Posted Nov 27, 2009
“They’re two of the most promising nutrients available for the prevention of cardiovascular disease and cancer,” says JoAnn E. Manson, professor of medicine at the Harvard Medical School and chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston. That’s an understatement.
Manson is a principal investigator for the new VITAL trial (WTamin D and Omeg>*-3 TriaL), which will test vitamin D and omega-3 fats from fish oil on heart disease, stroke, and cancers, especially of the colon, breast, and prostate. But the trial will also look at the supplements’ effect on other illnesses.
“We’re also interested in studying diabetes, high blood pressure, bone density, vision, memory loss, depression, autoimmune diseases, and other health outcomes,” says Manson.
And you may be eligible to participate.
Why launch a brand new trial to test high doses of vitamin D and omega-3 fats from fish? Don’t we already know they’re worth taking?
“Some people believe the evidence is already strong enough to recommend much higher intakes,” notes Harvard’s JoAnn Manson. “But we tend to forget the lessons of other nutrients – like vitamin E, vitamin C, B vitamins, folic acid, selenium, and beta-carotene.
“Large-scale trials didn’t confirm their benefits and even found some risks when they were consumed at high levels. So let’s not just jump on the bandwagon until we have clinical trials.”
Here’s what we know – and don’t know – about vitamin D and omega-3s from fish.
VITAMIN D
CANCER
The results were unexpected.
When researchers at Creighton University in Omaha, Nebraska, decided to give roughly 1,200 healthy postmenopausal women either a placebo or calcium (1,500 mg) plus vitamin D (1,000 IU) every day, they wanted to know if the two nutrients would keep bones from breaking.
Instead, they found that the women who were given both vitamin D and calcium were 77 percent less likely to be diagnosed with cancer – mostly of the breast – over the next four years.1
It didn’t take long for supplement makers to spring into action. “Emerging science suggests that vitamin D supports breast health,” boasts Centrum Ultra Women’s and other multivitamins. (Supplement makers love vitamin D because you can’t get much from food. See “How the Body Makes Vitamin D,” p. 4.)
But the story isn’t so simple.
“The study showed a significant reduction in total cancer, but it was too small to look at types of cancer,” cautions Manson. Only seven women who took a placebo – versus four who took vitamin D and calcium- were diagnosed with breast cancer. And even for total cancers, “the results need to be replicated.”
A much bigger trial – the Women’s Health Initiative – tested vitamin D (and calcium) or a placebo on 36,000 healthy women for an average of seven years. Vitamin D takers had no lower risk of breast cancer than placebo takers.2
“The Women’s Health Initiative was large scale, but it tested only 400 IU a day, which many believe is too low to prevent cancer or heart disease,” says Manson.
Clinical trials like the Creighton study and the Women’s Health Initiative randomly assigned people to take a vitamin or a placebo. In theory, trials can offer the clearest answers because vitamin takers and placebo takers are chosen at random from the same pool of subjects.
But researchers also weigh studies that investigate whether people with higher blood levels of vitamin D have a lower risk of cancer years later. Some of those studies find a lower risk, but others don’t.3
“In the Nurses’ Health Study, we saw an association between higher blood levels of vitamin D and a lower risk of breast cancer in women over 60,” says Elizabeth Bertone-Johnson of the University of Massachusetts. “That hasn’t always been replicated in other studies.
“In a nutshell, the evidence that vitamin D protects against breast cancer is suggestive but inconclusive,” says Bertone-Johnson.
The same could be said for the link between vitamin D and colorectal cancer. For example, in a study of 535 male health professionals and female nurses, those with high blood levels of vitamin D were only half as likely to be diagnosed with colon cancer as those with low levels.4 And in other studies, colon cancer patients with higher vitamin D levels are less likely to die of the disease.5
“The evidence is stronger for colorectal than for breast cancer,” says Manson. “In several studies, blood levels of vitamin D predict the risk of colorectal cancer, but not breast cancer.” But some studies find no link with colorectal cancer at all.3
In contrast, animal and test-tube studies offer a surplus of evidence that vitamin D protects against cancer.
“It’s plausible because vitamin D decreases cell proliferation and increases cell differentiation,” explains Manson. “It also curbs the growth of new blood vessels, which could stop cancers from growing. And it has powerful anti-inflammatory effects.”
But without clinical trials, those findings aren’t enough to act on. And some human evidence has caused some worry.
A 2006 study of Finnish male smokers found a higher risk of pancreatic cancer among those with higher blood levels of vitamin D.6
A 2009 study of (mostly nonsmoking) U.S. men and women found no link overall. However, in people from states with low sun exposure (in this study, Michigan, Minnesota, and Wisconsin), high blood vitamin D levels again were linked with a higher risk of pancreatic cancer.7
Another U.S. study found a lower risk of aggressive prostate cancer among those with the lowest vitamin D blood levels, but the risk didn’t rise with higher vitamin D levels.8
“It’s hard to know what to make of these findings without further research,” says Manson. “But it’s reassuring that most other studies haven’t shown these elevated risks.”
