Rest periods and can CFS people get really well?

[Kimsie]

How much niacin and the form of niacin is an individual thing, I think.

Adreno, When you took more than 250 mg of niacinamide per day, were you taking ribose? It might be that you didn't have enough of the purine synthesis pathway ingredients to use the niacinamide and so it ended up being methylated instead of being made into NAD?
I am not saying that I think you should take more niacinamide or ribose, because at this time I don't really think that increasing the NAD pool is the final answer, I'm just curious about why the niacinamide was causing problems with methylation.

Also, to anyone who wants to respond, what symptoms do you get when you have problems with methylation? All the data you people here give me is helpful and in our family, I think that the symptoms of our sons are caused by the use of the folate cycle as a producer of ATP through a pathway that uses 1 NADPH for each ATP produced, so folate gives one son symptoms and apparently the other son can use that pathway without needing any extra folate but he does need to take extra folate (about 2.5 mg) when he takes a lot of niacin.

Has anyone ever tried fasting for at least 10 days? Did it do anything for you?

By the way, I am doing some revision on my hypothesis because I think I need to include the NO/peroxynitrite cycle problems in it. I might start a new thread when I get it ready, since this thread is already so long.

 

[adreno]

Adreno, When you took more than 250 mg of niacinamide per day, were you taking ribose? It might be that you didn't have enough of the purine synthesis pathway ingredients to use the niacinamide and so it ended up being methylated instead of being made into NAD?

Ribose causes me to crash (blood sugar?) so I don't take it. I have been doing a trial run of NAD+ sublinguals in the last few days, but that doesn't make me feel great either. Cold limbs, malaise, weakness, headache, tachycardia. B6 seems to help with these symptoms. Also, I do not really feel like NAD+ increases my energy. Perhaps I'll just stick to my 250mg niacinamide in the future.

 

[nandixon]

I had checked out catalase supplements before, but I forgot last night that I had rejected them because catalase would not survive digestion.
Mya Symons was using several other things with the catalase, including baking soda which seems to help with PEM, so I am not convinced that it was the catalase that was helping in that case.

This morning I saw this study and it seems that catalase would have to be liposomal to be effective. I am going to do more research on this idea later today.

From the standpoint of trying to reduce the deleterious effects of hydrogen peroxide where, for example, there is a functional deficiency of catalase, I think the best/easiest thing to use is probably N-acetylcysteine (N-acetyl-L-cysteine; NAC).

NAC works in this regard in many different ways, acting both directly to scavenge H2O2 (if I remember correctly) and also indirectly to remove H2O2 (by numerous ways, including increasing glutathione by several different mechanisms; and also even by potentially inducing catalase).

Note that even in cases where a person is found to have a high cysteine to sulfate ratio, NAC should not be a problematic source of cysteine, not only because of the benefit it provides with respect to H2O2, but also because a significant amount of the cysteine it supplies for glutathione synthesis actually comes from cysteine that is released from a person's existing store of oxidized cysteine (i.e., cystine). In other words, it doesn't add to the cysteine/cystine pool as much as one might think.

In my own case, I'm suspicious I might have a functional deficiency of catalase, not due to a lack of NADPH (or NADH), but rather because of a defect in PEX13 (see my signature), which assists in importing proteins - including the enzyme catalase - into peroxisomes. Without catalase present, there is a buildup of H2O2 inside the peroxisome which inhibits several of the enzymes inside there and also generally creates ROS (free radical) conditions that can spill over to the mitochondria, for example.

Also, just to note that NAC (or vitamin C for that matter) should never be taken at the same time as any B12 and iron, as this triple combination apparently can create a highly pro-oxidant effect.

 

[Kimsie]

From the standpoint of trying to reduce the deleterious effects of hydrogen peroxide where, for example, there is a functional deficiency of catalase, I think the best/easiest thing to use is probably N-acetylcysteine (N-acetyl-L-cysteine; NAC).

