Are coenzyme B vitamins bunk?

Dog Person pointed out in another thread, that only dephosphorylated vitamins can enter tissues. I was surprised by this statement, as phosphorylated (activated, coenzyme) forms of vitamin B are touted as having higher bioavability.

I found a source confirming this:

"As only dephosphorylated vitamers can be transported into the cells (Coburn et al., 2003) the bioavailability of intact pyridoxal 5-phosphate upon oral intake would be low. Bioavailability of vitamin B6 from pyridoxal 5-phosphate requires hydrolysis of the phosphate group before absorption through the intestinal layer may occur."

http://www.efsa.europa.eu/en/scdocs/doc/afc_ej760_pyridoxal_op_en,0.pdf

So where does this leave coenzyme forms of vitamin B? Useless?

And could someone tell me why the vitamins are phosphorylated in the liver, only to be dephosphorylated before entering cells?

Gosh! Very interesting question. I changed from common B complex to activated B complex because of bioavailability. I would really like to hear some expert opinion.

Great find adreno. Maybe it's just another one of those BS marketing hype scenarios to get people to fork out more cash on pills.

Not to mention that most of those B-complex formulas are probably serious overkill on the mg content and how it also relates to further depleting B-2 stores.

I guess there could be an advantage for people with liver problems, who cannot effectively phosphorylate the vitamins.

But for people with normal liver function, there don't seem to be any advantage in bioavability. Some amount of ATP is used in the conversion, but I suspect this is negligible.

I guess using sublingual version wouldn't help? They still have to be dephosphorylated before entering cells, right?

Also, just to be clear, which vitamins are actually phosphorylated? Folate and B12 are methylated, not phosphorylated, if I understand correctly?

But would the same principle apply to methylated vitamins, i.e. would they have to be demethylated before entering cells?

So many questions...

adreno said:

I found a source confirming this:

http://www.efsa.europa.eu/en/scdocs/doc/afc_ej760_pyridoxal_op_en,0.pdf

Click to expand...

From the same source:

"The toxicity of vitamin B6 has been evaluated in several opinions. The principal toxicity of
concern associated with excess intakes of vitamin B6 (as pyridoxine hydrochloride) is neuronal
damage and sensory and motor effects. None of these effects have been specifically linked to
the pyridoxal 5-phosphate form of the vitamin.
Pyridoxal 5-phosphate did not cause clinical signs or lesions similar to those produced by
pyridoxine even when injected in maximum tolerated doses."

Yes, this brings up the question: why would P5P be any less toxic, if it's dephosphorylated to pyridoxine before entering the cell?

In the end they concluded that the safety, and max tolerated dose of the two forms is the same, though:

"The Panel considers that bioavailability and safety of pyridoxal 5-phosphate will not be significantly different from those of other forms of vitamin B6. Therefore and because of the fact that pyridoxal 5-phosphate is one of the vitamin B6 vitamers the safe upper use levels defined for vitamin B6 can be used for judging the safety of pyridoxal 5-phosphate."

This study found P5P more effective than pyridoxine for treating seizures:

Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy
http://adc.bmj.com/content/90/5/512

This article speaks another story:

"The biologically active form of vitamin B6, pyridoxal 5'-phosphate (PLP), is a cofactor in over 160 enzyme activities involved in a number of metabolic pathways, including neurotransmitter synthesis and degradation. In humans, PLP is recycled from food and from degraded PLP-dependent enzymes in a salvage pathway requiring the action of pyridoxal kinase, pyridoxine 5'-phosphate oxidase and phosphatases. Once pyridoxal 5'-phosphate is made, it is targeted to the dozens different apoenzymes that need it as a cofactor. The regulation of the salvage pathway and the mechanism of addition of PLP to the apoenzymes are poorly understood and represent a very challenging research field. Severe neurological disorders, such as convulsions and epileptic encephalopathy, result from a reduced availability of pyridoxal 5'-phosphate in the cell, due to inborn errors in the enzymes of the salvage pathway or other metabolisms and to interactions of drugs with PLP or pyridoxal kinase. Multifactorial neurological pathologies, such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and epilepsy have also been correlated to inadequate intracellular levels of PLP."

http://www.ncbi.nlm.nih.gov/m/pubmed/22201923/

So, it seems there are advantages after all. The activated vitamins act as cofactors in many biological processes, apparently in the activated form. This article also speaks of intracellular levels of PLP, something that contradicts the idea that only dephosphorylated vitamins can enter cells.

adreno, awesome! You ask the questions and you do the research to answer them.

I guess that at the end of the day, there is a good chance that there is value in purchasing the more expensive active forms.

Would this be your conclusion as well?

I do my best to answer the questions, but I could use some help from the experts. It is not quite clear to me yet.

