Rest periods and can CFS people get really well?

[adreno]

I'm in a bad PEM crash now, trying to rest my way out of it and taking small amounts of the NAD recipe supps, which I'd stopped four or five days ago because I thought I might be having hypogyclemia (it was at least partly anxiety attacks, blood sugar readings were normal. though my doc says it's the rate at which blood sugar drops that triggers hypogylemia, not the actual number.)

D-ribose seems to cause me symptoms of hypoglycemia, too. Cold limbs, tingling, anxiety/irritability. Also, there is a nasty crash as it wears off (which it does rather quickly), and it actually seems to leave me worse off than before I took it.

 

[adreno]

@Kimsie

Isn't our main problem that whatever way we increase NAD+, it will quickly get reduced to NADH, and then will not be able to be oxidized back to NAD+? So taking NAD precursors is perhaps just contributing to the problem of a low NAD/NADH ratio, and an overflow of electrons to be handled by the plasma membrane redox system?

Another way to describe this problem is accelerated aging.

So there is really no way out of this, other than regenerating the faulty mitochondria...would mitochondrial biogenesis work to correct the problem of the ETC?

Btw, the two major antioxidants of the PMRS are CoQ10 and a-tocopherol; those might have merit to supplement. Also resveratrol increases activity of the PMRS.

 

[ahmo]

@adreno I've had good results since introducing reseveratrol, helpful when I feel excess peroxynitrite.

 

[Mandarine]

Hi all,

this is my first post here so I hope you won`t understand it as a promotion..
Please excuse my incorrect kind of writing. I´m from germany ;-)

Suffering from ME since 6.5 years.

My experience by making a lot of rest periods is that I can reduce PEM and sometimes arise my Energylevel (presumably because of less PEM).
It´s much better for me to cut 1 hour activity into 6 short 10 minute peaces than being active for 20 Minutes without a break.


I followed this thread from the first day and it inspired me to take deeper look to NADH.

Discovered a supplement with a patented stabilized form of NADH by Dr. Birkmayer:

https://www.thefinchleyclinic.com/shop/nadh-20mg-sublingual-tablets-month-supply-p-621.html


Does anyone of you tried it?

Seems like this could solve the problem of oxidation.


Here is a study result: http://www.ncbi.nlm.nih.gov/pubmed/10071523


Here is a Video where Dr. Birkmayer talk about NADH. He developed the stabilized form.

At Minute 4 he talks about the effect to heart cells and heart function. Maybe it could improve POTS?

He also says that NADH lowers blood pressure and stimulates the immunsystem which maybe does not fit for many us.

At minute 12 he explains why NADH must be stabilized.

At minute 14:45 he says that the dosage for „CFS“ should be 60 to 80mg! (There has been the study linked above that showed improvements after 6 month taking 10mg of the stabilized NADH (ENADA) daily.
But I´m not sure if they really discriminated CF from CFS in this study.

At Minute 38 there are comparisons of different products.

I`d like to try it but it´s really expensive and hard to finance...
Regardless of the price I wanted to share the information. Maybe one of you can try it or already have experience with it to share.

Best regards

 

[adreno]

NADH won't work in the long run, because it can't be reduced to NAD+. I think it is more likely to make the NAD/NADH ratio even worse.

 

[Kimsie]

@Kimsie

Isn't our main problem that whatever way we increase NAD+, it will quickly get reduced to NADH, and then will not be able to be oxidized back to NAD+? So taking NAD precursors is perhaps just contributing to the problem of a low NAD/NADH ratio, and an overflow of electrons to be handled by the plasma membrane redox system?

Another way to describe this problem is accelerated aging.

So there is really no way out of this, other than regenerating the faulty mitochondria...would mitochondrial biogenesis work to correct the problem of the ETC?

Btw, the two major antioxidants of the PMRS are CoQ10 and a-tocopherol; those might have merit to supplement. Also resveratrol increases activity of the PMRS.

I think that taking NAD precursors along with ribose does push the ETC, and it does seem to help to some degree with symptoms, but it doesn't solve the underlying problem, so I agree with you.

I think that the level of damage in the ETC is related to the amount of ROS at the time the ETC complexes are built, and they are always in the process of being built, so anything that lowers ROS is good. I have read that CoQ10 works as an antioxidant but if the levels get too high it can do the opposite, so it is probably good to supplement, but only up to a certain point. I need to learn more about resveratrol, at this point I think it could help.

Hydroxy B12 shots in large doses such as 30 - 50 mg per day is probably good, because it appears to be what I call a "suicide" antioxidant when it comes to peroxynitrite, i.e. most molecules only get used once and then excreted.

We are trialing dried thyroid but it will be a few more weeks at least before I can report on the results. I have reason to hypothesize that it could change epigenetics, but I don't have any information about whether it would help people with CFS at this time. I do have strong reason to think that it can help my sons' symptoms.

I am taking a break from the research right now for a couple of weeks because I was working so hard at it I was getting burned out. I plan to get back to it and continue to post, especially on the epigenetics for dummies thread, as soon as I feel rested enough. I mean as soon as my brain is rested enough to really focus on the problem again, I don't have CFS, so resting in general isn't an issue with me.

