You are suggesting
here in this thread that working out your NAD+/NADH ratio, done indirectly via a pyruvate/lactate test, is a reliable measure of electron transport chain function and mitochondrial function.
Where did you come across this? I have never seen this test talked about as a way to gauge mitochondrial function/dysfunction or energy production. It certainly would be nice to have a good measure of mitochondrial health, but I'd need to see some studies indicating that the NAD+/NADH ratio is the way to measure this.
There are lots of studies showing relationships between lactate/pyruvate and NAD+/NADH. I guess to find them you have to use the right keywords. For example:
http://www.jbc.org/content/289/4/2344
which contains in the abstract statements such as:
"Free cytosolic [NAD+]/[NADH] ratio maintains cellular redox homeostasis and is a cellular metabolic readout."
...
"Pyruvate/lactate ratios show distinct metabolic phenotypes and are used to derive free cytosolic [NAD+]/[NADH] ratios."
...
"Determination of free cytosolic [NAD+]/[NADH] ratios using hyperpolarized glucose is applicable to a wide selection of cell types."
...
"This metabolic phenotyping may be a crucial tool to understand pathologies, and to diagnose and measure effects of therapies."
Also consider aging studies such as:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019194
which contains the statement that "Reduced mitochondrial activity of complex I–IV was also observed in aging animals, impacting both redox status and ATP production." The study uses NAD+/NADH as their redox status marker.
The way I found the specific formula I want to use is that I contacted a world-famous researcher and asked him if there was a way to measure the ratio using a cheap commonly available metabolite. He gave me a formula, and I'm still trying to verify how to use it.
The only mitochondrial function test I am aware of that ME/CFS patients sometimes use is the
Mitochondrial Function Profile test from Dr Myhill's practice. I understand that this test does not measure mitochondrial function directly, but via measuring metabolite levels.
The ATP test she is doing looks better than that. It looks like the researcher she uses is getting living mitochondria and stimulating them in various ways and measuring the ATP output by some kind of photoluminescence technique. It's awesome stuff! But I contacted him and he refuses to set up any new customer accounts and claims that he cannot even tell me who he does business with without "violating European law".
Measuring ATP output is unfortunately still kind of leading edge research. I have been searching for a group in the US who can do this commercially and so far I have struck out. I bet they do exist though. If I had more time and more resource I think they could be found.
Whereas there is good evidence from published studies to shown that various pesticides (organophosphates, pyrethroid and organochlorines) increase the risk of developing ME/CFS, there are no studies showing any links between mercury levels and ME/CFS.
Sometimes you may read an anecdote about mercury apparently worsening ME/CFS symptoms, but not much more than that.
I think the truth is more muddled than that.
First, you aren't searching very hard in Pubmed. For example:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253456/
which contains statements like "The affinity of mercury for sulfhydryl groups of the mitochondrial oxidative phosphorylation complex associated with destruction of mitochondrial membranes may contribute to chronic fatigue syndrome."
What I do not find are good studies that make population-wide assessments based on mercury burden. But running such a study is very difficult, because as the study I quote says:
"Diagnosis of mercury overload is difficult. The commonly used modalities (blood, urine, and/or hair levels) do not correlate with total body burden and offer little diagnostically useful information. "
So you can measure blood levels of mercury as low, when in fact the tissues are saturated with it. That makes it very problematic to study this issue, and it also explains why many studies fail to find association between symptoms and blood levels.
There are population studies, just not well designed or large enough to cause a widespread call to action:
http://www.ncbi.nlm.nih.gov/pubmed/16891999
http://www.ncbi.nlm.nih.gov/pubmed/11462117
The comment in the second study is that:
"We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered"
The other points to consider in asking for a decisive population study:
* Chronic Fatigue is already controversial for allopathic medicine, with many doctors thinking it is not a disease and that the people who complain of symptoms have psychiatric issues.
* Mercury is even more controversial, and what is worse the government through various organizations is giving an implicit blessing to mercury, which makes it very hard to get funding.
So you are asking a researcher to put his career on the line and do a large population study on a non-disease with a metal that will cause massive liability for dentists and dental associations if you conclusively prove its health effects.
Also note that if you eat canned tuna, in
this post I roughly indicate that you would get over 5 times more mercury neurotoxicity from a once weekly 70 gram (2.5 oz) tuna fish portion than from your amalgam fillings. The form of mercury in tuna fish is methylmercury, and this is far more toxic to neurons that the elemental mercury from dental fillings.
These are different forms of mercury with different metabolic pathways and different toxicity. The fish is organic mercury and the liver handles that disposal pathway. The amalgams are released as elemental mercury and convert to inorganic and more easily pass into the brain.
Quicksilver Scientific - which tests both forms - makes a big point of this showing how the fish based mercury is usually much higher, which is why they speciate their test and show the organic and inorganic forms separately. They measure the much smaller amounts of inorganic mercury - and its disposal pathway through urine - separately because it is much more deadly.
I had all my amalgams removed several years ago, though, just as a precaution.
Note I have heard cases where ME/CFS patients will feel dramatically worse after alpha lipoic acid, even just a single dose of a few hundreds milligrams, and take a while to recover. A single dose is not going to transport much mercury, so you can rule mercury out as the cause of this worsening. You can see ALA's known side effects
here.
I don't think the reports of individuals having an adverse reaction to any substance is a basis for making any other conclusion about the substance.
The chemical fact is that ALA converts to a dihydroxy form that is a two-thiol chelator with very very strong attraction to mercury. It passes intracellular and into the brain easily, and if the blood level of either type of mercury is higher than the level inside cells or inside the brain, ALA will move mercury into those compartments. Take enough of it in the wrong way, if you have high blood levels of mercury, and if you have a sensitivity to mercury, you will get symptoms.
