# T4 (Thyroxine)

Category: Hormones

Also known as: T4, thyroxine, levothyroxine

T4 (thyroxine) is a precursor hormone that has no intrinsic metabolic activity until it is converted into the active hormone T3 (triiodothyronine). Peat consistently argued that T4 is not the active thyroid hormone, and its function depends entirely on the liver's ability to…

11 passages · 3 authors · 2009–2022 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/t4-thyroxine

## Synthesis

**T4 (thyroxine)** is a precursor hormone that has no intrinsic metabolic activity until it is converted into the active hormone **T3 (triiodothyronine)**. [Source 1, 11] Peat consistently argued that T4 is not the active thyroid hormone, and its function depends entirely on the liver's ability to remove one iodine atom in the correct position. [Source 4, 8] Dinkov has written that T4 "has no hormonal effects" and that prescribing it as monotherapy is "stupid" because it is merely a precursor. [Source 11]

The clinical failure of T4 monotherapy is rooted in the flawed testing that led to its commercialization. In the 1940s, drug companies synthesized thyroxine and tested it on healthy, 25-year-old male medical students, concluding it worked identically to natural desiccated thyroid. [Source 1, 3, 6, 8, 10] Peat emphasized that this population had optimally functioning livers capable of efficient conversion, but the product was never tested on the population most affected by hypothyroidism: women. [Source 6, 8] Because estrogen antagonizes thyroid function and slows liver metabolism, women—especially those over 30—often cannot convert T4 to T3 effectively. [Source 1, 3, 8] In these individuals, T4 can accumulate and act as an *antithyroid agent*, competitively displacing T3 from tissues and worsening hypothyroid symptoms. [Source 2, 3, 9]

Mechanistically, when the liver is sluggish due to hypothyroidism, high estrogen, or stress, T4 is shunted into the *reverse T3 (rT3)* pathway rather than being activated to T3. [Source 3, 11] Reverse T3 functions as a direct antagonist at the receptor, blocking the effects of active thyroid hormone and slowing metabolism. [Source 11] Peat described cases where increasing T4 doses led to myxedema coma because the patient's body contained no detectable T3, a state immediately reversed by intravenous T3. [Source 2, 10] In brain tissue specifically, an excess of T4 that cannot be converted suppresses oxidative metabolism, as demonstrated in experiments where adding thyroxine to brain slices decreased oxygen consumption. [Source 2, 8, 9] The brain normally maintains a 1:1 ratio of T4 to T3 by concentrating T3 from the serum, but flooding the system with T4 disrupts this equilibrium. [Source 2, 8]

The conversion of T4 to T3 is heavily dependent on liver health and nutritional cofactors. **Selenium** is required for the local deiodinase enzymes that convert T4 to T3, and a deficiency will impair activation. [Source 4, 7] Prolonged stress, with elevated **adrenalin** and **cortisol**, promotes the conversion of T4 into reverse T3 rather than active T3. [Source 3] Peat noted that hypothyroid individuals are often deficient in magnesium, and supplementing thyroid hormone can unmask a severe deficiency that causes intolerance. [Source 3] Dinkov has added that because the half-life of T4 is approximately one week, daily dosing leads to accumulation that burdens an already compromised liver, potentially inducing *fibrosis* in tissues over time. [Source 5, 11] Roddy has cited evidence that T4 monotherapy can burden the liver and make patients feel progressively worse, referencing the experiences documented on forums like "Stop the Thyroid Madness." [Source 5]

Therapeutically, Peat recommended using a combination of T4 and T3 that mimics the physiological ratio secreted by the thyroid gland, or using T3 alone in frequent small doses. [Source 9, 10] He noted that while the standard synthetic combination uses a 4:1 ratio of T4 to T3, many people experience clearer thinking with a ratio closer to 3:1. [Source 9] Because T3 has a short half-life and acts quickly—Peat described chewing a 5 mcg chip of Cytomel to restore memory within minutes—it should be taken multiple times per day. [Source 2, 9] T4, by contrast, accumulates and reaches a steady concentration only after about two weeks. [Source 9] Peat was clear that monitoring therapy requires tracking **pulse rate**, **body temperature**, and symptoms, not merely TSH suppression, which can be driven to zero by T4 alone while the patient remains functionally hypothyroid. [Source 9, 10]

## People also ask

### Why does T4 monotherapy often fail in hypothyroid women?

Peat argued that estrogen slows liver metabolism, impairing the conversion of T4 to active T3, and that the drug was originally tested only on healthy young men with optimal liver function, not on the women most affected by hypothyroidism.