NAC works in this regard in many different ways, acting both directly to scavenge H2O2 (if I remember correctly) and also indirectly to remove H2O2 (by numerous ways, including increasing glutathione by several different mechanisms; and also even by potentially inducing catalase).

Note that even in cases where a person is found to have a high cysteine to sulfate ratio, NAC should not be a problematic source of cysteine, not only because of the benefit it provides with respect to H2O2, but also because a significant amount of the cysteine it supplies for glutathione synthesis actually comes from cysteine that is released from a person's existing store of oxidized cysteine (i.e., cystine). In other words, it doesn't add to the cysteine/cystine pool as much as one might think.

In my own case, I'm suspicious I might have a functional deficiency of catalase, not due to a lack of NADPH (or NADH), but rather because of a defect in PEX13 (see my signature), which assists in importing proteins - including the enzyme catalase - into peroxisomes. Without catalase present, there is a buildup of H2O2 inside the peroxisome which inhibits several of the enzymes inside there and also generally creates ROS (free radical) conditions that can spill over to the mitochondria, for example.

Also, just to note that NAC (or vitamin C for that matter) should never be taken at the same time as any B12 and iron, as this triple combination apparently can create a highly pro-oxidant effect.

I'll have to check into the pro-oxidant effect because we normally take NAC with C.

 

[nandixon]

I'll have to check into the pro-oxidant effect because we normally take NAC with C.

That's okay. It's NAC + B12 + iron, or vit C + B12 + iron, that has the pro-oxidant potential. It's some Russian work from several years ago. I think they were looking at using the effect for anti-tumor purposes within cancer cells, but I can't remember the details.

 

[Kimsie]

OK, we aren't taking them with iron. I am the only one in the family who takes any supplementary iron, and I always take it alone or sometimes with C, which is supposed to increase absorption.

 

[Kimsie]

I think I just figured out another very significant player in the vicious cycle that might explain how the NO/ONOO- part of the cycle gets going.

I already explained that the molybdenum cofactor relies on iron-sulfur clusters and that's why I think that sulfite oxidase is inhibited and the cysteine/sulfate ratios is high.

Well, uric acid is a main scavenger of peroxynitrite, and uric acid is formed by xanthine oxidase, another molybdenum cofactor enzyme! So serum uric acid is low in many of these illnesses but I think some people just hold on to the uric acid trying to get rid of the peroxynitrite, even when the uric acid is not activated. It has to be activated by ascorbate, and ascorbate is activated by GSH, which needs NADPH.

So all these things are interrelated in a vicious cycle - H2O2, GSH/GSSH levels, NADPH, BH4 levels, superoxide production, ONOO- levels, iron-sulfur damage and problems with the molybdenum cofactor for sulfite oxidase and xanthine oxidase and of course - the inhibition of the electron transport chain and the disruption of the energy production of the cell.

It is possible to get uric acid powder and it is absorbed in the intestine, but I wonder if it is the active form or not or if it matters very much?

 

[halcyon]

So serum uric acid is low in many of these illnesses

Do you have a reference for that?

It is possible to get uric acid powder and it is absorbed in the intestine, but I wonder if it is the active form or not or if it matters very much?

Isoprinosine can increase serum uric acid levels. It is seen as a negative side effect as elevated uric acid can cause a number of problems in the body. I'm not sure supplementing with uric acid would be a great idea.

 

[Kimsie]

Here's one. I think I should have said that altered serum uric acid levels are found in many of these illnesses.
Yes, I was toying around with the idea of supplementing with it, but someone mentioned inosine, and that is most likely a better way to go.

 

[adreno]

Note that many have reported negative reactions (worsening) to inosine, as it is a potent immunomodulator. It also increases mast cell degranulation.

 

[Kimsie]

Note that many have reported negative reactions (worsening) to inosine, as it is a potent immunomodulator. It also increases mast cell degranulation.

It seems that in these illnesses some people have high uric acid and others have low, so it is probably a good idea to have a serum uric acid to see which catagory a person is in.

