Three new studies strengthen the associations between suboptimal intake of either nutrient and risk of breast cancer
by Craig Weatherby
No single factor can explain why any individual develops breast cancer or any other malignancy.
But, in addition to certain genetic characteristics, evidence continues to accumulate for a link between breast cancer and lower blood levels of vitamin D and fish-derived omega-3s (EPA and DHA).
(For more on this, search our newsletter archive for “cancer”.)
Omega-3s are critical to the function of human cell membranes and the immune system, including the tendency toward or against chronic inflammation.
Inflammation tends to promote cancer growth, as does the excessive intake of pro-inflammatory omega-6 fatty acids that characterizes the average American diet.
Vitamin D and cancer: A 60-year-long research record
The body makes vitamin D when ultraviolet (UV) sunrays strike unprotected skin.
And the link between vitamin D intake and reduced cancer rates extends back to 1940, when pathologist Frank Apperly discovered that cancer rates rose along with distance from the sunny equator.
Unfortunately, Apperly's paper and its implications were largely overlooked.
The notion that vitamin D might play a key role in preventing cancer did not arise again until 1980, when Frank and Cedric Garland of the University of California, San Diego (UCSD) reported finding lower rates of colon cancer among people living in sunny latititudes.
The Garlands hypothesized that the apparent cancer-preventive effects of living in sunny climes might stem from UV-generated vitamin D: a proposition supported by contemporaneous research documenting anti-cancer effects exerted by vitamin D at the cellular level.
All other things being equal, darker-skinned people make less vitamin D per minute of sun exposure, compared with lighter-skinned people. This is because dark skin contains more of the skin pigment called melanin, which, like sunscreen, blocks UV sunrays.
Accordingly, African-Americans show a far higher prevalence of vitamin D deficiency and higher rates of colon and prostate cancers.
And the results of numerous test tube studies—and most epidemiological studies—indicate that having higher body levels of vitamin D exerts positive influences with regard to prevention of breast cancer (i.e., inhibit cell proliferation and promote cell differentiation).
As a group of leading American researchers wrote four years ago, “…high levels of vitamin D metabolites may be protective against breast cancer” (Bertone-Johnson ER et al. 2005).
Two new studies affirm breast cancer protection potential
This year, academic research teams in the United States and Germany added two more positive studies to the growing list of research suggesting that vitamin D may reduce breast cancer risk modestly in some women.
Worldwide data analysis links vitamin D to reduced breast cancer risk.
Scientists from the University of California, San Diego (UCSD) used data from GLOBOCAN—a new database developed by the World Health Organization—to compare rates of breast cancer among women in 107 countries (Mohr SB et al. 2008).
They calculated women’s exposure to UV sunrays in 107 countries, accessed WHO data on some of the women’s actual vitamin D blood levels, and estimated their vitamin D levels where blood-test data was not available.
The UCSD team’s analysis revealed a “dose-response” relationship between women’s vitamin D levels and the risk of breast cancer. That is, women in countries with higher average vitamin D levels had lower average rates of breast cancer.
And as expected, having higher average vitamin D levels correlated with greater average sun exposure.
The UCSD team made these comments (Mohr SB et al. 2008):
- “This is the first study, to our knowledge, to show that higher serum [blood] levels of vitamin D are associated with reduced incidence rates of breast cancer worldwide.”
- “The findings of the present study are consistent with the four [previously published] observational studies that reported an inverse association between oral intake of vitamin D and risk of breast cancer."
German case-control study links vitamin D to reduced breast cancer risk
In January of this year, scientists from the German Cancer Research Center in Heidelberg published the encouraging results of a “case-control” epidemiological study.
The Germans recruited 1,394 post-menopausal women aged 50-74 with breast cancer and collected blood samples and information on their lifestyles and various known breast cancer risk factors.
They then compared the women with 1,365 healthy post-menopausal controls of the same age.
The Germans found that post-menopausal women with higher vitamin D levels were significantly less likely to develop breast cancer.
