H
Harvey Balboner
Guest
3,5-diiodo-L-thyronine (T2)
This derivative of T3 was once thought to be inactive. In fact, most doctors and pharmacists (no offense to my brothers and sister who are involved in those fields) aren’t up to date on the latest research, so they continue to believe what some textbook from 1972 says. The fact is, T2 is indeed very active in terms of metabolic effects.
How do I know? Well, check this out. It’s been shown to increase hepatic oxygen consumption by about 30%. The authors of the study discovered that out of T4 and T3, only T2 was active in stimulating rapid hepatic oxygen consumption. They concluded that it acts rapidly and directly through activation of the mitochondria.(13)
In another study, T3 and T2 were compared in terms of Resting Metabolism (RM) and on the oxidative capacity of tissues that are metabolically active (liver, muscle tissue, brown adipose tissue or BAT, and heart). What they found was that T2 had a dose-dependent effect which increased RM and oxidative capacity. They found the greatest response to T2 was in liver and in BAT, which is exactly what you’d want, if fighting fat was a main concern. The effects again occurred rapidly and independent of protein synthesis. They stated that their results suggested isomers like T2 could be direct mediators of thyroid hormone regulation on energy metabolism.(14,15)
Yet another study also found increased hepatic oxidative capacity and thought that it was due to a direct action upon the mitochondria by T2.(16) Other studies had similar findings.(17,1 And yet another study showed the same thing: increased oxidative capacity and energy expenditure, causing them to deduce that T2 and T3 displayed similar effects.(19) T2 was also shown to have a similar effect to that of T3 on lipid metabolism with T2 actually doing a little better in some tissue.(20)
Okay, so it works in animals you say. What about humans? Although there isn’t a huge amount of research in humans, some does exist. By the way, everyone, here’s an inside tip about product development in the supplement industry. If you want to come up with something new and effective, chances are there isn’t a limitless amount of research on the compound. If there were, some drug company would have put it on the market already!
Anyhow, in one study, using human mononuclear blood cells, they found that T2 increased the rate of respiration significantly. (21) So, the efficacy appears to have been established. Can it significantly inhibit TSH like T3 and T4? Well, the studies are somewhat conflicting, but one thing seems to be prevalent amongst them all. That is, TSH inhibition isn’t nearly as severe with T2 as it is with T3.
One study showed that T2 is 13% less inhibitory on TSH levels, as compared to T3. (22) In yet another study, T3 and T2 suppressed TSH to similar levels; however, it took 15 mcg/100g body weight per day of T3 to accomplish this, while it took a whopping 200 mcg/100g body weight per day of T2 to accomplish the same thing. This means it took about 13 times more T2 to exert the same effect on TSH as T3. (23)
One last study. When researchers administered 100 ug/Kg of T3 and 800-1600 ug/Kg of T2 the following occurred: T3 rapidly decreased serum TSH levels within minimal levels after 24 hours. Seventy-two hours after application, TSH levels were still significantly lower than control levels. As far as the T2, TSH levels were transiently reduced and reached their lowest point at 24 hours and increased afterwards. Basal levels were reached 72 hours after an application.
What they found after analyzing the data was that there seemed to be a trend for a dose-dependent (meaning, the higher the dosage, the more TSH was inhibited) suppression of TSH by T2 which did not reach statistical significance. That means it didn’t do it to a significant degree with the dosages used.
Furthermore, it appears as though it took 100 times more T2 than T3 to finally exert the same amount of TSH inhibition. Even using 400 times more T2 than T3, it appears that T3 only allows TSH to be inhibited to just a slight degree less than T2.(24)
One Last Thing
I’ve recently been asked this same question by at least a dozen people. Since using T3 can cause a state of hyperthyroidism that will increase muscle catabolism (amongst other things), will T2 do the same? My answer is that it’s possible it could, to some small degree. It would probably take large doses, taken for prohibitively long times, and even then the amount would be much, much less than you might encounter while using T3.
Still, to be safe, I think you should be using something to offset the possibility, however remote, of muscle catabolism. Obviously, continue exercising (duh!). Secondly, eat the "prescribed" amount of protein, which is 1.5 grams per pound (or at least 1 gram per pound) of bodyweight.
