T4 needed for methylation?

[BadBadBear]

Hi - I have been trying to understand whether T4 is needed for methylation & whether anyone here has had issues like mine.

I started with normal levels of TSH & T4, but low T3. So I was put on T3, which did help some of the hypothyroid symptoms. My recent bloodwork shows OK levels of T3, and now low levels of T4 (below range). My doc has been hesitant to give me T4, because my levels were normal to start with.

However, what I'm reading is that T4 somehow moves riboflavin around (?) and is therefore directly involved with methylation? Is this right? It isn't just a storage form of thyroid??

If so, my low T4 levels need to be addressed?

One of my specific symptoms is that ~4 hours after I take my T3 (twice during the day), I have a peculiar episode of fatigue. I am wondering if this is caused by T3 going out of my system, or if it's a deficiency of something else caused by the T3. I wondered if my lackluster T4 levels get completely depleted then and I just flounder.

Sorry for the questions, it's just all foggy at the moment, and I'm trying hard to get it. I also would love to figure out this lagging fatigue thing that happens to me twice daily! I usually have to take a nap during one of the episodes, then it takes me another hour or so to really get back to normal.

- Michelle

 

[Helen]

Hi @BadBadBear ,

Sorry to hear about your problems, but hopefully an optimal treatment for your hypothyroidism would make a change.

T3 has a short half life and therefore it has to be taken 3-4 times a day. You will probably notice a maximum effect after about 2.5 hours, then it is fading away. Therefore it has to be met with another dose about 4 hours after the earlier.

I don´t think it is correct to treat the labvalues for T3 or T4. Low values indicate a need for treatment, but should be seen in a broader view. A knowledgeable doctor would treat you in another way, and evaluate your symptoms thourough based on the treatment as lab tests aren´t always valid or helpful. They measure hormones in blood , not in tissue.

This site (and book based on it) has lots of good information www.stopthethyroidmadness.com. Maybe it is too much with brain fog, so just ask again and I think you will get help from people that have made this journey before you.

 

[rwac]

Yea, splitting up that T3 pill into multiple doses is probably a good idea. I personally try to take not more than 5mcg per dose.

T4 will definitely help with smoothing out the dips. I take my T4 in one dose at night.

 

[ahmo]

My understanding is that T4 needs to be broken down into T3 to be utilized. It's also possible to have slow release T3 from a compounding chemist. I'm linking a vid by Rudy Dragone. I can't remember the contents, but I found his info the best for understanding about T3 dosing. Also linking a very interesting site, w/ a novel T3 protocol. Good luck getting it sorted....
http://recoveringwitht3.com/blog/what-circadian-t3-method

Rudy Dragone http://www.youtube.com/watch?feature=player_detailpage&v=8XGQYc3NZ0Q

 

[BadBadBear]

The main issue I have with dosing 4x per day is getting a time window to take iron... I have to take iron, and I am not supposed to take it w/in 4 hours of a T3 dose as it binds T3.

I tried taking iron at night when I wake up (usually around 3-4) but I found it really uncomfortable in my stomach while lying down - like it might come up. Then I tried taking T3 at that hour, and find myself WIDE awake.

So I am not sure how to accomplish the dosing schedule for T3 along with my other supplements? Can I trust that I will absorb it fully sublingually and then take iron an hour later?

@Helen, STTM was actually the place that I saw the info about T4 being needed for methylation. Thanks for the reminder of where to find the info that is confusing me!

This is cross posted from a discussion in the T3 yahoo group.

I am reading the recent book “Stop the Thyroid Madness II” edited by Janie Bowthorpe.
In Chapter 12 – Methylation, MTHFR and Thyroid Dysfunction, the following statement is made (p276):

Hypothyroid individuals, specifically those low in T4, are at risk for decreased levels of FAD… People who have low T4 levels have a slowed MTHFR enzyme because FAD levels are low. This means that the MTHFR enzyme can be functionally weak even without a MTHFR defect. In order for the MTHFR enzyme to function, whether defective or not, it needs FAD. If one is hypothyroid and specifically low in T4, the FAD levels are low and thus the function of the MTHFR is low.

Then this statement is highlighted:
Some physicians like to use Cytomel (T3) only, when treating hypothyroidism. This may not be adequate and now you know the reason why. Thyroxine (T4) is needed to help produce FAD which has many roles – one of which supports the MTHFR enzyme and increases the production of methylfolate.

FAD is flaven adenine dinucleotide, which is the most active form of riboflavin.

So I guess I'm poking around here to see if anyone has experience with this, or knows about it... It's not something I've seen referenced much over here.

 

[BadBadBear]

One more while my brain is working...

http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID:+3809170

Riboflavin metabolism in the hypothyroid human adult.
Cimino JA, Jhangiani S, Schwartz E, Cooperman JM.
Abstract
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.

