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T2 - The Fat Terminator?

By Dr. John M Berardi, Ph.D.
First published at www.thepowerstore.com, Sep 14 2001.

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Fat Termination

It's no secret that summer is right around the corner. Over the last week or so the weather has decided to show a few glimpses of what's to come, namely warm sun streaming down upon exposed arms, legs, chests, and other miscellaneous body parts that have been cloaked all winter long. You've gotta love this time of year, if for nothing more that the virtual "orgiastic feast for the senses" (as Cosmo Kramer would put it).

But as always, with the good comes the bad. And in most cases, that layer of body fat that has infiltrated the lean physiques most possessed last summer represents the bad. So as summer approaches thousands everywhere are looking for a quick and easy solution to dropping the fat and, as some of my students would say, "get their rip on". They want to quickly and efficiently terminate the fat.

Obviously exercise and nutritional intake are the major determinants of fat loss but few will argue that nutritional supplements can help in the termination of high levels of body fat by either increasing metabolic rate or maintaining metabolic rate while dieting, preserving lean tissue during dieting, and suppressing food intake. When we think of legal, over the counter fat loss supplements, obviously supplements like the ECA stack come to mind. However, many individuals have even tried to shed fat using several prescription medications like the thyroid hormones T3 and T4. For you chem. buffs, T3 is the compound 3,5,3'-triiodo-l-thyronine or just triiodothyronine while T4 is 3,5,3',5' Tetraiodothyronine or just thyroxine.

Thyroid Hormones

Although thyroid hormones are necessary for promoting normal developmental growth, don't confuse this with the muscle growth that occurs with resistance exercise. In addition thyroid hormones are involved in dozens of biological processes including:

- Increased oxygen consumption (metabolic rate)
- Increased thermogenesis (heat production)
- Increased number of beta adrenergic receptors in the heart, skeletal
muscle, adipose tissues, and lymphocytes (these receptors bind fat
mobilizing hormones)
- Increased sensitivity to catecholamines (fat mobilizing, fight or
flight hormones)
- Increased number of red blood cells and increased oxygen delivery
- Increased lypolysis
- Increased liver glycogen breakdown
- Increased liver glucose production
- Increased intestinal glucose absorption
- Increased protein turnover
- Decreased cholesterol levels

From looking over this list, it appears that thyroid hormones do some pretty exciting things in the body, all of which can be beneficial to weight trainers. But before I move on, I want to talk about some of the other effects of thyroid hormones that may not be so ideal for weight trainers.

- Increased heart rate and heart contractility
- Increased free radical production (due to decreased Superoxide
Dismutase concentrations)
- Increased GI motility
- Increased bone turnover (and potentially bone loss or high levels of
calcium in the blood)
- Increased cortisol levels
- Increased sex hormone binding globulin

How's The Thyroid Working?

Now that you've seen what thyroid hormones can do, let's talk about thyroid function. Much like any other hormone system there are tight controls regulating thyroid function. So under most normal circumstances, if thyroid concentrations are low in the blood then the thyroid is stimulated to produce more hormone. And if they are high in the blood, the thyroid will be inhibited and less will be produced. Of course there are a few exceptions to these rules. Disease states, prescription medication use, and interestingly, dieting can throw off this equilibrium. While most people don't have thyroid disorders or use meds that can alter thyroid function, most people do diet at some point in their lives. And during dieting, natural thyroid production is usually suppressed and this can eventually harm fat loss efforts.

Enter thyroid drugs. Some people, in an attempt to harness the fat burning powers of thyroid hormones, are taking T3 or T4 with or without dieting in order to either maintain normal thyroid hormone levels or in order to simply burn more fat than they would have been burning otherwise. However this use comes at a price. You see, too much thyroid hormone in the body can lead to a thyrotoxic state. Side effects of thyrotoxicosis include heart palpitations, nervousness, easy fatiguability, diarrhea, excessive sweating, heat intolerance, and tachycardia. Small to moderate doses of thyroid hormones, however will probably not lead to thyrotoxicosis.

In addition to the risk of thyrotoxicosis, both hormones are very suppressive of thyroid function and it appears that with extended use of these compounds, the thyroid is sluggish in restarting natural production (Vagenakis, et al., New England Journal of Medicine, 293(14): 681-684, 1975). In fact, in this study population, it took between 5-9 weeks for thyroid production to return to normal after suppression therapy. This has pretty dramatic consequences since during this period of thyroid suppression, metabolic rate will be much lower and there is good potential for fat gain.

So with the prescription drugs T3 or T4, the potential benefits of their use must be weighed against the after effects during the thyroid-suppressed period.

Over-The Counter Thyroid Hormone?

Recently, Biotest Laboratories has released a very interesting product that they are calling T2 (otherwise known as 3,5-diiodo-l-thyronine or just diiodothyronine). T2 is definitely a legitimate thyroid hormone, structurally very like T3 or T4. However this product is allowed to be sold as an over the counter dietary supplement due to the fact that is present in meat.

In the past, T2 was thought to be inactive, but many recent papers have shown T2 to have some pretty dramatic effects on metabolic processes. One issue of concern in the interpretation of this data is the fact most of these studies used hypothyroid rats that are producing very little thyroid hormone on their own. Therefore since these studies did not examine the effects of adding T2 into a normal thyroidal environment, they may not be totally applicable to individuals with normal thyroid functioning. In any case, the studies are certainly worth mentioning.

