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Blood Lactate in the Development of Anxiety Symptoms:  A Critical Examination of Pitts and McClure's Hypothesis and Experimental Study

Hanus J. Grosz, FACP, DPM; Barbara B. Farmer, BS
Arch Gen Psychiatry. 1969;21(5):611-619. doi:10.1001/archpsyc.1969.01740230099014.
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Pitts and McClure's Theory and Experiment  RECENTLY Pitts and McClure1-3 claimed to have demonstrated that symptoms of anxiety neurosis are caused by lactate ion, or more specifically, by the effect which excess of lactate ion has on ionized calcium in anxiety-prone subjects.Prompted by the finding that exercise tends to produce an excessive amount of lactic acid in patients with anxiety neurosis,4 Pitts and McClure hypothesized that "anxiety symptoms may have a common determining biochemical end mechanism involving the complexing of ionized calcium at the surface of excitable membranes"2 by lactate. They reasoned that lactate ion accumulates in excessive amounts, more than the normal percentage of ionized calcium becomes complexed with lactate. When the remaining free ionized calcium becomes reduced to clinically significant low concentrations, there will be interference with normal nerve conduction and activity. According to Pitts and McClure,

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