Colorectal cancer patients with vitamin D deficiency see worse outcomes

ABSTRACT: Investigators at Memorial-Sloan Kettering plan to tease out exactly how much vitamin D is enough to improve survival prospects.

Numerous epidemiological studies have strongly suggested that vitamin D has a protective effect against cancer, including breast, prostate, and colon. But the data for these studies were gathered before the cancer diagnosis (see Related Reading below). Researchers at New York's Memorial-Sloan Kettering Cancer Center have, for the first time, documented levels at the time of cancer diagnosis.

Kathleen Wesa, MD, and colleagues conducted a retrospective study of baseline vitamin D levels in newly diagnosed, stage IV colorectal cancer (CRC) patients to determine if serum levels at diagnosis could predict survival. Dr. Wesa is a physician-scientist in the integrative medicine service at MSKCC. One of her co-authors is Barrie Cassileth, PhD, chief of the integrative medicine service.

KATHLEEN WESA, MD

"Vitamin D levels of > 40 ng/ml are considered optimal for bone health, and recent data suggest that levels near 40 ng/mL may increase survival in patients with breast cancer. The optimal serum level of vitamin D for CRC patients is not known," wrote Dr. Wesa and colleagues (ASCO 2010 abstract 3615).

Frozen sera samples from the MSKCC sera bank were used for this analysis. The first 250 patients with serial plasma carcinoembryonic antigen (CEA) drawn within 30 days of a stage IV CRC diagnosis, and with survival data available, were included and vitamin D levels were measured. CEA measurements were obtained between 2005 and 2006.

According to the results, of the 250 patients, 153 had died as of April 2009. The median vitamin D level for all patients was 21.5 ng/mL, but the majority of patients (83%) were vitamin D deficient, which was defined as levels below 30 ng/mL. Only seven patients had serum vitamin D levels above 40 ng/mL.

FACT Vitamin D has a moment in the sun Two recent neurological studies found that high levels of vitamin D may protect against Parkinson's disease while low levels were associated with substantial cognitive decline in the elderly. This research builds on the body of literature that has also identified vitamin D as a protective agent in the heart-low levels seem to predispose people to hypertension and chronic vascular inflammation-and in the skeletal system (

Arch Neurol

67:808-811, 2010;

Arch Intern Med

170:1135-1141, 2010;

Recenti Prog Med

101:202-211, 2010;

Clin Biochem

online, June 17, 2010).

In univariate analysis, vitamin D was significantly associated with survival (P = .036). Patients with low vitamin D levels had survival outcomes that were about 1.5 times worse than those with normal levels. The authors concluded that most patients with newly diagnosed stage IV CRC are vitamin D deficient at the time of diagnosis and that higher vitamin D levels are associated with better survival.

Whether aggressive vitamin D repletion would improve outcomes in deficient CRC patients is not known, the authors stated. Dr. Wesa pointed out that trials using other isolated vitamin supplementation, or in mega-doses have not necessarily shown benefit and in some cases have been detrimental, such as with beta-carotene supplementation in male smokers.

"I don't know that it is necessarily appropriate for everyone to take high levels of vitamin D supplementation," she said. "We do not yet know what optimal serum vitamin D levels are for the cancer patient. Certainly low levels are associated with worse outcomes in many cancers, but the only way to answer the question of whether normalizing low vitamin D levels improve cancer outcomes is with a clinical trial. What may be most beneficial is for people throughout their lifetime to maintain normal levels of vitamin D for promoting health and wellness."

Dr. Wesa's group is currently enrolling vitamin D-deficient CRC patients in an ongoing phase II clinical trial that will look at what dose of vitamin D is required to achieve and maintain adequate vitamin D levels. Dr. Wesa said that they anticipate having preliminary results in approximately the next 12 months.

New European study reiterates relationship between prediagnostic vitamin D and colon cancer

The large-scale, long-term European Prospective Investigation into Cancer and Nutrition (EPIC) trial has collected data on prediagnostic vitamin D levels from more than 52,000 participants in several European countries, including Denmark, France, Greece, Germany, Italy, Spain, and the UK. A multinational group of researchers mined the EPIC database to take a closer look at the link between prediagnostic circulating vitamin D levels and the CRC risk (BMJ online, January 21, 2010).

For this nested case-control study, the authors focused on 1,248 cases of incident CRC that developed after enrollment into the cohort, and matched the cases to 1,248 healthy controls. Circulating vitamin D concentration was measured by enzyme immunoassay. Not surprisingly, the researchers came up with a strong inverse association between levels of prediagnostic vitamin D and CRC risk in this population. Lower levels (< 25 nmol/l) were associated with higher CRC risk, and higher concentrations (≥ 100 nmol/l) were associated with a lower CRC risk.

However, the investigators also found that a higher consumption of dietary vitamin D was not associated with a reduced risk of colorectal cancer. The optimal level of vitamin D supplementation still needs to be established through randomized trials before any change is made to public health recommendations, they said.

Visit www.ncbi.nlm.nih.gov/pmc/articles/PMC2809840/ to obtain a free copy of this study.

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Dr. Cassileth is a member of the Oncology News International editorial advisory board.