Levothyroxine treatment and gastric juice pH in humans: the proof of concept

[helvella]

Although this paper has a publication date of almost a year ago, I have only just noticed it.

The results of the study do not seem surprising but, as always, it is essential that the work is performed - otherwise we are just making assumptions.

Levothyroxine treatment and gastric juice pH in humans: the proof of concept.

Virili C1, Bruno G2, Santaguida MG3, Gargano L3, Stramazzo I1, De Vito C4, Cicenia A2, Scalese G2, Porowska B5, Severi C2, Centanni M1

Endocrine, 27 Apr 2022, 77(1):102-111

DOI: 10.1007/s12020-022-03056-1 PMID: 35477833 PMCID: PMC9242941

Abstract

Purpose

Despite the absorption of oral thyroxine (T4) occurs in the small bowel, several patients with gastric disorders show an increased need for T4. In vitro evidence suggested that medium pH variations interfere with T4 dissolution. This study was aimed at finding the proof of concept of a direct relationship between the minimal effective dose of T4 and the actual gastric juice pH.

Patients and methods

Among 311 consecutively thyroxine-treated patients, 61 bearing Hashimoto's thyroiditis (52 F/9 M; median age = 51 years) who complained persistent dyspepsia and/or upper abdominal symptoms following a noninvasive workup for gastrointestinal disorders, underwent EGDS with multiple biopsies and gastric juice pH measurement. All patients accepted to take thyroxine in fasting conditions, abstaining from eating or drinking for one hour.

Results

Thyroxine requirement increased along with the rising gastric pH (ρ = 0.4229; p = 0.0007). A multivariate analysis revealed that gastric pH was, beside body mass index, the far more important independent variable in determining the effective dose of T4 (p = 0.001). The ROC curve revealed that the pH threshold for an increased thyroxine requirement was at 2.28, being the AUC by 78%. Subdividing patients by the histologic findings, it appeared a significant increase (p = 0.0025) along with the progressive damage of gastric mucosa.

Conclusion

The in vivo measurement of gastric pH highlighted its key role in determining the minimal effective dose of oral T4 and may explain the interference of food, of some drugs and gut disorders on levothyroxine treatment.

Full paper freely accessible here:

europepmc.org/article/MED/3...

[jimh111]

Dr David Halsall the chief pathologist at Addenbrooke's suggests taking levothyroxine with fruit juice if you are worried about absorption. I've no time or inclination to read this study but Fig 2 suggests that if your stomach pH is below about 4 most people should not have a problem absorbing levothyroxine. Most fruit juices have a pH around or below 4 healthyeating.sfgate.com/ph... . Of course swallowing orange juice will not bring your stomach pH down to the same level but it should help. We could also try dissolving a levo tablet in fruit juice before swallowing it.

[helvella in reply to jimh111]

I suggest lemon or lime - but that is purely on the basis that there has been a study which looked at lemon, and several Pernicious Anaemia suffer regularly use lime juice.

And I have emailed authors of this paper with a couple of thoughts. If they get back, I'll post/reply.

[tattybogle]

well ... i might have been wrong ...so i thought i'd better admit it .. and this post looks like a useful place to do it.

after reading somebody's reply about taking their Levo sublingually, i went off looking for some evidence to confirm that a molecule of T4 is too 'big' to be absorbed through the oral mucous membranes ..( because i thought it was , and have written replies to that effect in the past)

and as well as the size of the molecules ( not that i really understand what a 'molecule' is 'proper' science has always baffled me.. i can understand what a tree is , and how a table is made out of it ...but not what 'a molecule' is.. )

anyway ~ i digress ~

so ....as well as the size of 'it' and 'whether T4 itself can squeeze through your gums or tongue to get to your blood' ~i also thought that gastric acid was an intrinsic part of the process for T4 to be absorbed ~ making a further reason why "sublingual" levo shouldn't work very well at all, and all that was happening when people "take it sublingually" was that the excipients dissolved in the mouth and the T4 was being swallowed later with either saliva or food particles .. (which is why i'm putting this find here on this post) .

While looking for some proof thatT4 can't be 'absorbed' sublingually and dissolving it in the mouth would therefore be a less effective way of getting T4 into the blood than swallowing it whole ,...... i seem ? to have found proof that it can be BETTER absorbed sublingually after all ? or at least i think i have .. does this study make sense ?... here endocrine-abstracts.org/ea/...

