Am J Physiol Renal Physiol. 2012 Jun 15;302(12):F1537-44. Epub 2012 Apr 11.
Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans.
Everaert I, Taes Y, De Heer E, Baelde H, Zutinic A, Yard B, Sauerhöfer S, Vanhee L, Delanghe J, Aldini G, Derave W.
Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
A polymorphism in the carnosine dipeptidase-1 gene (CNDP1), resulting in decreased plasma carnosinase activity, is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural scavenger/suppressor of ROS, advanced glycation end products, and reactive aldehydes, is readily degraded in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase activity might be advantageous to reduce diabetic complications. The aim of this study was to examine whether low carnosinase activity promotes circulating carnosine levels after carnosine supplementation in humans. Blood and urine were sampled in 25 healthy subjects after acute supplementation with 60 mg/kg body wt carnosine. Precooled EDTA-containing tubes were used for blood withdrawal, and plasma samples were immediately deproteinized and analyzed for carnosine and β-alanine by HPLC. CNDP1 genotype, baseline plasma carnosinase activity, and protein content were assessed. Upon carnosine ingestion, 8 of the 25 subjects (responders) displayed a measurable increase in plasma carnosine up to 1 h after supplementation. Subjects with no measurable increment in plasma carnosine (nonresponders) had ∼2-fold higher plasma carnosinase protein content and ∼1.5-fold higher activity compared with responders. Urinary carnosine recovery was 2.6-fold higher in responders versus nonresponders and was negatively dependent on both the activity and protein content of the plasma carnosinase enzyme. In conclusion, low plasma carnosinase activity promotes the presence of circulating carnosine upon an oral challenge. These data may further clarify the link among CNDP1 genotype, carnosinase, and diabetic nephropathy.
The subjects were given more than 4 grams of carnosine!! and the non-responders had no increase in carnosine serum levels. However the CNDP1 folk had an increase.
What I think is important to note is that nonresponders had an increase in carnosinase levels AND activity. For those of us supplementing with carnosine maybe this may decrease our limited supply (however I have no idea if carnosine is transported in the blood).
Is there a way to determine our CNDP type? Does anyone know if 23andme covers this?
Also here something on beta-alanine:
Amino Acids. 2012 Jul;43(1):57-65. Epub 2012 Feb 23.
Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis.
Stellingwerff T, Decombaz J, Harris RC, Boesch C.
Nestlé Research Center, Lausanne, Switzerland. email@example.com
Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose-response study demonstrated a large linear dependency (R2=0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis.