The Genetics of VO2: What is the impact of endurance genes on VO2 max in athletes?

Natasha BAdeRtscher

Age 18 | Toronto, ON

Edited by: Nicole Yoannou

Endurance athletes typically develop a very high VO ₂ max through training compared to nonendurance athletes. Training accounts for an average VO ₂ max improvement of 14% amongst athletes (Keller et al., 2010). Previous studies have indicated that VO ₂ max is also heavily influenced by genetics. Many studies that examine the genetic basis of VO ₂ max fail to consider all the relevant genes together. This paper aims to combine this information and determine whether one gene is the most significant for endurance athletes looking to improve their VO ₂ max. Thirteen research papers retrieved from the University of Toronto’s online database were used along with reliable online sources to compile the information used in this review. The papers analyzed examined eight genes: NRF1, NFE2L2, ADRB2, ACE, ACSL1, ACTN3, PPARA and COL5A1. Of these, four were found to impact VO ₂ max in endurance athletes (ACE, ACSL1, COL5A1, PPARA). The impact of these four genes ranged from 2% to 7%, suggesting a slight but notable implication. The ACTN3 gene was found to have an impact, but only in sprint and strength athletes. While the impact of individual genes was small, further studies need to examine the interaction effect of these genes on VO ₂ max. Also, studies need to be more controlled in that they should have more variability in the participants and require control groups for the results of the studies to be reliable, accurate and applicable to everyone.

INTRODUCTION

Professional endurance athletes are capable of having a higher, more developed VO ₂ max. VO ₂ can be trained, and specific workouts can target this. Genetics can account for 50% of VO ₂ max (Orysiak et al., 2013). So, then the question arises whether having a specific gene can be beneficial for an endurance athlete.

A gene is a hereditary unit made up of DNA that has instructions for a cell. Each gene codes for a protein or a function. VO ₂ max is the maximum oxygen uptake of a person. At a person’s maximum capacity, oxygen uptake plateaus and their aerobic system switches to anaerobic power production, meaning without oxygen. “VO ₂ max reflects the limitation of oxidative metabolism of active muscle cells (peripheral limitation) as well as the capacity for oxygen delivery by the heart and the vascular system (central limitation)” (Hoppeler, 2018, p. 1). Between sedentary individuals, VO ₂ max can vary greatly. Professional endurance athletes will develop a higher VO ₂ max than sedentary individuals because of its’ trainability. Their high levels of oxygen uptake indicate a more efficient cardiovascular system and use a high amount of oxygen during long-distance exercise. This efficiency helps to maintain glucose storage later used in the anaerobic system.

Professional male athletes can have a VO ₂ max of 80 ml O2 min−1 kg−1, which is on the high end of collected VO ₂ max data, and this value is about 15% lower for female professional athletes (Hoppeler, 2018). Endurance sports utilize type I slow-twitch fibres in muscles meaning the muscles use “oxygen in a more efficient manner during continuous muscle activity” (Lopez-Leon et al., 2015, p. 5). Examples of sports using type I slow-twitch muscle fibres are cycling, long-distance running, cross country skiing, wimming, and rowing. Additionally, VO ₂ max is a factor that can be tested and measured. A method of measuring VO ₂ max is by using a face mask to record the volume and gas concentration of an athlete’s inspired and expired air while performing an exercise test where the intensity is steadily increasing (University of Virginia, 2020).

Many of the studies currently available on VO ₂ max examine the influence of a single gene. These studies fail to consider the potential combined effect of multiple genes on VO ₂ max. Many athletes train hard to improve their VO ₂ max, so it would be important to know how close their current VO ₂ max is to their plateau based on their genetics. This paper will aim to determine if particular genes influence an endurance athlete’s VO ₂ max.

METHOD

This research paper combines information from several different studies downloaded from the University of Toronto’s online database. Keywords used in the search were: endurance, VO ₂ max, genes and training response. Inclusion criteria for a paper were: relevance, English language, human subjects, and ethical guideline adherence. The 24 initial papers retrieved were reviewed by reading their abstracts and examining the figures. After review, 13 did not meet the criteria and were excluded leaving 11 papers for further analyses (see Appendix A for papers used). It has been noted that most of the papers used have a publishing bias in that they were given grants for the research, but these were for financial purposes in the study and should not affect the results obtained in those studies.

RESULTS

When analyzing results from the research papers used, a total of 8 genes were identified, along with one paper identifying mitochondrial gene clusters. Most of these genes were found to have only a small impact on VO ₂ max. Figure 1 shows the results of the combined studies and the limited effect of these genes.

In the analyzed articles, individuals that were identified as having the gene being studied were tested for their change in VO ₂ max. They had the potential to develop this change in their VO ₂ max through the prescribed training. This is defined as the training response (Figure 1). A study by Keller et al. (2010) “reported an average 14% improvement in ... VO ₂ max in response to 6 wk of endurance training”. The COL5A1 gene had a 7% training response indicating that it is the gene with the biggest impact on an athlete’s VO ₂ max. Figure 1 shows that the impact of the genes on VO ₂ max is very small. Four genes (ACTN3, ADRB2, NFE2L2, NRF1) have no impact on VO ₂ max, and the other four genes (ACE, ACSL1, COL5A1, PPARA) have an impact ranging from 2-7%, which is very small. Though 7% training response should not be neglected in an athlete and is considered statistically significant, it is a small factor compared to the whole 50% heredity of VO ₂ max. Additionally, the ACE gene is the most common and studied gene in this area of research as it is the first gene identified to have a link to endurance sports (Gomez-Gallego, 2008). As seen in Figure 1, it was found that ACE had a 2.1% impact on VO2 max, but this is controversial as numerous studies have found no impact. To better understand these results, Table 1 shows the roles of the four genes found to influence VO2 max in humans (Table 1).

