Found this snippet earlier today. Mulling it over, I really am not sure if it is the most interesting thing I have read in quite a while. Or an empty article with virtually no reason to exist.
What is unusual is the very specific implication that the effect is from synthetic levothyroxine.
If there are any experienced biochemists around who would like to comment, I'd certainly like to read those comments.
Levothyroxine, a synthetic form of thyroid hormone, has been clinically used to treat thyroid hormone deficiency. UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, and UGTs-inhibition based drug-drug interaction has been widely reported. The aim of the present study is to investigate the inhibitory effect of levothyroxine towards UGT1A6-catalyzed 4-methylumbelliferone (4-MU) glucuronidation. The results showed that levothyroxine inhibited UGT1A6-catalyzed 4-MU glucuronidation reaction in a dose-dependent manner. Furthermore, Lineweaver-Burk and Dixon plots showed the inhibition of UGT1A6 by levothyroxine was best fit to competitive inhibition, and the inhibition kinetic parameter (Ki ) was determined to be 15.3 μM. Given that UGT1A6 is one of the most important UGT isoforms catalyzing the glucuronidation reaction of many important clinical drugs, including aspirin and serotonin, inhibition of UGT1A6 activity by levothyroxine will significantly influence the pharmacokinetic behaviour of these drugs. Therefore, clinical drug-drug interaction due to the inhibition of UGT1A6 by levothyroxine should paid much attention.
General information
Issue date: 2012
Document language: English
Journal: Latin American Journal of Pharmacy; vol. 31, no. 5
Origin: Colegio de Farmacéuticos de la Provincia de Buenos Aires
Rod, if it's proved synthetic Levothyroxine inhibits enzymes important to metabolising other drugs and affects dosing and how they work, I wouldn't call it an empty article.
Very complicated, Clutter. For example, ASA is used to inhibit platelet aggregation. Depending on enzymes and other factors, some people can be kept on a very small dose. Whilst others require a much higher dose. But this is usually only studied in research and not so much applied clinically. Most people are given 81 mg of ASA.
Now introduce the possibility that people taking synthetic T4 somehow metabolize ASA differently than 'normals'.........phew.
There would need to be a huge, whole heaping amount of research done because a small percentage of the population takes synthetic T4. Not to mention anyone on ASA therapy already has something wrong like they've had aortic grafting or stents or a blood clot to the brain.... very complicated. Lots and lots of variables.
It would make more sense to just monitor individual patients more closely.
Genetics factor in as well. For example a simple thing like caffeine: some people are fast metabolizers, some slow and some intermediate..... Or ethanol: Asians don't metabolize it well so they get drunker than Europeans and get vasodilation (red faces) on similar 'doses'.
I find it a bit odd that this article with all Chinese names as authors and whatnot is published in a journal out of Argentina. Albeit, a lot of very good research is coming out of Brazil since it's cheaper to do work there and the country is working hard at elevating its status as a centre for research excellence.... but still... Maybe I'm just an elitist snob. Oh heck, I am an elitist snob. There.
O I agree - it might be very important. But it is only a communication - not a full paper. It does not explain itself properly - like how have they determined that it is synthetic levothyroxine? What would happen if the person took a balanced amount of T3 as well? Is there an implication that desiccated thyroid might not have this effect? If it is a speculative few words, then it is only a teaser.
Rod, Given that synthetic Levothyroxine is the most widely prescribed thyroid hormone replacement (and possibly the only form available in whatever country the research too place) it may be the only one they researched.
The authors are from 'Yantai Mountain Hospital, Yantai, Shandong province, China', not that knowing helps much. It is classified as a "Short Communication" which it certainly lives up to. I agree with Rod, it would be interesting to know more. PR
Synthetic levothyroxine is not the same as that produced by the thyroid. It is the sodium salt.
On the same basis is it not the same as desiccated thyroid.
I don't know what difference use of the sodium salt makes (though it was quite an early choice) - but as a simple statement of fact, endogenous levothyroxine from a thyroid and synthetic levothyroxine are not identical.
My point about desiccated thyroid was partly based on the fact that it contains T3 as well. It was really a follow-on from the idea that taking T3 as well might make a difference.
Aspirin is synthetic. No doubt about it in most cases.
Sodium salicylate is commercially prepared by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100 atm) and high temperature (390K) - a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid.
Then follow the path described in your link.
However, there certainly are salicylates which could be, and sometimes are, obtained from plant sources, such as oil of wintergreen.
But, to be honest, I really don't give a fig whether something is "natural" or "synthetic". I want it to work effectively and have the minimum side effects. And I see the impact of what is currently dished out as the standard treatment for hypothyroidism not working effectively and seeming to cause many and serious side effects. Not in me (I swallow synthetic levothyroxine without any obvious problems) but in others. I see that desiccated thyroid works better in at least some. Why? I don't know.
Interestingly, levothyroxine can have a chromatographic peak indicating up to 1.0% liothyronine. (Though access to manufacturers' data to know whether this is exploited to the full, or they never find any, is unlikely to be available to any of us.)
Funnily, I had always thought that even subtle differences have been shown to have effects that were not appreciated until someone thought to look very closely. If you take the billiard ball approach, then your response appears sound. If, possibly, things are a bit more complicated (solvent not being pure water, dissociation happening more slowly than you might anticipate) then maybe the sodium does have an effect? Or something else about synthetic levothyroxine?
aDoctor, this is an interesting quandary to me. The 4:22 to 1 ratio always seems to be more of a concern for doctors than it does for patients. In the patient world this is not a topic of discussion, we just don't see it. If you do have a patient experiencing hyper symptoms you just do the obvious and reduce the dose slightly until they don't have hyper symptoms but we don't see any discussion about getting short term hyper symptoms from the T3 in NDT. I'll agree that in the long run we don't know if there are any effects from this although in the 100+ years NDT has been used I've never seen any studies reporting adverse effects.
I'm curious, have you had any patients that reported short term (few hours or less) hyper symptoms from taking NDT? Did reducing their dose fix that problem but leave them feeling hypo? PR
aDoctor, I quite agree that all thyroid medications are a compromise compared to what the body accomplishes naturally. I'm also aware that there are a wide range of ratios that may work for people. Dr. Blanchard has been using 98.5% T4 with 1.5% timed release T3 or NDT (+ or - 0.05%) successfully for many years although he does a lot of seasonal adjustment. And of course some people do just fine on T4 only and there are those that do not regain their health until they get on T3 only. The latter situation is rarely acknowledged by medicine. Given the amazingly wide range of variation in human biochemistry nothing should surprise us.
I do not have further symptoms, I'm just an old geezer endocrine patient with a curious mind and over a hundred years of family history dealing with endocrine imbalances, most of which hasn't been pretty. I had two hypo parents, one diagnosed, one not, so I am an outlier and do not react like your usual hypo patient which makes most doctors more of a problem than the problem. In our family T4 is a disaster whereas NDT is a lifesaver. I appreciate your comments. PR
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