Acetyl L- Glutathione, ATP, Baking Soda, Sam-e & Catalase = No PEM after exercise

[MeSci]

I'm well aware of the papers you are referring to and I am not disputing that there is a problem with excess lactate in muscle and gut in ME but that's not the same as having actual lactic acidosis which is very serious and can be fatal.

I'm very puzzled by your reply, which contradicts the papers and threads cited.

Excess production of lactate in muscle or gut can indeed lead to lactic acidosis, and we produce excessive lactate in muscle, some of us apparently also in the gut due to switching too quickly to anaerobic energy production. The lactate is taken away in the bloodstream to the liver, etc., to be broken down, but sometimes there is difficulty doing this for one or more reasons, and the pH of the blood falls abnormally low.

Lactic acidosis is not always serious. That depends on various things - how low the pH is, and a range of other factors.

Am I missing something?

 

[Sidereal]

I'm very puzzled by your reply, which contradicts the papers and threads cited.

Excess production of lactate in muscle or gut can indeed lead to lactic acidosis, and we produce excessive lactate in muscle, some of us apparently also in the gut due to switching too quickly to anaerobic energy production. The lactate is taken away in the bloodstream to the liver, etc., to be broken down, but sometimes there is difficulty doing this for one or more reasons, and the pH of the blood falls abnormally low.

Lactic acidosis is not always serious. That depends on various things - how low the pH is, and a range of other factors.

Am I missing something?

I just don't think we should be using terms like lactic acidosis when we mean something along the lines of somewhat elevated lactate in certain tissues under certain circumstances.

That KDM study did not demonstrate D-lactic acidosis in CFS patients. They did not measure D- (or L-) lactate concentrations in blood, stool or anywhere else. What they did was a stool analysis that found increased counts of two lactate-producing bacteria, Enterococcus faecalis and Streptococcus sanguinis, in CFS stools vs. normal controls. That's suggestive of increased lactate levels in CFS guts but doesn't prove it.

In normal humans these bacteria are also present, albeit in smaller numbers, as are plenty of other lactate-producing bacteria like lactobacilli and bifidobacteria and yet you don't see significant amounts of lactate in stools of healthy humans because a healthy microbiome also contains bacteria that utilise lactate and convert it to SCFAs like butyrate. There is a complex dynamic of bacterial cross-feeding in the gut whereby the products of bacterial fermentation are used to feed other bacteria. So, in studies where people who do not have ME/CFS supplement with lacto or bifido containing probiotics or various prebiotics that feed these bacteria, they often feel better and stool analysis shows increased butyrate even though those species don't directly produce butyrate. On the other hand, when I supplement with LAB I develop muscle pain, brain fog and an overall gross feeling because I can't clear that lactate.

So I don't doubt we have problems in this area but I do think we need to be careful about the language we use so that we don't leave ourselves exposed to more attacks from the medical profession.

 

[Sherlock]

bacteria that utilise lactate and convert it to SCFAs like butyrate.

Is this absorbed from the colon into the blood stream?

 

[Sidereal]

Is this absorbed from the colon into the blood stream?

I believe much of it is used as fuel for colonocytes but yes some of it is absorbed.

 

[Sherlock]

I believe much of it is used as fuel for colonocytes but yes some of it is absorbed.

Thanks, I'd also read years ago that SCFAs made in the colon from fiber are absorbed and used bodywide as fuel.

I asked because I'd read the claim that any vit K2 (which is fat soluble) which might be produced in the human colon cannot be absorbed in the colon -- that vit K2 can only be absorbed in the small intestine. Would you say that's false?

 

[Sherlock]

Thanks, I'd also read years ago that SCFAs made in the colon from fiber are absorbed and used bodywide as fuel.

I asked because I'd read the claim that any vit K2 (which is fat soluble) which might be produced in the human colon cannot be absorbed in the colon -- that vit K2 can only be absorbed in the small intestine. Would you say that's false?