### How can excess T4 act against thyroid function?

When the liver cannot convert T4 to T3, T4 can accumulate and competitively displace T3 from tissues, or be shunted into reverse T3, which blocks thyroid hormone receptors and suppresses metabolism.

### What nutrients support the conversion of T4 to T3?

The entry notes that selenium is required for the deiodinase enzymes that activate T4, and that magnesium deficiency can cause intolerance to thyroid supplementation when it is unmasked by treatment.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Current Trends in Nitric Oxide KMUD 2015

Ray Peat · Interview · 2015 · https://www.youtube.com/watch?v=6TquRcpR8RY

> **Herb Doctor:** A lot of problems with doctors prescribing that T4 is, that when someone is low thyroid and they take T4, their livers usually aren't active enough to convert the T4 into the active T3. Because T4 on its own doesn't have any action at all. It doesn't do anything. It has to be converted to T3. And if you take enough T4 you gonna turn off your brain's production of stimulating the thyroid gland (TSH) which naturally produces about one part T3 to four parts T4. So that's why taking the natural glandular ratio of 1:4 of T3 to T4 is what Dr. Peat is recommending.
>
> **Ray Peat:** In the 1940s, when drug companies synthesized thyroxin, they tested it on male medical students and said, "It work's just like real thyroid."
>
> **Herb Doctor:** That's T4, thyroxine.
>
> **Ray Peat:** Yea, T4. But the thing is that women with high estrogen compared to men always have a more sluggish liver. And women are the ones who especially... The 24-year old medical students seldom have liver problems. But a 40-year old female very often has a more sluggish liver so that thyroxine or T4 is very often causing problems in women.

### Source 2 — Life Supporting Substances Its Rain Making Time 2011 07 04

Ray Peat · Interview · Jul 4, 2011 · http://l-i-g-h-t.com/files/rarinmaking-time-life-supporting-substances.mp4

> **Ray Peat:** Several of them described their symptoms getting worse as they increased the dose. Some of them described strange noises in their heads or strange body sensations, that sometimes happen in hypothyroid people. So I read pretty thoroughly the animal research on T3 and saw that the brain, regardless of what is happening in your bloodstream, usually keeps a ratio of 1 to 1 (T4 to T3), even though the bloodstream might have 40 or 50 times more T4 than T3. The brain requires practically equal amounts to function. And an experimenter took slices of brain tissue in a dish, measuring their oxygen consumption, and showed that when thyroxine was added to the slice, the oxygen consumption decreased. Which is exactly the opposite of what T3 does when it's added to a tissue. So this is apparently what happens when someone goes into a coma while taking huge doses of thyroxine, or starts hallucinating when they are increasing their plain T4 dose. It's reaching such a concentration that the brain can no longer maintain its 1:1 ratio of T4 to T3. So it's actually displacing the T3 and causing hypothyroid symptoms, because T3 is the active hormone.

### Source 3 — Iodine, Supplement Reactions, Hormones and More KMUD - Ask Your Herb Doctor - 2016

Ray Peat · Interview · Feb 19, 2016 · https://www.youtube.com/watch?v=huW5IRBJKiY

> **Ray Peat:** Yeah. When people have suffered for a long time with a low thyroid they are likely to have extremely high adrenalin and cortisol levels and that causes them to turn T4 into reverse T3 blocking the actual active T3 hormone and then if they accumulate more and more T4 that will interfere competitively with the little bit of T3 that they do have, so they can exaggerate the state of their hypothyroidism if they’re in that extreme stressed state.
>
> **Andrew Murray:** Would you say that T4 perhaps is maybe only 10% as active as the active T3 hormone?
>
> **Ray Peat:** It really varies. In the 1940s, when they first synthesized it, they tested it on male medical students and it was exactly as effective as Armour natural thyroid and that’s because young men, 20-22 years old, have very good livers that can perfectly convert it, but even at the same age women are more likely to have problems with plain thyroxine.
>
> **Andrew Murray:** So when you talk about T4 being weakly active, how do you interpret that or how do you see T3 versus T4 in terms of orchestrating metabolic events?
>
> **Ray Peat:** Well the standard textbook idea is that T3 is 4 times more powerful than T4 but really if your liver is good you can get 100% of the benefit out of T4 and if you are a woman under stress with high oestrogen your liver isn’t going to convert any of it to the right active hormone, and the more you take – I’ve known of one woman who was hospitalized and got more and more hypothyroid the higher they raised her thyroxine dose - and as soon as they gave her T3 she came right out of the myxedema coma, but I have seen people in less extreme states who got more and more depressed or psychotic or whatever when they increased their thyroxine dose.

