new Watanabe study: markers of TCA and urea cycle dysfunction

[bobby]

http://www.nature.com/articles/srep34990

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles
Emi Yamano, Masahiro Sugimoto, Akiyoshi Hirayama, Satoshi Kume, Masanori Yamato, Guanghua Jin, Seiki Tajima, Nobuhito Goda, Kazuhiro Iwai, Sanae Fukuda, Kouzi Yamaguti, Hirohiko Kuratsune, Tomoyoshi Soga, Yasuyoshi Watanabe & Yosky Kataoka

doi:10.1038/srep34990
Received:23 June 2016
Accepted:21 September 2016
Published online:11 October 2016

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.

TCA cycle is the citric acid cycle, so this is in line with what Ron Davis (and others?) has been saying. exciting to see similar results in different research teams. Does anyone know if this is the Japanese team Bateman-Horne is cooperating with? (remember the video about the blood samples sent to Japan?)

The tricarboxylic acid cycle (TCA cycle) is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells. This cycle is also called the Krebs cycle and the citric acid cycle.

Some info on the urea cycle here. It's basically a metabolic process that transforms ammonium (=byproduct of breakdown of amino acids) into urea, which leaves the body via urine. If that system is faulty I guess nothing good can come from it, as both ammonium and urea are toxic to the human body.

 

[Cort]

http://www.nature.com/articles/srep34990

TCA cycle is the citric acid cycle, so this is in line with what Ron Davis (and others?) has been saying. exciting to see similar results in different research teams. Does anyone know if this is the Japanese team Bateman-Horne is cooperating with? (remember the video about the blood samples sent to Japan?)


Some info on the urea cycle here. It's basically a metabolic process that transforms ammonium (=byproduct of breakdown of amino acids) into urea, which leaves the body via urine. If that system is faulty I guess nothing good can come from it, as both ammonium and urea are toxic to the human body.

No kidding - the Aussies came out with something on renal function earlier this year...I haven't compared the two but will put the abstract below.

The Aussies really appear to be onto something with their metabolomics studies

http://www.tandfonline.com/doi/abs/...scroll=top&needAccess=true&journalCode=rftg20

Widespread pain and altered renal function in ME/CFS patients
Neil R. McGregor, Christopher W. Armstrong, Donald P. Lewis, Henry L. Butt & Paul R. Gooley
Pages 132-145 | Received 24 Apr 2016, Accepted 24 Jun 2016, Published online: 29 Jul 2016

Background: Widespread pain is noted in many patients with chronic fatigue syndrome (ME/CFS), fibromyalgia and temporomandibular disorders. These conditions usually start as a localized condition and spread to a widespread pain condition with increasing illness duration.

Purpose: To aim was to assess the changes in biochemistry associated with pain expression and alterations in renal function.

Methods: Forty-seven ME/CFS patients and age/sex-matched controls had a clinical examination, completed questionnaires, standard serum biochemistry, glucose tolerance tests and serum and urine metabolomes in an observational study.

Results: Increases in pain distribution were associated with reductions in serum essential amino acids, urea, serum sodium and increases in serum glucose and the 24-hour urine volume; however the biochemistry was different for each pain area. Regression modelling revealed potential acetylation and methylation defects in the pain subjects.

Conclusions: These findings confirm and extend our earlier findings. These changes appear consistent with repeated minor inflammatory-mediated alterations in kidney function resulting in essential amino acid deprivation and inhibition of protein synthesis and genetic translation within tissues.

 

[bobby]

@Cort I knew I had seen the urea thing before somewhere, but couldn't remember where exactly.

the more they discover about our metabolism, the more out of whack it turns out to be... not that I'm surprised!

just thinking out loud: what does the metabolism of other illnesses look like? (e.g. MS) I wonder if they have a bunch of weird things going on there too... Just worried they're looking at effect again, and not cause?

 

[Cort]

@Cort I knew I had seen the urea thing before somewhere, but couldn't remember where exactly.

the more they discover about our metabolism, the more out of whack it turns out to be... not that I'm surprised!

just thinking out loud: what does the metabolism of other illnesses look like? (e.g. MS) I wonder if they have a bunch of weird things going on there too... Just worried they're looking at effect again, and not cause?

Naviaux says that our metabolism looks like autism and some other diseases which I can't remember. He is doing a big study comparing the results of a bunch of diseases...including MS. My guess is that each will have a different metabolic signature - since they are different diseases they should if Naviaux is right about metabolomics ability to get at the source of things.

 

[Kathy Bungard]

So help me out here, after reading both of the studies cited above I'm wondering how many patients suffer problems that seem to be the natural result of such disordered metabolism?

I've had ME/CFS for 35 years and have developed arthritic gout in my feet. Both big toe joints are filled with not the usual crystals that most people think of when hearing about gout, but with what the podiatrist who did surgery to remove one of the joints (another nightmare story I won't bother you with right now) she said the joint was filled with gout that looked like 'cottage cheese'. Another 'anomaly', wouldn't you think then that tests would show I have the typical signs of 'gout' such as higher levels of uric acid? Well they don't, all those tests were normal.

So I 'have' gout in my feet, but I don't 'have' gout according to the standard medical tests. I should be used to the fact that nothing about my medical tests ever leaves me with anything but head scratching wonder.

Are there other illnesses/afflictions that are the result of such metabolic problems that are often found among patients?

 

[bobby]

@Kathy Bungard I don't have any answers, just wanted to say that I share your confusion. every time I think I (or they) have it figured out, something new pops up, like a never ending riddle

 

[Gijs]

@Kathy Bungard I don't have any answers, just wanted to say that I share your confusion. every time I think I (or they) have it figured out, something new pops up, like a never ending riddle

I feel the same Bobby. I also think it is a never ending riddle, probably it is! They are never going to find the cause of this disease. A test would be a welcome start.

 

[Seven]

I was researching hypomatabolic states and came across anorexic people and eating disorders have it.

So since we have gut issues, maybe there is something not allowing the food to be digested the right way where the vitamins (why we are so deficient in certain group bs, D....) or the metabolites are not getting generated properly.