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de Lorgeril and Salen BMC Medicine 2014, 12:54


Helping women to good health: breast cancer,
omega-3/omega-6 lipids, and related lifestyle
Michel de Lorgeril* and Patricia Salen

In addition to genetic predisposition and sex hormone exposure, physical activity and a healthy diet play important
roles in breast cancer (BC). Increased intake of omega-3 fatty acids (n-3) associated with decreased omega-6 (n-6),
resulting in a higher n-3/n-6 ratio compared with the western diet, are inversely associated with BC risk, as shown
by Yang et al. in their meta-analysis in BMC Cancer. High consumption of polyphenols and organic foods increase
the n-3/n-6 ratio, and in turn may decrease BC risk. Intake of high fiber foods and foods with low glycemic index
decreases insulin resistance and diabetes risk, and in turn may decrease BC risk. The modernized Mediterranean diet
is an effective strategy for combining these recommendations, and this dietary pattern reduces overall cancer risk
and specifically BC risk. High-risk women should also eliminate environmental endocrine disruptors, including those
from foods. Drugs that decrease the n-3/n-6 ratio or that are suspected of increasing BC or diabetes risk should be
used with great caution by high-risk women and women wishing to decrease their BC risk.

Please see related article:
Keywords: Polyphenols, Organic foods, Endocrine disruptors, Insulin, Diabetes, Cholesterol, Hypertension,
Mediterranean diet

Introduction the main ways of achieving this (first pregnancy before the
Breast cancer (BC) remains one of the commonest can- age of 20 years, breast feeding, late menstruation and early
cers – one in eight women will be diagnosed with BC menopause) are difficult to control.
in her lifetime [1] – and a leading cause of death from There are strong links between environmental/lifestyle
cancer. However, it remains a significant scientific and factors and BC, suggesting that modifying these factors
medical challenge. One of the crucial gaps identified is may result in decreasing BC risk, although there has
how to implement a sustainable preventive lifestyle been no randomized trial that clearly demonstrated this. As
strategy [2]. Both risk factors and protective factors changing these factors has been shown also to definitely
must be considered. Some risk factors, such as genetic reduce the risk of fatal diseases, notably cardiovascular
predisposition, cannot be modified, whereas others diseases in randomized trials, it is reasonable to propose
(unhealthy diet, sedentary lifestyle) can be avoided. these changes to high-risk women and to women who
Increasing protective factors may be crucial for women at wish to reduce their BC risk.
high risk (as evaluated by the National Cancer Institute’s For instance, dietary fats have been extensively studied in
(NCI’s) BC Risk Assessment Tool [3]) and in preventing the prevention of BC [4]. Neither animal fat nor a low-fat
recurrence and improving survival after BC diagnosis. diet has been linked to BC risk, whereas marine omega-3
Decreasing the length of time a woman’s breast tissue is fatty acids (n-3) may be protective [4]. In a meta-analysis of
exposed to estrogens may help prevent BC [1-3], although 21 independent prospective cohort studies, Zheng et al.
found a significant reduction of BC risk with marine n-3
* Correspondence: [5]. However, this meta-analysis highlights the difficulties in
Laboratoire TIMC-IMAG, CNRS UMR 5525, PRETA Cœur and Nutrition, and assessing the effects of specific dietary fats on BC risk. In
Faculté de Médecine, Université Joseph Fourier, Grenoble, France

© 2014 de Lorgeril and Salen; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public
Domain Dedication waiver ( applies to the data made available in this
article, unless otherwise stated.

