Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways

[MeSci]

You're staying away from Vitamin D? Por que?

-J

Here are some reasons.

 

[MeSci]

I honestly have no idea, I was hoping someone else would know.

Does this from our brilliant resident expert help?

Actually lactate and lactic acid are effectively the same thing in the context of body physiology. Lactic acid is hydrogen lactate CH3CHOHCOOH which at pH 7ish will be partly dissociated to H+ and (lactate)CH3CHOHCOO- ions. There will be sodium ions around as well and in solution the lactate ions (CH3CHOHCOO-) do not actually belong to either the hydrogen or the sodium. When solid lactic acid dissolves the release of lactate ions does not involve a redox change - just ionisation.

 

[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:. . .
Blimey - I must be obsessed!

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

Happy reading!!

Goodness! That will keep me busy for awhile. Thanks @MeSci!

 

[MeSci]

Bespoke diets based on gut microbes could help beat disease and obesity
Early trial showed use of computer algorithm to produce diet tailored to a person’s unique biological make-up had benefits for pre-diabetic subjects

Scientists have created bespoke diets using a computer algorithm that learns how individual bodies respond to different foods.

Researchers believe the tailored diets could help stem the rising tide of diabetes, heart disease and obesity, by personalising people’s daily meals and so helping them to adopt healthy eating habits.

The first results from the Personalised Nutrition Project, run by leading researchers in Israel, are due to be unveiled on Friday at the Human Microbiome conference in Heidelberg, Germany.

The project challenges the idea that general recommendations about healthy foods are suitable for everyone, and instead aims to produce optimised diets based on people’s unique biological make-up....

Definitely on the right track there, and hopefully the researchers are also taking into account the fact that the gut microbiome is largely determined by the person's diet. So after someone changes his/her diet to be best suited to his/her microbiome at a given time, s/he may need to tweak it again later as the microbiome changes.

 

[MeSci]

One is the conjugate base of the other, so they are different chemically. Biologically, it may be similar to comparing CO2 to bicarbonate - if your bicarbonate is low, your CO2 is typically also low, and they're often discussed interchangeably.

[Double-checks]. Yep, it doesn't really matter; lactic acid dissociates to lactate and H+ in blood.

...someone has already said this, now.

-J

But if your serum bicarbonate is low, doesn't it indicate that your blood is acidic? And CO2 dissolved in water makes it acidic, as in acid rain and the acidifcation of the oceans.

Apologies if I am making statements that others have already made - I still haven't caught up!

 

[MeSci]

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 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!

Just realised that it seems to be high urine creatinine that is referred to in this thread, although in some of @JaimeS's posts it looks as though she is referring to blood creatinine. Could she clarify this? I still haven't had time to look at her blog - sorry.

My serum creatinine has almost always tested normal, but I have one reading for urine when I was acutely ill in hospital with hyponatraemia - almost certainly caused by an ACE inhibitor - which appears rather high according to this reference range document. It wasn't a 24-hour result but shows as 5.42 mmol/l.

 

[JaimeS]

Just realised that it seems to be high urine creatinine that is referred to in this thread, although in some of @JaimeS's posts it looks as though she is referring to blood creatinine. Could she clarify this? I still haven't had time to look at her blog - sorry.

No, you're correct - urine creatinine is high. Not serum.

-J

 

[MeSci]

No, you're correct - urine creatinine is high. Not serum.

-J

Thanks.

 

[MeSci]

Could an answer to the diet dilemmas in this thread be a low-carb diet but add resistant starch? Resistant starch is not digested by the human gut, but IS digested by the microbiota. Especially the kind of resistant starch called RS2. It doesn't raise blood sugar, and I believe therefore doesn't ruin a low-carb diet. But the gut bugs would be much happier with it included in the diet.

Read Ripley's very first post in this thread, the section where he talks about RS2: and the links there may be good too:

http://forums.phoenixrising.me/inde...ge-is-it-the-key-weve-been-looking-for.26976/

Yes, there is a lot of potentially-useful stuff in that thread, but I think it's pertinent that @Ripley reported in this post that the site which I think he was using as his main info source has rowed back slightly on some of the earlier advice.

For the uninitiated, VLC is very low carb.

