HFE Genotype and Endurance Performance in Competitive Male Athletes

Abstract

Introduction: Hereditary hemochromatosis can cause individuals to absorb too much iron from their diet. Higher tissue iron content, below the threshold of toxicity, may enhance oxygen carrying capacity and offer a competitive advantage. Single nucleotide polymorphisms (SNP) in the homeostatic iron regulator (HFE) gene have been shown to modify iron metabolism and can be used to predict an individual's risk of hemochromatosis. Several studies have shown that HFE genotypes are associated with elite endurance athlete status; however, no studies have examined whether HFE genotypes are associated with endurance performance. Purpose: The objectives of this study were to determine whether there was an association between HFE risk genotypes (rs1800562 and rs1799945) and endurance performance in a 10-km cycling time trial as well as maximal oxygen uptake (V ˙O2peak ), an indicator of aerobic capacity. Methods: Competitive male athletes (n = 100; age = 25 ± 4 yr) completed a 10-km cycling time trial. DNA was isolated from saliva and genotyped for the rs1800562 (C282Y ) and rs1799945 (H63D) SNP in HFE. Athletes were classified as low risk (n = 88) or medium/high risk (n = 11) based on their HFE genotype for both SNP using an algorithm. ANCOVA was conducted to compare outcome variables between both groups. Results: Individuals with the medium-or high-risk genotype were ~8% (1.3 min) faster than those with the low-risk genotype (17.0 ± 0.8 vs 18.3 ± 0.3 min, P = 0.05). V ˙O2peak was ~17% (7.9 mL•kg −1 ⋅min −1 ) higher in individuals with the medium-or high-risk genotype compared with those with the low-risk genotype (54.6 ± 3.2 vs 46.7 ± 1.0 mL•kg −1 ⋅min −1 , P = 0.003). Conclusion: Our findings show that HFE risk genotypes are associated with improved endurance performance and increased V ˙O2peak in male athletes.

Contributions of HFE polymorphisms to brain and blood iron load, and their links to cognitive and motor function in healthy adults

“…Based on our and previous results, C282Y and H63D may exert beneficial effects in healthy individuals with low iron load, which may only become deleterious once a certain threshold of iron load is reached 53,56 . This theory has been discussed in relation to findings that placed the first occurrence and spread of the C282Y mutation centuries ago in some populations of Northern Europe, including Vikings, conferring advantages of increased body iron load in a challenging environment and living conditions 11,56,57 .…”

“…On the other hand, the limited literature on this topic has provided mixed findings, with some beneficial effects observed in HFE ‐pos individuals. A handful of articles have suggested a possible advantage of being carrier of HFE mutations on several outcomes, such as better olfactory function, better physical endurance performance and aerobic capacity, and lower deleterious effect of pollution on cognition 51‐54 . However, a meta‐analysis revealed a deleterious effect of being carrier of C282Y on memory performance 55 .…”

HFE Mutations in Neurodegenerative Disease as a Model of Hormesis

“…The C282Y HFE variant is fairly specific to Europeans and has a similar prevalence as HH, with a 1–5% prevalence in Europe and a frequency less than 1% in most non-Caucasian populations [ 41 , 42 ]. Interestingly, five separate studies have found that elite athletes carry HFE mutations nearly twice as frequently as ethnically matched control populations [ 86 , 87 , 88 , 89 , 90 ]. Furthermore, those with HFE mutations have a higher VO 2 max than those with WT HFE, suggesting improved efficiency of oxygen delivery [ 87 , 88 ].…”

“…Interestingly, five separate studies have found that elite athletes carry HFE mutations nearly twice as frequently as ethnically matched control populations [ 86 , 87 , 88 , 89 , 90 ]. Furthermore, those with HFE mutations have a higher VO 2 max than those with WT HFE, suggesting improved efficiency of oxygen delivery [ 87 , 88 ]. As H63D HFE causes systemically increased iron levels, it is possible that this leads to an increased rate of hemoglobin production for erythropoiesis and thus enhances oxygen delivery to the skeletal muscle to enhance athletic performance [ 88 ].…”

“…Furthermore, those with HFE mutations have a higher VO 2 max than those with WT HFE, suggesting improved efficiency of oxygen delivery [ 87 , 88 ]. As H63D HFE causes systemically increased iron levels, it is possible that this leads to an increased rate of hemoglobin production for erythropoiesis and thus enhances oxygen delivery to the skeletal muscle to enhance athletic performance [ 88 ]. The increased prevalence of HFE mutations in athletes suggests a metabolic advantage in HFE variant carriers.…”