Allegedly 'Harmless' Thyroid-Based Fat Burner 3,5-T2 Works Like a Charm, While Commonly Sold 3,3-T2 Could Mess W/ Your Blood Glucose Levels, Liver & Body Fat + Muscle

These are the kind of abs, you will see on products with T2 and/or T2 and other alleged fat-burners. Don't be fooled by the ads - even if it's the actually active form of diiodothyronine (T2), namely 3,5-T2, you're buying, the pills alone won't get you to the sub-10% body fat range you  may be dreaming of.

I've written about the thyroid hormone metabolite diiodothyronine aka T2 before. Accordingly, you will probably know that it has long been thought of as an inactive byproduct of the thyroid hormone metabolism (read previous T2-articles). You will also be aware of the fact that research shows that (a) this is not the case and that (b) only one of its two forms, namely 3,5-diiodothyronine (3,5-T2) shares the fat burning, metabolic effects of its big brother triiodothyronine aka T3.

Just like me, you probably don't know, however, why supplement companies are still stupid enough to use both 3,5- and 3,3-diiodothyronine in their allegedly fat burning supplements - "stupid", because we already knew it has no effect and even more stupid, since a recent study from the Universidade de São Paulo and the Houston Methodist Research Institute has shown that it will, in total contrast to 3,5-T2, of which the latest research by da Silva Teixeira et al. shows that it will reduce the blood glucose levels independently of insulin sensitization, impair the metabolism of glucose.

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Yes, you read that right: While 3,5-T2 burns fat (especially in the liver) and increases your metabolism, its cousin 3,3-T2 will do nothing for your BMR/RMR + glucose and fatty acid metabolism and can, on top of that, even impair your glucose metabolism and, as the data in Figure 1 shows, increase the amount of liver fat and food intake.

Figure 1: Effects of T3 (DT3 at 0.75 mg/kg), 3,5-T2 (D3,5-T2 at 1.25 and 12.5 mg/kg) and 3,3 T2 (D3,3-T2 at 1,25 mg/kg) on (A) body weight trajectory, (B) body fat (%), lean mass (%), (D) body temperature, (E) food intake, (F) liver fat, (G) heart weight & (H) TSH of diet-induced obese mice (da Silva Teixeira. 2016).

I guess this negative effect on your glucose metabolism alone should be reason enough to avoid supplements with the commonly used combination of 3,3- and 3,5-T2.

In man, there's a J-shaped correlation between blood glucose 3,5-T2 in (open boxes: all subjects; closed boxes: euthyroid patients), but no significant correlation with waist circumference (a proxy of visceral fat) and subcutaneous fat according to Pietzner et al. (2015).

What dosages are we talking about? Unfortunately, the study at hand provides no guideline as to how much of this thyroid metabolite is actually necessary to boost your overall, fat and glucose metabolism, because the regular way to calculate human equivalent doses (HED | learn how to do it) seems to be way off when we talk about thyroid hormones. Humans appear to need much lower doses of exogenous thyroid hormones to see the same effects as rodents; and the dose regimen that delivered the most significant effect in the study at hand would translate to hilariously high doses of 3,5-T2 - doses you can luckily (?) never get out of any of the T2-supplements on the market).

Plus: The fact that a 2015 study by Pietzner et al. suggests that, in healthy euthyroid human beings, there's a J-shaped correlation of circulating 3,5-T2 levels and glucose (p >> 0.05 for insulin, waist, and subc. fat) with the latter being more or less constant until a certain optimal 3,5-T2 level is achieved and the fasting glucose levels "explode" (see Figure to the left).

After all, you can only hope for the 3,5-T2 the Brazilian scientists who have been dabbling with diiodothyronines in previous studies, already, to counter the ill effects of 3,3-diiodothyronine (3,3-T2).

Figure 2: (A) Fasting blood glucose, (B) glucose response during glucose tolerance test and (B) insulin levels in diet-induced obese mice according to treatment (da Silva Teixeira. 2016).