used the ratio of n-3/n-6 in a meta-analysis 30% without altering n-6 levels. 12:54 Page 2 of 5 http://www. resulting in a significant comprising 274. but epidemiologic studies have yielded paragraph) interfere with the levels of both n-3 and n-6 in inconsistent results [18]. and examine their relationships results [20]. lated by the plant pigment polyphenols found in purple fruits such as grapes (and wines). Zheng et al. In the Los partly counteract the effect of estrogens. flavonoids are associated with a decreased BC risk a higher n-3/n-6 ratio had a significantly lower risk of BC: [16]. as marine n-3 Angeles Trial. in n-6 [7-9]. and the ability of the gut not illogical to pool data from diet and blood when analyz. and a different effect (if any) on cancers [7]. a major class of phytoestrogens. including the gut microbiota [17]. microbiota to transform isoflavones into equol probably ing relationships with BC risk. and mitochondria.7. One possible explanation is risk [7]. plums. whereas in the Lyon Diet Besides increased intake of n-3 and decreased intake Heart Study. whereas the im. as Yang et al. In the next section. when analyzing the associations be. and were more evident without adjustment for body mass index (BMI). related factors (insulin or adipokines). Thus.biomedcentral. found that the inverse asso. The vonoids and BC subgroup analyses. and this analyzed only dietary intake. lack of physical exercise and being overweight are well portance of BMI on BC risk during the pre-menopausal known [1-3]. it is crucial that n-6 is included in n-6 ratio. they found a 6% reduction in probably weakens the association between specific fla- BC risk per one-tenth increment of the n-3/n-6 ratio. are protective [5. and pharmacological factors that ure is associated with BC risk have produced inconsistent influence n-3/n-6 ratios. their plant substrate alpha-linolenic acid (ALA) is stimu- lished in BMC Cancer [10]. were stronger in East is likely to have weakened the associations between n-3/n-6 Asian populations compared with western populations ratio and BC risk. The endogenous synthesis of marine n-3 from the analyses. the bioavailability and association between the blood phospholipid n-3/n-6 ratio biological effect of flavonoids are dependent on many and BC risk (in four studies only) did not reach statistical factors. Equol is more biologically active (that is. In addition. and blueberries Breast cancer risk and n-3/n-6 ratios [13-15]. Several factors (discussed in the next reduce BC risk. In addition. The East Asian population issue suggests that other sex hormone levels and BC risk for post-menopausal foods/nutrients and related factors may be involved. timing of exposure to nonetheless correlations between dietary n-6 and n-3 and isoflavones (starting at or not before adolescence). as it is difficult to ac- pooled RR 0. we highlight some Finally. may reflect dietary intake. In addition. and risk. accurate fashion. estrogen exposure. This suggests that marine n-3 may Factors influencing n-3/n-6 ratios and BC risk influence BC risk partly through an effect on BMI or Among the main risk factors of BC. Polyphenol flavonoids increase marine n-3 by Yang et al. Other phytoestrogens more characteristic . It is. tal group with high n-6 intake. Women with data. that protection may require that women consume the and these various phospholipids have a different physiology high levels of soy typical of East Asian diets. There are the food source of isoflavones. if they have been recorded in a timely and women in the USA and Australia are equol producers [19].135 women with a total of 8. In most studies included in the meta-analysis ciations between marine n-3 and BC risk were significant by Yang et Lorgeril and Salen BMC Medicine 2014. crucial to bear modify the association between soy isoflavones and BC these differences in mind when interpreting the results. When the authors curately determine the intake of each flavonoid. but only about 30% of possible. the small studies examining whether equol expos- lifestyle. protection is only observed in studies conducted in East position of each phospholipid is not identical: it differs in Asian and not in western populations [18]. with BC risk. The lack of a significant relationship between is likely to weaken the associations. and this has been confirmed in controlled increase blood marine n-3 [12]. A typical example of BC risk and blood n-3/n-6 ratio is not unexpected.9]. the the corresponding fatty acids in blood and cells.99. These data are encouraging. environmental. these factors were not measured. because such complexity is provided by the soy flavonoids. red cell membranes. that is. did in their recent study pub.331 BC events increase in the n-3/n-6 ratio. whereas the association is less clear for pre- instance.90. however.82 to 0.10]. which again significance. which in turn may trials in which n-6 intakes were modified. n-3 and n-6 measured in phospholipids do not accurately Soy isoflavones. the fatty acid com. For women. more anti- potential confounders should be included in the analyses if estrogenic) than dietary isoflavones. for example. suggesting serum. and post-menopausal periods is still a matter of controversy Studies support an association between endogenous [6]. A meta-analysis suggests that each class of phospholipids. which only in post-menopausal women. there were fewer cancers in the group with of n-6 through consumption of foods rich in n-3 and poor low n-6 [8. As expected from the above from 11 independent prospective studies [10]. there were more cancers in the experimen. 95% CI 0. other substances are known to affect the n-3/ tween n-3 and BC risk. and it is woman’s menopausal status. omega-6 fatty acids (n-6) may play a role in BC menopausal women [11].. It has long been suspected that n-6 increase the that the high estrogen levels present before menopause risk of cancers.

