USPSTF: Evidence Insufficient That Vitamins Prevent Cancer

Roxanne Nelson

February 24, 2014

About half of all Americans take supplements, but doing so is unlikely to stave off either cancer or cardiovascular disease. In its latest report, the US Preventive Services Task Force (USPSTF) has concluded that there is insufficient evidence to determine whether vitamins help prevent either of these diseases.

However, the USPSTF does recommend against supplementing with either beta-carotene or vitamin E. This is a grade D recommendation. The evidence shows that there is no benefit to taking vitamin E, and that beta-carotene can increase the risk for lung cancer in some populations, according to USPSTF cochair Michael LeFevre, MD, MSPH.

The report, published in the February 25 issue of the Annals of Internal Medicine, is an update of the 2003 recommendations.

"Due to the uncertain benefit of vitamin supplements to prevent cardiovascular disease and cancer, healthcare professionals should use their best judgment and consider their patient's health history, values, and preferences when having conversations about nutritional supplements," Dr. LeFevre said in a statement.

Unlike the 2003 USPSTF recommendation, the update took into account evidence on additional supplements — such as vitamin D, calcium, selenium, and folic acid — for the primary prevention of cancer and cardiovascular disease.

Also considered was evidence on the use of vitamin E, which increased the certainty about its lack of effectiveness in preventing these 2 diseases.

Some Conflicting Data

The USPSTF made its recommendations on the basis of published literature on vitamins and their impact on health. Over the past few years, a number of studies have evaluated the benefits and harms of supplements with varying results.

One recent meta-analysis of 26 studies demonstrated that, overall, the data show that vitamin and/or mineral supplements do not prevent cancer or cardiovascular disease.

An earlier study of data from the large Women's Health Initiative showed that multivitamin use had no influence on the risk for common cancers, cardiovascular disease, or overall mortality in women.

However, 2 studies that evaluated the association between multivitamins and breast cancer found opposite results; one study found an increased risk with multivitamins and the other found a decreased risk.

Another study, conducted in 2012, indicated that the daily use of multivitamins might reduce the risk for cancer in men, as well as the risk of dying from the disease.

Notable Limitations

However, the trials evaluated by the USPSTF have some serious limitations, which were not mentioned in the update, explained Balz Frei, PhD, distinguished professor of biochemistry and biophysics at Oregon State University in Corvallis. "Many trials were of short duration and commenced late in life," he told Medscape Medical News.

Another limitation is that the USPSTF "lumps very diverse nutrient interventions together — with disparate study designs, end points, and datasets — when reporting their recommendation," said Dr. Frei, who is also director and endowed chair of the Linus Pauling Institute.

In addition, the USPSTF only focused on primary prevention of cardiovascular disease and cancer. "It did not review evidence for the support of normal biological functions or the use of supplementation to fill nutritional gaps in the average American diet," he explained.

Dr. Frei and his colleagues at the Linus Pauling Institute concur that the current evidence is insufficient to assess the benefits and harms of these supplements in relation to cancer and cardiovascular disease. They also agree with the USPSTF that beta-carotene supplements can increase the risk for lung cancer in those at high risk, and that single-nutrient vitamin E and beta-carotene supplements cannot prevent either disease.

However, they believe that it is likely premature to rule out any benefits of supplemental vitamin E.

"Taking a daily multivitamin is a safe, affordable, and simple way to help fill nutritional gaps and improve the micronutrient status of Americans," said Dr. Frei. "Adequate micronutrient status is needed for normal biological function and metabolism, and to support good overall health."

Gaps and Needs

"The paucity of studies and general lack of effect of any single nutrient or nutrient pair makes it difficult to draw meaningful conclusions on the balance of benefits and harms without a coordinated research effort and focus," according to the update. "A general lack of standardized methods to determine relevant serum nutrient levels, agreement on thresholds for sufficiency and insufficiency, or predictive validity of current mechanistic models further hinders progress in understanding potential benefits of dietary supplements."

The task force notes that evidence from in vitro, experimental, and population-based epidemiologic studies lends support to the hypothesis that oxidative stress plays a fundamental role in the initiation and progression of cancer and common cardiovascular diseases.

If this hypothesis is correct, some combination of specific supplements, specific dose, individual factors, and specific timing could be useful.

Although risk factors for cardiovascular disease are well established, those for cancer are "considerably more complex because of the heterogeneous nature of different cancer types and environmental and genetic influences," the task force writes. "The potential antioxidant and anti-inflammatory effects of many nutrient supplements are the basis for their proposed use to prevent cardiovascular disease and cancer."

Research has suggested that the oxidative properties of antioxidants can vary depending on a number of factors, including the concentration of the nutrient and the presence of other oxidants/antioxidants. Therefore, the USPSTF notes, the observed harmful association between beta-carotene and lung cancer in high-risk individuals suggests that other variables are involved that could influence whether beta-carotene acts as an antioxidant or a pro-oxidant.

In trying to disseminate this information, the USPSTF acknowledges that a "critical gap in the evidence" is the lack of studies conducted in groups generalizable to the entire American population. For example, they note that there have been 2 randomized controlled trials of multivitamins that suggested a preventative cancer benefit for men but not women.

In the future, trials need to be more representative of the population at large, and need sufficient power to demonstrate whether there are true differences between subgroups, the USPSTF points out. The taks force acknowledges that there are "significant challenges to studying nutrient supplementation using methods similar to those used in studying pharmaceutical interventions."

Ann Intern Med. 2014;160:271-281-281. Abstract


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