Vitamin Whiplash

Will taking vitamins help lower our risks for cancers or raise our risks? The very same vitamins have been implicated with both abilities, depending on the day and the news source, leaving consumers suffering vitamin whiplash.

While some claim that the jury is still out, decades of research, both clinical trials and epidemiological studies, continue to offer no support that we need vitamin supplements for optimal health, or that vitamins or special nutrients can help prevent chronic illnesses, such as cancers or heart disease. Yet, the sensationalized claims for the health attributes of various dietary supplements can be as dramatic as the scares about their dangers. A recent study of vitamin supplements and lung cancer has been in the news, reported as finding no evidence that multivitamins, vitamin C, vitamin E or folate help to prevent lung cancer, but that vitamin E can increase the risk of cancer. Before we panic that we’ve given ourselves lung cancer from having ever taken vitamin E, let’s look at what the study actually found. It’s an illuminating look at how we often hear only part of what studies actually find.

This month’s issue of the American Journal of Respiratory and Critical Care Medicine published the results of a paper looking at correlations between vitamin use, diet, personal and lifestyle characteristics, and the incidence of lung cancer. In 2000-2002, 24-page questionnaires were mailed to 364,418 adults ages 50-76 living in the Seattle-Puget Sound area of Washington state as part of the VITAL (Vitamins and Lifestyle) study. Twenty-one percent (77,721 adults) returned the questionnaires. Over the next four years, these researchers matched them with lung cancers listed on the Seattle–Puget Sound SEER cancer registry. The researchers, led by Dr. Christopher G. Slatore, M.D., of pulmonary and critical care medicine at the University of Washington in Seattle, concluded: “Supplemental multivitamins, vitamin C, vitamin E, and folate were not associated with a decreased risk of lung cancer.” But they went on to say that “supplemental vitamin E was associated with a small increased risk” and that “patients should be counseled against using these supplements to prevent lung cancer.”

Most media outlets gave equally disconcerting coverage, and if you merely glanced at the headlines and skimmed the news stories, you probably came away mistakenly thinking that vitamin E had been shown to be dangerous and that eating more fruits and vegetables were preventative. As the Washington Post printed:

Vitamin E Supplements May Raise Lung Cancer Risk

....Every increase in vitamin E of 100 milligrams per day was associated with a 7 percent rise in lung cancer risk — translating into a 28 percent increase in risk over 10 years for someone taking 400 milligrams of vitamin E daily. “This provides additional evidence that taking vitamin supplements does not help prevent lung cancer," said Eric Jacobs, strategic director of pharmacoepidemiology at the American Cancer Society. The society does not currently recommend use of any vitamin supplement to prevent malignancy, Jacobs said. However, “our dietary guidelines do recommend eating five or more servings of a variety of vegetables each day," he noted.

Let's look at what the study actually found. In their introduction, Dr. Slatore and colleagues said that fruits and vegetables have been said to be associated with a lower incidence of lung cancer — but the meta-analysis they referenced found the correlation among more than the 430,000 adults followed for 6-16 years had been confounded by smoking and was untenable. As Slatore and colleagues said:

Supplements are used by over half of adults in the United States, and a majority of them believe they are "good for health and well-being." This belief that supplements are helpful, or at least safe, is controversial because there is growing evidence to the contrary and some supplements are associated with an increased risk of death. A systematic review of randomized controlled trials found little evidence that vitamin supplementation prevents chronic disease, including cancer, and a National Institutes of Health (NIH) panel did not make recommendations about their use, noting the lack of research with "accurate and current data on the public’s total intake of these nutrients."

Findings

The Washington researchers were unable to find a single correlation that was tenable between any of the vitamins — including vitamin E — and lung cancer.

All of the odds ratios hugged either side of 1.0 — null — and all were splitting hairs. None were beyond random chance or statistical error for these types of studies: 21%, 8%, 2%, 5%, 1%, 3%, 20%, 3%, 19%, 7%, 5% 1%.... Nor was there a dose relationship between multivitamins, or any of the individual vitamins, and lung cancer. In other words, taking increasingly more vitamins wasn’t associated with increasingly greater or lower risks. Taking no vitamins and the most vitamins shared similar risks, with the numbers of pills in between showing no logical correlations.

