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Relationship btw B2 & B12 - Folate/Riboflavin

Tiger Lily 813

Senior Member
Messages
173
B2 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 : /
 
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picante

Senior Member
Messages
829
Location
Helena, MT USA
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.

It makes me tired, too, so I'm taking it 5 mg X 2/day. Here is one possible explanation:

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.
 

Changexpert

Senior Member
Messages
112
For those of you who get tired from taking B2, it may be because your liver is overloaded to convert B2 into the active form. There is an active coenzymated form of B2 called FMN that can be easily bought for a relatively cheap price. I did not notice much benefit from taking regular B2. On the other hand, FMN has been giving me so much stamina, a little different from energy. FMN gives me slight "oomph," and its effect is very long lasting. FMN makes me endure much more stress and keeps my brain clear throughout the day. I am still exploring coenzymated B's, and next thing I would like to try is coenzymated B1.

The benefit of coenzymated B is summarized on this post: http://www.curezone.org/forums/am.asp?i=1764073

On the other hand, there has been several studies on coenzymated B's saying that they cannot penetrate the cell membrane. I think regular vitamin B's might be good for people with normal liver function. Unfortunately, it is not uncommon for people with ME/CFS to have liver malfunction. It is also very possible that the liver is overloaded with fillers from the supplements. If you suspect liver malfunction, coenzymated vitamins will lift off burdens from the liver, giving time for the liver to recover while enjoying the benefit of vitamins.
 

Gondwanaland

Senior Member
Messages
5,092
Let's not forget that T4 hormone is needed to activate B2

http://ajcn.nutrition.org/content/47/3/481.full.pdf
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.
 
Messages
16
36.5mg of B2 took in the morning caused me drowsiness/tiredness so took 30g Zinc + 100mg Magnesium & perked up within 1/2 hour and could function normally for the rest of the day! Co-related?

Now reduced dosage to 18.25mg daily taken before bed + B3 niacin 25mg (can't tolerate higher due to Mthfr 677C>T?) + 500mg Magnesium + 25mg Zinc and this combo gave me good sleep throughout whole night, no more insomnia.
 
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Messages
61
B2 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 : /
wow, Niacin make me so energized
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Let's not forget that T4 hormone is needed to activate B2
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.

@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:
In 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.
Principles and Practice of Endocrinology and Metabolism by K.L. Becker

Synthesis 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.
Advanced Nutrition and Human Metabolism by Sareen Gropper & Jack Smith
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
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.
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.

I'm not really sure what to make of either situation (his or mine), but the B2 sure seems to throw a kicker into the methylation picture, doesn't it?
 
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Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
@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:

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.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
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.
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?
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
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?
Sorry, I thought you were talking about the role of thyroid in the conversion.
I don't think that AMP has to come from anywhere in particular. How could you tell where it was coming from?
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
I have to split my B1 and B2 pills into smaller doses. I do not always keep up. I have noticed that when I run out of B1/B2, I get more yellow color in my urine which I assume is coming from unused B12.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Eureka! I found this French study last night (quite by accident -- I wanted to know which organic acids to look at for riboflavin conversion):

Concentrations of riboflavin and related organic acids in children with protein-energy malnutrition
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.

Note: PEM = Protein-energy malnutrition
Note: Zn2+ is a cofactor!

I have been thinking for many months now (from discussions with @ahmo and @Gondwanaland) that T3 is the thyroid hormone involved in these riboflavin conversions. After all, T4 is a storage hormone.

In the US at least, the science still seems stuck on measuring and treating with inactive forms of hormones and vitamins. The studies they reference all used thyroxine, LOL. It's a lot like assuming that cyanocobalamin is the form of B12 our body uses.

But this study actually looked at the T3/T4 ratios, along with organic acids and all three forms of B2 (riboflavin, FMN and FAD).
 
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picante

Senior Member
Messages
829
Location
Helena, MT USA
If you search on 'phosphorylation of riboflavin'
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.