The Vitamin D and Omega-3 Trial (VITAL), which was completed in 2018, found that vitamin D did not reduce overall incidence of cancer, but it hinted at a decreased risk of cancer deaths. Now, in a secondary analysis of VITAL, a research team focused on the connection between taking vitamin D supplements and the risk of metastatic or fatal cancer. A report published by Paulette Chandler, MD, MPH, and colleagues in JAMA Network Open found that vitamin D was associated with an overall 17% risk reduction for advanced cancer.
When the team looked at only participants with a normal body mass index (BMI), they found a 38% risk reduction, suggesting that body mass may influence the relationship between vitamin D and a decreased risk of advanced cancer.
Paulette Chandler, MD, MPH
“These findings suggest that vitamin D may reduce the risk of developing advanced cancers,” said corresponding author Dr. Chandler, a primary care physician and epidemiologist at Brigham and Women’s Hospital, Harvard Medical School. “Vitamin D is a supplement that's readily available, cheap, and has been used and studied for decades. Our findings—especially the strong risk reduction seen in individuals with normal weight—provide new information about the relationship between vitamin D and advanced cancer.”
Information on VITAL
The VITAL study was a placebo-controlled investigation that took place over a span of more than 5 years. The VITAL study population included men who were aged 50 years or older and women 55 or older who did not have cancer when the trial began. The study population was racially and ethnically diverse. VITAL was designed to test the independent effects of vitamin D and omega-3 supplements, as well as to test for synergy between the two.
Participants were divided into four groups for treatment:
- Vitamin D (2000 IU/d) plus omega-3s
- Vitamin D plus placebo
- Omega-3s plus placebo
- Placebos for both.
Primary endpoints were the occurrence of major adverse cardiovascular events and the incidence of cancer. VITAL did not find a statistical difference in overall cancer rates, but researchers did observe a reduction in cancer-related deaths.
Secondary Analysis
In their secondary analysis, Dr. Chandler and colleagues followed up on the possible reduction in cancer deaths with an evaluation of advanced (metastatic or fatal) cancer among participants who did or did not take vitamin D supplements during the trial. They also examined the possible modifying effect of BMI.
Among the more than 25,000 participants in the VITAL study, 1,617 were diagnosed with invasive cancer over the next 5 years. This group included a broad mix of cancer types (breast, prostate, colorectal, lung, and others). Of the almost 13,000 participants who received vitamin D, 226 were diagnosed with advanced cancer compared to 274 who received the placebo. Of the 7,843 participants with a normal BMI (less than 25) taking vitamin D, only 58 were diagnosed with advanced cancer compared with 96 taking the placebo.
Photo caption: Getty
While the team's findings on BMI could be due to chance, there is previous evidence that body mass may affect vitamin D activity. Obesity and associated inflammation may decrease the effectiveness of vitamin D—possibly by reducing vitamin D receptor sensitivity or altering vitamin D signaling. In addition, randomized trials of vitamin D and patients with type 2 diabetes have found greater benefits of vitamin D in people with normal weights and no benefit among those with obesity.
Vitamin D deficiency is common among patients with cancer, with one study reporting rates of vitamin D deficiency as high as 72%. There is also evidence that higher amounts of body fat are associated with an increased risk for several types of cancer.
“Our findings, along with results from previous studies, support the ongoing evaluation of vitamin D supplementation for preventing metastatic cancer—a connection that is biologically plausible,” said Dr. Chandler. “Additional studies focusing on patients [with cancer] and investigating the role of BMI are warranted.”
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
