Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following Myocardial Ischemia-Reperfusion Injury

[helvella]

Given the current T3 climate in the UK, we'd better hope that the authors of this paper know something we don't! They say "using commercially available and inexpensive T3"! Ho, bloomin' ho.

All too likely to end up both not available and hugely expensive.

I love the word "safely" in there.

Front Physiol. 2017 Apr 12;8:225. doi: 10.3389/fphys.2017.00225. eCollection 2017.

Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following Myocardial Ischemia-Reperfusion Injury.

Rajagopalan V1,2, Zhang Y2, Pol C2, Costello C2, Seitter S2, Lehto A2, Savinova OV2, Chen YF2, Gerdes AM2.

Author information

1 Department of Basic Sciences, New York Institute of Technology-College of Osteopathic MedicineJonesboro, AR, USA.

2 Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic MedicineOld Westbury, NY, USA.

Abstract

Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury.

Methods: Adult female rats underwent left coronary artery ligation for 60 min or sham surgeries. At 2 months following surgery and T3 treatment (described below), the rats were subjected to functional, morphological, and molecular examination.

Results: Following surgery, the rats were treated with T3 (8 μg/kg/day) or vehicle in drinking water ad libitum following IR for 2 months. Oral T3 significantly improved left ventricular (LV) contractility, relaxation, and relaxation time constant, and decreased beta-myosin heavy chain gene expression. As it takes rats ~6 h post-surgery to begin drinking water, we then investigated whether modified T3 dosing initiated immediately upon reperfusion confers additional improvement. We injected an intraperitoneal bolus of T3 (12 μg/kg) upon reperfusion, along with low-dose oral T3 (4.5 μg/kg/day) in drinking water for 2 months. Continuous T3 therapy (bolus + low-dose oral) enhanced LV contractility compared with oral T3 alone. Relaxation parameters were also improved compared to vehicle. Importantly, these were accomplished without significant increases in hypertrophy, serum free T3 levels, or blood pressure.

Conclusions: This is the first study to provide a safe cardiac therapeutic window and optimized, clinically translatable treatment-monitoring protocol for myocardial IR using commercially available and inexpensive T3. Low-dose oral T3 therapy supplemented with bolus treatment initiated upon reperfusion is safer and more efficacious.

KEYWORDS:

cardiac physiology; heart function; ischemia-reperfusion injury; therapeutic protocol; thyroid hormones

PMID: 28446882

PMCID: PMC5388763

DOI: 10.3389/fphys.2017.00225

ncbi.nlm.nih.gov/pubmed/284...

[SilverAvocado]

I looked at this partly out of curiosity about what they called a low dose. 8mcg/kg/day, so if I was one of those rats I'd be on 800mcg! What would a high dose be?!

I've noticed in other papers about T3 used for other purposes than thyroid replacement the doses are head-spinningly high.

[helvella Administrator in reply to SilverAvocado]

Many animals require far higher doses of thyroid hormone than humans (well, most of us, there are a few who seem to need staggeringly high doses).

There was a paper (yes, I did post it here) about a vet who took dog levothyroxine and ended up massively over-dosed. Veterinary tablets are often high dose.

amjmed.com/article/S0002-93...

Around 44 micrograms per kilo in dogs against 1.7 micrograms per kilo in humans. Near enough, 25:1.

[SilverAvocado in reply to helvella]

Thanks!

[helvella Administrator in reply to SilverAvocado]

That paper includes this sentence:

On further questioning, the patient realized she had recently run out of her prescribed levothyroxine tablets and had been taking levothyroxine “dog tabs” 0.5 mg/d, thinking that would be the same as the 50-μg tablets she had been prescribed, inadvertently taking 10 times the prescribed dose.

Sometimes, I correct people here for mixing up milligrams and micrograms. I fully accept that, most of the time, it is not a serious mistake as we all understand what was meant. But this is a case of a medical professional getting confused. And suffering the consequences.