 

[rwac]

These two might be relevant.

http://www.ncbi.nlm.nih.gov/pubmed/24581448

Serum homocysteine levels are decreased in levothyroxine-treated women with autoimmune thyroiditis.
Owecki M1, Dorszewska J, Sawicka-Gutaj N, Oczkowska A, Owecki MK, Michalak M, Fischbach J, Kozubski W, Ruchała M.
Author information
Abstract
BACKGROUND:
Hyperhomocysteinemia is a well-known cardiovascular risk factor and its elevation is established in overt hypothyroidism. Since some authors suggest that chronic autoimmune thyroiditis per se may be considered as a novel risk factor of atherosclerosis independent of thyroid function, the analysis of classical cardiovascular risk factors might be helpful in evaluation the causative relationship. Data concerning the impact of thyroid autoimmunity in euthyroid state on homocysteine (Hcy) level is lacking. The aim of this study was to evaluate Hcy level in context of anti-thyroperoxidase antibodies (TPOAbs) in euthyroidism.

METHODS:
It is a case-control study. 31 euthyroid women treated with levothyroxine (L-T4) due to Hashimoto thyroiditis (HT) and 26 females in euthyroidism without L-T4 replacement therapy were enrolled in the study. All women with HT had positive TPOAbs. Forty healthy females negative for TPOAbs comparable for age and body mass index (BMI) participated in the study as controls. Exclusion criteria were a history of any acute or chronic disease, use of any medications (including oral contraceptives and vitamin supplements), smoking, alcoholism.

RESULTS:
TPOAbs titers were higher in both groups of HT patients versus the healthy controls. Hcy levels were found to be significantly lower in treated HT patients (Me 11 μmol; IQR 4.2 μmol) as compared with healthy controls (Me 13.35 μmol; IQR 6.34 μmol; p = 0.0179). In contrast, no significant difference was found between non treated HT and control group in Hcy level. The study groups and the controls did not differ in age and BMI. Furthermore, levels of TSH, FT4, TC, LDL, HDL and TAG did not differ between the study group and the control group.

CONCLUSION:
The main finding of the study is a decrease in Hcy level in treated HT as compared with healthy controls. Based on our observations one can also assume that correct L-T4 replacement was associated here with a decrease of Hcy. Furthermore, it seems that non treated HT in euthyroidism is not associated with Hcy increase, in contrast to overt hypothyroidism. This may be just another argument against the concepts about the role of "euthyroid HT" in the development of atherosclerosis.

http://jn.nutrition.org/content/134/11/2913?related-urls=yes&legid=nutrition;134/11/2913

Triiodothyronine Treatment Attenuates the Induction of Hepatic Glycine N-Methyltransferase by Retinoic Acid and Elevates Plasma Homocysteine Concentrations in Rats1,2

1. Kelly A. Tanghe,
2. Tim A. Garrow*, and
3. Kevin L. Schalinske3

+ Author Affiliations

1. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011 and
2. *Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801

1. ↵3To whom correspondence should be addressed. E-mail: kschalin@iastate.edu.

Abstract
Recent studies indicated that hormonal imbalances have a role in modulating the metabolism of methyl groups and homocysteine, interrelated pathways that when disrupted, are associated with a number of pathologies. Retinoic acid (RA) was shown to induce hepatic glycine N-methyltransferase (GNMT), a key regulatory protein in methyl group metabolism, and to reduce circulating homocysteine levels. Because thyroid status influences the hepatic folate-dependent one-carbon pool and retinoids can alter thyroid hormone levels, the aim of this study was to examine the interaction between retinoids and thyroid function. For hypothyroid studies, rats were administered 0.5 g/L propylthiouracil in the drinking water for 15 d, and RA [30 μmol/(kg · d)] for the final 5 d. For hyperthyroid studies, rats were treated with RA [30 μmol/(kg · d)] for 8 d and triiodothyronine [T3; 50 μg/(100 g · d)] the last 4 d. T3 treatment prevented the RA-mediated increase in GNMT activity. However, GNMT abundance remained elevated, indicating that GNMT regulation by T3 in RA-treated rats may be, at least in part, at the post-translational level. In addition, T3 treatment elevated plasma levels of homocysteine 177%, an elevation that was prevented by RA. T3-mediated hyperhomocysteinemia may be due to a 70% decrease in hepatic betaine-homocysteine S-methyltransferase, the enzyme that catalyzes folate-independent remethylation of homocysteine, whereas the RA-mediated stimulation of hepatic homocysteine remethylation by folate-dependent methionine synthase may contribute to lowering plasma homocysteine levels. These findings indicate that thyroid hormones, alone and in conjunction with RA, play an important role in the regulation of methyl group and homocysteine metabolism.

 

[BadBadBear]

Those are interesting... That last one is hard to read, though. I had low plasma cysteine on my last bloodtest for it (recently) so obviously T3 is not causing mine to be elevated too much. If anything, it would be good if my Hcy would go up a few points.

I am trying to split my T3 dose into 3 today - it's a small half tab that has to be split up. The tiny doses do lend themselves a bit more to being taken sublingually.