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Lesser Known T2 Thyroid Hormone Activates Mitochondria

Hip

Senior Member
Messages
17,824
I just came across some interesting articles about the T2 thyroid hormone (3,5 diiodo-L-thyronine), which is available as a supplement.

T2 has the ability to boost the fat burning energy metabolism in mitochondria (as well as reduce mitochondrial oxidative stress). Refs: 1 2 3 4

Since Fluge and Mella's research showed that the glucose energy metabolism may be blocked in ME/CFS patients, boosting mitochondrial fat burning (an alternative route for deriving energy) might be a way to compensate for this blockage, and thus a T2 supplement could be beneficial in ME/CFS.

Ron Davis thinks the glucose energy metabolism may be blocked in ME/CFS as well.

Also, the fact that quite a few patients have reported substantial improvements on the ketogenic diet — a diet which increases mitochondrial fatty acid oxidation just as T2 does (see the study) — suggests that T2 could offer ME/CFS patients similar benefits to ketogenesis, without needing to follow the restrictions of a ketogenic diet.

Here are excerpts from some T2 articles (note that these are marketing articles):
T2: The Lesser Known Thyroid Hormone

T2 is made by the deiodination of T3 and rT3 (possibly more so from rT3) and mimics the effects of T3 on energy metabolism. So while it does appear to be closely related to T3, it has been demonstrated to be metabolically active, possessing its own mechanisms of actions separate from T3.

T2 appears to be more specific to the mitochondria, as opposed to the DNA-based actions of T3.

The main source of T2 is most likely peripheral tissues (rather than the thyroid), partly evidenced by studies showing that skeletal muscle acts as a target for the hormone.

One theory is that T2 is the peripheral mediator of thyroid hormones’ effects on energy metabolism.

T2 rapidly affects mitochondrial respiratory parameters.

T2 may reverse impairments in mitochondria.

T2 activates SIRT1 and AMPK – important for healthy aging and preventing insulin resistance.

T2 increases mitochondrial capacity to import and oxidize fatty acids.

T2 (3,5-diiodo-L-thyronine) - The Best Legal Thyroid Supplement On Earth - Red Supplements

In one study using human mononuclear blood cells, T2 increased the rate of respiration significantly. This was without inhibiting TSH (thyroid stimulating hormone) nearly as severely as T3 and T4 do. This means you can use T2 WITHOUT shutting down the natural production of your body’s own thyroid hormones.

Another study also examined T2’s effect on TSH levels, and it took 13 times as much T2 to cause the same TSH inhibition that T3 did. Basically, it is much safer in respect to keeping your body in a state of homeostasis and ensuring natural and optimal organ function.

T2: The Best Thyroid Supplement

3,5 Diiodo-L-thyronine is the chemical name for T2. There is a 3,3 version but that is inactive, 3,5 is what you want.

Unlike T4 or T3 it will not shut down natural T4 or T3 production.

T2 functions very similar to T3 but unlike T3 it doesn’t burn muscle while it is burning fat. In fact T2 may convert your slow twitch muscle fiber to fast twitch fibers!


Medical Information on T2: DIIODOTHYRONINE: Uses, Side Effects, Interactions and Warnings - WebMD



T2 Supplement Brands:

iFORCE TT-33 — £24 for 90 x 50 mcg capsules

Antaeus labs: 3,5-T2 — £33 for 180 x 100 mcg capsules

THYRO-T2 — $34 for 60 x 100 mcg capsules.

RED BURNER — $32 for 90 capsules (but with the amount of T2 not specified).

SAN Nutrition T2 Xtreme — £36 for 90 x 100 mcg capsules

Note that some of these supplements contain T2 in the 3,3 diiodo-L-thyronine as well as the 3,5 diiodo-L-thyronine form. But apparently, only the 3,5 form has active effects.
 
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Hip

Senior Member
Messages
17,824
have you tried any of these?

I just found the iFORCE TT-33 available quite cheaply on the UK eBay for £12, so I ordered some. I have in the past tried low doses of T3 (liothyronine), from 5 to 20 mcg daily, but did not notice much from that.

But we will see if the mitochondrial effects of T2 have any benefits for ME/CFS.


The advantage of T2 is that not only does it ramp up the fat burning route of energy production, which may provide ME/CFS patients with extra energy, but also, T2 does not seem to reduce natural thyroid hormone production to any great degree, so it should be possible to elevate your T2 to supraphysiological levels using supplements, without lowering your T4 and T3 thyroid hormones through feedback mechanisms.
 
