BH4 topic

[triffid113]

An alternative way to increase BH4 levels, besides reducing its consumption by ammonia, is to reduce its consumption in the production of neurotransmitters by using the prescription monoamine oxidase inhibitor (MAOI) phenelzine (Nardil). Nardil prevents the breakdown of neurotransmitters and thus reduces the amount of BH4 that must be used to make those neurotransmitters in the first place.

I use only 7.5mg (1/2 tablet - tricky to cut) first thing in the morning drunk with ~250mg sodium ascorbate in a large glass of water (I crush the very unpleasant tasting half tablet in my mouth with some of the liquid). I additionally have to use at least 200mg of caffeine tablets - taken with or after breakfast (and often times more in the afternoon, e.g., 100-200mg extra) - to offset the paradoxically tiring effect that Nardil initially has... It's actually ultimately energizing.

Nardil, even when taken in the morning in such a small dosage, causes sleep problems for me at night that are overcome by using 0.25mg (1/2 tablet) of clonazepam (Klonopin) together with 500mg niacinamide (which reduces the amount of Klonopin necessary), and magnesium citrate (e.g., 200mg or more). (I also take these with sodium ascorbate in water.)

Nardil (and caffeine) in the morning, and Klonopin (and niacinamide and magnesium) at night, have given me some semblance of a life, after many years of not having one. I've been doing this regime for some 3 months now with very consistent results. (I'd tried Nardil a couple years ago with only an initial temporary success because I didn't understand how to use it.)

Nardil has previously been explored in published literature trials for CFS / ME with only modest results. I'm not sure that the researchers were aware of the apparently critical (at least for me) importance of caffeine, though.

Note that Nardil, by increasing the levels of BH4, is indirectly acting as a potent antioxidant.

I've not noticed any food interactions using the 7.5mg amount. Unfortunately, many doctors are reluctant to prescribe MAOI's, since when they first came out (many decades ago), a number of deaths occurred in patients taking much larger dosages who also ate preserved and/or other contraindicated foods (when the food interaction problem wasn't initially understood by the medical/scientific community). Hypertensive crisis I think is the primary worry, and my blood pressure, like the majority of people with CFS / ME, runs low, making a problem less likely anyway.

Nardil is very definitely NOT acting as an antidepressant in my case, and I doubt that 7.5mg would be considered a therapeutic antidepressant dose (typical dosage in depression is more like 45 to 90mg, if I remember correctly).

)
Do you know if (1) nardil has any benefit if you are COMT +/+ (like me)? (2) How nardil would work with someone who was homozygous for MAO A, as my father was?

 

[triffid113]

Oh, now I see nardil would not work for me because it raises blood pressure. Mine is very hgh when my adrenal gland if working (which is not during allergy season). I find these 3 supplements make my adrenal gland work (or appear to work anyway): DHEA (75mg), 1-3g tyrosine (prescribed by my doctor for thyroid), zinc as needed (75-150mg if I have a cold or rhinitis allergy that day, otherwise maybe 25mg).

I do not know how you can accept adrenal gland not working. I cannot so much as lift a finger when mine goes out and I have passed out from low blood pressure then. I become comatose eating salt, I mean like my life depends on it.

 

[triffid113]

I've been wondering about this. I was concerned that I'd change other properties of an amino acid besides just the pH. So if I added a buffering agent to other acidic amino acids such as L-carnitine or some other acidic substance such as alpha lipoic acid that wouldn't be a problem?

How do you know that carnitine and ALA are acidic? This is extremely important to me because I take so many vitamins that my insides are ripped up all the time and when my doctor added 2 new ones I could not take them because I would puke. I have reached my limit in pills, but it DOES seem like the whole mess adds up to acidic. I do not want to be changing the ph of my body with supplements, and I do not want to have an upset stomach from breakfast to lunch (in fact, it causes me to eat more than I want in an attempt to keep that load of pills down). Thanks.

 

[Lotus97]

How do you know that carnitine and ALA are acidic? This is extremely important to me because I take so many vitamins that my insides are ripped up all the time and when my doctor added 2 new ones I could not take them because I would puke. I have reached my limit in pills, but it DOES seem like the whole mess adds up to acidic. I do not want to be changing the ph of my body with supplements, and I do not want to have an upset stomach from breakfast to lunch (in fact, it causes me to eat more than I want in an attempt to keep that load of pills down). Thanks.

