High citrate used to be considered a marker for CFS (hypercitricemia). Then a UK study came out and said they couldn't find it and interest died. The problem was, to anybody who knew this science behind it, the UK study could never have found it because the protocol they used would never work. Citrate accumulates during sleep - and they tested awake fasting citrate. Citrate is also burned up during a fast. So their protocol was bogus. However, they did some very good research that showed some of the other putative CFS markers were probably incorrect, and so everyone simply presumed they were right about citrate too. Local research had already identified that early morning citrate was high, but that twenty four hour citrate was normal. This was not a constant problem, and might explain why symptoms are different in the morning compared to the evening. The UK research failed to take this into account.
(They also did not prove the other markers were not valid markers, only that they might
have been artifacts. This was because they could show the origin of the strange molecules, and how they were linked to things like glycine and serine deficiency. Essentially, the glycine and serine were being converted to something weird. They claimed this was from the urinary testing protocol, but this was never proven - they might still be valid markers of CFS. I haven't seen any follow up research, so I cannot comment on what was ultimately proven or not proven.)
Many of the problem foods in CFS are high citrate foods, including additives. It is probably the third most common additive after sugar and salt.
I don't know if citrate is really a problem, but it does bind calcium tightly, and also has an affinity for other divalent ions such as magnesium. As a rule I avoid it, just in case. There are plenty of other alternatives after all. It never made sense to me to use calcium citrate as a supplement.
My early research identified a defect with the enzyme aconitase as the likely cause of high citrate, but I don't know if current research would support it. Aconitase is required to use citrate in the Krebs (citric acid) cycle, but it cannot form properly in the absence of sufficient glutathione (and possibly reduced glutathione). Aconitase is also inactived by nitric oxide and destroyed by peroxynitrate. So many of the current biochemical theories of CFS would predict high citrate (and low mitochondrial function). What this means is we often have too much citrate. An implication of this is that if you want to take a citrate supplement, take it at lunchtime, and never at bedtime or early morning.
As an alternative model I have also postulated that citrate is deliberately released during sleep to combat oxidative stress - this would bind any free iron, a known source of oxidative stress.
I switched to a calcium citrate supplement last week, and it seems like it's made my muscle twitching a lot worse. I take it along with another cal/mag supplement (which I just realized also has some citrate in it), as I eat no dairy, so if I skip calcium for more than a day I get strong muscle cramps.
But on the flip side, I can't seem to find that 'balance' -- either that or the citrate is the problem. (Or not enough vitamin d? I'm getting tested for that later this week.)
I read somewhere that Cheney said citrate levels are high in CFS, and also read a post earlier today where a woman said when her doctor put her on calcium citrate, she went downhill about 50 percent!
Any info would be greatly appreciated. I've had this twitching off and on for years, but mostly OFF. And now it's on big time, plus also some RLS. ARGH.
THANKS IN ADVANCE,