### Source 4 — One Radio Network: COVID Testing, Exosomes, EMFs, Gray Hair, Vaccines, and Aging (June 15, 2020)

Ray Peat · Interview · Jun 15, 2020

> **Ray Peat:** T4 isn't the thyroid hormone. it's a precursor to the active hormone. And it's the same as as with women several times more frequently than men, but it can happen in men too that the conversion many things such as a selenium deficiency can make the liver and other tissues reluctant to convert the T4 to the active hormone. Prolonged stress hormones will tend to make it go the wrong direction towards reverse t3 rather than active t3 and getting a better diet, but the simplest thing is to use a combination such as natural. The traditional Armour thyroid was what thyroid treatment was based on for the first 50 or 60 years and then the drug companies got involved testing their t4 product on young male medical students healthy male young individuals and they said work just like the thyroid hormone just like the natural thing, but it's exactly slightly older women who they should have tested it one because you would have found that in women in their 30s and 40s, for example, just about as often as it improves things that makes things worse to take thyroxine.
>
> **Patrick Timpone:** I see so what if there are people that offer just I don't it's not desiccated I guess it just beef thyroid from grass-fed cows and that's what it is somehow they try it. I mean would you have to be careful taking that?

### Source 5 — Be your own expert, w/Danny Roddy

Danny Roddy · Interview · Sep 30, 2022

> **Kitty Martone:** ever, say that again, you don't think it's ever appropriate to just take T4?
>
> **Danny Roddy:** Yeah, it would probably burden the person's liver. And so Keith Littlewood had done, I think, investigation on this, or when he was on my podcast, he talked about a paper of talking about that inducing fibrosis in tissues. And I think the issue is when a person has lower thyroid function, this is kind of what we talked about earlier, they have a slower liver function. And the two go hand in hand. And so the liver has to predominantly convert or rather majorly convert the T4 into T3. And so triiodothyronine T3 is like the active thyroid hormone that has all the benefits. And so just giving the person more T4 to suppress the TSH, which is what the doctor is looking at, can burden their liver, which is already under-functioning, and then over time make them feel much, much, much worse. And so I'm sure you're familiar with kind of a famous forum called Stop the Thyroid Madness. Yeah, this was mainly women who were like, I've had 30 years of my life robbed from me from my doctor who prescribed me levothyroxine. like 30 years ago. And I'd like, I feel like a zombie and I can't wake up and I have all the symptoms of hypothyroidism, but I go to them and then they just give me more T4. And so it's just like an unscientific practice that is likely to make a person worse over time. And so anyways.

### Source 6 — Herb Doctors: Environmental Enrichment-Bad Science

Ray Peat · Interview · Aug 16, 2013 · http://l-i-g-h-t.com/files/herb-doctors-environmental-enrichment -bad-science.mp4

> **Andrew Murray:** Levothyroxine.
>
> **Caller:** Is that the same as the Synthroid?
>
> **Andrew Murray:** Yeah, that’s T4.
>
> **Caller:** OK, it’s T4; alright, now sometimes I get the 3 and the 4 mixed up, and I asked the doctor and the endocrinologist do I need to take the T3 as well as the T4 and he said that we convert T4 into T3 automatically. Yeah.
>
> **Caller:** Is that true?
>
> **Ray Peat:** The reason women have five to 10 times the number of thyroid problems of all sorts than men do, is that their liver is relatively unable to convert T4 to the active T3 hormone efficiently. In the 1940s when T4 was synthesised and brought out as a product, it was tested on male medical students and it worked in them just the same as Armour thyroid extract, but they didn’t bother testing it on the female population.
>
> **Caller:** Well, you know regularly to see how it’s doing and they keep telling me my thyroid is now normal.
>
> **Ray Peat:** Oh, well the old normal concentration in the blood of T4 and T3 when the gland was producing it and the liver was activating it or when a person was using Armour thyroid as a supplement, the ratio....

