The new Naviaux study is up! Metabolic features of CFS

Anomie

Active Member
http://www.pnas.org/content/early/2016/08/24/1607571113.long

Abstract

More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females.

We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways.

Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites.

Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

 
Last edited by a moderator:

Veet

Well-Known Member
A Homogeneous Metabolic Response to Heterogeneous Triggers.

Although the current study was not designed to examine the role of different triggering events, we collected some basic data. Possible triggering events fell broadly into five groups: biological (viral, bacterial, fungal/mold, and parasitic infections), chemical exposures, physical trauma, psychological trauma, and unknown. The specific biological and chemical exposures and the precise nature of the physical and psychological traumas were diverse, numbering more than a dozen in just this small sample. Several patients had multiple triggers that converged in the same year. Although biological triggers were most common, no single infectious agent or other stressor was statistically more prevalent, and comprehensive testing for biological exposures in the control group was beyond the scope of this study.
Despite the heterogeneity of triggers, the cellular response to these environmental stressors in patients who developed CFS was homogeneous and statistically robust. These data supported the notion that it is the unified cellular response, and not the specific trigger, that lies at the root of the metabolic features of CFS.
 

Remy

Administrator
So if the trigger doesn't matter and it's the cellular response, how does that explain why there are so many differences in how we all feel, symptoms we have etc. (I have not read the supplemental material)
I don't know for sure but probably much like in MCAS, there are a bundle of different cytokines that can express in different ways based on our genetics and individual experience. That means almost every person could present slightly differently because we are all different.

PS I haven't read the supplemental either. :)
 

h3ro

Active Member
So if the trigger doesn't matter and it's the cellular response, how does that explain why there are so many differences in how we all feel, symptoms we have etc. (I have not read the supplemental material)
It doesn't say the trigger doesn't matter, all it says is that they've identified a chemical signature and underlying biology that is present regardless of the cause or trigger. That doesn't mean that there isn't other parallel biology happening at the same time.

The study also identified other metabolites that were significantly out in many subjects but these aren't included in the "signature" as they weren't sensitive enough.

Only about 25% of the metabolite disturbances found in each person were needed for the diagnosis of CFS. About 75% of the metabolite abnormalities were unique to the individual and useful in guiding personalized treatment.
The paper even recommends using the metabolites that aren't needed for CFS diagnosis in treatment.
 

h3ro

Active Member
On reading in the supplementary materials, the top 10 metabolites in males vs females are 100% different, none shared at all.
 
How does this paper compare/contrast with this 2015 Australian metabolic profiling of study 34 female patients?: Full paper (via MEaustralia article) already discussed on Phoenix Rising, here.

That study flagged up: "six metabolites that were significantly different [...] aspartate and glucose were increased whereas acetate, glutamate, hypoxanthine, lactate, and phenylalanine de-creased in ME/CFS patients."

Whereas, this more recent Naviaux study lists: "The top six pathway disturbances in females were responsible for 83% of the metabolic impact. These were sphingolipids (35%); phospholipids (26%); glycosphingolipids (9%); purines (5%); microbiome (5%); and P5C, Arg, and Pro (3%)."

Is there a total lack of overlap (or is it just me)? Is that because this later study was able to analyze a lot more (or just different) metabolites (thanks to it's new mass spectrometer)? Certainly the substances listed in the Autralian study were more familiar to me, from my own Genova amino acids profile test (3 years ago, tying in with weirdly raised aspartic acid, and lowered essential aminos, as the paper described). While Naviaux collars far more unfamilar things, the most significant (apparently) being 'sphingolipids', which I'd not really heard of before.

All fascinating and promising, against the background of apparently rapid advances in the scope and efficiency of test equipment and computer systems modeling. :)
 
Last edited:

Issie

Well-Known Member
So if the trigger doesn't matter and it's the cellular response, how does that explain why there are so many differences in how we all feel, symptoms we have etc. (I have not read the supplemental material)
It's like my doc says - Dr Stephen Fry - if our bodies immune systems were working properly whatever pathogens we have wouldn't affect us adversely. For those of us whose immune systems don't detect, destroy or moderate we get severe inflammation and then the downward spiral starts. Getting our bodies to respond in an appropriate manner ----regardless of "the cause", is our key.

Dr Fry had me go lowfat, whole food vegan. Ive read numerous reports saying those with an autoimmune system issue - bodies can mistake animal proteins for our own proteins and then either allow what shouldn't be there or not attack it setting up an issue with detection. We know Lyme and Protomyzoa Rehumatica are two protozoa that evade the immune system. Both along with malaria cause biofilms which house pathogens, bacteria and virus. They all co exist hidden in biofilm that hardens in our veins and causes more circulatory dysfunction. We get POTS and other issues with blood flow and oxygen caused (in part) with these organisms and our own immune systems not working properly. This in turn causes pain, inflammation - FMS.

