Jacob Schor, ND, FABNO

June 1, 2014

In my neighborhood many cars sport bumper stickers proclaiming their drivers’ support of diversity; in this context they refer to a diversity of sexual orientations.  That’s not what this article is about.  Here the term diversity is used in another context, a diversity that refers to the range of choices a person makes in their daily diet.  

Patients frequently brag to me that they eat certain foods repeatedly in their daily diet because these foods are listed somewhere as ‘Super Foods’.  Thus they live on a narrow dietary range that may include blueberries, flax seeds, broccoli and whatever other few fad foods are on a particular list they have downloaded from the internet. This may not be the best approach to insuring good health.  Eating a diverse diet may be more important than any particular foods eaten.  That is, diversity may trump superiority.

This idea struck me while reading Ghadirian et al’s 2009 paper that reported on diet diversity and its effect on BRCA+ carriers’ risk for breast cancer.  This was  “… a case-only study … carried out in a French-Canadian population including 738 patients with incident primary BC comprising 38 BRCA mutation carriers. Diet diversity was assessed… [for] case-only odds ratio (COR) and 95% confidence interval (CI) while adjusting for age, body mass index, smoking, hormonal replacement therapy, and total energy intake. …. results reveal a strong and significant interaction between BRCA mutations and vegetable and fruit diversity (COR = 0.27;…) when comparing the upper to the lower quartiles. ….. The results of this study suggest that the combination of BRCA mutations and vegetable and fruit diversity may be associated with a reduced risk of BC.”  

Translating all this fancy talk tells us that women who were BRCA + and who ate the greatest variety of vegetables and fruit had a 73% reduction in cancer incidence compared to whose who ate a narrow range of choices. [1]  

Given the high risk BRCA carriers have for breast cancer, these finding are remarkable.  Advocating for increased dietary diversity is a reasonable goal not only for this patient group but probably for a wider range of patients at risk for numerous other cancer types.

In May 2013, Isa et al reported on the effect dietary diversity had on risk of bladder cancer in Chinese populations.  As we might expect high intake of red meat increased risk for bladder cancer (OR=1.8).  Some of their findings come as a surprise. High intake of leafy vegetables nearly tripled risk (OR=2.9), bulb vegetables and preserved vegetables more than doubled risk (OR=2.3 for each). An interesting list of foods were associated with lower: white fish consumption and vine fruits cut risk in half (OR=0.5), citrus fruits and potatoes even more  (OR=0.4) and flower vegetables even more so (OR=0.3).  Those subjects with the highest total fruit diversity had the lowest risk of developing cancer, 90% less than those subjects with the lowest diversity in fruit consumption. (OR=0.1). [2] 

Thus it seems we need to modify what we tell patients.  Rather than saying include lots of fruits and vegetables in your diet, we should be saying ‘include an ample quantity and diverse selection of fruits and vegetables in your diet’

This idea that we should eat a diverse selection of foods brings me back to the 1970s when the repeated mantra voiced by all my nutrition professors at Cornell was to “eat a variety of foods.”

Speaking of Cornell, the researcher who has best explained why food diversity might play a role in cancer prevention is still there. Rui Hai Liu is a professor in the Food Science Department has a Ph.D. in Toxicology (Cornell University 1993) along with a M.D. in Medicine and a M.S. in Nutrition and Food Toxicology. Dr. Liu’s research focuses on diet and cancer, the effects of functional foods and nutraceuticals on chronic disease risks, and bioactive compounds in natural products and herbal remedies for anticancer and antiviral activity. [3]   Liu made a name for himself a decade or so back by devising ways to measure the cancer inhibitory effect of various foods had on cancer growth.[4]     His lab published a series of papers describing the antiproliferative effect of specific foods, in particular fruits [5],   including apples [6-8],      strawberries  [9,10],     cranberries [11,12],    grapes [13]  and raspberries [14,15],    vegetables [16],   including tomatoes [17],  green beans, beets [18]  and onions [19] , and a range of other foods including  black beans [20] ,  nuts    and whole-wheat [21]. 

