I have not to date at least in this thread tackled the WINS  Trial itself, except to show that it is clinically irrelevant to the issue of optimal olive-oil consumption (and associated dietary fat proportions for optimal anticancer health), and have not suggested that not only is it clinically irrelevant, but also defective under scrutiny of evidence-based critical appraisal, and seeing this I think will help everyone further appreciate the issues involved (and also illustrate that by and large trials and study are presented in the literature uncritically, their conclusions then enshrined as truth and indeed, more critically, as practice-changing).  This is not what I do as an evidence-based medical researcher, and not what we allow here at No Surrender, as we will again witness here: 

Contra WINS

As  to  the WINS Trial, it's major - and illicit as I  will suggest - finding is that of a decreased risk of breast cancer recurrence at any site (local, regional, and distant) from a low-fat dietary intervention, although as I have already noted there was no benefit to overall survival.  But in doing an evidence-based critical appraisal of WINS, as I have, there are methodological compromises that make the trial insufficient to draw any such conclusion.

One Fatal Flaw

I will point out just one crippling flaw:  in the results data, the intervention group lost weight while the control group did not (weight loss of  (approximately  2.7 kg) and  this was throughout the entire 5 years of the intervention, and in fact easy computation using the trial's data shows that this weight loss is a statistically significant difference.  But this is a fatal flaw: the adverse influence of body weight and weight gain on survival after breast cancer is well established (Kroenke et al.;  Bastarrachea et al.; Zhand et al.; Galanis et al.; Daling et al., among many  others).  Indeed, the WINS investigators themselves have speculated (Blackburn & Wang, AJCN 2007) that their trial's low-fat diet caused modest weight loss which in turn drove improved insulin metabolism, hence reducing insulin's tumor-promoting effects and thus improving relapse-free survival.  But that of course undermines the power to conclude (1) the impact  of dietary fat reduction without weight loss, or (2) the impact of weight loss alone without dietary fat reduction, since it is not only conceivable, but likely on the accumulated evidence that weight loss was the critical correlative factor in driving any recurrence risk reduction, and that dietary fat reduction may have been irrelevant.  

And indeed, the same data base from WHI supports this, and contradicts WINS, when one examines the WHEL Trial findings which targeted not only lower dietary fat but also increased fruits, vegetables, and fiber, where in that case the trial intervention group did not lose weight, and consequently, no association with diet and survival was discovered. 

Another Fatal Flaw

Indeed, we have another critical flaw in the WINS methodology via another confounding factor besides weight loss, namely, physical activity: so, the study of Michelle Holmes and colleagues at Harvard (Am J Epidemiol, 2009), which reconfirmed their previous finding (JAMA 2005), found that physical activity was associated with decreased risk of breast cancer death among women with breast cancer, and this association was independent of dietary intake, and as I have suggested, this recent robust study found that physical activity confounded the association between diet and survival.  And although the LACE study failed to find a protective effect of physical activity on breast cancer recurrence or mortality although it was beneficial for breast cancer survivors in terms of total mortality, nonetheless the weight of the evidence supports that physical activity is associated with improved survival in women with breast cancer, as per the Nurses’ Health Study (NHS) and in 3 other cohort studies (Holick, Cancer Epidemiol Biomarkers Prev (2008); Irwin, JCO 2008; Pierce, JCO 2007).  And physical activity itself was correlated with lower intake of animal fat and higher intake of cereal fiber as shown by the  new NHS  re-analysis conducted by Michelle Holmes's team at  Harvard cited above.  In that recent study, intakes of dietary fat and cereal fiber were no longer associated with survival after adjustment for physical activity, yet higher physical activity was still associated with improved survival even after adjustment for diet.

An Alternate Explanation of WINS

Given this and other findings in similar agreement, we can conclude (1) that the most plausible explanation for the WINS is that energy restriction in the form of weight loss drove the recurrence risk  reduction (we have no WINS data on physical activity to  be able to speculate on that); and (2) that methodological compromises shown here of the WINS Trial renders its conclusion that dietary fat reduction is to be credited with effecting recurrence risk reduction illicit, as the trial failed to control for the confounding variable of weight loss (let alone physical exercise), and further suggesting as I have done that type of dietary fat can exercise a clinically significant contribution and hence matters in any dietary fat intervention study.

What the Evidence Shows: Conclusions

Therefore, as I have originally put forth, the WINS Trial is

1. clinically irrelevant to the issue of olive-oil-dominant dietary fat intake;

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2. exhibits methodological compromise that undermines it's capacity to draw the  conclusion it did;

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3. from the WINS data themselves, weight loss is a more plausible contributor to recurrence risk reduction than is the posited dietary fat reduction; and

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4. the  most evidence-based supported diet, overwhelmingly so, for all-mortality, cancer-mortality, breast-cancer-specific-mortality, and cardiovascular-mortality, reduction remains the higher-fat content (42 - 46%) olive-oil-dominant diet (Cretan Mediterranean Diet), and that the conclusions of the WINS Trial, even if licit - and they are not - are relevant solely to American/Western diets, and not to the Cretan Mediterranean Diet (CMD) where the overwhelming weight of robust and multiply confirming evidence correlates breast cancer risk , and breast cancer mortality, reduction with high consumption of olive oil, even under circumstances where the proportion of total calories from  fat intake  reaches 42 - 46%, as along as olive-oil is the near-exclusive source of fat.

Constantine Kaniklidis

Breast Cancer Watch

mailto:edge@evidencewatch.com - edge@evidencewatch.com