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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by myco on March 8, 2009, at 16:29:49
How Would inhibition of SULF1A3 in the gut affect the absorption and bioavailability of Nardil (Phenelzine sulphate)? Any risk for hepatotoxicity (or other bad sides) with this approach? I know inhibition of SULF1A3 will increase bioavailability of alot of things metabolized via sulfonation in the gut. Please advise.Thanks,
myco
Posted by Larry Hoover on March 8, 2009, at 17:22:01
In reply to Inhibition of SULF1A3 = increase NARDIL bioavail?, posted by myco on March 8, 2009, at 16:29:49
I can't find any evidence that phenelzine is a substrate of this enzyme. Do you have a reference for consideration?
Lar
Posted by myco on March 8, 2009, at 17:35:33
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » myco, posted by Larry Hoover on March 8, 2009, at 17:22:01
I can't find evidence either...this is my own personal research into how I, as a nardil user, may attempt to increase nardils bioavailability thus it's therapeutic effect. The idea was born out of reading this new study here:
""Inhibitory Effects of Herbal Extracts on the Activity of Human Sulfotransferase Isoform Sulfotransferase 1A3 (SULT1A3)"
Link: (http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf)
Can you offer any insight at all Larry? This is fascinating stuff.
Thanks again,
Myco
> I can't find any evidence that phenelzine is a substrate of this enzyme. Do you have a reference for consideration?
>
> Lar
Posted by Larry Hoover on March 8, 2009, at 19:31:22
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » Larry Hoover, posted by myco on March 8, 2009, at 17:35:33
> I can't find evidence either...this is my own personal research into how I, as a nardil user, may attempt to increase nardils bioavailability thus it's therapeutic effect. The idea was born out of reading this new study here:
>
> ""Inhibitory Effects of Herbal Extracts on the Activity of Human Sulfotransferase Isoform Sulfotransferase 1A3 (SULT1A3)"
>
> Link: (http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf)
>
> Can you offer any insight at all Larry? This is fascinating stuff.
>
> Thanks again,
> Myco
>
>
> > I can't find any evidence that phenelzine is a substrate of this enzyme. Do you have a reference for consideration?
> >
> > LarWhat you suggest is theoretically possible. The substrates they mentioned, ritodrine and dopamine are similar enough in structure to phenelzine that it looks like it too might be a substrate. The list of foods and herbs that inhibit this enzyme is also quite extensive. I can't think of any reason why you shouldn't consider trying this, but just be very careful about interactions with the MAOI effect.
Lar
Posted by myco on March 8, 2009, at 19:43:36
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » myco, posted by Larry Hoover on March 8, 2009, at 19:31:22
Do you happen to know what enzymes use phenelzine as a substrate in the gut? I'm waiting to hear back from various psychiatric researchers about this but they are sooooo slow.
> > I can't find evidence either...this is my own personal research into how I, as a nardil user, may attempt to increase nardils bioavailability thus it's therapeutic effect. The idea was born out of reading this new study here:
> >
> > ""Inhibitory Effects of Herbal Extracts on the Activity of Human Sulfotransferase Isoform Sulfotransferase 1A3 (SULT1A3)"
> >
> > Link: (http://www.jstage.jst.go.jp/article/bpb/32/1/105/_pdf)
> >
> > Can you offer any insight at all Larry? This is fascinating stuff.
> >
> > Thanks again,
> > Myco
> >
> >
> > > I can't find any evidence that phenelzine is a substrate of this enzyme. Do you have a reference for consideration?
> > >
> > > Lar
>
> What you suggest is theoretically possible. The substrates they mentioned, ritodrine and dopamine are similar enough in structure to phenelzine that it looks like it too might be a substrate. The list of foods and herbs that inhibit this enzyme is also quite extensive. I can't think of any reason why you shouldn't consider trying this, but just be very careful about interactions with the MAOI effect.