Compared with women having the lowest vitamin D blood levels, women with “high” levels were up to 69 percent less likely to have developed breast cancer, and even those whose vitamin D levels were only modestly higher were 43 percent less likely to have developed breast cancer.
Interestingly, this apparent preventive effect was stronger in women who’d never used post-menopausal hormone replacement therapy (HRT), compared with past and current users of HRT.
As they wrote, “Our findings strongly suggest a protective effect for post-menopausal breast cancer through a better vitamin D supply… with a stronger inverse association in women with low [vitamin D] concentrations…” (Abbas S et al. 2008).
How much vitamin D is enough? Is the sun a safe “source” of vitamin D?
In 2007, the UC San Diego team? behind the WHO data analysis described above conducted a review of the existing epidemiological evidence, and concluded that Americans are not getting nearly enough vitamin D—from sun, supplements, or foods—to provide optimal protection from breast cancer (Garland CF et al. 2007).
These findings fit- with virtually all similar analyses, which indicate that vitamin D blood levels in America and Europe fall far short of the levels associated with reduced risk of several cancers, osteoporosis, and certain autoimmune diseases.
The San Diego team’s literature search turned up two relevant studies, involving a total of 1,760 women.
And their analysis revealed that women with vitamin D blood levels of approximately 52 nanograms per liter (ng/ml) were 50 percent less likely to have developed breast cancer, compared with women whose vitamin D blood levels were less than 13 ng/ml.
Vitamin D blood levels in adult Americans range from 20-56 ng/ml, but a joint Harvard-German team determined that minimally protective blood levels start at 75 ng/ml, and the optimal level is about 100 ng/ml (Bischoff-Ferrari HA et al. 2006/2007).
The Harvard-German team noted that the currently US RDA of 400 IU cannot produce optimal blood levels.
In fact, the San Diego team estimates that it takes 4,000 IU of dietary vitamin D per day to maintain a blood level of 52 ng/ml. This amount is double the National Academy of Sciences’ recommended, but seriously outdated, upper intake limit of 2,000 IU per day.
Most vitamin D experts believe that the daily intake limit should be raised to 10,000 IU per day, and that the US RDA for vitamin D should be raised from 400 IU to 1,000 or 2,000 IU per day.
Alternately, the UCSD team noted that people could maintain a blood level of 52 ng/ml by consuming 2000 IU of vitamin D per day (from food and supplements) and spending about 12 minutes per day in the sun (Garland CF et al. 2007).
Most dermatologists and oncologists remain reluctant to change their sun-avoidance advice, and instead urge people to seek vitamin D solely from foods and supplements (Gilchrest BA 2007; Wolpowitz D, Gilchrest BA 2006).
While many vitamin D researchers disagree, the cautious mainstream medical stance seems prudent with regard to light-skinned people, who are vulnerable to UV-induced damage to cells and DNA, which can cause skin cancer.
But dark-skinned people—who suffer from a proven deficiency of vitamin D and enjoy natural sun block in their skin—run very little risk from sun exposure substantially in excess of the American average. For them, it makes sense to seek greater sun exposure and dietary vitamin D alike.
Two years ago a German dermatology researcher published a review paper that addressed the balance between sun exposure and cancer, and admonished skin doctors not to dismiss the strong body of evidence in favor of increased sun exposure (Reichrath J 2006):
- “We and others have shown that strict sun protection causes vitamin D deficiency in risk groups.
- “Dermatologists and other clinicians have to recognize that there is convincing evidence that the protective effect of less-intense solar UV radiation outweighs its mutagenic [DNA-damaging, cancer-promoting] effects.
- “Although further work is necessary to define an adequate vitamin D status and adequate guidelines for solar UV exposure, it is at present mandatory that public health campaigns and recommendations of dermatologists on sun protection consider these facts.
