Vitamin Information Center

The August 20, 2008 edition of the Journal of the American Medical Association (JAMA) reported that B Vitamins did not work effectively to prevent death or cardiovascular events in a population of patients with coronary artery disease or aortic valve stenosis. In the wake of this report, we’ve seen a vocal response from industry, claiming that the study is not credible, as it failed to acknowledge elements that could have altered the conclusions presented.

The study, conducted from 1999 through 2006, on 3,096 patients in two Norwegian hospitals, was headed by Dr. Marta Ebbing, M.D. at Haukeland University Hospital. Patients’ concerns about taking B vitamins to ward off cardiovascular problems, but at the same time, increasing the chance of cancer, resulted in the study being stopped prematurely.

The study divided participants into one of four groups; daily oral treatment of folic acid plus vitamin B12 and vitamin B6; folic acid plus vitamin B12; vitamin B6 alone; or a placebo. The doses of vitamins used in the groups were 0.8 milligrams of folic acid, 0.4 milligrams of B12 and 40 milligrams of B6.

One of many questions that quickly arose in study feedback was whether beta blockers, statins and anti-platelets were used for the duration of the study. The participants started the study while in their mid-60’s, and more than 75 percent of them had already been using the above mentioned drugs for existing heart disease.

Another issue with the study was that Norway does not add folic acid to its wheat as is done in the US, ostensibly, because they do not believe that fortified foods are necessary. This, in turn, meant that any folic acid, B-6 or B-12 through supplementation or other food that participants may have been taking at home was not factored into the study, and could have affected the results. Analysts also believe that the study involved too narrow a section of the population, and could not provide a proper answer to what B vitamin does for healthy people, arguing that folic acid supplementation should be considered from a preventative standpoint only.

With so many variables unaccounted for in the study, one might wonder how it still went on for years without intellectual intervention. Hindsight though, is 20/20, and the missing factors are quite evident in retrospective analysis.

Dr. Andrew Shao, of the Council for Responsible Nutrition (CRN), in an interview with NPIcenter, explained that groups like the CRN “try to caution against over-interpretation of results and broad sweeping conclusions that you hear from some people.” Shao added “B vitamins may not work for people who already have heart disease, but these studies don’t answer the question of whether the healthy population, if they take B vitamins on a regular basis over the course of decades, may be at a lower risk for heart disease.”

Industry frequently complains, in cases like this, about study design.

Shao observed, “The study was actually pretty well designed. Every study has limitations. No matter what, you’re always going to have limitations to a study, and it’s important to identify those limitations; if you’re overly critical of them, that is a really difficult position to have because no one is ever going to conduct the absolute perfect study that answers every question that anyone would possibly want to ask in the world.”

Despite what seem like flaws in the study, it is important to remember that a be-all, end-all cure was not the final goal for Dr. Ebbing and colleagues. The study was to see if B vitamin use would lower homocystein levels and help those with existing heart disease, not simply if B vitamin use would prevent heart disease, and it seems to have done that.

“You have a tool box of prevention, and there are all kinds of tools in there that you can use to try and keep yourself healthy and avoid disease,” said Shao. “Using supplements is just one of these tools, among a whole bunch. It is not THE tool, it is A tool. You have other components such as diet, stress, exercise [and] genetics, which is a tool you can’t do anything with but you’ve still got it. Supplements are just one of those tools. If that’s your outlook and you understand it… that’s where the benefit will be seen.”

Launched a decade ago, the federal program requiring folic acid to be added to widely consumed foods has been hailed as one of the great public-health success stories. Harnessing a seemingly harmless vitamin, it helped slash the number of babies born with spina bifida and other devastating “neural-tube” defects.

But scientists are beginning to debate whether Canadians’ growing consumption of the nutrient may also be taking a terrible, unplanned toll, triggering hundreds of extra cancers annually, even as it makes pregnancies safer.

One Canadian specialist says the federal government should now consider abandoning fortification altogether, and focus folic-acid efforts more narrowly on the young women who unquestionably benefit from the vitamin.