I just stumbled on an answer:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021393/
2011

There is, however, ongoing debate on whether bacterial synthesis of vitamin K in the intestine provides a significant supply of this vitamin in humans. The colon contains a large reservoir of bacterial vitamin K2 (~2 mg), but it is now undeniable that this pool represents only about 10% of normal human requirements and is, therefore, insufficient to satisfy these requirements. Furthermore, there is some evidence of poor bioavailability of this intestinal source of vitamin K. Bile salts are necessary for effective absorption of vitamin K, but are not present in the colon, and the intestinal synthesis of vitamin K is not sufficient to compensate for deficiency due to biliary obstruction. Moreover, intestinal menaquinones are enveloped within the bacterial membranes and are, therefore, poorly available for intestinal adsorption. Taken together, these data argue against the concept of the colon as a significant source of vitamin K for human use, so that patients at risk of deficiency remain those who cannot absorb vitamin K from the small intestine2.

Of course, there will be some argument to the contrary - as ever.

 

[Mya Symons]

I am posting an update. I tried exercising 4 times a week and I crashed with PEM. Right now I also have the stomach flu so I am sure that had a bit to do with it. I was doing fine limiting myself to 3 times a week. I am going to try again and stick with the 3 times after I recover from the flu.

My conclusion is the supplements help me, but, of course, they are not a cure. I didn't expect that. For anyone who hasn't tried supplements, however, I would still suggest trying them. The Pall Protocol (Nutricology.com) and the extra supplements Glutathione (L-Glutathione & S-Acetyl Glutathione), NADH, Methylcobalamin, Catalase, MSM, Beta Alanine, Essential Amino Acids, DL-Phenylalaline and Sam-e have helped me the most in reducing the Fibromyalgia pain. I do take a lot of supplements! I am taking the Superoxide Dismutase out for now because it is made from wheat and I want to make sure that wasn't the cause of the crash. I also take Sucralfate and Zofran an hour before I take the supplements so I won't have stomach problems and take a break from all supplements on the weekend.

I have been able to reduce my dosage of tramadol down to one before I go to bed because of these supplements. Before them, I was taking two more doses a day. Further, before the supplements I was still going through the day with pain. I don't have any during the day now. I do have it right before bed though. However, this is a really significant improvement for me. If you have Fibromyalgia, I would definitely recommend trying these supplements.

But, I am still not sure about the ME/CFIDS. I want to stress that I do not have severe ME/CFIDS. I do get PEM after exercise that is getting better with supplements, but it is not gone and I have to be very careful not to go past my limits. And, I am still trying to figure out what the limits are with the supplements.

 

[ahmo]

@Mya Symons thanks for the heads-up about SOD and wheat I've also been gettin a lot of benefit from adding in several of Pall's suggestions.

 

[MeSci]

I am posting an update. I tried exercising 4 times a week and I crashed with PEM. Right now I also have the stomach flu so I am sure that had a bit to do with it. I was doing fine limiting myself to 3 times a week. I am going to try again and stick with the 3 times after I recover from the flu.

Are you sure the 'stomach flu' isn't part of the PEM? My gut is often the first thing to be affected by PEM.

It's very unwise to exercise with any kind of flu. Your body will be telling you to rest - with good reason.

 

[Mya Symons]

Are you sure the 'stomach flu' isn't part of the PEM? My gut is often the first thing to be affected by PEM.

It's very unwise to exercise with any kind of flu. Your body will be telling you to rest - with good reason.

I am pretty sure it is stomach flu because my brother-in-law had it and came over to our house anyway. I might "beat him within an inch of his life" later when I get well. I am taking a break from exercise right now since I have the flu.

 

[Mya Symons]

I'm looking over the posts again and there is a lot of speculation on NADH and whether it is good or bad for those with ME/CFIDS. DId anyone ever come to a solid conclusion? I take it everyday and started taking it in the hopes that it would boost energy. However, it seems to actually help with pain for some reason. Maybe it is due to it's norepinephrine boosting properties.

What do you think? Is it good or bad for ME/CFIDS?

 

[Mya Symons]

I only recall the overall exercise science. No details, sorry.

It is lipid peroxidation, btw.

A point of interest: the same aldehyde dehydrogenase family that breaks down MDA is also involved in breaking down the 1st metabolite of alcohol: acetaldehyde. So people with bad PEM might also have bad
alcohol intolerance.