### Source 7 — Ray Peat Email Advice Depository — Post 932

Ray Peat · Email · Dec 17, 2022

> **Question:** From May 2018, I asked about case studies where thyroxine (T4) precipitates adrenal crises [references] Why does this happen? Would the same thing happen with T3?
>
> **Ray Peat:** Addison’s disease should be immediately recognizable by any medical student; prescribing thyroxine for Addison’s disease is the sort of thing they call medical mistakes, and try not to admit to in court. Active thyroid hormone is needed for the adrenals to use cholesterol to make the hormones, and nutritional deficiencies, especially vitamin A, can limit the ability to produce the steroids. Selenium is needed for local conversion of T4 to T3. Supplementing T4 will reliably increase T3 in healthy people, but not in sick people.

### Source 8 — Politics & Science: Two Hour Fundraiser II

Ray Peat · Interview · Feb 22, 2012 · http://l-i-g-h-t.com/files/politics-science-two-hour-fundraiser-2.mp4

> ## Thyroid Supplementation: T4 vs. T3
>
> **John Barkhausen:** I have a question from Brittany. She asks: "If you are trying to self-treat for hypothyroid based upon blood tests and symptoms, how much T4 would be considered too much to take? And is T4 even necessary at all?"
>
> **Ray Peat:** The problem with the commercialization of synthetic T4 that started in the late 1940s was that they tested it on male medical students who were about 25 years old and selected for good health. They found that it worked in them just like the real thyroid substance that had been in use for about 50 years at that time. The trouble is that it then became commercialized. Women have at least five times the incidence of thyroid problems because of the antagonism between estrogen and thyroid. The thyroid sluggishness that's so common in women shows up as a slow metabolism of the liver. Typically, a woman premenstrually will get drunk on a fraction of the alcohol that it takes to make a man drunk because the liver is slowed down by the antagonism between estrogen and thyroid and oxidative metabolism. It happens that thyroxine (T4) has to be activated in the liver by taking off one of the iodines in the right position to make it the active hormone called T3. If women are having low blood sugar symptoms or high estrogen symptoms—things that are the result of hypothyroidism—then T4 can very often not help or even make the problem worse. Some experimenters tried to argue that thyroid does something other than rev up the oxidative metabolism. They took slices of muscle, kidney, liver, brain, and heart, and added thyroxine (T4) to these cultured slices. They saw that the liver had a tremendous burst of oxidative activity, but the kidneys didn't do much, the muscles didn't do anything, and added to the brain, it actually suppressed oxidative metabolism. They said, "You see, oxidation isn't what thyroid really does. It just happens that the liver responds that way." But they were looking at the pre-hormone. The liver has to turn it into the active hormone before it can work in the muscles, kidneys, heart, and brain. It turns out that the brain concentrates the blood; it can have 40 times as much T4 as T3.

### Source 9 — Thyroid: Therapies, Confusion, and Fraud

Ray Peat · Article · 2009 · https://raypeat.com/articles/articles/thyroid.shtml

> In fact, the addition of thyroxine to brain slices suppressed their respiration by 6% during the experiment. Since most T3 is produced from T4 in the liver, not in the brain, I think that experiment had great significance, despite the ignorant interpretation of the author.
>
> An excess of thyroxine, in a tissue that doesn't convert it rapidly to T3, has an antithyroid action. (See Goumaz, et al., 1987.) This happens in many women who are given thyroxine; as their dose is increased, their symptoms get worse. The brain concentrates T3 from the serum, and may have a concentration 6 times higher than the serum (Goumaz, et al., 1987), and it can achieve a higher concentration of T3 than T4. It takes up and concentrates T3, while tending to expel T4. Reverse T3 (rT3) doesn't have much ability to enter the brain, but increased T4 can cause it to be produced in the brain.
>
> These observations suggest to me that the blood's T3:T4 ratio would be very "brain favorable" if it approached more closely to the ratio formed in the thyroid gland, and secreted into the blood. Although most synthetic combination thyroid products now use a ratio of four T4 to one T3, many people feel that their memory and thinking are clearer when they take a ratio of about three to one. More active metabolism probably keeps the blood ratio of T3 to T4 relatively high, with the liver consuming T4 at about the same rate that T3 is used.
>
> Since T3 has a short half life, it should be taken frequently. If the liver isn't producing a noticeable amount of T3, it is usually helpful to take a few micrograms per hour. Since it restores respiration and metabolic efficiency very quickly, it isn't usually necessary to take it every hour or two, but until normal temperature and pulse have been achieved and stabilized, sometimes it's necessary to take it four or more times during the day.
>
> T4 acts by being changed to T3, so it tends to accumulate in the body, and on a given dose, usually reaches a steady concentration after about two weeks.