This study also states that P5P cannot enter cells:

"Both pyridoxal and pyridoxal 5?-phosphate form Schiff bases with protein amino groups, but pyridoxal 5?-phosphate is cell membrane-impermeable."

http://www.sciencedirect.com/science/article/pii/0304383585901338

So when articles are taking about intracellular levels of P5P, maybe this is phosphorylation taking place within the cell.

I'm not knowledgeable in biochemistry, so this is essentially guesswork for me.

Right, the vitamin is phosphorylated within the cell:

"Riboflavin, commonly known as vitamin B2, is the precursor of flavin cofactors. It is present in our typical diet, and inside the cells it is metabolized to FMN and FAD."

http://www.ncbi.nlm.nih.gov/m/pubmed/20858216/

adreno said:

Right, the vitamin is phosphorylated within the cell

Click to expand...

Ok, so it seems that active B vitamins get dephosphorylated before entering the cell and then, inside the cell, get phosphorylated again. If this is indeed the case, I would suggest that the main benefit of the phosphorylated forms would be that their net consumption of ATP is zero.

adreno said:

Yes, this brings up the question: why would P5P be any less toxic, if it's dephosphorylated to pyridoxine before entering the cell?

In the end they concluded that the safety, and max tolerated dose of the two forms is the same, though:

"The Panel considers that bioavailability and safety of pyridoxal 5-phosphate will not be significantly different from those of other forms of vitamin B6. Therefore and because of the fact that pyridoxal 5-phosphate is one of the vitamin B6 vitamers the safe upper use levels defined for vitamin B6 can be used for judging the safety of pyridoxal 5-phosphate."

Click to expand...

Come on-! The wording of the above does NOT sound like science, but only conjecture! I know I can take 200mg P5P/day with no effect and I know that it protects the kidneys against glycation so I would do it if I wasn't so cheap. (I choose just the dose to make my homocysteine come out right - 50mg). The upper limit for B6 (if you are not going to be tested to prove otherwise for YOU) is 100mg/day.

Trif

I'm just wondering if there's any updates on this subject. I'm too tired to understand any of this so if anyone has arrived at a conclusion I'd like to hear it. I'm in the process of switching to b complexes without folic acid. If coenzymated forms aren't better, then a B50 I found without folic acid or B12 is looking more attractive.

nanonug said:

Ok, so it seems that active B vitamins get dephosphorylated before entering the cell and then, inside the cell, get phosphorylated again. If this is indeed the case, I would suggest that the main benefit of the phosphorylated forms would be that their net consumption of ATP is zero.

Click to expand...

Lotus : This and the fact they do not rely on a healthy liver as site of action is not after coming through the portal vein. What I cannot answer is the validity of sublingual coenzymated with the exception of b1 and certainly b2 due to limits on gi absorption.

adreno said:

This article speaks another story:

"The biologically active form of vitamin B6, pyridoxal 5'-phosphate (PLP), is a cofactor in over 160 enzyme activities involved in a number of metabolic pathways, including neurotransmitter synthesis and degradation. In humans, PLP is recycled from food and from degraded PLP-dependent enzymes in a salvage pathway requiring the action of pyridoxal kinase, pyridoxine 5'-phosphate oxidase and phosphatases. Once pyridoxal 5'-phosphate is made, it is targeted to the dozens different apoenzymes that need it as a cofactor. The regulation of the salvage pathway and the mechanism of addition of PLP to the apoenzymes are poorly understood and represent a very challenging research field. Severe neurological disorders, such as convulsions and epileptic encephalopathy, result from a reduced availability of pyridoxal 5'-phosphate in the cell, due to inborn errors in the enzymes of the salvage pathway or other metabolisms and to interactions of drugs with PLP or pyridoxal kinase. Multifactorial neurological pathologies, such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and epilepsy have also been correlated to inadequate intracellular levels of PLP."

http://www.ncbi.nlm.nih.gov/m/pubmed/22201923/

So, it seems there are advantages after all. The activated vitamins act as cofactors in many biological processes, apparently in the activated form. This article also speaks of intracellular levels of PLP, something that contradicts the idea that only dephosphorylated vitamins can enter cells.

Click to expand...

HI Adreno,

I can't give you any really great answers here. P5P, like Vit D, is one of those in the 5% total of group of the critical cofactors that can almost completely prevent active b12 startup on occasion. P5P is more often effective than B6 in this situation. It may be that the b6 is deadlocked by lack of ATP for the conversion or something. So no definitive answers here. Once again a situation were taking P5P might trigger hypokalemia and/or donut hole paradoxical folate insufficiency or other induced deficiencies in a way that seem weird to those not expecting or understanding it.

dbkita said:

Lotus : This and the fact they do not rely on a healthy liver as site of action is not after coming through the portal vein. What I cannot answer is the validity of sublingual coenzymated with the exception of b1 and certainly b2 due to limits on gi absorption.

Click to expand...

This is sort of the conclusion I made. So, would you say that there is an advantage to taking sublingual NAD over niacinamide?

adreno said:

This is sort of the conclusion I made. So, would you say that there is an advantage to taking sublingual NAD over niacinamide?

