This website is dedicated to the millions of thyroid patients who are being ignored and left to suffer unnecessarily, and to healthcare practitioners, who want to better serve those patients.

T2 Some Information

Some endocrinologists and other medical practitioners believe there is little (or no) information about the other thyroid hormones 3,5-diiodo-l-thyronine (T2) and Monoiodothyronine (T1). Tish, who is an active member of the American Natural Thyroid Hormone Support Group and myself, have done a little research into this subject. Some of the links are probably no good anymore since this research was done a long time ago,. There is some other interesting T stuff mixed in. Our comments are in parentheses.
The manufacturers of Armour Thyroid to USP (Forest Pharmaceuticals) have done no studies into the specific amount of T2, T1, calcitonin or any other T hormones that are naturally in the desiccated thyroid. All they say is that nothing has been added and nothing has been taken out in processing.

Also, the following is an extract from D. A. Versendaal and Dawn Versendaal-Hoezee, “Contact Reflex Analysis,” Hoezee Marketing, 1993, page 33.

“Natural desiccated porcine thyroid extract contains Thyroxine (T4) and Triiodothyronine (T3) hormones, as well as T2, T1 and calcitonin. T2 is considered necessary for production of the deiodinase enzyme that helps convert T4 into T3. T3 is the ‘active’ hormone that regulates the metabolism and is of short duration in the body. T4 has a much longer half-life in the body. T1’s physiological role was still being evaluated until very recently when it was found that T1 has an influence on the electrical input and charge of the brain and various mental disorders, including multiple sclerosis and Lou Gehrig’s syndrome, which can be a result of not enough T1 to recharge the brain”

Griffin James & Ojeda Sergio R, Text Book of Endocrine Physiology, pp
303-306, Oxford University Press, 2000

Public release date: 16-May-2004

Contact: Jonathan Modie
Oregon Health & Science University

Paper: Thyroid hormones and Mitochondria by Goglia F, Silvestri E, and Lanni A Two iodothyronines have been identified as effectors of the actions of thyroid hormones on energy metabolism: 3′,3,5-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2). Both have significant effects on BMR, but their mechanisms of action are not identical. T3 acts on the nucleus to influence the expression of genes involved in the regulation of cellular metabolism and mitochondria function; 3,5-T2, on the other hand, acts by directly influencing the mitochondrial energy-transduction apparatus. A molecular determinant of the effects of T3 could be uncoupling protein-3 (UCP-3), while the cytochrome-c oxidase complex is a possible target for 3,5-T2. In conclusion, it is likely that iodothyronines regulate energy metabolism by both short-term and long-term mechanisms, and that they act in more than one way in affecting mitochondrial functions.

Paper: Demonstration of in Vivo metabolic effects of 3,5 diiodothyronine by M cimmino, F Mion, F Goglia, Y Minaire and A Geloen

“3,5-T(2) exerts metabolic effects on energy expenditure, on both lipid beta-oxidation and leucine metabolism in hypothyroid rats. We conclude that 3,5-T(2) is a metabolically active iodothronine.”

Paper: Direct effects of 3,5,3′ -triiodothyronine and 3,5- diiodothyronine on mitochondrial metabolism in the goldfish Carassius auratus byLeary sc, Barton kn, Ballantyne JS

“State 3 oxidation of pyruvite was significantly higher for liver mitochondria treated with T2 and for red muscle mitochondria incubated with T3 when compared to control mitochoondria. Rapid elevation of state 3 rates of substrate oxidation by thyroid hormones may be important in mediating diurnal changes in mitochondrial metabolism. Significant increases in liver and red muscle mitochondrial state 4 rates were also observed for pyruvite in T2- and T3-treated mitochondrial and for glutamate in T3-treated

Paper: 3,5-diiodothyronine and 3,5,3′-triiodothyronine both improve cold tolerance of hypothyroid rats, but possibly via different mechanisms by Lanni A, Moreno M, Lombardi A, Goglia F (The tittle says it all.)


Paper: 3,5,-diiodothyronine (T2) regulates glucose-6-phosphate dehydrogenase activity in the rat by Lombardi A, Beneduce L, Moreno M, Diano S, etc.

T2/100 g BW (grams per body weight) affects G6PD activity 3-5 times more than the same dose of T3. These data provide the first evidence that T2 is a factor capable of regulating G6PD activity.

Paper: Action of thyroid hormones at the cellular level: the mitochondrial target by Goglia F, Moreno M, Lanni A.

Not only triiodo-L-thyronine, but also diiothyronines are active in regulating the energy metabolism. They influence resting metabolism in rats with 3, 5-diiodo-L-thyronine seeming to show a clearer effect.

