for both cell lines the DHA treatment produced a decrease of the lipid rafts in the order of about 20-30 %. It is worth noticing that after DHA incorporation lipid rafts exhibit two different height ranges. In fact, some lipid rafts have a higher height of 6-6.5 nm. In conclusion n - 3 PUFA are able to modify lipid raft biochemical and biophysical features leading to decrease of breast cancer cell proliferation probably through different mechanisms related to acyl chain length and unsaturation. While EPA may contribute to cell apoptosis mainly through decrease of AA concentration in lipid raft phospholipids, DHA may change the biophysical properties of lipid rafts decreasing the content of cholesterol and probably the distribution of key proteins.

[R.B.]

More about the importance of lipid rafts ^ (see previous post) and the possibility they have a very special role in HER2

This explains the active HER2 receptors (Docking stations built into the cells outer wall (membrane) into which the HER2 protein fits like a key) are only found in a particular areas of the double skin fat/protein/cholesterol bubbles that form the outer layer of cells (think bubble). The particular areas in which active HER2 receptors are apparently exclusively found are called lipid rafts (Special functional areas within the surface of the bubble that contain greater amounts of close packed fats)

It also explains that the docking locks come in three types, on activated by one HER2 protein (monomer), another type by a pair of HER2s (homodimer) and a third by an HER2 combined with another, probably specific, substance (heterodimer).

The results also suggest that there may be a connection between an increased number of HER2 docking locks and more numerous areas of lipid rafts in the cell membrane.

The HER2 protein may look something like this
http://en.wikipedia.org/wiki/File:Tr...mplex_1N8Z.png see Wikipedia http://en.wikipedia.org/wiki/HER2/neu

The paper explains DHA may alter the structure of the rafts so possibly disrupting the docking locks which ultimately may lead to higher cell death rates in cells expressing more HER2 receptors.

ABSTRACT

http://www.ncbi.nlm.nih.gov/pubmed/22749134

J Nutr Biochem. 2012 Jun 27. [Epub ahead of print]
Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression.
Ravacci GR, Brentani MM, Tortelli T Jr, Torrinhas RS, Saldanha T, Torres EA, Waitzberg DL.
Source

Department of Oncology Medical School, University of São Paulo, 01246-903 São Paulo, Brazil; Department of Gastroenterology Medical School, University of São Paulo-LIM 35, 01246-903 São Paulo, Brazil.
Abstract

In HER-2-overexpressing breast cells, HER-2 receptors exist on the cell surface as monomers, homodimers and heterodimers. For signal activation and transduction to occur, HER-2 must be localized to lipid rafts. Therefore, we hypothesized that the amount of lipid rafts on the cell membrane would be a factor in HER-2 signaling. To test this, we used HB4a (an untransformed human mammary epithelial cell line) and HB4aC5.2 cells. HB4aC5.2 cells are HB4a derivatives that have been transfected with five copies of pJ5E.c-ErbB-2 and express approximately 900 times more HER-2 than HB4a cells. In these cells, HER-2 overexpression was accompanied by increased lipid rafts in cell membranes, a hyperactivation of downstream Akt and ERK1/2 proteins, and an increased rate of cell growth compared to HB4a. In addition, HER-2 overexpression was associated with an increased activation of FASN, a key enzyme involved in cellular lipogenesis. Its final product, palmitate, is frequently used to synthesize lipid rafts. We further hypothesized that treatment with docosahexaenoic acid (DHA), an omega-3 fatty acid, would disrupt the lipid rafts and lead to a growth arrest. In HB4aC5.2 cells, but not HB4a cells, we found that DHA treatment disrupted lipid raft; inhibited HER-2 signaling by decreasing activation of Akt, ERK1/2 and FASN proteins; and induced apoptosis.Although little is known about lipid rafts, our data support the idea that disturbances in these microdomains induced by DHA may represent a useful tool for controlling the signaling initiated by HER-2 receptors and its therapeutic potential in the treatment of HER-2 positive breast cancer.