And, if your dad is a renegade pharmacist or doctor, you could even use some sort of anabolic concurrently. I don’t care which. Anything. Testosterone, trenbolone, boldenone, stanozolol, or if you want to go the legal route, Nandrosol, Androsol, Methoxy-7, or Tribex-500.
I’ve tried to present some of the evidence to you as best as possible. Again, I think you should make your own decision. Will I use it? Yep. I’m going to give it a go and compare its effects to that of T3 myself. I’m 100% sure it’ll work, but I’m going to have my TSH monitored and I’m going to compare the two using similar dosing regimens.
Looking at it objectively, however, I think you’ll see which is better. These are exciting times in this industry, aren’t they? Good luck and train hard.
References Cited
1. Lovejoy JC, et al. "A paradigm of experimentally induced mile hyperthyroidism: effects on nitrogen balance, body composition, and energy expenditure in healthy young men." J Clin Endocrinol Metab 1997 Mar;82(3):765-70
2. Zachwieja JJ, et al. "Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest." J Clin Endocrinol Metab 1999 Jan;84(1):207-12
3. Berne, Robert M, et al. Physiology 4th ed., 1998.
4. Muller MJ, Seitz HJ. "Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism." Klin Wochenschr 1984 Jan 16;62(2):49-55
5. Rubio A, et al. "Thyroid hormone and norepinephrine signaling in brown adipose tissue. II: Differential effects of thyroid hormone on beta 3-adrenergic receptors in brown and white adipose tissue." Endocrinology 1995 Aug;136( :3277-84
6. Chambers JB, et al. "The effects of propanolol on thyroxine metabolism and triiodothyronines production in man." J Clin Pharmacol 1982; 22: 110-16
7. Wilkins M.R, et al. "Effect of propanolol on thyroid homeostasis of healthy volunteers." Postgrad Med J 1985; 61: 391-4
8. Pasquali R, et al. "Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism." J Endocrinol Invest 1982 Jan-Feb;5(1):47-52
9. Serog P, et al. "Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects." Am J Clin Nutr 1982 Jan;35(1):24-35
10. Spaulding SW, et al. "Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man." J Clin Endocrinol Metab 1976 Jan;42(1):197-200
11. Kventy J, et al. "Effect of oral glucose feeding on thyroid hormone action in human mononuclear blood cells." Thyroidology 1990 Aug;2(2):53-7
12. Reinhardt W, et al. "Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects." Horm Res 1993;39(3-4):132-7
13. Horst C, et al. "Rapid stimulation of hepatic oxygen consumption by 3,5-di-iodo-L-thyronine." Biochem J 1989 Aug 1;261(3):945-50
14. Lanni A, et al. "Calorigenic effect of diiodothyronines in the rat." J Physiol 1996 Aug 1;494 (Pt 3):831-7
15. Goglia F, et al. "Action of thyroid hormones at the cellular level: the mitochondrial target." FEBS Lett 1999 Jun 11;452(3):115-20
16. Lanni A, et al. "Effect of 3,3’-diiodothyronine and 3,5-diiodothyronine on rat liver oxidative capacity." Molecular and Cellular Endocrinology. Volume 86, Issue 3. 1992
17. Lanni A, et al. J. Endocrinol. 136:59-64 1993.
18. O’Reilly I, Murphy MP. Acta Endocrinol. 127:542-546 1992.
19. Lanni A, et al. "3,5-Diiodo-L-thyronine and 3,5,3’-triiodo-L-thyronine both improve the cold tolerance of hypothyroid rats, but possibly via different mechanisms." Pflugers Arch 1998 Aug;436(3):407-14
20. Varghese S, Oommen OV. "Thyroid hormones regulate lipid metabolism in a teleost Anabas testudineus (Bloch)." Comp Biochem Physiol B Biochem Mol Biol 1999 Dec;124(4):445-50
21. J. Kvetny. Horm. Metab. Res. 24:322-325, 1992.
22. Moreno M, et al. "Effect of 3,5-Diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats." Life Sciences, Volume 62, No.26, pp. 2369-2377, 1998
This derivative of T3 was once thought to be inactive. In fact, most doctors and pharmacists (no offense to my brothers and sister who are involved in those fields) aren’t up to date on the latest research, so they continue to believe what some textbook from 1972 says. The fact is, T2 is indeed very active in terms of metabolic effects.