Study of the efficacy of sublingual route administration of levothyroxine Na nablets vs oral route in cases with refractory primary hypothyroidism

Mina Michael Nesim 1 , Yara Mohamed Eid 1 , Manal Mohamed Abu Shady 1 , Salah Huessein El Halawany 1 & Gehad Soliman El Shamy 2

1Ain Shams University, Cairo, Egypt;2October University, Cairo, Egypt

Background: Hypothyroidism is a common disorder, with a prevalence of approximately 5% and incidence of approximately 250/100,000 per year in the adult population, but both prevalence and incidence keep raising. Refractory hypothyroidism is defined by persistent TSH increase despite the administration of supra physiological weight-based dose of levothyroxine, which is usually >1.9ug/kg/d in patients with primary hypothyroidism.

Aim of the Work: To compare the efficacy of the sublingual levothyroxine Na tablets administration with respect to oral levothyroxine tablet in hypothyroid patients refractory to treatment.

Patients and Methods: This was a cross over clinical trial of 6 weeks duration that was conducted at 6th October and Ain Shams university hospitals on 40 subjects who were diagnosed 1ry hypothyroidism and who are documented to be refractory to treatment Thyroxine level was assessed using (Thyroxine absorption test) during standard oral Levothyroxine administration and 1 week after shifting to sublingual route Patients were shifted to the sublingual route on the same dose used with oral route administration Antiparietal cell antibodies, anti-TGA were measured. TSH and free T4 value were assessed finally after 6 weeks of sublingual route administration.

Results: Our study revealed highly statistically significant decrease in TSH level with Sublingual levothyroxine Na tablets (Eltroxin) compared to Oral levothyroxine tablets (Eltroxin) and also statistically significant increase in FT4 with Sublingual levothyroxine Na tablets after 1week compared to Oral levothyroxine tablets, while after 6 WEEKS sublingual levothyroxine Na tablets insignificant compared oral levothyroxine.

Conclusion: Our study revealed that sublingual levothyroxine Na tablet may be more effective than oral levothyroxine tablets in controlling TSH levels in refractory hypothyroidism and sublingual levothyroxine Na tablets may overcome some absorption problems of oral levothyroxine tablets. Autoimmune gastritis should be taken into consideration as an additional factor influencing the daily requirement of levothyroxine Na.

[tattybogle in reply to tattybogle]

oh... DoH! i 've just twigged they were all refractory to oral levo .... so that changes things a bit ... i got carried way thinking it said "sublingual was better" and didn't look at " better than what "

[helvella in reply to tattybogle]

If you imagine an atom as a billiard/snooker ball, the image below shows levothyroxine. The big purple is iodine. The black is carbon. The white is hydrogen.

If we are talking about levothyroxine in our mouths or swallowed, it will be "hydrated". That is, surrounded by molecules of water. Standard form is pentahydrate. Five water to one levothyroxine.

That makes it act as if it is bigger than the basic levothyroxine molecule. Like mud in a ball!

It is not impossible for it to transfer across but makes it less likely. And, inside our bodies, levothyroxine has to be taken into cells in order to be converted into T3. But that transfer is performed in a very special transporter - not just anywhere.

Molecular structure of levothyroxine

[tattybogle in reply to helvella]

Thankyou for the picture ,,and the snooker balls .... and the mud balls.

i understand a lot better like that

[tattybogle in reply to helvella]

So if i had a big enough microscope in the shed and looked at 'a bit of Levothyroxine with out any fillers in it '.. is that pretty much what i would see ? apart from presumably 'not being purple'

[helvella in reply to tattybogle]

Sort of!

Just had a look for a video - found the one below. Don't worry about the exact words or molecules involved. Just let your mind float and get what you can out of it. I'll try to find something more precisely on-topic.

youtube.com/watch?v=yk14dOO...(Not working as expected?)

[helvella]

So far as I am aware, there has been far too little research into T3, absorption, etc.

There are two tendencies!

First, those who think that T3 is hardly affected by anything.

Second, those who base their thoughts on knowledge and experience of levothyroxine.

Reality is probably both are not quite right! But there are reasons that both ideas exist.

Just did a quick search and realised immediately that it is a complicated area.

europepmc.org/search?query=...

Afraid I do not know anything about it. Your reply is sensible and deserves answers. Maybe re-post as a new question?