Can This Gene Benefit Your Athletic Performance? (NOS3)

The NOS3 gene codes for a protein also called NOS3, short for nitric oxide synthase 3. NOS3 is most abundant in the inner lining of the blood vessels, where it produces nitric oxide (NO) from the amino acid arginine [R, R].

NO is a messenger molecule with multiple functions in the immune, nervous, and circulatory systems. NOS-3 derived NO may help prevent heart disease, and some researchers believe that it improves athletic performance. They point to three main mechanisms for a potential athletic boost: increased blood flow, efficient energy production, and regulated heart rate [R, R].

Increased Blood Flow

Regular exercise stimulates NO production. This molecule activates a pathway that decreases the amount of free calcium in the vessels, causing them to relax. NO also protects vessel function by breaking down a free radical called superoxide. Overall, these two functions result in increased blood flow [R, R, R, R].

Increased blood flow causes more blood to reach the muscles, which is essential to provide nutrients, remove toxic byproducts, and maintain fluid balance. Additionally, sustained blood flow helps prevent muscle breakdown [R, R, R, R].

Optimized Energy Production and Use

Muscles obtain their energy from sugar breakdown. NO increases the amount of sugar taken up and broken down by muscle cells; it also prevents sugar storage as complex carbohydrates (glycogen) [R, R, R].

NO also increases oxygen supply with blood flow. However, high amounts of NO reduce oxygen consumption in the mitochondria by blocking a key enzyme called cytochrome oxidase. Scientists believe that this mechanism helps maintain energy reserves under conditions of low oxygen or high physical activity [R, R, R].

Adjusted Heart Rate

Nitric oxide can either increase or decrease heart rate, depending on the circumstances. NOS3-induced NO stimulates contractions in response to increased heart rate and blood flow, possibly by triggering calcium release [R, R].

However, very high NO levels decrease heart rate and energy use through 3 main mechanisms:

• Reducing the response to free calcium [R]
• Blocking the receptors that trigger contractions [R]
• Blocking oxygen consumption in the heart muscle [R]

This means that NO increases heart rate during moderate exercise but has the opposite effect during exhausting exercise. This may help maintain energy stores and improve heart function during intense physical activity [R, R].

The NOS3 gene produces an enzyme that makes nitric oxide. Research suggests that this messenger molecule may improve athletic performance by increasing blood supply to the muscles, optimizing energy production and use, and adapting heart rate to exercise.

Are You Built For Power And Strength?

The main SNP with the potential to affect athletic performance is rs2070744. Here, the rarer ‘C’ allele can be bound by a protein that blocks NOS3 expression, resulting in lower NOS3 levels [R].

Approximately 60% of the population has the ‘TT’ genotype, which is even more frequent in athletes who perform power sports such as short-distance running, jumping, throwing, and volleyball. According to one study, the ‘T’ allele is also associated with improved underwater finswimming; the authors suggest that it may help the body adapt to low oxygen [R, R, R, R].

In turn, the 'T' allele may be less advantageous for aerobic sports compared to anaerobic activities. Studies found, for example, that endurance athletes (aerobic) had fewer ‘T’ alleles (lower NOS3) than power athletes (anaerobic) [R, R].

An exception to this rule is swimming, where the ‘T’ allele is associated with both power and endurance performance. According to some researchers, this could reflect the fact that swimming is a complex sport in which athletes strongly rely on coordination and adaptability [R, R, R].

Strikingly, the ‘C’ allele is very frequent among elite soccer players. One possible reason for this association is that, in addition to combining power and endurance exercise, soccer requires high executive function in the brain. Moderate exercise increases dopamine, a neurotransmitter required for this function, while intensive exercise blocks it by producing too much NO [R, R].

Low NO release (and, thus, the ‘C’ allele) could therefore be advantageous to soccer players by increasing dopamine and thereby improving executive function.

The other relevant NOS3 polymorphism is rs1799983. 30% of the population carries at least one copy of its ‘T’ variant, which ultimately decreases NO production [R].

The major ‘G’ allele (increases NO) was linked to increased physical fitness in power sports. However, it was generally found as often in endurance athletes (cross-country skiers, biathletes, cyclers, runners, and rowers) as in sedentary people. Therefore, it doesn't necessarily make people more likely to exercise [R, R, R, R].

The more common (major) alleles of both NOS3 polymorphisms are associated with better athletic performance, especially in power sports. Surprisingly, the less common (minor) ‘C’ allele of rs2070744 was more frequent among elite soccer players.

How May NOS3 Variants Affect Athletic Performance?

In healthy people, the major alleles of both rs1799983 and rs2070744 have been associated with greater blood pressure reduction in response to exercise. These associations change somewhat in people with high blood pressure, so additional research is required to pin down the link [R, R, R, R, R, R].

The rest-and-digest (parasympathetic) nervous system may be altered in people with the minor alleles at both polymorphisms. In simpler terms, the hearts of people with the rs1799983-T and rs2070744-C alleles may not adapt as well to exercise [R].

Postmenopausal women with the rs1799983-T allele had lower heart rates and increased blood volume pumped per beat. Additionally, the right pumping chamber of the heart was enlarged in elite athletes with this allele. Whether these adaptations are beneficial or lead to irregular heart rate in the long term remains unknown [R, R, R, R].

The major alleles of both NOS3 polymorphisms are associated with improved athletic performance, possibly due to reduced blood pressure and heart rate adaptation to exercise.