>
> Lar
Posted by Larry Hoover on March 10, 2009, at 7:45:44
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » Larry Hoover, posted by myco on March 8, 2009, at 19:43:36
> Do you happen to know what enzymes use phenelzine as a substrate in the gut? I'm waiting to hear back from various psychiatric researchers about this but they are sooooo slow.
I've been thinking about this, and maybe it's not as benign as I first thought.
The only enzyme binding phenelzine that I know of is MAO. That's why it creates the need for food restrictions, of course.
These enzymes in the gut wall brush border are the first line of defense against ingested chemicals that could disturb the body's ability to self-regulate. If ingested dopamine got into the blood in high concentration, you could stroke out. The same with tyramine. Phenelzine just happens to be similar enough to those two in structure that it hits the same binding sites. It's not the gut enzymes that are the intended targets, of course. These are gate-keeper enzymes, not metabolic enzymes. MAO deactivates dopamine. Sulf enzymes add an extra blob onto the structure so that it can't fit into receptors. The sulphate blob also marks the molecule for excretion.
Theoretically, if you block these enzymes, you can become vulnerable to other ingested chemicals. Tyramine, with MAO blocked. Maybe other chemicals with the Sulf family blocked. Just recognize what you're thinking of messing around with. Your article did identify a number of foods that inhibit Sulf, and I'm sure that happens all the time, whether you know it or not. I have no idea if that leaves you vulnerable or not.
Lar
Posted by myco on March 10, 2009, at 13:13:31
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » myco, posted by Larry Hoover on March 10, 2009, at 7:45:44
So in your professional opinion Larry, do you think it best to abandon the study of this idea or take it extremely slow (very tiny doses) and 'watch' for negative response? I'm not superman here lol I have had a few mild bp food related issues. That being said though my interest in persueing this is very strong...but didn't curiousity kill the cat? lol
myco
> I've been thinking about this, and maybe it's not as benign as I first thought.
>
> The only enzyme binding phenelzine that I know of is MAO. That's why it creates the need for food restrictions, of course.
>
> These enzymes in the gut wall brush border are the first line of defense against ingested chemicals that could disturb the body's ability to self-regulate. If ingested dopamine got into the blood in high concentration, you could stroke out. The same with tyramine. Phenelzine just happens to be similar enough to those two in structure that it hits the same binding sites. It's not the gut enzymes that are the intended targets, of course. These are gate-keeper enzymes, not metabolic enzymes. MAO deactivates dopamine. Sulf enzymes add an extra blob onto the structure so that it can't fit into receptors. The sulphate blob also marks the molecule for excretion.
>
> Theoretically, if you block these enzymes, you can become vulnerable to other ingested chemicals. Tyramine, with MAO blocked. Maybe other chemicals with the Sulf family blocked. Just recognize what you're thinking of messing around with. Your article did identify a number of foods that inhibit Sulf, and I'm sure that happens all the time, whether you know it or not. I have no idea if that leaves you vulnerable or not.
>
> Lar
Posted by Larry Hoover on March 10, 2009, at 13:33:02
In reply to Re: Inhibition of SULF1A3 = increase NARDIL bioavail? » Larry Hoover, posted by myco on March 10, 2009, at 13:13:31
> So in your professional opinion Larry, do you think it best to abandon the study of this idea or take it extremely slow (very tiny doses) and 'watch' for negative response? I'm not superman here lol I have had a few mild bp food related issues. That being said though my interest in persueing this is very strong...but didn't curiousity kill the cat? lol
>
> mycoI'm emphasizing the unknown part. Considering the nature of the food components that naturally inhibit this enzyme, you've probably experienced it already. Intentionally causing significant inhibition might lead to adverse effects. Yes, an incremental dosing schedule is sensible.
