@Tiger Lily 813 Same here. B2 makes me really tired -- I always end up sleeping after taking it.
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The B2 made me very tired today, that's strange because most vitamins that assist methylation do the opposite for me.
Same here. B2 makes me really tired -- I always end up sleeping after taking it.
You can feel very tired when first starting with B2. Why? Because from your symptoms of low ferritin coupled with the nail ridges, thining and indents, it sounds like very little of your liver is/was working correctly. Thus, you may have accumulated a considerable amount of heavy metals. Your body can substitute mercury for copper, and lead, aluminum, nickel for iron and cadium for calcium. As soon as your body starts using the correct minerals from the liver when you add B2, the body then wants to rid itself of the heavy metals; as it no longer needs them. But as they come out of tissues and re-enter the bloodstream, they can disrupt the energy system considerably. Thus you can feel very tired. They can also cause may other symptoms. This is yet another reason I caution anyone from starting with high doses of B2.
In the hypothyroid rat the flavin adenine dinucleotide (FAD) content of the liver is similar to that observed in rats maintained on a riboflavin-deficient diet. Thyroxine regulates the enzyme flavin kinase.
Human adults with hypothyroidism have levels of erythrocyte glutathione reductase (EGR), an FAD-containing enzyme, in the range indicative of riboflavin deficiency, which can be corrected with thyroxine therapy.
wow, Niacin make me so energizedB2 and B3 make me tired whereas folate/B12 make me energized. I thought from those experiences and from some info on Mthfr.net that those groups had an inverse relationship... B3 is sometimes recommended to stop the discomfort of overmethylation caused by the folate. Feel free to chime in if my understanding is incorrect.
At any rate, yeah we need the full harmony and the complex was not quite enough : /
In previous discussions of this, we were trying to determine whether T4 was the form required, or whether it was the active form, T3, performing this function. In the studies I looked at, they used T4. However, that does not mean that the exogenous T4 was not being converted to T3 before performing this function. Since thyroxine is the standard treatment for hypothyroidism, of course they would use it in the studies.Let's not forget that T4 hormone is needed to activate B2
Principles and Practice of Endocrinology and Metabolism by K.L. BeckerIn addition, thyroid hormones increase the conversion of FMN to FAD by augmenting the converting enzyme, FAD pyrophosphorylase. Conversely, in hypothyroid states decreased formation of the riboflavin coenzymes FMN and FAD occurs, which produces a hepatic coenzyme profile that mimics true riboflavin deficiency.
[...]
Erythrocyte glutathione reductase, an FAD-dependent enzyme, can be used to define riboflavin nutriture.
In hypothyroid humans, erythrocyte glutathione reductase activity is reduced. T4 therapy results in normal levels of this enzyme, demonstrating that thyroid hormone regulates the enzymatic conversion of riboflavin to its active coenzyme forms in the human adult.
Advanced Nutrition and Human Metabolism by Sareen Gropper & Jack SmithSynthesis of FMN and FAD appears to be influenced by endproduct inhibition and hormones including ACTH, aldosterone, and the thyroid hormones, all of which accelerate the conversion of riboflavin into its coenzyme forms, apparently by increasing the activity of flavokinase.
This is an intriguing statement. When I first tried sublingual FMN last December, my low-back inflammation returned full force. Freddd concluded that I had become deficient in methylfolate by adding in the B2. At that time, I was trialing the B12 oils, so I was taking a good dose of Ad/MeB12.Freddd had a bad experience with B2 causing overmethylation for him, but that's only because he was taking loads and loads of methylfolate. And according someone who I consider much more knowledgeable than myself it was very likely also because he was B2 deficient. B2/R5P isn't a methyl donor. It's not going to cause overmethylation unless you're taking too much methylfolate.
@ahmo has been taking T3-only therapy, and she has experienced great success with taking FMN, which made me wonder whether both steps of the conversion process use thyroid hormone: riboflavin-to-FMN and FMN to FAD, and they do, although the second quote seems to be making an assumption, and it mentions ACTH and aldosterone along with thyroid hormones:
Yes, "riboflavin kinase" is synonymous with "flavokinase", the term used in that quote.I just want to point out that there is an enzyme riboflavin kinase which converts riboflavin to FMN. If you search on 'phosphorylation of riboflavin' there are many scholarly articles that together show how our understanding has developed over the past 70 years.
Sorry, I thought you were talking about the role of thyroid in the conversion.Yes, "riboflavin kinase" is synonymous with "flavokinase", the term used in that quote.
And unfortunately, "FAD pyrophosphorylase", the enzyme mentioned in the quote about FMN-to-FAD conversion, has quite a few synonyms (https://en.wikipedia.org/wiki/FMN_adenylyltransferase), the most common one being "FAD synthetase" (or synthase).
What's new to me is that the process for FMN-to-FAD conversion is called "adenylation", and as I understand it, that means attaching a molecule of adenosine monophosphate (AMP) to FMN. Which makes me wonder whether adenoB12 is of any help in this conversion. Doesn't the AMP have to come from ATP?
This simply shows my ignorance about AMP and ATP. I really have no clue whether AMP runs around all by itself in our cells. Enlighten me, please.I don't think that AMP has to come from anywhere in particular. How could you tell where it was coming from?
Riboflavin is the precursor of FMN and FAD, which are implicated in energy metabolism and electron transfer pathways. The conversion of riboflavin into FMN and FAD is catalyzed by riboflavin kinase and FMN adenylyltransferase (EC 2.7.7.2) in the presence of ATP and Zn2+ (30). T3 enhances riboflavin kinase activity (10, 13). The low T3 concentrations observed in PEM might be responsible for a reduction in riboflavin kinase activity, which would give rise to an insufficient conversion of riboflavin into its cofactors. Zinc deficiency, which was described previously in severely malnourished children (31, 32), might also be implicated in the impairment of riboflavin conversion into its cofactors. Along with the thyroid hormone concentrations observed in groups S and C, estimation of energy and zinc intakes in severely malnourished children (group S) and moderately malnourished children (group C) might help explain the observed riboflavin concentrations in group S.
Thanks for the suggestion, which has led me first to Uniprot, where I found that the cofactor is Zn or Mg (2+ charge for either). That's for the conversion to FMN.If you search on 'phosphorylation of riboflavin'
That's a cool site!Thanks for the suggestion, which has led me first to Uniprot, where I found that the cofactor is Zn or Mg (2+ charge for either). That's for the conversion to FMN.
The conversion to FAD is 'adenylation' of FMN, for which the cofactor is Mg2+, according to Uniprot.
I assume that's the current state of knowledge.