I'm sorry. My brain is functioning a bit better today and I am just getting through some of these posts. I am interested in finding out more about lipid peroxidation and scavengers. Do you have any idea what antioxidants would be good lipid peroxidation scavengers? I tried quercetin and rutin and they did not seem to help me much and where expensive. I take Vitamin C 4 times a day through the Pall Protocol. I wonder if that is enough to take care of the lipid peroxidation. What do you think?

It looks like the Beta Carotene and tocopherol in the Pall Protocol also reduce lipid peroxidation. I believe?

 

[ahmo]

@Mya Symons I've just this moment been compiling a list from Pall's site. I don't know whether these are specific to lipids, but are items that were in the different protocols he listed which interested me.


http://www.thetenthparadigm.org/therapy.htm Below taken from the varied protocols quoted by Pall:

flavonoids, including “bioflavonoids,” olive leaf extract, organic botanicals, hawthorn extract

Flavonoids (flavones, rutin, hesperetin and others)

Grape seed extract (flavonoid)

Four different flavonoid sources: Ginkgo biloba extract, cranberry extract, silymarin, and bilberry extract

Artichoke extract—as flavonoid source?

GABA agonists—GABA acts as an inhibitory neurotransmitter to lower NMDA activity—these include the drug neurotin (gabapentin)

Histamine blockers—mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation (Chapter 7) and may therefore be part of the cycle mechanism

Spirulina—blue-green alga is a concentrated antioxidant source


Carotenoids (alpha-carotene, bixin, zeaxanthin and lutein)-lipid (fat) soluble peroxynitrite scavengers

Other phosphatidyl polyunsaturated lipids—this and the phosphatidyl choline are predicted to help restore the oxidatively damaged mitochondrial inner membrane

Zinc—antioxidant properties and copper/zinc superoxide dysmutase precursor

Acetyl-L-carnitine—important for restoring mitochondrial function

Vitamin B6—balance glutamate and GABA levels, lowers excitotoxicity

Riboflavin 5’-phosphate; Vitamin B6 in the form of pyridoxal phosphate

a-Lipoic acid

Valine and isoleucine—branched chain amino acids known to be involved in energy metabolism in mitochondria, and may be expected,therefore, to stimulate energy metabolism; modest levels may also lower excitotoxicity

 

[Mya Symons]

@Mya Symons I've just this moment been compiling a list from Pall's site. I don't know whether these are specific to lipids, but are items that were in the different protocols he listed which interested me.


http://www.thetenthparadigm.org/therapy.htm Below taken from the varied protocols quoted by Pall:

flavonoids, including “bioflavonoids,” olive leaf extract, organic botanicals, hawthorn extract

Flavonoids (flavones, rutin, hesperetin and others)

Grape seed extract (flavonoid)

Four different flavonoid sources: Ginkgo biloba extract, cranberry extract, silymarin, and bilberry extract

Artichoke extract—as flavonoid source?

GABA agonists—GABA acts as an inhibitory neurotransmitter to lower NMDA activity—these include the drug neurotin (gabapentin)

Histamine blockers—mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation (Chapter 7) and may therefore be part of the cycle mechanism

Spirulina—blue-green alga is a concentrated antioxidant source


Carotenoids (alpha-carotene, bixin, zeaxanthin and lutein)-lipid (fat) soluble peroxynitrite scavengers

Other phosphatidyl polyunsaturated lipids—this and the phosphatidyl choline are predicted to help restore the oxidatively damaged mitochondrial inner membrane

Zinc—antioxidant properties and copper/zinc superoxide dysmutase precursor

Acetyl-L-carnitine—important for restoring mitochondrial function

Vitamin B6—balance glutamate and GABA levels, lowers excitotoxicity

Riboflavin 5’-phosphate; Vitamin B6 in the form of pyridoxal phosphate

a-Lipoic acid

Valine and isoleucine—branched chain amino acids known to be involved in energy metabolism in mitochondria, and may be expected,therefore, to stimulate energy metabolism; modest levels may also lower excitotoxicity

Thanks Amo. I forgot about the Flavinox, MVM-Antioxidant and NAC Enhanced Antioxidant for some reason (10 second memory :thumbdown . They have many of the things you mentioned and I am just remembering that they also help with lipo-peroxidation.

