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Intake of both processed and unprocessed red meat was associated with all-cause and cause-specific mortality, in part due to heme iron and nitrate or nitrite, reported researchers.

In a large U.S. cohort of more than 500,00 people, red meat intake was associated with increased risk of all-cause mortality during the median 15.6 years of follow-up (HR 1.26 for highest versus lowest fifth, 95% CI 1.23-1.29), with a similar impact for unprocessed and processed red meat at the same level of intake, Arash Etemadi, MD, PhD, of the National Cancer Institute in Bethesda, Md., and colleagues reported in.

The risk was higher too for death due to all the specific causes looked at -- cancer, diseases of the heart, stroke and other cerebrovascular diseases, respiratory disease, diabetes mellitus, infections, kidney disease, and chronic liver disease -- except Alzheimer's disease.

Heme iron and particularly nitrate or nitrite added in processing appeared to drive the associations with processed red meat, mediating 20.9% to 24.1% and 37.0% to 72.0%, respectively, of the increased mortality risks.

"This is the largest study, so far, to show increased mortality risks from different causes associated with consuming both processed and unprocessed red meat, and it underlines the importance of heme iron, nitrates, and nitrites in assessing the pathways related to health risks associated with red meat intake," wrote Etemadi and colleagues.

The group studied baseline dietary data on 536,969 people ages 50 to 71 years from the NIH-AARP Diet and Health Study -- a prospective cohort of the general population from six states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and two metropolitan areas (Atlanta and Detroit).

Participants completed a 124-item food frequency questionnaire on their intake of total meat, processed and unprocessed red meat (beef, lamb, and pork) and white meat (poultry and fish), heme iron, and nitrate/nitrite from processed meat.

The researchers then calculated daily intake of heme iron based on measurements of the heme iron content of a variety of fresh and processed meats, multiplied by the reported meat consumption. They divided all nutritional variables by the daily calorie intake and categorized the calorie adjusted values into fifths for the entire cohort.

Participants with higher red meat consumption were more likely to have diabetes, poor or fair perception of their health status, and less physical activity. They were less likely to have high socioeconomic status scores and to be college graduates or postgraduates.

The strongest associations were seen for death due to chronic liver disease (HR 2.30, 95% CI 1.78-2.99), followed by diabetes (HR 1.39, 95% CI 1.24-1.55), respiratory diseases (HR 1.38, 95% CI 1.29-1.48), and kidney disease (HR 1.35, 95% CI 1.16-1.58).

Additionally, dietary heme iron and nitrate/nitrite from processed meat were independently associated with increased risk of all-cause mortality and cause specific mortality.

The researchers also found that replacing red meat with white meat, particularly unprocessed white meat, was associated with reduced mortality risk. This was seen even without changing total meat intake.

They noted that people in the highest category of white meat intake had a 25% reduction in risk of all-cause mortality compared with those in the lowest intake level (HR 0.75, 0.74-0.77).

"The fact that poultry and fish intake are inversely related to risk and contain little of these agents adds plausibility to their causal interpretation," noted an accompanying editorial. While focusing largely on the impact of red meat consumption on the planet, it added, "The important conclusion is that the current patterns of consumption of red and processed meat are not good for humans."

Etemadi suggested that oxidative stress may be the underlying common mechanism for many of these findings.

Study limitations included potential measurement error, as well as the use of a single dietary assessment at the beginning of the follow-up which prevented evaluation of the changes in diet over this time period.

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