At a certain point in his research Liu measured the additive effects of these various foods when more than one were combined; that is, would apples and strawberries have more impact on cancer growth than either would alone?  His results were and continue to fascinate me.  The inhibition was more than additive.  In 2003 Liu reported that combinations of fruits and vegetables proved to be synergistic in action, more than the sum of their parts. [23]   This idea was confirmed by additional publications in 2004 [24]   and 2009. [25]  

Liu wrote, “…  the additive and synergistic effects of phytochemicals in fruit and vegetables are responsible for their potent antioxidant and anticancer activities, and that the benefit of a diet rich in fruit and vegetables is attributed to the complex mixture of phytochemicals present in whole foods …. This partially explains why no single antioxidant can replace the combination of natural phytochemicals in fruit and vegetables in achieving the health benefits….”(Liu 2003)

It also explains why diversity in diet is associated with such significant effects on cancer risk.

Scientists, and our patients, have a habit of looking for the cure to cancer (and everything else that ails them) by seeking the single phytochemical that will act as a magic bullet.  While we certainly have come across exciting data on particular chemicals and foods, it looks more and more like it’s the interaction of a multitude of these chemicals that really does the magic.

One measure of the effect of phytochemicals in foods is their antioxidant effect. Combining different fruits together increases the total antioxidant effect in a synergistic manner.  For those of you who are too young to remember Bucky Fuller, synergy refers to a phenomenon in which the whole is greater than the sum of the parts.  In this case, if you combine oranges, apples, grapes and blueberries into one mush, it will have a greater synergistic antioxidant effect than if you added up and totaled the individual effects of each of these fruits.  The total antioxidant effect of these fruits combined increases by a factor of five over what simple addition would predict.   

Nutrition experts have encouraged us to eat a wide variety of fruits and vegetables for years.  This certainly should bring the message home. 

In some ways I find these conclusions disappointing, being someone who has long appreciated a slice of fruit pie.  These data suggest that mixtures of blueberry, raspberry and cherry all cobbled together as pie filling would be better for health than a slice of pie made from any fruit alone.  This does not make me particularly happy, being a mono-fruit pie sort of guy.  Of course, there is another way to interpret this research:  never eat a slice of just one pie, always have at least a taste from several different pies.  The more pies you taste, the healthier they get for you.  Or rather than pie, stick with fruit cake. 

This synergistic effect goes far to explain the failure of the experimental trials in which a single food or vegetable has been singled out for testing. A single food will only provide the benefit of the phytochemicals contained in it without the synergistic multiplication that would have occurred if it were eaten with other foods. The more diverse the diet, the more likely synergy between phytochemicals will occur, enough to have an impact on cancer.

The pie wrecker as I tend to refer to Liu as, writes:

“It is now widely believed that the actions of the dietary supplements alone do not explain the observed health benefits of diets rich in fruits, vegetables and whole grains, because, taken alone, the individual antioxidants studies in clinical trials do not appear to have consistent preventive effects.  The isolated pure compound either loses it bioactivity or may not behave the same way as the compound in whole foods.” [Liu RH et al. J Nutr. (2004)]

This synergistic interaction between food phytochemicals also goes a long way to explaining the benefit seen associated with dietary food diversity.

Unfortunately while we live in a world with an amazing number of edible foods, few are commonly eaten.  A number of estimates are reported online.  The most common I find is that of the 20,000 species of edible plants in the world only 20 species provide 90% of our food supply  .   These estimates vary.  Another web posting claims “Today, 75 percent of the world’s food is generated from only 12 plants and five animal species.”[27]  

It matters little which of these estimates is most accurate.  The bottom line is that we eat a tiny portion of the foods available to us.  People can greatly increase the diversity in their diets.  Doing so may have great benefit.

No longer should we just challenge patients to eat 5-10 servings of fruits or vegetables per day, they should also increase the diversity of these food groups.  Our new question should be, “how many different types of fruit, vegetables, grains and nuts can you eat each week?” 

1. Ghadirian P, Narod S, Fafard E, Costa M, Robidoux A, Nkondjock A. Breast cancer risk in relation to the joint effect of BRCA mutations and diet diversity. Breast Cancer Res Treat. 2009 Sep;117(2):417-22. 

2.  Isa F, Xie LP, Hu Z, Zhong Z, Hemelt M, Reulen RC, Wong YC, et al. Dietary consumption and diet diversity and risk of developing bladder cancer: results from the South and East China case-control study. Cancer Causes Control. 2013 May;24(5):885-95. 

 3. June 1, 2014. http://blogs.cornell.edu/liulab/

4.  Liu, R.H. Cell culture models to assess bioactivity of functional foods and dietary supplements. ACS Symposium Series 956: 83-91, 2007.

