In this large cohort study, we observed that consumption of red meat, processed meat, white meat and fish was not significantly associated with increased or decreased risk of total mortality, cancer mortality and CVD mortality. However, there was an inverse association for men between the intake of white meat and total mortality. Furthermore, fish might have a favorable effect on CVD mortality.

Looking at the baseline characteristics the participants in this cohort may help explaining the null association between red and processed meat consumption and mortality we observed. On the one hand, red meat consumption was inversely associated with the use of dietary supplements, physical activity and fruit and fish consumption and positively associated with smoking and processed meat consumption, suggesting that the participants with moderate meat consumption had a beneficial profile of these risk factors for CVD and cancer. On the other hand, red meat consumption was inversely associated with age, blood pressure and BMI and was positively associated with vegetable consumption, suggesting that the participants with high red meat consumption had a beneficial profile of these risk factors for CVD and cancer. Adjusting for these factors in the multivariable Cox regression models, thus, attenuated the observed positive association between red meat consumption and overall mortality. However, in this respect, a limitation of this analysis has to be kept in mind: NHANES III only assesses food consumption with a simple food frequency questionnaire without the possibility of assessing portion sizes. Thus, we were not able to better categorize participants by using frequency and amount of food consumed per consumption event and also to calculate and adjust for energy intake as in previous studies to minimize confounding.11, 12 Nevertheless, food frequency questionnaire is an appropriate tool for ranking subjects according to food and nutrient intake even if they do not assess portion sizes in addition to consumption frequency.25 Unlike the cohorts in the analyses by Pan et al.12 and Sinha et al.,11 our cohort is not so strongly dominated by well-educated non-Hispanic white participants as NHANES III is representative for the US population. Additionally, measurement errors inherent in dietary assessments were inevitable, including misclassification of ham or cold cuts as unprocessed meat and inaccurate assessment of meat content in mixed dishes.25 Compared with analyses of the AARP11 and the Health Professionals and Nurses Health cohorts,12 the number of deaths due to cancer or CVDs is limited, and thus, we had sufficient power to determine a moderate association between red meat consumption and total mortality, but not moderate associations with cancer or CVD mortality.

Besides the very strong effects observed in the AARP11 and the Health Professionals and Nurses Health cohorts,12 some other recently published studies revealed only weak or even no associations between meat consumption and CVD mortality or cancer mortality.26, 27, 28 Moreover, depending of the cancer site there is more or less convincing evidence between meat consumption and an increased risk of cancer.5 Along with our weak results, we conclude that the strength of a possible association between meat consumption and total mortality still appears to be unclear and is likely very complex due to influences by various confounders. To support the evidence of a possible association between red/processed meat consumption and all-cause or cause-specific mortality, further research is warranted.

When looking at a dietary score instead of focusing on one specific group of foods, we observed a statistically significant inverse association between a good HEI score and total mortality, which was, however, only observed in men, but not in women. A possible stronger homogeneity in diet behavior among women, which would partially explain the difference between men and women, could not be observed in the baseline characteristics. A recently published study by Rathod et al.18 reported a moderate inverse association between a good HEI score and total mortality and CVD mortality in an elderly cohort. However, no studies looking at the association between HEI and mortality in adults have been published so far,29 but Akbaraly et al.30 observed statistically significant inverse associations between all-cause and CVD mortality and a good alternative HEI score in the Whitehall study. However, in an attempt to improve the original HEI to better predict major chronic disease risk, alternative HEI is a modified dietary index and results cannot be fully assigned to the HEI.31, 32

For cancer and CVD mortality, we found no association with HEI. Although HEI considers nutrients that are associated with chronic diseases, it is criticized that nutrients that have a protective role in the prevention are not taken into account in the construction of the HEI.33 It has, for example, been argued that n-6 and n-3 fatty acids and dietary fiber should be included to better predict CVD and cancer, which lead to the development of the alternative HEI.34, 35 The limited information of the HEI may partially explain the poor sensitivity of the HEI in assessing specific causes of death-like cancer and CVD. Our findings are consistent with recent findings that dietary indices are only weakly associated with clinical disease outcomes.14, 15, 36

The HEI scores in our analysis are based on only one 24-h dietary recall instead of being based on food frequency questionnaire capturing habitual dietary behavior. However, when looking at food consumption based on the food frequency questionnaire by HEI categories, we noted that those participants with a high HEI also had a more favorable diet, that is, high consumption of fruits and vegetables and rather low consumption of red and processed meat when compared with participants with low HEI. Interestingly, participants with a high score were more likely to have underlying diseases like hypertension and diabetes; nevertheless, they had a lower mortality rate than participants with a low HEI. It is likely that these participants have been advised by their treating physician or a dietician to change their dietary habits to improve their condition, for example, blood pressure or glucose levels. In general, higher HEI scores have been associated with higher energy and nutrient intakes, and also with higher concentrations of serum and red blood cell folate, serum vitamins C and E, and serum carotenoids and a lower mortality.18, 37, 38

In conclusion, our data do not support the previously observed association between high red and processed meat consumption and increased mortality, which may be explained by the rather crude dietary questionnaire used in NHANES III in contrast to other cohorts. However, our results do support the importance of a healthy diet for overall mortality, although it cannot explain specific causes of death-like cancer and CVD.