What's more, no supplement company can give you a guarantee that the 3,5-T3 in their products will fully counter the ill effects of 3,3-T2 on liver fat, the response to glucose tolerance tests, and the increased levels of insulin and appetite you can see in Figure 2 (and Figure 1, respectively) - no matter, how large the words "synergy" or "synergistically" are plastered all over the supplement bottle.

Read before using T2-products: "High-Dose 3,5-Diiodo-L-Thyronine (T2) Has Similar Side Effects as Regular Thyroid Hormones: Natural Thyroid Hormone Production ↓, Myocardial Stress ↑, Heart Weight ↑" | more.

So what's the verdict then: If you have understood that neither form of T2 is free of side effects (see "High-Dose 3,5-T2 Has Similar Sides as Regular Thyroid Hormones" | read it) and still want to use a T2-product, you better make sure it contains only the actually active 3,5-diiodothyronine (3,5-T2) and no 3,3-diiodothyronine) stupid supplement producers have put into the product to be able to claim that they would thus make sure to keep the side-effects at bay.

With a 3,5-T2 product you could at least hope for (a) weight loss / the prevention of weight gain, (b) fat loss and thus increases in relative lean mass, and, as the study at hand demonstrates (c) reduced liver fat and improved glucose tolerance and fasting glucose as well as insulin levels... all that, however, requires the product to be high-dosed - probably higher than the average fat burner you can buy at your favorite supplement shop (see red box for more information on the dosing regimen) | Comment!.

References:

• Pietzner, Maik, et al. "Translating pharmacological findings from hypothyroid rodents to euthyroid humans: is there a functional role of endogenous 3, 5-T2?." Thyroid 25.2 (2015): 188-197.

Laser Acupuncture as a Valuable Adjunct to Diet & Exercise Interventions!? 50% Higher Reduction in Waist & LDL/HDL Ratio + 80% Higher Reduction in Insulin in Recent Study

Laser "needles" may help you lose superfluous body weight.

Is it possible that the application of acupuncture by the means of a gallium Arsenide infrared (GaAlAs) laser with a wavelength at 904 nm and power of 5mW to the skin of post-menopausal women can actually improve the metabolic benefits of a combined diet + exercise regimen?

It sounds like a marketing gag, but the results of a recent study from the Cairo University (El-Mekawy. 2014) clearly indicates that the answer to the aforementioned question is "YES! It can!"

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The laser acupuncture was applied with an energy density of 2 J/cm2, a pulse radiation of 200 ns, and with a pulse frequency of 5000 Hz vertically with irradiation time 2 min/point, 3times/week for 12 weeks to the following acupuncture points:

Figure 1: Illustration of selected common acupuncture points (en.tcm-china.info).

Cv4 Guanyuan (3 cun inferior to the center of the umbilicus); Cv9 Shuifen (1 cun above the center of the umbilicus); Cv12 Zhongwan (4 cun above the center of the umbilicus); St25 Tianshu (2 cun lateral to the midline of the umbilicus); St36 Zusanli (one finger width lateral from the anterior crest of the tibia); Sp6 Sanyinjiao (3 cun directly above the tip of the medial malleolus); and St40 Fenglung (8 cun superior to the tip of the external malleolus).

Acupuncture and appetite control: This is not just an aliteration. The effects of classic acupuncture therapy on appetite control is also scientifically proven. Zhao et al. (2000), for example, found that "acupuncture can increase excitability of the satiety center, with a better long-term effect" (Zhao. 2000); and Liu et al. observed significant reductions of the levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) and corresponding reductions in food intake in rodents (Liu. 2001).

In addition to the three acupuncture sessions per week that was applied to 14 out of the 28 post-menopausal women with metabolic syndrome who participated in this study, all subjects had to run on a treadmill 3 times per week for 35 minutes (5 minute warm-up + 30 min at 60-75% of the heart rate reserve) and to adhere to an energy-restricted diet for 12 weeks:

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"All post-menopausal women followed an energy-restricted diet for 12 weeks. First, the recommended daily kilocalorie intake was computed by multiplying the Harris-Benedict equation by 1.55. Then, daily energy intake was restricted by 1000 kcal/day (daily kilocalorie requirement-1000 kcal). The diet caloric proportion of the protein, fat and carbohydrate was set at 15%, 30% and 55% respectively.

