When a client’s symptoms point toward possible mitochondrial dysfunction, I like to start with labs they’re likely to already have on hand — a CBC and CMP — before moving on to more specialized testing. Here’s how I approach that process.
Starting With the CMP
From the comprehensive metabolic panel, I look at bicarbonate, albumin, AST, and bilirubin. Albumin and AST are markers of liver function, which mitochondrial dysfunction can impair. Low bicarbonate can also be a sign of mitochondrial dysfunction, though there are other possible causes I’d need to rule out.
Low bilirubin can indicate oxidative stress — but I’d want to see uric acid and GGT alongside it, and I’d also recommend ordering alkaline phosphatase, since low bilirubin can show up with zinc deficiency as well as oxidative stress. Uric acid tends to run low in both cases. GGT runs high with oxidative stress, but it can also be elevated due to alcoholism, pancreatitis, or cholestasis, so it needs to be interpreted in context rather than in isolation.
Low CO2 could suggest pyruvate isn’t making it into the mitochondria, but I wouldn’t draw that conclusion from CO2 alone. Diet (high protein, low fruit and vegetable intake) could be contributing to the body’s acid load. Acid-elimination pathways could be impaired (Lambert & Abramowitz, 2021). BUN, creatinine, and eGFR give a read on kidney function.
Reading the CBC
On the CBC, I look for any values outside normal range that might point to anemia, then follow up by assessing the specific nutrients associated with the pattern that presents. Any cell type counts that are out of range are also worth investigating further.
Urinary Organic Acids Testing
Beyond bloodwork, a urinary organic acids test can be useful, since different mitochondrial metabolites show up depending on how well the mitochondria are functioning.
Fatty acid transport. If the carnitine transporter isn’t adequately moving fatty acids into the mitochondria for beta-oxidation, we can see elevated adipate and suberate, reflecting a shift toward omega oxidation. Elevated ethylmalonate can point to butyrate having trouble getting into the mitochondria.
Electron transport chain function. Pyruvate and lactate levels on this test are particularly informative. An elevated lactate to pyruvate ratio points toward electron transport chain dysfunction causing pyruvate to back up — pyruvate dehydrogenase reduces pyruvate to lactate whenever it’s not able to be used by the mitochondria. If the electron transport chain isn’t functioning properly, lactate can run as much as twenty times higher than pyruvate. If instead both pyruvate and lactate are elevated together, that pattern points toward a nutrient deficiency limiting pyruvate dehydrogenase itself, rather than an electron transport chain problem.
CoQ10 status. CoQ10 markers on the organic acids test are worth reviewing as well, since CoQ10 is required for the electron transport chain to function. HMG-CoA reductase is one of the enzymes along the CoQ10 production pathway; impairment there shows up as elevated hydroxymethylglutarate. CoQ10 deficiency can also show up as elevated TCA cycle intermediates — succinate, fumarate, and malate — since the TCA cycle’s throughput is limited by how well the electron transport chain (which requires CoQ10) is functioning.
Carnitine and Acylcarnitine Panels
A pattern of low free carnitine with high acylcarnitine suggests mitochondrial dysfunction is preventing acylcarnitine from entering the mitochondria — meaning long-chain fatty acids can’t get in for beta-oxidation, and carnitine can’t cycle back to pick up the next fatty acyl-CoA because it’s still holding onto the one that hasn’t been admitted.
The Takeaway
Mitochondrial dysfunction rarely shows up as one clean marker —but we can uncover the beginning of a pattern from standard bloodwork, and further clues from urinary organic acids, or a carnitine panel. Cross-referencing these results helps narrow down where in the process — fatty acid transport, the electron transport chain, or CoQ10 production — the bottleneck is likely occurring, which in turn shapes what kind of support might actually help.
The content of this blog is for educational purposes and is not intended as medical advice. Please work with a qualified healthcare provider for personalized guidance and lab interpretation.
Reference
Lambert, D. C., & Abramowitz, M. K. (2021). Obesity and the risk of low bicarbonate: A cohort study. Kidney Medicine, 3(4), 498–506.
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