- “Well-balanced recommendations on sun protection have to ensure an adequate vitamin D status, thereby protecting people against adverse effects of strict sun protection without significantly increasing the risk of developing UV-induced skin cancer.”
This advice was echoed in Q&A format in a story published earlier this month by the Associated Press (Marchione M 2008), in which AP medical correspondent Marilynn Marchione offered the following advice.
Her answer to the last question (underlined for emphasis) echoes our report on the American Cancer Society’s unscientific, counterproductive sun-avoidance campaign (see “Cancer Society’s Anti-Sun Ads Decried as Deceptive”):
Q: How much sun should I get?
A: Many experts believe just 15 minutes a few times a week without sunscreen is sufficient and safe for most light-skinned people, but this is controversial.
Q. What about food sources?
A. Vitamin D is in Salmon, Tuna and other oily fish, and is routinely added to milk.
Q: For years, we've been told to use sunscreen. Shouldn't we be worried about skin cancer?
A: Sunscreen is advised for longer periods outdoors, to prevent skin cancer. Skin cancer is rarely fatal. Melanoma, the deadliest kind, accounts for less than 2 percent of cancer deaths. The risks posed by other, more common cancers are far greater.”
In other words, dermatologists who trumpet the risk of cancer from sun exposure overlook the risks of excessive sun-avoidance, which may be much greater.
And, according to an intriguing paper published by Australian researchers last year, extreme sun-avoidance may be even more unhealthful than the epidemic of vitamin D deficiency to which it contributes.
The Aussies outlined other ways in which UV sunrays could reduce the risk of some cancers and autoimmune disorders, independent of their power to create vitamin D in the human body.
As they wrote, “Recognition of the beneficial effects of UVR [UV sunray] exposure has led to a reconsideration of sun avoidance policies. It is important to recognize that all of the beneficial effects of UVR exposure may not occur only through UVR-induced vitamin D synthesis.
“Thus, maintaining current sun avoidance policies while supplementing food with vitamin D may not be sufficient to avoid the risks of insufficient exposure to UVR” (Lucas RM, Ponsonby AL 2007).
Omega-3s show more anti-cancer potential
Last year, researchers from the Oregon Health and Science University published the results of a case-control study conducted in Shanghai, China.
Their introduction to their study described well the state of the science on omega-3s and breast cancer: “Although in vitro [test tube] and animal experiments have supported an… association between [higher] intake of long chain n-3 fatty acids… and [reduced] breast cancer risk, findings from population studies are inconsistent” (Shannon J et al. 2007).
Their findings affirmed the positive results of several prior epidemiological studies which indicate that higher intake of omega-3s—and an omega-6/omega-3 intake ratio lower than the US dietary average—may help prevent breast cancer.
As they wrote, “Our results support a protective effect of n-3 fatty acids on breast cancer risk and provide additional evidence for the importance of evaluating the ratio of fatty acids when evaluating diet and breast cancer risk” (Shannon J et al. 2007).
Now, a study from Japan adds substantial weight to the hypothesis that diets high in omega-3s and low in omega-6s discourage—but cannot always prevent—breast cancer development.
Doctors at the Aichi Cancer Center Research Institute in Nagoya collected dietary information and blood samples from 103 breast cancer patients and 309 women without cancer.
Most importantly, they measured the blood levels of fatty acids – including omega-3s – in all of the women.
As leading omega-3 researcher Joe Hibbeln, M.D., of the National Institutes of Health (NIH) is fond of saying, “the tissue is the issue”. In other words, compared with estimates based on dietary questionnaires, blood tests are a vastly more reliable way to measure people’s omega-3 intake.
The results fit with those of prior studies:
- Women with the highest estimated dietary intakes of omega-3s were only half as likely to have breast cancer, compared with women with the lowest intake (odds ratio = 0.51).
- Women with the highest actual blood levels of omega-3s were about 9 times less likely to have breast cancer, compared with women with the lowest blood levels (odds ratio = 0.11).
- Women with the highest blood levels of saturated fat were 12 times more likely to have breast cancer.
