Dietary Supplements Have No Effect on Mortality Risk

Pam Harrison

April 08, 2019

For the general population, taking dietary supplements does not reduce the mortality risk from either cardiovascular disease (CVD) or cancer, a large cohort study concludes.

"People should aim for achieving adequate nutrition through a healthy balanced diet rather than relying on supplements," lead author Fang Fang Zhang, MD, PhD, Tufts University, Boston, Massachusetts, told Medscape Medical News in an email.

One exception was taking a supplement of lycopene, which did appear to reduce the mortality risk from both CVD and cancer.

However, the study also found that taking a supplement could be detrimental: taking high-dose calcium supplements appeared to increase the risk of dying from cancer.

The study was published online April 8, 2019, in the Annals of Internal Medicine.

"Given over half of Americans take dietary supplements to improve their overall health, to maintain health, or to improve specific health conditions, it is important to assess the effect that dietary supplements might have on mortality risk," Zhang commented.

In the study, dietary supplement use in the previous 30 days was analyzed among 30,899 adults who participated in six cycles of the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2000 and to 2009 to 2010.

Nutrient intake from foods and supplements was also analyzed from 27,725 participants who provided one or two valid, 24-hour diet recall information.

The team categorized nutrient intake as being either "inadequate" — defined as levels of total nutrient intake from food and supplements below the estimated average requirement — or as "adequate" when nutrient intake were at levels specified in the Dietary Reference Intakes. Excess nutrient intake was determined by comparing participants' intake with levels above the Tolerable Upper Intake level.

​Study participants who reported taking dietary supplements had a mean age of 50.7 years, whereas the mean age of those who did not take dietary supplements was 42.8 years (P < .001).

"More than half of participants (51.2%) reported use of dietary supplements in the previous 30 days, and 38.3% reported use of MVM (multivitamin and mineral) supplements," Zhang and colleagues observe.

The most commonly used vitamin supplements included vitamin C (used by 40.3% of participants), vitamin E (used by 38.6%), and vitamin D (used by 37.6%).

The most commonly used mineral supplements were calcium (used by 38.6%), zinc (34.5%), and magnesium (33.3%).

In general, participants who took supplements had higher levels of total nutrient intake for all 25 nutrients assessed compared with nonusers. Even when the nutrient intake from supplement use was discounted, they still had higher nutrient intake levels from foods for 23 nutrients compared with non-supplement users, the researchers point out.

Interestingly, however, over half of all participants had inadequate intake of vitamin D, vitamin E, choline, vitamin K, and potassium. Fewer than 5% of all respondents consumed what investigators determined was "excess" intake for all nutrients except niacin.

"During a median follow-up of 6.1 years, 3613 deaths occurred, including 945 CVD deaths and 805 cancer deaths," the researchers report.

After multivariable adjustment, no dietary supplement except lycopene was associated with a lower mortality risk. Lycopene lowered the risk for all-cause mortality by 18% and death from cancer by 54%.

Nutrients From Food

Investigators then began to tease out the effects of nutrient intake from food compared to the same nutrient intake from supplements.

Initially, they observed that those who had adequate intakes of vitamin K and magnesium were at lower risk for all-cause mortality, while those who had an adequate intake of vitamin A, vitamin K, copper, and zinc had a lower risk of dying from CVD.

However, "when sources of nutrient intake were further evaluated, the lower all-cause mortality associated with adequate intake of vitamin K and magnesium was restricted to intake from foods [while] the lower CVD mortality was associated with adequate intake of vitamin A, vitamin K, zinc, and copper...restricted to intake from foods," Zhang and colleagues observe.

Importantly, excess intake of calcium was associated with a 62% higher risk of dying from cancer. This risk was confined to high-dose calcium supplements of 1000 mg/day or more, and not to calcium intake from food, the team notes.

At the same time, investigators also noted that vitamin D supplementation at doses in excess of 10 mcg/day — or about 400 IU/day — was associated with an increased risk of both all-cause and cancer mortality.

However, this effect was only seen in participants with adequate vitamin D levels, defined as a serum 25-hydroxyvitamin D level of 50 nmol/L or higher, and not in participants with serum 25-hydroxyvitamin D levels of less than 50 nmol/L.

"Thus, vitamin D supplement use at 400 IU/day or higher may have untoward effects among those with no sign of low vitamin D status," Zhang observed.

"For those with low vitamin D status, vitamin D supplements had no benefit or harm," she added.

Zhang noted that if a patient has a medical condition that could lead to malabsorption of nutrients from foods or if they follow specific dietary customs and practices, they may be at risk for nutritional deficiencies that require treatment with dietary supplements.

She also cautioned that it is important for physicians to ask about dietary supplement use among cancer patients because certain dietary supplements such as antioxidants may interfere with the treatments they are about to receive.

"Thus, patients with nutritional deficiencies may be evaluated separately as per their individual needs," she suggested.

However, for the general population, Zhang emphasized that foods are usually the most important source of nutrients and that physicians should counsel patients accordingly.

Approached for comment, Elizabeth Kantor, MD, from Memorial Sloan-Kettering Cancer Center in New York, agreed and added: "People should discuss decisions regarding use of dietary supplements with their healthcare providers."

Zhang has disclosed no relevant financial relationships, although one of her co-investigators has; see the publication for information. Kantor has disclosed no relevant financial relationships.

Ann Intern Med. Published online April 8, 2019. Abstract

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