Reducing Substances

Detection of non-specific reducing substances in urine was begun more than 50 years ago as a screening test for inborn errors of carbohydrate metabolism in pediatric patients. The clinical basis of this test goes back to the early-to-mid1960s when investigations showed a relationship between thepresence of reducing substances in the urine of newborns, and the presence of specific sugars [1,2]. The qualitative measurementof urinary reducing substances was accepted as a quick screening test of asymptomatic patients in the absence of any other screening procedure.

Home-brew reagents were eventually replaced by commercially available Clinitest tablets. Clinitest was usually run as a reflex test on urine samples with a negative dipstick glucose result. A negative dipstick glucose assay and a positive reducing test suggest that some substance other than glucose is present in the urine.These sugars include galactose, lactose, and fructose. However, Clinitest, which involves the reduction of colorless cupric ion to colored cuprous ion, is not specific for sugars. Many drugs produce a positive result [3].

Today, all states,within the United States require mandatory newborn screening for more than 30 inborn errors of metabolism using tandem mass spectrometry. This testing detects galactosemia, which is the most common inborn error of carbohydrate metabolism. Other diseases of carbohydrate metabolism (except diabetes) have much lower prevalence or are clinically more benign than galactosemia and do not require screening of asymptomatic newborns.

Based on this information, many laboratories have discontinued automatic reflex testing for reducing substances in children less than 2 years of age. Clinitest is only performed at the specific order of a physician.


  1. Fiser-Herman M, Petrovacki M. Urinary reducing substances in alkaptonuria. Clin Chim Acta 1958;3:248–252.
  2. Giovannini M, Consonni V, Calleri A. Research on urinary elimination of reducing substances in the first and second infancy: comparison of results obtained with paper and thin layer chromatography. Minerva Pediatr 1965;17:1702–1703.
  3. Young DS, Pestaner LC, Gibberman D. Effect of drugs on clinical laboratory tests. Clin Chem 1975;21:1D–432.
  4. Plapp, FV, Expanded Newborn Screening, Saint Luke’s Regional Laboratories Clinical Laboratory Letter, July 2005.
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