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.

Double Your Workout Volume With 3,4-DA - Chlorogenic Acid Metabolite, Dihydroxycinnamic Acid, Makes Rats Run 60% Longer, 30% Faster 90% Further!

Image 1 (sodahead.com): Another reason to supersize your cup of coffee; no not the girl, or ... well ;-)

Those of you who can no longer be without their well-deserved daily dose of SuppVersity news will probably remember the amazing weight loss effects an extract from green coffee beans yielded in a 2012 trial by Vinson et al. (cf. "GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks"; Vinson. 2012) and while I am still not convinced that you would see similar results in non-obese individuals, another recently published study by Novaes et al. does suggest that even those of you who don't think that they have another lbs of body fat to spare, could largely benefit not just from the caffeine, but also from the 0.5-1.0g of chlorogenic acid and the subsequent conversion of the latter into 250-500mg of 3,4-Dihydroxycinnamic acid (3,4-DA) even 400ml of regular coffee do contain (Chung. 2004; Novaes. 2012).

3,4-DA is like legal gear from the brown brew

Compared to placebo and vitamin C (25mg/kg), the hydrolyzed chlorogenic acid molecule, of which the 8-week-old male Wistar rats in the Noves study received either 5mg or 25mg per kg body weight (HED for 80kg human being: 65mg or 324mg) had almost incredibly potent "ergogenic" effects:

Figure 1: Time to fatigue (TTF), speed, workload and total distance covered (secondary axis) during exhaustive treadmill running after oral supplementation with placebo (control), vitamin C or 4,5 DA at doses of 5mg/kg and 25m/kg (based on Novaes. 2012)

As you can see in figure 1 the rodents in the high dose group ran 60% longer, 30% faster, 90% further and performed overall twice as much work (42 vs. 21 kg*m) than the rodents who had received the human equivalent of ~325mg vitamin C before a forced running test on a motor-driven treadmill.

Less ROS = Increased efficacy?!

Interestingly, the lactate levels of the 3,4-DA rodents were significantly lower and the remaining liver glycogen levels were significantly higher than in the placebo and vitamin C group (see figure 2).

Figure 2: Serum triglyceride (group effects non-significant) and lactate levels, hepatic glycogen content and protein arbonyl and malondialdehyde levels after the exercise (based on Novaes. 2012)

As Novaes et al. point out this suggests that the effect is partly mediated by a higher metabolic efficiency. The latter is probably a direct result of the profound reduction in reactive oxygen specimen, which have been associated with impairments of the cellular metabolism and subsequently reduced aerobic energy production (Atalay. 2002) - a hypothesis that would be supported by the reduced levels of protein carbonyl and malondialdehyde in the liver of the 3,4-DA treated rodents.

But don't we need ROS?

Image 2: Don't worry those love handles will go away - rather with the antioxidant + caffeine power of coffee than without it!

These observations are also quite revealing as the offer an alternative explanation for the previously mentioned possibly negative effects of antioxidants on the exercise-induced improvements in glucose metabolism (cf. "Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise"): If high doses of other anti-oxidants have the same beneficial effects on metabolic efficacy, it stands to reason that even weaker antioxidants than 3,4-DA would spare liver (and muscle) glycogen and thus reduce the exercise-induced expression of AMPK of which you may remember from posts like "AMPK II/III: Leucine, HMB and a Glimpse on Other AMPK Modulators" that it is expressed in response to intracellular glucose, or more specifically ATP depletion, and the subsequent increase in glucose (re-uptake).

A huge cup of coffee before your workout will therefore neither hamper the weight loss, nor the health effects of your workout, as long as you do actually make use of its ergogenic effect and train 60% longer, 30% faster, 90% further and perform overall twice as much work... just kiddin', if you train regularly you should be more concerned about keeping the amount of inflammation at bay - some is probably necessary, too much counter-productive, but that would the topic of another SuppVersity post. I for one am now going to get myself a nice cup of coffee...yummy!

Suggested reads on coffee:

• GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks.
• Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content.
• Only "Real", Not Decaffeinated Instant Coffee Increases Fatty Acid Oxidation. Revisited: Caffeine's Dose-Dependent Effects on Testosterone & Cortisol Response to Exercise
• Study Identifies Caffeic Acid Induced AMPK-α2 Activity Behind the Fat Burning, Insulin-Sensitizing & Life-Extending Effects of Coffee. Plus: Why Creatine & Coffee Don't Mix!

• all about coffee

References:

1. Atalay M, Laaksonen DE. Diabetes, oxidative stress and training. Journal of Sports Science and Medicine 2002 Jan; 1 - 14.
2. Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG, Kim CH. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 2004 Nov;18(14):1670-81.
3. Novaes RD, Gonçalves RV, Peluzio Mdo C, Natali AJ, Maldonado IR. 3,4-dihydroxycinnamic Acid attenuates the fatigue and improves exercise tolerance in rats. Biosci Biotechnol Biochem. 2012 May 23;76(5):1025-7.
4. Vinson JA, Burnham BR, Nagendran MV. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7. Epub 2012 Jan 18.