Acetyl L-Carnitine and L-Carnitine are quite sour. I don't know about GPLC or Acetly L-Carnitine Arginate. I bought Alpha Lipoic Acid in powder form and there's a warning on the container
Powder taste is unpleasant, chemical burning taste, capsule recommended. This powder is very acidic and should not be taken orally unless encapsulated or buffered.
Other supplements that can cause stomach/GI irritation are potassium chloride and quercetin. You could also check customer reviews at iHerb also because sometimes people talk about that. SSRIs can also cause problems with some people. This might be because serotonin in large part is manufactured in the gut.
PS - I like your new avatar

 

[triffid113]

Thanks, Lotus. I gave my father carnitine, not knowing. The next test I would have run on him was for tissue magnesium. I hope the carnitine did not take down his magnesium levels in order to be buffered. I believe he wound up short of magnesium and that dialysis either filtered it out or at least prevented his taking it as a supplement, which was the cause. But he wound up in dialysis due to the MTHFR1298AC. And some of the other defects in the methyl cycle, which caused his liver to not be able to handle the dye they used when they put a stent in him. When you have a lot of genetic defects it is hard to chart a course between them all. My father had no artery that was over 30% occulded, except for the ones that he had grown new blood vessels around. There is a lesson there...when you are very old and fragile, if you can avoid every stress (such as cold air - never going out in the winter, etc) then you can grow new blood vessels around occluded ones. My father could not be so coddled because he had to go out to dialysis 3x/week. We weren't coddlers...we didn't really understand coddling. My neighbor's doctor told him not to go out in the winter, so his wife goes out and keeps him home, and he is still alive with his heart condition. But somehow w/o coddling my father had grown the new blood vessels, so it HAD to be an electrolyte problem. The doctors said it was not, but I KNOW that serum magnesium is NOT refelective of magnesium levels in the heart. So they did not really know his electrolyte levels. Although I was giving my Dad carnitine, I did not supplement that in the last month of his life since he was in hospital. I will never know what part that played but it did not play the final fatal part.

 

[Lotus97]

triffid113
Methylation can be especially difficult for people who are particularly sick or weak. I've been finding this out the hard way for myself and I've heard of similar experiences from others.

 

[triffid113]

About reducing need for BH4 in making neurotransmitters...I do do something in that regard - it is small but could be significant. I never take supplements that contain phenylalanine (requires 2 BH4 to assimilate to dopamine), but only take tyrosine to help my thyroid and dopamine levels (requires only 1 BH4). There are many thyroid and neurotransmitter vitamin products out there that contain phenylalanine, my doctor even wanted me to take one, but I treat that as poison! I believe my father had PKU at the end but the phenylalanine was filtered out by dialysis...a nasty way to treat that.

I also take rhodiola which is a COMT inhibitor. Since I have TWO COMT +/+ defects (both +/+) you would think I would have no benefit from that, but rhodiola makes me feel more peaceful and saves me from low blood sugar attacks. Now that I am on DHEA I do not find I need it so much.

 

[Lotus97]

So does Lysine work as well as Arginine for reducing ammonia? I've been reading that too much NO (nitric oxide) could be a bad thing. An alternative source of Lysine could be from magnesium lysinate. Doctor's Best has a chelated magnesium supplement with magnesium glycinate/lysinate chelate.

I would caution anyone thinking of trying Nardil. Nardil and other MAO inhibitors have potentially deadly interactions with certain foods. I learned this from an episode of Castle where someone killed a guy who was taking Nardil by serving him cranberry juice mixed with balsamic vinegar This from eMedTV:
Cause of Nardil Food Interactions: The Tyramine Effect
Monoamines are a certain type of chemical in the body that include dopamine, norepinephrine, epinephrine, serotonin, melatonin, histamine, and several others. Monoamine oxidase is an enzyme that breaks down monoamines. MAOI medications block the action of monoamine oxidase, causing an increase in the level of monoamines in the body. In depression, the level of monoamines can be low, so increasing monoamines usually helps with depression symptoms.

Unfortunately, monoamine oxidase is also responsible for breaking down tyramine, a naturally occurring chemical that affects blood pressure. MAOI medications keep the body from breaking down tyramine and can lead to extremely high tyramine levels (which can be very dangerous). High levels of tyramine can cause a "hypertensive crisis" (dangerously high blood pressure).

 

[dbkita]

So does Lysine work as well as Arginine for reducing ammonia? I've been reading that too much NO (nitric oxide) could be a bad thing. An alternative source of Lysine could be from magnesium lysinate. Doctor's Best has a chelated magnesium supplement with magnesium glycinate/lysinate chelate.

There is very little lysinate in that Doctor's Best brand you are referring to if memory serves. The vast majority is glycinate. Sorry. I think there are lysine orotate supplements but I don't know how much orotate is healthy. The European Food Safety Agency set a no abnormal effect lower limit of like 50 mg / kg body weight. So that is for me like 3.5 grams allowance which can get consumed really quickly if you take multiple orotate supplements.

