Deciding what is appropriate to tell oncology patients to do can be complicated. Obviously one must be up to date on the research and how to interpret the data in the scientific journals. Yet these decisions often turn out to be partly subjective and risk of doing a patient harm often outweighs the potential for benefit. Over the last few weeks several patients have questioned our advice to avoid carrot juice while being treated for breast cancer. This has prompted a review of the reasoning behind this advice.
We will continue to advise breast cancer patients against consuming large or regular amounts of carrot juice. The decision to take this stand was made in 2011 after a study by Heather Greenlee et al of Columbia University in New York confirmed what we had suspected from earlier studies. Dr. Greenlee’s paper was published in the September 27, 2011 issue of Cancer. Greenlee’s study sought to answer the long time, often repeated concern expressed by oncologists that antioxidant supplement use during chemotherapy and radiation therapy might decrease the benefit of treatment increasing recurrence rates and decreasing long-term survival.
In this prospective study, the researchers sought associations between antioxidant use after breast cancer (BC) and outcomes in 2,264 women in the Life After Cancer Epidemiology (LACE) cohort. These women had been diagnosed with early stage primary BC between 1997 and 2000. They enrolled in the study on average 2 years after their initial diagnosis. Data on antioxidant use since diagnosis and other factors were collected and compared with recurrence and mortality. About 81% of the women in the cohort took antioxidant supplements.
Frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence. Those taking vitamin C had a 27% lower risk of recurrence and those taking vitamin E had a 29% lower risk (vitamin C: HR, 0.73; 95% CI, 0.55-0.97; vitamin E: HR, 0.71; 95% CI, 0.54-0.94). Vitamin E use was associated with a 24% decrease in mortality from any cause (HR, 0.76; 95% CI, 0.58-1.00).
On the other hand, frequent use of carotenoids appeared to double the risk of death from breast cancer (HR, 2.07; 95% CI, 1.21-3.56) and increase risk of mortality from all causes by 75% (HR, 1.75; 95% CI, 1.13-2.71). 
Let’s start with the Vitamin C and E results. These numbers look good. At first glance they suggest that taking either vitamin is useful for women with breast cancer. We need to be cautious with these data, as it is impossible to fully adjust for what is called “healthy user bias.” The women who take vitamins regularly are also likely to do other things that might also improve their health. For example in this study, the women taking vitamin C and E were thinner, exercised more, smoked less and ate better than the women that didn’t. While the researchers attempt to factor out these positive influences in their statistical analysis, one can never be sure they have been successful. While we may question whether or not they had a positive impact, there is no reason to think that taking vitamin C or E after being diagnosed with breast cancer interferes with the benefits of treatment.
The association found in this study that suggests taking carotenoids increases risk of mortality is perhaps the more important finding as this is an area in which we might potentially educate and influence our patients and the public. This is not a new discovery and should not come as a surprise.
A 2004 article in the American Journal of Clinical Nutrition that tracked dietary intake of carotenoids and essential fatty acids and the risk of breast cancer.
This was a population based case control study that looked at 414 cases of breast cancer. Dietary intake was estimated with questionnaires and interviews. Supplements were not used. The results were far from straightforward, confusing would be a decent description. Carotenoids appear to have amplified the effect of other influences, either increasing or decreasing risks.
No significant association was seen between dietary carotenoids and the risk of breast cancer. Yet in premenopausal women who ever smoked, there was an increased risk when the upper and lower quartiles of intake were compared. Premenopausal women who had ever smoked and who were in the upper 25% of gamma-carotene intake had a relative risk of 2.40 compared to those in the lower 25% of intake. On the other hand there was a reduced risk (0.57) related to beta-carotene in women who never had used hormone therapy. In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (1.92) and inversely associated in those with a high docosahexanoic acid (DHA) intake (0.52).  If nothing else about this study is clear, it certainly suggests that the role of betacarotene and breast cancer is not straightforward.
A relatively small 2007 study on Chinese women suggests that dietary betacarotene is protective against getting breast cancer in the first place. Huang and colleagues compared dietary information from 122 women diagnosed with breast cancer against women without cancer and found that those women in the upper 25% of carotenoid consumption had a 57% lower risk of breast cancer than the women in the loweste 25% of consumption. 
A study that same year, in this case on 254 women with ovarian diet reported a protective association between carotene consumption and cancer diagnosis. High total carotene intake was associated with a 67% decrease in risk of being diagnosed with ovarian cancer. 
These statistics might encourage us to ignore Greenlee’s findings but we have to remember we are looking at two different situations. Greenlee is looking at post diagnosis, and use during treatment, with the prevention of recurrence. These last two Chinese studies suggest carotene lowers risk of getting a first diagnosis of cancer.
Another 2007 paper, again looking at breast cancer patients, sought an association between dietary carotenoids and levels of oxidative stress. Researchers gathered data from 207 postmenopausal breast cancer survivors from the Women’s Healthy Eating and Living Study (WHEL) and that “Dietary carotenoid levels were not significantly associated with oxidative, stress indicators, although dietary lycopene and lutein/zeaxanthin were modestly associated with 8-OHdG levels….” However there was, “a significant inverse association between total plasma carotenoid concentrations and oxidative stress as measured by urinary 8-OHdG….” 
[the 8-OHdG test was described in some detail in a recent NMJ piece: http://naturalmedicinejournal.com/journal/2015-02/2015-spiritmed-annual-updates-environmental-medicine-conference%5D
Whether or not this later finding is good or bad is difficult to say. Keeping urinary 8-OHdG low is protective against getting cancer in the first place. As both chemotherapy and radiotherapy should increase this biomarker, one might wonder if the carotenoids might lessen treatment effectiveness.