It might be that the people who have negative reactions to inosine are already in the high category. Some illnesses pretty much always have low uric acid, for instance MS, and MS has been shown to improve with inosine supplementation and no one in that study had problems taking the inosine. But it looks as if with CFS a person could be high or low.

Or it might be that a person just has to take a small dose and see how they respond before trying a larger dose.

 

[Mij]

My uric acid was tested before I took Imunovir and it was normal. It did not raise uric acid but caused me to have a total relapse with added new symptoms. I took inosine for 3 months with no reaction, good or bad.

 

[adreno]

It seems that in these illnesses some people have high uric acid and others have low, so it is probably a good idea to have a serum uric acid to see which catagory a person is in.

It might be that the people who have negative reactions to inosine are already in the high category.

But what would be the symptoms of high uric acid? Would they be similar to the reports of swollen glands, increased heat, fatigue, malaise and other signs of immune stimulation?

In any case, I'd rather take prebiotics to raise uric acid. We need those SCFAs anyway.

 

[Kimsie]

I am thinking about 5-HTP. I know that some people here already use it as a sleep aid, but I think that it might help for another reason. 5-HTP bypasses the step in serotonin synthesis that uses BH4, so by sparing BH4 you will use up a little less NADPH. I am not sure how much BH4 is used for serotonin synthesis, but I know it is heavily used in the gut.

This should help with the NO/ONOO cycle a little.

It might seem that it would be a good idea to take L-dopa, too, but dopamine production has a short and long term regulator, but the regulator for serotonin appears to only take a few hours to change. I wouldn't mess with dopamine synthesis for that and for other reasons.

Of course a person shouldn't use 5-HTP if they take an SSRI.

 

[dannybex]

In my own case, I'm suspicious I might have a functional deficiency of catalase, not due to a lack of NADPH (or NADH), but rather because of a defect in PEX13 (see my signature), which assists in importing proteins - including the enzyme catalase - into peroxisomes. Without catalase present, there is a buildup of H2O2 inside the peroxisome which inhibits several of the enzymes inside there and also generally creates ROS (free radical) conditions that can spill over to the mitochondria, for example.

Slightly off topic, but for a year or so now, I've been extremely confused when it comes to NAD vs. NADH vs. NADPH. SO confusing…

@nandixon, can you explain these as if you were talking to a first grader?

NAD comes from nicotinic acid or niacin, but that's about as far as I understand it, then my brain goes to mush.

Thank you.

 

[Kimsie]

But what would be the symptoms of high uric acid? Would they be similar to the reports of swollen glands, increased heat, fatigue, malaise and other signs of immune stimulation?

In any case, I'd rather take prebiotics to raise uric acid. We need those SCFAs anyway.

It is likely that taking the NAD recipe can raise uric acid, since it is mostly ingredients for purine synthesis. It might be that the immune stimulation of inosine is from the sudden increase, and increasing the synthesis of purines should be able to raise uric acid without sudden spikes in inosine. Taking inosine would probably only help people who have low serum uric acid, but the NAD recipe helps with ATP and NAD/NADP pool synthesis.

My uric acid was tested before I took Imunovir and it was normal. It did not raise uric acid but caused me to have a total relapse with added new symptoms. I took inosine for 3 months with no reaction, good or bad.

Taking inosine would probably only help people who have low serum uric acid.

 

[Kimsie]

Slightly off topic, but for a year or so now, I've been extremely confused when it comes to NAD vs. NADH vs. NADPH. SO confusing…

@nandixon, can you explain these as if you were talking to a first grader?

NAD comes from nicotinic acid or niacin, but that's about as far as I understand it, then my brain goes to mush.

Thank you.

I am sure nandixon can explain a lot more but maybe this will help a little.

 

[sueami]

Checking in. With a warning. Be very strict about the rest periods.

I was doing quite well until Friday, my eighth day strictly adhering to this protocol. I had an awesome dream, woke full of insights and energy and felt generally well through the day. I increased activity levels without paying attention to what I was doing.