Each post-menopausal woman was given a booklet including a database of foods, and their energy and macronutrient values. The therapist asked each woman to select her foods freely, and give instructions about planning her meals to help adhere to the prescribed kilocalories and the assigned macro nutrient.

All women were advised to keep 3-day dietary records and interviewed by the therapist weekly. The therapist checked these records to ensure the total kilocalories per day did not exceed the previous calculated one, and give any advice about the meal plans when they did not meet the assigned mac ronutrient" (El-Mekawy. 2014).

Since all post-menopausal women had closely adhered to the assigned energy intake, the following beneficial effects of the laser acupuncture cannot have been caused by mere increases in dietary adherence.

Figure 2: Changes in body comp. and metabolic variables measured in the two groups (El-Mekawy. 2014).

An analysis of the statistical significance of the inter-group differences revealed that the laser acupuncture group showed a significantly greater decrease in the waist (P = 0.001) and hip (P = 0.001) circumferences, cholesterol (P = 0.04), and insulin levels (P = 0.043) than the control group. A result of which the Egyptian scientists rightly conclude that it suggests "that laser acupuncture is a valuable approach that could be added to the diet-exercise intervention to correct features of the MetS" (El-Mekawy).

Changes in body comp. w/ traditional acupuncture alone (Zhang. 2012).

What I still would like to know is how exactly the laser acupuncture therapy contributed to the improvements in body composition and glucose control. While we do know from previous studies that classic acupuncture therapy significantly reduces BMI and abdominal fat by reducing the abdominal visceral adipose tissue content (Zhang. 2011).

What we don't know for either classic TCM or laser acupuncture, though, is how the improvements in body composition and metabolic complications are achieved and thus whether similar effects may occur in metabolically healthy individuals like you and me.

Zhang et al. for example speculated that acupuncture would increase excitability of the satiety center of the ventromedial nucleus of the hypothalamus, so as to control the excessive appetite. In the study at hand, however, the rigid dietary control renders this argument void (this assumes that the subjects did not lie about their food intake). This leaves us with potential effects on the inner organs - more specifically the spleen, stomach, and kidney which are traditionally targeted by TCM acupuncturists | Comment on Facebook!

References:

• El-Mekawy, Hanan S., Abeer M. ElDeeb, and Hassan O. Ghareib. "Effect of laser acupuncture combined with a diet-exercise intervention on metabolic syndrome in post-menopausal women." Journal of Advanced Research (2014). 
• Liu, Z., et al. "Study on action of acupuncture on ventromedial nucleus of hypothalamus in obese rats." Journal of traditional Chinese medicine= Chung i tsa chih ying wen pan/sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine 21.3 (2001): 220-224.
• Zhang, Hong, et al. "Effects of acupuncture therapy on abdominal fat and hepatic fat content in obese children: a magnetic resonance imaging and proton magnetic resonance spectroscopy study." The Journal of Alternative and Complementary Medicine 17.5 (2011): 413-420.
• Zhao, M., Z. Liu, and J. Su. "The time-effect relationship of central action in acupuncture treatment for weight reduction." Journal of traditional Chinese medicine= Chung i tsa chih ying wen pan/sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine 20.1 (2000): 26-29.

Will 2015 Be the Year You Pick up The Kettlebells? Find Out If Your Strength, Fitness & Physique Would Benefit

2015 may offer a chance to get spice up your routine with kettlebells.

"Moderate evidence indicates that kettlebell training may be safe and effective for increasing certain functional strength and power measures and may show positive results with postural control in young, healthy populations," says a recent review of the literature in Physical Therapy Reviews (Girard. 2014) and does thus sound positively optimistic, but by far not as euphoric as some kettlebell warriors on the Internet.

Those of you who know me are probably aware that I am not a fan of kettle bells, but I am true to the motto of being open to good scientific evidence, like the one from the previously cited review by Girard et al. (2014).

