When patients are on T4 and or T3 should they always use some T2 as well?
• Yes, since most people are deficient in T2, the only way to get bio-identical ratios of the hormones with replenishment therapy, is to give T2 as well.
• Furthermore, taking T2 is particularly important where weight loss is required, since unlike T3 and T4, T2 only affects the mitochondria of the cells, not the nucleus, making it not only safer, but also treats obesity via a second distinct mechanism of action -always a good thing.
• Finally, theoretically at least, stimulation of the mitochondria by T2 may help delay ageing, since mitochondrial energy diseases and subsequent cell death is one of the current theories of aging.
What dosage is required?
• Dosage: 50mcg per day• Dosage Ratio of T4:T3:T2 is 4:1:2 (some say 4:1:1) eg 100mcg T4: 25mcg T3: 50mcg T2
What are the benefits of T2?
• Elevates Basal Metabolic Rate by stimulation of the mitochondria
• Fat loss (T2 is most active in BAT - brown adipose tissue)
• Increased energy
• May help prevent energy (mitochondrial) diseases
• Does not suppress TSH as much as T4 or T3 (T2 suppresses TSH 13-100 times less than T3 and T4 does)
What is the exact mechanism how T2 works differently to T4/T3
• T2 releases energy via a mitochondrial / ATP mechanism, not in the nucleus, by inducing the transcription of genes that control energy metabolism (which is how T3 and T4 works). There are a number of mechanisms whereby T2 increases mitochondrial energy production rates, resulting in increased ATP levels. These include:
• An increased influx of Ca++ into the mitochondria, with a resulting increase in mitochondrial dehydrogenases.
• This in turn would lead to an increase in reduced substrates available for oxidation.
• An increase in cytochrome oxidase activity has also been observed.
• This would hasten the reduction of O2, speeding up respiration. These and a number of other proposed mechanisms for the action of T2 are reviewed by Lannie et al.(J Endocrinol Invest 2001 Dec;24(11):897-913 Control of energy metabolism by iodothyronines.Lanni A, Moreno M, Lombardi A, de Lange P, Goglia F)
• The net result is increases ATP, which releases its energy via the following mechanisms:
• Increased Na+/K+ATPase. This is the enzyme responsible for controlling the Na/K pump, which regulates the relative intracellular and extracellular concentrations of these ions, maintaining the normal transmembrane ion gradient. Sestoft has estimated this effect may account for up to to 10% of the increased ATP usage (J Endocrinol Invest 2001 Dec;24(11):897-913 Control of energy metabolism by iodothyronines.Lanni A, Moreno M, Lombardi A, de Lange P, Goglia F)
• Increased Ca++-dependent ATPase. The intracellular concentration of calcium must be kept lower than the extracellular concentration to maintain normal cellular function. ATP is required to pump out excess calcium. It has been estimated that 10% of a cell's energy expenditure is used just to maintain Ca++ homeostasis. (Endocrinology 2002 Feb;143(2):504-10 Are the effects of T3 on resting metabolic rate in euthyroid rats entirely caused by T3 itself? Moreno M, Lombardi A, Beneduce L, Silvestri E, Pinna G, Goglia F, Lanni A)
• Substrate cycling. Hyperthyroidism induces a futile cycle of lipogenesis/lipolysis in fat cells. The stored triglycerides are broken down into free fatty acids and glycerol, then reformed back into triglycerides again. This is an energy dependent process that utilizes some of the excess ATP produced in the hyperthyroid state. Futile cycling has been estimated to use approximately 15% of the excess ATP created during hyperthyroidism. (Clin Endocrinol (Oxf) 1980 Nov;13(5):489-506 Metabolic aspects of the calorigenic effect of thyroid hormone in mammals. Sestoft L.)
• Increased Heart Work. This puts perhaps the greatest single demand on ATP usage, with increased heart rate and force of contraction accounting for up to 30% to 40% of ATP usage in hyperthyroidism (Annu Rev Nutr 1995;15:263-91 Thermogenesis and thyroid function. Freake HC, Oppenheimer JH.)
Is it necessary in the body?
• The answer is yes, but it is not essential - you can live without it, buts its not a good idea.
If people have a problem converting T4 to T3 would they have the same problem converting T3 to T2?
• Yes, which is why T2 should be taken.
How safe is T2?
• T2 is safer than T3 and T4 because it does not affect the nucleus (DNA) of the cells, only the mitochondria. Also T2 only minimally supresses TSH. However, negative feedback is a concern in the younger patient or using high doses, and doses should be cycled, using the lowest effective dose.
Would patients have to reduce their dosage of T4 and or T3 when starting T2?
• Threoterically, yes slightly. Practically, probably not.
Is T2 as important as T4/T3 in hypothyroidism?
• No but very necessary for weight loss and energy
At what dosage dose T2 normally suppress TSH?
• 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 (see references below) showed that T2 is 13% less inhibitory on TSH levels, as compared to T3. 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 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. 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.
Additional reading:
"Thermogenesis
and thyroid function" by HC Freake and JH Oppenheimer
"Are
the effects of T3 on resting metabolic rate in euthyroid rats entirely
caused by T3 itself?" by M Moreno, A Lombardi, L Beneduce, E Silvestri,
G Pinna, F Goglia, A Lanni
"Control of energy metabolism by iodothyronines" by A.Lanni,
M Moreno, A Lombardi, P de Lange, F Goglia
"Thyroid
hormone action on intermediary metabolism. Part III. Protein metabolism
in hyper- and hypothyroidism" by MJ Müller and HJ Seitz
"Metabolic
aspects of the calorigenic effect of thyroid hormone in mammals"
by L Sestoft
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
A Rubio, A Raasmaja and JE Silva