HEART ATTACK & STROKE
If you look at animal and laboratory studies, there’s no shortage of evidence that vitamin D might protect the heart.
“In animal models, when the vitamin D pathway is disrupted, it overactivates the reninangiotensin hormone system,” says Thomas Wang, an assistant professor of medicine at the Harvard Medical School and a cardiologist at Massachusetts General Hospital in Boston.
Over time, too much of those hormones can harm the heart.
“The system revs up when the body is under stress, which is a good thing in the short term,” Wang explains. “But over the long term, it’s not good to have sustained increased levels of these hormones. In fact, ACE inhibitors and many other therapies for cardiovascular disease are aimed at blocking the renin-angiotensin system.”
Vitamin D may act in other ways, “it seems to suppress inflammation, which plays a role in the progression of cardiovascular disease,” says Wang. “And it may act directly on the heart cells and cells in the walls of blood vessels.”
What about evidence in people?
When Wang and his colleagues tracked roughly 1,700 people in the Framingham Heart Study for five years, those with low vitamin D blood levels (below 15 ng/mL) had a 60 percent higher risk of heart disease than those with higher levels.9 And in a study of male health professionals, men with low blood levels of vitamin D were twice as likely to have a heart attack as men with high levels (above 30 ng/mL).10
“These studies show an association between low vitamin D levels and a higher risk of heart attacks, strokes, and other cardiovascular events, but they don’t prove that one causes the other,” says Wang.
Other research suggests that vitamin D may keep blood pressure from rising. In a study of roughly 600 men and 1,200 women, those with low vitamin D levels were three times more likely to be diagnosed with high blood pressure over the next four years than those with high vitamin D levels.11
“A fair amount of epidemiological data and a little data from small trials suggest that vitamin D may lower blood pressure,” says Wang. And that fits with the renin hypothesis because renin boosts blood pressure.
“One can imagine how the story fits together nicely,” says Wang. “But other hypotheses haven’t been borne out when trials are done, so we have to take it with a grain of salt until we have more data.”
OTHER OUTCOMES
The VITAL study was designed to see if vitamin D and omega-3s in fish oil can lower the risk of cancer, heart attacks, and strokes, but the study will also look at other problems. Among them:
Falls & fractures. Vitamin D can prevent falls and bone fractures in older people, but it only works if they take enough, says Bess Dawson-Hughes of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston.
She and her colleagues looked at the best trials that tested vitamin D or a placebo on falls. “There was no reduced risk of falling in trials where the dose was 200 to 600 International Units,” she explained at a recent meeting of the Institute of Medicine in Washington, D.C. (Her analysis has not yet been published.)
“When trials used doses of 700 to 1,000 units, we saw a significant 20 percent risk reduction of falls,” she added. “We concluded that fall risk reduction begins at 700 IU and increases progressively with higher doses.”
The picture was similar when Dawson-Hughes looked at studies that tested vitamin D on bones.12 “With lower-dose trials, we see no risk reduction for fracture, but for the higherdose trials, we see a risk reduction of 20 percent,” she explained.
Vitamin D helps the body absorb calcium, so it’s no surprise that the nutrient would curb the risk of broken bones. And researchers now think they know how vitamin D keeps people from failing.
“We have identified vitamin D receptors on the fast-twitch fibers in muscles that are the first responders when you are about to fall,” noted DawsonHughes. “So it’s biologically plausible that vitamin D will affect muscle, and we certainly know that (weaker] lower extremity muscles are a risk factor for falls.”
Her bottom line: “The results support the use of a higher dose of vitamin D defined as somewhat north of 700 International Units – to prevent falls and fractures.”
Type 2 diabetes. When researchers gave roughly 300 people without diabetes either vitamin D (700 IU) plus calcium (500 mg) or a placebo every day, their goal was to look primarily at bone, not blood sugar levels.
However, among people who started the study with impaired fasting blood sugar (higher than normal but not high enough to be classified as diabetes), those who got vitamin D and calcium had a smaller rise in blood sugar levels over three years than those who got a placebo.”
These and other findings suggest that vitamin D may lower the risk of diabetes, but “they need to be replicated in clinical trials,” concludes Dawson-Hughes.
Depression. “Lay publications were saying that vitamin D was good for mood, but I was surprised that there was very little in the literature,” says University of Massachusetts researcher Elizabeth Bertone-Johnson, who recently reviewed the evidence.14
The best evidence so far, she says, comes from a trial on roughly 350 overweight people in Norway.15
“Individuals randomized to a fairly high dose of vitamin D- 40,000 IU a week – had lower scores on a depressive symptoms scale after one year than those randomized to placebo.”
However, the trial had limitations, notes Bertone-Johnson. “We need additional studies to know if vitamin D plays a role in depression.”
Autoimmune disease. “Vitamin D has powerful anti-inflammatory effects, and there’s preliminary evidence that it may lower the risk of multiple sclerosis, rheumatoid arthritis, lupus, and autoimmune thyroid disease,” says Manson. “But we need much more data to reach firm conclusions.”
FISH OILS
HEART DISEASE
It started in the early 1970s, when Hans Olaf Bang and J