The U.S. government has not yet issued dietary advice in accordance with the fast-growing preponderance of lab and epidemiological evidence concerning the clear inhibitory effects of omega-3s on many common cancers.
This is disappointing, to say the least… especially in light of FDA approval of costly synthetic heart and mood drugs whose effects appear marginal, at best.
- Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer--results of a large case-control study. Carcinogenesis. 2008 Jan;29(1):93-9. Epub 2007 Oct 31.
- Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, Hankinson SE. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1991-7.
- Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. Review. Erratum in: Am J Clin Nutr. 2006 Nov;84(5):1253. dosage error in abstract. Am J Clin Nutr. 2007 Sep;86(3):809.
- Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. The role of vitamin D in cancer prevention. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review.
- Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11.
- Gilchrest BA. Sun protection and Vitamin D: three dimensions of obfuscation.J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):655-63. Epub 2007 Jan 11. Review.
- Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006 Apr 5;98(7):451-9.
- Giovannucci E. Vitamin D status and cancer incidence and mortality. Adv Exp Med Biol. 2008;624:31-42. Review.
- Goodstine SL, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne ST. Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women. J Nutr. 2003 May;133(5):1409-14.
- Holick MF. Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol. 2008;624:1-15. Review.
- Kuriki K, Hirose K, Wakai K, Matsuo K, Ito H, Suzuki T, Hiraki A, Saito T, Iwata H, Tatematsu M, Tajima K. Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese. Int J Cancer. 2007 Jul 15;121(2):377-85.
- Kuriki K, Wakai K, Hirose K, Matsuo K, Ito H, Suzuki T, Saito T, Kanemitsu Y, Hirai T, Kato T, Tatematsu M, Tajima K. Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as biomarkers for dietary intakes of fish, fat, and fatty acids. Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1791-8.
- Kuriki K, Wakai K, Matsuo K, Hiraki A, Suzuki T, Yamamura Y, Yamao K, Nakamura T, Tatematsu M, Tajima K. Gastric cancer risk and erythrocyte composition of docosahexaenoic acid with anti-inflammatory effects. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2406-15.
- Lucas RM, Ponsonby AL. Considering the potential benefits as well as adverse effects of sun exposure: can all the potential benefits be provided by oral vitamin D supplementation? Prog Biophys Mol Biol. 2006 Sep;92(1):140-9. Epub 2006 Feb 28. Review.
- Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonnière F, Body G, Le Floch O, Chajès V. N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France.Int J Cancer. 2002 Mar 1;98(1):78-83.
- Marchione M. May 16, 2008. Accessed online May 31, 2008 at http://www.intelihealth.com/IH/ihtIH/E/9273/24524/725368.html
- Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Breast J. 2008 May-Jun;14(3):255-60. Epub 2008 Apr 17.
- Reichrath J. The challenge resulting from positive and negative effects of sunlight: how much solar UV exposure is appropriate to balance between risks of vitamin D deficiency and skin cancer? Prog Biophys Mol Biol. 2006 Sep;92(1):9-16. Epub 2006 Feb 28. Review.
- Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study. Cancer Causes Control. 2007 Sep;18(7):775-82. Epub 2007 Jun 5.
- Saadatian-Elahi M, Toniolo P, Ferrari P, Goudable J, Akhmedkhanov A, Zeleniuch-Jacquotte A, Riboli E. Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study. Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1353-60.
- Schwartz GG, Blot WJ. Vitamin D status and cancer incidence and mortality: something new under the sun. J Natl Cancer Inst. 2006 Apr 5;98(7):428-30.
- Shannon J, King IB, Moshofsky R, Lampe JW, Gao DL, Ray RM, Thomas DB.Erythrocyte fatty acids and breast cancer risk: a case-control study in Shanghai, China.Am J Clin Nutr. 2007 Apr;85(4):1090-7.
- Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol. 2006 Feb;54(2):301-17. Epub 2006 Jan 4. Review.