I won't lie to you: I believe there are better muscle builders than kettlebells

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Speaking of which, the previously cited review found only five studies satisfied the eligibility criteria and were included in this review. The populations studied age range was 18–72 years old. Methodological scores based on the PEDro scale ranged from 3 to 7 out of 10. In those studies, ...

[k]ettlebell training demonstrated improvements for a number of strength measures: time 6 group for bench press ( P < 0.05) and back extension (P = 0.053), main effect for clean and jerk (P < 0.05) and certain power measures such as improved explosive strength comparable to a jump squat control (19.8% increase). Improved postural control was demonstrated in one study (P = 0.04)" (Girard. 2014).

What the kettlebells did not do in any of the five studies by Otto et al. (2012), Manoccia et al. (2013), Lake et al. (2012) and Jay et al. (2011 & 2013) was to have an effect on aerobic endurance as measured by VO2 Max.

Original photos from the study by McGill et al. (2014).

Isn't Kettlebell training bad for your back? No, it isn't. According to data from a 2012 study by McGill, kettlebell training rather than being bad for the back provides unique muscular pulses to the abdominals which, "[t]ogether with the muscle bracing associated with carries create kettlebell-specific training opportunities" makes McGill et al. conclude that the "unique loading patterns discovered during the kettlebell swing [...] which is opposite in polarity to a traditional lift" may in fact be the reason why "many individuals credit kettlebell swings with restoring and enhancing back health and function, although a few find that they irritate tissues" (McGill. 2014).

According to McGill et al. (2014) the "message for coaches is" that the kettlebell offers "several unique training opportunities", for example (a) the opportunity to train rapid muscle contraction-relaxation cycles emphasizing posterior chain power development about the hip. However, the large shear to compression load ratio on the lumbar spine created during swing exercises suggests that this training approach may be contraindicated for some individuals with spine shear load intolerance and (b) enhanced activation of the core musculature during the bottoms-up carry.

The non-significance of the oxygen uptake and thus the non-existence of conditioning effects may come as a surprise for those of you have already done kettlebell swings. Rightly so, as I would argue, because this result of the review is based mainly on the results of Jay et al. (2011) who invited 57 employees of a large pharmaceutical company for a physical examination. Of those only 43 showed up (motivation to work their assess off ↓) of whom 40 men and women in their mid-forties then trained for 20 minutes included a 5 –10 minute warm up and a 10–15 minute interval training consisting of 10 intervals of 30 seconds with rest period of 30–60 seconds which began with ZERO workload and was progressively intensified by the participants choice!

Kettlebell, weights, or ergometer, you have to work your ass off to make progress!

That's much in contrast to Fortner et al. (2014) who had their 14 young (18-25y), non-obese volunteers train three times a week for 8 weeks with 4.5kg and 8kg kettlebells for the female and male subjects, respectively in a "tabata style", i.e. at a twenty-second work to ten-second rest ratio and compared the VO2 response to a traditional protocol, consisting of four sets of work separated by ninety seconds of rest.

Figure 1: Subjective Borg RPE response to Tabata versus traditional kettlebell swing protocols in healthy, young adults. TAB- Tabata, TRADtraditional (left). % of peak VO2 value achieved during Tabata and traditional kettlebell swing protocols in healthy, young adults (right | Fortner. 2014).

As you can see in Figure 1 the response to the two different workouts was very different - despite the fact that the total number of swings from each individual's "tabata condition" (TBA) was equally divided into four sets for their "tradititional condition" (TRAD). From non-kettlebell studies, we know that training at an intensity like this, even if it's done for only a few minutes, will just as Fortner et al. say "safely and effectively provide multi-faceted exercise adaptations with a relatively short time investment" (Fortner. 2014) - an assumption that's backed by a 2011 study by Falatic et al. that used a 15s/15s protocol and elicited significant increases in VO2max in seventeen female NCAA Division I collegiate soccer players.

Figure 2: Energy expenditure during two-hand kettlebell exercise and graded treadmill walking (Thomas. 2014).

Furthermore, James et al.  (2014) were recently able to show that a KB routine consisting of 2-hand swings and sumo deadlifts with 3-minute rest periods produces similar metabolic responses to those of a moderate-intensity treadmill walking protocol designed for the improvement of aerobic fitness in 5 women, 5 men between 21 and 31 years of age - and, as you can see in Figure 2, it also burned a few extra calories.

