The Organic (Metabolic) acids we all excrete in our urine every day, represent key intermediary compounds of the many internal biochemical pathways underway within the body, as well as the metabolism of many exogenous compounds also.
The Citric Acid Cycle (CAC) in the mitochondrion of every cell for example, is comprised of nine organic acids and eight enzymes, and is the central metabolic pathway for the metabolism of all fuel molecules to the body, i.e. dietary carbohydrates, proteins, and fats.
Deficiencies in any of the CAC enzymes therefore causes an inefficient cycling of the organic acid intermediates, any number of which can then consequently increase in concentration in the urine. Metabolic anomalies such as these are commonly known as organic acidurias, and can indicate a well-established group of disorders classified under the term of Inborn Errors of Metabolism (IEM).
In such patients, urinary organic acid profiling reveals these greatly elevated organic acid intermediates due to the blocks in their metabolic pathways; any block which may arise from a defective or missing enzyme required for the pathway in question.
Inborn Errors of Metabolism however are generally rare and evident in early life. (Life-threatening symptoms may result from the toxic accumulations of substrates upstream of the metabolic block, deficiencies of products downstream of the block, or from intermediates of alternative biochemical pathways). Any block which may arise from a defective or missing enzyme, may also arise from the insufficient availability of a given substrate cofactor required in the pathway in question.
Less obvious or severe cases of variable enzyme activity or suboptimal function may be due to a number of other factors. Age, genetics, oxidative damage, toxic exposure, nutritional status, environmental circumstances and lifestyle, as well as malabsorption, effects of pharmacological drugs, and native abnormalities of nutrient utilisation, may all account for sub-optimal functioning of enzyme pathways, having a multitude of far-reaching effects on overall cellular health and body function.
In vitamin-dependent or vitamin-responsive disorders, many of which are inheritable (genetic) conditions, use of pharmacological doses of a vitamin (much higher than would commonly be prescribed without confirmation of this need), sufficiently overcome the metabolic blockage for normal function to occur with symptom resolution.
Megaloblastic anemia, Methylmalonic Aciduria, and B6-responsive anemia are just a few well-known disorders that respond favorably to high dose vitamin therapy, and circumvents the need for identification of single nucleotide polymorphisms (SNPs) by instead assessing the current live metabolic needs affected by all these above mentioned factors via urine. Administration of relatively high doses of the vitamin component of the corresponding coenzyme serves to restore enzymatic activity for many inheritable defects due to these SNPs.
Methylmalonic acid for example, has long been known as a marker for vitamin B12 deficiency. As serum levels of cobalamin (B12) decrease, levels of urinary methylmalonate increase. Therefore, methylmalonate serves as an effective ‘functional’ marker for B12 deficiency. The research of Miller et al., have recently shown that methylmalonate is a reliable index of defective enzyme activity, namely transcobalamin II (TCII), responsible for transporting B12 from the ileum to the tissues. This common polymorphism results in a decreased binding affinity of the enzyme for B12 with consequent compromised delivery of B12 to tissues, and overall decrease in B12 functional status.
Organic Metabolic Acid Profiling typically encompasses a panel of compounds analysed in urine, including the following key categories for metabolic consideration; Glycolysis and Citric Acid Cycle Metabolism, Fatty Acid Oxidation, Ketone Metabolism, Cofactor Need and Neurotransmitter Metabolism, as well as markers of detoxification and bacterial body flora metabolism.
These will often provide a wealth of clinically relevant information for truly tailored patient care, that could not be obtained any other way. The sheer power and clinical value of this test is however reliant on the lab analysis technology that is used to ensure the stability of the analytes being tested and the sufficiently detailed measurement of them. Gas Chromatography/Mass Spectrometry (GC/MS) represents the gold standard for organic acid analysis, without equivocation (despite commonly used Liquid Chromatography for such purposes), and its accuracy is further enhanced by the stability of analytes in storage afforded by dry urine dip-stick technology.
Organic acid analysis via GC/MS is so accurate it has helped to identify Diabetes Mellitus as not only a defect in glucose metabolism but also of Amino Acid and Fatty Acid metabolism as well, and often proves invaluable in the assessment and treatment of many multi-system and complex conditions such as Digestive Disorders, Weight Gain, Hypothyroidism, Mental Disorders, ADD, Anxiety, Depression, Chronic Fatigue, Fibromyalgia, Multiple Chemical Sensitivity etc…
When choosing a clinical assessment method for Urine Metabolic Organic Acid analysis, a stable dried urine sample, (sent without the need for refrigeration), to the lab for analysis via GC/MS, can be considered the far superior choice and will acquire the most referable results with which to derive clinical insights from and therefore efficacy of treatment.
Thus a simple first morning urine dip-stick should be all that is required to obtain stable, accurate and powerful insights into the overall metabolic status of your clients—encompassing numerous functional assessments for making one truly individualised and comprehensive clinical strategy.
The further interpretation insights now being provided by the lab and the increased utilisation of this powerful clinical tool in practice, make it an exciting and increasingly key component of the ever unfolding field of personalised medicine today.
ABOUT THE AUTHOR:
Warren Maginn holds a Bachelor Degree in Nutritional Medicine and is Research Nutrition’s National Technical Educator, carrying extensive technical knowledge in the field of Functional Medicine. Warren is also a Nutritional Medicine Practitioner and Lecturer for Endeavour College in Brisbane. He is passionate about assisting practitioners and students to gain greater technical insights from current functional medicine understanding and how to apply this knowledge in clinical practice.