Study: High iron intake linked to irregular heart rhythm in specific genetic variations

The study, funded by the Bill & Melinda Gates Foundation and involving data from 179,565 participants from the population-based cohort, found the link with irregular heart rhythm—aka atrial fibrillation (AF)—was especially prominent with iron intake exceeding 16.95 mg a day.

Specifically, high iron intake was associated with a 13% increase in the incidence of AF after adjusting for important covariates, and an increased iron intake was associated with an elevated occurrence of AF among risk gene carriers of 83 SNPs (genetic variations).

The findings are important, with AF significantly increasing the risk of stroke, heart failure and other cardiovascular diseases (CVDs) and the estimated number of AF cases growing—registering 59.7 million in 2019, double the number observed in 2009​.

"Strict control of iron intake, avoidance of excessive supplementation, and limiting iron-rich foods are key for those with iron overload or a high AF risk," the report concluded.

Some previous studies have suggested a connection between iron and atrial fibrillation, while others have contradicted this finding. When the body’s iron content increases, vital organs like the heart start to absorb iron, and excess iron can lead to myocardial diseases, pericarditis and arrhythmias​. However, no comprehensive evaluation has been performed on the association between dietary iron intake and the risk of atrial fibrillation.

Genetic mutations and polymorphisms are associated with the risk of atrial fibrillation​, but there is still controversy over the relationship between iron-related SNPs and the occurrence and development of atrial fibrillation.

The current study therefore used data from the UK Biobank cohort to explore the relationship between dietary iron intake and the risk of AF. It also examined whether the presence of specific genetic variants, comprising 165 SNPs related to AF and 20 SNPs related to iron, influenced the relationship.

Iron recommendations and intake

The NHS recommendation for daily iron intake in men and women (having periods) aged 19 and over is 8.7 mg and 14.8 mg, respectively, and 8.7mg for women aged 50 and over.

Iron deficiency tends to be the main concern in women, whereas a study of iron intake in countries across Europe recently found​ that in all countries analysed, the majority of men had a dietary iron intake markedly above a recommended intake of 9 mg/day—75% to 87% of men have a dietary iron intake above 9 mg/day. 

The UK, Sweden, Belgium and Serbia reported median/mean iron intake ranging from 10.5 to 11.6 mg/day; Norway, Finland, Lithuania, Italy, Hungary, Portugal, The Netherlands, Denmark, Iceland and Austria reported iron intake from 12.0 to 13.5 mg/day; France, Germany, Ireland and Spain reported iron intake from 14.8 to 16.0 mg/day; and Poland and Slovakia reported the highest intake between 17.2 and 22.7 mg/day. 

Cohort study

UK Biobank is a large population-based cohort of over 500,000 participants between the ages of  37 and 73 years who were recruited in 22 assessment centres in England, Wales and Scotland between 2006 and 2010.

Participants completed touchscreen self-reported questionnaires, online computer-assisted personal interviews and physical measurements during the baseline survey and five rounds of 24-hour dietary recalls between 2009 and 2012 using Oxford WebQ. 

The team categorized the collected iron intake data into low, moderate and high intakes using cut offs: 0% to 20% (≤10.08 mg), 20% to 80% (10.08–16.95 mg) and more than 80% (≥16.95 mg).

Participants were followed until death or through the end of the follow-up period (March, 31 2021), whichever came first. AF diagnoses were obtained from primary care records, hospital admission records and death registration.

Metascape and Fuma were used to analyze the pathway of the gene ontology corresponding to 83 SNPs. Metascape​ was used to analyze the enrichment of 62 genes corresponding to 83 SNPs. Fuma was used for insight into the directional biological significance of important genetic associations.

Resulting data suggested the high iron intake group was more likely to 65 years or younger, male, overweight and alcohol drinkers. Additionally, they were less likely to use iron supplements and had a lower prevalence of hypertension and smoke less.

There were 83 SNPs (11 iron-related SNPs) that promoted the occurrence of AF under high iron intake only when risk genes were present. A total of 65 SNPs found the corresponding genes. When considering only the risk genes, all 13 SNPs were associated with promoting the occurrence of AF through the intake of moderate and high levels of iron. These SNPs included rs11264280, rs12188351, rs17380837, rs2283038, rs34969716, rs67249485, rs73041705, rs79187193, rs9506925, rs2413450, rs4820268, rs5756506 and rs855791. Among them, there were four SNPs related to iron, namely rs4820268, rs2413450, rs5756506 and rs855791.

As a limitation of the study, the authors noted that the 24-hour dietary recall information is based on a single assessment at baseline, and eating habits may have changed during the follow-up period, leading to an underestimation of the association between intake and cognition. 

"High dietary iron intake increases the risk of atrial fibrillation, especially when iron intake exceeds 16.95 mg," the study concluded. "The association was particularly significant among the 83 SNPs associated with AF and iron, the individuals with these risk genes.

"Gene enrichment analysis revealed these genes are significantly involved in cardiac development and cell signal transduction processes. Strict control of iron intake, avoidance of excessive supplementation, and limiting iron-rich foods are key for those with iron overload or a high AF risk."

Source: Nutrients​
doi: 10.3390/nu16050593​
"High Dietary Intake of Iron Might Be Harmful to Atrial Fibrillation and Modified by Genetic Diversity: A Prospective Cohort Study"
Authors: Zierdi Habudele et al.