[R.B.]

BMC Cancer. 2012 Aug 15;12(1):355. [Epub ahead of print]
Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial.
Ghoreishi Z, Esfahani A, Djazayeri A, Djalali M, Golestan B, Ayromlou H, Hashemzade S, Asghari Jafarabadi M, Montazeri V, Keshavarz SA.
Abstract

ABSTRACT:
BACKGROUND:

Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy.
METHODS:

This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score".
RESULTS:

Twenty one patients (70 %) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7 %( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95 % CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95 % CI = ([MINUS SIGN]2.06 -0.02), p = 0.054).
CONCLUSIONS:

Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT01049295).

[rhondalea]

Thanks for that study.

During chemo, I took 4.252 grams of fish oil daily, for a total of 800mg DHA and 1600mg EPA. I thought it was ALCAR that prevented me from experiencing any neuropathy, but it now appears that the high dose fish oil may have played a role.

[R.B.]

BMC Med. 2012 May 21;10:50.
New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids.
de Lorgeril M, Salen P.
Source

Laboratoire Cœur & Nutrition, TIMC-IMAG, Université Joseph Fourier-CNRS, Faculté de Médecine, Grenoble, France. michel.delorgeril@ujf-grenoble.fr
Abstract

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent cardiovascular disease and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

PMID:
22613931
[PubMed - in process]
PMCID:
PMC3394202

Free PMC Article here http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394202/

[R.B.]

Lani kindly posted this comment / paper summary which identifies COX1 and COX2 related genes as possible targets in HER2 related cancer. Interestingly COX 1 and COX 2 are key enzymes in the Omega 6 pathways in that they convert Omega 6 fats to active derivatives. NSAIDS intervene in these pathways in different ways and prevent formation of these products. . . In very simplistic terms reducing the amount of plant based Omega 6 in the diet to under 4% of calories and increasing Omega 3 which competes for space in the cell membrane will also reduce the amount of Omega 6 COX products made by the body.

The full free version of the paper referred to in the above post includes the following comment. "In animal studies, omega-6 PUFAs have a strong mammary tumor-enhancing effect [21,22]. In order to exert their carcinogenic effects, they must first undergo an oxidative metabolization, mainly through the lipoxygenase and cyclooxygenase pathways [23,24]. " COX is the short form for cyclooxygenase, the same COX 1 and COX 2 family as Lani is talking about above. COX enzymes prefer Omega 6s. So give COX enzymes a ready supply of Omega 6 and the right conditions and they will get busy. Incidentally LOX enzymes prefer Omega 3s, but will also use Omega 6s particularly when Omega 3s are in short supply . . .



http://her2support.org/vbulletin/showthread.php?t=56001


"I have railed for years on the need to divide her2+ bc into subtypes in order to discover the best targets/ combination treatment for each subtype

I have also railed for years to encourage bone marrow sampling to discover if the disseminated tumor cells there could tell which patients needed systemic therapy as well as local treatment (surgery and/or radiation therapy) and to discover whether the initial therapy was successful or whether additional therapy against other targets is needed

I have not hidden that I believe in the cancer stem cell "theory" of breast cancer

Here scientists have found (in mice, but results corroborated when evaluating a cohort of human breast cancer patients accumulated by vantViver) that an 8 gene signature derived from cancer stem cells of her2+ breast cancer (in mice)
can stratify her2+ breast cancer patients prognoses and serve as targets for therapy.

Two of the genes can be affected by over the counter NSAIDs (cox1 and cox2) and an already FDA approved drug in use for many years -an iron chelator used for iron poisoning and inherited iron deposition diseases is available as well.

I am hopeful studies in this direction will help stratify her2+ breast cancer into groups (even though every patients tumor is unique) which can be treated similarly ie similar targets, turning her2+ breast cancer into an annoying chronic disease or even curing it.

