This paper behind a paywall shows that liquid T4 is much better than tablet-form in controlling and responding to therapy. I've appended the abstract to show study and results
Katarzyna Bornikowska, Małgorzata Maria Gietka-Czernel, Dorota Raczkiewicz, Wojciech Zgliczyński
Pharmacokinetics and Comparative Bioavailability of a Levothyroxine Sodium Oral Solution and Soft Capsule
DOI: 10.3390/jcm10225233
Abstract
Levothyroxine (LT4) is a standard therapy in hypothyroidism; however, its bioavailability and therapeutic effects might be affected by many factors. Data shows that therapy with liquid LT4 characterized by quicker pharmacokinetics provides better thyroid hormones control than tablet LT4. We addressed the quality of life (QoL) and efficacy of the new ethanol-free formula of liquid LT4 (Tirosint®SOL) treatment in 76 euthyroid patients with primary (PH, n = 46) and central hypothyroidism (CH, n = 30), and compared the results to retrospective data on equivalent doses of tablet L-T4 therapy. After 8 weeks of liquid LT4 therapy, we found a significant improvement in QoL in both PH and CH patients. TSH levels were unaltered in PH patients. Free hormone levels (fT4 and fT3) increased in all the patients, with the exception of fT3 in the CH group. SHBG and low-density lipoprotein (LDL) also improved. Liquid LT4 therapy provided a better thyroid hormone profile and improvement in patients’ QoL than the tablet form, which was possibly due to the more favorable pharmacokinetics profile resulting in better absorption, as suggested by the increased free thyroid hormone levels. In summary, this is the first study addressing the QoL in hypothyroid patients, including primary and central hypothyroidism, treated with liquid LT4 formula in everyday practice.
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I think this paper is available under a different title here mdpi.com/2077-0383/10/22/52... . I haven't had time to read it but it seems it is not placebo controlled. The paitents will know whether they are taking the liquid or tablet form. It would have been possible to get the patients to take a liquid and tablet with levothyroxine in one form thus achieving placebo control. The liquid form delivered slightly more homone which could have been achieved by adjust the tablet dose.
Liquid levothyroxine is a boon for the small number of patients who cannot absorb tablets. I have heard an endocrinologist say that many patients who have trouble absorbing levothyroxine tablets acheive very good absorption when they take the tablets with vitamin C (ascorbic acid) or fruit juice. I wonder if this study was deliberately not blinded so that good results could be presented for a much more expensive form of levothyroxine although they declare no conflict of interest. Perhaps a good quality placebo controlled study would have found no difference (for same absorbed dose) and not be published.
Edited. The study is partially financed by IBSA, a multinational pharmaceutical company that markets liquid levothyroxine.
IBSA brought Tirosint to the arena. I agree there might be a certain amount of bias in the study. And placebo controlled could help to offset this.
It isn't just about absorption though. Lots of the excipients in tablet forms of levo cause problems for people. If the Tirosint liquid form eliminates or even minimises these 'unwanted side effects', that has to be a good thing. How many people are prescribed umpteen other medicines that they might not need if they had a more effective form of T4 replacement.
Valid point about excipients although the liquid forms will also contain excipients (perhaps fewer and simpler?). No excuse for not doing a placebo controlled study. In my opinion this study should not have been published due to lack of placebo control and the authors wrongly stating there was no conflict of interest.
That's correct. I had seen this on the website but hadn't double checked it with the formal drug websites. I'm not against it use just think tablets should be used where possible, they are cheaper and may be more stable.
There is reason to think that liquids could be more stable!
Levothyroxine has issues with regards to water. At least in a gel or liquid, it will not change between hydration forms.
Further, it is clear that there can be reactions between levothyroxine and lactose. (And likely other possible excipients. There are papers pointing out that several current exceptions are poor choices.)
I'm on a trial of Tirosint. I like it two weeks in which I know isn't soon enough to tell levels. I like that it doesn't make me sick like levo and Synthoid did. I can hold down and digest my food. It looks like a vitamn D capsule. Good thing one would take first thing in the morning and one in the late afternoon/eveninf else you'd get confused which is which in you hand.