“It’s a double-edged sword,” said Young-In Kim, a gastroenterologist and folic-acid researcher at the University of Toronto.

“It was meant to prevent neural-tube defects, and it did a wonderful job. [But] for people with pre-cancerous cells, or undiagnosed colon cancer tumours, giving high-dose folic acid or having high folate levels might actually make their condition worse.”

Other experts, though, argue that fortifying food offers well-proven health advantages, while evidence of any cancer risk is inconclusive at best. In fact, the Society of Obstetricians and Gynecologists of Canada has advocated higher intake of folic acid supplements for some women, while the March of Dimes and American Medical Association in the United States have called for doubling the level of folic acid - or folate - that must be added to flours and other raw grains.

“You need more substance to show harm [from folate fortification], and there has been a clear absence of substance,” said Dr. Joel Ray, a scientist at St. Michael’s Hospital in Toronto who has studied folic acid. “We shouldn’t backtrack and change the direction of the program right now.”

Health Canada has reviewed what it calls the “inconsistent” evidence on the issue, and has no plans to alter or cancel the program, said Alastair Sinclair, a department spokesman.

“It is not possible to conclude that fortification has increased the rates of colorectal cancer incidence in Canada,” he said.

The folic-acid story revolves around birth defects, specifically those where the fetus’s neural tube, which becomes the brain and spinal cord, develops improperly, sometimes resulting in major disabilities. Folic acid seems to have a powerful preventive effect. A 2007 study concluded that rates of spina bifida and other neural-tube defects fell by about 50% - or about 110 babies a year - in the wake of the fortification program.

Adding the vitamin to food started on a voluntary basis in this country in 1996, and became mandatory for white flour, enriched pasta and cornmeal in late 1998. Evidence had shown that many women of child-bearing age did not heed expert advice to take folic acid pills, which have limited effect if started after a woman becomes pregnant.

The target was younger women, but the fortification program, following on the heels of one in the U.S., led to a doubling on average in the level of folic acid in all Canadians. Some experts suggest that is not a bad thing: There is evidence that it actually protects people against certain cancers.

Two hotly contested studies published last year, however, have fuelled concerns that elevated levels in North American bloodstreams may be having the opposite effect. A trial published in The New England Journal of Medicine had been designed to test whether folic acid prevented pre-cancerous colorectal polyps. In fact, it found that those subjects taking folate supplements were slightly more likely to have multiple polyps and to develop prostate cancer.

Animal studies, meanwhile, have suggested that the vitamin can prevent colorectal cancer in healthy individuals, but can also make it more likely that pre-cancerous polyps will convert into malignancies and that existing cancers will develop faster.

Then there is the history of folate. In the 1940s, physicians experimented with giving it to children suffering from leukemia, only to find that it accelerated the disease. That discovery led to the development of the first chemotherapy drugs - ones that actually countered the effects of natural folate, said Kim.

He was among the experts consulted by U.K. officials recently as they considered implementing fortification. The British decided last year to put the plan on hold.

Another 2007 study, meanwhile, noted that colorectal cancer rates rose suddenly in both Canada and the U.S. in the years after folic acid fortification started, and suggested there could be a link. The rates here climbed to almost five extra cases per 100,000 annually, before sliding back to a level that was still somewhat higher than before fortification.

That means that as many as 1,500 additional Canadians were diagnosed with colorectal cancer yearly after folate levels started to soar.

Dr. Joel Mason of Tufts University in Boston, who spearheaded the study, said there is not yet enough evidence to justify actually cancelling the fortification program, but called for more research on the possible cancer connection. He also suggests that anyone who is not a woman in her reproductive years think twice about taking folic acid supplements, which only add to the levels provided by fortification.

“We don’t know whether taking vitamin supplements and fortifying food [with folic acid] … actually accelerates cancer risk among susceptible people, but there is certainly a scientific basis for that possibility,” Mason said.

“We can’t afford to ignore it. It’s not a trivial phenomenon.”

Yet his and the New England Journal study have both come under stiff criticism.

