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. 2024 Oct 1:11:1437681.
doi: 10.3389/fnut.2024.1437681. eCollection 2024.

Dose-response relationship of serum ferritin and dietary iron intake with metabolic syndrome and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis

Lu Yu #  1   2   3   4 , Ting Que #  5 , Yifeng Zhou  2 , Zhengtao Liu  2   3   4   6   7
Affiliations

Dose-response relationship of serum ferritin and dietary iron intake with metabolic syndrome and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis

Lu Yu et al. Front Nutr. .

Abstract

Aim: This study aims to assess the dose-response impact of iron load on systemic and hepatic metabolic disorders including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD).

Methods: Serum ferritin (SF) and dietary iron intake were selected to represent the indicators of iron load in the general population. PubMed, EMBASE and Web of Science databases were searched for epidemiological studies assessing the impact of SF/dietary iron intake on MetS/NAFLD occurrence. All literature was published before September 1st, 2023 with no language restrictions.

Results: Fifteen and 11 papers were collected with a focus on connections between SF and MetS/NAFLD, respectively. Eight papers focusing on dietary iron and MetS were included in the following meta-analysis. For the impact of SF on MetS, the pooled odds ratio (OR) of MetS was 1.88 (95% CI: 1.58-2.24) for the highest versus lowest SF categories. In males, the OR was 1.15 (95% CI: 1.10-1.21) per incremental increase in SF of 50 μg/L, while for females, each 50 μg/L increase in SF was associated with a 1.50-fold higher risk of MetS (95% CI: 1.15-1.94). For connections between SF and NAFLD, we found higher SF levels were observed in NAFLD patients compared to the control group [standardized mean difference (SMD) 0.71; 95% CI: 0.27-1.15], NASH patients against control group (SMD1.05; 95% CI:0.44-1.66), NASH patients against the NAFLD group (SMD 0.6; 95% CI: 0.31-1.00), each 50 μg/L increase in SF was associated with a 1.08-fold higher risk of NAFLD (95% CI: 1.07-1.10). For the impact of dietary iron on MetS, Pooled OR of MetS was 1.34 (95% CI: 1.10-1.63) for the highest versus lowest dietary iron categories.

Conclusion: Elevated SF levels is a linear relation between the incidence of MetS/NAFLD. In addition, there is a positive association between dietary iron intake and metabolic syndrome. The association between serum ferritin and metabolic syndrome may be confounded by body mass index and C-reactive protein levels.

Keywords: dietary iron; dose–response relationship; meta-analysis; metabolic syndrome; non-alcoholic fatty liver disease; serum ferritin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of eligible literature selection. (A) Literature on the association between SF and MetS; (B) literature on the association between SF and NAFLD; (C) literature on the association between Dietary and MetS. SF, serum ferritin; MetS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease.
Figure 2
Figure 2
Forest plot of association between SF and MetS in cross-sectional studies. Pooled odds ratios of MetS compared between highest and lowest SF categories. SF, serum ferritin; MetS, metabolic syndrome.
Figure 3
Figure 3
Egger’s funnel plot analysis of publication bias (A) between SF and MetS, Egger’s test: p = 0.561. (B) Between NASH/NAFLD and control, Egger’s test: p = 0.104. (C) Between NASH VS NAFLD, Egger’s test: p = 0.417. (D) Between Dietary Iron and MetS, Egger’s test: p = 0.560. SF, serum ferritin; MetS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.
Figure 4
Figure 4
Forest plot of the association between Dietary Iron and MetS in cross-sectional studies. Pooled odds ratios of MetS compared between highest and lowest Dietary Iron categories. MetS, metabolic syndrome.
Figure 5
Figure 5
Sensitivity analyses of the association between SF/Dietary Iron and MetS /NAFLD. (A) Represents eliminated heterogeneity excluding a study of association between SF and MetS in cross-sectional studies. (B,C) Represent eliminated heterogeneity excluding studies of association between SF and NAFLD in cross-sectional studies. (D) Represent eliminated heterogeneity excluding studies of association between Dietary and MetS in cross-sectional studies. SF, serum ferritin; NAFLD, non-alcoholic fatty liver disease; MetS, metabolic syndrome.
Figure 6
Figure 6
Forest plot of association between SF and NAFLD in cross-sectional studies. (A) NAFLD/NASH patients against the control group; (B) NASH patients against NAFLD against SF, serum ferritin; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.
Figure 7
Figure 7
Dose–response relations between SF and risk of MetS/NAFLD in prospective studies. (A) Risk between SF and MetS in men estimates from a dose–response meta-analysis. (B) Risk between SF and MetS in women estimates from the dose–response meta-analysis. (C) Risk between SF and NAFLD estimates from the dose–response meta-analysis. SF, serum ferritin; MetS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease.
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Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Innovative Research Groups of National Natural Science Foundation of China (81721091), Major program of National Natural Science Foundation of China (91542205), National S&T Major Project (2017ZX10203205), Zhejiang International Science and Technology Cooperation Project (2016C04003), Zhejiang Provincial Natural Science Foundation of China (LY22H030008), Zhejiang medical S&T program (2021KY145 and 2022KY752), International Youth Exchange Program by China Association for Science and Technology (2020), Tianqing Liver Diseases Research Fund (TQGB20200114), Organ Transplantation Overseas Training for Youth Talents from Shulan Excellent Talent Project, CSCO (Chinese Society Of Clinical Oncology)-Bayer Tumor Research Funding (Y-bayer202001/zb-0003), Research fund from Chen Xiao-ping Foundation for Development of Science and Technology of Hubei Province (CXPJJH122002-078), Beijing iGandan Foundation (1082022-RGG022), Zhejiang Shuren University Basic Scientific Research Special Funds (2023XZ010), and Startup fund for Advanced Talents from Zhejiang Shuren University.

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