Cofactors For Pyruvate Dehydrogenase And Coenzymated B2 - Fad

[nullredvector]

Some enzymes or enzyme complexes require several cofactors. For example, the multienzyme complex pyruvate dehydrogenase[5] at the junction of glycolysis and the citric acid cyclerequires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), and the cosubstrates nicotinamide adenine dinucleotide (NAD+) and coenzyme A (CoA), and a metal ion (Mg2+). -Wiki

@haidut has mentioned PDH many times and it is a very important enzyme, which leads me to believe it's cofactors are very important too. Personally, if I go without lipoic acid I get excessive urination and my neuropathy flairs a bit. We all know how important Magnesium and niacinamide are. I don't know how important dietary B5 is (precursor for CoA). B1 also helps me tremendously.

What about B2 or more importantly active B2 or FAD. I wonder if there is any benefit to the active form (supp here). I seem to just pee out all the B2 I take but I have read elsewhere that a burdened liver has a hard time activating B vitamins. Any truth to that? Worth trying that supp out? What about B5?

 

[haidut]

@haidut has mentioned PDH many times and it is a very important enzyme, which leads me to believe it's cofactors are very important too. Personally, if I go without lipoic acid I get excessive urination and my neuropathy flairs a bit. We all know how important Magnesium and niacinamide are. I don't know how important dietary B5 is (precursor for CoA). B1 also helps me tremendously.

What about B2 or more importantly active B2 or FAD. I wonder if there is any benefit to the active form (supp here). I seem to just pee out all the B2 I take but I have read elsewhere that a burdened liver has a hard time activating B vitamins. Any truth to that? Worth trying that supp out? What about B5?

The goal is to avoid buildup of pyruvate so both PDH and pyruvate carboxylase are very important. The PDH you already mentioned and PDC is a biotin-dependent enzyme. So, even a small functional deficiency in either thiamine or biotin can immediately start to build up lactate. In clinical setting, buildup of lactate is usually treated with thiamine as the other cofactors of PDH seem to be usually not in a state that responds a lot to repletion except in extreme exhaustion/dehydration. Same with PDC - biotin is given even tough that enzyme has other cofactors.
Btw, I strongly suspect that a high dose thiamine and biotin can turn cancer into nothing more than pesky "fatigue syndrome" rather than a killer disease as it is now. The dose of thiamine would probably have to be 300mg-500mg if oral allithiamine is used, or 300mg-500mg IV thiamine Hcl, or 3,000mg - 5,000mg oral thiamine Hcl. Biotin doses would have to be in the range of the recent (and widely successful) clinical trial on multiple sclerosis - 300mg+ daily.
Biotin as a treatment for multiple sclerosis (MS) | Ray Peat Forum

 

[Tarmander]

The goal is to avoid buildup of pyruvate so both PDH and pyruvate carboxylase are very important. The PDH you already mentioned and PDC is a biotin-dependent enzyme. So, even a small functional deficiency in either thiamine or biotin can immediately start to build up lactate. In clinical setting, buildup of lactate is usually treated with thiamine as the other cofactors of PDH seem to be usually not in a state that responds a lot to repletion except in extreme exhaustion/dehydration. Same with PDC - biotin is given even tough that enzyme has other cofactors.
Btw, I strongly suspect that a high dose thiamine and biotin can turn cancer into nothing more than pesky "fatigue syndrome" rather than a killer disease as it is now. The dose of thiamine would probably have to be 300mg-500mg if oral allithiamine is used, or 300mg-500mg IV thiamine Hcl, or 3,000mg - 5,000mg oral thiamine Hcl. Biotin doses would have to be in the range of the recent (and widely successful) clinical trial on multiple sclerosis - 300mg+ daily.
Biotin as a treatment for multiple sclerosis (MS) | Ray Peat Forum

Haidut do you have a favorite source of allithiamine? I could not find a powder but did find ecological formulas 50mg pill:
Amazon.com: Allithiamine 50 mg 60 Capsules: Health & Personal Care

 

[haidut]

Haidut do you have a favorite source of allithiamine? I could not find a powder but did find ecological formulas 50mg pill:
Amazon.com: Allithiamine 50 mg 60 Capsules: Health & Personal Care

It is a great product but it has silicon dioxide in it. If you get the powder from CR it does NOT have silicon dioxide. Why they decided to put in into the pills is beyond me. I posted a study some time ago showing that oral allithiamine matches per mg IV thiamine Hcl. So, 100mg oral allithiamine would be equivalent to 100mg IV thiamine Hcl. This is as good as it gets for thiamine, which is notoriously hard to absorb and easy to get deficient in.
Biotin absorbs close to 100% orally, so no need for a special form there.

 

[extremecheddar]

Anyone found a good clean source of allithiamine? What is the safe dosage range?

 

[haidut]

Anyone found a good clean source of allithiamine? What is the safe dosage range?

As I said in my post above, the allithiamine powder from CR does not have silicon dioxide as opposed to the pills. I think the powder has no additives, or at least so the label says. You can import allithiamine from Japan but you'd have to buy several pounds to make the order and shipping cost effective.

 

[nullredvector]

I guess I have to experiment and see if high dose thiamine (I've got sulbutiamine on hand) and high dose biotin (still have a few grams left) can decrease my urine output like ALA can.

That's cardiovascular research powder for the allithiamine?

 

[BingDing]

FWIW, Renaissance Medical Supply Allithiamine powder sells the powder for $184/250g. There are a couple old threads where it is said thiamine HCL works as well as anything, so I am not sure if allithiamine is worth it.

 

[haidut]

I guess I have to experiment and see if high dose thiamine (I've got sulbutiamine on hand) and high dose biotin (still have a few grams left) can decrease my urine output like ALA can.

That's cardiovascular research powder for the allithiamine?

Yes, they used to sell both powder and capsules.

 

[haidut]

FWIW, Renaissance Medical Supply Allithiamine powder sells the powder for $184/250g. There are a couple old threads where it is said thiamine HCL works as well as anything, so I am not sure if allithiamine is worth it.

I posted a thread that shows taking 1,500mg in a single dose produces measurable elevations in plasma. However, taking just 100mg oral allithiamine produces higher plasma concentrations. The positive for thiamine Hcl is that it would probably be cheaper even if you take several grams per day.

 

[extremecheddar]

Yes, they used to sell both powder and capsules.

I can't seem to find the powder, only the capsules. Have a link?

 

[nullredvector]

Sulbutiamine is $12 for 25g. You can get it at powdercity

 

[ddjd]

is allithiamine considerably better than just thiamine HCL?