British experts on spina- bifida argued in a letter to The Lancet last year that the trial published in the New England Journal showed no significant evidence that folate can be carcinogenic. And, like Ray, they said the increased cancer rates identified in Mason’s study were likely just a result of stepped-up screening for colorectal cancer.

In the meantime, a study published last month in the World Journal of Gastroenterology offered a much rosier view of the vitamin. It found that after three years, patients who took folic acid supplements actually had a third as many of the polyps that can lead to colorectal cancer as those taking a placebo.

A diet lacking in B vitamins may result in cognitive problems, new findings suggest.

Vitamin B deficiency could result in cognitive impairment, according to new research published in Proceedings of the National Academy of Sciences.

Researchers from the Jean Mayer USDA Human Nutrition Research Centre on Ageing (HNRCA) at Tufts University found that mice given a diet which was deficient in three B-vitamins showed cognitive dysfunction as well as reductions in both brain capillary length and density.

The mice deficient in B-vitamins took longer to perform tasks such as navigating a water maze.

Dr Aron Troen, lead author of the study and assistant professor at Tufts University’s Friedman School of Nutrition Science and Policy, commented: “Mice fed a diet deficient in folate and vitamins B12 and B6 demonstrated significant deficits in spatial learning and memory compared with normal mice.”

Meanwhile, a separate study has suggested that regular walking could have a positive effect for people with memory problems.

A study published in the Journal of the American Medical Association suggested that individuals aged over 50 who go walking for over two-and-a-half hours a week can see significant improvements in memory problems

Not ready to quit smoking cold turkey? A new study shows that just cutting down on the number of cigarettes you smoke can reduce your risk of lung cancer.

Noting that “many smokers are unable or unwilling to completely quit smoking,” a team of researchers from Denmark set out to determine the impact reducing the amount people smoke could have on their lung health. Their findings appear in the Journal of the American Medical Association.

The researchers looked at data from nearly 20,000 men and women who had undergone two physical examinations with five to 10 years between checkups as part of a larger study. At both exams, participants filled out questionnaires on their lifestyle habits, including questions about how much and how often they smoked. Former smokers were asked about past habits and the amount of time since they had quit.

At the first checkup, participants were categorized as heavy smokers (15 or more cigarettes per day), light smokers (one to 14 cigarettes per day), ex-smokers and never smokers. At the second visit, the researchers divided the participants into further categories: continued heavy smokers, reducers (reduced smoking from 15 or more cigarettes per day by a minimum of 50% without quitting), continued light smokers, quitters (quit since the first examination), continued ex-smokers and never smokers.

Between exams, 832 people reduced their smoking by at least 50%, with the average reducer going from 22.2 cigarettes per day to 8.5 cigarettes per day. More than 7,300 participants remained categorized as heavy smokers, smoking an average of 20 cigarettes per day at both exams. Compared to those who continued to smoke heavily, reducers were older, more likely to be male and had smoked slightly more and for a longer period.

Participants were followed from their second examination for an average of 18 years, during which time 864 people developed lung cancer.

After analyzing the data, the researchers found that while consistent light smoking or quitting smoking after being a light smoker carried a bigger reduction in lung cancer risk, heavy smokers who managed to reduce their daily number of cigarettes from about 20 to fewer than 10 cut their risk by 27%.

But this finding doesn’t mean that if you are a smoker your goal shouldn’t still be to butt out altogether. The researchers note that other studies haven’t found that reducing the number of cigarettes smoked per day cuts the risk of heart attack or chronic obstructive pulmonary disease (COPD), and they conclude that the focus should be on quitting, not cutting down.

“More data from long-term studies of smoking reduction are warranted, but for the present, smoking cessation and not smoking reduction should still be advocated as the ultimate method of reducing harm from smoking,” they write.

You’ve been told for years that popping a multivitamin every day might help you live longer. But the daily-multi habit has been getting a bit of bad press lately.

First, ConsumerLab.com, a watchdog of the supplement industry, found that more than half of the 21 multis it tested had too much (or too little) of certain vitamins—or had been contaminated with dangerous substances like lead. Then a controversial paper from researchers in Denmark and other European countries, published in the Journal of the American Medical Association, made the claim that taking vitamins may actually shorten your life.