 

[dbkita]

About reducing need for BH4 in making neurotransmitters...I do do something in that regard - it is small but could be significant. I never take supplements that contain phenylalanine (requires 2 BH4 to assimilate to dopamine), but only take tyrosine to help my thyroid and dopamine levels (requires only 1 BH4). There are many thyroid and neurotransmitter vitamin products out there that contain phenylalanine, my doctor even wanted me to take one, but I treat that as poison! I believe my father had PKU at the end but the phenylalanine was filtered out by dialysis...a nasty way to treat that.

I also take rhodiola which is a COMT inhibitor. Since I have TWO COMT +/+ defects (both +/+) you would think I would have no benefit from that, but rhodiola makes me feel more peaceful and saves me from low blood sugar attacks. Now that I am on DHEA I do not find I need it so much.

The main aspect of Rhodiola is not its impact on COMT but its use as an adrenal adaptogen with the net effect that it tends to lower cortisol (or at least high output of cortisol). Can't remember the precise mechanism. Phosphatidyl serine also lower cortisol but via lowering ACTH signaling.

On the other hand I know some naturopaths and such swear by rhodiola to modulate the cortisol response perhaps to spare the adrenals during stress. Maybe the idea is to prevent the sensitivity of the adrenals to stress. Dunno.

I do know a friend of mine who was otherwise pretty healthy took rhodiola for since he heard it would help anabolism (lowered post exercise cortisol response?) but he dosed too high and ended up with too low a levels of cortisol for a while. Not so good.

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To answer your other question about carnitine it is an amino acid but is at most a weak acid.

If you are interested here is a link showing pKa values (log base 10 disassociation constant) for all the amino acids.
For example the pk1 column means the pH of the solution needed to protonate the COO- carboxyl group. In other words
in a strong acid with a pKa less than say 2.34 glycine will exist as COOH but above that will tend to be COO-. pk2 relates to protonation of the NH3+ group in a base.

For reference the pKa for L-carnitine is 3.8. The higher the pKa the less acidic is the compound if it were itself at high enough concentrations in a solvent. Certainly very strong acids have a pKa < -1.74 (note the minus sign)
(for more information: http://en.wikipedia.org/wiki/Acid_strength#Common_strong_acids)

In short carnitine is not inherently acidic. I only brought up lysine since it is generally sold only as lysine monohydrochloride. It is the HCL that can get you into trouble.

However, sometimes people taking things like carnitine, CoQ10, etc. can have reflux or gastritis because they alter the electron transport chain or increase mitochondrial activity and as they get absorbed in the gastric lining on the way down the GI tract, the parietal cells in the stomach can produce more acid which in theory can be a good thing but if your gastric lining is not in good shape, you may have adverse issues.

I fully empathize with all the pill taking. You might want to try to see if you can heal your gastric lining some or separate out those supplements that eat your insides. Good luck

 

[Lotus97]

There is very little lysinate in that Doctor's Best brand you are referring to if memory serves. The vast majority is glycinate. Sorry. I think there are lysine orotate supplements but I don't know how much orotate is healthy. The European Food Safety Agency set a no abnormal effect lower limit of like 50 mg / kg body weight. So that is for me like 3.5 grams allowance which can get consumed really quickly if you take multiple orotate supplements.

They don't specify what proportion is lysinate and what is glycinate.

 

[dbkita]

They don't specify what proportion is lysinate and what is glycinate.

I have read the Albion white paper. It is less than 10%. Up to you though if you want to try it. Good luck.

 

[Lotus97]

I have read the Albion white paper. It is less than 10%. Up to you though if you want to try it. Good luck.

Why would they even bother adding the lysinate if it's only 10%? Is that a marketing thing?

 

[dbkita]

Why would they even bother adding the lysinate if it's only 10%? Is that a marketing thing?

It's Albion's patent for chelated magnesium to supposedly enhance bioavailability and to reduce intestinal discomfort. As far as exactly why, you would have to ask one of their chemists sorry. There are multiple brands that use the Albion patent including Solgar Chelated Magnesium and Bluebonnet (the one I prefer). Again if you are looking to add lysine that is the wrong tree bark up imo.

 

[Lotus97]

It's Albion's patent for chelated magnesium to supposedly enhance bioavailability and to reduce intestinal discomfort. As far as exactly why, you would have to ask one of their chemists sorry. There are multiple brands that use the Albion patent including Solgar Chelated Magnesium and Bluebonnet (the one I prefer). Again if you are looking to add lysine that is the wrong tree bark up imo.

Lysine powder doesn't seem to bother me. I just thought others might be interested since it would double as a magnesium supplement. I was honestly just curious about why they included the lysinate. I've looked at so many different supplements over the past few years and I question why companies do certain things. I've noticed that Life Extension tends to put one extra special ingredient in many of their supplements that few if any other companies are selling. Maybe it does make the supplement more effective, but it's also about marketing. Other times the dosages of some of the ingredients in some of these combination formulas seem too low to do much of anything. Except for the nucleotides and pycnogenol in the Yasko multi Rich recommends, the dosages of the other ingredients seem very underwhelming. 6 tablets only have 100 mg TMG when TMG usually comes in 500 mg capsules and the b vitamins are pretty low for non active ones.