5.  Sun, J., Chu, Y-F., Wu, X., and Liu, R.H. Antioxidant and antiproliferative activities of fruits. J. Agric. Food Chem. 50 (25): 7449-7454, 2002.

6.  Liu, R. H., Eberhardt, M. V., Lee, C. Y. Antioxidant and antiproliferative activities of selected New York apple cultivars. New York Fruit Quarterly 9(2):15-17, 2001

 7. Eberhardt, M. V., Lee, C. Y., and Liu, R. H. Antioxidant activity of fresh apples. Nature 405(6789): 903-904, 2000.

 8. Liu, R.H. and Sun, J. Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation. J. Agric. Food Chem. 51 (6): 1718-1723, 2003

 9. Meyers, K.K., Watkins, C.B., Pritts, M.P., and Liu, R.H. Antioxidant and antiproliferative activities of strawberries. J. Agric. Food Chem. 51 (23): 6887-6892, 2003.

10.  Shin, Y.J,  Ryu, J.A., Liu, R.H., Nock, J.F.,  Polar-Cabrera, K., and Watkins, C.B.  Fruit quality, antioxidant contents and activity, and antiproliperative activity of strawberry fruit stored in elevated CO2 atmospheres.  J. Food Sci. 73 (6): S339-S334, 2008.

11.  Sun, J. and Liu, R.H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer Letters. 241: 124-134, 2006 (On line 12/27/05)

12.  He, X.J. and Liu, R.H. Cranberry phytochemicals: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J. Agric. Food Chem.54 (19): 7069-7074, 2006.

13.  Yang, J. Martinson, T.E., and Liu, R.H.  Phytochemical profiles and antioxidant activies of wine grapes.  Food Chemistry 116: 332-339, 2009.

14.  Weber, C., Liu, M, Li, X. Q., and Liu, R.H. Antioxidant capacity and anticancer properties of red raspberry. New York Fruit Quarterly 9(3):25-27, 2001.

15.  Liu, M, Li, X. Q., Weber, C., Lee, C. Y., Brown, J., and Liu, R. H. Antioxidant and antiproliferative activities of raspberries. J. Agric. Food Chem. 50 (10): 2926-2930, 2002.

16.  Chu, Y-F., Sun, J., Wu, X., and Liu, R. H. Antioxidant and antiproliferative activities of vegetables. J. Agric. Food Chem. 50 (23): 6910-6916, 2002.

17.  Dewanto, V., Wu, X., Adom, K. K., and Liu, R. H. Thermal processing enhances the nutritional value of tomatoes by increasing total antioxidant activity. J. Agric. Food Chem. 50 (10): 3010-3014, 2002

18.  Jiratanan, T. and Liu, R.H. Antioxidant activity of processed table beets (Beta vulgaris var conditiva) and green beans (Phaseolus vulgaris L.). J. Agric. Food Chem. 52 (9): 2659-2670, 2004

19.  Yang, J., Meyers, K.J., van der Heide, J. and Liu, R.H. Varietal differences in phenolic content, and antioxidant and antiproliferative activities of onions. J. Agric. Food Chem. 52 (21): 6787-6793, 2004

 20.  Dong, M., He, X.J. and Liu, R.H..  Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities. J. Agric. Food Chem. 55 (15): 6044-6051, 2007.

21.  Yang, J., Liu, R.H., and Halim, L. Antioxidant and antiproliferative activities of common edible nut. LWT-Food Science and Technology 42(1): 1-8.

22.  Okarter, N., Liu, C-S., Sorrells, M.E.,and Liu, R.H. Phytochemical content and antioxidant activity of six diverse varieties of whole wheat.  Food Chemistry 119 (1): 249-257, 2009.

23.  Liu, R. H. Health benefits of fruits and vegetables are from additive and synergistic combination of phytochemicals. Am. J. Clin. Nutr. 78(3S): 517S-520S, 2003

full text: http://ajcn.nutrition.org/content/78/3/517S.full.pdf+html

24.  Liu, R.H. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J. Nutr. 134(12S): 3479S-3485S, 2004.

Full text: http://jn.nutrition.org/content/134/12/3479S.full.pdf+html

25.  Yang, J. and Liu, R.H. Synergistic effect of apple extracts and quercetin 3-b-D-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro. J. Agric. Food Chem. 57 (18): 8581-8586, 2009.

26.  http://www.pfaf.org/user/AboutUs.aspx

 27.  FAO. 1999b  http://www.fao.org/docrep/007/y5609e/y5609e02.htm