Does Vitamin D reduce risk of developing advanced cancer? 38% reduction among those with normal weight, study shows
For several years, scientists have been trying to pin down the connection between vitamin D and cancer. In a new analysis, researchers say that Vitamin D was associated with an overall 17% risk reduction for advanced cancer. When the team led by Brigham and Women’s Hospital 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 decreased risk of advanced cancer.
“These findings suggest that vitamin D may reduce the risk of developing advanced cancers. 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,” writes corresponding author Dr Paulette Chandler, a primary care physician and epidemiologist in the Brigham’s Division of Preventive Medicine. The results have been published in JAMA Network Open.
What did the investigators find?
The team says that vitamin D deficiency is common, with one study reporting rates of vitamin D deficiency as high as 72% among cancer patients. There is also evidence that higher amounts of body fat are associated with an increased risk for several cancers.
Epidemiological studies have found that people who live near the equator, where exposure to sunlight produces more vitamin D, have lower incidence and death rates from certain cancers. In cancer cells in the lab and mouse models, vitamin D has also been found to slow cancer progression. But the results of randomized clinical trials in humans have not shown a clear answer. The Vitamin D and Omega-3 Trial (VITAL), which concluded in 2018, found that vitamin D did not reduce the overall incidence of cancer, but hinted at a decreased risk of cancer deaths. Now, in a secondary analysis of VITAL, experts have narrowed in on the connection between taking vitamin D supplements and the risk of metastatic or fatal cancer.
The trial was a rigorous, placebo-controlled study that was conducted for more than five years. It included men who were 50 or older and women 55 or older. The participants did not have cancer when the trial began. The participants were racially and ethnically diverse and included 20.2% of African-Americans.
The trial 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: vitamin D (2000 international units or IU per day) plus omega-3s; vitamin D plus placebo; omega-3s plus placebo; and placebos for both. Primary endpoints were 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.
In the secondary analysis, the investigators 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.
The analysis reveals that among 25,871 VITAL participants, 1,617 were diagnosed with invasive cancer over the next five years. This included a broad mix of cancers (breast, prostate, colorectal, and lung, among others). Of the 12,927 participants who received vitamin D, 226 were diagnosed with advanced cancer compared to 274 out of 12,944 who received the placebo. Of the 7,843 participants with a normal body mass index (BMI less than 25) taking vitamin D, only 58 were diagnosed with advanced cancer compared with 96 taking the placebo.
“This randomized clinical trial of daily high-dose vitamin D supplementation for 5 years reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort of adults without a diagnosis of cancer at baseline. The protective effect is apparent for those who have normal but not elevated body mass index,” state findings.
According to experts, while the findings on BMI could be due to chance, previous evidence indicates that body mass may affect vitamin D action. Obesity and associated inflammation may decrease the effectiveness of vitamin D, possibly by reducing vitamin D receptor sensitivity or altering vitamin D signaling, they explain. Besides, randomized trials of vitamin D and type 2 diabetes have found greater benefits of vitamin D in people with normal weights and no benefit among those with obesity.
The authors have called for additional studies and emphasize that even if vitamin D effects were modest, vitamin D supplementation at the studied levels is much less toxic and lower cost than many current cancer therapies. “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. Additional studies focusing on cancer patients and investigating the role of BMI are warranted,” recommends Chandler.