 

[dbkita]

I agree that the Yasko multivitamin is underwhelming. I think we have to remember though that Dr Yasko's research was initially aimed at children with autism and they generally need lower doses. I think Rich Vank adopted the multivitamin with its low doses (he even advocated not a full serving of six pills if I remember correctly) because so many people here have MCS.

 

[Lotus97]

I agree that the Yasko multivitamin is underwhelming. I think we have to remember though that Dr Yasko's research was initially aimed at children with autism and they generally need lower doses. I think Rich Vank adopted the multivitamin with its low doses (he even advocated not a full serving of six pills if I remember correctly) because so many people here have MCS.

My dad has MCS. I'm not sure if I have MCS or just the symptoms. What specifically in it helps MCS? There was a thread where someone said they switched from the Yasko multi to the Thorne and felt worse, but then switched back to the yasko and felt better. I ended up buying Imunil nucleotides partially because of that, but also BOGO. And it's supposed to be good for the immune system, but now I'm finding out immune supplements can be a double edged sword. At least on of the strains of my probiotics also increases cytokines. I'm going to look into pycnogenol too. If I were to recommend a low dose multi I'd recommend thornes. It doesn't have some of the fancy stuff, but it's cheaper than Yasko's and has some active b vitamins including folinic acid and methylfolate so you save money not having to buy those separately either.

 

[dbkita]

My dad has MCS. I'm not sure if I have MCS or just the symptoms. What specifically in it helps MCS?

Sorry I never said it helped MCS. Rich Vank recommended lower than the six pill serving because I believe he was afraid people with MCS would react negatively to it. I guess I did not make that clear.

 

[invisiblejungle]

The main aspect of Rhodiola is not its impact on COMT but its use as an adrenal adaptogen with the net effect that it tends to lower cortisol (or at least high output of cortisol). Can't remember the precise mechanism. Phosphatidyl serine also lower cortisol but via lowering ACTH signaling.

On the other hand I know some naturopaths and such swear by rhodiola to modulate the cortisol response perhaps to spare the adrenals during stress. Maybe the idea is to prevent the sensitivity of the adrenals to stress. Dunno.

I do know a friend of mine who was otherwise pretty healthy took rhodiola for since he heard it would help anabolism (lowered post exercise cortisol response?) but he dosed too high and ended up with too low a levels of cortisol for a while. Not so good.

So-called "adaptogenic" herbs are marketed as being able to both lower cortisol if it's too high or raise cortisol if it's too low, despite the fact that this doesn't seem to work out in actual practice. It's a tantalizing prospect, but when you really think about it, it hardly makes sense. How could a plant do both? Imagine if they discovered a new herb, and it was claimed that it can heal both hypothyroidism and hyperthyroidism. What kind of mechanism would allow that?

There is a lot of mix-up whenever ideas are translated from east to west, not just language-wise, but also conceptually. Western practitioners seem to prescribe adaptogens like ginseng, eleuthero, and rhodiola like candy, believing that they can help anybody. But these herbs are not used that way in oriental medicine. These are powerful herbs with powerful effects, and they are only for certain people with certain conditions.

One interesting idea in herbalism is related to locations: the herbs that grow in a specific locale are geared towards the people of that region. When we look at adaptogens, they mostly grow in harsh climates, especially cold, mountainous areas. Well, the people who live here are tough; the weak ones died out a long time ago. These people would naturally have resilient hormonal systems, so for them, high cortisol would be a much more common issue than low cortisol. (It's mostly the "weaklings" who end up with low cortisol lol) And we can see that the adaptogenic herbs do have a cortisol-lowering effect, as seen in numerous studied.

As far as I know, the only herb that's been shown to raise cortisol is rehmannia, a traditional Chinese herb that is used to replenish depleted kidney yin. Also, gemmotherapy is a relatively new branch of herbalism that evolved in France about 50 years ago. Instead of using the mature plants as in traditional herbalism, gemmotherapy uses the buds and shoots of young, growing plants. Sort of like plant stem cells. According to their literature, ribes nigrum (black currant) has a cortisol-lifting effect.

 

[dbkita]

Excellent post. I like the cold northern climate argument makes a lot of sense.

Anyways I agree. I think the reality is rhodiola tends to lower cortisol output. This can often be a bad thing for people who have inflammation or other chronic problems let alone stress. If stress is the problem and cortisol is high, then someone saying they want to lower their cortisol to say sleep, build muscle, etc. is a fool's errand imo since they have not corrected the underlying problem. Again some naturopaths push it to spare the adrenals. Personally I think it is a crock since their is no replacement for the bioidentical hormones if you have a serious condition like an autoimmune disease, etc.