Melatonin supplementation has become a well-known sleep enhancement drug due to the ability to evoke drowsiness. However, recently, it has become a highly researched drug with the reported ability to attenuate the negative effects of aging and vascular dysfunction, enhance immune function, and, for the topic of this post, help manage muscle loss after spinal cord injury, stroke, and other conditions that typically cause muscle atrophy. Melatonin has yet to be tested for performance benefits (to my knowledge at least). However, based on the results of many animals studies, the mechanisms seem to fit the bill for improvement in recovery from exercise (maybe).
The following is a little technical so bare with me....
Melatonin has shown to increase IGF-1 production as well as increase various muscle fiber types after stroke-induced muscle atrophy (Lee, et al 2012). IGF-1 is an upstream regulator of the mTOR signaling pathway, which is an initiator of skeletal muscle proliferation and satellite cell activation. The over expression of IGF-1 has been shown to promote the Pl3K/Akt/mTOR signaling pathway as well as inhibit atrophy signaling.
Melatonin also reportedly attenuates the affects of the cytokine group NF-kB, which is associated with different types of stress (Rodella, et al 2013). NF-kB can lead to a myriad of problems, including the activation of MaFbx/MuRF1, which are ubiquitin ligases and have been shown to decrease the size of cultured muscle cells and increase myosin heavy chain degradation. Melatonin also works to increase SIRT-1 expression (Rodella, et al 2013). SIRT-1 is sometimes known as the longevity protein because of its many anti-aging effects. SIRT-1 is expressed in multiple tissues of the body and has been found to have many positive effects.
In a study by Lee and colleagues, varying doses of melatonin were administered following focal ischemia in rats. Doses of melatonin were administered at 7 a.m. and 7 p.m. IGF-1 was shown to be significantly increased in the gastrocnemius and soleus muscles in the multiple dose group. Both MaFbx/MuRF1 were also shown to be down-regulated in multiple doses of melatonin including the multiple does group. Additionally, increases in fast and slow muscle isoforms were shown to increase with melatonin. In the gastrocnemius, the 7 a.m. and multiple dose group showed improvements in muscle fiber size in all muscle types. In the soleus muscle, the 7 a.m. group showed increases in all muscle fiber types. The results of this study suggest that melatonin has the potential to upregulate the anabolic hormone IGF-1 as well as increase size in various muscle fiber types.
In a study looking at muscle atrophy induced by castration, melatonin supplementation was found to be just as effective as testosterone in attenuating the losses in muscle. Castration caused great losses in muscle fiber diameter, which was avoided somewhat by both melatonin and testosterone. Melatonin-treated rats were found to have a higher concentration of IGF-1 than the control castrated animals. According to this study, apparently melatonin works on a pathway involved in signaling for IGF-1. IGF-1 is an upstream regulator of mTOR, which leads to increased protein synthesis, satellite cell activation, and cell proliferation. This particular study shows that it is possible to attenuate losses in muscle and upregulate IGF-1 production by simple melatonin supplementation. What I find to be even more novel is the fact that melatonin is just as effective as exogenous testosterone treatment in modulating these effects. Although the authors were unsure of the exact interaction between melatonin and IGF-1, the interaction certainly warrants further investigation.
Looking at one final study in Sprauge-Dawley rats that were given an animal model of spinal cord injury, melatonin improved the outcome of the experimentally-treated rats (Park, et al 2012). Melatonin-treated rats were found to have increased hind limb motor unit recruitment and less oxidative stress than control rats. Additionally, proapoptotic genes and genes that are responsible for autophagy signaling were attenuated in the treatment group.
Other interesting facts
It is well established that melatonin levels decrease with age, so perhaps melatonin supplementation may also be an effective way to decrease age-related losses of muscle. Even low lighting while you sleep can decrease your melatonin production by fifty percent (Pauley 2004), so this backs up the claims that it is better to have as little lighting as possible in your room while sleeping. Night shift workers tend to have higher cancer rates, and it is believed that this is due to disturbances in melatonin production (Schernhammer, et al 2004).
So how does this relate to performance? Based on the research, it would make sense that melatonin may have a benefit in recovery from exercise. I speculate that this is especially true for individuals who are dieting. Although much more research needs to be done, melatonin has been shown to increase IGF-1 levels. IGF-1 is a survival signal, which actives the muscle building friendly AKT pathway. This pathway allows for cell growth and inhibits cell death. These are two very good things.
During a fasted or dieted state, your cells may enter a “low energy state” or programmed cell death. This is due to the lack of appropriate amounts of energy (calories) or lack of a survival signal. This is a good thing to occur in fat cells but not your hard earned muscle. So an upregulation of IGF-1 would help muscle cells forgo this fate and would hopefully lead to greater retention in muscle while dieting. Additionally, these studies have shown that not only are you upregulating a survival signal, but you are down-regulating death signals. These particular signals are responsible for programmed cell death (apoptosis) or your cell essentially eats itself (autophagy). So to state it once again, while you are in a “low energy state” such as dieting, your cells are more likely to undergo cell death. If melatonin can down-regulate these death signals, there is a decrease in this likelihood. Even in a well fed state, this upregulation of IGF-1 and down-regulation of proapoptosis/autophagy signals along with protection from reactive oxygen species that occur with exercise cause all sorts of problems. They're been shown to decrease with melatonin use and may also allow for an increased recovery from tough workouts.
One obvious limitation with all this research is that melatonin is currently primarily studied in animals. However, comparative physiology opens the door to discovery in humans. Also, the fact that these mechanisms are still occurring in eukaryotic cells shows merit. Another limitation is that the enhancement of performance in a healthy individual is pure speculation on my part. But as I mentioned before when dieting, while your calories are low from a mechanistic standpoint, melatonin would make a nice addition to help decrease any loss of muscle.
The final limitation with this melatonin research is the doses I have seen reported in animals. Doses are typically set around 10 mg/kg. That is a huge amount of melatonin in a human. I have been currently playing around with four doses of 3 mg spread throughout the day. I also have been attempting to create large amounts of muscle damage using a lot of eccentric loading, so I will be interested to see what happens.
References
- Lee S, Shin J, Hong Y, Lee M, Kim K, Lee SR, Chang KT, Hong Y (2012) Beneficial effects of melatonin on stroke-induced muscle atrophy in focal cerebral ischemic rats. Laboratory Animal Research 28(1):47–54.
- Oner J, Oner H, Sahin Z, Demir R, Ustünel I (2008). Melatonin is as effective as testosterone in the prevention of soleus muscle atrophy induced by castration in rats. Anatomical Record 291(4):448–55.
- Park S, Lee SK, Park K, Lee Y, Hong Y, Lee S, Jeon JC, Hong Y (2012) Beneficial effects of endogenous and exogenous melatonin on neural reconstruction and functional recovery in an animal model of spinal cord injury. Journal of Pineal Research 52(1):107–19.
- Pauley SM (2004) Lighting for the human circadian clock: recent research indicates lighting has become a public health issue. Medical Hypotheses 63(4):588–96.
- Rodella LF, Favero G, Rossini C, Foglio E, Bonomini F, Reiter RJ, Rezzani R (2013) Aging and vascular dysfunction: beneficial melatonin effects. Age 35(1):103–15.
- Schernhammer ES, Rosner B, Willett WC, Laden F, Colditz GA, Hankinson SE (2004) Epidemiology of urinary melatonin in women and its relation to other hormones and night work. Cancer Epidemiol. Biomarkers Prev. 13(6):936–43.
