When Timing Matters - Melatonin: Incorrectly Timed it Ruins Your Glucose Metabolism - Studies Show Acute Increases in Glucose Excursions During OGTT of 186% With 5mg

Melatonin is one of the few supplements where timing is everything.

As of late the nutrient and supplement timing craze has started to abate. People begin to realize that timing doesn't always matter, and that you can still make gains if you don't consume your whey protein shake 2 minutes, but rather 60 minutes after your workout.

For some nutrients and supplements, timing does yet matter and with melatonin I want to introduce you to an example, where the beneficial effects are not just attenuated, but will actually turn against you.

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As a SuppVersity reader, you are well aware of the beneficial metabolic "side effects" of melatonin. Effects that are mostly related to its ability to re-align the circadian rhythm (learn more). As a SuppVersity reader, you will also know that circadian misalignments have been shown to augment markers of insulin resistance and inflammation, independently of sleep loss (Leproult. 2014). And, as a SuppVersity reader, I want you to be aware of the fact that taking melatonin at the wrong time points is going to induce just that: a circadian misalignment with all the negative consequences on your insulin sensitivity that messes with your internal clock is going to have.

Actually, I believe I've mentioned the seminal paper by Angelo Cagnacci et al. which is - at least to my mind - the first one to show that using melatonin the way only a dumbass would do, i.e. taking 1mg early in the morning, is going to ruin the insulin sensitivity of postmenopausal women.

Figure 1: Taken in the AM right before an oral glucose tolerance test, melatonin ruins postmenopausal women's insulin sensitivity. Glucose area under the curve, insulin and the amount of C-peptide that's required are increased (Cagnacci. 2001)

Just a couple of days ago a study from the University of Murcia in Spain confirmed that this problem is not one that occurs only in postmenopausal, but also in 21 young, healthy women (24 ± 6 y; body mass index: 23.0 ± 3.3 kg/m²). In said study, the oral glucose tolerance test (OGTT) was performed on four occasions: In the morning (9 AM), and evening (9 PM); each occurring 15 minutes after melatonin (5 mg) and placebo administration on 4 non-consecutive days.

And what Patricia Rubio-Sastre and her colleagues found clearly confirms the results Cagnacci et al. presented 13 years ago:

"Melatonin administration impaired glucose tolerance. When administered in the morning, melatonin significantly increased the incremental area under the curve (AUC) and maximum concentration (Cmax) of plasma glucose following OGTT by 186% and 21%, respectively, as compared to placebo; while in the evening, melatonin significantly increased glucose AUC and Cmax by 54% and 27%, respectively. The effect of melatonin on the insulin response to the OGTT depended on the time of day (P < 0.05). In the morning, melatonin decreased glucose tolerance primarily by decreasing insulin release, while in the evening, by decreasing insulin sensitivity."

If that's not enough to scare you away from stupid experiments that involve using melatonin as an "anti-oxidant" supplement at other time-points during the day than 1-2h before bed, you probably cannot be helped ;-)

Suggested: Melatonin the anabolic on-switch | learn more

Bottom line: Taking melatonin before a meal and / or anytime but 1-2h before bed is not just going to ruin its beneficial metabolic effects, it's actually going to ruin your insulin sensitivity. So, if you want to use it, make sure you do so at the correct time point.

Melatonin is not the only supplement, where timing appears to matter, by the way. If you want this post to be the first in a series of articles on supplements and other things where timing matters, let me know on Facebook - I may be inclined to write a couple of additional articles ;-)

References:

• Cagnacci, Angelo, et al. "Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women." Clinical endocrinology 54.3 (2001): 339-346.
• Leproult, Rachel, Ulf Holmbäck, and Eve Van Cauter. "Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss." Diabetes 63.6 (2014): 1860-1869.