Elsevier

Clinical Nutrition

Volume 40, Issue 4, April 2021, Pages 2401-2409
Clinical Nutrition

Original article
Dietary iron and vitamins in association with mortality

https://doi.org/10.1016/j.clnu.2020.10.038Get rights and content

Summary

Background & aims

Although disorders of iron metabolism are among the most common diseases and dietary intakes of vitamin A, B2, B6, C, E, and folic acid are known to affect the absorption or oxidation of iron, limited data are available on the association of dietary iron and these vitamins with mortality in the same population. Specifically, the holistic dietary vitamins intake and its combined effect with iron on mortality are unclear. The purpose of this study was to evaluate the association of dietary iron, holistic dietary vitamins, and their interactive effect with total and cause-specific mortality.

Methods

We evaluated the effects of dietary total/heme/non-heme iron, vitamins, and their interaction on all-cause/cardiovascular disease (CVD)/cancer mortality among 14,826 US adults in the National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative study. We developed a vitamin score to represent the holistic dietary intakes of vitamin A, B2, B6, C, E, and folic acid.

Results

A total of 2154 deaths occurred during a median follow-up of 9.3 years. Results from multivariate Cox proportional hazards models showed that higher vitamin score was associated lower risk of all-cause mortality (P-trend = 0.027). Negative interactions between dietary heme iron and vitamin score were observed on all-cause/CVD mortality. Dietary higher vitamins combined with lower heme iron was associated with lower risk of all-cause and CVD mortality (HR (95% confidence intervals (CIs)): 0.80 (0.64–0.98) and 0.55 (0.31–0.98), respectively). Higher dietary vitamins combined with higher total/non-heme iron was associated with lower risk of CVD mortality (HR (95%CIs): 0.69 (0.48–0.99) and 0.70 (0.48–0.99), respectively). These results remained significant even excluding participants with iron supplementation.

Conclusion

Our findings suggested that interactive effect of holistic dietary vitamins and iron play a protective role in decreasing all-cause and CVD mortality. Future studies, including cohort studies and clinical trials, are necessary to confirm these findings.

Introduction

Iron is an essential element for our body, since it participates in a wide variety of metabolic processes, including digestion of food, oxygen transport, and electron transport [1,2]. Iron is obtained mainly from dietary sources, which exists in the form of heme or non-heme iron [3,4].

Previous studies indicated that disorders of iron metabolism are among the most common diseases of diabetes, cardiovascular, pancreatic and colon cancer, and etc [[5], [6], [7], [8]]. However, results on the association of dietary iron with mortality were inconsistent. Dietary total iron was associated with risk of all-cause and cancer mortality in Belgian smoking man and Chinese adults, but no or significant association was found for cardiovascular disease (CVD) mortality in these two populations, respectively [9,10]. Some studies reported that higher dietary heme iron was related to higher risk of all-cause, CVD, and cancer mortality [[11], [12], [13], [14]], but others found no significant association [15]. Dietary non-heme iron was related to CVD mortality in Iowa postmenopausal women [12] whereas not in a Japan Collaborative Cohort (JACC) study [16]. Until now, limited data are available on dietary total/heme/non-heme iron with all-cause/CVD/cancer mortality in the same general population.

In addition, dietary intakes of vitamin A, B2, B6, C, E, and folic acid were known to affect the absorption or oxidation of iron in our body [[17], [18], [19], [20]]. To date, a total of three investigations were additionally adjusted for one or some of vitamin A, C, E, and folic acid in assessing the association of dietary total and heme iron with CVD mortality and the results were not changed in multivariable models [[12], [13], [14]]. Until now, no data on non-heme iron or mortality from all-cause or caner was reported. In addition, Hoydonck et al. developed a dietary oxidative balance score of vitamin C, β-Carotene and total iron intakes, which was observed to be positively associated with mortality risk from all-cause and cancer but not CVD in male smokers [9]. As we all know, vitamins do not be eaten isolated. Instead, they were eaten with combinations. To our knowledge, evidence on holistic effect of dietary vitamins or its interactive effect with iron on mortality is limited.

We therefore evaluated the association of dietary iron (total, heme, and non-heme), holistic intakes of vitamin A, B2, B6, C, E, and folic acid, and their interaction with mortality from all-cause, CVD and cancer in National Health and Nutrition Examination Survey (NHANES, 2003–2015).

Section snippets

Study population

The NHANES was a biannual, representative health survey of the United States population using highly stratified, multistage probability designs [21]. The survey is unique in that it combines interviews and physical examinations. The interview includes demographic, socioeconomic, dietary, and health-related questions [22]. The present investigation includes 3 two-year cycles (2003–2004, 2005–2006, and 2007–2008). We limited study sample to adults who were aged older than 18 years, were not

Characteristics of participants

During a median follow-up of 9.3 years, 2154 participants died. These deaths included 479 from all CVD and 466 from all cancers.

Compared with participants with iron intake smaller than median, participants with iron intake larger than median were significantly younger, tended to be males and current alcohol users, with higher prevalence of ever told had NCDs, higher dietary intakes of total energy, total, heme and non-heme iron, calcium, copper, fiber, vitamin A, B2, B6, C, E, folic acid and

Discussion

In this nationally representative sample of US adults, we observed that higher dietary heme iron was associated with higher CVD mortality while higher holistic intakes of vitamin A, B2, B6, C, E, and folic acid was associated with lower all-cause mortality. Results from interactive analysis suggest that higher holistic dietary vitamins combined with lower heme iron were associated with lower risk of all-cause and CVD mortality. Higher dietary vitamins combined with higher total/non-heme iron

Funding sources

This work was supported by grants from the National Natural Science Foundation of China (No. 82073536 and 81573134). The funding sponsors had no role in study design, data collection, statistical analysis and result interpretation, the writing of the report, and the decision to submit for publication.

Author's contributions

The authors’ responsibilities were as follows: XW: created the analytic design, analyzed the data, prepared the manuscript, and had primary responsibility for final content; WW and JG: created the analytic design, and interpreted the results; SH, LW, NL, YZ, TH, RS, YL, and CS: interpreted the results, and critically reviewed the manuscript. All authors read and approved the final manuscript.

Conflict of interest

The authors declare that they have no conflict of interests.

Acknowledgements

We thank the investigators, the staff, and the participants of the National Health and Nutrition Examination Survey for their valuable contribution. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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