More Than Restorative Sleep in a Pill: "Melatonin Loading" Ameliorates Oxidative Stress and Inflammation in Ultra-Endurance Event

Image 1: The Veleta Peak, certainly not
an easy trail (photo by David Adamson)

As a regular visitor of this blog, you are well familiar with the beneficial effects of sleep on general health, hormone levels and (exercise) performance. You will also have read about the anti-oxidant and neuroprotective effects of melatonin and be aware that melatonin supplementation may exhibit beneficial effects aside from improving sleep quality. A recent study (Ochoa. 2011) by scientists from the University of Granada in Spain provides further evidence for the "magic" of a hormone that - much to my surprise - is still widely available as an over-the-counter supplement.

In a double blind placebo controlled study, Julio J. Ochoa and his colleagues handed 5 capsules à 3mg melatonin or placebo to their 20 highly trained male subjects and instructed them to use the following unconventional (normally you would expect either administration immediately before the stressor, or supplementation at night, the days before the event) "loading protocol":

[...] one capsule 2 days before the test with dinner, three capsules on the previous day (breakfast, lunch, and dinner), one capsule the same day of the run, 1 hr before beginning the physical test

The test the athletes had to perform was a combination between mountain run and ultra-endurance, comprising a run (50km with a height difference of 2800m) to the top of ‘Pico Veleta’ (Sierra Nevada), the incline of which is considered "one of the hardest trials worldwide". Another factor to consider were the "highly changing climatic conditions with many temperature oscillations", which further increased the physical demands the runners were facing.

Figure 1: Melatonin levels in pg/mL before and after the run. Notice: I deliberately refrained from
using a logarithmic scale in order to pronounce both the major difference in initial melatonin levels,
as well as the significant drop in the melatonin supplemented group and the almost non-existent
amount of melatonin left in the non-supplemented group (data adapted from Ochoa. 2011)

Obviously this type of exerting exercise had significant effects on the oxidative stress marker measured in the sera of the 20 runners. Also profound, however, were the protective effects of the supplementation protocol:

Exercise was associated with a significant increase in TNF-α, IL-6, IL-1ra (in blood), and also an increase in 8-hydroxy-2′-deoxyguanosine (8-OHdG) and isoprostane levels (in urine), and indicated the degree of oxidative stress and inflammation induced. Oral supplementation of melatonin during high-intensity exercise proved efficient in reducing the degree of oxidative stress (lower levels of lipid peroxidation, with a significant increase in antioxidative enzyme activities); this would lead to the maintenance of the cellular integrity and reduce secondary tissue damage. Data obtained also indicate that melatonin has potent protective effects, by preventing over-expression of pro-inflammatory mediators and inhibiting the effects of several pro-inflammatory cytokines.

If it was not for potential deteriorations of the natural circadian rhythm of melatonin release, I would suggest everyone orders a batch of melatonin before the FDA catches wind that "it works" and takes it off the market. In view of the fact that melatonin is usually low in the course of the day and spikes at night, I would advice you change the supplementation protocol to taking (a potentially higher) dose in the evenings preceding your next Ironman + a single additional dose right before the event, in order to minimize the risk of whacking up your natural endocrine circadian rhythm.