I hope this approach can be used against other forms of cancer as well

Proteomics. 2012 Sep 19. doi: 10.1002/pmic.201200103. [Epub ahead of print]
Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice.
Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q, Chen H.
Source
Department of Biological Science, Centre for colon cancer, University of South Carolina, Columbia, SC 29208, USA.
Abstract
HER2 overexpression leads to mammary tumorigenesis and its elevated levels leads to increase in cancer stem cells (CSCs), invasion and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and western blotting. Ferittin Heavy Chain 1 was identified as a candidate gene which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14 and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID: 22997041"

[KDR]

Could this be summarized, i.e., what is a good ratio of O3 to O6 by example. Thank you.
Karen

[R.B.]

(In Progress - I will revisit this over the next few days and amend it - if I put it in a word folder I will be less motivated to get it finished (-



Hi KDR

I simply cannot believe it is over a year that I have been meaning to respond to your question !!!

The reason I did not respond straight away is that the answer is not simple, biology it seems rarely is.

I will try and summarize a few thoughts that may help identify key issues.

1. Omega 3 and 6 fats are families made from a basic Omega 3 and a basic Omega 6 building block, which cannot be made by mammals but which can be made by plants. The fact that these fat must be got in the diet, and are hugely influential in body function is of immeasurable functional significance. Each member of each family has different functions. In general terms Omega 6 products promote inflammation, blood vessel formation, cell migrations and related activities. Omega 3s tend to be counter inflammatory, reduce blood vessel formation etc. It is complex, and these are generalizations.

2. With the help of our cells, and or the bacteria in our guts, we can make almost all other fats. Bacteria make short fats. We can make a 16 carbon saturated fat palmitic acid, which can be elongated and double bonds added to make other fats including oleic acid; the fat found in olive oil. We also have mechanisms to break fats down to shorter units

3. The plant based Omega 6 is an 18 carbon chain, with 2 double bonds.

4. The plant based Omega 3 is an 18 carbon chain with 3 double bonds.

5 The plant based Omega 3 and 6 can be elongated and double bonds added to make longer fats. DHA and EPA are longer fats of the Omega 3 family. GLA has one more double bond, and arachidonic acid is a longer fat and has more double bonds; both are from the Omega 6 family.

6. Plant based Omega 3 and 6 is very common because it is found in all 'green' plant based material, but in relatively small amounts; parts per thousand. Plant based Omega 6 is only found in quantity in plant reproductive material, seeds nuts and grains. Plant based Omega 3 is occasionally found in quantity in seeds, nuts and grains but not very often.

7. So in a wild diet we would have got slightly more plant based Omega 3 than 6 for most of the year with a boost of mainly Omega 6 in the fruiting and seeding seasons. In the wild seeds and nuts were not that plentiful, and very much weather dependent. On a year round basis we are maybe looking at an average intake of about 2% of calories, maybe a bit more or less depending on the particular diet. Modern intake of the Omega 6 plant based fat is maybe 10% and up to 25%, so a vast increase over our pre agricultural ancestors. The main source by far is vegetable oils.

8 Our cells can convert the plant based fats using two enzymes to the longer fats in the family. Conversion becomes increasingly difficult as the fats get longer. Conversion is much more efficient at lower intake levels. Imbalances heavily disrupt conversion. Some people are genetically less efficient converters, maybe up to 40% less efficient, and more often include celtic types/ maybe descendents of people who dwelled near the oceans ( the ocean dweller bit is postulation).

9. Importantly and probably because of estrogen ( and progesterone?) women convert plant based fats to long chain fats eg plant based Omega 3 to DHA about 10 times more efficiently than men do. This is arguably of huge importance and helps define some of the gender differences. It also magnifies the effect of Omega 3 and 6 dietary imbalances and deficiencies. These fats are fundamental to the reproductive processes and pathways including the hormonal pathways. Breast tissue concentrates these fats in breast milk to supply them to the infant, so they have a particularly important role in the breast in general terms.

