Tuesday, July 4, 2017

10mg Melatonin Increase Diet-Induced Weight Loss in 30-D Study from 4% to 7% + Have Profound Antioxidant Effects

If you want to take melatonin, take it before bed and thus in sync with your circadian rhythm| learn more
If that's not your first visit at the SuppVersity, the fact that the sleep hormone melatonin is a powerful antioxidant won't be news for you. The fact that it may facilitate weight loss has been discussed in a previous SuppVersity article from September 2015 (read it), too. In the corresponding study, taking 1-3 mg melatonin helped women lose 7% body fat, and gain 3.5% lean mass ... albeit over a time of 12 months.

A new study does now suggest that melatonin can help you manage your body weight in the short run, too.
Learn more about the effects of Melatonin & co. at the SuppVersity

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That's partly due to its anti-inflammatory effects, but it's also because melatonin has been shown to increase the energy expenditure by activating brown adipose tissue (Jiménez‐Aranda 2013), to preserve mitochondrial function (Reiter 2016).
Figure 1: This figure summarizes the multiple actions of melatonin in reducing oxidative stress (Reiter 2016).
As the overview in Figure 1 tells you, melatonin also exerts immunomodulatory actions and beneficially affects the expression and secretion of some adipokines from fat cells. Furthermore, Szewczyk–Golec et al. (2017) highlight that ...
"[o]besity has been related to the chronic sleep disruption, another epidemic of the industrialized world and [a subsequent] deficiency of melatonin [which] may well contribute to obesity and its complications" (Szewczyk–Golec 2017).
Yet, while there's plenty of evidence of its weight loss benefits in rodents, its effects on the weight loss efforts of overweight/obese humans is missing... or it has been missing before  Szewczyk–Golec et al. decided to study if melatonin would affect the antioxidant level and concentration of circulating adipokines in obese human subjects on a calorie–restricted diet.

30 days of dieting with either melatonin or placebo 

To assess whether their hypothesis is accurate, the scientists recruited thirty volunteers with BMI ≥ 30 kg/m² (obesity class I or class II) who were then randomly and double-blindedly allocated to a melatonin (MEL) or a placebo (PL) group.
  • During the experimental period, 10 mg melatonin (LE–KAM, Zakroczym, Poland) or placebo (equivalent amount of lactose) were supplied in identical sachets to be taken orally in a single dose for 30 days, 1 hr before bedtime (learn why timing's important). 
  • All participants used a calorie–restricted diet (1000–1200 kcal/day for women and 1400–1600 kcal/day for men).
Before and after the 30-day intervention period, a standardized set of anthropometric measurements was performed. DXA scans, however, were not conducted.Accordingly, it is difficult to judge how much of the ~3.1kg extra-weight the subjects in the melatonin group lost was body fat.
In the Rasmussen study (1999), the testosterone levels of middle-aged male rats were not changed by boosting melatonin to 15-fold higher levels than you'd observe in young rats. What the administration of melatonin did, however, was to inhibit the age-related increases in visceral fat, leptin and insulin.
Will this work for men, too? In view of the antioxidant prowess of melatonin, this seems to be a stupid question, right? Well, the Internet is a place where rumors turn into truths when if they're just repeated often enough and one of those rumors/truths is: "Melatonin will reduce your testosterone levels". Now, we all know that this is bad news for any dieter, as low testosterone levels will favor the loss of muscle over fat mass. So, is that actually a relevant concern? This question is difficult to answer, because - as usually - there's conflicting evidence. In long-term studies like Rasmussen et al., scientists didn't observe negative effects of skyrocketing middle-aged male rats' melatonin levels to values that were 15-fold higher than those of young rats (Rasmussen 1999), though. What the melatonin did, however, was to ameliorate the age-related accumulation of visceral fat, as well as the increases in leptin and insulin (see Figure on the left).

