Low plasma carnosinase activity promotes carnosinemia following

21 Objectives A polymorphism in the CNDP1 gene, resulting in decreased plasma carnosinase activity, 22 is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural 23 scavenger/suppressor of reactive oxygen species, AGE’s and reactive aldehydes, is readily degraded 24 in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase 25 activity might be advantageous to reduce diabetic complications. The aim of this study was to 26 examine whether a low carnosinase activity promotes circulating carnosine levels following 27 carnosine supplementation in humans. 28 Methods Blood and urine was sampled, in 25 healthy subjects following acute supplementation 29 with 60mg/kg BW carnosine. Pre-cooled EDTA tubes were used for blood withdrawal and plasma 30 samples were immediately deproteinized and analyzed for carnosine and beta-alanine by HPLC. 31 CNDP1 genotype, baseline plasma carnosinase activity and protein content were assessed. 32 Results Upon carnosine ingestion, 8 of the 25 subjects (= responders) displayed a measurable 33 increase in plasma carnosine up to 1h following supplementation. Subjects with no measurable 34 increment in plasma carnosine (= non-responders) had an approximately 2-fold higher plasma 35 carnosinase protein content and an approximately 1.5-fold higher activity compared to the 36 responders. The urinary carnosine recovery was 2.6-fold higher in the responders versus non37 responders and was negatively dependent on both the activity and protein content of the plasma 38 carnosinase enzyme. 39 Conclusion A low plasma carnosinase activity promotes the presence of circulating carnosine upon 40 an oral challenge. These data may further clarify the link between CNDP1 genotype, carnosinase 41 and diabetic nephropathy. 42