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Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways

dannybex

Senior Member
Messages
3,573
Location
Seattle
I do have very low glycine which could be being used up in trying to make in trying to make creatine.

My glycine has always been low, and I wonder now if it's either the body's way of preventing endogenous oxalate production (if one is b-6 deficient), or is being used up because of endogenous oxalate production?
 

anne_likes_red

Senior Member
Messages
1,103
Glycine might be low due to burning energy through the phosphagen (creatine) pathway excessively? (Edit Duh - I just realised that's exactly what alicec said!.)
Over-using this pathway could also be very expensive on methyl donors. At least that's what I have written in my notes :)
I believe this may relate to the methylation of guanidinoacetate.
"The methylation of guanidinoacetate to form creatine consumes more methyl groups than all other methylation reactions combined."
...from: http://www.lef.org/Magazine/2003/9/abs/Page-02?p=1
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Really wish I'd known this diagram existed when I was trying to figure out the article:

Amino_acid_catabolism_revised.png

"Amino acid catabolism revised" by Mikael Häggström
 
Messages
58
Which physician has diagnosed the patients, and which city? i cannot recognize any of the authors.

Neil McGregor has worked with Tim Roberts, Henry Butt and Hugh Dunstan for something like 20 years on metabolic and biochemical aspects of CFS, looking for biomarkers and generating hypotheses based on metabolic anomalies in PWCFS. I know of them as back in the early 2000s they were one of something like 12 labs around the world that were consistently able to get some funding for CFS studies, and I had made arrangements to work in Hugh and Tim's lab for my graduate studies. Actually, I recall them having a small commercial lab for a while that was doing biochemical tests to support diagnoses of CFS.
They started at University of Newcastle, but have close connections with Sydney (which is an hour away) for patient populations.

Researchgate has been helpful at looking at past collaborators:
https://www.researchgate.net/profile/Neil_Mcgregor/publications?pubType=article

Click on "View all" under the top collaborators section to see past collaborations with Kenny de Meirleir and Jo Nijs.
 
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alicec

Senior Member
Messages
1,572
Location
Australia
My glycine has always been low, and I wonder now if it's either the body's way of preventing endogenous oxalate production (if one is b-6 deficient), or is being used up because of endogenous oxalate production?
I can't quote any figures but I think that the amount of glycine produced in the AGT pathway (ie leading glyoxylate to glycine and away from oxalate production) is a tiny drop in the ocean of glycine which washes the body. Glycine has a pivotal role in many pathways and it is more likely that low levels are in some way related to these other activities.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
I don't know if this is useful, but I've just had a dietary experience of down-regulating my peroxynitrite levels. I've been working on this issue throughout this year, with various strategies. My weight had begun creeping up, seemingly in response to the high carrot and nut/seed spread intake that my body requested to cope with peroxynitrite symptoms.

I decided to shift my meal times, hoping to be able to use up more energy during the day. I realized that I'd evolved my current meal pattern a year and a half ago to accompany my coffee enema regimen. Bone broth with no added fat or meat in the AM, and broth + fat + small portion of meat in PM. With carrots and seed spread especially in the PM. I've found that (surprise!) I've had better energy eating the higher density meal in AM, and greatly reduced peroxy symptoms, hence decreased intake to cope with it. Has my body been experiencing oxidative stress because I haven't been giving it enough fuel to function during my awake hours? :bang-head:
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,232
Location
Cornwall, UK
Just thinking aloud~
I can see ketogenic diet might be helpful, but it seems too demanding when you add in dairy-free (which is a big one for me). Paleo or near-paleo is probably easier.

I am still ploughing through this thread but will add this before I forget - I have been dairy-free (vegan) for 32 years so that bit isn't a problem. I have found that just cutting out gluten and reducing grains and sugar has helped a lot. More details in my profile.