In humans, ramping up the melatonin amplitude by a factor 6 (by administering 2mg of melatonin intranasally every day for 2 months) of young men (23-32 years), Terzolo et al. (1990) had previously observed no changes in the testosterone AUC over 24h. What the scientists did observe, though was a significant change in the 24-hour patterns of cortisol and testosterone, which displayed an anticipation of the morning acrophase of about 1.5 hours (not significant) for cortisol and three hours (P < 0.05) for testosterone. Why's that important? Well, the answer is easy: If you measure testosterone levels only once before and after melatonin supplementation at a given time of the day, you will observe changes in testosterone - significant reductions, because testosterone will then peak at 4 AM, not 7 AM and will thus have begun to decline again when you draw blood in the AM. So, while further studies would be highly appreciated, but the current evidence seems to refute the notion that there's a significant reduction in testosterone and the way melatonin affects the circadian rhythm may well explain why studies that measured testosterone only once in 24h may produce the misleading impression that melatonin would sign. reduce your testosterone levels.
With respect to the oxidative status of their subjects, the authors observed a melatonin-exclusive statistically significant increase in adiponectin (+22.6% | p = 0.029) and omentin-1 (+23.4% | p = 0.0044) and the significant reduction of the lipid oxidation marker MDA (-28.6% | p = 0.042), as well as like-wise melatonin-exclusive increases in glutathione peroxidase (GPX | +44.3% | P =  0.0049).
Figure 2: Changes in the anthropometric parameter from day 0 to day 30 (Szewczyk–Golec 2017).
Now, those changes are expected in overweight/obese subjects who lose weight, anyway. With melatonin being able to significantly augment them, the study at hand does, however, suggest that these benefits are more pronounced with melatonin.

Women Lose 7% Body Fat, Gain 3.5% Lean Mass in 12 Months-Long RCT | learn more
Against that background, it is a bit surprising (not to say disappointing) that Szewcyk-Golec et al. did not observe a difference in the diet's effects on the subjects' waist circumference, which would be expected with a concomitant 43% increase in weight loss and an augmented reduction in markers of oxidation and obesity-related adipokine levels. In the absence of reliable DXA data, the jury is thus still out there when it comes to what really counts when it comes to weight loss: the loss of body fat (not muscle).

Luckily, this is not the first "melatonin for weight loss" study. In fact, I've written about an even more exciting study in older women (56-73), in which the provision of 1-3 mg of melatonin (which is by the way rather the dosing I would recommend) helped them "Lose 7% Body Fat, Gain 3.5% Lean Mass in a 12 Months-Long RCT" (read the older article about melatonin and fat loss).
Melatonin is not the only supplement that may facilitate restorative sleep. Learn more in "Sleep Like an Athlete: Supplement Smart to Complement, not Replace Periodization & Basic Rules of Sleep Hygiene" | read more)
So, what's the verdict? While it appears to be likely and is supported by the previously cited 2015 study that melatonin facilitates weight and, more importantly, fat loss, the study at hand must still be considered preliminary evidence "that administration of this agent may be a useful adjunct in obesity treatment" that will also "facilitate the health improve-ment during obesity management" (Szewczyk–Golec 2017).

Future studies will have to be conducted with more participants, male participants and lean participants to know potential differences in the effects/efficacy of high and low doses of melatonin in different subject groups | Comment!
  • Jiménez‐Aranda, Aroa, et al. "Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats." Journal of pineal research 55.4 (2013): 416-423.
  • Szewczyk–Golec, et al. "Melatonin supplementation lowers oxidative stress and regulates adipokines in obese patients on a calorie–restricted diet." Oxidative Medicine and Cellular Longevity (2017): ahead of print.
  • Rasmussen, Dennis D., et al. "Daily melatonin administration at middle age suppresses male rate visceral fat, plasma leptin, and plasma insulin to youthful levels." Endocrinology 140.2 (1999): 1009-1012.
  • Reiter, Russel J., et al. "Melatonin as an antioxidant: under promises but over delivers." Journal of pineal research (2016).