Busting the 3,500kcal = 1lbs Weight Loss Myth! A Scientific Deconstruction of a Dumb Rule of Thumb Reveals that Women Need More, Men Less Than the "Rule" Predicts

Image 1: If you are still putting your Happy Meal on a scale, you should not wonder why your weight loss falls short of your "calculations" - especially if you happen to be a woman (img. elementsofwellness.com)

While I would hope that most of you have by now embraced the notion that a calorie is not a calorie (at least, when it comes to nutritional calories), I suspect that one or two of you have still just been reviewing how much "calories" they have already eaten, or how much "cardio" they will have to do to compensate for the piece of pizza they are going to eat tomorrow at a friends party... > "STOP!" < this is what you should tell yourselves whenever thoughts like that are passing your mind (well, unless you are in the end-stage of your prep for a bodybuilding contest, I guess ;-) After all, a very recent study that is based on the results of two large-scale weight-interventions (Heymsfield. 2012), i.e. the CALERIE study, conducted at the Pennington Biomedical Research Center and the Kiel study, which was named after the German town Kiel, where the 13-week weight loss intervention took place, confirms the fallacy of number games like that.

A physicists would know: A pound of fat weighs 500g, not 3,500kcal ;-)

In order to establish the "actual" energy deficit that was necessary to elicit the loss of 1lbs of body weight in the 98 obese subjects in the CALERIE and the Kiel studies (average initial BMI of ~35 (25-43) kg/m²; mean age of ~38y and ~34y for the female and male participants, respectively), Steven B. Heymsfield and his colleagues (re-)analyzed the detailed nutritional and weight loss data from the studies and came up with the more or, I should say, less surprising result that the still widely accepted rule that a caloric deficit of 3,500kcal would result in a 1lbs reduction of body weight has to be revised ...

Figure 1: Energy deficit (in kcal) that was necessary to shed 1lbs of body weight at different time-points (in weeks) of the -25% reduced energy intake and the 890kcal/day arm of the CALERIE study (data adapted from Heymsfield. 2012)

If you take a closer look at the data in figure 1, which shows the actual amount of energy (in kcal) that was necessary to shed 1lbs of body fat, it becomes obvious that there was actually not a single time-point in the 24week dietary intervention, when the men and the women on the -25% (figure 1, left) or 890kcal/day (figure 1, right) both lost 1lbs of body weight per 3,500kcal.

Women have a harder time losing weight than men, but retain more lean tissue

If we go by the logarithmic regressions (red and blue lines; coefficients of determination see figure 1), the following important trends become obvious:

Figure 2: (a) increase in calories necessary to shed 1lbs of BW from week 1 to week 24; (b) average calories necessary to shed 1lbs in men and women over the whole study period (data adapted from Heymsfield. 2012)

1. Independent of the degree of calorie reduction (low calorie = -25%; very low calorie = 890kcal per day) and the sex of the subject, the caloric deficit that was necessary to shed 1lbs of body weight (not fat!) increased from week 1 to the end of week 3 (cf. figure 2, a)
    
2. Both, the baseline, as well as the gradual increase in calorie reduction that was necessary to shed 1lbs of body weight in the course of the 24d study period was greater in the very low calorie arm of the CALERIE study (cf. figure 1 and figure 2, a). This, btw, is clearcut evidence for the fallacy of starvation diets.
    
3. On both diets, women had a significantly harder time losing weight than men. This was even more obvious in the low calorie (-25%) than in the very low calorie arm (cf. figure 2, b).

In that it is also important to note that the relation of fat free mass to total body weight loss (ΔFFM/ΔBW) was maximal (60% for men and 50% for women) at the beginning of the study, had a nadir after about 15 weeks (~40% for men and ~20% for women) and showed a trend to increase again at the end of the 24 week study period of the CALERIE study. In other words, while women have a harder time losing weight, they maintain more of their lean muscle mass, than men do. A results that was, at least with regard to total weight loss, supported by the results of the Kiel study (no data on body fat / fat free mass loss available).

My advice: Forget about the rule of thumb, about calories and body weight!

Other than Heymsfield et al. who obviously still believe that it will by whatever means be possible to calculate the exact amount of calories to shed 1lbs of body weight, my take home message from the results of this study is that all the calorie counting, the daily disappointment, when you step onto the scale and the notoriously unreliable dietary rules of dumb... ah,  pardon "thumb", are something you banish from your weight loss inventory, right away.

Feel lost without your calories? Don't know where and how to start? Afraid of throwing the scale out of the window? Then it's time to (re-)read the Intermittent Thoughts on Stocktaking, Goal Setting, -Tracking & -Resetting to Achieve a Healthy Weight & Shed Excess Body Fat

A food log, where you record food and not calories  (I mean I still eat food, you know, things like eggs, butter, a steak, potatoes... those things without nutritional information on it!), a general understanding of the macro-nutrient (fats, carbs, protein) ratios in those foods and a measuring tape to access your progress, is all it takes access and adapt your food (not energy!) intake and evaluate the success of your diet (which does not equal weight loss!)... and I guess I don't have to tell you that the results of the very low calorie (890kcal) arm of the CALERIE study clearly suggest that dieting on a single cup of broccoli and a single serving of chicken breast sprinkled with some olive oil, is not an option, regardless of your sex, do I?