### Source 10 — One Radio Network: Nothing is as it seems with COVID (July 20, 2020)

Ray Peat · Interview · Jul 20, 2020

> **Patrick Timpone:** So the plus, you know, plus, they'll stick around longer, those T3 and T4?
>
> **Ray Peat:** Yeah. In the late 1940s, when they were starting to synthesize T4 companies that became the major producer of Synthroid synthetic thyroxine. They tested their synthetic on 25-year-old male medical students, the healthiest population imaginable, and compared the glandular armor product with their synthetic. And they said, it worked exactly the same as the natural thyroid. So that was the basis now for 70 years, substituting for the natural, which had established all of our knowledge about thyroid hormone function. It was done on the basis of natural thyroid. The fact that it lowers... cholesterol, for example, immediately. There's no cholesterol excess problem if you don't have a thyroid problem. But since that idea that 25-year-old males respond to the synthetic the same way they do the natural, they failed to take into account the experiments that had already shown that estrogen was blocks the ability to convert thyroxine into the active hormone. And so they didn't test their product on even 25 year old females, much less 38 year old women at the peak of their estrogen in a very high proportion of middle aged women. Thyroxine, if it accumulates can even have an antithyroid action by suppressing your pituitary, showing zero TSH, and so no stimulation of the thyroid gland, and so no formation of T3. At the University of Oregon Medical School in the 1970s, a doctor had prescribed 100 micrograms, which was a moderate dose of thyroxine to a hypothyroid woman. And after a few months, she didn't improve. So he increased the dose to 200 over months, got it up to 400 micrograms of thyroxine per day. And she went into a myxedema coma and was taken into the medical school hospital where they found she had absolutely no detectable T3 in her body, explaining the coma. Her brain simply wasn't making carbon dioxide or energy.

### Source 11 — Episode 12: Georgi Dinkov Q&A on Pregnancy, Heredity, Children’s Health, Hypothyroidism, and More

Georgi Dinkov · Interview · Dec 4, 2020 · https://www.youtube.com/watch?v=WsM3tezRYxo

> **Georgi Dinkov:** If the thyroid gland is working and you do not have an iodine deficiency, I would not mess with it. Good, here the next questions are exactly on this topic of the thyroid gland. What do you think in general about reverse T3, because some people turn T4 into active T3, or into reverse. Yes. From the point of view of metabolic theory, what should be corrected first in this direction? So T4 in principle should never be prescribed as monotherapy. I do not know why modern medicine decided to do this. It is stupid, because T4 by itself is not — it has no hormonal effects; it is a precursor of T3. And conversion from T4 to T3 happens mainly in the liver. And so every person with even minimally troubled liver function, if you give them one such solid little dose of T4, the organism accepts this as an excess and tries to get rid of this excess. And the main mechanism for getting rid of this excess is conversion of T4 into reverse T3. T3 cannot be converted into reverse T3. That is, if you do thyroid therapy, the less dangerous version is to take only pure T3, because in the worst case it will turn into T1 and T2, which still have effects, but with weaker effect. That is, if the body decides it has an excess of T3, it will deactivate it into slightly weaker versions. Whereas T4 is not merely deactivated, but is converted into reverse T3, which functions as an antagonist, which means it directly leads to blocking the effects of thyroid hormone, and in fact leads to slowing, directly slowing metabolism. And now, that means that since T4 is the monotherapy — if you go to a doctor, everyone will prescribe you thyroxine. Now, if you are prescribed too high a dose for your liver to process in a given 24 hours, and the half-life of T4 is about one week, six to seven days, and according to the recommendations of most doctors it is taken every day. That means that no matter how small the dose is, if you take it every day, it starts accumulating.

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