A comparison with treadmill walking is yet not enough to confirm that kettlebell training is also superior to "regular" HIIT training. Personally, I suspect it isn't but it's at least a good way to diversify your training routines and create a new exercise stimulus that may even help you break through a plateau.

You're not interested in fitness? What about improve- ments in glucose tolerance, then? Samantha Leigh Greenwald found in her master thesis that kettlebell training can improve glucose clea- rance in young sedentary men" and concludes that the results of her study "suggest that kettlebell training may provide an inexpen- sive home-based approach for prevention or management of type 2 diabetes" (Greenwald. 2014).

Speaking of diversification: Another recent study by Budnar Jr, et al. who investigated the testosterone, GH and cortisol response to kettlebell training, indicates that "the kettlebell swing exercise might [in fact] provide a good supplement to resistance training programs" (Budnar Jr. 2014).

So, in case you are just working on your 2015 workout routine, you may want to give kettlebells a chance. In that you may, for example, replace one of your regular HIIT training sessions with a brief, but intense tabata-style kettle bell workout as it was described by James et al. (2014): 2-hand swings and sumo deadlifts with 3-minute | Comment on Facebook!

References:

• Falatic, Jonathan Asher. "The effects of kettlebell training on aerobic capacity." San José state University (2011).
• Fortner, Howard A., et al. "Cardiovascular and metabolic demands of the kettlebell swing using a Tabata interval versus a traditional resistance protocol." International Journal of Exercise Science 7.3 (2014): 2. 
• Greenwald, Samantha Leigh. The impact of an acute bout of kettlebell exercise on glucose tolerance in sedentary males. Diss. State University of New York at Buffalo, 2014.
• Jay, Kenneth, et al. "Kettlebell training for musculoskeletal and cardiovascular health: a randomized controlled trial." Scandinavian journal of work, environment & health (2011): 196-203.
• Jay, Kenneth, et al. "Effects of kettlebell training on postural coordination and jump performance: a randomized controlled trial." The Journal of Strength & Conditioning Research 27.5 (2013): 1202-1209.
• Lake, Jason P., and Mike A. Lauder. "Mechanical demands of kettlebell swing exercise." The Journal of Strength & Conditioning Research 26.12 (2012): 3209-3216.
• Manocchia, Pasquale, et al. "Transference of kettlebell training to strength, power, and endurance." The Journal of Strength & Conditioning Research 27.2 (2013): 477-484.
• McGill, Stuart M., and Leigh W. Marshall. "Kettlebell swing, snatch, and bottoms-up carry: back and hip muscle activation, motion, and low back loads." The Journal of Strength & Conditioning Research 26.1 (2012): 16-27. 
• Otto III, William H., et al. "Effects of weightlifting vs. kettlebell training on vertical jump, strength, and body composition." The Journal of Strength & Conditioning Research 26.5 (2012): 1199-1202.
• Thomas, James F., et al. "Comparison of Two-Hand Kettlebell Exercise and Graded Treadmill Walking: Effectiveness as a Stimulus for Cardiorespiratory Fitness." The Journal of Strength & Conditioning Research 28.4 (2014): 998-1006.

No Time? No Excuse! Three Minutes (One Minute All Out, Only) Exercise Per Week Suffice to Increase One's Skeletal Muscle Oxidative Capacity and Improve Metabolic Health!

HIIT your weaker self hard, with a total of one minute all out cycling.

It's the most often heard excuse you get, when you ask your sick overweight neighbor if he'd like to accompany you to the gym to do something for his health, first, and his physique, second. "Ah, I don't have the time to work out!"

Obviously, this is a "perceived lack of time" that is not real for 99.9% of the people, even if we're talking about 30 minutes of exercise every other day. And even if it was not, the results of a recent study from the McMaster University in Hamilton, Ontario, will totally steal their non-existent thunder and provide you with convincing arguments to drag them to the gym for a quick HIIT session (Gillen. 2014).