My concern my endo can't or wont answer: Does Tirosine have the Tirosene enzyme associated with with RET positive papillary thyroid cancer? The names are eerily similar.....especially for those us who had out thyroids taken for PTC.
What I don't like is paying out of pocket since my PPO won't cover it. That $300 is a lot for my tax bracket.
Up the thread, RedApple has listed the full ingredients of both Tirosint and Tirosint SOL.
Tirosint-SOL is a unique levothyroxine formulation that contains only 3 ingredients—levothyroxine, glycerol, and water. tirosintsol.com/the-tirosin...
I think the Tirosint capsule excipients are just levo, gelatin, glycerol and water.
It has no enzymes at all.
Levothyroxine has a backbone of thyronine - which, more or less, consists of two tyrosine molecules attached to each other.
Tyrosine is just one of the 20 standard amino acids we all need to make our cells.
As I see it, "Tiro" is just a latinised form of "thyro".
And Synthroid is just another levothyroxine. Nothing special about it. If you tried every single levothyroxine product available, you might find one as good (for you) as Tirosint.
What would be the ethics of doing a placebo controlled study in genuinely hypothyroid patients?
Would you volunteer to take part in a study where on the flick of a coin you either get the dose you need or nothing? That would be the effect if you simply do not absorb tablet form.
You misunderstand. In one phase patients would receive a real tablet and placebo capsule, in the other phase the tablet would be placebo and the capsule contain levothyroxine. This would be easy - but might not give the results the pharmaceutical company wants!
More important what's really needed is such a trial in a group of patients who are not doing well on tablets and who demonstrate poor or erratic levothyroxine absorption. I think the real answer for many patients will be some T3 in the form of liothyronine or NDT.
Consider someone who is taking 100 micrograms of levothyroxine as a liquid/gel. But when they were taking a tablet, they only absorbed 25%.
They will, at the toss of a coin, take 100 as a liquid and a placebo tablet resulting in 100 being absorbed. Or a placebo as liquid and 100 as a tablet of which they only absorb 25. Potentially a massive under-dose. (And it could be even worse.)
Now put your hands up if you would volunteer for that!
I still have to read the study but a quick glance shows that patients with malabsorption were excluded from the trial. In general patients would be started on tablets and moved to liquid if it is felt necessary. If there is malabsorption of tablets it is important to find out why, unless the reason is already known.
The subjects in this trial on tablets had slightly lower fT4 levels but curiously they declined to state the timing of levothyroxine ingestion and taking the blood. Liquid levothyroxine will be absorbed more rapidly and could give higher fT4 results if the blood is drawn shortly after taking the levo.
The aim of this trial seemed to be to 'con' people into believing liquid levo (profitable) magically results in better patient response with small differences in hormone levels. The absence of placebo control facilitates this objective. Maybe I'm too suspicious of big pharma but history suggests I should be.
I think the demonstration of much better pharmacodynamics is a strong indication that could override objections to the absence of a control group - who could take the formulation without bad effects and simply show equivalence in T4 takeup above the norm. I wonder however if this would constitute a satisfactory control group. Differences in detail, given the variability of the measurements could obscure the control group value
Did you mean pharmacokinetics? I haven't read the study yet but had in mind a cross-over study placebo controlled by giving a capsule and tablet in each phase with one of containing placebo and the other levothyroxine. Maybe I'm too suspicious but I don't trust research that is sponsored and has faults that could be deliberate. I'm not shooting the messenger, I'm grateful for all your posts.
If a patient reports persistent symptoms when switching between different levothyroxine tablet formulations, consider consistently prescribing a specific product known to be well tolerated by the patient. If symptoms or poor control of thyroid function persist (despite adhering to a specific product), consider prescribing levothyroxine in an oral solution formulation.
Hi all and SlowDragon 😊Thia is all very interesting.
Id like to ask a question that is slightly off track. Hope nobody minds.
I had a bowel obstruction 15 years ago and had a piece of my small bowel, (ileum) taken away. Does this mean I may benefit from liquid Thyroxin? Is it the Ileum where Thyrixin is absirbed?
i am concerned that ny tablets dont get absorbed properly in my small bowel.