I don't know when I will get round to looking at @JaimeS's famous blog :D but will also say before I forget:
  • My blood glucose has always tested normal except for one high reading when I was acutely ill.
  • My creatinine has almost always tested normal, but vegans and veggies tend to have lower creatinine than omnivores. ACE inhibitors and angiotensin receptor blockers can increase creatinine significantly, and I was on one of these for 7 years until 2014, so that could cancel out the vegan effect!
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,232
Location
Cornwall, UK
I did want to say that newer ketogenic diets are not as strict as the old 4:1 ratio; it seems that the neurological benefits accrue on less-strict diets. (But they are still limiting, obviously.) They are fat-intensive, adequate protein, low carbs (i.e., lots of above-ground vegetables, only limited starchy vegetables, and a few fruits (basically berries)).
I strongly second this! I would also suggest that one should avoid omega-6 fatty acids (especially heated, as they oxidise too readily) where possible, apart perhaps from gamma-linolenic acid (GLA). And I definitely agree (with @JaimeS and others?) that the anti-saturated-fat norm is almost certainly wrong, as recent research is finding, or at least there is little or no evidence that saturated fat is bad. I have posted a few threads on this, and on dietary fat generally. And coconut oil is a saturated fat, and I love it!
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,232
Location
Cornwall, UK
So guys, with this knowledge, assuming we're making two pills, hydrophobic (fatty) and hydrophilic (water soluble), what is in your ideal ME supplement?

Fatty, I'd say:
Vitamin A
Vitamin D
CoQ10
Omega-3s and 6s
Vitex agnus castus

Sorry if this has already been addressed - still nowhere near the end of the thread - but why would you supplement omega-6? Most people consume much too high an omega-6:eek:mega 3 ratio, and it is the ratio that counts. So what is really needed is to adjust the balance towards the omega-3, thus taking more omega-3 and reducing omega-6. Omega-6 is so ubiquitous in most diets that it's pretty hard to avoid. Even supplements are often in sunflower oil!

EDIT - don't know why the 'o' in one of the omegas came out as an 'Eek' - now corrected! :lol: (intentional)

EDIT 2 - it's turned into an 'Eek' again! Must be the effect of using a colon in front of an 'o'. Looks like I'm stuck with it.
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Good point, @MeSci ... brain isn't fully responsive today (worse than usual). I think I was thinking of something very specific when I wrote that - like something that contained omega3s and 6s - and I just wrote that component down so everyone would 'know what I meant'.

Now I can't remember what I meant in the first place... Maybe my brain will come more fully online later, it's early in the day where I am.

Brain fog = the worst

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
And I definitely agree (with @JaimeS and others?) that the anti-saturated-fat norm is almost certainly wrong, as recent research is finding, or at least there is little or no evidence that saturated fat is bad. I have posted a few threads on this, and on dietary fat generally. And coconut oil is a saturated fat, and I love it!

Did a vid on this for my students - the anti-saturated fat movement was started in the 1970s in a landmark study called the 'Seven Countries Study' in which they demonstrated that in countries that consume more saturated fat, incidences of (deaths as a result of?) heart disease were higher.

What we know now is that the researcher in question studied twenty some-odd countries, not seven, and cherry-picked the countries where the data best fit his theory... ignoring countries such as Chile, where there was low saturated fat intake and high heart disease, and Norway, which showed high saturated fat intake and low heart disease. Science at its absolute worst, yet he ended up on the cover of Time.

The grad school I went to, one of our nutrition books was called Nourishing Traditions. The author, Sally Fallon, professed that saturated fats were necessary for a healthy diet. It was published in the late 90s, and IMO that marks when people (at least those with nutrition experience) began to doubt the 'fats are bad' tract that had been selling well up until that time. Unfortunately, Sally was fond of the phrase 'diet dictocrats' and prone to exaggerating the evil of her detractors, as pioneers in health often do... or perhaps that was simply how her publicist wanted to package her ideas. It's like when anyone presents a good health idea you agree with but very poorly, and you're like, please stop talking, you're giving us all a bad name. It's more mainstream now, this idea that fats can be good for you, but I still hear doctors (and my nutrition students) constantly talking about a diet low in saturated fats.

