Sleepy Sunday: The Bone and Teeth Preserving Fat Loss Hormone Melatonin Should Not be Injected Twice a Day in Athletes Who Try to Gain Muscle Mass

She's doin' it right! If you want to optimize your natural melatonin production, a blindfold is the way to go.
Have you been out partying, yesterday? Saturday Night FeverSunday Morning Hangover? If so, I hope you made sure you'd get enough sleep and have not increased your already exuberant sleep debt even more! Why? Well, I could give you a thousand reasons, but what about the "dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness" (Dinges. 1997), the corresponding adverse effects on inflammatory cytokines (Vgontzas. 2004), the decrease in insulin tolerance and messed up (circadian) rhythmicity of cortisol (Spiegel. 1999), about which you've learned here at the SuppVersity that it is the actual reason cortisol can be "bad" for you (learn more).

I could continue this list endlessly, but...

... will rather use this opportunity to transition into the actual topic of this "sleepy Sunday" post: Melatonin and its (in parts surprising) effects as they have been observed in three recently published studies:
  • High dose melatonin injections will blunt the training induced adaptive hypertrophy response in rodents -- With a human equivalent dose of 1.6mg/kg the amount of melatonin a group of researchers from the Graduate School of Inje University in Korea injected into their rodents legs may was unquestionably excessive (Hong. 2014), the fact that this lead to a reduction in the exercise induced growth stimulus (4-weeks, 5x per week 1h on the treadmill at 11 m/min), however, may still sound counter-intiuitive to those of you who still subscribe to the "the more antioxidants I get, the better" hypothesis.
    Figure 1: It's easy to see that the extremely high dose of melatonin (10mg/kg, twice a day) blunted the increae in skeletal muscle mass in response to 4 weeks of 5x/week 1h treadmill running (Hong. 2014)
    Personally, I feel like we have seen more than enough scientific evidence to understand that melatonin's negative effects on the exercise-induced adapatation processes is a result if its profound anti-oxidant effects and stands right in line with the recently confirmed negative effects of 540mg(day vitamin E and 1000mg/day vitamin C on cellular adaptation to endurance training in humans (Paulsen. 2014) - in that case albeit without negative consequences on the already non-significant changes in muscle mass that occurred in response to the combined HIT + HIIT intensity training in the Paulsen study (learn more).
Learn more about melatonin and sleep in the last "Sleep Quickie", here at the SuppVersity | read more
No effects on testosterone or other hormones! The provision of exogenous melatonin in sensible amounts of 1-10mg per day will not reduce your testosterone levels - even in the long(er) term (Luboshitzky. 2000).
What the restoration of a "deteriorated" melatonin rhythm will do, though, is increase the nocturnal GH peak (Petterborg. 1991). And if you simply throw a couple of milligram on top of your natural production, just like the 12 healthy volunteers (men and women) in a 1986 study did, nothing will happen... well, at least nothing that pertains to the levels or 24-h rhythm of LH, GH, T4, testosterone or cortisol (Wright. 1986).
  • While blunting "good stress" is a bad thing, blunting bad stress will help you lose weight and stay lean -- This is at least what would explain the beneficial effects Beatriz de Luxan-Delgado and her colleagues from the Department of Morphology and Cellular Biology at the University of Oviedo in Spain observed in their most recent rodent experiment, in which they investigated the actions of daily melatonin administration on oxidative stress parameters and autophagic processes and found that the significant reduction in hepatic autophagy, as well as the reduced expression of the "fat storage protein ppar-gamma" (learn more) make melatonin "an interesting target molecule for the development of a potential therapeutic agent to curb body weight" (de Luxan-Delgado. 2014).
    Figure 2: Changes in selected relevant health parameters in humans and rodents in response to the administration of of 5mg/day and 0.5mg/kg/day melatonin (Kozirog. 2011; de Luxan-Delgado. 2014)
    Ok, I know another rodent study is not what you may have hoped for, but if you look at previous evidence from human studies you will be hard pressed to argue that the mechanisms the Spanish researchers observed in their rodent study were unrelated to the mprovements in blood pressure, lipid profile, and parameters of oxidative stress Kozirog et al. observed in patients with metabolic syndrome in response to the provision of 5 mg melatonin per day (2 hr before bedtime; see Figure 2, left based on Kozirog. 2011).
  • Melatonin may help us win the battle against bone loss -- Contemporary statistical analyses show that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide  No wonder that Sifat Maria and Paula A. Witt-Enderby get all psyched up about the potential use of melatonin for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone-grafting procedures in their epinomous recent review (Maria. 2014).

    Figure 3: schematic demonstrating the relationship between melatonin secretion and bone resorption over a 24-hr cycle (Maria. 2014)
    Actually, it doesn't take much more than a brief glimpse at Figure 3 to realize why melatonin could be the solution to an increasingly severe problem.

