T4 Has A Use Besides Being A Pro-hormone, Who Knew

I've been spending some time trying to absorb Dr. Ben Lynch's site, mthfr.net/ . One of many things I came across was this.

Proc Soc Exp Biol Med. 1987 Feb;184(2):151-3.

Riboflavin metabolism in the hypothyroid human adult.

Cimino JA, Jhangiani S, Schwartz E, Cooperman JM.


It had been shown that thyroxine regulates the conversion of riboflavin to riboflavin mononucleotide and flavin adenine dinucleotide (FAD) in laboratory animals. In the hypothyroid rat, the flavin adenine dinucleotide level of the liver decreases to levels observed in riboflavin deficiency. We have shown that in six hypothyroid human adults, the activity of erythrocyte glutathione reductase, an accessible FAD-containing enzyme, is decreased to levels observed during riboflavin deficiency. Thyroxine therapy resulted in normal levels of this enzyme while the subjects were on a controlled dietary regimen. This demonstrates that thyroid hormone regulates the enzymatic conversion of riboflavin to its active coenzyme forms in the human adult.


The MTHFR gene defect also relates to thyroid problems.

Dr. Lynch:

Simple question: are you saying that MTHFR can cause thyroid disorders? How could so many people with thyroid disorders also have MTHFR and one not cause the other? Thanks.

Dr. Lynch Replied:

"Both ways – hypothyroidism can cause MTHFR downregulation – just like it would be having a snp for the MTHFR gene.

The MTHFR snp can cause thyroid issues due to lower biopterin recycling which causes decreased tyrosine levels and thus thyroid hormones."

It never gets any simpler. We are one complicated little bio-physics, bio-chemistry machine. PR

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20 Replies

  • ...sounds interesting and meaningful - if only I could understand it all - some yes ! Was always better at drawing pictures and writing long flowery essays than studying the sciences ! I will however have another read and try harder :-) Thank you for posting - we need to be challenged from time to time - we also need to stay ahead of the game !

  • Marz, don't feel alone about understanding it all. I have read a lot but I still have to look up terms and reread articles, sometimes several times, to get it all to sink in. Even then I don't get all of it. There are a few things I have to work on in this piece. PR

  • I listened to a podcast once from that website. It was really interesting. Mentioned the importance of riboflavin (vit B2) and I think it also said that T4 played a role in the methylation cycle (note to all those on T3 only). I'll see if I can find the link. Just another opportunity for me to plug the importance of a B-complex containing all 8 B vitamins, not just taking B12 and folate on their own.

    I think it was this:


  • hampster1, I have listened to that presentation a couple of times, lots of interesting stuff. Hopefully Dr. Lynch will continue to learn about the thyroid connection part of MTHFR. Dr. Christianson is an ND in Phoenix who does a lot of thyroid work. There are a lot of good docs in the Phoenix area and Southwest Medical School is there which is one of the ND schools. If it wasn't so darn hot down there I'd even consider moving. PR

  • It seems to me that things work synergistically like the B vits. Would this not also be the case for thyroid medication/hormones. For instance if I'm not mistaken the thyroid produces not only T4 and T3 but also T1 T2 amongst others, and do we know if these should be taken in balance, and what we are missing health-wise if we aren't ?

  • flatfeet, I agree that there is much synergism involved, some of which we understand and a lot that we don't understand. As Rod mentioned riboflavin seems to be important in absorbing iron, doubtless that there are hundreds if not thousands of similar examples. My family does much better on NDT, some like Rod do just fine on T4 and many don't get well until they get T3 and yet we don't really have any understanding of why people react so differently to the various thyroid medications. T2 and T1 may have a biological role but we don't really know what it is. There is so much that is yet to be understood. PR

  • I am not in the slightest surprised that thyroxine can have direct effects. It always seemed likely to me but, at the same time, I have never seen proof.

    The nearest I had previously come to that has been the various organs/cell types of the body that do their own conversion rather than relying on conversion in the liver, etc. One example, hair follicles. However, just because they can and possibly usually do perform their own conversion never proved that they couldn't pick up T3 from the blood supply - if there was some available and they needed some.

    A more difficult example is the brain which both manages to do some of its own conversion and appears to need mechanisms for transporting both T4 and T3 across the blood-brain barrier. Again, no proof that T4 is actually needed. But a strong indicator that it can use T4 somehow.

    As so often...


  • Huh! Forget some important points.

    One thing that requires the products of riboflavin processing is colour vision - specifically our blue receptors. It appears that colour vision that depends on blue is affected by riboflavin deficiency. Colour perception is also likely to be affected by hypothyroidism. Was for me and someone else I know well.