There are two documents in this link intended to help anyone who is confused - Understanding Units and The Microgram:

dropbox.com/sh/3waycnbzhywi...

[TSH110 in reply to helvella]

helvella gosh I knew they needed more but not that much more! Perhaps because my tribe are sighthounds they are more sensitive to all drugs and need less. I wonder how much less - it is still a lot more than us.

[jimh111]

Thanks for posting, it's interesting. You can get the full pdf here journal.frontiersin.org/article/10.3389/fphys.2017.00225/pdf . It will be some time before I can read (and not understand, cardiology is far too complex). Noone knows if low T3 syndrome in cardiac cases is protective or harmful so this is a first step. It's probably the case that in different forms of heart disease T3 will be harmful but in these cases it looks like it will ultimately save lives.

[helvella Administrator in reply to jimh111]

It is not the first paper to identify T3 as (possibly) beneficial in ischaemia/reperfusion. And what might be a related issue, maintaining quality of organs for transplant.

[humanbean in reply to helvella]

maintaining quality of organs for transplant.

I wonder if T3 will still be imported for use in-house by the NHS for the use of the dead?

[helvella Administrator in reply to humanbean]

Oi humanbean!, black humour is restricted to qualified doctors. Can't have patients making such remarks.

[humanbean in reply to helvella]

Well, I'm registered as an organ donor, for what my wreck of a body is worth. It turns out it might be my only chance of ever getting NHS-sanctioned T3.

[Marz in reply to jimh111]

jimh111 - have you checked out the book - Thyroid and Heart Failure - on Amazon ? All research papers and you can look inside at the contents. T3 seems to be the star of the show ....

[jimh111 in reply to Marz]

Thanks, have printed off your comment as I will be extreemly busy the coming week.

[Marz in reply to jimh111]

amazon.co.uk/Thyroid-Heart-...

[jimh111 in reply to Marz]

£141.50 but deivery is free so that's OK!

[helvella Administrator in reply to jimh111]

Half that on ABE:

abebooks.co.uk/servlet/Sear...

[Marz in reply to jimh111]

I saved up for it - too many ex-pats with heart conditions around here who glaze over when I suggest a thyroid test could be appropriate. Worth every penny. You will be able to find all the papers on PubMed ....

[TSH110 in reply to jimh111]

jimh111 c.£90 if you are canny and get a new copy! 😳

[Teuchter in reply to Marz]

Thank you, Marz.

That book looks very interesting. I've been struggling with hypothyroidism​ for 15 years, and last year I had a heart attack, which has made life harder.

I'm now on 200mg a day of levothyroxine - I was on 150 before the heart attack - but feel I'm less energetic than ever. I strongly suspect some of the one-size-fits-all handful of heart tablets I have been prescribed, which includes beta-blockers. My cardiologist doesn't seem to think so, but then he doesn't think my hypothyroidism has anything to do with it either....

[Marz in reply to Teuchter]

Apparently people with good levels of T3 recover faster from heart events. Do you know if you are converting the 200 mcg T4 into the ACTIVE T3 ? Do you have some results to share.

Ferritin - Folate - B12 - VitD - if they are low in range they too can cause a problem with conversion and the heart.

You can click onto Look Inside - on the book and have a read .... As I am sure you know Liothyronine is T3. Mentioned often

If can also track down some papers for you about T3 ....

[Teuchter in reply to Marz]

The last blood test showed TSH 0.03 (0.1-4.0) and T4 14 (12-22).

I've never had T3, B12, etc tested because my relationship with my doctor's surgery has been nonexistent for 14 years, since I was diagnosed with: "Depression with hypochondriacal delusions."

The only good thing I can say is that they keep repeating my prescription, without questioning my consumption of levothyroxine (which I adjust myself according to how I feel).

So I never phone their surly and obstructive receptionists to book an appointment to see a GP roll his/her eyes and say "It's all in your head".