 

[ahmo]

Also, Passiflora (passionflower):

Several flavonoids have been isolated from P. incamata;

Maltol, an aromatic compound, has antioxidant properties;

 

[Gondwanaland]

It looks like the Beta Carotene and tocopherol in the Pall Protocol also reduce lipid peroxidation. I believe?

Gamma E (mixed tocopherols and tocotrienols) has been keeping my HDL above 90 for over a year now.

Bromelain helps with fat digestion.

 

[Gondwanaland]

I'm looking over the posts again and there is a lot of speculation on NADH and whether it is good or bad for those with ME/CFIDS. DId anyone ever come to a solid conclusion? I take it everyday and started taking it in the hopes that it would boost energy. However, it seems to actually help with pain for some reason. Maybe it is due to it's norepinephrine boosting properties.

What do you think? Is it good or bad for ME/CFIDS?

Urea cycle
The urea cycle is a metabolic pathway that results in the formation of urea using two ammonium molecules and one bicarbonate molecule.[1] This route commonly occurs in the hepatic cell of the liver. (The reactions related to the urea cycle produce NADH). This NADH can be produced in two different ways. One of these uses oxaloacetate. In the cytosol there are fumarate molecules. Fumarate can be transformed into malate by the actions of the enzyme fumarase. The malate suffers the actions of malate dehydrogenase enzyme and it becomes oxaloacetate and producing a molecule of NADH. After that, oxaloacetate will be recycled to aspartate, as transaminases prefer these keto acids over the others. This recycling maintains the flow of nitrogen into the cell.

 

[Mya Symons]

O.K. But then there is this:
The two NADH produced can provide energy for the formation of 4 ATP(cytosolic NADH provides only 1.5 ATP due to the glycerol-3-phosphate shuttle who transfers the electrons from cytosolic NADH to FADH2 and that gives 1.5 ATP), a net production of one high-energy phosphate bond for the urea cycle. However, if gluconeogenesis is underway in the cytosol, the latter reducing equivalent is used to drive the reversal of the GAPDH step instead of generating ATP

Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as G3PDH) (EC1.2.1.12) is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation ofapoptosis,[1]ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport.[2] In sperm, a testis-specificisoenzymeGAPDHS takes its role.

I'm still left confused. It sounds as if supplementing NADH could either provide energy for the cell in the form of ATP or interfere with GAPDH. Which is it most likely to do when a person has Fibromyalgia and/or ME/CFIDS?


Here is an interesting study that claims the FMS could be caused by enhanced gluconeogenesis with breakdown of muscle proteins, resulting from a deficiency of oxygen and other substances needed for ATP synthesis.

http://informahealthcare.com/doi/abs/10.3109/13590849208997961

If this is true, then I assume NADH would help FMS, at least, even if it interferes with GAPDH. Ouch, now my brain hurts! I don't know if I have this right or not.

 

[Sherlock]

Do you have any idea what antioxidants would be good lipid peroxidation scavengers?

I don't know, but sciency weight lifters probably still take melatonin, while AFAIK runners (who generate lots more ROS) take things like alcohol free beer. Those preferences aren't critical and will come and go.

From my point of view, the most important thing to take after exercise is a nap.. within 1-3 hours and having at least 1 minute of nap per minute of exercise. [And that might be a melatonin connection right there, of the DIY kind.]

 

[MeSci]

I don't know, but sciency weight lifters probably still take melatonin, while AFAIK runners (who generate lots more ROS) take things like alcohol free beer. Those preferences aren't critical and will come and go.

From my point of view, the most important thing to take after exercise is a nap.. within 1-3 hours and having at least 1 minute of nap per minute of exercise. [And that might be a melatonin connection right there, of the DIY kind.]

I can't nap, even if I'm sleepy. I can only sleep at night, and usually have to take something to help even then. Some nights that includes melatonin, but it's not definite in my mind that it works for me.