“There was no association for any level of vitamin E and lung cancer risk,” the authors reported, “but when examining the risk of lung cancer by the continuous variable of average 10-year intake of vitamin E, there was a [statistically] significantly elevated hazard ratio [of 5%] (1.05, 95% CL 1.00-1.09 per 100mg/day; p=0.03). After adjusting for intake of vitamin E from food sources...the results were no longer significant (1.04, 95% CL 1.00-1.09; p=0.08).” These untenable correlations held when they adjusted for confounding factors such as age, gender and smoking. [Yet, these researchers unexplicably still concluded that patients should be advised that taking vitamin E may be detrimental.]

To put this nonfinding into further perspective, according to the National Academy of Science, the Recommended Daily Intake for vitamin E is 15 milligrams (equivalent to 22 International Units (IU) of natural alpha-tocopherol or 33 IUs of the synthetic form used in this study). In other words, even this insignificant correlation only appeared associated with taking three or more times the recommended daily requirements every day for ten years. Someday, there may prove to be a role for toxic levels of some supplements to contribute to cancers, but this study provided no evidence of concern for most users.

Putting risks into perspective

Looking at the other characteristics of the participants and the odd ratios to lung cancers can help us better understand how irrelevant the correlations between vitamins, or fruits and vegetables, and cancer are that we hear in the news .

Fruits and vegetables have been claimed to be preventive, but like every study to date, the findings of Dr. Slatore and colleagues also didn’t support this belief. There was no tenable correlation between any number of daily servings of fruits and vegetables and lung cancer. Eating no fruits and vegetables was associated with an 8% lower risk than eating 3 servings a day, while eating 5 servings a day had a 9% lower risk than eating none. Just like vitamins, no correlation was above random chance.

Compare these correlations with being ‘overweight,’ which was associated with a 14% lower risk, while being ‘obese’ was associated with a 34% lower risk for lung cancer. Where were the headlines? “Obesity associated with a 34% lower risk for lung cancer!”

Having an advanced academic degree was associated with a 61% lower risk. This especially helps to remind us that correlations do not make for causes. If we followed popular thinking about correlations as causations, just imagine the headlines and calls for free and reduced diplomas for all to prevent lung cancer. “Diplomas lower risks for lung cancer!” :)

As we’ve learned, when it comes to correlations derived from population studies, it’s easy to be led astray and react to nonviable relative risks that aren’t true effects. They sound frighteningly significant, but can be due to random flukes, chance or mathematical computer modeling error. While relative risks less than 200% have long been recognized as inconsequential in epidemiological studies, a number of researchers are recommending that we raise the bar because even relative risks less than 900% are often not real and can often be explained by confounding factors. Relative risks in epidemiological studies that later prove out in clinical trials to have a causative role are often considerably more impressive than most of the numbers in the news used to scare us.

This study was a case in point. What was associated with the highest risk for lung cancer? Current smoking, with a 2,400% higher risk compared to those who’ve never smoked. And those who had quit under 10 years was associated with an 18-fold higher risk.

This study’s place in the body of evidence

This study was another nonfinding when it comes to today's belief in vitamins. According to these authors, just like other vitamin studies to date — observational and clinical trials — this study was unable to suggest a benefit for vitamins in lung cancer or a role in preventing cancer.

Nutritional science has long known and repeatedly demonstrated the value of vital nutrients for the prevention and treatment of deficiencies. There, the evidence is incontrovertible. A deficiency of vitamin C results in scurvy, a deficiency of folic acid in pregnant women can increase risk of spina bifida and neural tube defects in babies, a deficiency of vitamin B6 affects the neurological system, a deficiency of iron results in anemia, a deficiency of vitamin A can cause blindness and impaired immune system (and is the leading cause of preventable blindness and death among women and children in underdeveloped countries), etc. Vitamins and minerals have solid science in the treatment of deficiencies such as these. There are also specific medical conditions where deficiencies are known to occur due to heightened needs or difficulty meeting nutritional needs through foods, such as malabsorption after bariatric surgeries, certain illnesses, alcoholism, organ failure or surgery. For example, vitamin B6 deficiencies are seen in those taking certain medications such as cycloserie and penicillamine, or in babies with seizures due to a rare genetic pyridoxine-dependency. But the idea that most of us suffer deficiencies and need supplements isn’t supported.