Instead of resting quietly in front of the woodstove first thing in the morning, I talked to my husband, telling him about the dream and my insights.

Later on, I started surfing the internet on my tablet after several rest periods, not counting the surfing time towards my 3 daily hours/20 minutes max activity, because, I rationalized, I was lying down and how much energy could I really be using reading an article or three.

In the afternoon, my daughter wanted to go hang out with a friend who lives a 10 minute drive away. DH was busy working from home and I felt good, so I decided to take her.

And because the sweet potato glass noodles that are a staple of my breakfasts on my autoimmune protocol were at a shop just five minutes further from the friend's house, I stopped there. And because I was driving right by it on the way home, I stopped at the feed store to see if they had any fresh eggs.

By 6 pm I felt horrible. I couldn't even walk all the way to the bedroom without having to lie on the carpet to avoid passing out.

I'm back in a full-on crash, worse than my holiday crash, as bad as anything I've felt in this past year of CFS full time. I've been whacked over the head with the need to be very honest and very aware of activity levels. I'm starting day 4 of this latest recovery period. Feeling a tiny bit better. Waiting to see how day 8 feels.

A question, for @Kimsie : Why do I feel so much worse when I lay down than when I'm up and about? I'm thinking I must go into some alternate energy production process to move around that provides energy, presumeably at an unwanted cost. And when I'm resting, I'm in whatever default mode is broken for me, with no energy for anything except a bit of mitochondrial protection. It's been especially awful since Friday's crash within a crash.

I thank god for having learned and practice mindfulness meditation in the past. Not sure how I'd be managing to get through this otherwise.

 

[ahmo]

@sueami so sorry to hear

 

[Kimsie]

Checking in. With a warning. Be very strict about the rest periods.

I was doing quite well until Friday, my eighth day strictly adhering to this protocol. I had an awesome dream, woke full of insights and energy and felt generally well through the day. I increased activity levels without paying attention to what I was doing.

Instead of resting quietly in front of the woodstove first thing in the morning, I talked to my husband, telling him about the dream and my insights.

Later on, I started surfing the internet on my tablet after several rest periods, not counting the surfing time towards my 3 daily hours/20 minutes max activity, because, I rationalized, I was lying down and how much energy could I really be using reading an article or three.

In the afternoon, my daughter wanted to go hang out with a friend who lives a 10 minute drive away. DH was busy working from home and I felt good, so I decided to take her.

And because the sweet potato glass noodles that are a staple of my breakfasts on my autoimmune protocol were at a shop just five minutes further from the friend's house, I stopped there. And because I was driving right by it on the way home, I stopped at the feed store to see if they had any fresh eggs.

By 6 pm I felt horrible. I couldn't even walk all the way to the bedroom without having to lie on the carpet to avoid passing out.

I'm back in a full-on crash, worse than my holiday crash, as bad as anything I've felt in this past year of CFS full time. I've been whacked over the head with the need to be very honest and very aware of activity levels. I'm starting day 4 of this latest recovery period. Feeling a tiny bit better. Waiting to see how day 8 feels.

A question, for @Kimsie : Why do I feel so much worse when I lay down than when I'm up and about? I'm thinking I must go into some alternate energy production process to move around that provides energy, presumeably at an unwanted cost. And when I'm resting, I'm in whatever default mode is broken for me, with no energy for anything except a bit of mitochondrial protection. It's been especially awful since Friday's crash within a crash.

I thank god for having learned and practice mindfulness meditation in the past. Not sure how I'd be managing to get through this otherwise.

Thanks for sharing. I recommend using a timer. It's really hard to rest when you feel good.As you know, reading isn't resting, you have to rest your brain, too.

I think you might be right about stopping using glycolysis when you rest; in your case I am sure you are using the glycolysis pathway for energy and the lactic acid levels build up. When you take a total rest period it gives your body a chance to stop or slow the use of the excess glycolysis and use up some of that lactic acid so the levels don't get so high, but you don't have as much energy.