Thiamine participates as a cofactor in oxidative phosphorylation, and its absence is sorely missed.
Historically, this is a cause of lactic acidosis in the malnourished patient in who there is no other apparent cause of lactic acidosis.
Among its many uses, thiamine acts as a coenzyme with pyruvate dehydrogenase to form acetyl-CoA. So of course, if you completely abolish thiamine, there will be no entry for pyruvate into Krebs cycle. And even if it could enter, alpha-ketoglutarate dehydrogenase would also need thiamine as a coenzyme to convert alpha-ketoglutarate into succynyl coenzyme A. Thus, a deficiency of thiamine produces an excess of lactate by preventing pyruvate from becoming a substrate for oxidative metabolism.
It seems pretty difficult to become so thiamine deficient that it would produce a clinically relevant lactic acidosis. The case reports in the literature all seem to involve people on TPN in whom multivitamins are accidentally not administered.
Who gets thiamine deficient these days?
One can easily envision a developing world environment where this sort of nutritional deficiency is commonplace. However, it seems this problem can also exist in the nutritionally competent West. Specifically, people on long-term frusemide (a huge proportion of the ICU population) seem to have a thiamine deficiency due to a constant urinary loss. And yes, it is a deficiency which is relevant to their outcome- the patients in that study all had an improvement in their systolic function once thiamine was replaced at 100g IV per day, for 7 days.
In this way, one might argue that the hopelessly shocked cardiac patient could benefit from thiamine supplementation, and is unlikely to be harmed by it, which is a strong argument for supplementing everybody.
But of course these are occult thiamine deficits. Nobody expected those frusemide-intoxicated patients to develop a thiamine deficiency. The chronic alcoholic, on the other hand, is at risk of this every day; the term “wet beriberi” is used to describe the cardiovascular collapse which ensues, which is typically associated with a lactic acidosis.
Red cell transketolase is an enzyme of the pentose pathway which is affected by the presence of thiamine; its activity is decreased in the absence of thiamine (which it uses as a cofactor). Its increased activity with the addition of thiamine in the laboratory (measured by red cell NADH consumption) is used as an indirect evidence of thiamine deficiency.