 

[Kimsie]

Hi all,

this is my first post here so I hope you won`t understand it as a promotion..
Please excuse my incorrect kind of writing. I´m from germany ;-)

Suffering from ME since 6.5 years.

My experience by making a lot of rest periods is that I can reduce PEM and sometimes arise my Energylevel (presumably because of less PEM).
It´s much better for me to cut 1 hour activity into 6 short 10 minute peaces than being active for 20 Minutes without a break.


I followed this thread from the first day and it inspired me to take deeper look to NADH.

Discovered a supplement with a patented stabilized form of NADH by Dr. Birkmayer:

https://www.thefinchleyclinic.com/shop/nadh-20mg-sublingual-tablets-month-supply-p-621.html


Does anyone of you tried it?

Seems like this could solve the problem of oxidation.


Here is a study result: http://www.ncbi.nlm.nih.gov/pubmed/10071523


Here is a Video where Dr. Birkmayer talk about NADH. He developed the stabilized form.

At Minute 4 he talks about the effect to heart cells and heart function. Maybe it could improve POTS?

He also says that NADH lowers blood pressure and stimulates the immunsystem which maybe does not fit for many us.

At minute 12 he explains why NADH must be stabilized.

At minute 14:45 he says that the dosage for „CFS“ should be 60 to 80mg! (There has been the study linked above that showed improvements after 6 month taking 10mg of the stabilized NADH (ENADA) daily.
But I´m not sure if they really discriminated CF from CFS in this study.

At Minute 38 there are comparisons of different products.

I`d like to try it but it´s really expensive and hard to finance...
Regardless of the price I wanted to share the information. Maybe one of you can try it or already have experience with it to share.

Best regards

I believe that taking NADH can help if you can afford to take large amounts of it, but taking some niacin or niacinamide along with ribose and maybe some of the other ingredients in the NAD recipe can do the same thing for less money. I currently think that you don't need as much niacin or niacinamide as I was originally saying. I now think that up to 400 mg a day is enough.

Larger doses of niacinamide should help people who are overmethylated, but I am still not sure how to be certain if you are overmethylated. I am sure my sons are undermethylated, though.

 

[Kimsie]

NADH won't work in the long run, because it can't be reduced to NAD+. I think it is more likely to make the NAD/NADH ratio even worse.

I think that taking NADH is pretty much like taking the NAD recipe, except more expensive. I don't see why it would make the NAD/NADH ratio worse, unless it raises the ROS levels, which we don't really have any information if it does or not.

 

[adreno]

I think that taking NADH is pretty much like taking the NAD recipe, except more expensive. I don't see why it would make the NAD/NADH ratio worse, unless it raises the ROS levels, which we don't really have any information if it does or not.

Since the NADH can't be (sufficiently) oxidized to NAD+ in the ECTs, taking more NADH will only lead to a "surplus" of NADH and worsen the NAD/NADH ratio. The extra electrons then have to be dumped somewhere for NAD+ to be regenerated, and the PMRS can do this to a limited extent. The extra electrons can also latch onto O2 and create ROS. It is explained more clearly in this video:

 

[Kimsie]

Since the NADH can't be (sufficiently) oxidized to NAD+ in the ECTs, taking more NADH will only lead to a "surplus" of NADH and worsen the NAD/NADH ratio. The extra electrons then have to be dumped somewhere for NAD+ to be regenerated, and the PMRS can do this to a limited extent. The extra electrons can also latch onto O2 and create ROS. It is explained more clearly in this video:

Well, you could be right about that, but don't you think that having a larger concentration or pool of NAD/NADH in the mitochondria will increase the amount of electrons making it through the ETC, as in increasing the amount of one of the components in a chemical solution to increase the amount of the product of the reaction? Or is the improvement in symptoms due to an increase in sirtuin activity?

 

[sueami]

@Kimsie a whilr back you mentioned thudding heart sensation when lying down to nap. i am convinced now that is potassium depletion. americans are chronically under consuming k via diet. i encourage you to get a six pack of coconut water and drinking a bottle next time you feel it. don't drink nine bottles. but one or two is totally fine. play around with supplementing potassium and see if that resolves it.

 

[Kimsie]

@Kimsie a whilr back you mentioned thudding heart sensation when lying down to nap. i am convinced now that is potassium depletion. americans are chronically under consuming k via diet. i encourage you to get a six pack of coconut water and drinking a bottle next time you feel it. don't drink nine bottles. but one or two is totally fine. play around with supplementing potassium and see if that resolves it.

OK, I'm willing to give it a try. I always feel it constantly for almost 4 years any time I hold still whether standing, sitting, or lying.

 

[adreno]

D-ribose looks like bad news, as it causes advanced glycation:

D-ribose induces cellular protein glycation and impairs mouse spatial cognition.

 

[Kimsie]

D-ribose looks like bad news, as it causes advanced glycation:

D-ribose induces cellular protein glycation and impairs mouse spatial cognition.