What’s the real story? Health talked to leading nutrition experts at Harvard and Tufts universities to find out and to get some answers on this and other confusing info about vitamins.

Are multivitamins safe?
Vitamins have been recommended for years because they help you get key nutrients if your diet’s low on fruits and veggies—and may even help prevent cancer and heart disease. And it’s unlikely that one critical paper (speculating that vitamin supplements might upset your body’s natural healing process and boost your risk of death) will change that.

Longtime vitamin experts at Tufts University and the Linus Pauling Institute at Oregon State University continue to say multis aren’t dangerous and the paper’s findings are wrong. The paper analyzed previous studies, including many with people who were sick before taking vitamins, so there’s a good chance vitamins weren’t responsible for shortening their lives. Experts say the paper also ignored two major studies that found vitamins reduced the risk of death.

At the same time, the study from ConsumerLab.com shows that you can’t assume just any vitamin is safe. Because there are no uniform manufacturing rules for supplements, a multi may not contain what the bottle claims, could be contaminated with something from the manufacturing plant, or might have tainted ingredients.

Your best bet: Avoid the vitamins singled out by ConsumerLab.com (see “11 Multis to Avoid”), and stick with mainstream names like Centrum Silver and One-A-Day Women’s, which were found to be free of impurities and accurately labeled. Also, check vitamin bottles for the United States Pharmacopoeia (USP), NSF International (NSF), or ConsumerLab.com (CL) seals. The USP and NSF are nonprofit groups that verify whether companies offer contamination-free products and use good manufacturing practices. Not every brand has the seals—some don’t want to submit to testing—but those that do (Kirkland and Nature Made carry the USP seal, for instance) are reliable.

How much should I spend to get the biggest benefits?
Price isn’t a sign of quality. In fact, some of the priciest vitamins—like The Greatest Vitamin in the World and Eniva Vibe, which cost more than $39.95 per bottle—failed the Consumer Lab.com tests. A mainstream brand like One-A-Day Women’s is $8.99 for a bottle of 100 tablets at about 9 cents per day.

How do I find the right multi for me?
In your childbearing years, make sure your multi has 400 micrograms (mcg) of folic acid, which helps make and maintain new cells. And pregnant women should take a vitamin with 600 mcg of folic acid daily; this nutrient also reduces the incidence of neural tube birth defects like spina bifida.

A premenopausal woman should look for a multivitamin with iron to replace the iron lost during menstruation. Menopausal women should go without the iron. “Too much iron may raise the risk of heart disease,” says Meir Stampfer, PhD, professor of nutrition and epidemiology at Harvard School of Public Health.

If you’re taking a prescription, check with your doctor about risky interactions. (Vitamin E, for instance, may be a problem if you’re taking a blood thinner.) If you’re a cancer patient, you should ask your doctor about risks before taking vitamins. “Cancer cells need vitamins to grow, too,” Stampfer says. Plus, some vitamins can interfere with chemotherapy.

What’s the best way to avoid that queasy feeling after taking a multi?
“Consider switching brands,” Stampfer suggests. Trial and error is the best way to determine which brands won’t break down poorly in your stomach and lead to irritation. Also, take your multi with food because your body needs some fat (or lipids) to absorb some of the individual vitamins. The delivery method (pill, liquid, gummy bear) makes no difference. But vitamins in liquid form may degrade more quickly on the shelf.

How much of each vitamin should my multi have?
The amount per serving numbers on the label should match the government’s Dietary Reference Intakes (DRI). It’s OK if they’re higher as long as they don’t exceed the tolerable upper limit (UL). (To find the DRIs and ULs, While most vitamins are listed in milligrams (mg) or micrograms (mcg), the label may use IUs (international units) for vitamins A, D, and E. The DRIs are 2,300 IUs for vitamin A, 200 for D, and 22 for E. What about the label’s % Daily Value column? Look at it with a skeptical eye: Those numbers haven’t been updated since 1968.