Supplements or drinks with tricarboxylic acid cycle intermediates should be avoided though supplements with alpha ketoglutarate could be helpful. TET enzymes are 2-oxoglutarate dependent.enzymes that demethylate DNA. JmjC domain-containing proteins are 2-oxoglutarate dependent.enzymes that demethylate histones .Fumarate and succinate inhibit TET and JmjC domain-containing proteins. This could lead to DNA hypermethylation and histone hypermethylation. Malic acid could inhibit fumarate dehydratase by end product inhibition and lead to a build up of fumarate.
Accumulation of succinate and fumarate are associated with cancer due the inhibition of 2-oxoglutarate-dependent dioxygenases, such as TET and JmjC-domain containing proteins. Citrate is a competitive inhibitor of oxaloacetate for citrate synthase. Citrate synthase also produces coenzyme A which is needed by the 2-oxoglutarate complex. Citric acid from soft drinks could dysregulate the the 2-oxoglutarate complex. There is a lot of circumstantial evidence that citric acid has goofy effects on individuals witness Mountain Dew ads.
A lot of supplements contain tricarboxylic acid cycle intermediates. Calcium citrate contains citrate. Magnesium succinate contains succincate. Carnitine fumarate contains. fumarate. Citruline malate contains malate, TCA intermediates are everywhere is supplements.
But as always the key selling point of supplements is ‘better absorption’ and minerals, for example, minerals bound to citrate, can be well absorbed. A huge and very frequently deleterious factor not usually considered is what supplements are bound to. ‘Better absorption’ is the siren call of supplements. Chelated minerals are also avoided.