The traditional diet of Greece and cancer.

[R.B.]

Evidence Omega 3 DHA may improve the outcome of some chemotherapies




Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial
P Bougnoux,1,2* N Hajjaji,1,2 M N Ferrasson,1,2 B Giraudeau,3 C Couet,1,4 and O Le Floch1,2

http://www.ncbi.nlm.nih.gov/pmc/arti...6/?tool=pubmed

"Several research groups, including ours, have shown that docosahexaenoic acid (DHA), a lipid of marine algal origin mainly provided by diet, has, experimentally, the ability to increase the efficacy of anti-cancer agents."

"As DHA incorporates into cell membranes, this differential handling of ROS may account for the selectivity of DHA-induced tissue sensitisation by anti-cancer agents in tumour tissues compared with non-tumour tissues. Along this line, the lack of additional toxicity in non-tumour tissues has been consistently documented under conditions in which tumour tissue DHA was sensitised to chemotherapy (Hardman et al, 1999; Kato et al, 2002; Germain et al, 2003; Xue et al, 2007) or radiation therapy (Wen et al, 2003) in rodents.
On the basis of these results, we conducted a pilot phase II clinical trial in metastatic breast cancer patients to investigate the efficacy and safety of adding DHA to an ROS-generating chemotherapy regimen, that is an anthracycline-based regimen (FEC). We found that the combination was safe while retaining significant anti-tumour activity in the sub-population of patients with high plasma DHA incorporation, suggesting that DHA has a potential to specifically chemosensitise tumours."

[jhandley]

Researchers at the University of California, San Francisco reveal in the January 20, 2010 issue of the Journal of the American Medical Association (JAMA) that heart disease patients who have higher levels of omega-3 fatty acids experience a lower rate of reduction in telomere length over time. Telomeres, which are protective DNA sequences at the ends of chromosomes, shorten with the age of the cell, and their length is a marker of biological aging.
In their introduction to the article, Ramin Farzaneh-Far, MD and colleagues note that "Multiple epidemiologic studies, including several large randomized controlled trials, have demonstrated higher survival rates among individuals with high dietary intake of marine omega-3 fatty acids and established cardiovascular disease. On this basis, the American Heart Association recommends increased oily fish intake and the use of omega-3 fatty acid supplements for the primary and secondary prevention of coronary heart disease. The mechanisms underlying this protective effect are poorly understood but are thought to include anti-inflammatory, antiplatelet, antihypertensive, antiarrhythmic, and triglyceride-lowering effects."

[weety]

Wow! This is a fascinating thread. I read lots of it. . . and now, I'm set on improving my omega 3 uptake! Which nuts & seeds are high in omega-6 and which are higher in omega-3? I'm also confused about olive oil. Does it have omega-3?

[R.B.]

Hi Weety

Thanks for the kind thoughts.


Olive oil has a plant based 3:6 ratio of 1:10. and is about 10% Omega 6, and mainly Omega 9. We can make Omega 9 in the body. The useful parts of olive oil are the antioxidant compounds they contain, so virgin cold pressed is best. Commercial oils may be adulterated with cheaper high six oils - money again - bulking oils to obtain farm subsidies.

You will find info on seeds and nuts here. Nuts are a useful source of minerals.
http://nutritiondata.self.com/

Please do check out the vitamin D and iodine videos. Many are deficient in both.

Many of us are also mineral deficient due to depletion of minerals in the soil and refining of food, so lots of nutrient dense foods, bone broths, offal etc.


If you eat a lot of grain, fresh ground is better. Stephan regularly blogs on the best way to prepare grains to minimise the substances they contain that inhibit mineral uptake. http://wholehealthsource.blogspot.com/

[R.B.]

In essence Omega 3 and 6 fats alter the activation and activity of genes in breast cancer cells



Estrogen receptor-dependent genomic expression profiles in breast cancer cells in response to fatty acids

http://www.ncbi.nlm.nih.gov/pmc/arti...6/?tool=pubmed

"A case-case study that evaluated the association of dietary fat intake of selected fatty acids found that high intakes of linoleic acid in premenopausal breast cancer patients were associated with a threefold higher risk of ER− than ER+ tumors.[5]"


"A study of the dietary intake of fatty acids in premenopausal breast cancer patients found an association between linoleic acid intake and a higher risk of ER− than ER+ breast tumors.[5] The omega-3 fatty acids, EPA and DHA, are shown to inhibit the growth of ER− and ER+ breast cancer cells in vitro.[15,16]"

[R.B.]

http://www.ncbi.nlm.nih.gov/pubmed/20878979

Int J Cancer. 2010 Sep 28. [Epub ahead of print]
Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: A prospective cohort study.

Murff HJ, Shu XO, Li H, Yang G, Wu X, Cai H, Wen W, Gao YT, Zheng W.

Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Abstract

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFA) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RR) and 95% confidence intervals (CI) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid, or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR=2.06; 95% CI=1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids. © 2010 UICC.

Could you interpret this study please? WHat is PUFA?

THanks

[R.B.]

Sorry over familiarity with the terms on my part (-:

PUFA = polyunsaturated fatty acid

n3 = Omega 3

n6 = Omega 6

Marine 'PUFA' are likely to be mainly Omega 3 EPA and DHA

RR = relative risk

It looks like they split the groups into 3, and are saying that the group with the most Omega 6 and the least Omega 3 in the diet had approximately twice the risk of breast cancer of the group with the highest Omega 3 and lowest Omega 6.

They are saying at the most basic level that the results suggest risk of BC is more about the Omega 3:6 balance rather than the absolute amounts of Omega 3 or 6 in the diet.

I have not seen the whole paper, and Chinese dietary Omega 3 : 6 ratios historically would have been better that those in the west, so I just post this as another twig in the Omega 3 : 6 debate.


This is part of the pattern seen in this thread.

There is a French paper posted here somewhere looking at the risk that excised breast lumps were cancerous. They looked at the amount of long chain Omega 3 in the breast tissue v the number of lumps that were cancerous. They split the group into four. The women with the highest amounts of long chain Omega 3 had a 70% lower risk that the lumps were cancerous than the women with the lowest amounts of long chain Omega 3.

Thought provoking stuff (-:

[R.B.]

The plant based Omega 3 (as found in flax oil) may reduce the invasive potential of cancer cells a 1994 paper suggests. This is particularly interesting as it looks a breast fat tissue. ( found whilst looking for something unrelated as usual)


Alpha-Linolenic acid content of adipose breast tissue: a host determinant of
the risk of early metastasis in breast cancer
P. Bougnoux"2, S. Koscielny3, V. Chajes', P. Descamps4, C. Couet5 & G. Calais'
'Laboratoire de Biologie des Tuneurs and 2Clinique d'Oncologie et Radiotherapie, JE 313, Faculte de Medecine, 37032 Tours,
France; 3Departement de Statistique Medicale, Institut Gustave-Roussy, 94805 Vilejuif, France; 'Clinique Gvnecologique et
Obstetricale, CHU, 37044 Tours, France; 5Laboratoire de Nutrition, JE 313, Faculte de Medecine, 37032 Tours, France.

http://www.ncbi.nlm.nih.gov/pmc/arti...00054-0150.pdf


"Summuary: The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initia!ly localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of a-linolenic acid (18:3f,3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3,, were single factors significantly associated with an increased risk of metastasis."


"The main cause of death in breast cancer patients is the development of distant metastases. Since a reduced 18:3,3 content of breast adipose tissue appears to be the first determinant of their occurrence in our series of patients, dietary supplementation of breast cancer patients in conditions
leading to a replenishment of adipose stores of 18:3,3 might delay or even prevent their clinical appearance."

[pibikay]

Can someone knowledgable spell out what fors partof traditional Greek diest
Best of luck to all

[R.B.]

^Hi Pibikay I will try and respond soon. Time has been a little short lately.

The work below was in mice but fascinating none the less.


Fish oil prevents breast cancer cell metastasis to bone.

Biochem Biophys Res Commun. 2010 Oct 28. [Epub ahead of print]


Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N.

Department of Pathology, University of Texas Health Science Center at San Antonio, Texas, United States.
Abstract

The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.

[R.B.]

More of the same (-:



Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):237-41. Epub 2010 Apr 2.
Fatty acids and breast cancer: the role of stem cells.

Erickson KL, Hubbard NE.

Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643, USA. klerickson@ucdavis.edu
Abstract

Studies with animal models in vivo as well as with animal and human tumor cells in vitro suggest that specific fatty acids could reduce breast tumorigenesis. The most striking dietary fatty acid studies in animal models that show promise for reduction of breast cancer risk in humans are with conjugated linoleic acids (CLA) and n-3 fatty acids.Although a number of mechanisms have been proposed, the specific target of those fatty acids is not yet known. We sought to determine whether the effects of those fatty acids on terminally differentiated tumor cell seen could be due to alteration of breast cancer stem cells. The isomers, cis9, trans11-CLA and trans10, cis12-CLA, and the n-3 fatty acids, docosahexaenoic and eicosapentaenoic, reduced the proliferation of, and had increased toxicity towards, mammary tumor initiating cells. One mechanism involved in the effect of n-3 fatty acids may be due to alteration of the profile of prostaglandins. These results indicate that select fatty acids may be useful for preventing or reducing the risk of breast cancer as they may target the tumor initiating cell.

[R.B.]

And More (-:


J Nutr. 2010 Dec 22. [Epub ahead of print]
Marine Fatty Acid Intake Is Associated with Breast Cancer Prognosis.