I've more or less given up hope of ever feeling reasonably well again; these days I just stumble along and try not to think too much about things, especially the future. But if I thought T3 would help me, and I could afford to buy it, I might give it a go.

[Marz in reply to Teuchter]

Oh dear your post makes me sad. I hope you know from reading the posts here that you are not alone. Are you able to have some Private Testing done through Thyroid UK. Let me know and I will send you the info.

[Teuchter in reply to Marz]

Don't be sad!

I'm sorry if I sound a bit miserable; I really shouldn't; my daily life isn't intolerable: I'm not in constant pain, I'm not bedridden, and I am still working, albeit at a snail's pace.

I am very glad to have found this forum, and grateful for the support of its members, particularly of regular contributors like you.

I just (selfishly) took the opportunity to whinge a bit, which has lightened my burden and lifted my spirits, for which I thank you.

Regards

Geoff.

[janeb15]

There have been many papers written over the years relating to the use of T3 during and after heart surgery, and yet GP's panic at the thought of "overdosing" on thyroid replacement as they perceive it will damage heart function. It seems that there is some serious joining up of dots to be done.

[helvella Administrator in reply to janeb15]

The negative impact of hyperthyroidism, where T3 levels can be incredibly high, seems to have been taken not as a caution about massive overdosing, but as a ban on even barely adequate dosing.

[TSH110 in reply to helvella]

helvella is there any evidence that T3 is as dangerous as claimed in the doses we might take? Does it really cause heart attacks in those who are hypothyroid. How many are dying how often? I seem to remember reading some detailed research by Broda o'Barnes that would refute these claims. Wat is the truth of it as far as we know?

[helvella Administrator in reply to TSH110]

Would need to look things up to know.

I have my doubts as to how many actually die from excess thyroid hormone - other than a true thyroid storm.

[TSH110 in reply to helvella]

helvella so the information may exist. Do we know how many die in U.K. due to hypothyroidism/ lack of treatment hence lack of T3/T4? I can't be alone getting pretty close to meeting such an untimely end. I wonder if lack of T3 kills more than surfeit and can this be demonstrates by stats? I am sure Broda O'Barnes showed statistically NDT greatly protected against death from heart failure.

[helvella Administrator in reply to TSH110]

I have put in a request for some statistics - will post if I get anything useful.

[TSH110 in reply to helvella]

helvella Thanks!

[janeb15 in reply to TSH110]

When the late Dr. Lowe recommended T3 to my daughter back in 2002 he suggested that she increase the dose until such time as she noticed hyper symptoms. She did so until she reached a dose of 125 mcg which she maintained for many years. Her GP refused her any help and told her she was "dangerously hyperactive" even though her pulse remained in the low 50's (which was considerably better than the 38 it had been), she had very low blood pressure, her temperature never reached 37 and at times she could hardly get out of bed in the morning. We do believe that T3 kept her alive until we found a doctor in the USA who got to the bottom of her thyroid dysfunction which was merely a symptom of a much greater problem. She has now been able to reduce her T3 intake to 50-75mcg, and her pulse is in the mid 60's. I believe that the fears regarding T3 are overblown. I have been unable to find any evidence to the contrary. Jane x

[Marz in reply to janeb15]

amazon.co.uk/Thyroid-Heart-...

[silverfox7]

I know of one knowledgeable person on here who was given T3 to stabilise her heart after open heart surgery so it's not the devil some make out but like anything else it has to be used in a responsible manner.

[Marz in reply to silverfox7]

amazon.co.uk/Thyroid-Heart-...

[janeb15 in reply to Marz]

Thanks Marz. The area of cardiac/thyroid relationship is still in need of plenty of clarification it seems. I noticed that the British (apparently disappointing) contributor was Dr. Toft - enough said!! Jane x

[Marz in reply to janeb15]

Yes - I have the book so have been able to enjoy/appreciate the great research of others.

Yes I think it was before he retired from the BTF and changed his tune !