Paper: Calorigenic effect of diiodothyronines in the rat by Lanni A, Moreno M, Lombardi A, Goglia F,

These results suggest that T8 isomers might be mediators of the direct thyroid hormone regulation of energy metabolism.

Bodybuilding article: T2 The Fat Terminator? by John M Berardi (Article with citations.)

T2 may be benificial in rapid energy requiring situations like cold exposure or overfeeding. (This may be important for energy under stress, for which I was suffering a real lack of.)

In one human study, T2 significantly increased oxygen consumption in blood cells in vitro.

Paper: Effect of 3,5,3′ -triiodothyroinine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolis responses by Chopra IJ, Huang TS, Hurd RE, Solomon DH

The mondeiodination of 3,5-T2 to 3-T1 increased significantly only in the cebral cortex and liver and not in any other tissue.

(This information along with other sources indicate that T1 is needed by the brain. The brain has enzyme pathways that seem specificly there for production of T1. An article listed later also talks about the function of T1 in the brain)

Paper: Di-iodothyronine as part of the oestradiol and catechol oestrogen receptor-the role of iodine, thyroid hormones and melatonin in the aetiology of breast cancer. by Clur A.

The present author proposes that the tyrosyl residue in the hydrophobic oestrogen binding site of the oestrogen receptor is post translationally modified to monoiodotyrosine and hence 3,3′ di-iodothyronine monoamine (T2) by peroxidase activity. He has previously proposed that various monoamine receptors are also T2 based. The densities of these receptors are increased in hypothyroidism and they exert control over release of prolactin and other hormones, including melatonin at multiple sites in the hypothalamic-pituitary axis. Melatonin is a metabolite of serotonin and hence melatonin receptors may be T2 or rT3 based as well. These factors could be significant in the aetiology of breast cancer as high prolactin and melatonin levels may be protective. Oestrogen receptor density may be increased in hypothyroidism as is certain monoamine receptor density. This would amplify the effect of high circulation oestrogen levels in hypothyroidism and may help explain why hypothyroidism and low iodine intake are risk factors for breast, uterine and ovarian cancer.

(This paper indicates that estrogen receptor and melatonin status are influenced by thyroid hormones other than T3. Other studies have found that T2 production and RT3 production increase in hypothyroidism and there is a resultant increase in cellular sensitivity to estrogen.)

Well dodumented article: The Thyroid Handbook by Cy Willson (Article with citations)

T3 increases aerobic mitochondria function or respiration, but another thyroid hormone, T2 may actually be responsible for this action.

This increase in beta-3 number (from T2) means that it can increase the effectiveness of norephedrine and ephedrine. (Several articles demonstrate that without adequate amounts of the other thyroid hormones as would likely happen with T3 and T4 only therapy, more work is required from the adrenals. This would not be a benificial thing for the adrenally fatigued and I now suspect that those on T3 therapy recover from adrenal fatigue at a slower rate compared to those who are able to use Armour.)

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.

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.

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. 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.

Article: Health Musings (Paper 9D, The Thyroid) by Clifford S.
Garner, Ph.D.

AbstractIn one sense, a main T4 function is to regulate the rhythm of the heart (a person can have a perfect heart, yet have heart failure because T4 control is absent). If the thyroid stops functioning, or has been surgically removed (MDs are people who believe we have an excess of organs and a deficiency of drugs), the adrenals have to act as the heart’s backup. T4 deficiency tends to bring about symptoms such as fatigue, depression, headaches, cold hands and feet, and frequent subluxations of the spinal cervical vertebrae. (This may well explain why my adrenal situation was not improving, especially during excercise or other more strenuous activity when T3 demands exceeded supply. There was very little T4 in my blood to convert to T3 and therefore the adrenals had to excrete more hormones to try to compensate. Other reading I have done has pointed to the fact that in hypothyroidism or low blood levels of thyroid hormones more adrenalin is secreted in the body’s attempt to get the metabolic rate up. I imagine it would take a lot of adrenalin and possibly other hormones to compensate for a situation of T3 and T4 shortage as might happen in excercise while on T3 only replacement.)

The third major thyroid hormone (T1) controls the electrical input and charge of the brain. Symptoms of a T1 deficiency may include fatigue, depression, low self esteem, suicidal tendencies, and various mental disorders. Sometimes multiple sclerosis and Lou Gehrig’s syndrome are a result of not enough T1 to recharge the brain. (This may expalain my lack of motivation and mental lethargy. I later had a documentable experience with EEG (or neurofeedback) training that proved to me that the other thyroid hormones (besides T3) play important roles in brain function, specifically brain wave energy and activity. They also seem to have an impact on the richness and depth of my emotions, which I noticed very quickly after beginning Armour.)

