rs35767 — IGF1 C-1245T

The Anabolic Switch — IGF-1 and Your Muscle-Building Potential

Insulin-like growth factor 1 (IGF-1) is one of the most powerful anabolic hormones in the human body. It activates the PI3K/Akt/mTOR pathway¹¹ activates the PI3K/Akt/mTOR pathway
The canonical growth signaling cascade that controls muscle protein synthesis and hypertrophy, stimulates satellite cell activation²² satellite cell activation
Muscle stem cells that divide and fuse to repair damage and create new muscle tissue, and drives skeletal muscle hypertrophy in response to training. The rs35767 polymorphism sits in the promoter region of the IGF1 gene, 1,245 base pairs upstream of the transcription start site, where it regulates how much IGF-1 your body produces.

The T allele is associated with higher circulating IGF-1 levels compared to the C allele, and TT carriers tend to have greater muscle mass and superior athletic performance³³ greater muscle mass and superior athletic performance
Particularly in power and combined power-endurance sports like decathlon. This variant has emerged as one of the most replicated genetic markers for elite athletic performance.

The Mechanism

rs35767 is a regulatory variant located in the promoter region of the IGF1 gene on chromosome 12. The T-to-C substitution at position -1245 affects transcription factor binding and gene expression. Studies show the T allele leads to higher IGF-1 production, though the exact transcription factor interactions remain under investigation. Some research suggests the C allele may allow binding of C/EBPD transcription activator⁴⁴ C allele may allow binding of C/EBPD transcription activator
A DNA-binding protein that regulates gene expression, while other evidence indicates the T allele results in higher circulating levels through mechanisms that may involve altered promoter activity.

Once IGF-1 is secreted (primarily by the liver in response to growth hormone), it binds to IGF-1 receptors on muscle cells. This triggers a signaling cascade: PI3K converts PIP2 to PIP3, activating PDK1 and Akt. Akt then phosphorylates mTORC1, which activates ribosomal protein S6 and translation initiation factor eIF4E, ramping up protein synthesis. Simultaneously, Akt inhibits FoxO transcription factors, blocking the expression of muscle atrophy genes⁵⁵ blocking the expression of muscle atrophy genes
E3 ubiquitin ligases like atrogin-1 and MuRF1 that tag muscle proteins for degradation.

IGF-1 also activates muscle satellite cells—the stem cells responsible for muscle repair and growth. After intense exercise or muscle damage, satellite cells proliferate and differentiate into new myonuclei, contributing approximately half of the muscle mass gained during hypertrophy⁶⁶ half of the muscle mass gained during hypertrophy
Based on studies using viral IGF-1 delivery in animal models.

The Evidence

The rs35767 variant has been studied extensively in athletic populations. In a 2013 Israeli study of 87 power athletes and 78 endurance athletes⁷⁷ 2013 Israeli study of 87 power athletes and 78 endurance athletes
Including international and Olympic-level competitors, the T allele was significantly more frequent in top-level power athletes compared to national-level athletes. Among the elite power cohort, 4.8% carried the TT genotype versus 0% in non-athletic controls—a striking overrepresentation.

A 2022 study of decathlon athletes⁸⁸ 2022 study of decathlon athletes
Decathlon demands both power and endurance across 10 events found the TT genotype was significantly more prevalent among decathletes compared to other athlete groups, and TT carriers demonstrated superior speed performance. These findings align with the physiological role of IGF-1 in fast-twitch muscle fiber development and force production.

A 2024 meta-analysis⁹⁹ 2024 meta-analysis
Pooling data across multiple cohorts to increase statistical power confirmed the T allele as a favorable genetic marker for both power and endurance athletic performance, supporting the variant's role across multiple training modalities.

At the molecular level, a 2014 study of European adults¹⁰¹⁰ 2014 study of European adults
n=569 in discovery cohort measured circulating IGF-1 and found that carriers of the GG genotype (equivalent to TT on the minus strand) had significantly higher IGF-1 levels (218 ng/ml) compared to AA carriers (190 ng/ml, p=0.007). The higher IGF-1 group also showed better insulin sensitivity, suggesting metabolic benefits beyond muscle growth.

However, not all effects are beneficial. A Japanese longitudinal cohort of 1,506 individuals¹¹¹¹ Japanese longitudinal cohort of 1,506 individuals
Followed for long-term health outcomes found that TT carriers experienced faster decline in renal function over time compared to CC carriers, suggesting chronically elevated IGF-1 may have tradeoffs for kidney health.

Practical Actions

If you carry one or two T alleles, you have a genetic advantage for building muscle and responding to strength training. To capitalize on this:

Prioritize resistance training. Your elevated IGF-1 levels mean you're biochemically primed for hypertrophy. Focus on progressive overload—gradually increasing weight, volume, or intensity over time. TT carriers may see faster strength gains and better recovery from high-volume training compared to CC carriers.

Consume adequate protein. IGF-1 activates mTOR, the master regulator of protein synthesis, but mTOR needs amino acid availability to function. Aim for 1.6-2.2 g/kg body weight daily, with post-workout protein intake¹²¹² post-workout protein intake
20-40g within 2 hours of training to maximize the anabolic window when IGF-1 signaling is elevated.

Optimize sleep and recovery. Growth hormone (the primary driver of hepatic IGF-1 production) peaks during deep sleep. TT carriers producing more IGF-1 may benefit even more from adequate sleep (7-9 hours) for muscle repair and satellite cell activation.

Consider monitoring kidney function if you're TT. While the athletic benefits are clear, the Japanese cohort data suggests potential long-term renal effects. If you're a TT carrier pursuing intense athletic training, periodic monitoring of eGFR and creatinine may be prudent, especially as you age or if you have other kidney risk factors.

Interactions

rs35767 interacts with other variants in the IGF axis. rs7136446¹³¹³ rs7136446
An intronic IGF1 variant has also been associated with athletic performance and may compound with rs35767 to influence IGF-1 levels and muscle phenotype. Similarly, rs972936¹⁴¹⁴ rs972936
Another IGF1 intronic variant affects IGF-1 expression and has been linked to neurological outcomes and muscle force production.

Beyond the IGF1 gene, interactions with the growth hormone receptor and myostatin pathway are likely. Carriers of both the IGF1 T allele and myostatin rare R allele¹⁵¹⁵ myostatin rare R allele
Loss-of-function variants in MSTN that reduce this muscle growth inhibitor show even greater muscle mass and performance, suggesting an additive or synergistic effect.

For power athletes, the combination of rs35767 TT and ACTN3 RR¹⁶¹⁶ ACTN3 RR
Alpha-actinin-3, the "gene for speed" may represent an elite genetic profile for explosive strength and sprint performance.