Pyridoxal-5-phosphate: Depressogenic?

[Bravoncius Roxford]

Hello, I am new here. I don't know if this is the appropriate forum, but I think it is.

I have a weird question regarding a supplement. I stopped using P5P recently because it depresses me. To be more precise, it makes me anxious and angsty. I see people everywhere claiming how this wonderful active form of vitamin B6 makes gives them well-being, increased energy, etc. Now, to me, the effect of P5P is biphasic: it first does make me feel more alive and happier, but 24-48 hours latter I feel like crap. When I take P5P, about 4-6 hours latter I feel more alive and my mood brightens. However, about a day latter I just get negative feelings, a very agitated state of worrying about stuff. Basically, it makes me feel "uneasy". That is the word. I just feel uneasy, like I can't relax emotionally. Does anyone have similar experience? Probably not.

I was thinking about hypothesis for why P5P makes me feel this way. P5P is an enzyme co-factor for a lot of reaction in the body. Among them, is the conversion of 5-hydroxytrptophan into serotoin and l-dop into dopamine, as well as l-typtophan inot niacin.

Taking this into consideration and judging how P5P makes me feel, I have considered this: the first effect, increased feelings of aliveness and brightened mood, are probably caused by increased conversion of l-dopa into dopamine. I have taken a lot of dopaminergics in the past(amphetamine, methylphenidate, selegiline, rasagiline, etc) to know that this effect is dopaminergic. However, what I cannot explain is the deep feeling of angst and worry that I get one or two days latter. Considering the actions of P5P, I have considered three hypothesis:

1. P5P increases the conversion of l-dopa into dopamine, using up most of the decarboxylase enzyme and leaving little to convert 5-HTP into serotonin, leading to serotonin depletion.. Because tyrosine crosses the blood-brain barrier more effectively than tryptophan, and because both l-dopa and 5-HTP uses the same decarboxylase enzyme for conversion, the decarboxylase enzyme gets used up converting l-dopa into dopamine when a lot of P5P is available, so there is little left for converting the 5-HTP into serotonin. So the anxious and angsty feeling is caused by depletion of serotonin.

2. P5P actually increases the conversion of 5-HTP into serotonin, which in turn stimulates 5-HT1 and 5-HT2c receptors, triggering anxiety and restleness. So the feelings caused by P5P are due to increased serotonin.

3. P5P increases the conversion of typtophan into niacin, making less typtophan available to be converted into 5-HTP and latter into serotonin. So the feelings caused by P5P are due to serotonin depletion.

The reason why understaind the etiology of the anxiety and angst triggered by P5P is because both low and high levels of serotonin can cause anxiety and angst. If serotonin linearly either increased or decreased anxiety according to level, then I could counter the anxiogenic effects of P5P by taking typtophan, 5-HTP or eating lower carbs with more BCAAs(which lower serotonin). But because 5-HTP has dual effects, then it is impossible to device a strategy to counter the effects.

What do you guys think?

 

[Bravoncius Roxford]

Wow, 180 views and not replies? I guess it's just me.

 

[Dresden]

That stuff has such a bewildering array of biological actions that taking it longterm will likely cause all sorts of unintended, unwanted, and unknown side effects. I don't know how many mg's you are taking, but according to Wikipedia, if you take enough for a long enough period of time then you'll be looking at irreversible nervous system problems. Stop taking it.

 

[Bravoncius Roxford]

That stuff has such a bewildering array of biological actions that taking it longterm will likely cause all sorts of unintended, unwanted, and unknown side effects. I don't know how many mg's you are taking, but according to Wikipedia, if you take enough for a long enough period of time then you'll be looking at irreversible nervous system problems. Stop taking it.

I think it is the pyridoxine version of B6 that causes the irreversible damage to the peripheral nervous system, not pyridoxal.

But you are right, though: this stuff makes me feel like *shit*. I seldom use the word "shit" because it is such a strong word, but it really does apply here. They say all over the internet that it increases the synthesis of serotonin and dopamine, and makes you feel good, but this is not my experience. Sure, it does lift your mood and make you feel more alive a few hours after taking it, but the next day you feel suicidally bad. I don't know how to describe it. It is a state where your mind is hyper but at the same time foggy and you feel a constant angsty feeling like bad things are about to happen. It makes you feel "uneasy". Yes, that is the best word to describe how P5P makes you feel 1 or 2 days after taking it: uneasy. Angsty. Your mind is agitated and obsesses over bad things that might happen to you. That is the way to describe.

I am a fairly bright guy, but I have broke my mind trying to figure out why P5P makes me feel like this. I wouldn't be surprsed if it boosts the synthesis of dopamine, because it does make you feel more alive and upbeat the first 8-12 hours after you take it. But then why do you feel so awful the next day?

I have two theories. One is that P5P increases the conversion of l-dopa into dopamine, and thius leads to the aromatic decarboxylase enzyme being depleted, resulting in decreased conversion of 5HTP into serotonin. Conversely, it could be due to *increased* conversion of 5-HTP into serotonin, since too much serotonin can stimulate the 5-HTP2A receptors, leading to anxiety.

Because both too much and too little serotonin can lead to these symptoms, I have no way of knowing. I wish someone could elucidate this to me, but some things are never to be explained.

I hoped to understand the mechanism by which P5P causes this because then I could figure out a strategy to benefit from the increased aliveness and motivation it gives without the shitty feelings.

But you are right: since I can't explain it, it is best to just quit.