Organic-fed animals mainly diet adapted to specific have a higher n-3/n-6 ratio than con. the metabolites resulting from transformation by the gut microbiota. Okinawan diet for East Asians for instance. environmental. 2 high fiber. and decreasing plant and animal partly explain the favorable n-3/n-6 ratio [30. and vegetables. fiber intake. In BC risk. Organic animal fat also . In addition. and the combination of 1 Tailored to the capacity of each individual. High polyphenol Lorgeril and Salen BMC Medicine 2014. diet in East Asians [41] – has been shown to be effective. increase insulin resistance and diabetes risk Plant and marine n-3 Increase3 [36]. phenol content. Finally. it is crucial to identify ’hidden’ groups of are associated with an increased BC risk. recent studies have vonoids. Therefore. cological factors play an important role in BC risk and Another crucial point is the fact that organic plant foods BC survival. As a higher n-3/n-6 ratio cific professional exposure [33]. milk and of BC [39]. Optimal physical activity decreases insulin contain more polyphenols than similar conventional foods resistance. the Mediterranean diet – which has 4 By adhering to the modernized Mediterranean diet (see text). High dietary lignans women with early-stage BC. pattern – for instance. are associated Reducing BC risk with lower BC risk and better survival in post-menopausal In summary (see Table 1). ratio than non-organic foods. Plant and animal n-6 Decrease3 Whether or not statins. . breast cancer. and pharma- resulting in a higher n-3/n-6 ratio [7. and Age-associated weight gain Limit4 high n-3 are all inversely associated with diabetes risk. is associated with lower (polychlorobiphenyls) congeners and BC risk [32]. foods represents what many experts call a healthy dietary 3 Compared with a western-style diet. Table 1 How to reduce breast cancer risk and improve and the risk of diabetes and obesity [34]. and the risk and progression [23-26].biomedcentral. and n-3 [5. Adhering to a healthy dietary pattern – a milk products . all of which survival after diagnosis increase BC risk [1-3]. a number of lifestyle. Endocrine disruptors (particularly phthalates) increase insulin resistance. in particular of fla- Regarding food contaminants. the accumulated evidence shows BC [21. or high exposure to enterolignans. high fiber intake.7. Following the same line Alcohol (no more than 1 drink/day) Preferably wine of reasoning. are involved in increased BC risk. consumption Drugs suspected to increased BC risk Use caution of foods with a lower glycemic impact – that is. fruits. glycemic index. women should women whose occupational exposure to carcinogens is increase their consumption of n-3 and fiber and favor underrepresented in epidemiological studies. high-risk women should do everything they Organic foods (plant and animal sources) May be beneficial can to reduce their risk of insulin resistance.22].31]. such as the Okinawan consume non-contaminated fresh grass with a high poly. Studies low-GI foods. To reduce insulin resistance and diabetes. n-6. high polyphenols. Statins decrease n-3/n-6 Modernized Mediterranean diet2 Full adherence ratio [35]. 12:54 Page 3 of 5 http://www. diabetes risk. caution should High GI foods Decrease3 be applied prior to prescription. high n-3/n-6 ratio. high flavonoids. which this context. exposure. flavonoids [16]. remains Polyphenols Increase3 an area of controversy. GI.for instance. or a similar healthy ventional products [27-29].13]. which is a well-known strategy for decreasing both diabetes Insulin resistance and diabetic risk Decrease4 and BC [1-3] risks. This is not unexpected. and this may (including marine) n-3. These data are highly consistent. as we have shown in that in addition to genetic predisposition and estrogen rats that lignans increase blood n-3 without affecting n-6.10] Cholesterol-lowering statins Use caution are inversely associated with BC risk. Exposure to sex steroids Decrease tially influence both n-3/n-6 ratio and BC risk are the Physical activity Adopt optimal level1 cholesterol-lowering statins. Drugs Accordingly. Item Recommendations Other commonly encountered substances that poten. modernized Mediterranean diet [40]. Beside optimal physical activity. which increase the synthesis of marine n-3 and shown a strong association between estrogenic PCBs result in a higher n-3/n-6 ratio. by modifications of the above pro- cesses [35-38]. and low-GI Consider an alternative healthy diet in specific populations. when weighing up Fiber Increase3 the benefits and potential risks of of the western diet are the polyphenol lignans present been associated with a lower BC risk and better survival for in seeds. and are toxic to mitochondria [37]. organic foods have been shown have recently shown significant associations between to contain more polyphenols and have a higher n-3/n-6 BC risk and endocrine disruptors in women with spe. grains. BC. a low gly- Drugs suspected to increased insulin Use caution cemic index (GI) – is associated with a lower incidence of resistance and diabetic risk diabetes and a lower BC risk [1-3]. metabolic syn- Exposure to endocrine disruptors Decrease where possible drome and diabetes [1-3]. lower cholesterol. rather than polyphenol-poor concentrates Emphasis should be given to increasing plant and animal potentially contaminated with pesticides.

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