Did you look at the study? They gave the mice either the equivalent of 12 or 120 grams of ribose a day for a 130 pound person and at the 12 gram dose the glycation was the same as with 12 grams of glucose. The 120 gram dose raised glycation by about 30% but who is going to take that much? It looks like 12 grams raised it by about 10%, but so did glucose.

The spatial cognition was not affected at the 12 gram dose but only the 120 gram dose.

It's something to consider, but I think the title of the study makes it appear more extreme than when you read the study itself. I wonder if the ribose is worse than any other form of sugar when it is taken at 10 or 12 grams a day? Many people have much more than 12 grams of table sugar a day, and that also causes advance glycation. I'm not saying that we should eat sugar but most people don't get that fearful over eating a medium sized cookie or something else with 12 grams of sugar in it.

 

[adreno]

You can't directly translate the dosage to humans. As a rule of thumb, the human equivalent dosage (HED) is about 10 times less than the rodent dosage. The formula is as follows :

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

Human Km = 37

Mouse Km = 3

Rat Km = 6

I calculate that to 1g and 10g, respectively for a 65kg human.

 

[adreno]

Previous studies from our laboratory have demonstrated that in vitro glycation of bovine serum albumin, neuronal Tau and α-synuclein with Rib are much faster than with Glc7, 8, 9 and that Rib treatment promotes AGE production in HEK293T and SH-SY5Y cells.10 In this study, we confirmed the quick AGE formation effect of Rib in U251 and U87MG cells. These data demonstrate that Rib induces protein glycation and enhances the yield of AGEs in different types of cells. Furthermore, our recent data have shown that injection of Rib for 30 days leads to a significant higher level of AGEs in mouse serum and brain;10 in addition, according to results from the present work, administration with Rib for a shorter period (10 days) increased protein glycation in mouse serum and elevated the level of AGEs in the mouse brain. In contrast, Glc does not produce a significant glycation effect in vitro and in vivo under the same experimental conditions.11 These data together provide evidence that Rib is an efficient glycator that actively participates in protein glycation and AGE formation both inside (endogenous glycation) and outside the body (exogenous glycation).

d-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation

 

[Kimsie]

You can't directly translate the dosage to humans. As a rule of thumb, the human equivalent dosage (HED) is about 10 times less than the rodent dosage. The formula is as follows :

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

Human Km = 37

Mouse Km = 3

Rat Km = 6

I calculate that to 1g and 10g, respectively for a 65kg human.

I hadn't heard of that before. I would be a lot more convinced if you had some human studies for this.

 

[Tunguska]

D-ribose looks like bad news, as it causes advanced glycation:

D-ribose induces cellular protein glycation and impairs mouse spatial cognition.

The glycation was a concern for me from the start, because of structural problems, which is why I use ribose sparingly (given the absence of major positive effects) and didn't consume too close to protein (and also poly fats). What I didn't know that shows up in that study is that Rutin seems to be very good against AGEs. I missed it by a mile, quick search gives: https://www.ncbi.nlm.nih.gov/pubmed/16443355

 

[adreno]

Carnosine looks interesting [mice study]:

Previous studies have shown that brain mitochondria of 3xTg-AD mice show deficits in mitochondrial respiration. We have also found a similar age-dependent decrease in the activity of complex I (NADH-dehydrogenase), II (succinate-dehydrogenase), and IV (COX) in mitochondria isolated from the cortex and hippocampus of 3xTg-AD animals.

To test the effect of carnosine on such age-dependent mitochondrial deficits, treated and untreated 3xTg-AD mice were investigated for the activity of mitochondrial complexes I, II, and IV by employing a combination of blue-native poliacrylammide gel electrophoresis (BN-PAGE) and subsequent histochemical in-gel staining of isolated mitochondria from the hippocampus and cerebral cortex.

Data from these experiments indicate that, compared to control mice, hippocampal mitochondria of untreated 3xTg-AD mice show a strong deregulation in the activity of complexes I, II, and IV. Interestingly, carnosine-fed 3xTg-AD mice exhibited a complete recovery of all these deficits and in the case of complexes II and IV the activity was actually significantly higher compared to mitochondria of control animals.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058055/

 

[adreno]

Carnosine scavenges ROS in mitochondria:

It is suggested that NAD+ availability strongly affects cellular aging and organism lifespan: low NAD+availability increases intracellular levels of glycolytic triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate) which, if not further metabolized, decompose spontaneously into methylglyoxal (MG), a glycating agent and source of protein and mitochondrial dysfunction and reactive oxygen species (ROS). MG-damaged proteins and other aberrant polypeptides can induce ROS generation, promote mitochondrial dysfunction and inhibit proteasomal activity.

The muscle- and brain-associated dipeptide, carnosine, is an intracellular buffer which can delay senescence in cultured human fibroblasts and delay aging in senescence-accelerated mice. Carnosine's ability to react with MG and possibly other deleterious carbonyl compounds, and scavenge various ROS, may account for its protective ability towards ischemia and ageing.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874395/