Click to expand...

Good question. I would think so in that your body would have to go through less hoops (i.e. ATP steps) to make NAD and NADH, etc. You might want to try both. I.e. lower your niacinamide some and take a small dose of sublingual NAD.

Ironically though p5p is pretty orally bioavailable I seem to benefit from taking a sublingual p5p. But maybe it is placebo.
Gets hard to make clear dispassionate clinical observations of one's self sometime.

R5p sodium is highly bioavailable, but most people take riboflavin only for which absorption is linear to 30 mg then becomes exponential in saturation above that (e.g. 100 mg b2 probably nets you 35-40 mg tops). So if you take a sublingual b2 you might feel a difference. But if you had taken r5p sodium orally you might have been ok anyways.

dbkita said:

Good question. I would think so in that your body would have to go through less hoops (i.e. ATP steps) to make NAD and NADH, etc. You might want to try both. I.e. lower your niacinamide some and take a small dose of sublingual NAD.

Ironically though p5p is pretty orally bioavailable I seem to benefit from taking a sublingual p5p. But maybe it is placebo.
Gets hard to make clear dispassionate clinical observations of one's self sometime.

R5p sodium is highly bioavailable, but most people take riboflavin only for which absorption is linear to 30 mg then becomes exponential in saturation above that (e.g. 100 mg b2 probably nets you 35-40 mg tops). So if you take a sublingual b2 you might feel a difference. But if you had taken r5p sodium orally you might have been ok anyways.

Click to expand...

Hi Dbkita,


But maybe it is placebo. Gets hard to make clear dispassionate clinical observations of one's self sometime.

Yes it is. Unfortunately, nobody else can experience our bodies from the inside. Careful observation is essential. I remember one doc who kicked be out of his practice because he said of all the drugs and bad effects I had was that statistically some of them SHOULD have had a placebo effect so he decided that I had to be sabotaging them or having "placebo side effects". I was tracking everything every day. So then he called me hyper attentive with my body problems. I told him that ignoring all these things for decades has just made me sicker. I told him all I was hearing was "Blame the patient" based on provider ignorance".

I was the only witness to a car wreck where a young lady was t-boned by a person going through a stop sign. I had turned off her engine which was spewing gasoline all over, shooed away all the people smoking, took control of the scene, did a vital signs check and covered her with a blanket and prevented anybody from touching her until the EMTs got there. Later I got a call from the insurance investigator. As soon as she identified herself and said she had a few questions. I said "Yes, you want to know how she fractured the top of her skull". There was stunned silence and then she said "How did you know that?" I told her that in her shoes that is what I would be asking. I then described everything in detail.

Based on my experiences in yoga as well as healthcare has taught me a great deal about self observation. In dealing with 100+ docs through the years I can tell you this, essentially every one of them recognized B12 deficiency almost upon sight and t5 minutes of conversation and again every one of them interpreted otherwise as soon as they looked at the tests. Then of course when they did a treatment that had no possibility of working, now that we KNOW what worked (deadlock Quartet), any little day to day fluctuation they were willing to take credit fro and any day to day worsening was nothing, or placebo. They were very quick to say "placebo". Any idea that we could quickly observe effectiveness of b12 was thoroughly stomped in in the 50s by the AMA. The docs were threatened with persecution if they treated people with B12 for the placebo effects of better energy, relieve depression, heal skin lesions, decrease nausea etc. Basically they were taught to ignore the patients response to B12 and other vitamins 100% because it was all placebo. Why vitamins would have only placebo benefits became a rather tortured logical model. However with that in mind, they did everything they could to make sure people had none of those nasty placebo effects, thus preventing the people from healing. They cleaned those placebo having people out of the studies and hence only learned how to maintain illness.

I apply a repeatability and predictability test to these effects. If there are predictable and repeatable they are not placebo. Placebos don't have legs. I notice everything in passing. After I see something at least 3 times I systematize it if possible. People have all sorts of things occur. What happens are sometimes clues. Incorrect attribution to placebo effect misses important clues. Without the AMA's hostility to B12 and it's effects we might not all be here discussing the repercussions of suppressing active b12s for 50 years.

I have been experimenting with some home made daminana liqueur. Made with brandy, water, cinnamon and vanilla, and in various versions a few more flavoring variations and sweetened, it is quite a delight. So it has effects. One we both noticed is that for about 4 hours we both felt "good". It made the neurological physical sensations more pleasant and that is one of its known attributes as well as increasing libido. However, feeling good, all by itself is enough to increase mine. A tea and various concoctions of daminana is used as an herbal tonic. It is said to be most effective for those most run down. Whether libido increase is a placebo effect, an interpretation of "feeling good" or a real "measurable" effect (rats, male and female, become more sexually active with daminana) I couldn't say. But there is a real effect. Whether it helps heal the nerves or anything I can't say. But it does have repeatable and predictable effects.

Good luck.