    Figure 3 (taken directly from Maria. 2014) depicts a schematic demonstrating the relationship between melatonin secretion and bone resorption over a 24-hr cycle. As shown, both bone resorption (dotted line) and melatonin (solid line) display a diurnal rhythm with peaks occurring during the hours of darkness (filled in rectangles). Consequently, a suppression of nocturnal melatonin levels, either through light exposure at night (LAN) or through aging, increases bone resorption, i.e. the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood.

    Accordingly, only the restoration of the nocturnal melatonin peaks may - over time - protect against age- and lifestyle-induced bone loss by suppressing bone resorption. That this is more than just a hypothesis has been shown by Kotlarczyk et al. in 2012 with a relatively low dose of only 3mg of melatonin in perimenopausal women (Kotlarczyk. 2012). In younger individuals way below the 40+ and 60+ line in women and men, respectively (see Figure 4; Sack. 1986),  the younger folks will probably be able to achieve similar effects by paying more attention to their sleep hygiene.
Figure 4: At least in a 1986 study by Sack, women got into "melato-pause" earlier than men. While the melatonin production of the former dwindled in their late 40s, the men made it into the late 60s before their meltonin production broke away (Sack. 1986)
Bottom line: You don't have to stop partying on the weekend. If you make sure you get your 7-8h of restful sleep in a dark room / blindfolded and reduce the exposure to intense / blue light in the 2h before you head to bed, you can get all the antioxidant, obesity preventing, bone preserving benefits from your endogenous melatonin production while you are young without even having to think of blunting the exercise induced adaptive response.

Addendum for clarification (02/10/2014): If you want to support your natural melatonin production with 1-10mg/day that's perfectly fine for the "young" ones, as well - no chance this is going to hamper your gains.

If you belong to the group of over 40 and over 60-year old women and men (respectively), a small (1-10mg/day) dose of melatonin taken 1-2h before you head to bed may help you along without having to have any fear similar detrimental effects on skeletal muscle anabolism as they have been observed in the initially discussed study by Hong et al. (2014)

At least for those with low baseline levels, it does in fact appear to be more likely that the exact opposite will happen. Melatonin has after all been shown to prevent the apoptosis of muscle cells in cell and animal studies (Hibaoui. 2009; Kim. 2011) and is inversely related to the degree of sarcopenia (age-related muscle loss) in man (Lee. 2013)
  • Dinges, David F., et al. "Cumulative sleepiness, mood disturbance and psychomotor vigilance performance decrements during aweek of sleep restricted to 4-5 hours per night." Sleep: Journal of Sleep Research & Sleep Medicine (1997).
  • Hibaoui, Youssef, Emmanuelle Roulet, and Urs T. Ruegg. "Melatonin prevents oxidative stress‐mediated mitochondrial permeability transition and death in skeletal muscle cells." Journal of pineal research 47.3 (2009): 238-252.
  • Hong, Yunkyung, et al. "Melatonin treatment combined with treadmill exercise accelerates muscular adaptation through early inhibition of CHOP‐mediated autophagy in the gastrocnemius of rats with intra‐articular collagenase‐induced knee laxity." Journal of pineal research (2014).
  • Kim, Chi Hyun, Kyung Hwan Kim, and Yeong‐Min Yoo. "Melatonin protects against apoptotic and autophagic cell death in C2C12 murine myoblast cells." Journal of pineal research 50.3 (2011): 241-249.
  • Kozirog, Marzena, et al. "Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome." Journal of pineal research 50.3 (2011): 261-266. 
  • Lee, Jee-Yon, Jung-Ha Kim, and Duk-Chul Lee. "Urine melatonin levels are inversely associated with sarcopenia in postmenopausal women." Menopause (New York, NY) (2013). 
  • Luboshitzky, Rafael, et al. "Long-term melatonin administration does not alter pituitary-gonadal hormone secretion in normal men." Human reproduction 15.1 (2000): 60-65.
  • Maria, Sifat, and Paula A. Witt‐Enderby. "Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures." Journal of pineal research (2014).
  • Paulsen, G. "Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial." The Journal of Physiology (2014) Published online before print February 3, 2014, doi: 10.1113/jphysiol.2013.267419.
  • Petterborg, L. J., et al. "Effect of melatonin replacement on serum hormone rhythms in a patient lacking endogenous melatonin." Brain research bulletin 27.2 (1991): 181-185.
  • Sack, Robert L., et al. "Human melatonin production decreases with age." Journal of pineal research 3.4 (1986): 379-388.
  • Spiegel, Karine, Rachel Leproult, and Eve Van Cauter. "Impact of sleep debt on metabolic and endocrine function." The Lancet 354.9188 (1999): 1435-1439.
  • Vgontzas, A. N., et al. "Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines." Journal of Clinical Endocrinology & Metabolism 89.5 (2004): 2119-2126.
  • Wright, J., et al. "The effects of exogenous melatonin on endocrine function in man." Clinical endocrinology 24.4 (1986): 375-382.
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