Why? Well, as the headline of today's SuppVersity article says, the study shows that three (=3) minutes of all-out exercise per week (no typo or other mistake here!) will "Suffice to Increase Skelet al Muscle Oxidative Capacity and Improve Metabolic Health" (Gillen. 2014).

You can learn more about HIIT at the SuppVersity

Never Train To Burn Calories!

Tabata = 14.2kcal /min ≠ Fat Loss

30s Intervals + 2:1 Work/Rec.

Making HIIT a Hit Part I/II

Making HIIT a Hit Part II/II

HIIT Ain't For Everyone

Slackers, beware! The subjects of Gillen's study, fourteen overweight or obese men and women, who were recruited by poster advertisement from the McMaster Univerisity community, were not even as short in time as you were. While they still qualified as "sedentary based on their self-reported habitual physical activity", they actually did <2 data-blogger-escaped-u="">not "=zero" exercise sessions per week that lasted on average ≤ 30 min.

Participants were allocated into the male or female intervention group and matched for age, body mass index and VO₂ peak. The experimental protocol, itself consisted of familiarization and baseline testing that was followed by a 6 wk training intervention and post-training measurements. Over the course of the 6 week intervention period the subjects hit the gym only once a week, where they did

• 3x20 s all-out cycling efforts
• against a load corresponding to 0.05 kg/kg body mass,
• separated by 2 min of low intensity cycling (50 W)

The exercise was performed on an electronically braked ergometer (Veletron, RacerMate, Seattle, WA, USA). With the obligatory 2 min warm-up and 3 min cool-down at 50 W, the sessions lasted 10 minutes. That's more than just three minutes, but if you think about the exhausting part of the workout, only, it's actually not a three, not a ten, but a one minute workout.

Figure 1: Changes in BMI, parameters of blood glucose management (FPG - fasting peak blood glucose; FPI - fasting peak insulin; HOMA-IR, Gmax - maximal glucose levels in 24h; blood pressure (systolic & diastolic); MAP - mean arterial pressure; power output) in response to six weeks of once a week 3 min all out HIIT exercise (Gillen. 2014)

As you can see the once weekly workouts had a significant impact on both the parameters of glucose management and the cardiovascular and muscular fitness parameters (see Figure 1). The additional skeletal muscle biopsy samples the scientist obtained before and 72 h after training revealed that the above changes went hand in hand with an increase in maximal activity of citrate synthase and protein content of cytochrome oxidase 4 (p < 0.01, main effect) and increases in the maximal activity of b-hydroxy acyl CoA dehydrogenase in men only (p < 0.05).

All the aforementioned changes in protein expression will allow the participants to burn additional amounts of fat during exercise and at rest and could, in conjunction with the improvements in glucose management that was brought about by increases in GLUT4 glucose transporter activity on the muscle specifically, slow down their weight gain - in conjunction with dietary lifestyle changes, they would even favor fat over muscle loss.

If you've missed Saturday's HIIT vs. LISS efficacy comparison, check the article out now! And/or learn more about HIIT at the SuppVersity.

Bottom line: There is no debating, the "[s]hort-term interval training using a 10 min protocol that involved only 1 min of hard exercise, 3x/wk, stimulated physiological changes linked to improved health in overweight adults." (Glenn. 2014) Changes that may pay off in form of a handful of additional years on earth, if the subjects (a) stick to their new exercise protocol and (b) stop eating everything in sight, relatively indiscriminately.

Without dietary intervention, though, I am not sure if the relatively small amount of exercise will do anything but turn a profoundly unhealthy overweight individual into a slightly more healthy overweight individual. Moreover, it's unlikely that the protocol will produce similar benefits in lean, athletic individuals. For them it probably requires some more effort to stimulate fitness gains | Comment on Facebook.

References:

• Gillen, Jenna B., et al. "Three Minutes of All-Out Intermittent Exercise per Week Increases Skeletal Muscle Oxidative Capacity and Improves Cardiometabolic Health." PLOS ONE 9.11 (2014): e111489.

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.

Want to learn more about melatonin? The SuppVersity is the place to be.

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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.