Lactate & pyruvate

Lactate and pyruvate show the state of energy metabolism at cell level. Pyruvate is the end product of glycolysis and is normally processed further in the mitochondria into acetyl-CoA (citric acid cycle). When the mitochondria use pyruvate less well – for example with B1 deficiency, a lack of oxygen or disorders of the respiratory chain – more pyruvate is converted into lactate; the lactate/pyruvate ratio is therefore looked at with questions about mitochondrial function. Studies have observed partly raised lactate levels in ME/CFS and long COVID. Measurable in the organic acids panel.

What the lactate/pyruvate ratio shows

Lactate and pyruvate are constantly converted into each other in the cytoplasm by lactate dehydrogenase. Which side the balance lies on depends on how much NADH is present in the cell relative to NAD⁺: when there is a lot of NADH, it shifts towards lactate. NADH is produced in glycolysis and is normally passed on into the mitochondria via shuttle systems, where the respiratory chain converts it back into NAD⁺ and gains ATP in the process. The two values together therefore show two things: how much pyruvate is produced overall and how well the mitochondria process the NADH.

Low lactate and pyruvate – what does it mean?

When both values are low and their ratio is balanced, glycolysis is processing little glucose and the mitochondria are using pyruvate and NADH promptly. This is to be expected at rest, during fasting or on a low-carbohydrate diet, when the cells draw more energy from fatty acids and ketone bodies. An unremarkable or low ratio with raised pyruvate and lactate at the same time, by contrast, is observed when the bottleneck lies at pyruvate dehydrogenase while the respiratory chain is still processing NADH sufficiently.

High lactate/pyruvate ratio – what happens in the body?

A high ratio shows that NADH is building up in the cytoplasm: the respiratory chain is taking up fewer electrons because oxygen is lacking or individual complexes of the respiratory chain or coenzyme Q10 are not working sufficiently. The cell then switches to the lactate route to regenerate NAD⁺ for glycolysis, and obtains only a small part of the energy per glucose molecule that the mitochondria could supply. This becomes noticeable above all in organs with high energy demand – with rapid muscle fatigue on exertion and declining concentration. A high ratio occurs with a lack of oxygen in the tissues, with inherited and acquired disorders of the respiratory chain, with some medications and after alcohol, whose breakdown in the liver produces additional NADH.

The interpretation is given in your report.