How do I know? Well, check this out. It’s been shown to increase hepatic oxygen consumption by about 30%. The authors of the study discovered that out of T4 and T3, only T2 was active in stimulating rapid hepatic oxygen consumption. They concluded that it acts rapidly and directly through activation of the mitochondria.(13)
In another study, T3 and T2 were compared in terms of Resting Metabolism (RM) and on the oxidative capacity of tissues that are metabolically active (liver, muscle tissue, brown adipose tissue or BAT, and heart). What they found was that T2 had a dose-dependent effect which increased RM and oxidative capacity. They found the greatest response to T2 was in liver and in BAT, which is exactly what you’d want, if fighting fat was a main concern. The effects again occurred rapidly and independent of protein synthesis. They stated that their results suggested isomers like T2 could be direct mediators of thyroid hormone regulation on energy metabolism.(14,15)
Yet another study also found increased hepatic oxidative capacity and thought that it was due to a direct action upon the mitochondria by T2.(16) Other studies had similar findings.(17,1 And yet another study showed the same thing: increased oxidative capacity and energy expenditure, causing them to deduce that T2 and T3 displayed similar effects.(19) T2 was also shown to have a similar effect to that of T3 on lipid metabolism with T2 actually doing a little better in some tissue.(20)
Okay, so it works in animals you say. What about humans? Although there isn’t a huge amount of research in humans, some does exist. By the way, everyone, here’s an inside tip about product development in the supplement industry. If you want to come up with something new and effective, chances are there isn’t a limitless amount of research on the compound. If there were, some drug company would have put it on the market already!
Anyhow, in one study, using human mononuclear blood cells, they found that T2 increased the rate of respiration significantly. (21) So, the efficacy appears to have been established. Can it significantly inhibit TSH like T3 and T4? Well, the studies are somewhat conflicting, but one thing seems to be prevalent amongst them all. That is, TSH inhibition isn’t nearly as severe with T2 as it is with T3.
One study showed that T2 is 13% less inhibitory on TSH levels, as compared to T3. (22) In yet another study, T3 and T2 suppressed TSH to similar levels; however, it took 15 mcg/100g body weight per day of T3 to accomplish this, while it took a whopping 200 mcg/100g body weight per day of T2 to accomplish the same thing. This means it took about 13 times more T2 to exert the same effect on TSH as T3. (23)
One last study. When researchers administered 100 ug/Kg of T3 and 800-1600 ug/Kg of T2 the following occurred: T3 rapidly decreased serum TSH levels within minimal levels after 24 hours. Seventy-two hours after application, TSH levels were still significantly lower than control levels. As far as the T2, TSH levels were transiently reduced and reached their lowest point at 24 hours and increased afterwards. Basal levels were reached 72 hours after an application.
What they found after analyzing the data was that there seemed to be a trend for a dose-dependent (meaning, the higher the dosage, the more TSH was inhibited) suppression of TSH by T2 which did not reach statistical significance. That means it didn’t do it to a significant degree with the dosages used.
Furthermore, it appears as though it took 100 times more T2 than T3 to finally exert the same amount of TSH inhibition. Even using 400 times more T2 than T3, it appears that T3 only allows TSH to be inhibited to just a slight degree less than T2.(24)
One Last Thing
I’ve recently been asked this same question by at least a dozen people. Since using T3 can cause a state of hyperthyroidism that will increase muscle catabolism (amongst other things), will T2 do the same? My answer is that it’s possible it could, to some small degree. It would probably take large doses, taken for prohibitively long times, and even then the amount would be much, much less than you might encounter while using T3.
Still, to be safe, I think you should be using something to offset the possibility, however remote, of muscle catabolism. Obviously, continue exercising (duh!). Secondly, eat the "prescribed" amount of protein, which is 1.5 grams per pound (or at least 1 gram per pound) of bodyweight.
