Increasing Androgen Sensitivity

Introduction

While there is growing recognition of the importance of testosterone in popular culture—with countless online guides on boosting testosterone levels and even services offering full testosterone replacement therapy (TRT)—the critical role of the androgen receptor remains largely overlooked. These receptors are essential: without them, hormones like testosterone cannot exert their effects on the body.

Even for professional bodybuilders who attempt to hack their own biology by administering exogenous androgens (such as testosterone and anabolic steroids), their individual response will still largely depend on the availability of these receptor sites. You can think of the hormones circulating through the blood as keys which need to be bound the receptor sites such as the Androgen Receptor, to unlock their effects. The androgen receptor consists of several binding sites, however one in particular will determine your individual sensitivity to androgens.

The androgen receptor

Androgens, like DHT or Testosterone, bind to the Ligand Binding Domain (LBD) of the androgen receptor . However, this is only half the story, as the transcriptional response of the androgen receptor is largely determined by the N-terminal Domain (NTD). Whilst the NTD doesn’t bind to androgens directly, it does a powerful role over how the body responds to androgens, by binding to a variety of coactivators.

These coactivators can enhance the transcriptional response to androgens, so much so that even a weak androgen like androstenedione can have the same effect as DHT, the strongest naturally produced androgen! One of these cofactors is a key growth signalling protein called β-catenin, which is one of the downstream effectors of IGF-1 (insulin-like growth factor-1). This pathway is critical in understanding how IGF-1 is capable of enhancing muscle function – and even androgen driven pathologies like prostate cancer.

The length of the NTD determines how the androgen receptor interacts with these co-regulators, and therefore how sensitive it is to androgens. [1] The length of NTD is determined by genetics, specifically the number of ‘CAG repeats’. CAG refers to a sequence of nucleotides, which is are the fundamental building blocks of DNA. The longer the NTD, the more CAG repeats, the less sensitive an individual is to androgens.

The number of CAG varies between person to person, for some people being as few as 9 repeats, and on the high end as many as 37! Above 25 is considered a low sensitivity to androgens. The number of CAG repeats determined by your genetics influences your personality, ability to grow muscle, facial hair and more. A study on Taiwanese criminals even found that those involved in violent crime had far fewer CAG repeats against controls. [2]

Improving androgen receptor sensitivity with Carnitine

Researchers have found that androgen receptor function might be enhanced by supplementing with carnitine, a compound commonly found in meat. In a study involving 10 resistance-trained men, participants supplemented with L-carnitine in the form of L-carnitine L-tartrate (LCLT) for three weeks before undergoing muscle biopsies. The researchers aimed to explore how L-carnitine supplementation could influence the body’s response to exercise in the immediate post-training period. [3]

Training alone is known to influence androgen receptors, with AR mRNA (though not AR protein) levels shown to increase 48 hours post-training. [4] However, there is a notable lack of research on the immediate effects of resistance training on androgen receptors. It has been hypothesized that L-carnitine supplementation may help preserve androgen receptors in muscle tissue that undergoes breakdown during training, potentially enhancing recovery.

The test group consumed a total of 2g of L-carnitine daily, divided evenly between breakfast and lunch. Their morning training routine comprised typical compound movements, including bench press, squat, bent-over row, and shoulder press. Muscle biopsies from the quadriceps revealed a significant increase in androgen receptor (AR) content compared to the control group. Post-training supplementation especially boosted AR content beyond pre-training levels. Researchers also observed a higher cellular uptake of testosterone in the test group compared to the control.

The impact of carnitine supplementation on androgen signalling is so profound that it’s even been found analogous to testosterone replacement therapy. A study of 120 patients given either testosterone undecanoate, carnitine (2g of propionyl-l-carnitine per day with 2g acetyl-l-carnitine per day) or placebo, found that both testosterone and carnitine significantly improved erectile function and reduced fatigue. [5]

In fact, the carnitine protocol proved to be significantly more effective at improving nocturnal erections than testosterone. Acetyl-l-carnitine (ALCAR) might have an advantage in being better at crossing the blood brain barrier than other preparations. [6] In all measures, the carnitine protocol proved to be just as if not more effective than testosterone replacement, including in fatigue, mood and even heart function. The carnitines had the additional advantage of not increase prostate volume, unlike the testosterone group. However, once either intervention was stopped, all measures returned to baseline.

Now foods offers 500mg capsules of L-carnitine L-tartrate, meaning that 2 capsules with lunch and breakfast are needed to match the study protocol. Please consider purchasing through this link. Buying through this link helps to support this website at no additional cost.