10. A small amount of long chain fat Omega 3 and 6 can be got through the diet taking advantage of conversion by other animals. Long chain Omega 3s are primarily found in marine animals. Wild animals (pastured herbivores, fowl, etc) have higher Omega 3 levels than grain fed animals.

11. Omega 3 and 6 are rival siblings. The amount of each in the cell membranes reflects the amount in the diet. Both compete for the elongation conversion enzymes. An excess of either will create imbalances. Too much Omega 6 will magnify the effects of Omega 6, and too much Omega 3 will magnify the Omega 3 pathways at the expense of Omega 6 activity, which is why a balance is so important. It is not just the amount of Omega 3 and 6 that go out of balance but all their downstream products and effects. including inflammation, blood vessel formation, cell migration, cell structure, cell function at a host of levels etc etc.

In summary

You are aiming to balance plant based Omega 3 and 6, and get adequate long chain Omega 3s. Long chain Omega 6s are more readily available than 3s due to our modern food chain and higher plant based Omega 6 intake / body fat stores. Most but by no means not all will have adequate long chain Omega 6; for example breast feeding women are often lowish in long chain Omega 6.

As a vast generalization most vegetable oils are best avoided partially because they contain lots of Omega 6 and partly because of what processing does to them. Some have other useful properties - eg cold pressed olive is rich in antioxidants, so it is best to look them up, http://nutritiondata.self.com/ but the majority are high or very high in Omega 6, and often contain almost no Omega 3. They are starting to try and breed plants which are higher in Omega 9 or have a better 3:6 balance, but there is still the issue of processing and onward treatment in food preparation.

Most of us are short of Omega 3s so adding an Omega 3 rich source eg a little flax seed or oil - there are others - is logically a good idea.

Avoid industrial chicken which is very high in Omega 6, because they are fed almost exclusively on grains.

Many processed foods products will contain vegetable oils so are best avoided, and particularly so crisps cooked in vegetable oils; it is not just the vegetable oils per se but what treatment temperature cooking etc does to them which is arguably such an issue.

Try and get some oily marine foods / marine foods generally, and or supplement with fish oil in modest amounts. Omega 3 in fish muscle are in a different form to those in fish fats, and are metabolized differently, so marine foods provide a wider range of Omega 3 related products than fish oil, and marine foods contain lots of other useful nutrients.

Nuts are rich in minerals and other nutrients, and so I am ambivalent about them in larger quantities, and for them in smaller quantities.

Most have a historic excess of Omega 6, which the body likes to store in the body fats. Our omega 6 in body fat has increased from maybe 4% in the 1950s to up to 25% today. It can take a significant amount to time to re-balance the body fat content - years - but interestingly breast tissue changes much faster. So it is going to take a while to re-balance the body tissues.

There is some evidence that the benefits of fish oil e.g. EPA and DHA tail off around 2.5 to 3 grams (EPA plus DHA combined total) a day.

The optimal amount of plant based Omega 3 e.g. flax oil is less clear - the issues are very complex. Johana Budwig interestingly reported good results with flax oil and cottage cheese in the diet, and was robustly supported by her patients. The explanations were based in the knowledge of the day and lack clarity, but make some sense in a very fuzzy intuitive way - these fats are central to plant function; and plants derive their energy from light; Omega 3 it is suggested may have an important role in photosynthesis; Omega 6 is central to plant reproduction - so they may also have important roles in humans and have proved to do so. We do not really know as much about the metabolism of plant based Omega 3 as we should. Interestingly her suggestions also include sun (vitamin D), 'fermented foods' good for gut function / source of short chain fats, no refined foods etc - so lots that is familiar. Unfortunately there does not appear to be any references to her clinical notes etc, which information would provide a much clearer view of what her protocol was and how effective it was, so I post information about her with a cautionary caveat, and particularly as to some of the claims that are made by sites promoting 'her' protocol, which sites also often promote some pretty quirky treatments which good or bad should not be confused with my simple premis that Omega 3s and in this case plant based Omega 3 has highly influential roles in cellular metabolism.

