helvella - How much more potent is T3?

Introduction

The potency of T3 (as a multiple of T4) is the source of much confusion.

You can find claims of T3 being anything from fifteen times as potent, down to being around twice as potent. And many of these claims are not based on good science.

It is possibly best to start out by considering T4 to be totally inactive. And all thyroid hormone activity being due to T3 alone. (Even though not absolutely accurate, it causes far too much confusion to look at it any other way, at least to start with.)

The issue is that T3 is an active molecule, whereas T4 is not.

If a molecule of T4 is converted into a molecule of T3, it is then an active T3 molecule.

If it doesn’t get converted to T3, it is never active!

A Statistical Approach

Not all molecules of T4 get converted to T3. Broadly, we can look at six possibilities:

⚀ Some T4 molecules do not get absorbed into our bodies at all.
⚁ Some T4 molecules get converted into T3.
⚂ Some T4 molecules get converted to reverse T3 (rT3).
⚃ Some T4 molecules get “conjugated” with other molecules and become glucuronides.
⚄ Some T4 molecules get “conjugated” with other molecules and become sulfates.
⚅ Some T4 molecules get excreted without any conversion.

It is far better to think of this in terms of statistics than the potency of individual molecules. Which is why I have put dice against each option.

Imagine rolling dice for each T4 molecule to decide what will happen to them.

In statistics it is common to think of dice as being perfect – each roll having exactly the same chance of ending up showing each of its faces.

Roll a ⚀ and the T4 molecule doesn’t even get absorbed.
Roll a ⚁ and the T4 molecule gets converted into T3.

And so on…

If that really represented how our bodies handle T4, then exactly one sixth would be converted to T3.

Then you could argue that T3 is six times as potent as T4. Or a ratio of around 6:1.

A possibly more accurate way of describing what has happened is to say that T4 has zero potency. And one sixth of the T4 gets converted to T3.

It still ends up with a ratio of 6:1, but is closer to what happens.

However, in order to better describe what really happens, we have to acknowledge that the dice are biased. They do not roll true. They don’t come up ⚀ one in six rolls and ⚁ another one in six rolls, etc.

Starting at the first step, it is often suggested most of us can absorb around 60 to 80% of the T4 in a tablet. (One sixth is about 17%.). Thus, the chances of landing on ⚀ might be 20 to 40%. Or between slightly over one sixth to over two sixths (or one third).

But it could be very different if you have stomach issues which mean you absorb more or less. Or if you take a product such as an oral solution which is usually thought to be rather better absorbed. Maybe the range of absorption needs to be extended to something like 40 to 100%?

The dice rolls our bodies perform are affected by numerous factors. We don’t have figures for the chances of rolling ⚀ ⚁ ⚂ ⚃ ⚄ and ⚅ in our bodies. Even if there are general figures that are some sort of average from research, they won't be the figures that apply in your or my body.

In general, we don't even have much idea as to what affects these six steps. We know low selenium impairs thyroid enzymes involved in conversion. We know very low TSH can reduce T4 conversion. We know iron deficiency can impair conversion and utilisation of thyroid hormone. But we don't have a comprehensive picture which lists all the factors for each of the six steps.

For that reason, we simply have to look at the effect of T3 and not the theoretical potency.

Summary

In the past, a simple rule of thumb has been used. Of the T4 that is absorbed, roughly one third is converted to T3, one third to rT3 and one third follows another pathway. Hence, a ratio of 3:1 but based on the T4 which has been absorbed - not the T4 in the original tablet.

Now for a concrete example. Imagine taking a single 100 microgram tablet of T4, of which 75% is absorbed:

25% (25 micrograms) is converted to 21 micrograms of T3

25% (25 micrograms) is converted to 21 micrograms rT3

25% (25 micrograms) follows other pathways

25% (25 micrograms) is never absorbed and just passes through

(Numbers chosen for simplicity!)

This results in a ratio of 4.76:1. (Tablet dosage to actual T3 by weight.) If those figures were accurate, you'd need to take 4.76 micrograms of T4 to end up with one microgram of T3.

The T3 and rT3 are lighter molecules than T4. After all, each one has lost an iodine atom! That is why 25 micrograms of T4 converts to 21 micrograms of T3 or rT3 (rather than 25 micrograms) with the other 4 micrograms being free iodine that can be recycled or excreted. (Numbers are approximate.)

It is interesting that the UK, Germany and some other countries went for 20 microgram liothyronine tablets - which is much closer to 21 micrograms than the 25 microgram tablets used in many other countries.

If you want to apply these ideas to taking liothyronine (T3) tablets. You need to start by considering how well they are absorbed. Absorption of T3 is much better than T4 but likely still a bit short of 100%.

Please understand, this is an attempt at illustrating the issues. None of this is wholly accurate.

If you'd like a more comprehensive description and discussion about thyroid hormones and conversion, I recommend this article which has several helpful diagrams as well as detailed text:

Thyroid hormone journey: Metabolism
January 31, 2021

https://thyroidpatients.ca/2021/01/31/journey-metabolism/

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