Please spread that this is nonsense. :)

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
New endo just said,

"....is this due to oxidative damage....? ....Sounds like a Krebs Cycle issue....? ....Have you tried CoQ-10...? ....BCAAs?"

Discussed the study, he actually appeared to know what I was talking about. Holding off on judgement, but it's nice to get some proof that they're not all morons!

-J
 

Vasha

Senior Member
Messages
119
...
The grad school I went to, one of our nutrition books was called Nourishing Traditions. The author, Sally Fallon, professed that saturated fats were necessary for a healthy diet. It was published in the late 90s, and IMO that marks when people (at least those with nutrition experience) began to doubt the 'fats are bad' tract that had been selling well up until that time. Unfortunately, Sally was fond of the phrase 'diet dictocrats' and prone to exaggerating the evil of her detractors, as pioneers in health often do... or perhaps that was simply how her publicist wanted to package her ideas. It's like when anyone presents a good health idea you agree with but very poorly, and you're like, please stop talking, you're giving us all a bad name. . . .

-J

Exactly! Nourishing Traditions has so much good information in it, but described with worrying zeal. In fairness to Fallon, the late 90s was the height of the low-fat craze . . . and we were well into the obesity epidemic.

I strongly second this! I would also suggest that one should avoid omega-6 fatty acids (especially heated, as they oxidise too readily) where possible, apart perhaps from gamma-linolenic acid (GLA). And I definitely agree (with @JaimeS and others?) that the anti-saturated-fat norm is almost certainly wrong, as recent research is finding, or at least there is little or no evidence that saturated fat is bad. I have posted a few threads on this, and on dietary fat generally. And coconut oil is a saturated fat, and I love it!

@MeSci if you have them handy, would mind sharing one or two of these threads? No worries if not handy.
Do you have any thoughts on the place of medium-chain triglycerides, by chance? (Coconut oil is an example.)

Cholesterol, too has been apparently unfairly demonized, due to a correlation-not-causation problem. People with atherosclerosis have high cholesterol. Conclusion jumped to: cholesterol causes artery disease! Umm, actually, cholesterol is sent by the body to respond to the damage . . . Cholesterol is a critical component of cell walls, among other things. :whistle:

Vasha
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,232
Location
Cornwall, UK
@MeSci if you have them handy, would mind sharing one or two of these threads? No worries if not handy.
Do you have any thoughts on the place of medium-chain triglycerides, by chance? (Coconut oil is an example.)

Cholesterol, too has been apparently unfairly demonized, due to a correlation-not-causation problem. People with atherosclerosis have high cholesterol. Conclusion jumped to: cholesterol causes artery disease! Umm, actually, cholesterol is sent by the body to respond to the damage . . . Cholesterol is a critical component of cell walls, among other things. :whistle:

Vasha

I don't have any threads handy (where would I keep them?) but I did a search for the fat-related threads I have started and here they are:

http://forums.phoenixrising.me/index.php?threads/radio-program-on-dietary-fat-vs-carbs.36209/

http://forums.phoenixrising.me/index.php?threads/lack-of-evidence-for-dietary-fat-reduction.35444/

http://forums.phoenixrising.me/index.php?threads/anh-latest-dietary-advice.35123/

http://forums.phoenixrising.me/index.php?threads/humans-rodents-and-diet-a-critique.34923/

http://forums.phoenixrising.me/inde...arison-of-low-carb-and-high-carb-diets.34462/

http://forums.phoenixrising.me/inde...y-showing-low-carb-better-than-low-fat.33438/

http://forums.phoenixrising.me/index.php?threads/food-michael-pollan-on-bbc-radio-4.32849/

http://forums.phoenixrising.me/index.php?threads/low-carb-better-than-low-fat-in-several-ways.32370/

http://forums.phoenixrising.me/index.php?threads/sugar-worse-than-fat-say-doctors.27501/

http://forums.phoenixrising.me/inde...role-of-saturated-fat-in-heart-disease.26056/

Blimey - I must be obsessed! :lol:

There is some stuff about cholesterol in there too (in one or more of the above threads).

Happy reading!!
 
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