For at least a quarter of a century, pop nutrition has promoted the idea that our modern diets are pitifully inadequate in vitamins and nutrients and that many of us need to take supplements and beef up our fruits and vegetables to be healthy. It’s widely claimed that RDA and RDIs are inadequate to protect our health and that most people are undernourished. But it is simply not true that most people are poorly nourished, said Drs. Stephen Barrett, M.D., and Victor Herbert, M.D., J.D., M.A.C.P., F.R.S.M., in The Vitamin Pushers: How the “Health Food" Industry Is Selling America a Bill of Goods. Getting the tiny amounts of essential vitamins our bodies need isn’t difficult when food isn’t restricted. And “estimates of the nutrient content of our food supply by the U.S. Department of Agriculture indicate that the amounts of most nutrients available to the consumer have increased during this century,” said Dr. Alfred E. Harper, Ph.D., who was chairman of the Food and Nutrition Board of the National Research Council/National Academy of Sciences from 1978 to 1982. “Consumption of fruits, vegetables, cheese, skim milk, fish, poultry and pork — all excellent sources of essential nutrients — have increased.”

The needs for most nutritional situations were taken into account when the RDAs were determined, according to Drs. Barrett and Herbert. These include people taking prescription drugs, dieters, women of childbearing age, smokers, the elderly, postmenopausal women on estrogen, those with osteoporosis, those with chronic infections or stress, teenagers, alcoholics, vegetarians, pregnant women, and lactating women.

As Dr. Sidney M. Wolfe, M.D., lead author of Worst Pills, Best Pills, and colleagues wrote, the prevailing myth that the recommended daily allowances are just the amount of a vitamin or mineral needed to prevent deficiencies is not true. In establishing the RDA, the amount needed by the average person is first determined and then raised to cover the needs of 98% of the healthy population. “This number is set at a level that is often two to three times higher than people’s needs, resulting in a significant safety margin.”

There is also no medical evidence to support taking supplements when a specific deficiency doesn’t exist, said Dr. Wolfe. Sound nutritional science shows benefits of nutrients for improving health when deficiencies (scurvy, anemia, rickets, etc.) are present or at risk, but not for bettering health otherwise. Many claim that poor nutrition or nutritional deficiencies cause most, or even all, disease and health problems. Thus, they claim diseases and health problems be prevented or treated through nutrition and supplements, but such beliefs are not supported by the evidence or biological plausibility.

It’s also popularly believed that if a little is good, then mega-doses of nutrients and vitamins may offer added health benefits. It has increased vitamin sales, but after our body uses what it needs, much of those vitamins end up as expensive pee. But there has been no credible evidence to date to support that vitamins, whether in more fruits and vegetables or supplements, beyond that necessary to correct deficiencies, hold medicinal properties to prevent chronic diseases, like cancer or heart disease, or even treat certain diseases. High doses of vitamin C, for instance, have not proven to be an effective cancer treatment. And according to Mayo Clinic, for example, the evidence is lacking or poor, and well-designed clinical trials have not yet confirmed that high doses of vitamin B6 can treat attention deficit-hyperactivity disorder, autism, carpal tunnel, immune system impairments, asthma, strokes or kidney stones, as are sometimes claimed.

The U.S. Preventive Services Task Force — charged with issuing careful, evidence-based findings that are used to develop clinical guidelines for healthcare providers — recently reviewed the randomized clinical trials on vitamin supplementation to prevent cancers and heart disease, the main causes of death. It found insufficient evidence to recommend supplements of vitamins A, C or E; multivitamins with folic acid; or antioxidant combinations for the prevention of cancer or cardiovascular disease.

The body of evidence since the USPSTF review has continued to yield null findings for the benefits of vitamins and supplements in preventing heart disease, cancers or other chronic diseases. For example, a recent review of clinical trials using antioxidants (vitamins E, C, beta-carotene, or selenium) and B vitamins and evaluating the progression of atherosclerosis using B-mode ultrasound, intravascular ultrasound or angiography, found no evidence of any protective effect of vitamins. As Dr. Donald McCormick of the department of biochemistry at Emory University, Atlanta, Georgia, said of “optimal nutrition,” nearly half the population may be spending over $1.5 billion each year on vitamin and mineral supplements wrongly believing they are “securing” their health. “The presumption held by some that vitamin-mineral supplements may have the potential to prevent and treat certain chronic diseases, such as some cancers and cardiovascular disease...is derived from in vitro studies or from studies that were generally observational and often marginal in statistical significance or control,” he said. On the basis of the sound evidence on people, he said: “One can hope that the exuberant use of vitamin-mineral supplements may be tempered somewhat by such findings, which carefully separate fact from faith.”