Matt Pratt-Hyatt
Chief Science Officer, KBMO

1. Nutrition – Understanding reactants and co-factors

Our bodies use a lot of different molecules to function properly. These molecules include reactants (which help fuel different reactions) and co-factors (chemicals which are not destroyed in the reactions but are important to speed them up). Having the proper amounts of reactants and co-factors is important to maintain a healthy individual. These molecules are either acquired through diet, or made from other molecules in the body.

Urine markers to measure nutrient deficiencies
This section of compounds is helpful when making decisions around whether changes in diet or supplementation are required in order to help your patient. These markers are some of the most useful in terms of measuring a variety of deficiencies:

Alpha-ketoisovalerate/ Alpha-ketoisocaproate/ Alpha-keto-Beta-methylvalerate – Urinary elevations of these ketoacids can be caused by deficiencies in vitamin cofactors. The enzymes required for metabolism of these molecules need vitamins B1, B2, B3, B5 and lipoic acid to perform their reactions (1, 2).

Xanthurenate – Xanthurenic is a product of the kynurenine pathway which is one of the routes of tryptophan catabolism. When B6 is low, xanthurenate could build up in the body and be excreted in urine. Conditions that are correlated with high xanthurenate include inflammatory diseases and immune suppression (3).

Pyridoxic – Correlated with B6 intake. Low values could indicate the patient is deficient in B6 (4).

Pantothenic – Pantothenic, which is also known as B5, is an essential vitamin.  It is found in some foods and is vital in the synthesis of coenzyme A (CoA) (5).

Glutaric – Produced from the breakdown of both lysine and tryptophan. Elevations could indicate an insufficiency of B2. Very large buildups could indicate a rare organic aciduria. This is caused by deficiency of glutaryl-CoA dehydrogenase(6).

Formiminoglutamic acid (FIGLU) – Elevated levels of FIGLU could indicate folate, vitamin B12, or a rare genetic disorder FTD deficiency(7).

Methylmalonic Acid (MMA) – High values of MMA could indicate B12 deficiency. Patients taking B12 typically lowers MMA(8).

2. Assessing Oxalates

Oxalate is a compound that forms highly insoluble complexes with calcium. It accumulates in, and damages, various tissues. One of the primary areas is the kidney (9).

Besides local inflammation, oxalate also triggers the inflammasome which can then lead to auto-inflammatory disease (10).

Oxalate elevations can come from three different areas, the most common from diet. Many leafy greens and fruits are high in oxalates. The second is from yeast and other microbiota that form oxalates in the gut. Thirdly, certain genetic polymorphisms can lead to enzymes that are less efficient at clearing out oxalates, resulting in oxalate build-up in the body (this would potentially also lead to buildups in glycolic and glyceric (11, 12)).

Glycolic Acid – Glycolic Acid is a metabolite of the oxalate pathway. Deficiencies in either enzyme efficiency or inadequate amounts of B6 could lead to a buildup of glycolic acid. When seen in tandem with high oxalic acid, this could indicate a genetic predisposition to oxalate buildup (13). It could also indicate a predisposition to forming Primary Hyperoxaluria I (14).

Glyceric Acid – Glyceric Acid is a metabolite of the oxalate pathway and when seen in tandem with high oxalate could also indicate a genetic predisposition to oxalate buildup.  It could indicate a predisposition to form the disease Primary Hyperoxaluria II(14).

Want to Learn More?

If you’re interested in learning more about how organic acids can provide insights into nutritional deficiencies and oxalate levels in your patients, please contact us here.

The KBMO Diagnostics Metabolics Insights Profile (MIP) provides a full metabolic snapshot for your patients, including markers that can reveal issues such as nutritional deficiencies, microbial overgrowth, toxic exposure, oxalates, mitochondrial impairment, neurotransmitter imbalances and much more.

References:

1. K. Shibata, M. Sakamoto, Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans. J Nutr Sci Vitaminol (Tokyo) 62, 220-228 (2016).
2. A. Solmonson, R. J. DeBerardinis, Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem 293, 7522-7530 (2018).
3. M. A. Ciorba, Kynurenine pathway metabolites: relevant to vitamin B-6 deficiency and beyond. Am J Clin Nutr 98, 863-864 (2013).
4. J. Kelsay, A. Baysal, H. Linkswiler, Effect of vitamin B6 depletion on the pyridoxal, pyridoxamine and pyridoxine content of the blood and urine of men. J Nutr 94, 490-494 (1968).
5. P. M. Coates, Paul, M.C., Blackman, M., Blackman, M.R., Cragg, G.M., Levine, M., White, J.D., & Moss, J. (Eds.). (2004). Encyclopedia of Dietary Supplements (Online) (1st ed.). CRC Press. https://doi.org/10.1201/b13959.
6. S. Kolker et al., Diagnosis and management of glutaric aciduria type I–revised recommendations. J Inherit Metab Dis 34, 677-694 (2011).
7. P. T. Lascelles, D. Donaldson, “Formiminoglutamic Acid (FIGLU) Test” in Diagnostic Function Tests in Chemical Pathology. (Springer Netherlands, Dordrecht, 1989), 10.1007/978-94-009-1846-7_31, pp. 59-60.
8. T. Kwok et al., Use of fasting urinary methylmalonic acid to screen for metabolic vitamin B12 deficiency in older persons. Nutrition 20, 764-768 (2004).
9. L. Hagler, R. H. Herman, Oxalate metabolism. I. Am J Clin Nutr 26, 758-765 (1973).
10. T. Ermer, K. U. Eckardt, P. S. Aronson, F. Knauf, Oxalate, inflammasome, and progression of kidney disease. Curr Opin Nephrol Hypertens 25, 363-371 (2016).
11. L. K. Massey, H. Roman-Smith, R. A. Sutton, Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones. J Am Diet Assoc 93, 901-906 (1993).
12. Z. Li et al., A study of organic acid production in contrasts between two phosphate solubilizing fungi: Penicillium oxalicum and Aspergillus niger. Sci Rep 6, 25313 (2016).
13. E. Leumann, B. Hoppe, T. Neuhaus, Management of primary hyperoxaluria: efficacy of oral citrate administration. Pediatr Nephrol 7, 207-211 (1993).
14. D. J. Dietzen et al., Extraction of glyceric and glycolic acids from urine with tetrahydrofuran: utility in detection of primary hyperoxaluria. Clin Chem 43, 1315-1320 (1997).