 

[MeSci]

@brenda . A ways back (somewhere in this thread) you said you couldn't eat 3 tbsp of coconut oil. *whispers* make it into chocolate! Equal parts coconut oil and cocoa, and flavor with honey to taste. It is hard to stop eating it.

You can use xylitol as a natural low-GI/low-calorie sweetener unless you are avoiding polyols.

There are so many ways to use coconut oil - frying, roasting, spreading, etc., that I can't see any reason to avoid it due to a dislike of eating it neat. Mix it into most meals and you probably won't even know it's there. But I love the smooth mouth-feel that it gives.

 

[JaimeS]

But if your serum bicarbonate is low, doesn't it indicate that your blood is acidic? And CO2 dissolved in water makes it acidic, as in acid rain and the acidifcation of the oceans.

Apologies if I am making statements that others have already made - I still haven't caught up!

CO2 isn't what makes acid rain acidic. That's (predominantly) the sulfur from burning of coal and such that combines with hydrogen gas and oxygen to form H2SO4... sulfuric acid. Or so the textbooks I used to teach middle school science profess. Lord knows they're wrong often enough.

Low CO2 and low bicarbonate are associated with metabolic acidosis. Why these basic substances should be low in acidosis is its own messy story.

 

[MeSci]

CO2 isn't what makes acid rain acidic. That's (predominantly) the sulfur from burning of coal and such that combines with hydrogen gas and oxygen to form H2SO4... sulfuric acid. Or so the textbooks I used to teach middle school science profess. Lord knows they're wrong often enough.

Low CO2 and low bicarbonate are associated with metabolic acidosis. Why these basic substances should be low in acidosis is its own messy story.

Ah yes - I misremembered the acid rain bit. But then I learned that before global warming was a 'hot topic' (sorry) and we were more worried about acid rain and (possibly) ozone destruction.

So CO2 is high in acidosis? That's blood CO2, I guess. And respiratory CO2...? The answer may be here - it's a very informative site - but maybe you have it stored in your encyclopaedic brain.

I dip into the acid-base stuff from time to time but have trouble retaining it...

 

[Jonathan Edwards]

Ah yes - I misremembered the acid rain bit. But then I learned that before global warming was a 'hot topic' (sorry) and we were more worried about acid rain and (possibly) ozone destruction.

So CO2 is high in acidosis? That's blood CO2, I guess. And respiratory CO2...? The answer may be here - it's a very informative site - but maybe you have it stored in your encyclopaedic brain.

I dip into the acid-base stuff from time to time but have trouble retaining it...

I think you were right about CO2 making rain acidic, MeSci, but that was normal rain, which was still acidic when we were kids but not acidic enough to kill the trees. I think it got more acidic with lightning generating nitric acid too, but that can't have been too often.

 

[MeSci]

Ah yes - I misremembered the acid rain bit. But then I learned that before global warming was a 'hot topic' (sorry) and we were more worried about acid rain and (possibly) ozone destruction.

So CO2 is high in acidosis? That's blood CO2, I guess. And respiratory CO2...? The answer may be here - it's a very informative site - but maybe you have it stored in your encyclopaedic brain.

I dip into the acid-base stuff from time to time but have trouble retaining it...

D'oh - I meant "So CO2 is low in acidosis?"

Thanks, @Jonathan Edwards for reassuring me that my memory is not total crap. I now recall that atmospheric CO2 causes acidification via carbonic acid.

(Sorry - that site makes the common error of substituting 'loose' for 'lose' despite being an educational site.)

 

[Jonathan Edwards]

D'oh - I meant "So CO2 is low in acidosis?"

You probably meant both. In respiratory acidosis inadequate ventilation of the lungs leads to CO2 building up in the blood. CO2 combines with water to form carbonic acid. Some of that dissociates to generate hydrogen ions and that causes acidosis. On the other hand in metabolic acidosis the hydrogen ions come from lactic acid or some other organic acid produced by cells. The lactic acid dissociates to produce the hydrogen ions that cause the acidosis. However, some of these hydrogen ions combine with bicarbonate ions in the blood to form carbonic acid. Some of that dissociates to produce water and CO2, which stimulates overbreathing which blows off the CO2. That depletes your blood bicarbonate, which is in a sense a measure of the amount of CO2 stored in blood. There are also changes in bicarbonate excretion in the urine in both situations over a longer period of time.