- Significant increases in mitochondrial respiration and cytochrome
oxidase activity were found both in vitro and in vivo (1). These
increases lead to an increase in metabolic rate. Interestingly, these
effects are different from those of T3 and T4 due to the fact that T2
acts directly on the mitochondrial respiration while T3 and T4 must
first increase oxidative enzyme levels. This means that T2 has a much
more rapid stimulation of metabolic rate (1 hour for T2 vs 24 hours
for T3). Some authors have concluded that T2 may be beneficial in
rapid energy requiring situations like cold exposure or overfeeding
(2).

- Significant increases in resting metabolic rate (33%) were found
(1,3). Both T2 and T3 were able to stimulate the recovery of
metabolic rate to normal, euthyroid levels.

- Significant increases in the oxidative capacity of skeletal muscle,
brown adipose tissue, liver, and the heart were found (1,4). Both T2
and T3 promoted full recovery of oxidative capacity but T2 was most
active in the liver and the muscle while T3 was most active in the
liver.

- Significant increases in the liver activities of glucose-6-phosphate
dehydrogenase and malic enzyme were found (5,6). These enzymes are
necessary for fat metabolism.

- Significant increases in GH release were found. Both T2 and T3
increased GH release 5-fold (7).

- In the one human study I found, T2 Significantly increased oxygen
consumption in blood cells in vitro (8).

In most of the studies listed above, the doses of T2 required for physiological and biochemical effects to manifest were larger than the doses of T3 required. This is due to the fact that T2 has a lower receptor affinity for most thyroid hormone receptors than does T3.

So from these data, if the dose is right, T2 supplementation may offer most of the same benefits as T3 but might even be superior in rapidly stimulating metabolic rate. This could come in handy before a big Easter dinner or your weekly dietary cheat day.

The next question then is to ask whether or not T2 can suppress natural thyroid hormone (as measured by TSH concentrations) production like T3 can. This is where things get a little sketchy. In hypothyroid rats, T3 seems to have a much larger suppressive effect than does T2.

- Moreno et al found that it took 5x as much T2 to suppress TSH when
compared to T3 (7).
- Cimmino et al found that it took 25x as much T2 to suppress TSH when
compared to T3 (3).
- Ball et al found that 100x the dose of T2 lead to 5x less suppression
of TSH when compared to T3 (6).
- In vitro data by Everts et al showed that T2 was 100x less
suppressive than T3 (9).
- Finally, Horst et al showed that in euthyroid rats, while it took
over 100x as much T2 to suppress TSH compared with T3, even at these
doses, there were no major changes in body weight with T2
supplementation (10).

So from these data it is pretty clear that it takes a much large dose of T2 to suppress natural thyroid hormone production than T3.

Summary

Hopefully at this point you have a better understanding of how thyroid hormones work and why one would want to supplement with them. In addition, I hope you have a better understanding of T2. The other day a lady-friend of mine came up to me and asked me to give her my opinion as to whether on not she should take T2. And she asked me to tell her in layman's terms. So here's basically what I told her (unfortunately, the following is as "layman" as I get when talking about nutritional supplements); "From the data I've seen, it initially looks like T2 may really help to shed fat. However I have a few concerns. Since T2 is less active and has a lower affinity for the thyroid receptors in the cell than T3, larger doses of T2 are required to get the same fat-burning effects as you would get with T3. And although T2 is less suppressive than T3, the doses required to get full effectiveness may be enough to suppress natural thyroid production anyway. However I don't know the answers to this for sure and I'm fairly confident that no one does. I speculate, however, that the recommended dose of T2 is probably not going to cause much suppression of thyroid function. In addition this dose may have some effects on cellular metabolism but whether this dose dramatically increases fat loss, I can't be
certain."

"So in the end I can see one of four scenarios happening. First, the ideal scenario is that the doses of T2 recommended are effective and will not suppress thyroid function. This means lots of fat will be lost and there will be no rebound with cessation of use. Second, the does of T2 used are not very effective in fat loss and there will be little or no fat loss but at least there will be no suppression of thyroid function. So you wont get much leaner but you won't have any problems either. These are the two most likely scenarios. I sure hope the first one is the case but I can't be sure. There is just not enough data just yet."

"The third scenario is that people may take larger doses of T2 than recommended and lots of fat will be lost but there will also be thyroid suppression. This means that they must be prepared for the dreaded rebound and lower metabolic rate for a few weeks after going off the supplement. And the fourth scenario is that with higher than recommended doses, the thyroid will be suppressed and while some efficacy is evidenced, there will be a metabolic compromise. In response to suppression of the thyroid, T3 levels will go down. Since T3 which is responsible for several functions in the body that T2 isn't known to be active in, while you are on T2 you might not be getting all the benefits that T3 will promote. And again, when you go off, you will have a short rebound period of suppressed thyroid function."

So in the end, the question of whether T2 is a legitimate fat terminator is a tough one to answer. From the available data, there isn't a clear picture that I can present. However, I think that T2 is ultimately pretty safe at the recommended doses. Whether it works as well as some think is another question. Fortunately Biotest has asked me to investigate this very question in the lab so that we can have some real answers in the near future. Stay tuned for updates as to my progress.

References

1.Goglia et al. FEBS Letters. 452, 115-120 (1999).
2.Lombardi et al. Biochem J. 330, 521-526 (1998).
3.Cimmino et al. J of Endocrinology. 149, 319-325 (1996).
4.Lanni et al. J Physiology. 494(3), 831-837 (1996).
5.Lombardi et al. Endocrinology. 141, 1729-1734 (2000).
6.Ball et al. J Molec Endocrinology. 19, 137-147 (1997).
7.Moreno et al. Life Sciences. 62(26), 2369-2377 (1998).
8.Kvetny et al. Horm Metab Res. 24(7), 322-325 (1992).
9.Everts et al. Endocrinology. 136 (10), 4454-4461 (1995).