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In the 1960s, vitamin C held promise as a remedy for a host of ailments, from the common cold to cancer.
"It was considered the miracle drug," recalls Dana-Farber physician-scientist Charles Fuchs, MD, MPH.
Although the vitamin did not prove to be as versatile as hoped, Fuchs - who studies and treats gastrointestinal cancers such as colon cancer - is now working to better understand the health benefits of a nutrient with even more potential: vitamin D.
Activated by sunlight and present in some foods and supplements, vitamin D is already well known for helping the body control calcium and phosphate levels and maintain healthy bones.
But this commonly deficient nutrient is now being studied for its possible role in reducing the risk of many chronic conditions, among them infectious illnesses, heart disease, and autoimmune illnesses such as type 1 diabetes and multiple sclerosis.
In addition, some studies suggest that higher blood levels of vitamin D can lessen the chance of developing various cancers, or improve outcomes in patients already diagnosed with them.
Other research finds no connection or conflicting evidence, but some observers say vitamin D doses in some of these studies have been too low to make a difference.
Although investigators have looked at breast, colorectal, pancreatic, prostate, and other cancers, the evidence in favor of vitamin D appears strongest in colorectal and other digestive system cancers.
"I think the health benefits of vitamin D are compelling," says Fuchs. "It's probably premature to say we know for a fact that it is both preventive and improves cancer survival. But the data is certainly strongly supportive – especially in digestive system cancers."
Dana-Farber's Karen Emmons, PhD, who focuses on medically underserved populations, adds, "If the larger research literature and our own work continue to demonstrate the beneficial role of vitamin D in disease prevention, it would have huge public health implications."
Even if experts don't yet agree on vitamin D's specific role, many concur on two key points: More randomized clinical trials are needed, and the government's current recommendations for vitamin D daily intake - between 200 and 600 International Units (IUs) - are too low.
The national Institute of Medicine, an independent health advisor to decision makers, is examining the suggested intake and is expected to release a report this year. As the debate continues, public awareness of vitamin D is growing.
"The patients and survivors we see are far more informed about their risk of vitamin D deficiency than in the past," notes dietitian Stephanie Meyers, MS, RD/LDN, of Dana-Farber/Brigham and Women's Cancer Center.
"Many are now asking whether they should have their blood levels checked or take supplements."
Physicians can use a blood test commonly called a 25-hydroxy vitamin D test to measure how much of the nutrient is in the body. Although opinions vary, many consider a vitamin D level of around 30 nanograms per milliliter (ng/ml) or higher to be sufficient.
Fuchs says 35-40 ng/ml is ideal, but most Americans have inadequate levels - and rates are falling. Among the groups especially prone to shortages are older adults, people with dark skin, overweight individuals, people living in places with less sunlight, such as the Northeastern United States, and patients taking certain medications for cancer treatment.
Because food isn't a great source of vitamin D (you'd need about 10 glasses of fortified milk to get 1,000 IUs) and too much sun exposure can damage skin, many experts recommend taking vitamin D supplements.
Are you getting enough vitamin D?
The speculation that vitamin D levels influence cancer development is based on its role in helping regulate various cellular functions. Vitamin D may discourage cell proliferation, encourage natural cell death and differentiation, and hinder the growth of blood vessels that feed tumors. It also supports immune function and helps to reduce inflammation.
At Dana-Farber and Dana-Farber/Harvard Cancer Center, researchers are helping illuminate how vitamin D may play a beneficial role in colorectal cancer, health disparities, pediatric stem cell transplants, and overall disease prevention. Among the projects:
Working with Fuchs and others, Dana-Farber's Kimmie Ng, MD, MPH, is exploring the potential impact of vitamin D on cancer patients. A study she co-led found that colorectal cancer patients with the highest vitamin D levels in their blood were 48 percent less likely to die (from any cause) than those with the lowest vitamin D measurements.
The team examined the experiences of 304 participants in two long-running epidemiologic studies, the Nurses' Health Study and the Health Professionals Follow-Up Study.
Similarly, researchers at the Mayo Clinic recently found that patients with large B cell lymphoma and vitamin D shortages were twice as likely to die as those with adequate levels.