Patterson RE, Flatt SW, Newman VA, Natarajan L, Rock CL, Thomson CA, Caan BJ, Parker BA, Pierce JP.

Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093.
Abstract

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

[R.B.]

I found this whilst looking for something else.

It provides another reason to keep and eye on Omega 3 intake.



Am J Clin Nutr. 2008 Jul;88(1):216-23.
Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction.

Sun Q, Ma J, Campos H, Rexrode KM, Albert CM, Mozaffarian D, Hu FB.

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Abstract

BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations.

OBJECTIVE: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI.

DESIGN: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls.

RESULTS: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers.

CONCLUSIONS: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.

[R.B.]

Interesting that benefits were associated with fish rather than fish oil. I have only seen the extract of the paper so cannot comment.


J Nutr. 2011 Feb;141(2):201-6. Epub 2010 Dec 22.
Marine fatty acid intake is associated with breast cancer prognosis.

Patterson RE, Flatt SW, Newman VA, Natarajan L, Rock CL, Thomson CA, Caan BJ, Parker BA, Pierce JP.

Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. repatterson@ucsd.edu
Abstract

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

PMID: 21178081 [PubMed - in process]PMCID: PMC3021439 [Available on 2012/2/1]

Does anyone take DHA and EPA separately... if so how much?
Thanks

[R.B.]

Med Princ Pract. 2011;20(2):103-11. Epub 2011 Jan 20.
The protective effect of the Mediterranean diet: focus on cancer and cardiovascular risk.

Pauwels EK.

University of Pisa Medical School, Pisa, Italy. ernestpauwels @ gmail.com
Abstract

The lower occurrence of cancer and cardiovascular disease in the population around the Mediterranean basin has been linked to the dietary habits of the region. Indeed, this so-called Mediterranean diet is essentially different from the diets consumed in Western and Northern European countries and is rich in nuts, fruits, vegetables, legumes, whole-wheat bread, fish, and olive oil, with moderate amounts of red wine, which is mainly consumed during meals. Although a variety of cultural and religious traditions exist among the peoples of the Mediterranean area, olive oil, fish, and red wine hold a traditional and central position in the culinary routines of the region. The components of the diet contain an ample source of molecules with antioxidant and anti-inflammatory actions, among which omega-3 fatty acids, oleic acid, and phenolic compounds hold a prominent place. This review will summarize the results of important epidemiological studies that have investigated the protective effect of fish and olive oil on the risk of breast, prostate, and colorectal cancer and of wine on the risk of cardiovascular disease. The present review also aims to elucidate the various mechanisms by which various dietary components exhibit their beneficial action. In this respect, emphasis will be placed on the properties of omega-3 fatty acids from fish, oleic acid from olive oil, and phenolic compounds from olive oil and red wine.

[R.B.]

Synergistic effects of garlic and Omega 3 EPA

eicosapentaenoic acid = EPA
linoleic acid = common plant based Omega 6

Anticancer Agents Med Chem. 2011 Jan 26. [Epub ahead of print]
Anticancer Effects of Garlic and Garlic-derived Compounds for Breast Cancer Control.

Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K.

Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. tsubura@takii.kmu.ac.jp.
Abstract

Garlic and garlic-derived compounds reduce the development of mammary cancer in animals and suppress the growth of human breast cancer cells in culture. Oil-soluble compounds derived from garlic, such as diallyl disulfide (DADS), are more effective than water-soluble compounds in suppressing breast cancer. Mechanisms of action include the activation of metabolizing enzymes that detoxify carcinogens, the suppression of DNA adduct formation, the inhibition of the production of reactive oxygen species, the regulation of cell-cycle arrest and the induction of apoptosis. Selenium-enriched garlic or organoselenium compounds provide more potent protection against mammary carcinogenesis in rats and greater inhibition of breast cancer cells in culture than natural garlic or the respective organosulfur analogues. DADS synergizes the effect of eicosapentaenoic acid, a breast cancer suppressor, and antagonizes the effect of linoleic acid, a breast cancer enhancer. Moreover, garlic extract reduces the side effects caused by anti-cancer agents. Thus, garlic and garlic-derived compounds are promising candidates for breast cancer control.

[R.B.]

FADS 1 and 2 play a role in the creation of long chain polyunsaturated fats. There are genetic variants of FADS that make our ability to convert plant fats to long chain fats more or less efficient.

Those with less efficient conversion may have a greater need for food like fish which supply the long chain fats like DHA and EPA ready made.

Our ability to make EPA and DHA has a wide range of health and functional impacts, including the amount of EPA and DHA in breast milk.




Exp Biol Med (Maywood). 2010 Jul;235(7):785-95.
Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.

Simopoulos AP.

The Center for Genetics, Nutrition and Health, 2001 S Street NW, Washington, DC 20009, USA. cgnh@bellatlantic.net
Abstract

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

[SoCalGal]

Great update! Hello and thanks
Flori