The fourth major thyroid hormone is calcitonin, apparently not under pituitary control. When blood levels of calcium are too high, calcitonin is secreted, which makes more bone-forming cells (osteoblasts) and decreases formation of cells that break down bone (osteoclasts); these processes are tied in with the functions of a hormone secreted by the parathyroids.

Paper: Peripheral Metabolism of Thyroid Hormones: A Review by Greg Kelly, ND (This is an excellent paper with much information that I highly recommend reading. I did not copy sections out of it as there were so many things worth noting and it would take up a lot of space.)

This paper discusses the function of T2 and discusses the various enzyme pathways for thyroid hormone conversions in the body. From this paper, I understood that by replacing with only T3, and consequently impairing some enzyme pathways, depleting RT3, and lowering levels of other thryoid hormones, I was depriving various tissues of things they needed. I learned that T2 declines significantly with age and thus may be a player in age related physical slowing. The degradation of RT3 to T2 and then to T1 may be improtant and neccessary body response to hypothyroid and stress states as well as needed to be fully healthy and right. Certain levels of RT3 may in fact be neccessary to the body. The enzymes depleted by T3 only therapy would affect the brain and it’s ability to get adequate T1. The paper also covers how toxic metals disturb these enzyme pathways and may be responsible for why some people need such high levels of T3 to feel well.

Article: Gail’s Thyroid Tips (This article is written my a woman who has done a lot of research on hypothyroidism but who is not a researcher or Ph.D.)

To convert T4 into T3 (and T3 into T2), your tissues use an enzyme, deiodinase, to knock one of the iodine molecules off. Well, some of your tissues require a supply of T2 in order to make this enzyme (while other tissues are able to make deiodinase without T2). (This indicates that T3 only therapy does not result in the body being able to convert T3 to adequate levels of T2, T1, and T0 at least not in all tissues. Other research also indicates this. There are several enzyme pathways for thyroid hormone conversion and various tissues and organs will have more or less of certain ones. All T3 therapy depresses one major pathway and does not affect others. There is no way to guarantee that a person on all T3 therapy would be able to get adequate T2 and other hormones to be truly healthy.)

T2 is taken up by the cells and acts directly on the mitochondria. The T2 is used to produce ATP. ATP is the fuel for our cells; it is the energy our cells use to function. So you see, T2 is absolutely vital for the cells to function. Yes, it is true that a healthy thyroid gland does not make very much T2. But certain cells in the body depend on it.

New compound may act to keep thyroid activity in check

OHSU study finds T1 amine rapidly causes hypothermia, blood pressure drop, slow pulse

PORTLAND, Ore. Researchers have isolated a naturally occurring, thyroid hormone-derived compound that produces an inactive, torpid-like state in rodents and could someday help doctors stabilize surgical and trauma patients. Although the compound, 3-iodothyronamine T1 amine, for short is a derivative of thyroxine, an essential thyroid hormone that influences development, body temperature, metabolic rate and cardiac performance, it has the opposite effect of thyroxine, according to a study by scientists at Oregon Health & Science University, the University of California, San Francisco (UCSF) and Universita di Pisa, Italy.

The new findings suggest that T1 amine affects several organ systems. Consequently, if its molecular and cellular actions can be precisely described, physicians will be in a better position to treat a variety of cardiovascular and endocrine diseases, as well as mental health disorders, said David Grandy, Ph.D., associate professor of physiology and pharmacology, and cell and developmental biology in the OHSU School of Medicine.

“Here we thought we knew thyroid hormone so well, only to find out there’s this whole new aspect of it,” said Grandy, co-author of a study published in today’s online edition of the journal Nature Medicine. T1 amine’s “normal function in the body may be to counteract, or keep in check, thyroid hormone’s actions.”

In mice, T1 amine can induce profound hypothermia, slow heart rate and drop blood pressure, suggesting that it, or related molecules, might provide a valuable new means by which physicians can stabilize patients during surgery and trauma, Grandy said. Within minutes of administering T1 amine, mice appear to go into a “hypometabolic state.”

“Although they’re inactive and appear to be unmotivated, they definitely are not anesthetized. It almost looks like they’re playing dead and have stopped responding to their environment,” Grandy said. T1 amine has a “profound” effect on the heart where it “almost immediately causes a dramatic decrease in pumping and outflow,” Grandy said.