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Skippa

Anti-BS
Messages
841
Great, bookmarked, I look forwards to your results!

Anyone else tried this before? And what is the side effect profile like?
 

Hip

Senior Member
Messages
17,824
And what is the side effect profile like?

I think we are entering into unknown territory here, so it would be wise to start with cautiously low doses, and closely monitor yourself for any untoward side effects.

This paper about T2 safety says that:
the current literature and the results presented by Jonas et al (11) indicate that, in addition to increased metabolism and reduced fat mass, T2 administration also leads to suppression of the HPT axis, increased food intake, and cardiac hypertrophy.

A particular point of concern is the observation that the lower dose of T2 used by the authors exerts negligible effects on adiposity and metabolic outcomes, yet results in a marked suppression of the HPT axis leading to reduced levels of circulating T4 and T3 (and presumably TSH), with unknown long-term consequences.

The implication of this finding is that, for a given dose, the detrimental effects of T2 on the HPT axis may preferentially occur before the intended metabolic ones. Thus, for the time being, these new data should compel users of T2-containing supplements to assess their thyroid status, err on the side of caution, and limit their daily dose, as appropriate.

So this seems to be saying that if you take T2 doses high enough to produce fat loss, then this starts to have suppressive effects on the hypothalamic–pituitary–thyroid axis (HPT axis). However, for ME/CFS purposes, perhaps you may not need to take the high doses intended for fat loss; possibly lower doses below the threshold for these side effects may suffice.


T3 hormone also causes cardiac hypertrophy, and when people like bodybuilders use T3 for weight loss and fat loss (which they do with doses up to 60 mcg daily), they don't take T3 indefinitely, but just for a few months.


Here is a Google search on the various names for the T2 supplements.
 
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sb4

Senior Member
Messages
1,654
Location
United Kingdom
I'm of the opinion of dug wallace, in that the vast majority of modern diseases are mitochondrial problems. I think it plays a significant role in ME/CFS/POTS and could be a way out.

I have been using red light on my thyroid. Red light displaces nitric oxide from cytochrome c oxidase meaning oxygen can flow in and more ATP generated. I also think red light generates more ATP through other means.

Red light has been used for a whole bunch of things including improving peoples hashimotos.

I think it could be useful in conjunction with the T2...
 

Hip

Senior Member
Messages
17,824
@sb4, red light does increase ATP (see this post), but unfortunately this light only penetrates around 2 cm into the body, so it will not reach any of the organs or tissues deeper under the skin. Pity we don't have translucent bodies like jellyfish...
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
@sb4, red light does increase ATP (see this post), but unfortunately this light only penetrates around 2 cm into the body, so it will not reach any of the organs or tissues deeper under the skin. Pity we don't have translucent bodies like jellyfish...
Im pretty sure it goes further. Shine a powerful red light at your fingers and it passes all the way through such that you can see all the viens.

No doubt skin blocks a lot of it but you only need a bit to get through (1J/cm2) to do a lot of good.
 

Paralee

Senior Member
Messages
571
Location
USA
Whoopee!! MLM always says that the reason for T2 is undiscovered. I had read once the difference in the T's, but can't remember....most always the case. If it helps mitochondria it should be beneficial for the floxed people?

I have read about B2 helping the floxed and maybe the overdosed people on B6 recover (can't remember about that one for sure). I am going to check this out.

Thank you so much, @Hip !
 

Paralee

Senior Member
Messages
571
Location
USA
Wringing my hands, I think I would go with the Thyro T-2. I wish they were in pill form instead of capsule so you could cut them down easier. If I do this, no way will I take a whole one on the first and even second time.
 

Hip

Senior Member
Messages
17,824
@Paralee I have the iFORCE TT-33 I bought sitting in front of me, but won't be able to try it just yet, as I am currently testing another protocol. But I might sneak in just half a capsule of my T2 later this week.
 

Abha

Abha
Messages
267
Location
UK
I just found the iFORCE TT-33 available quite cheaply on the UK eBay for £12, so I ordered some. I have in the past tried low doses of T3 (liothyronine), from 5 to 20 mcg daily, but did not notice much from that.

But we will see if the mitochondrial effects of T2 have any benefits for ME/CFS.


The advantage of T2 is that not only does it ramp up the fat burning route of energy production, which may provide ME/CFS patients with extra energy, but also, T2 does not seem to reduce natural thyroid hormone production to any great degree, so it should be possible to elevate your T2 to supraphysiological levels using supplements, without lowering your T4 and T3 thyroid hormones through feedback mechanisms.