Lar
Posted by myco on March 12, 2009, at 0:59:43
In reply to Inhibition of SULF1A3 = increase NARDIL bioavail?, posted by myco on March 8, 2009, at 16:29:49
I know this is way to early but side effects were relatively hard. This is only my first dosing of Green Tea Extract with Nardil. Idea was/is to progress slowly over a number of weeks.
These are my first day observations using Green Tea Extract (300mg capsules with 50% EGCG; contains unknown amount of caffeine as well) combined with 125mg vitamin B6 (cofactor) in an attempt to augment/potentiate Nardil. EGCG (a natural decarboxylase inhibitor) is a compound in Green Tea Extract shown to inhibit a gut enzyme (SULT1A3) thus increasing bioavailability of some neuros (DA & SE) and, hopefully based on my theory to be tested, Nardil (similar in structure to DA). See posts above for explaination.
In support of this also, it has been shown that grapefruit juice (containing some similarly functioning compounds to green tea) potentiates the effects of Zoloft (sorry can't remember reference at the moment). So here we have the beginings of a lil study by myself (my dr would kill me for messing around with a maoi like this though without supervision lol) to use natural plant products to augment psych meds...a category (MAOI) that has never been tried (formally at least) this way before (to my knowledge)
Initial recording of experience:
8:50am - Two (2 X 300mg = 600mg total) Green Tea Extract (GTE) capsules taken on empty stomach (as suggested to increase bioavailability)
9:00am - Nardil (morning dose, 30mg, taken) with 125mg B6 tablet.
10:00am - starting to "not feel like myself" - mild headache coming on, don't feel awake (normally I do with only Nardil), somewhat stuffy or congested, missing that calm coolness that the morning dose of Nardil gives me. Drank two extra cups of Green Tea decaf (~10mg caffeine each).
11:00am - noon - I did eat chocolate so mabye having an effect on observations (my bad)
11:35am - headache still there (perhaps slightly worse), body aches, joint stiffness, definately moving slower than usual, beginning to get tired (unlike usual Nardil morning dose)
12:20pm - slight dizzyness (head rolling when eyes closed), inability to concentrate (unusual for Nardil), heavy feeling in chest (almost like forced breathing feeling), tiredness getting more intense (feel like going back to bed).
12:36pm - minor facial flushing/heat, headache turns to "fuzzyness" feeling, mild "twinges" or "blips" of sexual arousal
1:22pm - chest heavyness described earlier feels like it may be heart straining (not sure though - just wasnt comfy), no indication of increased heart rate
3:45pm - decided not to take additional dosage of GTE as planned with afternoon Nardil dose. Mild tinnitus, mild 'blips' of stimulation in my legs, concentration still poor, fuzzy headache persists, some feeling of 'ease' (mabye nardil coming on?), still very sleepy, feeling very "worn out"/not functional at all. perhaps a caffeine crash? (dunno)
5:30pm - still very tired, some of sides are easing, headache persists, still worn out, concentration and enthusiasm for the day is gone, will take a nap shortly = couldnt sleep though just layed there.
11:35pm...mild chronic headache remains...feeling better though.
I'm not sure on the role a heavy dose (although ive no idea what dose is in the caps) of caffeine has in these sides...certainly felt a heavy crash come on though but it started early. There was some signs that I recognize (at least I think) of increased dopamine - sleepyness does come from this initially for me and sexual arrousal. Some possible SE effects could relate to the sleepyness...although the decarboxylase inhibition would first build up 5htp not SE, to my understanding and L-dopa first before dopamine.Initial results here show that it may not be worth the trouble as this isnt a "comfy" augment as of yet (well only first day so I cant complain). I have a bad feeling about the chest issue but mabye I am, well I am lol, thinking about this to much. I so want to try again with a caffeine free GTE...will do friday. Also I want to lower the dose...related to this...i've no idea how much actual EGCG is in these products....i.e is 50% EGCG in a 300mg capsule equal to 150mg? Not sure...no response from the company via email.
To be continued....
This is the end of the thread.
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