"Previous research has shown that high blood levels of vitamin D seem to be associated with a 50-percent decreased risk of developing colon and rectal cancer," says Ng. "There has been less data on how vitamin D status affects survival in people who already have cancer. That's where we're trying to advance the field."
Studies show black people have much lower vitamin D blood levels than whites, largely because darker skin hampers one's ability to synthesize the nutrient from the sun's rays. Scientists say vitamin D deficiency could explain blacks' higher rates of colorectal and other cancers, particularly in the Northeast.
However, the ideal dose of vitamin D needed to raise these individuals' blood levels enough to prevent disease is not known, says Emmons, because most studies have involved predominantly white populations.
To help counter this lack of data, Emmons, Fuchs, and Edward Giovannucci, MD, ScD, of the Harvard School of Public Health, are leading a randomized clinical trial among some 320 African-American residents in the Boston area.
Over three months, participants receive either a placebo or one of three vitamin D pills containing 1,000, 2,000, or 4,000 IUs. While visiting participants' homes, investigators check to see whether the nutrient also affects blood pressure and insulin levels.
Project leaders hope to pave the way for future trials aimed at preventing cancer. Emmons notes, "If we can determine that African-Americans indeed benefit from vitamin D, then supplements could be a low-cost way to potentially reduce their disease burden. It's not the only factor to address, but it could be an important part of a comprehensive strategy."
Dana-Farber pediatric oncologist Christine Duncan, MD, and colleagues have been examining low vitamin D levels in children and adolescents after hematopoietic stem cell transplant.
In a recent study, Duncan and Erin Apfelbaum, RN, of Dana-Farber reported the widespread prevalence of vitamin D insufficiency (defined as under 30 ng/ml) and deficiency (under 20 ng/ml) in pediatric patients after transplant.
"We hope this will give us a better understanding of the risk factors and appropriate treatment for vitamin D deficiency in this group and help improve their quality of life," Apfelbaum says.
JoAnn Manson, MD, DrPH, a member of Dana-Farber/Harvard Cancer Center and chief of Preventive Medicine at Brigham and Women's Hospital, is leading a large-scale clinical trial to examine the effect of vitamin D and omega-3 fatty acids in preventing cancer, heart disease, stroke, and other chronic conditions.
The researchers hope to enroll 20,000 participants in this national five-year study that is expected to include 5,000 African-Americans. (Learn more about the study at www.vitalstudy.org.)
"An important goal of our study," says Manson, "is to understand whether vitamin D supplementation can reduce disparities in cancer and other outcomes that vary by race and ethnicity."
"This is an exciting field," Fuchs sums up. "Vitamin D probably explains something about cancer risk and cancer disparities, and we are working to understand its role in cancer survival."
Technically, vitamin D is a fat-soluble "prohormone" that the body converts into a vitamin. Humans get it through sun exposure (when the sun's ultraviolet rays hit the skin and trigger its production), from certain foods (such as fortified dairy products and oily fish), and in dietary supplements.
With millions of people around the world facing low vitamin D levels, Dana-Farber nutritionists offer some tips for boosting yours:
Food sources. Vitamin D-rich foods include salmon, sardines, tuna, cod liver oil, and vitamin D-fortified orange juice, milk, yogurt, and cereals.
Dietary supplements. Dana-Farber experts recommend a total daily intake of 1,000 International Units (IUs) for adults who do not get enough sun exposure. People with vitamin D deficiencies may need more until their levels rise. It's important to discuss the best dose for you with your doctor. For children and adolescents, the American Academy of Pediatrics recommends getting 400 IUs a day.
Which kind? The two major forms of vitamin D are vitamin D2, made naturally by plants, and D3 (cholecalciferol), which is manufactured by the body when skin is exposed to the sun's ultraviolet rays. Vitamin D3 is considered a more effective form than D2. Vitamin D supplements commonly come in pill, chewable, and concentrated liquid forms.
Sun exposure. Some health professionals suggest getting a modest amount of sun exposure (around 15 minutes daily) to raise vitamin D levels, while others warn against such an approach, due to the increased risk of skin cancer for some people. Ask your doctor what's best for you.
Watch your weight. Vitamin D is stored in body fat, and being overweight is associated with lower blood levels of the nutrient.
Paths of Progress Spring/Summer 2010 Table of Contents