Hi HiP and all on this thread.

I'm interested in your taking of IFORCE TT-33.I'll be watching for updates on that.It might help me burn off some unwanted body fat (T3 did that for me in past)
 
Messages
516
Honestly the only circumstance this would interest me is if non-responders to thyroid (like me) report responding to T2. Otherwise it's obviously a poor investment... I'm not particularly excited in this as a PDH workaround but rather as a weight loss tool as the last poster just wrote, not that that's very novel.
 

Hip

Senior Member
Messages
17,824
Otherwise it's obviously a poor investment

If it were obvious T2 was not going offer any benefits for ME/CFS, nobody would need to try it. But there is no crystal ball that can tell you this in advance. Experienced ME/CFS patients know that for all supplements and drugs, you can only really determine whether they are going to be of benefit for you when you try them.
 
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Messages
516
If it were obvious T2 was not going offer any benefits for ME/CFS, nobody would need to try it. But there is no crystal ball that can tell you this in advance. Experienced ME/CFS patients know that for all supplements and drugs, you can only really determine whether they are of benefit for you when you try them.
I know very well. I'm talking about non-thyroid responders (like me). It seems like a very poor bet unless there are such reports.
 

Hip

Senior Member
Messages
17,824
I know very well.

Please explain your thoughts and analysis. How do you know in advance that up-regulating mitochondrial fatty acid oxidation using T2 is not going be of benefit for ME/CFS? There are ME/CFS patients that have done well on the ketogenic diet, which like T2, up-regulates mitochondrial fatty acid oxidation.
 
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Messages
516
Please explain your thoughts and analysis. How do you know in advance that up-regulating mitochondrial fatty acid oxidation using T2 is not going be of benefit for ME/CFS? There are ME/CFS patients that have done well on the ketogenic diet, which like T2 up-regulates mitochondrial fatty acid oxidation.
I'm not talking about that. I'm saying I've been through at least 4 thyroid products that even in dangerous doses had zero effect due to unknown factors such as absorption, liver inactivation or product quality, and since T2 is such a similar substance it's rational to think it will be subjected to the same fate in my body. Now I'm not alone in not responding to thyroid products so this is a major question. So before I spend a dime I need to know 1) the T2 product is well-received in general and 2) typical non-responders like me get some effect from the product - before even questioning whether it may help with ME/CFS.

Now the mitochondrial fatty acid oxidation itself is of limited interest to me simply because that use is inherently limited to mainly benefiting outside the brain and because there are already well-known substances that do that e.g. carnitine combos [well and another reason but I didn't expect to get this far into it].

Edit: I keep forgetting we're writing it ME/CFS now [even though you just wrote it, lol]
 
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Paralee

Senior Member
Messages
571
Location
USA
@Hip , I think I'm going to order within a couple of days. I remember now that I read the T2 was for energy (and possibly some mood). The T3 was more to run the body efficiently. If you try it please post, but I don't see how a little bit would hurt. I felt so much better when I got on NDT. I'm trying to remember what was written somewhere about NDT not containing T2 but still escapes me.
 

Hip

Senior Member
Messages
17,824
mitochondrial fatty acid oxidation itself is of limited interest to me simply because that use is inherently limited to mainly benefiting outside the brain and because there are already well-known substances that do that e.g. carnitine combos

I think you are right that T2 will not boost mitochondrial fat burning much in the brain. This is because brain mitochondria possess only low amounts of the beta-oxidation enzymes needed to burn fat (ref: 1). The brain normally runs primarily on glucose (and possibly lactate as well, according to new theories); but because of its relative lack of beta-oxidation enzymes, the brain does not make much use of the fat in the blood as an energy source.

But T2 will increase fat burning energy production in the rest of the body, so may well help combat bodily fatigue and PEM issues in ME/CFS. And if the body is more energized by T2, that may indirectly benefit the brain.



Carnitine helps transport fatty acids across the mitochondrial membrane and into the mitochondria for burning, to create energy, and T2 does this also. But in addition, T2 also increases the rate of fatty acid oxidation (burning) in mitochondria.

See this study:
T2 was able to:

1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation

2) increase the importing of fatty acids into the mitochondrion.

And this study:
The results of the present study [show] a rapid T(2)-induced increase in the ability of mitochondria to import and oxidize fatty acids

So this suggests T2 increases both the rate of transport fatty acids into the mitochondria, as well as increasing the rate of burning of those fatty acids.

L-carnitine though may well have synergistic effects when taken in combination with T2.