    In the UK we have a yeast extract intended for spreading on toast called Marmite. Ram jam chock full of riboflavin. But if it cannot be metabolised as required, then it isn't going to do much good, is it?

  • Rod, I'm a great believer in 'all control of thyroid is local, in the tissues and organs throughout the human body.' This is of course where D1, D2 and D3 work their magic. Dr. Tata is his review of the 25th anniversary of nuclear receptors, Journal of Thyroid Research site, said that they thought there might be some T4 receptors, they just didn't know how they might work. Would they work like T3 receptors or something else. I remember just a couple of other mentions about the possibility of T4 receptors but no real science yet, certainly nothing that clearly shows they exist. I think you might have posted a link to another article in the JTR about "Purinergic Signaling", that one almost gave me a charley horse of the mind. I need to go back and read it a few more times. hindawi.com/journals/jtr/20... We are such a complex machine, we are a long way off from any thorough understanding. PR

  • I have a suspicion that some receptors might be able to work with T3 or T4 - possibly with different effects. Maybe they work for different periods, or have stronger/weaker effects from each other.

    The other megaissue is that the thyroid hormone has to get from outside to inside the cells. Hence transporters are of the utmost importance even if swimming in thyroid hormone if it can't get in there...

    Also, remember that I have posted several times that riboflavin appears to be an important factor in absorbing iron. Some of the expensive supplements (Floradix) contain quite a bit. Could low B2 be contributing to the widespread low iron levels we see in hypo?

  • Rod, for a receptor to work with both T4 and T3 they both would have to be able to get through the CoActivators and CoRepressers and I don't remember Dr. Hollenberg mentioning anything about T4, which of course doesn't mean that it isn't possible. As for the relationship between low B2 and low iron, that could well be, and probably is. You have looked at riboflavin and thought this through much more thoroughly than I have, but it makes sense to me. There must be all kinds of co-relationships going on in the body. Paul Robinson's CT3M is an excellent example. I was going to try that this winter until I realized doing so in cold weather probably wasn't a smart idea, and it has been cold this winter. Today however we are supposed to hit almost 60F, the rest of the week will not be the same unfortunately. PR

  • I don't understand all that but I know from personal experience that I can't manage without some T4 no matter how much T3 I take

  • Aurealis, interesting observation, once again proving the second rule in the world of thyroid: "There is no one size fits all, period, each of us has to find what works best in our own body." PR

  • Am slightly concerned as I take T3 only. I do take Nutri Advanced Nutri Thyroid and am wondering if that in anyway can give me a little T4 ? I took T4 in the beginning - then T4/T3 and for just over a year T3 only. Am feeling fine - but then I cannot see what is going on at a cellular level :-) I do appreciate your above comment - that we are all so different - however am just pondering ! Thank you PR...

  • Marz, I think the important thing is to take some Bs, which most of us do. Dr. Lynch is not much in favor of folate because it is synthetic and takes several steps to get it to the useful form. He prefers folinic acid or methylfolate but cautions people not to take large doses. Dr. Lowe took T3 for years and seemed to be just fine so there must be a way the body can compensate. This is what Dr. Lynch is talking about with the MTHFR gene defect, that you can compensate by proper diet and supplements. PR

  • PR - thank you.... am taking Nutri Advanced Thyro Complex x 2 daily. That contains Folic Acid and other bits and pieces...Am thinking of looking at my supplements and having an overhaul !

  • Thanks for posting. I've now spent all weekend reading about MTHFR. Wish I had of read as much when I was at Uni. :-)

  • shambles, you must have a younger mind. I've been reading it for a couple of weeks and I'm still working on it. PR

  • I very much doubt younger, it's a good 30 years since I went to uni :-( Found this subject new to me and interesting. It opened up a whole new prospective. I'd neither even considered delving into to mutated genes, methylation, just always thought genetic traits. It's a vast subject, too big for my small mind but I'll keep reading anyway.

  • shambles, if you would like to explore some more about mutated genes and methylation I would suggest an excellent BBC Horizon production called "The Ghosts In Your Genes" which covers the start of epigenetics.

    It is about 49 minutes. I've just started Nessa Carey's book "The Epigenetics Revolution", she does a wonderful job of explaining the concepts as they are introduced so that even a lay person, like myself, can understand what she is

    talking about. We are not only what we eat but what we think and what our forbearers have experienced and what we have experienced. All this often relates to the thyroid world. Patrick Holford has also written about methylation in many of his books. PR

    Lets try the Horizon link again.

    Well for some reason I can't get the link to go live but if you copy and paste into the URL bar it does work.

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