Assessing Mitochrondrial Function: the Organic Acid Test

Mitochondria are the last stop for extracting energy from food and oxygen. There are a multitude of reasons mitochondria may fail to perform efficiently, ranging from nutrient deficiencies to genetic mutations. Reactive oxygen species, from endogenous and exogenous sources, can be a significant challenge to mitochondrial function.¹ The electron transport chain is one of the main producers of reactive oxygen species.² Lab tests, combined with a thorough history and exam, are important in helping understand how mitochondrial function might be compromised and how to best direct potential treatment plans.

Organic Acid Test

One option for assessing mitochondrial function is an organic acid test. This evaluates the metabolites from digestion, assimilation, metabolism, and the production of ATP. The preferred specimen is a urine collection; these metabolites are more easily extracted from urine than plasma.¹ If one or more pathways is not functioning properly, the organic acids will "overflow” into the urine.³ A report may include 30-40 metabolites, including those from detoxification processes and gut flora.

Select Organic Acids and Related Metabolites

The organic acids ethylmalonate, adipate, and suberate are reflective of beta-oxidation. L-carnitine is necessary for carrying long-chain fatty acids across the mitochondrial membrane.⁴ If L-carnitine levels are inadequate, beta-oxidation might alternately take place in peroxisomes, creating elevated levels of adipate and suberate. Ethylmalonate, a breakdown product of butyrate, is also dependent on L-carnitine. Elevated succinate, fumarate, and malate may indicate inefficient energy production as they are part of mitochondrial oxidation.3 Markers that are indicative of carbohydrate metabolism are pyruvate, lactate, and beta-hydroxybutyrate. Metabolites of the citric acid cycle, some of which are mentioned previously, can also indicate variations in energy production.

CoQ10, another important component in proper mitochondrial function, is mostly lipoprotein bound making plasma measurement challenging. CoQ10 levels can be more easily quantified in leukocytes and platelets and may more accurately reflect tissue concentrations.¹ If lactate levels are high, and not in combination with elevated pyruvate, this may reflect deficient CoQ10 levels. It may also be useful to correlate CoQ10 levels with hydroxymethylglutarate (HMG), a cholesterol precursor. When HMG levels are high, cells may not be able to make adequate CoQ10 to meet tissue demands. Lactate, succinate, fumarate, and malate levels are also indicators of efficient energy production through CoQ10 utilization.³

If mitochondria are not functioning properly or efficiently, cells may not be able to make adequate ATP to meet energy demands. Lab testing can provide clues to where inefficiencies or problems lie within metabolism. It is important to remember these tests are not diagnostic, but they can help guide treatment options and evaluate progress. Correlating digestive function is also an important part of interpreting mitochondrial function information.

REFERENCES

1. Haas RH et al. Molecular Genetics and Metabolism. 2008;94(1):16-37. doi:10.1016/j.ymgme.2007.11.018.
2. Alfadda AA et al. Journal of Biomedicine and Biotechnology. 2012;2012:1-14. doi:10.1155/2012/936486.
3. Grisanti R et al. http://www.functionalmedicine.net/pdf/insider's guide_37.pdf. Published 2008. Accessed June 5, 2016.
4. Sowell J et al. Journal of Chromatographic Science. 2011;49(6):463-468. doi:10.1093/chrsci/49.6.463.