And, if your dad is a renegade pharmacist or doctor, you could even use some sort of anabolic concurrently. I don’t care which. Anything. Testosterone, trenbolone, boldenone, stanozolol, or if you want to go the legal route, Nandrosol, Androsol, Methoxy-7, or Tribex-500.
I’ve tried to present some of the evidence to you as best as possible. Again, I think you should make your own decision. Will I use it? Yep. I’m going to give it a go and compare its effects to that of T3 myself. I’m 100% sure it’ll work, but I’m going to have my TSH monitored and I’m going to compare the two using similar dosing regimens.
Looking at it objectively, however, I think you’ll see which is better. These are exciting times in this industry, aren’t they? Good luck and train hard.
References Cited
1. Lovejoy JC, et al. "A paradigm of experimentally induced mile hyperthyroidism: effects on nitrogen balance, body composition, and energy expenditure in healthy young men." J Clin Endocrinol Metab 1997 Mar;82(3):765-70
2. Zachwieja JJ, et al. "Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest." J Clin Endocrinol Metab 1999 Jan;84(1):207-12
3. Berne, Robert M, et al. Physiology 4th ed., 1998.
4. Muller MJ, Seitz HJ. "Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism." Klin Wochenschr 1984 Jan 16;62(2):49-55
5. Rubio A, et al. "Thyroid hormone and norepinephrine signaling in brown adipose tissue. II: Differential effects of thyroid hormone on beta 3-adrenergic receptors in brown and white adipose tissue." Endocrinology 1995 Aug;136( :3277-84
6. Chambers JB, et al. "The effects of propanolol on thyroxine metabolism and triiodothyronines production in man." J Clin Pharmacol 1982; 22: 110-16
7. Wilkins M.R, et al. "Effect of propanolol on thyroid homeostasis of healthy volunteers." Postgrad Med J 1985; 61: 391-4
8. Pasquali R, et al. "Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism." J Endocrinol Invest 1982 Jan-Feb;5(1):47-52
9. Serog P, et al. "Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects." Am J Clin Nutr 1982 Jan;35(1):24-35
10. Spaulding SW, et al. "Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man." J Clin Endocrinol Metab 1976 Jan;42(1):197-200
11. Kventy J, et al. "Effect of oral glucose feeding on thyroid hormone action in human mononuclear blood cells." Thyroidology 1990 Aug;2(2):53-7
12. Reinhardt W, et al. "Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects." Horm Res 1993;39(3-4):132-7
13. Horst C, et al. "Rapid stimulation of hepatic oxygen consumption by 3,5-di-iodo-L-thyronine." Biochem J 1989 Aug 1;261(3):945-50
14. Lanni A, et al. "Calorigenic effect of diiodothyronines in the rat." J Physiol 1996 Aug 1;494 (Pt 3):831-7
15. Goglia F, et al. "Action of thyroid hormones at the cellular level: the mitochondrial target." FEBS Lett 1999 Jun 11;452(3):115-20
16. Lanni A, et al. "Effect of 3,3’-diiodothyronine and 3,5-diiodothyronine on rat liver oxidative capacity." Molecular and Cellular Endocrinology. Volume 86, Issue 3. 1992
17. Lanni A, et al. J. Endocrinol. 136:59-64 1993.
18. O’Reilly I, Murphy MP. Acta Endocrinol. 127:542-546 1992.
19. Lanni A, et al. "3,5-Diiodo-L-thyronine and 3,5,3’-triiodo-L-thyronine both improve the cold tolerance of hypothyroid rats, but possibly via different mechanisms." Pflugers Arch 1998 Aug;436(3):407-14
20. Varghese S, Oommen OV. "Thyroid hormones regulate lipid metabolism in a teleost Anabas testudineus (Bloch)." Comp Biochem Physiol B Biochem Mol Biol 1999 Dec;124(4):445-50
21. J. Kvetny. Horm. Metab. Res. 24:322-325, 1992.
22. Moreno M, et al. "Effect of 3,5-Diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats." Life Sciences, Volume 62, No.26, pp. 2369-2377, 1998
