Source: www.medscape.com
Author: Roxanne Nelson

A growing amount of research suggests that vitamin D may be beneficial to cancer patients. In addition, laboratory, ecologic, and epidemiologic studies have shown some evidence that higher levels of vitamin D might lower the risk for colon, breast, endometrial, and prostate cancers.

But although the “evidence is intriguing,” an editorial published online April 6 in the Journal of Clinical Oncology speculates about how oncologists should disseminate this information in clinical practice. Editorialist Pamela J. Goodwin, MD, from the Samuel Lunenfeld Research Institute, Mount Sinai Hospital and Princess Margaret Hospital, in Toronto, Ontario, offers some suggestions to oncologists who are being asked to advise their patients about whether they should take vitamin D supplements. She emphasizes that her suggestions are of an interim nature.

“As results of ongoing and planned research become available, many unanswered questions will be resolved, and more definitive recommendations that can be embraced by oncologists will be forthcoming,” she notes in her editorial.

Low Levels Noted in Breast Cancer Patients
Interest in vitamin D has risen exponentially, Dr. Goodwin explains. The total number of published studies relating to vitamin D more than doubled from 1990 to November 2008, articles relating to cancer and vitamin D nearly tripled, and those specifically relating to breast cancer and vitamin D increased almost 6-fold.

The editorial was prompted by a report, published in the same issue of the Journal, that, at baseline, 74% of premenopausal women with breast cancer who received adjuvant chemotherapy and participated in a 1-year zoledronate intervention were vitamin D deficient. After 1 year of vitamin D3 supplementation (400 IU), the investigators found that sufficient levels, defined as 30 ng/mL or greater, were achieved by less than 15% of the white and Hispanic women and by none of the black women.

“Although the recommended dietary allowance of vitamin D in premenopausal women is only 200 IU daily, our study suggests that a dose of 400 IU daily is inadequate in breast cancer patients, even to maintain skeletal health, and is probably too low for meaningful anticancer effects,” the authors write. They also note that, in addition to determining optimal dosing, the effect of vitamin D supplementation on survival is still unknown.

“The problem is that the study did not look at different doses,” lead author Dawn L. Hershman, MD, MS, assistant professor of medicine and epidemiology at Columbia University, in New York City, told Medscape Oncology. “No one knows if repleation will have any health benefits at this point, other than improving bone health.”

These results, Dr. Goodwin points out, are similar to those of another recent study, which found that about three quarters of breast cancer survivors had insufficient levels of vitamin D (Am J Clin Nutr. 2008;88:133-139). The study authors suggest that clinicians consider monitoring vitamin D status in breast cancer patients.

Dr. Goodwin also notes that in a study conducted by her team (J Clin Oncol. 2008;26[15s]:511), the same proportion of patients with breast cancer had inadequate levels. As reported by Medscape Oncology, the study showed that women with very low levels of vitamin D at diagnosis were more likely to have aggressive disease, 94% more likely to develop metastases, and 73% more likely to die than those with normal levels of vitamin D at diagnosis.

Difficulty Selecting an Optimal Dose
Although there is a lack of high-level evidence, it is biologically plausible that vitamin D can have an effect on cancer risk or outcome, she writes. Oncologists must now decide how to advise patients, but selecting an optimal dose for supplementation can be problematic.

Dr. Goodwin explains that the “unpredictable relationship between vitamin D intake and blood levels” makes it difficult to recommend a standard dose for supplementation. Even though there are some minor disagreements about specific cut points, most experts suggest that a blood level of 25-OHD, considered to be the best marker of vitamin D status, of approximately 75 nmol/L (30 ng/mL) is required for vitamin D sufficiency.

Hypervitaminosis D has been associated with hypercalcemia and resulting complications, including renal stones and bone demineralization, she notes, but information regarding the effects of high levels of vitamin D on noncalcium-related outcomes “is lacking and is urgently needed.”

Above All, Do No Harm
Given this lack of information, what should oncologists recommend to their patients? Dr. Goodwin offers suggestions, but warns that her advice should be viewed as interim. Depending on age, current recommendations for vitamin D range from 200 to 600 IU per day. Given that there is sufficient evidence that vitamin D supplementation at these doses is associated with reduced mortality and improved bone health, clinicians should feel comfortable using them as a starting point.

However, as studies have indicated, many cancer patients will remain deficient at these levels, and higher supplementation might be needed. Oncologists, says Dr. Goodwin, should aim to achieve the benefits of adequate vitamin D levels, but they should also be guided by the principle, “above all, do no harm.” Rather than just endorsing an arbitrary higher dose, she recommends measurement of blood levels of 25-OHD as the most prudent approach to determine which patients might benefit from supplementation, as well as ensuring that the levels reached are advantageous.

Dr. Hershman agrees. “Since the recommended guidelines are low, and are likely to be increased soon, it is not unreasonable to check levels and replete patients that are deficient to the normal range,” she said.

These recommendations increase the potential for benefit while reducing the risk for harm. “There may be specific benefits and harms associated with vitamin D supplementation in cancer patients that are not present in the general population, despite the fact that these benefits and harms have not been conclusively demonstrated,” Dr. Goodwin writes. “As a result, oncologists making recommendations to individual patients should take a cautious approach.”

Dr. Goodwin has disclosed no relevant financial relationships.

Source:
J Clin Oncol. Published online before print April 6, 2009. Abstract, Abstract