A study by Posthumus et al. (2011) found that the least flexible athletes had more optimal endurance performance and, therefore, a lower steady-state VO ₂ (lower oxygen uptake plateau) rlated to the T allele of the COL5A1 gene. For the PPARA gene, those with the G allele had a higher endurance ability than those with the C allele (Lopez-Leon et al., 2015). Additionally, it can be noted that though Figure 1 shows no impact on VO ₂ max with the ACTN3 gene it is more related to strength than endurance and could affect VO ₂ max when testing sprint athletes (Wessner et al., 2016). This is because ACTN3 codes for a protein found in fast- twitch muscle fibres, and endurance athletes have been found to lack the genotype coding for fast-twitch fibres (NIH).

DISCUSSION & EVALUATION

This study aimed to investigate whether there was one gene that showed a significant impact and that would be greatly beneficial to endurance athletes regarding their VO ₂ max; however, this was not found. Instead, eight genes were identified as having the potential to be related to VO ₂ max, and only four of them had an impact. Since many genes influence VO ₂ max, it is hard to pinpoint one gene with a great impact or to study all the genes together.

Individually they all have small impacts; combined, they could have a greater influence on an athlete’s VO ₂ max. The genes ACE, ACSL1, COL5A1 and PPARA were found to have a small impact. The effect of these genes ranges from 2-7%, meaning that their effect is small compared to the effect that training can have on improvements for VO ₂ . What has not been noted above in the results is that in addition to genes, a study by Stepto et al. (2009) found a correlation between mitochondrial gene clusters and VO ₂ max as well as fat and carbohydrate oxidation gene clusters with VO ₂ max. This makes sense as endurance training is performed in the anaerobic state, using carbohydrates as fuel instead of glucose, hence showing its’ positive long-term effect on the up regulation of fat oxidative genes (Stepto et al., 2009). Another factor contributing to the high VO ₂ max of an endurance athlete is their muscular composition which is also influenced by genetics. Type I muscle fibres (slow twitch) have a “greater mitochondrial and capillary density” (Sarpeshkar and Bentley, 2010, p. 479) than type II muscle fibres (fast-twitch). Compared to strength athletes who have more fast-twitch fibres, endurance athletes display greater slow-twitch fibres and myoglobin, which contributes to their higher VO ₂ max.

When combining the 11 research papers used from the University of Toronto, in total, there were 512 male participants, 46 female participants, 302 participants where the gender was not specified, and 269 control individuals for a total of 1129 participants across all studies. Three studies also used data from the HERITAGE study. This was a study assessing the role of genes in a 20-week exercise program among families. The study had 230 male participants and 243 female participants. Additionally, two research papers did not conduct studies but rather did a literature review using databases. The lack of female participants presents the first limitation to this study as females and males have different physiological characteristics that could influence the results. Furthermore, only 3 of the 9 papers that conducted studies with humans had control groups. The absence of control groups makes it: difficult to compare the results obtained, less reliable, challenging to analyze the responses to interventions, and difficult to apply the results to the general population. There is also a lack of variability in the participants: notably, all studies examined people of Caucasian descent, which means the results cannot be applied to everyone. Many studies had a small sample size making the results less significant and less reliable. Also, studies tended to not look at all the variants of a gene but chose to focus on one allele, meaning that possible important results were excluded. External factors and the epigenetics of participants were not considered; however, these have significant effects on a person’s behaviours and genetics, making the results less reliable again. Lastly, three studies used data from the HERITAGE study; while they may have looked at different aspects, the results lack variability as the same data was used. All these limitations mentioned result in a lack of statistical power or significance. The studies also had strengths in that their methodologies were well thought out and were carried out in a precise manner, and most studies offer a pertinent discussion of their results even when no impact was found.

This present study has the limitation that it was difficult to find research that pertained to the subject, meaning that only one study was found for each gene. The COL5A1 gene and the ACE gene are exceptions as there were 2 studies and 3 studies, respectively, addressed these genes. Future studies should address these limitations, notably having more variability in the participants and having control groups. Also, since each gene has such a small impact on VO ₂ max, a combination of these genes should be tested in athletes in a study to determine their combined effect in comparison to the effect of training. Though this present study only examined endurance sports and athletes, sprint and strength athletes could also be studied either for their VO ₂ max or for genes that are common in athletes of those disciplines.

Findings such as those presented in this paper are important and relevant for endurance athletes and coaches. They can be used to determine whether VO ₂ max training should be a priority or not for the athlete. Once further studies about this topic are done, if an athlete knows their genomic profile, they can determine whether VO max is an athletic strength or a weakness which would greatly help their training and racing style.

**Figure 1:** Impact of each gene on VO2 max as identified by the training response

**Table 1:** Functions of genes found to effect VO2 max

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