Linda Lester, M.D., assistant professor of medicine in the Division of Endocrinology, Diabetes and Clinical Nutrition, OHSU School of Medicine, said physicians have limited means to rapidly reverse the effects of diseases that increase metabolism.

“The compound described in this article could provide a new tool to manage patients in acute hypermetabolic states, including hyperthyroidism,” she said. “The effectiveness of this compound in humans would have to be established prior to considering it as a new therapy, but the rodent studies described in this article support further evaluation.”

The molecule’s structure, its potency and speed of action suggest that it is a previously undiscovered neurotransmitter, said Thomas Scanlan, Ph.D., co-author on the paper and professor of pharmaceutical chemistry and cellular and molecular pharmacology at UCSF. “While changes in hormone levels may take a day to have their effect, neurotransmitters can act within minutes to hours,” Scanlan said. “T1 amine acts this quickly, and it has a chemical structure similar to dopamine or serotonin. Since it looks like a neurotransmitter and acts like a neurotransmitter, we hypothesize that it is a neurotransmitter.”

Scanlan, an expert on thyroid hormone chemistry and pharmacology, synthesized T1 amine. The researchers at OHSU and UCSF then found that the compound occurs naturally in the brains of rats and guinea pigs, and subsequently in the brains, heart, liver and blood of adult mice.

The prediction and ultimate discovery of T1 amine followed on the heels of a previous discovery made in the Grandy laboratory.
“For us, when we find a new receptor that is made by the body, it means there must be a naturally occurring molecule, or key, that turns it on,” Grandy said. “In our efforts to find this receptor’s natural key, or ligand, we tested hundreds of compounds. This analysis identified a small set of chemical groups that were important. Our interest turned to thyroid hormone because it contains each of these chemical groups following a simple chemical modification. What we couldn’t know ahead of time is that T1 amine would be the best fitting key for our trace amine receptor.”

The Grandy lab also was surprised to find that T1 amine’s effects on the body were opposite to those associated with thyroid hormone.
Promoting close collaborations between chemists and biologists, like that between researchers at OHSU and UCSF, is a central aim of OHSU’s chemical biology initiative, a developing program led by the Department of Physiology and Pharmacology that is to be housed in new research space now under construction on Marquam Hill.

“The program will bring together, on one campus, chemists and biologists who have the common aim of discovering small molecules that are potent regulators of biological processes and, maybe, prototypes for drugs,” said David Dawson, Ph.D., professor of physiology and pharmacology, and department chairman.

Demonstrating that T1 amine and the trace amine receptor “talk to one another” may help scientists better understand and treat depression, schizophrenia, movement disorders, obesity, trauma, stroke, diabetes and cardiovascular disease, Grandy said.
Now that the T1 amine compound has been found, and its biological effects observed, Grandy hopes to study its possible connections to drug dependency and other mental health disorders.

“Interestingly, amphetamines and Ecstasy turn this receptor on,” he said. “I’d like to think one direction that future studies will take addresses whether or not T1 amine might influence drug-taking behavior.”

Other study collaborators included: Katherine Suchland, Paul Kruzich, Dane Crossley II and James Bunzow, Department of Physiology and Pharmacology, OHSU; Matthew Hart, Department of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, UCSF; Grazia Chiellini, Sabina Frascarelli, Simonetta Ronca-Testoni, Riccardo Zucchi, Dipartimento di Scienze dell’Uomo e dell’Ambiente, Sezione di Biochimica, Universita di Pisa, Italy; Yong Huang and Emil Lin, Department of Biopharmaceutical Sciences, UCSF; and Daniel Hatton, Department of Behavioral Neuroscience, OHSU.

Further T2 Info

The link to this no longer works. But here is a copy of the article

This derivative of T3 was once thought to be inactive. In fact, most doctors and pharmacists (no offence to my brothers and sister who are involved in those fields) arent 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. Its 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) 3,5-diiodo-L-thyronine (T2)

This derivative of T3 was once thought to be inactive.

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 youd 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 isnt a huge amount of research in humans, some does exist. By the way, everyone, heres an inside tip about product development in the supplement industry. If you want to come up with something new and effective, chances are there isnt 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 isnt 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 didnt 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

Ive 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 its 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 dont care which. Anything. Testosterone, trenbolone, boldenone, stanozolol, or if you want to go the legal route, Nandrosol, Androsol, Methoxy-7, or Tribex-500.

Ive 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. Im going to give it a go and compare its effects to that of T3 myself. Im 100% sure itll work, but Im going to have my TSH monitored and Im going to compare the two using similar dosing regimens.

Looking at it objectively, however, I think youll see which is better. These are exciting times in this industry, arent 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


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