Diet was one of the best things I tried. It's possible that it will make a difference. But I don't have it tweaked enough to make "all the difference ". I do however, think the low fat may have been necessary for one reason. But it has side effects. I decided having worse brain function wasn't worth that affect. I hope I'm not causing myself more issues by adding in coconut products and that sort of fat. But, I feel better.

Also, Dr Fry, said to not use magnesium, and other Lyme docs say not to use calcium or iron. These are known to reinforce biofilm. However, my magnesium seems to have gotten too low (used up by pathogens to make biofilm) and I had to add back magnesium oil a few times a week. I still try to keep it low. I don't supplement the other two. I do feel better having a little more on board. I just hope I'm not contributing to more biofilm with its contents and more vein dysfunction. So far, it feels right.

This will be interesting to follow.

It seems they are looking into the methylation cycle. Many of us know our mutations and treating those with proper B Vitamins and supporting supplements does make a difference.

Looking forward to further research.

Issie
 

Justin

Active Member
I really hope this is the key to the Millions missing and suffering from the disease.

Now i hope that pharma with this data can start working on a solution.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
So if the trigger doesn't matter and it's the cellular response, how does that explain why there are so many differences in how we all feel, symptoms we have etc. (I have not read the supplemental material)
Ron Davis thinks that genetic differences may come into play - he's doing a gene study that he hopes to pair with the metabolomics results.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
It doesn't say the trigger doesn't matter, all it says is that they've identified a chemical signature and underlying biology that is present regardless of the cause or trigger. That doesn't mean that there isn't other parallel biology happening at the same time.

The study also identified other metabolites that were significantly out in many subjects but these aren't included in the "signature" as they weren't sensitive enough.



The paper even recommends using the metabolites that aren't needed for CFS diagnosis in treatment.
Right. From what I read Naviaux appears to believe that the metabolites unique to each person will be the best guide to treatment options
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
How does this paper compare/contrast with this 2015 Australian metabolic profiling of study 34 female patients?: Full paper (via MEaustralia article) already discussed on Phoenix Rising, here.

That study flagged up: "six metabolites that were significantly different [...] aspartate and glucose were increased whereas acetate, glutamate, hypoxanthine, lactate, and phenylalanine de-creased in ME/CFS patients."
Whereas, this more recent Naviaux study lists: "The top six pathway disturbances in females were responsible for 83% of the metabolic impact. These were sphingolipids (35%); phospholipids (26%); glycosphingolipids (9%); purines (5%); microbiome (5%); and P5C, Arg, and Pro (3%)."

Is there a total lack of overlap (or is it just me)? Is that because this later study was able to analyze a lot more (or just different) metabolites (thanks to it's new mass spectrometer)? Certainly the substances listed in the Autralian study were more familiar to me, from my own Genova amino acids profile test (3 years ago, tying in with weirdly raised aspartic acid, and lowered essential aminos, as the paper described). While Naviaux collars far more unfamilar things, the most significant (apparently) being 'sphingolipids', which I'd not really heard of before.

All fascinating and promising, against the background of apparently rapid advances in the scope and efficiency of test equipment and computer systems modeling. :)
The Naviaux study used a different method and looked at more metabolites. Even though the metabolites found were different, Davis believes the two studies are essentially show the same thing - a hypometabolic state in ME/CFS.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Excellent review of the role sphingoloids play in MEAction. Naviaux said Jaime did a great job.

http://www.meaction.net/2016/08/30/naviauxs-metabolism-paper-is-about-as-big-as-you-think/
Sphingolipid depletion would go a long way to explaining some of the abnormalities seen in CFS patients. Ceramides, a product of spingolipids, are responsible for the creation of ‘lipid rafts’, which mobilize and aggregate during infection. Lipid rafts also require cholesterol and other fatty molecules to function properly.

........

Downregulating sphingolipid synthesis in general, and ceramide synthesis in particular, could well be part of a host-defense response in the presence of these pathogens to prevent their entry, to decrease the risk of cellular apoptosis in response to infection. It’s also possible that the cells upregulate the creation of lipid rafts as a continued protective measure, resulting in the presence of fewer free lipids involved in this process.
He even explains how these findings may relate to Rituximab's success
 

Issie

Well-Known Member
Dr Goodman - neurologist and POTS doctor at Mayo, AZ has most of us doing a protocol for mitochondrial dysfunction. He says that the few test available to test for dysfunction are not enough. There is so much more that there aren't test for. CQ10 is one thing he has us take.

Also, I found it interesting that they mentioned an increase in peroxide. My having vitiligo and that possibly being because of higher peroxide levels and autoimmune issues - this is interesting. The body also ups peroxide to kill and eliminate pathogens. Probably a compensatory response that goes overactive.

Issie
 

Get Our Free ME/CFS and FM Blog!



Forum Tips

Support Our Work

DO IT MONTHLY

HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT

Shopping on Amazon.com For HR

Latest Resources

Top