The year 2007 seems to be when attention was focused on betacarotene. Another paper, again not looking at breast cancers but instead looking at 540 patients receiving radiation treatment for head and neck cancers reported that a higher dietary beta carotene intake was associated with 39% reduction in severe acute adverse effects. What is more important during the study period those with the higher betacarotene intake had a 37% significantly lower rate of local recurrence. 
A 2005 paper following a large cohort of women diagnosed with breast cancer also argues in favor of carotenoids, as high dietary betacarotene was associated with reduced risk of breast cancer recurrence. Rock et al sought whether diet affected breast cancer recurrence. They used plasma carotenoid concentration as a biomarker of total vegetable and fruit intake and sought an association with breast cancer recurrence. They followed 1,551 women who had been treated for breast cancer and were part of the WHEL cohort. Recall that the WHEL study attempted to train women to eat large quantities of vegetables and fruits each day as a way to reduce breast cancer recurrence. Compliance with this diet was not all that good. This paper was a substitute way to really compare those who actually followed the experimental diet with those who didn’t.
Measuring betacarotene in the blood was a way to figure out who of the total women enrolled in the study groups ate the most fruits and vegetables. While the original analysis of the WHEL data failed to find a benefit in the experimental high vegetable and fruit diet, this study did. “Women in the highest quartile of plasma total carotenoid concentration had significantly reduced risk for a new breast cancer event (HR, 0.57; 95% CI, 0.37 to 0.89), controlled for covariates influencing breast cancer prognosis.”  It seems now that while the initial study failed to find benefit, those women who followed directions actually did have some benefit.
This study might be seen to contradict our concern about betacarotene and breast cancer, but consider the WHEL cohort; these women were encouraged to consume large amounts of a variety of fruits and vegetables without a particular focus on carotenoid containing foods. Thus if their betacarotene levels were high, we must assume that levels of many phytonutrients were also elevated, chemicals such as lycopene and sulforaphane for example, chemicals that have anti-cancer action.
In fact an even more recent 2011 analysis of the WHEL cohort reported that high baseline consumption of vegetables alone was associated with a 31% reduction in recurrence risk and in women using tamoxifen a 44% reduction. High baseline consumption of cruciferous vegetables alone reduced risk by 35%. For women using tamoxifen who reported above average cruciferous vegetable intake and who were within third of all the women for total vegetable intake, risk of recurrence was reduced 52%. 
Carrot juice has been shown to boost blood levels of betacarotene. Drinking 8 ounces per day for 3 weeks increased total plasma carotenoids by 1.65 to 1.38 umol/L for depending on the type of carrot used in the juice. 
In practicing naturopathic oncology we are frequently asked to assess the potential risks versus benefits of adopting a dietary strategy or taking a specific supplement. This process always reminds me an old bakery scale we own, a remnant from my days baking bread. Assessing whether someone should do something is about more than just piling up studies on each side of the scale to see which side has more weight.
One of the primary teachings of Hippocrates that still remains a centerpiece of medical practice is the phrase, “primo non nocere”, which roughly translates, “first to not harm”. Studies are not weighed evenly in our practice. Studies that suggest the potential of harm get more weight. The answers to many of the questions we ask are not clear-cut or black and white.
While there are certainly some studies suggesting potential benefit of drinking carrot juice, raising serum levels and decreasing oxidative burden, we cannot forget Dr. Greenlee’s study. That paper suggests raising carotene levels may double risk of recurrence in women who have had breast cancer. The potential for increased risk, suggests caution.
1. Cancer. 2011 Sep 27. doi: 10.1002/cncr.26526. [Epub ahead of print]
Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort.
Greenlee H, Kwan ML, Kushi LH, Song J, Castillo A, Weltzien E, Quesenberry CP Jr, Caan BJ.
2. Am J Clin Nutr. 2004 May;79(5):857-64.
Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal,Canada.
Nkondjock A1, Ghadirian P.
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3. Asia Pac J Clin Nutr. 2007;16 Suppl 1:437-42.
Dietary carotenoids and risk of breast cancer in Chinese women.
Huang JP1, Zhang M, Holman CD, Xie X.
4. Br J Nutr. 2007 Jul;98(1):187-93. Epub 2007 Mar 19.
Intake of specific carotenoids and the risk of epithelial ovarian cancer.
Zhang M1, Holman CD, Binns CW.
5. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2008-15.
Plasma and dietary carotenoids are associated with reduced oxidative stress in women previously treated for breast cancer.
Thomson CA1, Stendell-Hollis NR, Rock CL, Cussler EC, Flatt SW, Pierce JP.
6. Nutr Cancer. 2007;59(1):29-35.
Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients.
Meyer F1, Bairati I, Jobin E, Gélinas M, Fortin A, Nabid A, Têtu B.
7. J Clin Oncol. 2005 Sep 20;23(27):6631-8.
Plasma carotenoids and recurrence-free survival in women with a history of breast cancer.
Rock CL1, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Newman VA, Hollenbach KA, Jones L, Caan BJ, Pierce JP.
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8. Breast Cancer Res Treat. 2011 Jan;125(2):519-27. doi: 10.1007/s10549-010-1014-9. Epub 2010 Jul 6.
Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study.
Thomson CA1, Rock CL, Thompson PA, Caan BJ, Cussler E, Flatt SW, Pierce JP.
9. Nutr Cancer. 2012;64(2):331-41. doi: 10.1080/01635581.2012.650779. Epub 2012 Jan 31.
Effects of a carrot juice intervention on plasma carotenoids, oxidative stress, and inflammation in overweight breast cancer survivors.
Butalla AC1, Crane TE, Patil B, Wertheim BC, Thompson P, Thomson CA.