I think I asked this question a while back but cant remember the responces I got.
Thabks SDYes, I SI B12, so levels are now showing as high.
If B12 shows as high in blood stream does that mean it is actually being sbsorbed though. This is the thing Im never sure about 🤭
D3, I take sublinguily too as levels were rock bottom.
I take C with my Thyroxin and Selenium and magnesium in the evening and Iron before bed.
I was wondering where abouts in the gastro system Thyroxin is absorbed.
This is something I can never seem to clarify. If I have some of my small bowel missing. is that affecting absorbsion.? if so would liquid T. help and if so how?
Would it be absorbed, like vitamin D through the membrane in my mouth and so by passing the gastric system?
Phew ! Quite a lengthy read ! My poor brain hurt towards the end. An excellent document and once more illustrates how much better medicine would be if 'experts' could work together. Eg Endocrinologists and Gastroenteroligists - instead of remaining in their boxes of expertise.
I am one of the few who cannot tolerate all levothyroxine tablets due to incipients. I have been hypothyroid for 15 years but it was only about 2 years ago that I had problems with the tablets, when I assume the incipients changed. Eventually 6 months ago, after feeling terrible for some time, my GP agreed to put me on liquid Thyroxine. It has definitely made a difference to the way I feel and my TSH level corrected once I found the right dose. One gripe is that it is so fiddly taking the liquid. First thing in the morning, find my glasses, shake the bottle, put the syringe in, turn it upside down and make sure you measure the correct amount into the syringe - quite difficult with arthritic hands. The other gripe is that it contains parabens which I don't like taking and will not agree with some people. I know I should be grateful that I can get this on the NHS - and I am. Can you get Tirosint in this country and if so will the NHS provide it? Is it even more expensive than liquid thyroxine?
A full list of all thyroid hormone products licensed in the UK (and many others):
helvella - Thyroid Hormone Medicines
I have created, and try to maintain, a document containing details of all thyroid hormone medicines in the UK and, in less detail, many others around the world.
Typical dose would be one 5 mL spoonful. (The idea is that the strength of solution would be selected to achieve that, if possible. But some might well need two spoonsful.) Thus, twenty spoonsful per bottle.
My Endocrinologist felt I wasn’t absorbing Synthroid well. I trialed Tirosint but found it dehydrating. So I took a little of both with the Endocrinologists OK. I went gluten free over this time.
Once the gluten free meal plan improved my gut health I was no longer able to tolerate Tirosint at all, I found it dehydrating, so informed the Endocrinologist I was dropping that thyroid medication.
I think going gluten free did the trick but Tirosint seemed to be helpful in the interim while the gut was in need of recovery. I think the manufacturer needs to produce different strengths of Tirosint if that is possible.
I only ever took 13 micrograms of Tirosint daily. Before going completely off it I tried drawing up half the capsule’s liquid in a syringe & making two capsules (for two separate days). I still could not maintain my weight. Tirosint enhanced my mood so I wish I could have tolerated it.
I have read in the past on this site (for weight loss) that if your labs are less than idea, you require more thyroid medication not less. However I felt (& looked) like I was completely going under, my body sent red flags 🚩 to stop it. I seem fine now on Synthroid while gluten free.
In hindsight I am thinking that the combo of Synthroid & Tirosint was never a good idea. That switching to another thyroid medication may have been smarter than this experimental combo.
Correction: I took only 13 micrograms Tirosint after reintroducing Synthroid again.
I am trying to get my endo to give me a trial of Tirosint ince I am having trouble with fillers in Mercury Pharma & Accord. I understand some of the liquid levo contains parabens. Is there one which is fairly pure and contains only what is absolutely necessary?
Sorry I replied to Doris11 instead!!! Wanted to find a liquid (Tirosint) which has no parabens and only the absolutely necc ingredients. I have developed a reaction to levo MP & Accord after 20 years!
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anyone on liquid T4 and if so, does it work for you?
High T4 but feeling better
T4/T3 conversion getting better
Results after 8 months of T3/T4 tablets 