In the end the acid-base status is indicated by blood pH, together with bicarbonate to tell you if a shift is of respiratory or metabolic origin (up or down).

 

[MeSci]

You probably meant both. In respiratory acidosis inadequate ventilation of the lungs leads to CO2 building up in the blood. CO2 combines with water to form carbonic acid. Some of that dissociates to generate hydrogen ions and that causes acidosis. On the other hand in metabolic acidosis the hydrogen ions come from lactic acid or some other organic acid produced by cells. The lactic acid dissociates to produce the hydrogen ions that cause the acidosis. However, some of these hydrogen ions combine with bicarbonate ions in the blood to form carbonic acid. Some of that dissociates to produce water and CO2, which stimulates overbreathing which blows off the CO2. That depletes your blood bicarbonate, which is in a sense a measure of the amount of CO2 stored in blood. There are also changes in bicarbonate excretion in the urine in both situations over a longer period of time.

In the end the acid-base status is indicated by blood pH, together with bicarbonate to tell you if a shift is of respiratory or metabolic origin (up or down).

Is it just me, or do others find all these interactions too complicated to get their heads round? It's great stuff, and I wish I could absorb it properly so that I could work with it to think of other potential related effects in ME.

For example, could these acid-base reactions reduce oxygen supply to the mitochondria, and thus impair our ability to produce ATP via oxidative phosphorylation?

I found this short document which may provide some clues. That suggests a possible link to PEM:

Impaired oxygen delivery: initially, a decrease in pH reduces the affinity of HgB for oxygen
immediately, thus enhancing the oxygen delivery to tissues (Bohr effect). By 12-36 hours, a decrease
in RBC glycolysis depletes 2,3-DPG, thus HgB gets an increased affinity for oxygen, thus impairing
oxygen tissue delivery

(my bolding)

Re Jonathan's post, this bit:

The lactic acid dissociates to produce the hydrogen ions that cause the acidosis. However, some of these hydrogen ions combine with bicarbonate ions in the blood to form carbonic acid. Some of that dissociates to produce water and CO2, which stimulates overbreathing which blows off the CO2. That depletes your blood bicarbonate

reminds me of when I had severe hyponatraemia, when I may have been overbreathing (which the idiot paramedics tried to alleviate by getting me to breathe through a carrier bag which had a hole in it, in the mistaken belief that I was having a panic attack, ignoring my protestations ), and I did turn out to have low - then very low - blood bicarbonate when I suffered a second episode 3 years later. OTOH all my muscles appeared to be in spasm so it may have been that my respiratory muscles were affected by that. My breathing was shallow, laboured and slightly fast. It could not be controlled by willpower, and it felt strongly as though it was physiologically driven.

Another pertinent thing is that sometimes I get an energy boost from oral sodium bicarbonate. Anyone else have this? It can be quite dramatic - my legs can go from being weak and leaden to strong and light - it's lovely!

 

[Jonathan Edwards]

Is it just me, !

No, everyone gets tied in knots with this stuff.

I have not been able to track down the full paper yet - has somebody found a way to do that?

 

[MeSci]

No, everyone gets tied in knots with this stuff.

Thank you - that makes me feel better!

 

[Jonathan Edwards]

Thanks for the link @Sidereal.

I found this paper heavy going. Lots of very complicated statistical adjustments and no raw data to eyeball - not my cup of tea really. I rather doubt any of the differences would explain any symptoms - the shifts are small. They might be signs of some underlying problem, I realise, and that might link to fatigue. The trouble is we do not even know who the controls were as far as I can see. Different diets and levels of activity might explain the differences I guess. I have to admit that I did not make it as far as reading the discussion though.

All in all not sure that I can get a grasp of it either.

 

[MeSci]

Well oxaloacetate is certainly an intermediate in many metabolic processes as well as the Kreb's cycle - urea cycle, gluconeogenesis, amino and fatty acid synthesis. Its role is always as a substrate/end-product of transaminations - those ubiquitous B6-dependant enzymes again. Accumulation of oxaloacetate could certainly signal global problems with them.

With so much complexity, it's amazing that things don't go wrong more often!

I wonder whether the B6 dependency you refer to could be relevant to the fact that a significant proportion of us appear somewhat intolerant of B6. I think I am one of these. For example, could it cause excessive accumulation of oxaloacetate?

If this has already been answered, ignore me - I will get there eventually!