I do think and the trial based evidence on this site supports a general premis that excess Omega 6 and lack of Omega 3 may increase the risk of cancer, and that the Omega 3 and 6 families and their downstream products have their own individual roles, some of which have received more research attention than others.

Getting adequate plant based and long chain Omega 3s and reducing excessive intake of plant based Omega 6s, as part of a healthy diet may well reduce the risk of cancer. Work by Budwig, anecdotal evidence etc raises the question if taking larger amounts of plant based Omega 3 and longer chain Omega 3s than would be found in the natural diet as a initial strategy to try and rebalance body fats, and cellular function at many levels, is a useful strategy in the prevention / slowing / reduction of recurrence etc.

The importance of wider diet, adequate vitamin D and related fat soluble vitamins, iodine, and a host of other nutrients, cannot be stressed enough. The Omega 3;6 balance may prove to be a highly significant factor in the risk of cancer, but it is only one of many.

[R.B.]

D6D is short hand for one of the two enzymes that convert the plant based Omega 3 and 6 to the long fats.


LA is the plant based Omega 6 linoleic acid

AA arachidonic acid is an important elongated fat made form the plant based Omega 6.

PGE2 is a downstream product of Omega 6

Excessive Omega 6 tends to overwhelm the D6D enzyme creating an excess of downstream product. Omega 3 if present would help counterbalance that effect.


Also see following post



Cancer Sci. 2013 Feb 18. doi: 10.1111/cas.12129. [Epub ahead of print]
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, Massachusetts, USA.
Abstract

Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE2 ), 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 PGE2 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 PGE2 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, PGE2 levels were increased in cancerous tissue, particularly in ER- patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE2 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.

© 2013 Japanese Cancer Association.

[R.B.]

As a follow on from the above the D6D conversion enzyme activity has been shown to have an important role in cancer promotion and blocking it has been shown to significantly reduce tumor growth.

They suggest blocking this pathway and increasing Omega 3 intake of both plant and long chain fats may be an interesting potential treatment strategy.

Increasing Omega 3 intake and reducing Omega 6 intake will help rebalance these pathways.


Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice
Chengwei He,1,4 Xiying Qu,1 Jianbo Wan,1 Rong Rong,1 Lili Huang,1 Chun Cai,2 Keyuan Zhou,2 Yan Gu,3 Steven Y. Qian,3 and Jing X. Kang1,2,*
Wolf-Hagen Schunck, Editor

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480421/

The whole article is available on the link above

"Arachidonic acid (AA), an omega-6 (n−6) polyunsaturated fatty acid, is converted through three major pathways– the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 epoxygenase pathways–into bioactive lipid mediator eicosanoids, including prostaglandins (PGs), leukotrienes (LTs), and epoxyeicosatrienoids (EETs), respectively [5], [6] (Figure S1). These metabolites have crucial roles in chronic inflammation and cancer [5]–[7]. Increased AA metabolism and eicosanoid formation is a common feature of various types of cancer cells [8], [9]. AA-derived pro-inflammatory eicosanoids, particularly PGE2 and LTB4 which are produced by tumor cells and their surrounding stromal cells, are key mediators in their crosstalk and can accelerate tumor growth and metastasis through several mechanisms [5], including: 1) directly activating their receptors on tumor cells to induce cell proliferation, survival, migration, and invasion through multiple signaling pathways in both autocrine and paracrine manners, 2) directly inducing cancer cells to secrete growth factors, pro-inflammatory mediators and angiogenic factors that turn a normal microenvironment into one that supports tumor growth and spread, and 3) directly binding receptors on stromal cells to promote a tumor-supportive microenvironment by inducing angiogenesis and evading attack by the immune system"

[Andrea Barnett Budin]

Should I be taking Krill Oil vs my Omega 3's?

I don't need a symposium answer, just a simple explanation for a simple girl, please.

RB, you are the go-to guy on this topic and you've always been sooo great to all of us, your Sisters. Thanks for remembering us.

Andi